Leprosy Mailing List – December 12, 2020
Ref.: (LML) Replacing opinions with evidence
From: Joel Almeida, London and Mumbai
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Dear Pieter and colleagues,
Several perspectives have been shared by esteemed colleagues. The heart of the matter is a contrast in epidemiological impact between front-line programs such as Karigiri, Uele and Shandong that demonstrated a 16% to 20% annual decline in new cases of HD (leprosy), and global practices that yield stagnation in the annual number of new cases (about 200,000 newly detected cases per year, disappointing annual decline of 0% to 3%). What explains this vast difference in outcomes/impact?
The acceptance of a 1% "relapse" rate appears to be at the root of this difference. How so? Fewer than 1% of cases newly detected by vigorous case-finding have anergy to the bacilli. Yet this small minority of newly detected cases, if left unprotected in endemic areas, is highly susceptible to reinfection and uniquely capable of shedding tens of millions of viable bacilli per day. A 100% cumulative recurrence rate among this tiny minority of newly detected patients would remain well within a 1% overall "relapse" rate. Yet it is this sub-1% rate of relapse that can result in 200,000 persons/year newly being detected with signs of HD.
Remarkable successes were created by inventive people at the front lines striving simply to do their best for their patients and their people. They were more closely associated with the grassroots than the ivory tower. Can we learn anything from their successes?
A good start is to dig below the surface of reported recurrence rates after the end of anti-microbial chemotherapy. They can be underestimated. This tends to happen in several ways..
Inadequate duration of follow-up
Visible recurrences among highly bacillated patients tend to start in year 6 after the end of MDT (multi-drug therapy), and continue well beyond 10 years.(1) Therefore follow-up truncated at 7 years (or even less) underestimates the frequency of re-infection, especially among persons with genetically determined anergy.
Inadequate BI criteria
Recognition of recurrence can be delayed by reliance on changes in average BI (bacillary index), instead of BI changes at single sites. Further, sequelae of past LL disease tend to delay the clinical suspicion of recurrence. Unavailability of skin smear facilities does not help.
Inappropriate populations
Follow-up in non-endemic areas does not reliably estimate the risk of reinfection in high-endemic areas. For example, reinfection rates in London (UK) are not expected to be very high.
Diluted denominators
Patients with a zero or low initial BI seldom suffer recurrence after MDT of any kind. Whenever included in estimates of recurrence rates, such patients dilute the denominator. This error is akin to diluting estimates of ovarian cancer risk by including boys in the denominator. That would lead to substantial under-estimates of the true risk. Similarly, if non-LL types of HD are included in the denominator then the recurrence rate among LL patients is likely to be underestimated. However, those with polar LL HD demand our special focus, as discussed further below. Recurrence rates among them need to be analysed separately.
Discussion
Prolonged anti-microbial protection of polar LL patients is important in endemic areas, for protecting individual patients against reinfection as well as to reduce transmission.
Polar LL HD patients form a small fraction of all newly diagnosed patients but uniquely are highly susceptible to (re)infection and - if denied prolonged anti-microbial protection - can shed tens of millions of viable bacilli per day.(2) This allows transmission to continue unchecked during covert bacillary multiplication in LL HD patients, without their knowledge or consent. Further, recurrence exposes nerves of LL HD patients to yet more damage induced by viable bacilli, again without their consent. Transmission newly blights the lives of hundreds of thousands of additional people each year, involving important physical, psychological, social, educational and economic consequences. Children are among those afflicted. It seems wiser to emulate successful programmes than needlessly to allow further damage among LL HD patients or continued transmission.
In Cebu (Philippines), even 24 months of MDT failed to extinguish most human sources of infection in an endemic area.(2) However, in Karigiri (India) anti-microbial protection of LL HD patients till smear negativity reduced the incidence rate of LL HD by 16%/year, until near-zero incidence of LL HD.(3) The dramatic successes of Karigiri, Shandong and Uele (16% to 20%/year decline in incidence rate) all relied on prolonged anti-microbial protection of LL HD patients.(4-6) We could help colleagues in endemic countries to expand and accelerate such demonstrable success, or at least give them the elbow room to succeed. If we are too quick to impose our views and (too often ineffective) interventions on them, the space and respect required for front-line innovation can be constricted.
Many enlightened private practitioners and centres of excellence in India are already striving to improve outcomes, in the best interests of their patients. In ensuring prolonged anti-microbial protection for LL HD patients in endemic areas, they are also helping to keep these patients out of the infectious pool. Prolonged anti-microbial protection for LL HD patients is often achieved by the usual drugs used till smear negativity, or else with monthly doses of 3 bactericidal drugs given after the conventional duration of MDT.
We are a community with noble values and principles, unique in our pre-occupation with a highly stigmatising and misunderstood disease that is considered by many to be a non-problem. Persons affected by HD typically champion inclusion. Far be it from us to champion exclusion of LL HD patients, especially exclusion from prolonged anti-microbial protection. Instead we could work shoulder to shoulder with those affected, as champions of inclusion. These are not only good things to do, and consistent with the Universal Declaration of Human Rights, but also wise and epidemiologically effective.
Joel Almeida
References
1. Balagon MF, Cellona RV, dela Cruz E et al. Long-Term Relapse Risk of Multibacillary Leprosy after Completion of 2 Years of Multiple Drug Therapy (WHO-MDT) in Cebu, Philippines. American Journal of Tropical Medicine and Hygiene, 2009; 81, 5: 895-9. reviewed and analysed further in 19a. Almeida J Recurrence rate among MB patients following RFT. LML 2 June 2019.
2. Davey TF, Rees RJ. The nasal dicharge in leprosy: clinical and bacteriological aspects. Lepr Rev. 1974 Jun;45(2):121-34.
3. Scheelbeek PFD, Balagon MVF, Orcullo FM et al. A retrospective study of the epidemiology of leprosy in Cebu: an eleven-year profile. PLoS Negl Trop Dis. 2013 Sep 19;7(9):e2444. doi: 10.1371/journal.pntd.0002444. eCollection 2013.
4. 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: 20a Almeida J. Karigiri, India: How transmission rapidly was reduced in a low-income population LML 29 October 2020
5. 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: 22a. Almeida J. What really happened in Shandong? LML 16 Nov 2019
6. 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: 23a. Almeida J. Reducing transmission in poor hyperendemic areas - evidence from Uele (DRC). LML 29 Nov 2019
= = = = =
P.S. UK policy states: "Multibacillary leprosy should be treated with a combination of rifampicin, dapsone and clofazimine for at least 2 years." Polar LL HD patients in endemic areas need at least as much anti-microbial protection as do patients in the UK.
As the COVID-19 pandemic response underlines,(7) the most effective public health measures can originate in any part of the globe. The front-line is where knowledge is turned into good outcomes and impact. An ounce of demonstration is worth a ton of promises. LML is inclusive rather than exclusive. This allows notable front-line successes in endemic countries to become more visible. Important claims are scrutinised here by nearly all of the world's most knowledgeable experts. That's why LML is so uniquely valuable. It helps in separating what works at the front-lines from what does not. It also provides informed answers to queries of various sorts. Every disease needs an LML. More importantly, the patients, professionals and populations of endemic countries need LML.Thank you to LML, its team, and all esteemed members in our unique community. We have one common enemy - the bacillus - and we are well on our way to defeating it.
Reference
7. Sridhar, D. COVID-19: what health experts could and could not predict. Nature Med 26, 1812 (2020). https://doi.org/10.1038/s41591-020-01170-z
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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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