Alemayehu Alem, Wassie Liya, Alemayehu Dawit Hailu, Adnew Bethlehem, Neway Sebsib, Tefera Dessalegn Abeje, Ayalew Sosina, Hailu Elena, Ayele Samuel, Seyoum Berhanu, Bobosha Kidist, Abebe Markos, Aseffa Abraham, Petros Beyene, Howe Rawleigh
Department of Microbial, Cellular and Molecular Biology, College of Natural and Computational Sciences, Addis Ababa University, Addis Ababa, Ethiopia.
Armauer Hansen Research Institute (AHRI), Addis Ababa, Ethiopia.
Front Public Health. 2024 Dec 2;12:1420685. doi: 10.3389/fpubh.2024.1420685. eCollection 2024.
Clinically diagnosed pulmonary tuberculosis (TB) (CDPTB) patients account for a huge proportion of TB. However, little is known about the genetic diversity and drug resistance profile of Complex (MTBC) strains in this group of patients.
Unmatched case-control study was conducted among 313 PTB patients to compare the genetic diversity of MTBC and their drug resistance profiles among CDPTB ( = 173) and bacteriologically confirmed pulmonary TB (BCPTB) ( = 140) patients. Lowenstein-Jensen (LJ) culture, geneXpert and acid fast staining were performed on sputum specimen collected from both CDPTB and BCPTB patients. Spoligotyping, whole genome sequencing (WGS) and phenotypic drug resistance testing (DST) were done for a subset of LJ grown MTBC isolates. Data was analyzed by STATA version 17 software and a -value <0.05 were considered statistically significant.
The proportion of lineage 3 was larger among CDPTB patients (31%, 13/42) compared to BCPTB patients (15%, 11/74) (-value <0.05). A higher proportion of MTBC isolates from CDPTB 16.6% (3/18) were phenotypically resistant to one or more anti-TB drugs than BCPTB 12% (4/33) (-value >0.05). A single lineage 3 strain resistant to all the primary anti-TB drugs was detected in one CDPTB by both DST methods.
The observed differences in the genotypes of MTBC isolates between CDPTB and BCPTB patients may be attributed to challenges in the identification of CDPTB that requires further investigation on sequenced genome of the MTBC strains for better understanding and recommendation based on the current finding. There was also primary drug resistant TB among culture positive CDPTB patients which would be otherwise missed by current national protocols.
临床诊断的肺结核(TB)(CDPTB)患者占结核病患者的很大比例。然而,对于这组患者中结核分枝杆菌复合群(MTBC)菌株的遗传多样性和耐药谱了解甚少。
在313例肺结核患者中进行了非匹配病例对照研究,以比较CDPTB(n = 173)和细菌学确诊的肺结核(BCPTB)(n = 140)患者中MTBC的遗传多样性及其耐药谱。对从CDPTB和BCPTB患者收集的痰液标本进行罗氏(LJ)培养、GeneXpert检测和抗酸染色。对一部分LJ培养的MTBC分离株进行了间隔寡核苷酸分型(Spoligotyping)、全基因组测序(WGS)和表型耐药性检测(DST)。数据采用STATA 17软件进行分析,P值<0.05被认为具有统计学意义。
与BCPTB患者(15%,11/74)相比,CDPTB患者中3型分支的比例更高(31%,13/42)(P值<0.05)。CDPTB中MTBC分离株对一种或多种抗结核药物表型耐药的比例为16.6%(3/18),高于BCPTB的12%(4/33)(P值>0.05)。通过两种DST方法在一名CDPTB患者中检测到一株对所有一线抗结核药物耐药的单一3型菌株。
CDPTB和BCPTB患者之间MTBC分离株基因型的观察差异可能归因于CDPTB识别方面的挑战,这需要对MTBC菌株的测序基因组进行进一步研究,以便根据当前发现更好地理解并提出建议。在培养阳性的CDPTB患者中也存在原发性耐药结核病,而目前的国家方案可能会遗漏这些病例。