Pangenome and genomic signatures linked to the dominance of the lineage-4 of Mycobacterium tuberculosis isolated from extrapulmonary tuberculosis patients in western Ethiopia.

BACKGROUND: The lineage 4 (L4) of Mycobacterium tuberculosis (MTB) is not only globally prevalent but also locally dominant, surpassing other lineages, with lineage 2 (L2) following in prevalence. Despite its widespread occurrence, factors influencing the expansion of L4 and its sub-lineages remain poorly understood both at local and global levels. Therefore, this study aimed to conduct a pan-genome and identify genomic signatures linked to the elevated prevalence of L4 sublineages among extrapulmonary TB (EPTB) patients in western Ethiopia. METHODS: A cross-sectional study was conducted at an institutional level involving confirmed cases of extrapulmonary tuberculosis (EPTB) patients from August 5, 2018, to December 30, 2019. A total of 75 MTB genomes, classified under lineage 4 (L4), were used for conducting pan-genome and genome-wide association study (GWAS) analyses. After a quality check, variants were identified using MTBseq, and genomes were de novo assembled using SPAdes. Gene prediction and annotation were performed using Prokka. The pan-genome was constructed using GET_HOMOLOGUES, and its functional analysis was carried out with the Bacterial Pan-Genome Analysis tool (BPGA). For GWAS analysis, Scoary was employed with Benjamini-Hochberg correction, with a significance threshold set at p-value ≤ 0.05. RESULTS: The analysis revealed a total of 3,270 core genes, predominantly associated with orthologous groups (COG) functions, notably in the categories of '[R] General function prediction only' and '[I] Lipid transport and metabolism'. Conversely, functions related to '[N] Cell motility' and '[Q] Secondary metabolites biosynthesis, transport, and catabolism' were primarily linked to unique and accessory genes. The pan-genome of MTB L4 was found to be open. Furthermore, the GWAS study identified genomic signatures linked to the prevalence of sublineages L4.6.3 and L4.2.2.2. CONCLUSIONS: Apart from host and environmental factors, the sublineage of L4 employs distinct virulence factors for successful dissemination in western Ethiopia. Given that the functions of these newly identified genes are not well understood, it is advisable to experimentally validate their roles, particularly in the successful transmission of specific L4 sublineages over others.

Prevalence of latent tuberculosis infection and associated risk factors in prison in East Wollega Zone of western Ethiopia.

BACKGROUND: Latent tuberculosis infection (LTBI) is the major source of active TB and is an obstacle to the strategy of World Health Organization to end TB by 2035. In Ethiopia, there are hundreds of prisons and they are conducive settings for the transmission of TB and could serve as the sources of infection to the general public. However, there is little data on the epidemiology of TB in prisons in Ethiopia. The objective of the present study was to estimate the prevalence of LTBI and evaluate associated risk factors in prisons in East Wollega Zone in western Ethiopia. METHODS: A cross-sectional design and systematic sampling technique were used to select 352 prisoners from a total of 2620 prisoners during the two months (May and June, 2019). The selected inmates were consented for their willingness to participate in the study. Thereafter, they were interviewed and 2ml of blood sample was collected from each prisoner and screened for LTBI using interferon-gamma release assay (IGRA). The data were analyzed using SPSS version 25 and logistic regression was used to model the likelihood of LTBI occurrence and to identify risk factors associated with LTBI. RESULTS: The prevalence of LTBI was 51.2% (95% CI: 46.45-57%) and higher prevalence was recorded in males (53%) than in females (43.5%) although the difference was not significant. Prisoners whose age ≥45 years (AOR = 2.48, 95%CI, 1.04-5.9), who chewed khat (AOR = 2.27; 95% CI, 1.27-4.19), who were prisoned over a year (AOR = 1.81, 95%CI, 1.04-3.18) and who were in overcrowded pens (AOR = 1.91, 95% CI, 1.002-3.65) were at higher risk of LTBI. CONCLUSIONS: The prevalence of LTBI in prisoners in West Wollega Zone of western Ethiopia was high and could serve as sources of infection to the public. Hence optimum handling of prisoners, and regular follow up and treatment of TB cases in prisons were recommended to minimize the burden of TB in the Zone.