Molecular characterization of pre-extensive drug resistant Mycobacterium tuberculosis in Northeast Brazil

In Fortaleza, the capital of Ceara State, Brazil, the detection rate of tuberculosis (TB) in 2018 was 65.5/100,000 inhabitants with a cure rate of 59.1%, which is higher than the country average. This study investigated the risk factors associated with drug-resistant tuberculosis (DR-TB) and identif...

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Published in:	Revista do Instituto de Medicina Tropical de São Paulo Vol. 62; pp. e4 - 10
Main Authors:	Campelo, Thales Alves, Lima, Luana Nepomuceno Costa, Lima, Karla Valéria Batista, Silva, Caroliny Soares, Conceição, Marília Lima da, Barreto, José Antonio Pereira, Mota, Aquiles Paulino Peres, Sancho, Soraya de Oliveira, Frota, Cristiane Cunha
Format:	Journal Article
Language:	English
Published:	Brazil Instituto de Medicina Tropical de Sao Paulo 01-01-2020 Instituto de Medicina Tropical Instituto de Medicina Tropical de São Paulo Universidade de São Paulo (USP)
Subjects:	Adult Antitubercular Agents - pharmacology Case-Control Studies Drug Resistance, Multiple, Bacterial - drug effects Drug Resistance, Multiple, Bacterial - genetics Female Genotype Geography, Medical Humans Microbial Sensitivity Tests Middle Aged Multidrug-resistant TB Multiplex Polymerase Chain Reaction Mutation - genetics Mycobacterium tuberculosis Mycobacterium tuberculosis - drug effects Mycobacterium tuberculosis - genetics Mycobacterium tuberculosis - isolation & purification Original Phenotype Pre-extensively drug-resistant TB Pregnancy Primary resistance Prospective Studies Risk Factors Socioeconomic Factors TROPICAL MEDICINE Tuberculosis, Multidrug-Resistant - microbiology Pre-extensively drug-resistant TB Multidrug-resistant TB Mycobacterium tuberculosis Primary resistance Risk factors
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Summary:	In Fortaleza, the capital of Ceara State, Brazil, the detection rate of tuberculosis (TB) in 2018 was 65.5/100,000 inhabitants with a cure rate of 59.1%, which is higher than the country average. This study investigated the risk factors associated with drug-resistant tuberculosis (DR-TB) and identified the drug-resistance phenotype and resistance-conferring mutations. The geographic distribution of DR-TB in Fortaleza, Brazil, was also determined. From March 2017 to February 2018, 41 DR-TB isolates and 69 drug-susceptible pulmonary TB isolates were obtained from patients seen at a referral hospital in Fortaleza, Brazil. Samples were subjected to phenotypic and genetic analysis of resistance; the spatial distribution of the participants was also analyzed. Primary resistance was high (50.9%) among participants. The following risk factors for DR were identified: being female ( p = 0.03), having diabetes ( p < 0.01), history of previous TB disease ( p < 0.01), and the number of intra-domiciliary contacts ( p < 0.01). Analysis by multiplex allele-specific polymerase chain reaction detected mutations in the genes katG (65.8%) , rpoB (43.9%), inhA promoter (14.6%), and gyrA (9.8%). Sequencing identified mutations in the the genes katG (75.6%), inhA promoter (19.5%), rpoB (85.4%), and gyrA (100%). There was no mutation in the rrs gene. Spatial analysis showed DR-TB isolates distributed in areas of low socioeconomic status in the city of Fortaleza. Our results emphasized the importance of detecting resistance to TB drugs. The resistance found in the gene gyrA is of concern due to the high number of pre-extensive DR-TB cases in Fortaleza.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 CONFLICT OF INTERESTS The authors declare no conflict of interests. AUTHORS’ CONTRIBUTIONS Cristiane Cunha Frota: conception, design, analysis and interpretation of data, article writing and critical review; Thales Alves Campelo: laboratory assays, analysis and interpretation of data, article writing and critical review; Caroliny Soares Silva, Aquiles Paulino Peres Mota and Soraya de Oliveira Sancho: laboratory assays, analysis and interpretation of data, article writing; Luana Nepomuceno Gondim Costa Lima, Marília Lima da Conceição and Karla Valéria Batista Lima: laboratory assays, analysis and interpretation of data, article writing and critical review; José Antonio Pereira Barreto: analysis and interpretation of data, article writing. All the authors read and approved the final version of the manuscript.
ISSN:	1678-9946 0036-4665 1678-9946
DOI:	10.1590/s1678-9946202062004