Yes / Mycobacterium africanum (Maf) causes a substantial proportion of human tuberculosis in some countries of West Africa, but little is known on this pathogen. We compared the genomes of 253 Maf clinical isolates from Ghana, including N = 175 Lineage 5 (L5) and N = 78 Lineage 6 (L6). We found that the genomic diversity of L6 was higher than in L5 despite the smaller sample size. Regulatory proteins appeared to evolve neutrally in L5 but under purifying selection in L6. Even though over 90% of the human T cell epitopes were conserved in both lineages, L6 showed a higher ratio of non-synonymous to synonymous single nucleotide variation in these epitopes overall compared to L5. Of the 10% human T cell epitopes that were variable, most carried mutations that were lineage-specific. Our findings indicate that Maf L5 and L6 differ in some of their population genomic characteristics, possibly reflecting different selection pressures linked to distinct ecological niches. / Supported by the Wellcome Trust Intermediate Fellowship awarded to DYM (Grant Number 097134/Z/11/Z) and by the Swiss National Science Foundation (grants 310030_166687, IZRJZ3_164171 and IZLSZ3_170834), the European Research Council (309540-EVODRTB) and SystemsX.ch.

Objetivos: Identificar e comparar grupos de pacientes potencialmente de risco para tuberculose zoonótica (TBz), investigando a existência de fatores associados. Apresentar a distribuição espacial dos casos de tuberculose (TB) em bovinos e dos casos humanos. Método: Trata-se de estudo descritivo de casos confirmados de TB por todas as formas clínicas, residentes no estado de São Paulo, do período de 2006 a 2015. Definiram-se seis grupos potenciais de risco para TBz conforme critérios estabelecidos pela literatura. A análise descritiva foi realizada separadamente para pacientes menores de 15 anos e pacientes com 15 anos ou mais de idade, comparando os grupos identificados com a população de estudo por meio do teste do Qui-quadrado/Exato de Fisher. A existência de associação entre TB intestinal e/ou ganglionar (aceita como proxy de caso suspeito de TBz) e as exposições de interesse foi investigada pelas estimativas da odds ratio bruta e ajustada, com os respectivos intervalos de 95% de confiança, usando regressão logística. . A distribuição dos casos suspeitos foram apresentados em mapas temáticos. Resultados: Aplicados os critérios estabelecidos para o estudo, foram incluídos 190.368 casos de TB por todas as formas clínicas. Dentre estes: 134 tinham menos de 15 anos e residiam em municípios com até 20.000 habitantes (grupo A); os demais tinham 15 anos ou mais, sendo 1.238 trabalhadores rurais (grupo B); 201 magarefes (grupo C); 1.012 residiam em municípios com até 20.000 habitantes e com rebanhos infectados pela TB (grupo D); 2.776 imigrantes sul americanos (grupo E); e 160 imigrantes africanos (grupo F). Os grupos B e F foram os que mais apresentaram características semelhantes à TBz descrita na literatura, destacando-se no grupo B as maiores proporções de casos de residentes em municípios com caso de TB em bovinos e das formas intestinal e ganglionar periférica. Enquanto que no grupo F verificou-se maior proporção de casos com a forma clínica ganglionar periférica e de coinfecção HIV/TB. Os grupos A, C e D também apresentaram características distintas em relação ao total de casos de TB e associadas à TBz segundo a literatura, porém de maneira menos nítida. O grupo E não apresentou características relacionadas aos casos típicos da TBz. Dentre os pacientes menores de 15 anos de idade, após ajustes, destacaram-se como fatores associados à TB ganglionar e/ou intestinal, residir em município com menores índices de urbanização e com casos de TB em bovino conforme registro oficial. Entte os pacientes com 15 anos ou mais de idade, destacaram-se as associações com a ocupação de trabalhador rural e com a de magarefe. A distribuição dos tipos de rebanhos bovinos foi ampla sendo registrados casos da doença em animais em praticamente todas as regiões do estado. Conclusões: Os dados de vigilância da TB humana e animal, permitiram identificar grupos de pacientes com características associadas à TBz, salietando a importância da aplicação da proposta de Saúde Única, além de oferecerem subsídios para o desenvolvimento de um componente para TBz na vigilância da TB no estado de São Paulo, assim como, para pesquisas sobre o tema. / Objectives: To identify and compare groups of patients potentially at risk for zoonotic tuberculosis (zTB), investigating the existence of associated factors. To present the spatial distribution of cases of tuberculosis (TB) in cattle and human cases. Method: This is a descriptive study of confirmed cases of TB by all clinical forms, residents in the state of São Paulo, from 2006 to 2015. Six potential risk groups for zTB were defined according to literature. The descriptive analysis was performed separately for patients younger than 15 years and patients 15 years of age or older, comparing the groups identified with the study population using the Chi-square / Fisher\'s Exact test. The existence of an association between intestinal and/or ganglion TB (accepted as a proxy for a suspected zTB case) and the exposures of interest was investigated by the estimates of the crude and adjusted odds ratio, with the respective 95% confidence intervals, using logistic regression. The distribution of suspected cases was presented in thematic maps. Results: After applying the criteria established for the study, 190,368 TB cases were included in all clinical forms. Among them: 134 were less than 15 years old and lived in municipalities with up to 20,000 inhabitants (group A); the others were 15 years old or over, with 1,238 rural workers (group B); 201 magarefes (group C); 1,012 resided in municipalities with up to 20,000 inhabitants and with herds infected by TB (group D); 2,776 South American immigrants (group E); and 160 African immigrants (group F). Groups B and F were the ones that presented the most similar characteristics to the zTB described in the literature. In group B, the highest proportions of cases of residents in municipalities with cases of TB in cattle and of the intestinal and peripheral ganglion forms were highlighted. While in the F group there was a higher proportion of cases with peripheral ganglionic form and HIV / TB co-infection. Groups A, C and D also presented distinct characteristics in relation to total TB cases and associated with TB, according to the literature, but less clearly. Group E did not present characteristics related to typical zTB cases. Among patients younger than 15 years of age, after adjustments, they were identified as factors associated with lymph node and/or intestinal TB, living in a municipality with lower rates of urbanization and with cases of TB in cattle according to official records. Among the patients aged 15 years and over, the associations with the occupation of rural workers and magarefe stood out. The distribution of bovine herd types was extensive and cases of the disease were recorded in animals in practically all regions of the state. Conclusions: Human and animal TB surveillance data allowed the identification of groups of patients with characteristics associated with zTB, stressing the importance of applying the One Health proposal, as well as providing subsidies for the development of a component for zTB in TB surveillance in the state of São Paulo, as well as for research on the subject.

Bovine tuberculosis (TB) is a contagious neglected zoonosis of cattle that is prevalent but under-investigated in Cameroon, hence this study was designed to assess the epidemiology of bovine TB in cattle, risks for M. bovis infection in cattle and humans; and public health implications of zoonotic bovine TB in the highlands of Cameroon. A retrospective study of meat inspection records (1994 – 2010) was done to estimate the prevalence of TB lesions in slaughtered cattle in the North West region. The prevalence of bovine TB and anti-bovine TB antibodies in live cattle based on tuberculin skin tests (2 surveys) and immune-chromatographic assays respectively were carried out in the Western and Adamawa highlands of Cameroon. The performance of the tuberculin tests for bovine TB diagnosis in cattle using various tuberculin skin test cut-off points against the detection of anti-bovine TB antibodies (hypothesised risks of exposure) was compared. Suspected TB lesions from slaughtered cattle and infected human sputa were cultured on Lowentein – Jesen and Middlebrook 7H9 media to isolate mycobacteria agents for molecular genotyping using genomic deletion analysis and spoligotyping. Risk factors for exposure and transmission of zoonotic bovine TB infection of cattle and cattle professionals, and its public health significance were determined using structured questionnaires. Seventeen years of meat inspection record revealed that suspect TB lesions were identified in 599 of 129,165 slaughtered cattle at the Bamenda abattoir. The lungs and associated lymph nodes (over 60%) were the most affected tissues. Other results showed that the prevalence of anti-bovine TB antibodies in cattle in the study regions was 37.17%. Chi square statistics revealed that irrespective of the tuberculin test cut-off value (P<0.05; χ2>48), strong associations existed between the detection of anti-bovine TB antibodies and disease status. A 95% confidence interval analysis of the comparative cervical tuberculin tests revealed that the prevalence rates were 4.67% – 7.15%, 12.02% – 15.67% and 20.56% – 24.98% at the ≥ 4mm, ≥ 3mm and ≥ 2mm cut-off points, respectively. Overall, the best test performance was realised at ≥ 3-mm, though the ≥ 2-mm cut-off point predicted more positive reactors. Age, sex, breed and husbandry practices served as significant (P<0.05) risks to the prevalence and exposure of bovine TB in cattle. The feedbacks from cattle professionals suggested that there was high possibility of cattle to cattle and cattle to human transmission of bovine TB such as intimate and repeated animal / animal and animal / human interactions, consuming unpasteurised milk and eating raw meat. Genomic deletion analysis of cultured isolates showed evidence of M. tuberculosis from cattle and M. bovis from human while spoligotyping identified five cattle M. bovis strains; and four spoligotype patterns that had not been previously described anywhere. The study has important epidemiological and public health implications requiring prompt and decisive actions from the Cameroonian authority towards controlling zoonotic bovine TB in both humans and animals. A multidisciplinary approach is needed for further collaborative research and effective control strategies such as enhancing the awareness of people to this deadly disease through continuous education, proper food handling and personal hygiene, healthy husbandry practices and maintenance of the environment.