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Universit? Paris-Sud. Universit? Paris Saclay. Institut de Biologie Int?grative de la Cellule. I2BC. UMR9198. CEA. CNRS. Gif-sur-Yvette cedex, France / Universidade Federal do Rio de Janeiro. P?s-Gradua??o Instituto de Microbiologia Professor Paulo de G?es. Rio de Janeiro, RJ, Brazil. Universit? Paris-Sud. Universit? Paris Saclay. Institut de Biologie Int?grative de la Cellule. I2BC. UMR9198. CEA. CNRS. Gif-sur-Yvette cedex, France. Universit? Paris-Sud. Universit? Paris Saclay. Institut de Biologie Int?grative de la Cellule. I2BC. UMR9198. CEA. CNRS. Gif-sur-Yvette cedex, France / Funda??o Oswaldo Cruz. Instituto Oswaldo Cruz. Laborat?rio de Biologia Molecular Aplicada a Micobact?ria. Rio de Janeiro, RJ, Brazil. Universit? Paris-Sud. Universit? Paris Saclay. Institut de Biologie Int?grative de la Cellule. I2BC. UMR9198. CEA. CNRS. Gif-sur-Yvette cedex, France. London School of Hygiene & Tropical Medicine. Faculty of Infectious and Tropical Diseases. London, UK. Universit? Paris-Sud. Universit? Paris Saclay. Institut de Biologie Int?grative de la Cellule. I2BC. UMR9198. CEA. CNRS. Gif-sur-Yvette cedex, France / Institut Pasteur de Madagascar. Unit? des Mycobact?ries. Antananarivo, Madagascar. Institut Pasteur de Madagascar. Unit? des Mycobact?ries. Antananarivo, Madagascar. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. National Institute for Public Health and the Environment. Bilthoven, the Netherlands / Radboud University Nijmegen Medical Centre. Department of Medical Microbiology. Nijmegen, the Netherlands. Swiss Tropical & Public Health Institute. Basel, Switzerland / University of Basel. Basel, Switzerland. Swiss Tropical & Public Health Institute. Basel, Switzerland / University of Basel. Basel, Switzerland. Universidade de S?o Paulo. Faculdade de Medicina de Ribeir?o Preto. Ribeir?o Preto, SP, Brazil. Funda??o Oswaldo Cruz. Instituto Oswaldo Cruz. Laborat?rio de Biologia Molecular Aplicada a Micobact?ria. Rio de Janeiro, RJ, Brazil. Universidade Federal do Rio de Janeiro. P?s-Gradua??o Instituto de Microbiologia Professor Paulo de G?es. Rio de Janeiro, RJ, Brazil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Universit? Paris-Sud. Universit? Paris Saclay. Institut de Biologie Int?grative de la Cellule. I2BC. UMR9198. CEA. CNRS. Gif-sur-Yvette cedex, France / Universidade de S?o Paulo. Faculdade de Medicina de Ribeir?o Preto. Ribeir?o Preto, SP, Brazil. Lineage 1 (L1) is one of seven Mycobacterium tuberculosis complex (MTBC) lineages. The objective of this study was to improve the complex taxonomy of L1 using phylogenetic SNPs, and to look for the origin of the main L1 sublineage prevalent in Para, Brazil. We developed a high-throughput SNPs-typing assay based on 12-L1-specific SNPs. This assay allowed us to experimentally retrieve SNP patterns on nine of these twelve SNPs in 277 isolates previously tentatively assigned to L1 spoligotyping-based sub lineages. Three collections were used: Par?-Brazil (71); RIVM, the Netherlands (102), Madagascar (104). One-hundred more results were generated in Silico using the PolyTB database. Based on the final SNPs combination, the samples were classified into 11 clusters (C1-C11). Most isolates within a SNP-based cluster shared a mutual spoligotyping-defined lineage. However, L1/EAI1-SOM (SIT48, sp. 40) and L1/EAI6-BGD1 (SIT591, sp. 23) showed a poor correlation with SNP data and are not monophyletic. L1/EAI8-MDG and L1/EAI3-IND belonged to C5; this result suggests that they share a common ancestor. L1.1.3/SIT129, a spoligotype pattern found in SNPs-cluster C6, was found to be shared between Par?/Brazil and Malawi. SIT129 was independently found to be highly prevalent in Mozambique, which suggests a migration history from East-Africa to Brazil during the 16th?18th slave trade period to Northern Brazil.

24 páginas, 3 figuras, 1 tabla. The sequence data generated by this study has been deposited on SRA (https://www.ncbi.nlm.nih.gov/sra) under the accession number PRJNA670836. Extended data is available here: https://github.com/fmenardo/MTBC_L1_L3. DOI: https://doi.org/10.5281/zenodo.4609804 (Menardo, 2021)., Background: Lineage 1 (L1) and 3 (L3) are two lineages of the Mycobacterium tuberculosis complex (MTBC) causing tuberculosis (TB) in humans. L1 and L3 are prevalent around the rim of the Indian Ocean, the region that accounts for most of the world's new TB cases. Despite their relevance for this region, L1 and L3 remain understudied. Methods: We analyzed 2,938 L1 and 2,030 L3 whole genome sequences originating from 69 countries. We reconstructed the evolutionary history of these two lineages and identified genes under positive selection. Results: We found a strongly asymmetric pattern of migration from South Asia toward neighboring regions, highlighting the historical role of South Asia in the dispersion of L1 and L3. Moreover, we found that several genes were under positive selection, including genes involved in virulence and resistance to antibiotics. For L1 we identified signatures of local adaptation at the esxH locus, a gene coding for a secreted effector that targets the human endosomal sorting complex, and is included in several vaccine candidates. Conclusions: Our study highlights the importance of genetic diversity in the MTBC, and sheds new light on two of the most important MTBC lineages affecting humans., This work was supported by the Swiss National Science Foundation (grants 310030_188888, CRSII5_177163, IZRJZ3_164171 and IZLSZ3_170834) and the European Research Council (309540 EVODRTB and 883582-ECOEVODRTB).

Funda??o Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Programa de P?s-Gradua??o em Pesquisa Cl?nica e Doen?as Infecciosas. Rio de Janeiro, RJ, Brasil / Funda??o Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laborat?rio de Bacteriologia e Bioensaios em Micobact?rias. Rio de Janeiro, RJ, Brasil / Funda??o Oswaldo Cruz. Instituto Oswaldo Cruz. Laborat?rio de Biologia Molecular Aplicada a Micobact?rias. Rio de Janeiro, RJ, Brasil. Universidade Federal do Rio Grande do Sul. Programa de P?s-Gradua??o em Biologia Celular e Molecular. Porto Alegre, RS, Brasil / Secretaria Estadual de Sa?de do Rio Grande do Sul. Centro Estadual de Vigil?ncia em Sa?de. Centro de Desenvolvimento Cient?fico e Tecnol?gico. Porto Alegre, RS, Brasil. Funda??o Oswaldo Cruz. Escola Nacional de Sa?de P?blica Sergio Arouca. Centro de Refer?ncia Professor H?lio Fraga. Laborat?rio de Refer?ncia Nacional para Tuberculose e outras Micobacterioses. Rio de Janeiro, RJ, Brasil. Universidade do Estado do Par?. Instituto de Ci?ncias Biol?gicas e da Sa?de. P?s-Gradua??o Biologia Parasit?ria na Amaz?nia. Bel?m, PA, Brasil / Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Universidade do Estado do Par?. Instituto de Ci?ncias Biol?gicas e da Sa?de. P?s-Gradua??o Biologia Parasit?ria na Amaz?nia. Bel?m, PA, Brasil / Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Laborat?rio de Geoprocessamento. Ananindeua, PA, Brasil. International Institute of Information Technology. Department of Data Science. Bangalore, India. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Secretaria Estadual de Sa?de do Rio Grande do Sul. Centro Estadual de Vigil?ncia em Sa?de. Centro de Desenvolvimento Cient?fico e Tecnol?gico. Porto Alegre, RS, Brasil. Universidade de S?o Paulo. Faculdade de Medicina. Departamento de Cl?nica M?dica. Ribeir?o Preto, SP, Brasil. Universidade de S?o Paulo. Faculdade de Medicina. Departamento de Cl?nica M?dica. Ribeir?o Preto, SP, Brasil. Funda??o Oswaldo Cruz. Instituto Oswaldo Cruz. Laborat?rio de Biologia Molecular Aplicada a Micobact?rias. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de G?es. Laborat?rio de Micobact?rias. Rio de Janeiro, RJ, Brasil. Universidade Federal de S?o Paulo. Departamento de Microbiologia, Imunologia e Parasitologia. S?o Paulo, SP, Brasil. Instituto Adolfo Lutz. Centro de Bacteriologia. N?cleo de Tuberculose e Micobacterioses. S?o Paulo, SP, Brasil. Universit e Paris-Saclay. Ecologie Systematique Evolution. Centre National de la Recherche Scientifique. AgroParisTech, Orsay, France. Funda??o Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laborat?rio de Bacteriologia e Bioensaios em Micobact?rias. Rio de Janeiro, RJ, Brasil. Funda??o Oswaldo Cruz. Instituto Oswaldo Cruz. Laborat?rio de Biologia Molecular Aplicada a Micobact?rias. Rio de Janeiro, RJ, Brasil. Coordena??o Geral de Vigil?ncia das Doen?as de Transmiss?o Respirat?ria de Condi??es Cr?nicas. Bras?lia, DF, Brasil. Funda??o Oswaldo Cruz. Instituto Oswaldo Cruz. Laborat?rio de Gen?tica Molecular de Microrganismos. Rio de Janeiro, RJ, Brasil. Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de G?es. Laborat?rio de Micobact?rias. Rio de Janeiro, RJ, Brasil. Funda??o Oswaldo Cruz. Instituto Oswaldo Cruz. Laborat?rio de Biologia Molecular Aplicada a Micobact?rias. Rio de Janeiro, RJ, Brasil. Universidade do Estado do Par?. Instituto de Ci?ncias Biol?gicas e da Sa?de. P?s-Gradua??o Biologia Parasit?ria na Amaz?nia. Bel?m, PA, Brasil / Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Molecular-typing can help in unraveling epidemiological scenarios and improvement for disease control strategies. A literature review of Mycobacterium tuberculosis transmission in Brazil through genotyping on 56 studies published from 1996-2019 was performed. The clustering rate for mycobacterial interspersed repetitive units - variable tandem repeats (MIRUVNTR) of 1,613 isolates were: 73%, 33% and 28% based on 12, 15 and 24-loci, respectively; while for RFLP-IS6110 were: 84% among prison population in Rio de Janeiro, 69% among multidrug-resistant isolates in Rio Grande do Sul, and 56.2% in general population in S?o Paulo. These findings could improve tuberculosis (TB) surveillance and set up a solid basis to build a database of Mycobacterium genomes

CNPq (207,071/2014-4), CAPES (Finance Code 001), Swiss National Science Foundation (grants 310030_166687 and IZRJZ3_164171) Universidade do Estado do Par?. Instituto de Ci?ncias Biol?gicas e da Sa?de. P?s-Gradua??o em Biologia Parasit?ria na Amaz?nia. Bel?m, PA, Brasil / Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. International Institute of Information Technology. Department of Data Science. Bangalore, India. Universidade do Estado do Par?. Instituto de Ci?ncias Biol?gicas e da Sa?de. P?s-Gradua??o em Biologia Parasit?ria na Amaz?nia. Bel?m, PA, Brasil. University of Basel. Basel, Switzerland / Swiss Tropical & Public Health Institute. Basel, Switzerland. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Centro de Inova??es Tecnol?gicas. Ananindeua, PA, Brasil. Universidade do Estado do Par?. Instituto de Ci?ncias Biol?gicas e da Sa?de. P?s-Gradua??o em Biologia Parasit?ria na Amaz?nia. Bel?m, PA, Brasil / Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Universidade Federal do Esp?rito Santo. N?cleo de Doen?as Infecciosas. Vit?ria, ES, Brasil. Funda??o Oswaldo Cruz. Instituto Oswaldo Cruz. Laborat?rio de Gen?tica Molecular de Microrganismos. Rio de Janeiro, RJ, Brasil. Universidade do Estado do Par?. Instituto de Ci?ncias Biol?gicas e da Sa?de. P?s-Gradua??o em Biologia Parasit?ria na Amaz?nia. Bel?m, PA, Brasil. Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Professor Paulo de G?es. Laborat?rio de Micobact?rias. Rio de Janeiro, RJ, Brasil. University of Basel. Basel, Switzerland / Swiss Tropical & Public Health Institute. Basel, Switzerland. Funda??o Oswaldo Cruz. Instituto Oswaldo Cruz. Laborat?rio de Biologia Molecular Aplicada a Micobact?rias. Rio de Janeiro, RJ, Brasil. Universidade do Estado do Par?. Instituto de Ci?ncias Biol?gicas e da Sa?de. P?s-Gradua??o em Biologia Parasit?ria na Amaz?nia. Bel?m, PA, Brasil / Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Funda??o Oswaldo Cruz. Instituto Oswaldo Cruz. Laborat?rio de Biologia Molecular Aplicada a Micobact?rias. Rio de Janeiro, RJ, Brasil / Funda??o Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Programa de P?s-Gradua??o em Pesquisa Cl?nica e Doen?as Infecciosas. Rio de Janeiro, RJ, Brasil / Funda??o Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laborat?rio de Bacteriologia e Bioensaios em Micobact?rias. Rio de Janeiro, RJ, Brasil. BACKGROUND The evaluation of procedures for drug susceptibility prediction of Mycobacterium tuberculosis based on genomic data against the conventional reference method test based on culture is realistic considering the scenario of growing number of tools proposals based on whole-genome sequences (WGS). OBJECTIVES This study aimed to evaluate drug susceptibility testing (DST) outcome based on WGS tools and the phenotypic methods performed on isolates of M. tuberculosis Lineage 1 from the state of Par?, Brazil, generally associated with low levels of drug resistance. METHODOLOGY Culture based DST was performed using the Proportion Method in L?wenstein-Jensen medium on 71 isolates that had been submitted to WGS. We analysed the seven main genome sequence-based tools for resistance and lineage prediction applied to M. tuberculosis and for comparison evaluation we have used the Kappa concordance test. FINDINGS When comparing the WGS-based tools against the DST, we observed the highest level of agreement using TBprofiler. Among the tools, TB-profiler, KvarQ and Mykrobe were those which identified the largest number of TB-MDR cases. Comparing the four most sensitive tools regarding resistance prediction, agreement was observed for 43 genomes. MAIN CONCLUSIONS Drug resistance profiling using next-generation sequencing offers rapid assessment of resistanceassociated mutations, therefore facilitating rapid access to effective treatment.

Universidade Federal de Goi?s. Hospital das Cl?nicas. Goi?nia, GO, Brazil. Funda??o Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Programa de P?s-gradua??o em Pesquisa Cl?nica e Doen?as Infecciosas. Rio de Janeiro, RJ, Brazil / Funda??o Oswaldo Cruz. Instituto Oswaldo Cruz. Laborat?rio de Biologia Molecular Aplicada em Micobacterias. Rio de Janeiro, RJ, Brazil. Universidade Federal de Goi?s. Hospital das Cl?nicas. Goi?nia, GO, Brazil. Universidade Federal de Goi?s. Hospital das Cl?nicas. Goi?nia, GO, Brazil. Funda??o Oswaldo Cruz. Instituto Oswaldo Cruz. Laborat?rio de Biologia Molecular Aplicada em Micobacterias. Rio de Janeiro, RJ, Brazil / Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Professor Paulo de G?es. Rio de Janeiro, RJ, Brazil. Instituto de Biomedicina Dr. Jacinto Convit. Instituto de Biomedicina. San Jose, Caracas, Venezuela / Universidad de Las Am?ricas. Facultad de Ciencias de La Salud. One Health Research Group. Quito, Ecuador. Funda??o Oswaldo Cruz. Centro de Refer?ncia Professor H?lio Fraga. Rio de Janeiro, RJ, Brazil. Funda??o Oswaldo Cruz. Centro de Refer?ncia Professor H?lio Fraga. Rio de Janeiro, RJ, Brazil. Funda??o Oswaldo Cruz. Centro de Refer?ncia Professor H?lio Fraga. Rio de Janeiro, RJ, Brazil. Funda??o Oswaldo Cruz. Centro de Refer?ncia Professor H?lio Fraga. Rio de Janeiro, RJ, Brazil. Funda??o Oswaldo Cruz. Centro de Refer?ncia Professor H?lio Fraga. Rio de Janeiro, RJ, Brazil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. International Institute of InformationTechnology - Bangalore. Department of Data Science. Bangalore, India. Corporaci?n para Investigaciones Biol?gicas. Medell?n, Colombia. Corporaci?n para Investigaciones Biol?gicas. Medell?n, Colombia. Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Professor Paulo de G?es. Rio de Janeiro, RJ, Brazil. Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Professor Paulo de G?es. Rio de Janeiro, RJ, Brazil. Funda??o Oswaldo Cruz. Instituto Oswaldo Cruz. Laborat?rio de Biologia Molecular Aplicada em Micobacterias. Rio de Janeiro, RJ, Brazil. Funda??o Oswaldo Cruz. Instituto Oswaldo Cruz. Laborat?rio de Biologia Molecular Aplicada em Micobacterias. Rio de Janeiro, RJ, Brazil. Institute of Tropical Medicine. Mycobacteriology Unit. Antwerp, Belgium. Institute of Tropical Medicine. Mycobacteriology Unit. Antwerp, Belgium. Universidade Federal de Goi?s. Instituto de Patologia Tropical e Sa?de P?blica. Goi?nia, GO, Brazil. Funda??o Oswaldo Cruz. Instituto Oswaldo Cruz. Laborat?rio de Biologia Molecular Aplicada em Micobacterias. Rio de Janeiro, RJ, Brazil. Human tuberculosis (TB) is caused by members of the Mycobacterium tuberculosis complex (MTBC), including Mycobacterium tuberculosis var. tuberculosis (MTB) and Mycobacterium tuberculosis var. africanum (MAF). While MTB is isolated worldwide, MAF is almost completely restricted to the African continent, and despite the historical proximity between Brazil and Africa during the slave trade, no case of TB being caused by MAF has been reported in Brazil to date. We hereby describe the first case of TB caused by MAF in Brazil comparing its genome against the published ones. A female patient who had never visited Africa presented with clinical symptoms typical of pulmonary TB. Based on 16S rRNA gene sequencing, the cultured isolate was identified as belonging to MTBC and partial sequence of the hsp65 gene was identical to that of MAF. This was confirmed by genotyping based on detection of Single Nucleotide Polymorphism (SNP), Region of Difference (RD) and spoligotyping. The isolate presented the Shared International Typing (SIT) 181. In the whole-genome comparison against MAF genomes available on published EMBL-EBI European Nucleotide Archive (ENA), the Brazilian genome (MAFBRA00707) was identified as belonging to Lineage 6 and clustered with isolates from The Gambia. This is the first report of the isolation of MAF from a patient from Brazil, without evidence of having any contact with an African index case

This work was funded by Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (CAPES), Institut d'Estudis Catalans (IEC) and the Swiss National Science Foundation (grants 310030_166687 and IZRJZ3_164171). Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Go?s. Rio de Janeiro, RJ, Brazil. Universidade do Estado do Par?. Programa de P?s-gradua??o em Biologia Parasit?ria na Amaz?nia. Bel?m, PA, Brazil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Universidade do Estado do Par?. Programa de P?s-gradua??o em Biologia Parasit?ria na Amaz?nia. Bel?m, PA, Brazil. Universidade do Estado do Par?. Programa de P?s-gradua??o em Biologia Parasit?ria na Amaz?nia. Bel?m, PA, Brazil. Universidade do Estado do Par?. Programa de P?s-gradua??o em Biologia Parasit?ria na Amaz?nia. Bel?m, PA, Brazil. Universidade Federal do Par?. Hospital Universit?rio Jo?o de Barros Barreto. Bel?m, PA, Brazil. Universidade Federal do Par?. Hospital Universit?rio Jo?o de Barros Barreto. Bel?m, PA, Brazil. University of Delhi. Delhi College of Engineering. New Delhi, India. Universidade do Estado do Par?. Programa de P?s-gradua??o em Biologia Parasit?ria na Amaz?nia. Bel?m, PA, Brazil / Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Funda??o Oswaldo Cruz. Instituto Oswaldo Cruz. Laborat?rio de Biologia Molecular Aplicada as Micobact?rias, Rio de Janeiro, RJ, Brazil. Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Go?s. Rio de Janeiro, RJ, Brazil. Universidade Federal do Cear?. Departamento de Patologia e Medicina Legal. Fortaleza, CE, Brazil. Swiss Tropical & Public Health Institute. Basel, Switzerland / University of Basel. Basel, Switzerland. Swiss Tropical & Public Health Institute. Basel, Switzerland / University of Basel. Basel, Switzerland. Funda??o Oswaldo Cruz. Instituto Oswaldo Cruz. Laborat?rio de Biologia Molecular Aplicada as Micobact?rias, Rio de Janeiro, RJ, Brazil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil / Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Tuberculosis (TB) is an infectious disease with a higher risk for infection and disease among household contacts (HHC). Here, we report a molecular epidemiology-based approach to study disease transmission and the genetic characteristics of Mycobacterium tuberculosis (Mtb) strains among HHC in the city of Belem, the capital of the state of Para in north Brazil. The study included 63 TB patients belonging to 26 HHC groups (HHC1 to HHC26). Spoligotyping and 24-loci Mycobacterial Interspersed Repetitive Unit - Variable Number of Tandem Repeat (MIRU-VNTR) revealed indistinguishable bacterial genotypes among 26 patients in 14 (53.8%) HHC groups. Drug susceptibility testing (DST) revealed that 45 (71.4%) of the Mtb isolates were multidrug resistant. The major cluster composed of isolates from five HHCs and on three of these, whole genome sequencing (WGS) was performed confirming their high genetic similarity. These results pinpoint the need for improved vigilance for TB control in households in the city of Bel?m. When comparing WGS versus phenotypic resistance detection methods as DST and Minimum Inhibitory Concentration (MIC) our data suggest that depending on the colonies selection, results may present variation.

Universidade Federal Rural da Amaz?nia. Instituto da Sa?de e Produ??o Animal. Bel?m, PA, Brazil. Universidade Federal Rural da Amaz?nia. Instituto da Sa?de e Produ??o Animal. Bel?m, PA, Brazil / Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Centro de Refer?ncia Professor H?lio Fraga. Rio de Janeiro, RJ, Brazil. Universidade Federal do Par?. Bel?m, PA, Brasil. Universidade do Estado do Par?. Bel?m, PA, Brasil. Universidade do Estado do Par?. Bel?m, PA, Brasil / Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Background: Tuberculosis is an infectious disease caused by the Mycobacterium tuberculosis complex has already been identified in a great number of wild species. Captive animals may have a potential source for zoonoses, because is related to factors such as cohabitation, direct contact with the public, presence of biological vectors, nutritional deficiencies, absence of sanitary barriers, precautionary hygienic measures and sanitary vigilance. In Brazil, there is little information on tuberculosis in captivity animals, and little attention is given to the risks of disease transmission from humans. The aim of this study was to report the first diagnosed case of tuberculosis Tapirus terrestris in Brazilian Amazon region. Case: One Tapirus terrestris was kept by local zoobotanic foundation in city of Marab?, Southeast of Par? state, Brazilian Amazon, and became ill. Physical examination revealed cough, sneezing, nasal outflow, dyspnea, hyperthermia and lethargy, leading to death. Necropsy demonstrated severe pulmonary alterations: thickening of the inter-alveolar septa, alveolar emphysema, and miliary nodules with dimensions up to 5 mm, which were yellowish-white, caseous, and sometimes calcified. Additionally, large areas of caseous compaction of the parenchyma, characteristic of caseous tuberculosis. Histopathological analysis revealed a process characteristic of mycobacterial infection, with alveoli filled with caseous exudate and thickened septa and fibrocytes, in addition to recently formed tubercles, some with caseous necrosis, calcifications and Langhans cells. In the Ziehl-Neelsen staining, alcohol-acid resistant bacilli were observed in the mesenteric lymph nodes. No mycobacterial growth was observed in Lowenstein-Jensen culture medium. A nested PCR followed by a sequencing assay targeting the hsp65 gene and M. tuberculosis complex member was detected. Water and M. tuberculosis H37Rv were used as negative and positive controls, respectively. Discussion: This article reports the first case of tuberculosis in T. terrestris in Amazonia. The case of infection was caused by a complex of Mycobacterium tuberculosis, as well as reports of other studies described in wild animals. This record presented clinical and pathological similarity with the cases of a tapir and coati at the zoo of Curitiba, and non-human primates in bioteries in Bel?m. The disease was reported, also, in a T. indicus female in Bangkok, Thailand. In another study with two tapirs there was positivity of tuberculin test result in a Swedish zoo. In necropsy findings of tuberculosis in a Malayan tapir showed multiple white, caseous nodules spread throughout the lungs. Studies have shown that lesions can be in various organs, among them the mediastinal and mesenteric lymph nodes, liver, spleen, kidneys, ovaries, serosa, diaphragm, intestines and uterus. For exemple in a case of disseminated tuberculosis caused by M. tuberculosis in a Malayan tapir were described multiple granulomes, some coalescent, characterized by necrotic caseous centers, with some Langhans giant cells and a discrete fibrotic zone. In the present work, the results of the anatomopathological and molecular assays confirmed the clinical suspicion of respiratory infection and established the conclusive diagnosis of pulmonary tuberculosis caused by M. tuberculosis complex member. It is worth noting that tuberculosis is an important zoonotic disease affecting survival of the species, posing an extinction threat and also a public health concern.

This study was supported by the Instituto Evandro Chagas, Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (CAPES) and the Programa de P?s-gradua??o em Biologia Parasit?ria/Universidade Estadual do Par?. Universidade do Estado do Par?. Programa de P?s-gradua??o em Biologia Parasit?ria da Amaz?nia. Bel?m, PA, Brasil. Universidade do Estado do Par?. Programa de P?s-gradua??o em Biologia Parasit?ria da Amaz?nia. Bel?m, PA, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Laborat?rio de Geoprocessamento. Ananindeua, PA, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. This study described the frequency and variety of multidrug-resistant tuberculosis (MDR-TB) cases in Par? State, Brazil. In order to record the epidemiology and spacial distribution of the disease, antimicrobial susceptibility testing (AST) and the proportion method were used. The AST was performed on 848 samples at the Instituto Evandro Chagas and a central public health laboratory in that State. Of all patients enrolled in the study, 358 (42.2%) were resistant to at least one antituberculosis (anti-TB) drug. The percentage of primary, acquired resistance and combined MDR-TB was 30.4%, 69.3% and 42.2% respectively. MDR-TB was detected in 223 (26.3%) samples. Primary MDR-TB was found in 14% of previously treated patients, while 48% exhibited acquired resistance and 62% exhibited combined resistance. Of all age groups, from 25 to 36 years old (mean age 38.7 ? 15) showed the highest proportion of resistant cases (26.3%). Seven cities in the State presented 59.6% of the cases documented in the study. These findings reflect the poor quality of the healthcare for patients in these cities. We further suggest that clinicians need to observe their patients more directly during treatment and test them more often for anti-TB drug sensitivity. The number of TB cases in Par? did not vary significantly during the period studied, but researchers did notice a slight increase in the proportion of drug-resistant cases related to the total number of cases reported in Par?. This change in the resistance rates reflects the need to improve the quality of health services for TB care. A concentration of TB cases was observed in some municipalities and in the neighborhoods of the Bel?m City. Este estudo descreveu a frequ?ncia e variedade de casos de tuberculose multirresistente (TBMR) no Estado do Par?, Brasil. A fim de registrar a epidemiologia e a distribui??o espacial da doen?a, foram utilizados testes de suscetibilidade antimicrobiana (TSA) e do m?todo proporcional (MP). O TSA foi realizado em 848 amostras no Instituto Evandro Chagas e em um laborat?rio central de sa?de p?blica naquele Estado. De todos os pacientes inclu?dos no estudo, 358 (42,2%) eram resistentes a pelo menos um medicamento antituberculose (anti-TB). A porcentagem das resist?ncias prim?ria, adquirida e TBMR foi de 30,4%, 69,3% e 42,2%, respectivamente. A TBMR foi detectada em 223 (26,3%) amostras. A TBMR prim?ria foi encontrada em 14% dos pacientes tratados anteriormente, enquanto que 48% apresentaram a resist?ncia adquirida e 62% exibiram resist?ncia combinada. De todos os grupos et?rios, o de 25-36 anos (m?dia de idade de 38,7 ? 15) apresentou a maior propor??o de casos resistentes (26%). Sete cidades do Estado apresentaram 59,6% dos casos documentados no estudo. Estes resultados refletem a baixa qualidade dos cuidados de sa?de com os doentes nestas cidades. Observa-se ainda, a necessidade de maiores cuidados dos m?dicos para com os pacientes durante o tratamento e realiza??o, com maior frequ?ncia, dos testes de sensibilidade aos medicamentos anti-TB. O n?mero de casos de TB no Par? n?o variou significativamente durante o per?odo estudado, por?m os pesquisadores notaram um ligeiro aumento na propor??o de casos resistentes aos medicamentos relacionados com o n?mero total de casos notificados no Estado. Esta mudan?a nas taxas de resist?ncia reflete a necessidade de melhorar a qualidade dos servi?os de sa?de para a aten??o ? TB. A concentra??o de casos de tuberculose foi observada em alguns munic?pios e nos bairros da Cidade de Bel?m.