Friday, November 29, 2019

FW: (LML) Reducing transmission in poor hyperendemic areas - evidence from Uele (DRC)


Leprosy Mailing List – November 29,  2019

Ref.:   (LML) Reducing transmission in poor hyperendemic areas - evidence from Uele (DRC)

From:  Joel Almeida, London and Mumbai

Dear Pieter and colleagues,


A remarkably effective attempt was made in the Uele region (in the north-eastern part of what once was called Zaire, now Democratic Republic of Congo) to reduce transmission using anti-microbials,(1) without segregation and during a time of declining GDP per capita. The initial number of unregistered cases was 22/10,000 population.


The control programme


Patients self-reported for diagnosis, skin smears and skin biopsies were taken. Patients then continued living at home, without segregation. Mobile HD teams visited patients at fixed sites, at monthly intervals. Once a year patients at each site were visited by a physician. Training, re-training and supervision of HD paramedical workers was provided by an HD centre. This centre also provided in-patient treatment as necessary, orthotics, rehabilitation and research facilities. The anti-microbial chemotherapy is described later.



The socio-economic background


GDP per capita was low and declining.




Figure 1. Real GDP per capita in DRC, 1960-2018 (source: Trading Economics)


 A steep decline in GDP per capita began in about 1975 and then temporarily levelled off until about 1990. Later GDP declined again.



The outcomes


The outcomes are shown below, starting in 1975. This was just after the HD control programme had gone through a decade-long transition period owing to political changes. From 1975 the mobile HD teams were more numerous, better equipped and better trained. 




Figure 2. Newly detected patients with MB HD/100,000 population /year, 1975-1988 in Uele, DRC. (Almeida J 2019, based on ref 1)


The raw observations show a decline in newly detected MB patients. The "absence of mutilations" among newly diagnosed patients throughout the period was noted. MB patients formed fewer than 16% of all newly diagnosed patients.


It is useful to look at the period from 1978 onwards (year 4 in Fig. 2). By then any backlog of unregistered MB patients accumulated prior to 1975 was likely to have been registered.




Figure 3. Newly detected patients with MB HD /100,000 population /year, 1978-1981 in Uele (DRC), using prolonged anti-microbial protection (dapsone) for MB patients (Almeida J 2019, based on Tonglet et al, ref 1)


The decline in newly detected MB patients was rapid (about 17%/year). This occurred without increase in GDP per capita and without segregation of HD patients.


Prolonged anti-microbial protection with dapsone was used until 1981. During 1981, closely supervised 1-year experimental multi-drug regimens (including 6 months of daily rifampicin) were introduced for MB patients.  




Figure 4. Newly detected patients with MB HD / 100,000 population / year, 1978-1981 in Uele (DRC), using 1-year multiple drug regimens including daily rifampicin. (Almeida J 2019, based on Tonglet et al, ref. 1)


The decline in newly detected MB patients slowed down once prolonged anti-microbial protection was withdrawn. 1 year of anti-microbial protection, despite including daily rifampicin for 6 months, did not suffice to maintain the earlier rapid decline of HD.


Was the decline only apparent rather than real? In 1984 total population surveys were done in 2 towns of the Uele area. Individuals were examined by an experienced paramedical worker and a doctor. No new MB patient was found among about 20,000 persons examined. Apparently not many MB patients remained unregistered. By contrast, nomadic people in an isolated part of the Uele area were found in 1984 to have a high prevalence of HD of about 460 per 10,000 population. This was similar to the prevalence of HD in the general population prior to the introduction of effective anti-microbial chemotherapy in the 1950s. (1)





This evidence of rapid decline in HD with prolonged anti-microbial protection bears similarities to the observed rapid decline of HD in Shandong (China).(2, 3)



Figure 5. New case detection rate in Wenshan/Yunnan (upper line) and Weifang/Shandong (lower line), China. (Almeida J, 2019 based on Li et al, ref 2)




Figure 6. New MB cases detected over time in Shandong province, China. 1955-1983. (Almeida J, 2019 based on Li et al, ref 3)


The evidence from Uele post-1981 and Yunnan post-1986, with a levelling-off in the decline of new HD patients, indicate the crucial importance of prolonged anti-microbial protection for MB patients. Both places also used BCG from the 1970s, as did Shandong.


All these observations above can be explained in important part by the following.



Figure 7. Recurrence rate among MB patients in each year following release from 24 months of MDT (Almeida J 2019, based on Balagon et al, ref 4)


Recurrence of disease among LLp patients is relatively frequent 6 or more years after 24 months of MDT.  Recurrence can occur by endogenous relapse or exogenous re-infection, and is currently a central fact of the epidemiology of HD. This central fact cannot be ignored safely, otherwise our outcomes are likely to be disappointing and our predictions and models unrealistic. 




Figure 8. Newly detected MB patients over time, worldwide. 1985-2017 (Almeida J, 2019, based on WHO, Weekly Epidemiological Records). Fixed duration 1-year anti-microbial protection mostly replaced prolonged anti-microbial protection by the year 2000. Since the late 1990s, the definition of MB has remained constant.


Recurrence among LLp patients after MDT is apparently keeping the HD endemic alive. It is also exposing the unfortunate individuals to avoidable damage. It is a major reason why children continue to develop HD. This gap in our defences undermines all our other worthy efforts to interrupt transmission, such as active case-finding, contact tracing, BCG vaccination and MDT.


The emerging picture of the epidemiology of HD in Figure 9 helps explain observations, including previously unexplained features of transmission including in affluent countries. That can be discussed in more detail at another time.




Figure 9. Epidemiology of Hansen's Disease for interruption of transmission. (Almeida J, 2019)


Implications for action


Our effective response can be to protect LLp patients against recurrence. This can be achieved with post-MDT chemoprophylaxis for all LL patients. That will shut down a major source of concentrated viable bacilli. As the evidence from prolonged anti-microbial protection in Uele and Shandong shows, it is more effective to treat the source of infection than to allow that source to continue. Looking for those infected by the source is helpful, but it is not as effective as shutting down the source. Just as looking for smoke is helpful in fighting fires, but putting out the fire is even more effective. (See also LML 4 Nov 2019, 18 Sept 2019, 9 July 2019) 


Post-MDT chemoprophylaxis for LL patients is the critical intervention that can shut down a major neglected source of concentrated viable HD bacilli. That can open the door to a rapid decline in HD leading to near-zero transmission. It is also an essential part of competent case management, helping to protect the individual patient from avoidable damage. The evidence from Uele can embolden even the poorest hyperendemic area to strive for interruption of transmission, although increases in income would be highly desirable. Our improvements in field programmes can be from a springboard of demonstrable success. If we improve on the Uele approach by including active search for LL patients and contact tracing, we might achieve an even more rapid decline in HD than 17% to 20%/year. Whatever else we do or fail to do, let's include post-MDT chemoprophylaxis for LL patients so that we can end HD. 


Joel Almeida





सभी एलएल रोगियों के लिए पोस्ट-एमडीटी केमोप्रोफिलैक्सिस के साथ एमडीटी को मजबूत करने से हम हैनसन रोग में तेजी से गिरावट प्राप्त कर सकते हैं और लगभग शून्य संचरण तक पहुंच सकते हैं।


Ao reforçar o PQT com quimioprofilaxia pós-PQT para todos os pacientes com LL, podemos alcançar um rápido declínio na hanseníase e atingir transmissão quase zero.


En renforçant la PCT avec la chimioprophylaxie post-PCT pour tous les patients LL, nous pouvons parvenir à un déclin rapide de la maladie de hansen et à une transmission presque nulle.


Al reforzar la MDT con quimioprofilaxis post-MDT para todos los pacientes con LL podemos lograr una disminución rápida de la enfermedad de Hansen y alcanzar una transmisión casi nula.





1. 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.


2. 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.  


3. 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.


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.

LML - S Deepak, B Naafs, S Noto and P Schreuder

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Tuesday, November 26, 2019

FW: (LML) Key biological facts about drug-resistant bacteria


Leprosy Mailing List – November 26,  2019

Ref.: (LML)    Key biological facts about drug-resistant bacteria

From:  Joel Almeida, London and Mumbai


Dear Pieter and colleagues,



It seems helpful to remind ourselves of the key biological facts about drug resistant bacteria. Drug-resistance is a threat that can block our path to ending Hansen's Disease (HD), and could even increase HD. The study from Rosa et al (Brazil) demonstrated how real and near that threat is.


1. Drug resistant bacteria arise by spontaneous mutation, independent of drug treatment. 


That said, mutagens tend to increase mutation. There is some evidence for stressors such as sub-lethal concentrations of drug being randomly mutagenic (not specific to the drug), by way of intracellular oxidative stress. 


Spontaneous mutation occurs from drug-susceptibility to drug-resistance and vice versa.



2. The equilibrium frequency of drug-resistant mutants is given by the ratio of the respective rates of mutation to and from drug-resistance when the replication rate of each sub-population is equal. 


For example, drug-resistant mutants in an untreated bacterial population will maintain a frequency of 1 in 1000 if the rates of mutation to and from resistance are 1 in 10^-12 and 1 in 10^-9 respectively.


When replication rates are unequal, it is necessary to apply an appropriate fraction to obtain the equilibrium frequency.



3. Monotherapy kills drug-susceptible bacteria (S) and spares drug-resistant bacteria (R)


In formal terms, by definition (where t = time)


R(t+1)/R(t) > S(t+1)/S(t)


Therefore, R(t+1)/S(t+1) > R(t)/S(t)


Monotherapy selects drug-resistant mutants. That is an inescapable fact.


The more bactericidal the drug, the more effectively and rapidly it increases the frequency of drug-resistant mutants. 



4. Monotherapy selects mutants resistant to a single drug and therefore hastens eventual multiple-drug resistance.



Therefore, MDT is preferable to monotherapy and multi-drug chemoprophylaxis against HD is much safer than single-drug chemoprophylaxis. This is especially true because LL patients with subtle signs can easily be mistaken for disease-free contacts.


It would be good for us to swim with the tide of scientific knowledge rather than against it. Otherwise our practices unintentionally might increase HD instead of ending it. It is better to end HD.


Joel Almeida


Further reading


Rosa PS, D'Espindula HRS, Melo ACL et al. Emergence and transmission of drug/multidrug-resistant Mycobacterium leprae in a former leprosy colony in the Brazilian Amazon. Clinical Infectious Diseases. 1 July 2019, ciz570, 


Benjak A, Avanzi C, Singh P et al. Phylogenomics and antimicrobial resistance of the leprosy bacillus Mycobacterium leprae. Nature Communications volume 9, Article number: 352 (2018)


Lederberg J, Lederberg EM. Replica plating and indirect selection of bacterial mutants J Bacteriol. 1952 Mar; 63(3): 399–406


Elseth, G. D. and Baumgardner, K. D. Population Biology. New York: van Nostrand, 1981.


Martinez JL, Baquero F. Mutation Frequencies and Antibiotic Resistance.  
Antimicrobial Agents and Chemotherapy Jul 2000, 44 (7) 1771-1777; DOI: 10.1128/AAC.44.7.1771-1777.2000


Almeida, JG. A Quantitative Basis for Sustainable Anti-Mycobacterium leprae Chemotherapy in Leprosy Control Programs. Int J Lepr (1992) 60(2):255-268.


Kohanski MA, DePristo MA, Collins JJ (2010) Sublethal antibiotic treatment leads to multidrug resistance via radical-induced mutagenesis. Mol Cell 37: 311–320  


Colijn C, Cohen T, Ganesh A, Murray M (2011) Spontaneous Emergence of Multiple Drug Resistance in Tuberculosis before and during Therapy. PLoS ONE 6(3): e18327.


Zuber JA, Takala-Harrison S Multidrug-resistant malaria and the impact of mass drug administration Infect Drug Resist. (2018) Mar 1;11:299-306. doi: 10.2147/IDR.S123887. eCollection 2018.


Rijnders B, Rokx C, Antiretroviral Monotherapy for HIV: Game Over or Future Perspectives?, Clinical Infectious Diseases, Volume 69, Issue 9, 1 November 2019, Pages 1506–1508,

LML - S Deepak, B Naafs, S Noto and P Schreuder

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Contact: Dr Pieter Schreuder <<


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Sunday, November 24, 2019

FW: (LML) Regarding reasons of getting zero-leprosy in Shandong, China


Leprosy Mailing List – November 24,  2019

Ref.: (LML)   Regarding reasons of getting zero-leprosy in Shandong, China

From:  Shen Jianping, Nanjing, China

Dear Pieter,


I have seen several discussions at Leprosy Mailing List about reasons of zero-leprosy happened in Shandong province in China. I have discussed with my colleagues working at National Center for Leprosy Control in Nanjing, China and also have contacted with Prof Zhang Furen, the director of Skin Hospital of Shandong province, China about the reasons of getting zero-leprosy in Shandong.

We all agree that getting zero-leprosy in Shandong province is not a single reason. The isolated treatment of patients in leprosy hospital, DDS monotherapy, MDT implementation, rapid economic development in Shandong and early detection of new leprosy patients which all together contributed to the zero-leprosy in Shandong province.


Best regards,


Dr Shen Jianping

National Center for Leprosy Control,China

LML - S Deepak, B Naafs, S Noto and P Schreuder

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Thursday, November 21, 2019

FW: (LML) PPT on leprosy



Leprosy Mailing List – November 21,  2019

Ref.:  (LML)  PPT on leprosy

From:  Henk Eggens, Santa Combo Dão, Portugal


Dear Pieter and Dr. Sheetal,


You may find presentations on aspects of leprosy on YouTube:

1. This overview in 6 minutes: Very informative and basic.

 2. On Youtube: Search for 'Lepclip'.

in English:
in Hindi:

More on Youtube: Nine more 'Lepclips' exist in English on different aspects of clinical leprosy.  




Henk Eggens

Former NLR leprosy advisor


Henk Eggens


LML - S Deepak, B Naafs, S Noto and P Schreuder

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FW: (LML) PPT on leprosy

Leprosy Mailing List – November 21,  2019

Ref.:   (LML)  PPT on leprosy

From:  Sheetal Amte-Karajgi, Maharashtra, India


Dear Pieter,


I need a presentation on leprosy immediately and I don't have access to computer to make it. Can somebody  help me with that?


Also can you add my associate Madhavi Kadrekar to our list?  Her email id is



Thanks a lot.


Warm regards,

Dr. Sheetal Amte- Karajgi   

MBBS, M.A.(Social Entrepreneurship), D.Sc.(honoris causa)                                            
Chief Executive Officer (Maharogi Sewa Samiti, Warora)
Young Global Leader 2016 (World Economic Forum)
Fellow (World Innovation Organisation),USA; Fellow (INK)
Academy Member (Global Teacher Prize, UK)
Member-Young Leaders' Council (AIMA)
Advisor (Express Healthcare)
Advisor (Indian Institute of Public Health, Delhi)
Address: At & Post : Anandwan, Tahsil: Warora, District: Chandrapur, Maharashtra, India, Pin: 442 914 
Mobile: +919822465834 

LML - S Deepak, B Naafs, S Noto and P Schreuder

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Contact: Dr

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Monday, November 18, 2019

FW: (LML) Is the use of an eponym for leprosy inappropriate?


Leprosy Mailing List – November 18,  2019

Ref.: (LML)    Is the use of an eponym for leprosy inappropriate?

From:  Joel Almeida, London and Mumbai


Dear Pieter & colleagues,


Dr. Butlin (LML 15 Nov 2019) shone a spotlight on a violation of ethics, human rights and criminal law, by Armauer Hansen (AH). Use of demonstrably or potentially harmful interventions in humans is proscribed by law. Currently anyone subjected to a demonstrably harmful intervention, especially without full informed consent, can approach the court for remedies. Civil society organisations increasingly assist persons who have experienced HD, so that their rights are protected and compensation paid when ordered by a court, or in out-of-court settlements. AH's experience therefore has current relevance. We are a compassionate community, so we place a high value on respect for human rights, ethics, and avoiding negligence. Even if we were not so compassionate, it would be wise for us to prefer the right thing to the merely expedient thing. That's why the evidence from randomised controlled trials is important even when it happens to be inconvenient.


However, Dr. Butlin after highlighting the violation by AH, then suggested, "There might be no objection to incorporating the name Hansen into the name of the bacteria which cause leprosy, since Armauer Hansen was the discoverer of this bacterium." Once that is accepted, it is a small step to naming the disease after the causative organism (Hansen's bacilli). Even Dr. Butlin might therefore find Hansen's Disease or hanseniasis an unobjectionable label (derived from the causative organism, as in brucellosis.)  


HD is nowhere described as "a state of corruption or decay". By contrast, a google search for "definition of leprosy" provides a rude shock. That definition is part of the English language, for better or worse. Languages are evolved by common usage rather than by central diktat. Similar difficulties might arise in other languages. Unsurprisingly, people who have experienced the disease prefer to use the label "Hansen's Disease". Most of them might never have heard of AH or the highly regrettable episode highlighted. I would not like to be told that I have been diagnosed with "a state of corruption and decay", when I have only HD.


Dr. Butlin also suggests using a name linked to the pathology. This could be helpful to patients. The late great Dr. Fritschi, of the Schieffelin centre, Karigiri (India), made a distinction between self-limting and progressive forms of HD. He considered that these were two distinct pathological processes with distinct prognoses and distinct public health implications. Such distinction in terminology is a well established concept in the case of growths. They are widely described as "benign" or "malignant". Nobody fears benign growths because they are not "cancer". There is no reason for anyone to fear self-limiting infections with Hansen's bacillus. These generally have an excellent prognosis with or without specific treatment, and are usually non-infectious even without treatment.


In Yakusu/Sombe near Kisangani, DRC, lay people have long been able to distinguish between "bad" HD and self-limiting skin lesions. The late great Dr. Stanley Browne wrote, "The skin lesions of active leprosy carried no stigma, but ulcerating extremities were feared because they were thought to be contagious. The older people were very skilled in differentiating leprosy from other conditions, especially fungaI infections. They could also readily distinguish pre-tuberculoid skin lesions from the scarcely visible prelepromatous macules, which they called "the mother of the bad leprosy". (1)  


Dr. Fritschi instructed patients with a single, small, well-defined (and probably self-limiting) anaesthetic patch to use a neutral label for their condition. I recall he advised using some suitable jargon, such as maculo-anaesthetic dermatosis (it was some time ago and my recollection of the details is inexact). His approach allowed many patients to preserve their jobs, marriages, educations etc. Incidentally, the Schieffelin centre in Karigiri was one of the world's leading population-based HD control programmes, with meticulous contact tracing and record-keeping. As a result, many people were diagnosed with a single well-defined smear-negative anaesthetic patch, BI zero, and no other clinical signs of disease. If they went to Dr. Fritschi, they emerged with a neutral label.


Other forms of the disease are unfortunately not yet harmless in some endemic countries, even after diagnosis. In an ideal world every HD patient would receive competent case management. Anti-microbial protection would be adequately prolonged for patients with LL disease, nerve function would be monitored at least every 3 months using graded monofilaments, prednisolone would be used when needed, pain would be managed well, thalidomide or its substitutes would be provided promptly and safely, irreversible physical damage would be repaired competently, psychological scars would be tended, reconstruction and rehabilitation would be effective, access to social security would be assured, legal redress for wrongs would be swift, and HD would be considered a largely harmless disease. In the real world, HD continues to damage people unnecessarily even after they are diagnosed. This keeps fear alive. In these circumstances, those with a single self-limiting anaesthetic patch and no other signs of disease might prefer a neutral label. Even the relatively non-stigmatising "HD" could be reserved for the "bad" forms of the disease that are unlikely to self-heal. The best solution, of course, is to actually implement all that we know to be good and important. That is our shared dream. Then all forms of HD will become truly harmless, and we will even end HD.


What are the thoughts of the persons among us who have experienced any form of HD? Does the Fritschi approach of neutral jargon offer any advantages? Is there concern about wrongly honouring a person (AH)  who violated the law and civilised norms? What thoughts and reflections arise?


Joel Almeida





1. Browne SG. Self-healing Leprosy: Report on 2749 Patients. Lepr. Rev. ( 1974), 45, 104- 111.

LML - S Deepak, B Naafs, S Noto and P Schreuder

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