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RefWorks
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Genetic Diversity and Molecular Epidemiology of Mycobacterium tuberculosis in Roraima State, Brazil
Mariana Bento Tatara
Mariana Bento Tatara
Laboratory of Research in Health Science, Faculty of Health Science, Federal University of Grande Dourados, Dourados, Brazil;
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João Perdigão
João Perdigão
Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal;
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Miguel Viveiros
Miguel Viveiros
Institute of Hygiene and Tropical Medicine (IHMT), Global Health and Tropical Medicine (GHTM), University NOVA of Lisbon, Lisbon, Portugal;
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Afrânio Kritski
Afrânio Kritski
School of Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil;
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Kesia Esther da Silva
Kesia Esther da Silva
Laboratory of Research in Health Science, Faculty of Health Science, Federal University of Grande Dourados, Dourados, Brazil;
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Flávia Patussi Correia Sacchi
Flávia Patussi Correia Sacchi
Referent Center of Tuberculosis and Leprosy, Dourados Municipal Health Secretary, Dourados, Brazil;
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Camila Camioli de Lima
Camila Camioli de Lima
Laboratory of Research in Health Science, Faculty of Health Science, Federal University of Grande Dourados, Dourados, Brazil;
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Paulo César Pereira dos Santos
Paulo César Pereira dos Santos
Laboratory of Research in Health Science, Faculty of Health Science, Federal University of Grande Dourados, Dourados, Brazil;
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Jaciara de Lourdes do Carmo Guimarães Diniz
Jaciara de Lourdes do Carmo Guimarães Diniz
Nucleus of Research in Medical Microbiology, Faculty of Medicine, Federal University of Rio Grande, Rio Grande, Brazil;
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Pedro Eduardo Almeida Silva
Pedro Eduardo Almeida Silva
Nucleus of Research in Medical Microbiology, Faculty of Medicine, Federal University of Rio Grande, Rio Grande, Brazil;
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Pedro Gomes
Pedro Gomes
Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal;
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Mônica Maria Quirino Gomes
Mônica Maria Quirino Gomes
Central Laboratory of Public Health of Roraima, Boa Vista, Brazil;
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Eunice Atsuko Totumi Cunha
Eunice Atsuko Totumi Cunha
Central Laboratory of Public Health of Mato Grosso do Sul, Campo Grande, Brazil;
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José Roberto Lapa e Silva
José Roberto Lapa e Silva
School of Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil;
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Isabel Portugal
Isabel Portugal
Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal;
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Julio Croda
Julio Croda
Oswaldo Cruz Foundation, Campo Grande, Brazil;
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School of Medicine, Federal University of Mato Grosso do Sul, Campo Grande, Brazil;
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Monica Kramer de N. Andrade
Monica Kramer de N. Andrade
Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
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National border areas are special places for the spread of Mycobacterium tuberculosis (MTB). These regions concentrate vulnerable populations and constant population movements. Understanding the dynamics of the transmission of MTB is fundamental to propose control measures and to monitor drug resistance. We conducted a population-based prospective study of tuberculosis (TB) to evaluate molecular characteristics of MTB isolates circulating in Roraima, a state on the border of Venezuela and Guyana. Eighty isolates were genotyped by IS6110-RFLP (restriction fragment length polymorphism), spoligotyping, and 24-locus mycobacterial interspersed repetitive unit-variable number of repeats tandem (MIRU-VNTR). Drug susceptibility tests were performed by using the proportion method and GeneXpert® MTB/RIF (Cepheid, Sunnyvale, CA). Isolates showing a phenotypic resistance profile were submitted to polymerase chain reaction (PCR) and sequencing. Spoligotyping showed 40 distinct patterns with a high prevalence of Latin-American and Mediterranean (LAM), Haarlem (H), and the “ill-defined” T clades. Mycobacterial interspersed repetitive unit -VNTR and IS6110-RFLP showed clustering rates of 21.3% and 30%, respectively. Drug resistance was detected in 11 (15.1%) isolates, and all were found to have primary resistance; among these, six (8.2%) isolates were streptomycin mono-resistant, four (5.4%) isoniazid mono-resistant, and one (1.3%) multidrug resistant. This is the first study on the molecular epidemiology and drug resistance profile of MTB from Roraima. Herein, we describe high diversity of genetic profiles circulating in this region that may be driven by the introduction of new strain types because of large population flow in this region. In summary, our results showed that analyses of these circulating strains can contribute to a better understanding of TB epidemiology in the northern Brazilian border and be useful to establish public health policies on TB prevention.
- Supplemental Materials (MS Word 22 KB)
Author Notes
Financial support: This work was supported by Conselho Nacional de Desenvolvimento Científico (Chamada MCTI/CNPq/MS-SCTIE grants 404237/2012-6) and by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES/MEC/Brazil) grant 88881.064961/2014-01. M. B. T received a scholarship from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). J. P. was supported by a post doc fellowship (SFRH/BPD/95406/2013) from Fundação para a Ciência e Tecnologia.
Authors’ addresses: Mariana Bento Tatara, Kesia Esther da Silva, Camila Camioli de Lima, and Paulo César Pereira dos Santos, Laboratory of Research in Health Science, Faculty of Health Science, Federal University of Grande Dourados, Dourados, Brazil, E-mails: marianabtatara@gmail.com, kesia.eds@gmail.com, camiolidelima.camila@gmail.com, and paulo.cesar.pds@gmail.com. João Perdigão, Pedro Gomes, and Isabel Portugal, Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal, E-mails: jrlperdigao@gmail.com, p-gomes-d@hotmail.com, and iportugal@ff.ulisboa.pt. Miguel Viveiros, Institute of Hygiene and Tropical Medicine (IHMT), Global Health and Tropical Medicine (GHTM), University NOVA of Lisbon, Lisbon, Portugal, E-mail: mviveiros@ihmt.unl.pt. Afrânio Kritski and José Roberto Lapa e Silva, School of Medicine, Federal University of Rio de Janeiro. Rio de Janeiro, Brazil, E-mails: kritskia@gmail.com and jrlapa@hotmail.com. Flávia Patussi Correia Sacchi, Referent Center of Tuberculosis and Leprosy, Dourados Municipal Health Secretary, Dourados, Brazil, E-mail: fpatussi@gmail.com. Jaciara de Lourdes do Carmo Guimarães Diniz and Pedro Eduardo Almeida Silva Nucleus of Research in Medical Microbiology, Faculty of Medicine, Federal University of Rio Grande, Rio Grande, Brazil, E-mail: jaciara_1988@hotmail.com and pedrefurg@gmail.com. Mônica Maria Quirino Gomes, Central Laboratory of Public Health of Roraima, Boa Vista, Brazil, E-mail: quirinomonica@yahoo.com.br. Eunice Atsuko Totumi Cunha, Central Laboratory of Public Health of Mato Grosso do Sul, Campo Grande, Brazil, E-mail: euniceatsuko@uol.com.br. Julio Croda, Oswaldo Cruz Foundation, Campo Grande, Brazil, E-mail: juliocroda@gmail.com. Monica Kramer de N. Andrade, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil, E-mail: monicakra@gmail.com.
ProCite
RefWorks
Reference Manager
BibTeX
Zotero
EndNote
-
1.
Rendon A, Centis R, Zellweger JP, Solovic I, Torres-Duque C, Cordeiro CR, de Queiroz Mello F, Manissero D, Sotgiu G, 2018. Migration, TB control and elimination: whom to screen and treat. Pulmonology 24: 99–105.
-
2.
IBGE, 2018. Censo Demográfico 2018: Características da População. Available at: https://cidades.ibge.gov.br/brasil/rr/panorama. Accessed December 19, 2018.
-
3.
Saúde Md, 2017. Indicadores prioritários para o monitoramento do Plano Nacional pelo Fim da Tuberculose como Problema de Saúde Pública no Brazil. Boletim Epidemiológico 48: 1–11.
-
4.
CIR, 2018. Atuação do Conselho Indígena de Roraima. Available at: http://www.cir.org.br/site/?page_id=158. Accessed December 10, 2018.
-
5.
Belo EN, Orellana JD, Levino A, Basta PC, 2013. Tuberculosis in Amazonian municipalities of the Brazil-Colombia-Peru-Venezuela border: epidemiological situation and risk factors associated with treatment default [article in Portuguese]. Rev Panam Salud Publica 34: 321–329.
-
6.
Correia Sacchi FP et al. 2018. Genetic clustering of tuberculosis in an indigenous community of Brazil. Am J Trop Med Hyg 98: 372–375.
-
7.
Machado LNC, Marcondes NR, Leite CQF, Santos ACB, Pavan FR, Baldin VP, Castilho AL, Siqueira VLD, Baeza LC, Berghs H, 2014. First baseline of circulating genotypic lineages of Mycobacterium tuberculosis in patients from the Brazilian borders with Argentina and Paraguay. PLoS One 9: e107106.
-
8.
Marques M, Cunha EAT, Evangelista M, Basta PC, Marques AMC, Croda J, 2017. Antituberculosis-drug resistance in the border of Brazil with Paraguay and Bolivia [Article in Portuguese]. Rev Panam Salud Publica 41: e9.
-
9.
WHO, 2017. Global Tuberculosis Report 2017. Geneva, Switzerland: World Health Organization.
-
10.
Coelho AGV, Zamarioli LA, Reis CMPV, de Lima Duca BF, 2007. Avaliação do crescimento em cordas na identificação presuntiva do complexo Mycobacterium tuberculosis. J Brasileiro Pneumologia 33: 707–711.
-
11.
Giampaglia CMS, Martins MC, Chimara E, Oliveira RS, Vieira GBdO, Marsico AG, Mello FCQ, Fonseca LdS, Kritski A, Telles MAdS, 2007. Diferenciação entre Mycobacterium tuberculosis e outras Micobactérias com ácido ρ-nitrobenzóico utilizando o sistema MGIT960 Int J Tuberc Lung Dis 11: 803–807.
-
12.
Arora J, Kumar G, Verma AK, Bhalla M, Sarin R, Myneedu VP, 2015. Utility of MPT64 antigen detection for rapid confirmation of Mycobacterium tuberculosis complex. J Glob Infect Dis 7: 66–69.
-
13.
Ministério da Saúde, Secretaria de Vigilância em Saúde, Departamento de Vigilância Epidemiológica, Brazil, 2008. Manual Nacional de Vigilância Laboratorial da Tuberculose e Outras Micobactérias. Brasilia, Brazil: Ministério da Saúde.
-
14.
Maningi NE, Daum LT, Rodriguez JD, Said HM, Peters RPH, Sekyere JO, Fischer GW, Chambers JP, Fourie PB, 2018. Multi- and extensively drug resistant Mycobacterium tuberculosis in South Africa: a molecular analysis of historical isolates. J Clin Microbiol 56: e01214–e012117.
-
15.
Boehme CC, Nabeta P, Hillemann D, Nicol MP, Shenai S, Krapp F, Allen J, Tahirli R, Blakemore R, Rustomjee R, 2010. Rapid molecular detection of tuberculosis and rifampin resistance. New Engl J Med 363: 1005–1015.
-
16.
Van Embden J, Cave MD, Crawford JT, Dale J, Eisenach K, Gicquel B, Hermans P, Martin C, McAdam R, Shinnick T, 1993. Strain identification of Mycobacterium tuberculosis by DNA fingerprinting: recommendations for a standardized methodology. J Clin Microbiol 31: 406–409.
-
17.
Kamerbeek J, Schouls L, Kolk A, Van Agterveld M, Van Soolingen D, Kuijper S, Bunschoten A, Molhuizen H, Shaw R, Goyal M, 1997. Simultaneous detection and strain differentiation of Mycobacterium tuberculosis for diagnosis and epidemiology. J Clin Microbiol 35: 907–914.
-
18.
Supply P, Mazars E, Lesjean S, Vincent V, Gicquel B, Locht C, 2000. Variable human minisatellite‐like regions in the Mycobacterium tuberculosis genome. Mol Microbiol 36: 762–771.
-
19.
Brudey K, Driscoll JR, Rigouts L, Prodinger WM, Gori A, Al-Hajoj SA, Allix C, Aristimuño L, Arora J, Baumanis V, 2006. Mycobacterium tuberculosis complex genetic diversity: mining the fourth international spoligotyping database (SpolDB4) for classification, population genetics and epidemiology. BMC Microbiol 6: 23.
-
20.
Demay C, Liens B, Burguière T, Hill V, Couvin D, Millet J, Mokrousov I, Sola C, Zozio T, Rastogi N, 2012. SITVITWEB–a publicly available international multimarker database for studying Mycobacterium tuberculosis genetic diversity and molecular epidemiology. Infect Genet Evol 12: 755–766.
-
21.
Vitol I, Driscoll J, Kreiswirth B, Kurepina N, Bennett KP, 2006. Identifying Mycobacterium tuberculosis complex strain families using spoligotypes. Infect Genet Evol 6: 491–504.
-
22.
Supply P, Allix C, Lesjean S, Cardoso-Oelemann M, Rüsch-Gerdes S, Willery E, Savine E, de Haas P, van Deutekom H, Roring S, 2006. Proposal for standardization of optimized mycobacterial interspersed repetitive unit-variable-number tandem repeat typing of Mycobacterium tuberculosis. J Clin Microbiol 44: 4498–4510.
-
23.
Peres RL et al. 2018. Risk factors associated with cluster size of Mycobacterium tuberculosis (Mtb) of different RFLP lineages in Brazil. BMC Infect Dis 18: 71.
-
24.
Dantas NGT, Suffys PN, da Silva Carvalho W, Gomes HM, De Almeida IN, De Assis LJ, Augusto CJ, Gomgnimbou MK, Refregier G, Sola C, 2015. Genetic diversity and molecular epidemiology of multidrug-resistant Mycobacterium tuberculosis in Minas Gerais state, Brazil. BMC Infect Dis 15: 306.
-
25.
Ribeiro FKC, Pan W, Bertolde A, Vinhas SA, Peres RL, Riley L, Palaci M, Maciel EL, 2015. Genotypic and spatial analysis of Mycobacterium tuberculosis transmission in a high-incidence urban setting. Clin Infect Dis 61: 758–766.
-
26.
de Mello SB, Silva BCN, 2005. Roraima: problemas de desenvolvimento sustentável em uma região de fronteira. Redes 10: 129–149.
-
27.
Fraser B, Willer H, 2016. Venezuela: aid needed to ease health crisis. Lancet 388: 947–949.
-
28.
Benedetti MSG, 2018. Relatório Anual de Epidemiologia de Roraima 2017. Boa Vista, Brazil: Secretaria de Saúde do Estado de Roraíma, Governo do Estado de Roraíma.
-
29.
Lagos J, Couvin D, Arata L, Tognarelli J, Aguayo C, Leiva T, Arias F, Hormazabal JC, Rastogi N, Fernandez J, 2016. Analysis of Mycobacterium tuberculosis genotypic lineage distribution in Chile and neighboring countries. PLoS One 11: e0160434.
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