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Background: Efforts to eradicate tuberculosis (TB) are threatened by diabetes mellitus (DM), which confers a 3-fold increase in the risk of TB disease. The changes in the memory phenotypes and functional profiles of Mycobacterium tuberculosis (Mtb)-specific T cells in latent TB infection (LTBI)-DM participants remain poorly characterised. We, therefore, assessed the effect of DM on T-cell phenotype and function in LTBI and DM clinical groups. Methods: We compared the memory phenotypes and function profiles of Mtb-specific CD4+ and CD8+ T cells among participants with LTBI-DM (n=21), LTBI-only (n=17) and DM-only (n=16). Peripheral blood mononuclear cells (PBMCs) were stimulated with early secretory antigenic 6 kDa (ESAT-6) and culture filtrate protein 10 (CFP-10) peptide pools or phytohemagglutinin (PHA). The memory phenotypes (CCR7/CD45RA), and functional profiles (HLA-DR, PD-1, CD107a, IFN-γ, IL-2, TNF, IL-13, IL-17A) of Mtb-specific CD4+ and CD8+ T cells were characterised by flow cytometry. Results: Naïve CD4+ T cells were significantly decreased in the LTBI-DM compared to the LTBI-only participants [0.47 (0.34-0.69) vs 0.91 (0.59-1.05); (p<0.001)]. Similarly, CD8+ HLA-DR expression was significantly decreased in LTBI-DM compared to LTBI-only participants [0.26 (0.19-0.33) vs 0.52 (0.40-0.64); (p<0.0001)], whereas CD4+ and CD8+ PD-1 expression was significantly upregulated in the LTBI-DM compared to the LTBI-only participants [0.61 (0.53-0.77) vs 0.19 (0.10-0.28); (p<0.0001) and 0.41 (0.37-0.56) vs 0.29 (0.17-0.42); (p=0.007)] respectively. CD4+ and CD8+ IFN-γ production was significantly decreased in the LTBI-DM compared to the LTBI-only participants [0.28 (0.19-0.38) vs 0.39 (0.25-0.53); (p=0.030) and 0.36 (0.27-0.49) vs 0.55 (0.41-0.88); (p=0.016)] respectively. CD4+ TNF and CD8+ IL-17A production were significantly decreased in participants with LTBI-DM compared to those with LTBI-only [0.38 (0.33-0.50) vs 0.62 (0.46-0.87); (p=0.004) and 0.29 (0.16-0.42) vs 0.47 (0.29-0.52); (0.017)] respectively. LTBI-DM participants had significantly lower dual-functional (IFN-γ+IL-2+ and IL-2+TNF+) and mono-functional (IFN-γ+ and TNF+) CD4+ responses than LTBI-only participants. LTBI-DM participants had significantly decreased dual-functional (IFN-γ+IL-2+, IFN-γ+ TNF+ and IL-2+TNF+) and mono-functional (IFN-γ+, IL-2+ and TNF+) central and effector memory CD4+ responses compared to LTBI-only participants. Conclusion: Type 2 DM impairs the memory phenotypes and functional profiles of Mtb-specific CD4+ and CD8+ T cells, potentially indicating underlying immunopathology towards increased active TB disease risk. [ABSTRACT FROM AUTHOR]

Background: The incidence of oropharyngeal candidiasis among people living with human immunodeficiency virus in Africa is on the rise. Oropharyngeal candidiasis is mainly caused by C.albicans ; however, a shift in the etiology towards non- Candida albicans species is increasing. In addition, there are variations in the epidemiological distribution of Candida species causing oropharyngeal candidiasis among people living with human immunodeficiency virus in Africa., Objective: This review aimed to determine the prevalence of oropharyngeal candidiasis and the distribution of Candida species among people living with human immunodeficiency virus in Africa., Materials and Methods: This systematic review protocol was registered in the base PROSPERO database prior to its conduct (CRD42021254473). The Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocol guidelines (PRISMA-P) were followed for this study. The PubMed, Scopus and EMBASE databases were searched to identify published studies published between 1 st January 2000 and 8 th October 2022. The eligible studies were included in the meta-analysis and analyzed using a random effects model. The risk of bias of the included studies was assessed using the Joanna Briggs Institute quality assessment tool for prevalence studies., Results: The database search yielded 370 titles from PubMed (n=192), EMBASE (n=162) and SCOPUS (n=16). Fourteen studies with a total of 3,863 participants were included in the meta-analysis. The pooled prevalence of oropharyngeal candidiasis was 49.0% (95% CI: 37% - 62%). A total of 2,688 Candida isolates were reported; approximately 76.6% (n=2,060) were C. albicans , and 21.7% (n=582) were non- C. albicans . Among the non- Candida albicans species, C . glabrata was the most common isolate (29.6%), followed by C . tropicalis (27.7%), C . krusei (17.0%), C . parapsilosis (8.1%) and C . dubliniensis (5.2%). Out of 14 studies, 7 (50.0%) had a low risk of bias, 5 (35.7%) had a moderate risk of bias, and 2 (14.3%) had a high risk of bias., Conclusion: Almost half of people living with HIV in Africa have oropharyngeal candidiasis, and C. albicans remains the most frequent cause of oropharyngeal candidiasis., Competing Interests: Declaration of Competing interests The author(s) declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Oropharyngeal Candida species are part commensal microflora in the the oral cavity of health individuals. Commensal Candida species can become opportunist and transition to pathogenic causes of oropharyngeal candidiasis (OPC) in individuals with impaired immunity through ecological cues and expression of virulence factors. Limited studies have evaluated virulence attributes of oropharyngeal Candida species among people living with human immunodeficiency virus (PLHIV) with OPC on antiretroviral therapy (ART) in Uganda., Objective: Evaluation of the Virulence Attributes of Oropharyngeal Candida Species Isolated from People Living with Human Immunodeficiency Virus with Oropharyngeal Candidiasis on Antiretroviral Therapy., Methods: Thirty-five (35) Candida isolates from PLHIV with OPC on ART were retrieved from sample repository and evaluated for phospholipase activity using the egg yolk agar method, proteinase activity using the bovine serum albumin agar method, hemolysin activity using the blood agar plate method, esterase activity using the Tween 80 opacity test medium method, coagulase activity using the classical tube method and biofilm formation using the microtiter plate assay method in vitro ., Results: Phospholipase and proteinase activities were detected in 33/35 (94.3%) and 31/35 (88.6%) of the strains, respectively. Up to 25/35 (71.4%) of the strains exhibited biofilm formation while esterase activity was demonstrated in 23/35 (65.7%) of the strains. Fewer isolates 21/35 (60%) of the strains produced hemolysin and coagulase production was the least virulence activity detected in 18/35 (51.4%)., Conclusion: Phospholipase and proteinase activities were the strongest virulence attributes of oropharyngeal Candida species., Competing Interests: Declarations Competing Interests The author(s) declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.