Abstract
Infections with multiple strains of Mycobacterium tuberculosis are now widely recognized as a common occurrence. Identification of patients infected with multiple strains provides both insight into the disease dynamics and the epidemiology of tuberculosis. Analysis of Mycobacterial Interspersed Repetitive Unit-Variable-Number Tandem Repeats (MIRU-VNTR) has been shown to be highly sensitive in detecting multiple M. tuberculosis strains even in sputum. The goal of this study was to identify cases of multiple M. tuberculosis strain infections among patients diagnosed with pulmonary tuberculosis in Southwestern Uganda and assessment of factors associated with multiple strain infections. DNA extracted directly from 78 sputum samples, each from an individual patient, was analyzed using the standard 24 loci MIRU-VNTR typing. Five (6.4%) of the 78 patients were infected with multiple strains of M. tuberculosis with all of them being the newly diagnosed cases while two-thirds of them were co-infected with HIV. Exact regression analysis projected that the natives were more likely to harbor multiple strains (OR; 0.981, 95% CI 0–7.926) as well as those with a high microbial load (OR; 0.390, 95% CI 0–3.8167). Despite these findings being not statistically significant due to the small sample size, this points to a critical component of disease dynamics that has clinical implications and emphasizes a need for a study using a larger cohort. It is also essential to study the potential factors associated with higher risk of exposure to newly diagnosed and HIV positive patients at the community level. In addition, our ability to detect multiple M. tuberculosis strains using the standard 24 loci MIRU-VNTR typing especially with allelic diversity in loci 2059 and 3171, which are excluded from the 15-locus MIRU-VNTR, lead us to recommend the use of this genotyping technique, especially in areas with tuberculosis endemicity similar to this study.
Highlights
Tuberculosis (TB), caused by members of the Mycobacterium tuberculosis complex (MTBC), is one of humanity’s oldest scourges and one of the leading causes of death from a single infectious agent globally, accounting for about 1.5 million fatalities and 10 million new cases each y ear[1–3]
This study aimed at identifying multiple MTBC strain infections among patients with pulmonary tuberculosis (PTB) in a high TB incidence area using MIRU-VNTR analysis and determining factors that could be associated with mixed strains infection in this area
MIRU-VNTR typing was performed on 78 sputum samples, each from an individual PTB patient
Summary
Tuberculosis (TB), caused by members of the Mycobacterium tuberculosis complex (MTBC), is one of humanity’s oldest scourges and one of the leading causes of death from a single infectious agent globally, accounting for about 1.5 million fatalities and 10 million new cases each y ear[1–3]. Mycobacterial Interspersed Repetitive Units-variable Number of Tandem Repeats (MIRU-VNTR) analysis, initially developed in 2 00117, identifies such changes in the genome by varying the copy of repeats in highly variable regions of the MTBC genome[18,19]. This method was found to be adequate for large-scale prospective studies due to its short turnaround time but still lacked the discriminatory power required for long-term, population-based studies in order to account for a large number of samples and recent strain evolution. It has been shown that multiple MTB strain infections are more common among people living in high TB burdened a reas[4,7,11,23] and accurate identification of this condition provides insight into the disease trends and helps in the management and control of TB16,24–27
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