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[Preprint]. 2023 Sep 28:rs.3.rs-3324330.
doi: 10.21203/rs.3.rs-3324330/v1.

Effect of mixed Mycobacterium tuberculosis infection on rapid molecular diagnostics among patients starting MDR-TB treatment in Uganda

Kevin Komakech  1 , Lydia Nakiyingi  1 , Ashab Fred  1 , Beatrice Achan  1 , Moses Joloba  1 , Bruce J Kirenga  2 , Willy Ssengooba  1
Affiliations

Effect of mixed Mycobacterium tuberculosis infection on rapid molecular diagnostics among patients starting MDR-TB treatment in Uganda

Kevin Komakech et al. Res Sq. .

Update in

Abstract

Background: 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.

Methods: 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.

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 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 (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.

Keywords: Accuracy; GeneXpert; LPA; Mixed MTB infection.

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Conflict of interest statement

Competing interests The authors declare no competing interests.

References

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