Leprosy Mailing List – August 7, 2023
Ref.: (LML) Are we opposed to success?
From: Joel Almeida, Mumbai, India
Dear Pieter and colleagues,
Are we opposed to stopping reinfection of those patients who remain susceptible to reinfection after 12 months of MDT? Must they incur an increased risk of ENL and unwitting transmission to others?
Is there some endemic area where rapid decline in the incidence rate of MB (multibacillary) HD (leprosy) was achieved without protecting highly bacillated patients against reinfection? No such area is easy to recall.
Exemplary projects in low income endemic areas achieved 16% to 20% per year decline in the incidence rate of MB and LL (lepromatous) HD [1-3] Such impactful projects invariably protected anergic patients against reinfection. This was achieved, mostly inadvertently, through prolonged anti-microbial protection for highly bacillated patients. Inadvertently, because there was not yet direct evidence of reinfection. Eventually, studies in Brazil provided direct evidence of reinfection in HD [4] and other studies in Brazil even suggested human genetic predisposition to recurrent HD.[5] Are we opposed to incorporating this knowledge into highly effective action?
Would it be a bad idea for India, Brazil and Indonesia to achieve 16 to 20% annual decline in the incidence rate of MB HD, as demonstrated by exemplary projects in low-income endemic areas? [1-3] Nearly 80% of all new cases occur in those 3 countries.
There is also a documented association between the risk of recurrent HD and new HD cases among children, as reported from an endemic area of Brazil.[6] This too points to reinfection rather than exclusively endogenous relapse as an explanation for recurrent HD in endemic areas. Are we against weakening this association? Are we determined to expose children and others to transmission from reinfected anergic LL patients? A single nose blow from a highly bacillated HD patient who is unprotected can contain millions of viable bacilli.[7] How are we supposed to reduce transmission if we allow such a tsunami of viable bacilli from reinfected patients to continue?
Further, would it be a bad idea to reduce the risk of the swollen, painful nerves of ENL? The risk of painful neuritis during months 13 to 24 after the start of anti-microbials was boosted by 600% when anti-microbials were withdrawn from LL patients after only 12 months. [8]
Based on the accumulating evidence, neglect of anergic previously treated patients in endemic areas can maintain transmission in even well-run programmes. It is transmission that opens the door to infection, disease, reactions, ENL, nerve damage, deformity etc.
We have effective options. Anti-microbial protection demonstrably reduces the risk of reinfection. In India, a recurrence rate of only 1.27/100 patient-years of follow-up was found in a prolonged MDT group compared to 4.29/100 patient-years in a fixed 24 months MDT group (p<0.01), among patients with an initial BI (log bacillary index) of 4+ or more.[9] Further, nearly half of the recurrences in that study relied on regular skin smear microscopy for detection, but reliable skin smear microscopy is not available everywhere. Elsewhere, expert clinicians were reported to detect signs of recurrence five times more frequently than well trained but non-expert health workers.[10] But expert clinicians are not available everywhere. Given all this, must anergic LL patients after 12 months of MDT be excluded from anti-microbial protection in endemic areas?
The world's most impactful intervention against HD transmission, in FS Micronesia, included prolonged anti-microbial protection, alongside expert skin camps and mass multiple drug administration (Rifampicin + Ofloxacin + Minocycline). [11, 12] In armadillo territory the further precaution of avoiding contact with armadillos or armadillo-contaminated soil is probably wise. But every endemic hot spot can aim for, and achieve, much greater than 20%/year decline in the incidence rate of MB HD, by emulating the FSM strategy. There is no need to regress to single drug use for prophylaxis, or to depict HD patients who shed zero bacilli as being dangerous to their contacts.
Highly bacillated patients in endemic areas are known to often show conversion of lepromin status upon receiving MIP vaccine/Mw [13] It is the remaining 10 to 30% of highly bacillated LL patients who remain in need of anti-microbial protection even if they receive MIP vaccine. They have a disproportionate impact on transmission because of the astronomical numbers of viable bacilli that they are capable of developing and shedding.
Given all this, must anergic LL patients after 12 months of MDT be excluded from anti-microbial protection in endemic areas? They are already excluded from many important things. Must they alone be banished to the pre-antimicrobial era? Are we opposed to protecting them against reinfection in endemic areas? Available options include either post-MDT chemoprophylaxis (e.g. fully supervised Rifampicin or Rifapentine + Ofloxacin or Moxifloxacin + Minocycline) or the more affordable option of simply prolonging MDT.
Each physician is empowered and even required to act in the best interests of patients. That may be partly why so many colleagues in endemic areas, including some who themselves have experienced HD, are looking beyond 12 months of MDT for highly bacillated patients. They are ensuring prolonged anti-microbial protection for their highly bacillated patients in endemic areas. In doing so, they are not only reducing the risk of painful ENL neuritis but also helping to reduce transmission. This is the nucleus of success in efforts to stop transmission. Success is unstoppable partly because every bit of new evidence points more clearly to the underlying realities; and partly because the easily avoidable suffering of people experiencing HD is not a comforting sight.
Are we opposed to success?
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. Stefani MMA, Avanzi C, Buhrer-Sekula S, Benjak A, Loiseau C, Singh P Whole genome sequencing distinguishes between relapse and reinfection in recurrent HD cases. PLoS Negl Trop Dis 2017; 11: e0005598
5. Sartori PVU, Penna GO, Bührer-Sékula S et al. Human Genetic Susceptibility of Leprosy Recurrence. Scientific Reports 2020 volume 10, Article number: 1284
6. Gonçalves FG, Belone AFF, Rosa PS, Laporta GZ. Underlying mechanisms of leprosy recurrence in the Western Amazon . BMC Infectious Diseases (2019) 19:460
7. Davey TF, Rees RJ. The nasal dicharge in leprosy: clinical and bacteriological aspects. Lepr Rev. 1974 Jun;45(2):121-34
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
9. Girdhar BK, Girdhar A, Kumar A. Relapses in multibacillary leprosy patients: effect of length of therapy. Lepr Rev 2000;71:144–53.
10. Balagon MF, Cellona RV, Cruz E, Burgos JA, Abalos RM, Walsh GP, et al. 2009. Long-term relapse risk in multibacillary leprosy after completion of 2 years of multiple drug therapy (WHO-MDT) in Cebu, Philipplines. Am. J Trop. Med. Hyg. 81(5), 895-899.
11. WORKSHOP ON THE PREVENTION OF LEPROSY, POHNPEI, FEDERATED STATES OF MICRONESIA. 25-27 MAY 1999 sponsored by the Sasakawa Memorial Health Foundation Tokyo, Japan and the Western Pacific Regional Office of the World Health Organization. Int J Lepr, 67 (4) (SUPPLEMENT)
12. Diletto C, Blanc L, Levy L. Leprosy chemoprophylaxis in Micronesia. Lepr Rev. 2000;71(Suppl):S21–3.
13. Sharma P, Misra RS, Kar HK et al. Mycobacterium w. vaccine, a useful adjuvant to multidrug therapy in multibacillary leprosy: A report on hospital based immunotherapeutic clinical trials with a follow up of 1-7 years after treatment. Lepr Rev 2000; 71 : 179-92.
LML - S Deepak, B Naafs, S Noto and P Schreuder
LML blog link: http://leprosymailinglist.blogspot.it/
Contact: Dr Pieter Schreuder << editorlml@gmail.com
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