Single-Dose Rifapentine in Household Contacts of Patients with Leprosy.

BACKGROUND: Previous studies have suggested that a single dose of rifampin has protective effects against leprosy in close contacts of patients with the disease. Rifapentine was shown to have greater bactericidal activity against Mycobacterium leprae than rifampin in murine models of leprosy, but data regarding its effectiveness in preventing leprosy are lacking. METHODS: We conducted a cluster-randomized, controlled trial to investigate whether single-dose rifapentine is effective in preventing leprosy in household contacts of patients with leprosy. The clusters (counties or districts in Southwest China) were assigned to one of three trial groups: single-dose rifapentine, single-dose rifampin, or control (no intervention). The primary outcome was the 4-year cumulative incidence of leprosy among household contacts. RESULTS: A total of 207 clusters comprising 7450 household contacts underwent randomization; 68 clusters (2331 household contacts) were assigned to the rifapentine group, 71 (2760) to the rifampin group, and 68 (2359) to the control group. A total of 24 new cases of leprosy occurred over the 4-year follow-up, for a cumulative incidence of 0.09% (95% confidence interval [CI], 0.02 to 0.34) with rifapentine (2 cases), 0.33% (95% CI, 0.17 to 0.63) with rifampin (9 cases), and 0.55% (95% CI, 0.32 to 0.95) with no intervention (13 cases). In an intention-to-treat analysis, the cumulative incidence in the rifapentine group was 84% lower than that in the control group (cumulative incidence ratio, 0.16; multiplicity-adjusted 95% CI, 0.03 to 0.87; P = 0.02); the cumulative incidence did not differ significantly between the rifampin group and the control group (cumulative incidence ratio, 0.59; multiplicity-adjusted 95% CI, 0.22 to 1.57; P = 0.23). In a per-protocol analysis, the cumulative incidence was 0.05% with rifapentine, 0.19% with rifampin, and 0.63% with no intervention. No severe adverse events were observed. CONCLUSIONS: The incidence of leprosy among household contacts over 4 years was lower with single-dose rifapentine than with no intervention. (Funded by the Ministry of Health of China and the Chinese Academy of Medical Sciences; Chinese Clinical Trial Registry number, ChiCTR-IPR-15007075.).

Profile of the leprosy endemic in the district of Murrupula, Nampula, Mozambique: A population-based study.

BACKGROUND: Leprosy is a neglected chronic infection caused by Mycobacterium leprae, that is curable. The magnitude of the disease and severity of the debilitation it causes renders leprosy a public health problem. This study aimed to analyze the endemic profile of leprosy in the Murrupula district and evaluate the socioeconomic, clinical, and serological profiles of leprosy contacts. METHODS: A cross-sectional study of patients with leprosy diagnosed between 2013 and 2017 and their household and community contacts was conducted in Murrupula District, Nampula Province, Mozambique. Interviews, simplified dermatoneurological examinations, Mycobacterium leprae flow (ML Flow) tests, and Mitsuda tests were performed. RESULTS: Most of the leprosy cases were multibacillary. The patients had some degree of physical disability. ML Flow positivity was more common in household contacts of the patients diagnosed with leprosy and in community individuals who spontaneously presented for testing. In total, 17 patients were diagnosed with leprosy. CONCLUSIONS: This study revealed an active chain of transmission, hidden prevalence, and operational deficiencies in leprosy surveillance and care. The results suggest that the implementation of a public health policy for leprosy prevention and control in Nampula Province is necessary. In future, the possibility of expanding the policy to the entire country should be considered.

Leprosy among new child cases in China: Epidemiological and clinical analysis from 2011 to 2020.

BACKGROUND: Leprosy, caused by Mycobacterium leprae infection, mainly affects skin and peripheral nerves and may further lead to disability and deformity if not treated timely. The new case detection rate of leprosy in children reflects the active transmission of leprosy infection. This study aims to present the epidemiology and clinical characteristics of new leprosy cases in children in China from 2011 to 2020. METHODOLOGY/PRINCIPAL FINDINGS: All data from leprosy patients younger than 15 years old were extracted from the Leprosy Management Information System in China (LEPMIS). Statistical Package for the Social Sciences (SPSS) version 12.0 was used for descriptive and analytical statistics of the epidemiological and clinical indicators by the Mann-Whitney test, Kruskal-Wallis test, and Fisher's exact test. And geographical distribution was analyzed by ArcGIS 10.5. A total of 152 pediatric new cases of leprosy were found over the last decade. The new case detection rate of pediatric leprosy cases decreased from 0.13 to 0.02 per 1,000,000 population over the last ten years. New pediatric cases had a higher new case detection rate in Guizhou, Sichuan, and Yunnan Provinces. All but 7 provinces in China achieved zero new child case for consecutive five years. The onset of leprosy peaked between 10 and 14 years of age, and the male to female ratio was 1.71:1. Pediatric patients were predominantly infected from symptomatic household adult contacts HHCs. Multibacillary leprosy (MB) was the most common. However, a low proportion of patients developed leprosy reaction and grade 2 disability. CONCLUSIONS/SIGNIFICANCE: The new case detection rate of pediatric leprosy cases has decreased over the past ten years in China. Spatial analysis indicated clusters in high-endemic areas. Leprosy transmission has stopped in the majority of provinces in China. However, sporadic cases may continue to exist for a long time. Active surveillance especially contact tracing should be focused on in future plan for management of leprosy, and interventions in leprosy clusters should be prioritized.

A social network approach for the study of leprosy transmission beyond the household.

BACKGROUND: Mycobacterium leprae was the first microorganism directly associated with a disease, however, there are still important gaps in our understanding of transmission. Although household contacts are prioritized, there is evidence of the importance of extrahousehold contacts. The goal of this article is to contribute to our understanding of the transmission of leprosy ex-household. METHODS: We compare co-location data of 397 leprosy cases and 211 controls drawn from the Centro de Dermatologia Sanitária D. Libânia in Fortaleza, Brazil. We collected lifetime geolocation data related to residence, school attendance and workplace and developed novel methods to establish a critical distance (Rc) for exposure and evaluated the potential for transmission for residence, school and workplace. RESULTS: Our methods provide different threshold values of distance for residence, school and workplace. Residence networks demonstrate an Rc of about 500 m. Cases cluster in workplaces as well. Schools do not cluster cases. CONCLUSIONS: Our novel network approach offers a promising opportunity to explore leprosy transmission. Our networks confirm the importance of coresidence, provide a boundary and suggest a role for transmission in workplaces. Schools, on the other hand, do not demonstrate a clustering of cases. Our findings may have programmatic relevance.

Spatial Modeling of leprosy disease in east java province with spatially varying regression coefficients models.

Indonesia ranks third with the most leprosy cases globally. East Java is the province that has the highest leprosy cases. The Provincial Government socialized the East Java Leprosy Eradication Program, which targets a maximum of one leprosy case per 10,000 residents. We propose spatially varying regression coefficients models to evaluate the effects of risk factors on of leprosy cases in East Java, use Geographically Weighted Generalized Poisson Regression and Geographically Weighted Negative Binomial Regression (GWNBR) models. The best models GWNBR categorize municipalities into six groups based on variables that have a significant impact on leprosy cases. The percentage of households with access to adequate sanitation is a significant factor in determining leprosy cases in all municipalities in East Java. We can conclude that clean and healthy living behavior, health facilities, and health workers significantly affect the number of leprosy cases in East Java.

Detection of anti-M. leprae antibodies in children in leprosy-endemic areas: A systematic review.

BACKGROUND: Leprosy elimination primarily targets transmission of Mycobacterium leprae which is not restricted to patients' households. As interruption of transmission is imminent in many countries, a test to detect infected asymptomatic individuals who can perpetuate transmission is required. Antibodies directed against M. leprae antigens are indicative of M. leprae infection but cannot discriminate between active and past infection. Seroprevalence in young children, however, reflects recent M. leprae infection and may thus be used to monitor transmission in an area. Therefore, this literature review aimed to evaluate what has been reported on serological tests measuring anti-M. leprae antibodies in children without leprosy below the age of 15 in leprosy-endemic areas. METHODS AND FINDINGS: A literature search was performed in the databases Pubmed, Infolep, Web of Science and The Virtual Health Library. From the 724 articles identified through the search criteria, 28 full-text articles fulfilled all inclusion criteria. Two additional papers were identified through snowballing, resulting in a total of 30 articles reporting data from ten countries. All serological tests measured antibodies against phenolic glycolipid-I or synthetic derivatives thereof, either quantitatively (ELISA or UCP-LFA) or qualitatively (ML-flow or NDO-LID rapid test). The median seroprevalence in children in endemic areas was 14.9% and was stable over time if disease incidence remained unchanged. Importantly, seroprevalence decreased with age, indicating that children are a suitable group for sensitive assessment of recent M. leprae infection. However, direct comparison between areas, solely based on the data reported in these studies, was impeded by the use of different tests and variable cut-off levels. CONCLUSIONS: Quantitative anti-PGL-I serology in young children holds promise as a screening test to assess M. leprae infection and may be applied as a proxy for transmission and thereby as a means to monitor the effect of (prophylactic) interventions on the route to leprosy elimination.

The challenge of concomitant infections in the coronavirus disease 2019 pandemic era: Severe acute respiratory syndrome coronavirus 2 infection in a patient with chronic Chagas disease and dimorphic leprosy.

Coronavirus disease 2019 (COVID-19) was first officially described in Brazil on February 26th, 2020. The accumulation of reports of concomitant infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and pathogens that cause diseases endemic to tropical countries, such as dengue and chikungunya fever, has started to draw attention. Chagas disease and leprosy remain public health problems in many developing countries, such as Brazil. In this manuscript, we describe a case of concomitant leprosy, Chagas disease, and COVID-19, highlighting the cutaneous manifestations of SARS-CoV-2 infection and the clinical behavior of household contacts who previously received prophylactic Bacillus Calmette-Guérin vaccines.

Patients with skin smear positive leprosy in Bangladesh are the main risk factor for leprosy development: 21-year follow-up in the household contact study (COCOA).

BACKGROUND: Leprosy transmission is ongoing; globally and within Bangladesh. Household contacts of leprosy cases are at increased risk of leprosy development. Identification of household contacts at highest risk would optimize this process. METHODS: The temporal pattern of new case presentation amongst household contacts was documented in the COCOA (Contact Cohort Analysis) study. The COCOA study actively examined household contacts of confirmed leprosy index cases identified in 1995, and 2000-2014, to provide evidence for timings of contact examination policies. Data was available on 9527 index cases and 38303 household contacts. 666 household contacts were diagnosed with leprosy throughout the follow-up (maximum follow-up of 21 years). Risk factors for leprosy development within the data analysed, were identified using Cox proportional hazard regression. FINDINGS: The dominant risk factor for household contacts developing leprosy was having a highly skin smear positive index case in the household. As the grading of initial slit skin smear of the index case increased from negative to high positive (4-6), the hazard of their associated household contacts developing leprosy increases by 3.14 times (p<0.001). Being a blood relative was not a risk factor, no gender differences in susceptibility were found. INTERPRETATION: We found a dominance of a single variable predicting risk for leprosy transmission-skin smear positive index cases. A small number of cases are maintaining transmission in the household setting. Focus should be performing contact examinations on these households and detecting new skin smear positive index cases. Conducting slit-skin smears on new cases is needed for predicting risk; such services need supporting. If skin smear positive cases are sustaining leprosy infection within the household setting, the administration of single-dose rifampicin (SDR) to household contacts as the sole intervention in Bangladesh will not be effective.

The role of an active surveillance strategy of targeting household and neighborhood contacts related to leprosy cases released from treatment in a low-endemic area of China.

OBJECTIVE: Early diagnosis remains the primary goal for leprosy management programs. This study aims to determine whether active surveillance of patients with leprosy and their contact individuals increased identification of latent leprosy cases in the low-endemic areas. METHODS: This cross-sectional survey was carried out between October 2014 and August 2016 in 21 counties throughout Shandong Province. The survey was conducted among patients with leprosy released from treatment (RFT) and their contacts from both household and neighbors. RESULTS: A total of 2,210 RFT patients and 9,742 contacts comprising 7877 household contacts (HHCs), including 5,844 genetic related family members (GRFMs) and 2033 non-genetic related family members and 1,865 contacts living in neighboring houses (neighbor contacts, NCs), were recruited. Among identified individuals, one relapsed and 13 were newly diagnosed, giving a detection rate of 0.12%, corresponding to 120 times the passive case detection rate. Detection rates were similar for HHCs and NCs (0.114% vs. 0.214%, P = 0.287). Analysis of the family history of leprosy patients revealed clustering of newly diagnosed cases and association with residential coordinates of previously-diagnosed multibacillary leprosy cases. CONCLUSION: Active case-finding programs are feasible and contributes to early case detection by tracking HHCs and NCs in low-endemic areas.

Operational failures of leprosy control in household social networks with overlapping cases in endemic areas in Brazil. / Falhas operacionais no controle da hanseníase em redes de convívio domiciliar com sobreposição de casos em áreas endêmicas no Brasil.

OBJECTIVE: To analyze institutional/programmatic vulnerability of health services in the development of health care actions for people affected by leprosy and contact surveillance. METHODS: This was a cross-sectional study conducted in 2017 based on primary data from a sample of leprosy cases notified between 2001-2014 with overlapping cases in household social networks (HSN) in municipalities in the states of Bahia, Piauí and Rondônia, Brazil. RESULTS: A total of 233 leprosy cases were analyzed, 154 (66.1%) belonged to HSN with 3 or more leprosy cases. In 53.2% of cases, 2 or more generations were affected, this being an outcome associated with absence of dermato-neurological examination (prevalence ratio 1.32; confidence interval [95%CI 1.10;1.59]; p-value=0.004). CONCLUSION: Operational failures in the surveillance of leprosy contacts in areas of high endemicity reinforce the character of institutional/programmatic vulnerability in HSN contexts with more than one case of leprosy in the three states analyzed.

Real-time PCR-based quantitation of viable Mycobacterium leprae strain from clinical samples and environmental sources and its genotype in multi-case leprosy families of India.

The potential role of environmental M. leprae in the transmission of leprosy remains unknown. We investigated role of environment as a possible source of viable M. leprae responsible for transmission of leprosy. The samples were collected from 10 multi-case leprosy families comprising, slit skin smear (SSS) from 9 multibacillary (MB), 16 paucibacillary cases (PB), 22 household contacts, and 38 environmental soil samples. The quantum of viable M. leprae was estimated by qRT-PCR using 16S rRNA gene from soil and SSS. Genotypes of M. leprae were determined by gene sequencing. We could observe presence of viable M. leprae in 11 (44%) leprosy cases (M. leprae 16S rRNA gene copies range from 1.78 × 102 to 8.782 × 109) and 4 (18%) household contacts (M. leprae 16S rRNA gene copies range from 2.54 × 103 and 7.47 × 104). Remarkably, presence of viable M. leprae was also noted in 10 (53%) soil samples where in M. leprae 16S rRNA gene copies ranged from 4.36 × 102 to 7.68 × 102. M leprae subtype 1D was noted in most of the leprosy cases their household contacts and in the surrounding soil samples indicating source of infection in household contacts could be from environment or patients. M. leprae 16S rRNA copies were approximately similar in both PB cases and soil samples along with presence of SNP type 1 subtype 1D in both samples indicating source of M. leprae from patients to contacts was either from patients or environment or both.

Molecular epidemiology and transmission dynamics of leprosy among multicase families and case-contact pairs.

BACKGROUND: Human-to-human transmission of Mycobacterium leprae among household contacts of active leprosy cases is significant, and surveillance of household contacts is vital to interrupting the transmission chain for this disease. This study was conducted to identify similarities in M. leprae strains, based on genomic single nucleotide polymorphisms (SNPs), among cases and their household contacts and in multicase families in order to decipher possible associations, transmission links, various clinical conditions of index cases that enhance person-to-person transmission, and timelines for transmission patterns. METHODS: PCR for M. leprae DNA detection (amplification of the Rlep gene) and SNP subtyping of M. leprae strains was performed for 61 index cases and one of their household contacts. Additionally, we studied six families with multiple cases of leprosy, to understand timelines of infectivity and its relation to severity of the disease in the index cases. RESULTS: Index cases with lepromatous (LL) and borderline lepromatous (BL) leprosy, together with a positive bacteriological index (BI) for M. leprae, result in a higher percentage of their contacts subclinically infected with M. leprae, with odds ratios (OR) of 6.6 (95% confidence interval (CI) 1.6-27.6) for BL and LL, and 7.07 (CI 1.41-35.41) for BI-positive index cases. 75% of the case-contact pairs had a similar SNP subtype of M. leprae. The timeline of infection in multicase families revealed that contacts were infected during the BI-positive period of the index case. CONCLUSION: Using molecular methods, we determined that positivity for M. leprae DNA in contacts of index leprosy cases was attributed to clinical characteristics of leprosy in the index cases. LL and BL forms of leprosy, together with positive BI, contributed to dissemination of infection to household contacts. In conclusion, we found a relationship between SNP subtypes within index case-contact pairs. This method can help decipher the transmission patterns and identify individuals at risk of contracting leprosy.

Incidence of and Factors Associated With Leprosy Among Household Contacts of Patients With Leprosy in Brazil.

Importance: Despite progress toward reducing global incidence, leprosy control remains a challenge in low- and middle-income countries. Objective: To estimate new case detection rates of leprosy among household contacts of patients with previously diagnosed leprosy and to investigate its associated risk factors. Design, Setting, and Participants: This population-based cohort study included families registered in the 100 Million Brazilian Cohort linked with nationwide registries of leprosy; data were collected from January 1, 2007, through December 31, 2014. Household contacts of patients with a previous diagnosis of leprosy from each household unit were followed up from the time of detection of the primary case to the time of detection of a subsequent case or until December 31, 2014. Data analysis was performed from May to December 2018. Exposures: Clinical characteristics of the primary case and sociodemographic factors of the household contact. Main Outcomes and Measures: Incidence of leprosy, estimated as the new case detection rate of leprosy per 100 000 household contacts at risk (person-years at risk). The association between occurrence of a subsequent leprosy case and the exposure risk factors was assessed using multilevel mixed-effects logistic regressions allowing for state- and household-specific random effects. Results: Among 42 725 household contacts (22 449 [52.5%] female; mean [SD] age, 22.4 [18.5] years) of 17 876 patients detected with leprosy, the new case detection rate of leprosy was 636.3 (95% CI, 594.4-681.1) per 100 000 person-years at risk overall and 521.9 (95% CI, 466.3-584.1) per 100 000 person-years at risk among children younger than 15 years. Household contacts of patients with multibacillary leprosy had higher odds of developing leprosy (adjusted odds ratio [OR], 1.48; 95% CI, 1.17-1.88), and the odds increased among contacts aged 50 years or older (adjusted OR, 3.11; 95% CI, 2.03-4.76). Leprosy detection was negatively associated with illiterate or preschool educational level (adjusted OR, 0.59; 95% CI, 0.38-0.92). For children, the odds were increased among boys (adjusted OR, 1.70; 95% CI, 1.20-2.42). Conclusions and Relevance: The findings in this Brazilian population-based cohort study suggest that the household contacts of patients with leprosy may have increased risk of leprosy, especially in households with existing multibacillary cases and older contacts. Public health interventions, such as contact screening, that specifically target this population appear to be needed.

Effect of a conditional cash transfer programme on leprosy treatment adherence and cure in patients from the nationwide 100 Million Brazilian Cohort: a quasi-experimental study.

BACKGROUND: Indirect financial costs and barriers to health-care access might contribute to leprosy treatment non-adherence. We estimated the association of the Brazilian conditional cash transfer programme, the Programa Bolsa Família (PBF), on leprosy treatment adherence and cure in patients in Brazil. METHODS: In this quasi-experimental study, we linked baseline demographic and socioeconomic information for individuals who entered the 100 Million Brazilian Cohort between Jan 1, 2007, and Dec 31, 2014, with the PBF payroll database and the Information System for Notifiable Diseases, which includes nationwide leprosy registries. Individuals were eligible for inclusion if they had a household member older than 15 years and had not received PBF aid or been diagnosed with leprosy before entering the 100 Million Brazilian Cohort; they were excluded if they were partial receivers of PBF benefits, had missing data, or had a monthly per-capita income greater than BRL200 (US$50). Individuals who were PBF beneficiaries before leprosy diagnosis were matched to those who were not beneficiaries through propensity-score matching (1:1) with replacement on the basis of baseline covariates, including sex, age, race or ethnicity, education, work, income, place of residence, and household characteristics. We used logistic regression to assess the average treatment effect on the treated of receipt of PBF benefits on leprosy treatment adherence (six or more multidrug therapy doses for paucibacillary cases or 12 or more doses for multibacillary cases) and cure in individuals of all ages. We stratified our analysis according to operational disease classification (paucibacillary or multibacillary). We also did a subgroup analysis of paediatric leprosy restricted to children aged up to 15 years. FINDINGS: We included 11 456 new leprosy cases, of whom 8750 (76·3%) had received PBF before diagnosis and 2706 (23·6%) had not. Overall, 9508 (83·0%) patients adhered to treatment and 10 077 (88·0%) were cured. After propensity score matching, receiving PBF before diagnosis was associated with adherence to treatment (OR 1·22, 95% CI 1·01-1·48) and cure (1·26, 1·01-1·58). PBF receipt did not significantly improve treatment adherence (1·37, 0·98-1·91) or cure (1·12, 0·75-1·67) in patients with paucibacillary leprosy. For patients with multibacillary disease, PBF beneficiaries had better treatment adherence (1·37, 1·08-1·74) and cure (1·43, 1·09-1·90) than non-beneficiaries. In the propensity score-matched analysis in 2654 children younger than 15 years with leprosy, PBF exposure was not associated with leprosy treatment adherence (1·55, 0·89-2·68) or cure (1·57, 0·83-2·97). INTERPRETATION: Our results suggest that being a beneficiary of the PBF, which facilitates cash transfers and improved access to health care, is associated with greater leprosy multidrug therapy adherence and cure in multibacillary cases. These results are especially relevant for patients with multibacillary disease, who are treated for a longer period and have lower cure rates than those with paucibacillary disease. FUNDING: CONFAP/ESRC/MRC/BBSRC/CNPq/FAPDF-Doenças Negligenciadas, the UK Medical Research Council, the Wellcome Trust, and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-Brazil (CAPES).

Hot spots of leprosy in the endemic area of São Luís, Maranhão State, Northeastern Brazil.

BACKGROUND: Despite the decreasing of leprosy cases in Brazil, its occurrence remains high in certain Brazilian cities. The aim of the study was to analyze the spatial pattern of leprosy in São Luís, capital of Maranhão State, Northeastern Brazil. METHODOLOGY: An ecological study was carried out based on secondary data from leprosy cases and contacts reported in the Notification of Injury Information System in2015, and information on residency domiciles in three districts in the city. RESULTS: A positive correlation was found between the leprosy cases and the average number of residents per household, and households with open sewage, garbage accumulated, with street identification, persons without income, dependents and the poor. A negative correlation between cases and households with a sidewalk, literate people and 60 years old or more were identified. The seropositivity of contacts examined using the ML Flow test was of 23.19%. The disease presents a heterogeneous spatial pattern, with hyperendemic clusters. CONCLUSIONS: The spatialization of both leprosy cases and contacts and the identification of areas presenting the highest concentration of the disease in each district is important and constitutes an important tool to subsidize disease-control actions.

The challenge of concomitant infections in the coronavirus disease 2019 pandemic era: Severe acute respiratory syndrome coronavirus 2 infection in a patient with chronic Chagas disease and dimorphic leprosy

Abstract Coronavirus disease 2019 (COVID-19) was first officially described in Brazil on February 26th, 2020. The accumulation of reports of concomitant infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and pathogens that cause diseases endemic to tropical countries, such as dengue and chikungunya fever, has started to draw attention. Chagas disease and leprosy remain public health problems in many developing countries, such as Brazil. In this manuscript, we describe a case of concomitant leprosy, Chagas disease, and COVID-19, highlighting the cutaneous manifestations of SARS-CoV-2 infection and the clinical behavior of household contacts who previously received prophylactic Bacillus Calmette-Guérin vaccines.

Protocol, rationale and design of PEOPLE (Post ExpOsure Prophylaxis for LEprosy in the Comoros and Madagascar): a cluster randomized trial on effectiveness of different modalities of implementation of post-exposure prophylaxis of leprosy contacts.

BACKGROUND: Leprosy is an ancient infectious disease with a global annual incidence that has plateaued above 200,000 new cases since over a decade. New strategies are required to overcome this stalemate. Post-exposure prophylaxis (PEP) with a single dose of Rifampicin (SDR) has conditionally been recommended by the World Health Organization (WHO), based on a randomized-controlled-trial in Bangladesh. More evidence is required. The Post ExpOsure Prophylaxis for Leprosy (PEOPLE) trial will assess effectiveness of different modalities of PEP on the Comoros and Madagascar. METHODS: PEOPLE is a cluster-randomized trial with villages selected on previous leprosy-incidence and randomly allocated to four arms. Four annual door-to-door surveys will be performed in all arms. All consenting permanent residents will be screened for leprosy. Leprosy patients will be treated according to international guidelines and eligible contacts will be provided with SDR-PEP. Arm-1 is the comparator in which no PEP will be provided. In arms 2, 3 and 4, SDR-PEP will be provided at double the regular dose (20 mg/kg) to eligible contacts aged two years and above. In arm 2 all household-members of incident leprosy patients are eligible. In arm 3 not only household-members but also neighbourhood contacts living within 100-m of an incident case are eligible. In arm 4 such neighbourhood contacts are only eligible if they test positive to anti-PGL-I, a serological marker. Incidence rate ratios calculated between the comparator arm 1 and each of the intervention arms will constitute the primary outcome. DISCUSSION: Different trials on PEP have yielded varying results. The pivotal COLEP trial in Bangladesh showed a 57% reduction in incidence over a two-year period post-intervention without any rebound in the following years. A study in a high-incidence setting in Indonesia showed no effect of PEP provided to close contacts but a major effect of PEP provided as a blanket measure to an entire island population. High background incidence could be the reason of the lack of effect of PEP provided to individual contacts. The PEOPLE trial will assess effectiveness of PEP in a high incidence setting and will compare three different approaches, to identify who benefits most from PEP. TRIAL REGISTRATION: Clinicaltrials.Gov. NCT03662022. Initial Protocol Version 1.2, 27-Aug-2018.

Quantitative PCR for leprosy diagnosis and monitoring in household contacts: A follow-up study, 2011-2018.

Household contacts (HHC) of leprosy patients exhibit high-risk of developing leprosy and contact tracing is helpful for early diagnosis. From 2011 to 2018,2,437 HHC were examined in a clinic in Rio de Janeiro, Brazil and 16S qPCR was used for diagnosis and monitoring of contacts. Fifty-four HHCs were clinically diagnosed with leprosy at intake. Another 25 exhibited leprosy-like skin lesions at intake, 8 of which were confirmed as having leprosy (50% of which were qPCR positive) and 17 of which were diagnosed with other skin diseases (6% qPCR positive). In skin biopsies, qPCR presented a sensitivity of 0.50 and specificity of 0.94. Furthermore, 955 healthy HHCs were followed-up for at least 3 years and skin scrapings were collected from earlobes for qPCR detection. Positive qPCR indicated a non-significant relative risk of 2.52 of developing the disease. During follow-up, those who progressed towards leprosy exhibited 20% qPCR positivity, compared to 9% of those who remained healthy. Disease-free survival rates indicated that age had a significant impact on disease progression, where patients over 60 had a greater chance of developing leprosy [HR = 32.4 (3.6-290.3)]. Contact tracing combined with qPCR may assist in early diagnosis and age is a risk factor for leprosy progression.

Leprosy: prevalence and factors associated with seropositivity for anti-NDO-LID antibodies in children under 15 years of age.

BACKGROUND: A high prevalence of leprosy among children under 15 years of age indicates the need to implement actions to prevent new cases of the disease. Serological tests have been developed with the aim of helping to control the disease by indicating, through seropositivity, the presence of infection. OBJECTIVE: To analyze the prevalence and factors associated with seropositivity rate for anti-NDO-LID antibodies in children under 15 years of age, contacts of leprosy patients. METHOD: We performed a cross-sectional study with 210 children under 15 years old of age. Of them, 50 were household contacts and 160 were neighborhood contacts living in the municipality of Cuiabá, state of Mato Grosso, in 2016. The data were obtained from interviews and the NDO-LID rapid test during home visits from February to July 2016. For the analysis, we used Poisson regression and prevalence ratio. RESULTS: Seropositivity in contacts was 6.2%. Variables associated with seropositive tests included sex (PR = 1.05; 95% CI: 1.01 - 1.08), race/skin color (PR = 0.95; 95% CI: 0.90 - 0.99), residence area (PR = 1.05; 95% CI: 1.01 - 1.09), and number of people per household (PR = 1.06; 95% CI: 1.02 - 1.08). STUDY LIMITATIONS: The small sample size, besides leading to wide confidence intervals, may have been a limitation for the identification of associated factors. CONCLUSIONS: The prevalence of seropositivity was high. Variables associated with NDO-LID seropositivity included female sex, not to be brown skinned, live in urban areas, and live with five or more people.

[Overlapping of new leprosy cases in household contact networks in two municipalities in North and Northeast Brazil, 2001-2014]. / Sobreposição de casos novos de hanseníase em redes de convívio domiciliar em dois municípios do Norte e Nordeste do Brasil, 2001-2014.

The study aimed to analyze the magnitude and sociodemographic profile of leprosy cases linked to household contact networks with overlapping of the disease in two Brazilian municipalities (counties), one in the North and the other in the Northeast, from 2001 to 2014. This was a cross-sectional, descriptive, analytical study based on primary and secondary data from new leprosy cases in Picos, Piauí State, and Rolim de Moura, Rondônia State. "Overlapping" was defined as new cases with the occurrence of at least one more leprosy case in the individual's household contact network. Each household contact network consisted of the index case (first reported case), co-prevalent cases (contacts that became new cases), and household contacts of the index case. A total of 437 new cases treated by the INTEGRAHANS North-Northeast and Piauí projects were assessed, of which 287 (65.7%) were in Picos and 150 (34.3%) in Rolim de Moura. Of all the cases assessed, 129 (44.9%) in Picos and 98 (65.3%) in Rolim de Moura reported overlapping. There were proportionally more females in Rolim de Moura (n = 95, 63.3%) and males in Picos (n = 147, 51.2%); in the 41-60-year age bracket (Rolim de Moura n = 70, 46.7%; Picos n = 115, 40.1%); with elementary schooling (Rolim de Moura n = 80, 54%; Picos n = 125, 44.5%); and individuals living in the same household with up to 3 persons in Rolim de Moura (n = 105, 70%) and with more than 4 persons in Picos (n = 287, 100%). Overlapping of leprosy cases in household contact networks was considerably high in the contexts analyzed here, displaying aspects of expanded vulnerability. This perspective should be considered and integrated into leprosy surveillance and control activities.

Objetivou-se analisar a magnitude e o perfil sociodemográfico de casos de hanseníase vinculados a Redes de Convívio Domiciliar (RCD) com sobreposição da doença em dois municípios brasileiros, um da Região Norte e outro da Nordeste, de 2001 a 2014. Estudo transversal, descritivo e analítico, com base em dados primários e secundários de casos novos de hanseníase em indivíduos residentes em Picos, no Estado do Piauí, e em Rolim de Moura, no Estado de Rondônia. "Sobreposição" foi definida como casos novos com ocorrência de pelo menos mais um caso de hanseníase em sua RCD. Cada RCD foi composta por caso referência (primeiro caso notificado), casos coprevalentes (contatos que se tornaram casos novos) e contatos domiciliares de caso referência. Um total de 437 casos novos abordados pelos projetos INTEGRAHANS Norte-Nordeste e Piauí foram avaliados, 287 (65,7%) em Picos e 150 (34,3%) em Rolim de Moura. Do total de casos avaliados, 129 (44,9%) em Picos e 98 (65,3%) em Rolim de Moura relataram a ocorrência de sobreposição. Verificou-se maior frequência de pessoas do sexo feminino em Rolim de Moura (n = 95, 63,3%) e do masculino em Picos (n = 147, 51,2%); na faixa etária entre 41-60 anos de idade (Rolim de Moura n = 70, 46,7%; Picos n = 115, 40,1%); com ensino fundamental (Rolim de Moura n = 80, 54%; Picos n = 125, 44,5%) e que morava no mesmo domicílio com até 3 pessoas em Rolim de Moura (n = 105, 70%) e com mais de 4 pessoas em Picos (n = 287, 100%). A sobreposição de casos de hanseníase em RCD apresentou magnitude considerável nos contextos analisados, demonstrando aspectos de vulnerabilidade ampliada. Essa perspectiva deve ser considerada e integrada às ações de vigilância e controle da hanseníase.

El objetivo fue analizar la magnitud y el perfil sociodemográfico de los casos de hanseniasis vinculados a Redes de Convivencia Domiciliaria (RCD) con superposición de la enfermedad en dos municipios brasileños, uno de la región norte y otro de la nordeste, de 2001 a 2014. Estudio transversal, descriptivo y analítico, a partir de datos primarios y secundarios de casos nuevos de lepra con residentes en Picos, en el Estado de Piauí, y en Rolim de Moura, en el Estado de Rondônia. "Superposición" fue definida como casos nuevos con ocurrencia de por lo menos más de un caso de lepra en su RCD. Cada RCD estaba compuesta por un caso referencia (primer caso notificado), casos coprevalentes (contacto que se convirtió en casos nuevos) y contactos domiciliarios de caso referencia. Un total de 437 casos nuevos abordados por los proyectos INTEGRAHANS Norte/Nordeste y Piauí fueron evaluados, 287 (65,7%) en Picos y 150 (34,3%) en Rolim de Moura. Del total de casos evaluados, 129 (44,9%) en Picos y 98 (65,3%) en Rolim de Moura informaron la ocurrencia de superposición. Se verificó una mayor frecuencia de personas del sexo femenino en Rolim de Moura (n = 95, 63,3%) y masculino en Picos (n = 147, 51,2%); en la franja etaria entre 41-60 años de edad (Rolim de Moura n = 70, 46,7%; Picos n = 115, 40,1%); con enseñanza fundamental (Rolim de Moura n = 80, 54%; Picos n = 125, 44,5%) y que vivía en el mismo domicilio con hasta 3 personas en Rolim de Moura (n = 105, 70%) y con más de 4 personas en Picos (n = 287, 100%). La superposición de casos de lepra en RCD presentó una magnitud considerable en los contextos analizados, demostrando aspectos de vulnerabilidad ampliada. Esta perspectiva debe ser considerada e integrada en las acciones de vigilancia y control de la lepra.