Dear Pieter,
In response to the enquiry from an LML colleague:
1. An overview
M. leprae may be viewed as an arsonist which survives outside human hosts, but ignites inflammation in the nerves of many infected persons. We need to put out the fires within nerves before permanent damage; and we need to suppress M. leprae. Sufficient funding and skilled personnel are required.
2. Holes in our defences
Currently, we have eliminated the “fire brigade”. The firemen are the skilled leprosy workers who can visit leprosy patients near their homes. These skilled workers can monitor nerve function and ensure prompt anti-inflammatory treatment. About 85% of the nerve function impairment is “silent”, without physical signs or symptoms of inflammation ([i]). Therefore patients cannot be relied on to complain in time. We need, urgently, to train and appoint these skilled leprosy workers. Otherwise, in India alone, as many as 300,000 people (50% of multibacillary patients) will newly suffer permanent nerve damage and visible deformity over the next 10 years.
The largest number of people currently susceptible to M. leprae is probably polar lepromatous patients. They have almost no specific immunity, and show a very high bacterial load in skin smears. They require prolonged treatment. Instead, they currently receive only a year or less of protection against M. leprae. After that they remain vulnerable to the proliferation of endogenous or exogenous M. leprae. This is not their fault. It is our fault.
M. leprae flourishes, and people suffer visible deformity, because of our easily avoidable “own goals”. We have bred the “arsonist”, M.leprae, by withdrawing anti-microbial treatment from “polar lepromatous” patients and eliminating skin smear services. And we have eliminated the “fire brigade”: the skilled leprosy workers who can monitor nerve function. The people of India pay a heavy price for our policy errors, in terms of a “bonfire” of human nerves. We can correct the errors.
3. Environmental M. leprae
According to the literature, if you visit and stay in the home of Indian leprosy patients already treated with MDT, your risk of developing disease is multiplied several-fold compared to the local population's risk [ii]. This remains true after the patients have apparently been "cured" by MDT.
M. leprae, when dried in the Indian shade, remain viable for up to 5 months [iii]. M. leprae ingested by amoebae remain similarly viable for at least 8 months [iv]. If an individual with low specific immunity comes into contact with such M.leprae, replication can resume. The cycle of transmission can be maintained indefinitely even if M. leprae do not replicate outside hosts. The duration of extra-human survival may prove to be longer than 8 months, if more prolonged studies are undertaken. In Norway, a phenolic glycolipid specific to M. leprae was found in the environment decades after the last human case [v]. It seems prudent to presume that dried M. leprae, which measure under 10 microns, can become airborne along with other dust. It is not necessary for an infectious patient to sneeze directly into your face. Similarly, it seems prudent to presume that water-borne M. leprae can eventually reach susceptible humans. It is not necessary for an infectious patient to rub M. leprae into your skin abrasions.
Our claims and promises about interrupting transmission deserve to be tested robustly and rapidly on a small island with a relatively high incidence rate of leprosy. Otherwise we might become so pre-occupied with “pie in the sky” that we neglect to “pluck low-hanging fruit.”
4. The burden of leprosy
"Burden of disease" has a very specific meaning in the scientific community. It has a clear unit of measurement for non-fatal conditions: YLD (years lived with disability). YLD is defined as "the prevalence of each sequela multiplied by the relevant disability weight adjusted for comorbidity." ([vi]) Other usages of the term "burden" place leprosy patients at a disadvantage relative to those afflicted by other diseases.
The “burden of leprosy”, by this standard definition, has increased during the past 30 years and continues to increase. This fact will help us more easily to mobilise the necessary political commitment and funding to fight leprosy.
We also need to re-examine our claims about prevalence. Most of the 5 million plus “leprosy patients” in 1985 had been smear negative for years or even decades. Many of them did not require any further anti-microbial treatment. By current definitions, they were already “cured.” In areas with rapid socio-economic advances, or rapid de-forestation, the incidence of leprosy is known to decline. Elsewhere, changes in prevalence are largely cosmetic, owing to decreased duration of MDT. The bottom line is that we score an “own goal” if we continue to use non-standard definitions of "burden of leprosy".
5. Moving forward
Let’s unite now to prevent permanent nerve damage and visible deformity among 300,000 more Indians over the next 10 years. Let’s measure, report and reduce the number of patients who newly develop visible deformity during the first 2 years after the start of MDT. Let’s identify polar lepromatous patients upon diagnosis, and ensure their long-term protection against M. leprae. Let's not be content with claims and promises about interrupting transmission, but launch a robust test on a small island. Let’s use the standard definition of “burden of disease”.
At all times, let's keep our eyes firmly fixed on the bonfire of human nerves, which we can stop.
Regards,
Joel Almeida
References
[i] Richardus JH et al. Incidence of acute nerve function impairment and reactions in leprosy: a prospective cohort analysis after 5 years of follow-up. Int. J. Epidemiol. (2004) 33 (2): 337-343.
[ii] P. Vijayakumaran et al. Does MDT Arrest Transmission of Leprosy to Household Contacts? Int. J. Lepr. (1998) 66(2): 125-130.
[iii] Desikan KV, Sreevatsa. Extended studies on the viability of Mycobacterium leprae outside the human body. Lepr Rev. 1995 Dec;66(4):287-95.
[iv] Wheat HW et al. Long-term Survival and Virulence of Mycobacterium leprae in Amoebal Cysts. PLoS Negl Trop Dis. 2014 Dec; 8(12): e3405
[v] Kazda J, Irgens L, Kolk A. Acid fast bacilli found in sphangnum vegetation of coastal Norway containing Mycobacterium leprae specific phenolic glycolipid-I. Int J Lepr. 1990;58:353-357.
[vi] Murray et al, GBD 2010: design, definitions, and metrics (comment). The Lancet Vol 380 December 15/22/29, 2012, pages 2063-2066.
LML - S Deepak, B Naafs, S Noto and P Schreuder
LML blog link: http://leprosymailinglist.blogspot.it/
Contact: Dr Pieter Schreuder << editorlml@gmail.com
