Leprosy Mailing List – February 19, 2025
Ref.: (LML) Understanding silent neuropathy
From: Joel Almeida, Mumbai, India
Dear Pieter and colleagues,
"Silent" neuropathy is responsible for 85% of new nerve function impairment after the start of anti-microbials in humans. (1) No signs of inflammation, by contrast with "reactions". How do nerves suffer damage in the absence of the clinical or histopathological signs of inflammation? (no rubor, calor, tumor, dolor, i.e., no redness, warmth, swelling, pain).
We now know that PGL-1 directly can induce nitric oxide synthase in perineural macrophages. An excess of Nitric Oxide destroys the mitochondria in axons of nerves. (2) Even without any signs of neuritis or inflammation or reaction, the recipient of inadequate anti-microbial treatment can by this mechanism suffer "silent" nerve damage.
We also know that as many as half of the entire population ever exposed to an unprotected LL HD patient can show cellular evidence of current/past HD infection. (3, 4) Yet half of the entire population does not typically develop persistent physical signs of HD. That is because self-healing without sequelae is the typical outcome of human HD infection.
Most asymptomatic persons/contacts are completely harmless to others. Even TT patients shed few if any bacilli. Any viable bacilli in asymptomatic persons are likely to be dormant and harmless until provoked by anti-microbial drugs. Then the previously dormant bacilli are forced into action. They start pumping out the anti-microbials. (5) Instead of harmless dormant bacilli, the asymptomatic person now has harmful active bacilli.
The real trouble, unlike with other mycobacterial infections, is that the HD bacilli mostly inhabit the nerves and perineural tissues. Once a dose of anti-microbials is given and dormant bacilli are activated, PGL-1 can induce nitric oxide synthase and the mitochondria in nerve axons can be destroyed. Thereafter only a relentless and sustained assault on the bacilli by adequate concentrations of anti-microbial drugs will eliminate all bacilli. Elimination of all bacilli in turn reduces the risk of nerve damage occurring through "silent neuropathy".
That is why it is both merciful and competent to insist on full anti-microbial treatment if at all even a single dose of anti-microbials is given to an asymptomatic person. HD bacilli once activated are highly dangerous to nerves, and most of the damage occurs silently.
With all sincerity,
Joel Almeida.
References
1. Croft RP, Nicholls PG, Steyerberg EW et al. A clinical prediction rule for nerve-function impairment in leprosy patients. Lancet (2000) 355(9215):1603-6. doi: 10.1016/s0140-6736(00)02216-9.
2. Madigan CA, Cambier CJ, Kelly-Scumpia et al A Macrophage Response to Mycobacterium leprae Phenolic Glycolipid Initiates Nerve Damage in Leprosy. Cell (2017) 170(5):973-985. e10. doi: 10.1016/j.cell.2017.07.030.
3. Godal T, Negassi K (1973). Subclinical Infection in Leprosy. British Medical Journal 3: 557-559
4. Dockrell H et al, Possible transmission of Mycobacterium leprae in a group of UK leprosy contacts. Lancet. Volume 338, Issue 8769 p739-743September 21, 1991
5. Machado D, Lecorche E, Mougari F et al (2018) Insights on Mycobacterium leprae Efflux Pumps and Their Implications in Drug Resistance and Virulence. Front. Microbiol. 9:3072. doi: 10.3389/fmicb.2018.03072
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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 << editorlml@gmail.com
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