在乌干达，混合结核分枝杆菌感染对开始耐多药结核病治疗的患者快速分子诊断的影响。
Effect of mixed Mycobacterium tuberculosis infection on rapid molecular diagnostics among patients starting MDR-TB treatment in Uganda.
机构信息
Department of Medical Microbiology, Mycobacteriology (BSL-3) Laboratory, Makerere University, Kampala, Uganda.
Department of Medicine, School of Medicine, Makerere University, Kampala, Uganda.
出版信息
BMC Infect Dis. 2024 Jan 10;24(1):70. doi: 10.1186/s12879-023-08968-5.
BACKGROUND
Mixed M. tuberculosis (MTB) infection occurs when one is infected with more than one clonally distinct MTB strain. This form of infection can assist MTB strains to acquire additional mutations, facilitate the spread of drug-resistant strains, and boost the rate of treatment failure. Hence, the presence of mixed MTB infection could affect the performance of some rapid molecular diagnostic tests such as Line Probe Assay (LPA) and GeneXpert MTB/RIF (Xpert) assays.
METHODS
This was a cross-sectional study that used 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 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.
RESULTS
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 male's 3/31 (9.7%) and among middle-aged adults, 4/30 (33.3%). Lineage 4 of MTB contributed 3/5 (60.0%) 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 (P = 0.04) independently predicted the presence of mixed MTB infection.
CONCLUSIONS
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.
背景
当一个人同时感染两种以上具有明显遗传差异的结核分枝杆菌（MTB）株时，就会发生混合 MTB 感染。这种形式的感染可以帮助 MTB 菌株获得额外的突变，促进耐药菌株的传播，并提高治疗失败的速度。因此，混合 MTB 感染的存在可能会影响某些快速分子诊断测试的性能，如线探针分析（LPA）和 GeneXpert MTB/RIF（Xpert）检测。
方法
这是一项横断面研究，使用 2017 年 10 月至 2019 年 10 月期间参加 STREAM 2 临床试验筛选的参与者的痰液标本。从周边医疗机构的 62 例 MTB 涂片阳性和利福平耐药患者的样本中，进行 Xpert 和 LPA 检测，作为试验入选的筛选试验。从 2020 年 11 月开始，检索并处理储存的痰液样本，使用标准的 24 个基因座分枝杆菌插入重复单元-可变数串联重复（MIRU-VNTR）来确定是否存在混合 MTB 株感染。对至少有 20/24 个 MIRU-VNTR 基因座扩增的样本进行分析。对 LPA 和 Xpert 检测结果不一致的样本的培养分离物进行琼脂比例药物敏感性试验（DST）。分析混合 MTB 株的存在对 Xpert 和 LPA 检测结果的影响。
结果
总共 62 个样本中的 53 个（85%）具有可分析的 MIRU-VNTR 结果。混合 MTB 感染的总患病率为 5/53（9.4%）。男性患病率最高，为 3/31（9.7%），中年人群为 4/30（33.3%）。MTB 谱系 4 占混合 MTB 感染的 5/5（60.0%）。混合 MTB 株感染会增加 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），但不会增加 LPA 的几率。HIV 阳性（P=0.04）独立预测了混合 MTB 感染的存在。
结论
混合 MTB 株感染的存在可能会影响 GeneXpert 检测的性能，但不会影响 LPA。对于利福平耐药可能性高的患者，应考虑替代快速方法，如 LPA。
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