Polymorphisms in Immune Genes and Their Association with Tuberculosis Susceptibility: An Analysis of the African Population

Wycliff Wodelo,1 Eddie M Wampande,1,2 Alfred Andama,3 David Patrick Kateete,1 Kenneth Ssekatawa4,5 1Department of Immunology and Molecular Biology, School of Biomedical Science, College of Health Science, Makerere University, Kampala, Uganda; 2Department of Veterinary Medicine, School of Veterinary Medicine and Animal Resources, College of Veterinary Medicine, Animal Resources and Biosecurity, Makerere University, Kampala, Uganda; 3Department of Medical Microbiology, School of Medicine, College of Health Science, Makerere University, Kampala, Uganda; 4Department of Science, Technical and Vocational Education, Makerere University, Kampala, Uganda; 5Africa Center Excellence in Materials Product Development and Nanotechnology (MAPRONANO ACE), Makerere University, Kampala, UgandaCorrespondence: Eddie M Wampande, Email [email protected]: Tuberculosis remains a global health concern, with substantial mortality rates worldwide. Genetic factors play a significant role in influencing susceptibility to tuberculosis. This review examines the current progress in studying polymorphisms within immune genes associated with tuberculosis susceptibility, focusing on African populations. The roles of various proteins, including Toll-like receptors, Dendritic Cell-Specific Intercellular Adhesion Molecule-3 Grabbing Non-Integrin, vitamin D nuclear receptor, soluble C-type lectins such as surfactant proteins A and D, C-type Lectin Domain Family 4 Member E, and mannose-binding lectin, phagocyte cytokines such as Interleukin-1, Interleukin-6, Interleukin-10, Interleukin-12, and Interleukin-18, and chemokines such as Interleukin-8, monocyte chemoattractant protein 1, Regulated upon activation, normal T-cell expressed and secreted are explored in the context of tuberculosis susceptibility. We also address the potential impact of genetic variants on protein functions, as well as how these findings align with the genetic polymorphisms not associated with tuberculosis. Functional studies in model systems provide insights into the intricate host-pathogen interactions and susceptibility mechanisms. Despite progress, gaps in knowledge remain, highlighting the need for further investigations. This review emphasizes the association of Single Nucleotide Polymorphisms with diverse aspects of tuberculosis pathogenesis, including disease detection and Mycobacterium tuberculosis infection.Keywords: tuberculosis, polymorphisms, immune genes, African populations, genetic variants, Mycobacterium tuberculosi

Bronchoalveolar Lavage Enzyme-Linked Immunospot for Diagnosis of Smear-Negative Tuberculosis in HIV-Infected Patients

Peripheral blood interferon-gamma release assays (IGRAs) have sub-optimal sensitivity and specificity for diagnosis of active pulmonary tuberculosis (TB). However, assessment of local immune responses has been reported to improve the accuracy of TB diagnosis.We enrolled HIV-infected adults with cough ≥2 weeks' duration admitted to Mulago Hospital in Kampala, Uganda and referred for bronchoscopy following two negative sputum acid-fast bacillus smears. We performed an ELISPOT-based IGRA (T-SPOT.TB®, Oxford Immunotec, Oxford, UK) using peripheral blood and bronchoalveolar lavage (BAL) fluid mononuclear cells, and determined the accuracy of IGRAs using mycobacterial culture results as a reference standard.94 HIV-infected patients with paired peripheral blood and BAL IGRA results were included. The study population was young (median age 34 years [IQR 28-40 years]) and had advanced HIV/AIDS (median CD4+ T-lymphocyte count 60 cells/µl [IQR 22-200 cells/µl]). The proportion of indeterminate IGRA results was higher in BAL fluid than in peripheral blood specimens (34% vs. 14%, difference 20%, 95% CI 7-33%, p = 0.002). BAL IGRA had moderate sensitivity (73%, 95% CI 50-89%) but poor specificity (48%, 95% CI 32-64%) for TB diagnosis. Sensitivity was similar (75%, 95% CI 57-89%) and specificity was higher (78%, 95% CI 63-88%) when IGRA was performed on peripheral blood.BAL IGRA performed poorly for the diagnosis of smear-negative TB in a high HIV/TB burden setting. Further studies are needed to examine reasons for the large proportion of indeterminate results and low specificity of BAL IGRA for active TB in high HIV/TB burden settings

Nesting records of the scaly-breasted illadopsis Illadopsis albipectus in Uganda

Volume: 26Start Page: 22End Page: 2

Morphological traits of jackfruit (Artocarpus heterophyllus Lam.): Indicators of diversity, selection and germplasm dispersion in Uganda

Uganda is one of the African countries with increasing production demands of jackfruit since it has gained popularity as a food and nutrition security crop with therapeutic benefits. However, the jackfruit germplasm in Uganda had not been adequately characterized to guide its production and there were reports of farmer-selection against inferior varieties. Therefore, this study comprehensively catalogued the morphological diversity of jackfruit to foster purpose-driven cultivation of jackfruit in Uganda; identified varieties and traits prone to negative selection to guide germplasm conservation efforts and established germplasm dispersion patterns to inform exchange programs of germplasm found suitable for commercial production. This was achieved using 47 qualitative and 30 quantitative traits of 249 jackfruit trees from four ethno-varieties, three administrative regions and three agro-ecological zones analyzed for the Shannon index (H'), coefficient of variation (CV), heritability (H2), and genetic advance as percentage of the mean (GAM). Seed surface color was the most variable qualitative trait (H' = 3.16) and number of fruits per tree (H2 = 99.83) and fruit weight (GCV = 69.45, PCV = 69.76) were the most diverse quantitative traits. Ethno-varieties of low economic value registered low diversity (Serebere: H' = 0.92, Namata: H' = 1.04), depicting negative selection against undesired varieties. The qualitative morphological diversity of jackfruit was highest in the Central region (H' = 1.07) and lowest in Eastern Uganda (H' = 1.02). Given the positive correlation between tree age and trunk circumference (r = 0.99, p = 0.001), the Central region with the oldest trees, largest trunks and samples with associations in Eastern and Western regions, is presumed the center of jackfruit diversity and pioneer of jackfruit cultivation in Uganda. In conclusion, jackfruit diversity in Uganda is still robust despite selection constraints. However, for future jackfruit improvements, it is vital to conserve the less preferred ethno-varieties

Investigation of OMNIgene·SPUTUM performance in delayed tuberculosis testing by smear, culture, and Xpert MTB/RIF assays in Uganda.

OMNIgene·SPUTUM (OM-S) is a sample transport reagent designed to work with all tuberculosis diagnostics while eliminating the need for cold chain. OM-S-treated sputum samples were assayed in several tests after multiday holds. Raw sputa from 100 patients underwent direct smear microscopy, were manually split and assigned to the OM-S group [OM-S added at collection (no other processing required) and tested after 0- to 5-day holds at room temperature] or standard-of-care (SOC) group (NaOH/N-acetyl l-cysteine decontamination, all tested on day of collection). Concentrated smear microscopy, Lowenstein Jensen (LJ) culture, and mycobacteria growth indicator tube (MGIT) culture were performed. For patients with negative direct smear, a second sample was split, with SOC (raw sputum) and OM-S portions (sediment) tested in the Xpert MTB/RIF (Xpert) assay. OM-S group and SOC group results were strongly concordant on all four tests [range, 89% (MGIT)-97% (Xpert)]. OM-S MGIT, LJ, and Xpert tests were in statistical agreement with SOC MGIT as reference. OM-S specimens had lower culture contamination rates (3% vs. 10% LJ; 2% vs. 5% MGIT) but required, on average, 5.6 additional days to become MGIT-positive. The findings suggest that samples held/transported in OM-S are compatible with smear microscopy, LJ or MGIT culture, and Xpert, and perform comparably to fresh sputum samples. Larger feasibility studies are warranted

Investigation of OMNIgene·SPUTUM performance in delayed tuberculosis testing by smear, culture, and Xpert MTB/RIF assays in Uganda.

OMNIgene·SPUTUM (OM-S) is a sample transport reagent designed to work with all tuberculosis diagnostics while eliminating the need for cold chain. OM-S-treated sputum samples were assayed in several tests after multiday holds. Raw sputa from 100 patients underwent direct smear microscopy, were manually split and assigned to the OM-S group [OM-S added at collection (no other processing required) and tested after 0- to 5-day holds at room temperature] or standard-of-care (SOC) group (NaOH/N-acetyl l-cysteine decontamination, all tested on day of collection). Concentrated smear microscopy, Lowenstein Jensen (LJ) culture, and mycobacteria growth indicator tube (MGIT) culture were performed. For patients with negative direct smear, a second sample was split, with SOC (raw sputum) and OM-S portions (sediment) tested in the Xpert MTB/RIF (Xpert) assay. OM-S group and SOC group results were strongly concordant on all four tests [range, 89% (MGIT)-97% (Xpert)]. OM-S MGIT, LJ, and Xpert tests were in statistical agreement with SOC MGIT as reference. OM-S specimens had lower culture contamination rates (3% vs. 10% LJ; 2% vs. 5% MGIT) but required, on average, 5.6 additional days to become MGIT-positive. The findings suggest that samples held/transported in OM-S are compatible with smear microscopy, LJ or MGIT culture, and Xpert, and perform comparably to fresh sputum samples. Larger feasibility studies are warranted