Leprosy Mailing List – March 20, 2020
Ref.: (LML) Helping small Pacific populations to become HD-free
From: Joel Almeida, London and Mumbai
Dear Pieter and colleagues,
There are many atolls and small islands scattered over millions of square miles in the Pacific Ocean. Some have very small populations. Access is difficult. People from some of these islands have the right to move freely to and from the USA, and they often exercise this right.
Some esteemed colleagues have been discussing with me how best to eliminate HD from these small island populations.
One approach being tried is to use two annual rounds of population-wide chemoprophylaxis, accompanied by multi-year chemoprophylaxis for contacts of cases. Rifampicin is being proposed instead of the rifampicin+ofloxacin+minocycline (ROM) previously given population-wide in some Pacific islands (1). That population-wide ROM, including two separate doses for many individuals, had very little long-term impact. HD returned after a lull. That may well have been because the mass drug campaigns failed to diagnose LLp patients who lacked obvious physical signs..
What is likely to happen with the rifampicin-only approach?
"De novo" LL disease is known to show few or no obvious physical signs. A single dose of rifampicin kills roughly 90% of viable bacilli. Therefore each dose of rifampicin is likely to produce a roughly 10-fold boost in the frequency of rifampicin-resistant mutant bacilli in the surviving bacillary population of a person with missed HD. After 2 annual doses of rifampicin, such persons are likely to show a 100-fold boost in the frequency of rifampicin-resistant bacilli among their surviving bacilli. If undiagnosed LLp persons happen also to be contacts of newly diagnosed HD patients, they will be due to receive a further dose of rifampicin. This third dose is likely to contribute to a frequency of rifampicin-resistant mutants 1000-fold greater than in rifampicin-naive bacillary populations. These pre-selected bacillary populations with boosted rifampicin-resistant mutants, especially in persons with missed LLp HD, can then serve as the main source of HD bacilli in the human population.
Therefore, the intervention is likely to be followed by an eventual resurgence of HD in the population, but this time with rifampicin-resistant HD. This resurgence will likely be temporarily disguised by the delay of obvious physical signs in persons with the LLp genome(s), and by the incubation period of other types of HD in those newly infected. This delay is likely to be measured in years rather than months. So, the eventual impact will not become apparent until some years have passed.
Drug-resistance is of great help to HD bacilli, but unhelpful to the people of these islands. It could enable HD to continue for generations. This form of HD, however, will be more dangerous because of rifampicin-resistant bacilli.
Excluding covert "de novo LL" HD would help greatly. Therefore, the most reliable sequence of measures is probably:
1. Clinical examination and serology to exclude covert undiagnosed LL disease. If positive serology, then skin smears to identify LL patients so that they can be given prolonged anti-microbial protection (eg., not just MDT but also subsequent monthly multi-drug chemoprophylaxis to protect them against recurrence of HD). All newly diagnosed HD patients to receive MDT.
2. A dose of multi-drug chemoprophylaxis in the remaining population.
3. A few days later, BCG (re)vaccination in those who received the chemoprophylaxis. Or, MIP vaccine in place of BCG.
This can probably be implemented best by a mobile team of well-trained professionals who visit each atoll once or twice a year. They can supervise the campaign and train local general-purpose health staff (eg., for nerve function monitoring and prompt appropriate steroid use when needed). This approach could well lead to a sustained 20%/year decline in HD ending in near-zero transmission, with near-zero new disability and declining stigma.
The use of multi-drug chemoprophylaxis, instead of rifampicin on its own, would avert a legacy of rifampicin-resistant HD. Instead, we could achieve an HD-free Pacific.
Joel Almeida
References
1. Diletto C, Blanc L, Levy L. Leprosy chemoprophylaxis in Micronesia. Lepr Rev. 2000;71(Suppl):S21–3.
LML - S Deepak, B Naafs, S Noto and P Schreuder
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