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To describe the impact of nutritional interventions on the outcomes of children with short bowel syndrome (SBS). This was a retrospective descriptive observational review where data were obtained from the patient's medical records. Children with SBS between the ages of 0 and 24 months who obtained this diagnosis between January 2005 and December 2015 at a tertiary paediatric hospital in Cape Town were investigated. There were 46 patients (62% male, 38% female) included in the study. The median duration of parenteral nutrition (PN) support was one month (0.6, 2.2 months), after which 83% of patients were weaned from PN. Enteral nutrition was commenced in 96% of patients, with the majority (n = 36; 82%) starting on day six (±6; range 1–29 days) postoperatively and 80% of patients attaining full feeds at median 1.2 months (0.2, 36 months). Patients displayed a mean weight and length gain of 15 g/day (±4; range 19–92 g) and 2 cm/month (±1.4; range 0.25–4 cm) respectively. The main complications were PN-associated cholestasis (n = 17), fat malabsorption (n = 13) and vitamin D deficiency/insufficiency (n = 5). This study showed that early initiation of PN support was attained, and that most patients were able to achieve enteral autonomy. [ABSTRACT FROM AUTHOR]

Background: The doctor–patient relationship is important in determining the quality of healthcare provided. This study aimed to identify patient preferences regarding dress code, conduct and resources used by doctors during consultations in the public healthcare sector, Bloemfontein. Information from this study can be of benefit in determining policies and dress codes within hospitals and medical schools. Methods: This was a descriptive, cross-sectional study. Self-administered anonymous questionnaires were distributed at Bloemfontein's National District Hospital to patients 18 years and older, waiting in the pharmacy and consultation queues. Results: Of the 500 questionnaires distributed 410 were analysed. Patients preferred doctors to wear formal attire. For female doctors this included a neat blouse (77.9%), smart pants (62.5%) or straight-cut jeans (51.4%) and flat pumps (56.3%). Patients preferred male doctors to wear collared shirts (52.4% and 57.6% for long- and short-sleeved shirts, respectively) with smart pants (66.8%) or straight-cut jeans (45.9%), and smart shoes (70.3%). Patients did not condone eating and drinking by doctors during consultations; work-related calls were deemed acceptable. The use of technological resources was not preferred. Conclusion: Patients in the public healthcare sector prefer a formal, professional consulting environment that is determined largely by the doctor’s attire and conduct during the consultation. [ABSTRACT FROM AUTHOR]

The lion (Panthera leo) was extirpated from the Cape region of South Africa during the mid-nineteenth century. Whilst historically classified as a distinct subspecies known as the Cape lion (P. l. melanochaita), recent molecular studies challenge the distinctiveness of this population, suggesting that it represents the southernmost population of the species' Southern Clade. The Cape lion is often cited as having a distinctive skull morphology, which has justified its subspecific classification, but only a limited number of specimens have been available for examination, so that the Cape lion's skull morphology has not been satisfactorily understood. In this study we collected morphometric data from a greatly enlarged sample of 22 Cape lion skulls, including 12 adults, constituting the largest sample size analysed for this possible subspecies. The results suggest that (1) morphological characteristics of the skull previously thought to distinguish the Cape lion are not diagnostic, and (2) nor is the skull morphology of male and female Cape lions distinct from that of males and females of other southern African lions. Our results independently support those based on molecular investigations, which suggest that the Cape lion was not distinct from other lions within the Southern Clade., (© 2024. The Author(s).)

Sporotrichosis is a disease that arises from a fungal infection caused by members of the Ascomycete genus Sporothrix. The disease has a unique history in South Africa, due to an association with gold mines, where large numbers of mine workers were infected in the 1930s and 1940s. This was likely driven by hot humid conditions and timber supports used in these mine shafts. Furthermore, the disease is the most common subcutaneous fungal infection amongst the general population in South Africa, and the large number of immunocompromised individuals increases the public health risk in the country. Sporothrix is a genus in the Ophiostomatales, a fungal order primarily associated with environmental habitats. Unsurprisingly, sporotrichosis therefore has a documented history of sapronotic transmission from contaminated plant material. This review provides insights into the understanding of sporotrichosis and Sporothrix species, with a particular emphasis on the South African situation. We highlight knowledge gaps, particularly regarding the ecological factors influencing the occurrence and distribution of these species, which in turn affect the patterns of sporotrichosis. We also emphasise a need for ongoing proactive research and surveillance to prevent future outbreaks of sporotrichosis, an emerging disease with growing health implications worldwide., (© 2024 University of Pretoria. Mycoses published by Wiley‐VCH GmbH.)

In this paper, it is aimed, for the first time, at deriving simple models, leveraging the trend analysis in order to estimate the future greenhouse gas emissions associated with coal combustion. Due to the expectations of becoming the center of global economic development in the future, BRICS-T (Brazil, the Russian Federation, India, China, South Africa, and Turkiye) countries are adopted as cases in the study. Following the models' derivation, their statistical validations and estimating accuracies are also tested through various metrics. In addition, the future greenhouse gas emissions associated with coal combustion are estimated by the derived models. The results demonstrate that the derived models can be successfully used as a tool for estimating the greenhouse gas emissions associated with coal combustions with accuracy ranges from at least 90% to almost 98%. Moreover, the estimating results show that the total amount of greenhouse gas emissions associated with coal combustions in the relevant countries and in the world will increase to 14 BtCO 2eq and 19 BtCO 2eq by 2035, with an annual growth of 2.39% and 1.71%, respectively. In summary, the current study's findings affirm the usefulness of trend analysis in deriving models to estimate greenhouse gas emissions associated with coal combustion., (© 2024. The Author(s).)

Background: The traditional HIV treatment cascade aims to visualise the journey of each person living with HIV from diagnosis, through initiation on antiretroviral therapy (ART) to treatment success, represented by virological suppression. This representation has been a pivotal tool in highlighting and quantifying sequential gaps along the care continuum. There is longstanding recognition, however, that this may oversimplify the complexity of real-world engagement with HIV services in settings with mature high-burden HIV epidemics. A complementary "cyclical" cascade has been proposed to represent the processes of disengagement at different points on the care continuum, with multiple pathways to re-engagement, although the feasibility of implementing this at scale has been uncertain. This study aimed to populate, refine, and explore the utility of a cyclical representation of the HIV cascade, using routine data from a high-burden HIV setting., Methods and Findings: This observational cohort study leveraged person-level data on all people living with HIV in the Western Cape (WC), South Africa, who accessed public health services in the 2 years prior to 31 December 2023. Programme data from disease registers were complemented by data from pharmacy and laboratory systems. At study closure, 494 370 people were included, constituting 93% of those of those estimated to be living with HIV in the province, of whom 355 104 were on ART. Substantial disengagement from HIV care was evident at every point on the cascade. Early treatment emerged as a period of higher risk of disengagement, but it did not account for the majority of disengagement. Almost all those currently disengaged had prior experience of treatment. While re-engagement was also common, overall treatment coverage had increased slowly over 5 years. The transition to dolutegravir-based regimens was dramatic with good virological outcomes for those in care, notwithstanding a clearly discernible impact of the Coronavirus Disease 2019 (COVID-19) pandemic on viral load (VL) testing. People currently engaged and disengaged in care are similar with respect to age and gender. Those who died or disengaged recently were previously distributed across a range of cascade statuses, and a substantial proportion of those newly initiating and re-initiating treatment were no longer on treatment 6 months later. The main limitation of this study was incomplete evidence of HIV testing, linkage to HIV-specific services, and out-of-facility mortality., Conclusions: Using routine data, it was possible to populate and automate a cyclical cascade of HIV care that continuously captured the nonlinear care journeys of individuals living with HIV. In this generalised mature HIV epidemic, most people are treatment experienced. Disengagement is common and occurs at various points along the cascade, making it challenging to identify high-impact intervention opportunities. While historical HIV cascades remain valuable for target setting and service monitoring, they can be complemented with insights from more detailed cyclical cascades., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Euvrard et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: Guidelines and essential medicine lists (EMLs) bear similarities and differences in the process that lead to decisions. Access to essential medicines is central to achieve universal health coverage. The World Health Organization (WHO) EML has guided prioritization of essential medicines globally for nearly 50 years, and national EMLs (NEMLs) exist in over 130 countries. Guideline and EML decisions, at WHO or national levels, are not always coordinated and aligned. We sought to explore challenges, and potential solutions, for decision-making to support trustworthy medicine selection for EMLs from a Grading of Recommendations, Assessment, Development and Evaluations (GRADE) Working Group perspective. We primarily focus on the WHO EML; however, our findings may be applicable to NEML decisions as well., Study Design and Setting: We identified key challenges in connecting the EML to health guidelines by involving a broad group of stakeholders and assessing case studies including real applications to the WHO EML, South Africa NEML, and a multiple sclerosis guideline connected to a WHO EML application for multiple sclerosis treatments. To address challenges, we utilized the results of a survey and feedback from the stakeholders, and iteratively met as a project group. We drafted a conceptual framework of challenges and potential solutions. We presented a summary of the results for feedback to all attendees of the GRADE Working Group meetings in November 2022 (approximately 120 people) and in May 2023 (approximately 100 people) before finalizing the framework., Results: We prioritized issues and insights/solutions that addressed the connections between the EML and health guidelines. Our suggested solutions include early planning alignment of guideline groups and EMLs, considering shared participation to strengthen linkage, further clarity on price/cost considerations, and using explicit shared criteria to make guideline and EML decisions. We also provide recommendations to strengthen the connection between WHO EML and NEMLs including through contextualization methods., Conclusion: This GRADE concept article, jointly developed by key stakeholders from the guidelines and EMLs field, identified key conceptual issues and potential solutions to support the continued advancement of trustworthy EMLs. Adopting structured decision criteria that can be linked to guideline recommendations bears the potential to advance health equity and gaps in availability of essential medicines within and between countries., Competing Interests: Declaration of competing interest Tamara Kredo is a member of the South African National Essential Medicines List Committee and Standard Treatment Guidelines; Co-lead of South African GRADE Network; Cochrane Board member; Member of the National Advisory Group on Immunisation. Trudy Leong is a member of the SA GRADE Network. Michael McCaul is a Member of the South African Primary Health Care and Adult Hospital Level Expert Review Committee; Founding member of the SA GRADE Network. The remaining authors are all members of the GRADE Working Group, however, have no other interests to declare., (Copyright © 2024. Published by Elsevier Inc.)

Ongoing SARS-CoV-2 infections are driven by the emergence of various variants, with differential propensities to escape immune containment. Single nucleotide polymorphisms (SNPs) in the RNA genome result in altered protein structures and when these changes occur in the S -gene, encoding the spike protein, the ability of the virus to penetrate host cells to initiate an infection can be significantly altered. As a result, vaccine efficacy and prior immunity may be diminished, potentially leading to new waves of infection. Early detection of SARS-CoV-2 variants using a rapid and scalable approach will be paramount for continued monitoring of new infections. In this study, we developed minor groove-binding (MGB) probe-based qPCR assays targeted to specific SNPs in the S -gene, which are present in variants of concern (VOC), namely the E484K, N501Y, G446S and D405N mutations. A total of 95 archived SARS-CoV-2 positive clinical specimens collected in Johannesburg, South Africa between February 2021 and March 2022 were assessed using these qPCR assays. To independently confirm SNP detection, Sanger sequencing of the relevant region in the S -gene were performed. Where a PCR product could be generated and sequenced, qPCR assays were 100% concordant highlighting the robustness of the approach. These assays, and the approach described, offer the opportunity for easy detection and scaling of targeted detection of variant-defining SNPs in the clinical setting., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Ealand, Gordhan, Machowski and Kana.)

African horse sickness is an equine orbivirus transmitted by Culicoides Latreille biting midges. In the last 80 years, it has caused several devastating outbreaks in the equine population in Europe, the Far and Middle East, North Africa, South-East Asia, and sub-Saharan Africa. The disease is endemic in South Africa; however, a unique control area has been set up in the Western Cape where increased surveillance and control measures have been put in place. A deterministic metapopulation model was developed to explore if an outbreak might occur, and how it might develop, if a latently infected horse was to be imported into the control area, by varying the geographical location and months of import. To do this, a previously published ordinary differential equation model was developed with a metapopulation approach and included a vaccinated horse population. Outbreak length, time to peak infection, number of infected horses at the peak, number of horses overall affected (recovered or dead), re-emergence, and Rv (the basic reproduction number in the presence of vaccination) were recorded and displayed using GIS mapping. The model predictions were compared to previous outbreak data to ensure validity. The warmer months (November to March) had longer outbreaks than the colder months (May to September), took more time to reach the peak, and had a greater total outbreak size with more horses infected at the peak. Rv appeared to be a poor predictor of outbreak dynamics for this simulation. A sensitivity analysis indicated that control measures such as vaccination and vector control are potentially effective to manage the spread of an outbreak, and shortening the vaccination window to July to September may reduce the risk of vaccine-associated outbreaks., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 de Klerk et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Tobacco use and obesity are major public health problems and part of the leading causes of preventable disease and death worldwide. The prevalence of overweight children has escalated over the years; making the weight gain in children a critical issue for health professionals and academics alike. This study examines the association between maternal tobacco use and body weight abnormalities among South African children., Data and Methods: The study uses data from the National Income Dynamics Study (NIDS), conducted from 2008 to 2017. The survey is available in five waves which have been merged into a panel dataset of 211,718 children aged between 0 to 5 years old, drawn from a nationally representative sample of households followed across time. Thus, the subgroup of children aged between 6 and 15 years old was excluded from the analysis. The empirical investigation employs a logistic regression model to estimate the marginal effect of maternal smoking on childhood overweight prevalence measured by three anthropometric based proxies, namely risk of child overweight, child overweight and child obesity. This framework assumes unobserved child characteristics to be uncorrelated with independent variables (random effect assumption); hence allowing to control for time-invariant sociodemographic factors which are likely to affect child nutritional health., Results: In addition to sociodemographic and health characteristics of mothers, empirical findings suggest that maternal smoking exhibits a significant odds and/ or probability of weight abnormalities in children. Notably, children of smoking mothers are likely to be obese, overweight, or at risk of becoming overweight with a possible coexistence of mother-child overweight. Similarly, weight irregularities in children are likely to increase with mother's age. Conversely, married mothers although associated with increased odds of children having high BMI, display a reduced probability of children being abnormally weighted. Finally, child support grant has the potential to improve children nutritional health as children whose mothers are recipient of such grant have a negative probability of having high BMI., Conclusion: Overall, maternal smoking contributes to child overweight and/or obesity in south Africa; suggesting that maternal healthy lifestyle could be an alternative strategic tool to fight against overweight in children. However, mothers' inability to remain and/or follow a healthy life style is plausible as age increases, with spillover effect on child care. Thus, policymakers should prioritize programs to reduce smoking, especially amongst pregnant women and caregivers, to minimise the risk of overweight in children. Promoting the consumption of healthy foods accompanied by physical activity may reduce mothers' stress levels and their incentive to self-medicate using tobacco substances. In addition, comprehensive action programs including child support grant and recommendations for treatment plans that address the problems of children who are already suffering from overweight, remain essential., Competing Interests: he authors have declared that no competing interests exist., (Copyright: © 2023 Nkomo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The prevalence and distribution of African alphaviruses such as chikungunya have increased in recent years. Therefore, a better understanding of the local distribution of alphaviruses in vectors across the African continent is important. Here, entomological surveillance was performed from 2014 to 2018 at selected sites in north-eastern parts of South Africa where alphaviruses have been identified during outbreaks in humans and animals in the past. Mosquitoes were collected using a net, CDC-light, and BG-traps. An alphavirus genus-specific nested RT-PCR was used for screening, and positive pools were confirmed by sequencing and phylogenetic analysis. We collected 64,603 mosquitoes from 11 genera, of which 39,035 females were tested. Overall, 1462 mosquito pools were tested, of which 21 were positive for alphaviruses. Sindbis (61.9%, N = 13) and Middelburg (28.6%, N = 6) viruses were the most prevalent. Ndumu virus was detected in two pools (9.5%, N = 2). No chikungunya positive pools were identified. Arboviral activity was concentrated in peri-urban, rural, and conservation areas. A range of Culicidae species, including Culex univittatus , Cx. pipiens s.l., Aedes durbanensis , and the Ae. dentatus group, were identified as potential vectors. These findings confirm the active circulation and distribution of alphaviruses in regions where human or animal infections were identified in South Africa.

Identifying factors associated with alcohol use changes during pregnancy is important for developing interventions for people with HIV (PWH). Pregnant PWH (n = 202) initiating antiretroviral therapy in Uganda and South Africa completed two assessments, 6 months apart (T1, T2). Categories were derived based on AUDIT-C scores: "no use" (AUDIT-C = 0 at T1 and T2), "new use" (AUDIT-C = 0 at T1, >0 at T2), "quit" (AUDIT-C > 0 at T1, =0 at T2), and "continued use" (AUDIT-C > 0, T1 and T2). Factors associated with these categories were assessed. Most participants had "no use" (68%), followed by "continued use" (12%), "quit" (11%), and "new use" (9%). Cohabitating with a partner was associated with lower relative risk of "continued use." Borderline significant associations between food insecurity and higher risk of "new use" and between stigma and reduced likelihood of "quitting" also emerged. Alcohol use interventions that address partnership, food security, and stigma could benefit pregnant and postpartum PWH.

Introduction: Scalable psychological treatments to address depression among adolescents are urgently needed. This is particularly relevant to low-income and middle-income countries where 90% of the world's adolescents live. While digital delivery of behavioural activation (BA) presents a promising solution, its feasibility, acceptability and effectiveness among adolescents in an African context remain to be shown., Methods and Analysis: This study is a two-arm single-blind individual-level randomised controlled pilot trial to assess the feasibility, acceptability and initial efficacy of digitally delivered BA therapy among adolescents with depression. The intervention has been coproduced with adolescents at the study site. The study is based in the rural northeast of South Africa in the Bushbuckridge subdistrict of Mpumalanga province. A total of 200 adolescents with symptoms of mild to moderately severe depression on the Patient Health Questionnaire Adolescent Version will be recruited (1:1 allocation ratio). The treatment group will receive BA therapy via a smartphone application (the Kuamsha app) supported by trained peer mentors. The control group will receive an enhanced standard of care. The feasibility and acceptability of the intervention will be evaluated using a mixed methods design, and signals of the initial efficacy of the intervention in reducing symptoms of depression will be determined on an intention-to-treat basis. Secondary objectives are to pilot a range of cognitive, mental health, risky behaviour and socioeconomic measures; and to collect descriptive data on the feasibility of trial procedures to inform the development of a further larger trial., Ethics and Dissemination: This study has been approved by the University of the Witwatersrand Human Research Ethics Committee (MED20-05-011) and the Oxford Tropical Research Ethics Committee (OxTREC 34-20). Study findings will be published in scientific open access peer-reviewed journals, presented at scientific conferences and communicated to participants, their caregivers, public sector officials and other relevant stakeholders., Trial Registration Numbers: This trial was registered on 19 November 2020 with the South African National Clinical Trials Registry (DOH-27-112020-5741) and the Pan African Clinical Trials Registry (PACTR202206574814636)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Background: Congenital heart disease (CHD) is a leading non-infectious cause of pediatric morbidity and mortality worldwide. Although the etiology of CHD is poorly understood, genetic factors including copy number variants (CNVs) contribute to the risk of CHD in individuals of European ancestry. The presence of rare CNVs in African CHD populations is unknown. This study aimed to identify pathogenic and likely pathogenic CNVs in South African patients with CHD., Methods: Genotyping was performed on 90 patients with nonsyndromic CHD using the Affymetrix CytoScan HD platform. These data were used to identify large, rare CNVs in known CHD-associated genes and candidate genes., Results: We identified eight CNVs overlapping known CHD-associated genes ( GATA4 , CRKL , TBX1 , FLT4 , B3GAT3 , NSD1 ) in six patients. The analysis also revealed CNVs encompassing five candidate genes likely to play a role in the development of CHD ( DGCR8 , KDM2A , JARID2 , FSTL1 , CYFIP1 ) in five patients. One patient was found to have 47, XXY karyotype. We report a total discovery yield of 6.7%, with 5.6% of the cohort carrying pathogenic or likely pathogenic CNVs expected to cause the observed phenotypes., Conclusions: In this study, we show that chromosomal microarray is an effective technique for identifying CNVs in African patients diagnosed with CHD and have demonstrated results similar to previous CHD genetic studies in Europeans. Novel potential CHD genes were also identified, indicating the value of genetic studies of CHD in ancestrally diverse populations.

Advocating for healthy environments is a matter of justice. Changes in environments have tremendous impacts on the health of communities, and oftentimes, individuals are unable to safeguard themselves through individual actions alone. Efforts frequently require collective action and are often most effective when led by the communities most impacted. In this spirit, we launched "Vibrations" , an African environment photo essay contest. Through funding and publicity, we aimed to support community-led environmental improvement and education initiatives presently taking place on the continent. We received nearly two dozen submissions and selected eight winners. The winners come from five countries (Ghana, Kenya, Mozambique, Nigeria, and South Africa) and have taken on a range of projects aimed at improving environments across a variety of African regions. Projects included efforts to combat pollution, create environmentally conscious school curricula, utilize clean energy sources, and spread awareness about environmental justice concerns in local communities. It is our hope that this report highlights these transformative community-driven efforts, promotes continued conversations on environmental justice in Africa, and encourages meaningful action via policy changes and collaborations throughout the African continent and beyond.

Shuni virus is associated with neurologic and febrile illness in animals and humans. To determine potential vectors, we collected mosquitoes in South Africa and detected the virus in species of the genera Mansonia, Culex, Aedes, and Anopheles. These mosquitoes may be associated with Shuni virus outbreaks in Africa and emergence in other regions.

There is now wide recognition that grassroots community organizing is a uniquely necessary approach for contending with the persistent and escalating socioeconomic inequities that manifest as disparities across many societal domains, including housing, safety, education, and mental and physical health. The articles in this special issue report findings from studies designed to increase understanding of community organizing processes and produce actionable knowledge that can enhance these and other similar efforts to create more equitable and just cities and regions. These studies examine a variety of community organizing campaigns, initiatives, and networks in North America, as well as one in Bulgaria, and one in South Africa. These groups are building social power and demanding economic, racial, educational, and environmental justice. In this introductory article, we highlight some of the themes that emerge from this set of studies and make recommendations for future roles that research can play in advancing collective understanding and the practical objectives of grassroots organizing initiatives., (© 2021 Wiley Periodicals LLC.)

Mosquitoes in the Aedes and Culex genera are considered the main vectors of pathogenic flaviviruses worldwide. Entomological surveillance using universal flavivirus sets of primers in mosquitoes can detect not only pathogenic viruses but also insect-specific ones. It is hypothesized that insect-specific flaviviruses, which naturally infect these mosquitoes, may influence their vector competence for zoonotic arboviruses. Here, entomological surveillance was performed between January 2014 and May 2018 in five different provinces in the northeastern parts of South Africa, with the aim of identifying circulating flaviviruses. Mosquitoes were sampled using different carbon dioxide trap types. Overall, 64,603 adult mosquitoes were collected, which were screened by RT-PCR and sequencing. In total, 17 pools were found positive for insect-specific Flaviviruses in the mosquito genera Aedes (12/17, 70.59%) and Anopheles (5/17, 29.41%). No insect-specific viruses were detected in Culex species. Cell-fusing agent viruses were detected in Aedes aegypti and Aedes caballus . A range of anopheline mosquitoes, including Anopheles coustani , An. squamosus and An. maculipalpis , were positive for Culex flavivirus-like and Anopheles flaviviruses. These results confirm the presence of insect-specific flaviviruses in mosquito populations in South Africa, expands their geographical range and indicates potential mosquito species as vector species.

While some healthcare systems have shifted to molecular diagnostics, culture still remains the gold standard for tuberculosis diagnosis, but it is limited by its long duration to a positive result. Methods to reduce time to culture positivity (TTP) are urgently required. We determined if growth factor supplementation in the mycobacterial growth indicator tube (MGIT) culture system reduces TTP. MGITs were supplemented with fresh culture filtrate (CF) as a source of growth stimulatory molecules from axenic Mycobacterium tuberculosis culture. Different volumes of CF and media components were tested. The performance of these modified MGITs was assessed with sputum from HIV-TB co-infected individuals. Reducing the volume of MGIT cultures and removal of detergent from cultures grown to generate CF had a marginal but significant benefit on reducing TTP. In a subset of specimens, CF inhibited growth. Following optimization of methods, a reduced TTP occurred in specimens with low bacillary load as measured by GeneXpert, smear microscopy and colony forming units. Three specimens that were negative under standard conditions flagged positive following CF supplementation. Our data provide preliminary evidence that addition of CF to MGIT cultures can enhance detection of M. tuberculosis in HIV-TB co-infected patients with low sputum bacillary loads., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: There is a paucity of recent data and knowledge on mosquito diversity and potential vectors of arboviruses in South Africa, with most of the available data dating back to the 1950s-1970s. Aedes and Culex species are the major vectors of some of the principal arboviruses which have emerged and re-emerged in the past few decades., Methods: In this study we used entomological surveillance in selected areas in the north-eastern parts of South Africa from 2014 to 2018 to assess mosquito diversity, with special emphasis on the Aedes species. The impact of trap types and environmental conditions was also investigated. Identification of the blood meal sources of engorged females collected during the study period was carried out, and DNA barcodes were generated for selected species., Results: Overall, 18.5% of the total Culicidae mosquitoes collected belonged to the genus Aedes, with 14 species recognised or suspected vectors of arboviruses. Species belonging to the Neomelaniconion subgenus were commonly collected in the Bushveld savanna at conservation areas, especially Aedes mcintoshi and Aedes circumluteolus. Aedes aegypti was present in all sites, albeit in low numbers. Temperature was a limiting factor for the Aedes population, and they were almost exclusively collected at temperatures between 18 °C and 27 °C. The cytochrome oxidase subunit I (COI) barcode fragment was amplified for 21 Aedes species, and for nine of these species it was the first sequence information uploaded on GenBank., Conclusion: This study provides a better understanding of the diversity and relative abundance of Aedes species in the north-east of South Africa. The information provided here will contribute to future arboviral research and implementation of efficient vector control and prevention strategies.

HIV-1 must overcome host antiviral restriction factors for efficient replication. We hypothesized that elevated levels of bone marrow stromal cell antigen 2 ( BST-2 ), a potent host restriction factor that interferes with HIV-1 particle release in some human cells and is antagonized by the viral protein Vpu, may associate with viral control. Using cryopreserved samples, from HIV-1 seronegative and seropositive Black women, we measured in vitro expression levels of BST-2 mRNA using a real-time PCR assay and protein levels were validated by Western blotting. The expression level of BST-2 showed an association with viral control within two independent cohorts of Black HIV infected females (r=-0.53, p=0.015, [n =21]; and r=-0.62, p=0.0006, [n=28]). DNA methylation was identified as a mechanism regulating BST-2 levels, where increased BST-2 methylation results in lower expression levels and associates with worse HIV disease outcome. We further demonstrate the ability to regulate BST-2 levels using a DNA hypomethylation drug. Our results suggest BST-2 as a factor for potential therapeutic intervention against HIV and other diseases known to involve BST-2 ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling Editor declared a shared affiliation, though no other collaboration, with one of the authors [MC]., (Copyright © 2021 Singh, Ramsuran, Naranbhai, Yende-Zuma, Garrett, Mlisana, Dong, Walker, Abdool Karim, Carrington and Ndung’u.)

Background: Anopheles arabiensis is a major malaria vector, recently implicated as contributing to ongoing residual malaria transmission in South Africa, which feeds and rests both indoors and outdoors. This species is, therefore, not effectively targeted using core malaria vector control interventions alone. Additionally, increasing resistance to available insecticides necessitates investigations into complementary non-insecticide-based vector control methods for outdoor-resting mosquitoes. The feasibility of the sterile insect technique (SIT) as a complementary vector control intervention is being investigated in South Africa. Successful implementation of an SIT programme largely depends on inundating a target insect population with sterilized laboratory-bred males. Therefore, knowledge of the native population size and dispersal ability of released sterile laboratory-reared males is critical. In this study, we estimated the male An. arabiensis population size and the dispersal of released males in an area targeted for a pilot sterile male release programme., Methods: Three separate releases were performed within a 2-year period. Approximately 5000-15,000 laboratory-reared male An. arabiensis (KWAG) were produced and marked for mark-release-recapture experiments. To recapture released mosquitoes, cloth tubes were deployed in widening concentric circles. The average dispersal distance of released males was calculated and the wild male An. arabiensis population size was estimated using two Lincoln index formulae. The natural population was sampled concurrently and Anopheles species diversity examined., Results: The Anopheles gambiae complex and An. funestus group species made up the majority of wild collections along with other anophelines. The An. arabiensis population size was estimated to be between 550 and 9500 males per hectare depending on time of year, weather conditions and method used. Average dispersal distance of marked males ranged from 58 to 86 m. Marked males were found in swarms with wild males, indicating that laboratory-reared males are able to locate and participate in mating swarms., Conclusions: It was logistically feasible to conduct mark-release-recapture studies at the current scale. The population size estimates obtained may provide a guideline for the initial number of males to use for a pending SIT pilot trial. It is promising for future SIT trials that laboratory-reared marked males participated in natural swarms, appearing at the right place at the right time.

Species of Armillaria are distributed globally and include some of the most important pathogens of forest and ornamental trees. Some of them form large long-living clones that are considered as one of the largest organisms on earth and are capable of long-range spore-mediated transfer as well as vegetative spread by drought-resistant hyphal cords called rhizomorphs. However, the virus community infecting these species has remained unknown. In this study we used dsRNA screening and high-throughput sequencing to search for possible virus infections in a collection of Armillaria isolates representing three different species: Armillaria mellea from South Africa, A. borealis from Finland and Russia (Siberia) and A. cepistipes from Finland. Our analysis revealed the presence of both negative-sense RNA viruses and positive-sense RNA viruses, while no dsRNA viruses were detected. The viruses included putative new members of virus families Mymonaviridae, Botourmiaviridae and Virgaviridae and members of a recently discovered virus group tentatively named "ambiviruses" with ambisense bicistronic genomic organization. We demonstrated that Armillaria isolates can be cured of viruses by thermal treatment, which enables the examination of virus effects on host growth and phenotype using isogenic virus-infected and virus-free strains.

We investigated the effect of early antiretroviral treatment (ART) initiation on HIV status disclosure and social support in a cluster-randomized, treatment-as-prevention (TasP) trial in rural South Africa. Individuals identified HIV-positive after home-based testing were referred to trial clinics where they were invited to initiate ART immediately irrespective of CD4 count (intervention arm) or following national guidelines (control arm). We used Poisson mixed effects models to assess the independent effects of (a) time since baseline clinical visit, (b) trial arm, and (c) ART initiation on HIV disclosure (n = 182) and social support (n = 152) among participants with a CD4 count > 500 cells/mm 3 at baseline. Disclosure and social support significantly improved over follow-up in both arms. Disclosure was higher (incidence rate ratio [95% confidence interval]: 1.24 [1.04; 1.48]), and social support increased faster (1.22 [1.02; 1.46]) in the intervention arm than in the control arm. ART initiation improved both disclosure and social support (1.50 [1.28; 1.75] and 1.34 [1.12; 1.61], respectively), a stronger effect being seen in the intervention arm for social support (1.50 [1.12; 2.01]). Besides clinical benefits, early ART initiation may also improve psychosocial outcomes. This should further encourage countries to implement universal test-and-treat strategies.

Background: There has been a steady increase in the use of electronic media and instant messaging among healthcare professionals, where it has been almost universally adopted in the workplace. The use of WhatsApp and its perceived benefits in healthcare have been extensively studied; however, there are concerns regarding the potential for ethical breaches in confidentiality through shared electronic patient information., Objectives: To identify the usage characteristics and incidence of shared patient information with WhatsApp use in a team of medical doctors in an unobserved and unregulated setting., Methods: We conducted a retrospective cross-sectional content analysis of WhatsApp messages (n=3 340) among a team of 20 doctors in a South African district hospital over 6 months. All messages found within this time period were allocated unique identifiers. The text and image messages were thematically grouped into four categories, i.e. clinical care, resource allocation, social and administrative. Messages that contained patient-identifying information were included in the analysis., Results: Of a total of 3 340 messages sent, 220 (6.6%) contained patient-identifying information. Of these, 109 (3.3%) contained non-anonymised patient information, while in 111 (3.3%) messages, the information was anonymised. The likelihood of sharing patient identifiers was proportionally much higher in shared images (odds ratio (OR) 5.1; 95% confidence interval (CI) 3.2 - 8.2; p<0.0001) compared with text messages, and in messages that related to clinical care (OR 9.3; 95% CI 2.2 - 38.8; p=0.0023) compared with those sent for resource allocation, and social or administrative purposes., Conclusions: Non-anonymised patient identifiers were found in 3.3% of messages, constituting the potential for breaching patient confidentiality. While WhatsApp groups have significant utility in co-ordinating aspects of clinical care, resource allocation, as well as social and administrative functions, the safe use of WhatsApp should be promoted to ensure that patient confidentiality is maintained.

The COVID-19 pandemic has strained healthcare delivery systems in a number of southern African countries. Despite this, it is imperative that malaria control and elimination activities continue, especially to reduce as far as possible the number and rate of hospitalisations caused by malaria. The implementation of enhanced malaria control/elimination activities in the context of COVID-19 requires measures to protect healthcare workers and the communities they serve. The aim of this review is therefore to present innovative ideas for the timely implementation of malaria control without increasing the risk of COVID-19 to healthcare workers and communities. Specific recommendations for parasite and vector surveillance, diagnosis, case management, mosquito vector control and community outreach and sensitisation are given.

Background: ST-segment elevation myocardial infarction (STEMI) is one of the main contributors to morbidity and mortality in South Africa (SA). Timeous intervention by means of percutaneous coronary intervention (PCI) or fibrinolysis can significantly improve the outcome of STEMI., Objectives: To determine the median time interval between diagnosis and fibrinolysis in patients presenting to centres within the drainage area of Tygerberg Hospital, Cape Town, SA, and compare it with the European Society of Cardiology (ESC) recommendation of 10 minutes., Methods: A retrospective medical record review of patients presenting to the abovementioned centres between 1 March 2017 and 28 February 2018 was performed. The primary presenting centre, time between diagnosis and fibrinolysis and discharge medication were recorded, in addition to other relevant demographic information., Results: A total of 492 patients were identified, of whom 447 were included in the study. Three hundred and eighteen patients received fibrinolysis, of whom 18 (5.7%) were treated within 10 minutes of diagnosis. The median time interval between diagnosis and fibrinolysis was 67 (interquartile range (IQR) 32.5 -122.5) minutes., Conclusions: Most patients received fibrinolysis >10 minutes after diagnosis, which indicates suboptimal therapy when compared with the ESC guidelines. Future studies should investigate the factors prolonging this therapeutic delay.

An important component of South Africa's malaria elimination agenda is identifying the entomological drivers of residual transmission, especially those that present opportunities for enhanced vector control. Seasonal mosquito density correlates directly with malaria transmission in South Africa. Transmission is highest during the warm rainy season and lowest but not entirely absent during the cooler dry season. The factors that sustain dry-season mosquito survival remain unknown. The aim of this project was therefore to investigate seasonal change in metabolic rate to determine the presence or absence of winter dormancy in malaria vector mosquitoes. Metabolic rate, determined by CO 2 production during closed-system respirometry, was measured from wild anophelines collected from KwaZulu-Natal Province, South Africa. Monthly sampling spanned all four seasons (summer, autumn, winter, and spring) in 2017. Anopheles arabiensis and An. parensis specimens formed the majority of the total 437 identified specimens (n = 216 and n = 162, respectively). Metabolic rate data from wild-caught mosquitoes showed no significant seasonal disparities for An. arabiensis and An. parensis males and females. Further laboratory experiments assessed the effect of manipulated photoperiod, representing seasonal day-length changes, on the metabolic rate of colonized An. arabiensis mosquitoes. Simulations of midwinter (10 h:14 h light dark) and midsummer (14 h:10 h) day-length showed no significant effect on the metabolic rate of these mosquitoes. Age (in days) had a significant effect on the metabolic rate of both male and female colonized adult An. arabiensis mosquitoes which may be linked to developmental factors during maturation of adults. These data suggest that the South African populations of the malaria vector species An. arabiensis and An. parensis do not curtail their breeding and foraging activities during the colder and drier winter months. Overwintering by diapause does not appear to be triggered in the adult mosquito stage in An. arabiensis. However, their respective population densities do decrease considerably during winter leading to reduced malaria transmission and the opportunity for control by winter larviciding of known breeding sites., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

This meeting report is based on presentations given at the first Drug Safety Africa Meeting in Potchefstroom, South Africa from November 20-22, 2018 at the North-West University campus. There were 134 attendees (including 26 speakers and 34 students) from the pharmaceutical industry, academia, regulatory agencies as well as 6 exhibitors. These meeting proceedings are designed to inform the content that was presented in terms of Safety Pharmacology (SP) and Toxicology methods and models that are used by the pharmaceutical industry to characterize the safety profile of novel small chemical or biological molecules. The first part of this report includes an overview of the core battery studies defined by cardiovascular, central nervous system (CNS) and respiratory studies. Approaches to evaluating drug effects on the renal and gastrointestinal systems and murine phenotyping were also discussed. Subsequently, toxicological approaches were presented including standard strategies and options for early identification and characterization of risks associated with a novel therapeutic, the types of toxicology studies conducted and relevance to risk assessment supporting first-in-human (FIH) clinical trials and target organ toxicity. Biopharmaceutical development and principles of immunotoxicology were discussed as well as emerging technologies. An additional poster session was held that included 18 posters on advanced studies and topics by South African researchers, postgraduate students and postdoctoral fellows., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Little is known about the genotypic make-up of HIV-1 DNA genomes during the earliest stages of HIV-1 infection. Here, we use near-full-length, single genome next-generation sequencing to longitudinally genotype and quantify subtype C HIV-1 DNA in four women identified during acute HIV-1 infection in Durban, South Africa, through twice-weekly screening of high-risk participants. In contrast to chronically HIV-1-infected patients, we found that at the earliest phases of infection in these four participants, the majority of viral DNA genomes are intact, lack APOBEC-3G/F-associated hypermutations, have limited genome truncations, and over one year show little indication of cytotoxic T cell-driven immune selections. Viral sequence divergence during acute infection is predominantly fueled by single-base substitutions and is limited by treatment initiation during the earliest stages of disease. Our observations provide rare longitudinal insights of HIV-1 DNA sequence profiles during the first year of infection to inform future HIV cure research.

Objective: The vital status of patients lost to follow-up often remains unknown in antiretroviral therapy (ART) programmes in sub-Saharan Africa because medical records are no longer updated once the patient disengages from care. Thus, we aimed to assess the outcomes of patients lost to follow-up after ART initiation in north-eastern South Africa., Methods: Using data from a rural area in north-eastern South Africa, we estimated the cumulative incidence of patient outcomes (i) after treatment initiation using clinical records, and (ii) after loss to follow-up (LTFU) using data from clients that have been individually linked to Agincourt Health and Demographic Surveillance System (AHDSS) database. Aside from LTFU, we considered mortality, re-engagement and migration out of the study site. Cox proportional hazards regression was used to identify covariates of these patient outcomes., Results: Between April 2014 and July 2017, 3700 patients initiated ART and contributed a total of 6818 person-years of follow-up time. Three years after ART initiation, clinical record-based estimates of LTFU, mortality and documented transfers were 41.0% (95% CI: 38.5-43.4%), 1.9% (95% CI 1.0-3.2%) and 0.1% (95% CI 0.0-0.9%), respectively. Among those who were LTFU, the cumulative incidence of re-engagement, out-migration and mortality at 3 years were 38.1% (95% CI 33.1-43.0%), 49.4% (95% CI 43.1-55.3%) and 4.7% (95% CI 3.5-6.2%), respectively. Pregnant or breastfeeding women, foreigners and those who initiated ART most recently were at an increased risk of LTFU., Conclusion: LTFU among patients starting ART in north-eastern South Africa is relatively high and has increased in recent years as more asymptomatic patients have initiated treatment. Even though this tendency is of concern in light of the prevention of onwards transmission, we also found that re-engagement in care is common and mortality among persons LTFU relatively low., (© 2019 The Authors. Tropical Medicine & International Health Published by John Wiley & Sons Ltd.)

The genital tract of African women has been shown to differ from what is currently accepted as 'normal', defined by a pH≤4.5 and lactobacilli-dominated microbiota. Adolescent girls and young women (AGYW) from sub-Saharan Africa are at high risk for HIV, and we hypothesized that specific biological factors are likely to be influential. This study aimed to compare characteristics of vaginal health in HIV-negative AGYW (16-22-years-old), from two South African communities, to international norms. We measured plasma hormones, vaginal pH, presence of BV (Nugent scoring), sexually transmitted infections (multiplex PCR for Chlamydia trachomatis, Neisseria gonorrhoea, Trichomonas vaginalis, Mycoplasma genitalium) and candidiasis (Gram stain) in AGYW (n = 298) from Cape Town and Soweto. Cervicovaginal microbiota was determined by 16S pyrosequencing; 44 genital cytokines were measured by Luminex; and cervical T-cell activation/proliferation (CCR5, HLA-DR, CD38, Ki67) was measured by multiparametric flow cytometry. 90/298 (30.2%) AGYW were negative for BV, candidiasis and bacterial STIs. L. crispatus and L. iners were the dominant bacteria in cervicovaginal swabs, and the median vaginal pH was 4.7. AGYW with L. crispatus-dominant microbiota (42.4%) generally had the lowest cytokine concentrations compared to women with more diverse microbiota (34/44 significantly upregulated cytokines). Frequencies of CCR5+CD4+ T-cells co-expressing CD38 and HLA-DR correlated positively with interleukin (IL)-6, TNF-α, GRO-α, macrophage inflammatory protein (MIP)-1α, and IL-9. While endogenous oestrogen had an immune-dampening effect on IL-6, TNF-related apoptosis-inducing ligand (TRAIL) and IL-16, injectable hormone contraceptives (DMPA and Net-EN) were associated with significantly lower endogenous hormone concentrations (p<0.0001 for oestrogen and progesterone) and upregulation of 34/44 cytokines. Since genital inflammation and the presence of activated CD4+ T cells in the genital tract have been implicated in increased HIV risk in South African women, the observed high levels of genital cellular activation and cytokines from AGYW may point towards biological factors increasing HIV risk in this region., Competing Interests: The authors have declared that no competing interests exist.

Objectives: Perceived income adequacy is positively associated with self-rated health (SRH) and quality of life (QOL) among adults in higher-income countries. Additionally, older individuals often report higher levels of income adequacy. However, it is unclear if these associations, documented primarily in high-income countries, are also evident across economically and culturally distinctive low- and middle-income countries., Methods: Data were drawn from the World Health Organization's Study on global AGEing and adult health (SAGE), a study of adults aged 50 years or older in China, Ghana, India, Mexico, the Russian Federation, and South Africa. Smaller samples of younger adults (18-49 years) were included for comparison purposes. Participants reported income adequacy, SRH, and QOL. Associations between age and income adequacy and between income adequacy and SRH/QOL were examined using country-specific logistic regression analysis., Results: Older adults in China and Russia were more likely to report better income adequacy than their 18- to 49-year-old counterparts; however, the opposite was observed in Ghana and India. SRH and QOL improved as income adequacy increased in all countries., Discussion: As expected, income adequacy was correlated with SRH and QOL. However, the relationship between age and income adequacy varied cross-culturally, potentially due to differences in familial and governmental financial support., (© The Author(s) 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Southern Africa (South Africa as well as neighboring countries) has not had an infrastructure for testing the safety of new drugs or other therapeutic entities, including plant-based or herbal treatments coming from the indigenous cultures, according to the current practice and regulatory requirements. Simultaneously, Southern Africa is challenged by very high rates of immune deficiency diseases which have further led to the resurgence of diseases such as tuberculosis, which is commonly thought to be eradicated, at least in Western cultures. Thus, there is high medical need for affordable, effective and safe treatments, but up to now there has been no local expertise and capabilities for state-of-the-art drug testing. Based on an initiative funded by the South African Department of Science and Technology, the Potchefstroom campus of North-West University was chosen for the establishment of a center of excellence for doing rodent-based drug testing research. The centerpiece of the Pre-Clinical Drug Development Platform (PCDDP) is a new rodent vivarium for breeding of SPF rats and mice and associated laboratories for conducting a wide range of physiological and pharmacological studies. Notably, the vivarium has become the first AAALAC-accredited animal facility in Sub-Sahara Africa and is qualified for conducting GLP studies. The establishment of safety pharmacology models is a first priority of the PCDDP, including expertise in studies to examine electrophysiological effects in vitro, and potential CNS, cardiovascular and respiratory effects. The intention is to offer the rodent-based safety pharmacology testing not only to local academic and company-related scientists, but also to those throughout South Africa and neighboring countries., (Copyright © 2018 Elsevier Inc. All rights reserved.)

This paper discusses the sustainability of livestock systems, emphasising bidirectional relations with animal health. We review conventional and contrarian thinking on sustainability and argue that in the most common approaches to understanding sustainability, health aspects have been under-examined. Literature review reveals deep concerns over the sustainability of livestock systems; we recognise that interventions are required to shift to more sustainable trajectories, and explore approaches to prioritising in different systems, focusing on interventions that lead to better health. A previously proposed three-tiered categorisation of 'hot spots', 'cold spots' and 'worried well' animal health trajectories provides a mental model that, by taking into consideration the different animal health status, animal health risks, service response needs and key drivers in each system, can help identify and implement interventions. Combining sustainability concepts with animal health trajectories allows for a richer analysis, and we apply this to three case studies drawn from North Africa and the Middle East; Bangladesh; and the Eastern Cape of South Africa. We conclude that the quest for sustainability of livestock production systems from the perspective of human and animal health is elusive and difficult to reconcile with the massive anticipated growth in demand for livestock products, mainly in low- and middle-income countries, as well as the aspirations of poor livestock keepers for better lives. Nevertheless, improving the health of livestock can contribute to health sustainability both through reducing negative health impacts of livestock and increasing efficiency of production. However, the choice of the most appropriate options must be under-pinned by an understanding of agro-ecology, economy and values. We argue that a new pillar of One Health should be added to the three traditional sustainability pillars of economics, society and environment when addressing livestock systems.

A key strategy of the South African national response to HIV is the scale-up of HIV counselling and testing (HCT) in the 15-49 years age group. The integrated school health policy aims to guide the roll out of youth-friendly health services including the provision of HCT in schools. Using a discrete choice experiment to examine preferences regarding the attributes of HCT service packages, this study identifies barriers to and facilitators of HCT among high school learners. Monetary considerations were found to have the strongest effect of any attribute on choice, whilst confidentiality was found to be a primary concern for learners considering HCT. Policy makers and service providers must ensure that confidentiality is maintained, and could consider using monetary incentives as a way of increasing uptake of HCT. Programmes designed to reduce social stigma and improve education and knowledge dissemination around HCT and HIV, are vital in creating demand for HCT and changing attitudes among young people.

Background: Osteogenesis imperfecta is a heritable disorder of bone connective tissue. Type III has a high incidence in the black pop-ulation of South Africa. Affected people experience numerous fractures, bone pain and progressive disability. Until the introduction of bisphosphonates to reduce fracture incidence, treatment revolved around orthopaedic and supportive care. Objective. To assess the subjective attitude of patients towards pamidronate treatment., Methods: Thirty black patients with osteogenesis imperfecta type III treated at Universitas Hospital were approached and 26 were included in this study. Patients or their parents were interviewed using a standardised researcher-administered questionnaire, either in person or by telephone., Results: Most patients reported a reduction in symptoms, a feeling of increased wellbeing, increased strength and rated the pamidronate treatment highly. The intravenous route of administration and the side-effects experienced were bearable. Overall all patients would recommend this treatment to other affected persons., Conclusion: This is first study to look at bisphosphonate treatment for osteogenesis imperfecta type III in black South Africans. The treatment is well tolerated and highly rated by the patients. Reported improvements and side-effects are similar to those reported in other populations. Using this form of treatment in this population is supported by these findings.

Background: The use of injectable progestin-only contraceptives has been associated with increased risk of HIV acquisition in observational studies, but the biological mechanisms of this risk remain poorly understood. We aimed to assess the effects of progestins on HIV acquisition risk and the immune environment in the female genital tract., Methods: In this prospective cohort, we enrolled HIV-negative South African women aged 18-23 years who were not pregnant and were living in Umlazi, South Africa from the Females Rising through Education, Support, and Health (FRESH) study. We tested for HIV-1 twice per week to monitor incident infection. Every 3 months, we collected demographic and behavioural data in addition to blood and cervical samples. The study objective was to characterise host immune determinants of HIV acquisition risk, including those associated with injectable progestin-only contraceptive use. Hazard ratios (HRs) were estimated using Cox proportional hazards methods., Findings: Between Nov 19, 2012, and May 31, 2015, we characterised 432 HIV-uninfected South African women from the FRESH study. In this cohort, 152 women used injectable progestin-only contraceptives, 43 used other forms of contraception, and 222 women used no method of long-term contraception. Women using injectable progestin-only contraceptives were at substantially higher risk of acquiring HIV (12·06 per 100 person-years, 95% CI 6·41-20·63) than women using no long-term contraception (3·71 per 100 person-years, 1·36-8·07; adjusted hazard ratio [aHR] 2·93, 95% CI 1·09-7·868, p=0·0326). HIV-negative injectable progestin-only contraceptive users had 3·92 times the frequency of cervical HIV target cells (CCR5+ CD4 T cells) compared with women using no long-term contraceptive (p=0·0241). Women using no long-term contraceptive in the luteal phase of the menstrual cycle also had a 3·25 times higher frequency of cervical target cells compared with those in the follicular phase (p=0·0488), suggesting that a naturally high progestin state had similar immunological effects to injectable progestin-only contraceptives., Interpretation: Injectable progestin-only contraceptive use and high endogenous progesterone are both associated with increased frequency of activated HIV targets cells at the cervix, the site of initial HIV entry in most women, providing a possible biological mechanism underlying increased HIV acquisition in women with high progestin exposure., Funding: The Bill and Melinda Gates Foundation and the National Institute of Allergy and Infectious Diseases., Competing Interests: Declaration of interests We declared no competing interests., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

In this study different garden refuses were investigated to ascertain their efficiency to act as carbon sources in a denitrification system. Six different garden refuse materials were studied: commercial and domestic garden refuse raw (CGR RAW, DGR RAW), immaturely composted domestic and commercial garden refuse (DGR 10 and CGR 10 respectively), commercial garden refuse composted by Dome Aeration Technology and by "turned windrow" technology (DAT and TW). Different concentrations of synthetic nitrate solution were used to assess the efficiency of each substrate. The results demonstrate that all substrates were able to sustain the denitrification process. However, due to its higher C/N ratio the CGR RAW was the better performing of the materials, reaching 100% removal after 8 and 12h for the 100 and 500 mg L(-1) respectively and after 11 days for 2000 mg L(-1). Kinetic studies revealed that the zero-order reaction better describes the process indicating a denitrification rate independent from the nitrate concentrations investigated when 100 and 500 mg L(-1) of nitrate were used. The study demonstrated the suitability of organic municipal solid wastes to sustain denitrification, opening a new scenario towards a low cost and in situ solution for treatment of landfill leachate by using wastes, otherwise disposed of in landfill., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Viruses can evade immune surveillance, but the underlying mechanisms are insufficiently understood. Here, we sought to understand the mechanisms by which natural killer (NK) cells recognize HIV-1-infected cells and how this virus can evade NK-cell-mediated immune pressure., Methods and Findings: Two sequence mutations in p24 Gag associated with the presence of specific KIR/HLA combined genotypes were identified in HIV-1 clade C viruses from a large cohort of infected, untreated individuals in South Africa (n = 392), suggesting viral escape from KIR+ NK cells through sequence variations within HLA class I-presented epitopes. One sequence polymorphism at position 303 of p24 Gag (TGag303V), selected for in infected individuals with both KIR2DL3 and HLA-C*03:04, enabled significantly better binding of the inhibitory KIR2DL3 receptor to HLA-C*03:04-expressing cells presenting this variant epitope compared to the wild-type epitope (wild-type mean 18.01 ± 10.45 standard deviation [SD] and variant mean 44.67 ± 14.42 SD, p = 0.002). Furthermore, activation of primary KIR2DL3+ NK cells from healthy donors in response to HLA-C*03:04+ target cells presenting the variant epitope was significantly reduced in comparison to cells presenting the wild-type sequence (wild-type mean 0.78 ± 0.07 standard error of the mean [SEM] and variant mean 0.63 ± 0.07 SEM, p = 0.012). Structural modeling and surface plasmon resonance of KIR/peptide/HLA interactions in the context of the different viral sequence variants studied supported these results. Future studies will be needed to assess processing and antigen presentation of the investigated HIV-1 epitope in natural infection, and the consequences for viral control., Conclusions: These data provide novel insights into how viruses can evade NK cell immunity through the selection of mutations in HLA-presented epitopes that enhance binding to inhibitory NK cell receptors. Better understanding of the mechanisms by which HIV-1 evades NK-cell-mediated immune pressure and the functional validation of a structural modeling approach will facilitate the development of novel targeted immune interventions to harness the antiviral activities of NK cells.

In eThekwini, South Africa, the production of agricultural fertilizers from human urine collected from urine-diverting dry toilets is being evaluated at a municipality scale as a way to help finance a decentralized, dry sanitation system. The present study aimed to assess a range of human and environmental health hazards in source-separated urine, which was presumed to be contaminated with feces, by evaluating the presence of human pathogens, pharmaceuticals, and an antibiotic resistance gene. Composite urine samples from households enrolled in a urine collection trial were obtained from urine storage tanks installed in three regions of eThekwini. Polymerase chain reaction (PCR) assays targeted 9 viral and 10 bacterial human pathogens transmitted by the fecal-oral route. The most frequently detected viral pathogens were JC polyomavirus, rotavirus, and human adenovirus in 100%, 34% and 31% of samples, respectively. Aeromonas spp. and Shigella spp. were frequently detected gram negative bacteria, in 94% and 61% of samples, respectively. The gram positive bacterium, Clostridium perfringens, which is known to survive for extended times in urine, was found in 72% of samples. A screening of 41 trace organic compounds in the urine facilitated selection of 12 priority pharmaceuticals for further evaluation. The antibiotics sulfamethoxazole and trimethoprim, which are frequently prescribed as prophylaxis for HIV-positive patients, were detected in 95% and 85% of samples, reaching maximum concentrations of 6800 μg/L and 1280 μg/L, respectively. The antiretroviral drug emtricitabine was also detected in 40% of urine samples. A sulfonamide antibiotic resistance gene (sul1) was detected in 100% of urine samples. By coupling analysis of pathogens and pharmaceuticals in geographically dispersed samples in eThekwini, this study reveals a range of human and environmental health hazards in urine intended for fertilizer production. Collection of urine offers the benefit of sequestering contaminants from environmental release and allows for targeted treatment of potential health hazards prior to agricultural application. The efficacy of pathogen and pharmaceutical inactivation, transformation or removal during urine nutrient recovery processes is thus briefly reviewed., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The incidence and severity of infections in childhood is typically greater in males. The basis for these observed sex differences is not well understood, and potentially may facilitate novel approaches to reducing disease from a range of conditions. We here investigated sex differences in HIV-infected children in relation to antiretroviral therapy (ART) initiation and post-treatment outcome. In a South African cohort of 2,101 HIV-infected children, we observed that absolute CD4+ count and CD4% were significantly higher in ART-naïve female, compared to age-matched male, HIV-infected children. Absolute CD4 count and CD4% were also significantly higher in HIV-uninfected female versus male neonates. We next showed that significantly more male than female children were initiated on ART (47% female); and children not meeting criteria to start ART by >5 yrs were more frequently female (59%; p<0.001). Among ART-treated children, immune reconstitution of CD4 T-cells was more rapid and more complete in female children, even after adjustment for pre-ART absolute CD4 count or CD4% (p=0.011, p=0.030, respectively). However, while ART was initiated as a result of meeting CD4 criteria less often in females (45%), ART initiation as a result of clinical disease in children whose CD4 counts were above treatment thresholds occurred more often in females (57%, p<0.001). The main sex difference in morbidity observed in children initiating ART above CD4 thresholds, above that of TB disease, was as a result of wasting and stunting observed in females with above-threshold CD4 counts (p=0.002). These findings suggest the possibility that optimal treatment of HIV-infected children might incorporate differential CD4 treatment thresholds for ART initiation according to sex.

Colonization by Lactobacillus in the female genital tract is thought to be critical for maintaining genital health. However, little is known about how genital microbiota influence host immune function and modulate disease susceptibility. We studied a cohort of asymptomatic young South African women and found that the majority of participants had genital communities with low Lactobacillus abundance and high ecological diversity. High-diversity communities strongly correlated with genital pro-inflammatory cytokine concentrations in both cross-sectional and longitudinal analyses. Transcriptional profiling suggested that genital antigen-presenting cells sense gram-negative bacterial products in situ via Toll-like receptor 4 signaling, contributing to genital inflammation through activation of the NF-κB signaling pathway and recruitment of lymphocytes by chemokine production. Our study proposes a mechanism by which cervicovaginal microbiota impact genital inflammation and thereby might affect a woman's reproductive health, including her risk of acquiring HIV., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Reasons for Performing Study: Equine herpesvirus 1 (EHV-1) is one of the most common causes of infectious abortion in mares. Analysing the demography of outbreaks and detailing subsequent reproductive performance of affected mares will assist in the management of future (threatened) epizootics., Objectives: To examine the epidemiology and reproductive outcomes of 2 EHV-1 abortion epizootics with very different patterns of morbidity., Study Design: Epidemiological and reproductive data were analysed retrospectively following abortion epizootics associated with EHV-1, but initiated via different routes, among unvaccinated mares on 2 Thoroughbred farms in South Africa., Methods: Aborting mares were assigned to either the EHV-1 abortion cohort via positive immunostaining (Farms 1 and 2) or quantitative PCR (Farm 2) on tissue samples, or to the non-EHV abortion cohort., Results: During their respective epizootics, EHV-1 abortions affected 9/30 (30.0%) and 18/316 (5.7%) of the pregnant mares on Farms 1 and 2, respectively; there were also 25 (7.9%) non-EHV abortions on Farm 2. Epizootic differences included: durations (Farm 1 = 135 days; Farm 2 = 34 days), intervals between first and subsequent abortions (Farm 1 = 39 days; Farm 2 = 2 days) and intervals to confirmation of EHV-1 (Farm 1 = 40 days; Farm 2 = 2 days). The median (range) age of EHV-1 abortion mares (8.0; 5-18 years) in both epizootics was similar but significantly younger (P = 0.004) than the 25 non-EHV-1 abortion mares (11.0; 4-24 years) on Farm 2. Gestation stage (median; range) of EHV-1 (291.5; 277-313) and non-EHV-1 (211.9; 61-339 days) abortions were significantly different (P = 0.001). The post abortion complications and subsequent reproductive outcomes had no significant association with EHV-1 abortion., Conclusions: The marked difference in morbidity between the 2 epizootics may be associated with routes of introduction or intervention strategy dictated by availability of molecular diagnostic techniques. Unexpectedly, EHV-1 was not more commonly associated with post abortion complications., (© 2014 EVJ Ltd.)

It is widely believed that epidemics in new hosts diminish in virulence over time, with natural selection favoring pathogens that cause minimal disease. However, a tradeoff frequently exists between high virulence shortening host survival on the one hand but allowing faster transmission on the other. This is the case in HIV infection, where high viral loads increase transmission risk per coital act but reduce host longevity. We here investigate the impact on HIV virulence of HIV adaptation to HLA molecules that protect against disease progression, such as HLA-B*57 and HLA-B*58:01. We analyzed cohorts in Botswana and South Africa, two countries severely affected by the HIV epidemic. In Botswana, where the epidemic started earlier and adult seroprevalence has been higher, HIV adaptation to HLA including HLA-B*57/58:01 is greater compared with South Africa (P = 7 × 10(-82)), the protective effect of HLA-B*57/58:01 is absent (P = 0.0002), and population viral replicative capacity is lower (P = 0.03). These data suggest that viral evolution is occurring relatively rapidly, and that adaptation of HIV to the most protective HLA alleles may contribute to a lowering of viral replication capacity at the population level, and a consequent reduction in HIV virulence over time. The potential role in this process played by increasing antiretroviral therapy (ART) access is also explored. Models developed here suggest distinct benefits of ART, in addition to reducing HIV disease and transmission, in driving declines in HIV virulence over the course of the epidemic, thereby accelerating the effects of HLA-mediated viral adaptation.

Purpose: Social capital is essential for the successful development of young people. The current study examines direct measures of social capital in young people in five urban global contexts., Methods: The Well-Being of Adolescents in Vulnerable Environments is a global study of young people aged 15-19 years living in disadvantaged, urban settings. Respondent-driven sampling was used to recruit approximately 500 participants from each site. The sample included 2,339 young people (mean age 16.7 years; 47.5% female). We examined the associations between social capital in four domains-family, school, peers, and neighborhood and demographic characteristics-using gender-stratified ordinary least-squares regression. We also examined associations between self-reported health and the four social capital domains, which was minimal., Results: School enrollment was positively associated with social capital for young women in Baltimore, Delhi, and Shanghai; the association was less consistent for young men. The same pattern is true for perceived wealth. Unstable housing was associated with low familial social capital in all groups except young women in Shanghai and young men in Ibadan and Johannesburg. Being raised outside a two-parent family has a widespread, negative association with social capital. Self-reported health had a mainly positive association with social capital with the most consistent association being neighborhood social capital., Conclusions: Different types of social capital interact with social contexts and gender differently. Strategies that aim to build social capital as part of risk reduction and positive youth development programming need to recognize that social capital enhancement may work differently for different groups and in different settings., (Copyright © 2014 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

The global adolescent population is larger than ever before and is rapidly urbanizing. Global surveillance systems to monitor youth health typically use household- and school-based recruitment methods. These systems risk not reaching the most marginalized youth made vulnerable by conditions of migration, civil conflict, and other forms of individual and structural vulnerability. We describe the methodology of the Well-Being of Adolescents in Vulnerable Environments survey, which used respondent-driven sampling (RDS) to recruit male and female youth aged 15-19 years and living in economically distressed urban settings in Baltimore, MD; Johannesburg, South Africa; Ibadan, Nigeria; New Delhi, India; and Shanghai, China (migrant youth only) for a cross-sectional study. We describe a shared recruitment and survey administration protocol across the five sites, present recruitment parameters, and illustrate challenges and necessary adaptations for use of RDS with youth in disadvantaged urban settings. We describe the reach of RDS into populations of youth who may be missed by traditional household- and school-based sampling. Across all sites, an estimated 9.6% were unstably housed; among those enrolled in school, absenteeism was pervasive with 29% having missed over 6 days of school in the past month. Overall findings confirm the feasibility, efficiency, and utility of RDS in quickly reaching diverse samples of youth, including those both in and out of school and those unstably housed, and provide direction for optimizing RDS methods with this population. In our rapidly urbanizing global landscape with an unprecedented youth population, RDS may serve as a valuable tool in complementing existing household- and school-based methods for health-related surveillance that can guide policy., (Copyright © 2014 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)