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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. [ABSTRACT FROM AUTHOR]

Differential diagnosis of tuberculosis (TB) and latent TB infection (LTBI) remains a public health priority in high TB burden countries. Pulmonary TB is diagnosed by sputum smear microscopy, chest X-rays, and PCR tests for distinct Mycobacterium tuberculosis (Mtb) genes. Clinical tests to diagnose LTBI rely on immune cell stimulation in blood plasma with TB-specific antigens followed by measurements of interferon-γ concentrations. The latter is an important cytokine for cellular immune responses against Mtb in infected lung tissues. Sputum smear microscopy and chest X-rays are not sufficiently sensitive while both PCR and interferon-γ release assays are expensive. Alternative biomarkers for the development of diagnostic tests to discern TB disease states are desirable. This study’s objective was to discover sputum diagnostic biomarker candidates from the analysis of samples from 161 human subjects including TB patients, individuals with LTBI, negative community controls (NCC) from the province South Omo, a pastoral region in Ethiopia. We analyzed 16S rRNA gene-based bacterial taxonomies and proteomic profiles. The sputum microbiota did not reveal statistically significant differences in α-diversity comparing the cohorts. The genus Mycobacterium, representing Mtb, was only identified for the TB group which also featured reduced abundance of the genus Rothia in comparison with the LTBI and NCC groups. Rothia is a respiratory tract commensal and may be sensitive to the inflammatory milieu generated by infection with Mtb. Proteomic data supported innate immune responses against the pathogen in subjects with pulmonary TB. Ferritin, an iron storage protein released by damaged host cells, was markedly increased in abundance in TB sputum compared to the LTBI and NCC groups, along with the α-1-acid glycoproteins ORM1 and ORM2. These proteins are acute phase reactants and inhibit excessive neutrophil activation. Proteomic data highlight the effector roles of neutrophils in the anti-Mtb response which was not observed for LTBI cases. Less abundant in the sputum of the LTBI group, compared to the NCC group, were two immunomodulatory proteins, mitochondrial TSPO and the extracellular ribonuclease T2. If validated, these proteins are of interest as new biomarkers for diagnosis of LTBI.

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Bovine tuberculosis (bTB) is a serious animal health problem in Ethiopia, ranking among the top three livestock diseases. If the factors contributing to the spread and persistence of bTB are not managed, the situation may get worse. Therefore, prioritizing bTB control is essential. A retrospective study was conducted to evaluate the effect of repeated skin testing and slaughter on subsequent bTB prevalence and herd demographic changes in Holeta dairy farm. A total of 810 Friesian (F) * Boran (B) crosses, and pure Boran animals were involved in the study; all animals on the farm, except calves <6 months of age, were tested using single intradermal comparative cervical tuberculin test (SICCTT). On the basis of 21.3% prevalence in the first-round test in December 2014, three successive rounds of test and slaughter were conducted. During this period, the prevalence of bTB infection exhibited an oscillating pattern. It initially declined to 8.4% (n = 496) during the second-round test but then experienced resurgence, reaching 24.8% (n = 503) in the third-round. Finally, the prevalence decreased to 5.4% in the fourth-round test. The time interval between successive SICCTT tests varied from 0.95 years to 1.84 years. The test and slaughter intervention resulted in the culling of a substantial number of cows (n=342). With an increased culling rate, the average age of the herd and the average number of lactations per cow decreased. Similarly, animal entries and exits also influenced the breed composition of the herd. During the first round test, over 63% of the herd was composed of 50% HF*B crosses, followed by pure Boran, and 75% HF*B crosses, respectively. However, between the first and fourth test rounds, the proportion of Borans declined to 5%, while high-grade (75% HF*B) animals increased almost fivefold. In conclusion, the findings of this study showed the effect of prolonged time interval between consecutive tests which might result in failure of test and slaughter intervention, hence, due attention should be given on maintaining the recommended regular time interval (2-6 months) during consecutive test and slaughter procedures. Finally, the study recommends further study on assessing other alternative control strategies such as test and segregation methods to reduce the economic impact of culling of bTB reactor animals at a farm level. [ABSTRACT FROM AUTHOR]

Bovine tuberculosis (bTB) is a serious animal health problem in Ethiopia, ranking among the top three livestock diseases. If conditions that favor the transmission and persistence of bTB are not addressed, the situation will get worse; hence bTB control should be priority. However, interventions are influenced by several "non-biological" factors. A cross-sectional study was conducted to assess farmers' knowledge, attitude, and practice (KAP) using a structured questionnaire administered to 307 respondents. A multi-stage sampling procedure was employed to select study subjects. Accordingly, 55% of participants knew about bTB; of which 36.4% knew basic information, and the remaining (18.6%) knew nothing except the name bTB. Less than 2.0% of the farmers knew about zoonotic importance of bTB. The knowledge among dairy farmers varied depending on farm size, milk-shed (MS), training received, veterinary consultation, and years of farming experience. Using multivariable analysis, farmers from medium and large-scale farms knew more about bTB than those from small scale farms, by a factor of 2.8 and 7.7, respectively. Similarly, farmers who had been farming for more than 6 years and farmers from Selale MS had higher odds of being knowledgeable about bTB, by 5.7 and 10.4 times compared to other MS, respectively. Only 12% of participants were aware of the test and slaughter control method. Likewise, only 18% of the farmers tended to avoid buying cattle from risky sources. The finding revealed a lack of knowledge on the production loss incurred (12%) and the probability of human infection (1.9%); instead, a substantial proportion of farmers (25%) believed that bTB infection could affect the dairy market. In conclusion, the present study highlighted knowledge, attitude, and practice gaps that, if addressed using tailor-made training, might assist in reducing the consequences of the disease. [ABSTRACT FROM AUTHOR]

In 2016, the World Health Organization (WHO) estimated that there were 147,000 cases and 12,500 deaths worldwide from tuberculosis, which is predominantly caused by Mycobacterium bovis. However, because of the [...]