Review of Current Evidence and Comparison of Guidelines for ...
Review of Current Evidence and Comparison of Guidelines for ...
Review of Current Evidence and Comparison of Guidelines for ...
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EUR/03/5045931<br />
page 9<br />
current treatment is adequate. The difficulty in interpreting evidence in HIV positive patients is<br />
compounded by the fact that many patients may currently be receiving anti-retroviral therapy,<br />
thereby boosting their immune systems. However, it is not known what will happen to those<br />
patients in the long term if they fail on their anti-retroviral treatments <strong>and</strong> have a reduction in<br />
their CD4 counts.<br />
This new evidence looking at HIV <strong>and</strong> syphilis co-infection has led to many <strong>of</strong> the conclusions<br />
about treatment regimes in all stages <strong>of</strong> disease, both in HIV positive <strong>and</strong> negative patients. In<br />
the main, the guidelines propose that treatment <strong>for</strong> syphilis in patients with HIV should be no<br />
different from guidelines in HIV negative patients. Specific differences in treatment are as<br />
follows; the CDC guidelines suggest a possible three dose <strong>of</strong> benzathine penicillin at day 1, day<br />
8 <strong>and</strong> day 15 in early syphilis. Due to concern about higher levels <strong>of</strong> asymptomatic neurosyphilis<br />
in HIV positive patients (Rolfs study found a higher level <strong>of</strong> CSF changes in the HIV positive<br />
group) CDC recommends the examination <strong>of</strong> CSF in all HIV positive individuals with late<br />
syphilis <strong>and</strong> consideration <strong>of</strong> this in early syphilis. United Kingdom guidelines propose treating<br />
all HIV positive patients with treatment <strong>for</strong> neurosyphilis. CSF examination is advisable in all<br />
HIV positive patients in the European guidelines; otherwise treatment is the same as <strong>for</strong> HIV<br />
negative patients. There are no specific guidelines <strong>for</strong> the treatment <strong>of</strong> HIV/syphilis co-infected<br />
patients in Russian Federation.<br />
It is recommended in all guidelines that all patients who are diagnosed with syphilis should be<br />
tested <strong>for</strong> HIV.<br />
Syphilis in Pregnancy<br />
To add to a complex situation in terms <strong>of</strong> pathogenesis <strong>and</strong> treatment <strong>of</strong> syphilis, the challenge in<br />
pregnancy is finding treatment which will treat the mother adequately, while not harming the<br />
fetus, <strong>and</strong> either treat or prevent infection in the fetus. A recent Cochrane review has looked at<br />
the various regimes used (100). Singh <strong>and</strong> McCloskey have written a review article on syphilis<br />
in pregnancy that also mentions Australian guidelines (101). As in other areas <strong>of</strong> syphilis<br />
management there has been no comparison made about the relative efficacy <strong>of</strong> different<br />
penicillins (5).<br />
The CDC guidelines recommend using the same regimes as <strong>for</strong> the relevant stage <strong>of</strong> syphilis as<br />
in non-pregnant patients but with a possible second dose at day 8 <strong>for</strong> BBP in early syphilis (5).<br />
This is based on research showing that due to physiological changes in pregnancy a single IM<br />
dose <strong>of</strong> 2.4 mu benzathine penicillin remains at treponemicidal levels (>0.018 µg/ml) in serum<br />
<strong>for</strong> three times longer in non-pregnant than pregnant women (102). Watson-Jones et al.<br />
completed a prospective cohort trial <strong>of</strong> 1688 pregnant women in Tanzania (103). A total <strong>of</strong> 382<br />
women with positive syphilis serology were given a single dose <strong>of</strong> BBP (2.4mu IM). This<br />
showed no increased risk <strong>of</strong> adverse pregnancy outcome <strong>for</strong> women with positive syphilis<br />
serology treated with BBP compared with 950 seronegative women. Stillbirth rate was 2.3% in<br />
seropositive treated women <strong>and</strong> 2.5% in seronegative women. Low-birth-weight live births were<br />
6.3% in seropositive treated women <strong>and</strong> 9.2% in seronegative women. Alex<strong>and</strong>er <strong>and</strong> colleagues<br />
followed CDC guidelines (i.e. single dose BBP) in 448 pregnant women with early syphilis, with<br />
a success rate <strong>of</strong> 98.2% in preventing congenital syphilis (104). However, a study in Africa<br />
found if two doses <strong>of</strong> BBP one week apart were used in pregnant women with early syphilis<br />
there were lower rates <strong>of</strong> congenital syphilis <strong>and</strong> infant mortality, with higher birth weights (25).<br />
A PBP regime is recommended in the United Kingdom guidelines reflecting concern over