Leprosy Mailing List – September 16 , 2020
Ref.: (LML) The neglected multitude of previously treated patients
From: Joel Almeida, London and Mumbai
Dear Pieter and colleagues,
The WER (Weekly Epidemiological Record) provides useful clues to what is happening, even though the precision and reliability of reports might be no better than it ought to be. I believe we are at a special point in the millennia-long history of the endemic. We now have enough understanding to match the spectacular past achievement of 20%/year decline in newly detected MB patients, leading rapidly to near-zero transmission. By contrast, even Norway showed no more than 10%/year decline. We know how to do better. The short communication below shows why.
There is no merit in doing the wrong things, even if they temporarily become fashionable. Science works best in an atmosphere of open discussion (like LML). We are waging a war on a tiny but highly damaging enemy, the bacillus. And we are doing this in order to transform human lives for the better. The whole world deserves an opportunity to do what really works, each individual contributing their special talents. In this age of video and easy translation, we can even reach out to hear the voices and experiences of people affected by HD who are otherwise poorly connected. They could help open our eyes to what is really happening.
Joel Almeida
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The neglected multitude of previously treated patients
In 2019, according to the WHO Weekly Epidemiological Record (WER), 3893 HD (leprosy) cases across the globe were reported as relapses after completion of MDT (multi-drug therapy), and 15 517 patients had restarted treatment for HD. 202,185 newly detected HD patients (all types) were reported. About 10% of HD patients tested yielded drug-resistant bacilli.
The trend in the number of newly detected MB (multibacillary) HD patients is probably the most reliable number for tracking the endemic. That is because MB HD rarely self-heals, and sooner or later these patients come to the attention of health services. MB HD cannot easily be swept under the carpet. Therefore, the number of newly detected MB patients/year is less susceptible to artefacts than are many other measures.
In India, following intensified case-finding with examination of contacts, plus a greater financial incentive to report non-G2D patients than G2D patients, newly reported MB HD patients declined at only 1% per year between 2015 and 2020 (based on WER data). These numbers suggest that claims about the rapid decline of HD in India (and elsewhere) might be somewhat out of touch with reality.
Figure 1. MB patients newly reported worldwide, by year of reporting until 2019 (see attached file). Stagnation over time, or possibly a slight increase, is apparent.
What does all this mean epidemiologically?
The number of previously treated persons with newly recognised bacillary multiplication was equivalent to about one-tenth of the number of newly detected HD patients of all types. And about one-sixth of the likely number of newly detected MB HD patients.
How long does it take to discern new bacillary multiplication in previously treated HD patients? Over 6 years in research projects with careful follow-up of subjects (2,3,4). Under typical conditions of health care in endemic areas, with absence of skin smear facilities, probably more than 6 years and nearer 10 years or more.
Further, MB HD and LLp (polar lepromatous) HD are significantly over-represented among those newly showing bacillary multiplication. LLp HD patients, in particular, uniquely have the genomes (5,6,7,8) that permit astronomical numbers of viable bacilli to be harboured and shed in high concentration. (9) *
Prevalence = Incidence rate x duration
Putting all that together, the hidden prevalence of previously treated patients with bacillary multiplication (and potential excretion) equals or exceeds the number of newly detected MB HD patients (by as much as nearly two-fold).
In short, the endemic is probably being maintained in recent decades by the neglected multitude of previously treated MB HD patients. Especially neglected LLp HD patients, many of whom are struggling with serious physical and other disabilities in addition to extreme poverty. (10)
There is considerable room for improvement in our epidemiological understanding and public health interventions, as well as in our respect for the human rights of the neglected.
As Article 25 of the Universal Declaration of Human Rights states:
"(1) Everyone has the right to a standard of living adequate for the health and well-being of himself and of his family, including food, clothing, housing and medical care and necessary social services, and the right to security in the event of unemployment, sickness, disability, widowhood, old age or other lack of livelihood in circumstances beyond his control."
Article 25 has particular force in HD, because improved medical (and other) care for the neglected multitude promises to improve life not only for them, but also for the entire population of HD endemic areas.
Continued anti-microbial neglect and other neglect of previously treated LLp HD patients is likely to be the single biggest obstacle to ending the transmission of HD, apart from being gratuitously cruel to those persons. If we seek first the improved anti-microbial protection (and comprehensive care) of the neglected multitude, all other things will be added unto us. This includes a likely end to transmission, as demonstrated in provinces where prolonged anti-microbial protection was ensured. That was followed by a rapid decline in newly detected MB HD patients/year, (11,12) even sustained until near-zero transmission. (13)
The voices of neglected previously treated HD patients might well help open our eyes, ears and minds to what is actually happening at the front-lines. We are a community of integrity, compassion and science. Therefore, we remain open to clues and keep making the improvements necessary. By respecting Article 25 of Universal Declaration of Human Rights, above all in the case of previously treated LLp HD patients, we too can end the transmission of HD.
Joel Almeida
* No other environmental sources of bacilli, apart from infected armadillos, can rival the spectacularly high concentration of astronomical numbers (hundreds of millions or billions) of viable bacilli as found in the nasal excretions of untreated persons with LLp HD. If it were possible for bacilli to not just survive in soil, amoebae, sphagnum moss etc., but actively to multiply prolifically, then we could cultivate the bacilli simply by growing them in such samples. No soil or amoebae or moss etc. have yet been discovered to permit prolific cultivation of the bacilli. Untreated LLp patients and infected armadillos so far remain the only known sources of such astronomical numbers of highly concentrated viable bacilli. This brings zero transmission within reach, especially in continents without armadillos.
Summary in translation
पहले से इलाज किए गए एमबी एचडी (कुष्ठ) के मरीज उपेक्षित हैं। यह फिर से संक्रमण की अनुमति देता है, खासकर एलएलपी एचडी वाले लोगों में। इस तरह एचडी का संचरण जारी रहता है। लंबे समय तक एंटी-माइक्रोबियल संरक्षण, स्वास्थ्य देखभाल बढ़ाई, और बेहतर सामाजिक-आर्थिक देखभाल, पहले से इलाज किए गए एलएलपी एचडी रोगियों के लिए एचडी के प्रसार को समाप्त कर सकता है। इस तरह की सुरक्षा मानव अधिकारों की सार्वभौमिक घोषणा के अनुच्छेद 25.1 का भी सम्मान करेगी।
Pacientes MB HD (hanseníase) tratados anteriormente são negligenciados. Isso permite a reinfecção, especialmente entre aqueles com HD Virchowian. É assim que a transmissão de HD continua. A proteção antimicrobiana prolongada, cuidados de saúde aprimorados e o cuidado socioeconômico aprimorado para pacientes em HD Virchowian tratados anteriormente podem acabar com a disseminação da HD. Tal proteção também respeitaria o Artigo 25.1 da Declaração Universal dos Direitos Humanos.
Pasien MB HD (kusta) yang sebelumnya dirawat saat ini diabaikan. Hal ini memungkinkan terjadinya infeksi ulang, terutama di antara mereka dengan LL HD polar. Begitulah transmisi HD berlanjut. Perlindungan anti-mikroba yang berkepanjangan, peningkatan perawatan kesehatan, dan perawatan sosial ekonomi yang lebih baik, untuk pasien HD LL kutub yang dirawat sebelumnya dapat menghentikan penyebaran HD. Perlindungan tersebut juga akan menghormati Pasal 25.1 dari Deklarasi Universal Hak Asasi Manusia.
Les patients atteints de MB HD (lèpre) précédemment traités sont actuellement négligés. Cela permet la réinfection, en particulier chez ceux avec LL HD polaire. C'est ainsi que se poursuit la transmission HD. Une protection antimicrobienne prolongée, amélioration des soins de santé et de meilleurs soins socio-économiques pour les patients HD LL polaires préalablement traités peuvent arrêter la propagation de la HD. Une telle protection respectera également l'article 25.1 de la Déclaration universelle des droits de l'homme.
Los pacientes con MB HD (lepra) tratados anteriormente están siendo desatendidos actualmente. Esto permite la reinfección, particularmente entre aquellos con HD LL polar. Así es como continúa la transmisión HD. La protección antimicrobiana prolongada, mejor cuidado de la salud, y la atención socioeconómica mejorada para los pacientes con HD polar LL tratados previamente pueden detener la propagación de la HD. Dicha protección también respetará el artículo 25.1 de la Declaración Universal de Derechos Humanos.
以前に治療されたMB HD（ハンセン病）患者は無視されます。これにより、特にLLp HD患者の再感染が可能になります。これがHD伝送が続く方法です。以前に治療されたLLp HD患者の長期的な抗菌保護、改善されたヘルスケア、および改善された社会経済的ケアは、世界からの感染を取り除くことができます（アルマジロのある大陸を除く）。そのような保護はまた、世界人権宣言の第25.1条を尊重します。
References
1 WHO. WER No 36, 2020, 95, 417–440
2. Penna GO, Bu¨hrer-Se´kula S, Kerr LRS, et al. Uniform multidrug therapy for leprosy patients in Brazil (U-MDT/CT-BR): Results of an open label, randomized and controlled clinical trial,among multibacillary patients. PLoS Negl Trop Dis 2017; 11(7): e0005725.
3. Butlin CR, Aung KJM, Withington S et al. Levels of disability and relapse in Bangladeshi MB leprosy cases, 10 years after treatment with 6m MB-MDT. Lepr Rev (2019) 90, 388–398.
4. 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.
5. Gaschignard J, Grant AV, Thuc NV, Orlova M, Cobat A, Huong NT, et al. (2016) Pauci- and Multibacillary Leprosy: Two Distinct, Genetically Neglected Diseases. PLoS Negl Trop Dis 10(5): e0004345. https://doi.org/10.1371/journal.pntd.0004345
6. Chakravarrti MR, Vogel F. A twin study on leprosy Georg Thieme Publishers, Stuttgart, Germany; 1973.
7. Cambri G, Mira MT. Genetic Susceptibility to Leprosy—From Classic Immune-Related Candidate Genes to Hypothesis-Free, Whole Genome Approaches. Front. Immunol., 20 July 2018 | https://doi.org/10.3389/fimmu.2018.01674
8. Sartori PVU, Penna GO, Bührer-Sékula S et al. Human Genetic Susceptibility of Leprosy Recurrence. Scientific Reports (2020) volume 10, Article number: 1284
9. Davey TF, Rees RJ. The nasal dicharge in leprosy: clinical and bacteriological aspects. Lepr Rev. 1974 Jun;45(2):121-34.
10. Rao PS, Mozhi NM, Thomas MV. Leprosy affected beggars as a hidden source for transmission of leprosy. Indian J Med Res. 2000 Aug;112:52-5.
11. 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: 11 a. Almeida J. What really happened in Shandong? LML 16 Nov 2019
12. 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: 12a. Almeida J. Reducing transmission in poor hyperendemic areas - evidence from Uele (DRC). LML 29 Nov 2019
13. Shumin Chen, Yunchun Zheng, Min Zheng, Demin Wang. Rapid survey on case detection of leprosy in a low endemic situation, Zhucheng County, Shandong Province, The People's Republic of China. Lepr Rev (2007) 78, 65–69.
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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