Geospatial correlations and variations in child mortality and stunting in South Africa: Evaluating distal vs structural determinants.

South Africa has one of the highest child mortality and stunting rates in the world. Flexible geoadditive models were used to investigate the geospatial variations in child mortality and stunting in South Africa. We used consecutive rounds of national surveys (2008-2017).

Treatment adherence and clinical outcomes amongst in people with drug-susceptible tuberculosis using medication monitor and differentiated care approach compared with standard of care in South Africa: a cluster randomized trial.

Background: Poor treatment adherence contributes to lower treatment completion and higher loss to follow-up among people with tuberculosis (PWTB). Medication monitors have shown some evidence of improved adherence.

Methods: We conducted a cluster randomised trial in 18 primary health clinics in South Africa between May 2019-February 2022.

Navigating complex care pathways-healthcare workers' perspectives on health system barriers for children with tuberculous meningitis in Cape Town, South Africa.

Tuberculous meningitis (TBM) occurs when tuberculosis (TB) bacilli disseminate and seed into the meninges, triggering a severe inflammatory response that often leads to brain infarction. It is the most severe and debilitating form of childhood TB with high mortality, and children who survive TBM often suffer lifelong physical and neuro-disability resulting in emotional, social, and economic burdens for families. In the early stages the symptoms may be non-specific and so the diagnosis is often made late when the patient already has significant brain injury.

WHO global research priorities for antimicrobial resistance in human health.

The WHO research agenda for antimicrobial resistance (AMR) in human health has identified 40 research priorities to be addressed by the year 2030. These priorities focus on bacterial and fungal pathogens of crucial importance in addressing AMR, including drug-resistant pathogens causing tuberculosis. These research priorities encompass the entire people-centred journey, covering prevention, diagnosis, and treatment of antimicrobial-resistant infections, in addition to addressing the overarching knowledge gaps in AMR epidemiology, burden and drivers, policies and regulations, and awareness and education.

Strengthening the Application of the DAIDS GCLP Guidelines: The Implementation of an Integrated Laboratory Oversight Framework.

The Division of AIDS (DAIDS) Good Clinical Laboratory Practice (GCLP) Guidelines establish a framework to guide the oversight of laboratories supporting DAIDS-sponsored clinical research or trials. Compliance with these guidelines promotes data reliability, validity, and safety of the clinical research or trial participants and laboratory staff and ensures adherence to regulatory requirements. Acknowledgment and adoption of the DAIDS GCLP Guidelines are critical in building laboratory capacity and preparedness for conducting clinical trials.

Profiling IgG and IgA antibody responses during vaccination and infection in a high-risk gonorrhoea population.

Development of a vaccine against gonorrhoea is a global priority, driven by the rise in antibiotic resistance. Although Neisseria gonorrhoeae (Ng) infection does not induce substantial protective immunity, highly exposed individuals may develop immunity against re-infection with the same strain. Retrospective epidemiological studies have shown that vaccines containing Neisseria meningitidis (Nm) outer membrane vesicles (OMVs) provide a degree of cross-protection against Ng infection.

Target regimen profiles for tuberculosis treatment.

Simpler, shorter, safer and more effective treatments for tuberculosis that are easily accessible to all people with tuberculosis are desperately needed. In 2016, the World Health Organization (WHO) developed target regimen profiles for the treatment of tuberculosis to make drug developers aware of both the important features of treatment regimens, and patient and programmatic needs at the country level. In view of recent ground-breaking advances in tuberculosis treatment, WHO has revised and updated these regimen profiles.

Twice-Yearly Lenacapavir or Daily F/TAF for HIV Prevention in Cisgender Women.

Background: There are gaps in uptake of, adherence to, and persistence in the use of preexposure prophylaxis for human immunodeficiency virus (HIV) prevention among cisgender women.

Methods: We conducted a phase 3, double-blind, randomized, controlled trial involving adolescent girls and young women in South Africa and Uganda. Participants were assigned in a 2:2:1 ratio to receive subcutaneous lenacapavir every 26 weeks, daily oral emtricitabine-tenofovir alafenamide (F/TAF), or daily oral emtricitabine-tenofovir disoproxil fumarate (F/TDF; active control); all participants also received the alternate subcutaneous or oral placebo.

Mosaic HIV-1 vaccine regimen in southern African women (Imbokodo/HVTN 705/HPX2008): a randomised, double-blind, placebo-controlled, phase 2b trial.

Background: HIV type 1 (HIV-1) remains a global health concern, with the greatest burden in sub-Saharan Africa. Despite 40 years of research, no vaccine candidate has shown durable and protective efficacy against HIV-1 acquisition. Although pre-exposure prophylaxis in groups with high vulnerability can be very effective, barriers to its use, such as perceived low acquisition risk, fear of stigma, and concerns about side-effects, remain.

A pilot cross-sectional study of non-communicable diseases in TB household contacts.

Background: Data on the prevalence of non-communicable diseases (NCDs) in TB household contacts (HHCs) are limited, yet important to inform integrated screening and care for NCD within contact investigations. It is also unclear if screening these contacts reveals more people with NCDs than individuals in the same neighbourhood.

Method: We conducted a pilot cross-sectional study in South Africa and Tanzania, enrolling adult HHCs of TB and individuals in neighbourhood households (controls).

Reaching for 90:90:90 in Correctional Facilities in South Africa and Zambia: Virtual Cross-Section of Coverage of HIV Testing and Antiretroviral Therapy During Universal Test and Treat Implementation.

Background: People in correctional settings are a key population for HIV epidemic control. We sought to demonstrate scale-up of universal test and treat in correctional facilities in South Africa and Zambia through a virtual cross-sectional analysis.

Methods: We used routine data on 2 dates: At the start of universal test and treat implementation (time 1, T1) and 1 year later (time 2, T2).

Implications of subclinical tuberculosis for vaccine trial design and global effect.

Tuberculosis is a leading cause of death from an infectious agent globally. Infectious subclinical tuberculosis accounts for almost half of all tuberculosis cases in national tuberculosis prevalence surveys, and possibly contributes to transmission and might be associated with morbidity. Modelling studies suggest that new tuberculosis vaccines could have substantial health and economic effects, partly based on the assumptions made regarding subclinical tuberculosis.

Optimizing the cascade of prevention to protect people from tuberculosis: A potential game changer for reducing global tuberculosis incidence.

The provision of tuberculosis preventive treatment is one of the critical interventions to reduce tuberculosis incidence and ultimately eliminate the disease, yet we still miss appropriate tools for an impactful intervention and treatment coverage remains low. We used recent data, epidemiological estimates, and research findings to analyze the challenges of each step of the cascade of tuberculosis prevention that currently delay the strategy implementation. We addressed research gaps and implementation bottlenecks that withhold key actions in tuberculosis case finding, testing for tuberculosis infection, provision of preventive treatment with safer, shorter regimens and supporting people to complete their treatment.

The Hidden Epidemic of Isoniazid-Resistant Tuberculosis in South Africa.

Isoniazid-resistant tuberculosis (Hr-TB) is often overlooked in diagnostic algorithms because of reliance on first-line molecular assays testing only for rifampicin resistance. To determine the prevalence, outcomes, and molecular mechanisms associated with rifampin-susceptible, isoniazid-resistant TB (Hr-TB) in the Eastern Cape, South Africa. Between April 2016 and October 2017, sputum samples were collected from patients with rifampin-susceptible TB at baseline and at Weeks 7 and 23 of drug-susceptible TB treatment.

Prevalence and associated risk factors of chlamydia and gonorrhoea infections among men who have sex with men in Durban, South Africa.

Despite significant research on the prevalence of STIs in South African men who have sex with men (MSM), recent data on the prevalence and risk factors for curable STI infections among this key populations are limited. This study determined the prevalence of and risk factors associated with Neisseria gonorrhoeae and Chlamydia trachomatis infections among MSM. The sample consisted of 200 MSM resident in Durban.

Factors associated with reactogenicity to an investigational HIV vaccine regimen in HIV vaccine trials network 702.

Background: Reactogenicity informs vaccine safety, and may influence vaccine uptake. We evaluated factors associated with reactogenicity in HVTN 702, a typical HIV vaccine efficacy trial with multiple doses and products.

Methods: HVTN 702, a phase 2b/3 double-blind placebo-controlled trial, randomized 5404 African participants aged 18-35 years without HIV to placebo, or ALVAC-HIV (vCP2438) at months 0, 1 and ALVAC-HIV (vCP2438) + Bivalent Subtype C gp120/MF59 at months 3, 6, 12 and 18.

Lung outcomes and related risk factors in patients after SARS-CoV-2 infection: a hospitalised single-centre cohort from Johannesburg, South Africa.

Background: Sequelae post-SARS-CoV-2 infection, including lung and functional impairment, pose a significant challenge post-recovery. We explored the burden and risk factors for post-COVID-19 sequelae in an African population with prevalent comorbidities including tuberculosis (TB) and HIV.

Methods: We conducted an observational cohort study on hospitalised adults with confirmed SARS-CoV-2 infection from 20 March to 06 October 2021 at Chris Hani Baragwanath Academic Hospital, South Africa.

Pharmacokinetics and safety of coformulated bictegravir, emtricitabine, and tenofovir alafenamide in children aged 2 years and older with virologically suppressed HIV: a phase 2/3, open-label, single-arm study.

Background: Coformulated bictegravir, emtricitabine, and tenofovir alafenamide is a single-tablet regimen and was efficacious and well tolerated in children and adolescents with HIV (aged 6 years to <18 years) in a 48-week phase 2/3 trial. In this study, we report data from children aged at least 2 years and weighing 14 kg to less than 25 kg.

Methods: We conducted this open-label, multicentre, multicohort, single-arm study in South Africa, Thailand, Uganda, and the USA.

HLA-A*23 Is Associated With Lower Odds of Acute Retroviral Syndrome in Human Immunodeficiency Virus Type 1 Infection: A Multicenter Sub-Saharan African Study.

The role of human leukocyte antigen (HLA) class I and killer immunoglobulin-like receptor molecules in mediating acute retroviral syndrome (ARS) during human immunodeficiency virus type 1 (HIV-1) infection is unclear. Among 72 sub-Saharan African adults, HLA-A*23 was associated with lower odds of ARS (adjusted odds ratio, 0.10 [95% confidence interval, .

Safety and Immunogenicity of the H56:IC31 Tuberculosis Vaccine Candidate in Adults Successfully Treated for Drug-Susceptible Pulmonary Tuberculosis: A Phase 1 Randomized Trial.

Background: H56:IC31 is a candidate vaccine against tuberculosis (TB) with the potential to reduce TB recurrence rate. It is thus important for future clinical trials to demonstrate safety and immunogenicity of H56:IC31 in individuals treated for TB.

Methods: Twenty-two adults confirmed to be Mycobacterium tuberculosis negative (by 2 GeneXpert tests or 2 sputum cultures) after 4-5 months of TB treatment, and not more than 28 days after completion of TB treatment, were randomized to receive 2 doses of H56:IC31 (5 mg H56:500 nmol IC31; n = 16) or placebo (n = 6) 56 days apart.

Knowledge, attitudes and practices of oral HIV pre-exposure prophylaxis (PrEP) among healthcare workers in the Ekurhuleni District, South Africa.

Background: Prevention of new HIV infections is crucial for controlling the HIV epidemic. Despite HIV pre-exposure prophylaxis (PrEP) being one of the highly effective approaches to preventing HIV, and being freely available through primary healthcare clinics (PHCs), the uptake of HIV PrEP in South Africa (SA) is low.

Objective: To understand knowledge, attitudes and practices (KAPs) of healthcare workers responsible for generating demand for HIV PrEP services, or identifying clients eligible for HIV PrEP services in PHCs in Ekurhuleni District, South Africa.