Leprosy Mailing List – February 8, 2019
Ref.: (LML) Interrupting transmission: the critical improvement
From: Joel Almeida, London and Mumbai
Dear Pieter,
We know that untreated persons with the polar LL (LLp) type of Hansen's Disease generally have the highest bacterial loads. Histopathology typically shows globi. One such patient, if left without anti-microbial protection, can nurture, harbour and excrete more viable M. leprae than hundreds of thousands of patients with the BT type of HD.
Further, genes contribute to the observed polarisation of immune response in HD (1). Monozygotic twins with disseminated types of HD were reported to show a 70% concordance of HD type while dizygotic twins showed only a 20% concordance (2). In other words, LLp status seems linked to genetic status. These patients probably start off as LLp (sometimes recognised as "de novo MB") and then remain susceptible to reinfection after MDT.
Since M. leprae remain viable in the environment for at least 5 months in the shade (3), the spread of M. leprae despite MDT is probably maintained as follows:
From
A. an unprotected LLp patient (before or after MDT)
To
B. the environment, with viability retained for 5 months
To
C. another unprotected LLp patient, within 5 months.
D. Repeat the cycle of transmission.
In households with several persons having the LLp genetic profile, transmission can skip the environmental step.
This cycle of transmission probably explains why chemotherapy or chemoprophylaxis of limited duration show a disappointing impact, with children being infected and even disfigured. Further, re-treatment of LLp patients, if delayed until after clinical signs of relapse/reinfection, still allows the spread of M. leprae during the new sub-clinical phase.
The challenge, therefore, is two-fold:
a) Detect and identify LLp patients more promptly
b) Protect them against M. leprae for longer than the standard duration of MDT.
Such prolonged anti-microbial protection was used in Shandong Province in China. Implementation was so efficient that the outcome was steady and sustained interruption of transmission, even before the introduction of MDT (3). Interestingly, India's GDP per capita lagged behind China's by only 5 years. But India then discouraged skin smears and started withdrawing anti-microbial protection prematurely from LLp patients. Unsurprisingly, HD control in India lags China by more than 5 years. In some Indian hot spots, the observed incidence rate of HD has even been increasing.
Recognising LLp patients more promptly is a challenge, because the clinical signs are very subtle. Sometimes, no more than a slight induration of the skin. The challenge is even greater when skin smears are unavailable.
Prolonged protection of LLp patients is easy and cheap to do. We need merely prolong MDT for an LLp patient. Without this, it becomes very difficult to reduce transmission. If we protect LLp patients against re-infection, we can better protect the eyes, limbs, minds, livelihoods and relationships of not only LLp patients but also everyone else who is susceptible to M. leprae.
I spent several years examining and biopsying every single relapsed patient in a population of nearly half million people in India, followed by histopathology and mouse foot pad tests. Every single known case of HD and household contact was accounted for. That intense front-line experience tends to open one's eyes and mind to clues about what's really happening clinically, microbiologically, immunologically and epidemiologically. All of us continue to learn and ask searching questions as steadily more pieces of the HD jigsaw are uncovered by great colleagues in the basic and applied sciences.
How did our lax approach to treatment arise?
We have not routinely been stratifying outcomes of MDT by the type of HD (LLp / other). So, we condone a relapse/reinfection rate of under 'n' % per year. Unfortunately, the LLp genes are probably so infrequent that every LLp patient could show relapse/reinfection and still the relapse/reinfection rate would remain below n%. But a single LLp patient can harbour and excrete more M. leprae than hundreds of thousands of patients with the BT type of HD. Consequently, M. leprae can continue to spread with full force, even while we condone "low" relapse/reinfection rates.
It's an easy mistake to make, and we were inexpert enough to make it. We're all human, so there's no shame in making mistakes. The important thing is to understand what is happening and take corrective action.
Once we start providing prolonged anti-microbial protection (MDT) to persons with LLp, we can have more hope of a sustained reduction in transmission of M.leprae just as happened in Shandong Province. Half-hearted chemical isolation does not work, as shown by the continuing transmission of M. leprae in so many MDT programmes. It has to be highly efficient and effective chemical isolation to interrupt transmission at the source. That source is mainly unprotected LLp patients, through no fault of their own.
Let's join together and make this critical improvement. We are capable of saving more limbs, eyes, minds, livelihoods and relationships among susceptible people in endemic areas. Let's do it. Let's ensure prolonged anti-microbial protection for LLp patients.
O principal desafio no controle de HD é a proteção de pacientes com LL polar contra a re-infecção do M. leprae ambiental. Caso contrário, forçamos os pacientes com LLp a permanecer como as principais fontes de infecção para os outros e para o meio ambiente. Então a transmissão continua apesar da PQT e da quimioprofilaxia.
Le principal défi en matière de contrôle de la HD est la protection des patients LL polaires contre une réinfection à partir de M. leprae dans l'environnement. Sinon, nous obligerons les patients LLp à rester la principale source d'infection pour les autres, et la transmission se poursuit malgré la PCT et la chimioprophylaxie.
Joel Almeida
References
1. Gaschignard J, Grant AV, Thuc NV, Orlova M, Cobat A, Huong NT, et al. (2016) Pauci- and Multibacillary Leprosy: Two Distinct, Genetically Neglected Diseases. PLoS Negl Trop Dis 10(5): e0004345. https://doi.org/10.1371/journal.pntd.0004345
2. Chakravarrti MR, Vogel F. A twin study on leprosy Georg Thieme Publishers, Stuttgart, Germany; 1973.
3. Desikan KV, Sreevatsa. (1996) Extended studies on the viability of Mycobacterium leprae outside the human body. Lepr Rev 66(4):287-95
4. Li Huan-Ying, Pan Yu-Lin, and Wang Yang. (1985) Leprosy Control in Shandong Province, China, 1955-1983; Some Epidemiological Features. Int J Lepr 53(1): 79-85.
LML - S Deepak, B Naafs, S Noto and P Schreuder