March 2019 digital v1

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VOL 5 | ISSUE 11 

PAGES 100 

MARCH 2019 

FUTUREMEDICINEINDIA.COM 

No 1 

INFECTIOUS 

KILLER AGAIN 

TUBERCULOSIS IS BACK TO THE FORE DUE TO MICROBIAL 

RESISTANCE AND A WANT OF NOVEL DRUG REGIMENS 

TECHNOLOGY CASE REPORT STRAIGHT TALK SCIENTIFIC REPORT 

NGS BREAKS NEW 

GROUND IN TB CARE 

WHEN PARKINSON’S 

STRIKES EARLY 

NOBEL LAUREATE 

PROF ADA E YONATH 

GENETIC TARGET 

FOR CRC

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editor’s note 

editor’s note 

March 2019 / Vol. 5 / Issue 11 

Founder AUGUST & 2018 Editor / Vol: 5 / Issue: 4 

CH Unnikrishnan 

Executive Editor 

S Harachand 

Science Editor 

Dr Rajanikant Vangala 

Consulting Editors 

Dr Founder Shivanee & Editor Shah 

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Dear Doctor, 

We say with much pride that technology is changing the paradigm in 

today’s Dear medicine. Doctor We also get much excited about the stories of newgeneration 

techniques like gene sequencing and editing, 3D printing, deep 

learning We know and you artificial are busy. intelligence, It is always which reassuring are revolutionizing that the trust the way and we faith do of 

diagnosis hundreds and of treatments patients in today. your Certainly, healing touch these keeps are great you achievements 

busy in this noble 

of the profession. brave new In the scientific hectic world practice, that it’s need quite to be natural acknowledged that you might and miss 

accepted. out on some of the latest developments in emerging medicine. In this era 

But, of innovation, the same medical time, we science tend to is getting forget a redefined sad reality: almost Millions by of the people day. Old 

are technologies still dying due are to being simple replaced infections by in the many new parts in the of the blink world of an including eye. Robots 

India. and This artificial is because intelligence the last are antibiotics taking over that a we good invented part of sixty the years procedures, 

ago while are becoming genomics less and effective molecular and science the microbes unveil the that mysteries we successfully of life further. 

countered We are decades fortunate ago to have are getting such breakthroughs stronger and have as they started help fighting specialists back like 

more you aggressively. rise above the Tuberculosis expectations is back of today’s the fore informed as the patient. No.1 infective 

disease that kills people even in this era of genomic medicine. The most 

unfortunate 

Similarly, it 

part 

is also 

is that 

a time 

this is 

when 

despite 

India 

the 

is 

scientific 

witnessing 

community’s 

revolutionary 

best 

growth in 

efforts to find novel pathways for developing new antibiotics. Our cover 

healthcare industry, especially in the private sector, wherein an increasing 

story in this edition tries to get to the depths of this glaring contradiction. 

number of doctors are taking up multiple roles of clinician, researcher and 

Serendipitously, we also met Prof Ada E Yonath, the chemistry Nobel 

entrepreneur. This requires expansion of your focus to a wider canvas. In 

Laureate whose pioneering work on ribosomes and their structure and 

this context, it becomes important how a busy professional like you can 

functions opened up a whole new avenue for developing new and more 

keep pace with these latest developments in a quick and easy way. 

effective antibiotics. You can read more about the encounter in Straight 

Talk. 

Inside, At Future you’ll Medicine, also find which a beautifully is conceived illustrated and story crafted on by India a team generously of senior 

honouring journalists, its great scientists clinicians and doctors, with the our nation’s aim highest is to help honour, you do as just well that. We 

as are US-based equipped genomics to bring scientist you the Dr latest Amitabha from Chaudhuri’s the science well of care explained from across 

scientific the world report in an on interesting the alarming and growth convenient of inherited way, supplemented colorectal cancer by and the best 

new of generation views and treatments. analyses from the masters in each field. We present you this 

specialised knowledge vehicle that plugs you into the emerging world of 

Happy care seamlessly. reading Come, let’s join hands in this information journey. 

CH Unnikrishnan 

editor@futuremedicineindia.com 

C H Unnikrishnan 

editor@futuremedicineindia.com 

www.futuremedicineindia.com futuremedicineindia FutureMedIndia 

AUGUST 2018/ FUTURE MEDICINE / 3

TECHNOLOGY CASE REPORT ORTHOPAEDICS SCIENTIFIC REPORT 

Vol 5 Issue 11 

March 2019 

₹ 250.00 


PAGES 100 

MARCH 2019 


No 1 

INFECTIOUS 

KILLER AGAIN 

TUBERCULOSIS IS BACK TO THE FORE DUE TO MICROBIAL 

RESISTANCE AND A WANT OF NOVEL DRUG REGIMENS 

NGS BREAKS NEW 

GROUND IN TB CARE 


STRIKES EARLY 

CHALLENGES OF 

SKELETAL TB 

GENETIC TARGET 

FOR CRC 

30 

TECHNOLOGY 

NGS BREAKS 

NEW PATH 

IN TB CARE 

REGULAR FEATURES 

06 Letters 

08 News updates 

14 Policy 

32 Drug approvals 

56 Research snippets 

60 Hospital news 

62 Scientific report 

66 Cosmetic surgery 

68 Public health 

70 Devices&gadgets 

74 Pharma 

80 Research 

82 Products 

85 Guidelines 

92 Events 

96 Calendar 

98 Holy grail 

Columns 

16 THE CATALYST 

Muralidharan Nair 

48 THE CELLVIEW 

Dr Rajani Kanth Vangala 

46 

CASE REPORT 

FIGHTING OFF 

SWINE FLU 

Swine flu can be one of 

the most severe acute 

respiratory distress syndromes 

36 

STRAIGHT TALK 

“EVERYBODY HAS 

TO DEVELOP THE 

WAY THEY ARE. 

TAKING ADVICE 

IS LIKE COPYING 

SOMEONE” 

Prof Ada E Yonath

50 

ORTHOPAEDICS 

SKELETAL 

TUBERCULOSIS 

THE CHALLENGES 

Occurrence of 

osteoarticular 

tuberculosis recorded 

a rising trend among 

extrapulmonary TB 

world over 

18 

COVER STORY 

WAR TO END 

A SCOURGE 

India is battling to eliminate 

TB by 2025 — to vanquish an 

infectious malady that has been 

haunting humanity for ages 

40 

EDUCATION 

MBBS INTERNS 

MAY SOON GET 

UNIFORM STIPEND 

MCI BOG’s decision is 

seen as a move to end the 

discrimination 

faced by medical interns in 

the country 

76 

A strong pipeline 

of novel drugs will 

ensure that we are 

well-prepared to 

treat any form of 

the disease, which 

will be essential to 

meeting global and 

national targets for 

TB eradication. 

Dr Mel Spigelman 

President and CEO 

Global Alliance for TB 

Drug Development 

(TB Alliance) 

FRONTIER LIFELINE 

NUTRIGENETICS 

CLINIC

CASE REPORT EDUCATION RESEARCH ONCO SURGERY 

letters to the editor 

A HARROWING 

SWALLOW 

INTERNSHIP 

FOR FOREIGN 

GRADUATES? 

Eye opener 

FLUID DIAGNOSIS 

FOR DEMENTIA 

₹ 250.00 


PAGES 100 

FEBRUARY 2019 


STARTING TO 

FORGET 

THE SPECTRE OF ALZHEIMER’S LOOMS LARGE OVER 

INDIA’S FAST-EXPANDING POPULATION OF THE AGED 

NOVEL SURGICAL 

OPTIONS FOR 

BREAST CANCER 

Dear Editor, 

The cover story ‘Starting to 

Forget’ in the February issue 

was an eye opener. When 

read, frankly, even we medical 

students felt so less informed 

about this complex disease. 

Our curriculum as of now 

touches just a tip of what 

you have covered in this story 

about AD.We realise that we 

are taught only the basics of 

this neurodegenerative disease 

and the world has advanced 

so much in understanding 

its vast intricacies, though 

uncertainties still prevail in the 

treatment regime. 

Sabu Varghese and 

Anil Kothari 

Nagpur. 

Unique experience 

Dear sir, 

The ‘First & Most Unique’ 

series in Future Medicine truly 

brings interesting and curious 

things that gets introduced or 

uniquely exists in the country’s 

medical arena. The style of 

best narration and pictorial 

expression adapted in this 

series actually makes me feel 

as if I have seen or visited 

the place. Congratulations for 

introducing such an amazing 

column, which I am sure, other 

readers too would enjoy the 

same way. 

Sarita Mehra 

Researcher 

Jaipur 

Well brought out 

Hi, 

Read the latest issue of Future 

Medicine. Really informative 

and well brought out. Wish 

you all success for the same. 

Thanks & regards 

Dr DB Anantha Narayana 

Managing Trustee, Delhi 

Pharmaceutical Trust, 

and Former Head, Naturals 

Research for Foods, Unilever 

Research Centre, Bangalore. 

Top class 

Hello, 

Seen copies of Future 

Medicine. Top class production 

quality and great compilation 

of articles. Congrats. 

MG Arun 

Executive Editor 

India Today, 

Mumbai. 

Very useful 

Dear Editor, 

The article about ‘Fluid 

diagnosis for dementia’ was 

really informative. Grateful 

for bringing out such a very 

useful but at the same not 

easily available information to 

the medical professionals 

like me. 

Dr Sukumar Acharya 

Vadodara, Gujarat. 

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news updates 

India to regulate more 

med devices as drugs 

The health ministry 

has notified eight 

more medical equipment, 

including all implantable 

devices, as “drugs” 

effective from April 1, 

2020. 

This step will enable 

the regulation of some of 

the widely used medical 

devices along the lines of 

pharmaceutical products 

to ensure their quality and 

safety. 

The notified list 

includes all implantable 

medical devices, CT 

scan equipment, MRI 

equipment, defibrillators, 

dialysis machine, PET 

equipment, X-ray machine 

and bone marrow cell 

separator. 

This is in addition 

to the 27 categories of 

devices that were notified 

as drugs till last year, 

including blood pressure 

monitoring devices, 

digital thermometers and 

glucometers that were 

notified in December 

2018. 

The decision was 

taken after consultation 

with the Drugs Technical 

Advisory Board, according 

to the ministry. A Gazette 

notification was issued to 

this effect. 

The move is lauded by 

healthcare NGOs saying 

that the decision would 

help ensure the quality of 

the diagnostic equipment 

as well as the safety of 

the patients. Majority 

of medical devices are 

unregulated in India, as 

there is no regulatory 

framework for medical 

devices, currently. 

Odisha approves 

DACP scheme 

Odisha has approved a 

new Dynamic Assured 

Career Progression (DACP) for 

government doctors working 

in the eastern Indian state. 

The scheme assures 

promotion for all government 

doctors. 

“As per the new provision, 

all the Odisha Medical and 

Health Services (OMHS) cadre 

officers will get three assured 

promotions after 7, 14 and 21 

years of continuous service 

from their entry-level,” a 

notification issued by the 

Chief Minister’s Office stated. 

This will encourage the 

members and bring about 

greater commitment and 

dedication, the statement 

read. 

Around 2000 of the total 

3600 doctors in the state are 

likely to benefit from the new 

DACP scheme, reports said. 

Doctors have been 

protesting the proposed 

OMHS Cadre Rules, 2018 

alleging that the new rules 

are aimed at regulating 

the method of recruitment, 

promotion and condition of 

service of medical officers. 

The central government 

started DACP in 2008. 

Subsequently, nearly 15 

state governments have 

implemented it. 

AstraZeneca, 

NASSCOM to 

promote NCD 

care 

D 

rug major AstraZeneca 

has joined hands with 

the National Association 

of Software and Services 

Companies (NASSCOM) 

IoT Centre of Excellence 

to set up an accelerator 

programme to support Indian 

start-ups for developing 

innovative solutions to noncommunicable 

diseases 

(NCDs) care in India. 

AstraZeneca and 

NASSCOM will incubate 

start-ups in bringing new 

concepts that can help in 

the management of noncommunicable 

diseases 

(NCDs). 

The two organizations 

have signed a memorandum 

of understanding (MoU) to 

start an incubation centre in 

Bengaluru, recently. 

Start-ups will have access 

to NASSCOM’s innovation 

labs, development resources, 

cloud services and mentoring 

support, including the 

opportunity to showcase 

their innovations in national 

and global platforms. This 

opportunity 

will be open for 

companies or 

individuals who 

are working in 

therapeutic areas 

like diabetes, 

cardiovascular, 

8 / FUTURE MEDICINE / March 2019

India and Norway extend 

cooperation on child health 

The governments of 

India and Norway have 

extended cooperation within 

the health sector for a period 

of three years starting from 

2018 to 2020. 

A memorandum of 

understanding (MoU) between 

the Norwegian Ministry of 

Foreign Affairs, Government of 

Norway and Ministry of Health 

and Family Welfare, India has 

been signed to this effect, 

recently. 

The extension of the 

Norway India Partnership 

Initiative (NIPI) will include 

areas related to maternal, 

newborn, child health etc. The 

cooperation will continue to 

focus on innovative, catalytic 

and strategic support. 

The best practices in 

maternal and new-born child 

health carried out under the 

National Health Mission and 

NIPI shall be shared for global 

dissemination and learning. 

In the recent World Health 

Assembly, Family Participatory 

Care, an initiative of NIPI was 

showcased as an India case 

study. 

Norway and India had 

agreed in 2006 to collaborate 

towards achieving Millennium 

Development Goals 4 (MDG 4) 

to reduce child mortality. 

cancer and respiratory 

medicine. 

SC frees Saridon 

from list of 

banned FDCs 

The Supreme Court of India 

has exempted Saridon 

from the list of banned fixeddose 

combinations (FDCs) in 

the country. 

FDCs contain more than 

two active ingredients in a 

fixed proportion. 

Saridon, which 

is a combination of 

propyphenazone, paracetamol 

and caffeine, is a popular 

analgesic brand promoted by 

Piramal Enterprises Limited 

(PEL), Mumbai 

PEL had challenged the 

ban of Saridon in the SC 

listing it under the irrational 

combination of drugs. In 

September 2018, SC allowed 

the company to continue 

manufacturing, distribution 

and sale of the FDC through 

an interim order staying the 

ban. 

Now with the lifting of the 

ban, Saridon will be available 

across the country. 

Last year, India’s health 

ministry slapped a ban on 

over 300 FDCs as an 

expert committee set up of 

for the purpose concluded 

that there was no therapeutic 

justification for such 

combinations. 

Saridon is one of the 

leading brands in India›s 

analgesics market, which 

is estimated to be worth 

around Rs 2,050 crores as of 

December 2018. 

Haryana revises 

NPA to stop 

private practice 

The government of 

Haryana has decided to 

increase the non-practicing 

allowance (NPA) for medical 

officers to 20% of the basic 

pay, in accordance with the 

recommendations of the 7th 

Pay Commission. The revised 

NPA will be implemented with 

retrospective effect from May 

1, 2018. 

The decision is expected 

to benefit 272 medical 

PRIVATE 

PRACTICE 

officers, assistant medical 

officer, senior medical officer, 

dental surgeon and director of 

ESI healthcare department. 

Medical officers who will 

be eligible for NPA include 

government employees 

posted against a clinical post, 

reports said. 

NPA is aimed at 

prohibiting the private 

practice of government 

medical officers in public 

interest and the allowance 

would be admissible only in 

such cases and circumstances. 

The total pay combined with 

NPA should not exceed Rs 

2,24,550 per month. 

The government medical 

March 2019 / FUTURE MEDICINE / 9

officers have been demanding 

to revise the NPA as 

recommended by the 7th Pay 

Commission. 

Kareena to lead 

Serum’s vaccine 

campaign 

Serum Institute of India, 

the vaccine maker, has 

roped in the Bollywood 

actress Kareena Kapoor Khan 

to spread awareness on the 

importance of vaccination and 

immunisation across India. 

Kareena is the campaign 

ambassador for Swasth 

Immunised India – a 

nationwide vaccination and 

immunisation campaign. 

Serum has joined hands with 

Network 18 for the campaign 

that will focus on the need for 

childhood immunisation. 

Kareena will be advocating 

the urgency and the need for 

vaccination in the nation-wide 

campaign lasting for a year. 

The awareness campaign 

comes at a time when the 

number of non-vaccinators is 

increasing the world over. 

According to the figures 

available with the ministry 

of health, India has a 

vaccination cover of about 

70 percent. The country was 

able to successfully eradicate 

smallpox and polio through 

intensive immunisation efforts. 

However, the diphtheria 

outbreak in some regions 

of the country again turned 

the spotlight on possible 

vaccination gaps. 

Serum Institute of India 

is now the world’s largest 

vaccine manufacturer by the 

number of doses produced 

and sold globally. The Punebased 

company’s portfolio 

includes vaccines for polio, 

diphtheria, tetanus, pertussis, 

Hib, BCG, hepatitis B, measles, 

mumps and rubella. It is 

estimated that about 65% 

of the children in the world 

receive at least one vaccine 

manufactured by Serum. 

UK surcharge 

unfair: Indian 

doctors 

Indian doctors and 

healthcare professionals 

in the UK are campaigning 

against an “unfair” doubling of 

a health surcharge slapped on 

professionals from outside the 

European Union (EU) living 

and working in Britain. 

UK increased the 

“Immigration Health 

Surcharge”, which was 

introduced in April 2015, to 

GBP 400 from GBP 200 per 

year from December last 

year. 

The surcharge 

was applicable 

to all in the UK 

on a work, 

study or 

family visa for 

longer than six 

months. The hike 

was imposed as part 

of raising additional funds 

for the country’s state-funded 

National Health Service (NHS). 

The payment is made at 

the time of the immigration 

application. The person 

is required to pay the fee 

annually until he or she is 

granted indefinite leave to 

remain (ILR) in the UK or 

returns to their home country 

at the end of their visa period. 

Clinicians wishing to 

work in the UK were already 

facing burdensome processes 

relating to regulation and 

immigration, and this 

surcharge was only going to 

see UK losing out on quality 

healthcare professionals from 

non-EU countries, said a letter 

sent to UK home secretary 

from the British Association 

of Physicians of Indian Origin 

(BAPIO) seeking a rethink on 

the surcharge. 

MCI BOG nod for 2 super specialties in paediatrics 

Medical Council of India 

Board of governors 

(MCI BOG) has given 

recognition to DM in 

paediatric neurology course 

from the next academic year 

onwards. 

The new super specialty 

course in paediatric neurology 

has been included in the Post 

Graduate Medical Education 

Regulations, 2000 via an 

official notification in the 

Gazette of India. 

According to the 

notification, doctors qualified 

in MD in paediatrics or MD 

in general medicine can join 

DM (Paediatric Neurology) 

programme. 

All India Institute of 

Medical Sciences (AIIMS), 

New Delhi had approached 

the court seeking to start 

the super specialty course. 

Currently, the department 

of paediatrics, AIIMS, New 

Delhi offers one seat for DM 

(Paediatric Neurology). 

Also, the BOG has 

given its go-ahead to the 

inclusion of M Ch in paediatric 

orthopaedics in the Post 

Graduate Medical Education 

Regulations, 2000. 

The prior requirement 

or feeder qualification for 

M Ch (Paediatric 

Orthopaedics) will be MS in 

orthopaedics. 


INDIA HONOURS ITS 

ASHOK LAXMANRAO KUKADE 

A Physician, 

author and 

founder of 

Vivekananda 

Hospital and 

Research Centre, 

He has been 

honoured for his 

commendable 

service to the 

needy in the 

backward, 

drought-prone 

region of Latur, 

Maharashtra. 

MAMMEN CHANDY 

Pioneer in 

developing 

the field of 

haematology and 

bone marrow 

transplantation in 

India. Dr Chandy 

is currently 

director at Tata 

Medical Centre, 

Kolkata and is 

chair of Human 

Genome Task 

Force, India. 

The profession of care has been well 

recognised with the nation’s highest 

honour this time. The number of 

Padma Awards bestowed on members 

from the field of medicine was one of the 

highest in 2019. 15 doctors, who have 

contributed immensely to the field, have 

been honoured with Padma Awards this 

year in recognition of their invaluable 

service to the suffering lot as well as their 

contribution to the profession in terms of 

research and innovation. 

JAGAT RAM 

TSERING NORBOO 

Director of 

PGIMER 

Chandigarh. 

He developed 

innovative 

paediatric 

cataract surgery 

to cure an earlier 

incurable birth 

defect. 

SMITA AND RAVINDRA KOLHE 

Husband and wife doctor duo who 

worked for the uplift of the poor tribals 

helping to eradicate malnutrition from 

one of Maharashtra’s poorest regions of 

Melghat. 

Consultant 

Physician 

Mahabodhi 

Karuna Charitable 

Hospital 

Choglamsa. 

He has treated 

several patients 

in the difficult 

terrain, from 

remote areas of 

Ladakh for over 

50 years and 

is specialised 

in high altitude 

medicine. 


GREAT CLINICIANS 

SHYAMA PRASAD MUKHERJEE SHADAB MOHAMMAD PRATAB SINGH HARDIA 

Ranchi-based 

doctor who 

is known for 

charging minimal 

consultation 

fee for medical 

treatment. 

The 83-yearold 

doctor 

has helped 

provide quality 

health care to 

many poor in 

Jharkhand. 

Professor 

and Head of 

Department 

of Oral and 

Maxillofacial 

Surgery at King 

George’s Medical 

University, 

Lucknow. 

80-year old 

ophthalmologist 

from Indore 

specialised 

in cataract 

surgeries and 

myopia, provides 

free services to 

the poor patients 

SANDEEP GULERIA RAMASWAMI VENKATASWAMI OMESH KUMAR BHARTI 

Senior consultant 

surgeon at 

Indraprastha 

Apollo Hospitals 

and professor 

at AIIMS. He led 

the team which 

conducted the 

first successful 

cadaver renal 

transplant in 

India. 

Pioneer of hand 

and reconstructive 

surgery helping 

millions of people, 

whose arms 

got severed in 

accidents. Founder 

of Institute for 

Research and 

Rehabilitation 

of Hand and 

Department of 

Plastic Surgery 

at Government 

SMCH, Chennai. 

Epidemiologist 

who developed 

low-cost antirabies 

treatment 

protocol at 

1/10th of the 

prevailing costaccepted 

as part 

of WHO protocol 

globally. 

ILIAS ALI R V RAMANI SUDAM KATE 

Pioneer of 

laprascopic 

surgery in the 

North East. 

He developed 

no scalpel 

vasectomy and 

popularised 

family planning. 

Founder of 

Sankara Eye 

Foundation 

working on 

80:20 model 

for providing 

affordable 

eyecare services 

across the 

nation. 

Indian social 

activists doctor 

known for his 

pioneering 

work in the 

field of sicklecell 

anaemia in 

India. He has 

helped diagnose 

and treat over 

3000 sickle cell 

patients from 

the rural tribal 

communities of 

Maharashtra, 

Gujarat and MP. 


policy 

GUIDELINES FOR NANO 

DRUGS 

The draft guidelines look at easing the evaluation process of nanotech-based 

medicines in India 

The Department of Biotechnology 

(DBT) and Indian Society of 

Nano Medicine has come out 

with guidelines for evaluation of 

nanopharmaceuticals in India. 

The guidelines are being framed 

in the backdrop of growing research 

and development and usage of 

nanomedicine in the country. According 

to reports, the nanomedicine market 

in the country is estimated to grow 

to around $1.6 billion in 10-15 years. 

Considering the growth of healthcare 

market in the country, which is 

expected to be in the top three among 

world healthcare markets by 2020, the 

need of the hour is to set standards for 

nano pharmaceuticals. 

The guidelines aim to ensure 

quality, safety and efficacy as well as 

to encourage the commercialisation 

of nanotechnology-based innovation 

with high benefit to risk ratio, says the 

document. 

DBT has given special emphasis 

to promoting nanobiotechnology that 

have applications in various sectors of 

life sciences. It has been funding R&D 

in this area since 2007, and various 

scientists and stakeholders have felt 

the need to have specific guidelines 

for the evaluation of products in 

various sectors of biological sciences 

developed through interventions of 

nanotechnology. 

Nano pharmaceuticals is an 

emerging field that combines 

nanotechnology with pharmaceutical 

and biomedical science to improve 

efficacy and safety profile via targeted 

drug delivery. Alteration into nanoscale 

for drug delivery may significantly alter 

the pharmacokinetic, biodistribution 

and toxicokinetic parameters of 

conventional/traditional drugs, 

raising various concerns related to 

quality, safety and efficacy of nano 

pharmaceutical products, says the 

guideline. Considering the complexity 

of nanomaterial behaviour in the 

SPECIFIC SCIENTIFIC 

EVIDENCE IS REQUIRED 

FOR APPROVAL OF ANY 

NANO PHARMACEUTICAL 

AND STRATEGIES FOR 

PHARMACOVIGILANCE 

biological environment, certain degree 

of uncertainty may be inherent to such 

system. 

Charting the course 

There are no uniform, internationally 

acceptable guidelines for 

nanopharmaceuticals. The usual 

consensus for evaluation of quality, 

safety and efficacy of nanotechnologybased 

products is to have a ‘case 

by case approach’, taking into 

consideration of the physical, chemical 

and biological characteristics of the 

nanoparticle used and the route of 

administration, the indication for which 

the product is intended to be used and 

other related aspects. 

These guidelines apply to 

nanopharmaceuticals in the form of 

a finished formulation as well as an 

API of a new molecule or an already 

approved molecule with altered 

dimensions, properties or phenomenon 

associated with the application 

of nanotechnology intended to 

be used for diagnosis, treatment, 

mitigation or prevention of diseases 

in human beings. In the guidelines, 

nanopharmaceuticals have 

been classified according to 

their degradability, organicity, 

function and status of 

approval. Accordingly, the safety and 

efficacy data requirements have been 

described. 

Specific scientific evidence 

required for approval of any nano 

pharmaceutical and the strategies for 

pharmacovigilance of such products 

has also been incorporated in these 

guidelines. Each application should 

be considered on its own merit of 

the data submitted using scientific 

judgment and logical argument. For 

the new generation of nanomaterials, 

the development of methods for safety 

testing and risk assessment, and a 

better availability of quality data on 

nanomaterials for regulatory purposes 

are essential. 

The guidelines define nano 

pharmaceutical as a pharmaceutical 

preparation containing nanomaterials 

intended for internal or external 

application on the body for the 

purpose of therapeutics, diagnostics 

and any other health benefit. These 

are the products that contain materials 

in the size scale range of 1 to 100nm 


in at least one dimension. However, 

if the particle size is >100nm and 

10%. 

Less stringent? 

The guidelines also stipulate various 

steps for the development of a 


column 

the catalyst 

An OYO model for 

hospital beds! 

An aggregator model like that of OYO is a possibility to 

leverage the capacity utilisation agenda of providers 

MURALIDHARAN NAIR 

The healthcare industry has entered a 

phase which will be characterised by 

unprecedented opportunities for the 

growth for affordable healthcare service 

offerings. Even while the government aspires 

to strengthen the public delivery system, it is 

certain that much of the emerging demand 

will have to be met by the private sector. 

At the same time, it will not be wrong to 

say that, barring a few exceptions, quality 

affordable care models do not exist in India. 

One of the key reasons for this has been the 

intrinsic belief by the incumbent class that 

we are highly cost-effective compared to the 

global context, which, in my view, has little 

relevance as a justification. However, things 

are poised to change, given the irreversibility 

of public demand, policy direction and a shift 

in payer profile to the institutional from the 

individual. Given this context, the following 

could emerge as the key imperatives and 

responses from industry in the times to 

come: 

1. Adopting design to cost method: In my 

observation, one key reason for despair 

among providers with the emerging price 

expectations of mass healthcare schemes is 

rooted in their approach to find a solution 

through what I call a performance-plus 

model, i.e., an incremental improvement over 

the current state. However, what they need is 

a holistic approach that aims to redesign 

the capex and opex model to achieve the 

target cost of delivery. This is called the 

Design-to-Cost approach, which has been 

prevalent for long in the manufacturing 

and automotive industries. This will entail 

fixing the total cost of delivery first and then 

evolving an optimal cost structure of fixed 

and variable costs. It will be based on firstprinciple 

analysis (not accepted industry 

norms) to rationalise layout design, human 

resource, material consumption and medical 

technology, formulary design, backed by 

an unrelenting focus on buying efficiency 

and commercial excellence, and clinical 

excellence. 

2. Volume will be King: Economies of scale 

and asset sweating will be a critical enabler 

for managing efficiency. Capacity planning 

and dynamic pricing models (driven by 

available capacities), akin to the hospitality 

industry, will become increasingly relevant for 

healthcare industry. The economic unit size 

for a multi-speciality tertiary care hospital 

will move closer to 1,000 beds from the 

current levels of 250-300 beds, even though 

capacity phasing during ramp up will have to 

be planned with much greater care than is 

typically done at present. 

3. OYO model for hospital beds: The kind of 

efficiency that will be needed in the future 

will not lend itself to the high quantum 

of unutilised capacities that exists on an 

average, even for well-managed hospitals, 

owing to demand variability. It is quite likely 

that we will witness in the not-so-distant 

future a capacity aggregator model like 

OYO, which will possibly be an intermediary 

between patients and providers and payers 

to best leverage the capacity utilisation 

agenda of the providers for optimum 

benefit to patients and payers. This is not 

as impractical as it may seem at first glance. 

Barring a small percentage (less than 10 

percent) of procedures, clinician stickiness 

will come down further within 

the mass healthcare space as the credibility 

of empanelled hospitals gain ground with 

time. 

The author has long-standing association with 

EY India but the views are strictly personal. 


cover story 


WAR TO 

END 

A SCOURGE 

India is battling to eliminate TB by 2025 — 

to vanquish an infectious malady that has 

been haunting humanity for ages 

S HARACHAND 

In the year 1821, John Keats, one of the most celebrated 

English poets, died of consumption at the age of 25. 

Centuries later, that ‘consumptive disease’ still takes a 

toll of millions of lives the world over in a more lethal form, 

despite tremendous strides made by modern medicine to 

curb diseases caused by bacterial infectious agents. 

The history of tuberculosis is, perhaps, as old as 

humanity itself. Though mankind survived the onslaught 

of many a foul contagion that threatened to wipe it out 

through the ages, tuberculosis (TB) turned out to be a 

particularly resilient adversary. 


TB is one of the top 10 causes of death today and the 

leading cause of death from a single infectious agent. More 

people die from TB than HIV. In 2017, the infection caused 

nearly 1.3 million deaths, excluding the 300,000 HIV-positive 

people who lost their lives to TB that year, according to WHO 

estimates. Ten million people developed the disease during 

the year, including 1 million children. 

India has the world’s highest burden of TB, accounting for 

27 percent of all cases and over 30 percent of all TB-related 

deaths. 

Recognised as the leading infectious killer, TB is now 

getting unprecedented attention in India. Signalling an 

increased commitment, the health ministry has announced 

an ambitious nationwide campaign to end TB by 2025, five 

years ahead of UN’s Sustainable Development Goals. The 

National Strategic Plan (NSP) for TB elimination 2017-25, with 

an estimated cost of Rs 16,649 crore, banks on public-private 

partnership to ensure that every TB patient has access to 

quality diagnosis, treatment and support. The NSP provides 

goals and strategies for the country’s response to the disease 

during the period. 

Missing millions and gaps in reporting 

Home to a quarter of the 8.6 million cases of TB that 

occur worldwide, India also has the dubious distinction of 

Novel additions 

No new antibiotic has been developed to 

fight tuberculosis for several decades. The 

emergence of more lethal drug-resistant strains 

of Mycobacterium tuberculosis is now forcing 

a change in the status quo. The urgency to 

address MDR TB prompted a fast-track approval 

of some of these treatments well before the 

availability of their safety and efficacy data from 

phase 3 programmes. 

Bedaquiline 

The first drug to treat TB in more than forty 

years, bedaquiline was approved in 2012 by the 

US FDA as a part of the accelerated approval for 

use in MDR and XDR TB. 

In the following year,. the WHO gave a 

conditional recommendation to use bedaquiline 

(BDQ) in MDR TB patients where other standard 

regimens cannot be designed. 

The drug belongs to a new class of drugs 

called the diarylquinolines which blocks the 

proton pump for ATP synthase of mycobacteria. 

Data from clinical studies have shown an 

increased risk of death with BDQ treatment. 

Johnson & Johnson, the maker of the medicine, 

also warns of QT prolongation with the use of 

the drug. 

Phase 3 studies are ongoing to assess the 

safety and efficacy of BDQ. 

BDQ was introduced at six sites in 5 Indian 

states under Conditional Access Programme 

(CAP) in March 2016. In the absence of phase 3 

data, the Drug Controller General of India (DCGI) 

approved the use of BDQ under RNTCP through 

conditional access. 

900 patients have been initiated on a BDQcontaining 

regimen at 21 sites as of the end of 

2017. The programme will expand the usage 

of BDQ to all states as per their preparedness, 

according to TB India Report 2018. 

Delamanid 

Delamanid belongs to a new class of TB drugs 

called nitroimidazoles. In 2014, the WHO issued 

interim policy guidance on the use of delamanid 

(DLM) in MDR-TB regimen in adult patients with 

pulmonary TB. The drug received approval in 

Europe, Japan and South Korea in the same 

year. The WHO extended the use of DLM to 

children aged 6-17 years in 2016, following a 

review of data from a 6-month safety, efficacy 

and pharmacokinetic trial of paediatric patients. 

These data were also considered to be of 

very low certainty based on GRADE evidence 

assessment. 

In mid-October 2017, Otsuka Pharmaceutical 

announced the final results of Trial 213 to 

the public during the annual UNION World 


in anti-TB armamentarium 

Conference on Lung Health in Mexico. 

The phase 3, multicentre, randomized, 

double-blind, placebo-controlled clinical 

trial compared two regimens for the 

treatment of MDR-TB in adult pulmonary 

TB patients. 

The trial data found that the longer 

MDR-TB regimen, used as the optimised 

background regimen, had an overall 

treatment success rate of 81%, much 

higher than the global value of 54% 

reported to WHO. 

Studies to evaluate the efficacy of DLM 

in children with MDR TB (Otsuka 233) and 

paediatric MDR TB HIV patients (Otsuka 

232) are underway. 

National TB programmes and other 

stakeholders are advised to only add 

DLM to a longer MDR-TB regimen when it 

cannot be composed according to WHO 

recommendations. When an effective and 

well-tolerated longer MDR-TB regimen can 

be otherwise composed, the addition of 

delamanid can be avoided. 

In August 2017, DCGI issued permission 

to import formulations of DLM (50 mg) 

tablets to treat pulmonary MDR-TB in adult 

patients. Accordingly, the guidelines were 

prepared for use of 400 courses of DLM in 

7 states. 

Rifapentine 

Rifapentine, a rifamycin antibiotic, inhibits 

RNA polymerase in MTB. The drug was 

approved by the US FDA in combination 

with isoniazid (INH) for the treatment 

of latent TB infection (LTBI) in patients 

two years of age and older at high risk 

of progression to TB disease in 2014, 

following a priority review. 

Weekly regimen of rifapentine with 

isoniazid for three months has been 

found effective in the prevention of active 

tuberculosis 

India’s health ministry may allow the 

import of rifapentine for the treatment 

of LTBI, waiving off the local clinical trials 

requirement, otherwise mandatory for 

all new drugs to be introduced in India, 

reports said. 

Pretomanid 

Pretomanid is an experimental bicyclic 

nitroimidazole-like molecule currently 

undergoing phase 3 trials. The compound 

was shown efficacious at doses of 100– 

200 mg daily in studies conducted on 

adult patients with pulmonary TB. Also, 

no evidence of mutagenicity has been 

detected in genotoxicity studies and no 

significant cytochrome P450 interactions. 

This compound has been developed by TB 

Alliance. 

Trials explore new strategies to tackle TB 

Clinical trials of several novel drug regimens are currently underway as part of efforts to tackle 

drug resistance and stop TB infection in its tracks 

STREAM (Standardised Treatment Regimen 

of Anti-Tuberculosis Drugs for Patients with 

MDR TB) is an ongoing study supported 

by USAID. It is a multi-centre international 

randomized control trial to evaluate 

shortened regimens for patients with MDR 

TB. 

STREAM Stage 1 is phase 3 study which 

compares the standard WHO MDR- 

TB regimen with a 9-month, modified 

Bangladesh Regimen. The study has been 

completed and results are pending. 

STREAM Stage 2 aims to compare 6 and 

9-month bedaquiline-containing regimen 

against the WHO and Bangladesh regimen 

in a phase 3 study. 

NeXT (New Treatment Regimen for Patients 

with Multi-drug Resistant Tuberculosis), an 

open-label RCT of a 6-9-month, injectionfree 

regimen containing bedaquiline, 

linezolid, levofloxacin, ethionamide/high 

dose isoniazid and pyrazinamide, is currently 

in phase 3. 

NiX-TB, a phase 3 study of bedaquiline, 

pretomanid and linezolid in patients with 

XDR-TB and MDR-TB for 6 months, with an 

option of 9 months, has been completed. 

TB-PRACTECAL (Pragmatic Clinical Trial 

for a More Effective Concise and Less Toxic 

MDR-TB Treatment Regimen(s)) is a multicentre, 

open label, multi-arm, randomized, 

controlled, phase 2-3 trial evaluating short 

treatment regimens containing bedaquiline 

and pretomanid in combination with 

existing and re-purposed anti-TB drugs 

for the treatment of biologically confirmed 

pulmonary MDR-TB. 

IMPAACT 2005 is a phase1/2 study to 

evaluate the pharmacokinetics, safety and 

tolerability of DLM in combination with 

optimised multidrug background regimen 

(OBR) for MDR-TB in HIV-infected and 

HIV-uninfected children with MDR-TB. It is 

currently enrolling non-US participants in 

Botswana, India, South Africa and Tanzania. 

endTB is a phase 3, randomized, controlled, 

open-label, non-inferiority, multi-country 

trial evaluating the efficacy and safety of 

new combination regimens for MDR-TB 

treatment. 

DELIBERATE is evaluating the drug-drug 

interactions and combined QT effects of 

bedaquiline and delamanid in a phase 2 

programme. 

DRAMATIC is a proposed investigational 

regimen combining two new drugs, BDQ 

and DLM, with three anti-TB agents of 

known potency, linezolid (LZD), levofloxacin 

(LFX), and clofazimine (CF), to provide a 

shorter, better-tolerated and more effective 

MDR-TB treatment regimen for persons with 

fluoroquinolone-susceptible MDR-TB. 


“TB Alliance looks to 

dramatically shorten the 

duration of TB therapy” 

Mel Spigelman is the President 

Dr and Chief Executive Officer of the 

Global Alliance for TB Drug Development 

(TB Alliance). He is a leader in 

developing a regimen-based paradigm 

of TB drug development – a faster 

and more efficient approach, which is 

emerging as the gold standard within 

the TB drug research field. A recipient 

of the American Cancer Society’s Clinical 

Oncology Career Development Award 

(1985-1988), Dr Spigelman is presently 

the Co-Chair of the Working Group 

on New Drugs of the WHO Stop TB 

Partnership. Edited excerpts from an 

interview with FM 

Can you kindly brief us on the 

current status of TB Alliance’s TB 

clinical programmes? 

TB Alliance is conducting three latestage 

clinical trials to evaluate new drug 

regimens for various forms of TB. Two 

of the trials, known as Nix-TB and ZeNix, 

are evaluating three-drug (bedaquiline+ 

pretomanid+ linezolid), six-month 

regimens for the most resistant cases 

of TB, including XDR-TB. Another trial, 

Dr Mel Spigelman 

called SimpliciTB, is evaluating a fourdrug 

– bedaquiline + pretomanid+ 

moxifloxacin+ pyrazinamide - regimen 

to treat both drug-sensitive TB in four 

months and multidrug-resistant TB in 

six, respectively. 

What are the latest drug regimens 

to tackle MDR/XDR TB? 

The World Health Organization 

recently released new treatment 

guidelines for treating drug-resistant TB. 

Currently, the recommended treatment 

duration ranges from about 9 to 20 

months. For the longer treatment 

regimens, WHO no longer prioritises the 

use of injectable drugs in the treatment 

of drug-resistant TB. There are multiple 

different regimens in a variety of clinical 

trials, including STREAM, TB-PRACTECAL, 

endTB and NeXT in addition to the trials 

sponsored by TB Alliance. 

Multi-drug resistance poses a 

formidable challenge to bring TB 

pandemic under control. How does 

TB Alliance strategize to deal with this 

growing threat? 

Our strategy is to develop novel 

TB drug regimens that are shorter, 

safer, more effective and affordable. 

Treatments with those characteristics 

could both cure people with drugresistant 

TB and prevent resistance from 

emerging in the first place. A strong 

pipeline of novel drugs will ensure that 

we are well-prepared to treat any form 

of the disease, which will be essential to 

meeting global and national targets for 

TB eradication. 

In what ways does TB Alliance 

address the question of affordability of 

the new TB regimens in the developing 

harbouring about a third of the ‘missing 3 

million TB cases’ that do not get diagnosed 

or notified. India, along with Indonesia and 

Nigeria, accounts for 80% of the global 

shortfall in the reporting of TB cases. 

A study reported in The Lancet in 2016 

found that prescriptions and drug sales 

exceeded the number of cases recorded in the 

national registry by almost 2 million, clearly 

indicating improper reporting from the private 

sector. This failure in reporting continues 

to hamper an effective implementation of 

eradication strategies. 

The scenario is 

expected to change 

as the reporting of 

TB has been made 

compulsory 

Dr George Mothy 

Justin 

Pulmonologist 

As much as 60-70% of patients access 

private health care providers as the first 

point of care, including for TB, according to 

National Sample Survey Office. The majority 

of the patients take prescriptions from private 

hospitals due to the dysfunctional public 

sector. 

“A ubiquitous private sector and low 

notification rates have been one of the 

major impediments in getting a sense of the 

magnitude of the TB challenge,” points out Dr 

Sameer Kumta, Senior Programme Officer, TB, 

Gates Foundation, India. 


world where TB is a major 

healthcare problem? 

In line with our “AAA” mandate, 

we are committed to ensuring that 

all drugs and regimens we work 

on will be affordable, available and 

adopted around the world. We derisk 

the research and development 

of our work through the financial 

support from our donors, which 

lowers the bar for our commercial 

partners to get involved. We also 

ensure that all molecules in which 

we invest can be manufactured at a 

very reasonable cost of production. 

In addition, we will give royaltyfree 

licenses to our products to 

multiple, high-quality manufacturers 

in the developing world to generate 

generic competition. Through generic 

competition, as we have seen in many 

fields, prices can be reduced to their 

lowest sustainable levels. 

One of the stated goals of TB 

Alliance is making ultra-short, simple 

treatment regimens for battling 

TB. How far has the organization 

succeeded in achieving this 

objective? 

We have developed the largest 

single portfolio of potential new TB 

therapeutics ever assembled. Our goal 

is to discover or partner with others 

on multiple new chemical entities 

that do not have cross-resistance 

with presently available anti-TB drugs, 

and which can be given together in 

regimens that are safe enough to be 

used in all TB patients and effective 

enough to dramatically shorten the 

duration of TB therapy. We now have 

multiple new drug candidates in our 

pipeline that, in combination with 

those of other organisations, have 

the potential to deliver a very short 

treatment for virtually all patients with 

active TB. 

What is TB Alliance’s most crucial 

therapeutic intervention in TB 

management? 

Children with TB have long been 

the neglected of the neglected, 

with an estimated 1 million children 

developing TB each year. To date, 

we have seen major progress in the 

global uptake of child-friendly TB 

medicines introduced by TB Alliance 

and our partners, with 

over 900,000 treatment courses 

ordered by 88 countries and counting 

since becoming available at the end 

of 2015. These new formulations of 

first-line treatment, which are 

available in India, come in WHOapproved 

doses and are designed 

to be easy for children to take: 

fruit flavoured for palatability and 

dissolvable in water. Looking ahead, 

we hope to introduce novel TB drug 

regimens that are shorter, safer, 

effective and affordable, suitable for 

every person with TB. 

Most Indians prefer seeking care from the private sector 

first, resulting in under-reporting of TB, he adds. 

India declared TB a notifiable disease way back in 2012. 

However, the reporting of the disease is abysmally low from 

the private health care sector in the northern regions of the 

country where the incidence of TB is very high. 

“The scenario is expected to change as the reporting of 

TB has been made compulsory,” says Dr George Mothy Justin, 

Head of the Department, Respiratory Medicine, Medical Trust 

Hospital, Kochi, India. 

Last year, India made non-reporting of TB a punishable 

offence. Failure to report TB cases can now invite punishment 

under relevant sections of Indian Penal Code. 

INDIA TARGETS TO 

END TB BY 2025 

India has set an ambitious target to 

eliminate TB by 2025. The goal is to 

end the country’s leading infectious 

disease five years ahead of the global 

target of 2030. 

The government has announced 

the National Strategic Plan (NSP), with 

an estimated cost of Rs 16,649 (USD 

2,485 million), to ensure access to 

diagnosis, treatment and support for 

all TB patients. 

The new scheme looks to expand 

public-private partnership models 

and use information technology tools 

for monitoring the programme and 

treatment adherence. Community 

engagement is the hallmark of the 

programme and it is becoming a 

social movement, according to the 

Union health minister JP Nadda. 

The new NSP adopts a multipronged 

approach, which aims 

to detect all TB patients, with 

an emphasis on reaching TB 

patients seeking care from private 

providers, and undiagnosed TB 

in high-risk populations. It aims 

to treat all patients irrespective of 

where they seek care, adopting a 

patient-centric approach and to 

prevent the emergence of TB in 

susceptible population groups and 

build empowered instaitutions and 

human resources to streamline 

implementation, Nadda said. 

The implementation of NSP will be 

a combined effort of all stakeholders 

working towards the same goals. A 

restructured Central TB Department 

(CTD) at the ministry of health will 

oversee the implementation of the 

plan by coordinating the work of the 

National TB Control Board. State TB 

cells will continue to oversee the work 

at state and district levels. 


NOTIFY ON NIKSHAY: 

INDIAN MEDICAL 

ASSOCIATION 

E 

ven though India declared TB a 

notifiable disease in the year 2012, 

the level of notification has not risen to 

expectations. All medical practitioners 

in the country have to notify their TB 

patients to the government registry. 

However, a review of the state-wise 

notification data from 2018 showed 

that the percentage of notification from 

the private health sector in the Indian 

states of Uttar Pradesh, Maharashtra, 

Bihar Rajasthan, Gujarat, Madhya 

Pradesh is a mere 28%. Among these 

six states, Bihar is leading in private 

notification at 40%, according to the 

Indian Medical Association (IMA), which 

carried out the survey. 

IMA, the umbrella organisation 

of Indian clinicians, has recently 

urged private doctors to notify every 

tuberculosis patient and register them 

on Nikshay, a web-enabled application 

developed by India’s health ministry. 

Nikshay is an online tool which aims 

to create a database of all TB patients 

for monitoring and research purposes. 

Notification allows access to free drugs 

and diagnostic tests, nutritional and 

patient-centric support that ensures 

patients adhere to the treatment and 

incentives. 

Doctors in the private sector have a 

huge role to play in reporting TB cases 

and adhering to the Standards for TB 

Care in India (STCI). STCI needs to be 

followed uniformly across the private 

sector. 

With the largest burden of 

tuberculosis in the world, the Indian 

government is working towards a TBfree 

India by 2025. Notification of every 

TB patient is the single most important 

intervention to meet the government’s 

vision of a TB-free India. 

India accounts for 

a quarter of the 8.6 

million cases of TB 

that occur worldwide. 

India also accounts for 

a third of the ‘missing 

3 million TB cases’ that 

do not get diagnosed or 

notified. 

Leading pulmonologists like Dr George are sceptical 

whether India would be able to bring down its numbers 

within the stipulated timelines, considering the slow pace 

of diagnosis and unusually protracted treatment regimens 

practiced in India’s TB hotspots. 

Treating latent TB: A daunting task 

Also, at 40%, the proportion of people with latent TB is 

higher in India owing to poor diagnosis and ineffective 

treatment. People with latent TB infection (LTBI) do not 

show any symptoms nor do they infect others. The infection, 

however, won’t go away unless treated along the lines of 

active TB. 

The WHO recommends treating only those with active 

diseases in high-burden countries like India, a stand criticised 

by many TB experts. Targeting LTBI, along with the active 

disease, is important to eliminate TB, they assert. 

Recent reports indicate that the government is 

considering to bring all LTBI patients too under the purview 

of treatment. Treating asymptomatic TB patients would 

be a daunting task in India as the numbers can be huge. 

Policymakers plan to tackle the enormous LTBI population in 

a phased manner, targeting the high-risk group with priority 

to achieve the goal. 

Among those included in the high-risk group and 

identified to receive LTBI treatment by the NSP are those 

on long-term corticosteroids, immunosuppressants, the HIVinfected 

and juvenile contacts of sputum-positive index cases. 

Since children are more susceptible to develop severe 

forms of disseminated TB, those above six years of age, who 

are in close contact of TB patients, will be evaluated. After 

excluding active TB cases, they will be given 10 mg/kg of 

isoniazid (INH) administered daily for a minimum period of six 

months irrespective of their BCG or nutritional status. 

INH preventive therapy will also be considered for all HIV 

infected children, all tuberculin skin test (TST) positives who 


BATTLE FOR BEDAQUILINE 

Bedaquiline is the first anti-TB drug 

developed in over four decades. 

The cost of the treatment goes up to 

$30,000 for a six-month course. 

A diarylquinoline 

antimycobacterial agent, bedaquiline’s 

cure rates for patients have been 

reported at over 80%. 

The drug also has fewer sideeffects 

compared to the old anti-TB 

injectable drugs which can even 

cause deafness. 

By 2016, at least 35 countries 

have introduced shorter regimens 

for treatment of MDR/RR-TB and 89 

countries and territories had started 

using bedaquiline, shows WHO Global 

TB Report 2017. 

Nevertheless, the drug still 

remains out of reach for most lowand 

middle-income countries. To 

date, only 25,000 people around the 

world have received bedaquiline and 

two-thirds of these patients have 

been in South Africa. South Africa 

is among those small number of 

countries which have negotiated a 

greatly reduced price of $400 from 

Johnson & Johnson, the maker of the 

drug. 

The drug maker Johnson & 

Johnson, in its latest filing, seeks 

extended patent protection to 

bedquiline in India. The company›s 

current patent expires in 2023. If 

granted, the drug will enjoy exclusive 

marketing rights till 2027. 

Since India is considered the hub 

of generic medicines of the world, the 

additional patent could further delay 

the availability of low-priced versions 

of this life-saving medicine and will 

also indirectly impact many countries 

in the world, say those opposing the 

patent in India. 

Activists demanded J&J to 

slash the price for the blockbuster 

tuberculosis drug at the opening of 

49th Union World Conference on 

Lung Health in the Netherlands in 

October last year. 

There is a greater chance 

of curing MDR-TB patients who 

otherwise look at an abysmal curerate 

of 50 percent, but this can only 

happen if J&J cuts the price for 

bedaquiline to a dollar a day, they 

maintained. 

J&J said in a statement that 

their new price of $400 per course 

is “genuinely a special effort that we 

set to encourage rapid scale-up of 

bedaquiline in countries with a high 

TB burden”. 

Controversies over pricing have 

the potential to further damage an 

already fragile environment for TB 

research and development. 

Since its approval as part of 

USFDA’s Fast Track accelerated 

approval process in 2012, J&J 

has donated 60,000 bedaquiline 

treatments to patients in such 

high-TB-burden countries as China, 

India and South Africa, the company 

said. 

In 2017, J&J formed a 

collaboration with India’s Institute 

of Microbial Technology (IMTech), 

focused on discovering safer, more 

effective oral treatments and multidrug 

regimens for MDR-TB. 

J&J has tied up with the 

International Union Against 

Tuberculosis and Lung Disease 

to include bedaquiline in the STREAM 

study, a multicentre international trial 

to evaluate the medicine in patients 

with MDR-TB. Final study results are 

expected as early as 2023. 

are receiving immunosuppressive therapy and a child born to 

a mother who was diagnosed to have TB during pregnancy. 

The health ministry is likely to allow the import of 

rifapentine for the treatment of LTBI, waiving off the local 

clinical trials requirement that is mandatory for all new drugs 

introduced in India, according to reports. 

A weekly regimen of rifapentine with isoniazid for three 

months has been found effective in the prevention of active 

tuberculosis 

But the implementation of treating LTBI can still be 

challenging as people without any obvious symptoms have to 

adhere to a months-long regimen of multiple pills which often 

have undesirable side-effects. 

“If you start checking, you will come to know that a good 

proportion of the Indian population has asymptomatic TB. 

We have systems in place to rapidly detect the disease with 

nearly 100% accuracy. And we have effective medicines 

to treat even MDR TB. But the question is, will everybody 

detected with asymptomatic, latent TB be willing to follow 

the treatment course,” asks Dr Sunil Nair, Assistant Professor, 

Pulmonary Medicine, Medical College, Trivandrum. Places like 

Kerala have brought down TB cases dramatically through 

effective intervention. The situation, however, is not so in 

other parts of the country, where the infection is more 

rampant. 

Unlike earlier days, we now have GeneXpert machines 


in place to quickly diagnose TB in every 

district. Soon the facility will be brought to 

the taluk level. Nevertheless, the availability 

of the diagnostic facility doesn’t mean that 

everybody goes for testing. If one tests 

positive for diabetes, he wouldn’t hesitate 

to share the status with his friends. It is not 

usually the case with TB. In many cases, the 

person wouldn’t share the information with 

even his family members. Tuberculosis, like 

HIV, still has a lot of stigmas. People may 

not go forward to test TB as eagerly as they 

go for other diseases, comments Dr Nair. 

Challenge of drug resistant TB 

While the increasing number of deaths 

are attributed to delayed diagnosis and 

inadequate treatment, the emergence of 

multi-drug resistant strains presents the 

most formidable challenge to the efforts 

of containing TB. Again, India tops the list 

of the three countries which account for 

nearly half of the world’s cases of MDR/ 

RR TB. There are around 1.5 lakh cases of 

MDR TB in India. Of this, nearly 12% are in 

Mumbai, which is considered the epicentre 

of the MDR TB. Unlike drug-sensitive TB, the 

success rate for curing MDR-TB is only 33 

percent. 

Even though, drugs to treat MDR TB 

is currently available, not all Indian clinics 

have access to these novel treatments. Both 

bedaquiline and delamanid — novel anti-TB 

drugs — were introduced in India through 

a conditional access programme and 

included in the Revised National TB Control 

Programme (RNTCP). Their availability is 

limited to a handful of patients from select 

cities. 

For instance, the 400 doses of 

delamanid that India received from Otsuka 

Pharma as part of a phase 3 programme 

were rolled out in seven states in November 

last year. High costs remain a major barrier 

to patients accessing these treatments, 

which are yet to come out with their safety 

and efficacy data from phase 3 trials. 

Even with the latest treatment, 

India is achieving a cure rate of only around 

47% on average at the national level. 

India-wide, around 15-20% of MDR TB 

patients die. There are very few diseases 

with such a high mortality rate. Many 

cancers have a better cure rate. This makes 

The government 

has backed 

the NSP with a 

historic resource 

commitment of 

Rs 12,000 crores 

over three years, 

while it increased 

investment in 

research and 

development to 

$6 million. 

Dr Sameer Kumta 

Senior Programme 

Officer, TB 

Gates Foundation 

India 

CHALLENGE OF TUBERCULOSIS 

16,00,000 

died of tuberculosis infection in 2017 

TB kills 

someone every 

18 

seconds 

India accounts 

for 27% of all TB 

cases in the world 

and 30% of all TBrelated 

death 

Uttar Pradesh 

3,29,092 

Gujarat 

1,23,665 

Maharashtra 

1,50,293 

Madhyapradesh 

1,19,117 

10,00,000 

children get sick with TB 

each year 

Rajasthan 

1,35,428 

Bihar 

1,03,255 


TREATMENT 

SUCCESS RATE 

83% 

54% 

30% 

TB MDR-TB XDR-TB 

SOURCE: WHO 

WHO REMOVES INJECTABLE DRUGS 

FROM MDR REGIMENS 

The WHO has revamped the treatment 

guidelines for MDR and rifampicinresistant 

(RR-TB) even as multi-drug 

resistance poses a threat to the End TB 

Strategy. 

The guidance, based on a review of 

the recent evidence on priority questions 

in MDR/RR-TB treatment, was formulated 

by the Guideline Development Group 

(GDG). 

“The new WHO recommendations, 

based on the most recent available 

evidence, signal an important departure 

from previous approaches to treat 

MDR/RR-TB. Injectable agents are no 

longer among the priority medicines 

when designing longer MDR-TB 

regimens. Fully oral regimens should thus 

become the preferred option for most 

patients,” stated Dr Tereza 

Kasaeva, Director of WHO’s Global TB 

Programme. 

The evidence included the recently 

completed phase 3 trials of delamanid 

(Otsuka’s Trial 213) and the standardised 

9-12-month shorter MDR-TB regimen 

(STREAM Stage 1), as well as individual 

data for 13,100 patients treated with 

longer MDR-TB regimens in 40 countries 

and over 2,600 patients treated with 

the shorter MDR-TB regimen from 15 

countries. Additional trial data from 

patients under 18 years of age allowed 

a review of recommendations for the 

use of bedaquiline and delamanid in 

children. 

Fluoroquinolones (levofloxacin or 

moxifloxacin), bedaquiline and linezolid 

are strongly recommended for use in 

longer regimens, which are completed 

with other medicines ranked by their 

relative balance of effectiveness to 

potential toxicity. 

The shorter MDR-TB regimen may be 

offered to eligible patients who agree to 

a briefer treatment. Shorter regimens for 

MDR may, however, be less effective than 

an individualized longer regimen and 

that requires a daily injectable agent for 

at least four months. Regimens that vary 

substantially from the recommended 

composition and duration like the 

FLUOROQUINOLONES 

(LEVOFLOXACIN OR 

MOXIFLOXACIN), BEDAQUILINE 

AND LINEZOLID ARE 

STRONGLY RECOMMENDED 

FOR USE IN LONGER 

REGIMENS 

standardized 9-12-month shorter MDR- 

TB regimen in which the injectable 

agent is replaced by bedaquiline can 

be explored under operational research 

conditions. 

The recommendations apply 

generally to children and adults, to 

people living with HIV (PLHIV) and to 

MDR/RR-TB patients who have additional 

resistance to fluoroquinolones or other 

agents. 

Bedaquiline may now be given to 

children aged 6 years and more and 

delamanid from 3 years of age. 

Supportive measures to improve 

diagnostics and other programmatic 

components will be critical. Ahead 

of enrolment on MDR-TB treatment, 

all patients should be appropriately 

counselled to enable participatory 

decision-making. Patient-centred support 

for medication adherence and active TB 

drug safety monitoring and management 

(aDSM) are essential for anyone starting 

an MDR-TB regimen. 


IDRI’S TB VACCINE ENTERS PHASE 2 TRIALS 

An experimental vaccine, called 

ID93, developed by scientists at the 

Infectious Disease Research Institute 

(IDRI) in Seattle, has advanced to phase 

2 clinical testing. 

The TB vaccine candidate combines 

ID93, a fusion of 4 mycobacterium 

tuberculosis antigens with diverse roles 

in pathogenesis, with the adjuvant 

GLA-SE, a synthetic toll-like receptor 

4 (TLR4) agonist, formulated in a 

squalene oil and water nano-emulsion 

that has a significant safety track 

record. 

“The four antigens representing 

different families of mycobacterium 

tuberculosis (MTB) proteins have 

been shown to be recognised in 

MTB-exposed individuals. RV1813 is a 

conserved hypothetical protein that 

is upregulated under hypoxic growth 

and predicted to be localised in the 

outer membrane. RV2608 (PPE42) is a 

probable outer membrane-associated 

PPE (pro-pro-glu motif-containing) 

protein. RV3619 (ESXV) and RV3620 

(ESXW) are secreted proteins belonging 

to the ESAT-6 family of virulence 

factors,» says Rhea Coler, Senior. Vice 

President, Preclinical & Translational 

Science at IDRI. 

Explaining the role of the adjuvant, 

Rhea Coler 

STUDIES HAVE SHOWN 

THAT ID93+GLA-SE 

IS EFFICACIOUS 

PROPHYLACTICALLY 

AS WELL AS 

THERAPEUTICALLY 

Coler said, GLA-SE skews the immune 

response to a TH1 type immune 

response with induction of CD4+ T 

cells. Human immune correlates of 

protection against TB have not yet 

been identified. T-helper 1 (TH1) type 

cellular immunity is known to be crucial 

for controlling MTB infection and thus 

vaccine strategies aim to elicit these 

subsets. 

Recently, studies have shown 

evidence that antibodies may also 

contribute to controlling disease in 

latently infected individuals. 

Pre-clinical studies using mice, 

guinea pigs and non-human primates, 

have shown that ID93+GLA-SE is 

efficacious prophylactically as well as 

therapeutically. The vaccine significantly 

improved TB treatment outcomes 

over antibiotics alone and allowed the 

duration of antibiotic treatment to be 

reduced by 30%. 

Therapeutic efficacy of ID93+GLA- 

SE is associated with enhanced TH1 

responses, improved MTB clearance, 

and reduced pulmonary inflammation. 

“In mice and humans, we have 

observed immune responses 6-12 

months after immunization,’’ Coler 

adds. 

As a part of the efforts to make 

the vaccine affordable for those who 

need it, IDRI is planning to transfer the 

technology involved in the production 

of the vaccine to 3 different facilities in 

Africa and Asia. 

TB a big challenge. 

TB kills more than 1,400 people every day, or around 

480,000 Indians every year, as per official estimates. 

India accounts for nearly 10% of the global burden of HIVassociated 

TB. According to the India TB Report 2018, 87,000 

HIV-associated TB patients are being diagnosed annually. HIV 

prevalence among incident TB patients is estimated to be 

4%. The mortality in TB/HIV co-infected patients is very high 

and 12,000 people die every year from this condition. 

Prevention as centrepiece? 

Alongside free diagnosis and treatment, the NSP provides 

an incentive for nutritional support. “In India, undernutrition 

is a driver of TB,” comments Dr Sameer. Undernutrition and 

TB have a bidirectional relationship. While undernutrition 

increases the risk of TB, contracting the disease increases 

the risk of malnutrition, thereby culminating in an intercausal 

cycle for the two diseases. 

India has practically doubled the budget to meet the 

target of eliminating TB by 2025. “The government has 

backed the NSP with a historic resource commitment of Rs 

12,000 crores over three years, while it increased investment 

in research and development to $6 million,” comments Dr 

Sameer. 

Some experts are of the opinion that the current budget 

allocation may still be way below the actual requirement. 

Considering the enormity and the urgency of the situation, 

both the regular, drug-susceptible TB as well as the drugresistant 

TB need additional expenditure. 

In order to achieve the target of ending TB by 2025, India 

needs to reduce new TB cases by 10 percent every year. But 

recent reports indicate that the country is nowhere near the 

number. Moreover, India needs to pay more attention to a 

preventive strategy. The goals can’t be translated to reality 

until prevention becomes the centrepiece of India’s TB policy, 

warn experts. 


technology 

NGS BREAKS NEW PATH 

IN TB CARE 

Integration of NextGen Sequencing can reduce the Mycobacterium tuberculosis 

disease burden 

DR RAJANI KANTH VANGALA 

In order to have an effective 

treatment for tuberculosis (TB), 

there is an urgent need to modify 

the current treatment regime, which 

includes low efficacy, high toxicity and 

long duration drugs, and consumes 

significant resources. In 2015 alone, 

there have been 10.4 million TB 

infections and 1.8 million deaths, 

making TB one of the top 9 killers in 

the world, higher than HIV/AIDS. This 

unsatisfactory situation is mainly due 

to the development of drug resistant 

TB, which is immune to isoniazid and 

rifampicin. The three different types of 

resistance include multi-drug resistance 

(MDR), extensive drug-resistance 

(XDR) and totally drug-resistance 

(TDR), based on the exact strain of 

Mycobacterium tuberculosis responsible 

for the infection. 

At the same time, there has 

been the emergence of “offlabel” 

repurposed drugs such as 

oxazolidinones, carbapenems and 

clofazimine, which are being used to 

treat highly-resistant TB cases. The 

identification of the type of infection 

and proper diagnosis have been found 

to be the most important factor that 

determines the clinical outcome 

in such cases, even as drug-resistant 

strains are becoming a major global 

challenge. This challenge can only 

be addressed by genetic analysis to 

understand its complex biology and the 

mechanisms of drug-resistance. 

In this respect, one of the most 

important technological advances is 

whole-genome sequencing (WGS), 

which was first reported by Cloe et 

al in 1998, sequencing the M. 

tuberculosis strain H37Rv. This 

has significantly improved our 

understanding of the bacterial strain 


about its physiology, metabolism, and 

pathogenicity. 

Diagnosing resistance 

The advent of NextGen Sequencing 

(NGS) technologies, combined with 

bioinformatics tools, has enabled 

the establishment of new platforms 

for better diagnosis and potential 

therapeutic approaches. Generation 

of large-scale genomic data in less 

time and at a lower cost (Metzker, 

2010) has led to its use in various 

clinical scenarios, such as drug 

susceptibility, diagnosis and genetic 

diversity (Satta et al., 2017). Zhang 

et al (2013) analyzed 161 clinical 

isolates in China and Casali et al 

(2014) analyzed 1000 M. tuberculosis 

genomes using WGS technology, 

leading to the identification of 28 

intergenic regions (IGRs) associated 

with drug resistance, 10 IGR single 

nucleotide polymorphisms (SNPs), 72 

new genes and 11 non-synonymous 

SNPs. Several other uncharacterized 

genes, intergenic regions and SNPs 

were also reported to be associated 

with drug resistance phenotypes by 

other research groups (Anderson et 

al., 2014; Ali et al., 2015; Pankhurst 

et al., 2016). Further improvements, 

like the use of direct clinical samples 

or biospecimens, without the need 

for costly infrastructure has also 

changed the ease with which data 

can be generated. NGS can now be 

directly applied to clinical isolates using 

tabletop machines without the need for 

too much pre-processing and in very 

short times. 

The quality and depth of the 

complete genome sequence provided 

by NGS has helped in the development 

of MDR/XDR-TB diagnostics. It has also 

helped in comparative genomic analysis 

to understand genomic diversity 

and the evolution of drug-resistant 

pathogens (Liu et al., 2014). Some of 

the recent NGS-based studies focusing 

on the evolution of XDR M. tuberculosis 

have shown that a single patient can 

have both a susceptible ancestor for 

fluoroquinolones as well as resistant 

bacteria (Zhang et al. 2016). One of 

the most important limiting steps yet 

in NGS is cumbersome bioinformatics 

and data inconsistencies about 

correlations between gene mutations 

and phenotypic drug susceptibility test 

(DST). However, the emergence of a 

new generation of sequencing, enabling 

long reads of up to 100kb (Lee et al 

2016), has resulted in a reduction of 

fragment assemblies. Presently there 

are three third-generation technology 

platforms, namely Pacific Biosciences 

(PacBio) Single Molecule Real Time 

(SMRT) sequencing, Illumina Tru-seq 

Synthetic Long-Read technology and 

Oxford Nanopore Technologies’ MinION. 

These technologies are now making 

whole-genome sequencing much 

faster and simpler. In addition, recent 

publications have generated data on 

mythelomes that suggest that MTases 

activities, which are up-regulated, 

contribute to genome modifications 

and mutations leading to the evolution 

of drug resistance in MDR-TB clinical 

isolates (Leung et al., 2017). 

THE QUALITY AND DEPTH 

OF THE COMPLETE GENOME 

SEQUENCE PROVIDED BY 

NGS HAS HELPED IN THE 

DEVELOPMENT OF 

MDR/XDR-TB DIAGNOSTICS 

Enabling faster detection 

Some of the important challenges 

which need urgent attention include, 

DNA extraction, the need for culture 

for WGS, understanding the molecular 

mechanisms of drug resistance and 

large-scale data analysis. Starting 

with DNA extraction, there are many 

technologies in this arena, and an 

evaluation of these will help in selecting 

the best. For example, Nextera DNA 

Flex / Nextera XT / Nextera mate 

Pair work on an Illumina platform 

with as low as 1ng of DNA. The 

new concept of DNA isolation from 

saliva without culturing has gained 

a lot of momentum as it reduces 

the time required and gives faster 

results. However, this also comes 

with its own difficulties in removing 

human DNA and other potential 

contaminants. Furthermore, this gets 

more complicated due to the use of 

nonspecific primers. Some of the new 

technologies which are picking up this 

challenge are differential lysis protocol 

followed by DNA extraction using a 

NucleoSpin tissue-kit or Illumina MiSeq 

sequencer with 87% success rate 

(Doughty et al 2014), SureSelectXT 

target enrichment system (Agilent 

Technologies) with 83% success (Brown 

et al., 2015). Further developments are 

required to evolve these technologies 

for lower cost and improved diagnosis. 

As we are still at a nascent stage of 

understanding the evolution of drugresistant 

phenotypes using NGS, tools 

for automated pipeline, like Mykrobe 

Predictor TB, TB Profiler, CASTB, 

PhyResSE and KvarQ, are enabling 

faster detection of drug resistance 

and lineage-specific mutations from 

raw, whole genome sequence of M. 

tuberculosis. 

The future of M. tuberculosis 

management will not only depend 

on NGS technologies but also in 

developing direct DNA isolation 

for sequencing, along with better 

bioinformatics. Such developments 

might help us finally realize the goals 

of the StopTB partnership and reduce 

disease burden. 


drug approvals 

Priority review for 

upadacitinib to treat RA 

AbbVie said the US FDA has 

accepted upadacitinib for 

priority review for the treatment 

of adult patients with moderate 

to severe rheumatoid arthritis. 

Upadacitinib is an 

investigational once-daily oral 

JAK1-selective inhibitor being 

studied for multiple immunemediated 

diseases. 

The new drug application 

is supported by data from the 

global upadacitinib SELECT 

phase 3 rheumatoid arthritis 

programme evaluating more 

than 4,000 patients with 

moderate to severe rheumatoid 

arthritis across five of six phases 

3 studies. In all SELECT phase 

3 studies, upadacitinib met all 

primary and ranked secondary 

endpoints. 

Upadacitinib is also under 

review by the European 

Medicines Agency for the same 

indication. 

The SELECT phase 

3 rheumatoid arthritis 

programme evaluates more 

than 4,900 patients with 

moderate to severe rheumatoid 

arthritis in six studies, five of 

which support a regulatory 

submission for upadacitinib. 

Ropeginterferon 

for polycythaemia 

in EU 

PharmaEssentia announced 

that the European 

Commission (EC) has approved 

ropeginterferon alfa-2b 

(Besremi) as monotherapy 

in adults for the treatment 

of polycythaemia vera 

(PV) without symptomatic 

splenomegaly. 

The EU market 

authorization makes 

ropeginterferon alfa-2b the 

first and the only approved 

treatment for PV, independent 

of previous hydroxyurea 

exposure, based on phase III 

clinical data. 

Ropeginterferon alfa-2b 

will be available as a solution 

for injection in a pre-filled pen 

in two dosage strengths of 250 

microgram/0.5 ml and 500 

microgram /0.5 ml. 

Ropeginterferon alfa- 

2b is a novel, long-acting, 

predominately single isomer 

mono-pegylated proline 

interferon with improved 

pharmacokinetic properties. 

It is administered once 

every 2 weeks, or once every 

4 weeks during long-term 

maintenance, and is the first 

interferon approved for PV. 

Turoctocog alfa 

for haemophilia A 

treatment 

The US FDA has approved 

turoctocog alfa pegol, 

N8-GP (Esperoct) for the 

treatment of adults and 

children with haemophilia A. 

Turoctocog alfa pegol 

is indicated for use in 

adults and children with 

haemophilia A (congenital 

factor VIII deficiency) for 

routine prophylaxis to reduce 

the frequency of bleeding 

episodes, Novo Nordisk 

announced. 

The approval is based on 

the results from the clinical 

programme conducted in 

270 previously treated people 

(PTPs) with severe haemophilia 

A and more than 5 years of 

clinical exposure. Turoctocog 

alfa was shown to provide 

effective routine prophylaxis in 

people with severe haemophilia 

A through a simple, fixed 

dosing regimen of one injection 

every 4 days in adults and 

adolescents or every 3-4 days 

in children. 

Turoctocog alfa is an 

extended half-life factor VIII 

molecule for replacement 

therapy, which provides a 1.6- 

fold half-life prolongation in 

adults/adolescents and a 1.9- 

fold half-life prolongation in 

children, compared to standard 

half-life factor VIII products. 

Polatuzumab 

combo for B-cell 

lymphoma 

Polatuzumab vedotin 

in combination with 

bendamustine plus rituximab 

(BR) has been granted priority 

review by the US FDA for the 


treatment of people with 

relapsed or refractory (R/R) 

diffuse large B-cell lymphoma 

(DLBCL). 

The GO29365, a global, 

phase Ib/II randomized study, 

showed that polatuzumab 

vedotin plus BR improved 

median overall survival 

compared to BR alone in 

people with R/R DLBCL not 

eligible for a hematopoietic 

stem cell transplant. The 

study also showed that 40 

percent of people treated with 

polatuzumab vedotin plus BR 

achieved a complete response 

(CR), while only 18 percent of 

people treated with BR alone 

achieved a CR. 

Polatuzumab is developed 

by Genentech, a member of 

the Roche Group. 

Renexus to treat 

macular disease 

The US FDA has granted 

Fast Track designation 

for NT-501 or Renexus for 

the treatment of macular 

telangiectasia type 2 

(MacTel), Neurotech 

Pharmaceuticals said. 

Renexus is a novel 

cell-based drug delivery 

system. Human-derived 

cells encapsulated in a 

semipermeable hollow fibre 

membrane device release 

US FDA panel okays esketamine 

nasal spray for depression 

The Janssen 

Pharmaceutical 

Companies of Johnson 

& Johnson announced 

that the US Food and 

Drug Administration (FDA) 

recommended the use 

of esketamine (Spravato) 

for treatment resistant 

depression. 

The 

psychopharmacologic 

drug advisory committee 

and drug safety and risk 

management advisory 

committee of US FDA jointly 

voted that data support 

the favorable benefit-risk 

profile of esketamine nasal 

spray CIII for adults living 

with treatment-resistant 

depression. 

Esketamine is thought 

to work differently than 

currently approved therapies 

for major depressive 

disorder (MDD). If approved, 

esketamine would provide 

the first new mechanism of 

action in 30 years to treat 

this debilitating mental 

illness. 

ciliary neurotrophic factor 

(CNTF) demonstrated to 

reduce photoreceptor cell loss 

in animal models of retinal 

degeneration. 

The implanted Renexus 

device results in sustained 

The committees based 

their support on the safety 

and efficacy data from five 

phase 3 studies in patients 

with treatment-resistant 

depression: three short-term 

studies; one maintenance 

of effect study; and one 

long-term safety study. In 

addition, the esketamine 

research programme 

provided supportive data 

from three Phase 2 studies 

and 19 phase 1 studies in 

patients with treatmentresistant 

depression and 

healthy volunteers. 

Esketamine is a 

glutamate receptor 

modulator, thought to help 

restore synaptic connections 

in brain cells in people 

with the major depressive 

disorder. 


Breakthrough Therapy 

Designations for esketaine 

for treatment-resistant 

depression and for a second 

indication, major depressive 

disorder with imminent risk 

for suicide. 

delivery of CNTF localized to 

the retina, the light-sensing 

tissue in the back of the 

eye. MacTel is a rare macular 

degenerative disease typically 

diagnosed in middle age. 

Patients rarely experience total 

vision loss, but the disease 

nonetheless has a significant 

impact, through visual loss, on 

a patient’s quality of life. 

Based on the positive 

phase 2 results, two parallel 

phase 3 studies were initiated. 

Macular telangiectasia 

(MacTel), or idiopathic 

juxtafoveal macular 

telangiectasia, is a rare 

neurodegenerative disease 

with characteristic alterations 

of the retinal vasculature and 

localized retinal degeneration. 

Triclabendazole 

to treat 

fascioliasis 

N 

ovartis said triclabendazole 

(Egaten) has won approval 

from the US FDA for the 

treatment of fascioliasis in 

patients six years of age and 

older. 

Triclabendazole is 

currently the only medicine 

for fascioliasis recommended 

by the WHO and is on the 

WHO Model List of Essential 

Medicines. 

Fascioliasis, commonly 

known as liver fluke infestation, 

is a neglected tropical disease 

that infects 2.4 million people 

worldwide, with an additional 

180 million at risk of infection. 

It is caused by two species 


of parasitic flatworms or 

trematodes that mainly affect 

the liver (Fasciola hepatica 

or Fasciola gigantica). Both 

species can infect humans 

following ingestion of larvae in 

contaminated water or food 

(mainly raw or undercooked 

vegetation). The larvae mature 

into adult worms in the biliary 

tract. No continent is free from 

fascioliasis; human cases have 

been reported from more than 

70 countries worldwide. 

Orphan drug 

designation for 

cryptococcosis 

medicine 

Orphan drug 

designation has 

been granted to a lead 

drug candidate, APX001 

for the treatment of 

cryptococcosis, said Amplyx. 

APX001 had previously 

received orphan drug 

designation for the treatment 

of invasive candidiasis, 

invasive aspergillosis, 

coccidioidomycosis, and rare 

mold infections caused by 

Scedosporium spp., Fusarium 

spp., and Mucorales fungi 

(including Mucor spp., and 

Rhizopus spp.). 

APX001A, the active moiety 

of APX001, inhibits the highly 

conserved fungal enzyme Gwt1, 

compromising growth of major 

fungal pathogens. 

APX001 is currently in 

Oral dapagliflozin for type-1 diabetes 

EMA has recommended a new indication for 

dapagliflozin (Forxiga) for use as an oral adjunct 

treatment to insulin in adults with type-1 diabetes 

(T1D). 

Dapagliflozin, a selective sodium glucose 

cotransporter-2 (SGLT2) inhibitor, is the first oral 

medicine to receive a positive recommendation 

from the EMA for use in T1D as an adjunct to 

insulin in patients, AstraZeneca said. 

The DEPICT clinical programme 

consists of two trials, DEPICT-1 and -2, 

with the primary efficacy endpoint at 

24 weeks and a long-term extension up 

to 52 weeks. Both trials demonstrated 

that dapagliflozin, when given as an oral 

adjunct to adjustable insulin in adults with 

inadequately-controlled T1D, showed 

significant reductions from baseline in 

HbA1c, weight and total daily insulin 

dose at 24 and 52 weeks, vs. placebo, 

at both 5mg and 10mg doses. 

Dapagliflozin is also under 

regulatory review in the US and 

Japan for use as an adjunct 

treatment to insulin in adults 

with T1D. 

phase 2 clinical trial evaluating 

the efficacy and safety of both 

IV and oral APX001 for the 

first-line treatment of patients 

with fungal infections. 

Cryptococcosis is an 

infectious disease of the 

lungs or central nervous 

system caused by the 

fungus Cryptococcus (either 

Cryptococcus neoformans or 

Cryptococcus gattii), which 

is typically found in the 

environment and inhaled. 

Brain infections due to the 

fungus Cryptococcus are called 

cryptococcal meningitis. 

Split-dosing 

regimen of 

daratumumab 

The US FDA has approved 

a split-dosing regimen 

for daratumumab (Darzalex) 

providing healthcare 

professionals and patients with 

multiple myeloma an option to 

split the first infusion over two 

consecutive days. 

The US FDA approval 

is based on data from the 

phase 1b Equuleus clinical 

study, which demonstrated 

daratumumab pharmacokinetic 

concentrations were 

comparable at the end of 

weekly dosing, regardless of 

whether the first dose was 

administered as a split infusion 

or as a single infusion. 

Daratumumab is the first 

CD38-directed antibody to 

receive regulatory approval to 

treat multiple myeloma. In the 

US, Darzalex (daratumumab) 

first received FDA approval 

in November 2015 as a 

monotherapy for patients with 

multiple myeloma who have 

received at least three prior 

lines of therapy, including a 

proteasome inhibitor (PI) and 

an immunomodulatory agent, 

or who are double refractory to 

a PI and an immunomodulatory 

agent, Janssen said. 

Benralizumab for 

HES get orphan 

drug tag 


Orphan Drug designation 

benralizumab (Fasenra) for the 

treatment of hypereosinophilic 

syndrome (HES). 

HES is a group of rare, 

potentially fatal disorders 

characterised by high numbers 

of eosinophils in blood and 

tissues, which can cause 


progressive damage to any 

organ in the body. 

Benralizumab is a 

monoclonal antibody that binds 

directly to IL-5 receptor on 

eosinophils and attracts natural 

killer cells to induce rapid and 

near-complete depletion of 

eosinophils via apoptosis. 

Benralizumab was 

developed by AstraZeneca with 

MedImmune. 

Dacomitinib to 

treat NSCLC 

in Europe 

The Committee for Medicinal 

Products for Human Use 

(CHMP) of the European 

Medicines Agency (EMA) has 

adopted a positive opinion 

recommending dacomitinib 

45 mg (Vizimpro) for the firstline 

treatment advanced or 

metastatic non-small cell lung 

cancer (NSCLC) with epidermal 

growth factor receptor (EGFR)- 

activating mutations, according 

to Pfizer. 

Dacomitinib is an oral, 

once-daily, irreversible panhuman 

epidermal growth 

factor receptor kinase inhibitor. 

Dacomitinib was approved 

by the US FDA in 2018 for the 

first-line treatment of patients 

with metastatic NSCLC with 

EGFR exon 19 deletion or 

exon 21 L858R substitution 

mutations as detected by an 

FDA-approved test. It was also 

recently approved in Japan for 

EGFR gene mutation-positive, 

inoperable or recurrent NSCLC 

The Marketing 

Authorization Application 

(MAA) for dacomitinib 

was based on results from 

ARCHER 1050, a randomized, 

multicentre, multinational, 

open-label, phase 3 study 

conducted in patients with 

locally advanced unresectable, 

or metastatic NSCLC harbouring 

EGFR exon 19 deletion or 

exon 21 L858R substitution 

mutations, an Eastern 

Cooperative Oncology Group 

(ECOG) performance status of 

0 or 1; with no prior therapy for 

metastatic disease or recurrent 

disease with a minimum of 

12 months disease-free after 

completion of systemic therapy. 

Pexidartinib to 

treat TGCT gets 

priority review 

Daiichi Sankyo said 

pexidartinib for the 

treatment of tenosynovial giant 

cell tumour (TGCT) has been 

granted priority review by US 

FDA. 

TGCT, also referred to 

as pigmented villonodular 

synovitis (PVNS) or giant cell 

tumour of the tendon sheath 

(GCT-TS), is a non-malignant 

tumour of the joint or tendon 

sheath, which can be locally 

aggressive and debilitating in 

some patients. There are no 

currently approved systemic 

therapies for TGCT. 

The NDA is based on results 

of the pivotal phase 3 ENLIVEN 

study of oral pexidartinib, the 

first placebo-controlled study 

of a systemic investigational 

therapy in patients with TGCT. 

Pexidartinib is an 

investigational oral small 

molecule that potently inhibits 

CSF1R (colony stimulating 

factor-1 receptor), which is 

a primary growth driver of 

abnormal cells in the synovium 

that cause TGCT. Pexidartinib 

also inhibits c-kit and FLT3-ITD. 

Nanobody drug 

for aTTP 

The US FDA cleared 

caplacizumab-yhdp 

(Cablivi), an anti-vWF 

Ospemifene for vaginal 

dryness 

The US FDA has expanded 

use of ospemifene 

(Osphena) to include 

treatment of moderate to 

severe vaginal dryness due 

to menopause. 

Vaginal dryness and 

itching are symptoms of 

vulvar and vaginal atrophy. 

Ospemifene is an 

oestrogen receptor 

nanobody, in combination 

with plasma exchange and 

immunosuppression for 

the treatment of acquired 

thrombotic thrombocytopenic 

purpura (aTTP) in adults. 

Caplacizumab is the 

first FDA approved therapy 

specifically indicated for the 

treatment of aTTP. 

Caplacizumab targets von 

Willebrand factor (vWF), a 

protein in the blood involved 

in hemostasis. It is designed to 

inhibit the interaction between 

vWF and platelets. 

agonist/antagonist with 

tissue selective effects. 

It is available in 60 mg 

tablets which were initially 

approved in 2013 to 

treat moderate to severe 

dyspareunia due to 

menopause. 

The approval has been 

on the basis of safety 

and efficacy data from 

a confirmatory phase 

3 randomized, doubleblind, 

placebo-controlled 

multicentre study evaluating 

ospemifene in patients with 

moderate to severe vaginal 

dryness. 

The data showed that 

treatment with ospemifene 

led to a statistically 

significant improvement 

in self-reported, most 

bothersome symptom of 

vaginal dryness as well as 

a statistically significant 

increase in the proportion 

of superficial cells and a 

corresponding statistically 

significant decrease in the 

proportion of parabasal cells 

on a vaginal smear; mean 

reduction in vaginal pH 

between baseline and week 

12 was also statistically 

significant. 

Caplacizumab is Sanofi›s 

first Nanobody-based medicine 

to receive approval in the US. 

Nanobodies are a novel 

class of proprietary therapeutic 

proteins based on singledomain 

antibody fragments 

that contain the unique 

structural and functional 

properties of naturallyoccurring 

heavy chain only 

antibodies. 

The treatment received 

FDA Fast Track designation and 

was evaluated under Priority 

Review. 


straight talk 

“EVERYBODY HAS TO 

DEVELOP THE WAY THEY 

ARE. TAKING ADVICE IS LIKE 

COPYING SOMEONE” 

Less focus on basic science and limited 

support for discovery research are the 

two issues the scientific community as 

well as governments all over the world 

should be seriously worried about 

today. Big pharmaceutical companies 

ignoring the serious threat of microbial 

resistance to existing antibiotics and 

not thinking about developing new 

ones is another dangerous trend that 

the world is facing at present, says 

PROF ADA E YONATH. 

The Chemistry Nobel Laureate, who 

was in India in February to deliver the 

keynote address at the International 

Conference on Advanced Chemical and 

Structural Biology - 2019 in Chennai, 

spoke to Future Medicine at length 

in an exclusive interview with Editor 

C H UNNIKRISHNAN. Edited excerpts: 

One of the key objectives of your path-breaking work on 

ribosomes was to help the development of new antibiotics. 

But, has it really resulted in the introduction of any in the 

market, especially in a situation where the existing ones are 

becoming less effective due to bacterial resistance? 

There are quite a few in the development stage across 

the globe, targeting ribosomes. But, in general, it seems that 

many of the big companies do not think that antibiotics are a 

profitable business for them. It is very unfortunate, and I wish 

they would think beyond profit and would take up more such 

projects and introduce them in the market quicker, considering 

the urgent need to save human life as antimicrobial resistance 

is a crucial health issue now. 

Why can’t big pharmaceutical companies, who often talk 

eloquently about philanthropy and social responsibility, 

work on these novel pathways, including your discovery, to 

develop new products that help combat this serious issue? 

There were several companies that showed interest in 

developing new products targeting proteins. Nothing much 

has happened so far as hardly anyone really worked to take it 

up. I know that the investment that is required to develop new 

drugs is high and that’s why they found it not profitable. I do 

not know if there are other reasons as well. One should ask 

them (the industry). 

You have been very vocal about the imminent health crisis 

that can manifest if there are no new antibiotics developed 

against multi-drug resistant bugs quickly. Do you think 

governments and not-for-profit organisations should step in? 

I don’t think governments can get into the business of 

product development and production, though it can facilitate 

and support research. It is the industry that should take them 

up. But, as you rightly said, one thing is sure that the crisis of 

drug resistant bacteria is going to be big in the world if there 

are no new antibiotics that enter the market soon. 

After your path-breaking work on identifying the ribosome 

structure and crystallising them, are there more research or 


Prof Ada E Yonath 

PHOTO: UMESH GOSWAMI 


slug 

progressive work on the same happening to 

take it forward? 

Not on the same, but yes, there are 

many good works happening around. The 

researchers are thinking in different ways and 

are exploring new mechanisms to target the 

ribosome, among others and also to find out 

different factors that cause natural mutation 

within the bacteria that gives them resistance. 

There aren’t anything in the same way, which 

I know; though we don›t think ours was the 

best. We are also exploring further. 

Multi-drug resistant tuberculosis is a 

very serious medical challenge in India and 

also in many other Asian countries. How 

do we explain the resistance mechanism in 

I think there is 

scope for exploring 

new antibiotics 

for treating 

drug-resistant 

tuberculosis, 

targeting 

ribosomes. 

tuberculosis, where drugs are not targeting 

ribosomes? 

There are also some tuberculosis drugs 

targeting ribosomes of late. But, most of 

the existing drugs target cell walls, cell 

cycles and checkpoint controls and other 

pathways. Although we have not focused 

on tuberculosis as such so far, I think there 

is scope for exploring new antibiotics for 

treating drug-resistant tuberculosis, targeting 

ribosomes. 

How do bugs continue to develop 

resistance to more and more antibiotics? 

It is part of the natural survival 

[mechanism] of organisms. As I said before, 

there are natural mutations that take place 


Nobel Laureate Prof. Ada E Yonath 

shared the world’s most coveted 

prize in chemistry with Dr Thomas Steitz 

and Prof. Venkataraman Ramakrishnan 

in 2009. Her pioneering work on 

ribosomal crystallography helped in the 

precise identification of the structure 

and functions of ribosomes and it 

opened up immense possibilities of 

targeting ribosomes for developing 

new antibiotics. The first Israeli woman 

to win a Nobel Prize, Prof Yonath 

accepted her postdoctoral positions 

at Carnegie Mellon University in 1969 

and MIT in 1970. She was also group 

leader with Heinz-Gunter Wittmann at 

the Max-Planck Institute for Molecular 

Genetics in Berlin. She was the visiting 

professor at the University of Chicago 

in 1977-78 and then headed one of the 

Max-Planck Institute’s research unit at 

DESY in Hamburg, Germany in parallel to 

her research activities at the Weizmann 

Institute. 

Yonath focuses on the mechanisms 

underlying protein biosynthesis by 

ribosomal crystallography, a research 

line she pioneered over twenty years 

ago despite considerable skepticism on 

the part of the international scientific 

community. Ribosomes translate RNA 

into protein, and because they have 

PROF ADA E YONATH 

slightly different structures in microbes 

when compared to eukaryotes such 

as human cells, they are often a target 

for antibiotics. In 2000 and 2001, she 

determined the complete high-resolution 

structures of both ribosomal subunits 

and discovered within the otherwise 

asymmetric ribosome, the universal 

symmetrical region that provides 

the framework and navigates the 

process of polypeptide polymerisation. 

Consequently, she showed that the 

ribosome is a ribozyme that places 

its substrates in stereochemistry 

suitable for peptide bond formation 

and for substrate-mediated catalysis. 

In 1993, she visualised the path taken 

by the nascent proteins, namely the 

ribosomal tunnel, and recently revealed 

the dynamic elements enabling its 

involvement in elongation arrest, gating, 

intra-cellular regulation and nascent 

chain trafficking into their folding space. 

Additionally, Yonath elucidated the 

modes of action of over twenty different 

antibiotics targeting the ribosome, 

illuminated mechanisms of drug 

resistance and synergism, deciphered 

the structural basis for antibiotic 

selectivity and showed how it plays a key 

role in clinical usefulness and therapeutic 

effectiveness, thus paving the way for 

structure-based drug design. 

For enabling ribosomal crystallography, 

Yonath introduced a novel technique— 

cryo bio-crystallography, which became 

routine in structural biology and allowed 

intricate projects otherwise considered 

formidable. 

At the Weizmann Institute, Yonath 

is the incumbent of the Martin S. and 

Helen Kimmel Professorial Chair. She 

is also a member of the United States 

National Academy of Sciences, the 

American Academy of Arts and Sciences, 

the Israel Academy of Sciences and 

Humanities, the European Molecular 

Organisation and the European Academy 

of Sciences and Art. In 2014, Prof. 

Yonath was named a member of the 

Pontifical Academy of Sciences by Pope 

Francis. Her other awards and honours 

include the Israel Prize (2002), Harvey 

Prize (2002), Massry Prize (2004), 

Paul Karrer Gold Medal (2004), Horvitz 

Prize (2005), Wolf Prize in Chemistry 

(2006), Rothschild Prize in Life Sciences 

(2006), The EMET Prize for Art, Science 

and Culture in life sciences (2006), Paul 

Ehrlich and Ludwig Darmstaeder Prize 

(2007), Albert Einstein World Award of 

Science (2008), Wilhelm Exner Medal 

(2010) and Honorary Doctorates from 

several universities. 

within the living organisms as a process of getting adapted to 

their living environment and there is constant fight that takes 

place between one and the other for survival. 

Do you think Indian scientists could have achieved more 

had the government been more supportive and encouraging 

in research and development here? 

I don’t know about the support system in India. So, I 

can’t comment on that. But I can say that Indian scientists 

have been doing well in many areas. There is good science 

done in India, which may not be in antibiotics or new drug 

development. But it is cleverer in many other areas. Also, there 

are good Indian scientists outside the country who are brilliant 

and much more capable than others. 

The problem that I really see now everywhere is a lack 

of support for basic science. Original discoveries should 

be encouraged by governments and other systems. Basic 

science that tries to understand what is not 

understood so far brings real changes in 

the society and that should be the focus of 

research. 

I know that your best advice to young 

and aspiring scientists is not to seek advice. 

Could you elaborate on this? 

Because everybody has to develop the 

way they are. Let the young minds grow with 

what he or she is really passionate about. It 

is the self-curiosity that leads one to discover 

new things and that is the kind of research 

that the world is looking for and will help 

it progress. Taking advice is like copying 

someone else, and it will not work the same 

way for the other or result in anything new. 


education 

MBBS INTERNS MAY SOON 

GET UNIFORM STIPEND 

MCI BOG’s decision is seen as a move to end the discrimination 

faced by medical interns in the country 

UNIFORM STIPEND 

In a significant move, the Medical 

Council of India (MCI) Board of 

Governors has sought suggestions 

from stakeholders on the demand for 

a uniform stipend for MBBS interns 

across the country. The move is likely 

to benefit thousands of medical 

interns, particularly those in private 

medical colleges. In order to introduce 

uniform stipend for medical interns, 

the Graduate Medical Education (GME) 

Regulations 1997 will be amended. 

The Board of Governors (BOG) 

issued a public notice in this 

regard on January 25, 2019. The 

stakeholders were requested to give 

their suggestions within 15 days. The 

notice says, “All candidates pursuing 

compulsory rotation internship at 

the institution from which the 

MBBS course was completed 

shall be paid stipend on par 

with the stipend being paid 

to the interns of the state 

government medical 

institution/ central 


institution in the state/ 

union territory where the 

₹23,500 

Central government 

medical colleges 

₹20,000 

West Bengal, Delhi, 

Chhattisgarh, Odisha, 

Assam and Kerala etc. 

₹6,000 

Maharashtra 


institution is located.” It further said, 

“All concerned are requested to give 

their comments/ suggestions within 15 

days to bring the above amendment in 

regulations for payment of stipend to 

interns.” 

A long-time demand 

Students of private medical colleges 

have been demanding stipend on 

par with students of state and central 

government medical institutions for 

quite some time. At present, students 

of many of the private medical colleges 

are being paid a meagre amount as 

stipend. There were also cases of 

interns not being paid. There have 

been many incidents of MBBS interns 

resorting to protests for a reasonable 

stipend. 

In many states, MBBS interns of 

state-run medical colleges are also 

being paid very less. They have been 

demanding an increase in stipend for 

a long time. In Maharashtra, medical 

interns are currently being paid a 

stipend of Rs 6,000 per month. But 

in states like West Bengal, Delhi, 

Chhattisgarh, Odisha, Assam and 

Kerala, medical interns are being paid a 

monthly stipend of Rs 20,000 or more. 

Recently, Union Ministry of 

Health and Family Welfare 

had increased the stipend 

of MBBS interns at central 


colleges to Rs 23,500 

from Rs 17,000. 

Medical interns of 

various states have 

been conducting 

continuous protests, 

demanding a 

hike in their 

THERE ARE APPREHENSIONS 

THAT THE MOVE DOESN’T 

PROVIDE MUCH RELIEF TO 

MEDICAL INTERNS IN PRIVATE 

MEDICAL COLLEGES 

stipend. Last year, medical interns in 

Maharashtra staged an indefinite strike 

demanding a 40 per cent increase in 

stipend. Students under government 

quota in two private medical colleges 

in Karnataka had also staged protests 

last year against the non-payment of 

stipend. In Andhra Pradesh, medical 

interns of S.V. Ruia Government Medical 

College recently boycotted their duty 

as they had not been paid stipend for 

several months. The present move of 

the BOG is aimed at bringing an end to 

the discrimination faced by medical 

interns in the country. 

Burden to fall on students? 

Welcoming the move, Mohamed 

Asif Patel, Joint Secretary, Grant 

Government Medical College, Mumbai, 

said, “It will benefit medical interns 

across the country. The job interns 

do across the country is the same 

and therefore the stipend should also 

be uniform. The interns are working 

more than 60 hours in a week. In 

Maharashtra, medical interns are paid 

just Rs 6,000.” He added that the 

move will benefit medical interns in 

private medical colleges too, provided 

clear guidelines are set by the MCI. 

However, there are apprehensions 

that the move doesn’t provide much 

relief to medical interns in private 

medical colleges as they are likely 

to charge stipend amount as part of 

the course fee. Commenting on the 

development, Dr P A Fazal Gafoor 

MD, Director, MES Academy of Medical 

Sciences, said, “It should be inbuilt in 

the fee. If it is made mandatory, the 

increased stipend will be inbuilt in 

the fee of students from next batch 

onwards. The house surgency stipend is 

also included in the course. If increased, 

it will fall on the students.” 


case reports 


STRIKES EARLY 

Parkinson’s disease is often misdiagnosed or missed in young adults 

Josh (name changed) is a 30-year-old man, who was 

healthy, happily married, regularly went to the gym and 

had a good job and a relatively stress-free life. For the 

past several months, however, he seemed to have become 

lethargic and withdrawn, and appeared unhappy and 

depressed to his family members. He also had mild stiffness on 

the left side of the body. While this did not impact his lifestyle 

and exercise regimen, he had become slower than normal. 

Josh underwent a complete evaluation, including routine blood 

workup, metabolic profile and was also tested for possible 

infections. Results from all the tests were normal. Josh was still 

not convinced and wanted to know why he was feeling this 

way. 

Josh then consulted Dr. Anil Venkitachalam, a consultant 

neurologist and a specialist in movement disorders at Nanavati 

Hospital, Mumbai, for further assessment. Dr. Venkitachalam 

examined him and noticed a difference in his left arm swing, 

but there were no other obvious problems. However, the 

slowness on left side, together with a lack of emotions and 

underlying depression, was indicative of early Parkinson’s 

disease. 

Even though Parkinson’s disease is commonly associated 

with tremors involving one of the hands, it is 

also associated with slowness of movement. 

The slowness of movement can be subtle, 

where one may simply stop swinging the 

arm while walking, or speech may become 

slurred. Until a few years ago, the only way to 

diagnose Parkinson’s was by identifying the 

four key symptoms that included slowness, 

tremor, rigidity and postural instability. 

However, there are many who do not present 

with these symptoms and often the disease is 

EVEN THOUGH PD IS COMMONLY 

ASSOCIATED WITH TREMORS 

INVOLVING ONE OF THE HANDS, 

IT IS ALSO ASSOCIATED WITH 

SLOWNESS OF MOVEMENT 


misdiagnosed. It is therefore important to confirm the disease 

with a more quantitative test. The DaT scan or dopamine 

transporter scan is a single photon emission computerized 

tomography (SPECT) imaging technique that determines the 

levels of the dopamine transporter in the striatum. SPECT 

visualizes the radiolabeled isotope that binds to the dopamine 

transporter, effectively quantifying the transporter levels. These 

transporters are important for the reuptake of dopamine at the 

synaptic cleft and have been shown to be reduced by 50-70% 

in patients with Parkinson’s disease. Josh was confirmed to 

have Parkinson’s disease after having an abnormal DaT scan. 

There is no known cause for Parkinson’s disease. It 

is believed that there are multifactorial reasons for the 

degeneration of dopaminergic neurons, which ultimately 

affects overall bodily movements. In addition to tremors 

and slowness of movement, patients with Parkinson’s often 

experience depression and pain, and may have disorders 

related to sleeping, eating, urination and constipation. 

Over the past 2 decades, significant research has been 

done on the disease. While there is no known cure at this 

time, there are several drugs in the market to symptomatically 

manage the disease. Research has focused on refining the 

existing treatment options, developing new surgical equipment 

for advanced interventional therapy, improving physician 

skill sets and so on. The current gold standard for treating 

Parkinson’s disease is the oral administration of carbidopalevodopa. 

Levodopa is a natural chemical that can cross the 

blood brain barrier with the help of carbidopa, and then 

get converted to dopamine. Other drugs include dopamine 

agonists that mimic dopamine. However, these are not as 

effective as carbidopa-levodopa. 

With Josh being so young, it was a challenge for him 

and his family to accept that he was diagnosed with such a 

degenerative disorder with no known cure. He was started 

on an oral medication with dopamine agonists that increase 

dopamine levels in the brain, along with a recommendation 

for vigorous lifestyle changes, including increased physical 

activities like cardiovascular exercises, healthy diet to include 

more fiber and fluids, and stress reduction. This treatment has 

thus far been effective for Josh. However, he has a long journey 

ahead with Parkinson’s disease. As the disease progresses, his 

symptoms are likely to change, and oral medication will likely 

become ineffective. As per Dr. Venkitachalam, oral medications 

are suitable for the first 5-7 years of the disease, when the 

symptoms are relatively stable and well controlled. After that, 

treatment will most likely need to be changed as the side 

effects of the drugs kick in and the absorption of dopamine 

from the gastrointestinal tract decreases. 

In cases where symptoms of Parkinson’s disease kick in 

early in life, oral medications would need to be eventually 

replaced with other advanced therapy options. These may 

need to be considered for Josh. The deep brain stimulation 

surgery involves implanting electrodes in the brain connected 

to a pacemaker that sends electrical pulses to specific areas 

within the brain. This treatment is effective for 

patients who demonstrate a good response 

to levodopa. Alternatively, for patients who 

experience fluctuations in plasma levodopa 

levels upon oral intake of carbidopa-levodopa, 

transdermal patches of dopamine agonists 

and infusion therapies such as apomorphine 

and levodopa- carbidopa intestinal gel are 

available. 

Patients must be closely monitored, and 

regular visits to the treating neurophysician 

every 3-4 months is advised. Associated 

symptoms should be treated, and the 

drug choices/doses adjusted, based on 

disease progression. As both motor and 

non-motor symptoms are associated with 

Parkinson’s Disease, often, falls and fractures 

IN CASES WHERE SYMPTOMS OF 

PD KICK IN EARLY IN LIFE, ORAL 

MEDICATIONS WOULD NEED 

TO BE EVENTUALLY REPLACED 

WITH OTHER ADVANCED 

THERAPY OPTIONS 

add to the disability in these patients and 

multidisciplinary treatment may be needed 

during the course of the disease. 

Even though Parkinson’s Disease is 

classically thought to be a disease that affects 

the elderly and tremors in the hand are often 

the most common symptom that is noticed, 

in Josh’s case, there was no tremor and he 

was really young. Dr. Venkitachalam stresses 

that often Parkinson’s disease is misdiagnosed 

or missed in young adults as the symptoms 

are not looked at collectively. “It is important 

to consider Parkinson’s disease beyond age 

and tremors, and look for additional clinical 

clues such as depression, constipation, pain, 

slowness and lethargy. It is also important to 

remember that Parkinson’s disease is the only 

neurodegenerative disorder where treatment 

is available. Early diagnosis and treatment can 

help an affected patient have a normal quality 

of life.” 

DR SHIVANEE SHAH 


case reports 

RECREATING THE IMPOSSIBLE; 

REGENERATING HOPE 

How abdominal fat turns saviour to help regrow irreparably lost tissue 

Pulak Pal (name changed) was working 

in his hairpin manufacturing factory when he 

42-year-old 

accidentally put his hands into a machine and 

the fingers of his right hand got crushed. Pulak’s right 

middle finger got a deep gash, the thumb was completely 

crushed and worst of all, the index finger got severed at 

the base. The injury was so severe that all nearby hospitals 

advised amputation of the fingers. However, Pulak’s family 

did not give up and eventually took him to Apollo Gleneagles 

Hospitals, Kolkata. 

His case was forwarded to Dr. Srinjoy Saha, Consultant, 

Plastic, Aesthetic, Reconstructive & Burns Surgery. Dr. Saha 

methodically carried out the initial investigations to assess the 

extent of damage. He asked for all necessary investigations and 

a pre-anesthetic check to determine if Pulak could be taken 

up for early surgery. While the X-ray showed multiple fractures 

and crushed bones in the hand, advanced examinations of the 

fingers revealed poor blood circulation with about 80% of the 

tissue already dead or dying and only about 20% still healthy. 

Based on these findings, Dr. Saha discussed various treatment 

options available with the patient and his family during the 

initial consultation. He said Pulak could either amputate 

the fingers like the other doctors in previous hospitals had 

suggested, or he could try to save them using stem cells 

present inside abdominal fat. However, there would be no 

guarantee of saving the fingers and the process would be 

cumbersome for at least a 3-week period. Faced with a choice 

between a 3-week hardship or a lifetime of loss, Pulak and his 

family decided to save his fingers and give the new option of 

regenerative medicine a try. 

Regenerative medicine is the science of replacing, 

engineering, or regenerating human cells, tissues, or organs 

to restore or establish normal form and function. It is an 

exciting new way of treatment, utilizing the body’s own cells 

to heal damaged tissues and form new ones. Stem cells have 

an enormous capacity to self-renew and differentiate into 

multiple cell types. Stems cells used to be harvested from 

foetal sources such as amniotic fluid or the umbilical cord. 

Today they can be harvested from adult tissues such as bone 

marrow and more recently, from adipose tissues or body fat. 

Adipose tissue-derived stem cells (ADSCs) are relatively easy to 

harvest by subcutaneous lipo-aspiration and can be induced 

to differentiate into different cell types as needed in the 

laboratory. 

In this particular case involving massive 

bone and soft-tissue damage, however, lipoaspirated 

cells would not work. More than 

just cells were required to regenerate the 

fingers, since the soft tissue of the fingers 

and its blood supply was also missing. 

Abdominal fat has been found to have a 

well-defined structure with a rich network 

of blood vessels, lymphatics, stem cells 

and macrophages, among others. Dr. Saha 

combined the principles of plastic surgery 

and regenerative medicine to try a novel 

technique using flaps made up entirely of 

abdominal fat. Such a flap would provide 

stem cells, along with the required blood 

supply and the necessary infection-resistance 

to the fractured and crushed finger bones. 

MORE THAN JUST CELLS WERE 

REQUIRED TO REGENERATE THE 

FINGERS, SINCE THE SOFT TISSUE 

OF THE FINGERS AND ITS BLOOD 

SUPPLY WAS ALSO MISSING 

He made two incisions in the subcutaneous 

component of the abdomen, creating two 

tunnels through the abdominal fat in which 

he placed the thumb and the index finger. 

The patient was discharged a day after the 

surgery and spent time at home while his 

thumb and index finger regenerated within 

his abdomen. “Pulak was a very cooperative 

patient. Such placement is difficult to bear for 

a day, let alone for the 3 weeks that it took for 

complete regeneration”, remarked Dr. Saha. 

After 3 weeks, the fingers were separated from 

the abdomen. The fingers were covered with 

abdominal fatty tissue, which had developed 

new blood supply from the base of the fingers. 


Excess fat was trimmed away until a healthy 

layer of soft-tissue remained around the bones 

of the fingers, such that the thickness of the 

newly reconstructed fingers matched that of 

the other fingers. Dr. Saha covered these softtissues 

partially with abdominal skin taken as 

flaps. He performed one more surgery where 

he covered the remaining raw areas of the 

fingers with skin grafts harvested from the 

thigh. Reconstruction of the thumb and index 

finger was finally complete. During this entire 

period of treatment, Pulak was required to 

visit the hospital for a day only to perform his 

surgeries; and was on minimal medications 

including antibiotics and pain killers, that too 

for a limited time. Within 6 months from his 

injury, Pulak regained complete movement and 

control of all fingers of his working right hand, 

and easily performed all necessary hand and 

finger movements. Outside of work, Pulak is 

passionate about playing carrom. “I am even 

able to play and win carrom tournaments 

again, besides performing all my routine work,” 

exclaims an elated Pulak. 

The regenerative procedure faced several 

stiff challenges. Finger bones were fractured, 

crushed and lost at places. Ensuring coverage 

and survival of the finger bones without 

bone death or new infection was an uphill 

task. Pulak’s crushed soft tissues had been 

found to be infected with multi-drug resistant 

Klebsiella during admission. Ensuring adequate 

control and limiting the read of infection was 

also a difficult challenge. Abdominal fat, with 

its inherent structure, vascularity, stem cell 

potential and infection-fighting capability, can 

do wonders. This case is a perfect example 

of how the “abdominal fat pad flap” improves 

vascularity, protects from infections, and allows 

for regeneration of lost tissue. Dr. Saha has 

now achieved successful regeneration of finger 

tissue in six patients. He credits his success to 

his patients, saying that “the patient is the real 

hero as he must be willing to spend 3 weeks 

with his fingers inserted in his abdomen, and 

then perform physiotherapy religiously to gain 

adequate hand function”. Dr. Saha is excited 

with the success of this technique and hopes 

that more and more plastic surgeons will get 

involved in successfully saving fingers instead 

of amputating them. 



case reports 

FIGHTING OFF SWINE FLU 

Swine flu can be one of the most severe acute respiratory distress syndromes 

Elbualy Mohamed Ali, a Kenyan national, 

was visiting New Delhi to support a 

close relative who was undergoing 

treatment for a cancerous condition. Much 

to his dismay, during his stay as a caregiver, 

Ali quite suddenly developed high fever, 

severe breathlessness and persistent cough. 

A concerned Kenyan acquaintance of Ali 

referred him to Dr Sudha Kansal, a senior 

consultant in the Department of Respiratory 

Medicine, Critical Care and Sleep Medicine 

at the Indraprastha Apollo Hospital in New 

Delhi. 

During preliminary examination, Dr 

Kansal thought that Ali’s condition was due 

PRIMARY INVESTIGATIVE 

CHEST X-RAY INDICATED 

BILATERAL CHEST OPACITIES 

AND CONFIRMED A CHEST 

INFECTION 

to community-acquired pneumonia with 

respiratory failure and suspected obstructive 

sleep apnoea. In addition, Ali was also a 

known hypertensive and a type II diabetic. 

Primary investigative chest X-ray indicated 

bilateral chest opacities and confirmed a 

chest infection. To further determine the 

causative agent, blood culture, sputum 

culture, complete blood counts and kidney 

and liver function tests were carried out. 

Simultaneously, Ali was placed on a noninvasive 

ventilator to facilitate his breathing 

and started on injection azithromycin and 

ceftriaxone. 

Though a diagnosis of communityacquired 

pneumonia was relatively apparent 

because of the sudden onset of fever and 

quickly deteriorating respiratory symptoms, 

atypical pneumonia, possibly due to a viral 


or mycoplasma etiology was also considered. Much 

to everybody’s surprise, the throat swab RT-PCR turned 

out to be positive for swine flu. This diagnosis required 

immediate action. Within 18 hours of being admitted, Ali 

was started on the anti-viral tablet, oseltamivir, a well-known 

antiviral agent used to treat influenza type A virus, including 

swine flu. 

In spite of the prompt diagnosis and quick treatment, 

Ali’s condition started deteriorating and his oxygenation 

level was not improving with the noninvasive ventilator. 

Since these were concerning signs, he was intubated and 

subsequently moved to prone ventilation support due to 

severe hypoxia. However, this was not effective either and 

his blood oxygenation levels remained low. His condition 

continued to worsen, and a decision was taken to move 

him back to a supine position, and Veno-venous 

Extracorporeal Membrane Oxygenation (ECMO) support 

was initiated. As the name suggests, ECMO is an 

extracorporeal technique that allows the exchange of 

blood gases to occur outside the body through a specially 

designed equipment. It is used in children and adults with 

cardiac and respiratory failure when blood carbon dioxide 

levels need to be reduced and blood oxygenation needs 

to be normalized after failing mechanical ventilation, while 

allowing the lungs to rest to recover from the injury caused 

due to infection, trauma etc. 

The ECMO support comes with its own set of challenges. 

For patients on ECMO, it is necessary that the blood 

flows at an appropriate rate for the exchange of gases to 

occur. Patients are put on anticoagulants such as heparin 

to prevent clotting of the circuit, which requires close 

monitoring of blood clotting time. Due to the use of 

heparin, there is always the impending danger of internal 

bleeding which can sometimes be fatal, especially if it 

occurs in the brain. It has been observed that about 20- 

30% of patients on ECMO may have internal bleeding due to 

heparin. 

While Ali’s activated clotting time was being closely 

monitored, he developed significant gastrointestinal 

bleeding. His heparin levels were therefore re-titrated and 

blood products were transfused to prevent further bleeding. 

As he also had multiple episodes of generalized seizures 

while on ECMO, Ali was immediately started on antiepileptic 

drugs. Seizures might have been precipitated by conditions 

such as metabolic encephalopathy as no focal deficit, 

suggesting a brain bleed, was noticed. A brain CT scan 

would have been ideal to determine bleeding in the brain; 

however, this could not be done as the patient could not 

be moved to CT scan department due to ongoing ECMO. Ali 

was kept on minimum sedation so that he could be closely 

monitored, and his neurological status could be continuously 

assessed. 

Ali’s condition slowly recovered after being on ECMO 

support for 8 days. He was then weaned off the ECMO over 

two days and maintained on ventilator 

support. However, by now, Ali had 

developed critical illness myo-neuropathy 

and was very weak. A tracheostomy was 

needed to assist his breathing and slowly 

the ventilator support was stopped after 

3 days. After this, he gradually recovered. 

Intensive chest physiotherapy and 

limb therapy were started. Wheelchair 

mobilisation was done. He had to undergo 

considerable physiotherapy to regain his 

strength before he could be discharged. 

It was a difficult journey for both the 

patient and the medical team, especially 

since Ali’s condition deteriorated so rapidly, 

with the ventilator being ineffectual and him 

developing multiple generalized seizures 

IT WAS A DIFFICULT JOURNEY 

FOR BOTH THE PATIENT AND 

THE MEDICAL TEAM, ESPECIALLY 

SINCE THE PATIENT’S CONDITION 

DETERIORATED SO RAPIDLY, 

WITH THE VENTILATOR BEING 

INEFFECTUAL 

and GI bleeding. However, Ali 

was one of the lucky severe swine flu 

infected patients who survived and 

eventually regained his strength to normalcy. 

Dr Kansal would like to specially thank Dr 

Rajesh Chawla, Dr Mukesh Goel, the entire 

ICU team, and the perfusionist for their 

tireless efforts in bringing Ali back to health. 

Dr Kansal mentions that in the past 

season, they had 20 swine flu patients 

who required ventilator support, 5 of who 

had to be given ECMO, and of these, only 2 

survived. She stresses that “swine flu can be 

one of the most severe ARDS, that must be 

diagnosed early on. If the patient does not 

start improving with mechanical ventilation, 

ECMO therapy should be considered”. While 

ECMO can be expensive, early treatment is 

imperative, although there is no guarantee 

that it will work for everyone. 



column 

the cellview 

Taking the lead 

India can play a major role in world TB space by developing 

supplementary technologies 

DR RAJANI KANTH 

VANGALA 

The author is medical 

scientist and former 

director of SGRF, 

Bangalore 

The very fact that the sequencing 

costs are coming down should make 

multidrug-resistant Mycobacterium 

tuberculosis (MDR-TB) more manageable. 

However, that is not the case. Development 

of novel technologies and a reduction 

in costs and infrastructure barriers are 

important to the reduction of disease burden 

and better management. It is high time 

that India embraces this fact and develops 

research capabilities in two very important 

aspects of tuberculosis diagnostics. The first 

tool is a biospecimen/sputum collection 

system, which will enable direct, wholegenome 

sequencing, and the second is 

building robust bioinformatics capabilities for 

improved data analysis. 

Historically, tuberculosis detection has 

relied heavily on microscopy as the first-line 

diagnosis, which often fails in the detection 

of drug-resistant genotypes of the bacterium. 

Traditional, culture-based diagnosis of TB 

typically takes several weeks, owing to the 

slow growth rate of M. tuberculosis. Some 

technical advances have resulted in liquid 

culture and an automated detection system 

called mycobacteria growth indicator tube 

(MGIT), which takes less than a fortnight 

(Pfyffer et al., 1997). India, with increasing 

infections of TB, can very much take the 

lead in supplementing these technologies 

by conducting large-scale, genome-wide 

studies, in collaboration with companies or 

research groups focusing on biospecimen 

collection systems. Some of the tools 

developed in this direction are SureSelelctXT 

target enrichment, MolYsis Basic5 kit 

(Molzym, Germany) and NucleoSpin Tissue- 

Kit (Machery-Nagel, Duren, Germany). 

Any NGS workflow will not be complete 

without sequence data analysis, which 

requires expertise in information technology 

and clinical-data analytical capabilities - 

both of which are already possessed by the 

Indian scientific community, both commercial 

and academic. In the past few years, there 

has been an explosion of bioinformatics 

platforms for both expert and non-expert 

analysis and the interpretation of MTB 

NGS data. The majority of existing tools 

provide cloud-based WGS pipeline to start 

processing from the raw sequence. There are 

two important data consortiums, namely 

ReseqTB and CRyPTIC, which have 

accumulated large datasets and maintain 

genomic and phenotypic data. New 

advancements have resulted in several 

WGS tools, of which Mykrobe predictor is 

currently compatible with both Illumina and 

Oxford Nanopore WGS data. However, there 

is still a large gap in improving data quality 

assessment (control parameters like base 

score, quality score etc), which are presently 

done by platforms like FastQC. There are 

additional steps needed, like trimming and 

combination of multiple sequencing files. 

Easy-to-use, web-based tools, like Galaxy 

Cloudman and Cloud Virtual Resources, 

can facilitate user better outcomes. There 

is also a need to work on providing more 

computational space for data storage and 

on developing a tailored analytical software 

collection for customization. Another 

important area where there is a large gap 

is NGS data reporting, including sequence 

variants (single nucleotide polymorphism – 

SNPs), deletions, insertions and structural 

variants. 

These opportunities are some of the 

important aspects that will need large-scale 

collaborations for improved clinical research. 

India can play a major role in emerging as a 

leader in managing TB, not just here, but for 

the world at large. 


orthopaedics 

SKELETAL TUBERCULOSIS 

THE CHALLENGES 

Occurrence of osteoarticular tuberculosis recorded a rising trend among 

extrapulmonary TB world over 

DR VINOD KUMAR B P 

Mycobacterium tuberculosis is 

an organism that causes multisystemic 

involvement. Although 

pulmonary tuberculosis is the major 

manifestation of the disease, multifocal 

and extra pulmonary tuberculosis has 

gained medical attention since the 

emergence of HIV. In the late 1980s, 

the world was on its way to control 

tuberculosis. However, an increase in 

the incidence of diabetes mellitus, HIV 

etc. led to a comeback of tuberculosis. 

The world experienced a rising trend 

in the occurrence of extra-pulmonary 

tuberculosis crossing all socioeconomic 

barriers. Lymphadenopathy 

and tuberculosis of the spine account 

for the lion’s share of extra pulmonary 

tuberculosis. Then comes tuberculosis 

of the hip, the knee and the foot, in 

that order. In the foot, the decreasing 

order of occurrence are calcaneum, 

talus, 1st metatarsal and naviculum. 

The evolution of MDR and XDR TB 

have led to further challenges in the 

management of tuberculosis. XDR –TB 

is a rare type of multi drug resistant 

TB that is resistant to isoniazid and 

rifampicin, plus fluoroquinolones and 

at least one of three injectable second 

line drugs such as amikacin, kanamycin 

or capreomycin. 

X- ray misses early lesions, and 

any obvious bony destruction may not 

be apparent for up to 3 months from 

the time of occurrence of the disease. 

The advantage of X- ray is that it can 

be taken in vertical as well as a loadbearing 

position, as against MRI. Even 

though MRI is the gold standard in the 

diagnosis, its over-sensitivity is an issue. 

However, it is quite efficient in early 

diagnosis, assessing the progression 

and finding out the skip-lesions. 

CT scan is the choice in occipitocervical 

and sacroiliac TB lesions 

and in defining the extent of bony 

destruction. 


Diagnosing extra-pulmonary TB 

Tuberculosis is the ninth leading cause 

of death as far as the global burden 

of diseases is concerned. In 2016, an 

estimated 1.3 million TB deaths were 

reported among HIV-negative people 

(1.7 million in 2000) and an additional 

374,000 deaths were seen among 

HIV-positive people. (Global incidence 

– 10,400,000, Indian incidence – 

2,790,000, Indian Deaths - 435,000.) 

The revised national tuberculosis control 

programme suggests a daily regime, 

instead of the DOTS regime. 

If you suspect extra pulmonary 

tuberculosis in a patient and if the 

disease tissue is available, it is advisable 

to do a CBNAAT (Cartridge Based 

Nucleic Acid Amplification Test). CBNAAT 

is a polymerase chain reaction which 

also detects rifampicin resistance as it 

targets an rpoB gene of mycobacterium. 

Another test, MGIT (Micobacteria Growth 

Indicator Tube) is also preferred. It is a 

test to isolate mycobacterium from all 

types of clinical specimens, pulmonary 

as well as extra pulmonary, except 

those from blood and urine. After the 

processed specimen is inoculated, the 

MGIT tube is monitored until positive 

or till the end of the testing protocol. 

If MTB is detected, we may start anti- 

TB drugs after evaluation for drug 

resistance and liver and kidney function 

tests. 

Spinal tuberculosis 

The other major developments are in 

the management of spinal tuberculosis. 

• A course of 6 to 12 months of ATT 

instead of the old practice of 18-24 

months. 

• Hong Kong operation, the “Middle 

Path Regime’’ of a great Indian 

orthopaedic surgeon, Prof. Tuli, and 

the newer “Millennium Doctrine’’ based 

on the cardinal principles for the 

management of spinal tuberculosis. 

• Nonsurgical treatments that yield 

good results as elective surgeries in 

spinal instability, para-spinal abscess 

CHART TO DIAGNOSE 

EXTRA PULMONARY TUBERCULOSIS 

CBNAAT 

Tissue + 

MTB 

CULTURE OF MTB IN 

CLINICAL SPECIMENS USING 

TB MGIT, THE CURRENT 

GOLD STANDARD, IS MORE 

SENSITIVE THAN SMEAR 

BIOPSY 

and spinal cord compression in place of 

surgical intervention. 

• Posterior surgical approaches which 

are less morbid to the patients and 

more surgeon-friendly gaining more 

acceptance than anterior approaches 

that better anterior reconstruction and 

neurological decompression. 

Culture of MTB in clinical specimens 

using TB MGIT, the current gold 

standard, is more sensitive than smear 

biopsy. The drawback is a longer 

incubation period of 10-14 days. If 

it turns out to be MDR TB, it would 

have caused more destruction by the 

time the results are in. Newer, ultrafast 

modalities of GeneXpert test and 

Line Probe Assay have revolutionized 

Extra Pulmonary Tuberculosis 

MGIT 

No MTB 

High Clinical Suspicion 

Other Tests 

ATT MTB+ D/D 

the management of tuberculosis. The 

Xpert MTB RIF Assay detects DNA 

of mycobacterium and rifampicin 

resistance in 2 hours. LPA also detects 

resistance to isoniazid, quinolones and 

second-line injectables, thus detecting 

MDR as wells as XDR TB in 48 hrs. 

These tests are to be done on biopsy 

specimens in addition to TB MGIT 

culture and histopathology. 

The emergence of MDR and atypical 

lesions made biopsy and culture 

mandatory procedures. The biopsy 

specimen should be from granulation 

tissue rather than from an abscess 

to make a prompt diagnosis. Biopsy 

with a 11 G needle instead of fine 

needle aspiration cytology is advised 

in the present practice to diagnose 

tuberculosis. 

Here, I am describing a case 

which was really challenging for me to 

manage: An 80-year-old grandma came 

with complaints of inability to walk and 

back pain in a devastated condition 

at our OP clinic. Clinically, she had loss 

of sleep and appetite, chills and fever 

due to UTI, a neurogenic bladder and 

extensor plantar response. She was 

posted for surgical decompression and 


instrumentation at another hospital for 

‘? Tuberculosis/Tumour spine’. Clinical 

examination, blood investigation, 

Mantoux test, X-ray evaluation, 

ultrasound evaluation and MRI scan 

had revealed left renal calculus, 

cystitis / pyelonephritis, destruction 

at D6/7, end plate destruction and 

normal pedicles. It was clinically and 

radiologically diagnosed as tuberculosis 

of the spine. 

The grandma and her bystanders 

were not willing for any type of surgery, 

even a CT guided biopsy. After getting 

well informed consent, ATT was started. 

A therapeutic trial of ATT based on 

clinical and radiological evidence is 

legitimate only in a population setting 

treating large numbers of tuberculosis 

cases under a national programme. 

After starting ATT (DOTS regime), she 

was mobilized in wheel chair with the 

help of spinal brace and rehabilitation 

within two weeks of starting the 

treatment. 

Another challenge is in getting 

to the end point of treatment. Back 

pain can persist due to mechanical 

causes as well as deformity even after 

a healed status. MRI may show soft 

tissue image and sterile abscess after 

complete eradication of infection. Also, 

a late onset paraplegia (a delayed 

presentation of old healed TB spine) 

with progressive neurology and a highgrade 

kyphosis also poses challenges to 

the orthopedic surgeon. 

Follow up Assessment 

Hematological findings on 11/4/2016 

showed ESR-60; Total Count -10300 

polymorphs- 63 lymphocytes- 30 

eosinophil- 7, HB-9.5, LFT/RFT-normal, 

GRBS-117, urine - severe UTI, uric acid- 

6.5, Mantoux test – positive 14 mms. 

X-ray showed: D6/7, end plate disease 

with pedicle intact. 

Catheterized since there was 

neurogenic bladder and UTI. 

21.7.2016: Hemetologically - 

HB=10.4, ESR-20 

23.9.2016: HB- 11.8 

26/5/2016: Catheter removal done. 

Her urination became normal. 

X-ray AP and lateral view: TB spine showing end plate destruction at D6/7 

MRI T1 & T2 weighted images: End plate destruction with soft tissue swelling. 

After 9 months of ATT: The follow up x-ray showed definite evidence of healing. 

Clinically, she walks well, no physical illness, increase in appetite and weight gain. 

She lives with good physical status in accordance with her age. 

X- Ray of thoracic spine AP and lateral view: 6 months follow up 

2 years’ follow up: Patient has no fresh complaint. 


TUBERCULOSIS OF HIP 

A 38-year-old gentle man 

presented with severe hip 

pain, true shortening, all 

movements painfully restricted. 

ESR was at 70, Mantoux test 

positive, CBNAAT test positive, 

Histopathology also positive. He 

was on bed rest with traction for 

2 months and on ATT. Now he is 

undergoing ATT. 

X-ray pelvis showing both hips 

with destruction of right hip 

(head of femur and acetabulum). 

TUBERCULOSIS OF THE KNEE 

32-year-old gentleman, welder by 

profession, presented with right knee 

pain since 3 yrs. According to his words 

the complaint started after a hit to his 

knee with an iron bar while working. 

In the last one-year period he could 

do work only for 4 months (the other 

8 months were spent on treatment 

from various other health facilities). His 

personal history revealed that he has 

no diabetes, jaundice, hypertension, 

recurrent fever or HIV. The complaint 

stated as a sudden onset of pain 3 years 

back following hit to an iron rod, with 

a swelling disproportionate to the pain. 

Now presented with swelling around 

right knee. O/E: Patient walks with 

antalgic gait, horse shoe swelling around 

knee with increased temperature, 

patellar tap was present along with 

synovial thickening. Fixed flexion 

deformity of 20 degrees then flexion 

possible up to 90 degrees but with pain. 

Clinically a diagnosis of chronic synovitis 

was made. The case is interesting for its 

3-year duration, and the MRI report of 

pigmented villo-nodular synovitis. 

THE CASE IS INTERESTING 

FOR ITS 3-YEAR DURATION, 

AND THE MRI REPORT OF 

PIGMENTED VILLO-NODULAR 

SYNOVITIS 

Investigations 

HB: 11.7, TC-4200, P-69%, L-23%, E-6%, 

M-2%. ESR-80. RBS: 143mgs, HBS 

Ag, HCV, HIV – negative X-ray showed 

osteoporosis. 

MRI report indicated synovial 

thickening, 2 punched out lesions at 

Biopsy result of synovectomy specimen. 

the femoral condyles, pigmented villo 

nodular synovitis to be considered. After 

proper preoperative checkup partial 

synovectomy and biopsy done under 

spinal anesthesia. 

Medial para- patellar incision, 

synovium was thickened with increase in 

vascularity. Synovial fluid sent for culture 

and sensitivity - the result after 72 hours 

was sterile. Drain removed after 24 

hours; collection was 50 ml only. Wound 

inspection done on 3rd day which was 

clean. Patient was discharged on 3rd 

day. Suture removal was done after 14 

days. Quadriceps exercises started from 

second day onwards. The biopsy report 

came after 2 weeks and it was a typical 


tuberculous granuloma. Liver function test 

and renal function test was normal. He was 

registered in government DOTS regime. 

By 2 months, the pain and swelling 

disappeared. By 6 months, ESR become 

25. Completed chemotherapy by 9 months. 

Rejoined in his company at Ernakulam after 7 

months post op. 

2yrs follow up 

Patient has no complaints. On examination 

terminal 10 degrees of flexion limited. 

Otherwise healthy. 

Differential diagnosis 

1. Tuberculosis. 2. Pigmented villo-nodular 

synovitis 3. Rheumatoid arthritis 4. Seronegative 

arthropathy. 

Tuberculosis of the knee causes triple 

dislocation due to hamstring spasm and 

contracture. These are flexion, posterior 

dislocation, lateral rotation and adduction of 

tibia. In advance cases in adults, arthrodesis 

is done by using Charnley’s compression 

arthrodesis. Other causes of triple deformity 

are polio and rheumatoid arthritis. DOTS 

treatment was for 6 months with 2 months 

of four-drug regime and 4 months two-drug 

regime. At my request, the medical officer 

in charge of DOTs programme extended 

treatment up to 9 months 

X-ray AP and lateral view of right knee showing 

peri articular osteoporosis 

The author is additional 

professor in Orthopedics, 

Govt. Medical College, 

Kollam, India. 

TUBERCULOSIS OF CALCANEUM 

Biopsy result of curetted specimen from calcaneus 

Radiological and clinical photograph of a healed lesion tuberculosis of calcaneum 

at 6 months 

Tuberculosis affecting this bone 

is a rare occurrence even though 

infections are not uncommon 

in calcaneum, especially in 

compound injuries. Co-morbid 

conditions like diabetes, arterial 

diseases, smoking, alcoholism 

etc. are other contributing 

factors. 

A 35-year-old gentleman 

presented with a non-healing 

ulcer at the lateral aspect of 

foot. Two years back, he had 

a swelling at the same region; 

for which he underwent an 

incision and drainage (I &D) in 

a local hospital. At that time the 

ulcer was healed in 2 weeks. 

The 2nd recurrence occurred 

after 8 months, but at that time 

there was no ulcer, only pain, 

which was cured by NSAIDs 

and footwear modification 

(micronized rubber shoes). 

Now he presented with a nonhealing 

ulcer at the lateral aspect 

of foot at the same region of 

I&D. It started 1 month back 

with a swelling at the lateral 

aspect of the foot. An I&D was 

done at a local hospital for the 

same. Culture and sensitivity 

of pus yielded heavy growth of 

coagulase positive staphylococci 

sensitive to cloxacillin and 

gentamicin. X-ray showed a 

lytic lesion at the antero-lateral 

portion of the calcaneum. 

With the help of C-Arm, 

we identified the lytic lesion, 

thorough debridement was 

done, and the specimen was 

sent for histopathology. The lytic 

space was filled with vancomycin 

impregnated purified Ca SO4 

(Stimulan). Suture removal was 

done at 10 days post operatively, 

then a below-knee plaster cast 

was given. 

After 6 weeks it was 

converted to a walking cast for 

six more weeks and then he was 

allowed full weight bearing. 

The case was managed with 

the DOTS regime protocol. Follow 

up X-ray and clinical picture at 3 

months shows well healed scar 

and consolidating lesion. 



esearch snippets 

Fibrinogen induces spine 

elimination in Alzheimer’s 

Mario Merlini et al unveiled 

the role of the blood-clotting 

protein fibrinogen in blood in 

causing the characteristic cognitive 

decline of Alzheimer’s disease. 

Cerebrovascular alterations are a 

key feature of Alzheimer’s disease 

(AD) pathogenesis. The researchers 

used state-of-the-art imaging 

technology to produce the first 

three-dimensional volume images 

of Alzheimer’s disease. The images 

of the brains of patients with 

Alzheimer’s disease and mouse 

models were studied. The bloodprotein 

fibrinogen was seen to leak 

from the blood into the brain, where 

it activated the brain’s immune 

cells triggering them to destroy 

neuronal synapses. Fibrinogen then 

induces spine elimination leading 

to cognitive deficits mediated by 

CD11b-CD18 microglia activation. 

Fibrinogen-induced spine elimination 

was prevented by inhibiting 

reactive oxygen species (ROS) 

generation or by genetic elimination 

of CD11b. In the mouse models, 

this genetic elimination showed 

to reduce neuroinflammation, 

synaptic deficits and cognitive 

decline. The research thus unveils 

that fibrinogen-induced spine 

elimination and cognitive decline 

via CD11b leads to cerebrovascular 

damage with immune-mediated 

neurodegeneration and may have 

important implications in AD and 

related conditions. 

Source: Neuron Feb 5,t 2019 DOI: https://doi. 

org/10.1016/j.neuron.2019.01.014 

Ovarian cyst surgery 

often unnecessary 

Wouter Froyman et al shows 

evidence promoting a watchful 

waiting approach towards non-cancerous 

ovarian cyst. The researchers performed 

a two-year study involving 1919 women 

from 10 different countries, including 

the UK, Belgium, Sweden and Italy, who 

were diagnosed with non-cancerous 

ovarian cysts. The average age of the 

women in the study was 48, and the 

average size of the cyst was 4cm. Out of 

the 1919 women in the trial, 20 percent 

had cysts that disappeared of their 

own accord, and 16 percent underwent 

surgery. Overall, in 80 percent of cases 

either the cyst resolved or did not need 

intervention. Only 12 women were 

subsequently diagnosed with ovarian 

cancer, making the risk of cancer 0.4 

percent. The rate of other complications, 

such as ovarian twisting or cyst rupture 

was 0.4 percent and 0.2 percent 

respectively. The researchers suggest 

that the risk of malignancy and acute 

complications is low if adnexal masses 

with benign ultrasound morphology are 

managed conservatively, invasive surgical 

procedures can be avoided. 

Source: The Lancet Oncology February 05, 2019 

https://doi.org/10.1016/S1470-2045(18)30837-4 

Oral delivery of insulin 

via ingestible capsule 

A 

bramson et al. developed an 

ingestible drug delivery vehicle that 

can be used for oral administration 

of insulin. The capsule is designed 

to be able to self-reorient from any 

starting position so as to attach to 

the gastric wall. This ingestible selforienting 

millimeter-scale applicator 

(SOMA) autonomously positions itself 

with the gastrointestinal tissue. Within 

the capsule, a needle is attached to a 

compressed spring that is held in place 

by a disk made of sugar which gets 

dissolved on reaching the stomach. 

It then deploys its needles fabricated 

from active pharmaceutical ingredients 

directly through the gastric mucosa while 

avoiding perforation and delivers the 

active pharmaceutical ingredient. The 

approach successfully provided active 

insulin delivery in pigs and rat models. 


The study demonstrates a less invasive 

method of drug delivery which can be 

used to deliver insulin and other protein 

drugs. 

Source: Science 08 Feb 2019: Vol. 363, Issue 

6427, pp. 611-615 DOI: 10.1126/science. 

aau2277 http://science.sciencemag.org/ 

content/363/6427/611 

Gut microbiome may 

alter symptoms of 

schizophrenia 

Peng Zheng et al have found that 

people with schizophrenia have 

a significant difference in their gut 

microbiomes compared to people 

without the disorder which may be 

linked to the altered neurologic function. 

The researchers collected stool samples 

from 53 schizophrenia patients who 

were taking medication, five samples 

from schizophrenia patients who were 

not taking medication and from 69 

people who did not have schizophrenia. 

Gene sequencing of the samples 

was done to isolate gut microbiome 

bacteria. They divided the bacteria they 

found into operational taxonomic units 

(OTUs). Out of 854 OTUs, they found 

56 that appeared only in schizophrenia 

patients and 64 that appeared only 

in the control group. They also noted 

that the gut microbiomes of the 

schizophrenia patients had overall lower 

diversity than the control group. The 

study also reported the presence of a 

smaller subset of bacteria that were 

clearly different between schizophrenia 

patients and those without the disorder. 

On introducing samples of the subset 

from the schizophrenia patients into 

the microbiomes of healthy mice, the 

mice displayed behaviour changes. The 

research reveals a plausible link between 

schizophrenia microbiome which may 

alter neurochemistry and neurologic 

function in ways that may be relevant to 

schizophrenia pathology. 

Source: Science Advances 06 Feb 2019: Vol. 5, no. 

2, eaau8317 DOI: 10.1126/sciadv.aau8317 http:// 

advances.sciencemag.org/content/5/2/eaau8317 

Binge-watching of 

TV shows raises 

colorectal cancer risk 

Long H Nguyen et al shows sedentary 

behavior as a contributory factor to 

the dramatic rise in colorectal cancer 

(CRC) among people under the age 

of 50. The study specifically looked at 

TV viewing time and increased risk of 

young-onset CRC, after adjusting for 

putative risk factors, including obesity 

and physical activity. The study subjected 

89,278 American women between 25 

and 42 years at the start of the study, 

in 1991. The research documented 118 

incident cases of young-onset CRC 

over 22 years of follow-up. The study 

found that in women with 7.1–14 hours 

of TV watching per week had a multivariable 

relative risk (RR) of 1.12, which 

further increased for greater than 14 

e-cigarette chemical 

flavourings may 

impair lung function 

Hae-Ryung Park et al found 

evidence suggesting the 

potentially harmful effect of 

two chemicals used to flavour 

e-cigarettes on human lungs. 

Diacetyl and 2,3-pentanedion, 

widely used to flavour electronic 

cigarettes, were found to impair 

the function of cilia in the human 

airway by inducing transcriptomic 

changes. Researchers identified that 

RNA-Sequencing of primary normal 

human bronchial epithelial (NHBE) 

cells showed a total of 163 and 568 

differentially expressed genes in 

cells that were exposed to diacetyl 

and 2,3-pentanedione, respectively. 

The cells were cultured at an airliquid 

interface (ALI) to mimic 

the in vivo airway characteristics. 

The expression of multiple genes 

involved in cilia biogenesis was 

also found to be significantly 

downregulated in reverse 

transcription polymerase chain 

reaction (RT-PCR) test of NHBE 

cells. These flavouring substances 

commonly used as food flavouring 

substances are not proven safe for 

inhalation apart from consumption. 

The study sheds new light on the 

likely adverse effect of e-cigarettes 

on the lungs. 

Source: Scientific Reports volume 9, Article 

number: 1400 (2019) https://www.nature. 

com/articles/s41598-018-37913-9 


hours per week. This association was 

observed among participants without 

a CRC family history and was more 

pronounced for rectal cancer. Overweight 

or obese participants were pronounced 

to be more susceptible. Researchers 

suggest further studies to be conducted 

to elucidate the underlying biological 

mechanism that may explain this 

phenomenon. 

Biomarkers open new gateways 

towards precision medicine for pain 

Niculescu et al open door towards 

precision medicine for pain, 

with the objective to determine 

the severity of a patient’s suffering. 

The study tracked hundreds of 

participants to identify biomarkers 

that can help determine the severity 

of a patient’s pain. The researchers 

were able to find a handful of genes 

that correlated to pain state and of 

future emergency department (ED) 

visits for pain. The genes which the 

scientists were able to correlate with 

pain were MFAP3, GNG7, CNTN1, 

LY9, CCDC144B, and GBP1. Using 

bioinformatic drug repurposing 

analyses, they were able to find 

novel drug compounds that would 

selectively target these genes and 

could be used to not only measure 

pain level but also inform the drug 

discovery process to use these 

genetic biomarkers to create more 

personalized treatments for pain. 

MFAP3, which had no prior evidence 

in the literature for involvement 

in pain, showed the most robust 

empirical evidence acting as a strong 

predictor for pain in the independent 

cohorts. The breakthrough research 

could help overcome the massive 

negative impact of untreated pain 

on quality of life, helping determine 

the appropriateness of treatment, 

and the severe addiction gateway 

potential of existing opioid-based 

pain medications. 

Source:MolecularPsychiatry(2019) https:// 

www.nature.com/articles/s41380-018-0345- 

5#Sec23 

Source: JNCI Cancer Spectrum, Volume 2, Issue 4, 

1 November 2018, pky073,https://doi.org/10.1093/ 

jncics/pky073 

Transplanted β cells 

rapidly restore glucose 

tolerance in mice 

Leonardo Velazco-Cruz et al 

demonstrated a breakthrough study 

by converting human pluripotent stem 

cells (hPSCs) into stem cell-derived 

β cells (SC-β cells) as a promising 

alternative source for diabetes cell 

replacement therapy. The researchers 

developed functioning healthy SC-β 

cells in vitro using an enriched serumfree 

media. On transplanting them into 

mice, the cells began to produce insulin 

and respond to blood sugar within 

days. Researchers introduced a new 

differentiation strategy which focused 

on modulating transforming growth 

factor β (TGF-β) signaling. This helps 

in controlling cellular cluster size, and 

express β cell markers and undergo GSIS 

(glucose stimulated-insulin secretion). 

The capacity of these cells to undergo 

GSIS with dynamic insulin release makes 

them a promising cell source for diabetes 

cellular therapy. This study provides 

insights into the role of TGF-β signaling 

in functional maturation where TGF-β 

inhibition has been shown to promote 

the replication of the cells. This helped 

protect against stress-induced loss of the 

phenotype and reduced apoptosis in a 

mouse model, which give hope 

for developing a potential cure for 

treating type 1 diabetes in the near 

future. 

Source: Stem Cell Reports | VOLUME 12, ISSUE 

2, P351-365, FEBRUARY 12, 2019 DOI: 10.1016/j. 

stemcr.2018.12.012 

—Compiled by Divya Choyikutty 


hospital news 

Apollo Hospitals honoured with 

postal stamp 

Governor of Tamil Nadu released a postal 

stamp commemorating the pioneering 

efforts of the chairman of Apollo Hospitals, Dr 

Pratap C Reddy’s in preventive healthcare in 

India, recently. 

Since its establishment in 1983, Apollo 

Hospitals pioneered innumerable initiatives in 

healthcare management. 

“Dr Reddy and Apollo are synonymous 

with healthcare excellence in the world. 

They excel in end to end healthcare of 

consumers from 140 plus countries and have 

many firsts including the recent launch of 

South East Asia’s first ever Proton Cancer Care 

Therapy centre. Preventive Care was 

first pioneered in India by Dr Pratap Reddy 

and today I am happy to commend his 

dedication to disease prevention through this 

special stamp,” Banwarilal Purohit, 

the governor of Tamil Nadu, said on the 

occasion. 

Apollo’s Preventive Healthcare initiatives 

have been working tirelessly for almost four 

decades to ensure that Dr Pratap Reddy’s 

dream is realised, said Preetha Reddy, Vice 

Chairperson of Apollo Hospitals in a statement. 

“We take pride in having touched 20 million 

lives through our preventive healthcare 

endeavours. It is a very significant moment for 

the entire Apollo family as a special preventive 

healthcare commemorative stamp is being 

released, in recognition of our efforts,” she 

said. 

New hospital in Lucknow 

President Ram Nath Kovind inaugurated 

the Apollomedics Super Specialty hospital 

in Lucknow. It is the 72nd hospital of Apollo 

Hospitals Enterprise, Asia’s largest hospital 

chain, which has a total bed capacity of 

10000 across India. The group also runs 

3500 pharmacies, over 90 primary care and 

diagnostics clinics, and more than 160 Apollo 

Munich Insurance branches. 

Dr S Natarajan 

elected 

president of 

AIOS 

S Natarajan, chairman 

Dr and managing director, 

Aditya Jyot Eye Hospital, 

Mumbai has been elected 

as president of All India 

Ophthalmological Society. 

Established in the year 

1930, AIOS has continuously 

grown over the years and 

currently has over 20,000 

life members. The key 

objectives of the society are 

cultivation and promotion 

of the study and practice of 

ophthalmic sciences, research 

and manpower development 

with a view to render service 

to the community and to 

promote social contacts 

among ophthalmologists of 

the country. 

Max sells controlling stake in Max Bupa to True North 

The Board of Max India on Tuesday 

approved the sale of its 51% stake in 

Max Bupa Health Insurance Company 

(Max Bupa), to the leading Private Equity 

firm True North. The all cash transaction 

values Max Bupa at an enterprise value of 

Rs 1,001 crore and is subject to requisite 

regulatory approvals. Bupa, the existing 

joint venture partner in Max Bupa, remains 

committed to the joint venture and will 

continue to play an active role in the 

company as before through its Board 

positions and knowledge exchange 

initiatives. 

At the conclusion of the transaction, 

True North will nominate 

directors on Max Bupa’s 

Board, while Max India’s 

nominated directors 

will step down. The use 

of the Max brand will 

be phased out over a 

period of two years and 

replaced with a suitable 

name. The Bupa brand 

name will continue as 

before. 

True North 

Analjit Singh 

Founder & 

Chairman 

Max Group 

(formerly known as India Value Fund 

Advisors) is an active investor in Indian 

assets. It has built deep knowledge and 

skills in the Indian market, investing in 

more than 40 Indian businesses over the 

last 19 years through its 6 investment 

funds with a combined corpus of over US$ 

2.8 billion. Over the years, True North has 

made productive investments across the 

financial services and healthcare sector, to 

the tune of Rs 5,700 crore. 

The transaction will lead to a cash 

inflow of Rs 511 crore for Max India. The 

company intends to utilize the proceeds to 

invest in both existing and new business 

opportunities which are currently under 

evaluation. 


scientific report 

TARGETING GENETIC BASIS OF 

CRC WITH NOVEL THERAPIES 

Identifying high-risk patients carrying known disease through genetic testing 

should be part of colorectal cancer screening 

CORAL MIRIAM MAGDALENE AND 

AMIT CHAUDHURI 

Colorectal cancer (CRC) is the third 

most common cancer with an 

estimated global incidence of 

1.8 million. In India, the incidence and 

prevalence of the disease is 27,605 and 

53,700 respectively with a mortality 

of 19,548 (https://www.uicc.org/newglobal-cancer-data-globocan-2018). 

Although the incidence rates of CRCs 

are lower in India compared to the 

Western countries, the mortality rates 

are higher due to their late-stage 

presentation and lack of effective 

therapies. The risk factors for developing 

CRC, include age, gender, race, family 

history, inheritance, and inflammatory 

bowel disease. Lifestyle factors which 

attribute to this burden include physical 

inactivity, obesity, a diet low in fruits 

and fibres, smoking and alcohol 

consumption. More than 90% of the 

CRCs occur in people who are 50 

years older in Western countries, but in 

India, there is a mounting incidence of 

younger people presenting with latestage 

disease. 

In general, about 75% of the CRCs 

are sporadic while 25% are familial. 

Among the familial, the vast majority 

is familial adenomatous polyposis 

(FAP), an autosomal dominant disease 

caused by the loss-of-function (LOF) 

mutation in the adenomatous polyposis 

coli (APC) gene on chromosome 5q21. 

A less prevalent familial CRC is Lynch 

syndrome (LS), an autosomal dominant 

disease also known as Hereditary nonpolyposis 

CRC caused by mutations in 

one of the DNA mismatch repair (MMR) 

genes, such as MSH2, MSH6, MLH1, and 

PMS2. In India, the prevalence of familial 

colorectal cancer is 10-15% (Maharaj, 

Shukla et al. 2014). This could be a gross 

underestimation because of lack of 

systematic genetic screening, cost of the 

test and strong social stigma. In a recent 

study, we identified several FAP and 

Lynch syndrome families who would 

normally not undergo genetic testing 

FAP, AN AUTOSOMAL 

DOMINANT DISEASE CAUSED 

BY THE LOSS-OF-FUNCTION 

(LOF) MUTATION IN THE 

ADENOMATOUS POLYPOSIS 

COLI (APC) GENE ON 

CHROMOSOME 5Q21 

but for our research initiative (Majumder, 

Shah et al. 2018, Majumder, Shah et al. 

2018). 

The common symptoms of CRC are 

altered bowel habits, rectal bleeding, 

constipation, diarrhea, unexplained 

weight loss, etc. with rectal bleeding 

being the most important symptom 

(Loh, Majid et al. 2013). Colorectal 

cancer is treated based on the 

presentation stage of the disease and 

the age of the patient. Surgery is still 

the mainstay of treatment for a locally 

advanced tumourr that is resectable. 

Adjuvant chemotherapy or radiation 

therapy is decided depending on 

the stage and clearance of resection 

margins. In the case of nodes positive 

stage III and IV cancers, where surgery 

is not feasible, chemotherapy is used as 

the first line of treatment. Improvements 

in surgery and combination 

chemotherapies in the last 20 years 

have doubled the 5-year survival of 

CRCs, yet the global mortality remains 

at ~50%. As discussed below, colorectal 

cancer serves as a poster-child of our 

understanding of the molecular basis of 

carcinogenesis, which is applicable to all 

cancers in general. 

Accumulation of mutations 

Bert Vogelstein and his team from 

John Hopkins University studied 

familial colorectal cancer in the 80s 

and 90s to reveal for the first time 

the mechanism of cancer progression 

occurring by stepwise accumulation of 

mutations in oncogenes and tumour 

suppressor genes. Oncogenes, such 

as RAS, BRAF, PI3K endow cancer 

cells to divide incessantly and survive 

indefinitely creating a dependence 

of cancer cells to their presence, 

referred to as genetic addiction. 

Mutations resulting in the activation 

of oncogenes (gain-of-function) are 

therefore a hallmark of cancer. By 

contrast, tumour suppressor genes, 

such as APC (adenomatous polyposis 

coli), TP53, TGF-β (transforming growth 

factor-β) prevent cells from growing 

aberrantly and typically lose their 

function (loss-of-function), which is 

the second hallmark. Vogelstein’s 

work demonstrated how mutations 


BENIGN TO 

MALIGNANT 

Sequential mutations in 

KRAS, TGF-β and PT53 

transform pre-malignant 

colonic epithelial cells to 

become cancerous 

Shedded 

dead cells 

Low 

Villus 

Colon cancer progression 

Colonic 

crypts 

Normal 

epithelium 

Dysplastic 

epithelium 

Early 

adenoma 

Late 

adenoma 

Carcinoma & 

Metastasis 

High 

Paneth 

cells 

Wnt 

Signaling 

APC 

KRAS TGF-β PT53 

Normal Colon Benign pre-malignant Malignant 

in oncogenes and tumour suppressor 

genes occur in a sequential pattern to 

transform normal colon epithelial cells 

into colorectal cancer (see figure). The 

mechanistic basis for the two-hit model 

of cancer initiation gained scientific 

acceptance through these studies, in 

which the transformation of healthy 

epithelial cells requires at least two 

hits, one that takes out the function 

of a tumour suppressor gene, and 

the other that activates oncogenes. 

Over 80% of sporadic CRC is caused 

by the inactivation of APC resulting in 

colon cancer cell survival. The second 

hit is the activation of RAS oncogene 

that results in cellular transformation 

and formation of adenoma. Additional 

mutations in TP53 pushes the cells to 

become an adenocarcinoma. 

The genetic foundation emerging out of 

these studies has a profound impact on 

cancer treatment and the development 

of novel therapies. Successful targeted 

therapies inhibiting the function of 

overexpressed genes, such as HER2 

in breast cancer, or EGFR in colorectal 

cancer or gain of function mutations in 

EGFR (epidermal growth factor receptor) 

in non-small-cell lung cancer, or BRAF 


FAMILY PEDIGREE OF LYNCH SYNDROME 

The proband (II.2) indicated by a black arrow, was diagnosed with a relapsed colorectal cancer. 

The heterozygous germline MLH1 mutation was found in the proband and his brother (II.6) 

who was also diagnosed with colorectal cancer and had undergone surgery. All other family 

members lacked the MLH1 germline mutation. 

MLH1 gene mutation 

in melanoma are grounded on the 

concept of driver mutations and genetic 

addiction. Metastatic CRCs are treated 

with monoclonal antibodies that starve 

the tumour of nutrients and oxygen 

by preventing the growth of blood 

vessels, such as Avastin or Zaltrap 

that bind VEGF (vascular endothelial 

growth factor), or Cyramza, which 

binds VEGF receptor-2 (VEGFR2). A 

subset of colorectal cancer patients 

overexpressing EGFR protein is treated 

with monoclonal antibodies Erbitux 

or Vectibix that block EGFR signalling. 

In 2018, a novel inhibitor targeting 

neurotrophin receptor (NTRK) fusions, 

Vitrakvi was approved for all solid 

tumours that express these fusions 

including CRC. Overall, NTRK fusions 

are rare in cancers; however, the 

presence of this fusion in colon 

cancer can be treated. The use of 

EGFR monoclonal antibodies Erbitux 

or Vectibix to treat colon cancer in 

India is limited, however, published 

reports indicate superior overall 

survival of Vectibix compared to 

Erbitux in combination with Folfox in 

metastatic colorectal cancer with wildtype 

KRAS (Pathak, S et al. 2018). The 

anti-angiogenic therapies or targeted 

therapies have extended limited 

benefit and new therapies are needed 

to treat this deadly disease. 

diagnosed with colorectal cancer. 

A slash through the shape indicates a deceased member. Roman numerals indicate generations. 

Cancer immunotherapy has 

produced long-term benefit and has 

given a new lease of life to 15-20% of 

patients with terminal disease, who had 

exhausted all therapies. The therapy 

boosts patients’ immune system by 

targeting a group of receptors called 

checkpoint control proteins. The three 

checkpoint control proteins currently 

targeted by monoclonal antibodies 

are cytotoxic T-lymphocyte associated 

protein-4, CTLA-4 (targeted by Yervoy), 

programmed cell-death protein-1, PD-1 

(targeted by Opdivo and Keytruda) 

and programmed cell-death proteinligand-1, 

PD-L1 (targeted by Tecentriq 

and Imfinzi). In colorectal cancer, Opdivo 

and Keytruda have been approved 

to treat 10-15% of tumours with 

microsatellite instability (MSI) phenotype. 

These tumours carry a high number of 

mutations and show an overall response 

of over 70% to checkpoint inhibition. 

The correlation between high tumour 

mutation burden (TMB) first reported 

in colon cancer has been reproduced 

in other cancer types qualifying this 

feature as a critical biomarker of patient 

selection (Le, Durham et al. 2017). In 

India, the incidence of MSI ranges from 

5-10% (Maharaj, Shukla et al. 2014). 

However, the prohibitively high cost of 

checkpoint inhibitor antibodies will have 

limited utility in India. 

Checkpoint inhibitors 

Use of high TMB as a biomarker of 

patient selection has left over 75% 

of colorectal cancers and 70% of all 

cancers untreatable with checkpoint 

blockade therapy. To expand the utility 

of these powerful therapies into other 

cancers, the field is actively pursuing 

discovery of novel biomarkers for 

patient selection, combining checkpoint 

inhibitors with other therapies to make 

tumours more immunogenic and 

sensitizing them to immune-mediated 

attack. There is also a concerted effort 

from the industry to develop vaccines 

against tumour-specific neoantigens 

to induce an immunological response. 

Limited results from ongoing clinical 

trials in melanoma and ovarian cancer 

suggest that vaccines can skew the 

immunological balance towards a more 

inflammatory phenotype permissive to 

T cell-mediated killing of tumour cells 

(Ott, Hu et al. 2017, Tanyi, Bobisse et al. 

2018). 

We have shown in two recent 

studies that in familial colorectal 

cancer - familial adenomatous coli 

(FAP) and Lynch syndrome, cancerspecific 

mutations are immunogenic 

and an interventional approach with 

vaccines may be feasible (Majumder, 

Shah et al. 2018, Majumder, Shah et al. 

2018). The progression of colon cancer 

through an intermediate polyp-stage is 

an ideal intervention point for vaccine 

therapy since the immune system is not 

tolerized to the neoantigens that appear 

during polyp development. Further 

research is required to identify whether 

neoantigens in polyps are private, or 

shared between patients, whether 

multiple polyps in the same individual 

have a similar mutational profile, and 

what fraction of the mutations are 

immunogenic. In addition, clinical use 

of vaccines will rely on good delivery 

mechanisms and use of optimal 

adjuvants if the delivery route is through 

peptides. 

In conclusion, our understanding 

of the molecular mechanisms of colon 

cancer carcinogenesis has exploded 

in recent years with the use of next 


GENETIC SCREENING FOR COLON CANCER PREVENTION 


old Jignesh was 

suffering from weight loss 

52-year 

and changes in bowel 

movement. A similar incident in his 

brother had already been diagnosed 

as cancer. Jignesh did not want to take 

any chances and got a PET scan and 

an endoscopy mediated biopsy done. 

Biopsy results came out to be positive 

for colon cancer and Jignesh consulted 

Dr Rakshit Shah, consultant surgical 

oncologist, at the Kailash Cancer Hospital 

and Research Centre (KCHRC), Goraj, 

Gujarat. D. Shah reviewed the family 

history and endoscopy results carefully. 

Based on the endoscopy results showing 

the presence of >100 polyps in the 

colon and the biopsy results, Dr Shah 

performed a colectomy. In the meantime, 

because of the family history and the 

extent of polyps, Dr Shah strongly 

suspected Jignesh to have Familial 

Adenomatous Polyposis (FAP). 

FAP is an autosomal dominant 

disorder that is caused due to a 

mutation in the adenomatous polyposis 

coli (APC) gene. The APC protein is a 

tumour suppressor gene and carriers 

with a mutation in the APC gene 

resulting in an inactive APC protein are at 

an almost 100% risk of colon cancer by 

the age of 40. 

To confirm the diagnosis and to 

test other family members, Dr Shah 

counselled Jignesh and 26 of his family 

members to agree to undergo genetic 

testing. A total of 10 family members 

carried the mutation in the APC gene. 6 

members were diagnosed with polyps, 

3 of which were diagnosed with cancer 

and all 6 immediately underwent 

prophylactic colectomy. 4 members 

were younger and did not have polyps 

as yet. However, they have a strong 

predisposition of getting polyps and 

colon cancer later and are advised 

to undergo regular colonoscopies to 

monitor the generation of polyps. 

Colon cancer can also be triggered 

due to mutations in the DNA mismatch 

repair genes MLH1, MSH2, MSH6, and 

PMS2 or EPCAM gene which results in 

inactive MSH2 protein. These mutations 

result in the Lynch syndrome or 

hereditary nonpolyposis colorectal cancer 

(HNPCC). Patients with Lynch syndrome 

also have an increased risk of developing 

colorectal cancer. Aneesh was one such 

In these cases, family 

history is very important 

and the entire family should 

be counselled for genetic 

testing to ensure adequate 

surveillance 

Dr Rakshit Shah 

Consultant surgical oncologist 

patient who had come to Dr Shah with a 

relapsed case of colorectal cancer. After 

genetic testing, he had a mutation in the 

MLH1 gene. His family members were 

also counselled and underwent genetic 

testing. However, of the 13 members 

tested, only Aneesh and his brother 

were positive and the remaining family 

members were relieved to have been 

tested negative. 

As per Dr Shah, some of the major 

challenges in getting patients to undergo 

genetic testing is the cost factor or the 

worry regarding social stigma. For these 

cases, the testing was done for free by 

MedGenome Labs, Bangalore. Further, 

because of the existing family history, 

these families willingly agreed for the 

testing. 

Once operated, there is no need to 

undergo further treatment. However, 

colectomies may result in liquid stools 

with an increase in frequency of bowel 

movements per day. While this may 

not seem very enticing to someone to 

undergo prophylactic surgery, Dr Shah 

strongly advocates that “prevention is 

better than cure.” He advices that in such 

cases, family history is very important 

and the entire family should be 

counselled for genetic testing to ensure 

adequate surveillance and prophylactic 

therapy. 

Currently, there are no targeted 

therapies to block the tumour-promoting 

changes that happen in FAP and Lynch 

syndrome patients. However, there is 

some hope that boosting the immune 

system of individuals after colectomy 

may prevent or delay the progression to 

full-blown colon cancer. 

generations sequencing technology and 

advanced data analysis tools. A range 

of novel targetable driver mutations, 

including gene fusions have been 

reported in these studies (Seshagiri, 

Stawiski et al. 2012, Dienstmann, 

Vermeulen et al. 2017). In India, 

colorectal cancer is usually detected 

at an advanced stage with limited 

treatment options. Identifying high-risk 

patients carrying known 

risk alleles through genetic testing 

should be part of colorectal cancer 

screening awareness programmes. 

MSIhi tumours stand to benefit the 

most by checkpoint blockade therapy. 

Finally, vaccines should be considered in 

neoadjuvant setting to delay recurrence 

or in familial cancer after surgical 

removal of polyps. 

The authors are with MedGenome Inc., 

Foster City California 


cosmetic surgery 

BREAST IMPLANTS CARRY 

LYMPHOMA RISK: US FDA 

The world’s leading drug regulator finds an increasing number of unique cases 

of implant-associated large cell lymphoma 

Binita Ashar, MD, of the FDA’s 

Centre for Devices and 

Radiological Health issued a 

statement on known risk of lymphoma 

from breast implants. 

One of the most important roles 

we have as a public health agency is 

educating patients and health care 

providers about both the benefits and 

risks of medical products, including 

breast implants. 

I know there are many choices of 

breast implants available to patients, 

including the size, implant fill and 

surface texture. We want to provide 

patients with the most up-to-date 

information about the variety of breast 

implants available so that patients 

and providers can have thorough and 

thoughtful discussions weighing the 

benefits and risks of different products. 

We also want to be transparent in 

sharing the information we regularly 

gather and analyse in a way that 

provides important context to help 

inform these discussions. 

Today, we are providing an update 

regarding the number of cases of breast 

implant-associated anaplastic large cell 

lymphoma (BIA-ALCL), a type of non- 

Hodgkin’s lymphoma and a known risk 

from breast implants. In 2011, the FDA 

was the first public health agency in 

the world to communicate about the 

risks of BIA-ALCL, warning women that 

the available information at the time 

indicated that there is a risk for women 

with breast implants for developing this 

disease. Since then, we have regularly 

updated the information available on 

our website regarding known BIA-ALCL 

cases, including deaths and known risks. 

We hope that this information 

prompts providers and patients to have 

important, informed conversations 

about breast implants and the risk of 

BIA-ALCL. At the same time, we remain 

committed to working in partnership 

with all stakeholders to continue to 

study, understand and provide updates 

about this important public health issue. 

Today, the agency is providing an 

updated number of medical device 

reports (MDRs), also known as adverse 

event reports. After thorough data 

analysis, we are reporting that, as 

of September 2018, the agency has 

received a total of 660 total medical 

device reports regarding BIA-ALCL cases 

since 2010. Of the 660 MDRs, our indepth 

analysis suggests that there are 

457 unique cases of BIA-ALCL, including 

9 patient deaths. 

We understand that the information 

presented shows an increase of 246 

new MDRs since last year. Given 

the agency’s continued efforts to 

communicate with stakeholders 

about BIA-ALCL risks and our work 


to encourage patients and providers 

to file MDRs with the agency, these 

types of increases in the MDRs are 

to be expected and may include 

past cases that were not previously 

reported to the FDA. The increased 

number of MDRs contributes to our 

evolving understanding of BIA-ALCL 

and represents a more thorough and 

comprehensive analysis. 

The number of unique cases is 

lower than the total number of reports 

because the FDA’s medical device 

reporting system allows patients, 

providers and manufacturers to each file 

their own reports even if it’s about the 

same case, which can lead to duplicative 

reports of BIA-ALCL. Through our review 

of each report, our team of experts 

works to remove duplicative information 

and analyse the data provided to help 

better understand what these reports 

may or may not tell us about the 

benefits and risks of the device. For 

example, our analysis of these reports 

is better when there is a wide range of 

information provided concerning the 

breast implant texture and implant fill, 

and other helpful details like a patient’s 

age, how long a patient has been 

implanted, and time from implantation 

to diagnosis. This information 

helps us understand how and why 

this lymphoma may be occurring. 

Unfortunately, not every report provides 

thorough information about each case, 

including what type of breast implant 

(e.g., surface texture) the patient 

received, which makes it more difficult 

to know if any particular breast implant 

characteristic is associated with BIA- 

ALCL or if higher reports of BIA-ALCL 

are simply due to a higher implantation 

rate of a particular manufacturer. In 

the interest of transparency, on our 

webpage, we provide a breakdown 

of the data and an analysis of that 

information that was provided to the 

agency. 

For patients, we know the 

information regarding breast implants 

can be overwhelming, which is why 

we are committed to continuing our 

efforts to provide up-to-date publicly 

IT IS DIFFICULT TO KNOW IF 

ANY PARTICULAR BREAST 

IMPLANT CHARACTERISTIC IS 

ASSOCIATED WITH BIA-ALCL 

available resources to help understand 

the known benefits and risks of 

implants. We encourage patients to 

review our website and read specific 

device labelling, including patient 

labelling information, for any product 

they may consider implanting. Choosing 

to obtain a breast implant is a very 

personal decision that patients and 

their providers should make based on 

individual needs and with the most 

complete information about products. 

We are also aware that our 

counterparts in different countries 

are taking certain actions or may be 

reporting different information about 

breast implant safety than the FDA. 

The different devices approved in each 

country, availability of products, variation 

in market share, extent of medical 

device adverse event reporting, and 

availability of information regarding the 

total number of implants sold differs 

from country to country. This makes 

it difficult for the regulatory bodies of 

different countries to compare data and 

determine risk rates on a global scale. 

We recognize the limitations of 

medical device reports, which is why 

we review other sources of information, 

including medical literature and 

the Patient Registry and Outcomes 

for Breast Implants and Anaplastic 

Large Cell Lymphoma Aetiology and 

Epidemiology (PROFILEdisclaimer 

icon). PROFILE collects real-world 

data regarding patients who have a 

confirmed diagnosis of BIA-ALCL. 

In addition to updating our medical 

device reports, we are issuing a Letter 

to Health Care Providers to encourage 

those who regularly treat patients, 

including primary care physicians and 

gynaecologists, to learn about BIA-ALCL 

in patients with breast implants. We 

want to ensure that all providers who 

treat patients with breast implants have 

information regarding identification, 

diagnosis and treatment. Patients are 

more likely to seek routine care from 

primary care physicians, gynaecologists 

and others besides their treating plastic 

surgeon. 

Dr. Binita Ashar is a general surgeon and 

the director of the Division of Surgical 

Devices in the FDA’s Center for Devices and 

Radiological Health. 


public health 

MEASLES IN EUROPE 

WHO URGES EU NATIONS TO ADDRESS IMMUNISATION GAPS 

Measles killed 72 children and adults in the European region in 2018 

In light of measles data for the year 

2018 showing a rising number of 

deaths from the viral infection, the 

WHO has urged European countries to 

target their interventions to those places 

and groups where immunization gaps 

persist. 

More children in the WHO European 

region are being vaccinated against 

measles than ever before; but progress 

has been uneven between and within 

countries, leaving increasing clusters of 

susceptible individuals unprotected, and 

resulting in a record number of people 

affected by the virus in 2018. 

Measles killed 72 children and 

adults in the European region in 2018. 

According to the WHO’s monthly country 

reports for January to December 2018 

(received as of 01 February 2019), 

82 596 people in 47 of 53 countries 

contracted measles. In countries 

reporting hospitalisation data, nearly 

2/3 (61%) of measles cases were 

hospitalized. The total number of people 

infected with the virus in 2018 was the 

highest this decade: 3 times the total 

reported in 2017 and 15 times the 

record low number of people affected 

in 2016. 

The surge in measles cases in 2018 

followed a year in which the European 

region achieved its highest ever 

estimated coverage for the second dose 

of measles vaccination (90% in 2017). 

More children in the region received the 

full two-dose series on time, according 

to their countries’ immunisation 

schedules, in 2017 than in any year since 

THE SURGE IN MEASLES 

CASES IN 2018 FOLLOWED 

A YEAR IN WHICH THE EU 

ACHIEVED ITS HIGHEST 

EVER ESTIMATED COVERAGE 

FOR THE SECOND DOSE OF 

MEASLES VACCINATION 

WHO started collecting data on the 

second dose in 2000. Coverage with the 

first dose of the vaccine also increased 

slightly to 95%, the highest level since 

2013. However, progress in the region, 

based on achievements at the national 

level, can mask gaps at subnational 

levels, which are often not recognised 

until outbreaks occur. 

“The picture for 2018 makes it 

clear that the current pace of progress 

in raising immunization rates will be 

insufficient to stop measles circulation. 

While data indicate exceptionally high 

immunization coverage at regional 

level, they also reflect a record number 

affected and killed by the disease. This 

means that gaps at local level still offer 

an open door to the virus,” stated Dr 

Zsuzsanna Jakab, in a WHO release. 

Increasing susceptibility 

While immunization coverage has 

improved overall in the region, many 

people remain susceptible. 

Estimated coverage with the second 


dose of measles vaccine was below the 

95% threshold to prevent circulation 

(that is, to achieve “herd immunity”) in 

34 countries of the region in 2017. 

Subnational coverage rates point 

to disparities even within countries. 

Suboptimal coverage for either dose sets 

the stage for transmission in the future. 

The European Vaccine Action Plan 

2015–2020 (EVAP) lays out a strategy 

endorsed by all 53 member states to 

eliminate both measles and rubella. 

Most importantly, at least 95% of 

every population needs to be immune, 

through two doses of vaccination or 

prior exposure to the virus, to ensure 

community protection for everyone 

– including babies too young to be 

vaccinated and others who cannot be 

immunized due to existing diseases and 

medical conditions. 

“In adopting EVAP, all countries in the 

European region agreed that elimination 

of measles and rubella is possible and 

is also a cost-effective way to protect 

people of all ages from avoidable 

suffering and death,” according to 

Dr Nedret Emiroglu, Director of the 

Division of Health Emergencies and 

Communicable Diseases, WHO Regional 

Office for Europe. 

Forty-three European countries 

interrupted transmission of endemic 

measles for at least 12 months as of 

the end of 2017. Some of them, also 

managed to limit the spread of the 

virus following importation to very few 

cases in 2017 and 2018, showing that 

elimination of the disease is well within 

reach for the whole Region. “Progress 

in achieving high national coverage is 

commendable. However, it cannot make 

us blind to the people and places that 

are still being missed. It is here that we 

must now concentrate increased efforts. 

We should never become complacent 

about our successes but continue to 

strive to reach the final mile. Together 

we can make this happen,” concludes Dr 

Emiroglu. 

Suboptimal coverage 

Many factors contribute to suboptimal 

immunization coverage and the spread 

of measles. To prevent outbreaks and 

eliminate measles, countries need to 

sustain high national and subnational 

immunization coverage with two doses 

of measles-containing vaccine, as well 

as identify and address all pockets 

of underimmunization among their 

populations. 

FORTY-THREE EU COUNTRIES 

INTERRUPTED TRANSMISSION 

OF ENDEMIC MEASLES FOR AT 

LEAST 12 MONTHS AS OF THE 

END OF 2017 

The regional office continues to 

work with countries in the region to 

enhance their immunization and disease 

surveillance systems. This includes 

building capacities and providing 

guidance to: 

• ensure that all population groups 

have equitable access to vaccination 

services and that these are convenient 

SPURT IN NUMBERS 

Measles cases and MCV1 & MCV2 coverage 

in the WHO European Region, 2009-2018 

Number of measles cases 

90000 

80000 

70000 

60000 

50000 

40000 

30000 

20000 

10000 

0 

94 

73 

7884 

93 

80 

30604 

• identify who has been missed in the 

past and reach them with the vaccines 

they need 

• ensure that health workers are 

vaccinated to prevent transmission in 

health facilities and that they 

have sufficient technical knowledge 

about vaccines and the immune 

system to feel confident in 

recommending vaccination to their 

patient 

• strengthen trust in vaccines and 

health authorities 

• secure access to a timely and 

affordable supply of vaccines 

• improve outbreak detection and 

response 

• listen and respond to people’s 

concerns and respond to any health 

event that could be potentially related 

to vaccine safety. 

Most of the countries struggling 

with suboptimal immunization coverage 

against measles in the Region are 

middle-income countries. The regional 

office is working with these countries 

to implement a coordinated strategy to 

address targeted programme areas, the 

WHO said. 

2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 

Measles cases 

94 

83 

33254 

95 

83 

26788 

95 

89 

32857 

Data sources : 1. Measles cases - monthly aggregated and case-based data reported by Member States to WHO/Europe 

or via ECDC/TESS by as of 01 Feb 2019. 2. MCV1 and MCV2 coverage - WHO/UNICEF Estimates of National Immunization 

Coverage (WUENIC) as of 08 Nov 2018. 

MCV1 = first dose of measled - containing vaccine; MCV2 = second dose of measles-containing vaccine 

Year 

94 

89 

18869 

MCV1 coverage 

94 

89 

28413 

93 

88 

5273 

95 

90 

25863 

MCV2 coverage 

82596 

100 

90 

80 

70 

60 

50 

% Coverage 


devices&gadgets 

Interoperable insulin pump 

gets US FDA nod 

DBS for epilepsy 

therapy launched 

M 

edtronic has launched 

Deep Brain Stimulation 

(DBS) for medically-refractory 

epilepsy in the US. 

DBS therapy uses a 

surgically implanted medical 

device for epilepsy. It delivers 

controlled electrical pulses to 

a target in the brain called 

the anterior nucleus of the 

thalamus (ANT), which is 

part of a network involved in 

seizures. 

Recently, the US FDA 

granted pre-market approval 

for Medtronic DBS therapy 

for epilepsy as an adjunctive 

treatment for reducing the 

frequency of partial-onset 

seizures in individuals 18 

years of age or older who are 

refractory, or drug-resistant, 

to three or more antiepileptic 

medications. 

The approval was based 

on results from the SANTE 

(Stimulation of the Anterior 

Nucleus of the Thalamus 

in Epilepsy) trial, wherein 

patients had a median seizure 

frequency reduction of 75 

percent at seven years postimplant. 

Similar to a cardiac 

pacemaker, it delivers electrical 

stimulation to precisely 

targeted areas of the brain as 

adjunctive treatment for several 

neurological disorders. 

In addition to medically 

refractory epilepsy, DBS 

therapy is currently approved 

in many locations around the 

world, including the US and 

Europe, for the treatment 

The US FDA approved 

Tandem Diabetes 

Care’s t: Slim X2 insulin 

pump with interoperable 

technology for delivering 

insulin under the skin. 

Referred to as an 

alternate controller enabled 

(ACE) infusion pump, it 

allows patients to tailor 

diabetes management 

to their individual device 

preferences. 

The interoperable t: 

Slim X2 pump works by 

delivering insulin under 

of the disabling symptoms 

of essential tremor and 

recent and longer-standing 

Parkinson’s disease. The device 

is also useful to treat chronic 

intractable primary dystonia 

and severe, treatment-resistant 

obsessive-compulsive disorder, 

the company said. 

Intravitreal 

implant to treat 

uveitis launched 

Fluocinolone acetonide 

intravitreal implant (Yutiq) 

the skin at set or variable 

rates. It can be digitally 

connected to automatically 

communicate with and 

receive drug dosing 

commands from other 

diabetes management 

devices, such as AID 

systems. AID systems 

typically consist of a pump, 

CGM, and software to 

control the system. 

The t: Slim X2 insulin 

pump was reviewed 

through the de novo 

pathway 

has been launched in the US, 

EyePoint Pharmaceuticals, 

Inc said. Yutiq is a three-year 

micro-insert for the treatment 

of chronic non-infectious 

uveitis affecting the posterior 

segment of the eye. 

The company has also 

launched EyePoint 

Assist, a programme 

to ensure access to 

Yutiq for eligible 

patients. 

One microinsert 

of Yutiq 

has the ability 

to deliver up 

to three years of 

The FDA reviewed 

interoperable t: Slim X2 

pump performance data 

demonstrating that the 

device can dose insulin 

accurately and reliably and 

at the rates and volumes 

programmed by the user. 

The FDA also assessed 

the ability of the pump to 

communicate with external 

devices with appropriate 

reliability, cybersecurity and 

fail-safe modes, Tandem 

said 

fluocinolone acetonide, a 

commonly used steroid, 

with continuous dosing that 

avoids the peaks and valleys 

of local corticosteroids, the 

current standard of care, the 

company said. 

Yutiq utilizes Durasert 

drug delivery technology 

and is an intravitreal 

micro-insert 

containing 

0.18 mg of 

fluocinolone 

acetonide, 

designed to 

release consistently 

for up to 36 months. 


Robotic catheter 

for lung biopsy 

gets clearance 

The US FDA cleared the 

Ion endoluminal system 

to enable minimally invasive 

biopsy in the peripheral lung, 

Intuitive Surgical said. 

The Ion system uses 

an ultra-thin articulating 

robotic catheter that can 

move 180 degrees 

in all directions. The 

outer diameter of the 

catheter is 3.5 mm, 

which physicians can 

navigate through small 

and tortuous airways to 

reach nodules in any airway 

segment within the lung. 

The Ion system’s flexible 

biopsy needle 

can also pass 

through very 

tight bends 

via Ion’s catheter 

to collect tissue in 

the peripheral lung. 

The catheter’s 2mm 

working channel can 

also accommodate 

other biopsy tools, such 

as biopsy forceps or 

cytology brushes, if 

necessary. 

The system’s fibre optic 

shape sensor technology 

provides the physician 

with the precise location 

and shape information of 

the catheter throughout 

the navigation and biopsy 

process. 

The Ion system easily 

integrate into existing lung 

nodule biopsy workflows, 

as well as existing imaging 

technology, including 

fluoroscopy, radialendobronchial 

ultrasound, and 

cone-beam CT. 

Bone loss 

treatment device 

gets approvals 

NuVasive received 510(k) 

clearance from the US FDA 

as well as European CE mark 

approval for its Precice Bone 

Transport System for use in 

segmental bone loss treatment 

in the tibia and femur resulting 

from trauma or infection. 

The Precice Bone 

Transport System includes 

an implantable, magnetic 

intramedullary nail with a dual 

slot designed to support the 

transport of an intercalary 

bone segment to facilitate 

healthy regeneration. Following 

implantation, an external 

remote controller is used 

to precisely move the bone 

segment up to 10 centimetres 

based on the specific needs of 

each patient. 

It provides an all-internal 

solution compared to 

traditional external fixation 

systems which require patients 

to wear an external device for 

an extended period of time, 

with the potential for increased 

pain and risk of infection. 

Indications for the Precice 

Bone Transport System include 

treatment of acute bone 

defects up to 10 centimeters. 

The stainless-steel device 

provides the strength and 

stability needed to treat more 

complex segmental defects 

due to trauma or infection 

including infected non-unions, 

segmental defect and chronic 

bone infections. 

Neuromodulator 

to treat bladder 

wins CE mark 

S 

timRouter Neuromodulation 

System developed by 

Bioness has received CE Mark 

Approval in Europe for the 

treatment of overactive bladder 

(OAB). 

In the US, the StimRouter 

currently has FDA approval for 

the treatment of chronic pain 

of a peripheral nerve origin as 

US FDA clears DR 800 imaging system 

Agfa NV has received FDA 

510(k) clearance for its DR 800 

multipurpose imaging system with 

tomosynthesis. 

Tomosynthesis is used to synthesize 

tomographic slices from a single 

tomographic sweep. 

The DR 800 includes Agfa’s 

tomosynthesis algorithms for iterative 

reconstruction, which deliver images 

with less noise and fewer artefacts. 

These algorithms also enable faster 

image reconstruction overcoming the 

usual slow iterative reconstruction 

process. 

The DR 800 comes standard with 

Dynamic MUSICA, for both static and 

dynamic images. This image processing 

software enhances noise suppression, 

offers superb brightness control, reduces 

veiling glare, and plays a significant role 

in enabling potential dose reduction. 

The MUSICA Digital TomoSynthesis 

software powers the tomosynthesis 

reconstruction, automatically 

presenting images with 

optimal contrast 

and providing 

consistent image 

quality across the 

individual slices and 

images. 


Philips launches cardio 

imaging system 

Royal Philips has launched 

IntelliSpace Cardiovascular 

4.1, its next-generation 

cardiovascular image and 

information management 

system. 

The new version builds on 

the existing paediatric reporting 

capabilities, recognizing the 

important and unique nature 

of the paediatric environment. 

Clinicians can now complete 

their workflows more efficiently 

in a web browser, while 

integration with Philips Forcare 

enables the sharing of patient 

data between health systems 

and hospitals. IntelliSpace 

Cardiovascular 4.1 aggregates 

patient information into one 

solution to provide a holistic 

view to facilitate betterinformed 

decision-making. 

The addition of the webbased 

paediatric module to 

IntelliSpace Cardiovascular 

4.1 provides a complete echo 

solution that aggregates data 

into one system. The paediatric 

module also includes new 

z-score packages, which are 

a common way to chart serial 

measurements in paediatric 

cardiology practices. 

an adjunct to other non-drug 

therapeutic options. 

Bioness is, currently, 

enrolling patients for a US FDA 

IDE study to support the use of 

the system for the treatment of 

OAB in the US. 

Unlike traditional 

treatments that include 

invasive sacral nerve 

stimulation systems and 

externalized percutaneous 

needle stimulation procedures 

requiring frequent clinic visits, 

the StimRouter provides 

patients with a minimally 

invasive, permanent treatment 

that puts the patient in control 

of their therapy at home. 

The StimRouter procedure 

requires only one small incision 

and is completed in about 30 

minutes while the patient is 

awake under local anaesthesia. 

A hand-held remote allows 

patients to control their 

symptoms by delivering gentle 

stimulating pulses to the tibial 

nerve to reduce the chronic 

urge to urinate. 

Kiran launches 

colour doppler in 

India 

Kiran Medical Systems has 

launched SonoRad V9 Color 

Doppler in India. 

SonoRad V9 can be used 

for a wide range of clinical 

applications. 

SonoRad V9 comes 

with features like 38 cm 

depth penetration, 4D, real 

skin imaging, tomographic 

ultrasound imaging, panoramic 

imaging, real-time doppler 

auto-trace, anatomical 

M-mode with special 3 cursors, 

advanced ergonomics with 

omni-directional mechanic 

arm and 19” LED Monitor with 

170-degree wide view. 

It supports wide variety 

of probes to suit major 

applications like obstretics/ 

gynaecology and radiology. 

SonoRad V9 supports 

cardiology features like TDI 

as well and CW/PW/HPRF 

is available with supporting 

probe. 

US FDA okays 

AdvantageRib 

System 

SIG Medical said the US 

FDA has granted 510(k) 

clearance for its enhanced 

AdvantageRib System, 

K183317. 

This product marks the 

third rib fracture 510k that SIG 

Medical is commercializing. 

The latest 510k features 

new implants to treat 

patients along the 

entire 

spectrum of bone quality 

and modifications to existing 

implants to improve surgeon 

experience. 

AdvantageRib, in a limited 

market release, has been 

utilized in over 50 rib fractures 

with the first patient treated 

nearly 2 years ago. 

SIG Medical plans to 

make AdvantageRib available 

nationwide. The US full market 

launch is slated to occur at 

the 2019 Chest Wall Injury 

Society (CWIS) Annual Meeting 

where the leading experts 

gather to focus on operative 

care of patients with chest wall 

injuries. 


pharma 

ADVANCED WOUND THERAPY 

India will be potentially a huge market for wound care products 

KAYAPAN SATYA DHARSHAN 

The state of Indian pharma Industry 

is wider and larger in all aspects 

compared to Indonesian pharma 

industry. India has its own technologies 

and expertise which is being widely 

acknowledged in SE Asia. The wound 

care market in India has seen a huge 

upsurge in recent years due to growing 

incidences of untreated chronic, acute, 

cancer radiotherapy and burn wounds 

coupled with the largely ineffective 

traditional methods of treating them. 

Rising prevalence of diabetes and 

cancer, attempts to lower the duration 

of hospital stay in order to reduce the 

healthcare expenses and the growing 

inclination towards products that 

enhance therapeutic outcomes are also 

driving the demand for advanced wound 

care products. Traditional methods of 

wound treatment are still being mostly 

followed and now India is covering the 

wound care market in higher growth 

rate. 

Advanced wound care products are 

designed to cure and treat complex 

wounds, such as diabetic foot ulcers, 

venous ulcers, and pressure ulcers. 

Advanced wound management is based 

on the principle of moisture therapy. In 

advanced wound management, moisture 

is provided to the wound site to allow 

cells to heal and repair naturally. The 

rising incidence of hard-to-heal wounds 

and their growing adoption (due to their 

high efficacy) are driving the growth of 

this product segment. 

MARKET DYNAMICS 

Drivers 

• Growing prevalence of diabetes 

• Rapid growth in the geriatric 

population 

• Developments and innovations in 

wound care products 

• Increasing funding for wound care 

research 

• Awareness programs for wound care 

treatment and management 

Restraints 

• High cost of advanced wound care 

products 

• Risk associated with wound care 

products 

Opportunities 

• Emerging economies 

• Increasing research in the field of 

advanced wound care 

• Potential application of stem cell 

therapy in wound care 

• Growing popularity of active wound 

care products 

Challenges 

• Increasing number of acquisitions 

• Survival of new entrants and small 

players 

Developments and innovations in 

wound care products drives the 

global wound care market 

The development of new products 

is another major factor driving the 

growth of the wound care market. 

The continuous development of 

new products provides end users 

with advanced options for wound 

treatment (especially in the case of 

hard-to-heal wounds). 

Target Audience 

• Wound care product manufacturers 

• Wound care associations 

• Research and consulting firms 

• Distributors of wound care devices 

• Contract manufacturers of wound care 

products 

• Healthcare institutes (hospitals, 

medical schools, diagnostic centres, 

and outpatient clinics) 

• Research institutes 

• Venture capitalists 

• Insurance providers (payers) 

• Government bodies 

By wound type, the market is 

classified into chronic wounds and 

acute wounds. The chronic wounds 

segment is estimated to account for 

the largest share of the global wound 

care market. The large share of this 

segment can be attributed to the 

rising incidence of diabetic foot ulcers, 

pressure ulcers, and other types of 

chronic wounds. 

The author is Founder and 

Chairman of Dermozone, 

an Indonesia based 

wound care and skincare 

products company. 


FRONTIER LIFELINE 

NUTRIGENETICS CLINIC 

Nutrigenetics clinic offers personalised diet after 

assessing the gene-diet interaction status from 

patients’ DNA samples 

NARRATION: C H UNNIKRISHNAN 

PHOTO: UMESH GOSWAMI 

She is cute and brilliant. The 

15-year-old Tess Katungi’s 

favourite food is fried chicken 

and finger chips. It›s her second visit to 

Chennai›s well-known heart specialty 

hospital, Frontier Lifeline Hospital, 

and most of the doctors and staff 

members at this hospital have already 

become her friends as she has been 

here with her mother for some days 

now after a successful open-heart 

surgery. Her first visit to this hospital 


was almost six months ago to consult 

the chief surgeon Dr K M Cherian after 

she was diagnosed with a type of 

congenital heart disease in Uganda, 

her home nation. 

Tess’s surgery was a great success. 

She needs to have physiotherapy and 

a couple of post-surgery check-ups 

now at the hospital, and she will be 

back at her school in Kampala in the 

next few weeks. 

But what makes Tess most happy is 

that she can again have her favourite 

food, chicken, which had been a strict 

no-no for her since she was diagnosed 

with the heart disease at a Kampala 

hospital last year. 

“Her nutrigenetic assessment 

allows her to include chicken in her 

diet, though there are a few more 

things we are adding to her diet with a 

personalised diet plan that will 

keep her well and healthy, now as well 

as in future, with no recurring health 

issues,” says Tess’s dietitian at Frontier 

Lifeline Hospital, which started the 

country’s first nutrigenetics clinic fully 

integrated with a specialty hospital 

setup. 

Nutrigenetics, which evaluates and 

analyse gene-diet interaction status 

from patients’ DNA samples to deliver 

a personalised DNA-DIET, helps to 

enhance treatment outcome as well as 

boost and maintain desired immunity 

levels to prevent diseases in future. 

Pioneering Concept 

Many of us still do not have much 

idea about genetics in India. Thus, the 

biggest challenge that this Chennai 

nutrigenetics centre had to undertake 

was to create awareness. 

“Through genetic counselling, we 

give basic introduction about the 

subjects of genetics and nutrigenetics. 

We explain the process involved and 

what all one can expect to see as the 

outcome. We also collate the incidence 

of genetic diseases through family 

history and the patent’s current lifestyle, 

including his or her BMI and 

medical history,” says Beula Daniel, 

Chief Dietitian and Head - Nutrigenetics 

Clinic, Frontier Lifeline Hospital. 

The patients enrolled in the 

clinic for nutrigenetic assessment 

are also asked to do a blood test 

that measures levels of lipids or 

fats, including cholesterol and 

triglycerides. These data would be 

utilised for assessing the individual’s 

current health portfolio, added 

Beula Daniel. 

In recent times, with the 

With the technology 

advancements, 

especially in the area 

of genomics and DNA 

testing, we aim to offer 

the individuals modified 

nutrition based on 

their genetic character 

and a personalized 

diet plan achieved 

through informed diet 

counselling. 

Dr. KM Cherian 

Founder and CEO 

Frontier Lifeline Hospital 


slug 

advancement of molecular tools, 

the two branches of nutritional 

genomics — namely Nutrigenetics and 

Nutrigenomics — have become the 

front-runners in the field of nutritional 

research. Both these concepts stem 

from the fact that the genetic makeup 

of every individual is different. In other 

words, no two individuals react exactly 

the same way to a food substance, 

and at the same time, no single food 

substance has exactly the same impact 

on the gene expression patterns of 

two individuals. 

According to Dr C N Ramchand, 

Scientific Advisor for Frontier Lifeline 

Nutrigenetics Clinic and an Adjunct 

Professor, Faculty of Science, 

Engineering and Technology at 

Swinburne University of Technology, 

Australia, Nutrigenetics aims to 

identify genetic susceptibility to 

diseases and the ways in which very 

small difference in our genes can alter 

the effects that nutrient intake has 

on the body. By understanding and 

analysing these variations, specific 

dietary and disease prevention advice 

can be given, based on personal 

genetic makeup. 

For example, Apolipoprotein A1 

(ApoA1) plays an important role in 

serum cholesterol metabolism. Studies 

clearly indicate that a polymorphism 

close to the ApoA1 gene determines 

NUTRIGENETICS AIMS TO 

IDENTIFY GENETIC 

SUSCEPTIBILITY TO DISEASES 

AND THE WAYS IN WHICH 

VERY SMALL DIFFERENCE IN 

OUR GENES CAN ALTER THE 

EFFECTS THAT NUTRIENT 

INTAKE HAS ON THE BODY 

how polyunsaturated fatty acid (PUFA) 

intake affects plasma HDL cholesterol 

levels. In this context, it would make 

sense for some people to consume 

higher amounts of PUFAs than others, 

depending on genotype, to reduce 

the risk associated with cardiovascular 

disease (CVD). 

More specifically, Eicosapentaenoic 

acid (EPA) is a PUFA which is abundant 

in fish oils and is prescribed as a dietary 

supplement to prevent CVD. 

On the other hand, Nutrigenomics 

initially concerned itself with the effects 

of nutrients on the expression of an 

individual’s genetic makeup. 

Of late, this definition has been 

broadened to encompass nutritional 

factors that protect the genome 

from damage. Thus, nutrigenomics is 

concerned with the impact of dietary 

components on the genome, proteome 

and metabolome, added 

Dr Ramchand. 

Hospital Integrated Functioning 

While several technology providers 

have recently entered this novel 

healthcare segment in the country, 

most of them still cater to the 

consumer as service aggregators and 

are not attached with a hospital where 

all the assessment and treatment 

components are integrated for better 

patient outcome. 

In this context, the Frontier Lifeline 

initiative is unique. 

“After the enrolment, we first collect 

the recommended volume of blood 

sample for DNA isolation (around 3-5 

ml). While the nutrigenetics report 

would take 45 to 60 days, including 

shipping of samples, processing and 

the design of diet plans, once the 

genetic interpretation is delivered, 

the patients would be referred to the 

inhouse cardiologist, physiotherapist 

and dietitian.” said Ramya Koshi, 

Genetics Counsellor at the clinic. 

The assigned cardiologist would 

assess the patients’ lifestyle record 

and genetic results to recommend 

any medical advice. Simultaneously, 

the hospital’s physiotherapist would 

recommend physical activities which 

would be beneficial according to 


the patent’s genetic result and the 

dietitian would assess his or her 

current lifestyle and food intake 

pattern to recommend a personalised 

diet plan as per the genetic result, 

evaluating the nutrition requirement. 

This first, integrated centre in 

nutrigenetics also offers health 

supplement products made in-house, 

on a case to case basis, if required. 

“Our food and nutrition department 

has formulated and introduced 

multigrain, multiprotein and golden 

milk mix from 36 grains and other 

natural sources. These products are 

helping diabetic and cardiovascular 

patients by reducing bad cholesterol, 

normalising glucose levels and 

boosting antioxidants and immunity 

levels,” added Koshi. 

The improvements from these 

recommendations could be assessed 

after 6 months with a blood test and 

BMI analysis, she added. 

Trend Setting 

While patients suffering from 

cardiovascular diseases, obesity, 

hypertension and diabetes can do 

the test to find the right diet, healthy 

individuals of any age group can also 

enroll in such clinics as nutrigenetics is 

emerging as a trend towards precision 

diet. More importantly, individuals 

having a strong family history of 

genetic diseases can test themselves 

Through genetic 

counselling, we give 

basic introduction 

about the subjects 

of genetics and 

nutrigenetics. We 

explain the process 

involved and what 

all one can expect to 

see as the outcome. 

Beula Daniel 

Chief Dietitian and Head 

Nutrigenetics Clinic 

Frontier Lifeline Hospital 

to prevent the onset of such 

diseases by enrolling for a genetic 

diet plan. 

For instance, dietary components 

can selectively activate or deactivate 

gene expression by inducing 

changes in DNA methylation, histone 

modifications and alteration in 

microRNA (miRNA) expression, 

without any change in the DNA 

sequence (called as ‘epigenetic 

regulation’). The best and most 

well-studied example is Curcumin 

(diferuloylmethane), a component 

of the golden spice Curcuma longa, 

commonly known as turmeric. It has 

been determined to induce epigenetic 

changes, thereby preventing various 

kinds of cancer. Hence, it is quite 

vivid that approaching a disease 

condition with a molecular vision 

definitely helps in an adjuvant 

treatment modality in addition or 

conjunction with the mainstream 

therapy for a given condition. Also, 

gaining knowledge about the genetic 

makeup of every healthy individual 

will undoubtedly help in preventing 

diseases through the prescription 

of a customized diet regimen, says 

Dr Ramchand. 

This is part of a series that features India’s 

First & Most Unique institutions, facilities, 

technologies, products etc in the medical 

and healthcare space. 


esearch 

COMBATING MALARIA: THE GENOMIC WAY 

Genome-wide analysis of the malarial parasite provides clues on potential drug targets 

ANIKET PRATAPNENI 

New methods of treatment and 

prevention have emerged to treat 

malaria from the growing field 

of genetics. The first of these methods 

involves targeting the Plasmodium 

genome. By conducting genome-wide 

analyses, researchers have been able 

to identify core genes of the malarial 

parasite that offer targets for new drugs. 

One of the most important of these 

studies – and possibly indicative of the 

future course of the disease treatment 

– was conducted at the University of 

Melbourne. The researchers used genetic 

analysis and basic biology to discover 

what could be an instrumental chink in 

malaria’s armour of mutability. 

Atovaquone is an anti-malarial 

drug that was not under use for fear 

of the development and spread of 

resistance. However, the study showed 

that although malaria parasites can 

develop resistance to atovaquone, but 

they cannot spread it. The mutation that 

makes it possible to resist atovaquone 

also render it impossible for the parasite 

to survive the subsequent step of its life 

cycle – entering a mosquito. And since 

malaria cannot be transferred from one 

person to another, the atovaquoneresistant 

parasite cannot spread. This 

illuminates a new strategy for managing 

drug resistance. The mutation pathway 

that results in this genetic quandary can 

be targeted by drug developers while 

creating new drugs. 

‘Partner’ drugs 

Researchers at the Wellcome Sanger 

Institute and the University of South 

Florida used a new, specialized 

technique – piggyBac-transposon 

insertional mutagenesis – to inactivate 

random Plasmodium falciparum genes 

and incorporated a newly developed 

sequencing tool to identify the relative 

importance of each gene in terms of 

survival. They found that around fifty 

percent (over 2,600 out of 5,400) of 

the genes were essential for its growth 

and propagation in erythrocytes – a list 

of 2,600 targets for drug developers. 

In addition, approximately 1,000 of 

those 2,600 targets are common to all 

Plasmodium species, and although their 

exact functions are currently unknown, 

their status as integral genes make them 

DRUGS TARGETING GENES 

WOULD BE EXTREMELY 

EFFECTIVE AS ‘PARTNER’ 

DRUGS, WORKING IN TANDEM 

WITH ARTEMISININ 

potential targets for anti-malarial drugs. 

Many of these genes were also found to 

be involved in a proteasome pathway 

that is responsible for degrading proteins 

in the cell, which is thought to be 

linked to artemisinin resistance. Thus, 

drugs targeting these genes would be 

extremely effective as ‘partner’ drugs, 

working in tandem with artemisinin. 

Extinction by gene drive? 

The second of these new methods 

involves targeting the Anopheles 

genome. In a recent study, genetic 

engineers used CRISPR/Cas9 to render 

a population of Anopheles gambiae 

mosquitos – Africa’s primary malariaspreading 

mosquito species – incapable 

of producing offspring within twelve 

generations. Based on the results of 

further trials using this tool, it could 

be the first to be able to eliminate 

an entire species of disease-carrying 

mosquitos. The tool used to create 

such a groundbreaking effect was a 

gene drive. These use the CRISPR/Cas9 

‘scissor’ enzyme to insert themselves 

into an organism’s genome at specific 

loci. This gene drive in particular exploits 

a recessive Anopheles gene called 

doublesex. If a female mosquito inherits 

two copies of the broken doublesex 

gene, it develops like a male, which 

are incapable of biting – and therefore 

infecting – humans. Any mosquito that 

inherits only one copy of the exploited 

gene will develop normally. The gene 

drive was designed to circumvent the 

natural laws of inheritance. Normally, 

if a parent carries two different alleles 

of a gene, the offspring will have a 

50% chance of inheriting either one. 

However, with the doublesex gene 

drive, more than 95% of the offspring 

inherited the exploited gene, allowing 

it to spread through the population 

much faster. Once all the members of 

a generation carried two copies of the 

gene drive – which took between 8 and 

12 generations in the study – none of 

the mosquitos were capable of laying 

eggs or biting, forcing the population to 

die out without biting other organisms. 

The gene drive creates the prospect of 

causing the extinction of malaria-carrying 

species, which could eventually result in 

the extinction of malaria itself. 

Author is a student at 

TISB, Bangalore. He 

interned at Professor 

Bobby Kasthuri’s lab at 

the University of Chicago 

and will be pursuing 

undergraduate studies 

in the field of molecular 

biology. 


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products 

DALETHYNE: NEW HOPE 

IN WOUND CARE! 

Dalethyne derivatives allow unhindered execution of the healing process 

Wound and skin care is one of 

the fast-emerging markets in 

India for innovative products 

not only from within the country but 

also from outside. These areas of care, 

which saw several new releases in the 

recent past, has seen the launch of 

an innovative series from Indonesia, 

giving new hope for clinicians who 

treat unsolved chronic and acute burn 

wounds. These products, developed 

around the key ingredient—dalethyne 

and its derivatives, work on the 

basis of their interaction with the 

proteins that regulate wound healing in 

the human body. 

According to the innovator, PT 

Dermazone Pratama Indonesia, 

dalethyne is a breakthrough in 

medicinal science. Obtained from a 

process of fatty acid segregation of 

extra virgin olive oil, dalethyne has 

proven with anti-microbial, fungicidal 

and antiviral qualities with deep-skin 

penetration. 

Kayapan Satya Darshan, the 

inventor of dalethyne and the 

founder and chairman of Dermazone 

Pratama, said that these molecules — 

synthesized in-house — were docked 

with various proteins involved in the 

process of wound healing and the 

binding energies of the molecules were 

calculated by the prediction of their Ki 

values. 

“Dalethyne derivatives exhibited 

sufficient propensity to inhibit the 

inflammation-causing agents and at the 

same time allow unhindered execution 

of the healing process,” he said in an 

interview with Future Medicine. 

“It has proven anti-microbial, 

fungicidal and antiviral quality 

with deep skin-penetrable quality. 

Investigations have revealed that 


dalethyne reduces inflammation and 

accelerates wound healing,” he added. 

A research paper* published in 

Science PG in 2018 validates the 

docking methodology of dalethyne 

saying: “The binding interactions of 

the molecules thus calculated were 

compared with that of the native 

ligand.” 

The report states that, in the 

normal wound healing process, 

platelet activation after the wound 

appearance causes the release of a 

pro-inflammation cytokine such as 

TNF-α and IL-1β, which will activate the 

macrophage. 

“The wound will also activate 

MMP-9 and COX-2. The further 

release of IL-1β and IL-6 will inhibit 

the fibroblast production, keratinocyte 

proliferation and migration; which 

will delay the epithelization and 

granulation process. The inhibition of 

the fibroblast proliferation will cause 

a decrease of FGF-2 synthesis and 

therefore will also decrease the TGF- β1 

expression regulation. This process will 

cause a decrease of endothelial cell 

proliferation and thus will delay the 

neoangiogenesis and vasculogenesis. 

At the same time, these phenomena 

will delay the wound healing process. In 

the present work, dalethyne derivatives 

have been predicted to have the ability 

to suppress the inflammation-causing 

agent, such as MMP-9 and COX-2. 

It could also lessen the increased 

oxidative stress and modulate the 

expression of the growth factors (FGF-2 

and TGF-β1) and inflammation mediator 

(IL-1β and IL-6), which helps to fix the 

wound healing process. In the purview 

of the pharmacology involved in the 

wound healing process, it was observed 

that the dalethyne derivatives showed 

effective interactions with the amino 

acid residues present in the active site 

of the proteins, MMP-9 and COX-2. This 

accounted for the conducive inhibitory 

effects of these molecules towards the 

respective receptors,” the report said. 

Moreover, the simple structure of 

the dalethyne derivatives resembling 

the native ligand attributed to the 

inability to these molecules to bind with 

the proteins involved in the process of 

cell proliferation and re-epithelization. 

From these observations, it can thus be 

inferred that the dalethyne derivatives 

exhibited sufficient propensity to inhibit 

the inflammation-causing agents and 

at the same time allow unhindered 

execution of healing process, the paper 

cited. 

“The results thus provide an insight 

Investigations have 

revealed that dalethyne 

successfully reduces 

inflammation and 

accelerates wound healing. 

Kayapan Satya Darshan 

Founder and Chairman 

Dermazone Pratama 

for the structure of the dalethyne 

derivatives that would facilitate their 

activity as wound healing agents. 

Subsequently, the in-house synthesized 

molecules can be suitably formulated 

into a pharmaceutical dosage form 

that can be efficiently used for 

the treatment of different types of 

wounds,” Science PG paper concluded. 

“Investigations have revealed 

that dalethyne successfully reduces 

inflammation and accelerates wound 

healing. It has been patented in several 

countries under my name and this 

patent is certified as a Novel Innovation 

Patent in Geneva,” Satya Darshan 

confirms. 

The Jakarta-based company, which 

has also introduced a range of nonprescription 

products, including acne 

wax, face wash and face scrub along 

with a series of baby care products. 

It has appointed Delhi-based Alniche 

Life Sciences, a specialty healthcare 

company, to handle its marketing and 

sales of its wound care products. The 

company is also in talks with Indian 

companies to market its consumer 

health products. 

* Kayapan Satya Dharshan. Docking Studies 

for Assessment of Wound Healing Potential of 

Dalethyne Derivatives: An in-silico Approach. 

Computational Biology and Bioinformatics. 

Vol. 6, No. 2, 2018, pp. 36-50. doi: 10.11648/j. 

cbb.20180602.12 


guidelines 

ASBrS RECOMMENDS GENETIC 

TESTING FOR ALL PEOPLE 

WITH BREAST CANCER 

All patients with a 

diagnosis of breast 

cancer should undergo 

expanded panel testing, 

proposes the new 

consensus guideline 

by American Society of 

Breast Surgeons 

American Society of Breast 

Surgeons (ASBrS) has released 

Consensus Guideline on 

Genetic Testing for Hereditary Breast 

Cancer in February 2019. Literature 

review included large datasets, basic 

science publications, and recent 

updated national guidelines. 

Recommendations: 

1. Breast surgeons, genetic 

counsellors, and other medical 

professionals knowledgeable in 

genetic testing can provide patient 

education and counselling and make 

recommendations to their patients 

regarding genetic testing and arrange 

testing 

When the patient’s history and/or 

test results are complex, referral to a 

certified genetic counsellor or genetics 

professional may be useful. Genetic 

testing is increasingly provided through 

multi-gene panels. There are a wide 

variety of panels available, with different 

genes on different panels. There is 


a lack of consensus among experts 

regarding which genes should be tested 

in different clinical scenarios. There is 

also variation in the degree of consensus 

regarding the understanding of risk and 

appropriate clinical management of 

mutations in some genes. 

2. Genetic testing should be made 

available to all patients with a personal 

history of breast cancer 

Recent data support that genetic 

testing should be offered to each 

patient with breast cancer (newly 

diagnosed or with a personal history). 

If genetic testing is performed, such 

testing should include BRCA1/BRCA2 

and PALB2, with other genes as 

appropriate for the clinical scenario and 

family history. For patients with newly 

diagnosed breast cancer, identification 

of a mutation may impact local 

treatment recommendations (surgery 

and potentially radiation) and systemic 

therapy. Additionally, family members 

may subsequently be offered testing 

and tailored risk reduction strategies. 

3. Patients who had genetic testing 

previously may benefit from updated 

testing 

Every patient being seen by a 

breast surgeon, who had genetic 

testing in the past and no pathogenic 

variant was identified, should be 

re-evaluated and updated testing 

considered. In particular, a patient 

who had negative germline BRCA1 

and 2 testing, who is from a family 

with no pathogenic variants, should 

be considered for additional testing. 

Genetic testing performed prior to 

2014 most likely would not have had 

PALB2 or other potentially relevant 

genes included and may not have 

included testing for large genomic 

rearrangements in BRCA1 or BRCA2. 

4. Genetic testing should be made 

available to patients without a history 

of breast cancer who meet NCCN 

guidelines 

Unaffected patients should be 

informed that testing an affected 

relative first, whenever possible, is 

more informative than undergoing 

testing themselves. When it is not 

feasible to test the affected relative 

first, then the unaffected family 

member should be considered for 

testing if they are interested, with 

careful pre-test counselling to explain 

the limited value of “uninformative 

negative” results. It is also reasonable 

to order a multi-gene panel if the 

family history is incomplete (i.e., a case 

of adoption, the patient is uncertain 

of the exact type of cancer affecting 

family members, among others) or 

other cancers are found in the family 

history. 

5. Variants of uncertain significance 

are DNA sequences that are NOT 

clinically actionable 

This type of result needs to be 

considered as inconclusive, and the 

patient should be managed based on 

their risk factors and not influenced by 

this result. 

Summary of data reviewed 

The National Cancer Institute estimates 

for 2018 were that more than 266,000 

new cases of invasive breast cancer 

would be diagnosed in the US, and 

more than 40,000 patients would die 

from the disease. Approximately 10% 

of breast cancers are associated with 

a pathogenic germline variant in one 

of several different genes. More than 

50% of pathogenic germline variants 

are mutations in the BRCA1 and BRCA2 

genes. Using genetic testing to identify 

patients who are at increased risk to 

develop breast cancer enables patients 

to take steps to reduce this risk. There 

are several risk management strategies 

available for individuals at increased 

risk (e.g., chemoprevention along with 

enhanced screening; risk-reducing 

surgeries). 

Unfortunately, in the current state of 

medical practice, a significant number 

of pathogenic mutation carriers remain 

undetected and undiagnosed. These 

are largely women with “moderate 


BREAST 

CANCER IN US 

Every patient being seen by 

a breast surgeon, who had 

genetic testing in the past and 

no pathogenic variant was 

identified, should be 

re-evaluated and updated 

testing considered 

266,000 

new cases of invasive 

breast cancer would be 

diagnosed 

40,000 

patients would die 

from the disease 

SOURCE: THE NATIONAL CANCER INSTITUTE 

penetrance” mutations, but even 

women with BRCA1 or 2 mutations may 

not be identified. There is an unmet 

challenge to improve our identification 

and diagnosis of patients who have an 

inherited increased lifetime risk of breast 

cancer. 

Access to genetic counselling and 

testing 

There are fewer barriers to genetic 

testing now than previously, and testing 

is less costly and being offered by more 

labs. The indications for who should 

be offered testing are ever increasing - 

each guideline update casting a wider 

net, and there is more public awareness. 

However, some barriers remain - one 

of which is the limited availability of 

genetic counselling nationwide for 

patients and their family members. 

Increased access to testing would likely 

lead to more patients pursuing testing 

and improving rates of identification of 

gene carriers. Breast surgeons are well 

positioned to be a resource for patients 

who may benefit from testing. Breast 

surgeons can identify individuals who 

are suitable for testing, inform patients 

of the risks and benefits, provide 

access to genetic testing, and also 

discuss risk management strategies for 

those patients who test positive. For 

patients with less common mutations, 

strong consideration should be given 

to consultation with cancer genetics 

specialists. 

Hereditary breast cancer 

syndromes 

Hereditary mutations to be considered 

include BRCA 1&2, PALB2, and other 

hereditary breast cancer syndromes, 

which include but are not limited 

to Li-Fraumeni syndrome (TP53 

pathogenic variant), Cowden syndrome 

(PTEN pathogenic variant), Hereditary 

diffuse gastric cancer syndrome (CDH1 

pathogenic variant), and Peutz-Jegher 

syndrome (STK11 pathogenic variant). 

Impact of genetic testing results on 

management recommendations 

10% 

breast cancers are 

associated with a 

pathogenic germline 

variant in one of several 

different genes 

Identification of patients with 

pathogenic variants in these genes can 

influence patient management in terms 

of high-risk screening and risk reduction 

as well as therapeutic options related 

to surgery, radiation, and systemic 

therapies. For example, identifying that 

a breast cancer patient has a BRCA1 

pathogenic variant provides that patient 

the opportunity to learn of her elevated 

risk for contralateral breast cancer as 

well as of ovarian cancer and to make 

educated decisions to reduce those 

risks. 

Studies are underway to determine 

whether these patients also might 

benefit from PARP inhibitors being 

included in their adjuvant therapy 

regimen. Another example is that 

radiation is relatively contraindicated 

in patients with TP53 pathogenic 

variants (associated with Li-Fraumeni 

Syndrome) due to their increased risk of 

developing radiation-induced secondary 

malignancies. Identifying a patient who 

has a pathogenic variant that indicates 

high hereditary breast cancer risk 

can have a profound impact on that 

patient’s health and management. 

Additionally, it has a potential 

impact on that patient’s family 

members who should be counselled 

to consider testing for the mutation 

identified in the family, the result of 

which can guide their risk of breast 

cancer development and consideration 

of risk management strategies. The 

genetic testing information should be 

considered together with the details of 

each patient’s case including age, family 

history, medical history, and contributing 

risk factors, as well as careful review 

of existing management guidelines. It 

is important to understand that risk 

of development of breast and other 

cancers and risk management guidelines 

vary both by the mutated gene and 

the penetrance of the specific genetic 

mutation. Additionally, not all pathogenic 

variants identified are medically 

actionable. Just because a hereditary 

pathogenic mutation that predisposes 

to breast cancer is identified does not 

mean that the risk-reducing mastectomy 


is indicated. 

Risk-reducing mastectomy can be 

considered in BRCA1, BRCA 2, PTEN, 

and TP53. Consideration may also be 

appropriate for patients with mutations 

in other genes when combined with 

a significant family history of breast 

cancer. Patients with BRCA1 or BRCA2 

pathogenic variants should consider 

risk-reducing bilateral salpingooophorectomy 

after child-bearing or 

between the ages of 35-40 to reduce 

ovarian and fallopian tube cancer risk. 

Women with BRCA1 should consider 

oophorectomy between ages 35-40, 

while BRCA2 carriers should consider 

it between ages 40-45. Prophylactic 

oophorectomy in premenopausal 

women with BRCA2 pathogenic variants 

has also been shown to reduce the risk 

of breast cancer by about 50%. There 

is also breast cancer risk reduction from 

RRSO in BRCA1 patients but to a lesser 

degree. 

For patients with mutations in 

ATM, CDH1, CHEK2, NBN, NF1, PALB2, 

and STK11, enhanced screening is 

recommended; however, currently, the 

data are not sufficient to support riskreducing 

mastectomy in the absence 

of other factors such as a strong family 

history. There are substantial gaps in 

our ability to predict individual risks 

associated with mutations in some of 

these genes. Risk is modulated by age, 

family history, and in some cases, the 

specific mutation in a particular gene. 

For the aforementioned syndromes, the 

guidelines broadly support considering 

mammography with tomosynthesis and 

breast MRI with and without contrast for 

annual screening due to the elevated 

risk for breast cancer. 

For BARD1, MSH2, MLH1, MSH6, 

PMS2, EPCAM, BRIP1, RAD51C, RAD51D, 

there are some data suggesting an 

elevated lifetime risk of breast cancer; 

however, there is insufficient evidence to 

support the change in breast cancer risk 

management based on the presence 

of a mutation alone. Mutations in 

these genes may be associated with 

an increased risk of gynaecological 

cancers, which may warrant specific 

management. MSH2, MLH1, MSH6, and 

PMS2 are associated with the Lynch 

Syndrome, a multi-organ predisposition 

syndrome that requires multidisciplinary 

management. The list of actionable 

genes and recommendations for 

screening and risk management 

continually evolves as additional 

information becomes available. 

Limitations of genetic testing 

Health care providers and patients 

need to know that genetic testing 

is one of several tools for assessing 

breast cancer risk. Not every genetic 

test yields a straightforward answer 

with clear guidance on how to proceed 

for optimal care. Patients should be 

made aware that negative test results 

do not necessarily mean they are not 

IT IS CRITICAL TO LOOK 

BROADLY AT THE PATIENTS’ 

OTHER CONTRIBUTING 

FACTORS, SOME OF WHICH 

ARE: AGE, MEDICAL HISTORY, 

LIFESTYLE, EXPOSURES, AND 

FAMILY HISTORY 

at increased risk for developing breast 

cancer. Many factors contribute to a 

patient’s lifetime risk of breast cancer, 

and genetic testing is an effort to 

better define one of these elements 

(the measurable inherited risk). When 

counselling patients about their lifetime 

risk of breast cancer, it is critical to 

look broadly at the patients’ other 

contributing factors, some of which are: 

age, medical history, lifestyle, exposures, 

and family history. 

For patients who test positive for 

a pathogenic variant, it is important 

to gain a detailed understanding of 

that variant when advising on risk 

management strategies – details such as 

the penetrance of the cancer risk among 

carriers (how likely is the patient to 

actually develop breast cancer). 

Penetrance varies among the 

identified hereditary cancer syndromes. 

In other words, not all carriers of 

pathogenic genetic variants will develop 

breast cancer, and the level of risk varies 

with the gene affected and likely the 

variant as well. For example, some types 

of CHEK2 and ATM variants have low 

penetrance while other types are more 

highly penetrant. Just because a patient 

test positive for a hereditary breast 

cancer syndrome does not mean that 

the patient will develop breast cancer. 

It is important to note that these 

calculators are constrained by the 

limitations of the studies that provide 

the underlying odds ratios used to 

generate the absolute risk estimates and 

do not account for modification of those 

odds ratios by age, mutation position, 

family history, or polygenic background 

risk. 

Pre-and post-test counselling 

Before testing, patients need to 

be made aware of the implications 

that the test result can have (pretest 

counselling); and when results 

become available, patients should be 

reminded of these implications and 

be provided the appropriate clinical 

context for the results to make informed 

decisions (post-test counselling). All 

genetic testing should be performed 

in the setting of informed consent. 

The American College of Surgeons 

Commission on Cancer accreditation 

program mandates that cancer risk 

assessment, counselling, and genetic 

testing services be provided to patients 

by a physician who does risk assessment 

regularly and/or is qualified to do testing 

or a qualified genetic professional either 

on site or by referral. 

A systematic review of the literature 

indicates that pre-test counselling, 

whether by a geneticist, breast 

surgeon, oncology nurse, or other 

medical professional with expertise and 

experience in cancer genetics reduces 

distress, improves risk perception 

accuracy, and improves follow through 

for testing. 

Breast surgeons who are 


Current rates of 

identifying a VUS with 

newer multi-gene panel 

testing is reported to be 

between 

6.7-41.7% 

knowledgeable in cancer genetics 

can initiate and guide genetic testing 

for their patients. Pre-test counselling 

should include discussion of the types of 

results (true positive = pathogenic, true 

negative = benign (although without a 

known positive in a family, it may also be 

inconclusive as well), and inconclusive = 

variant of uncertain significance (VUS)). 

Other potential issues of testing should 

also be reviewed, such as inconclusive 

results, misperception of true risk, and 

discrimination. 

Patients 

need to 

know there are 

limitations to this 

testing including noninformative 

results or negative 

tests as well as the reality of the 

evolving science. It is important to 

educate patients on the benefits of 

testing as a vehicle to knowing better 

their individual risk and empowerment 

to consider interventions to manage or 

reduce that risk. It can be helpful to set 

expectations for when the test results 

will be available. 

Post-test counselling is important 

regardless of the actual result. The 

current best practice is for all patients 

who undergo genetic testing to have 

some form of post-test counselling. 

By NCCN guidelines, this can occur 

in person or remotely. This allows for 

patients’ questions to be answered and 

for a thorough debriefing. If a result is 

negative or non-informative (such as a 

variant of uncertain significance – VUS) 

then the patient’s other risk factors for 

breast cancer (age, medical history, 

family history, etc.) need to be evaluated 

to formulate the appropriate risk 

management plan. 

Depending on the level of risk for 

breast cancer, strategies to manage 

that risk can be discussed, including 

enhanced screening imaging (annual 

mammogram and breast MRI); 

chemoprevention (endocrine therapy 

to lower risk); lifestyle modification with 

respect to obesity, tobacco use, and 

alcohol consumption; and exogenous 

hormone use among others. 

For patients who test positive for 

a pathogenic variant, a clear review of 

the state of evidence for that specific 

syndrome is imperative. To make 

educated decisions, patients need 

to know about the spectrum of risk 

management strategies. Ultimately, a 

customized plan for the patient is the 

goal with their informed consent. In this 

discussion, a frank statement of the level 

of risk reduction for each intervention 

is needed. For example, risk-reducing 

mastectomy and reconstruction in a 

BRCA1-positive 35-year-old patient 

leads to much greater risk reduction for 

breast cancer mortality than that same 

intervention in a 65-year-old patient. 

The surgeon should discuss these 

issues and refer to other specialists 

(such as gynaecologic oncologists, 

gastroenterologists, etc.) for other 

organs at risk as appropriate. For 


complex 

scenarios, referral to 

a genetics professional 

is recommended. 

Multi-gene panel testing 

Genetic testing has expanded in scope 

and availability since 2013 when the 

U.S. Supreme Court ruling in Association 

for Molecular Pathology v. Myriad 

Genetics, Inc. increased the testing 

options. Increased competition has 

helped to lower the cost. Improvements 

in technology, like next-generation 

sequencing, has made testing for more 

than one gene at a time a reality. which 

can improve the cost-effectiveness and 

efficiency of testing. 

While BRCA1 and BRCA2 remain 

the most likely genes to be mutated in 

a family with high breast and ovarian 

cancer risk, panel testing can allow 

for more comprehensive coverage of 

less common syndromes that can also 

confer hereditary cancer risk. Numerous 

recent studies have shown that panel 

testing can significantly increase the 

rate of detection of pathogenic variants, 

with the most frequently identified 

pathogenic variants (outside of BRCA1 

and BRCA2) being in PALB2, CHEK2, 

and ATM. 

There is a comparatively limited 

understanding of individual breast 

cancer risk associated with mutations 

in genes other than BRCA1 and BRCA2. 

However, the presence of mutations 

in PALB2, ATM, truncating mutations 

in CHEK2, and possibly other genes 

are likely to be associated with lifetime 

breast cancer risks of greater than 

20% and therefore, in the US, at least 

support a decision for enhanced 

surveillance with annual mammography 

with tomosynthesis and breast MRI 

with contrast. Mutations in other 

genes may also reach this threshold, 

although the rarity of such mutations 

and the possibility of subtype-specific 

predisposition make risk estimation 

more challenging. A multi-gene panel 

may include genes with varying degrees 

of evidentiary support and “actionability.” 

This testing method is optimal when 

the individual genes included are 

clinically valid and comprehensively 

address the details of each patient’s 

case. Panel testing can be considered 

for patients who qualify for hereditary 

breast cancer testing to more efficiently 

and cost-effectively evaluate genes that 

confer risk and impact management 

recommendations. 

When genetic testing is being 

recommended based on phenotypic 

syndromes (for example three or more 

close family members affected by 

breast cancer at any age) then multigene 

panel testing is likely to be more 

efficient in evaluating patients. In fact, 

THE PRESENCE OF MUTATIONS 

IN PALB2, ATM, TRUNCATING 

MUTATIONS IN CHEK2, AND 

POSSIBLY OTHER GENES ARE 

LIKELY TO BE ASSOCIATED 

WITH LIFETIME BREAST 

CANCER RISKS 

the most recent NCCN guidelines allow 

that panel testing will largely replace 

sequential gene sequencing (i.e., the 

older approach of evaluating BRCA 

pathogenic variants first, then selecting 

additional genes if BRCA tests are 

negative).1 Insurance companies are 

urged to incorporate the advantages 

of panel testing into their algorithms 

to allow hereditary cancer syndrome 

testing for patients at high risk. 

Surgeons, genetic counsellors, and 

other health care professionals who 

order panel testing for breast cancer 

patients or their family members should 

at a minimum test the breast cancer 

genes that are clinically actionable given 

the current state of medical evidence. 

Testing of additional genes can also 

be performed at the discretion of the 

ordering physician or as directed by the 

family history. 

Variant of uncertain significance 

Variants of uncertain significance are 

DNA sequences that are not clinically 

actionable. This type of result needs 

to be considered as inconclusive. For 

example, a patient who receives a 

genetic testing result of “BRCA1 variant 

of uncertain significance” should not 

be recommended for a change in 

management based on that test result 

alone. No clinical treatment plan or risk 

management plan should be influenced 

by a VUS. These are DNA sequences 

about which the lab is still accruing data 

for definitive classification as to benign 

or pathogenic. 

The vast majority are re-classified 

as benign when enough data are 

collected. Usually, it takes several years 

for the reclassification to take place. The 

American College of Medical Genetics 

has published guidelines for reporting 

DNA sequence variations. The rate of 

identifying VUSs can be high when 

new syndromes are identified but 

that rate decreases as data regarding 

those genes and the VUSs are accrued. 

Current rates of identifying a VUS with 

newer multi-gene panel testing is 

reported to be between 6.7-41.7%. 

There are still VUSs identified with 

BRCA1/2 testing. However, the rates 

are generally much lower, ranging from 

2-5%, now that testing of these two 

syndromes has been available for more 

than 20 years. In general, patients with 

VUSs should be managed based on 

their family history, medical history, age, 

and other factors that influence breast 

cancer risk. No weight should be given 

to the VUS found, and co-segregation 

among affected family members is not 

conclusive evidence of pathogenicity. 

This statement was developed by 

the panel members on February 10, 

2019. 

—Courtesy: American Society of Breast 

Surgeons 


events 

ICACSB-2019 calls for innovation 

in biopharmaceuticals 

The three-day meet re-emphasizes the need for developing 

new drugs and antibiotics 

FM BUREAU, CHENNAI 

Bacterial resistance to existing 

antibiotics is a severe problem 

in the field of medicine at 

present. Structural studies on 

ribosomes from multi-resistant 

bacteria and comparisons to previous 

ribosome structures revealed novel 

structural motifs, essential for protein 

biosynthesis. These are not located 

in the primary ribosomal active sites, 

hence there is no effective mechanism 

for their modification, which leads to 

resistance to antibiotics. These findings 

prompted the design of antibiotics 

with desired structures that can be 

optimized in terms of their chemical 

properties, toxicity, cellular penetration 

IN ORDER TO OVERCOME THE 

PROBLEM OF BACTERIAL 

RESISTANCE, ANTIBIOTICS 

NEED TO BE MODIFIED AND 

NEW DRUG DISCOVERY 

PURSUED 

and species-specificity, said Israeli 

Nobel Laureate Prof. Ada E Yonath, 

reiterating her views on the urgent 

need for quick and specific efforts on 

the development of new antibiotics. 

She was delivering her keynote 

address at the 5th International 

Conference of Advanced Chemical and 

Structural Biology organised by PRIST 

Deemed University. 

Echoing similar views, Prof TP 

Singh, Department of Biophysics, All 

India Institute of Medical Science, New 

Delhi, said that in order to overcome 

the problem of bacterial resistance, 

antibiotics need to be modified and 

new drug discovery pursued. 

Delivering his keynote lecture on 

the topic — Protein Antibiotics as New 

Generation Weapons Against Invading 

Microbes — Singh added: “Here we 

propose an entirely new concept of 

introducing innate immune proteins 

from different species. It has been 

well known that the proteins of the 

innate immune system provide the 

first line of defence against infecting 

microbes. These proteins recognize the 

conserved motifs that are present on 


the cell walls of bacteria.” 

The three-day conference, which 

consisted of six plenary sessions, five 

keynote addresses, 15 short lectures 

and 117 posters, brought together 

several scientists from countries that 

were hitherto unrepresented in the 

conference. 

Senior scientists from premium 

research institutions in countries such 

as Israel, South Korea, Japan, France, 

China, Singapore, Sweden, Germany, 

USA and India participated in the 

conference. 

“The objective was to effectively 

spread the message of chemical 

and biological science researchers 

all over the world. It also offers new 

networking opportunities amongst 

scientists and young research scholars 

from all over the world to create an 

immense outreach for academic 

circles and research industries,” 

informed Dr Dhurairajan Senthilnathan 

from Center for Computational 

Chemistry, PRIST University, and 

convener, ICACSB. 

Presenting a plenary lecture on 

Noncanonical DNAs: Structure, function 

and modulation, Kyeong Kyu Kim from 

Department of Molecular Biology, 

Sungkyunkwan University School of 

Medicine, South Korea, said that most 

DNA in the genome is considered 

to be present as B-form, but new 

evidence suggests that DNA structures 

are highly polymorphic. “Therefore, 

We propose an 

entirely new concept 

of introducing innate 

immune proteins from 

different species. 

Prof TP Singh 

Department of Biophysics 

AIIMS, New Delhi 

many sequence-specific noncanonical 

DNA or non-B DNA conformations 

transiently exist in the genome, 

often in response to changes in the 

cellular environment or when bound 

to proteins, and thus their presence 

or mutation is relevant to various 

diseases, including tumours.” 

Keeping abreast of advancements 

in chemical and structural biology 

is key to making significant inroads 

to attack problems that have an 

interdisciplinary nature, and provides 

a research base for advancing 

biopharmaceutical research. The 

innovations and research in this field 

are already impacting the society 

positively and hence we could expect 

more innovations that will contribute 

to the sustainability of human beings 

in this century, said Dr N Ethirajalu, vice 

chancellor, PRIST University. 


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calendar 

Upcoming conferences 

MARCH 

1-2 GASTROENTEROLOGY 

ISTH–ILBS Symposium on 

Coagulopathy in Liver Disease 

2019 

New Delhi 

1-3 GYNECOLOGY 

ISAR Conference 

Mumbai 

2-3 GASTROENTEROLOGY 

ISTH–ILBS Symposium on 

Coagulopathy in Liver Disease 

2019 

New Delhi 

2-3 HEPATOLOGY 

Master Class in Liver Disease 

Edition (MCLD) 

Chennai 

8-10 NEUROLOGY 

ISAR Conference 

New Delhi 

8-10 DIABETES 

International Diabetes Summit 

(IDC) 

Pune 


Joint Annual Conference of 

Indian Epilepsy Society and 

Indian Epilepsy Association 

New Delhi 

9-10 GYNECOLOGY 

India Fertility Show-2019 

Bangalore 

9-11 IMMUNODEFICIENCY 

DISEASES 

International Conference on 

Primary Immunodeficiency 

Diseases 

Mumbai 

11-12 CARDIOLOGY 

ICCA Stroke 2019 - Acute Stroke 

Interventions and Carotid 

Stenting 

New Delhi 

16-17 NEUROSURGERY 

Indo Japan Neurosurgical 

Meeting (IJNM) 

Secunderabad 

24-25 EDUCATION & TRAINING 


Medical & Health Science 

(ICMHS) 

Pune 

28-29 EDUCATION & TRAINING 

28- 

Mar 3 



(ICMHS) 

Panjim 

CARDIOLOGY 

India Live Conference 

Mumbai 

APRIL 

4-6 SPINE CONGRESS 

Spine Congress 

New Delhi 

5-7 ORTHOPEDICS 

3rd Annual Jaipur Shoulder 

Knee Course (JSKC) 

Jaipur 

7 HEALTHTECH 

Hitcon South Gujarat 

Surat 

19-20 WELLNESS AND 

HEALTHCARE 

National Conference on 

Healthcare Management 

(Symhealth) 

Pune 

27-28 GYNAECOLOGY 

Hysterectomy Summit 

Mumbai 

26 HEALTHTECH 

Futuristic Healthcare Summit 

(FHS) 

Bengaluru 

29-30 MEDICAL T RAINING 



(ICMHS) 

Chennai 

MAY 

3-5 MED EQUIPMENT 

MEDIKO India (MEDIKA) 

Hyderabad 

23 CLINICAL TRIAL 

Annual Clinical Trials Summit 

(Clinical Trials Asia) 

Mumbai 

26-11 PHYSICAL THERAPY 

FM UQ: Functional Mobilization 

Upper Quadrant 

New Delhi 

23-24 CLINICAL GENETICS 

CRO/Sponsor Summit 2019 

Hyderabad 


Asian And Oceanian Myology 

Center Meeting (AOMC Meeting) 

Mumbai 

JUNE 

7-9 GYNAECOLOGY 

Annual Conference of the Indian 

Association of Gynaecological 

Endoscopists 

Ahmedabad 

8-9 OPHTHALMOLOGY 

28-30 EXPO 

National Conference on 

Community Ophthalmology 

Chennai 

India Med Expo (IME) 

Bengaluru 

JULY 

4-7 ANAESTHESIOLOGY 

9th National Conference of 

the Academy of Regional 

Anaesthesia of India 

Coimbatore 

5-6 MICROBIOLOGY 

World Congress on Microbial 

Infectious Diseases 

Goa 

5-7 DERMATOLOGY 

Dermatology and Allied 

Specialites Summit (DAAS) 

New Delhi 

5-7 DERMATOLOGY 

Dermatology and Allied 

Specialites Summit (DAAS) 

New Delhi 

AUGUST 


Ophthall (OPH) 

Hyderabad 

3-4 SURGERY 

World Congress & Summit on 

Surgery 

New Delhi 


India International Optical & 

Ophthalmology Expo (IIOO 

EXPO) 

Hyderabad 

9-11 CARDIOLOGY 

Echo Nagpur Summit 

Nagpur 

The announced dates of the conferences may change 


YOU CAN’T FIND PATIENTS’ FEAR, 

ANXIETY AND PAIN IN ANY LAB REPORT 

PROF K RAJASEKHARAN NAIR 

Eminent neurologist and well-known writer 

As a medical teacher who had his initial medical 

training in the early 1960s, and then taught 

post- and post-postgraduate medical students 

throughout his teaching career, I have seen implausible 

advances in imaging technologies, electrophysiological 

studies, investigative and therapeutic tools and the 

entry of molecular and genetic engineering in medicine. 

In the bargain, good old clinical medicine with a 

stethoscope, a knee hammer, a tuning fork and pins and 

needles has gradually withered away. But the rituals 

of using these instruments are continued, to pretend 

that clinical medicine methods are still practiced. In 

many large hospitals, the medical history of patients is 

taken by the junior-most doctors or the nurses who are 

overburdened by their routine work. They stick to the 

protocols of history-taking given in each specialty. 

The patients are in awe of these protocols and they 

forget to tell their problems. The youngsters have 

forgotten the usefulness and the palliative nature of 

haptics as no one now teaches how to touch or feel 

the patients. Nor do they realize that a compassionate 

hearing can have a curative effect and that a kind touch 

can alleviate pain. 

For them, after all, clinical medicine is dead already. 

Is it really so? 

In the final count, medicine is, as it always was, a 

deep transaction narrowed down to two - the patient 

and the doctor: One trying to comfort and heal, and 

the other seeking the same. The plethora of lab results, 

imaging reports and histopathological studies mean 

very little to the patient who sits across the table of 

the doctor or lies down on the hospital bed diseased, 

desolate and depressed. His fears, anxiety, anger and 

sadness are not reflected in any of the reports which his 

doctor received from his labs. He is not really bothered 

whether his brain tumour is glioblastoma multiforme or 

a glioma grade 2. 

He prays and expects his doctor would tell him 

that he would recover soon. Soothing words could be 

placebos as well. 

These days, it is mandatory that all relevant 

investigations are prescribed, and new treatment 

technologies used, to treat ailments. They certainly help 

to arrive at correct conclusions and definite diagnoses. 

But patients should never be told about their ailments 

and the treatment planned in a rough manner. After 

all, like placebos which please the people, there are 

nocebos too (which bring pain, distress and anguish) 

both in drugs and dialogues. 

Why can’t we at least show some humaneness and 

empathy even if the patient has a fatal illness? 

The doctors too will become patients one day or the 

other, and then only, will they know the anxiety, the fear 

of mortality and the terrible unpleasantness of the pills 

given, cuttings done and inexorable bills they accrue for 

the diseases. 


Sep 30 th - Oct 2 nd , 2019 - Mumbai, India 

REGISTRATIONS OPEN 

Early bird ends on 

15 th June, 2019 

Abstract submission 

ends on 1 st July, 2019 

NextGen Genomics, Biology, Bioinformatics and Technologies (NGBT) Conference is an international 

meeting organized by SciGenom Research Foundation (SGRF), a not-for-profit organization working to 

promote Science, Research and Education in India and rest of Asia. 

HIGHLIGHTS 

• Learn about cutting edge developments in 

genomics, biology, bioinformatics, drug 

discovery, plant and animal sciences 

• Network with scientists of global repute 

• Meet national and international genomics, 

biology and technology companies 

• Interact with leaders from drug industry 

• Explore collaboration opportunities 

• Scholarship opportunities for students to support 

their participation at the meeting 

KEY FOCUS AREA 

• Genomics technologies 

• Population genomics 

• Clinical/Medical genomics 

• NIPT/Liquid biopsy 

• Precision (personalized) medicine 

• Cancer genomics 

• CRISPR/CAS9 

• Gene editing 

• Signal transduction 

• Cancer immunology 

• Biomarkers 

• Drug discovery 

• Metagenomics 

• Plant genomics/sciences 

• Agriculture genomics/sciences 

• Veterinary genomics/sciences 

• Wildlife genomics/conservation 

100+ 

Speakers 

Ms. Ms. Kamalika Das Das 

+91- 8374 27 4074 

800+ 

Delegates 

ngbt2019@sgrf.org 

300+ 

Posters 

www.sgrfconferences.org 

100+ 

Scholarships & Awards

RNI Number KERENG/2012/44529

March 2019 digital v1

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