Wednesday, July 29, 2026

Fw: Ref.: (LML) Sensitivity of mLAMP


 

Leprosy Mailing List –  July 29,  2026

 

Ref.:  (LML) Sensitivity of mLAMP

From: Joel Almeida, Mumbai, India

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Dear Pieter and colleagues,

mLAMP can be used in two distinct ways, to simultaneously detect M. leprae and/or M. lepromatosis: 

a) in total population surveys using nasal swabs and mLAMP with a relatively quick cut-off  time (few minutes) to distinguish between high-shedders and casual carriers of trivial numbers of bacilli.

b) to aid clinical diagnosis using skin smears or biopsies with a long cut-off time (e.g. 1 hour) to permit maximum sensitivity.

Wang et al (2025) wrote: "The M. leprae HiFi-LAMP assay has high specificity and sensitivity with a limit of detection (LOD) of 43 copies/25 μL reaction. Both sensitivity and specificity of the HiFi-LAMP assay were 100% for 130 purified DNA from nasal and oral samples."
https://doi.org/10.1016/j.ijid.2025.107835
> 43 copies of RLEP are contained in only 2 bacilli.

Persons with lived experience need not explore the underlying biology. mLAMP kits that provide a clear colour change (by using dyes) would seem ideal for field use. For detecting cryptic asymptomatic LL high-shedders, the amplification kinetics at that template concentration are dominated by near-immediate primer saturation (relatively rapid colour change when dyes are used).

With all sincerity,

Joel Almeida



PS 

Missing small numbers of bacilli in someone with PB HD or subclinical infection is not necessarily disastrous, because many of such persons resolve on their own without ever becoming high-shedders of bacilli and they are at low risk of visible deformities compared to MB HD. There is no need to target them with fear or prejudice. Good clinical examination is helpful, together with investigations (that can include mLAMP with plenty of time allowed for maximum sensitivity).

Missing even a single high-shedding LL is disastrous not just for the individual, who can suffer visible deformity before diagnosis, but also for the population. Missing such a person allows the floodgates of infection to remain open. This produces a continuous stream of secondary cases at risk of deformity, including further cryptic asymptomatic LL.

Davey and Rees (1974 Lepr Rev 45(2):121-34) showed that cryptic asymptomatic and unprotected LL HD cases can shed as many as 10^7 viable bacilli/day (or even per nose blow). By contrast, zero of 208 unprotected BL HD cases showed a bacillary index (BI) of 5+ or 6+ in nasal smears, whereas many unprotected LL HD cases did so. BB, BT and TT cases are even less likely than BL HD to shed many bacilli. Unprotected LL HD seems overwhelmingly important to transmission, and to reseeding the surroundings.

Further, subclinical infection is widespread in endemic areas (Godal and Negassi 1973 BMJ 3 (5880): 557-559) yet in many endemic areas <1 in 10k population/year are newly detected with signs of HD. If 50% of all persons in an endemic area have ever been infected, then over a 70 year lifespan an asymptomatic ever-infected contact has >98% probability of safely self-limiting or eliminating the bacilli - without showing signs, sequelae or onward transmission. Natural macrophage defences seem important. Most of the genomic polymorphisms known to modify  the risk of HD, and LL HD, are related to macrophage function. (Mi, Liu, Zhang 2024 hLife 2:6–17).

Reinfection, especially of persons with genomes predisposing to LL type of HD, is another important challenge. (Uaska Sartori et al, 2020 Sci Rep 10, 1284, Goncalves et al Gonçalves et al (2019) https://doi.org/10.1186/s12879-019-4100-6, Stefani et al (2017)  https://doi.org/10.1371/journal.pntd.0005598).

This is why ending HD transmission requires nasal swabs to be taken from ALL asymptomatics in a cluster. Only then can all the unique sources of concentrated viable bacilli in a cluster, undetected and unprotected LL HD high-shedders, be found and protected. They receive full free treatment and regular check-ups to protect their nerves. Given all that, extending and expanding primary health care via persons with lived experience and basic training is extremely helpful for rapidly reducing transmission, monitoring muscle weakness, encouraging completion of treatment and more.

 

____________________________________________________________________________

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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