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Background: Resistance to tuberculosis (TB) drugs has become a major threat to global control efforts. Early case detection and drug susceptibility profiling of the infecting bacteria are essential for appropriate case management. The objective of this study was to determine the drug susceptibility profiles of difficult-to-treat (DTT) TB patients in Ghana., Methods: Sputum samples obtained from DTT-TB cases from health facilities across Ghana were processed for rapid diagnosis and detection of drug resistance using the Genotype MTBDR plus and Genotype MTBDR sl . v2 from Hain Life science., Results: A total of 298 (90%) out of 331 sputum samples processed gave interpretable bands out of which 175 (58.7%) were resistant to at least one drug (ANY r ); 16.8% (50/298) were isoniazid-mono-resistant (INH r ), 16.8% (50/298) were rifampicin-mono-resistant (RIF r ), and 25.2% (75/298) were MDR. 24 (13.7%) of the ANY r were additionally resistant to at least one second line drug: 7.4% (2 RIF r , 1 INH r , and 10 MDR samples) resistant to only FQs and 2.3% (2 RIF r , 1 INH r , and 1 MDR samples) resistant to AMG drugs kanamycin (KAN), amikacin (AMK), capreomycin (CAP), and viomycin (VIO). Additionally, there were 4.0% (5 RIF r and 2 MDR samples) resistant to both FQs and AMGs. 81 (65.6%) out of 125 INH-resistant samples including INH r and MDR had katG -mutations (MT) whereas 15 (12%) had inhApro -MT. The remaining 28 (22.4%) had both katG and inhA MT. All the 19 FQ-resistant samples were gyrA mutants whereas the 10 AMGs were rrs (3), eis (3) as well as rrs , and eis co-mutants (4). Except for the seven pre-XDR samples, no sample had eis MT., Conclusion: The detection of several pre-XDR TB cases in Ghana calls for intensified drug resistance surveillance and monitoring of TB patients to, respectively, ensure early diagnosis and treatment compliance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Otchere, Morgan, Asare, Osei-Wusu, Aboagye, Yirenkyi, Musah, Danso, Tetteh-Ocloo, Afum, Asante-Poku, Laryea, Poku, Bonsu, Gagneux and Yeboah-Manu.)

Despite advancements made toward diagnostics, tuberculosis caused by Mycobacterium africanum (Maf) and Mycobacterium tuberculosis sensu stricto (Mtbss) remains a major public health issue. Human host factors are key players in tuberculosis (TB) outcomes and treatment. Research is required to probe the interplay between host and bacterial genomes. Here, we explored the association between selected human/host genomic variants and TB disease in Ghana. Paired host genotype datum and infecting bacterial isolate information were analyzed for associations using a multinomial logistic regression. Mycobacterium tuberculosis complex (MTBC) isolates were obtained from 191 TB patients and genotyped into different phylogenetic lineages by standard methods. Two hundred and thirty-five (235) nondisease participants were used as healthy controls. A selection of 29 SNPs from TB disease-associated genes with high frequency among African populations was assayed using a TaqMan® SNP Genotyping Assay and iPLEX Gold Sequenom Mass Genotyping Array. Using 26 high-quality SNPs across 326 case-control samples in an association analysis, we found a protective variant, rs955263, in the SORBS2 gene against both Maf and Mtb infections ( P BH  = 0.05; OR = 0.33; 95% CI = 0.32-0.34). A relatively uncommon variant, rs17235409 in the SLC11A1 gene was observed with an even stronger protective effect against Mtb infection (MAF = 0.06; PBH = 0.04; OR = 0.05; 95% CI = 0.04-0.05). These findings suggest SLC11A1 and SORBS2 as a potential protective gene of substantial interest for TB, which is an important pathogen in West Africa, and highlight the need for in-depth host-pathogen studies in West Africa., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Asante-Poku, Morgan, Osei-Wusu, Aboagye, Asare, Otchere, Adadey, Mnika, Esoh, Mawuta, Arthur, Forson, Mazandu, Wonkam and Yeboah-Manu.)

Buruli ulcer (BU) is a chronic necrotizing disease of the skin and subcutaneous fat tissue. The causative agent, Mycobacterium ulcerans , produces mycolactone, a macrolide toxin, which causes apoptosis of mammalian cells. Only a small proportion of individuals exposed to M. ulcerans develop clinical disease, as surrounding macrophages may control the infection by bacterial killing at an early stage, while mycolactone concentration is still low. Otherwise, bacterial multiplication leads to in higher concentrations of mycolactone, with formation of necrotizing lesions that are no more accessible to immune cells. By typing a cohort of 96 Ghanaian BU patients and 384 endemic controls without BU, we show an association between BU and single nucleotide polymorphisms (SNPs) in iNOS (rs9282799) and IFNG (rs2069705). Both polymorphisms influence promoter activity in vitro . A previously reported SNP in SLC11A1 ( NRAMP , rs17235409) tended to be associated with BU. Altogether, these data reflect the importance of IFNG signaling in early defense against M. ulcerans infection.