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Background: We evaluated continuous quality improvement (CQI) targeting antenatal HIV care quality in rural South Africa using a stepped-wedge cluster-randomised controlled trial (Management and Optimisation of Nutrition, Antenatal, Reproductive, Child health, MONARCH) and an embedded process evaluation. Here, we present results of the process evaluation examining determinants of CQI practice and 'normalisation.' Methods: A team of CQI mentors supported public-sector health workers in seven primary care clinics to (1) identify root causes of poor HIV viral load (VL) monitoring among pregnant women living with HIV and repeat HIV testing among pregnant women not living with HIV, and (2) design and iteratively test their own solutions. We used a mixed methods evaluation with field notes from CQI mentors ('dose' and 'reach' of CQI, causes of poor HIV care testing rates, implemented change ideas); patient medical records (HIV care testing by clinic and time step); and semi-structured interviews with available health workers. We analysed field notes and semi-structured interviews for determinants of CQI implementation and 'normalisation' using Normalisation Process Theory (NPT) and Tailored Implementation of Chronic Diseases (TICD) frameworks. Results: All interviewed health workers found the CQI mentors and methodology helpful for quality improvement. Total administered 'dose' was higher than planned but 'reach' was limited by resource constraints, particularly staffing shortages. Simple workable improvements to identified root causes were implemented, such as a patient tracking notebook and results filing system. VL monitoring improved over time, but not repeat HIV testing. Besides resource constraints, gaps in knowledge of guidelines, lack of leadership, poor clinical documentation, and data quality gaps reduced CQI implementation fidelity and normalisation. Conclusion: While CQI holds promise, we identified several health system challenges. Priorities for policy makers include improving staffing and strategies to improve clinical documentation. Additional support with implementing clinical guidelines and improving routine data quality are needed. Normalising CQI may be challenging without concurrent health system improvements. [ABSTRACT FROM AUTHOR]

Since Chagas disease, melioidosis, and Legionnaires' disease are all potentially life-threatening infections, there is an urgent need for new treatment strategies. All causative agents, Trypanosoma cruzi , Burkholderia pseudomallei , and Legionella pneumophila , express a virulence factor, the macrophage infectivity potentiator (MIP) protein, emerging as a promising new therapeutic target. Inhibition of MIP proteins having a peptidyl-prolyl isomerase activity leads to reduced viability, proliferation, and cell invasion. The affinity of a series of pipecolic acid-type MIP inhibitors was evaluated against all MIPs using a fluorescence polarization assay. The analysis of structure-activity relationships led to highly active inhibitors of MIPs of all pathogens, characterized by a one-digit nanomolar affinity for the MIPs and a very effective inhibition of their peptidyl-prolyl isomerase activity. Docking studies, molecular dynamics simulations, and quantum mechanical calculations suggest an extended σ-hole of the meta -halogenated phenyl sulfonamide to be responsible for the high affinity.

Background: Young (ages 18-35 years) men are inadequately engaged in HIV prevention and treatment globally, including in South Africa, increasing the likelihood of them having sexually transmissible HIV (i.e. living with HIV but with high viral loads). We sought to understand how men's experiences of poverty and violence, impacted on transmissible HIV, directly or indirectly via mental health and substance misuse., Setting: Rural communities in northern KwaZulu-Natal, South Africa., Methods: Cross-sectional population-based random selection (September 2018-June 2019), assessing transmissible HIV (living with HIV and viral load ≥400 copies/mL) via dried blood spots, and socio-demographic data. Structural equation models (SEM), assessed direct and indirect pathways from food insecurity and violence experience to transmissible-HIV, with mediators common mental disorders, alcohol use, gender inequitable attitudes and perceptions of life chances., Results: 2,086 young (ages 18-36 years) men and 8.6%(n=178) men had transmissible HIV. In SEM no direct pathways between food insecurity, or violence experience, and transmissible HIV. Poor mental health and alcohol use mediated the relationship between violence experience and food insecurity and transmissible HIV. Life chances also mediated the food insecurity to transmissible HIV pathway., Conclusions: There was a high level of transmissible HIV in a representative sample of young men. The analysis highlights the need to address both the proximate 'drivers' poor mental health and substance misuse, as well as the social contexts shaping these among young men, namely poverty and violence experience. Building holistic interventions that adequately engage these multiple challenges is critical for improving HIV among young men., Competing Interests: Conflict of Interest Statement The authors have no conflict of interests to report.

Background: Recent population-representative estimates of sexually transmitted infection (STI) prevalence in high HIV burden areas in southern Africa are limited. We estimated the prevalence and associated factors of 3 STIs among adolescents and young adults (AYA) in rural South Africa., Methods: Between March 2020 and May 2021, a population-representative sample of AYA aged 16 to 29 years were randomly selected from a Health and Demographic Surveillance Site in rural KwaZulu-Natal, South Africa, for a 2 × 2 factorial randomized controlled trial. Participants in 2 intervention arms were offered baseline testing for gonorrhea, chlamydia, and trichomoniasis using GeneXpert. Prevalence estimates were weighted for participation bias, and logistic regression models were used to assess factors associated with STIs., Results: Of 2323 eligible AYA, 1743 (75%) enrolled in the trial. Among 863 eligible for STI testing, 814 (94%) provided specimens (median age of 21.8 years, 52% female, and 71% residing in rural areas). Population-weighted prevalence estimates were 5.0% (95% confidence interval [CI], 4.2%-5.8%) for gonorrhea, 17.9% (16.5%-19.3%) for chlamydia, 5.4% (4.6%-6.3%) for trichomoniasis, and 23.7% (22.2%-25.3%) for any STI. In multivariable models, female sex (adjusted odds ratio [aOR], 2.24; 95% CI, 1.48-3.09) and urban/periurban (vs. rural) residence (aOR, 1.48; 95% CI, 1.02-2.15) were associated with STIs; recent migration was associated with lower odds of STI (aOR, 0.37; 95% CI, 0.15-0.89). Among those with an STI, 53 (31.0%) were treated within 7 days; median time to treatment was 11 days (interquartile range, 6-77 days)., Conclusions: We identified a high prevalence of curable STIs among AYA in rural South Africa. Improved access to STI testing to enable etiologic diagnosis and rapid treatment is needed., Competing Interests: Conflict of Interest and Sources of Funding: J.J. has received in-kind research support from Binx Health. All other authors declare no conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Sexually Transmitted Diseases Association.)