Saturday, August 10, 2024

Fw: Ref.: (LML) Infolep monthly overview of new publications on leprosy. August, 2024.

 

 

Leprosy Mailing List –  August 10,  2024

 

Ref.:  (LML) Infolep monthly overview of new publications on leprosy. August, 2024.

 

From:  Roos Geutjes & Sophie Vissers, Amsterdam, the Netherlands



 



Dear colleagues, 

We are happy to be sharing this months newsletter as it contains many interesting resources like:

  • Webinar recording of the Leprosy Research Initiative Spring Meeting
  • Reflection of Y. Sasakawa on what's needed to achieve zero leprosy publishied in the Bulletin of the WHO
  • Multiple literature reviews grasping evidence and research gaps 
  • Publications in English, Portuguese and Spanish
  • Case reports on atypical presentations of leprosy
  • Funding calls and new events

Additionally, we have some thrilling news about our website! You might have already noticed it, but a couple of days ago we went live with our new website! We are very happy with the improvements in navigation functionality and search speed. We have also added "Online Courses" to the menu, and a new section on "News and Events", and a link to our new eLearning platform which will be launched in October.
 
To help you make the most of these updates, here's a quick guide on using the new search menu: Via the button "Search Resources," you are now able to search for scientific publications, practical resources, online courses, information, and organizations in one menu. You can narrow your search by using the filter options. Moreover, we are interested in hearing about your experiences with the new website, especially any feedback you may have.

Warm regards,


Roos Geutjes & Sophie Vissers

www.infolep.org
info@infolep.org





Practical Materials



PAHO's initiative for the elimination of communicable diseases [PAHO webinar recording]


Highlights of LRI Spring Meeting 2024 [Leprosy Research Initiative webinar recording] 


An Introduction and Practical Guide to Community Engagement and Involvement in Global Health Research [The Global Health Network online course]






Highlighted Publications



What's needed to achieve zero leprosy
Sasakawa Y. Bulletin of the World Health Organization. 2024.


Heuristic Segmentation Assisted Deep-Spatial Feature Learning Model for Leprosy Detection
Jitendra R, Simha JB, Abhi S, et al. SN Computer Science. Springer Science and Business Media LLC. 2024.


Role of multisegmental nerve ultrasound in the diagnosis of leprosy neuropathy
De Martino Luppi A, Ferreira GE, Borges IS, et al. PLOS ONE. Public Library of Science (PLoS). 2024; 19 (7) : 1-15.


Lessons learned from chemoprophylaxis programmes for neglected diseases and diseases of poverty in Latin America: a systematic review
Cordeiro WDM, Rocha AMD, Silva TL, et al. Caderno Pedagógico. South Florida Publishing LLC. 2024; 21 (7) : 1-28.


Validation of an instrument for assessing leprosy care in children and adolescents.
de Sousa G, Mendonça I, Morita L, et al. Revista brasileira de enfermagem. 2024; 77 (2) : 1-9.


Current Therapeutic Strategies for the Management of Leprosy
Verma I, Singh D, Dhanawat M, et al. Emerging Approaches to Tackle Neglected Diseases: From Molecule to End Product. BENTHAM SCIENCE PUBLISHERS. 2024.






New publications


Feel free to contact us to receive full-text versions if these cannot be found through the Infolep portal.



Socio-cultural and Environmental Risk Factors for Leprosy in Jaffna District, Sri Lanka
Sivaganesh S, Pathmeswaran A. Jaffna Medical Journal. Sri Lanka Journals Online. 2024; 36 (1) : 16-23.


Immunohistochemical and histopathological analyses of cutaneous innervation to improve the diagnostic efficacy in hansen disease skin lesion
Costa EAFD, Amadeu TP, Illarramendi X, et al. Arquivos de Neuro-Psiquiatria. Georg Thieme Verlag KG. 2024; 82 (05) : 1-10.


Deep Semantic Segmentation Assisted Region-of-Interest Sensitive Deep Spatio-Textural Feature Learning Framework for Leprosy Detection and Classification
Jitendra R, Simha JB, Abhi S, et al. SN Computer Science. Springer Science and Business Media LLC. 2024.


Long-term storage stability of PGL-I coated ELISA plates for anti-Mycobacterium leprae IgM detection.
Fogaça M, Saavedra D, Sousa M, et al. Journal of microbiological methods. 2024.


Leprosy in the Heartland.
Keegan A, Gubbrud J, Hockhausen K, et al. South Dakota medicine : the journal of the South Dakota State Medical Association. 2023; 76 (11) : 486-493.


Leprosy Health Promotion during COVID-19 Pandemic in Indonesia
Rahayu T, Wicitra A, Lestari YD, et al. Journal of Community Empowerment for Health. Universitas Gadjah Mada. 2024; 7 (1) : 1-5.


Neutrophilic leukocytosis and erythema nodosum leprosum in leprosy: insights from a retrospective observational study
Feitosa da Silva Barboza M, de Andrea Hacker M, Maria Sales A, et al. Frontiers in Immunology. Frontiers Media SA. 2024.


Vitiligo after borderline lepromatous leprosy: common immunological implications
Sequeira CM, Cupertino F, Cunha JM, et al. Portuguese Journal of Dermatology and Venereology. Publicidad Permanyer, SLU. 2024.


Exploring Active Case Detection Approaches for Leprosy Diagnosis in Varied Endemic Settings: A Comprehensive Scoping Review.
Brown H, Fastenau A, Penna S, et al. Life. MDPI AG. 2024; 14 (8) : 1-15.


Is there a lack of a glucose monitoring and management protocol for preventing hyperglycemia and glucocorticoid-induced diabetes mellitus in leprosy reactions?
Antunes DE, Santos DFD, Thomazelli JA, et al. PLOS Neglected Tropical Diseases. Public Library of Science (PLoS). 2024; 18 (7) : 1-6.


Hidden leprosy in a low-endemic area in southern Brazil: changes in endemicity following an active search
Vitiritti B, Lima FR, de Castilho NT, et al. The Brazilian Journal of Infectious Diseases. Elsevier BV. 2024; 28 (4) : 1-6.


Diagnostic Utility of Multiplex Polymerase Chain Reaction in Patients of Clinically Suspected Pure Neuritic Leprosy by Identifying Mycobacterium leprae in Skin Biopsy Samples and Nasal Swabs.
Pathak V, Sharma A, Sharma A, et al. The American journal of tropical medicine and hygiene. 2024.


Subconjuntos de linfócitos B nas lesões cutâneas da hanseníase tuberculoide, indeterminada, virchowiana e estados reacionais
Froes Junior LAR. Universidade de São Paulo. Agência de Bibliotecas e Coleções Digitais. 2024.


Hanseníase na atenção básica: saberes e práticas dos profissionais da Estratégia Saúde da Família
Gomes de Oliveira Grangeiro S, Wanderley Lopes Gomes K, de Amorim Duarte V, et al. Revista de APS. 2024.


Perfil Epidemiológico da Hanseníase no Território de Identidade Sertão Produtivo - Bahia no Período de 2018 a 2023,
Costa RADS, Magalhães ACR, Silva YN, et al. Revista Contemporânea. South Florida Publishing LLC. 2024; 4 (7) : 1-21.



A retrospective analysis thyroid function and ultrasonography in a group of subjects with lepramatous leprosy in Turkey
Ozkan Z, Kanat Z, Alatas O, et al. PLOS Neglected Tropical Diseases. Public Library of Science (PLoS). 2024; 18 (7) : 1-9.


Leprosy knowledge among primary care physicians in Southern Brazil: are we underdiagnosing?
de Cássia Francisco P, Kliemann BS, Tarlé RG. International Journal of Dermatology. Wiley. 2024.


Feasibility and accuracy of mobile QT interval monitoring strategies in bedaquiline-enhanced prophylactic leprosy treatment.
Bergeman A, Nourdine S, Piubello A, et al. Clinical and translational science. 2024; 17 (8) : 1-7.  


Molecular and Serological Surveillance for Mycobacterium leprae and Mycobacterium lepromatosis in Wild Red Squirrels (Sciurus vulgaris) from Scotland and Northern England.
Zhou Z, van Hooij A, Wassenaar G, et al. Animals : an open access journal from MDPI. 2024; 14 (13) : 1-15.  


The Ocular Findings among Patients with Leprosy in South-Eastern Region, Tanzania
Nyamsaya DS, Makunja C, Mhina C, et al. East African Scholars Journal of Medical Sciences. SASPR Edu International Pvt. Ltd. 2024; 7 (07) : 303-307.


An inventory of potential medicinal plants common in Purba and Paschim Medinipur districts of West Bengal, India to Treat leprosy
Kumar Samanta A, Kumar Maity S. Flora and Fauna. 2024.


Leprosy Presenting With Scleroderma and Cataract: A Clinical Conundrum
Ahmed S, Patel M, Chakole S, et al. Cureus. Springer Science and Business Media LLC. 2024.


Leprosy and its impact on the quality of life of people with physical disabilities: a scoping review
Araujo DMD, Silva ECDSE, Gomes HVDS, et al. Revista Brasileira de Enfermagem. FapUNIFESP (SciELO). 2024; 77 (suppl 3) : 1-10.


Letter to the editor regarding Association between asthma, rhinitis and atopic dermatitis with leprosy: A case-control study
Shah S, Mahajan R, Ajithkumar K, et al. Indian Journal of Dermatology, Venereology and Leprology. Scientific Scholar. 2024.


The role of economic factors in shaping and constituting the household burden of neglected tropical diseases of the skin: Qualitative findings from Ghana and Ethiopia
Hailemichael Y, Novignon J, Owusu L, et al. Social Science & Medicine. Elsevier BV. 2024.


The effect of antireaction medications on the association between periodontitis and leprosy reactions: An important methodological issue in periodontal medicine.
Sacramento I, Gomes-Filho I, da Cruz S, et al. Journal of periodontology. 2024.


Impact of COVID-19 on the neglected tropical diseases: a scoping review
Butala CB, Cave RNR, Fyfe J, et al. Infectious Diseases of Poverty. Springer Science and Business Media LLC. 2024; 13 (1) : 1-16.


Análise Epidemiológica da Hanseníase em Goiânia de 2016 a 2020: Estratégia de Intervenção Através de Revisão Sistemática
Facure CG, Alencar PESD, Carneiro TB, et al. Revista Ibero-Americana de Humanidades, Ciências e Educação. Revista Ibero-Americana de Humanidades, Ciencias e Educacao. 2024; 10 (7) : 2902-2916.


Desenvolvimento de dispositivo eletroquímico e sua aplicação na detecção de anticorpos voltados para o diagnóstico de hanseníase
de Oliveira IKP. Centro de Ciências Exatas e de Tecnologia. Universidade Federal de São Carlos. 2024.


Incidencia de la lepra en Cuba en el decenio del 2012 al 2022
Flores CR. Columna Médica. 2024.






Case Reports



Ulnar nerve abscess in lepromatous leprosy: Insights from three cases confirmed via ultrasound imaging
Krishnan L, Vendhan S, Vasudevan B, et al. Leprosy Review. Lepra. 2024; 95 (2) : 1-6.


Hansen Disease.
McHugh J, Vaillant J, Pritt B. Mayo Clinic proceedings. 2024.


Unveiling the clinical and epidemiological significance of Mycobacterium lepromatosis detection in a patient with severe lepra reaction from India.
ingh S, Singh I, Herlekar R, et al. The Australasian journal of dermatology. 2024.


Systemic Lupus Erythematosus Complicated with Mycobacterium Leprae Infection: a Rare Case Report.
Fernando N, Welhenge C, Premaratna R, et al. Asian Pacific Journal of Tropical Medicine. Medknow. 2024; 17 (7) : 329-332.


A case report and literature review: Mycobacterium leprae infection diagnosed by metagenomic next-generation sequencing of cerebrospinal fluid.
Zhao C, Liu Z. BMC infectious diseases. 2024; 24 (1) : 1-7.


Lepromatous Leprosy and Charcot Neuroarthropathy of Insensate Feet: A Case Report.
Kress G, Swerdlow M, Shin L. Cureus. 2024; 16 (5) : 1-5.


Case Report: Nonalcoholic Hepatic Steatosis Associated with Type-2 Leprosy Reaction.
Orozco K, Cubillos J, Genes M, et al. The American journal of tropical medicine and hygiene. 2024.


Análise Epidemiológica de Mortalidade e Classe Operacional dos Casos Notificados de Hanseníase entre 2014 e 2023 no Estado de Goiás
Santos CKM, Miranda MCR, Júnior IFS, et al. The Brazilian Journal of Infectious Diseases. Elsevier BV. 2024.


Avaliação da qualidade de vida de pacientes com hanseníase atendidos em hospitais de referência no Estado do Maranhão
de Area Leão Pereira da Silva J. Programa de Pós-Graduação em Saúde do Adulto. Universidade Federal do Maranhão. 2024.


Changing Scenario of Hansen's Disease
Jagirdar P. Dr. Pankaj Jagirdar. 2024.


De novo histoid leprosy
Malik N, Chaurasia P, Reddy A, et al. BMJ Case Reports. BMJ. 2024.


Serum lipocalin-2 levels in leprosy
Kaushal I, Kumar B, Dogra S. Indian Journal of Dermatology, Venereology and Leprology. Scientific Scholar. 2024.


Uncustomary and rare presentation of Hansen's disease 'a mimicker' - A narrative review
Yadav V, Verma D, Mendiratta V, et al. Leprosy Review. Lepra. 2024; 95 (2) : 1-11.


Leprosy mimicking sinonasal tumor : A case report
Nefyanti AA, Amin S, Djawad K. Journal of Pakistan Association of Dermatologists. 2024.


Childhood leprosy in Buenos Aires: four cases report
Merenzon S, L. Costa A, Frare C, et al. Archivos Argentinos de Pediatria. Sociedad Argentina de Pediatria. 2024; 122 (6) : 1-6.


Case Report: Recurrent Type 2 Leprosy Reaction Associated with Multiple Nerve Function Impairments Refractory to Steroids: A Therapeutic Challenge.
Khurana A, Sharath S, Panchal A, et al. The American journal of tropical medicine and hygiene. 2024.


Fenômeno de Lúcio: relato de caso
Almeida Pastana R, Bezerra JV, Zimermano Coimbra B, et al. Brazilian Journal of Health Review. 2024.


Desafíos en el Cuidado de la Lepra Lepromatosa: Un Estudio de Caso en un Hombre de 78 años
Falconí-Pelaéz S, Reyes-Galarza JA. Ciencia Latina Revista Científica Multidisciplinar. Asociacion Latinoamericana para el Avance de la Ciencia. 2024; 8 (4) : 409-422.


A case report of de novo histoid leprosy in a Nigerian male: A diagnostic dilemma
Anaje CC, Okpala CI, Enechukwu NA, et al. Tropical Doctor. SAGE Publications. 2024.


A case report on imaging findings of rare segmental necrotizing granulomatous neuritis of leprosy involving ulnar nerve.
Netam S, Gupta N, Chandrakar N. Qatar medical journal. 2024; 2024 (3) : 1-7.


Borderline lepromatous leprosy: A case report
Fernando N, Welhenge C, Premaratna R, et al. Asian Pacific Journal of Tropical Medicine. Medknow. 2024; 17 (7) : 329-332.





News & Events



The entry into force of the Protocol to the African Charter on Human and Peoples' Rights relating to the Rights of Persons with Disabilities in Africa (African Commission on Human and Peoples Right press release)


Landmark disability rights treaty comes into force across Africa (Sightsavers news article)


Leprosy Pension: UP Government Provides Leprosy Pension to 12,000 Disabled Individuals (The Times of India news article)


African Disability Conference 2024
September 2-4, 2024; Nairobi, Kenya.
The theme of the conference is: "Persons with Disabilities in a Post-Pandemic World: Redefining the Inclusive Development & Humanitarian Agenda in Africa". To receive your registration link, email the events team.


COR-NTD Meeting for the Pacific Islands
September 25-26, 2024; Brisbane, Australia. 
The goal of the 2nd annual Regional COR-NTD Meeting for the Pacific Islands is to bring together key stakeholders to address how to eliminate lymphatic filariasis, scabies, trachoma, leprosy and other NTDs from the region.


NNN Conference 2024
October 1-3, 2024; Kuala Lumpur, Malaysia.
The NNN Annual Conference 2024 will take place from 1st of October - 3rd of October, 2024, in Kuala Lumpur Malaysia. The theme for the conference is: "Collaboration for Change: Fostering Global Equity and Strengthening Community Engagement in NTDs." Registration is open.


Conference on Neglected Tropical Diseases 2024
May 2025; Nairobi, Kenya.
The 1st edition of the Conference on Neglected Tropical Diseases, organized by AME is tentatively scheduled in May 2025 in Nairobi, Kenya, as a hybrid meeting. The abstract-driven conference proposes a platform to disseminate new advancements, real-world data, implementation challenges, and novel governing models to discuss and generate solutions for cross-cutting topics and ultimately reduce the disease burden and societal impact of NTDs. This proposal supports the progress in foundational pillars of the WHO Roadmap by facilitating evidence-based program implementation, leveraging the cross-cutting approach, and providing a forum to discuss a paradigm shift toward country ownership of elimination programs.



Consultancy Anesvad
Evaluation of the contribution of Fundación Anesvad to the World Health Organization "road map for neglected tropical diseases 2021-2030". Check the link for the Terms of Reference. Deadline for application is Augst 16, 2024.


Dr. Ritu Ghosh appointed Executive Director (Global Partnership for Zero Leprosy news article)


Online RSTMH Research in Progress meeting
August 29, 2024; 9am - 4.30pm BST; online. 
The Royal Society of Tropical Medicine & Hygiene event specifically hosted for early career researchers. This event focusses on funding, publishing, dissemination of scientific results. You have to register in advance and costs for non-members £5 per person.


Change of dates! 7th Conference – 7th Community Based Rehabilitation (CBR) /Community Based Inclusive Development (CBID)
September 9-12, 2024; Entebbe, Uganda. 
The 7th Community Based Rehabilitation (CBR) /Community Based Inclusive Development (CBID) Africa Conference is organized by CBR Africa Network (CAN) and hosted by the Government of Uganda spearheaded by the Ministry of Gender, Labour and Social Development (MGLSD). The three-day CBR/CBID Africa conference will provide a platform for various stakeholders to come together, exchange ideas on the role of CBR/CBID in promoting disability inclusive development. Early bird registation deadline is August 15th.


World Health Summit 2024
October 13-15, 2024; Berlin, Germany; hybrid event.
The theme of the conference is: "Building Trust for a Healthier World". You can join the event online live from all around the world for free and without any registration required. Simply click on the session of your interest in the program and get the broadcasting link. Registration is open for on-site participation.


NHIR Global Health Research -- Researcher-led funding call bands 1 to 3 
GHR – Researcher-led funds research that aims to improve health outcomes for the most vulnerable people in low and middle income countries (LMICs). Research must address evidence needs that are locally identified and prioritised, and must promote health equity, aligning with the aims of Sustainable Development Goal 3. Funding ranges from £250,000 to 7 million over a period up to 5 years depending on the band of application. 
Please check out the website for all eligibility criteria. Deadline for applications is 6th of November, 2024.






Links



Info Hansen - A innovative hub for knowledge sharing about Hansen's Disease
 


ALLF - Official website of the Association des Léprologues de Langue Française
 


LML - Leprosy Mailing List - a free moderated email list that allows all persons interested in leprosy to share ideas, information, experiences and questions
 


InfoNTD - Information on cross-cutting issues in Neglected Tropical Diseases (NTDs)


ILEP newsletter archive


GPZL newsletter subscription


WHO Goodwill Ambassador's Leprosy Bulletin


Leprosy Review


Leprosy Review Repository (1928-2001)


Fontilles Revista de Leprología


Indian Journal of Leprosy


Hansenologia Internationalis


HARP - database of Hansen's Disease Antimicrobial Resistance Profiles




GDPR & the Infolep newsletter

 
New EU data protection regulations came into force on 25 May 2018. We have been reviewing our practices with regards to the GDPR, including our privacy statement and mailing list.

Infolep sends out monthly e-mails with an overview of recent publications on leprosy and related issues. The purpose of this activity is to keep subscribers up to date.

Infolep will only process the data we have (names, email addresses) for the purpose of sending you the newsletter. We take your security seriously and will never share your contact details with anyone else.

You can update your preferences or unsubscribe from this list at any time.






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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Saturday, August 3, 2024

Fw: Ref.: (LML) Response regarding SDR-PEP for LML

 

Leprosy Mailing List –  August 3,  2024

 

Ref.:  (LML) Response regarding SDR-PEP for LML

From:  Wim van Brakel, Nieuwegein, the Netherlands


Dear Pieter,

 

We are aware of the ongoing discussion about PEP in the Leprosy Mailing List and would like to respond to the messages posted by Dr Almeida on the LML of 17 July 2024 and in many previous issues. At NLR, we endorse the implementation of SDR-PEP within routine leprosy services with the aim to reduce the risk of developing leprosy among contacts of new cases. This is based on current evidence and in alignment with the global WHO Guidelines for the Diagnosis, Treatment and Prevention of Leprosy (2018). SDR-PEP should be integrated in leprosy control programmes, which requires investment in several programme components, including training of health workers, active case detection through contact screening and community education about leprosy and PEP.

 

We have observed that where PEP is implemented as part of routine leprosy control programmes as an ongoing intervention, the incidence of leprosy is reducing, especially of child cases and cases with Grade 2 disability. Publications about this are forthcoming in peer-reviewed journals.

 

We believe that engaging in discussions through open-access, peer-reviewed medical journals is effective to build a robust evidence base and we second Prof Epco Hasker's proposal that the ongoing discussion about PEP be continued in such journals. This will allow a thorough evaluation of new data and claims about these by a broader community of medical professionals and scientists. NLR is committed to supporting the publication of more scientific evidence as it becomes available to further inform and enhance our collective understanding and approach to leprosy prevention and treatment.

 

More information on prevention of leprosy and on how to implement SDR-PEP can be found at: https://www.leprosy-information.org/key-topics/prevention-leprosy. For questions about PEP, please contact Dr Liesbeth Mieras (L.Mieras@nlrinternational.org) or the undersigned.

 

Reference:

https://iris.who.int/bitstream/handle/10665/274127/9789290226383-eng.pdf

 

 

Wim van Brakel

Medical Director NLR

On behalf of the NLR technical team

W.vanBrakel@nlrinternational.org


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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Tuesday, July 30, 2024

Fw: Ref.: (LML) Visible deformity after HD (leprosy) chemoprophylaxis among India tribals

 

 

Leprosy Mailing List – July 30,  2024

 

Ref.:  (LML) Visible deformity after HD (leprosy) chemoprophylaxis among India tribals

From:  Joel Almeida, Mumbai, India


 

Dear Pieter and colleagues,

Jannine Ebenso (ref: (LML) 24 July 2024) enquires whether high MB (multibacillary) HD (leprosy) numbers and high G2D (grade 2 disability / visible deformity) numbers in Dadra Nagar Haveli might be backlog cases. And if Karigiri's successes might be illusory.

The short answer is "No". That is because

The Schieffelin Centre in Karigiri from 1962 to 1997 did repeated surveys: starting with total population (door to door), contact tracing surveys, school surveys etc. (1-4) It was among the world's earliest and largest series of population-based epidemiological studies after the advent of effective chemotherapy. It produced tens of classic papers that advanced our understanding of the epidemiology of HD apart from introducing the world first to large-scale use of dapsone and then to large-scale use of MDT (originally until smear negativity). What Jannine Ebenso apparently became aware of regarding contact tracing and screening in the late 1990s through SAPEL/LEC drives was known to colleagues in Karigiri as early as 1962. The 16% annual decline in new LL (lepromatous) HD demonstrated by Karigiri is real.

Dadra Nagar Haveli (DNH) did door-to-door surveys repeated several times a year. The findings of the meticulous Indian national sample survey of around 2011 (5) are consistent with the repeated DNH surveys. The near-zero G2D (grade 2 disability / visible deformity) among newly detected HD cases in DNH prior to the introduction of SDR PEP / LPEP is real, as is the dramatic increase in G2D / visible deformity after the introduction of SDR PEP / LPEP.

The same national sample survey went systematically door to door in the various states of India, including Maharashtra and Gujarat. Maharashtra had only 8.43 G2D/million population accumulated among newly detected HD patients while Gujarat had only 2.88 G2D/million population similarly accumulated. (5) By contrast, DNH had near zero G2D/million population/year among newly detected HD patients before the introduction of SDR-PEP / LPEP. After SDR-PEP this shot up to  50+/million population/year G2D among newly detected HD patients (6-9).

Further, the foreign investigators in DNH themselves reported a near-zero baseline level of G2D (visible deformity) among newly detected HD patients in DNH prior to the introduction of LPEP / SDR PEP. Their own reports then documented the dramatic increase in G2D among newly detected HD patients in DNH after the introduction of LPEP/SDR PEP. (6-9)  Nevertheless, they declared SDR PEP / LPEP to be safe. Some of these same investigators were then shown in Annex 1 of the WHO treatment and prevention guidelines of 2018 as having financial conflicts of interest.

 

  

The burden of excess G2D/visible deformity following SDR PEP / LPEP among household contacts, neighbours and social contacts of newly diagnosed HD patients falls disproportionately on HD patients and their families. This infliction of grievous hurt and visible deformity is contrary to their human rights and amounts to a particularly egregious form of discrimination against them. G2D / visible deformity tends to indicate underlying permanent nerve damage. Affected limbs tend to deteriorate steadily: going slowly but relentlessly from repeated painless wounds and infections, to attrition of extremities, to disintegration of extremities and too often to eventual amputation. Visible deformity also tends to evoke extreme social exclusion and extreme destitution. All this among persons who had no symptoms or signs of HD and did nothing wrong apart from being family members or neighbours or social contacts of a newly diagnosed HD patient. Worse, tribals (a particularly vulnerable group with 24% illiteracy) formed a majority of the DNH population.

We are a non-mercenary and noble-minded community dedicated to beating HD, with full respect for the Universal Declaration of Human Rights, the Nuremberg code on human experimentation and all relevant legislations and precedents. We have great talents in endemic countries. Are we against shaking off the yoke of any individuals or organisations who have financial conflicts of interest, and instead setting free the capable professionals in endemic countries to protect the best interests of their own people? Then we can match or exceed the 16%/year decline in incidence rate of LL HD that was achieved by Karigiri even in a low-income population near the equator. Average incomes are still conspicuously low in that area, and reinfection of LL HD patients is no longer prevented after the introduction of fixed duration treatment. Addition of MIP vaccine for highly bacillated patients could well accelerate the decline of new LL HD beyond 16%/year.

 

Raising funds is not the main reason for fighting HD, but investment too tends to chase good outcomes and epidemiological impact. Seeking first the health and wellbeing of the people we serve is likely to be the surest route to success in every  sense.

 



Thanks to Jannine Ebenso for her comments.

With all sincerity,

Joel Almeida


References

 1.      Rao PSS, Karat ABA, Kaliaperumal VG.Incidence of leprosy in Gudiyatham Taluk, South India. Indian J. Med.Res. 60 (1972) 97-105.

2.     Rao PSS, Karat ABA, Kaliaperumal VG, Karat S.Prevalence of leprosy in Gudiyatham Taluk, South India. Part I. Specific rates with reference to age, sex
and type. Int. J. Lepr. 40 (1972) 157-163.

3.     Rao PSS, Karat ABA, Karat S. Epidemiological studies in leprosy in Gudiyatham Taluk. II. Patterns of familial aggregation of leprosy in an endemic area. Lepr. Rev. 40 (1969) 93-98.1.      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.     Jesudasan K, Bradley D, Smith PG, Christian M. The effect of intervals between surveys on the estimation of incidence rates of leprosy. Lepr Rev (1984) 55, 353-359

5.     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.

6.     Barth-Jaeggi T, Steinmann P, Mieras L, et al. Leprosy Post-ExposureProphylaxis (LPEP) programme: study protocol for evaluating the feasibility and impact on case detection rates of contact tracing and single dose rifampicin. BMJ Open 2016;6:e013633.doi:10.1136/bmjopen-2016-013633.

7.      Mieras L, Singh MK, Manglani PR et al. A single dose of rifampicin to prevent leprosy; quantitative analysis of impact on perception, attitudes and behaviour of persons affected, contacts and community members towards leprosy in India, Nepal and Indonesia. Lepr Rev (2020) 91, 314–327 doi:10.47276/lr.91.4.314

8.      Steinmann P, Cavaliero A, Aerts A et al. The Leprosy Post-Exposure Prophylaxis (LPEP) programme: update and interim analysis. Lepr Rev (2018) 89, 102–116

9.      Richardus JH, Tiwari A, Barth-Jaeggi T et al. Leprosy post-exposure prophylaxis with single-dose rifampicin (LPEP): an international feasibility programme. Lancet Glob Health. Lancet Glob Health. 2021 Jan;9(1):e81-e90. doi: 10.1016/S2214-109X(20)30396-X.

 


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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Monday, July 29, 2024

Fw: Ref.: (LML) Does Rifampicin PEP for household contacts alter the risk of multibacillary HD?

 

Leprosy Mailing List –  July 28,  2024

 

Ref.:  (LML) Does Rifampicin PEP for household contacts alter the risk of multibacillary HD?

From: Joel Almeida, Mumbai, India 


 

Dear Pieter and colleagues,

 

Thanks to Epco Hasker for his comments. (Ref.: (LML), 24 July 2024).

 

He rightly indicates that the comparison of arm 2 (household SDDR PEP) with arm 1 (non PEP) showed an excess of new MB HD cases in arm 2. This comparison was between the ENTIRE arm 2 and the ENTIRE arm 1 populations. No sub-group involved. It is a comparison explicitly described in the published protocol: "Incidence rate ratios calculated between the comparator arm 1 and each of the intervention arms will constitute the primary outcome". (1) The said analysis was inexplicably omitted by Hasker et al, but it reveals a 65% excess of new MB HD in the SDDR PEP household contacts arm (IRR 1.655, 95% c.i. 1.0203 to 2.6834). 

 

Beyond that Epco Hasker and associates did several things that were not pre-defined in the protocol analysis. Such post-hoc analysis tends to be unreliable for superiority trials because post-hoc regrouping or exclusions or re-allocation of subjects can mislead even the best-intentioned analyst. This danger is heightened when the trial data are not shared openly. Further, Poisson regression assumes that the dependent variable has a Poisson distribution. This distribution expresses the probability that a given number of events will occur in a fixed interval, assuming that these events occur at a known constant rate on average and that each event is independent of the others. This assumption might not be safe in the present context because incident cases can be the source of further incident cases.

 

The most remarkable part of the Hasker et al report is the section on adverse outcomes. (2) "We did not conduct active follow-up for adverse events. Probably there were no serious adverse events since none were reported." However, the Helsinki Declaration requires that the protocol include "provisions for treating and/or compensating subjects who are harmed as a consequence of participation in the research study." Simply closing one's eyes to adverse events is not sufficient. We now know that the LPEP study in DNH showed a vast boost of G2D (visible deformity) following SDR-PEP for household contacts, neighbours and social contacts. A similar boost in G2D / visible deformity cannot be excluded in the PEOPLE trial run by Hasker et al. This is what people need to know before they give informed consent to HD chemoprophylaxis: their risk of G2D (visible deformity) is likely to be boosted greatly.

 

Hasker asks why those who did not receive SDDR PEP might have developed MB HD. MB HD is caused by M. leprae, above all the concentrated viable bacilli shed by undiagnosed or reinfected LL (lepromatous) HD patients. The published protocol stated, "Leprosy diagnosis will be clinical, based on the presence of three cardinal signs: patch with loss of sensation, enlarged peripheral nerves and/or slit-skin smear (SSS) positive for acid fast bacilli. All leprosy cases diagnosed will be verified by experienced leprosy national control program staff." This is unpromising for diagnosis of LL HD patients, because the first two of the three listed cardinal signs are often absent from new "de novo" LL HD patients. Wherever diagnosis of LL HD is unreliable, HD will spread. Hasker et al could consider improving their skills, so as to miss fewer "de novo" LL patients.

We are still learning about mycobacteria, anti-mycobacterials, immune responses, etc. The biology shows surprising twists. More twists are sure to emerge. The twists extend beyond the release of TLR-9 ligands from M. leprae by the use of anti-mycobacterial drugs and the consequent cytokines storm of ENL.(3) The people of Comoros, like those in DNH, periodically go barefoot and might well be co-infected by protective environmental (non TB non HD) mycobacteria that are susceptible to anti-M.leprae drugs. Killing such protective mycobacteria by HD chemoprophylaxis would be like knocking out the BCG-style natural wide-spectrum vaccination (5-10) which possibly had helped to limit MB HD and G2D / visible deformity among the Comorians. 

 

There is more. For example, rifampicin plasma concentrations decline rapidly following a single dose. This exposes M. leprae for a significant period to relatively low concentrations of rifampicin. Mycobacterial tolerance can be provoked by exposure to inhibitors of RNA polymerase such as rifampicin. RNA polymerase-specific phenotypic resistance/tolerance is demonstrably triggered by the transient increased expression of the beta subunit of RNA polymerase (rpoB) which in turn is due to divergent effects of rifampicin on two rpoB-rpoC promoters. Usually expression from Promoter I inhibits expression from Promoter II. Rifampicin preferentially inhibits Promoter I allowing maximal rpoB expression and mycobacterial growth. In one type of rpoB-accumulating mycobacteria (labelled Type V), rifampicin is followed not by inhibition but by division of cells and growth.(11) Whether or not this partly or wholly explains the "intense transmission" reported from places such as Alta Floresta (Mato Grosso, Brazil) following PEP RDU / LPEP / SDR PEP, we cannot exclude an increase in the virulence of M. leprae arising from phenotypic changes induced by rifampicin.


Whatever the underlying biology, the likely impact on those who receive HD chemoprophylaxis and then develop G2D (visible deformity) is hastened destitution. That in itself is an additional risk factor for HD.

 

Worryingly, exposure of mycobacteria to rifampicin combined with other drugs (eg., isoniazid) still caused up-regulation of rpoB.(11) Therefore the unintended harms of HD chemoprophylaxis might prove surprisingly hard to shake off. Other antimycobacterials too might hold surprises. Human beings need to be protected even (or especially) if they are on low incomes in endemic countries.

 

Thanks to Epco Hasker for his questions. Nearly all of the most knowledgeable HD experts in the world are on LML, and nearly all are duly respectful of human rights and ethics. Are Hasker and associates opposed to respect for the patients and populations of endemic areas? Surely not.

 

With all sincerity,

 

Joel Almeida

 

References

 

1.     Ortuno-Gutierrez N, Younoussa A, Randrianantoandro A, et al.Protocol, rationale and design of PEOPLE (Post ExpOsure Prophylaxis for LEprosy in the Comoros and Madagascar): a cluster randomized trial on effectiveness of different modalities of implementation of post-exposure prophylaxis of leprosy contacts. BMC Infect Dis 2019; 19: 1033.

 

2.     E Hasker, Y Assoumani, A Randrianantoandro et al. Post-exposure prophylaxis in leprosy (PEOPLE): a cluster randomised trial. The Lancet Global health, 2024, 12(6), e1017e102614.    

 

3.    Dias AA, Silva CO, Santos JPS, Batista-Silva LR, Acosta CCD, Fontes ANB, et al. DNA sensing via TLR-9 constitutes a major innate immunity pathway activated during erythema nodosum leprosum. J Immunol(2016) 197:1905–13. 10.4049/jimmunol.1600042

 

5.    Pinheiro RO, Schmitz V, de Andrade Silva BJ et al.  Innate Immune Responses in Leprosy. Front Immunol. 2018; 9: 518. Published online 2018 Mar 28. doi: 10.3389/fimmu.2018.00518

 
6.      Kleinnijenhuis J,Quintin J, Preijers F et al. Bacille Calmette-Guérin induces NOD2-dependent nonspecific protection from reinfection via epigenetic reprogramming of monocytes. Proc Natl Acad Sci U S A. 2012 Oct 23; 109(43): 17537–17542. Published online 2012 Sep 17. doi: 10.1073/pnas.1202870109

7.      Fine PEM, Floyd S, Stanford J et al. Environmental mycobacteria in northern Malawi: implications for the epidemiology of tuberculosis and leprosy. Epidemiol Infect, 2001; 126: 379–387.

8.      Denise L, Faustman AL, Hostetter ER. Multiple BCG vaccinations for the prevention of COVID-19 and other infectious diseases in type 1 diabetes. Cell Rep Med. 2022 Sep 20; 3(9): 100728. Published online 2022 Aug 15.   doi: 10.1016/j.xcrm.2022.100728

9.      Zhou,J, Jingzhu Lv, Carlson C et al. Trained immunity contributes to the prevention of Mycobacterium tuberculosis infection, a novel role of autophagy. Emerg Microbes Infect. 2021; 10(1): 578–588. Published online 2021 Mar 30. doi: 10.1080/22221751.2021.1899771

10.    Jensen KJ, Larsen N, Biering-Sørensen S.Heterologous Immunological Effects of Early BCG Vaccination in Low-Birth-Weight Infants in Guinea-Bissau: A Randomized-controlled Trial  J Infect Dis. 2015 Mar 15; 211(6): 956–967. Published online 2014 Sep 9. doi: 10.1093/infdis/jiu508

 

11.     Zhu J-H, Wang B-W, Pan M. Rifampicin can induce antibiotic tolerance in mycobacteria via paradoxical changes in rpoB transcription Nature Commun. 2018 Oct 11;9(1):4218. doi: 10.1038/s41467-018-06667-3.

 


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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