Fw: Ref.: (LML) Long-lasting adverse impact of chemoprophylaxis & what actually works

 

 

Leprosy Mailing List –  July 9,  2026

 

Ref.:  (LML) Long-lasting adverse impact of chemoprophylaxis & what actually works

From: Joel Almeida, Mumbai, India

____________________________________________________________________________

 

 

Dear Pieter and colleagues,

Brazil tried short-term chemoprophylaxis (PEP in PEPHans pilots 2016-2019) and then rejected it. The attached figure underlines how scientifically robust and beneficial this rejection was. Despite more intensive contact tracing in recent years, the former PEPHans areas* show a long-lasting higher risk of MB and G2D (visible deformity at diagnosis) compared to non-PEP Maranhão municipalities. 

Understanding the biology of macrophages is important for rapidly and safely eliminating concentrated viable bacilli from human clusters.

Intact macrophage defences are the primary reason most infected individuals never develop signs of disease,(1) despite widespread asymptomatic subclinical infection in endemic areas.(2) However, M. leprae debris including DNA in macrophage cytosol subverts natural macrophage defences via the highly conserved and universal cGAS-STING-IRF3-IFNB-OASL cascade, suppressing autophagy and vitamin D-induced cathelicidin.(3) Short-term chemoprophylaxis damages bacilli by anti-microbial action, producing debris in macrophage cytosol, but does not outlast the bacillary debris given the suppression of autophagy. Nor does it prevent subsequent reinfection or regrowth in disarmed macrophages. Bacillary replication is via cell pole elongation (4) with increased surface area and surface virulence factors per bacillus, including Mce1A for cell entry (5) and PGL1 for “silent” non-inflammatory damage to axonal mitochondria via perineural macrophage iNOS and excess nitric oxide.(6)

Accordingly, a boost in phenotypically high-virulent bacilli is expected to outlast chemoprophylaxis. Also, the circulation of these high-virulent bacilli is predicted to boost the risk of MB HD and G2D, as illustrated in the attached figure. 

A central requirement for rapidly eliminating concentrated viable bacilli from human clusters is to conserve natural macrophage defences: boost nutrition, use BCG or MIP or similar vaccines (macrophage autophagy boosters), confine anti-microbial use to high-shedding asymptomatic LL (millions of bacilli in nasal swabs) or persons with physical signs of HD. Continue socio-economic improvements (literacy, employment etc).

São Luís in Maranhão is producing among the world's most rapid declines of new MB HD: eg from 279 new MB in 2023 to only 200 in 2025. With addition of nasal swabs for rapid semi-quantitative mLAMP to detect cryptic asymptomatic LL high-shedders, followed by full anti-microbial treatment with regular check-ups to preserve nerve function, such high-endemic low-income places can end transmission within weeks rather than decades. Periodic mop-up rounds would be needed to confirm and sustain the success.

Is it a bad idea to conserve natural macrophage defences?

With all sincerity,

Joel Almeida

References                 

1.                 Mi Z, Liu H, Zhang F. (2024) Advances in thepathogenic, genetic and immunological studies of leprosy. hLife 2024;2:6–17.

 

2.                 Godal T, Negassi K (1973). Subclinical infectionin leprosy. Br Med J. 3 (5880): 557-559

 

3.                 deToledo-Pinto TG, Ferreira ABR, Ribeiro-Alves M et al. (2016)STING-Dependent 2′-5′ Oligoadenylate Synthetase–Like Production Is Required forIntracellular Mycobacterium leprae Survival. The Journal of InfectiousDiseases, Volume 214, Issue 2, 15 July 2016, Pages 311–320,https://doi.org/10.1093/infdis/jiw144

 

4.                 Hannebelle MT, Ven JX, Toniolo C et al.(2020)  A biphasic growth model for cell poleelongation in mycobacteria. Nature Communications 11:452https://doi.org/10.1038/s41467-019-14088-z

 

5.                 Fadlitha VB, Yamamoto F, Idris I, Dahlan H, SatoN, Aftitah VB, et al. (2019) The unique tropism of Mycobacterium leprae to thenasal epithelial cells can be explained by the mammalian cell entry protein 1A.PLoS Negl Trop Dis 13(3): e0006704.https://doi.org/10.1371/journal. pntd.0006704

 

6.                 MadiganCA, Cambier CJ, Kelly-Scumpia et al (2017). A macrophage response toMycobacterium leprae phenolic glycolipid initiates nerve damage in leprosy. Cell. 170(5):973-985. e10.
- - - -

* PEPHans municipalities:

a) Mato Grosso: Alta Floresta, Apiacás, Carlinda, Nova Bandeirantes, Nova Monte Verde, Paranaíta, Rondonópolis;
 b) Pernambuco: Afrânio, Cabrobó, Dormentes, Lagoa Grande, Orocó, Petrolina, Santa Maria da Boa Vista;
 c) Tocantins: Araguaína, Colinas do Tocantins

____________________________________________________________________________

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/545872bd-b279-4f56-89c7-6b39ac7f8e20n%40googlegroups.com.