Assessment of Clinical, Histopathological, and Bacteriological Findings in Treated Leprosy Patients with Persistent Skin Lesions: A Retrospective Cohort Study.

Since the introduction of multidrug therapy (MDT), various disabilities/morbidities due to leprosy have been prevented. However, there is a subset of patients in whom the skin lesions do not resolve completely or remain unchanged despite a full course of MDT, which is a great source of anxiety to the patient and their family members. Hence, we tried to ascertain the putative causes and risk factors of persistent skin lesions (PSLs) by analyzing the clinical, histopathological, bacteriological, and drug resistance patterns. This is a retrospective, cohort study wherein 35 patients who had PSLs after completion of MDT were included. The majority of the patients were 18 to 30 years of age, with males predominating. Borderline tuberculoid leprosy was the most common clinical spectrum observed (71.4%). The majority had PSLs distributed predominantly over photo-exposed sites (upper limbs > trunk > face). Eight patients (22.8%) had a history of contact with leprosy patients in their family, and six patients (17.1%) had associated comorbidities. Improvement in histopathological parameters such as a decrease in granuloma fraction was observed in 22 patients (62.8%) with PSLs after release from treatment in comparison with baseline. Four patients (11.4%) were noted to have drug resistance (three to rifampicin and one to dapsone). Thus, our study emphasizes that leprosy patients with PSLs after completion of MDT should undergo histopathological evaluation and drug resistance studies.

Cuidado clínico farmacêutico e estratégia para o uso racional e adesão ao tratamento em pacientes com hanseníase numa Policlínica do Recife / Pharmaceutical clinical care and strategy to rational use and adhesion to treatment in Hansen's disease patients at a policlinic from Recife

Introdução: a hanseníase é uma doença de fácil diagnóstico, possuindo tratamento e cura. Quando diagnosticada tardiamente, pode trazer graves consequências para os portadores e seus familiares. Uma vez que o tratamento da hanseníase está inserido no componente estratégico da assistência farmacêutica, são exigidos cuidados e orientação. Há necessidade de intervenção clínica farmacêutica, com objetivo de acompanhar prescrições medicamentosas, analisando a adesão dos pacientes ao tratamento com a promoção de ações de educação em saúde, além de minimizar a ocorrência de eventos adversos relacionados aos fármacos do tratamento com possível redução de custos associados aos agravos. Objetivo: realizar o monitoramento para identificar e tratar as possíveis intercorrências que estão comumente presentes no tratamento de hanseníase. Metodologia: a realização do estudo deu-se com o acompanhamento dos pacientes atendidos no serviço de referência a partir da aplicação de questionários em consultas periódic as, vis to que a adesão ao tratamento, reduç ão dos eventos adver sos e controle dos comunic antes são de suma impor tância para o controle epidemiológico. Resultados: os principais sintomas dos indivíduos acometidos foram dormência e eritema nodoso hansênico. A maioria utilizava como tratamento o esquema multibacilar e talidomida. O acometimento relatado dos pacientes foi em nível moderado. Os pacientes possuíam comorbidades como hipertensão, artrose e diabetes. O acompanhamento clínico foi relatado como positivo pela maioria dos entrevistados. Conclusão: o desfecho do estudo mostra que a adesão do paciente é crucial para o êxito do tratamento e o acompanhamento do farmacêutico clínico constitui um pilar positivo, contribuindo para a prevenção de agravos e conscientização da comunidade.

Introduction: Hansen's disease is an easily diagnosed disease, with treatment and cure available. When diagnosed late, it can bring serious consequences for patients and their families. Since the treatment of Hansen's disease is part of the strategic component of pharmaceutical assistance, care and guidance are required. There is a need for clinical pharmaceutical intervention, aiming to monitor drug prescriptions, analyze patients' adherence to treatment while promoting health education actions, in addition to minimizing the occurrence of adverse events related to treatment drugs with possible reduction in costs associated to grievances. Objective:thus, the present study aimed to monitor, identify, and treat possible complications commonly present in the treatment of Hansen's disease. Methodology: The study was carried out with the follow-up of patients seen at the reference service, through the application of questionnaires in periodic appointments, since adherence to treatment, reduction of adverse events and control of communicants are of short importance for epidemiological control. Results:The main symptoms of Hansen's disease patients were numbness and leprosy nodosum erythema. Most used the multibacillary scheme and thalidomide as treatment. The reported involvement of patients was at a moderate level. Patients had other comorbidities such as hypertension, arthrosis and diabetes. The clinical assistance was reported as positive by most interviewees. Conclusion: The outcome of the study shows that patient's compliance is crucial for the success of treatment and the clinical pharmacist's accompaniment is a positive pillar, contributing to the prevention of complications and community awareness.

Correlated geometric models of order k and its application to intensive care unit and leprosy data.

Geometric models are used to analyse the discrete time until the occurrence of an event of interest (success or consecutive successes). In two real data sets, named leprosy and intensive care unit (ICU), the events correspond, respectively, to abandoning the clinical treatment of leprosy, where abandonment corresponds to four consecutive patient absences from treatment, and the patient's discharge from the ICU. The distribution proposed in this article, called the correlated geometric distribution of order k (or correlated k-order geometric distribution), k≥1 , consists of including a correlation parameter in the geometric distribution of order k, thus considering the dependence between patient responses until the occurrence of the event. This model proves to be a better option for real data analysis where the effect of individual correlation is considered. The model is applied to real leprosy data to estimate the treatment abandonment probability. Bayesian methods are used to determine the parameter estimators of the models and to evaluate regression models. The covariates are related to the probability of the event by an appropriate link function chosen by Bayesian selection criteria. A diagnostic analysis evaluates the models fit by posterior randomized quantile residuals and influential observations by ψ -divergence measures. This methodology is illustrated by simulation studies and real ICU admission data analysis. Studies show a good fit of the proposed model. Real data analyses also find that the probabilities of the event of interest can be overestimated or underestimated when modeled without considering the effect of dependency on the model.

Disease Burden and Current Therapeutical Status of Leprosy with Special Emphasis on Phytochemicals.

BACKGROUND: Leprosy (Hansen's disease) is a neglected tropical disease affecting millions of people globally. The combined formulations of dapsone, rifampicin and clofazimine (multidrug therapy, MDT) is only supportive in the early stage of detection, while "reemergence" is a significant problem. Thus, there is still a need to develop newer antileprosy molecules either of natural or semi-synthetic origin. OBJECTIVES: The review intends to present the latest developments in the disease prevalence, available therapeutic interventions and the possibility of identifying new molecules from phytoextracts. METHODS: Literature on the use of plant extracts and their active components to treat leprosy was searched. Selected phytoconstituents were subjected to molecular docking study on both wild and mutant types of the Mycobacterium leprae. Since the M. leprae dihydropteroate synthase (DHPS) is not available in the protein data bank (PDB), it was modelled by the homology model method and validated with the Ramachandran plot along with other bioinformatics approaches. Two mutations were introduced at codons 53 (Thr to Ile) and 55 (Pro to Leu) for docking against twenty-five selected phytoconstituents reported from eight plants that recorded effective anti-leprosy activity. The chemical structure of phytochemicals and the standard dapsone structure were retrieved from the PubChem database and prepared accordingly for docking study with the virtual-screening platform of PyRx-AutoDock 4.1. RESULTS: Based on the docking score (kcal/mol), most of the phytochemicals exhibited a higher docking score than dapsone. Asiaticoside, an active saponin (-11.3, -11.2 and -11.2 kcal/mol), was proved to be the lead phytochemical against both wild and mutant types DHPS. Some other useful phytoconstituents include echinocystic acid (-9.6, -9.5 and -9.5 kcal/mol), neobavaisoflavone (-9.2, -9.0 and -9.0 kcal/mol), boswellic acid (-8.90, -8.90 and -8.90 kcal/mol), asiatic acid (-8.9, -8.8 and -8.9 kcal/mol), corylifol A (-8.8, 8.0, and -8.0), etc. Overall, the computational predictions support the previously reported active phytoextracts of Centella asiatica (L.) Urban, Albizia amara (Roxb.) Boivin, Boswellia serrata Roxb. and Psoralea corylifolia L. to be effective against leprosy. CONCLUSION: A very small percentage of well-known plants have been evaluated scientifically for antileprosy activity. Further in vivo experiments are essential to confirm anti-leprosy properties of such useful phytochemicals.

Cost-effectiveness of incorporating Mycobacterium indicus pranii vaccine to multidrug therapy in newly diagnosed leprosy cases for better treatment outcomes & immunoprophylaxis in contacts as leprosy control measures for National Leprosy Eradication Programme in India.

Background & objectives: The elimination goal for leprosy as a public health problem at the national level was achieved in 2005 in India. However, the number of new cases reporting annually remained nearly the same during the last 10-15 years. Moreover, a substantial number of these new cases reported disabilities for the first time. Therefore, besides multidrug therapy (MDT), newer strategies with focus on effectively decreasing the number of new cases, optimizing the treatment of detected cases, averting disabilities and arresting the transmission of the disease are required. So the objective of this study was to assess the cost-effectiveness of Mycobacterium indicus pranii (MIP) vaccine implementation in National Leprosy Eradication Programme (NLEP) for newly diagnosed leprosy patients as well as their contacts to arrest/decrease the transmission and occurrence of new cases. Methods: This was a model-based estimation of incremental costs, total quality-adjusted life years (QALYs) gained, new cases averted, deaths averted, incremental cost-effectiveness ratio (ICER) and budget impact of the vaccination intervention. This model included the addition of MIP treatment intervention to the newly detected leprosy patients as well as vaccination with MIP to their contacts. Results: Using the societal perspective, discounted ICER was estimated to be ₹73,790 per QALY gained over a five-year time period. Probabilistic sensitivity analysis (PSA) was assessed by varying the values of input parameters. Majority (96%) of simulations fell in North East quadrant of cost-effectiveness plane, which were all below the willingness to pay threshold. Interpretation & conclusions: Introduction of MIP vaccination in the NLEP appears to be a cost-effective strategy for India. Significant health gains were reduction in the number of new leprosy cases, decreased incidence and severity of reactions during treatment, and after release from treatment, prevention of disabilities, thus reducing the cost as well as stigma of the disease.

An assessment of the reported impact of the COVID-19 pandemic on leprosy services using an online survey of practitioners in leprosy referral centres.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has led to governments implementing a variety of public health measures to control transmission and has affected health services. Leprosy is a communicable neglected tropical disease caused by Mycobacterium leprae and is an important health problem in low- and middle-income countries. The natural history of leprosy means that affected individuals need long-term follow-up. The measures recommended to reduce transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can create barriers to health services. We evaluated the impact of the COVID-19 epidemic response on leprosy services and disease management. METHODS: We conducted a cross-sectional online survey with healthcare professionals in leprosy referral centres. RESULTS: Eighty percent of leprosy diagnostic services were reduced. All respondents reported that multidrug therapy (MDT) was available but two reported a reduced stock. Clinicians used alternative strategies such as telephone consultations to maintain contact with patients. However, patients were not able to travel to the referral centres. DISCUSSION: This study highlights the effects of the initial phase of the SARS-CoV-2 pandemic on leprosy services in a range of leprosy-endemic countries. Many services remained open, providing leprosy diagnosis, MDT and leprosy reaction medications. Centres developed innovative measures to counter the negative impacts of the COVID-19 pandemic.

Relapse in leprosy and drug resistance assessment in a tertiary hospital of the state of Espírito Santo, Brazil.

INTRODUCTION: Leprosy recurrence is the reappearance of the disease after treatment with current schemes and discharged for cure and may have variable incubation periods. METHODS: This is a descriptive observational study of leprosy recurrence in Espírito Santo diagnosed between January 2018 and January 2020. RESULTS: One hundred and ninety-two cases were available, of which 30 were diagnosed with leprosy recurrence. CONCLUSIONS: In 25 cases, the incubation period was 5-15 years after the first treatment, favoring bacillary persistence. In the remaining 5 cases, the disease had recurred after 15 years, pointing to reinfection as none of them exhibited drug resistance.

Relapse in leprosy and drug resistance assessment in a tertiary hospital of the state of Espírito Santo, Brazil

Abstract INTRODUCTION: Leprosy recurrence is the reappearance of the disease after treatment with current schemes and discharged for cure and may have variable incubation periods. METHODS: This is a descriptive observational study of leprosy recurrence in Espírito Santo diagnosed between January 2018 and January 2020. RESULTS: One hundred and ninety-two cases were available, of which 30 were diagnosed with leprosy recurrence. CONCLUSIONS: In 25 cases, the incubation period was 5-15 years after the first treatment, favoring bacillary persistence. In the remaining 5 cases, the disease had recurred after 15 years, pointing to reinfection as none of them exhibited drug resistance.

Multiple dimensions of healthcare management of leprosy and challenges to its elimination. / Múltiplas dimensões da gestão do cuidado à hanseníase e os desafios para a eliminação.

OBJECTIVE: To analyze assistance provided to people affected by leprosy through multiple dimensions of Care Management. METHOD: Exploratory single case study with a mixed methods approach conducted at a referral service in a Southern Brazil municipality. Content analysis and webQDA software were used for data treatment. RESULTS: Participants included health professionals, people with leprosy and their family members. leprosy incidence was found to indicate its dissemination in the study setting, despite its low endemicity. Predominance of multibacillary cases and diagnoses with grade 2 disability indicate shortcomings in early detection efficacy. Contradictions were found in multiple dimensions of Care Management, leading to the understanding that the challenges in fighting leprosy are not only biological, but also socially determined. CONCLUSION: The presented challenges demonstrate the health care network's frailty regarding lowering this disease's rate and the need for effective public policies to confront diseases that, similarly to leprosy, are determined by social inequality.

Addressing the drug-resistant tuberculosis challenge through implementing a mixed model of care in Uganda.

Worldwide, Drug-resistant Tuberculosis (DR-TB) remains a big problem; the diagnostic capacity has superseded the clinical management capacity thereby causing ethical challenges. In Sub-Saharan Africa, treatment is either inadequate or lacking and some diagnosed patients are on treatment waiting lists. In Uganda, various health system challenges impeded scale-up of DR-TB care in 2012; only three treatment initiation facilities existed, with only 41 of the estimated 1010 RR-TB/MDR-TB cases enrolled on treatment yet 300 were on the waiting list and there was no DR-TB treatment scale-up plan. To scale up care, the National TB and leprosy Program (NTLP) with partners rolled out a DR-TB mixed model of care. In this paper, we share achievements and outcomes resulting from the implementation of this mixed Model of DR-TB care. Routine NTLP DR-TB program data on treatment initiation site, number of patients enrolled, their demographic characteristics, patient category, disease classification (based on disease site and human immunodeficiency virus (HIV) status), on co-trimoxazole preventive therapy (CPT) and antiretroviral therapy (ART) statuses, culture results, smear results and treatment outcomes (6, 12, and 24 months) from 2012 to 2017 RR-TB/MDR-TB cohorts were collected from all the 15 DR-TB treatment initiation sites and descriptive analysis was done using STATA version 14.2. We presented outcomes as the number of patient backlog cleared, DR-TB initiation sites, RR-TB/DR-TB cumulative patients enrolled, percentage of co-infected patients on the six, twelve interim and 24 months treatment outcomes as per the Uganda NTLP 2016 Programmatic Management of drug-resistant Tuberculosis (PMDT) guidelines (NTLP, 2016). Over the period 2013-2015, the RR-TB/MDR-TB Treatment success rate (TSR) was sustained between 70.1% and 74.1%, a performance that is well above the global TSR average rate of 50%. Additionally, the cure rate increased from 48.8% to 66.8% (P = 0.03). The Uganda DR-TB mixed model of care coupled with early application of continuous improvement approaches, enhanced cohort reviews and use of multi-disciplinary teams allowed for rapid DR-TB program expansion, rapid clearance of patient backlog, attainment of high cumulative enrollment and high treatment success rates. Sustainability of these achievements is needed to further reduce the DR-TB burden in the country. We highly recommend this mixed model of care in settings with similar challenges.

Ampliação de uso da claritromicina para o tratamento de pacientes com hanseníase resistente a medicamentos / Expansion of the use of clarithromycin for the treatment of resistant leprosy patients to medicines

INTRODUÇÃO: A hanseníase é uma doença que afeta principalmente pele e nervos periféricos, podendo causar neuropatia e complicações em longo prazo. Os pacientes são classificados como pacientes com hanseníase paucibacilar (PB) ou hanseníase multibacilar (MB). Alguns destes pacientes ainda podem desenvolver resistência aos medicamentos utilizados na poliquimioterapia (PQT), especialmente a rifampicina e ofloxacino. As informações sobre a resistência global a medicamentos na hanseníase são bastante escassas. Contudo, a literatura sugere que a prevalência de resistência a rifampicina foi estimada em 1,4% em casos novos e 8% em pacientes recidivados. O esquema terapêutico substitutivo para os casos de intolerância grave ou contraindicação à rifampicina atualmente preconizado pelo Ministério da Saúde é limitado a um único regime terapêutico, e não contempla casos com resistência associada a ofloxacino. Com base em opiniões de especialistas, padrões de resistência e atividade conhecida de alternativas antibacterianas, a Organização Mundial de Saúde (OMS) recomenda a utilização da claritromicina, assim como outras opções terapêuticas, no tratamento da hanseníase resistente a medicamentos. Dessa forma, a SVS/MS demandou à Conitec a análise da proposta de ampliação de uso da claritromicina para o tratamento de pacientes com hanseníase resistente a rifampicina, com ou sem resistência associada a ofloxacino, no SUS. PERGUNTA: Claritromicina é eficaz, segura e custo-efetiva no tratamento de pacientes adultos com hanseníase resistente a medicamentos? TECNOLOGIA: Claritromicina. Evidências clínicas: Foi encontrada apenas uma publicação, sendo um ensaio clínico randomizado (ECR) avaliando pacientes com hanseníase MB recém-diagnosticados. Os desfechos referentes a índice bacteriológico, índice morfológico e eventos adversos não apresentaram diferença estatisticamente significante entre os tratamentos com claritromicina, clofazimina e dapsona e com rifampicina, clofazimina e dapsona, avaliados no estudo. Desse modo, não foi possível observar superioridade ou inferioridade, quanto à eficácia e segurança, no uso da claritromicina para o tratamento da hanseníase resistente à rifampicina, com ou sem resistência associada a ofloxacino. Todos os desfechos tiveram a certeza da evidência classificada como muito baixa. Avaliação econômica: O esquema terapêutico com claritromicina é mais custoso do que a PQT, com eficácia e segurança consideradas semelhantes. Dois medicamentos utilizados em ambos os esquemas (clofazimina e dapsona) são atualmente doados pela OPAS; a comparação de baseou nos valores de tratamento com rifampicina e claritromicina (R$ 9,71 versus R$ 565,75). Comparado com a PQT, o regime com claritromicina apresentou um custo incremental de R$ 556,04, para o tratamento completo (12 meses) de pacientes com hanseníase resistente a rifampicina, com ou sem resistência associada a ofloxacino, no SUS. Análise de impacto orçamentário: Para estimar o impacto orçamentário da ampliação de uso da claritromicina, considerou-se uma taxa de difusão de 100% desde o primeiro ano da ampliação de uso até o quinto ano (2021 - 2025). No cenário principal, em que se considerou 13 pacientes a cada ano, verificou-se um impacto orçamentário incremental de R$ 35.638,85, acumulados ao longo dos cinco anos (2021 - 2025). No cenário epidemiológico, são esperados 1950 pacientes em 5 anos, considerando-se a proporção de resistência a medicamentos de 1,4% dos casos novos e 8% dos casos recidivados de hanseníase. A estimativa do impacto acumulado pode variar entre R$ 13.707,25 e R$ 1.069.165,50, em um cenário considerando a abordagem epidemiológica. MONITORAMENTO DO HORIZONTE TECNOLÓGICO: De acordo com os critérios adotados, não foram localizados medicamentos em desenvolvimento clínico para a doença. Assim também não foi localizada patente vigente para a claritromicina. CONSIDERAÇÕES FINAIS: O uso de claritromicina, como parte de um esquema terapêutico, possui eficácia e segurança semelhantes ao regime com rifampicina. Além disso, o regime com claritromicina se mostrou mais custoso na avaliação econômica e na análise de impacto orçamentário. Apesar da escassez de evidências e maior custo, a OMS recomenda o uso de claritromicina nos casos de resistência à rifampicina, com ou sem resistência associada ao ofloxacino. Isto indica que poderá haver boa aceitabilidade da tecnologia pelas partes interessadas e sem importantes barreiras na implementação deste. RECOMENDAÇÃO PRELIMINAR DA CONITEC: O Plenário da Conitec, em sua 91ª Reunião Ordinária, no dia 08 de outubro de 2020, deliberou que a matéria fosse disponibilizada em Consulta Pública com recomendação preliminar favorável à ampliação de uso da claritromicina para o tratamento de pacientes com hanseníase resistente a medicamentos no SUS, condicionada a apresentação de dados de vida real e conforme preconizado pelo Ministério da Saúde. Os membros da Conitec consideraram que a claritromicina será mais uma alternativa terapêutica para a hanseníase resistente a medicamentos, a qual possui poucas opções terapêuticas disponíveis no SUS e apresenta importante escassez de estudos sobre o seu tratamento. CONSULTA PÚBLICA: Foram recebidas 18 contribuições, sendo oito técnico-científicas e 10 sobre experiência ou opinião. Destas, 16 concordaram com a recomendação inicial da Conitec, uma não concordou e não discordou e uma discordou. Os assuntos mais citados foram: a escassez de evidências sobre o tema, a necessidade de se conduzir ensaios clínicos com pacientes com hanseníase no Brasil, a importância de se disponibilizar mais uma alternativa terapêutica para a hanseníase resistente, o número crescente de pacientes que não respondem mais à PQT e a comparação com os demais medicamentos disponíveis no SUS. Ao final, o Plenário da Conitec entendeu que não houve mudança em seu entendimento sobre o tema, fazendo com que sua recomendação preliminar fosse mantida. RECOMENDAÇÃO FINAL DA CONITEC: O Plenário da Conitec, em sua 93ª Reunião Ordinária, no dia 08 de dezembro de 2020, deliberou por unanimidade recomendar a ampliação de uso da claritromicina para o tratamento de pacientes com hanseníase resistente a medicamentos, condicionada a apresentação de dados de vida real em três anos e conforme Protocolo Clínico e Diretrizes Terapêuticas do Ministério da Saúde. Além disso, o Plenário apontou a necessidade de se conduzir ensaios clínicos que avaliem a eficácia e segurança de outros medicamentos com potencial terapêutico (como levofloxacino e moxifloxacino) no tratamento da hanseníase resistente a medicamentos no Brasil, a fim de se produzir evidências sobre o tema. Assim, foi assinado o Registro de Deliberação nº 578/2020. DECISÃO: ampliar o uso da claritromicina para o tratamento de pacientes com hanseníase resistente a medicamentos , condicionada a apresentação de dados de vida real em três anos e conforme Protocolo Clínico e Diretrizes Terapêuticas do Ministério da Saúde, no âmbito do Sistema Único de Saúde - SUS, conforme Portaria nº 65, publicada no Diário Oficial da União nº 248, seção 1, página 815, em 29 de dezembro de 2020.

Leprosy post-exposure prophylaxis in the Indian health system: A cost-effectiveness analysis.

India has the highest burden of leprosy in the world. Following a recent WHO guideline, the Indian National Leprosy Programme is introducing post-exposure prophylaxis with single-dose rifampicin (SDR-PEP) in all high-endemic districts of the country. The aim of this study is to estimate the long-term cost-effectiveness of SDR-PEP in different leprosy disability burden situations. We used a stochastic individual-based model (SIMCOLEP) to simulate the leprosy new case detection rate trend and the impact of implementing contact screening and SDR-PEP from 2016 to 2040 (25 years) in the Union Territory of Dadra Nagar Haveli (DNH) in India. Effects of the intervention were expressed as disability adjusted life years (DALY) averted under three assumption of disability prevention: 1) all grade 1 disability (G1D) cases prevented; 2) G1D cases prevented in PB cases only; 3) no disability prevented. Costs were US$ 2.9 per contact. Costs and effects were discounted at 3%. The incremental cost per DALY averted by SDR-PEP was US$ 210, US$ 447, and US$ 5,673 in the 25th year under assumption 1, 2, and 3, respectively. If prevention of G1D was assumed, the probability of cost-effectiveness was 1.0 at the threshold of US$ 2,000, which is equivalent to the GDP per capita of India. The probability of cost-effectiveness was 0.6, if no disability prevention was assumed. The cost per new leprosy case averted was US$ 2,873. Contact listing, screening and the provision of SDR-PEP is a cost-effective strategy in leprosy control in both the short (5 years) and long term (25 years). The cost-effectiveness depends on the extent to which disability can be prevented. As the intervention becomes increasingly cost-effective in the long term, we recommend a long-term commitment for its implementation.

Exclusão da rifampicina para quimioprofilaxia de contatos de pacientes com hanseníase / Exclusion of rifampicin for chemoprophylaxis of contacts of leprosy patients

INTRODUÇÃO: O termo mais amplamente utilizado para a quimioprofilaxia e/ou imunoprofilaxia é "profilaxia pós-exposição (PEP)". A PEP pode ser usada para expressar quimioprofilaxia ou imunoprofilaxia, ou ainda, para ambas. Embora a intervenção seja simples, a administração de uma única dose de rifampicina aos contatos de um caso índice de hanseníase, como mais uma ferramenta de redução da transmissão da doença, depende de planejamento para sua operacionalização, de modo a não causar danos às pessoas afetadas, cujos contatos deverão receber a PEP. Além disso, a PEP nunca havia sido instituída na rotina de serviços de hanseníase no Brasil. CONDIÇÃO CLÍNICA: A hanseníase é uma doença infecciosa causada por uma bactéria chamada Mycobacterium leprae (bacilo de Hansen) (6), (7), (8). A sua transmissão ocorre principalmente pelas vias aéreas superiores, por meio das secreções e do ar (7), (8), (9), e não por objetos utilizados pelo paciente (1), (8). A doença acomete principalmente os nervos superficiais da pele e troncos nervosos periféricos, mas também pode afetar olhos, mucosas e órgãos internos (6), (8). TECNOLOGIA: rifampicina 300mg, cápsula e 20mg/ml, suspensão oral. PROJETO PEP-HANS: Por meio da Portaria SCTIE/MS nº 32, de 30/06/2015, a rifampicina dose única foi incorporada no SUS para a quimioprofilaxia de contatos de doentes de hanseníase para realização do referido estudo. A pesquisa foi realizada entre os anos de 2016 a 2018, em municípios selecionados dos estados do Mato Grosso, Pernambuco e Tocantins, uma vez que tais estados configuram importantes áreas endêmicas no país e os municípios atenderam aos critérios de elegibilidade do estudo. TRATAMENTO: O protocolo de tratamento consistiu em rifampicina 600mg (2 comprimidos de 300mg) em dose única, administrado no segundo mês de tratamento do caso índice (aproximadamente 4 semanas do início do tratamento do caso índice); em crianças acima de 5 anos de idade, a administração seria de 450mg rifampicina e, em crianças ou adultos com peso inferior a 30 kg, a recomendação foi administrar rifampicina 10 a 20mg/kg. JUSTIFICATIVA DE EXCLUSÃO: a área demandante avaliou que a tecnologia deveria ser desincorporada, uma vez que o projeto de pesquisa foi concluído em 2018, conforme relatório final do projeto PEP-Hans. Para ampliação de uso da rifampicina para a quimioprofilaxia de contatos de doentes de hanseníase no âmbito do Sistema Único de Saúde, há necessidade de condução de outros estudos sobre o assunto. A CGDE/SVS/MS está encaminhando duas propostas ao DECIT/SCTIE/MS: um estudo multicêntrico de quimioprofilaxia pós-exposição para contatos e um estudo de avaliação e monitoramento dos contatos que foram submetidos à quimioprofilaxia pelo PEP-Hans. RECOMENDAÇÃO PRELIMINAR DA CONITEC: Pelo exposto, o plenário da Conitec, em sua 85ª reunião ordinária, realizada no dia 04 de fevereiro de 2020, recomendou, por unanimidade, a exclusão no SUS da rifampicina 300mg e 20mg/ml para quimioprofilaxia de contatos de pacientes com hanseníase. CONSULTA PÚBLICA: Foram recebidas 127 contribuições, sendo 121 técnico-científicas e 6 contribuições de experiência e opinião. A maioria concordou com a recomendação inicial da Conitec pela exclusão, sendo os principais argumentos no sentido de que as evidências do benefício da quimioprofilaxia são limitadas e a preocupação de não induzir resistência bacteriana à rifampicina que é o único bactericida do arsenal terapêutico da doença. A Sociedade Brasileira de Dermatologia (SBD) e demais profissionais de saúde participaram da consulta pública e as suas considerações foram devidamente apreciadas. RECOMENDAÇÃO FINAL: Os membros da Conitec presentes na 87ª reunião ordinária, no dia 03 de junho de 2020, deliberaram, por unanimidade, recomendar a exclusão da rifampicina para a quimioprofilaxia de contatos de pacientes com hanseníase no Sistema Único de Saúde. Foi assinado o Registro de Deliberação nº 517/2020. DECISÃO: excluir a rifampicina para quimioprofilaxia de contatos de pacientes com hanseníase, no âmbito do Sistema Único de Saúde ­ SUS, conforme a Portaria nº 18, publicada no Diário Oficial da União nº 112, seção 1, página 143, em 15 de junho de 2020.

Leprosy: Treatment and management of complications.

In the second article in this continuing medical education series, we review the treatment of leprosy, its immunologic reactions, and important concepts, including disease relapse and drug resistance. A fundamental understanding of the treatment options and management of neuropathic sequelae are essential to reduce disease burden and improve patients' quality of life.

Geographic and socioeconomic factors associated with leprosy treatment default: An analysis from the 100 Million Brazilian Cohort.

BACKGROUND: Although leprosy is largely curable with multidrug therapy, incomplete treatment limits therapeutic effectiveness and is an important obstacle to disease control. To inform efforts to improve treatment completion rates, we aimed to identify the geographic and socioeconomic factors associated with leprosy treatment default in Brazil. METHODOLOGY/PRINCIPAL FINDINGS: Using individual participant data collected in the Brazilian national registries for social programs and notifiable diseases and linked as part of the 100 Million Brazilian Cohort, we evaluated the odds of treatment default among 20,063 leprosy cases diagnosed and followed up between 2007 and 2014. We investigated geographic and socioeconomic risk factors using a multivariate hierarchical analysis and carried out additional stratified analyses by leprosy subtype and geographic region. Over the duration of follow-up, 1,011 (5.0%) leprosy cases were observed to default from treatment. Treatment default was markedly increased among leprosy cases residing in the North (OR = 1.57; 95%CI 1.25-1.97) and Northeast (OR = 1.44; 95%CI 1.17-1.78) regions of Brazil. The odds of default were also higher among cases with black ethnicity (OR = 1.29; 95%CI 1.01-1.69), no income (OR = 1.41; 95%CI 1.07-1.86), familial income ≤ 0.25 times Brazilian minimum wage (OR = 1.42; 95%CI 1.13-1.77), informal home lighting/no electricity supply (OR = 1.53; 95%CI 1.28-1.82), and household density of > 1 individual per room (OR = 1.35; 95%CI 1.10-1.66). CONCLUSIONS: The findings of the study indicate that the frequency of leprosy treatment default varies regionally in Brazil and provide new evidence that adverse socioeconomic conditions may represent important barriers to leprosy treatment completion. These findings suggest that interventions to address socioeconomic deprivation, along with continued efforts to improve access to care, have the potential to improve leprosy treatment outcomes and disease control.

Leprosy services in primary health care in India: comparative economic cost analysis of two public-health settings.

OBJECTIVES: The WHO recommends inclusion of post-exposure chemoprophylaxis with single-dose rifampicin in national leprosy control programmes. The objective was to estimate the cost of leprosy services at primary care level in two different public-health settings. METHODS: Ingredient-based costing was performed in eight primary health centres (PHCs) purposively selected in the Union Territory of Dadra and Nagar Haveli (DNH) and the Umbergaon block of Valsad district, Gujarat, India. All costs were bootstrapped, and to estimate the variation in total cost under uncertainty, a univariate sensitivity analysis was performed. RESULTS: The mean annual cost of providing leprosy services was USD 29 072 in the DNH PHC (95% CI: 22 125-36 020) and USD 11 082 in Umbergaon (95% CI: 8334-13 830). The single largest cost component was human resources: 79% in DNH and 83% in Umbergaon. The unit cost for screening the contact of a leprosy patient was USD 1 in DNH (95% CI: 0.8-1.2) and USD 0.3 in Umbergaon (95% CI: 0.2-0.4). In DNH, the unit cost of delivering single-dose of rifampicin (SDR) as chemoprophylaxis for contacts was USD 2.9 (95% CI: 2.5-3.7). CONCLUSIONS: The setting with an enhanced public-health financing system invests more in leprosy services than a setting with fewer financial resources. In terms of leprosy visits, the enhanced public-health system is hardly more expensive than the non-enhanced public-health system. The unit cost of contact screening is not high, favouring its sustainability in the programme.

Grade 2 disabilities in leprosy patients from Brazil: Need for follow-up after completion of multidrug therapy.

BACKGROUND: Leprosy continues to be a public health problem in many countries. Difficulties faced by health services include late diagnosis, under-reporting of new cases, adequate monitoring of disabilities and treatment. Furthermore, systematic follow-up after completion of treatment is important, when new disabilities may occur, or existing disabilities may get worse. The objective of the present study was to determine the prevalence of leprosy-associated grade 2 disabilities (G2D) after completion of multidrug therapy (MDT) and to identify factors associated with G2D. METHODS: We performed a cross-sectional study of 222 leprosy cases registered in Vitória da Conquista, Bahia state, Brazil from 2001-2014. We performed a clinical examination of the study participants and collected socio-economic and clinical information by interview. We identified factors associated with grade 2 disability (G2D) using logis tic regression. RESULTS: In total, 38 (17.1%) participants were diagnosed with G2D, and 106 (47.7%) with grade 1 disabilities (G1D). The following independent factors were significantly associated with G2D: occurrence of leprosy reaction (adjusted OR = 2.5; 95%CI = 1.09-5.77), thickening and/or tenderness of one or more nerve trunks (adjusted OR = 3.0; CI = 1.13-8.01) and unemployment (adjusted OR = 7.17; CI = 2.44-21.07). CONCLUSIONS: This study shows that physical disabilities remain after completion of MDT and frequently occur in an endemic area in Brazil. Finding new ways to reduce the burden of disability are urgently needed, and may include systematic follow-up of patients after treatment completion combined with evidence-based preventative measures.

Household expenditure on leprosy outpatient services in the Indian health system: A comparative study.

BACKGROUND: Leprosy is a major public health problem in many low and middle income countries, especially in India, and contributes considerably to the global burden of the disease. Leprosy and poverty are closely associated, and therefore the economic burden of leprosy is a concern. However, evidence on patient's expenditure is scarce. In this study, we estimate the expenditure in primary care (outpatient) by leprosy households in two different public health settings. METHODOLOGY/PRINCIPAL FINDINGS: We performed a cross-sectional study, comparing the Union Territory of Dadra and Nagar Haveli with the Umbergaon block of Valsad, Gujrat, India. A household (HH) survey was conducted between May and October, 2016. We calculated direct and indirect expenditure by zero inflated negative binomial and negative binomial regression. The sampled households were comparable on socioeconomic indicators. The mean direct expenditure was USD 6.5 (95% CI: 2.4-17.9) in Dadra and Nagar Haveli and USD 5.4 (95% CI: 3.8-7.9) per visit in Umbergaon. The mean indirect expenditure was USD 8.7 (95% CI: 7.2-10.6) in Dadra and Nagar Haveli and USD 12.4 (95% CI: 7.0-21.9) in Umbergaon. The age of the leprosy patients and type of health facilities were the major predictors of total expenditure on leprosy primary care. The higher the age, the higher the expenditure at both sites. The private facilities are more expensive than the government facilities at both sites. If the public health system is enhanced, government facilities are the first preference for patients. CONCLUSIONS/SIGNIFICANCE: An enhanced public health system reduces the patient's expenditure and improves the health seeking behaviour. We recommend investing in health system strengthening to reduce the economic burden of leprosy.

Perfil socioeconômico dos pacientes atendidos pelo Centro de Referência em Reabilitação da Hanseníase da Zona da Mata Mineira / Socioeconomic profile of the patients attended at the Reference Center for Rehabilitation of Leprosy of the Southeast of Minas Gerais State

A hanseníase é uma doença crônica, infectocontagiosa, causada pelo bacilo de Hansen (Mycobacterium leprae), que acomete peles e nervos periféricos, com alto poder incapacitante e forte estigma social, provocando um sofrimento aos seus portadores, para além de seus sintomas físicos. Tendo os indicadores sociais um papel determinante nesse processo, objetivou-se traçar o perfil socioeconômico dos pacientes atendidos pelo Centro de Referência em Reabilitação da Hanseníase da Zona da Mata Mineira. Para tanto, foram analisados 99 prontuários e suas respectivas fichas de abordagem social, dos usuários atendidos de janeiro de 2004 a junho de 2011. Os resultados apontam o predomínio de pacientes do sexo masculino (54,5%), advindos de áreas urbanas (84,8%), com baixa escolaridade (54,5%) e renda familiar igual ou inferior a dois salários mínimos (60,6%), em faixa etária que compreende a população economicamente ativa, residindo em casa própria (69,7%), com infraestrutura adequada (73,7%), porém convivendo com uma média de quatro ou mais pessoas neste mesmo espaço (24,2%). Tais resultados demonstram que os protocolos de intervenções clínicas devem integrar-se às medidas de melhoria das condições de vida da população para uma efetiva política de controle da doença, uma vez que sua ocorrência está diretamente relacionada às desigualdades sociais existentes.

Leprosy is a chronic disease, infectious contagious, caused by bacillus Mycobacterium leprae, that affects skins and peripheral nerves, with a high power disabling and strong social stigma, promoting suffering to patients beyond their physical symptoms. As the social indicators a key role in this process, it was aimed to trace the socioeconomic profile of the patients attended at the Reference Center for Rehabilitation of Leprosy of the Southeast of Minas Gerais State. For that, 99 patients records and their respective social approach files, from patients attended between January 2004 and June 2011, were analyzed. The results indicate most of men (54.5%), from urban areas (84.8%) with low education level (54.5%) and a familiar income equal to or less than two minimum wages (60,6%), in economically active age group, living in own home (69.7%) with a suitable infrastructure (73.7%) but living with an average of four or more people in the same house (24.2%). These results show that measures to improve people's living conditions should be integrated into clinical protocol interventions, for an effective disease control policy, since its occurrence is directly related to the existing social differences.