Leprosy Mailing List – September 7, 2026
Ref.: (LML) Long-lasting adverse impact of chemoprophylaxis & what actually works
From: Joel Almeida, Mumbai, India
Dear Pieter and colleagues,
The initial letters were on July 9 and 11 ( LML https://leprosymailinglist.blogspot.com/2026/07/ ). They were concerned solely with the raw data that demonstrate serious long-lasting harm from short-term chemoprophylaxis, as illustrated by Brazil (PEPHans municipalities vs non-PEP Maranhão municipalities). Nothing to do with the views of any fundraising organization.
The signals of harm in that raw data from Brazil (and convergent data from Dadra Nagar Haveli in India) align with well-established underlying biology. It was elucidated first by Zhijian Chen's group that discovered cGAS-STING (1) and then by de Toledo-Pinto et al (2) who demonstrated that lipofection of macrophages with M. leprae DNA triggered cGAS-STING - iRF3 - IFNbeta - OASL upregulation, resulting in the suppression of autophagy & cathelicidin anti-microbial peptide.
In this case the stakes are high: human eyes, hands, feet. Robust scientific knowledge can help serve as a shield for potential recipients of short-term chemoprophylaxis. The signals of harm are not only from epidemiological outcomes but also exactly as predicted by well-established highly conserved macrophage biology. Concealment of risks and harms is the exact opposite of what is required for informed consent.
Data & Safety Monitoring Boards (DSMB) likewise are unable to protect recipients of experimental interventions if a true untreated control group is omitted. When the control intervention (SDR-PEP) itself shows an excess of incident MB in raw data then the DSMB can no longer provide the necessary safety net. Similarly, cutting short the duration of observation can conceal the future stream of excess deformity in the intervention arm.
All this occurs against a backdrop of frequent self-limiting or elimination of bacilli by natural macrophage defences (including vit D-induced cathelicidin and autophagy). 25% or more of persons in an endemic area show evidence of infection (serology or Lymphocyte transformation). Yet in many endemic areas the range of new case detection rates is only 0.3 to 1.5 per 10k population/year. (WHO updates) This means that the probability of an individual developing clinical signs over a 70-year remaining lifespan ranges from 0.21% to 1.04% for the general population, and 0.84% to 4.11% for individuals who are infected. In other words, >95% of ever-infected persons and >99% of the general population will die of some unrelated cause without showing lasting signs or sequelae or onward transmission. These are the people in whom the very macrophage defences that protect them were to be subverted by short-term chemoprophylaxis of one sort or another. Sabotaging macrophage defences is the exact opposite of protection. It is a "worst practice", based on the evidence.
Who are the victims? Too many of them are on low incomes and with minimal schooling. The safety of their eyes, hands and feet is not optional. If their macrophages are sabotaged, they are more likely to develop "silent" nerve damage in mitochondria of motor axons, with visible deformity as the very first detectable sign of HD (leprosy). Visible deformity to them means loss of livelihood, ostracism, mental distress and utter destitution. Is that our goal? For safe and rapid interruption of transmission, we have the Find Treat End strategy.
There is no reason for the hundreds of experts on LML to settle for anything less than the scientific method: mechanistic knowledge, raw epidemiological data and robust scientific inference. Together with respect for human dignity. Even low income people, and they above all, deserve safety of their eyes, hands, feet.
With all sincerity,
Joel Almeida
References
1. Science. 2013 February 15; 339(6121): . doi:10.1126/science.1232458.
2. J Inf Dis 2016 DOI: 10.1093/infdis/jiw144
____________________________________________________________________________
LML - S Deepak, B Naafs, S Noto and P Schreuder
LML blog link: http://leprosymailinglist.blogspot.it/
Contact: Dr Pieter Schreuder << edit...@gmail.com
You received this message because you are subscribed to the Google Groups "Leprosy Mailing List" group.
To unsubscribe from this group and stop receiving emails from it, send an email to leprosymailinglist+unsubscribe@googlegroups.com.
To view this discussion visit https://groups.google.com/d/msgid/leprosymailinglist/d4a7c394-7212-4bc7-8f1d-804e979696e0n%40googlegroups.com.
No comments:
Post a Comment