The PEP++ study protocol: a cluster-randomised controlled trial on the effectiveness of an enhanced regimen of post-exposure prophylaxis for close contacts of persons affected by leprosy to prevent disease transmission.

BACKGROUND: Leprosy is an infectious disease with a slow decline in global annual caseload in the past two decades. Active case finding and post-exposure prophylaxis (PEP) with a single dose of rifampicin (SDR) are recommended by the World Health Organization as measures for leprosy elimination. However, more potent PEP regimens are needed to increase the effect in groups highest at risk (i.e., household members and blood relatives, especially of multibacillary patients). The PEP++ trial will assess the effectiveness of an enhanced preventive regimen against leprosy in high-endemic districts in India, Brazil, Bangladesh, and Nepal compared with SDR-PEP. METHODS: The PEP++ study is a cluster-randomised controlled trial in selected districts of India, Brazil, Bangladesh, and Nepal. Sub-districts will be allocated randomly to the intervention and control arms. Leprosy patients detected from 2015 - 22 living in the districts will be approached to list their close contacts for enrolment in the study. All consenting participants will be screened for signs and symptoms of leprosy and tuberculosis (TB). In the intervention arm, eligible contacts receive the enhanced PEP++ regimen with three doses of rifampicin (150 - 600 mg) and clarithromycin (150 - 500 mg) administered at four-weekly intervals, whereas those in the control arm receive SDR-PEP. Follow-up screening for leprosy will be done for each individual two years after the final dose is administered. Cox' proportion hazards analysis and Poisson regression will be used to compare the incidence rate ratios between the intervention and control areas as the primary study outcome. DISCUSSION: Past studies have shown that the level of SDR-PEP effectiveness is not uniform across contexts or in relation to leprosy patients. To address this, a number of recent trials are seeking to strengthen PEP regimens either through the use of new medications or by increasing the dosage of the existing ones. However, few studies focus on the impact of multiple doses of chemoprophylaxis using a combination of antibiotics. The PEP++ trial will investigate effectiveness of both an enhanced regimen and use geospatial analysis for PEP administration in the study communities. TRIAL REGISTRATION: NL7022 on the Dutch Trial Register on April 12, 2018. Protocol version 9.0 updated on 18 August 2022 https://www.onderzoekmetmensen.nl/en/trial/23060.

Population-wide administration of single dose rifampicin for leprosy prevention in isolated communities: a three year follow-up feasibility study in Indonesia.

BACKGROUND: Indonesia ranking third in the world, regarding leprosy burden. Chemoprophylaxis is effective in reducing risk of developing leprosy among contacts. 'Blanket approach' is an operational strategy for leprosy post-exposure prophylaxis in which all members of an isolated community, high endemic for leprosy are screened and given a single dose of rifampicin (SDR) in the absence of signs and symptoms of leprosy. The objective is to assess the operational feasibility of a population-wide 'blanket' administration of SDR for leprosy prevention in isolated communities in a remote island. METHODS: A prospective follow-up study was conducted in the year 2014, 2015 and 2016 in Lingat village of Selaru Island, Indonesia. During the first two visits, screening and SDR were provided, whereas only screening was conducted during the third visit. The demographic and clinical data were used for a descriptive analysis of the project coverage and leprosy epidemiology. RESULTS: During the first two visits, 1671 persons (88%) were screened, 1499 (79%) received SDR, and 213 (11%) were excluded based on the exclusion criteria. During the first two visits, 43 (2.6%) cases were diagnosed with leprosy with a rate of 2263 per 100,000 population. The prevalence was highest in the age groups 15-24 and 25-49 years. Total, 14 (33%) cases had MB and 29 (67%) PB leprosy. Two cases (5%) had grade 2 disability. During the third visit, 10 new leprosy cases, with no grade 2 disability, were detected out of 1481 screened persons at the rate of 484 cases per 100,000 population (n = 2065 population in 2016). Among those screened during the third visit, there was a 50% reduction of leprosy among those who had previously received SDR compared to those who had not. CONCLUSION: With adequate planning and some additional investment, it is feasible to implement a blanket approach of chemoprophylaxis in a remote island of Indonesia, although effort needs to be made to cover as many people as possible in the first visit. Contingency plans need to be made to actively follow this village closely in the coming years and continue leprosy elimination efforts until no new cases are found any more.

An enhanced regimen as post-exposure chemoprophylaxis for leprosy: PEP+.

The ongoing transmission of Mycobacterium (M.) leprae reflected in a very slow decline in leprosy incidence, forces us to be innovative and conduct cutting-edge research. Single dose rifampicin (SDR) as post-exposure prophylaxis (PEP) for contacts of leprosy patients, reduces their risk to develop leprosy by 60%. This is a promising new preventive measure that can be integrated into routine leprosy control programmes, as is being demonstrated in the Leprosy Post-Exposure Programme that is currently ongoing in eight countries.The limited (60%) effectiveness of SDR is likely due to the fact that some contacts have a preclinical infection beyond the early stages for which SDR is not sufficient to prevent the development of clinical signs and symptoms of leprosy. An enhanced regimen, more potent against a higher load of leprosy bacteria, would increase the effectiveness of this preventive measure significantly.The Netherlands Leprosy Relief (NLR) is developing a multi-country study aiming to show that breaking the chain of transmission of M. leprae is possible, evidenced by a dramatic reduction in incidence. In this study the assessment of the effectiveness of an enhanced prophylactic regimen for leprosy is an important component. To define the so called PEP++ regimen for this intervention study, NLR convened an Expert Meeting that was attended by clinical leprologists, public health experts, pharmacologists, dermatologists and microbiologists.The Expert Meeting advised on combinations of available drugs, with known efficacy against leprosy, as well as on the duration of the intake, aiming at a risk reduction of 80-90%. To come to a conclusion the Expert Meeting considered the bactericidal, sterilising and bacteriostatic activity of the potential drugs. The criteria used to determine an optimal enhanced regimen were: effectiveness, safety, acceptability, availability, affordability, feasibility and not inducing drug resistance.The Expert Meeting concluded that the enhanced regimen for the PEP++ study should comprise three standard doses of rifampicin 600 mg (weight adjusted when given to children) plus moxifloxacin 400 mg given at four-weekly intervals. For children and for adults with contraindications for moxifloxacin, moxifloxacin should be replaced by clarithromycin 300 mg (weight adjusted).

The Leprosy Post-Exposure Prophylaxis (LPEP) programme: update and interim analysis.

Innovative approaches are required to further enhance leprosy control, reduce the number of people developing leprosy, and curb transmission. Early case detection, contact screening, and chemoprophylaxis currently is the most promising approach to achieve this goal. The Leprosy Post-Exposure Prophylaxis (LPEP) programme generates evidence on the feasibility of integrating contact tracing and single-dose rifampicin (SDR) administration into routine leprosy control activities in different settings. The LPEP programme is implemented within the leprosy control programmes of Brazil, Cambodia, India, Indonesia, Myanmar, Nepal, Sri Lanka and Tanzania. Focus is on three key interventions: tracing the contacts of newly diagnosed leprosy patients; screening the contacts for leprosy; and administering SDR to eligible contacts. Country-specific protocol adaptations refer to contact definition, minimal age for SDR, and staff involved. Central coordination, detailed documentation and rigorous supervision ensure quality evidence. Around 2 years of field work had been completed in seven countries by July 2017. The 5,941 enrolled index patients (89·4% of the registered) identified a total of 123,311 contacts, of which 99·1% were traced and screened. Among them, 406 new leprosy patients were identified (329/100,000), and 10,883 (8·9%) were excluded from SDR for various reasons. Also, 785 contacts (0·7%) refused the prophylactic treatment with SDR. Overall, SDR was administered to 89·0% of the listed contacts. Post-exposure prophylaxis with SDR is safe; can be integrated into the routines of different leprosy control programmes; and is generally well accepted by index patients, their contacts and the health workforce. The programme has also invigorated local leprosy control.

The NLR SkinApp: Testing a Supporting mHealth Tool for Frontline Health Workers Performing Skin Screening in Ethiopia and Tanzania.

Background: The prevalence of skin diseases such as leprosy, and limited dermatological knowledge among frontline health workers (FHWs) in rural areas of Sub-Saharan Africa, led to the development of the NLR SkinApp: a mobile application (app) that supports FHWs to promptly diagnose and treat, or suspect and refer patients with skin diseases. The app includes common skin diseases, neglected tropical skin diseases (skin NTDs) such as leprosy, and HIV/AIDS-related skin conditions. This study aimed to test the supporting role of the NLR SkinApp by examining the diagnostic accuracy of its third edition. Methods: A cross-sectional study was conducted in East Hararghe, Ethiopia, as well as the Mwanza and Morogoro region, Tanzania, in 2018-2019. Diagnostic accuracy was measured against a diagnosis confirmed by two dermatologists/dermatological medical experts (reference standard) in terms of sensitivity, specificity, positive predictive value, and negative predictive value. The potential negative effect of an incorrect management recommendation was expressed on a scale of one to four. Results: A total of 443 patients with suspected skin conditions were included. The FHWs using the NLR SkinApp diagnosed 45% of the patients accurately. The values of the sensitivity of the FHWs using the NLR SkinApp in determining the correct diagnosis ranged from 23% for HIV/AIDS-related skin conditions to 76.9% for eczema, and the specificity from 69.6% for eczema to 99.3% for tinea capitis/corporis. The inter-rater reliability among the FHWs for the diagnoses made, expressed as the percent agreement, was 58% compared to 96% among the dermatologists. Of the management recommendations given on the basis of incorrect diagnoses, around one-third could have a potential negative effect. Conclusions: The results for diagnosing eczema are encouraging, demonstrating the potential contribution of the NLR SkinApp to dermatological and leprosy care by FHWs. Further studies with a bigger sample size and comparing FHWs with and without using the NLR SkinApp are needed to obtain a better understanding of the added value of the NLR SkinApp as a mobile health (mHealth) tool in supporting FHWs to diagnose and treat skin diseases.

Implementation of genetic screening test to reduce the incidence of dapsone hypersensitivity syndrome among patients with leprosy in Papua, Indonesia: a study protocol.

INTRODUCTION: The mainstay of leprosy treatment is multidrug treatment (MDT), which contains rifampicin, dapsone and clofazimine. The occurrence of dapsone hypersensitivity syndrome (DHS), a sudden, potentially fatal and traumatic adverse reaction due to dapsone, may affect treatment adherence and may result in fatality if untreated. Before MDT administration, screening for HLA-B*13:01 in patients with leprosy can potentially reduce DHS risk. The study aims to assess the effectiveness of using a screening test for HLA-B*13:01 in reducing the incidence of DHS and to evaluate the feasibility of using the quantitative PCR-based screening tool as DHS predictors before dapsone administration using individual patient testing in a referral centralised-lab model. METHODS AND ANALYSIS: A total of 310 newly diagnosed patients with leprosy will be recruited from health centres in two highly endemic districts in Indonesia. Dried blood will be taken on filter paper as the specimen receptacle to collect DNA from the patients and transported at room temperature to the leprosy referral laboratory before MDT administration. Checking for HLA-B*13:01 from human DNA is performed using the Nala PGx 1301 V.1 kit. The results will be shared with the leprosy health workers on the site via phone call and courier. Patients with a positive test result will be treated with MDT without dapsone, and patients with a negative result will be treated with complete MDT. Physical examination (weight, height, skin, muscle and nerve function examination), complete blood tests (including renal function test) will be carried out at baseline. Follow-up will be performed at the fourth and eighth weeks to observe any development of adverse drug reactions. ETHICS AND DISSEMINATION: The ethical approval for the study was issued by the Ethical Committee of the National Institute of Health Research and Development, Ministry of Health, Indonesia. Written informed consent will be sought from all participants.

Development of a questionnaire to determine the case detection delay of leprosy: A mixed-methods cultural validation study.

BACKGROUND: Delay in case detection is a risk factor for developing leprosy-related impairments, leading to disability and stigma. The objective of this study was to develop a questionnaire to determine the leprosy case detection delay, defined as the period between the first signs of the disease and the moment of diagnosis, calculated in total number of months. The instrument was developed as part of the PEP4LEP project, a large-scale intervention study which determines the most effective way to implement integrated skin screening and leprosy post-exposure prophylaxis with a single-dose of rifampicin (SDR-PEP) administration in Ethiopia, Mozambique and Tanzania. METHODOLOGY/PRINCIPAL FINDINGS: A literature review was conducted and leprosy experts were consulted. The first draft of the questionnaire was developed in Ethiopia by exploring conceptual understanding, item relevance and operational suitability. Then, the first draft of the tool was piloted in Ethiopia, Mozambique and Tanzania. The outcome is a questionnaire comprising nine questions to determine the case detection delay and two annexes for ease of administration: a local calendar to translate the patient's indication of time to number of months and a set of pictures of the signs of leprosy. In addition, a body map was included to locate the signs. A 'Question-by-Question Guide' was added to the package, to provide support in the administration of the questionnaire. The materials will be made available in English, Oromiffa (Afaan Oromo), Portuguese and Swahili via https://www.infolep.org. CONCLUSIONS/SIGNIFICANCE: It was concluded that the developed case detection delay questionnaire can be administered quickly and easily by health workers, while not inconveniencing the patient. The instrument has promising potential for use in future leprosy research. It is recommended that the tool is further validated, also in other regions or countries, to ensure cultural validity and to examine psychometric properties like test-retest reliability and interrater reliability.

Implementation approaches for leprosy prevention with single-dose rifampicin: A support tool for decision making.

BACKGROUND: In the past 15 years, the decline in annually detected leprosy patients has stagnated. To reduce the transmission of Mycobacterium leprae, the World Health Organization recommends single-dose rifampicin (SDR) as post-exposure prophylaxis (PEP) for contacts of leprosy patients. Various approaches to administer SDR-PEP have been piloted. However, requirements and criteria to select the most suitable approach were missing. The aims of this study were to develop an evidence-informed decision tool to support leprosy programme managers in selecting an SDR-PEP implementation approach, and to assess its user-friendliness among stakeholders without SDR-PEP experience. METHODOLOGY: The development process comprised two phases. First, a draft tool was developed based on a literature review and semi-structured interviews with experts from various countries, organisations and institutes. This led to: an overview of existing SDR-PEP approaches and their characteristics; understanding the requirements and best circumstances for these approaches; and, identification of relevant criteria to select an approach. In the second phase the tool's usability and applicability was assessed, through interviews and a focus group discussion with intended, inexperienced users; leprosy programme managers and non-governmental organization (NGO) staff. PRINCIPAL FINDINGS: Five SDR-PEP implementation approaches were identified. The levels of endemicity and stigma, and the accessibility of an area were identified as most relevant criteria to select an approach. There was an information gap on cost-effectiveness, while successful implementation depends on availability of resources. Five basic requirements, irrespective of the approach, were identified: stakeholder support; availability of medication; compliant health system; trained health staff; and health education. Two added benefits of the tool were identified: its potential value for advocacy and for training. CONCLUSION: An evidence-informed SDR-PEP decision tool to support the selection of implementation approaches for leprosy prevention was developed. While the tool was evaluated by potential users, more research is needed to further improve the tool, especially health-economic studies, to ensure efficient and cost-effective implementation of SDR-PEP.

Prolonged delays in leprosy case detection in a leprosy hot spot setting in Eastern Ethiopia.

BACKGROUND: Leprosy or Hansen's disease is known to cause disability and disfigurement. A delay in case detection of leprosy patients can lead to severe outcomes. In Ethiopia, the disability rates caused by leprosy among new cases are relatively high compared to other endemic countries. This suggests the existence of hidden leprosy cases in the community and a delay in timely detection. To reduce disability rates, it is crucial to identify the factors associated with this delay. This study aimed to determine the extent of delay in case detection among leprosy cases in Eastern Ethiopia. METHODS: This cross-sectional explorative study was conducted in January and February 2019 among 100 leprosy patients diagnosed ≤6 months prior to inclusion. A structured questionnaire was used to collect data, including the initial onset of symptoms, and the reasons for delayed diagnosis. Descriptive statistics, including percentages and medians, were used to describe the case detection delay. Logistic regression analysis was carried out to evaluate the predictors of delay in case detection of >12 months. FINDINGS: The median age of patients was 35 years, with a range of 7 to 72 years. The majority were male (80%) and rural residents (90%). The median delay in case detection was 12 months (interquartile range 10-36 months) among the included patients. The mean delay in case detection was 22 months, with a maximum delay of 96 months. The overall prevalence of disability among the study population was 42% (12% grade I and 30% grade II). Fear of stigma (p = 0.018) and experiencing painless symptoms (p = 0.018) were highly associated with a delay in case detection of >12 months. CONCLUSIONS: Being afraid of stigma and having painless symptoms, which are often misinterpreted as non-alarming at the onset of the disease, were associated with a delay in case detection. This study showed the need to increase knowledge on early symptoms of leprosy among affected communities. Furthermore, it is important to support initiatives that reduce leprosy related stigma and promote health worker training in leprosy control activities.

PEP4LEP study protocol: integrated skin screening and SDR-PEP administration for leprosy prevention: comparing the effectiveness and feasibility of a community-based intervention to a health centre-based intervention in Ethiopia, Mozambique and Tanzania.

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).

The long-term impact of the Leprosy Post-Exposure Prophylaxis (LPEP) program on leprosy incidence: A modelling study.

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.

Leprosy post-exposure prophylaxis with single-dose rifampicin (LPEP): an international feasibility programme.

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.

The State of Affairs in Post-Exposure Leprosy Prevention: A Descriptive Meta-Analysis on Immuno- and Chemo-Prophylaxis.

OBJECTIVE: Annually, over 200,000 people are diagnosed with leprosy, also called Hansen's disease. This number has been relatively stable over the past years. Progress has been made in the fields of chemoprophylaxis and immunoprophylaxis to prevent leprosy, with a primary focus on close contacts of patients. In this descriptive meta-analysis, we summarize the evidence and identify knowledge gaps regarding post-exposure prophylaxis against leprosy. METHODS: A systematic literature search according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology was conducted by searching the medical scientific databases Cochrane, Embase, Pubmed/MEDLINE, Research Gate, Scopus and Web of Science on Jan. 22, 2020, using a combination of synonyms for index terms in four languages: "leprosy" and "population" or "contacts" and "prevention" or "prophylaxis." Subsequently, Infolep.org and Google Scholar were searched and the "snowball method" was used to retrieve other potentially relevant literature. The found articles were screened for eligibility using predetermined inclusion and exclusion criteria. RESULTS: After deduplication, 1,515 articles were screened, and 125 articles were included in this descriptive meta-analysis. Immunoprophylaxis by bacillus Calmette-Guérin (BCG) vaccination is known to provide protection against leprosy. The protection it offers is higher in household contacts of leprosy patients compared with the general population and is seen to decline over time. Contact follow-up screening is important in the first period after BCG administration, as a substantial number of new leprosy patients presents three months post-vaccination. Evidence for the benefit of re-vaccination is conflicting. The World Health Organization (WHO) included BCG in its Guidelines for the Diagnosis, Treatment and Prevention of Leprosy by stating that BCG at birth should be maintained in at least all leprosy high-burden regions. Literature shows that several vaccination interventions with other immunoprophylactic agents demonstrate similar or slightly less efficacy in leprosy risk reduction compared with BCG. However, most of these studies do not exclusively focus on post-exposure prophylaxis. Two vaccines are considered future candidates for leprosy prophylaxis: Mycobacterium indicus pranii (MiP) and LepVax. For chemoprophylaxis, trials were performed with dapsone/acedapsone, rifampicin, and ROM, a combination of rifampicin, ofloxacin, and minocycline. Single-dose rifampicin is favored as post-exposure prophylaxis, abbreviated as SDR-PEP. It demonstrated a protective effect of 57% in the first two years after administration to contacts of leprosy patients. It is inexpensive, and adverse events are rare. The risk of SDR-PEP inducing rifampicin resistance is considered negligible, but continuous monitoring in accordance with WHO policies should be encouraged. The integration of contact screening and SDR-PEP administration into different leprosy control programs was found to be feasible and well accepted. Since 2018, SDR-PEP is included in the WHO Guidelines for the Diagnosis, Treatment and Prevention of Leprosy. CONCLUSION: Progress has been made in the areas of chemoprophylaxis and immunoprophylaxis to prevent leprosy in contacts of patients. Investing in vaccine studies, like LepVax and MiP, and increasing harmonization between tuberculosis (TB) and leprosy research groups is important. SDR-PEP is promising as a chemoprophylactic agent, and further implementation should be promoted. More chemoprophylaxis research is needed on: enhanced medication regimens; interventions in varying (epidemiological) settings, including focal mass drug administration (fMDA); specific approaches per contact type; combinations with screening variations and field-friendly rapid tests, if available in the future; community and health staff education; ongoing antibiotic resistance surveillance; and administering chemoprophylaxis with SDR-PEP prior to BCG administration. Additionally, both leprosy prophylactic drug registration nationally and prophylactic drug availability globally at low or no cost are important for the implementation and further upscaling of preventive measures against leprosy, such as SDR-PEP and new vaccines.

[Acceptability of chemoprophylaxis in an endemic area for leprosy: the PEP-Hans Brazil Project]. / Aceitabilidade da quimioprofilaxia em área endêmica para a hanseníase: projeto PEP-Hans Brasil.

The aim was to analyze the acceptability of chemoprophylaxis with single-dose rifampicin (PEP) in contacts, index leprosy cases, and health professionals and related factors that can influence adherence. A qualitative content analysis study was performed after application of semi-structured interviews according to the protocol proposed in the LPEP program (2016) drafted at Alta Floresta, Mato Grosso State, Brazil, in July 2016. Study participants included individuals with leprosy, contacts, and health professionals. The QRS NVivo software version 10 was used. A total of 80 individuals were contacted, including 54 (67%) contacts, 11 (14%) index cases, and 15 (19%) health professionals. 94% of the contacts (51/54) took PEP. Three PEP categories were identified: understanding, acceptance, and expectation towards the intervention. Understanding proved to be related to care by the health team. Acceptance (or lack thereof) of the medication was related to fear, trust, and protection, the strategy's operability, self-esteem, and insecurity regarding the intervention. Expectation towards the intervention was related to wellbeing, prevention of the disease, sequelae, decrease in public expenditures, and expanded access. Participants acknowledged the relevance of the PEP strategy based on the possibility of interrupting the transmission chain, reduction in new cases, and improved quality of life. Insecurity in taking the medication and the possibility of the disease manifesting itself had a negative influence on acceptance of PEP, while prior information on the PEP strategy helped strengthen trust in the health professionals and the medication's acceptance.

O objetivo deste artigo foi analisar a aceitabilidade da quimioprofilaxia com rifampicina em dose única (PEP) entre os contatos, casos índices de hanseníase e profissionais da saúde e fatores relacionados que possam influenciar na adesão. Realizou-se um estudo qualitativo de análise de conteúdo após aplicação de entrevistas semiestruturadas segundo protocolo proposto no programa LPEP (2016), realizado em Alta Floresta, Mato Grosso, Brasil, em julho de 2016. Participaram do estudo indivíduos notificados com hanseníase, contatos e profissionais da saúde. Utilizou-se o software QRS NVivo versão 10. Foram contatados 80 indivíduos, sendo 54 (67%) contatos, 11 (14%) casos índices e 15 (19%) profissionais de saúde. Dentre os contatos, 94% (51/54) tomaram PEP. Foram identificadas 3 categorias quanto à PEP: compreensão, aceitação e expectativa da intervenção. A compreensão se mostrou relacionada ao cuidado da equipe de saúde. Aceitar ou não a medicação revelou-se relacionada ao medo, confiança e proteção, operacionalidade da estratégia, autoestima e insegurança quanto à intervenção. A expectativa da intervenção relacionou-se ao bem-estar, prevenção da doença e de sequelas, diminuição de gastos públicos e ampliação do acesso. Houve reconhecimento da relevância da estratégia PEP pela possibilidade de interrupção da cadeia de transmissão, diminuição de casos novos e melhora na qualidade de vida. A insegurança em tomar a medicação e de a doença se manifestar influenciaram negativamente à aceitação da PEP; por outro lado, as informações prévias sobre a estratégia PEP contribuíram para o fortalecimento da confiança nos profissionais de saúde e para a aceitabilidade da medicação.

El objetivo fue analizar la aceptabilidad de la quimioprofilaxis con rifampicina en dosis única (PEP) entre los contactos, casos índices de hanseniasis y profesionales de salud, así como los factores relacionados que puedan influenciar en la adhesión al tratamiento. Se realizó un estudio cualitativo de análisis de contenido, tras la realización de entrevistas semiestructuradas, según el protocolo propuesto en el programa LPEP (2016), realizado en Alta Floresta, Mato Grosso, Brasil, en julio de 2016. Participaron en el estudio individuos diagnosticados con hanseniasis, contactos y profesionales de la salud. Se utilizó el software QRS NVivo versión 10. Se contactó con 80 individuos, siendo 54 (67%) contactos, 11 (14%) casos índices y 15 (19%) profesionales de salud. Entre los contactos 94% (51/54) tomaron PEP. Se identificaron 3 categorías respecto a la PEP: comprensión, aceptación y expectativa de intervención. La comprensión estuvo relacionada con el cuidado del equipo de salud. El aceptar o no la medicación estuvo relacionado con el miedo, confianza y protección, operatividad de la estrategia, autoestima e inseguridad de la intervención. La expectativa de la intervención estuvo relacionada con el bienestar, prevención de la enfermedad, así como secuelas, disminución de gasto público y ampliación del acceso. Existió un reconocimiento de la relevancia de la estrategia PEP por la posibilidad de interrupción de la cadena de transmisión, disminución de casos nuevos y mejora en la calidad de vida. La inseguridad en tomar la medicación y de que la enfermedad se manifestara influenciaron negativamente en la aceptación de la PEP, por otro lado, la información previa sobre la estrategia PEP contribuyó al fortalecimiento de la confianza en los profesionales de salud y a la aceptabilidad de la medicación.

The Development of a Mobile Application to Support Peripheral Health Workers to Diagnose and Treat People with Skin Diseases in Resource-Poor Settings.

The high prevalence of skin diseases in resource-poor settings, where health workers with sufficient knowledge of skin diseases are scarce, calls for innovative measures. Timely diagnosis and treatment of skin diseases, especially neglected tropical diseases (NTDs) that manifest with skin lesions, such as leprosy, is crucial to prevent disabilities as well as psychological and socioeconomic problems. Innovative technological methods like telemedicine and mobile health (mHealth) can help to bridge the gap between the burden of skin diseases and the lack of capable staff in resource-poor settings by bringing essential health services from central level closer to peripheral levels. Netherlands Leprosy Relief (NLR) has developed a mobile phone application called the 'SkinApp', which aims to support peripheral health workers to recognize the early signs and symptoms of skin diseases, including skin NTDs, and to start treatment promptly or refer for more advanced diagnostic testing or disease management when needed. Further research is needed to determine how greatly mHealth in general and the SkinApp in particular can contribute to improved health outcomes, efficiency, and cost-effectiveness.

Neglected Tropical Diseases, Cross-Cutting Issues Workshop, 4-6 February 2015, Utrecht, the Netherlands: meeting report.

In the last decade, work on neglected tropical diseases (NTDs) has gained momentum. This was accelerated by the London Declaration on NTDs in January 2012. Work on NTDs has expanded worldwide and many countries have set up NTD control and elimination programs. However, the work has focussed disproportionately on preventive treatment. There is an urgent need for more attention and resources to work with people with NTD-related morbidity and disability. A lot can be gained in the fight against NTDs by combining knowledge and experience from cross-cutting fields. For this reason a workshop was organized bringing together scientists, experts and practitioners from different NTD backgrounds to explore options for cross-cutting strategies, interventions and research in the field of NTDs, particularly focusing on issues related to morbidity management and disability, in the broadest sense. The workshop produced an inventory of cross-cutting issues, an overview of knowledge gaps and research questions, proposals for pilot (research) projects and a list of recommendations. One of the main recommendations is based on the need for baseline data: to review existing indicators used for monitoring and surveillance of NTD-related morbidity and disability in order to identify common indicators that can be shared across NTDs.

Leprosy Post-Exposure Prophylaxis (LPEP) programme: study protocol for evaluating the feasibility and impact on case detection rates of contact tracing and single dose rifampicin.

INTRODUCTION: The reported number of new leprosy patients has barely changed in recent years. Thus, additional approaches or modifications to the current standard of passive case detection are needed to interrupt leprosy transmission. Large-scale clinical trials with single dose rifampicin (SDR) given as post-exposure prophylaxis (PEP) to contacts of newly diagnosed patients with leprosy have shown a 50-60% reduction of the risk of developing leprosy over the following 2 years. To accelerate the uptake of this evidence and introduction of PEP into national leprosy programmes, data on the effectiveness, impact and feasibility of contact tracing and PEP for leprosy are required. The leprosy post-exposure prophylaxis (LPEP) programme was designed to obtain those data. METHODS AND ANALYSIS: The LPEP programme evaluates feasibility, effectiveness and impact of PEP with SDR in pilot areas situated in several leprosy endemic countries: India, Indonesia, Myanmar, Nepal, Sri Lanka and Tanzania. Complementary sites are located in Brazil and Cambodia. From 2015 to 2018, contact persons of patients with leprosy are traced, screened for symptoms and assessed for eligibility to receive SDR. The intervention is implemented by the national leprosy programmes, tailored to local conditions and capacities, and relying on available human and material resources. It is coordinated on the ground with the help of the in-country partners of the International Federation of Anti-Leprosy Associations (ILEP). A robust data collection and reporting system is established in the pilot areas with regular monitoring and quality control, contributing to the strengthening of the national surveillance systems to become more action-oriented. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the relevant ethics committees in the countries. Results and lessons learnt from the LPEP programme will be published in peer-reviewed journals and should provide important evidence and guidance for national and global policymakers to strengthen current leprosy elimination strategies.

Negligible risk of inducing resistance in Mycobacterium tuberculosis with single-dose rifampicin as post-exposure prophylaxis for leprosy.

Post-exposure prophylaxis (PEP) for leprosy is administered as one single dose of rifampicin (SDR) to the contacts of newly diagnosed leprosy patients. SDR reduces the risk of developing leprosy among contacts by around 60 % in the first 2-3 years after receiving SDR. In countries where SDR is currently being implemented under routine programme conditions in defined areas, questions were raised by health authorities and professional bodies about the possible risk of inducing rifampicin resistance among the M. tuberculosis strains circulating in these areas. This issue has not been addressed in scientific literature to date. To produce an authoritative consensus statement about the risk that SDR would induce rifampicin-resistant tuberculosis, a meeting was convened with tuberculosis (TB) and leprosy experts. The experts carefully reviewed and discussed the available evidence regarding the mechanisms and risk factors for the development of (multi) drug-resistance in M. tuberculosis with a view to the special situation of the use of SDR as PEP for leprosy. They concluded that SDR given to contacts of leprosy patients, in the absence of symptoms of active TB, poses a negligible risk of generating resistance in M. tuberculosis in individuals and at the population level. Thus, the benefits of SDR prophylaxis in reducing the risk of developing leprosy in contacts of new leprosy patients far outweigh the risks of generating drug resistance in M. tuberculosis.

Towards a toolkit for cross-neglected tropical disease morbidity and disability assessment.

BACKGROUND: Neglected tropical diseases (NTDs) are a group of often chronic and disabling infectious conditions, closely related to poverty and inequities. While it is estimated that millions of people are affected, accurate and internationally comparable data about NTD-related morbidity and disability are lacking. Therefore we aimed to develop and pilot a toolkit to assess and monitor morbidity and disability across NTDs. METHODS: A cross-sectional, non-random survey design with a mixed methods approach was used. We conducted a literature review on existing tools to assess and monitor disability, followed by a Delphi study with NTD experts to compile a prototype toolkit. A first-phase validation study was conducted in Northeast Brazil among people with Chagas disease, leishmaniasis, leprosy and schistosomiasis. RESULTS: Instruments included were the clinical profile, WHODAS, P-scale, SRQ, WHOQOL-BREF and WHOQOL-DIS. Most questions in the various instruments were readily understood with the exception of the WHOQOL-BREF, where additional explanations and examples were often needed. The respondents were very appreciative of the instruments and found it valuable to have the opportunity to talk about these aspects of their condition. CONCLUSIONS: Our findings support the acceptability and relevance of five of the six instruments tested and the concept of a cross-NTD toolkit.