Leprosy Mailing List Blog: (LML) Single-dose rifampicin chemoprophylaxis

Leprosy Mailing List – July 20, 2018

Ref.: (LML) Single-dose rifampicin chemoprophylaxis

From: Wim van Brakel, Amsterdam, the Netherlands

Dear Pieter,

I would like to respond to the criticisms raised by Dr Almeida to the publication by Tiwari et al. I agree with Dr Almeida that we should prevent harm and avoid exaggerated claims. In my view, respect for scientific standards includes refraining from comparing work of fellow scientists with 'rain dances'. In science, it is always best to stick to the facts.

1. A 95% confidence interval is NOT a test of inference (statistical significance), but merely a way to present descriptive statistics related the sample variability in a way that provides much more information than a mere standard deviation. It is true of course, that one can predict from a 95%CI of a difference or a ratio (odds ratio or relative risk) whether or not this difference or ratio is significant at the 5% level. But the CI itself is not a test of significance, nor does it provide a p-value, and Tiwari and colleagues do not interpret it as such either.

2. Tiwari and colleagues are not making a claim about generalizable efficacy of SDR-PEP based on this study in Lingat Village (PEP post-exposure prophylaxis). They merely report observations. They observed 50% less new cases among those who had received SDR-PEP than among those who had not. They recommend a further follow-up visit to this community to collect additional data, which may or may not be sufficient to show a statistically significant effect of SDR-PEP. However, in situation like this, with very small numbers, we may succeed in eliminating leprosy without ever reaching statistical significance.

3. The study in Lingat village aimed "to assess the operational feasibility of the population-wide 'blanket' administration of SDR for leprosy prevention in isolated communities, by documenting the implementation process and initial results of a pilot project in a remote island of Indonesia." Therefore, Tiwari and colleagues never aimed to demonstrate the efficacy of SDR-PEP in this small community.

4. The conditions described in Lingat village most closely resemble those in rifampicin chemoprophylaxis trial conducted on a number of high-endemic islands the Flores Sea, Indonesia (Bakker et al, 2005). In this study, number of cases detected during follow-up where large enough to allow statistical significance testing and risk reduction of 63% was reported, comparing the blanket island community with the control group (adjusted hazard ratio 0.37 (0.17-0.80). This effect was sustained after 6 years and 10 years. Unfortunately, the 10-year follow-up was never published. Both the 6-year follow-up in this study and the 6-year follow-up in the COLEP trial, which was published, show that SDR-PEP actually prevents development of leprosy in 50-60% of non-household, non-blood-related contacts.

5. Scientific rigour is very important. All available evidence about rifampicin chemoprophylaxis was recently submitted to the most rigorous systematic review one can wish for (the WHO guidelines procedures). The WHO Guidelines Committee concluded that the evidence for SDR-PEP was sufficiently strong for WHO to support its implementation (see http://www.searo.who.int/entity/global_leprosy_programme/en/).

Our view is that we should use all possible means that have been shown to be effective, even if partly, in our fight against leprosy. If we start implementing SDR-PEP now, using the locally most appropriate strategy, we can then replace it with a better regimen or a combination with immune-prophylaxis as and when that becomes available. If there were even half the scientific evidence for the effectiveness of a rain dance as we have for SDR-PEP, many of our farmers would currently be dancing in their fields to try and end the current period of drought.

With kind regards,

Wim van Brakel

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Wim van Brakel, MD MSc PhD

Head Technical Department

Netherlands Leprosy Relief (NLR)

Wibautstraat 137k

1097DN Amsterdam

Netherlands

Tel. +31 20 5950529

Email: w.v.brakel@leprastichting.nl

URL: www.leprosyrelief.org