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
Universidade Federal do Ceará , Faculdade de Medicina, Departamento de Patologia e Medicina Legal , Fortaleza , Ceará , Brazil.
Instituto Evandro Chagas , Seção de Bacteriologia e Micologia, Ananindeua , Pará , Brazil.
Rev Inst Med Trop Sao Paulo. 2020 Feb 7;62:e4. doi: 10.1590/S1678-9946202062004. eCollection 2020.
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.
在巴西塞阿拉州首府福塔莱萨，2018年结核病（TB）的检出率为每10万居民65.5例，治愈率为59.1%，高于全国平均水平。本研究调查了与耐多药结核病（DR-TB）相关的危险因素，并确定了耐药表型和赋予耐药性的突变。还确定了巴西福塔莱萨DR-TB的地理分布。2017年3月至2018年2月，从巴西福塔莱萨一家转诊医院的患者中获得了41株DR-TB分离株和69株药物敏感型肺结核分离株。对样本进行了耐药性的表型和基因分析；还分析了参与者的空间分布。参与者中的原发耐药率很高（50.9%）。确定了以下DR的危险因素：女性（p = 0.03）、患有糖尿病（p < 0.01）、既往有结核病病史（p < 0.01）以及家庭内接触者数量（p < 0.01）。通过多重等位基因特异性聚合酶链反应分析检测到katG基因（65.8%）、rpoB基因（43.9%）、inhA启动子（14.6%）和gyrA基因（9.8%）发生突变。测序确定了katG基因（75.6%）、inhA启动子（19.5%）、rpoB基因（85.4%）和gyrA基因（100%）发生突变。rrs基因未发生突变。空间分析显示DR-TB分离株分布在福塔莱萨市社会经济地位较低的地区。我们的结果强调了检测结核病药物耐药性的重要性。由于福塔莱萨大量存在广泛耐药前的DR-TB病例，gyrA基因中发现的耐药性令人担忧。
