Genotyping and drug resistance patterns of Mycobacterium tuberculosis strains observed in a tuberculosis high-burden municipality in Northeast, Brazil

Abstract

Objectives: This study has used a combination of clinical information, spoligotyping, and georeferencing system to elucidate the genetic diversity of the Mycobacterium tuberculosis isolates circulating in a TB-prevalent municipality of Northeast Brazil.

Methods: A total of 115 M. tuberculosis strains were isolated from pulmonary tuberculosis patients from January 2007 to March 2008 in Fortaleza. Drug susceptibility and spoligotyping assays were performed and place of residence of the patients were georeferenced.

Results: Of the M. tuberculosis strains studied, 51 (44.3%) isolates were resistant to at least one drug (R-TB) and 64 (55.7%) were sensitive to all the drugs tested (S-TB). A high frequency of resistance was found in previously treated cases (84%) and among new cases (16%; p<0.001). A total of 74 (64%) isolates were grouped into 22 spoligotyped lineages, while 41 (36%) isolates were identified as new. Among the predominant genotypes, 33% were Latim American Mediterranean (LAM), 12% Haarlem (H), and 5% U. There was no association of geographic distribution of RT-TB patients as compared to the controls and also the geographic location to the spoligotype patterns. The geospatial analysis revealed that 24 (23%) patients (hot spot zones) either shared the same residence or lived in a close neighborhood of a case. Among these concentration zones, the patients lived in the same residence and shared a common genotype pattern and resistance pattern.

Discussion: It was observed that the spoligopatterns family distribution was similar to that reported for South America, prevailing the LAM and H lineages. A high rate-case among the resistant TB group occurs as a result of transmitted and acquired resistance. A more effective surveillance program is needed in order to succeed in reducing tuberculosis in Northeast Brazil.

Fig. 1

Dendogram of Brazilian M. tuberculosis strains. Spoligotypes results from 115 representative strains generated by Bionumerics software (Applied Maths) using the unweighted pair group method of averages (UPGMA).

Fig. 2

Map of the municipality of Fortaleza showing the geographic origin of 105 M. tuberculosis isolates included in the study, 2007–2008. District boundaries are marked with black thin outline. The identified family lineages are represented in the legend (strain genotypes as listed in Fig. 1).

Fig. 3

Map of the municipality of Fortaleza showing the 105 M. tuberculosis isolates included in the study by residential location, 2007–2008. +, resistant TB isolates; (●) sensitive TB isolates; (□) squares with letters (A–K) represent TB patients located either in the same residence or in a close neighborhood.