First Baseline of Circulating Genotypic Lineages of Mycobacterium tuberculosis in Patients from the Brazilian Borders with Argentina and Paraguay

Background At the triple border Brazil/Paraguay/Argentina there is easy mobility from one city to another for economic and tourism activities. This constant and fast population mobility is mainly to visit Iguazu Falls, in the Iguazu River, on the border of the Brazilian state of Paraná and the Argentina. As the incidence of tuberculosis is high in this setting, our study aimed to establish a first baseline of circulating genotypic lineages of Mycobacterium tuberculosis. Methodology/Principal Findings This study included 120 patients from 10 cities in southwestern Paraná, Brazil with pulmonary symptoms, from July 2009 to July 2011. Information about sex, age, clinical features and address was collected by reviewing the national tuberculosis notification database. Of these, 96 (80%) isolates were identified as M. tuberculosis and 22 (22.9%) were drug resistant (20, 20.8% INH mono-resistant and 2, 2.1% multidrug-resistant). All isolates were subjected to genotyping by Spoligotyping and MIRU-VNTR typing. The distribution of the isolates analyzed by spoligotyping revealed 30 distinct patterns. The four mainly detected clades were Latin American and Mediterranean (LAM), ill-defined T, Haarlem (H) and S. The MIRU-VNTR showed 85 distinct patterns. Spoligotyping combined to MIRU-VNTR allowed 90 distinct patterns. Conclusions/Significance Our study demonstrated that there is significant molecular diversity in circulating M. tuberculosis, with predominance of the LAM and T clades in cities of southwestern Paraná, Brazil, bordering Argentina and Paraguay.

[1]  S. Zanetti,et al.  Molecular characterization of Sardinian Mycobacterium tuberculosis isolates by IS6110 restriction fragment length polymorphism, MIRU-VNTR and rep-PCR. , 2010, The New Microbiologica.

[2]  P. Hunter,et al.  Numerical index of the discriminatory ability of typing systems: an application of Simpson's index of diversity , 1988, Journal of clinical microbiology.

[3]  J. Braga,et al.  Transmissão da tuberculose na tríplice fronteira entre Brasil, Paraguai e Argentina , 2011 .

[4]  Leen Rigouts,et al.  Mycobacterium tuberculosis complex genetic diversity: mining the fourth international spoligotyping database (SpolDB4) for classification, population genetics and epidemiology , 2006, BMC Microbiology.

[5]  A. Bunschoten,et al.  Rapid detection and simultaneous strain differentiation of Mycobacterium tuberculosis complex bacteria by spoligotyping. , 1998, Methods in molecular biology.

[6]  D. Chauhan,et al.  Molecular typing of Mycobacterium tuberculosis isolates from a rural area of Kanpur by spoligotyping and mycobacterial interspersed repetitive units (MIRUs) typing. , 2008, Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases.

[7]  Philip Supply,et al.  Variable human minisatellite‐like regions in the Mycobacterium tuberculosis genome , 2000, Molecular microbiology.

[8]  Nalin Rastogi,et al.  Proposal for Standardization of Optimized Mycobacterial Interspersed Repetitive Unit-Variable-Number Tandem Repeat Typing of Mycobacterium tuberculosis , 2006, Journal of Clinical Microbiology.

[9]  L. G. Espanha,et al.  Characterization of the genetic diversity of Mycobacterium tuberculosis in São Paulo city, Brazil , 2011, BMC Research Notes.

[10]  N Rastogi,et al.  Spacer oligonucleotide typing of bacteria of the Mycobacterium tuberculosis complex: recommendations for standardised nomenclature. , 2001, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.

[11]  Kovalev Sy,et al.  Genetic analysis of mycobacterium tuberculosis strains isolated in Ural region, Russian Federation, by MIRU-VNTR genotyping. , 2005 .

[12]  A. Kucknoor,et al.  A novel surface protein of Trichomonas vaginalis is regulated independently by low iron and contact with vaginal epithelial cells , 2006, BMC Microbiology.

[13]  Philip Supply,et al.  Automated High-Throughput Genotyping for Study of Global Epidemiology of Mycobacterium tuberculosis Based on Mycobacterial Interspersed Repetitive Units , 2001, Journal of Clinical Microbiology.

[14]  M. Hirata,et al.  Screening and Characterization of Mutations in Isoniazid-Resistant Mycobacterium tuberculosis Isolates Obtained in Brazil , 2004, Antimicrobial Agents and Chemotherapy.

[15]  C. Locht,et al.  High-resolution minisatellite-based typing as a portable approach to global analysis of Mycobacterium tuberculosis molecular epidemiology. , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[16]  B. Foxman,et al.  Molecular epidemiology: focus on infection. , 2001, American journal of epidemiology.

[17]  P. Barnes,et al.  current concepts Molecular Epidemiology of Tuberculosis , 2003 .

[18]  M. Hirata,et al.  Genotyping of Mycobacterium tuberculosis isolates from a low-endemic setting in northwestern state of Paraná in Southern Brazil. , 2010, Memorias do Instituto Oswaldo Cruz.

[19]  P. Barnes,et al.  Molecular epidemiology of tuberculosis. , 2003, New England Journal of Medicine.

[20]  Nalin Rastogi,et al.  SITVITWEB--a publicly available international multimarker database for studying Mycobacterium tuberculosis genetic diversity and molecular epidemiology. , 2012, Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases.

[21]  Nalin Rastogi,et al.  Mycobacterium tuberculosis population structure shift in a 5-year molecular epidemiology surveillance follow-up study in a low endemic agro-industrial setting in São Paulo, Brazil. , 2013, International journal of mycobacteriology.

[22]  N. Kurepina,et al.  Genetic analysis of mycobacterium tuberculosis strains isolated in Ural region, Russian Federation, by MIRU-VNTR genotyping. , 2005, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.