Exploring the wound healing potential of Lobostemon fruticosus using in vitro and in vivo bioassays.

ETHNOPHARMACOLOGICAL RELEVANCE: Lobostemon fruticosus (L.) H.Buek is a perennial and woody shrub of the Boraginaceae family, found in the Cape region of South Africa. The leaves and twigs are used to treat dermatological conditions such as wounds, burns, ringworm, erysipelas and eczema. Anti-inflammatory, antibacterial, antiviral and anti-proliferative activities of L. fruticosus have been reported. However, there is a void in research which reports on the wound healing properties of this plant. AIM OF THE STUDY: Aligned with the traditional use of L. fruticosus, our study aimed to use in vitro and in vivo bioassays to confirm the wound healing potential of the plant. MATERIALS AND METHODS: An aqueous methanol extract (80% v/v) of L. fruticosus was prepared using a sample collected from the Western Cape Province of South Africa and chromatographically profiled by ultra-performance liquid chromatography coupled to mass spectrometry (UPLC-MS). The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity assay was performed to determine the non-toxic concentrations of the extract for subsequent use in the in vitro scratch assay. Both the human keratinocyte (HaCaT) and fibroblast (BJ-5ta) cell lines were employed in the in vitro scratch assay. The in vivo caudal fin amputation assay was used to assess the wound healing potential of L. fruticosus, by monitoring fin regeneration in zebrafish larvae treated with the plant extract at various concentrations. RESULTS: Six major compounds were tentatively identified in the L. fruticosus extract namely; globoidnan A, globoidnan B, rutin, rabdosiin, sagerinic acid and rosmarinic acid. The potentially toxic pyrrolizidine alkaloids were also identified and quantitatively confirmed to be present at a low concentration of 119.58 ppm (m/m). Treatment of HaCaT and BJ-5ta cells with the plant extract in the scratch assay resulted in an increase in cell migration, which translates to accelerated wound closure. After 24 hr treatment with 100 µg/mL of extract, wound closure was recorded to be 91.1 ± 5.7% and 94.1 ± 1.3% for the HaCaT and BJ-5ta cells, respectively, while the untreated (medium) controls showed 72.3 ± 3.3% and 73.0 ± 4.3% for the two cell lines, respectively. Complete wound closure was observed between 24 and 36 hr, while the untreated control group did not achieve 100% wound closure by the end of the observation period (48 hr). In vivo, the crude extract at 100 µg/mL accelerated zebrafish caudal fin regeneration achieving 100.5 ± 3.8% regeneration compared to 68.3 ± 6.6% in the untreated control at two days post amputation. CONCLUSIONS: The study affirms the wound healing properties, as well as low toxicity of L. fruticosus using both in vitro and in vivo assays, which supports the traditional medicinal use. Other in vitro assays that target different mechanisms involved in wound healing should be investigated to support the current findings.

Microbial community profiling in intestinal tract of indigenous chickens from different villages.

Village chickens (Gallus gallus domesticus) are commonly reared in rural households of South Africa and other developing countries. They play a vital role as a primary source of protein through the provision of meat and eggs. The chicken gut microbiota plays an important role in chicken's immune system, its health, physiological development of the gut, digestion of food, nutrient absorption and productivity. Thus, it is imperative to critically investigate the chicken microbial composition in order to develop effective disease control measures and increase production. In this present study, microbial DNA was isolated from 34 non-descript mixed gender matured village chickens' intestinal contents followed by high throughput Illumina sequencing targeting 16S rRNA gene. Senwamokgope village had the largest microbiota composition as compared to Itieleni and Thakgalang villages. Overall, Firmicutes (74%) was the most abundant phylum observed, followed by Proteobacteria (8%), Actinobateria (5%), and Bacteroidota (3%). At the genus level, Lactobacillus was the dominant bacteria. Other genera found included Sphingomonas (7%), Cutibacterium (4%), and Clostridium_sensu_stricto_1 (2%). The richness of female intestinal microbiota was higher compared to the male microbiota. The findings of this study provide baseline information that can assist to better understand the chicken gut microbiota and its interaction with diseases and parasites.

Cohort profile: Rahima Moosa Mother and Child Hospital maternal HIV cohort, Johannesburg, South Africa.

PURPOSE: The Rahima Moosa Mother and Child Hospital (RMMCH) maternal HIV cohort originated from data systems that were developed to support HIV-related birth care and track outcomes of a complete birth cohort of HIV-exposed infants at Rahima Moosa Hospital and their mothers living with HIV. PARTICIPANTS: Supported by the Empilweni Services and Research Unit, maternal and infant data from 13 654 pregnant women living with HIV who delivered their infants (and a subset also attended antenatal care) were collected at RMMCH in Johannesburg, South Africa since 2013. Maternal data were collected using counsellor-administered interviews and the 2013-2018 subset of this cohort was linked to the National Health Laboratory Services (NHLS) national HIV cohort-a longitudinal cohort of people living with HIV accessing care in the public sector antiretroviral therapy programme in South Africa that can observe national access to HIV care through laboratory testing data. FINDINGS TO DATE: Topics addressed by the cohort include antenatal care history, HIV treatment exposure, delivery/birth management, prophylaxis and maternal blood results relevant to HIV captured at delivery. The cohort was also one of the first to describe implementation of early infant diagnosis procedures in South Africa including evaluations of novel point-of-care testing strategies demonstrating improvements in uptake of HIV care among infants accessing point-of-care services. FUTURE PLANS: Annual linkage of infant delivery and testing data to longitudinal laboratory test data in the NHLS national HIV cohort is planned to allow for analysis of both infant continuity of care outcomes and as well as evaluation of maternal-infant pair treatment and mobility outcomes in the post partum and later period.

A possible later stone age painting of a dicynodont (Synapsida) from the South African Karoo.

The Horned Serpent panel at La Belle France (Free State Province, South Africa) was painted by the San at least two hundred years ago. It pictures, among many other elements, a tusked animal with a head that resembles that of a dicynodont, the fossils of which are abundant and conspicuous in the Karoo Basin. This picture also seemingly relates to a local San myth about large animals that once roamed southern Africa and are now extinct. This suggests the existence of a San geomyth about dicynodonts. Here, the La Belle France site has been visited, the existence of the painted tusked animal is confirmed, and the presence of tetrapod fossils in its immediate vicinity is supported. Altogether, they suggest a case of indigenous palaeontology. The painting is dated between 1821 and 1835, or older, making it at least ten years older than the formal scientific description of the first dicynodont, Dicynodon lacerticeps, in 1845. The painting of a dicynodont by the San would also suggest that they integrated (at least some) fossils into their belief system.

T-cell responses to ancestral SARS-CoV-2 and Omicron variant among unvaccinated pregnant and postpartum women living with and without HIV in South Africa.

SARS-CoV-2 cell-mediated immunity remains understudied during pregnancy in unvaccinated Black African women living with HIV (WLWH) from low- and middle-income countries. We investigated SARS-CoV-2-specific T-cell responses 1 month following infection in 24 HIV-uninfected women and 15 WLWH at any stage during pregnancy or postpartum. The full-length spike (FLS) glycoprotein and nucleocapsid (N) protein of wild-type (WT) SARS-CoV-2, as well as mutated spike protein regions found in the Omicron variant (B.1.1.529) were targeted by flow cytometry. WT-specific CD4+ and CD8+ T cells elicited similar FLS- and N-specific responses in HIV-uninfected women and WLWH. SARS-CoV-2-specific T-lymphocytes were predominantly TNF-α monofunctional in pregnant and postpartum women living with and without HIV, with fever cells producing either IFN-γ or IL-2. Furthermore, T-cell responses were unaffected by Omicron-specific spike mutations as similar responses between Omicron and the ancestral virus were detected for CD4+ and CD8+ T cells. Our results collectively demonstrate comparable T-cell responses between WLWH on antiretroviral therapy and HIV-uninfected pregnant and postpartum women who were naïve to Covid-19 vaccination. Additionally, we show that T cells from women infected with the ancestral virus, Beta variant (B.1.351), or Delta variant (B.1.617.2) can cross-recognize Omicron, suggesting an overall preservation of T-cell immunity.

Piloting the Inclusion of the Key Populations Unique Identifier Code in the South African Routine Health Information Management System: Protocol for a Multiphased Study.

BACKGROUND: The global community has set an ambitious goal to end HIV/AIDS as a public health threat by 2030. Significant progress has been achieved in pursuing these objectives; however, concerns remain regarding the lack of disaggregated routine data for key populations (KPs) for a targeted HIV response. KPs include female sex workers, transgender populations, gay men and other men who have sex with men, people who are incarcerated, and people who use drugs. From an epidemiological perspective, KPs play a fundamental role in shaping the dynamics of HIV transmission due to specific behaviors. In South Africa, routine health information management systems (RHIMS) do not include a unique identifier code (UIC) for KPs. The purpose of this protocol is to develop the framework for improved HIV monitoring and programming through piloting the inclusion of KPs UIC in the South African RHIMS. OBJECTIVE: This paper aims to describe the protocol for a multiphased study to pilot the inclusion of KPs UIC in RHIMS. METHODS: We will conduct a multiphased study to pilot the framework for the inclusion of KPs UIC in the RHIMS. The study has attained the University of Johannesburg Research Ethics Committee approval (REC-2518-2023). This study has four objectives, including a systematic review, according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines (objective 1). Second, policy document review and in-depth stakeholder interviews using semistructured questionnaires (objective 2). Third, exploratory data analysis of deidentified HIV data sets (objective 3), and finally, piloting the framework to assess the feasibility of incorporating KPs UIC in RHIMS using findings from objectives 1, 2, and 3 (objective 4). Qualitative and quantitative data will be analyzed using ATLAS.ti (version 6; ATLAS.ti Scientific Software Development GmbH) and Python (version 3.8; Python Software Foundation) programming language, respectively. RESULTS: The results will encompass a systematic review of literature, qualitative interviews, and document reviews, along with exploratory analysis of deidentified routine program data and findings from the pilot study. The systematic review has been registered in PROSPERO (International Prospective Register of Systematic Reviews; CRD42023440656). Data collection is planned to commence in September 2024 and expected results for all objectives will be published by December 2025. CONCLUSIONS: The study will produce a framework to be recommended for the inclusion of the KP UIC national rollout. The study results will contribute to the knowledge base around the inclusion of KPs UIC in RHIMS data. TRIAL REGISTRATION: PROSPERO CRD42023440656; https://tinyurl.com/msnppany. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/55092.

Experiences of ecosystem changes on food services of mopane woodland communities in Vhembe, South Africa.

Mopane woodlands have been shifting. While it is important to understand the spatial patterns that characterise this phenomenon, it is even more important to understand the impacts of shifting Mopane woodlands on rural communities that rely on them. This study sought to establish the impacts of shifting mopane woodlands on the production of indigenous plant food in Ward 12 of Musina local municipality in the Vhembe District municipality in the Limpopo province of South Africa. To accomplish this, the study utilised a hybrid inductive approach involving thematic-based questionnaire interviews and an exploratory view to gain insight into the narratives of focus group participants. Results revealed that seven (7) out of eleven (11) indigenous plant foods are becoming extinct, thereby limiting food sources of indigenous and local people who used to rely on them. The spatial pattern of the plant foods that are still available has now changed as they no longer grow within the reach of local communities. The community members are struggling to adapt to these changes. From these observations, we recommend that local and regional levels' policies related to natural resource management should consider the unique challenges faced by communities experiencing disruptive ecosystem changes and provide the necessary support for sustainable adaptation.

Modelling drought in South Africa: meteorological insights and predictive parameters.

South Africa has grappled with recurring drought scenarios for over two decades, leading to substantial economic losses. Droughts in the Western Cape between 2015 and 2018, especially in Cape Town was declared a national disaster, resulting in the strict water rationing and the "day zero" effect. This study presents a set of simulations for predicting drought over South Africa using Artificial Neural Network (ANN), using Standard Precipitation Index (SPI) as the drought indicator in line with the recommendations of the World Meteorological Organization (WMO). Furthermore, different meteorological variables and an aerosol parameter were used to develop the drought set in four distinct locations in South Africa for a 21-year period. That data used include relative humidity (rh), temperature (tp), soil wetness (sw), evapotranspiration (et), evaporation (ev) sea surface temperature (st), and aerosol optical depth (aa). The obtained R2 values for SPI3 ranged from 0.49 to 0.84 and from 0.22 to 0.84 for SPI6 at Spring Bok, Umtata 0.83 to 0.95 for SPI3, and 0.61 to 0.87 for SPI6; Cape Town displayed R2 values from 0.78 to 0.94 for SPI3 and 0.57 to 0.95 for SPI6, while Upington had 0.77-0.95 for SPI3, and 0.78-0.92 for SPI6. These findings underscore the significance of evapotranspiration (et) as a pivotal parameter in drought simulation. Additionally, the predictive accuracy of these parameter combinations varied distinctly across different locations, even for the same set of parameters. This implies that there is no single universal scheme for drought prediction. Hence, the results are important for simulating future drought scenarios at different parts of South Africa. Finally, this study shows that ANN is an effective tool that can be utilized for drought studies and simulations.

Estimation of vaccine effectiveness against SARS-CoV-2-associated hospitalization using sentinel surveillance in South Africa.

BACKGROUND: COVID-19 vaccine effectiveness (VE) studies leveraging systematic surveillance in sub-Saharan Africa are limited. We assessed the effectiveness of two vaccines (Pfizer BNT162b2 and Johnson & Johnson Ad26.COV2.S) against SARS-CoV-2-associated hospitalization in South African adults aged ≥18 years. METHODS: We conducted a test-negative case-control study using pneumonia surveillance data in South Africa. Inpatients with physician-diagnosed lower respiratory tract infection or suspected COVID-19, testing SARS-CoV-2 positive or negative from June 2021-March 2022, were cases or controls, respectively. Fully vaccinated individuals received one Ad26.COV2.S dose or two BNT162b2 doses ≥14-days before enrollment. VE was estimated using multivariable logistic regression for Delta- and Omicron BA.1/BA.2-predominant periods, stratified by age and HIV status. RESULTS: The study included 925 cases and 1890 controls; 38 (4%) cases and 186 (10%) controls were fully vaccinated with BNT162b2, and 30 (3%) cases and 94 (5%) controls with Ad26.COV2.S. The vaccine effectiveness of BNT162b2 against SARS-CoV-2-associated hospitalization over Delta and Omicron BA.1/BA.2 periods was 91% (95% CI: 52%, 98%) and 33% (-16%, 86%), respectively. The vaccine effectiveness of Ad26.COV2.S against hospitalization over Delta and Omicron BA.1/BA.2 periods was 72% (-36% ,94%), and -19% (-130%, 39%), respectively. The vaccine effectiveness of BNT162b2 against hospitalization over the Delta period was 94% (50%, 99%) and 89% (27%, 98%) among adults aged ≥60 years and HIV-uninfected, respectively. CONCLUSIONS: The BNT162b2 vaccine was effective against SARS-CoV-2-associated hospitalization during the Delta period for adults aged ≥18 years, ≥60 years and those HIV-uninfected. VE for Ad26.COV2.S was inconclusive, potentially due to limited sample size or residual confounding. These findings highlight the utility of sentinel surveillance for estimating VE.

Pandemic preparedness: why humanities and social sciences matter.

Whilst many lessons were learned from the COVID-19 pandemic, ongoing reflection is needed to develop and maintain preparedness for future outbreaks. Within the field of infectious disease and public health there remain silos and hierarchies in interdisciplinary work, with the risk that humanities and social sciences remain on the epistemological peripheries. However, these disciplines offer insights, expertise and tools that contribute to understanding responses to disease and uptake of interventions for prevention and treatment. In this Perspective, using examples from our own cross-disciplinary research and engagement programme on vaccine hesitancy in South Africa and the United Kingdom (UK), we propose closer integration of expertise, research and methods from humanities and social sciences into pandemic preparedness.

Access to and provision of sexual and reproductive health services in Ekurhuleni, South Africa: Experiences and coping strategies of migrant women and healthcare workers.

The importance of universal access to health services including sexual and reproductive health and rights (SRHR) services by migrant populations and the fundamental role of healthcare workers in providing SRHR services, requires a balanced understanding of the experiences of both migrants and healthcare workers. This study explored the experiences of migrant women in accessing and utilising SRHR services and the experiences of healthcare workers in providing SRHR and HIV services in Ekurhuleni, South Africa. In-depth interviews were conducted with five internal migrants, eight international migrant women aged 18-49 years, and four healthcare workers. Migrant women were selected using snowball sampling while healthcare workers were purposively sampled. Migrant women face multifaceted challenges including but not limited to language barriers, discrimination based on migration status, cultural and religious hurdles when accessing and utilising SRHR and HIV services. Similarly, healthcare workers encounter challenges in providing SRHR and HIV services to migrant women which include language barriers and having migrants who seek services without referral documentation and legal migration documents. Training healthcare workers on cultural sensitivity and integration of migrant friendly services in the health policy may improve migrant women's experiences in accessing and utilising as well as healthcare workers' experiences in providing SRHR services.

L'importance de l'accès universel aux services de santé, y compris les services de santé et de droits sexuels et reproductifs (SDSR) pour les populations migrantes et le rôle fondamental des agents de santé dans la fourniture de services SDSR, nécessitent une compréhension équilibrée des expériences des migrants et des agents de santé. Cette étude a exploré les expériences des femmes migrantes en matière d'accès et d'utilisation des services SDSR et les expériences des agents de santé dans la fourniture de services SDSR et VIH à Ekurhuleni, Afrique du Sud. Des entretiens approfondis ont été menés avec cinq migrants internes, huit femmes migrantes internationales âgées de 18 à 49 ans et quatre agents de santé. Les femmes migrantes ont été sélectionnées à l'aide d'un échantillonnage boule de neige tandis que les travailleurs de la santé ont été échantillonnés à dessein. Les femmes migrantes sont confrontées à des défis multiformes, notamment les barrières linguistiques, la discrimination basée sur le statut migratoire, les obstacles culturels et religieux lors de l'accès et de l'utilisation des services SDSR et VIH. De même, les agents de santé rencontrent des difficultés pour fournir des services SDSR et VIH aux femmes migrantes, notamment des barrières linguistiques et le fait que les migrantes recherchent des services sans documents de référence ni documents de migration légaux. La formation des agents de santé à la sensibilité culturelle et à l'intégration de services adaptés aux migrants dans la politique de santé peut améliorer les expériences des femmes migrantes en matière d'accès et d'utilisation, ainsi que les expériences des agents de santé dans la fourniture de services SDSR.

Prevalence of co-infections with Ehrlichia spp. or Theileria spp. in dogs naturally infected with babesiosis in the Eastern Cape province.

BACKGROUND: Canine babesiosis and ehrlichiosis are tick-borne infections of great significance in South Africa. Theileriosis in dogs in South Africa is still poorly understood. Co-infection with multiple tick-borne diseases has been documented and is perceived as a common occurrence in South Africa. OBJECTIVES: The main objective of this study was to determine the prevalence of co-infections with Ehrlichia canis or Theileria equi in dogs with babesiosis in the Eastern Cape province. There is a lack of data on canine tick-borne disease distribution in this region. Possible associations of population characteristics and haematological and biochemistry measures with a co-infection of E. canis or T. equi in these dogs were also investigated. METHOD: The study population included 150 dogs naturally infected with babesiosis that presented to the Mdantsane State Veterinary Clinic between January 2021 and November 2021. Quantitative polymerase chain reaction was used to confirm the Babesia spp. that the dogs were infected with and to identify co-infections. Association with co-infection for the following parameters were evaluated: sex, breed, age, duration of illness, leukocyte count, band neutrophil count, monocyte count, platelet count, ARC, and serum globulin concentration. Positive and negative predictive values of monocytosis, leukopenia, band neutrophilia, thrombocytopenia, and non-regenerative absolute reticulocyte count for co-infection were also calculated. RESULTS: Babesia rossi was identified in 149/150 samples and B. vogeli in only 1/150 samples. A co-infection prevalence of 2.0% (3/149; 95% CI: 0.4-5.7) with B. rossi and E. canis was found. No other co-infections were reported. No investigated variables showed significant associations with co-infections. Monocytosis, in particular, was not associated with co-infection. CONCLUSION: Co-infection with other tick-borne diseases in dogs with babesiosis is uncommon in the Eastern Cape province. These findings raise the possibility that B. rossi may have a protective effect against other tick-borne diseases.

Sexually transmitted infections and bacterial vaginosis among adolescent girls and young women in the early postpartum period: a cross-sectional study.

BACKGROUND: Universal antiretroviral treatment (ART) for pregnant women has reduced mother-to-child transmission risk significantly. However, not all women on ART are virally suppressed during pregnancy and lactation. In addition to poor adherence to ART, co-infections particularly other sexually transmitted infections (STIs) are known to increase the risk of HIV acquisition and HIV transmission. While the prevalence of STIs during pregnancy has been well studied, the prevalence of STIs in the postpartum period and its association with HIV viral suppression are underreported. METHODS: In this cross-sectional study, we determined the prevalence of STIs among adolescent girls and young women (AGYW) living with HIV (WLHIV) and without HIV (WNLHIV) at their 6-14 week postnatal clinic visit in a high HIV prevalence district in South Africa. All women were examined for STI-related symptoms and had vaginal swabs collected and stored for later STI testing. Vaginal swabs were tested for Trichomonas vaginalis (T.vaginalis), Chlamydia trachomatis (C. trachomatis), Neisseria gonorrhoeae (N. gonorrhoea) and herpes simplex virus-2 (HSV-2) using PCR. All women were tested for bacterial vaginosis (BV) using the Nugent scoring criteria. WLHIV had a blood sample collected for HIV viral load, Hepatitis B and syphilis. RESULTS: Included in this analysis were 82 WLHIV and 102 WNLHIV. Between 6 and 14 weeks postpartum, 40 (21.7%) AGYW tested positive for any STI and among these 15 (37.5%) were symptomatic and received empirical treatment. C. trachomatis was most commonly detected (10.9%), followed by HSV-2 (7.7%), T. vaginalis (3.8%) and N. gonorrhoea (1.6%). WLHIV were more likely to test positive for an STI (OR 2.0; 0.96-3.96) and BV (OR 4.2; 95%CI 2.1-8.1) compared to WNLHIV. Among WLHIV on ART, 70.5% had an undetectable plasma viral load (PVL) and 20.5% had a PVL > 1000 copies/ml. Testing positive for any STI or BV at the postpartum visit was not associated with PVL > 1000 copies/ml (OR 1.33; 95%CI 0.38-4.64). CONCLUSION: We report a high prevalence of largely asymptomatic STIs and BV in the early postpartum period and STIs in WLHIV were not associated with unsuppressed PVL.The high STI positivity rate among WNLHIV has implications for HIV risk during the postpartum period, and subsequently breastfeeding transmission.

The management of community-acquired pneumonia in adults at a rural regional hospital in KwaZulu Natal.

BACKGROUND: Pneumonia stands as a significant global contributor to mortality, particularly in South Africa, where it ranks as the second leading cause of death. The country's high prevalence of HIV infection compounds this issue, significantly increasing mortality rates associated with community-acquired pneumonia (CAP). OBJECTIVE: This study aimed to audit CAP patient management at a regional rural hospital in KwaZulu-Natal. METHOD: A retrospective review of patient files from September to December 2016 was undertaken. Data extraction from clinical files, conducted according to inclusion criteria, was transferred to a data collection sheet and analyzed using SPSS version 21. RESULTS: The review encompassed 124 patient files over four months, revealing that 117 (94.4%) patients were not managed by the Standard Treatment Guidelines and Essential Medicines List for South Africa. Of the patients admitted with CAP, 54% were HIV positive, and 49 (39.5%) patients succumbed to the illness. Notably, none of the patients underwent assessment using a severity score. CONCLUSION: The findings underscore a need for more adherence to South African guidelines for managing CAP among staff at the rural regional hospital. This leads to severe consequences, exemplified by the high mortality rate. Urgent intervention is required to incorporate severity assessment scores into pneumonia evaluations, thus enabling appropriate clinical management. CONTRIBUTION: This study sheds light on the significant impact of CAP within the South African hospital context, delineating critical gaps in clinical care and emphasizing the imperative to address clinical inertia.

Neurological Symptoms and Cause of Death Among Young Children in Low- and Middle-Income Countries.

Importance: The emergence of acute neurological symptoms in children necessitates immediate intervention. Although low- and middle-income countries (LMICs) bear the highest burden of neurological diseases, there is a scarcity of diagnostic and therapeutic resources. Therefore, current understanding of the etiology of neurological emergencies in LMICs relies mainly on clinical diagnoses and verbal autopsies. Objective: To characterize the association of premortem neurological symptoms and their management with postmortem-confirmed cause of death among children aged younger than 5 years in LMICs and to identify current gaps and improve strategies to enhance child survival. Design, Setting, and Participants: This cross-sectional study was conducted between December 3, 2016, and July 22, 2022, at the 7 participating sites in the Child Health and Mortality Prevention Surveillance (CHAMPS) network (Bangladesh, Ethiopia, Kenya, Mali, Mozambique, Sierra Leone, and South Africa). Minimally invasive tissue sampling was performed at the CHAMPS sites with specimens from deceased children aged younger than 5 years. This study included deceased children who underwent a premortem neurological evaluation and had a postmortem-confirmed cause of death. Data analysis was performed between July 22, 2022, and January 15, 2023. Main Outcomes and Measures: Descriptive analysis was performed using neurological evaluations from premortem clinical records and from postmortem determination of cause of death (based on histopathology, microbiological testing, clinical records, and verbal autopsies). Results: Of the 2127 deaths of children codified during the study period, 1330 (62.5%) had neurological evaluations recorded and were included in this analysis. The 1330 children had a median age of 11 (IQR, 2-324) days; 745 (56.0%) were male and 727 (54.7%) presented with neurological symptoms during illness before death. The most common postmortem-confirmed neurological diagnoses related to death were hypoxic events (308 [23.2%]), meningoencephalitis (135 [10.2%]), and cerebral malaria (68 [5.1%]). There were 12 neonates with overlapping hypoxic events and meningoencephalitis, but there were no patients with overlapping meningoencephalitis and cerebral malaria. Neurological symptoms were similar among diagnoses, and no combination of symptoms was accurate in differentiating them without complementary tools. However, only 25 children (18.5%) with meningitis had a lumbar puncture performed before death. Nearly 90% of deaths (442 of 511 [86.5%]) with neurological diagnoses in the chain of events leading to death were considered preventable. Conclusions and Relevance: In this cross-sectional study of children aged younger than 5 years, neurological symptoms were frequent before death. However, clinical phenotypes were insufficient to differentiate the most common underlying neurological diagnoses. The low rate of lumbar punctures performed was especially worrying, suggesting a challenge in quality of care of children presenting with neurological symptoms. Improved diagnostic management of neurological emergencies is necessary to ultimately reduce mortality in this vulnerable population.

Prevalence and factors associated with external HIV-related stigma in the South African population: Results from the 2017 population-based household survey.

External HIV-related stigma remains pervasive, and its effect debilitating among PLHIV in South Africa, even though the country has made many advances against HIV. External HIV-related stigma impedes both HIV prevention and access to health care and reduces the quality of treatment and care received. This study examined the prevalence of and factors associated with higher levels of HIV-related stigma among youth and adults 15 years and older in South Africa. The analysis used a nationally representative population-based household survey data collected using a multistage cluster random sampling design. Exploratory factor analysis was used to calculate the primary outcome (higher and lower HIV stigma index scores above and below the mean, respectively), based on the total number of factors retained from the 10 item self-reported questions relating to attitudes and beliefs against PLHIV. Bivariate and multivariate generalised linear models with a log link and binomial distribution were fitted to estimate crude and adjusted risk ratios (ARR) with 95% confidence intervals (CI) for factors associated with external HIV-related stigma. Of 38 919 respondents, 49% (49.8%; 95% CI: 48.6-51.1) were categorised as having higher levels of external HIV-related stigma. Higher levels of HIV-related stigma were significantly associated with those who had secondary level education than those with no education/primary education [ARR = 1.14 (95% CI: 1.05-1.24), p = 0.002], those employed than unemployed [ARR = 1.08 (95% CI: 1.02-1.14), p = 0.006], those in rural areas than urban areas [ARR = 1.15 (95% CI: 1.07-1.23), p<0.001], those who were aware of their HIV status than not aware [ARR = 1.34 (95% CI: 1.12-1.61), p<0.001], those who were HIV positive than HIV negative [ARR = 1.09 (95% CI: 1.02-1.17), p = 0.018], and those with no correct HIV knowledge and myth rejection than their counterparts [ARR = 1.09 (95% CI: 1.03-1.15), p = 0.002]. The findings highlight the need for peer-facilitated HIV-stigma reduction interventions targeting all types of educational institutions and the strengthening of work-based interventions. The findings emphasise the prioritisation of rural informal settings/tribal areas when developing and implementing HIV stigma reduction interventions. The study suggests that stigma reduction should be considered an important component of HIV testing and awareness. Addressing public misconceptions about HIV can mitigate externalised stigma.

Validation of the parents' version of the KINDLR and Kiddy Parents questionnaire in a South African context.

BACKGROUND: This study aimed to assess the usefulness of the parent version of the KINDLR and the additional items of the Kiddy Parents questionnaire in the South-African context and to validate it as an appropriate tool for measuring health-related quality of life (HRQoL). METHOD: The ExAMIN Youth SA study was designed to investigate lifestyle behaviours, including psychosocial factors that may adversely impact on cardiovascular health of children. Construct validity was examined by using exploratory and confirmatory factor analysis, while internal consistency was tested by Cronbach's alpha. The final factor structure was confirmed by model fit indices. RESULTS: The study included children (n = 1088) aged between 5 and 10 years in North-West, South Africa. The reliability coefficients of the original factors could not be reproduced in this data set, with the Cronbach's alphas ranging between 0.46 and 0.78. With exploratory factor analysis, including the additional items, our data supported a 7-factor structure with acceptable internal consistency (Cronbach's alpha: 0.68-0.79; Omega: 0.75-0.85) and acceptable model fit indices (CFI: 0.91; TLI: 0.90; RMSEA: 0.05; SRMR: 0.07). Two factors (emotional wellbeing and everyday functioning) further split into separate factors for positive and negative experiences related to each of these dimensions. CONCLUSION: We confirmed a new factor structure of the parent version of the KINDLR and the additional items of the Kiddy Parents questionnaire, which can be used in the African context. Although the new factor structure has great overlap with the original structure, some items did not contribute to the factors as expected. Language and cultural differences between the original German group and the current South African study group resulted in a different factor structure.

Kidney damage and associated risk factors in the rural Eastern Cape, South Africa: A cross-sectional study.

BACKGROUND: The colliding epidemic of infectious and non-communicable diseases in South Africa could potentially increase the prevalence of kidney disease in the country. This study determines the prevalence of kidney damage and known risk factors in a rural community of the Eastern Cape province, South Africa. METHODS: This observational cross-sectional study was conducted in the outpatient department of the Mbekweni Community Health Centre in the Eastern Cape between May and July 2022. Relevant data on demography, medical history, anthropometry and blood pressure were obtained. The glomerular filtration rate was estimated using the Chronic Kidney Disease Epidemiology Collaboration Creatinine (CKD-EPICreatinine) equation and the re-expressed four-variable Modification of Diet in Renal Disease (MDRD) equation, without any adjustment for black ethnicity. Prevalence of kidney damage was defined as the proportion of individuals with low eGFR (<60mL/min per 1.73m2). The presence of proteins in the spot urine samples was determined with the use of test strips. We used the logistic regression model analysis to identify the independent risk factors for significant kidney damage. RESULTS: The mean (±standard deviation) age of the 389 participants was 52.3 (± 17.5) years, with 69.9% female. The prevalence of significant kidney damage was 17.2% (n = 67), as estimated by the CKD-EPICreatinine, with a slight difference by the MDRD equation (n = 69; 17.7%), while the prevalence of proteinuria was 7.2%. Older age was identified as a significant risk factor for CKD, with an odds ratio (OR) = 1.08 (95% confidence interval [CI]: 1.06-1.1, p < 0.001). Hypertension was strongly associated with proteinuria (OR = 4.17, 95% CI 1.67-10.4, p<0.001). CONCLUSIONS: This study found a high prevalence of kidney damage (17.2%) and proteinuria (7.97%) in this rural community, largely attributed to advanced age and hypertension, respectively. Early detection of proteinuria and decreased renal function at community health centres should trigger a referral to a higher level of care for further management of patients.

Efficacy and safety of autologous whole blood clot in diabetic foot ulcers: a randomised controlled trial.

OBJECTIVE: Diabetic foot ulcers (DFUs) present a significant global health challenge, resulting in high morbidity and economic costs. Current available treatments often fail to achieve satisfactory healing rates, highlighting the need for novel therapies. This study evaluated the safety and efficacy of a novel autologous whole blood clot (AWBC)-a blood-based, biodegradable provisional matrix-in conjunction with standard of care (SoC) when compared to SoC alone in the treatment of hard-to-heal DFUs. METHOD: A multicentre, prospective, blinded assessor, randomised controlled trial was conducted at 16 sites across the US, South Africa and Turkey. A cohort of patients with hard-to-heal DFUs was enrolled and randomised to either the AWBC group or the control group. The primary endpoint was complete wound closure at 12 weeks, while secondary endpoints included time to heal and percentage area reduction (PAR) at four and eight weeks. Data were analysed using both intention-to-treat (ITT) and per-protocol (PP) populations. RESULTS: The cohort included 119 patients. AWBC treatment resulted in a significantly higher healing rate compared to the control in both ITT (41% versus 15%, respectively; p=0.002) and PP populations (51% versus 18%, respectively; p=0.0075). AWBC treatment also resulted in a shorter mean time to heal and higher durability of wound closure. Safety analysis showed a similar incidence of adverse events (AEs) between groups, with no device-related AEs. CONCLUSION: The AWBC system, by modulating the wound microenvironment and providing a functional extracellular matrix, offered a promising new approach to treating hard-to-heal DFUs, demonstrating superior healing outcomes compared to SoC alone in this study.

Can verbal autopsies be used on a national scale? Key findings and lessons from South Africa's national cause-of-death validation study.

BACKGROUND: Verbal autopsy (VA), though imperfect, serves as a vital tool to determine cause-of-death, particularly for out-of-facility deaths, but challenges persist in integrating VA into Civil Registration and Vital Statistics systems. OBJECTIVE: To describe the challenges and successes of collecting a national sample of verbal autopsy interviews in South Africa to obtain the cause of death profile in 2017/18. METHODS: We recruited next of kin from 27 randomly selected sub-districts (10.5%) across South Africa between September 2017 and April 2018. Trained fieldworkers conducted face-to-face interviews using the WHO2016 VA instrument, with physicians certifying underlying causes of death. Feasibility was evaluated based on response rates, participation, and data quality. RESULTS: Of the total 36,976 deaths registered, only 26% were identified during recruitment, with a 55% overall response rate for VA interviews. Physician-reviewed VA data were deemed of good quality for assigning underlying causes of death in 83% of cases. By comparing cause-specific mortality fractions, physician-reviewed VA identified 22.3% HIV/AIDS and InterVA-5 identified 18.5%, aligning with burden of disease estimates, while Statistics South Africa reported 4.9% HIV/AIDS. CONCLUSIONS: The study demonstrated the feasibility of using VA on a national scale, but immense challenges in identifying and recruiting next of kin highlight the importance of formalising VAs within the country's death notification system.

• Main findings: Next of kin of 9 730 decedents were approached at the time of registration of death and 55% consented to be approached later and agreed to do a VA interview by a trained field-worker; 83% of physician-reviewed VA data were considered high-quality for determining underlying causes and 22.3% of all the deaths were due to HIV/AIDS, much higher than the proportion reported in the national statistical office.• Added knowledge: Implementing the VA on a national scale was achievable but significant challenges in recruiting next of kin, emphasising a need to formalise VAs within the country's death notification system.• Global health impact for policy and action: Accurate cause-of-death data are crucial for policymakers to make informed decisions about the country's health system and could be supported by using VAs, particularly for the deaths that occur outside health facilities.