Spatial distribution pattern of new leprosy cases under 15 years of age and their contacts in Sobral, Ceará, Brazil.

This study's objective was to analyze the spatial distribution pattern of new leprosy cases under 15 years and their contacts. A cross-sectional descriptive study covering sociodemographic characteristics and spatial analysis was carried out. The participants were from the city of Sobral, Ceará and the study was conducted between August 2014 and September 2015. Contacts were identified by the persons responsible for the children. Seropositivity was determined with the NDO-LID antigen, and positive cases were plotted on Voronoi polygons. Nine new cases of leprosy under 15 years of age have been found. The average number of people living with the cases was higher than the number of people living with non-household contacts. All household contacts were aware of other leprosy cases and had a higher rate of seropositive tests than non-household contacts. The index cases lived in the poorest regions of the municipality and hyper-endemic areas. Spatial analysis revealed a cluster of subclinical infection within a radius of 102 meters, suggesting that non-household transmission is related to proximity with seropositive individuals. In conclusion, the search for new leprosy cases cannot be restricted to household contacts.

Spatial distribution pattern of new leprosy cases under 15 years of age and their contacts in Sobral, Ceará, Brazil / Distribuição espacial de novos casos de hanseníase em menores de 15 anos e de seus contatos em Sobral, Ceará, Brasil

Abstract This study's objective was to analyze the spatial distribution pattern of new leprosy cases under 15 years and their contacts. A cross-sectional descriptive study covering sociodemographic characteristics and spatial analysis was carried out. The participants were from the city of Sobral, Ceará and the study was conducted between August 2014 and September 2015. Contacts were identified by the persons responsible for the children. Seropositivity was determined with the NDO-LID antigen, and positive cases were plotted on Voronoi polygons. Nine new cases of leprosy under 15 years of age have been found. The average number of people living with the cases was higher than the number of people living with non-household contacts. All household contacts were aware of other leprosy cases and had a higher rate of seropositive tests than non-household contacts. The index cases lived in the poorest regions of the municipality and hyper-endemic areas. Spatial analysis revealed a cluster of subclinical infection within a radius of 102 meters, suggesting that non-household transmission is related to proximity with seropositive individuals. In conclusion, the search for new leprosy cases cannot be restricted to household contacts.

Resumo O objetivo deste estudo foi analisar o padrão de distribuição espacial de novos casos de hanseníase em menores de 15 anos e seus contatos. Estudo transversal, descritivo, abrangendo características sociodemográficas e análise espacial. Os participantes eram de Sobral, Ceará e o estudo foi realizado entre agosto de 2014 e setembro de 2015. Os contatos foram identificados pelos responsáveis pelas crianças. A soropositividade foi determinada com o antígeno NDO-LID e os casos positivos foram plotados em polígonos de Voronoi. Nove novos casos de hanseníase em menores de 15 anos foram encontrados. O número médio de pessoas que conviviam com os casos foi superior ao número de pessoas que conviviam com contatos não domiciliares. Todos os contatos domiciliares sabiam de outros casos de hanseníase e apresentaram maior taxa de testes soropositivos do que os contatos não domiciliares. Os casos índice residiam nas regiões mais pobres do município e em áreas hiperendêmicas. A análise espacial revelou um agrupamento de infecção subclínica em um raio de 102 metros, sugerindo que a transmissão não domiciliar está relacionada à proximidade com indivíduos soropositivos. Concluindo, a busca por novos casos de hanseníase não pode se restringir aos contatos domiciliares.

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.

Aspectos epidemiológicos e espaciais de escolares avaliados na Campanha Nacional de Hanseníase em Sobral - Ceará, Brasil / Epidemiological and spatial aspects of schoolchildren in National Leprosy Campaign in Sobral ­ Ceará, Brazil

Objetivo: Descrever os aspectos epidemiológicos dos escolares da rede pública de educação, na faixa etária de cinco a quatroze anos, que participaram da Campanha Nacional de Hanseníase, em 2016. Método: Estudo transversal com dados de escolares de cinco a quatorze anos de Sobral, Ceará. Empregou-se o teste de associação Qui-quadrado de Pearson e o diagrama de Voronoi associado a matriz de distância linear e de proximidade. Resultados: Foram incluídos 1.216 escolares, dos quais 18,1% tinham casos de hanseníase na família, 31,7% apresentaram manchas no corpo e destes, 19,4% referiram ter algum caso de hanseníase na família. Dos 386 escolares que relataram mancha no corpo, 41,3% são do sexo masculino e 34,8% residiam na zona urbana. Conclusão: Evidenciou-se prevalência de manchas nos escolares do sexo masculino, residentes na zona urbana, com distância mínima espacial (de até 10 km) dos escolares com manchas para os casos que tiveram hanseníase na família. (AU)

Objectives: Describe the epidemiological aspects of schoolchildren in the public education system, aged five to fourteen years, who participated in the National Leprosy Campaign in 2016. Methods: Cross-sectional study with data from schoolchildren aged five to fourteen years, from Sobral, Ceará. Pearson's Chi-square association test and the Voronoi diagram associated with the linear distance and proximity matrix were used. Results: 1.216 students were included, of which 18.1% had cases of leprosy in the family, 31.7% had cases without leprosy, 19.4% reported some case of leprosy in the family. Of the 386 schoolchildren who relate to the body, 41.3% are male and 34.8% live in the urban area. Conclusion: There was a prevalence of spots in male students living in the urban area, with a minimum spatial distance (up to 10 km) of students with spots for cases with leprosy in the family. (AU)

Objetivos: Describa los aspectos epidemiológicos de los escolares en el sistema de educación pública, de cinco a catorce años, que participaron la Campaña Nacional contra la Lepra en 2016. Métodos: Estudio transversal con datos de escolares de cinco a catorce años, de Sobral, Ceará. Se utilizaron la prueba de asociación Chi-cuadrado de Pearson y el diagrama de Voronoi asociado con distancia lineal y la matriz de proximidad. Resultados: Se incluyeron 1.216 estudiantes, de los cuales 18.1% tenían casos de lepra en la familia, 31.7% tenían casos sin lepra, 19.4% informaron algún caso de lepra en la familia. De los 386 escolares que se relacionan con el cuerpo, 41.3% son hombres y 34.8% viven en el área urbana. Conclusión: Hubo una prevalencia de manchas en estudiantes varones que viven en el área urbana, con una distancia espacial mínima (hasta 10 km) de estudiantes con manchas para casos de lepra en la familia. (AU)

Evaluation of 16S rRNA qPCR for detection of Mycobacterium leprae DNA in nasal secretion and skin biopsy samples from multibacillary and paucibacillary leprosy cases.

Mycobacterium leprae bacilli are mainly transmitted by the dissemination of nasal aerosols from multibacillary (MB) patients to susceptible individuals through inhalation. The upper respiratory tract represents the main entry and exit routes of M. leprae. Therefore, this study aimed to evaluate the sensitivity and specificity of real-time quantitative polymerase chain reaction (qPCR) in detecting M. leprae in nasal secretion (NS) and skin biopsy (SB) samples from MB and paucibacillary (PB) cases. Fifty-four NS samples were obtained from leprosy patients at the Dona Libânia National Reference Centre for Sanitary Dermatology in Ceará, Brazil. Among them, 19 MB cases provided both NS and SB samples. Bacilloscopy index assays were conducted and qPCR amplification was performed using specific primers for M. leprae 16S rRNA gene, generating a 124-bp fragment. Primer specificity was verified by determining the amplicon melting temperature (Tm = 79.5 °C) and detection limit of qPCR was 20 fg of M. leprae DNA. Results were positive for 89.7 and 73.3% of NS samples from MB and PB cases, respectively. SB samples from MB patients were 100% positive. The number of bacilli detected in NS samples were 1.39 × 103-8.02 × 105, and in SB samples from MB patients were 1.87 × 103-1.50 × 106. Therefore, qPCR assays using SYBR Green targeting M. leprae 16S rRNA region can be employed in detecting M. leprae in nasal swabs from leprosy patients, validating this method for epidemiological studies aiming to identify healthy carriers among household contacts or within populations of an endemic area.

Presence of Mycobacterium leprae genotype 4 in environmental waters in Northeast Brazil.

INTRODUCTION:: This study quantified Mycobacterium leprae bacilli in environmental water samples from five municipalities in the State of Ceará by quantitative polymerase chain reaction (qPCR) and compared the identified genotypes with those obtained from leprosy patient biopsies. METHODS:: We collected five replicas from each of the 30 selected reservoirs and skin lesion biopsies from 25 new leprosy cases treated at a reference center in Fortaleza, Ceará from 2010 to 2013. The 16S rRNA gene region of M. leprae was amplified by qPCR and a standard curve was created with the pIDTBlue 16SrRNAMlep plasmid. The Juazeiro do Norte water samples and the biopsies were genotyped (single nucleotide polymorphism [SNP] 1 to 4) and the SNP 4 genotypes were subtyped. RESULTS:: Of the 149 water samples analyzed, 54.4% were positive for the M. leprae DNA. The M. leprae bacilli copy number ranged from 1.42 × 10 -1 to 1.44 × 10 + 2 . Most biopsies showed SNP type 4 (64%), while all samples from Juazeiro do Norte were SNP type 4, with subtype 4-N appearing at the highest frequency. CONCLUSIONS:: We suggest that environmental waters containing M. leprae bacilli play an important role in disease transmission, justifying PGL-1 seropositivity in individuals living in areas where there is no reported case, and in leprosy cases individuals who report no previous contact with other case. Therefore, further investigation is needed to clarify disease transmission in this region and to explore the role of the environment. We also suggest that in this area surveillance for leprosy cases should be intensified.

Presence of Mycobacterium leprae genotype 4 in environmental waters in Northeast Brazil

Abstract INTRODUCTION: This study quantified Mycobacterium leprae bacilli in environmental water samples from five municipalities in the State of Ceará by quantitative polymerase chain reaction (qPCR) and compared the identified genotypes with those obtained from leprosy patient biopsies. METHODS: We collected five replicas from each of the 30 selected reservoirs and skin lesion biopsies from 25 new leprosy cases treated at a reference center in Fortaleza, Ceará from 2010 to 2013. The 16S rRNA gene region of M. leprae was amplified by qPCR and a standard curve was created with the pIDTBlue 16SrRNAMlep plasmid. The Juazeiro do Norte water samples and the biopsies were genotyped (single nucleotide polymorphism [SNP] 1 to 4) and the SNP 4 genotypes were subtyped. RESULTS: Of the 149 water samples analyzed, 54.4% were positive for the M. leprae DNA. The M. leprae bacilli copy number ranged from 1.42 × 10 -1 to 1.44 × 10 + 2 . Most biopsies showed SNP type 4 (64%), while all samples from Juazeiro do Norte were SNP type 4, with subtype 4-N appearing at the highest frequency. CONCLUSIONS: We suggest that environmental waters containing M. leprae bacilli play an important role in disease transmission, justifying PGL-1 seropositivity in individuals living in areas where there is no reported case, and in leprosy cases individuals who report no previous contact with other case. Therefore, further investigation is needed to clarify disease transmission in this region and to explore the role of the environment. We also suggest that in this area surveillance for leprosy cases should be intensified.

Can baseline ML Flow test results predict leprosy reactions? An investigation in a cohort of patients enrolled in the uniform multidrug therapy clinical trial for leprosy patients in Brazil.

BACKGROUND: The predictive value of the serology to detection of IgM against the Mycobacterium leprae-derived phenolic glycolipid-I/PGL-I to identify leprosy patients who are at higher risk of developing reactions remains controversial. Whether baseline results of the ML Flow test can predict leprosy reactions was investigated among a cohort of patients enrolled in The Clinical Trial for Uniform Multidrug Therapy for Leprosy Patients in Brazil (U-MDT/CT-BR). METHODS: This was a descriptive study focusing on the main clinical manifestations of leprosy patients enrolled in the U-MDT/CT-BR from March 2007 to February 2012 at two Brazilian leprosy reference centers. For research purposes, 753 leprosy patients were categorized according to a modified Ridley-Jopling (R&J) classification and according to the development of leprosy reactions (reversal reaction/RR and erythema nodosum leprosum/ENL), and whether they had a positive or negative bacillary index/BI. RESULTS: More than half of the patients (55.5 %) reported leprosy reaction: 18.3 % (138/753) had a RR and 5.4 % (41/753) had ENL. Leprosy reactions were more frequent in the first year following diagnosis, as seen in 27 % (205/753) of patients, while 19 % (142/753) developed reactions during subsequent follow-up. Similar frequencies of leprosy reactions and other clinical manifestations were observed in paucibacillary (PB) and multibacillary (MB) leprosy patients treated with U-MDT and regular MDT (R-MDT) (P = 0.43 and P = 0.61, respectively). Compared with PB patients, leprosy reactions were significantly more frequent in MB patients with a high BI, and more patients developed RR than ENL. However, RR and neuritis were also reported in patients with a negative BI. At baseline, the highest rate of ML Flow positivity was observed in patients with a positive BI, especially those who developed ENL, followed by patients who had neuritis and RR. Among reaction-free patients, 81.9 % were ML Flow positive, however, the differences were not statistically significant compared to reactional patients (P = 0.45). CONCLUSIONS: MB and PB patients treated with R-MDT and U-MDT showed similar frequencies of RR and other clinical manifestations. Positive ML Flow tests were associated with MB leprosy and BI positivity. However, ML Flow test results at baseline showed limited sensitivity and specificity for predicting the development of leprosy reactions.

Correlation between clinical tests and electroneuromyography for the diagnosis of leprosy neuropathy.

BACKGROUND: In leprosy, sensory function of nerves is evaluated with monofilaments test and the motor function with voluntary muscle test, however electroneuromyography is considered as the gold-standard tool. OBJECTIVES: This study aimed: i) to evaluate the correlation between clinical tests and electroneuromyography for the diagnosis of leprosy neuropathy; and ii) to identify the prevalence of leprosy neuropathy and the most compromised peripheral nerves in leprosy. METHODS: We analysed the data from a nested case-control study that identified 166 patients diagnosed with leprosy neuropathy confirmed by electromyography. This study was designed for an analysis of correlation between the diagnostic tests. RESULTS: The most prevalent type of the neural damage was the sensory and motor multiple mononeuropathy, observed in 62 (37.3%) cases. The highest prevalence was the ulnar nerve in 67 (40.3%) cases. Agreement specified by nerves was moderate, ranging from k = 0.58 in the deep peroneal nerve to k = 0.41 in the posterior tibial nerve). Overall agreement between the clinical tests and electroneuromyography was very poor. Monofilaments test with k = 0.02 (95% CI 0.00-0.12) and voluntary muscle test with 0.16 (95% CI 0.04 to 0.28, P = 0.01). CONCLUSIONS: There is a low to moderate correlation between clinical tests (monofilaments and voluntary muscle tests) and the electroneuromyography examination. The most prevalent type of neural impairment was the sensory and motor multiple mononeuropathy, and the most affected nerve was the ulnar.