Leprosy Mailing List – June 22, 2019
Ref.: (LML) Interruption of transmission - post-MDT chemoprophylaxis for LL patients
From: Joel Almeida, London and Mumbai
Dear Pieter,
Two prefectures in China both showed a reasonably good rate of decline in disease incidence from 1955 to 1985.(1) These were Weifang prefecture in Shandong province and Wenshan prefecture in Yunnan province.
In 1986 MDT was introduced. Wenshan/Yunnan used fixed-duration MDT. Weifang/Shandong used prolonged MDT, with patients treated until smear negativity. The Figure compares the epidemiological impact of the two policies.
The Figure. New cases detected/100,000 population in Wenshan/Yunnan (upper line) and Weifang/Shandong (lower line). MDT was introduced in 1986. Rate of decline in new case detection following fixed duration MDT vs prolonged MDT. (based on Li et al 1995)
With fixed-duration MDT, the decline of disease incidence levelled off from about 9% per year to about 0% per year (upper line, Wenshan/Yunnan). By contrast, the decline of disease incidence accelerated from about 13% per year to about 20% per year after the introduction of MDT, but only when MDT for MB patients was prolonged (Weifang/Shandong, lower line). The difference is attributable, in important part, to Weifang/Shandong's continuing anti-microbial protection of LL patients after 24 months of MDT.
Other factors probably contributing to the difference include greater socio-economic advancement and greater BCG coverage in Weifang/Shandong. However, a direct before/after comparison is also available for Wenshan/Yunnan. There, the GDP per capita and the BCG coverage both continued to increase with time. Despite this, the decline levelled off once fixed-duration MDT was introduced in Wenshan/Yunnan. Therefore fixed-duration MDT demonstrably had a negative influence on the rate of decline, despite the other improvements.
The most important point is that 20% annual decline in disease incidence is achievable. Weifang/Shandong demonstrated this. We need just to start protecting LL patients against recurrence, after the standard duration of MDT. Monthly post-MDT chemoprophylaxis using 2 or 3 bactericidal drugs is likely to be nearly 100% effective for this.
As noted in previous contributions here, the cumulative risk of recurrence among unprotected LLp patients in endemic areas after 24 months of MDT can be as high as 75%. This unnecessarily exposes them to further deterioration of nerve function. Further, a single untreated LLp patient with recurrent disease has been shown to shed over a billion bacilli per day, including tens of millions of viable bacilli (3). No other known source, apart from armadillos, shows such dense concentration of viable bacilli. Asia and Africa are not known to have armadillos.
Post-MDT chemoprophylaxis, to prevent recurrence among LL patients, is the critical intervention that can unlock the potential of all our other interventions and innovations. Because it is the only intervention, apart from MDT, which interrupts transmission at source. Post-MDT chemoprophylaxis for LL patients can help unlock and multiply the potential of all our other interventions and innovations including contact tracing, active case finding, PEP, PEP++, improved diagnostic tests, BCG, M. Indicus Pranii (MIP) vaccine, and all candidate mycobacterial vaccines. Unless we interrupt transmission at source, we will be like misguided firefighters who focus on distributing gas masks and blankets while ignoring the fire.
Experiences elsewhere also offer clues. Failure to protect LL patients after MDT helps to explain the stagnation of disease incidence in endemic zones of Cuba. This is despite the use, for almost two decades now, of vigorous practices including contact tracing, pre-clinical serological diagnosis, post-exposure chemoprophylaxis (PEP) and BCG (4). A disappointing rate of decline is seen also in Dadra Nagar Haveli (DNH) in India, which not only has been using PEP but also probably has the world's most intensive case-finding efforts. The case-finding is so intensive that fewer than 0.5% of newly detected patients in DNH show visible deformity at diagnosis. This contrasts with more than 5% found in other endemic parts of the world. Still, viable bacilli continue to spread with troubling force in the well-implemented programmes of Cuba and DNH. Continuing transmission is attributable largely to recurrent disease among LL patients after the end of MDT (endogenous relapse + exogenous re-infection). Such recurrences of disease are difficult to detect, but they can provide astronomical numbers of viable bacilli over sustained durations. This severely reduces the epidemiological impact of all our other interventions and innovations. The fire consequently continues unchecked despite all our other worthy efforts.
Shandong's success was achieved with financial investment from the (then) Sasakawa Memorial Health Foundation - now known as the Sasakawa Health Foundation. Shandong's achievement of near-zero transmission is an important milestone in the history of public health. The Foundation invested, and ended the disease there. Generations of people in Shandong will thank all who contributed to this great achievement. Generations elsewhere will thank Shandong for showing the way to success. Shandong's victory points to the critical intervention: anti-microbial protection of LL patients after the standard duration of MDT. Now we can spread the victory to other endemic areas. We need just to start using monthly post-MDT chemoprophylaxis (eg., rifampicin+moxifloxacin+minocycline) for LL patients.
Incidentally, Wenshan/Yunnan received other financial support, from global sources. That funding apparently constrained Yunnan to use fixed duration MDT. Shandong's policy was demonstrably more effective. We need to remain respectful of the best local talent and their unique insights.
We are all life-long students. The evidence is our teacher. There is no shame in past mistakes, since we are all human. The important thing is to correct mistakes. When careful analysis of the evidence is contrary to our prior understanding, our minds are open to more effective policies. We choose the ethical, compassionate and epidemiologically effective approach. The alternative now would be wilful negligence towards LL patients and the people around them. Such negligence would keep the endemic alive. We are too conscientious and compassionate to inflict negligence on the people we serve.
Cuba's endemic zones and DNH already have been implementing nearly all of the currently favoured practices, with disappointing impact on the incidence rate of disease. It would be better to interrupt transmission and achieve a 20% annual decline in the incidence rate of new cases, like Shandong, instead of settling for the relative stagnation observed elsewhere. We can visualise a world which, in 2030, has a 90% lower incidence rate of disease than is observed currently. We know how to achieve that: add monthly post-MDT chemoprophylaxis for LL patients, to our other worthy efforts.
Shandong showed that the Goodwill Ambassador's life-long ambition of interrupting transmission is demonstrably achievable. We can, and will, reduce the recurrence rate among LLp patients from as high as 75% to 0%. We can, and will, behave conscientiously towards all LL patients after MDT, respecting their human rights and providing them with competent case management services including monthly post-MDT chemoprophylaxis. Once we act in this honourable, conscientious, scientific, humane and compassionate way, we will interrupt transmission just as Shandong did.
Joel Almeida
Translations
हम जानते हैं कि नए एमबी रोगियों की संख्या को 20% प्रति वर्ष कैसे कम किया जाए। हम एक ऐसी दुनिया की कल्पना कर सकते हैं जिसमें 2030 तक नए एमबी रोगियों की संख्या 90% तक कम हो जाती है। हम जानते हैं कि इसे कैसे प्राप्त करें: एमडीटी के बाद एलएल रोगियों के लिए मासिक केमोप्रोफिलैक्सिस का उपयोग करें। उदाहरण के लिए, रिफैम्पिसिन + मोक्सीफ्लोक्सासिन + मिनोसाइक्लिन मासिक में लगभग 100% प्रभावकारिता होगी। एमडीटी के बाद एलएल रोगियों में बीमारी की पुनरावृत्ति को रोका जा सकेगा। इसके बिना हमारे सभी अन्य प्रयासों और नवाचारों पर बहुत कम प्रभाव पड़ने की संभावना है।
Sabemos como reduzir o número de novos pacientes com MB em 20% ao ano. Podemos imaginar um mundo em que os novos pacientes com MB sejam reduzidos em 90% até 2030. Sabemos como obtê-lo: Use a quimioprofilaxia mensal para pacientes com LL após a MDT. Por exemplo, Rifampicina + Moxifloxacina + Minociclina mensalmente terá quase 100% de eficácia. A recorrência da doença após a MDT será evitada. Sem isso, todas as nossas outras intervenções e inovações provavelmente terão pouco impacto.
Nous savons comment réduire le nombre de nouveaux patients atteints de MB de 20% par an. Nous pouvons imaginer un monde dans lequel les nouveaux patients atteints de MB seront réduits de 90% avant 2030. Nous savons comment l'obtenir: Utilisez la chimioprophylaxie mensuelle pour les patients LL après la PCT. Par exemple, la rifampicine + moxifloxacine + minocycline mensuelle aura une efficacité de presque 100%. La récurrence de la maladie chez les patients LL après la PCT sera prévenue. Sans cela, tous nos autres efforts et innovations n'auront probablement que peu d'impact.
References
1. 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.
2. Li HY, Pan YL, Wang Y. Leprosy control in Shandong Province, China, 1955-1983; some epidemiological features. Int J Lepr Other Mycobact Dis. 1985 Mar;53(1):79-85
3. Davey TF, Rees RJ. The nasal dicharge in leprosy: clinical and bacteriological aspects. Lepr Rev. 1974 Jun;45(2):121-34.
4. Beldarraín-Chaple E. Historical Overview of Leprosy Control in Cuba. MEDICC Rev. 2017 Jan;19(1):23-30.
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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