Study of respiratory symptoms among sputum positive

flctnowfedgment 

;;r.:: First of all I thank ALLAH the All Mighty, the Gracious, all 

knowing for his aid and guidance. 

My extreme thanks and gratefulness to the pioneer (])r: .Jllimecf 

jf.mr 9Vl. rr: 5tto6aslier professor ofChest Diseases Zagazig Faculty of 

Medicine, for his great effort, guidance, and moral support all through this 

work. 

I'd like to express my deepest gratitude to CDr. CEnsaf.Jl6tfef 

\ qawacf .Jlzazy, professor of Bacteriology Zagazig Faculty of 

Medicine for his valuable supervision, continuous encouragement all 

through this study. 

My thanks and appreciation to Dr. qelian Safali Osman 

lecturer of Chest Diseases Zagazig Faculty of Medicine for her strict 

supervision and revision ofwork. 

My thanks and appreciation to a»: ::Mostafa Ibrahim 

"=1 (j{alJa6 lecturer of Chest Diseases Zagazig Faculty ofMedicine for his 

-, ·1. 

patience and strict supervision and his invaluable advice helped me a lot. 

My appreciation to CDr. Hosam .J/.f-5liar!ig.1V), assistant 

professor ofBacteriology Faculty ofMedicine, Zagazig University, for his 

help in practical part ofbacteriology. 

Finally, more thanks for all the staffofChest Department, Zagazig 

Faculty of Medicine, especially t». WflJ{FD 9rt(YJ{)I9rt9rtp.([) 

S:J{oV:M..J/.!N for his great help and support. my patients, my colleagues, 

nursing staff and thanks to every one made any effort for this work to be a 

reality.

CONTENTS 

• Introduction and aim of the work ---------------------------- 1 

• Review of Literature --------------------------------------------- 4 

Tuberculous mycobacteria -------------------------------- 4 

Components of tuberculous lesion --------------------- 10 

Pulmonary tuberculosis ----------------------------------- 23 

Primary pulmonary tuberculosis ------------------ 

Post primary pulmonary tuberculosis 32 

Miliary tuberculosis 40 

Diagnosis of pulmonary tuberculosis-------------------- 44 

• Patients and methods -------------------------------------------- 67 

• Res ults -------------------------------------------------------------- 81 

• Discussion ---------------------------------------------------------- 113 

• Summary and conclusion -------------------------------------- 129 

• Recommen dati0 ns ------------------------------------------------ 136 

• References --------------------------------------------------------- 137 

• APpen dix ----------------------------------------------------------- 177 

• Arabic Summary ------------------------------------------------- 

Page 

26

......-r... 

ABBREVIAnONS

I * 

************************ 

* * 

* }l66reviations * 

* JlC'l{ * 

Acquired cellular resistance 

'* JlCD}l 

JlPCB 

Adenosin deaminase 

Acid fast bacilli 

* 

*' 

: .J/-fCDS 

'*' 

* 

Qf CIA 

*flJn • 

}l'I'S 

*' C13JlL 

*' C13Cq 

'* cBSJl 

Acquired immune deficiency syndrome 

Alveolar macrophage. 

American Thoracic Society 

Broncho - alveolor lavage 

Bacillus calmette guerin 

Bovine serum albumin 

* 

: 

* *' 

*' 

*' 

'* 

: anc Center disease control and prevention : 

* * 

: C'M1 

*'CPC 

Cell - mediated immunity 

Cetyl pridinium chloride *' 

: 

: CSp 

'* CI 

Cerprospinal fluid 

Computrazid tomography 

: 

*' 

'* CI£ Cytotoxic T lymphocyte *' 

* * 

'* C¥Qt Chest X ray '* 

: rJ)9v! Diabetes mellitus : 

*' (J)J{}l Deoxy Nucleic acid '* 

: rJ)TJ[ Delyed type hypersensitivity : 

* *' - * 

************************ 

j

I 

.'X 

, 

.. 'I..... 

- 

_1- 

I '* 

************************ 

*' (p:JtD Purified protein derivative *' 

* *' 

*' PSCB Phosphate buffer saline *' 

: Sr:D Standard deviation : 

* 7'(}3 Tuberculosis *' 

: ry(]3S}l Tuberculostearic acid : 

: crqP(]3 Transforming growth factor B : 

cy'1fP Tumor necrosis factor *' 

* 7'V Tuberculin unit *' 

: VS}l United states ofAmerica : 

: 'f/'}l/Q Ventilation I 

'* 

perfusion : 

*' 

rvCJI.5W 

* 

Vascular cell adhesion molecule 

*' 

Wc.BCs White Blood Cell 

*' *' 

1IVJ[o World Health Organization 

* *' 

'* A2 *' 

Chi - square 

'* *' z. rrsp '* 

Zephiran. Trisodium phosphate. 

: Z.:N: Ziehel-neelsen : 

'* *' *' 

* * 

*' 

'* 

* *' 

'* 

'* 

*' 

'* 

*' 

'* *' 

'* * 

************************ 

II

INlTRODUCTION 

AND 

AIM OF THE \\fORK

J_- 

IntnJducttOn 

The most important factor responsible for the increased rates ofTB 

IS the pandemic of HlV infection (Telzak, 1997).The pandemic ofHIV 

infection has changed tuberculosis, an endemic disease, to an epidemic one 

world wide (Barnes, 1997).The risk ofdeveloping active tuberculosis for 

dually infected person in calculated to be 30 times higher than person 

infected only with M. tuberculosis (Harries and Maher, 1996). 

Diagnosis of pulmonary tuberculosis (TB) made by many means 

clinical, radiological, skin testing, serology, bacteriology and pathology. 

The first 4 give picture of suspicious, bacteriology and pathology confirm 

the diagnosis. bacteriological diagnosis and serology (except direct smear 

examination of sputum) are expensive and may take long period as culture 

(Mobasher, 1993). Many authors hope to settle rules for early diagnosis of 

tuberculosis and pick up the cases. The American Thoracic Society 

(ATS) (1992) and Centers for Disease Control and prevention (CDC), 

have recommended that " pulmonary tuberculosis should always be 

included in the differential diagnosis ofpersons with pulmonary signs or 

symptoms and appropriate diagnostic measures should be instituted", 

CDC (1994) have issued guidelines on the prevention of TB 

transmission in work place these guidelines emphasize the need for 

controls, the most important being the early identification ofpatients with 

active TB, in this sequence Cohen et al. (1996) found a significant 

correlation between symptoms ofcough, sputum and weight loss and smear 

positive for TB. In our locality Mobasher et al. (1997) found that 

radiological picture was the corner stone on which the specialists depend in 

the diagnosis ofpulmonary TB. National Tuberculosis Control Program 

(1998) stressed that annual risk ofinfection in Egypt was 16/100,000 and 

the total number ofnew smear +ve cases was 9,920 case. 

2

·1. v · 

R£\fIEYi 

OF 

UT£RATUR£

Tuberculous Mycobacteria 

The most common agent ofpulmonary tuberculosis is the acid fast 

bacillus M.TB. It's a species of the genus mycobacterium, family 

mycobacteriacae, order actinomycetales (Jeraff, 1986). There are five 

closely related mycobacteria grouped in the M. tuberculosis complex: M. 

tuberculosis, M. bovis, M. africanum, M. microti and M. canetti 

(Vansoolingen et aI., 1997 and 1998). 

Morphology and growth requirements: 

Mycobacterial tuberculosis (M.TB) is a slender, straight or slightly 

curved rod, 0.5 I-l in length and 0.34 ).l in breadth. The bacilli are non 

motile, gram positive, aerobic, and do not form spores or capsules (ATS, 

1987). The growth requirements of mycobacteria on artificial media 

include potassium, magnesium, phosphorus, and sulfur. Ammonium salts 

or egg ingredients provide a nitrogen source, and glucose or glycerol 

supply a carbon source. The optional pH range for growth is 6.5 to 7.0. 

Although mycobacteria are strict aerobes, a CO2 concentration between 5 % 

and 10 % is necessary for their primary recovery on solid media. The 

incubation conditions should include high humidity and atemperature of 

35 to 37°C (Zheng and Roberts, 1999). 

Cell wall structure: 

The cell envelope essentially distinguishes species of the 

. I mycobacterium genus from other prokarytes. Mycobacteria in general give 

.W 

a weakly positive response to the gram stain,are phylogenetically more 

closely related to gram positive bacteria (Draper, 1982), and lackthe 

4

1@wwof£iterature 

classic endotoxic lipopolysaccharide associated with gram negative 

bacteria. However, similarties to gram negative cell walls include the 

paucity of peptidoglycan and the fact that mycobacterial cell walls contain 

meso-diaminopimelic acid (DAP) and an outer lipid barrier. This 

mycobacterial cell walls exhibit many of the characteristics of gram 

positive bacteria and some qualities of gram negative bacteria, but most 

importantly, possess their own unique features (McNeil et al., 1994). 

The cell wall of mycobacteria is composed ofthree layers enclosing 

a plasma membrane, which is also a three- layered structure. Chemically, 

the wall is very complex, and unlike of either gram positive or gram 

negative organisms, it contains an abundance of complex lipophilic 

macromolecules, many of which are unique to the organism and are 

biologically very active (Brennan, 1989). 

The most distinctive attribute ofthe mycobacterial cell envelope is 

the mycolic acid. In case of mycobacterium tuberculosis, the mycolic acid 

contain 70 to 90 carbon atoms (Minnikin and Good Fellow, 1980). They 

constitute more than 50% by weight ofthe mass ofisolated cell envelops 

and apparently interact via powerful hydrophobic binding to form a lipid 

shell surrounding the organism. This property is undoubtedly responsible 

for the lipid barrier and consequent endogenous resistance to know drugs 

(McNeil et aI., 1994). 

Lipids account for approximately 60% ofthe dry weight ofthe wall 

and cofer properties that enable the organism to resist adverse 

environmental conditions. The backbone ofthe mycobacterial cell wall is a 

covalent structure consisting of two polymers covalently linked by 

phosphodiester bonds, a peptidoglycan and an arabinogalactan, to this 

5

qrwwo/£iterttlUW 

covalent structure, a large number ofother complex materials are attached, 

which are responsible for immunogencity and tuberculin activity ofwall 

preparation. The most important of them are wax D., cord factor, sulfatides, 

mycosides and poly. L. glutamic acid (Brennan, 1989). 

Antigenic structure: 

Mycobacteria contain many umque immuno-reactive substances, 

most of which are components ofthe cell wall (Goren, 1982). In spite of 

intensive study for more than 50 years the antigenic composition ofM. TB 

is not clearly defined (young et al., 1985). Immuno - reactivity has been 

demonstrated in lipids, polysaccharides and protein components. Since 

protective immunity to mycobacterial infections is mediated primarily by 

the cellular arm of the immune system proteins are regarded as the key 

immunogens. Few antigens that compose this complex mosaic have been 

obtained in chemically pure form to permit full evaluation of their 

immunolgic potential (Edward and Kirkpatrick, 1986). 

• The most common antigenic mycobacterial substances include: 

1- Polysaccharides : The protein - free polysaccharides (arabinogalactans 

and arabinomannans) are immunogenic and serologically active. The 

significance of these humoral antibodies, however, has not been 

established (Brennan, 1989). 

2- Phosphatidyl Inositol Mannosides (PIMS) : These are a family of 

amphipathic polar lipids, present in the plasma membrane of 

.. 

_L mycobacteria and related organisms. They serve an important structural 

role. There is renewed interest in these components, and a beliefthat 

they are important lipoteichoic acid - like polymers with a role in 

6

-.......... 

?ifui:w of£iter4tt1n 

Secreted antigens can serve important functions for bacterial 

survival. They are grouped into (Orme et aI., 1993) : 

(I) Proteins functioning at the bacterial surface or outside the bacterium, 

like the three fibronectin - binding proteins ofthe antigen 85 complex 

or superoxidedismutase. 

(2) Cell wall proteins which become released, like the 38 KDa 

glycolipoprotein or the Lulanine dehydrogenase protein. 

- 

The following is a group ofM. TB antigens which are listed in the 

WHO bank :- Heat shock proteins 71 KDa, 65 KDa, 14 KDa, and 12KDa, 

phosphate biding protein 38 KDa, L- alanine dehydrogenase 44 KDa, 

membrane- associated 35 KDa protein, Fibronectin-binding protein 55KDa 

and 30/31KDa, potential signal peptide 19 KDa, 14 KDa protein, 10KDa 

protein, 100 KDa protein, 45 KDa protein. 47 KDa protein, and 43KDa 

protein (Richeldi et aI., 1995). 

9

antigen-specific receptors in the bone marrow, when exposed to the antigen 

for which they have a receptor, these T and B cells respond by clonal 

proliferation, greatly increasing their number. 

In tuberculosis, T cells appear to have two main functions 

(Dannenberg, 1999) : 

(l) Killing poorly activated rnacrophages In which the bacilli are 

multiplying. 

(2) Producing cytokines that activate macrophages can now kill or inhibit 

ingested bacilli. 

B cells produce antibodies, the production ofwhich is enhanced by 

differentiation into plasma cells. Plasma cells are frequently found in 

tuberculous lesions. B cells (when activated) also increase the production 

ofIFN-y by NK cells (Yuan et al., 1994). 

T cells can be divided into a variety of ways based on (Dannenberg and 

--_/ I Tomashefski, 1998) : 

(l) Their surface markers (CD4 and CDs T cells). 

(2) The cytokines they produce (Th, and Th 2 T cells). 

(3) Their functions (helper, regulatory and cytotoxic T cells). 

T cells can be divided into two subsets, Th, and Th2, on the basis of 

the cytokines they produce (Mosmann & Sad, 1996 and Barish & 

1_-1 Rosewasser, 1997). Although some T cells show a mixed (i.e 

heterogeneous) cytokine pattern (Furie and Randolph, 1995). 

14

" 

L. 

@?wwo(L:iterature 

leukocytes are attracted into the area and then further activated. (Sugisaki, 

1998). 

Cytokines "knock-out" mice are mrce which the DNA for a 

particular cytokine or its receptor has been deleted from the genome. These 

mice have provided insights into the importance of various cytokines 

(Kaufmann and Ladel, 1994) (e.g. TNF-a) in acquired resistance to the 

tubercle bacillus. Some studies, can never prove that a given cytokine is 

completely responsible for such resistance because cytokines have many 

interaction with each other. Therefor, elimination ofone cytokine affects 

many others in the network. In other words, the elimination of any other 

cytokine in the network could produce the same effect because of such 

interactions and interdependency (Kaufmann, 1995 and Cooper & Flynn, 

1995). 

Recombinant cytokines and cytokine inhibitors have found several 

clinical (Asnis & Gaspari, 1995 and Feldmann et al., 1996), and 

potentially clinical (Abbas et al., 1996) applications and are being 

evaluated in the treatment oftuberculosis (Johnson et al., 1996 and 1997). 

18

LJ I 

!((rWW0/Literature 

Immune mechanisms 

A) Cell-mediated immunity (Acquired cellular resistance) : 

Cell- mediated immunity (CMI) can be defined as a beneficial host 

response characterized by an expanded population of specific T. 

lymphocytes. That, in the presence of microbial antigens, produce 

cytokines locally. These cytokines attract monocytes/macrophages from the 

blood stream into the lesion and activate them, interferon-v (IFN- y) and 

tumor necrosis factor-a (TNF-a) are major macrophage-activating 

cytokines (Belosevic et al., 1988 and Celada & Nathan, 1994). INF-yalso 

induces interleukin 2 (IL-2) receptors in monocyte macrophages, after 

which IL-2 becomes an additional activating cytokine for these phagocytes 

(Holter et aI., 1987). Activated macrophages produce reactive oxygen 

(Klebanoff, 1988) and nitrogen intermediates (Liew and Cox, 1991), 

lysosomal enzymes, and other factors that kill and digest tubercle bacilli 

(Remick and Friedland, 1997). Acquired cellular resistance (ACR) is 

characterized by the presence of a local population of activated 

(microbicidal) macrophages, produced by eMI (Dannenberg, 1989) (i.e 

By the cytokines ofantigen-stimulated lymphocytes) (Barnes et al., 1990). 

In the 1960, Machaness showed that acquired cellular resistance 

once produced, was non specific. Activated macrophages could destroy or 

inhibit many types of facultative intracellular bacteria, not just the type that 

caused their activation. However, once these activated macrophages have 

disappeared, following the healing of the primary infection, only the 

specific bacterial species could rapidly produce them a gain. This rapid 

"recall" response is due to the presence ofexpanded populations oflong 

lived (i.e. non dividing) recirculating Th. lymphocytes (memory cells) with 

19

B) Delyed- type hypersensitivity (DTH) 

Delyed type hypersensitivity (DTH) is immunologically the same 

process as CMI, involving Th1- type T cells and their cytokines frequently 

use. The terms tissue damaging DTH or cytotoxic DTH to represent the 

immunologic reaction that causes caseous necrosis. Such necrosis develops 

locally wherever, the tuberculin-like antigens form the bacillus reach 

excessive concentration (Dannenberg, 1999). CMI and DTH immunologic 

processes produced by the host play key roles in the pathogenesis of 

tuberculosis (Dannenberg, 1991). The relationship between CM! and DTH 

in the control offacultative intracellular microorganisms has been a subject 

of debate for most of 20 th century. From a histologic study of the 

tuberculous lesions and the bacillary growth curves it as apparent that both 

CMI and DTH inhibit the multiplication ofthe tubercle bacillus equally 

well. CMI does so, by activating macrophages to kill the bacilli they ingest. 

Tissue damaging DTH does so by destroying bacilli-laden, non activated 

macrophages and near by tissues there by eliminating the intracellular 

environment that is so favorable for bacillary growth (Luri, 1964 and 

Dannenberg, 1991). 

Thus, the immune system ofboth tuberculin positive hosts with good 

CM! and tuberculin positive hosts with poor CM! can arrest bacillary 

growth. The host with poor eMI does so, however, with much damage to 

its own tissues. Eventually, the host with good eMI may recover, but the 

host with poor CMI dies from excessive tissue destruction (Dannenberg, 

1999). Tissue-damaging DTH causing local necrosis stops the initial 

.i. I bacillary growth within nonactivated macrophages. Which gives the host 

time for eMI to develop local macrophage activation such cytotxic DTH 

can never take the place of CMI because the bacilli that escape from the 

21

. ,,/ 

--...._- ! 

edge of necrotic areas are ingested by perifocal macrophages. If the 

perifocal macrophages have been sufficiently activated by eMI, they can 

destroy the ingested bacilli. Otherwise, the bacilli again grow 

intracellularly until again tissue, damaging DTH kills the macrophages, 

enlarging the caseous necrotic area (Dannenberg, 1999). 

22

..... -. '.., 

gf{ww0/£iteratttn 

Pulmonary tuberculosis 

Transmission of pulmonary tuberculosis: 

For many years tuberculosis was thought to be transmitted 

genetically and even today patients who have little or no idea oftheory of 

infection when informed of the diagnosis of tuberculosis may express 

surprise because it's not in may family doctor (Seaton et aI., 1989). 

Riley (1974), found that tuberculosis is transmitted by air borne 

spread from person to person via infected respiratory secretions. Inhalation 

of droplet nuclei containing the tubercle bacillus may result in infection. 

Respiratory droplets are produced when someone with pulmonary 

tuberculosis coughs or in the case of laryngeal tuberculosis, with speaking 

or singing, While these respiratory droplets are air borne, water evaporates, 

leaving 1-5 urn particles called droplet nuclei. Because oftheir small size, 

these droplet nuclei may remain suspended in air currents for hours and, 

when inhaled may escape the host's. When these droplet nuclei reach the 

alveoli infection may result (Riley, 1974). 

Infectiousness ofa tuberculous patient is dependent on the number of 

tubercle bacilli expelled into the air. The bacilliary load is related to a 

number of factors, including presence of disease in the lungs, cavity 

formation, disease in the airways or pharynx, presence or induction of 

cough. Failure of the patient to cover the mouth while coughing, and 

presence of AFB on microscopic examination ofsputum specimens. The 

period of infectiousness may be prolonged with in appropriate therapy of 

tuberculosis (CDC 1990). 

23

I I 

Interpersonal spread of tuberculosis may be enhanced in areas of 

overcrowding, poor air circulation, or recirculated, unfiltered air. Rates of 

tuberculosis infection in exposed contacts of individuals with active 

tuberculosis may also be dependent on the duration of exposure (Onorato 

and Ridzon 1995). In a study of a student with laryngeal tuberculosis, 

infection was noted as little as 5 hours ofexposure (Braden, 1995). 

Pathogenesis of pulmonary tuberculosis 

The development of pulmonary tuberculosis from its onset to its 

various clinical manifestations is dependent upon a series ofinteractions or 

"battles" between the host and the bacillary invader (Lurie, 1964 and 

Dannenberg 1993). 

An inhaled unit of one to three bacilli is ingested by an alveolar 

macrophage. Either the bacillus is destroyed before any lesion is produced 

or it multiplies within the alveolar macrophage, which dies and reduces the 

amplified infection agent. Many of the bacilli are then ingested by and 

grow within monocyte\macrophage that have emigrated from the blood 

stream. The cells accumulate at the site, fanning a microscopic lesion. 

When the host becomes tuberculin positive a caseous center develops in 

this lesion. A lesion with a small caseous center (up to 2mm in diameter) 

may enlarge or may heal (or stabilize) before it is detectable by 

radiography (Dannenberg and Tomashefski. 1998). 

A larger caseous lesion may also heal or stabilize, or it may enlarge, 

shedding bacilli into the blood and lymph. Alternatively, a caseous lesion 

may liquefy and form a cavity (from which the bacilli enter the bronchial 

tree). In the liquefied caseum, the bacilli will grow extracellularly (for the 

first time), and from the cavity they spread to other parts ofthe lung and to 

24

". 

!/(fWWof£itcrature 

Primary pulmonary tuberculosis 

The first infection with the tubercle bacillus is known as primary 

tuberculosis and usually includes involvement ofthe draining lymph nodes 

in addition to the initial lesion. The combination ofthe Primary or Ghon 

focus and the draining lymph nodes is known as the primary complex 

(Leitch, 2000). 

The Primary infection is associated with a small lesion in the lung. 

The location of which is determined by the distribution ofventilation and 

therefore is most common in the mid and lower zones. The organisms are 

taken up by macrophages and form a small area of consolidation with 

exudation and cellular infiltration, the pulmonary component of the 

primary or Ghon focus. At an early stage ofthe primary infection, possibly 

within a few hours, bacilli are transported through the lymphatics to the 

regional lymph nodes where there is a very marked reaction (Mc Nicol et 

al., 1995). 

Symptoms of primary pulmonary tuberculosis 

The great majority of primary tuberculosis infection are probably 

Symptomless, at least in young adults and adolescents (Daniels, 1948), the 

infection being overcome without the individual being aware of it. A 

proportion may experience a brief febrile illness at the time oftuberculin 

conversion which is indistinguishable from the many febrile illness of 

childhood. Occasionally, typical primary tuberculosis may occur in elderly 

people who have lost their tuberculin sensitivity (Leitch, 2000). 

When tuberculosis is common primary infection is almost invariable, 

but it only produces symptoms in a minority < 10% and these symptoms 

26

gf{wUJof£iterature 

are not normally major (Me Nicol et al., 1995). In those cases, perhaps 

-" I those with more severe infection or low host resistance, the child may be 

unwell with loss ofappetite, fretfulness and failure to gain weight. Cough 

is not usual, but may occur, and may mimic the paroxysms of whooping 

cough when lymph nodes or tuberculous granulation tissue impinge on the 

bronchial wall. Wheeze may be a result of the same process. Sputum 

production is rare in children (Seaton, 1989). 

Signs of primary pulmonary tuberculosis: 

In most cases there are no detectable physical SIgnS with severe 

disease. The child may appear unwell, fretful and debilitated. Auscultation 

of the chest is usually unrewarding but occasionally crepitation may be 

heard over an extensive primary focus and wheezes may result from 

pressure of glands on bronchi. More extensive physical signs may be 

present ifthere is segmental or lobar exudation or collapse (Seaton, 1989). 

Chest Radiology 

Radiological changes are found at the time of tuberculin conversions 

III 7-30% ofyoung adults, being higher in those exposed to a known source 

of infection (Daniels 1948 and Davies, 1961). The prevalence of 

radiological changes in children varies in different populations, in a 

Nigerian Series 79% had lymph adenopathy and 68% had parenchymale 

lesion (Aderele, 1980). In primary tuberculosis parenchymale involvement 

can happen in any segment of the lung (Weber, 1968 and Danek, 1979). 

The most common radiographic appearance ofprimary tuberculosis 

IS a normal radiograph. Hilar or paratracheallymph node enlargement with 

or without a parenchymal infiltrate is a characteristic finding in primary 

27

...... 1 

.L 

"......."-- 

TB. In 15 % of the cases, bilateral hilar adenopathy may be present and 

could be confused with sarcoidosis. Usually, the adenopathy is unilateral. 

Unilateral hilar adenopathy and unilateral hilar and paratracheal 

adenopathy are equally common. Massive hilar adenopathy may herald a 

complicated course. Atelectasis with an obstructive pneumonia may result 

from bronchial compression by inflamed lymph nodes or from a caseous 

lymph node that ruptures in to a bronchus (Rossman and Oner-Eyuboglu, 

1998). 

In the primary infection then is only sight predilection for the upper 

lobes ; also, anterior as well as posterior segments can be involved. The air 

space consolidation appears as a homogeneous density with ill-defined 

borders, and cavitation IS rare except in malnourished or other 

immunocompromised patients. Miliary involvement at the onset occurs in 

less than 3% of cases, most commonly in children under 2-3 years ofage 

(Rossman and Mayock, 1999). 

Complication of primary pulmonary tuberculosis: 

1) Progressive disease at the site ofthe lung lesion: 

This is uncommon but if it does occur it tends to proceed to 

cavitation and breakdown presenting as a typical tuberculous lesion but in 

an unusual site (McNicol et al., 1995). 

2) The formation oftubuerculoma : 

Occasionally the granulomatous lesion progresses slowly resulting in 

a circumscribed rounded lesion with surrounding fibrosis and often some 

calcification which persists indefinitely. The finding of such a lesion in 

later life may raise the suspicion of a carcinoma (McNicol et al., 1995). 

28

.... 

£fwwoj"£itertltua 

3) Erythema nodosum : 

Erythema nodosum has been reported to have accompanied primary 

tuberculosis infection in 1-2(1'0 of British (Daniels, 1948 and Thompson, 

1952) and 5-15% of Scandinavian cases (Crofton, 1954). It is rare below 

the age of seven, with an increase in frequency up to puberty. It is 

commoner in girls than boys at all ages and after puberty 80.90% ofcases 

are in females (Ustvedt, 1977). 

The characteristic feature of erythema nodosum is the presence of 

tender dusky-red slightly nodular lesions on the anterior surfaces ofthe 

legs, although lesions are occasionally also found on the anterior surfaces 

of the thighs, the extensor surfaces ofthe forearms and rarely on the face 

and breasts. The nodules are usually 5-20 mm in diameter, have ill- defined 

margins and may become confluent. They usually resolve over a week or 

two, the red color fading to purple and then brown, the brownish pigment 

often persisting for several weeks. Recurrent crops oflesions may occur 

(Leitch, 2000). 

4) Phlyctenular conjunctivitis: 

This condition reflects hypersensitivity to the tubercle bacillus, but 

unlike erythema nodosum is not necessarily confined to the first weeks of 

infection. It usually occurs within the first year (Price and McManus 

1943), is most often seen in children and is said to be commoner in those 

with poor social backgrounds and in non-European communities in Africa 

and America (Miller et al., 1963). The lesion is usually seen in one eye but 

may occur in both either simultaneously or successively. It begins with 

irritation, lachrymation or photophobia. The characteristic finding is ofa 

small 1-3 mm shiny yellowish or grey bleb at the limbus with a sheaf of 

29

....- I 

._. J 

f(fuew0/£iteroture 

dilated vessels runmng out towards it from the edge ofconjunctival sac 

(Seaton, 1989). 

5) Bronchiectasis 

Distention by mucus, caseous tissue or secondary infection beyond a 

bronchial stenosis may result in bronchiectasis, especially following lobar 

or segmental lesions (Roberts and Blair, 1950). The incidence is reduced 

by prompt chemotherapy and by the use ofcorticosteriod drugs (Gerbeaux 

et al., 1965). 

6) Broncholith 

Calcification III a pnmary focus, or more commonly in a lymph 

node, may later be extruded into a brorchus as a broncholith, which may 

declare itself with haemoptysis. Such broncholith may be seen through the 

bronchoscope, but are best left well alone (Leitch, 2000). 

7) Pneumonitis / collapse: 

These radiological appearances are due to lobar or segmental 

consolidation/collapse, and are associated with enlarged tuberculous lymph 

nodes at the hilum. The middle lobe is most often affected. The 

radiographic appearances may be due to collapse, inflammatory exudation, 

caseous pneumonia or any combination of these. Collapse is produced 

either by pressure of the lymph node on the bronchus or by the spread of 

tuberculosis granulation tissue into the bronchus with resultant stenosis or 

by discharge of caseous material from the lymph node through the 

bronchial wall (Seaton, 1989). 

30

-I 

..I 

1f[wwof£iterature 

The commonest cause is the inflammatory exudate, either monocytic 

or polymorphonuclear. Epithelial tubercles may also be present (Seal, 

1971). The exudate is probably due to the discharge ofcaseous material 

into the bronchial lumen with aspiration into a segment or lobe and a 

resultant exudative hypersensitivity reaction to the contained 

tuberculoprotein. Actual caseous pneumonia appears to be very unusual 

although small areas of caseation may occur (Crofton, 1954 and Leitch, 

2000). 

8) Pleural effusion 

Pleural effusion may sometimes accompany pnmary pulmonary 

tuberculosis in children under the age of puberty (Aderele 1980). Both 

pleural surfaces are then studded with tubercles and intensely inflamed. 

There is exudation of fluid and the pericardium may be similarly affected 

pleural and pericardial effusions tend to occur at or shortly after the time of 

Iry infection and are regarded as complications ofthe lry lesion (McNicol 

et al., 1995). 

31

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,t. I 

I 

¥rruew ofLiterature 

Predisposing Factors for TB (Seaton, 1989) : 

1) Nutrition: Malnutrition is believed to predispose to tuberculosis. 

2) Housing: Poor housing conditions with overcrowding such as still exist 

in many common lodging houses may contribute to the disease (Patel, 

1985 and Capewell, 1986). 

3) Occupation : Tuberculosis is commoner among the health service 

professions due to an increased risk of exposure to the disease 

(Festenstein 1984 and Geiseler et al., 1987). Workers in occupations 

giving rise to pulmonary silicosis such as masons, quarry workers, 

knife, grinders and coalminers have a greater risk of developing 

tuberculosis (Snider, 1978 ). 

4) Alcoholism: Tuberculosis is common in alcoholics, contributory factors 

probably being malnutrition, adverse social factors and a direct effect of 

alcohol on host defenses (Smith and Palmer, 1976). 

5) Cigarette smoking : Cigarette smoking is a principal cause of 

preventable diseases and premature death world- wide. It is implicated 

in a large number of diseases in the different body systems. Smoking is 

considered as the chief contributor to chronic pulmonary disease in 

adults (Alcalde et al., 1996 ). 

The studies that were carried out to explore the role of smoking in 

developing active IB revealed controversial results, probably because of 

the interference of other factors, such as age, alcohol consumption or 

socioeconomic status. However, a significant positive correlation was 

found between the degree ofsmoking and the release ofintracellular and 

extra cellular reactive oxidants in peripheral blood (Richards et al., 1989). 

33

Also, smoking was recognized as a toxic factor capable ofreducing host 

immune defense mechanism (Crofton et al., 1992), and reported to disturb 

oxidant lanti-oxidant homeostasis via attraction and stimulation of 

macrophages and neutrophils liberating oxidants (Mobasher, 1993). 

6) Steriod and other immunosuppressent drugs In 

immunocompromised patients, tuberculosis is most often the result of 

reactivation of a latent focus, but it is some times a primary infection. 

In such patients, tuberculosis is usually more sever and rapidly 

progressive than in immunocompetent patients, mortality is higher, and 

extrapulmonary involvement is more frequent (Barnes et al., 1991). 

In all immunosuppressed patients, the morphology oftuberculous 

lesions reflects poor host resistance. As, in corticosteriod- treated patients, 

tuberculous lesions show abundant caseation with little or no encapsulation 

or granulamatous reaction. Large numbers ofbacteria are usually present 

within the lesions (Dannenberg and Tomasbefski, 1998 ). 

7) Other diseases : Diseases associated with impaired cellular immunity 

such as Hodgkin's disease, leukemia, lymphoma and AIDS may 

predispose to reactivation (Lovie et al., 1986 and Handwerger et aI., 

1987). Diabetes mellitus potentiates TB through (Mobasber, 1993) : 

a) compromising the host defense mechanisms. 

b) Producing local tissue acidosis and electrolyte imbalance, that impair 

repair. 

c) Favoring the growth and viability of the bacilli by increasing sugar 

glycerol and nitrogenous substances in the blood 

34

.... - 

-i 

1ffviewof£iterature 

• N.B. 

Dannem berg and Tomaihefski (1998), considered the exogenous 

reinfection and Haematogenous spread ofdisease as adult tuberculosis. 

Clinical Features of post-primary pulmonary tuberculosis 

TB as: 

Leitch (2000), summarized symptoms presentations ofpost primary 

1) Symptom free discovered on routine radiography. 

2) Persistent cough ± sputum. 

3) General malaise 

4) Weight loss. 

5) Recurrent colds 

6) Pneumonia which proves to be tuberculous. 

7) Haemoptysis 

Mc Nicol et al. (1995), found that symptom, of TB unlike disease 

such as asthma where the symptoms are characteristic and the diagnosis is 

based on the history, the symptoms oftuberculosis are non-specific and 

generally do no more than point to the need for investigation. It is also clear 

that active disease may be present without any symptoms at all. Early 

diagnosis and treatment demand a high index of suspicion. 

The significance ofthe symptoms depend very much on the patient, 

the adolescent or young adult with a subacute illness with fever, weight 

36

loss and persistent productive cough almost certainly has the disease if he 

or she lives in an area where tuberculosis is endemic or if he or she is a 

member of a group that has a high incidence ofthe disease, such as some of 

immigrant communities in developed countries. The same symptoms in a 

native of a developed country would not immediately suggest the diagnosis 

and it would be more useful to consider other possibilities first (McNicol et 

al., 1995). 

Rossman and Mayock (1999), divided the symptoms into two 

categories constitutional and pulmonary. The most common constitutional 

symptom is fever, low grade at the onset but becoming marked ifthe 

disease progresses. Characteristically, the fever develops in the late 

afternoon and may not be accompanied by pronounced symptoms with 

defervescence, usually during sleep, sweating occurs. The classic (night 

sweats) other signs of toxemia such as malaise, irritability, weakness, 

unusual fatigue, headache and weight loss, may be present with the 

development of caseation necrosis and concomitant liquefaction, ofthe 

"'1 caseation, the patient usually notices cough and sputum, often associated 

LI I 

with mild haemoptysis. Chest pain may be localized and pleuritic. 

Shortness of breath usually indicates extensive disease with wide spread 

involvement of the lung and parenchyma or some form oftracheobronchial 

obstruction and therefore usually occurs late in the course ofthe disease. 

Physical signs 

There may be no physical signs in pulmonary tuberculosis even with 

relatively advanced disease but there may be pallor, a hectic flush or 

cachexia in sever disease (Leitch, 2000). Physical examination ofthe chest 

is often completely normal early in the disease. The principal finding over 

37

kfrwwo/£itertlture 

In 95 percent of localized pulmonary TB, the lesions be present in 

the apical or posterior segment ofthe lower lobes, although reactivation TB 

may affect any lung segment (Rossman, and Mayock, 1999). Although 

Poppius and Thomander (1957), found that the anterior segment ofthe 

upper lobe is almost never the only manifested area ofinvolvement. And 

David (1976), also found, if only the anterior segment ofthe upper lobe is 

affected, TB is extremely unlikely. 

The most common pattern ofreactivation TB is ofa focal air spaces. 

Consolidation in patchy or confluent nature. Frequently, linear densities 

connect to the ipsilateral hilum. Cavitation is common, but lymph node 

enlargement is rare. Because the lesions are usually chronic, destruction of 

tissue, fibrosis, calcification, and volume loss are usually present in the 

affected lung. The combination ofpatchy pneumonitis fibrosis calcification 

should always suggest chronic granulomatous disease, usually TB 

(Rossman and Oner-Eyuboglu, 1998). 

The cavities that develop in tuberculosis are characterized by a 

moderately thick wall, a smooth inner surface, and the lack of an air-fluid 

level. Cavitation is frequently associated with endobronchial spread of 

disease. Radiographically, it appears as multiple small aciner shadows 

endobronchial spread may produce extensive areas ofbronchopneumonia. 

(Rossman and Mayock, 1999). 

39

-- 

1(rVliwoj"£iteratttre 

Miliary Tuberculosis 

Miliary tuberculosis defines the presence of innumerable, tiny, 

discrete tuberculous lesions in the lungs and other organs owing to the 

seeding of these tissues by blood borne tubercle bacilli. The word (miliary) 

was used originally by John Jacob Manget in 1700 to denote the small size 

of such lesions, generally less than 2 mm in diameter or approximately the 

size of millet seeds (Sahn and Neff, 1974). 

Miliary tubercles may be oftwo types, depending on the resistance 

of the host. The compact (hard) tubercle with epithelioid cells and 

occasional giant cells (i.e. The proliferative type of lesion with or without 

caseous centers) and the loosely formed exudative type or (soft) tubercle. 

The exudative type contains more bacilli, which continue to multiply. This 

type usually undergoes early and complete caseation and progresses 

rapidly. Tubercles with mixed hard and soft characteristics are also 

common (Dannenberg and Tomashefski, 1998). 

Symptoms of miliary tuberculosis: 

The clinical presentation of miliary tuberculosis may vary 

significantly. Common symptoms include fever, weakness, anorexia, 

weight loss, and cough. Fever may be continuous but is often low grade 

and intermittent. Fever is common even among patients with underlying 

malignancy and in those immunosuppressed from cancer, chemotherapy or 

other causes. Less common symptoms include headache, abdominal pain, 

and dyspnea. Headache is ominous and often signifies the presence of 

tuberculous meningitis (Munt,1971 and Prout & Benatar, 1980). 

40

.----. i 

-,,-' .l 

Abdominal pam IS less specific but has been associated with 

involvement ofthe peritoneum or partial intestinal obstruction secondary to 

lymph node or omental involvement. Dyspnea, when present, may be the 

result of underlying lung disease or ofdecreased diffusing capacity 2ry to 

extensive interstitial tubercles (Williams et al., 1973). The symptoms are 

usually protracted, averaging between 3 and 15 weeks except, in 

immunosuppressed patients or those with serious co-existing disease in 

whom the onset may be more abrupt (Divinagracia and Harris, 1999). 

Physical signs: 

The signs most often present on physical examination III elder 

include fever, tachycardia, and adventitious sounds on pulmonary 

examination. Splenomegaly and lymphodenopathy, although common m 

children, frequent findings in adult. Hepatomegaly is common; studies 

from Groote shur Hospital in South Africa documented hepatomegaly in 

50% to 65% ofpatients, most ofwhom are adults (Maartens et aI., 1990). 

Choroidal tubercles are gray, gray-whit, or yellowish lesions usually less 

than one quarter the size ofthe optic disc and appearing within 2 mm ofthe 

optic nerve. They are usually multiple bilateral, with one to five found in 

the choroid of both eyes. Histologically they are similar to other 

tuberculous lesions and may be either caseating or non caseating 

granuloma (Massaro et aI., 1964). 

Cutaneous manifestations of miliary tuberculosis are discrete, dull 

erythematous macules and papules that are initially the size ofa pin head. 

They may become capped by tiny vesicles that after rupturing, have 

papules with a central crust. The lesions are most frequently localized on 

thighs, buttocks, genitalia, and extremities. They usually number no more 

41

or I 

than 20-30. More than 20 cases have been repeated and in one case, this 

cutaneous manifestation was the only sign of inadequate antituberculous 

therapy (Rietbroek et aI., 1991). 

Chest radiographs: 

The chest radiograph IS the single most important means for 

detecting miliary tuberculosis. The classic pattern of diffuse, bilateral, 

symmetrical, discrete, pinpoint 2 to 3 mm densities. Some ofthe apparent 

variations in the size ofthe lesions are due to densities in various depths of 

the lung parenchyma superimposed on the chest film. At first the tiny 

nodules may have faint, hazy outlines, but they sharpen as they grow 

larger. Often they appear more numerous at the central and basal areas of 

the film because of the greater thickness of the lung at these sites 

(Divinagracia and Harris, 1999). 

Classification of tuberculosis: 

Information derived from the history, physical examination, PPD 

-... _I tuberculin skin test result, chest radiograph, and microbiological studies is 

4-1 I 

used to classify TB case. Classification scheme used by the American 

Thoracic society and CDC is provided as (Gochuico and Bernardo, 

1997): 

Class 0 

Class I 

Class 2 

Class 3 

No exposure; no infection 

exposure; no infection 

Infection, no disease (i.e, +ve PPD reaction but no evidence of 

active TB) 

Disease, clinically active 

42

£(ww0L£iterature 

Class 4 

Class 5 

Disease, not clinically active (i.e. evidence ofprevious TB or 

following therapy for tuberculous disease). 

Suspected disease, diagnosis pending 

Classification ofa given case allow stratification that aids in that aids 

In the monitoring of treatment and the development of epidemiologic 

profiles by Public health officials. 

43

it 

fifuew oj"£iterature 

Diagnosis of pulmonary TB 

The diagnosis of pulmonary tuberculosis is not easy. Clinical signs 

are non specific and may be confused with many chest diseases. 

Radiological changes increase the suspicion of pulmonary tuberculosis. 

Examination of the sputum smear is helpful and has a high positive 

predictive value (Gordin, 1990). 

• Chest radiograph in pulmonary TB 

The chest radiograph remains the most widely used and the most 

valuable tool in the diagnosis of pulmonary TB. Radiographic findings 

accurately reflect the pathologic process that occurs in the development of 

primary and reactivation TB (try TB traditionally been a disease ofinfants 

and children) (Bloch et aI., 1989). 

In patients who have signs and symptoms suggesting pulmonary TB 

standard posterior-anterior and lateral radiograph of the chest should be 

obtained. Apical, lordotic or oblique views may aid in visualizing lesions 

obscured by bony structures and the heart. Bronchography may be useful in 

the definition of bronchial stenosis or bronchiactasis (Bass et aI., 1990). 

The traditional appearance ofreactivation TB in the chest is a focal 

infiltrate and/or cavity in the apical or posterior segment ofan upper lobe 

or perhaps in the superior segment ofa lower lobe. While these traditional 

concepts of TB are still valid, a significant change in the pattern of 

pulmonary TB has occurred in the past 30 years, with a much greater 

incidence of primary TB in adults. This change was first pointed out in 

1977, that noted a high incidence of nontraditional radiographic finding in 

adults with TB (Khan et aI., 1977). These non traditional findings reflected 

44

A 

I High resolution computed tomography (HRCT) 

I 

- 

-. . 1 

I 

1 

I 

I 

"A' 

a 

HRCT, The terms used to interpret HRCT findings in the active cases by 

Hatipoglu et al., (1996) 

1) Centrilobular nodule or linear structures : Well defined lesions 1-4 mm 

thick, separated by more than 2mm from the pleural surface or 

interlobular septa. 

2) " Tree in bud " appearance : A branching linear structure with more 

than one contiguous branching site. 

3) Macronodule : A nodule 5-8 mm in diameter 

In addition ,consolidation (lobular ,subsegmental ,segmental ,lobar ) 

bronchial wall thickening, cavitation (single, multiple), emphysema , 

bronchovascular distortion, fibrotic changes, pleural thickening, 

bronchiectasis, lymphadenopathy, parenchymal calcification pleural 

effusion, ~niliary nodules, and ground glass appearances were noted. 

Skin tests 

I a- Tuberculin test:- 

Tuberculin skin test is the standard method for identifying persons 

infected with M. tuberculosis. (ATSICDC, 1990). 

Sensitivity, specificity and positive predictive value of the tuberculin 

1 skin test (Blach, 1998). Although the tuberculin skin test is now the only 

method for detecting M. tuberculusis infection, the test is neither 100 

percent sensitive nor 100 percent specific. Sensitivity is a test's ability to 

correctly identify persons who have a condition (e.g Those infected with.

An induration of 2 1Omm is classified as positive in all persons who 

do not meet any of the above criteria but who belong to one is more of the 

following groups having high risk for TB. Injected-dmg users know to be 

HIV seronegative persons who have other medical conditions that have 

been reported to increase the risk for progressing from latent TB infection 

to active TB, including diabetes mellitus, conditions requiring prolonged 

high-dose corticosteroid therapy and other immunosuppressive therapy 

(including bone marrow and organ transplantation), chronic renal failure, 

some hematologic disorders (e.g. leukemias and lymphomas). Other 

specific malignancy (e.g. carcinoma of the head or neck). Weight loss of 

210 % below ideal body weight, silicosis, gastrectomy and jegunoileal 

bypass. Residents and employees of high risk. Children < 4 years of age or 

infants, children and adolescents exposed to adults in high-risk categories. 

Congegate setting: prisons, jails, nursing homes and other long- 

tern1 facilities for the elderly, l~ealth care facilities (including some 

residential mental health facilities), and homeless shelters. 

An induration of > 15mm is classified as positive in persons who do 

not meet any of the above criteria (Bloch, 1998). 

b- Medical research council test: 

A new diagnostic test for TB has been described that can be done as 

two skin tests, or from blood samples based on the reaction to 38.A and 

38.G peptide of 38 kDa. Reaction to peptide 38.A identifies people who 

have had BCG vaccination or previous TB, or those who have active TB. 

Reaction to 38.G identifies people the first two of these categories but not 

the third, as people with active TB lose the T-cell response to it. Thus, the

!fffwwoj"£iterature 

smaller volumes. Quality and quantity of sputum specimens were assessed 

independently. The likelihood of a positive smear is increased three-folds, 

and that of a culture two folds when sputum quality is good, irrespective of 

sputum quantity. In specimens of sufficient quantity, both smear and 

culture positivity are doubled when compared to specimens with a volume 

of less than 3m!. More than 80 % of positive smears and cultures are 

originated from specimens of good quality and of sufficient quantity. 

Macroscopical evaluation of sputum specimens contributes to optimizing 

laboratory diagnosis, and may have a financial impact on the cost involved 

in the diagnosis ofpulmonary TB (Weyer, 1990 and kramer et aI., 1990). 

2) Sputum induction: 

There are several methods for obtaining sputum from the cooperative 

patients with non productive cough. One ofthese methods is the inhalation 

of warm, aerosolized hypertonic (5 % -10 % ) saline which irritates the 

lungs enough to induce both coughing and the production ofa thin, watery 

specimen. After induction, patient may cough and produce additional good 

quality specimens, which should also be submitted to the laboratory (ATS, 

1990). It has been concluded that in addition to obtaining sputum from 

patients who are unable to expectorate, sputum induction may have a useful 

role in improving the care detection rate ofsmear positive pulmonary TB, 

particularly in areas where facilities for more invasive and expensive 

techniques such as fibreoptic bronchoscopy are not available (Parry et aI., 

1995). 

3) Bronchoscopic specimens: 

When neubulization is ineffective or an immediate diagnosis is 

needed bronchoscopy is the next best choice because this procedure 

51

provides additional material for study (Washings, bmshings, and biopsy 

specimens) and can help one obtain rapid diagnosis of tuberculosis (Zheng 

and Roberts, 1999). 

Wallace et al. (1981), found that in 41 patients proved to have TB, 

cultures of specimens, taken during fiberoptic bronchoscopy, were positive 

in 39 cases. The post-bronchoscopy sputum was the most helpfull specimen 

in the diagnosis of pulmonary tuberculosis in patients with repeated 

negative sputum by direct smear and in whom sputum could not be 

produced (Abd-El-Hakim et al., 1987). Also Osman et al,, (1995), 

concluded that fiberoptic bronchoscopy is a valuable diagnostic tool for 

pulmonary mycobacterial infection. 

The local anesthetics used during fiberoptic bronchoscopy may be 

lethal to M. tuberculosis, so specimens for culture should be obtained with 

a minimal amount of anesthesia. However irritation of bronchial tree during 

the fiberoptc bronchoscopy procedure will frequently leave the patient with 

productive cough. This post-bronchoscopy sputum was the only source of 

positive inaterial in some study (Rossman and Oner- Eyuboglu, 1998). 

4) Gastric lavage : 

Gastric lavage may be necessary for children and some adult patients 

who are unable to expectorate sputum, gastric lavage is a specimen of 

alternative choice, although it my not be as good as induced sputum for 

culturing (Pomputius et al., 1997). Some of gastric contents should be 

aspirated early in the morning, after the patient has fasted at least 8-10 

hours, and preferably while the patient is still in bed (ATS, 1990).

I _ 

gfrwwof£iterature 

If the stomach is empty about 20ml ofsterile water is introduced 

slowly through the tube and withdrawn. Gastric specimens must be 

processed immediately since the acidity and enzyme content ofthe gastric 

juice are harmful to the mycobacteria. If transport will be delayed more 

than 4 hours, the specimen should be neutralized with disodium phosphate 

or sodium carbonate buffer salt to a pH of7.0. In children with suspected 

pulmonary TB, gastric lavage yielded a positivity of 81.5 % for AFB 

beside its satisfactory results, gastric lavage technique was well accepted 

by mothers and health staff, and was very cost-effective (Migliori et al., 

1990). 

5) Laryngeal swabs: 

Laryngeal swabs are an alternative to gastric lavage. They are 

simpler to perform and less uncomfortable for the patient. The operator 

should be gowned and masked and the swabs taken in pairs. The first swab 

usually makes the patient cough and the second often collects the better 

specimen (Seaton, 1989). 

6) Other specimens: 

In a case of extrapulmonary TB, it is occasionally necessary to 

examme specimens other than pulmonary secretions as, urine, CSF, joint 

and pleural fluids, and tissue biopsy material (Kubica et al., 1989). 

• Processing of specimens 

In order to recover mycobacteria from specimens that contain large 

numbers of normal flora, decontamination of the specimen is needed. 

Mycobacteria are slow growing and have an extended generation time (20 

to 22 hours) compared with that ofcommon bacterial flora (40 to 60 min), 

53

f 

2) The 2 nd role for the smear is m monitoring the patient's response to 

therapy, if a patient is grossly positive at the start oftreatment 

The most commonly used technique is the Ziehl-Neelsen stain, this 

necessitates the use of hot carbolfuchsin followed by decolorization with 

acid and alcohol, and counter staining with methylene blue. The bacilli 

appear as red rods on a blue back ground. When large numbers ofsmears 

have to be examined staining with auramine followed by fluorescence 

microscopy is more rapid. However, this can give rise to false positive as a 

result of artifacts and it is advisable to check all positive with Ziehl 

Nee1sen stain. The same slide can be over stained by the Ziehl-Neelsen 

technique (McNicol et ai, 1995). 

Procedures ofacidfast staining are oftwo general types: 

• Z.N. is a hot acid-fast stain in which the fixed smears are poured with 

carbol-fuchsin and gently heated till the steam rises. The smears are 

decolourized with 25 % sulfuric acid and 95 % alcohol. After washing 

with water the smears are counter-stained with 0.1% methylen blue, 

then washed and dried for examination (Rao et al., 1982). 

• Kinyoun is a cold acid fast stain in which, kinyoun's carbolfuchsin 

with basic fuchsin and phenol are used in concentration higher than that 

of Z.N. stain. Acid alcohol was employed as decolourizer, while 

malachite green as the counter stain (Levy et aI., 1988). 

Wilson et al. (1981), reported that, the fluorochrome method can be 

-.t 1 used to facilitate and enhance rapid examination of smears for 

mycobacteria. Also Bates et al. (1982), found that, in fluorescence 

microscopy. The number oforganisms has been estimated to average 3.65 

56

1 

-I 

times the number seen with the Z.N.stain. Mobasher et at (1984), reported 

the advantages of the fluorescent microscopy as follow: 

a) The bright fluorescent bacilli are much more obvious owing to increased 

contrast against the dark background . 

b) The bacilli can be recognized at a lower magnification. 

c) The time required to search a smear effectively is much reduced. 

d) It is difficult or impossible with Z.N. method to detect bacilli towards 

r: the periphery ofthe field, however the fluorescence microscopy, the out 

-;;. J in tissue. 

1 

of focus images of the stained organisms can be detected even at the 

extreme edges ofthe field. 

David et aI. (1989), described nachtblau stain which stained the 

AFB blue. They used neutral red or pyronine as a counter-stain. They 

claimed that the blue bacilli against the red or yellow back ground are 

easier to detect. Thomas et al. (1988), used silver salts to stain the M.T.B. 

Toman (1979), found that false positive acid-fast smear may result 

from: 1) The presence ofacid fast particles other than tubercle bacilli such 

as certain food particles like waxes and oils, saprophytic AFB like M. 

Kansasii or nocardia species, spores ofbacillus subtilis, fibers, pollens and 

scratches on the slide. 

2) Contamination through accidental transfer ofbacilli from one positive 

+J smear to another negative one. 

57

1 

I 

rJ(fview o[£iterature 

On the other hand, false negative acid-fast smear may be due to 

inadequate. Collection of sputum, Storage ofspecimen, Preparation ofthe 

smear, Staining of slides and Examination ofthe smears. 

2) Cultivating M. TB 

The definitive diagnosis of mycobacterial disease demands that the 

causative agent be recovered on culture medium, and identified by using a 

number ofdifferential in vitro tests.(Zheng and Roberts, 1999) 

Kent and Kubica, (1985), defined The ideal medium for isolation of 

mycobacterial should: 

I) Support rapid and luxuriant growth of small numbers ofmycobacteria 

2) Permit preliminary differentiation of isolates on the basis ofpigment 

production and colony morphology. 

3) Inhibit the growth ofcontaminants. 

4) Be economical and simple to prepare from readily available ingredients 

and 

5) Enable the performance of drug susceptibility tests 

Many different media are available for cultivating mycobacteria, most 

are variations of either egg-potato base (Lowenstein-Jensen Medium and 

American Thoracic Society Medium) or serum agar base (Middle Brook 

7HIO and 7HII) media. Each medium has advantages and disadvantages, 

,.f.l and they compliment each other, the advantages ofegg media as L.T media 

are that, they can be stored in refrigerator for several months, less likely to 

become contaminated during preparation, and also yield a greater number 

58

•r 

?f(wwofLiterature 

The major drawbacks of the BACTEC system are the use of 

radioactive substrates and the necessity ofspecialized instrumentation. It 

has also suffered from problems with needle-heater defects, leading to 

cross mycobacteria ofbottles (Murray, 1991). 

A more recent addition to the culture alternatives has been the 

adaptation of the septi-chek system for mycobacteriology. This system 

employs a middle brook broth based system with a paddle that has 

chocolate agar, middle brook agar, and an egg-based medium similar to L.J 

agar. Several studies have demonstrated the recovery in this system to be 

comparable or superior to that with BACTEC, and better than that with a 

conventional medium. It can also, be combined with an additional medium 

to increase overall recovery. The speed ofrecovery does not appear to be as 

fast with the BACTEC system, but it is faster than with conventional 

media. This system does not use radioactive substrates and requires no 

instrumentation (Whittier et aI., 1992). 

3) Animal inoculation 

With the more refined culture methods available today, and with the 

processing of multiple specimens from the same patient, it is not necessary 

to resort to animal inoculation. However, in few rare instances, guinea pig 

inoculation may be used when (ATS, 1990) :- 

A) Specimens are consistently contaminated on culture. 

b) Specimens are positive on microscopy but repeatedly negative on culture 

or 

c) Specimens are aseptically collected where organisms may be few in 

number, and every attempt is made to establish the diagnosis. 

61

j - 

Immunological techniques in the diagnosis of mycobacterial 

infection 

Engvall and Perlman (1972), were the first who described the 

ELISA, they reported that it is very sensitive and simple method for 

detection and measurement of antibodies in sera. Nassau et aI. (1976), 

used ELISA for diagnosis of tuberculosis using concentrated culture filtrate 

of M.TB using concentrated as antigen. They found that 84% of sputum 

positive cases were positive by that test and only 8% false positive 

reactions were observed. They also concluded that serum dilution of I: 100 

gave good discrimination between sera from tuberculous patients and 

controls. They reported that ELISA proved to be satisfactory for detection 

of antimycobacterial antibodies. They postulated that the use of specific 

antigen should increase the specificity ofthe test. 

The major limiting factor in the serodiagnosis of tuberculosis is that 

no single species specific antigen of mycobacterium tuberculosis has been 

shown to be significantly elevated in all cases ofactive tuberculosis. On the 

contrary, most ofthe antibody response in tuberculosis is directed towards 

those antigens common to all mycobacteria and, to some extent, present in 

other genera. Sensitive assays show that virtually all individuals have such 

antibodies (Grange et aI., 1980). In spite of that many research 

laboratories have demonstrated that ELISA measurement ofIgG antibody 

to mycobacterial antigen can be used for the serologic diagnosis of 

tuberculosis (Shim et aI., 1989). 

Other serodiagnostic techniques including radio-immunoassay (RIA) 

and inhibition of monoclonal antibodies, had less extensive studies but 

appear promising (ATS, 1990). 

62

Cigarette smokers were categorized into 3 groups. Mild, moderate, 

and heavy smokers, according to the number ofpack years (Miller et 

at, 1982) Mild < 20 pack years. Moderate 20-49 pack years and 

heavy >49 pack years) where pack years calculated as follow: 

Pack year = No ofcig! day X duration in years 

b- History ofpresent illness: 

Including general and respiratory symptoms (cough, expectoration, 

r chest pain, dyspnea and chest wheezes) (Mobasher, 1993). Leitch (2000), 

20 

suspected plumonary tuberculosis on clinical grounds when (persistent 

cough with or without sputum, haemoptysis, general malaise, weight loss, 

and recurrent colds and symptoms free discovered on routine radiograph) 

were present. Weight loss was defined as greater than 4.5kg or 10% of 

ideal body weight within last 6 months (Cohen et at, 1996). Dyspnea was 

classified from (grade 0) to (grade III) by Mobasher (1993). 

(1) Grade 0 : dyspnea on extraordinary effort. 

(2) Grade I : dyspnea on ordinary effort. 

(3) Grade II : dyspnea on slight effort. 

(4) Grade III : dyspnea at rest. 

Some symptoms were stressed upon chest pain were asked about the 

nature and site. Hamoptysis was classified into degrees by Muren, (1982), 

and Mobasher (1993): mild, moderate and severe. 

"'Mild = occasionally blood - streaked sputum, 

'" Moderate = persistent blood streaked sputum and frank blood, 

69

"'Sever or massive = coughing up 150 cc more at once, 400 mIl or more of 

.. - blood within 3 home or 600 ml of blood within 24 hours 

.J 

r-- 

(c) Past history: 

Past history of medical importance were asked for stressing the 

importance ofpredisposing factor for TB e.g D.M. and past history oftreatment 

ofcorticosteriod and other immunosuppressive therapy (ATS, 1990). 

Past history suggestive of TB diseases e.g. : acquired hip joint 

disease leading to limping, sinus, recurrent ischiorectal abscesses, port's of 

spine, contact to known TB-case and pervious thoracithesis or 

lymphadenopathy (Mobasher, 1993). 

(2) Full clinical examination: - 

General and local examination with special concern about facial 

appearance toxic face or pallor and body built and scar ofBCG. 

Local chest signs as post-tussive rales and bronchial breathing as 

these are the principle finding oftuberculosis specially in the apeces of the 

lungs (Rossman and Mayock, 1995). 

(3) Radiological examination: 

A)Plain CXR: 

Postero-anterior view offull-sized ordinary CXR were done to show 

the radiographic features suggestive ofpulmonary T B, opacities mainly in 

the upper zones, patchy or nodular opacities, presence ofcavity or cavities, 

presence of calcification, bilateral opacities especially if in upper zone(s) 

and opacities that persist after several weeks (and thus are less likely due to 

70

acute pneumonia (Leitch, 2000). The National TB Association of the 

USA (1961), classified radiographic features into three groups: 

(1) Minimal: 

Lesions of slight to moderate density, with no demonstrable 

cavitation. They may involve a small port of one or both lungs, but the total 

extent, regard less ofdistribution, should not exceed the volume of lung on 

one side that occupies the space above the second chondrosternal junction 

and the spine of the fourth or the body ofthe fifth thoracic vertebra. 

(2) Moderately advanced: 

Lesions may be present III one or both lungs, but the total extent 

should not exceed the following limits disseminated lesion of slight to 

moderate density that may extend throughout the total volume ofone lung 

or the equivalent in both lungs; dense and confluent lesions limited in 

extent to one-third the volume of one lung; total diameter of cavitation, if 

present, must be less than 4 em. 

(3) Far advanced: 

B) CT. 

Lesions more extensive than moderately advanced. 

C.T. was done to exclude other possible associating agents e.g 

tumour, 15 patient did C.T to exclusion of malignancy and after 

microbiological examination, there were 12 active TB. smear +ve and 3 

cases were smear -ve. 

71

-. -I 

(4) Tuberculin skin test: 

Tuberculin test was done to support the establishment of diagnosis in 

cases with negative smear. It was performed by injecting 5 tuberculin units 

(Tu) in O.lml of PPD intradermally (Mantoux technique) in the volar 

aspect of the left forearm. Special 1 ml disposable syringes graduated in 

hundredth of milliliters were used with 26 gauge 10 mm needles of short 

bevel. A separate sterile syringe and needle were used for each person 

tested. A little more than 0.1 of tuberculin was then removed and the 

volume subsequently adjusted to exactly 0.1 ml by ejecting the extra 

solution, and then slowly ejected. The injection to be valid-should raise a 

flat, anearnic wheal with pronounced pits and a steep borderline. The test 

was read after 48 and/or 72 hours. The reading was limited to a single 

aspect ofthe reaction, the induration. The site was carefully palpated and if 

an induration was present, its limits were deter mined and its largest 

transverse diameter was measured in millimeters by using soft flexible 

transparent roller calibrated in millimeters. Positive tuberculin test was 

indicated if the indurated area was 10 mm or more (ATS, 1990 and 

Arnadottir et al., 1996). 

(5) Routine investigations: 

Complete blood picture (to detect any heamatologic disorders as Hb, 

and lymphocytic percentage). Erythorcyte sedimentation rate (ESR) as its 

elevation is compatible with tuberculosis, post prandial blood sugar (for 

detection ofdiabetic risk) (Rossman and Mayock, 1995). 

72

,"--- - 

(6) Mycobacterial investigations: 

These were done in the mycobacteriology laboratory, Microbiology 

and Immunology Department Faculty of Medicine Zagazig University. 

A-Samples: 

Sputum collection: The patients were given clean plastic containers 

and instructed to give morning sputum after deep coughing into the 

containers. The sputa were transported without delay to the laboratory. 

Three successive sputum samples were collected for each negative cases. 

In patients who did not produce sputum, the specimens were induced 

sputum samples taken with an air- powered neublizer with 0.45% Nacl 

solution for 15 minutes (Cohen et al., 1996). 

If induced sputum was failed or a mount was unfit for diagnosis and 

so fiberoptic bronchoscop was done and this occurred for 15 patients 

bronchoscopic lavage was taken and BAL was sent for laboratory. 

(Funahashia et aI., 1983). 

All previous specimens were subjected to direct Kinyoun's staining 

after decontamination and concentration. 

B- Specimen processing: (Digestion decontamination method) (Ratnan 

• Reagent and equipment. 

- Sodium hydroxide 5% solution 

't-- - Nsacetyl L. cystein (NALC) 

- Phosphate buffer (pH = 6.8) 

- A plastic centrifuge tube (50 ml) 

and Marchy,1988). 

73

- Centrifuge. 

- Vortex Mixer. 

- Phenol can 

- Electric slide warmer 

• Procedure 

A morning sputum sample or bronchial lavage was transferred to 50 

ml plastic centrifuge tube, and an equal volume ofNALC-NaOH solution 

was added and mixed well. The tube was allowed to stand for 15-18 

minutes (not more than 20 minutes) at room temperature for 

decontamination. Then, the sample was diluted to a 50 ml volume with a 

sterile 0.067 M phosphate buffer saline (PBS), pH 6.8 to neutralize NaOH 

and centrifuged at 2800 rpm at room temperature for 15 minutes. The 

supernatant was poured off into a beaker containing 10% phenol, whereas 

the deposit was resuspended in 2 ml of a sterile 0.2% bovine serum 

albumin (BSA) in physiological saline (pH 6.8), then spread on the middle 

2/3 of glass slide, after drying the slide on electric slide warmer at 65 C for 

2 minutes (Ratnan and Marchy,1988). 

c- Kinyoun '8 staining technique: It's modified Z. N (cold method) in 

which: 

1- high concentration ofcarbol fuchisin . 

2- devoid of direct heat which has lethal effect ofTB bacilli, 

3- The concentration of specimen by centrifugation conducted in this 

method increase the capacity to detect mycobacteria (Saceanu et al., 

1993 and Fodor, 1995). 

74

Name: 

Sex: 

Residence: 

Smoking: 

Duration: 

Passive: 

Current smoker: 

Other diseases (known diagnosis) : 

Local 

1- Cough 

2- Expectoration 

3- Haernoptysis 

Dry 

Productive 

Duration 

Periodicity 

Sheet ofTB 

Personal history 

Night 

Day 

C/O 

Age: 

Mari tal state : 

Occupation: 

Type : 

Degree of smoking: 

Ex. Smoker: 

Other: 

Amount 

Colour 

Odour 

Aspect 

Duration of expectoration 

Mild 

Moderate 

Severe 

Number ofattacks 

Duration 

79

J.. 

r 

RESULTS

i 

r- 

value 92.80/0. Tuberculin test sensitivity was 75.3 and specificity was 50% 

+ve predictive value was 87.9%. 

Table (17) shows that, specificity and +ve predictive value was 

improved when measured for combined symptoms and CXR and tuberculin 

test as for (Cough + expectation and weight loss) combined specificity was 

78.1% and +ve predictive value of90.6% and when combined with typical 

CXR was 90.6%, 94% respectively while combined manifestations that 

only presented in smear +ve cases had a specificity, sensitivity, negative 

and positive predictive value of 100%, 7.8%, 18.4%. and 100%. 

Tables (18, 19) show that, symptoms presentation among smear +ve 

cases for AFB with special references to age group < 20y, 20-40y and> 40 

there were non significantly difference in cough, chest pain, fever and 

weight loss and another were significantly higher in > 40y as in chest 

wheeze, dyspnea and night sweats and anorexia P < 0.05 and expectoration 

was significantly higher in age group 20-40y and lower in < 20y (58.3%), 

p= 0.0001

1 r-- 

.....- 

..., I 

p= 0.0002, shortest mean duration was haemoptysis = 1.3m ± 0.71 and 

longest chest wheezes 13.97 M ± 15.9 in smear +ve for AFB. 

(Table 22), show that mean duration of general symptoms among 

smear +ve and smear -ve cases for AFB there was highly significant 

difference as regard duration offever p= 0.001, shortest mean duration was 

fever = 1.38 M ± 0.55 M and longest was anorexia 2.8 M ± 1.6 M in smear 

+ve for AFB versus 2.05 M ± 1.8 M and 2.1 M ± l,SM in smear -ve cases 

for AFB respectively. 

(Table 23) shows that, III smear +ve cases for AFB duration of 

respiratory symptoms as percentage presentation per month before 

diagnosis, chest pain and haemoptysis seeked medical advise through 1s 

month were 69.8%, 70% respectively. While the symptoms (Cough 

expectoration and dyspnea) mostly represented in 1-3 months with high 

percentage. 42.7%,43.3%,36.4% respectively but 

Table (24) shows that, in smear +ve cases for AFB duration ofnon 

respiratory symptoms fever, night sweating, weight loss and anorexia, no 

any patients presented beyond more than 6M and fever night sweats 

represented early through 1st month 64.5%, 56.50/0 and weight loss and 

anorexia 1-3 month 55% and 54.8% respectively. 

Table (25) shows, a high significant difference of typical CXR 

presentation in smear +ve 83.7% than smear -ve 59.4 % for AFB P = 0.006 

far advanced lesion was significantly higher in smear +ve 48.1 % for AFB 

than in smear -ve 25% for AFB, P = 0.001 and mild lesions was 

statistically significant in smear -ve than in smear +ve, P = 0.03. 

84

Table (26) shows that, there was high significant difference between 

" smokers with typical CXR in smear +ve than in smear -ve for AFB, P= 

0.001, among smear + for AFB typical CXR smoker 85.5% and in smoker 

81.4% but there is a high difference between typical and atypical in smoker 

smear +ve patients 85.5% and 14.5% respectively, and also there was non 

significance in smear -ve for AFB p> 0.05 typical smoker CXR in smear 

ve 60% and non smoker 59.1% and there is no significance increase in 

smoker smear -ve as regard typical and atypical presentation 60%, 40% in 

smear +ve smoker for advanced = 47.7% and 30% in smear -ve for AFB. 

L 

1"-- Minimal lesions in smear +ve 20%, 50% in smear -ve for AFB. 

. "< 

Table (27) showed positive significant correlation between smoking 

degree and CXR extent r = 0.43, P < 0.05. 

Tables (28, 29) show that, positive significant correlation between 

haemoptysis and CXR extent r = 0.49 P = 0.001 and also, there was 

significant association between haemoptysis and CXR (Cavitation and 

extent), cavitary haemoptysis in smear +ve represent 66.3% and in smear- 

ve for AFB 15.4%, P = 0.001. 

Table (30) shows that, CT findings in smear +ve and smear -ve for 

AFB were non significant P > 0.05 in smear -ve for AFB nodular single 

cavity, multiple small cavities and pleural effusion was 0% and represents 

33%, 33%, 16.5% and 25% in smear +ve for AFB. Calcified nodule was 

16.75% in smear +ve and 66% in smear -ve and consolidation was 41.7% 

in smear +ve and 33% in smear -Yeo 

Table (31) shows that, correlation between CT and X- ray finding it 

was non significant P > 0.05. Consolidation 40%, calcification and single 

cavity represented in both CXR + CT by 26.7% bronchial dilation not 

85

\ P = 0.001 mean number of 1 st hours (67.5 ± 29.2) mm in smear +ve cases 

- 

J 

I 

d 

2 11 

J r'-- 

I 

hours (107.6 ± 34.4) mm and lymphocyte percentage also were 

significantly higher in smear +ve for APB P = 0.03 and mean percentage 

(28.8% ± 11.750/0). 

Table (39) showed a negative significant correlation between ESR 

and Hb content, r = - 0.22, P < 0.01. 

87

2 -?=,! 

--- 

M>.i!ll . - -.*-r-.*,y-- . 1 

- -. 

u:,:-,* G*-+&L-, -- 

. i 

+- ..VX .- 

-- -- - - - A:,: ;' 

\ .,, -dLx, . - I 1 

\, !:T-&% hi

1 

(6) Prevalence of cough among smear +ve and smear -ve case for AFB 

Subject Smear +ve for AFH Smear -ve for AFB Xl P 

Symptom No = 154 0/0 No =32 % 

Cough (with) 150 97.4 20 62.5 41.05 O.OOIHS 

Without 4 2.6 12 37.5 

(7) Prevalence of expectoration among smear +ve and smear -ve cases 

for AFB. 

Subject Smear +ve for AFB Smear -ve for AFB Xl P 

Res. Symptom No % No % 

Expectoration with 134 87.0 16 50 23.25 O.OOOlHS 

Without 20 13.0 16 50 

(8) Prevalence of dyspnea among smear +ve and smear -ve cases for 

AFB with special reference to its grade. 

Dyspnea I II III Xl P 

Smear +ve No: 77 46 31 0 

Percentage 

50% 59.7 40.3 0.0 0.054 

5.84 

Smear -ve No: 15 10 4 1 

Percentage 

48% 66.7 26.7 6.7 

l)()

(12) Prevalence of non respiratory symptoms among smear +ve and 

smear -ve cases for AFB. 

Subject Smear +ve for AFH Smear -ve for AFB X 2 

Symptoms No % No % 

Fever with 93 60.4 17 53.1 0.58 0.44 

Without 61 39.6 15 46.9 

Night sweating with 62 40.3 13 40.6 0.0 0.97 

Without 

92 59.7 19 59.4 

Weight loss with 80 51.9 10 31.4 3.27 0.04 S 

Without 

74 48.1 22 68.6 

Anorexia with 42 27.3 8 25.0 0.07 0.79 

Without 112 72.7 24 75.0 

l)J 

P

'd 

1 

re, 

4 

S 

re, 

V1 

u 

-. 

6 

0 

s 

W 

B 

CD 

s 

7 

+ 

*C 

re,

.iIi-'· . (13) Distribution of combined clinical symptoms (Cough, expectoration 

and weight loss) among smear +ve and smear -ve cases for AFB. 

Smear +ve for AFB Smear -ve for AFB X 2 

Comb clinical No(154) % No(32) % 5.47 0.019S. 

with 68 44.2 7 23% 

without 86 55.8 25 77% 

(14) Distribution of combined clinical manifestation (Cough, 

expectoration and weight loss) plus typical CXR presentation in 

smear +ve and smear -ve cases for AFB. 

Combined clinical Smear +ve for AFB Smear -ve for AFB X 2 

+ typical CXR 

NO 0/0 NO 0/0 

Yes 47 30.5 3 9.8% 6.03 

No 107 69.5% 29 91.2% 

P 

P 

0.014 

(IS) Comparison between smear +ve and smear -ve cases for AFB as 

regard presence of combined manifestations ( Cough, Haemptysis, 

dyspnea, fever, loss of weight, typical CXR presentation and +ve 

tuberculin skin test). 

Smear +ve for AFB Smear -ve for AFB X 2 

No % No % 

Yes 12 7.8% 0 0% 2.67 0.1 NS 

No 142 92.2% 32 100% 

95 

S 

P

Expectoration 

Chest pain 

Haemoptysis 

Dyspnea 

Night sweats 

,,- -- 

Fever , 

.-?A: 

Anorexia I 

....... 

X 

>

(17) Specificity and sensitivity of combined symptoms plus CXR and 

tuberclin skin test among smear +ve cases for AFB. 

Combined symptoms Sensitivity Specificity +ve predictive value -ve predictive value 

Cough, expectration and weight loss 44.2 78.1 90.6% 22.5 

Previous symptoms and typical CXR 30.5 90.6% 94 21.3% 

Cough, haemptysis, dyspnea, weight 7.8 100 100 18.4 

loss, fever, typical CXR and positive 

tuberculin

i 

I*... [.;'!I 

7 $,' 

\... ..y,. 

< , . 1 

>- .-

....' ." 

T- 

I 

(23) Duration of respiratory symptoms among smear +ve cases for 

AFB. 

s 1M s3M s6M s 12M ;:::IY 

No 150 41 64 24 9 12 

Cough 97.4% 27.5 42.7 16.0 6,0 8.1 

Expect No 134 31 58 23 9 13 

87% 23.1 43.3 17.2 6,8 9.8 

Haemptysis No 80 56 23 1 0 0 

53% 70.0 28,8 1.3 0.0 0.0 

Chest No 45 7 12 6 0 20 

wheeze 

29.2% 15.6 26.7 13.3 0,0 44.4 

Chest pain No 53 37 12 2 1 1 

34.4% 69.8 22.6 3.8 1.1 1.9 

Dyspnea No 77 26 28 6 7 10 

50% 338 36.4 7.8 9.1 13.0 

103

'·'--1 

38) Mean ± SD of laboratory investigations among smear +ve and 

smear -ve cases for AFB. 

Smear +ve for AFB Smear -ve for AFB t P 

Mean SD Mean SD 

lsth 67.5 29.2 37.9 19.1 5.48 0.001 

ESR 2ndh 1076 34.4 682 26.5 6.1 0.001 

HB G/dl 10.6 19 11.0 2.04 1.14 0.25 

WBC XIOJ/mm 7.6 3.6 86 3.8 1.14 0.14 

'-_. 

Lymphyt % 288 II 75 24.0 10.7 2.12 0.03 sig. 

.'-- 

39) Correlation between ESR (mm) and haemoglobin (gm/dL). 

r P 

ESR versus haemoglobin -0.22

--- I 

.--- 

120 

100 • 

• • 

- • • • 

80 •• • • 

60 • • i. .. 

40 • 

20 • • 

• ... 

0 r---- .....,._--- -----------r- ----,----- ··_---1---- • 

----1 

0 2 4 6 8 10 12 14 16 

Fig. (7) : Correlation between HB (g/dl) and ESR (mm). 

112

DISCUSSION

person with cough, chest pain for one month or more, or blood spitting at 

any time confined to home for one month or more on account of illness. 

Teklu (1993) has used the definition oftuberculosis "suspect" as patient 

with: 1- Cough and haemoptysis for 2 weeks. 

2- Cough and any other respiratory symptoms with constitutional 

symptoms in any combination (Fever, night sweets, poor appetite, 

weight loss and weakness) for 4 weeks. 

Cohen et al (1996) found a significant correlation between 

symptoms "cough, sputum and weight loss" and "smear positive TB". Also 

they found that, the presence ofcough, sputum and weight loss for less than 

2 weeks and the absence oftypicalCXR were strong negative predictors of 

tuberculosis. So this study was done for assessment of specificity and 

sensitivity of respiratory symptoms in diagnosis of active sputum positive 

pulmonary tuberculosis. 

The method used In this study was microscopic examination of 

sputum for AFB (acid fast bacilli), using kinyouns staining, concentration of 

specimens by centrifugation conducted in this method increase the capacity to 

detect mycobacteria (Saceanu et aI., 1993 and Fodor, 1995) and also it has 

advantages ofdevoid ofdirect heat which has lethal effect on tubercle bacilli, 

and it has a higher significant in recovery ofmycobacteria in comparison with 

directed ZN method (Refaat, 1999). CDC (1996) stressed the importance of 

direct smear +ve sputum in infection. It have many advantages as it is the 

easiest and quickest procedure to be performed, and it provides the physician 

with confirmation of the diagnosis, also because it gives a quantitative 

estimation of the number of bacilli being excreted, the smear is of vital 

114

»----/ 

J r> 

1 

....-' 

-e, 

In this study (Table 20), there were significant association between 

smoking and some symptoms either in smear +ve or in smear -ve cases for 

AFB. In smear +ve cases smokers statistical significant difference was 

found than non smokers, as regard expectoration, dyspnea, weight loss, and 

chest wheezes, and in cases of smear -ve for APB significant higher 

association was present in cough, expectoration and chest wheezes than 

smear -ve non smokers. Other symptoms showed non significant 

differences. It was reported by Alcaid et al. (1996) that, smokers routinely 

present with respiratory symptoms, simulating that produced by TB, 

namely prolonged cough, expectoration, dyspnea, anorexia and weight loss. 

So this explains why dyspnea, weight loss and expectation were 

significantly associated with smoking in tuberculous patients. 

Table (2 J) elucidates the mean duration ofrespiratory symptoms, 

mean duration of haemoptysis showed statistically significant difference 

between smear +ve and smear -ve cases for APB. The lowest mean 

duration was for haemoptysis (1.3 month) followed by chest pain (2.32 

month) in smear +ve cases and the highest was for chest wheezes. 

(l3.97month) followed by dyspnea (6.35 month) and cough represented( 

3.6 month) and expectation (3.9 month). Similar results were obtained by 

Madebo and Lindtjorn (1999) found mean duration for each symptoms. 

Cough (5.7 month), expectoration (3.8 month) haemoptysis (1.6 month), 

chest pain (4.3 month) and dyspnea (2.5 month). Other authors most of 

them worked on the mean duration of symptoms in toto as Niijima et al. 

(1990) in Japan, mean duration was (3.5 month) and Pirkis et al (1996) 

from Australia mean duration of symptoms 72.9± 84.9 day, and also 

Wandwalo and Morkve (2000) found mean duration of symptoms was 

185 day. 

122

1 

r--- 

tJJircussion 

In this study (tab. 22), mean duration ofnon respiratory symptoms 

revealed significant difference between smear +ve and smear -ve cases for 

fever. The shortest mean duration was fever (1.38 month) in smear +ve 

cases. Regarding mean duration (tab. 21, 22) it was noted that haemoptysis, 

chest pain and fever had shortest duration and that documented as these 

symptoms were agonizing so when patient contract any of it, he urgently 

seeks medical advise. 

Analysis of duration of symptoms monthly (tab. 23,24), only (28%) 

were diagnosed within one month. And 70% of haemoptysis were 

diagnosed in Ist month followed by 69.8% of chest pain, and no any 

haemoptitic case delayed after 6 month, all the other symptoms mostly 

represented at 1-3 month except chest wheezes that delayed to one year, 

and that results was accepted as it confirm the mean duration of symptoms 

and also in this study as regard general symptoms no any patients 

represented more than 6 month. And as regard fever and night sweats it not 

beyond 3 months in agreement with this study, Teklu (1993), elucidated 

chest pain and haemoptysis were the symptoms most agonizing patients to 

seek medical advice. 

In this study. (tab. 25) it was significantly higher presentation of 

typical CXR lesions in smear +ve than in smear -ve cases for AFB, and 

also far advanced lesions was significantly higher in smear +ve (48.1 %) 

than smear -ve (5.7%) cases and in contrast mild lesions was higher in 

smear -ve than in smear +ve cases in agreement with this results Barnes et 

aI. (1988) found high significance of typical CXR presentation in smear 

+ve than in smear- ve cases and also. Cohen et al. (1996) reported that 

typical CXR in smear +ve (79%) was significantly higher than smear -ve 

for TB (40%), similar results were recorded by Gamal EL Din (1997) and 

123

caseation, the patient usually notice cough and sputum, often associated 

with haemoptysis (Rossman and Mayock, 1999). 

In this study CT was done for 15 patient, 12 was smear +ve and 3 

was smear -ve for AFB. The findings were non significantly different, 

although some findings appeared only in smear +ve cases as, nodular and 

micronodular, single cavity, multiple small cavities and pleural effusion. 

When CT findings were compared with CXR notification some findings 

were not apparent in CXR as this in CT e.g. pleural effusion appeared in 3 

cases by CT and only one in CXR, multiple small cavities in 2 cases by 

C.T. only in one case in CXR, nodular and micro nodular in 4 cases by CT 

and only 2 in CXR (tab. 30, 31 ). Many authors reported the role of CT in 

diagnosis of pulmonary T8 as by Lee et al., (1995 and 1996), they 

concluded that thin section CT is accurate in specific diagnosis of 

pulmonary tuberculosis, by enabling differentiation ofactive tuberculosis 

from inactive lesion, CT also assists in the management oftuberculosis. 

Table (32) tuberculin skin test positivity in smear +ve cases were 

significantly higher than in smear - ve cases. It was 75.3% in smear +ve 

and 500/0 in smear -ve cases. Similar results were obtained by Stead (1969) 

and Holden et al. (1971) and in our locality similar results reported by 

Osman 1993 and Gamal El Din (1997). This results can be explained as 

tuberculin test does not discriminate between active TB, past infection with 

mycobacteria or BeG vaccinated (Kox, 1995). And also, anergic state was 

attributed to compartmentalization of sensitize CD4 + T cells to sites of 

active disease may playa role (Rohrbach and william, 1986). Also, ATS 

(1978), reported that anergy may not always be due to failure of the 

immune system to responde but may be the result ofpositive suppressive 

reaction. 

125

£Jisctt.fsion 

Table (33) showed, mean induration oftuberculin test in smear +ve 

-»---- 17.5 mm was highly significant than in smear -ve 13.2 mm cases, in this 

study +ve tuberculin test in smear -ve cases can be explained as most of 

them were BCG vaccinated, or they get infection and diseased. 

When clinical symptoms presentation in smear +ve cases were 

compared as regard tuberculin test results (tab. 34) no any symptoms was 

significantly different, and in agreement with this results Garnal EI Din 

(1997) found the same result. Their was non significant association 

between tuberculin skin test and smoking among cases with smear +ve or 

smear -ve for APB. But tuberculin test positvity was higher in non smoker 

79.7% than in smoker 72.2% in smear +ve cases, also Garnal EI Din 

(1997) found lower reactivity in smoker than in non smoker and this can be 

explained by Sibille and Reynolds (1990) as tobacco smoke could alter 

native and acquired resistance to mycobacterial tubercle bacilli, and 

exposure to tobacco smoke causes morphological and functional changes in 

the alveolus macrophage with multiple defects in macrophage/monocyte 

and CD4 lymphocyte immune responses. The smoking recognized as a 

toxic factor capable of reducing host defense (Crofton et al., 1992). 

In this study their was non significant difference of BCG vaccination 

between smear +ve (88.3%) and smear -ve (81.3%) (tab. 36), but 

percentage was higher in smear +ve cases than in smear -ve this explained 

as BCG has lower degree in protection. Also Altet et al. (1993) concluded 

that, the low degree of protection afforded by the BeG vaccination 

program, and the known harmful effects it causes, make this method of 

little value, and not advisable in tuberculosis programs, also Murhekar et 

al. (1995), revealed the similar conclusion that III VIew of the low 

protective effectiveness of BeG vaccination against pulmonary 

126

), 

....--. 

*;- I 

i 

SUMMAR1( 

AND 

CONCLUSION

... 

J 

I 

Summary andConclitsion 

Summary 

This work was conducted to asses specificity and sensitivity of 

respiratory symptoms in the diagnosis of active sputum positive pulmonary 

tuberculosis and this study included 186 patients all with TB like picture. 

All patients complaining from respiratory symptoms. Their ages ranged 

from Ia years to 76 years. 

All patients were submitted to the following: 

- Full medical history. 

- Clinical examination. 

Radiological investigation, postero-anterior view offull- sized ordinary 

CXR that prove to be TB like picture, and C.T. chest was done for ] 5 

patients. 

,,-"·1 - Tuberculin skin test. 

Routine laboratory investigations (e. g. CBC, ESR, and post prandial 

blood sugar). 

- Direct- smear sputum examination using Kinyoun's staining methods. 

- Sputum negative for AFB were taken as control group. 

• The results of this study elucidated that: 

(1) Prevalence of cough on smear +ve for AFB was 97.4% highly 

significant than those of smear -ve for control cases 62.5% 

(P < 0.001). Expectoration percentage in smear +ve for AFB was 87% 

129

.Jo.. -- 

.-1'. 

SU1ltlltdryt/1tifConclit.nOn 

fever 35.5% haemoptysis 28.8%. No patients complaint from general 

symptoms of more than 6 month duration, but this statement is not 

holding good in respiratory symptoms exceed that period and all 

except haemoptysis. Analysis of mean duration of each symptom 

showed that haemoptysis and fever among smear positive for AFB 

were the shortest duration 1.3 ± 0.71 months and 1.38 ± 0.6 months 

respectively a result was significantly higher than smear -ve control 

group P < 0.002. Mean duration of cough and expectoration in smear 

positive tuberculous cases were 3.6 ± 3.5 months and 3.9 ± 3.7 

months respectively and showed non significant deference in 

comparison with smear +ve tuberculous cases and smear -ve control 

group, P > 0.05. The highest mean duration was chest wheezes 

followed by dyspnea 13.97 ± 15.9 months, 6.35 ± 10.1 months 

respectively, P> 0.05 .. 

(5) Symptoms which were significantly higher in smear +ve than in smear 

-ve for AFB (Cough, expectoration and weight loss) when combined 

represents 44.20/0 in smear +ve and 23% in smear -ve and was 

significantly different (P < 0.019) and when added to typical CXR 

presentation the significance was increased P < 0.014. And noted in this 

study some combined symptoms (Cough either dry or productive and 

haemoptysis and dyspnea and fever and loss of weight) with typical 

CXR and +ve tuberculin skin test only presented in smear +ve for 

AFB. And not present in smear -ve for AFB. 

(6) Some risk factors (TB contact and D.M and smoking). Prevalence of 

smoking in smear +ve 58.4% and smear -ve 31.3% was significantly 

different between smear +ve and smear -ve for AFB (P < 0.01) and 

131

41.7%, 33%, calcified nodules 16.75%, 66% nodular and micro 

nodular 33% ,0% and single cavity 33%, 0% , multiple small cavities 

16.75% , 0%, bronchial dilatation 16.75%,33% and pleural effusion 

25%, 0% and there were non significantly difference in CT finding in 

comparison to CXR findings of the same patients only bronchial 

dilatation appeared in C.T (13.3%) CXR 0% pleural effusion in CT 

20% and in CXR (6.7%) and multiple small cavities in CT 13.3% and 

in CXR 6.7%. 

(9) Specificity and sensitivity of symptoms were for cough 37.5% , 97.4% 

expectoration 50%, 87%, chest pain 71%, 34.4%, haemoptysis 59.4%, 

51.9%, dyspnea 53. I%, 50%, fever 46. I%, 60.4% night sweating 

59.4%, 40.3%, weight loss 65.6%,51.9% and anorexia 75%,37.3% 

and CXR typical 78.1 % , 58.4% and +ve tuberculin skin test 50%, 

75.3%. When these separate symptoms were combined with each 

other specificity was improved as combined (Cough + expectoration 

and weight loss) specificity 78.1 % and sensitivity 44.2% and when 

these combined symptoms added to typical CXR presentation 

specificity 90.6% and sensitivity 30.5% and when cough dry or 

productive, haemoptysis, dyspnea, weight loss, fever and typical CXR 

presentation and +ve tuberculin test specificity = 100% sensitivity 

7.8% and positive predictive value 1000/0 and negative predictive 

value 18.4%. 

(lO) Symptoms presentation according to age group < 20y, 20- 40y and 

>40y in smear +ve cases expectoration were significantly higher in 

age f,JTOUp 20-40y 91.1 % and > 40y 94.1 % and lower in

Sum1lldrytlndConclitstOn 

group> 40y 64.7% and lower in young group < 20y (33.3%) and 

chest wheezes was significantly higher in older group> 40y 54.9% 

and 0% in younger group < 20y and night sweats and anorexia were 

significantly higher in older group > 40y. Represented 56.8% and 

52.9% respectively and the rest of symptoms cough. Chest pain fever 

and weight loss were distributed nearly with near percentage in all 

groups. 

lJ4

..... 

SUlIlfltdry11MConclU.non 

Conclusions 

1- Haemoptysis, chest pain and fever were the symptoms urging the patient 

to seek medical advise rapidly in comparison to other symptoms. 

2- Haemoptysis in middle age group, dyspnea, anorexia and night sweating 

in elderly age group and expectoration in both middle and elderly age 

group were statistically significant symptoms among sputum +ve cases 

for AFB in relation to age groups. 

3- Specificity ofcommon respiratory symptoms are as follow: 

Chest pain 71%, Haemptysis 59.4%, dyspnea 53.1%, expectoration 

50% and cough 37.5% 

4- Specificity of common general symptoms are as follow: 

Anorexia 75%, weight loss 65.6%, night sweat 59.4% and fever 

46.6%. 

..,.--- 5- Sensitivity ofcommon respiratory symptoms proved to be : 

Cough 97.4%, expectoration 87%, haemptysis 51.9%, dyspnea 50% 

and chest pain 34.4%. 

6- Sensitivity of common general symptoms are:- 

Fever 60.4%, weight loss 51.9%, night sweat 40.3% and anorexia 

27.3% 

7- In an Egyptian community Cough dry or productive, haemoptysis, 

dyspnea, weight loss and fever among smokers were highly suggestive 

of pulmonary tuberculosis. This statement holds more good when TB 

like picture and +ve tuberculin test are present. 

115

I ... _- 

." I 

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