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Abstract Introduction When COVID-19 hit the world in 2019, an enhanced focus on diagnostic testing for SARS-CoV-2 was essential for a successful pandemic response. Testing laboratories stretched their capabilities for the new coronavirus by adopting different test methods. The necessity of having external quality assurance (EQA) mechanisms was even more critical due to this rapid expansion. However, there was a lack of experience in providing the necessary SARS-CoV-2 EQA materials, especially in locations with constrained resources. Objective We aimed to create a PT (Proficiency testing) programme based on the Dried Tube Specimens (DTS) method that would be a practical option for molecular based SARS-CoV-2 EQA in Low- and Middle-Income Countries. Methods Based on previous ISO/IEC 17043:2010 accreditation experiences and with assistance from the US Centers for Disease Control and Prevention, The Supranational Reference Laboratory of Uganda (adapted the DTS sample preparation method and completed a pilot EQA program between 2020 and 2021. Stability and panel validation testing was conducted on the designed materials before shipping to pilot participants in six African countries. Participants received a panel containing five SARS-CoV-2 DTS samples, transported at ambient conditions. Results submitted by participants were compared to validation results. Participants were graded as satisfactory (≥ 80%) or unsatisfactory (

Summary: Within the penile microbiome, bacteria associated with seroconversion, immunology, and cells (BASIC species) enhance HIV susceptibility in heterosexual uncircumcised men by inducing foreskin inflammation and HIV target cell recruitment. This phase 1/2 clinical trial randomizes HIV-uninfected Ugandan men (n = 125) to either oral tinidazole, topical metronidazole, topical clindamycin, or topical hydrogen peroxide to define impact on ex vivo foreskin HIV susceptibility, penile immunology, and BASIC species density. Antimicrobials are well tolerated, and 116 (93%) participants complete the protocol. Topical metronidazole and oral tinidazole reduce the inner foreskin tissue density of HIV-susceptible CD4+ T cells (predefined primary endpoint). Antimicrobials also have varying but substantial effects on reducing prepuce inflammation and BASIC species density, reducing density of foreskin T cell subsets, and increasing foreskin epithelial integrity. Immune alterations correlate strongly with changes in the abundance of BASIC species. Clinical interventions targeting the penile microbiota, particularly topical metronidazole, may reduce HIV susceptibility in uncircumcised men.

Abstract Introduction Family planning knowledge is poor and use is low in Ugandan fishing communities. We compared the effectiveness of enhanced family planning (FP) education with routine counselling on FP knowledge and use. Methods Individuals aged 15–49 years were randomly assigned to intervention or control arm. The intervention constituted enhanced FP education based on a simplified handout extracted from the WHO FP guidance tool called, “Family planning: A global handbook for FP providers” which participants took home for additional reading. The control arm constituted FP counselling following Uganda Ministry of Health guidelines. FP knowledge score and contraceptive prevalence rate (CPR) were compared between trial arms at baseline and at 12 months. Negative binomial regression models were used to estimate the effect of the intervention on FP knowledge and use. Results Overall, 1410 participants were screened to enrol 1004 (502 per study arm, 48.5% women). Subsequently, 384 (76.5%) and 383 (76.3%) completed the 12 months’ follow-up in the intervention and control arms respectively. At baseline, a median FP knowledge score of 8 and a

Summary: Background: Observational studies have investigated the effect of serum lipids on kidney function, but these findings are limited by confounding, reverse causation and have reported conflicting results. Mendelian randomization (MR) studies address this confounding problem. However, they have been conducted mostly in European ancestry individuals. We, therefore, set out to investigate the effect of lipid traits on the estimated glomerular filtration rate (eGFR) based on serum creatinine in individuals of African ancestry. Methods: We used the two-sample and multivariable Mendelian randomization (MVMR) approaches; in which instrument variables (IV's) for the predictor (lipid traits) were derived from summary-level data of a meta-analyzed African lipid GWAS (MALG, n = 24,215) from the African Partnership for Chronic Disease Research (APCDR) (n = 13,612) & the Africa Wits-IN-DEPTH partnership for Genomics studies (AWI-Gen) dataset (n = 10,603). The outcome IV's were computed from the eGFR summary-level data of African-ancestry individuals within the Million Veteran Program (n = 57,336). A random-effects inverse variance method was used in our primary analysis, and pleiotropy was adjusted for using robust and penalized sensitivity testing. The lipid predictors for the MVMR were high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides (TG). Findings: We found a significant causal association between genetically predicted low-density lipoprotein (LDL) cholesterol and eGFR in African ancestry individuals β = 1.1 (95% CI [0.411–1.788]; p = 0.002). Similarly, total cholesterol (TC) showed a significant causal effect on eGFR β = 1.619 (95% CI [0.412–2.826]; p = 0.009). However, the IVW estimate showed that genetically predicted HDL-C β = −0.164, (95% CI = [−1.329 to 1.00]; p = 0.782), and TG β = −0.934 (CI = [−2.815 to 0.947]; p = 0.33) were not significantly causally associated with the risk of eGFR. In the multivariable analysis inverse-variance weighted (MVIVW) method, there was evidence for a causal association between LDL and eGFR β = 1.228 (CI = [0.477–1.979]; p = 0.001). A significant causal effect of Triglycerides (TG) on eGFR in the MVIVW analysis β = −1.3 ([−2.533 to −0.067]; p = 0.039) was observed as well. All the causal estimates reported reflect a unit change in the outcome per a 1 SD increase in the exposure. HDL showed no evidence of a significant causal association with eGFR in the MVIVW method (β = −0.117 (95% CI [−1.252 to 0.018]; p = 0.840)). We found no evidence of a reverse causal impact of eGFR on serum lipids. All our sensitivity analyses indicated no strong evidence of pleiotropy or heterogeneity between our instrumental variables for both the forward and reverse MR analysis. Interpretation: In this African ancestry population, genetically predicted higher LDL-C and TC are causally associated with higher eGFR levels, which may suggest that the relationship between LDL, TC and kidney function may be U-shaped. And as such, lowering LDL_C does not necessarily improve risk of kidney disease. This may also imply the reason why LDL_C is seen to be a poorer predictor of kidney function compared to HDL. In addition, this further supports that more work is warranted to confirm the potential association between lipid traits and risk of kidney disease in individuals of African Ancestry. Funding: Wellcome (220740/Z/20/Z).

Abstract Background Maternal mortality is still a challenge in Uganda, at 336 deaths per 100,000 live births, especially in rural hard to reach communities. Distance to a health facility influences maternal deaths. We explored women’s mobility for maternal health, distances travelled for antenatal care (ANC) and childbirth among hard-to-reach Lake Victoria islands fishing communities (FCs) of Kalangala district, Uganda. Methods A cross sectional survey among 450 consenting women aged 15–49 years, with a prior childbirth was conducted in 6 islands FCs, during January-May 2018. Data was collected on socio-demographics, ANC, birth attendance, and distances travelled from residence to ANC or childbirth during the most recent childbirth. Regression modeling was used to determine factors associated with over 5 km travel distance and mobility for childbirth. Results The majority of women were residing in communities with a government (public) health facility [84.2 %, (379/450)]. Most ANC was at facilities within 5 km distance [72 %, (157/218)], while most women had travelled outside their communities for childbirth [58.9 %, (265/450)]. The longest distance travelled was 257.5 km for ANC and 426 km for childbirth attendance. Travel of over 5 km for childbirth was associated with adolescent girls and young women (AGYW) [AOR = 1.9, 95 % CI (1.1–3.6)], up to five years residency duration [AOR = 1.8, 95 % CI (1.0-3.3)], and absence of a public health facility in the community [AOR = 6.1, 95 % CI (1.4–27.1)]. Women who had stayed in the communities for up to 5 years [AOR = 3.0, 95 % CI (1.3–6.7)], those whose partners had completed at least eight years of formal education [AOR = 2.2, 95 % CI (1.0-4.7)], and those with up to one lifetime birth [AOR = 6.0, 95 % CI (2.0-18.1)] were likely to have moved to away from their communities for childbirth. Conclusions Despite most women who attended ANC doing so within their communities, we observed that majority chose to give birth outside their communities. Longer travel distances were more likely among AGYW, among shorter term community residents and where public health facilities were absent. Trial registration PACTR201903906459874 (Retrospectively registered). https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=5977 .

Abstract Background In Sub-Saharan Africa, herbal therapy continues to be utilized for HIV-1 disease management. However, the therapeutic benefits of these substances remain ambiguous. To date, little is known about the effects of these plant extracts on chronic CD4 + T-cell activation and exhaustion which is partly driven by HIV-1 associated microbial translocation. Methods Effects of Azadirachta indica, Momordica foetida and Moringa oleifera ethanol: water mixtures on cell viability were evaluated using the Guava PCA system. Then, an in-vitro cell culture model was developed to mimic CD4+ T cell exposures to antigens following HIV-1 microbial translocation. In this, peripheral blood mononuclear cells (PBMCs) isolated from HIV negative (n = 13), viral load 1000 copies per mL (n = 6) study participants from rural Uganda were treated with Staphylococcus enterotoxin B (SEB). Then, the candidate plant extract (A. indica) was added to test the potential to inhibit corresponding CD4+ T cell activation. Following BD Facs Canto II event acquisition, variations in %CD38, %CD69, Human Leukocyte Antigen -DR (HLA-DR), Programmed cell death protein 1 (PD-1), T-cell immunoglobulin and mucin domain-containing protein 3 (Tim-3), interferon gamma (IFN γ) and interleukin 2 (IL-2) CD4 + T cell expression were evaluated. Results Following exposure to SEB, only A. indica demonstrated a concentration-dependent ability to downregulate the levels of CD4 + T cell activation. At the final concentration of 0.500 μg/mL of A. indica, a significant downregulation of CD4 + CD38 + HLA-DR+ expression was observed in HIV negative (p

Objectives: To explore whether community health worker household-based maternal health visits improve antenatal care and skilled birth attendance among hard-to-reach fishing villages on Lake Victoria, Uganda. Methods: This quasi-experimental 18-month prospective study involved 486 consenting women aged 15–49 years, who were pregnant or had a pregnancy outcome in the past 6 months, from 6 island fishing communities. The community health worker household-based intervention (community health workers’ household visits to provide counseling, blood pressure measurement, anemia, and HIV testing) involved 243 women from three fishing communities. Random effects logistic regression was used to determine the association between the community health worker intervention and antenatal care and skilled birth attendance among women who had at least 5 months of pregnancy or childbirth at follow-up. Results: Almost all women accepted the community health worker intervention (90.9% (221/243)). Hypertension was at 12.5% (27/216) among those who accepted blood pressure measurements, a third (33.3% (9/27)) were pregnant. HIV prevalence was 23.5% (52/221). Over a third (34.2% (69/202)) of women tested had anemia (hemoglobin levels less than 11 g/dL). The community health worker intervention was associated with attendance of first antenatal care visit within 20 weeks of pregnancy (adjusted odd ratio = 2.1 (95% confidence interval 0.6–7.6)), attendance of at least four antenatal care visits (adjusted odd ratio = 0.9 (95% confidence interval 0.4–2.0)), and skilled birth attendance (adjusted odd ratio = 0.5 (95% confidence interval 0.1–1.5)), though not statistically significant. Conclusion: Community health workers have a crucial role in improving early antenatal care attendance, early community-based diagnosis of anemia, hypertensive disorders, and HIV among women in these hard-to-reach fishing communities.

Abstract Background Uganda has one of the highest maternal deaths at a ratio of 336 per 100,000 live births. As Uganda strives to achieve sustainable development goals, appropriate antenatal care is key to reduction of maternal mortality. We explored women’s reported receipt of seven of the Uganda guidelines components of antenatal care, and associated factors in hard to reach Lake Victoria island fishing communities of Kalangala district. Methods A cross sectional survey among 486 consenting women aged 15–49 years, who were pregnant at any time in the past 6 months was conducted in 6 island fishing communities of Kalangala district, Uganda, during January–May 2018. Interviewer administered questionnaires, were used to collect data on socio-demographics and receipt of seven of the Uganda guidelines components of antenatal care. Regression modeling was used to determine factors associated with receipt of all seven components. Results Over three fifths (65.0%) had at least one ANC visit during current or most recent pregnancy. Fewer than a quarter of women who reported attending care at least four times received all seven ANC components [(23.6%), P

Abstract Background The foreskin is the main site of HIV acquisition in a heterosexual uncircumcised man, but many men in endemic countries are reluctant to undergo penile circumcision (PC). Observational studies suggest that proinflammatory anaerobic bacteria are enriched on the uncircumcised penis, where they may enhance HIV susceptibility through increased foreskin inflammatory cytokines and the recruitment of HIV-susceptible CD4+ target cells. This trial will examine the impact of systemic and topical antimicrobials on ex vivo foreskin HIV susceptibility. Methods/design This randomized, open-label clinical trial will randomize 125 HIV-negative Ugandan men requesting voluntary PC to one of five arms (n = 25 each). The control group will receive immediate PC, while the four intervention groups will defer PC for 1 month and be provided in the interim with either oral tinidazole, penile topical metronidazole, topical clindamycin, or topical hydrogen peroxide. The impact of these interventions on HIV entry into foreskin-derived CD4+ T cells will be quantified ex vivo at the time of PC using a clade A, R5 tropic HIV pseudovirus assay (primary endpoint); secondary endpoints include the impact of antimicrobials on immune parameters and the microbiota of the participant’s penis and of the vagina of their female partner (if applicable), assessed by multiplex enzyme-linked immunosorbent assay and 16S rRNA sequencing. Discussion There is a critical need to develop acceptable, simple, and effective means of HIV prevention in men unwilling to undergo PC. This trial will provide insight into the causative role of the foreskin microbiota on HIV susceptibility, and the impact of simple microbiota-focused clinical interventions. This may pave the way for future clinical trials using low-cost, nonsurgical intervention(s) to reduce HIV risk in uncircumcised heterosexual men. Trial registration ClinicalTrials.gov, NCT03412071. Retrospectively registered on 26 January 2018.

Introduction: Family planning (FP) is a key element in the conduct of research and is essential in managing family sizes. Although fishing communities (FCs) are targeted populations for HIV prevention research, their FP practices are poorly understood. We explored barriers and facilitators of FP use in FCs of Lake Victoria in Uganda. Methods: We employed a mixed-methods approach comprising a cross-sectional survey, in-depth interviews, and focus group discussions in 2 FCs. Multivariable logistic regression was used to analyze quantitative data and a thematic approach to generate themes from the qualitative data. Results: Up to 1410 individuals participated in the survey and 47 in the qualitative study. Just over a third (35.6%) used FP. The most commonly used methods were condoms, pills, and injectables. In Kigungu community, participants whose religion was Anglican and Muslim were more likely to use FP than Catholics (adjusted odds ratio [aOR] 1.45; 95% CI 1.05-1.99 and aOR 1.45; 95% CI 1.05-2.07, respectively). Participants were more likely to use FP if they had satisfactory FP knowledge compared to those with no satisfactory FP knowledge (aOR 1.79; 95% CI 1.23-2.61), or if they were married compared to their single counterparts (aOR 1.84; 95% CI 1.32-2.57). In both communities, participants were more likely to use FP if they had 2 or more sexual partners in the past 12 months than those with less than 2 sexual partners (aOR 1.41 95% CI 1.07-1.87 and aOR 2.60; 95% CI 1.36-4.97). Excessive bleeding and delayed fecundity; fertility desire; gender preferences of children; method stock outs and lack of FP trained personnel constituted barriers to FP use. There were also cultural influences in favor of large families. Conclusion: FP use in FCs is suboptimal. Barriers of FP use were mainly biomedical, religious, social, and cultural, which underscores a need for FP education and strengthening of FP service provision in FCs.

Background: Uganda has one of the highest maternal deaths in sub-Saharan Africa, with a mortality ratio of 336 per 100 000 live births. Early regular antenatal care (ANC) helps prevent adverse outcomes, including deaths, through prevention, identification, treatment, and/or referral of at-risk women. We explored ANC practices and associated factors among women from hard-to-reach Lake Victoria islands fishing communities in Kalangala district, Uganda. Methods: A cross-sectional survey among 486 consenting women aged 15 to 49 years, who were pregnant or had a birth or abortion in the past 6 months was conducted in 6 island fishing communities of Kalangala district, Uganda, during January to May 2018. ODK software interviewer-administered questionnaires were used to collect data on sociodemographics and ANC practices. Regression modeling using STATA version 15 was used to determine factors associated with ANC visits. Results: Women’s median (range) age was 26 (15-45) years, 63% (304/486) had up to primary level education, 45% (219/486) were housewives (stay home mums), 87% (423/486) were married. ANC visits ranged from 0 to 10, with over three-fifths of women having their first visit late after 3 months of being pregnant (63%, 198/316). Women without a history of pregnancy loss (adjusted odds ratio [AOR] = 1.8, 95% CI 1.1-3.0), those not staying with their partners (AOR = 2.5, 95% CI 1.1-6.0), and those whose partners were working in fishing-related activities (AOR = 1.8, 95% CI 1.0-3.0) were likely to have started care late. Women from communities with a public health facility and those with partners working in none fishing-related activities had the highest predicted number of visits. Conclusion: Antenatal practices among these communities are characterized by late start of care. Community-led early ANC awareness interventions are needed. Targeted health policies need to consider public ANC facilities for each island for improved antenatal outcomes and maternal health.

IntroductionTetanus infection associated with men who had male circumcision has been reported in East Africa, suggesting a need for tetanus toxoid-containing vaccines (TTCV).ObjectiveTo determine the prevalence of tetanus toxoid antibodies following vaccination among men seeking circumcision.MethodsWe enrolled 620 consenting men who completed a questionnaire and received TTCV at enrollment (day 0) prior to circumcision on day 28. Blood samples were obtained at day 0 from all enrollees and on days 14, 28 and 42 from a random sample of 237 participants. Tetanus toxoid (TT) IgG antibody levels were assayed using EUROIMMUN. Analyses included prevalence of TT antibodies at enrollment and used a mixed effects model to determine the immunological response.ResultsMean age was 21.4 years, 65.2% had knowledge of tetanus, 56.6% knew how tetanus was contracted, 22.8% reported ever receipt of TTCV, and 16.8% had current/recently healed wounds. Insufficient tetanus immunity was 57.1% at enrollment, 7.2% at day 14, 3.8% at day 28, and 0% at day 42. Antibody concentration was 0.44IU/ml (CI 0.35-0.53) on day 0, 3.86IU/ml (CI 3.60-4.11) on day 14, 4.05IU/ml (CI 3.81-4.29) on day 28, and 4.48IU/ml (CI 4.28-4.68) on day 42. TT antibodies increased by 0.24IU/ml (CI 0.23, 0.26) between days 0 and 14 and by 0.023IU/ml (CI 0.015, 0.031) between days 14 and 42 days. Immunological response was poorer in HIV-infected clients and men aged 35+ years.ConclusionInsufficient immunity was common prior to TTCV, and a protective immunological response was achieved by day 14. Circumcision may safely be provided 14 days after vaccination in HIV-uninfected men aged less than 35 years.