Leprosy Mailing List – August 8, 2026
Ref.: (LML) Long-lasting adverse impact of chemoprophylaxis & what actually works
From: Ben Naafs, Munnekeburen, the Netherlands
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Dear Pieter,
I read with interest the points made by Benedict Quao (LML, August 4, 2026) and in his reaction on Joël Almeda’s contributions about PEP. LML is an open forum for raising doubts and having reasoned discussions between the different actors active in the field of leprosy. PEP is one the items that is discussed most frequently in the past years. I hope that more persons will share their views on this subject. For me it was a trigger again. I will follow his points.
1. Interpretation of the PEP data.
I fully agree that there could well be a serious selection basis.
A longer pre-intervention period should indeed be included.
However, I think that a short time intervention like PEP will not kill all bacilli in a MB patient. All MB patients will stay MB patients. PEP may even induce a more active disease with reactivity and more nerve damage (which is the worry of Joël). The follow up in PEP studies is not specifically looking for this, one looks mainly for new diseases developing and according to me often for too short period of time. That the contact tracing is more intensive in PEP then in non-PEP areas should not occur in a good PEP trial.
A good PEP trial should indeed require analyses of the baseline situation and in mine opinion have a long enough follow-up.
2. Interpretation of STING/OASL
I go with the interpretation that the autophagy is regulated by the infective burden and less by the dead bacilli.
3. Persistence of bacterial debris.
It is very likely that dead bacteria (debris) after killing stay in the macrophages and disappear slowly. It is certainly shown in biopsies over time that it disappears very slowly particularly Lipoarabinomannan (LAM). Thus, this is demonstrated.
4. Emergence of “high-virulence” bacilli.
In a macrophage most bacilli are already death. Short “treatment” (PEP) will kill a few more. The remaining living bacteria continue dividing. Whether they do it faster I do not know. It may look as if the MI in the beginning goes up quicker, but I also doubt high-virulence. That means for me that they infect more easily, and I agree that has never been shown.
5. Linking these mechanisms to increased MB disease and disability.
I agree that the mentioned theories of mechanisms do not hold. But the observation that there are more active disease and more nerve damage could be true. But you must look for it. Killing bacteria expose other antigenic determinants leading to immunoreactivity and even reactions and thus more nerve damage. It was seen in the seventies when one tried Rifa monotherapy and it was one of the reasons that in the 80th leprologists warned against it, (Among others Thuur Cap (Jozef Arthur Cap) and Jan Warndorff. As far as I have seen the PEP programs did not look specifically for it.
6. Expected effect of chemoprophylaxis
I wonder whether you may call PEP chemoprophylaxis. It is in fact a too short “treatment” particularly for MB patients. Each time after a trial one was basically dissatisfied and started a new, stronger or longer treatment and at a moment added BCG. You say the limited efficacy may not be interpreted as harm. You have not looked for harm such as nerve damage or reactions. But it diminishes trust in the health worker when it has only a limited effect. (And to me that is harm}
And an extra remark: from HIV we know that only 20% of infected people can develop leprosy. That is why for the borderline patients BCG is so helpful. This fact is not taken in account as far as I read the PEP articles.
7. Asymptomatic “high shedders” as main reservoir of transmission.
There may be high shedders, but I cannot define them. But probably most MB are shedders. When you treat them properly the reservoir for transmission most likely goes down, ergo the number of new patients.
A. An open door. But be aware that some MB patients, particularly the ones that are undertreated, (something that is due to the too short MB treatment in the WHO advice), may be asymptomatic as active MB patients. I feel these could be the ones Joël means. But wait for his answer.
B. If you do a good survey, you will find in high endemic area’s a great number of patients who seem “asymptomatic” to a less experienced leprologist. Thus, we can’t say that is not demonstrated. Concerning the nasal carriers: The nose is like a vacuum cleaner and most people in a high endemic area may have temporarily live and dead bacilli in the nose. Look at the PGL-1 serology in these areas. It is unlikely that they do not contribute to the M. leprae pool. Concerning mLAMP, this is still being studied. But when used properly it may be an important extra tool to study and thereafter become useful against the M. leprae pool.
C. Indeed, DNA does not indicate live bacilli only the presence of bacilli dead or alive. RNA detection is needed.
Dear Benedict, my thanks for your extensive analyses and I hope my views will stimulate additional discussions on this important area.
High Regards,
Ben
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LML - S Deepak, B Naafs, S Noto and P Schreuder
LML blog link: http://leprosymailinglist.blogspot.it/
Contact: Dr Pieter Schreuder << edit...@gmail.com
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