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2.
PLoS Negl Trop Dis ; 15(12): e0010035, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34898634

RESUMO

BACKGROUND: Leprosy and cutaneous leishmaniasis (CL) are neglected tropical diseases (NTDs) affecting the skin. Their control is challenging but the integration of skin NTDs control programs is recommended to improve timely detection and treatment. However, little is known about the occurrence of leprosy and CL in the same individuals, and what are the characteristics of such patients. This study aimed to identify and characterize patients diagnosed with both leprosy and CL (i.e., outcome) in the hyperendemic state of Mato Grosso, Brazil. Also, we investigated the demographic risk factors associated with the period between the diagnosis of both diseases. METHODOLOGY/PRINCIPAL FINDINGS: A retrospective cohort study was conducted with patients diagnosed between 2008 and 2017. From the leprosy (n = 28,204) and CL (n = 24,771) databases of the national reporting system, 414 (0.8%; 414/52,561) patients presenting both diseases were identified through a probabilistic linkage procedure. This observed number was much higher than the number of patients that would be expected by chance alone (n = 22). The spatial distribution of patients presenting the outcome was concentrated in the North and Northeast mesoregions of the state. Through survival analysis, we detected that the probability of a patient developing both diseases increased over time from 0.2% in the first year to 1.0% within seven years. Further, using a Cox model we identified male sex (HR: 2.3; 95% CI: 1.7-2.9) and low schooling level (HR: 1.5; 95% CI: 1.2-1.9) as positively associated with the outcome. Furthermore, the hazard of developing the outcome was higher among individuals aged 40-55 years. CONCLUSIONS/SIGNIFICANCE: Leprosy and CL are affecting the same individuals in the area. Integration of control policies for both diseases will help to efficiently cover such patients. Measures should be focused on timely diagnosis by following-up patients diagnosed with CL, active case detection, and training of health professionals.


Assuntos
Coinfecção/epidemiologia , Leishmaniose Cutânea/epidemiologia , Hanseníase/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil/epidemiologia , Criança , Pré-Escolar , Coinfecção/diagnóstico , Doenças Endêmicas , Feminino , Humanos , Leishmaniose Cutânea/diagnóstico , Hanseníase/diagnóstico , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
3.
Vaccine ; 39(50): 7230-7237, 2021 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-34688497

RESUMO

Leprosy is an infectious disease caused by Mycobacterium leprae leading to irreversible disabilities along with social exclusion. Leprosy is a spectral disease for which the clinical outcome after M. leprae infection is determined by host factors. The spectrum spans from anti-inflammatory T helper-2 (Th2) immunity concomitant with large numbers of bacteria as well as antibodies against M. leprae antigens in multibacillary (MB) leprosy, to paucibacillary (PB) leprosy characterised by strong pro-inflammatory, Th1 as well as Th17 immunity. Despite decades of availability of adequate antibiotic treatment, transmission of M. leprae is unabated. Since individuals with close and frequent contact with untreated leprosy patients are particularly at risk to develop the disease themselves, prophylactic strategies currently focus on household contacts of newly diagnosed patients. It has been shown that BCG (re)vaccination can reduce the risk of leprosy. However, BCG immunoprophylaxis in contacts of leprosy patients has also been reported to induce PB leprosy, indicating that BCG (re)vaccination may tip the balance between protective immunity and overactivation immunity causing skin/nerve tissue damage. In order to identify who is at risk of developing PB leprosy after BCG vaccination, amongst individuals who are chronically exposed to M. leprae, we analyzed innate and adaptive immune markers in whole blood of household contacts of newly diagnosed leprosy patients in Bangladesh, some of which received BCG vaccination. As controls, individuals from the same area without known contact with leprosy patients were similarly assessed. Our data show the added effect of BCG vaccination on immune markers on top of the effect already induced by M. leprae exposure. Moreover, we identified BCG-induced markers that differentiate between protective and disease prone immunity in those contacts.


Assuntos
Vacina BCG , Hanseníase , Antígenos de Bactérias , Humanos , Hanseníase/prevenção & controle , Mycobacterium leprae , Pele , Vacinação
4.
PLoS Negl Trop Dis ; 15(9): e0009769, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34543282

RESUMO

BACKGROUND: Leprosy is a chronic infectious disease caused by Mycobacterium leprae, the annual new case detection in 2019 was 202,189 globally. Measuring endemicity levels and burden in leprosy lacks a uniform approach. As a result, the assessment of leprosy endemicity or burden are not comparable over time and across countries and regions. This can make program planning and evaluation difficult. This study aims to identify relevant metrics and methods for measuring and classifying leprosy endemicity and burden at (sub)national level. METHODS: We used a mixed-method approach combining findings from a systematic literature review and a Delphi survey. The literature search was conducted in seven databases, searching for endemicity, burden and leprosy. We reviewed the available evidence on the usage of indicators, classification levels, and scoring methods to measure and classify endemicity and burden. A two round Delphi survey was conducted to ask experts to rank and weigh indicators, classification levels, and scoring methods. RESULTS: The literature review showed variation of indicators, levels, and cut-off values to measure leprosy endemicity and/or burden. The most used indicators for endemicity include new case detection rate (NCDR), new cases among children and new cases with grade 2 disability. For burden these include NCDR, MB cases, and prevalence. The classification levels 'high' and 'low' were most important. It was considered most relevant to use separate scoring methods for endemicity and burden. The scores would be derived by use of multiple indicators. CONCLUSION: There is great variation in the existing method for measuring endemicity and burden across countries and regions. Our findings contribute to establishing a standardized uniform approach to measure and classify leprosy endemicity and burden at (sub)national level, which would allow effective communication and planning of intervention strategies.


Assuntos
Técnica Delfos , Doenças Endêmicas , Saúde Global , Hanseníase/epidemiologia , Efeitos Psicossociais da Doença , Humanos
5.
PLoS Negl Trop Dis ; 15(8): e0009651, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34383768

RESUMO

BACKGROUND: The number of new leprosy cases is declining globally, but the disability caused by leprosy remains an important disease burden. The chance of disability is increased by delayed case detection. This review focusses on the individual and community determinants of delayed leprosy case detection. METHODS: This study was conducted according to the PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analysis). The study protocol is registered in PROSPERO (code: CRD42020189274). To identify determinants of delayed detection, data was collected from five electronic databases: Embase.com, Medline All Ovid, Web of Science, Cochrane CENTRAL, and the WHO Global Health Library. RESULTS: We included 27 papers from 4315 records assessed. They originated in twelve countries, had been published between January 1, 2000, and January 31, 2021, and described the factors related to delayed leprosy case detection, the duration of the delayed case, and the percentage of Grade 2 Disability (G2D). The median delay in detection ranged from 12 to 36 months, the mean delay ranged from 11.5 to 64.1 months, and the percentage of G2D ranged from 5.6 to 43.2%. Health-service-seeking behavior was the most common factor associated with delayed detection. The most common individual factors were older age, being male, having a lower disease-symptom perception, having multibacillary leprosy, and lack of knowledge. The most common socioeconomic factors were living in a rural area, performing agricultural labor, and being unemployed. Stigma was the most common social and community factor. CONCLUSIONS: Delayed leprosy case detection is clearly correlated with increased disability and should therefore be a priority of leprosy programs. Interventions should focus on determinants of delayed case detection such as health-service-seeking behavior, and should consider relevant individual, socioeconomic, and community factors, including stigmatization. Further study is required of the health service-related factors contributing to delay.


Assuntos
Diagnóstico Tardio/estatística & dados numéricos , Pessoas com Deficiência/estatística & dados numéricos , Hanseníase/complicações , Hanseníase/epidemiologia , Tempo para o Tratamento/estatística & dados numéricos , Humanos , Hanseníase/diagnóstico , Hanseníase/tratamento farmacológico , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Fatores de Risco , Estigma Social , Fatores Socioeconômicos
7.
PLoS Negl Trop Dis ; 15(8): e0009654, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34424909

RESUMO

INTRODUCTION: Since ancient times leprosy has had a negative perception, resulting in stigmatization. To improve the lives of persons affected by leprosy, these negative perceptions need to change. The aim of this study is to evaluate interventions to change perceptions and improve knowledge of leprosy. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a pre-post intervention study in Fatehpur and Chandauli districts, Uttar Pradesh, India. Based on six steps of quality intervention development (6SQuID) two interventions were designed: (1) posters that provided information about leprosy and challenged misconceptions, and (2) meetings with persons affected by leprosy, community members and influential people in the community. The effect of the interventions was evaluated in a mixed-methods design; in-depth interviews, focus group discussions, and questionnaires containing a knowledge measure (KAP), two perception measures (EMIC-CSS, SDS) and an intervention evaluation tool. 1067 participants were included in Survey 1 and 843 in Survey 2. The interventions were effective in increasing knowledge of all participant groups, and in changing community and personal attitudes of close contacts and community members (changes of 19%, 24% and 13% on the maximum KAP, EMIC-CSS and SDS scores respectively, p<0.05). In Survey 1, 13% of participants had adequate knowledge of leprosy versus 53% in Survey 2. Responses showed stigmatizing community attitudes in 86% (Survey 1) and 61% (Survey 2) of participants and negative personal attitudes in 37% (Survey 1) and 19% (Survey 2). The number of posters seen was associated with KAP, EMIC-CSS and SDS scores in Survey 2 (p<0.001). In addition, during eight post-intervention focus group discussions and 48 interviews many participants indicated that the perception of leprosy in the community had changed. CONCLUSIONS/SIGNIFICANCE: Contextualized posters and community meetings were effective in changing the perception of leprosy and in increasing leprosy-related knowledge. We recommend studying the long-term effect of the interventions, also on behavior.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Hanseníase/epidemiologia , Hanseníase/psicologia , Percepção Social , Adulto , Feminino , Grupos Focais , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Análise de Regressão , Estigma Social , Inquéritos e Questionários , Adulto Jovem
8.
BMJ Open ; 11(8): e046125, 2021 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-34446483

RESUMO

INTRODUCTION: Leprosy, or Hansen's disease, remains a cause of preventable disability. Early detection, treatment and prevention are key to reducing transmission. Post-exposure prophylaxis with single-dose rifampicin (SDR-PEP) reduces the risk of developing leprosy when administered to screened contacts of patients. This has been adopted in the WHO leprosy guidelines. The PEP4LEP study aims to determine the most effective and feasible method of screening people at risk of developing leprosy and administering chemoprophylaxis to contribute to interrupting transmission. METHODS AND ANALYSIS: PEP4LEP is a cluster-randomised implementation trial comparing two interventions of integrated skin screening combined with SDR-PEP distribution to contacts of patients with leprosy in Ethiopia, Mozambique and Tanzania. One intervention is community-based, using skin camps to screen approximately 100 community contacts per leprosy patient, and to administer SDR-PEP when eligible. The other intervention is health centre-based, inviting household contacts of leprosy patients to be screened in a local health centre and subsequently receive SDR-PEP when eligible. The mobile health (mHealth) tool SkinApp will support health workers' capacity in integrated skin screening. The effectiveness of both interventions will be compared by assessing the rate of patients with leprosy detected and case detection delay in months, as well as feasibility in terms of cost-effectiveness and acceptability. ETHICS AND DISSEMINATION: Ethical approval was obtained from the national ethical committees of Ethiopia (MoSHE), Mozambique (CNBS) and Tanzania (NIMR/MoHCDEC). Study results will be published open access in peer-reviewed journals, providing evidence for the implementation of innovative leprosy screening methods and chemoprophylaxis to policymakers. TRIAL REGISTRATION NUMBER: NL7294 (NTR7503).


Assuntos
Hanseníase , Etiópia , Estudos de Viabilidade , Humanos , Hanseníase/diagnóstico , Hanseníase/tratamento farmacológico , Hanseníase/prevenção & controle , Moçambique , Tanzânia
9.
EBioMedicine ; 68: 103379, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34090257

RESUMO

BACKGROUND: Leprosy, a chronic infectious disease caused by Mycobacterium leprae, is often late- or misdiagnosed leading to irreversible disabilities. Blood transcriptomic biomarkers that prospectively predict those who progress to leprosy (progressors) would allow early diagnosis, better treatment outcomes and facilitate interventions aimed at stopping bacterial transmission. To identify potential risk signatures of leprosy, we collected whole blood of household contacts (HC, n=5,352) of leprosy patients, including individuals who were diagnosed with leprosy 4-61 months after sample collection. METHODS: We investigated differential gene expression (DGE) by RNA-Seq between progressors before presence of symptoms (n=40) and HC (n=40), as well as longitudinal DGE within each progressor. A prospective leprosy signature was identified using a machine learning approach (Random Forest) and validated using reverse transcription quantitative PCR (RT-qPCR). FINDINGS: Although no significant intra-individual longitudinal variation within leprosy progressors was identified, 1,613 genes were differentially expressed in progressors before diagnosis compared to HC. We identified a 13-gene prospective risk signature with an Area Under the Curve (AUC) of 95.2%. Validation of this RNA-Seq signature in an additional set of progressors (n=43) and HC (n=43) by RT-qPCR, resulted in a final 4-gene signature, designated RISK4LEP (MT-ND2, REX1BD, TPGS1, UBC) (AUC=86.4%). INTERPRETATION: This study identifies for the first time a prospective transcriptional risk signature in blood predicting development of leprosy 4 to 61 months before clinical diagnosis. Assessment of this signature in contacts of leprosy patients can function as an adjunct diagnostic tool to target implementation of interventions to restrain leprosy development. FUNDING: This study was supported by R2STOP Research grant, the Order of Malta-Grants-for-Leprosy-Research, the Q.M. Gastmann-Wichers Foundation and the Leprosy Research Initiative (LRI) together with the Turing Foundation (ILEP# 702.02.73 and # 703.15.07).


Assuntos
Biomarcadores/sangue , Perfilação da Expressão Gênica/métodos , Redes Reguladoras de Genes , Hanseníase/diagnóstico , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Criança , Progressão da Doença , Feminino , Regulação da Expressão Gênica , Humanos , Hanseníase/sangue , Hanseníase/genética , Aprendizado de Máquina , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Análise de Sequência de RNA , Adulto Jovem
10.
PLoS Negl Trop Dis ; 15(5): e0009436, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-34038422

RESUMO

BACKGROUND: Leprosy is an infectious disease caused by Mycobacterium leprae. As incidence begins to decline, the characteristics of new cases shifts away from those observed in highly endemic areas, revealing potentially important insights into possible ongoing sources of transmission. We aimed to investigate whether transmission is driven mainly by undiagnosed and untreated new leprosy cases in the community, or by incompletely treated or relapsing cases. METHODOLOGY/PRINCIPAL FINDINGS: A literature search of major electronic databases was conducted in January, 2020 with 134 articles retained out of a total 4318 records identified (PROSPERO ID: CRD42020178923). We presented quantitative data from leprosy case records with supporting evidence describing the decline in incidence across several contexts. BCG vaccination, active case finding, adherence to multidrug therapy and continued surveillance following treatment were the main strategies shared by countries who achieved a substantial reduction in incidence. From 3950 leprosy case records collected across 22 low endemic countries, 48.3% were suspected to be imported, originating from transmission outside of the country. Most cases were multibacillary (64.4%) and regularly confirmed through skin biopsy, with 122 cases of suspected relapse from previous leprosy treatment. Family history was reported in 18.7% of cases, while other suspected sources included travel to high endemic areas and direct contact with armadillos. None of the countries included in the analysis reported a distinct increase in leprosy incidence in recent years. CONCLUSIONS/SIGNIFICANCE: Together with socioeconomic improvement over time, several successful leprosy control programmes have been implemented in recent decades that led to a substantial decline in incidence. Most cases described in these contexts were multibacillary and numerous cases of suspected relapse were reported. Despite these observations, there was no indication that these cases led to a rise in new secondary cases, suggesting that they do not represent a large ongoing source of human-to-human transmission.


Assuntos
Hanseníase/epidemiologia , Hanseníase/transmissão , Mycobacterium leprae/fisiologia , Animais , Tatus/microbiologia , Vacina BCG/administração & dosagem , Quimioterapia Combinada , Humanos , Hansenostáticos/uso terapêutico , Hanseníase/tratamento farmacológico , Recidiva , Viagem
11.
Int J Infect Dis ; 108: 96-101, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33991682

RESUMO

OBJECTIVES: To identify patterns of spatial clustering of leprosy. DESIGN: We performed a baseline survey for a trial on post-exposure prophylaxis for leprosy in Comoros and Madagascar. We screened 64 villages, door-to-door, and recorded results of screening, demographic data and geographic coordinates. To identify clusters, we fitted a purely spatial Poisson model using Kulldorff's spatial scan statistic. We used a regular Poisson model to assess the risk of contracting leprosy at the individual level as a function of distance to the nearest known leprosy patient. RESULTS: We identified 455 leprosy patients; 200 (44.0%) belonged to 2735 households included in a cluster. Thirty-eight percent of leprosy patients versus 10% of the total population live ≤25 m from another leprosy patient. Risk ratios for being diagnosed with leprosy were 7.3, 2.4, 1.8, 1.4 and 1.7, for those at the same household, at 1-<25 m, 25-<50 m, 50-<75 m and 75-<100 m as/from a leprosy patient, respectively, compared to those living at ≥100 m. CONCLUSIONS: We documented significant clustering of leprosy beyond household level, although 56% of cases were not part of a cluster. Control measures need to be extended beyond the household, and social networks should be further explored.


Assuntos
Hanseníase , Análise por Conglomerados , Comores , Humanos , Hanseníase/diagnóstico , Hanseníase/epidemiologia , Hanseníase/prevenção & controle , Madagáscar/epidemiologia , Análise Espacial
13.
Infect Dis Poverty ; 10(1): 36, 2021 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-33752751

RESUMO

BACKGROUND: Leprosy is known to be unevenly distributed between and within countries. High risk areas or 'hotspots' are potential targets for preventive interventions, but the underlying epidemiologic mechanisms that enable hotspots to emerge, are not yet fully understood. In this study, we identified and characterized leprosy hotspots in Bangladesh, a country with one of the highest leprosy endemicity levels globally. METHODS: We used data from four high-endemic districts in northwest Bangladesh including 20 623 registered cases between January 2000 and April 2019 (among ~ 7 million population). Incidences per union (smallest administrative unit) were calculated using geospatial population density estimates. A geospatial Poisson model was used to detect incidence hotspots over three (overlapping) 10-year timeframes: 2000-2009, 2005-2014 and 2010-2019. Ordinal regression models were used to assess whether patient characteristics were significantly different for cases outside hotspots, as compared to cases within weak (i.e., relative risk (RR) of one to two), medium (i.e., RR of two to three), and strong (i.e., RR higher than three) hotspots. RESULTS: New case detection rates dropped from 44/100 000 in 2000 to 10/100 000 in 2019. Statistically significant hotspots were identified during all timeframes and were often located at areas with high population densities. The RR for leprosy was up to 12 times higher for inhabitants of hotspots than for people living outside hotspots. Within strong hotspots (1930 cases among less than 1% of the population), significantly more child cases (i.e., below 15 years of age) were detected, indicating recent transmission. Cases in hotspots were not significantly more likely to be detected actively. CONCLUSIONS: Leprosy showed a heterogeneous distribution with clear hotspots in northwest Bangladesh throughout a 20-year period of decreasing incidence. Findings confirm that leprosy hotspots represent areas of higher transmission activity and are not solely the result of active case finding strategies.


Assuntos
Hanseníase , Bangladesh/epidemiologia , Criança , Humanos , Incidência , Hanseníase/epidemiologia , Estudos Retrospectivos , Risco
14.
PLoS Negl Trop Dis ; 15(3): e0009209, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33651814

RESUMO

BACKGROUND: Leprosy is a chronic bacterial infection caused by Mycobacterium leprae, which may lead to physical disability, stigma, and discrimination. The chronicity of the disease and disabilities are the prime contributors to the disease burden of leprosy. The current figures of the disease burden in the 2017 global burden of disease study, however, are considered to be under-estimated. In this study, we aimed to systematically review the literature and perform individual patient data meta-analysis to estimate new disability weights for leprosy, using Health-Related Quality of Life (HRQOL) data. METHODOLOGY/PRINCIPAL FINDINGS: The search strategy included all major databases with no restriction on language, setting, study design, or year of publication. Studies on human populations that have been affected by leprosy and recorded the HRQOL with the Short form tool, were included. A consortium was formed with authors who could share the anonymous individual-level data of their study. Mean disability weight estimates, sorted by the grade of leprosy disability as defined by WHO, were estimated for individual participant data and pooled using multivariate random-effects meta-analysis. Eight out of 14 studies from the review were included in the meta-analysis due to the availability of individual-level data (667 individuals). The overall estimated disability weight for grade 2 disability was 0.26 (95%CI: 0.18-0.34). For grade 1 disability the estimated weight was 0.19 (95%CI: 0.13-0.26) and for grade 0 disability it was 0.13 (95%CI: 0.06-0.19). The revised disability weight for grade 2 leprosy disability is four times higher than the published GBD 2017 weights for leprosy and the grade 1 disability weight is nearly twenty times higher. CONCLUSIONS/SIGNIFICANCE: The global burden of leprosy is grossly underestimated. Revision of the current disability weights and inclusion of disability caused in individuals with grade 0 leprosy disability will contribute towards a more precise estimation of the global burden of leprosy.


Assuntos
Pessoas com Deficiência , Carga Global da Doença , Hanseníase/patologia , Qualidade de Vida , Humanos
15.
PLoS Negl Trop Dis ; 15(3): e0009279, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33788863

RESUMO

BACKGROUND: The Leprosy Post-Exposure Prophylaxis (LPEP) program explored the feasibility and impact of contact tracing and the provision of single dose rifampicin (SDR) to eligible contacts of newly diagnosed leprosy patients in Brazil, India, Indonesia, Myanmar, Nepal, Sri Lanka and Tanzania. As the impact of the programme is difficult to establish in the short term, we apply mathematical modelling to predict its long-term impact on the leprosy incidence. METHODOLOGY: The individual-based model SIMCOLEP was calibrated and validated to the historic leprosy incidence data in the study areas. For each area, we assessed two scenarios: 1) continuation of existing routine activities as in 2014; and 2) routine activities combined with LPEP starting in 2015. The number of contacts per index patient screened varied from 1 to 36 between areas. Projections were made until 2040. PRINCIPAL FINDINGS: In all areas, the LPEP program increased the number of detected cases in the first year(s) of the programme as compared to the routine programme, followed by a faster reduction afterwards with increasing benefit over time. LPEP could accelerate the reduction of the leprosy incidence by up to six years as compared to the routine programme. The impact of LPEP varied by area due to differences in the number of contacts per index patient included and differences in leprosy epidemiology and routine control programme. CONCLUSIONS: The LPEP program contributes significantly to the reduction of the leprosy incidence and could potentially accelerate the interruption of transmission. It would be advisable to include contact tracing/screening and SDR in routine leprosy programmes.


Assuntos
Busca de Comunicante/métodos , Hanseníase/epidemiologia , Hanseníase/prevenção & controle , Programas de Rastreamento/métodos , Prevenção Primária/métodos , Brasil , Humanos , Índia , Indonésia/epidemiologia , Hansenostáticos/uso terapêutico , Mianmar/epidemiologia , Nepal/epidemiologia , Profilaxia Pós-Exposição/métodos , Rifampina/uso terapêutico , Sri Lanka/epidemiologia , Tanzânia/epidemiologia
16.
PLoS Negl Trop Dis ; 15(2): e0009146, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33630836

RESUMO

BACKGROUND: Worldwide, around 210,000 new cases of leprosy are detected annually. To end leprosy, i.e. zero new leprosy cases, preventive interventions such as contact tracing and post-exposure prophylaxis (PEP) are required. This study aims to estimate the number of people requiring PEP to reduce leprosy new case detection (NCD) at national and global level by 50% and 90%. METHODOLOGY/PRINCIPAL FINDINGS: The individual-based model SIMCOLEP was fitted to seven leprosy settings defined by NCD and MB proportion. Using data of all 110 countries with known leprosy patients in 2016, we assigned each country to one of these settings. We predicted the impact of administering PEP to about 25 contacts of leprosy patients on the annual NCD for 25 years and estimated the number of contacts requiring PEP per country for each year. The NCD trends show an increase in NCD in the first year (i.e. backlog cases) followed by a significant decrease thereafter. A reduction of 50% and 90% of new cases would be achieved in most countries in 5 and 22 years if 20.6 and 40.2 million people are treated with PEP over that period, respectively. For India, Brazil, and Indonesia together, a total of 32.9 million people requiring PEP to achieve a 90% reduction in 22 years. CONCLUSION/SIGNIFICANCE: The leprosy problem is far greater than the 210,000 new cases reported annually. Our model estimates of the number of people requiring PEP to achieve significant reduction of new leprosy cases can be used by policymakers and program managers to develop long-term strategies to end leprosy.


Assuntos
Hansenostáticos/uso terapêutico , Hanseníase/terapia , Profilaxia Pós-Exposição , Adolescente , Brasil , Criança , Pré-Escolar , Busca de Comunicante , Humanos , Índia , Indonésia , Hanseníase/diagnóstico , Hanseníase/epidemiologia , Modelos Teóricos , Adulto Jovem
17.
iScience ; 24(1): 102006, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33490914

RESUMO

To end the decade-long, obstinately stagnant number of new leprosy cases, there is an urgent need for field-applicable diagnostic tools that detect infection with Mycobacterium leprae, leprosy's etiologic agent. Since immunity against M. leprae is characterized by humoral and cellular markers, we developed a lateral flow test measuring multiple host proteins based on six previously identified biomarkers for various leprosy phenotypes. This multi-biomarker test (MBT) demonstrated feasibility of quantitative detection of six host serum proteins simultaneously, jointly allowing discrimination of patients with multibacillary and paucibacillary leprosy from control individuals in high and low leprosy endemic areas. Pilot testing of fingerstick blood showed similar MBT performance in point-of-care (POC) settings as observed for plasma and serum. Thus, this newly developed prototype MBT measures six biomarkers covering immunity against M. leprae across the leprosy spectrum. The MBT thereby provides the basis for immunodiagnostic POC tests for leprosy with potential for other (infectious) diseases as well.

18.
Lancet Glob Health ; 9(1): e81-e90, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33129378

RESUMO

BACKGROUND: Innovative approaches are required for leprosy control to reduce cases and curb transmission of Mycobacterium leprae. Early case detection, contact screening, and chemoprophylaxis are the most promising tools. We aimed to generate evidence on the feasibility of integrating contact tracing and administration of single-dose rifampicin (SDR) into routine leprosy control activities. METHODS: The leprosy post-exposure prophylaxis (LPEP) programme was an international, multicentre feasibility study implemented within the leprosy control programmes of Brazil, India, Indonesia, Myanmar, Nepal, Sri Lanka, and Tanzania. LPEP explored the feasibility of combining three key interventions: systematically tracing contacts of individuals newly diagnosed with leprosy; screening the traced contacts for leprosy; and administering SDR to eligible contacts. Outcomes were assessed in terms of number of contacts traced, screened, and SDR administration rates. FINDINGS: Between Jan 1, 2015, and Aug 1, 2019, LPEP enrolled 9170 index patients and listed 179 769 contacts, of whom 174 782 (97·2%) were successfully traced and screened. Of those screened, 22 854 (13·1%) were excluded from SDR mainly because of health reasons and age. Among those excluded, 810 were confirmed as new patients (46 per 10 000 contacts screened). Among the eligible screened contacts, 1182 (0·7%) refused prophylactic treatment with SDR. Overall, SDR was administered to 151 928 (86·9%) screened contacts. No serious adverse events were reported. INTERPRETATION: Post-exposure prophylaxis with SDR is safe; can be integrated into different leprosy control programmes with minimal additional efforts once contact tracing has been established; and is generally well accepted by index patients, their contacts, and health-care workers. The programme has also invigorated local leprosy control through the availability of a prophylactic intervention; therefore, we recommend rolling out SDR in all settings where contact tracing and screening have been established. FUNDING: Novartis Foundation.


Assuntos
Hansenostáticos/uso terapêutico , Hanseníase/prevenção & controle , Profilaxia Pós-Exposição/métodos , Saúde Pública/métodos , Rifampina/uso terapêutico , Estudos de Viabilidade , Humanos , Medicina de Precisão/métodos
19.
s.l; s.n; 2021. 9 p. tab.
Não convencional em Inglês | SES-SP, CONASS, HANSEN, HANSENIASE, SESSP-ILSLACERVO, SES-SP | ID: biblio-1146973

RESUMO

Background: Innovative approaches are required for leprosy control to reduce cases and curb transmission of Mycobacterium leprae. Early case detection, contact screening, and chemoprophylaxis are the most promising tools. We aimed to generate evidence on the feasibility of integrating contact tracing and administration of single-dose rifampicin (SDR) into routine leprosy control activities. Methods The leprosy post-exposure prophylaxis (LPEP) programme was an international, multicentre feasibility study implemented within the leprosy control programmes of Brazil, India, Indonesia, Myanmar, Nepal, Sri Lanka, and Tanzania. LPEP explored the feasibility of combining three key interventions: systematically tracing contacts of individuals newly diagnosed with leprosy; screening the traced contacts for leprosy; and administering SDR to eligible contacts. Outcomes were assessed in terms of number of contacts traced, screened, and SDR administration rates. Findings Between Jan 1, 2015, and Aug 1, 2019, LPEP enrolled 9170 index patients and listed 179 769 contacts, of whom 174782 (97·2%) were successfully traced and screened. Of those screened, 22 854 (13·1%) were excluded from SDR mainly because of health reasons and age. Among those excluded, 810 were confirmed as new patients (46 per 10 000 contacts screened). Among the eligible screened contacts, 1182 (0·7%) refused prophylactic treatment with SDR. Overall, SDR was administered to 151 928 (86·9%) screened contacts. No serious adverse events were reported. Interpretation Post-exposure prophylaxis with SDR is safe; can be integrated into different leprosy control programmes with minimal additional efforts once contact tracing has been established; and is generally well accepted by index patients, their contacts, and health-care workers. The programme has also invigorated local leprosy control through the availability of a prophylactic intervention; therefore, we recommend rolling out SDR in all settings where contact tracing and screening have been established(AU).


Assuntos
Rifampina/uso terapêutico , Profilaxia Pós-Exposição/métodos , Hanseníase/prevenção & controle , Estudos de Viabilidade , Programas de Rastreamento , Saúde Pública/métodos , Medicina de Precisão/métodos , Hansenostáticos/uso terapêutico
20.
s.l; s.n; 2021. 14 p. tab, graf.
Não convencional em Inglês | SES-SP, CONASS, HANSEN, HANSENIASE, SESSP-ILSLPROD, SES-SP, SESSP-ILSLACERVO, SES-SP | ID: biblio-1292662

RESUMO

The Leprosy Post-Exposure Prophylaxis (LPEP) program explored the feasibility and impact of contact tracing and the provision of SDR to eligible contacts of newly diagnosed leprosy patients in states or districts of Brazil, India, Indonesia, Myanmar, Nepal, Sri Lanka and Tanzania. This study investigated the long-term impact of the LPEP program on the leprosy new case detection rate (NCDR). Our results show that LPEP could reduce the NCDR beyond the impact of the routine leprosy control programme and that many new cases could be prevented. The benefit of LPEP increases gradually over time. LPEP could accelerate the time of reaching predicted NCDR levels of 2040 under routine program by up to six years. Furthermore, we highlighted how the impact varies between countries due to differences in the number of contacts per index patient screened and differences in leprosy epidemiology and national control programme. Generally, including both household contacts and neighbours (> 20 contacts per index patient) would yield the highest impact.


Assuntos
Humanos , Prevenção Primária/métodos , Busca de Comunicante/métodos , Profilaxia Pós-Exposição , Hanseníase/prevenção & controle , Hanseníase/epidemiologia , Rifampina/uso terapêutico , Sri Lanka/epidemiologia , Tanzânia/epidemiologia , Brasil , Programas de Rastreamento , Mianmar/epidemiologia , Índia , Indonésia/epidemiologia , Nepal/epidemiologia
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