Leprosy Mailing List – September 10, 2026
Ref.: (LML) Long-lasting adverse impact of chemoprophylaxis & what actually works
From: Ben Naafs, Munnekeburen, the Netherlands
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Dear Pieter,
With reference to the letter by Joel dated 7 September 2026, I have rechecked the mentioned paper from Maranhão to see whether I had missed the part about harm to the patients and contacts in it. However, the original papers did not look for it. Their conclusion does not mention harm due to chemoprophylaxis. It says: “The disease distribution was partly explained by poverty indicators. LPEP influences the spatial dynamic of the disease and results highlighted the relevance of systematic contact surveillance for leprosy elimination.”
The chemoprophylaxis trial in Dadra Nagar Haveli district has also no data on harm, it shows only acceptance.
However, Joël refers to: Almeida JG, Talhari S, Salgado CG, Kumar B, Talhari CC, Goncalves HS. Visible deformity after HD (leprosy) chemoprophylaxis among tribal people in India: Quantitative analysis of data extracted from published sources. Indian J Lepr. 2025; 97:175-188. That says:” A particularly serious concern is the paradoxical rise in grade 2 disabilities (G2D) following SDR campaigns in areas such as Dadra and Nagar Haveli. This may reflect progression of subclinical infections despite chemoprophylaxis or diagnostic delays stemming from false reassurance among contacts”.
The cGAS-STING pathway is a central mechanism of innate immunity that detects double-stranded DNA and translates it into transcriptional and other cellular effector responses. Beyond its canonical role in antiviral defence, the pathway senses diverse endogenous DNA species generated as byproducts during various contexts of cell stress. In this capacity, cGAS-STING impacts tissue homeostasis and antitumor immunity, but it is also associated with a number of inflammatory disorders. (Cell Volume 189, Issue 13p3849-3870June 25, 2026)
According to Pinto at al: “thus, our data uncover a pro-mycobacterial role for OASL during M. leprae infection that directs the host immune response toward a niche that permits survival of the pathogen” This means there is no damage to the pathogen.
What does it all mean for possible damage after PEP is given to Leprosy patients and contacts? In my opinion, PEP {killing a few bacilli} will not substantially increase the M. Leprae DNA already present in the cells, to expect that more INF-gamma and IL2 will increase the damage via the cGAS Pathway. The suppression of autophagy may even be beneficial.
Indeed, robust scientific knowledge will benefit the patient. But the findings Joël refers to, are not that robust. Particularly since his interpretation is dubious.
I fully agree that the period of observation is too short, and this is what makes DSMB data not very valuable concerning either a positive effect or eventually harm. As other authors also have mentioned it is for the implementers of the chemoprophylaxis trials to show that no harm is done.
He is completely right that in an endemic area everyone will be infected at some time. It are only the ones who can sustain M. leprae in their cells who can develop leprosy as a disease. This minority can be protected by their adaptive immunity. (hence BCG vaccination). The potential polar LL patients may not be protected at all. The elimination by macrophages is thus only for the minority. His statement that macrophage defences are sabotaged by chemoprophylaxis, if it is true, has yet to be proven.
All leprosy workers are aware of the problems that leprosy constitutes and try to solve it. For one group that solution is PEP but whether it works is doubted by a great number of the LML readers. This doubt has been voiced many, many, times by Joël. But since the awareness is already there, repeating it too often is not necessary.
Warm regards,
Ben
Note from LML Board:
Many valuable observations have been made in these discussions about PEP. Many have pointed out the importance of proper research before implementing any intervention (not only regarding PEP, but other issues such as MDT-U, lifelong or 5 years of MDT for MB high shedders, etc.). We recognise that there may be challenges in finding resources for such research. In any case, this kind of bipartisan dialogue on LML is important.
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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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