Komakech Kevin, Nakiyingi Lydia, Fred Ashab, Achan Beatrice, Joloba Moses, Kirenga Bruce J, Ssengooba Willy
Makerere University.
Makerere University Lung Institute, Makerere University College of Health Sciences.
Res Sq. 2023 Sep 28:rs.3.rs-3324330. doi: 10.21203/rs.3.rs-3324330/v1.
We evaluated the effect of mixed-MTB strain infection on the performance of Line Probe Assay (LPA) and GeneXpert MTB/RIF (Xpert) assays among patients initiating MDR-TB treatment in Uganda.
This was a cross-sectional study using sputum specimens collected from participants screened for STREAM 2 clinical trial between October 2017 and October 2019. Samples from 62 MTB smear-positive patients and rifampicin-resistant patients from the peripheral health facilities were processed for Xpert and LPA as screening tests for eligibility in the trial. From November 2020, processed stored sputum samples were retrieved and genotyped to determine the presence of mixed-MTB strain infection using a standard 24-locus Mycobacterial Interspersed Repetitive Unit-Variable Number Tandem-Repeat (MIRU-VNTR). Samples with at least 20/24 MIRU-VNTR loci amplified were considered for analysis. Agar proportional Drug Susceptibility Test (DST) was performed on culture isolates of samples that had discordant results between LPA and Xpert. The impact of the presence of mixed-MTB strain on Xpert and LPA test interpretation was analyzed.
A total of 53/62 (85%) samples had analyzable results from MIRU-VNTR. The overall prevalence of mixed-MTB infection was 5/53 (9.4%). The prevalence was highest among males 3/33 (9.7%) and among middle-aged adults, 4/30 (13.3%). Lineage 4 of MTB contributed 3/33 (9.1%) of the mixed-MTB infection prevalence. Having mixed MTB strain infection increased the odds of false susceptible Xpert test results (OR 7.556, 95% CI 0.88-64.44) but not for LPA. Being HIV-positive () independently predicted the presence of mixed MTB infection.
The presence of mixed-MTB strain infection may affect the performance of the GeneXpert test but not for LPA. For patients with high pre-test probability of rifampicin resistance, an alternative rapid method such as LPA should be considered.
我们评估了混合结核分枝杆菌菌株感染对乌干达开始耐多药结核病治疗患者的线性探针分析（LPA）和GeneXpert MTB/RIF（Xpert）检测性能的影响。
这是一项横断面研究，使用从2017年10月至2019年10月为STREAM 2临床试验进行筛查的参与者收集的痰标本。从周边医疗机构收集的62例结核分枝杆菌涂片阳性且耐利福平的患者样本，作为该试验合格性的筛查检测，进行Xpert和LPA检测。从2020年11月起，检索已处理保存的痰标本并进行基因分型，使用标准的24位点分枝杆菌散布重复单位-可变数目串联重复序列（MIRU-VNTR）来确定是否存在混合结核分枝杆菌菌株感染。至少20/24个MIRU-VNTR位点扩增的样本纳入分析。对LPA和Xpert结果不一致的样本培养分离株进行琼脂比例法药敏试验（DST）。分析混合结核分枝杆菌菌株的存在对Xpert和LPA检测结果判读的影响。
共有53/62（85%）的样本通过MIRU-VNTR获得了可分析结果。混合结核分枝杆菌感染的总体患病率为5/53（9.4%）。患病率在男性中最高，为3/33（9.7%），在中年成年人中为4/30（13.3%）。结核分枝杆菌谱系4占混合结核分枝杆菌感染患病率的3/33（9.1%）。混合结核分枝杆菌菌株感染增加了Xpert检测结果假敏感的几率（比值比7.556，95%置信区间0.88 - 64.44），但对LPA检测结果无此影响。HIV阳性独立预测混合结核分枝杆菌感染的存在。
混合结核分枝杆菌菌株感染的存在可能影响GeneXpert检测的性能，但对LPA检测无影响。对于利福平耐药预测试验概率高的患者，应考虑使用LPA等替代快速方法。
