Leprosy Mailing List – November 17, 2023
Ref.: (LML) Florida, Yunnan, Brazil & reducing transmission of HD
From: Joel Almeida, Mumbai, India
Dear Pieter & colleagues,
Almost everyone would like to replace low incomes with high incomes, and illiteracy or poor schooling with ample schooling. However, it is not easy to transform incomes overnight. Does HD (leprosy) necessarily have to keep spreading until everyone is well schooled and has a good income? Is there any alternative until such time as everyone has plenty of schooling and income?
Fig. 1 Newly detected MB cases over time
Persons with MB HD seldom self-heal. If not diagnosed promptly, they simply accumulate and are diagnosed eventually. Too often, delay in diagnosis permits irreversible nerve damage and visible deformity. The 5-year moving average of newly detected MB HD cases is a reasonably useful indicator of the underlying epidemiology.
From about 1993 active case-finding and MDT were stepped up greatly. This appears to have uncovered a backlog of accumulated, previously undiagnosed MB cases. Just when the number of newly detected MB cases reached an all-time high, HD was declared to be a non-problem. Since then, HD services have been curtailed greatly. Once the backlog of accumulated undiagnosed MB cases was cleared, the number of newly detected MB cases per year stagnated, despite widespread increases in income.
Prior to 1995 several places had achieved dramatic and reasonably well-documented declines in the incidence rate of MB HD, including Karigiri (India, 1), Uele (DR Congo, 2) and Weifang/Shandong (China, 3). All of them had relatively low income levels at the time (see graphs below). All had ensured prolonged anti-microbial protection for LL (lepromatous) patients. This was the widespread practice until the late 1990s. Thereafter even anergic LL patients were taken off anti-microbial protection after only 12 doses of rifampicin..
Fig. 2 New case detection rate over time compared between Wenshan (Yunnan, upper line) & Weifang (Shandong, lower line)
From the late 1980s Wenshan (Yunnan) introduced fixed-duration treatment (FDT or MDT for no more than 24 months). By contrast.Weifang (Shandong) used prolonged MDT lasting at least until smear negativity (3). The course of the endemic diverged markedly (Fig. 2). In Weifang (lower line) the rapid, relentless decline in new cases led to near-zero transmission. In Yunnan, despite vast increases in income, the decline in MB HD has remained notably slower: between only 5%/year and 10%/year.(4) Yunnan today has a much higher GDP per capita than Shandong did in the late 1980s and early 1990s. Despite this markedly higher income, Yunnan continues to show a slower decline than 1980s Shandong in new HD cases. The difference in income levels between 1980s Shandong and 2020 Yunnan is the exact opposite of that predicted by claims that, in the battle against HD bacilli, improvements in income levels are more important than astute use of anti-microbials.
Fig 3. Yunnan GDP per capita over time
Fig 4. Shandong GDP per capita over time
Elsewhere, Florida is not noted for conspicuously low incomes, compared to many HD endemic countries. Yet a few people in Florida develop signs of LL HD or MB HD each year even if they have never travelled to an endemic country and are not destitute. Intermittent contact with armadillo-contaminated soil appears sufficient for transmission of HD bacilli. Relatively high incomes apparently offer only limited protection against HD bacilli, once a genomically susceptible host encounters concentrated viable bacilli.
In Brazil, the type of HD in the presumed index case was a dominant factor in the risk of newly detected HD among contacts. The type of index case had a greater influence than even the illiteracy or relatively limited schooling of some contacts. (5)
Discussion
Everyone wants people to be well schooled and to earn a comfortable living. However, availability of concentrated viable HD bacilli and genomically susceptible hosts appears to be an even weightier factor in transmission than the income or schooling level of people. This is not to disparage the prime importance of improving living standards among people who have desperately low incomes and little or no schooling. It is merely to keep alive the legitimate hope and expectation of people in endemic areas that astute use of anti-microbials can achieve in more places what it demonstrably achieved in some places. There is no need to condemn people to anti-microbial neglect on the basis that they (or their descendants) will one day be well-schooled and have sufficient income.
Unprotected anergic LL patients can shed millions of viable HD bacilli per day or even per nose blow (6) Unprotected genomically susceptible hosts (genomically anergic LL patients with [re]infection or armadillos) are the key sources of concentrated viable bacilli. Anti-microbials are capable of protecting anergic LL patients against (re)infection in endemic areas. Armadillos and armadillo-contaminated soil can be avoided.
Rapid declines in the incidence rate of even MB HD were demonstrated in Karigiri (India), Uele (DR Congo) and Weifang/Shandong (China) all at a time of relatively low incomes (1-3). It is one thing to look for the victims of the HD bacilli, in order to prevent irreversible nerve damage. Would it be a bad idea to ask where the HD bacilli came from in the first place, and to shut down the sources of concentrated viable bacilli? India wisely favours reverse contact tracing, where the source index case is sought to be identified and treated. When done well, that is likely to have greater epidemiological impact than waiting for people to become infected before intervening. It is also less stigmatising than stereotyping all HD patients, including those who shed zero bacilli, as being dangerous to contacts.
Withdrawing anti-microbial protection from LL patients in endemic areas after only 24 months of MDT is known to increase the risk of recurrence/reinfection from 1.27/100 patient-years of follow-up in the group treated till smear negativity, to 4.29/100 patient-years in the fixed 24 months MDT group (p<0.01) (7). Withdrawing MDT after only 12 months also increases the risk of painful ENL neuritis by 600% during months 13 to 24 after the start of MDT (8). One solution is fully supervised post-MDT chemoprophylaxis for LL patients, with multiple drugs (eg. ROM - rifampicin or rifapentine + ofloxacin or moxifloxacin + minocycline ). The more affordable alternative is simply to prolong MDT.
Are we really determined to sit on our hands until income and schooling levels improve generally? Are we really determined to exclude anergic LL patients in endemic areas from anti-microbial protection once they complete 12 doses of rifampicin? Must they suffer bouts of excruciating ENL neuritis before they are re-admitted to anti-microbial protection? Would it be a bad idea to reduce the incidence rate of MB HD rapidly, as was achieved in several well-documented projects? (1-3)
Joel Almeida
References
1. Norman G, Bhushanam JDRS, Samuel P. Trends in leprosy over 50 years in Gudiyatham Taluk, Vellore, Tamil Nadu. Ind J Lepr 2006. 78(2): 167-185. reviewed and analysed further in: 1a. Almeida J. Karigiri, India: How transmission rapidly was reduced in a low-income population. LML 29 Oct 2020
2. Tonglet R, Pattyn SR, Nsansi BN et al. The reduction of the leprosy endemicity in northeastern Zaire 1975/1989 J.Eur J Epidemiol. 1990 Dec;6(4):404-6 reviewed in: 2a. Almeida J. Reducing transmission in poor hyperendemic areas - evidence from Uele (DRC). LML 29 Nov 2019
3. Li HY, Weng XM, Li T et al. Long-Term Effect of Leprosy Control in Two Prefectures of China, 1955-1993. Int J Lepr Other Mycobact Dis. 1995 Jun;63(2):213-221. reviewed & analysed further in: 3a. Almeida J. What really happened in Shandong? LML 16 Nov 2019
4. Chen X, Shui T-J (2021) The state of the leprosy epidemic in Yunnan, China 2011–2020: A spatial and spatiotemporal analysis, highlighting areas for intervention. PLoS Negl Trop Dis 15(10): e0009783. https://doi.org/10.1371/journal.pntd.0009783
5. Teixeira CSS, Pescarini JM, Alves FJO. Incidence of and Factors Associated With Leprosy Among Household Contacts of Patients With Leprosy in Brazil. JAMA Dermatol. 2020;156(6):640-648. doi:10.1001/jamadermatol.2020.0653
6. Davey TF, Rees RJ. The nasal dicharge in leprosy: clinical and bacteriological aspects. Lepr Rev. 1974 Jun;45(2):121-34
7. Girdhar BK, Girdhar A, Kumar A. Relapses in multibacillary leprosy: effect of length of therapy. Lepr Rev. 2000 Jun;71(2):144-53
8. Balagon MV, Gelber RH, Abalos RM, Cellona RV. Reactions following completion of 1 and 2 year multidrug therapy (MDT). Am J Trop Med Hyg 2010;83:637–44. Analysed further in 8a. Almeida J, LML 24 Mar 2023
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