Mycobacterium tuberculosis mixed infections and drug resistance in sub-Saharan Africa: a systematic review.

Background: Sub-Saharan Africa, is a region that records high rates of TB infection. Mycobacterium tuberculosis mixed strain infection, especially when the strains involved are of different susceptibilities, is an area of great interest because it is linked with an increased risk of treatment failure and transmission of resistant strains within the population. This paper reviewed original studies that reported MTB mixed infection and heteroresistance in the region between 2010 and 2020 to understand the extent of mixed strain infection and heteroresistance in the region. This information is very critical in the control of TB and ending the TB epidemic by 2035 as per the World Health Organization's vision. Methods: pubmed, Scopus, JSTOR, AJOL, and Google Scholar databases were searched through both key terms and subject headings. The literature was screened, assessed for the quality and evidence synthesized. Results: Eighteen original articles were included in this review after having met the inclusion criteria. The frequency of mixed strain infection reported in these studies varied between 2.8% and 21.1% while drug resistance range between 0.06% to 19% depending on the study design and the drug susceptibility screening technique utilized. The majority of the studies (50%) utilized Spoligotyping in conjunction with MIRU-VNTR typing in the detection of mixed infections. Conclusion: Despite the scarcity of data on mixed infections and heteroresistance in sub-Saharan Africa, various studies have revealed that these conditions are frequent in the region than previously thought. Given the evidence of the effect of mixed infections on drug resistance and treatment outcome, we conclude that mixed infection is an unavoidable topic for future studies.

Detection of Mycobacterium tuberculosis multiple strains in sputum samples from patients with pulmonary tuberculosis in south western Uganda using MIRU-VNTR.

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.

Rifampicin and isoniazid drug resistance among patients diagnosed with pulmonary tuberculosis in southwestern Uganda.

Multidrug-resistant tuberculosis (MDR-TB) has become a major threat to the control of tuberculosis globally. Uganda is among the countries with a relatively high prevalence of tuberculosis despite significant control efforts. In this study, the drug resistance of Mycobacterium tuberculosis to rifampicin (RIF) and isoniazid (INH) was investigated among patients diagnosed with pulmonary tuberculosis in Southwestern Uganda. A total of 283 sputum samples (266 from newly diagnosed and 17 from previously treated patients), collected between May 2018 and April 2019 at four different TB diagnostic centres, were assessed for RIF and INH resistance using high-resolution melt curve analysis. The overall prevalence of monoresistance to INH and RIF was 8.5% and 11% respectively, while the prevalence of MDR-TB was 6.7%. Bivariate analysis showed that patients aged 25 to 44 years were at a higher risk of developing MDR-TB (cOR 0.253). Furthermore, among the newly diagnosed patients, the prevalence of monoresistance to INH, RIF and MDR-TB was 8.6%, 10.2% and 6.4% respectively; while among the previously treated cases, these prevalence rates were 5.9%, 23.5% and 11.8%. These rates are higher than those reported previously indicating a rise in MTB drug resistance and may call for measures used to prevent a further rise in drug resistance. There is also a need to conduct frequent drug resistance surveys, to monitor and curtail the development and spread of drug-resistant TB.

Diversity of Mycobacterium tuberculosis Complex Lineages Associated with Pulmonary Tuberculosis in Southwestern, Uganda.

Uganda is among the 22 countries in the world with a high burden of tuberculosis. The southwestern region of the country has consistently registered a high TB/HIV incidence rate. This study is aimed at characterizing the Mycobacterium tuberculosis complex (MTBC) genotypic diversity in southwestern Uganda. A total of 283 sputum samples from patients with pulmonary tuberculosis were genotyped using specific single nucleotide polymorphism markers for lineages 3 and 4. Most of the patients were males with a mean age of 34. The lineage 4 Ugandan family was found to be the most dominant strains accounting for 59.7% of all cases followed by lineage 3 at 15.2%. The lineage 4 non-Ugandan family accounted for 14.5% of all cases while 4.2% showed amplification for both lineage 4 and lineage 3. Eighteen samples (6.4%) of the strains remained unclassified since they could not be matched to any lineage based on the genotyping technique used. This study demonstrates that a wide diversity of strains is causing pulmonary tuberculosis in this region with those belonging to the lineage 4 Ugandan family being more predominant. However, to confirm this, further studies using more discriminative genotyping methods are necessary.

Low concentrations of Lactobacillus rhamnosus GG (Yoba®) are safe in male Drosophila melanogaster.

OBJECTIVE: The purpose of the study was to generate information on the safety of probiotics, thus the study objectives were to evaluate the effects of Yoba® on basic physiochemical properties. The study assessed male w1118 Drosophila melanogaster which were provided food supplemented with Yoba® at 1%, 3%, 6%, and 12% on motor function, total protein, catalase activity, and hydrogen peroxide scavenging activity and lifespan. RESULTS: Yoba® at high concentration (≥ 6%) increased locomotor activity in Drosophila melanogaster, however, total protein, catalase, and hydrogen peroxide scavenging activity were significantly higher at 1% Yoba® compared to 3%, 6%, and 12% Yoba®. Yoba consumed at 1% was associated with greater physiological benefits in Drosophila melanogaster. Findings in the study offer a rationale for the consumption of Yoba® at 1% in humans as is currently being promoted by the Yoba for Life consortium, however, high concentrations of Yoba® would disrupt physiological function as shown by this study.