Human N-acetyltransferase 2 (NAT2) gene variability in Brazilian populations from different geographical areas

Introduction: Several polymorphisms altering the NAT2 activity have already been identified. The geographical distribution of NAT2 variants has been extensively studied and has been demonstrated to vary significantly among different ethnic population. Here, we describe the genetic variability of human N-acetyltransferase 2 (NAT2) gene and the predominant genotype-deduced acetylation profiles of Brazilians.Methods: A total of 964 individuals, from five geographical different regions, were genotyped for NAT2 by sequencing the entire coding exon.Results: Twenty-three previously described NAT2 single nucleotide polymorphisms (SNPs) were identified, including the seven most common ones globally (c.191G>A, c.282C>T, c.341T>C, c.481C>T, c.590G>A, c.803A>G and c.857G>A). The main allelic groups were NAT2*5 (36%) and NAT2*6 (18.2%), followed to the reference allele NAT2*4 (20.4%). Combined into genotypes, the most prevalent allelic groups were NAT2*5/*5 (14.6%), NAT2*5/*6 (11.9%) and NAT2*6/*6 (6.2%). The genotype deduced NAT2 slow acetylation phenotype was predominant but showed significant variability between geographical regions. The prevalence of slow acetylation phenotype was higher in the Northeast, North and Midwest (51.3%, 45.5% and 41.5%, respectively) of the country. In the Southeast, the intermediate acetylation phenotype was the most prevalent (40.3%) and, in the South, the prevalence of rapid acetylation phenotype was significantly higher (36.7%), when compared to other Brazilian states (p < 0.0001). Comparison of the predicted acetylation profile among regions showed homogeneity among the North and Northeast but was significantly different when compared to the Southeast (p = 0.0396). The Southern region was significantly different from all other regions (p < 0.0001).Discussion: This study contributes not only to current knowledge of the NAT2 population genetic diversity in different geographical regions of Brazil, but also to the reconstruction of a more accurate phenotypic picture of NAT2 acetylator profiles in those regions

Estratégias para bloquear a transmissão da hanseníase em município hiperendêmico \2013 Mossoró/RN

Submitted by Gilvan Almeida ([email protected]) on 2017-01-02T12:28:13Z No. of bitstreams: 1 license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5)Approved for entry into archive by Anderson Silva ([email protected]) on 2017-05-09T15:19:23Z (GMT) No. of bitstreams: 2 mauricio_nobre_ioc_dout_2016.pdf: 11440817 bytes, checksum: 2eb2e40e8608d11d797cadbcb0753fc6 (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5)Made available in DSpace on 2017-05-09T15:19:23Z (GMT). No. of bitstreams: 2 mauricio_nobre_ioc_dout_2016.pdf: 11440817 bytes, checksum: 2eb2e40e8608d11d797cadbcb0753fc6 (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) Previous issue date: 2016Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, BrasilA hanseníase é um importante problema de saúde pública no mundo com 213.899 casos novos notificados em 2014. No Brasil foram diagnosticados 31.064 casos, com diferentes níveis de endemicidade entre os estados. O Rio Grande do Norte apresenta um dos menores coeficientes de detecção de casos novos (CDCN) da doença no país, com 7,98 casos por 100.000 habitantes em 2014. Apesar disso, em alguns municípios do Estado esse coeficiente é hiperendêmico, como em Mossoró/RN onde este estudo foi realizado. Com o objetivo de executar estratégias para interromper a transmissão do Mycobacterium leprae, realizou-se o mapeamento dos coeficientes de detecção da doença por bairros do município, observando que a endemia é mais frequente em áreas de rápida urbanização e precárias condições de moradia. Duas dessas áreas foram selecionadas para atividades de controle. Em uma delas realizou-se exame de escolares para detectar casos novos da doença e para identificar suas possíveis fontes de infecção. Na outra, realizou-se sorologia para hanseníase em idosos com o objetivo de detectar casos multibacilares (MB) da doença. Em oito escolas 1.385 crianças foram examinadas e 18 novos casos de hanseníase paucibacilar (PB) foram detectados (1,3%). Foram realizadas visitas domiciliares e 160 comunicantes desses casos foram examinados, resultando no diagnóstico de outros seis casos da doença (3,75%). Entre 145 professores e funcionários das escolas nenhum caso foi diagnosticado, mostrando que os contatos sociais não desempenharam papel importante como fonte de infecção para esses escolares. Nove dos comunicantes com hanseníase MB atual ou pregressa foram considerados possíveis fontes de infecção pelo M. leprae; em três desses casos a família das crianças não tinha conhecimento do diagnóstico do contato Na segunda estratégia realizou-se pesquisa de anticorpos contra o bacilo de Hansen em 504 idosos e dois novos casos de hanseníase MB foram detectados, um deles sem qualquer sinal clínico evidente. Essa estratégia mostrou-se importante pela elevada taxa de detecção de casos MB entre homens idosos (1%). Adicionalmente, os dados de 541.090 casos de hanseníase notificados no Brasil entre 2001-2013 foram analisados, mostrando que o CDCN por faixa etária é influenciado pelos casos MB no sexo masculino. Observou-se que o CDCN da hanseníase MB em homens eleva-se rapidamente após 19 anos de idade atingindo um pico de 44,8/100.000 habitantes entre 65-69 anos. A razão de chances para hanseníase MB foi duas vezes maior para homens em comparação às mulheres, observando-se o mesmo para doentes com 60 ou mais anos de idade comparados aos mais jovens. O estudo demonstrou ainda que a carga bacilar em 2.253 casos diagnosticados na Fiocruz (Rio de Janeiro/RJ) foi significativamente maior em homens do que em mulheres. Esses achados são relevantes e sugerem que estratégias específicas devam ser adotadas para detectar e tratar casos de hanseníase MB nesses grupos populacionais, reduzindo a transmissão da doença. Conclui-se que a busca de casos MB é essencial para interromper a infecção pelo M. leprae na comunidade, mas que esse objetivo não será atingido sem a adoção de políticas públicas que promovam educação em saúde e melhores condições de habitaçãoHansen\2018s disease (HD) is an important public health problem in the world with 213,899 new cases detected in 2014. In Brazil 31,064 new cases were diagnosed with considerable differences in the endemicity level among states. Rio Grande do Norte presents one of the lowest new cases detection rates (NCDR) of the disease in the country, with 7.98 new cases per 100,000 in 2014. Despite this, in some municipalities within the state the NCDR is hyper-endemic, as in Mossoró/RN where this study was conducted. With the objective of developing strategies to halt Mycobacterium leprae transmission, NCDR by municipality neighborhoods were mapped showing that disease occurs more frequently in areas of rapid urbanization and bad housing conditions. Two of these areas were chosen for development of control activities. In one of them school children were surveyed in order to detect new cases of the disease and to identify their possible infection sources. In the other area, serology for HD was carried out in elderly population to detect multibacillary (MB) cases. In eight schools 1,385 children were checked for skin lesions and 18 new cases of paucibacillary (PB) HD were detected (1.3%). Home visits were performed and 160 contacts of these cases were examined, resulting in six additional HD new cases diagnosed (3.75%). Among 145 school teachers and employees no new case was diagnosed, showing that social contacts did not play an important role as source of infection for these school children. Nine of their close contacts with present or past MB disease were considered as a possible source of M. leprae; in three cases the children\2018s family did not know about the contact\2018s diagnosis The second strategy tested 504 elderly people for specific antibodies against Hansen\2018s bacillus and two new HD MB cases were detected, one of them without any clinical signs of HD disease. This strategy was important because of its high detection rate of MB cases among elderly men (1%). Additionally, data of 541,090 HD cases notified in Brazil from 2001-2013 were analyzed showing that NCDR by age group are mainly influenced by MB cases in male sex. NCDR of males with MB disease increased steeply above 19 years of age and peaked at 44.8/100,000 population in 65-69 years age group. The odds ratio for MB leprosy was twice higher for men compared to women and the same was observed for patients aged 60 or more years old compared to younger cases. Moreover, this study showed that bacillary load from 2,253 HD cases diagnosed at Fiocruz (Rio de Janeiro/RJ) was significantly higher in male than in female patients. These findings are relevant and suggest that specific strategies should be adopted to diagnose and treat MB cases in these population groups, reducing disease transmission. We conclude that active search for MB cases is essential to halt M. leprae transmission, but this objective will not be attained without adoption of public policies that promote health education and improvements in habitation condition

Human migration, railways and the geographic distribution of leprosy in Rio Grande do Norte State – Brazil

Submitted by Sandra Infurna ([email protected]) on 2018-01-02T15:15:30Z No. of bitstreams: 1 euzenir_sarno_etal_IOC_2016.pdf: 492103 bytes, checksum: 5fcef27563a5e2d28f729b36993f6fd9 (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2018-01-02T15:32:52Z (GMT) No. of bitstreams: 1 euzenir_sarno_etal_IOC_2016.pdf: 492103 bytes, checksum: 5fcef27563a5e2d28f729b36993f6fd9 (MD5)Made available in DSpace on 2018-01-02T15:32:52Z (GMT). No. of bitstreams: 1 euzenir_sarno_etal_IOC_2016.pdf: 492103 bytes, checksum: 5fcef27563a5e2d28f729b36993f6fd9 (MD5) Previous issue date: 2015Hospital Giselda Trigueiro. Natal, RN, Brasil / Universidade Federal do Rio Grande do Norte. Instituto de Medicina Tropical do Rio Grande do Norte. Natal, RN, Brasil /Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Pós-Graduação em Medicina Tropical. Rio de |Janeiro, RJ, Brasil.Universidade Federal do Rio Grande do Norte. Instituto de Medicina Tropical do Rio Grande do Norte. Natal, RN, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Pós-Graduação em Medicina Tropical. Rio de |Janeiro, RJ, Brasil./ Weill Cornell Medical College. Division of Infectious Diseases and Center for Global Health. New York, NY, USA.Universidade Federal do Rio Grande do Norte. Departamento de Arquitetura. Natal, RN, Brasil.Instituto Nacional de Seguridade Social. Mossoró, RN, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ. Brasil.Universidade Federal do Rio Grande do Norte. Instituto de Medicina Tropical do Rio Grande do Norte. Natal, RN, Brasil / Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais (INCT/DT). Salvador, BA, Brasil.Introduction—Leprosy is a public health problem in Brazil where 31,044 new cases were detected in 2013. Rio Grande do Norte is a small Brazilian state with a rate of leprosy lower than other areas in the same region, for unknown reasons. Objectives—We present here a review based on the analysis of a database of registered leprosy cases in Rio Grande do Norte state, comparing leprosy's geographic distribution among municipalities with local socio-economic and public health indicators and with historical documents about human migration in this Brazilian region. Results—The current distribution of leprosy in Rio Grande do Norte did not show correlation with socio-economic or public health indicators at the municipal level, but it appears related to economically emerging municipalities 100 years ago, with spread facilitated by railroads and train stations. Drought-related migratory movements which occurred from this state to leprosy endemic areas within the same period may be involved in the introduction of leprosy and with its present distribution within Rio Grande do Norte

Multibacillary leprosy by population groups in Brazil: Lessons from an observational study

<div><p>Background</p><p>Leprosy remains an important public health problem in Brazil where 28,761 new cases were diagnosed in 2015, the second highest number of new cases detected globally. The disease is caused by <i>Mycobacterium leprae</i>, a pathogen spread by patients with multibacillary (MB) leprosy. This study was designed to identify population groups most at risk for MB disease in Brazil, contributing to new ideas for early diagnosis and leprosy control.</p><p>Methods</p><p>A national databank of cases reported in Brazil (2001–2013) was used to evaluate epidemiological characteristics of MB leprosy. Additionally, the databank of a leprosy reference center was used to determine factors associated with higher bacillary loads.</p><p>Results</p><p>A total of 541,090 cases were analyzed. New case detection rates (NCDRs) increased with age, especially for men with MB leprosy, reaching 44.8 new cases/100,000 population in 65–69 year olds. Males and subjects older than 59 years had twice the odds of MB leprosy than females and younger cases (OR = 2.36, CI95% = 2.33–2.38; OR = 1.99, CI95% = 1.96–2.02, respectively). Bacillary load was higher in male and in patients aged 20–39 and 40–59 years compared to females and other age groups. From 2003 to 2013, there was a progressive reduction in annual NCDRs and an increase in the percentage of MB cases and of elderly patients in Brazil. These data suggest reduction of leprosy transmission in the country.</p><p>Conclusion</p><p>Public health policies for leprosy control in endemic areas in Brazil should include activities especially addressed to men and to the elderly in order to further reduce <i>M</i>. <i>leprae</i> transmission.</p></div

Annual indicators for leprosy in Brazil (2001–2013)

<p>Annual indicators for leprosy in Brazil (2001–2013)</p

Mean new case detection rates (NCDR) of leprosy by time period, according to age group–Brazil (2001 to 2013).

<p>Mean new case detection rates (NCDR) of leprosy by time period, according to age group–Brazil (2001 to 2013).</p

Mean new case detection rates (NCDR) of leprosy by Brazilian state (2001 to 2013).

<p>Mean new case detection rates (NCDR) of leprosy by Brazilian state (2001 to 2013).</p

Sex ratio of leprosy cases detected without disabilities, by operational classification according to age group–Brazil.

<p>MB: multibacillary, PB: paucibacillary.</p

Mean new case detection rates (NCDR) of leprosy in Brazil (2001–2013).

<p>3a) NCDR by sex according to age group. 3b) NCDR by sex and operational classification according to age group. MB: multibacillary, PB: paucibacillary.</p

Bacillary index of leprosy cases at diagnosis by sex according to age groups–Ambulatório Souza Araújo, Fiocruz/RJ, Brazil (1990–2014).

<p>5a = All cases; 5b = MB cases. * = extremes, dots = outliers, horizontal bar = median, box = 25–75 percentiles.</p