Leprosy Mailing List – March 15, 2020
Ref.: (LML) The "reproductive numbers" in COVID-19 and HD
From: Joel Almeida, Mumbai, India
Dear Pieter and colleagues,
The COVID-19 pandemic has highlighted a key parameter: R(0), the "reproductive number". (1) How many new infections does a single infection produce? This allows an estimate of the maximum number of people likely to be infected in a human population:
1-1/R(0). In COVID-19, given an estimated R(0) of 2.5, the likely maximum fraction of the population that eventually will become infected is 60%. If the true R(0) is higher, the maximum fraction will also be higher. Control measures tend to reduce R(0). So does immunity develop by sub-clinical infection.
The "reproductive number" is useful in understanding the epidemiology of transmission in HD (Hansen's disease) too.
In HD there is a huge difference in the number of bacilli shed/day by persons with LL disease compared to persons with even BL and BT forms. Persons with untreated LL disease can shed tens of millions of viable bacilli per day, whereas others shed several orders of magnitude fewer, and sometimes even no bacilli. (2) One untreated person with LL disease is therefore equivalent to millions of untreated persons with other types of HD. Therefore, the parameter of greatest epidemiological consequence is the reproductive number of LL disease.
We can work backwards from the maximum observed fraction of the population with LL disease (cumulative incidence) to estimate the R(0) of HD in hyper-endemic areas, in the presence of limited-duration MDT.
Given an average age of acquiring LL HD about 35 years
average remaining life expectancy 40 years
incidence rate of all types of HD in endemic areas under 5 in 10,000 population/yr
fraction of LL HD among all newly diagnosed patients 1%
We get a cumulative incidence of LL HD in the region of 2 in 10,000 population.
The reproductive number R(0) of LL HD in hyperendemic areas using limited-duration MDT can therefore be estimated as 1.0002.
That is, one person with LL HD produces roughly one new person with LL HD. The bacilli seem to be clinging on precariously to the human population. This suggests that interruption of transmission is nearer at hand than sometimes believed. This is in areas without armadillos.
However, in families with a concentration of LLp genomes, the R(0) of LL HD is likely to be much higher than 1.0002. One person with LLp disease can give rise to several new persons with LLp disease, as is observable in multiple-patient households. The fraction of the children in such a family developing LLp disease can be as high as 100%.
HD therefore appears to be an infectious disease that is self-limiting in human populations, but can flare up in families with offspring who have a concentration of the LLp genome. This gives rise to strong clustering around persons with LL disease (households, workplaces etc), and around families with multiple persons developing LL disease.
All this has practical implications for interrupting transmission. Our focus in interrupting transmission needs to be on reducing the R(0) of LL HD to less than one. That will spell the end of HD transmission. What should we do?
1. Ensure that a person with LL disease never again is neglected during their lifetime. Ensure that bacilli can never regain a foothold in such a person. This is not only for their protection from damage cause by bacilli, and to uphold their human dignity and rights, but also to help reduce the R(0) of LL HD in the population to less than one. Signs of recurrence can be masked by sequelae of past active infection, delaying the diagnosis of recurrence. Prolonged anti-microbial protection for all LL HD patients is therefore the safest approach, for their own benefit and the benefit of the whole population.
2. Ensure that drug resistance is delayed. Drug-resistance can multiply the R(0) of LL HD. Avoid the use of single drugs for treatment or prophylaxis. Persons with undiagnosed LL HD who are given a single dose of rifampicin can play a disproportionately important role in the selection and transmission of drug-resistant HD bacilli. Selecting drug-resistant mutant bacilli could maintain the R(0) above one and allow the bacilli to continue spreading for generations despite all our other efforts.
3. Ensure prompt diagnosis of HD, especially LLp (de novo LL) HD. This is easily excluded by the use of skin smears, or serology and PCR. However, the clinical signs can often be so subtle that even experienced clinicians miss the early signs. Reliable skin smears need to be restored especially in endemic areas, supplemented by more sensitive tests whenever possible.
HD appears to be a disease that is maintained precariously in human populations (outside the Americas, where armadillos live) by human errors. We can keep correcting our errors, take effective action, and confidently look forward to interrupting transmission.
Joel Almeida
References
1. Anderson RM, Hesterbeek H, Klinkenberg D, Hollingsworth TD. How will country-based mitigation measures influence the course of the COVID-19 epidemic? Lancet.com. Published Online March 6, 2020 https://doi.org/10.1016/S0140-6736(20)30567-5
2. Davey TF, Rees RJ. The nasal dicharge in leprosy: clinical and bacteriological aspects. Lepr Rev. 1974 Jun;45(2):121-34.
LML - S Deepak, B Naafs, S Noto and P Schreuder
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