Leprosy Mailing List – October 20, 2019
Ref.: (LML) Single-dose rifampicin PEP increased the risk of MB disease
From: Joel Almeida, London and Mumbai
Dear Pieter and colleagues,
Prof. Smith (LML Oct 15, 2019) in the course of discussing the MALTALEP trial report 2019 (1) raises concerns about
'post hoc analysis', 'subgroup analysis', 'data dredging'
These concerns seem unjustifiable for the following reasons:
The MALTALEP protocol (1) defined outcomes as incident "clinical leprosy" among contacts within 2 years. The authors of the MALTALEP report 2019 (2) subsequently reported incident cases in MB and PB sub-groups, as is routine in HD. MB clinical disease has far greater clinical and epidemiological significance than PB clinical disease. The authors rightly displayed the excess of MB clinical disease in the SDR-PEP treated group (vs. controls). Those observations were published. That seems unobjectionable.
Therefore, their published observation showing 268% excess MB clinical disease within 2 years, in the SDR-PEP group compared to the control group, (2) cannot justifiably be criticised. Their published observations are facts that cannot be wished away. Further, the main problem with monotherapy (SDR-PEP) is that it selects drug-resistant HD bacilli among undiagnosed LL patients who are wrongly classed as disease-free contacts and given SDR-PEP monotherapy.
Given accumulated scientific evidence, multi-drug chemoprophylaxis seems vastly safer and more effective than SDR-PEP monotherapy. Some ILEP members have already been moving towards multi-drug chemoprophylaxis instead of relying on SDR-PEP. That seems wise. We simply cannot afford to select drug-resistant HD bacilli or to increase MB disease.
The example protocol for safe and effective interruption of transmission (LML 15 October 2019) outlined a way forward in the light of accumulated evidence. It can be refined and then fleshed out with locally-appropriate details. This is the process we used very successfully at WHO HQ to develop and then disseminate a highly effective new life-saving TB strategy. That strategy has since saved tens of millions of lives across the globe and helped transform TB from a neglected disease to a well resourced fight to save lives. Dr. Styblo's demonstrated success in Tanzania paved the way for the highly effective TB strategy. We can similarly build on demonstrable success, in order to end HD and save nerves, limbs, eyes, minds, relationships and livelihoods.
We know enough to match or exceed Shandong's achievement of 20%/year decline in incidence rate of HD leading to zero transmission. Let's keep constructively pursuing not what harms and selects drug-resistant bacilli (eg., SDR-PEP for contacts) but what is highly effective and safe. Currently that is
1. MDT (MB or PB multi-drug therapy rather than monotherapy) reinforced with
2. Multi-drug chemoprophylaxis (rather than rifampicin on its own) for
a) LL patients (monthly doses after MDT) and for
b) contacts (single dose).
That will take into account crucial evidence to date, and be worthy of the support of all concerned. Together with BCG (or MIP vaccine) that maximises our chance of succeeding strongly as Shandong did. The example protocol (LML 15 October 2019) outlined this in more detail. We need to act as if we want really to defeat the bacilli as Shandong did, and not merely to select drug-resistant bacilli as monotherapy (SDR-PEP) does. Let's do our best to achieve a 20%/year decline in incidence rate leading to near-zero transmission. Shandong demonstrated that this is possible.
Joel Almeida
References
1. Richardus RA, Alam K, Pahan D et al. The combined effect of chemoprophylaxis with single dose rifampicin and immunoprophylaxis with BCG to prevent leprosy in contacts of newly diagnosed leprosy cases: a cluster randomized controlled trial (MALTALEP study). BMC Infect Dis. 2013 Oct 3;13:456. doi: 10.1186/1471-2334-13-456.
2. Richardus R, Alam K, Kundu K et al. Effectiveness of single-dose rifampicin after BCG vaccination to prevent leprosy in close contacts of patients with newly diagnosed leprosy: A cluster randomized controlled trial. International Journal of Infectious Diseases 88 (2019) 65–72.
3. Li HY, Weng XM, Li T et al. Long-Term Effect of Leprosy Control in Two Prefectures of China, 1955-1993. Int J Lepr Other Mycobact Dis. 1995 Jun;63(2):213-221.
LML - S Deepak, B Naafs, S Noto and P Schreuder
LML blog link: http://leprosymailinglist.blogspot.it/
Contact: Dr Pieter Schreuder << editorlml@gmail.com
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