Leprosy Mailing List – January 10, 2024
Ref.: (LML) Why does HD continue to spread in India?
From: Joel Almeida, Mumbai, India
Dear Pieter and colleagues,
Why does HD (leprosy) continue to spread in India, despite great efforts?
Why does HD continue to spread in India?
The Indian government has given priority to efforts against HD. In recent years India has been conducting periodic active case detection drives from door-to-door in endemic areas, augmenting routine ongoing case detection efforts. However, the decline in the incidence rate of MB (multibacillary) HD patients has been remarkably slow: only about 3%/year.
In one hot spot, the new case detection rate of HD even rose by several hundred percent within only 3 years, with highly bacillated undiagnosed or previously treated patients respectively being identified later.(1)
By contrast, some successful Indian projects in low income areas documented a decline of 16%/year in the incidence rate of MB HD or LL HD.(2) 16%/year in a successful project vs 3%/year more widely is a marked difference. What might explain this difference?
The National Sample Survey in India
The National Sample Survey in India in or around 2011 (3) did door-to-door surveys among a stratified random sample of the entire Indian population, backed by experienced clinicians. From this reasonably reliable survey, it was estimated that the upper confidence limit of the number of previously undiagnosed HD patients in India was 381,000 patients. (This corresponds to an upper estimate of point prevalence of around 3 HD patients/10,000 population. HD in India appears to be somewhat less eliminated than we would like it to be). 40% of these previously undiagnosed patients had signs of MB HD.
What are the sources of concentrated viable HD bacilli?
The WHO Weekly Epidemiological Record (4) previously had reported the proportion of actively detected Indian HD patients with a BI (bacillary index) greater than 3+ log units. The said proportion was 1% in India. Therefore, assuming for present purposes that all patients with BI > 3+ have LL HD, it seems likely that as many as 4000 LL HD patients remain undiagnosed and untreated in India at any given time. This number tends to reduce as active case-finding gains frequency and intensity. However, even with intensive active case-finding, undiagnosed "de novo" LL HD patients tend to be missed wherever clinical expertise or smear microscopy are lacking.
Incidentally, persons with the early stages of "de novo" LL HD tend to show the least conspicuous signs among all new HD patients. They typically show no patches, not even clear enlargement of peripheral nerves. However, "de novo" LL HD patients still tend to show millions of densely packed acid-fast bacilli in nasal smears even before physical signs become prominent. (5)
The WHO Weekly Epidemiological Record (6) in 2023 reported that re-treatment was found necessary in 7600 Indian HD patients during the preceding year. LL HD patients tend to be over-represented among all patients requiring re-treatment, partly because they include patients with genomically linked anergy. Such over-representation of LL HD is likely in India where 95% of all MB patients are reported to have completed the 12 monthly doses of rifampicin in MDT.(6)
An LL patient denied anti-microbial protection can develop and shed as many as ten million viable bacilli per day, or even per nose blow, before or after anti-microbial treatment. (5) Accordingly, several thousand unprotected LL patients in India are likely to be shedding astronomical numbers of viable HD bacilli at any given time. These are likely to include around 4000 previously undiagnosed LL patients plus several thousand more previously treated LL HD patients.
Recurrence after MDT among genomically anergic LL patients is more frequent than we would like. It can arise either by endogenous relapse or exogenous reinfection or both. (7-12) Therefore, previously treated LL HD patients with anergy are likely to form an important source of concentrated viable HD bacilli in endemic areas of India. In well-run programmes, expert clinicians reduce the number of missed LL HD patients. In such areas, and possibly elsewhere too, previously treated but reinfected anergic LL HD patients could well form the dominant source of concentrated, viable bacilli.
Implications and effective action
The evidence suggests that HD will continue to spread in India for decades, unless
a) "De novo" LL HD is diagnosed more reliably and promptly, especially in the absence of prominent physical signs.
b) Previously treated LL patients in endemic areas are protected against reinfection. One option is post-MDT chemoprophylaxis with fully supervised potent drugs (e.g., rifapentine or rifampicin + moxifloxacin + minocycline - PMM instead of just ROM - rifampicin + ofloxacin + minocycline). For destitute patients, or in low income areas, MDT itself could serve as "poor person's" post-MDT chemoprophylaxis. Not optimal, but better than zero anti-microbial protection for anergic LL HD patients in endemic areas.
Allowing HD patients and professionals to succeed
Are we really keen to exclude previously treated LL HD patients from anti-microbial protection? Must they be excluded until painful ENL neuritis drives them to seek help? Would we be as quick to exclude them if we ourselves had LL HD with genomically linked anergy and lived in an endemic hot spot? Especially if we had experienced a bout of excruciatingly painful ENL? Would we still be deaf to the pleas of other HD patients for good anti-microbial protection in endemic areas?
Some well-informed health professionals have themselves experienced HD. They tend to show more than usual compassion and respect for HD patients. It is within our power to emulate their compassion. How are they supposed to do their best for HD affected patients and populations if we handcuff them with restrictions? In places such as Karigiri (2) and Uele (13) professionals armed with compassion and respect for all achieved rapid decline in the incidence rate of MB HD. The only "party line" they followed was compassion and good professional standards. They set out to provide excellent care for their patients and populations, and ended up with world-leading outcomes and epidemiological impact.
HD transmission in India appears to be maintained by the exclusion of LL HD patients from anti-microbial protection, before diagnosis or after 12 doses of intermittent rifampicin. It is within our power as a well-informed, compassionate, influential community respectful of human rights and facts, to stand shoulder to shoulder with patients and populations at risk. We could allow LL patients in endemic areas to have anti-microbial protection beyond just 12 doses of rifampicin. In doing so, we can hope to match the successful projects that achieved rapid, well-documented decline of MB HD. (2,13,14) Are we opposed to the rapid decline of MB HD in endemic areas?
Best,
Joel
References
1. Gitte S, Rewaria L, Santaram V, Jamil S. Descriptive Study of High Leprosy Endemic Pockets and Exploring Occurrence Factors of Multicase Families in the Village of Salaunikhurd of Chhattisgarh State. Int J Med. Public Health. 2021; 11(2):113-117
2. 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: 3a. Almeida J. Karigiri, India: How transmission rapidly was reduced in a low-income population. LML 29 Oct 2020
3. Katoch K, Aggarwal A, Yadav VS, Pandey A. National sample survey to assess the new case disease burden of leprosy in India. Indian Journal of Medical Research, 2017; 146(5): 585-605.
4. WHO WER 1998, 73, 153-160
5. Davey TF, Rees RJ. The nasal dicharge in leprosy: clinical and bacteriological aspects. Lepr Rev. 1974 Jun;45(2):121-34
6. WHO WER 2023, 98, 409–430
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. Singh I, Ahuja M, Lavania M, Pathak VK, Turankar RP, Singh V, et al. Efficacy of fixed duration multidrug therapy for the treatment of multibacillary leprosy: A prospective observational study from Northern India. Indian J Dermatol Venereol Leprol 2023;89:226-32.
9. 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
10. Sartori PVU, Penna GO, Bührer-Sékula S et al. Human Genetic Susceptibility of Leprosy Recurrence. Scientific Reports 2020 volume 10, Article number: 1284
11. Gonçalves FG, Belone AFF, Rosa PS, Laporta GZ.Underlying mechanisms of leprosy recurrence in the Western Amazon . BMC Infectious Diseases (2019) 19:460
12. Narang T, Almeida JG, Kumar B, Rao PN, Suneetha S, Frade MAC, et al. Fixed duration multidrug therapy (12 months) in leprosy patients with high bacillary load – Need to look beyond. Indian J Dermatol Venereol Leprol. 2024;90:64-7. doi: 10.25259/IJDVL_278_2023
13. 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: 13a. Almeida J. Reducing transmission in poor hyperendemic areas - evidence from Uele (DRC). LML 29 Nov 2019
14. 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: 14a. Almeida J. What really happened in Shandong? LML 16 Nov 2019
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