After extensive exposure to Mycobacterium tuberculosis (Mtb), most individuals acquire latent Mtb infection (LTBI) defined by a positive tuberculin skin test (TST) or interferon-γ release assay (IGRA). To identify mechanisms of resistance to Mtb infection, we compared transcriptional profiles from highly exposed contacts who resist TST/IGRA conversion (resisters, RSTRs) and controls with LTBI using RNAseq. Gene sets related to carbon metabolism and free fatty acid (FFA) transcriptional responses enriched across 2 independent cohorts suggesting RSTR and LTBI monocytes have distinct activation states. We compared intracellular Mtb replication in macrophages treated with FFAs and found that palmitic acid (PA), but not oleic acid (OA), enhanced Mtb intracellular growth. This PA activity correlated with its inhibition of proinflammatory cytokines in Mtb-infected cells. Mtb growth restriction in PA-treated macrophages was restored by activation of AMP kinase (AMPK), a central host metabolic regulator known to be inhibited by PA. Finally, we genotyped AMPK variants and found 7 SNPs in PRKAG2, which encodes the AMPK-γ subunit, that strongly associated with RSTR status. Taken together, RSTR and LTBI phenotypes are distinguished by FFA transcriptional programs and by genetic variation in a central metabolic regulator, which suggests immunometabolic pathways regulate TST/IGRA conversion.

In South Africa, young women are at disproportionate risk of HIV infection with about 2363 new infections per week in 2015. Proper condom use is one of the most effective HIV/AIDS prevention strategies among sexually active persons. Understanding factors associated with male condom use in this key population group is important to curb the spread of HIV. This study determined practices and predictors of male condom use among sexually active young women in South Africa. The 2012 National HIV Communication Survey measured the extent of exposure to communication activities for HIV prevention among men and women aged 16–55 years in South Africa. We performed a secondary data analysis on a subset of this survey, focussing on 1031 women aged 16–24 years who reported having had sex in the past 12 months. We determined predictors of male condom use using the unconditional multivariable logistic regression model. Of the 1031 young women, 595 (57.8%) reported using a male condom at last sex, 68.4% in women aged 16–19 years and 54.5% in women aged 20–24 years (p < 0.001). Delayed sexual debut [20 years or above] (Adjusted Odds Ratio [aOR] 2.1, 95% CI: 1.2 to 3.7, p = 0.006); being a student (aOR 1.6, 95% CI: 1.2 to 2.3, p = 0.005); and exposure to HIV communication programmes (aOR 3.1, 95% CI: 1.2 to 8.6, p = 0.025) were significantly associated with male condom use at last sex. Male condom use was a common practice among young women and was associated with delayed sexual debut and exposure to HIV communication programmes. Behavioral interventions and HIV communication programmes should therefore encourage young women to delay initiation of sex and promote usage of male condoms.

Background: QuantiFERON-TB-Gold-in-tube (QFT-GIT) is an interferon-gamma release assay (IGRA) used to diagnose latent tuberculosis infection. Limited data exists on performance of QuantiFERON-TB Gold-Plus (QFT-Plus), a next generation of IGRA that includes an additional antigen tube 2 (TB2) while excluding TB7.7 from antigen tube 1 (TB1), to measure TB specific CD4+ and CD8+ T lymphocytes responses. We compared agreement between QFT-Plus and QFT-GIT among highly TB exposed goldminers in South Africa. Methods: We enrolled HIV-negative goldminers in South Africa, aged ≥33 years with no prior history of TB disease or evidence of silicosis. Blood samples were collected for QFT-GIT and QFT-Plus. QFT-GIT was considered positive if TB1 tested positive; while QFT-Plus was positive if both or either TB1 or TB2 tested positive, as per manufacturer's recommendations. We compared the agreement between QFT-Plus and QFT-GIT using Cohen’s Kappa. To assess the specific contribution of CD8+ T-cells, we used TB2−TB1 differential values as an indirect estimate. A cut-off value was set at 0.6. Logistic regression was used to identify factors associated with having TB2-TB1>0.6 difference on QFT-Plus. Results: Of 349 enrolled participants, 304 had QFT-Plus and QFT-GIT results: 205 (68%) were positive on both assays; 83 (27%) were negative on both assays while 16 (5%) had discordant results. Overall, there was 94.7% (288/304) agreement between QFT-Plus and QFT-GIT (Kappa = 0.87). 214 had positive QFT-Plus result, of whom 202 [94.4%, median interquartile range (IQR): 3.06 (1.31, 7.00)] were positive on TB1 and 205 [95.8%, median (IQR): 3.25 (1.53, 8.02)] were positive on TB2. A TB2-TB1>0.6 difference was observed in 16.4% (35/214), with some evidence of a difference by BMI; 14.9% (7/47), 9.8% (9/92) and 25.3% (19/75) for BMI of 18.5-24.9, 18.5-25 and >30 kg/m 2, respectively (P=0.03). Conclusion: In a population of HIV-negative goldminers, QFT-Plus showed high agreement with QFT-GIT, suggesting similar performance.

Background: Mobile health (mHealth) technologies are increasingly used in contact tracing and case finding, enhancing and replacing traditional methods for managing infectious diseases such as Ebola, tuberculosis, COVID-19, and HIV. However, the variations in their development approaches, implementation scopes, and effectiveness introduce uncertainty regarding their potential to improve public health outcomes. Objective: We conducted this systematic review to explore how mHealth technologies are developed, implemented, and evaluated. We aimed to deepen our understanding of mHealth’s role in contact tracing, enhancing both the implementation and overall health outcomes. Methods: We searched and reviewed studies conducted in Africa focusing on tuberculosis, Ebola, HIV, and COVID-19 and published between 1990 and 2023 using the PubMed, Scopus, Web of Science, and Google Scholar databases. We followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines to review, synthesize, and report the findings from articles that met our criteria. Results: We identified 11,943 articles, but only 19 (0.16%) met our criteria, revealing a large gap in technologies specifically aimed at case finding and contact tracing of infectious diseases. These technologies addressed a broad spectrum of diseases, with a predominant focus on Ebola and tuberculosis. The type of technologies used ranged from mobile data collection platforms and smartphone apps to advanced geographic information systems (GISs) and bidirectional communication systems. Technologies deployed in programmatic settings, often developed using design thinking frameworks, were backed by significant funding and often deployed at a large scale but frequently lacked rigorous evaluations. In contrast, technologies used in research settings, although providing more detailed evaluation of both technical performance and health outcomes, were constrained by scale and insufficient funding. These challenges not only prevented these technologies from being tested on a wider scale but also hindered their ability to provide actionable and generalizable insights that could inform public health policies effectively. Conclusions: Overall, this review underscored a need for organized development approaches and comprehensive evaluations. A significant gap exists between the expansive deployment of mHealth technologies in programmatic settings, which are typically well funded and rigorously developed, and the more robust evaluations necessary to ascertain their effectiveness. Future research should consider integrating the robust evaluations often found in research settings with the scale and developmental rigor of programmatic implementations. By embedding advanced research methodologies within programmatic frameworks at the design thinking stage, mHealth technologies can potentially become technically viable and effectively meet specific contact tracing health outcomes to inform policy effectively.

Male circumcision (MC) reduces HIV transmission risk by up to 60% in heterosexual men. However, uptake of medical male circumcision (MMC) is low in traditionally circumcising communities of South Africa. We assessed knowledge, attitudes, and practices to identify factors predicting acceptability of MMC among males in the Alfred Nzo District. A cross-sectional study was conducted among males aged 15–49 years in this district. Logistic regression was used to identify factors predicting acceptability of MMC. We interviewed 343 males who had a median age of 19 years (interquartile range (IQR): 16–25 years). Of these, 77% (95% confidence interval (CI): 72–82) were circumcised: 77% (95% CI: 71–82) were circumcised in a traditional setting and 21% (95% CI: 16–26) in a medical setting. The median score of knowledge about the benefits of MMC was 62.5% (IQR: 37.5–75.0), with 59% (95% CI: 53–64) demonstrating a positive attitude towards MMC and 68% (95% CI: 63–73) accepting involvement of health workers in MC. Excellent knowledge (adjusted odds ratio (aOR): 3.07, 95% CI: 0.99–9.58, p = 0.053), awareness (aOR: 3.26, 95% CI: 1.08–9.86, p = 0.037), and positive attitude towards MMC (aOR: 2.35, 95% CI: 1.30–4.25, p = 0.005) were associated with acceptability of MMC. Participants demonstrated good knowledge and acceptance of the MMC programme. Knowledge, attitude, and awareness were significant predictors of MMC acceptability.

Background: Although tuberculosis preventive therapy guidelines support testing for tuberculosis infection in household contacts (HHCs), this adds operational complexity and cost and has often been abandoned. To understand utility of testing, we determined prevalence and risk factors for tuberculosis infection and tuberculosis preventive therapy eligibility among HHCs. Methods: In a cross-sectional study conducted from July 2021 to September 2022 in Lesotho, South Africa, and Tanzania, we enrolled people with microbiologically confirmed pulmonary tuberculosis and their HHCs. HHCs were screened and tested for tuberculosis and tuberculosis infection using Xpert Ultra and QuantiFERON-TB-Gold-Plus, respectively. Generalized linear modelling was used to determine factors associated with tuberculosis infection, using robust standard errors. Tuberculosis preventive therapy eligibility was determined using World Health Organization criteria. Results: We enrolled 342 people with pulmonary tuberculosis and 964 HHCs: 61.9% (597/964) were female with a median age of 18 years (interquartile range, 8–39 years). Overall, tuberculosis prevalence was 3.4% (25/739; 95% confidence interval [CI], 2.2%–4.9%), while tuberculosis infection prevalence was 48.7% (348/714; 95% CI, 45.0%–52.5%). Having tuberculosis infection increased with age per year (adjusted odds ratio [aOR], 1.02; 95% CI, 1.01–1.03), being from Lesotho (aOR, 1.82; 95% CI, 1.04–3.20), previous tuberculosis history (aOR, 2.25; 95% CI, 1.05–4.79), and being HIV negative (aOR, 2.30; 95% CI, 1.31–4.04). Overall, 62.2% (518/833; 95% CI, 58.8%–65.5%) were eligible for tuberculosis preventive therapy. Conclusions: Almost half of tuberculosis-exposed HHCs aged ≥5 years had tuberculosis infection. Approximately two-thirds of HHCs were eligible for tuberculosis preventive therapy, implying that providing tuberculosis preventive therapy without prior testing for tuberculosis infection may be warranted in this population. Further work on cost-effectiveness is warranted when new tests become available. Clinical Trials Registration: ISRCTN10003903.