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Background: Alcohol use is a well-established potentially modifiable risk factor for suicide, yet few studies have investigated the impact of alcohol restrictions on suicide rates, particularly in low- and middle-income countries., Methods: We used data from nationally representative annual surveys of postmortem investigations in 2017 (n=6117) and 2020/21 (n=6586) to estimate changes in suicide rates associated with the COVID-19 pandemic and related alcohol restrictions., Findings: Age standardised suicide mortality rates per 100 000 were 10.91 (10.64, 11.18) in 2017 and 10.82 (10.56, 11.08) in 2020/2021, with approximately 4.4 times more deaths among males than females in both periods. No significant differences were observed between overall suicide rates during the 2020/2021 pandemic period compared with 2017 (risk ratio=1.04 (1.00, 1.07)), but in the 15-24-year age group, suicide rates were 11% higher among males and 31% higher among females than in 2017. Partial alcohol restrictions during the pandemic were not associated with lower suicide risk. However, the shift from partial to full restriction on the sale of alcohol was associated with an 18% (95% CI 10% to 25%) reduction in suicides for both sexes combined and a 22% (95% CI 13% to 30%) reduction in suicides among men, but no significant reduction among women., Interpretation: Our findings offer some support for the hypothesis that restricting access to alcohol at a population level is associated with a reduction in suicide rates and suggests that restricted access to alcohol may have been one of the reasons global suicide rates did not increase during the pandemic in some countries., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Background: Neonatal Cardiac Surgery has developed significantly since its advent, with improved outcomes, survival, and physiological repair. Limited programs offer neonatal cardiac surgery in emerging economies. We report our experience with neonates undergoing cardiac surgery in our cardiac surgery program., Methods: We performed a secondary data analysis on all neonates aged ≤ 30 days undergoing congenital cardiac surgery from April 1, 2017 to March 31, 2020, including outcomes up to 30-days post-surgery., Results: A total of 859 patients underwent cardiac surgery at our center, of these 81 (9.4%) were neonates. The proportion of neonates increased annually (8.7%, 9.6%, and 10.2%). There were 49 (60%) male patients, and 32 (40%) had surgery in the second week of life. Fourteen (17%) were premature, four (5%) had a major chromosomal abnormality, five (6%) a major medical illness, and eight (10%) a major noncardiac structural anomaly. The Risk Adjustment for Congenital Heart Surgery (RACHS) categorization of surgery was predominantly RACHS 3; n = 28 (35%) and 4; n = 23 (29%). Hours in the intensive care unit (ICU) were extensive; median 189 [interquartile range (IQR): 114-286] as were hours of ventilation; median 95 [IQR 45-163]. Almost 60% (n = 48) of procedures were complicated by sepsis, as defined in our database. The in-hospital mortality rate was 16% (n = 13); the 30-day mortality rate was 19.8% (n = 16)., Conclusion: The proportion of neonates in our service increased over the period. Focused strategies to shorten prolonged ICU stay and decrease rates of bacterial sepsis in neonates are needed. A multidisciplinary, collaborative heart-team approach is crucial for best outcomes., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Pre-exposure prophylaxis (PrEP) is an HIV prevention strategy that can reduce the risk of HIV acquisition by more than 90% if taken consistently. Although South Africa has been implementing PrEP since 2016, initially for selected population groups before expanding access to more people, there is a dearth of research focused on PrEP among adolescent boys and young men (ABYM), despite them experiencing high rates of HIV infection. To address this gap, we compared PrEP initiation rates by service delivery points (SDPs) among ABYM in KwaZulu-Natal, South Africa., Methods: We conducted a population-based prospective study in 22 SDPs from July 2021 to July 2022 in KwaZulu-Natal, South Africa. Sexually active ABYM aged 15-35 years who tested HIV negative were recruited at purposively selected PrEP SDPs (i.e., healthcare facilities, secondary schools and Technical Vocational Education and Training (TVET) colleges, and community-based youth zones). We collected baseline quantitative data from each participant using self-administered electronic questionnaires built into REDCap, including demographic information such as age, sex, employment status and level of education, as well as PrEP initiation outcomes. We extracted data from REDCap and exported it to Stata version 17.0 for analysis, and then eliminated discrepancies and removed duplicates. We described baseline characteristics using summary and descriptive statistics (median, interquartile range [IQR] and proportions) and reported PrEP initiation proportions overall and by SDPs., Results: The study included 1104 ABYM, with a median age of 24 years (interquartile range (IQR): 21-28)). Almost all participants were black African (n = 1090, 99%), with more than half aged 15-24 years (n = 603, 55%) and 45% (n = 501) aged 25-35 years. The majority (n = 963; 87%) had attained a secondary level of education. Overall PREP initiation rate among adolescent boys and young men was low: among 1078 participants who were eligible for PrEP, 13% (n = 141) were started on PrEP. Among the participants who were initiated on PrEP, over three quarters (78%, n = 58) were initiated from high schools, compared with community-based youth zones (40%, n = 37), TVET colleges (26%, n = 16) and healthcare facilities (4%, n = 30)., Conclusions: This study provided evidence suggesting that expanding PrEP services to non-traditional settings, such as high schools, TVET colleges, and community-based organizations, may have a potential to increase PrEP access among ABYM in South Africa., (© 2024. The Author(s).)

Introduction: Despite the numerous efforts and initiatives, males with HIV are still less likely than women to receive HIV treatment. Across Sub-Saharan Africa, men are tested, linked, and retained in HIV care at lower rates than women, and South Africa is no exception. This is despite the introduction of the universal test-and-treat (UTT) prevention strategy anticipated to improve the uptake of HIV services. The aim of this study was to investigate linkage to and retention in care rates of an HIV-positive cohort of men in a high HIV prevalence rural district in KwaZulu-Natal province, South Africa., Methods: From January 2018 to July 2019, we conducted an observational cohort study in 18 primary health care institutions in the uThukela district. Patient-level survey and clinical data were collected at baseline, 4-months and 12-months, using isiZulu and English REDCap-based questionnaires. We verified data through TIER.Net, Rapid mortality survey (RMS), and the National Health Laboratory Service (NHLS) databases. Data were analyzed using STATA version 15.1, with confidence intervals and p-value of ≤0.05 considered statistically significant., Results: The study sample consisted of 343 male participants diagnosed with HIV and who reside in uThukela District. The median age was 33 years (interquartile range (IQR): 29-40), and more than half (56%; n = 193) were aged 18-34 years. Almost all participants (99.7%; n = 342) were Black African, with 84.5% (n = 290) being in a romantic relationship. The majority of participants (85%; n = 292) were linked to care within three months of follow-up. Short-term retention in care (≤ 12 months) was 46% (n = 132) among men who were linked to care within three months., Conclusion: While the implementation of the UTT strategy has had positive influence on improving linkage to care, men's access of HIV treatment remains inconsistent and may require additional innovative strategies., (© 2024. The Author(s).)

Background: Human papillomavirus (HPV) vaccination programs are a key intervention in protecting individuals against HPV-related disease. HIV1-infected individuals are at increased risk of HPV-associated cancers. This study was conducted to evaluate the potential role of prophylactic HPV vaccines in preventing new HPV infections among participants with perinatally acquired HIV who received the quadrivalent HPV vaccine at least five years before this study., Methods: This cross-sectional study was conducted at Newlands Clinic, Harare, Zimbabwe. The clinic provided the Gardasil quadrivalent HPV vaccine (4vHPV) to 624 adolescents living with HIV starting in December 2015. Vaginal and penile swabs were collected and tested for HPV types from the study participants who had received the 4vHPV vaccine 5-6 years before enrolment., Results: We present the results of 98 participants (44.6% female) vaccinated at a median age of 15 years (IQR 12-16). The mean amount of time since vaccination was 6 years (SD: ±0.4). The HPV-positive rate amongst the analyzed swabs was 69% (68/98). Among 30/98 (31%) HPV-positive participants, 13/98 (13%) had low-risk HPV types, and 17/98 (17%) had high-risk HPV types. Twelve participants tested positive for HPV18, only one participant tested positive for HPV16, and an additional four (4.3%) tested positive for either type 6 or 11, with respect to vaccine-preventable low-risk HPV types., Conclusion: The Gardasil quadrivalent HPV vaccine (4vHPV) was expected to protect against infection with HPV types 16, 18, 6, and 11. We demonstrated a possible waning of immunity to HPV18 in 17% of the participants, and an associated loss in cross-protection against HPV45. We observed a relatively high prevalence of 'opportunistic non-vaccine HPV types' or 'ecological niche occupiers' in this cohort, and suggest further research on the involvement of these types in cervical and other genital cancers. Our study is one of the few, if not the first, to report on HPV vaccine immunoprotection among people living with HIV (PLWH), thereby setting a baseline for further studies on HPV vaccine effectiveness among PLWH.

Background: Antimicrobial stewardship principles guide the clinical use of antimicrobials, including vancomycin, but paediatric vancomycin prescribing practices have not been evaluated in South Africa., Objectives: To document the use, prescribing practices and monitoring of intravenous vancomycin and the spectrum of bacteria isolated on microbiological culture in children treated with intravenous vancomycin during a 12-month period at Red Cross War Memorial Children's Hospital (RCWMCH)., Method: A retrospective audit of intravenous vancomycin use in children admitted to RCWMCH during 2019 was performed., Results: All 158 vancomycin prescription episodes for 143 children were included. Overall usage of intravenous vancomycin was 63 days of therapy per 1000 patient days (interquartile range [IQR]: 38-72). The median starting dose was 15 mg/kg per dose (IQR: 14-15) and median daily dose was 45 mg/kg per day (IQR: 43-60). Vancomycin was prescribed as empiric (127/158, 80%) and directed (31/158, 20%) treatment. The median duration of treatment for the directed group (7 days) was longer than the empiric group (4 days) ( p = 0.001). Vancomycin serum trough concentrations were performed in 65/98 (66%) episodes where vancomycin treatment exceeded 3 days, with only 16/65 (25%) of these samples obtained before the fourth dose. Prolonged antibiotic treatment of 14 days or more was not associated with Gram-positive bacteria on culture (odds ratio [OR]: 1.02, 95% confidence interval [CI]: 0.17-4.2)., Conclusion: Dosing errors, prolonged empiric treatment and inappropriate vancomycin monitoring were problems associated with vancomycin prescriptions., Contribution: The study identified multiple opportunities for improved vancomycin prescribing and monitoring. Further research and implementation of improved prescribing practices could contribute to the preservation of vancomycin as an effective antibiotic., Competing Interests: The authors declare that they have no financial or personal relationships that may have inappropriately influenced them in writing this article., (© 2023. The Authors.)

Ending AIDS by 2030 would depend on how successful health systems are in linking people living with HIV (PLHIV) into care. The World Health Organization recommended the 'Universal Test and Treat' (UTT) strategy - initiating all individuals testing positive on antiretroviral therapy (ART) irrespective of their CD4 count and clinical staging. This study aimed to explore the enablers and barriers to linkage to HIV care among adults with a new HIV diagnosis in a high-HIV prevalent rural district in South Africa. A qualitative study was undertaken to explore patients' perceptions of enablers and barriers of linkage-to-care, using a life-story narration and dialogue approach. In-depth interviews were conducted with 38 HIV-positive participants sampled from a cohort of 1194 HIV-positive patients recruited from December 2017 to June 2018. Participants were selected based on whether they had been linked to care or not within 3 months of positive HIV diagnosis. Interviews were thematically analysed using a general inductive approach. Of the 38 participants, 22 (58%) linked to care within three months of HIV-positive diagnosis. Factors that facilitated or inhibited linkage-to-care were found at individual, family, community, as well as health systems levels. Enablers included a positive HIV testing experience, and assistance from the fieldwork team. Support from family, and friends, as well as prior community-based education about HIV and ART were also noted. Individual factors such as acceptance of HIV status, previous exposure to PLHIV, and fear of HIV progressing, were identified. Barriers to linkage included, denial of HIV status, dislike of taking pills, and preference for alternative medicine. Negative experiences with counselling and health systems inefficiency were also noted as barriers. Perceived stigma and socio-economic factors, such as lack of food or money to visit the clinic were other barriers. Community-based and health system-level interventions would need to focus on clinic readiness in providing patients with necessary and effective health services such as proper and adequate counselling. This could increase the number of patients who link to care. Finally, interventions to improve linkage-to-care should consider a holistic approach, including training healthcare providers, community outreach and the provision of psychological, social, and financial support., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objectives: Pulmonary hypertension (PH) secondary to obstructive sleep apnea (OSA) is an uncommon but serious perioperative risk factor in children undergoing surgery for adenotonsillar hypertrophy. Routine pre-operative echocardiography is commonly requested if severe OSA is suspected. We investigated the incidence of PH in children with suspected OSA and explored the association between PH and OSA severity., Methods: A prospective study of children aged 1-13 years with suspected OSA admitted for overnight oximetry (OO) and echocardiography at a pediatric referral hospital in Cape Town, South Africa from 2018 to 2019. OSA severity was defined by McGill Oximetry Score (MOS): MOS 1-2 (mild-moderate) and MOS 3-4 (severe). PH was defined as mean pulmonary arterial pressure (mPAP) ≥20 mmHg estimated on echocardiographic criteria. Children with congenital heart disease, underlying cardio-respiratory or genetic disorders, and severe obesity were excluded., Results: One hundred and seventy children median age 3.8 years (IQR 2.7-6.4) were enrolled and 103 (60%) were female. Twenty-two (14%) had a BMIz >1.0 and 99 (59%) had tonsillar enlargement grade 3/4. One hundred and twenty-two (71%) and 48 (28%) children had mild-moderate and severe OSA, respectively. Echocardiographic assessment for PH was successful in 160 (94%) children of which eight (5%) had PH with mPAP 20.8 mmHg (SD 0.9): six with mild-moderate OSA and two with severe OSA. No significant difference in mPAP and other echocardiographic indices was observed in children with mild-moderate (16.1 mmHg; SD 2.4) and severe OSA (15.7 mmHg; SD 2.1). Similarly, no clinical and OSA severity differences were observed in children with and without PH., Conclusion: PH is uncommon in children with uncomplicated OSA and there is no association of PH with severity of OSA measured by OO. Routine echocardiographic screening for PH in children with clinical symptoms of OSA without co-morbidity is unwarranted., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

HIV linkage, and retention are key weaknesses in South Africa's national antiretroviral therapy (ART) program, with the greatest loss of patients in the HIV treatment pathway occurring before ART initiation. This study investigated linkage-to and early-retention-in-care (LTRIC) rates among adults newly diagnosed with HIV in a high-HIV prevalent rural district. We conducted an observational prospective cohort study to investigate LTRIC rates for adults with a new HIV diagnosis in South Africa. Patient-level survey and clinical data were collected using a one-stage-cluster design from 18 healthcare facilities and triangulated between HIV and laboratory databases and registered deaths from Department of Home Affairs. We used Chi-square tests to assess associations between categorical variables, and results were stratified by HIV status, sex, and age. Of the 5,637 participants recruited, 21.2% had confirmed HIV, of which 70.9% were women, and 46.5% were aged 25-34 years. Although 82.7% of participants were linked-to-care within 3 months, only 46.1% remained-in-care 12 months after initiating ART and 5.2% were deceased. While a significantly higher proportion of men were linked-to-care at 3 months compared to women, a significant proportion of women (49.5%) remained-in-care at 12 months than men (38.0%). Post-secondary education and child support grants were significantly associated with retention. We found high linkage-to-care rates, but less than 50% of participants remained-in-care at 12 months. Significant effort is required to retain people living with HIV in care, especially during the first year after ART initiation. Our findings suggest that interventions could target men to encourage HIV testing., (© 2022. The Author(s).)

Background: South Africa had an estimated 7.5 million people living with HIV (PLHIV), accounting for approximately 20% of the 38.4 million PLHIV globally in 2021. In 2015, the World Health Organization recommended the universal test and treat (UTT) intervention which was implemented in South Africa in September 2016. Evidence shows that UTT implementation faces challenges in terms of human resources capacity or infrastructure. We aim to explore healthcare providers (HCPs)' perspectives on the implementation of the UTT strategy in uThukela District Municipality in KwaZulu-Natal province., Methods: A qualitative study was conducted with one hundred and sixty-one (161) healthcare providers (HCPs) within 18 healthcare facilities in three subdistricts, comprising of Managers, Nurses, and Lay workers. HCPs were interviewed using an open ended-survey questions to explore their perceptions providing HIV care under the UTT strategy. All interviews were thematically analysed using both inductive and deductive approaches., Results: Of the 161 participants (142 female and 19 male), 158 (98%) worked at the facility level, of which 82 (51%) were nurses, and 20 (12.5%) were managers (facility managers and PHC manager/supervisors). Despite a general acceptance of the UTT policy implementation, HCPs expressed challenges such as increased patient defaulter rates, increased work overload, caused by the increased number of service users, and physiological and psychological impacts. The surge in the workload under conditions of inadequate systems' capacity and human resources, gave rise to a greater burden on HCPs in this study. However, increased life expectancy, good quality of life, and immediate treatment initiation were identified as perceived positive outcomes of UTT on service users. Perceived influence of UTT on the health system included, increased number of patients initiated, decreased burden on the system, meeting the 90-90-90 targets, and financial aspects., Conclusion: Health system strengthening such as providing more systems' capacity for expected increase in workload, proper training and retraining of HCPs with new policies in the management of patient readiness for lifelong ART journey, and ensuring availability of medicines, may reduce strain on HCPs, thus improving the delivery of the comprehensive UTT services to PLHIV., (© 2023. The Author(s).)

Background: Pre-exposure prophylaxis (PrEP) is an emerging biomedical prevention intervention. Documenting PrEP service delivery models (SDMs) that promote linkage to and continuation of PrEP will inform guidelines and maximise roll-out., Objectives: To synthesise and appraise the effectiveness and feasibility of PrEP SDMs designed to promote linkage to PrEP care among adolescent girls and young women (AGYW) and men in sub-Saharan Africa (SSA)., Eligibility Criteria: Primary quantitative and qualitative studies published in English and conducted in SSA were included. No restrictions on the date of publication were applied., Sources of Evidence: Methodology outlined in the Joanna Briggs Institute reviewers' manual was followed. PubMed, Cochrane library, Scopus, Web of Science and online-conference abstract archives were searched., Charting Methods: Data on article, population, intervention characteristics and key outcomes was charted in REDCap., Results and Conclusion: Of the 1204 identified records, 37 (met the inclusion criteria. Health facility-based integrated models of PrEP delivery with family planning, maternal and child health or sexual and reproductive services to AGYW resulted in PrEP initiation of 16%-90%. Community-based drop-in centres (66%) was the preferred PrEP outlet for AGYW compared with public clinics (25%) and private clinics (9%). Most men preferred community-based delivery models. Among individuals who initiated PrEP, 50% were men, 62% were <35 years old and 97% were tested at health fairs compared with home testing. Integrated antiretroviral therapy (ART)-PrEP delivery was favoured among serodiscordant couples with 82.9% of couples using PrEP or ART with no HIV seroconversions. PrEP initiation within healthcare facilities was increased by perceived client-friendly services and non-judgemental healthcare workers. Barriers to PrEP initiation included distance to travel to and time spent at health facilities and perceived community stigma. PrEP SDMs for AGYW and men need to be tailored to the needs and preferences for each group. Programme implementers should promote community-based SDMs to increase PrEP initiation among AGYW and men., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Adolescent girls and young women (AGYW) aged 15-24 years and adolescent boys and young men (ABYM) aged 15-34 years represent one of the populations at highest risk for HIV-infection in South Africa. The National Department of Health adopted the universal test and treat (UTT) strategy in 2016, resulting in increases in same-day antiretroviral therapy initiations and linkage to care. Monitoring progress towards attainment of South Africa's 95-95-95 targets amongst AGYW and ABYM relies on high quality data to identify and address gaps in linkage to care. The aim of this study is to describe the current approaches for engaging AGYW and ABYM in the treatment continuum to generate knowledge that can guide efforts to improve linkage to, and retention in, HIV care among these populations in KwaZulu-Natal, South Africa., Methods and Analysis: This is a mixed methods study, which will be conducted in uMgungundlovu district of KwaZulu-Natal, over a 24-month period, in 22 purposively selected HIV testing and treatment service delivery points (SDPs). For the quantitative component, a sample of 1100 AGYW aged 15-24 years and ABYM aged 15-35 years old will be recruited into the study, in addition to 231 healthcare providers (HCPs) involved in the implementation of the UTT program. The qualitative component will include 30 participating patients who were successfully linked to care, 30 who were not, and 30 who have never tested for HIV. Key informant interviews will also be conducted with 24 HCPs. Logistic regression will be used to model the primary outcomes on SDP types, while a time to event analysis will be conducted using a Cox regression model and adjusting the standard errors of the hazard ratio for the clustering of participants within SDPs. For qualitative data, a general inductive approach of analysis will be used., Dissemination: Findings from the study will be communicated to the study population and results will be presented to stakeholders and at appropriate local and international conferences. Outputs will also include a policy brief, peer reviewed journal articles and research capacity building through research degrees., Competing Interests: The authors declare no competing interest., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Background: Candida bloodstream infection (BSI) causes appreciable mortality in neonates and children. There are few studies describing the epidemiology of Candida BSI in children living in sub-Saharan Africa., Methods: A retrospective descriptive study was conducted at three public sector hospitals in Cape Town, South Africa. Demographic and clinical details, antifungal management and patient outcome data were obtained by medical record review. Candida species distribution and antifungal susceptibility testing results were obtained from the National Health Laboratory Service database., Results: Of the 97 Candida BSI episodes identified during a five-year period, 48/97 (49%) were Candida albicans (C. albicans), and 49/97 (51%) were non-C. albicans species. The overall incidence risk was 0.8 Candida BSI episodes per 1000 admissions at Red Cross War Memorial Children's Hospital. Of the 77/97 (79%) Candida BSI episodes with available clinical information, the median age (interquartile range) at the time of BSI was 7 (1-25) months, 36/77 (47%) were associated with moderate or severe underweight-for-age and vasopressor therapy was administered to 22/77 (29%) study participants. Most of the Candida BSI episodes were healthcare-associated infections, 63/77 (82%). Fluconazole resistance was documented among 17%, 0% and 0% of C. parapsilosis, C. tropicalis and C. albicans isolates, respectively. All Candida isolates tested were susceptible to amphotericin B and the echinocandins. The mortality rate within 30 days of Candida BSI diagnosis was 13/75 (17%). On multivariable analysis, factors associated with mortality within 30 days of Candida BSI diagnosis included vasopressor therapy requirement during Candida BSI, adjusted Odds ratio (aOR) 53 (95% confidence interval 2-1029); hepatic dysfunction, aOR 13 (95% CI 1-146); and concomitant bacterial BSI, aOR 10 (95% CI 2-60)., Conclusion: The study adds to the limited number of studies describing paediatric Candida BSI in sub-Saharan Africa. Non-C. Albicans BSI episodes occurred more frequently than C. albicans episodes, and vasopressor therapy requirement, hepatic dysfunction and concomitant bacterial BSI were associated with an increase in 30-day mortality., (© 2023. The Author(s).)

Background: Surgery remains an adjunctive treatment for drug-resistant tuberculosis (DR-TB) treatment failure despite the use of bedaquiline. However, there are few data about the role of surgery when combined with newer drugs. There are no outcome data from TB endemic countries, and the prognostic significance of pre-operative PET-CT remains unknown., Methods: We performed a prospective observational study of 57 DR-TB patients referred for surgery at Groote Schuur Hospital between 2010 and 2016. PET-CT was performed if there was nodal disease or disease outside the area of planned resection but did not influence treatment decisions. 24-month treatment success post-surgery (cure or treatment completion), including all-cause mortality, was determined., Findings: 35/57 (61.4%) patients (median age 40 years; 26% HIV-infected) underwent surgery and 22/57 (38.6%) did not (11 patients were deemed unsuitable due to bilateral cavitary disease and 11 patients declined surgery). Treatment failure was significantly lower in those who underwent surgery compared to those eligible but declined surgery [15/35 (43%) versus 11/11 (100%); relative risk 0.57 (0.42-0.76); p < 0.01). In patients treated with surgery, a post-operative regimen containing bedaquiline was associated with a lower odds of treatment failure [OR (95%CI) 0.06 (0.00-0.48); p = 0.007]. Pre-operative PET-CT (n = 25) did not predict treatment outcome., Interpretation: Resectional surgery for DR-TB combined with chemotherapy was associated with significantly better outcomes than chemotherapy alone. A post-operative bedaquiline-containing regimen was associated with improved outcome; however, this finding may have been confounded by higher use of bedaquiline and less loss to follow-up in the surgical group. However, PET-CT had no prognostic value. These data inform clinical practice in TB-endemic settings., Funding: This work was supported by the South African MRC (RFA-EMU-02-2017) and the EDCTP (TMA-2015SF-1043 & TMA- 1051-TESAII)., Competing Interests: There are no conflicts of interest to declare for any authors., (© 2022 Published by Elsevier Ltd.)

Introduction: Recent advances in the HIV care continuum have shown that an individual diagnosed with HIV should be initiated on antiretroviral therapy as soon as possible regardless of the CD4 count levels and retained in HIV care services. Studies have reported large losses in the HIV continuum of care, before and after the era of universal test and treat. Several systematic reviews have reported on the strategies for improving linkage to and retention in HIV treatment and care. The purpose of this overview of systematic reviews is to identify HIV care interventions or service delivery models (SDMs) and synthesise evidence on the effects of these to link adolescent girls and young women (AGYW) and adolescent boys and young men (ABYM) to care and retain them in care. We also aim to highlight gaps in the evidence on interventions and SDMs to improve linkage and retention in HIV care of AGYW and ABYM., Methods and Analysis: An electronic search of four online databases: PubMed, Cochrane Database of Systematic Reviews, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Web of Science will be performed to identify systematic reviews on the effects of linkage to and retention in HIV care interventions or SDMs for AGYW aged 15-24 years and ABYM aged 15-35 years. Our findings on the effects of interventions and SDMs will be interpreted considering the intervention and or SDMs' effectiveness by the time period, setting and population of interest. Two or more authors will independently screen articles for inclusion using a priori criteria., Ethics and Dissemination: Ethics approval is not required for this study as only published secondary data will be used. Our findings will be disseminated through peer-reviewed publication, conference abstracts and through presentations to stakeholders and other community fora. The findings from this overview of systematic reviews will inform mixed-methods operations research on HIV intervention programming and delivery of HIV care services for AGYW and ABYM in South Africa., Prospero Registration Number: CRD42020177933., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Despite enormous increases in the proportion of people living with HIV accessing treatment in sub-Saharan Africa, major gender disparities persist, with men experiencing lower rates of testing, linkage to treatment, and retention in care. In this study, we investigated the barriers and facilitating factors to HIV treatment among men in uThukela, a high-HIV-burdened district in KwaZulu-Natal province, South Africa. We conducted a qualitative study including nine Black African male participants who were recruited from 18 health care facilities in uThukela District, KwaZulu-Natal province. In-depth interviews were conducted with participants who linked to care and those who did not link to care at 3-month post HIV diagnosis. We used Atlas.ti for thematic analysis. Data were coded and linked to broader themes emerging across interviews. The median age was 40 years (interquartile range [IQR]: 31-41). This study identified the following key themes which emerged as barriers to HIV treatment among men in uThukela District: lack of emotional readiness, perceived medication side effects, fear of treatment non-adherence, perceived stigma and confidentiality concerns, and poor socioeconomic factors. We identified the following enabling factors to HIV treatment among men: fear of HIV progressing, acceptance of status, disclosure, support from family and friends, positive testing experience, and accessibility of antiretroviral treatment. This study revealed barriers and enabling factors to HIV treatment among men. These factors are important to inform the design of targeted intervention strategies aimed at improving linkage and retention to HIV treatment among men.

Introduction: Pre-exposure prophylaxis (PrEP) is an effective prevention intervention that can be used to control HIV incidence especially among people who are at increased risk for HIV such as adolescent girls and young women (AGYW) and adolescent boys and young men (ABYM). In South Africa, various approaches of delivering PrEP have been adopted at different service delivery points (facility-based only, school-based only, community-based only and hybrid school-facility and community-facility models) to overcome challenges associated with individual, structural, and health systems related barriers that may hinder access to and uptake of PrEP among these populations. However, little is known about how to optimize PrEP implementation and operational strategies to achieve high sustained uptake of good quality services for AGYW and ABYM. This study aims to identify effective and feasible PrEP models of care for improving PrEP uptake, continuation, and adherence among AGYW and ABYM., Methods and Analysis: A sequential explanatory mixed-methods study will be conducted in 22 service delivery points (SDPs) in uMgungundlovu district, KwaZulu-Natal, South Africa. We will recruit 600 HIV negative, sexually active, high risk, AGYW (aged 15-24 years) and ABYM (aged 15-35 years). Enrolled participants will be followed up at 1-, 4- and 7-months to determine continuation and adherence to PrEP. We will conduct two focus group discussions (with 8 participants in each group) across four groups (i. Initiated PrEP within 1 month, ii. Did not initiate PrEP within 1 month, iii. Continued PrEP at 4/7 months and iv. Did not continue PrEP at 4/7 months) and 48 in-depth interviews from each of the four groups (12 per group). Twelve key informant interviews with stakeholders working in HIV programs will also be conducted. Associations between demographic characteristics stratified by PrEP initiation and by various service-delivery models will be assessed using Chi-square/Fishers exact tests or t-test/Mann Whitney test. A general inductive approach will be used to analyze the qualitative data., Ethics and Dissemination: The protocol was approved by the South African Medical Research Council Health Research Ethics Committee (EC051-11/2020). Findings from the study will be communicated to the study population and results will be presented to stakeholders and at appropriate local and international conferences. Outputs will also include a policy brief, peer-reviewed journal articles and research capacity building through research degrees., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: the authors declare no competing interest.

Background: IgE to galactose alpha-1,3 galactose (alpha-gal) causes alpha-gal syndrome (delayed anaphylaxis after ingestion of mammalian meat). Development of sensitization has been attributed to tick bites; however, the possible role of other parasites has not been well studied., Objective: Our aims were to assess the presence, relative abundances, and site of localization of alpha-gal-containing proteins in common ectoparasites and endoparasites endemic in an area of high prevalence of alpha-gal syndrome, as well as to investigate the ability of ascaris antigens to elicit a reaction in a humanized rat basophil in vitro sensitization model., Methods: Levels of total IgE, Ascaris-specific IgE, and alpha-gal IgE were measured in sera from patients with challenge-proven alpha-gal syndrome and from controls without allergy. The presence, concentration, and localization of alpha-gal in parasites were assessed by ELISA, Western blotting, and immunohistochemistry. The ability of Ascaris lumbricoides antigen to elicit IgE-dependent reactivity was demonstrated by using the RS-ATL8 basophil reporter system., Results: Alpha-gal IgE level correlated with A lumbricoides-specific IgE level. Alpha-gal protein at 70 to 130 kDa was detected in A lumbricoides at concentrations higher than those found in Rhipicephalus evertsi and Amblyomma hebraeum ticks. Immunohistochemistry was used to localize alpha-gal in tick salivary acini and the helminth gut. Non-alpha-gal-containing A lumbricoides antigens activated RS-ATL8 basophils primed with serum from subjects with alpha-gal syndrome., Conclusion: We demonstrated the presence, relative abundances, and site of localization of alpha-gal-containing proteins in parasites. The activation of RS-ATL8 IgE reporter cells primed with serum from subjects with alpha-gal syndrome on exposure to non-alpha-gal-containing A lumbricoides proteins indicates a possible role of exposure to A lumbricoides in alpha-gal sensitization and clinical reactivity., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: In order to improve targeted therapeutic approaches for children with atopic dermatitis (AD), novel insights into the molecular mechanisms and environmental exposures that differentially contribute to disease phenotypes are required. We wished to identify AD immunological endotypes in South African children from rural and urban environments., Methods: We measured immunological, socio-economic and environmental factors in healthy children (n = 74) and children with AD (n = 78), in rural and urban settings from the same ethno-linguistic AmaXhosa background in South Africa., Results: Circulating eosinophils, monocytes, TARC, MCP-4, IL-16 and allergen-specific IgE levels were elevated, while IL-17A and IL-23 levels were reduced, in children with AD regardless of their location. Independent of AD, children living in a rural environment had the highest levels of TNFα, TNFβ, IL-1α, IL-6, IL-8, IL-21, MCP-1, MIP-1α, MIP-1β, MDC, sICAM1, sVCAM1, VEGFA, VEGFD and Tie2, suggesting a generalized microinflammation or a pattern of trained immunity without any specific T H polarization. In contrast, IL-15, IL-22, Flt1, PIGF and βFGF were highest in urban children. Rural healthy children had the lowest levels of food allergen-specific IgG4. Early life nutritional factors, medications, animal exposures, indoor environment, sunlight exposure, household size, household income and parental education levels were associated with differences in circulating cytokine levels., Conclusions: This study highlights the immunological impact of environmental exposures and socio-economic status in the manifestation of immune endotypes in children with AD living in urban and rural areas, which are important in selecting appropriately matched immunological therapies for treatment of AD., (© 2021 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: Infections due to resistant bacteria are associated with severe illness, increased risk for complications, hospital admissions, and higher mortality. Inappropriate use of antibiotics, which contributes to increased antibiotic resistance (ABR), is common in healthcare settings across the globe. In Cameroon, antibiotics have been reported as high as 45-70% of prescriptions. We sought to investigate the knowledge, attitudes, and perceptions regarding appropriate antibiotic use and ABR of medical doctors practicing in tertiary hospitals in Yaoundé, Cameroon., Methods: We conducted a cross-sectional survey using a 54-item self-administered questionnaire sent via email to medical doctors working in the four major tertiary hospitals of Yaoundé. The questionnaire recorded socio-demographics, perceptions on antibiotic use and ABR, sources and usefulness of education on ABR, and clinical scenarios to appraise knowledge., Results: A total of 98/206 (48%) doctors responded. Years of experience ranged between 1 and 17 years. Most participants agreed that ABR is a problem nationwide (93%) and antibiotics are overused (96%), but only one third (32%) thought that ABR was a problem in their wards. Most respondents (65%) were confident that they use antibiotics appropriately. We found a mean knowledge score of 56% (± 14), with prescribers not influenced by patient-exerted pressure for antibiotic prescribing scoring better compared to those influenced by patients (67% vs 53%, p = 0.01). Overall, most participants (99%) expressed interest for further education on both appropriate antibiotic use and ABR., Conclusion: Confidence of prescribers in their ability to appropriately use antibiotics conflicts with the low level of knowledge on antibiotic use in this group of doctors. Moreover, the opinion of the majority, that ABR is not a problem in their own backyard is in keeping with similar studies in other countries and is of significant concern. Introduction of formal antibiotic stewardship programmes in Cameroon may be a useful intervention., (© 2021. The Author(s).)

Background: Previous studies have shown that a child's risk of developing atopic disease is impacted by both genetic and environmental factors. Because small children spend the majority of their time in their homes, exposure to microbial factors in their home environment may be protective or risk factors for development of atopic diseases, such as atopic dermatitis., Methods: Dust samples from the homes of 86 Black South African children 12 to 36 months old were collected for analysis of the bacterial microbiome. This case-control study design included children with and without atopic dermatitis from rural and urban environments., Results: Significant differences in bacterial composition and diversity were found when comparing children with and without atopic dermatitis. Furthermore, house dust microbiota was significantly different in rural and urban areas. Differences were best accounted for by higher relative abundance of Ruminococcaceae, Lachnospiraceae, and Bacteroidaceae families in rural compared with urban houses. Levels of Ruminococcaceae were also found to be significantly depleted in the house dust of rural children with atopic dermatitis as compared to control children., Conclusions: House dust composition may be an important risk factor for the development of atopic disease, and this association may be driven in part by the gut microbiome. Low levels of the Ruminococcaceae family from Clostridia class in particular may explain the association between urban living and atopy. However, further research is needed to elucidate these links., (© 2021 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: Environmental exposures are involved in the pathogenesis of the allergic phenotype and in determining which individual triggers a person becomes sensitized to. Atopic dermatitis (AD) may modulate these effects through increased penetration through the skin modifying the immune system and AD may be triggered or intensified by environmental exposures. These exposures and immune-modulating factors may differ in urban and rural environments., Objectives: To compare house dust composition in urban and rural settings and correlate them with AD outcomes., Methods: Dust samples were collected from the beds of 156 children aged 6 months to 3 years. 42% of participants had atopic dermatitis. Samples were analyzed for bacterial endotoxin, fungal (β-1,3-glucan) levels, and house dust mite, cockroach, dog, cat, mouse, and peanut allergen. Exposures were compared in urban and rural environments and in participants with and without AD., Results: Endotoxin but not fungal β-glucan exposure is higher in the environment of healthy controls than children with AD in both urban and rural settings. House dust mite allergen exposure is high in urban and rural settings with Dermatophagoides detected in 100% of samples. Cat and dog allergen exposure mirrors pet ownership patterns which differ slightly between groups and environments. Mouse allergen exposure is higher in urban homes., Conclusion: Environmental endotoxin may be protective against AD in both urban and rural settings. There are marked differences in allergen exposure in urban and rural settings, but these are unlikely to be important protective or risk factors., (© 2021 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Implementation of a National Health Insurance (NHI) in South Africa requires a reliable, standardized health information system that supports Diagnosis-Related Groupers for reimbursements and resource management. We assessed the quality of inpatient health records, the availability of standard discharge summaries and coded clinical data and the congruence between inpatient health records and discharge summaries in public-sector hospitals to support the NHI implementation in terms of reimbursement and resource management. We undertook a cross-sectional health-records review from 45 representative public hospitals consisting of seven tertiary, 10 regional and 28 district hospitals in 10 NHI pilot districts representing all nine provinces. Data were abstracted from a randomly selected sample of 5795 inpatient health records from the surgical, medical, obstetrics and gynaecology, paediatrics and psychiatry departments. Quality was assessed for 10 pre-defined data elements relevant to NHI reimbursements, by comparing information in source registers, patient folders and discharge summaries for patients admitted in March and July 2015. Cohen's/Fleiss' kappa coefficients (κ) were used to measure agreements between the sources. While 3768 (65%) of the 5795 inpatient-level records contained a discharge summary, less than 835 (15%) of diagnoses were coded using ICD-10 codes. Despite most of the records having correct patient identifiers [κ: 0.92; 95% confidence interval (CI) 0.91-0.93], significant inconsistencies were observed between the registers, patient folders and discharge summaries for some data elements: attending physician's signature (κ: 0.71; 95% CI 0.67-0.75); results of the investigation (κ: 0.71; 95% CI 0.69-0.74); patient's age (κ: 0.72; 95% CI 0.70-0.74); and discharge diagnosis (κ: 0.92; 95% CI 0.90-0.94). The strength of agreement for all elements was statistically significant (P-value ≤ 0.001). The absence of coded inpatient diagnoses and identified data inaccuracies indicates that existing routine health information systems in public-sector hospitals in the NHI pilot districts are not yet able to sufficiently support reimbursements and resource management. Institutional capacity is needed to undertake diagnostic coding, improve data quality and ensure that a standard discharge summary is completed for every inpatient., (© The Author(s) 2021. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine.)

Evidence on the relationship between lifestyle, socio-economic factors and pesticide exposure and urinary concentrations of organophosphate (OP) pesticide metabolites among children is generally incomplete. This study investigated the relationship between socio-economic factors and reported pesticide exposures and the sum of three urinary concentrations of dialkyl phosphate metabolites (DAP) among boys living in the rural areas of the Western Cape, South Africa. Data was collected during a cross-sectional study of 183 boys from three agricultural intense areas. Measurements included a questionnaire on socio-economic and pesticide exposures and urinary DAP concentrations. Most boys (70%) lived on farms with a median age of 12 years (range: 5.0-19.5 years). Children aged >14 years had lower DAP urine concentrations (median = 39.9 ng/ml; β = -68.1 ng/ml; 95% CI: -136.8, 0.6) than children aged 9 years and younger (median = 107.0 ng/ml). DAP concentrations also varied significantly with area, with concentrations in the grape farming area, Hex River Valley (median = 61.8 ng/ml; β = -52.1; 95% CI: -97.9, -6.3 ng/ml) and the wheat farming area, Piketberg (median = 72.4 ng/ml; β = -54.2; 95% CI: 98.8, -9.7 ng/ml) lower than those in the pome farming area, Grabouw (median = 79.9 ng/ml). Other weaker and non-significant associations with increased DAP levels were found with increased household income, member of household working with pesticides, living on a farm, drinking water from an open water source and eating crops from the vineyard and or garden. The study found younger age and living in and around apple and grape farms to be associated with increased urinary DAP concentrations. Additionally, there were other pesticide exposures and socio-economic and lifestyle factors that were weakly associated with elevated urinary DAP levels requiring further study. The study provided more evidence on factors associated to urinary DAP concentrations especially in developing country settings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Allergens can act as disease-triggering factors in atopic dermatitis (AD) patients. The aim of the study was to elucidate the molecular IgE sensitization profile in children with and without AD living in urban and rural areas of South Africa., Methods: Specific IgE reactivity was assessed in 166 Black South African children aged 9-38 months using a comprehensive panel of microarrayed allergens. According to clinical characterization children fell in four groups, urban AD cases (n = 32), urban controls (non-AD, n = 40), rural cases (n = 49) and rural controls (non-AD, n = 45)., Results: IgE reactivity to at least one of the allergens was detected in 94% of urban and 86% of rural AD children. House dust mite (HDM; 81% urban, 74% rural AD) and animal-derived allergens (50% urban, 31% rural AD) were the most frequently recognized respiratory allergens, whereas IgE to pollen allergens was almost absent. Urban AD children showed significantly higher frequency of IgE reactivity (50%) to mouse lipocalin, Mus m 1, than rural AD children (12%). The most frequently recognized food allergens were from egg (63% urban, 43% rural AD), peanut (31% vs 41%), and soybean (22% vs 27%), whereas milk sensitization was rare. α-gal-specific IgE almost exclusively occurred in rural children (AD: 14%, non-AD: 49%)., Conclusion: Molecular allergy diagnosis detects frequent IgE sensitization to HDM, animal but not pollen allergens and to egg, peanut, and soy, but not milk allergens in African AD children. Urban AD children reacted more often to Mus m 1, whereas α-gal sensitization is more common in rural children likely due to parasite exposure., (© 2020 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Objective: Children and adolescents living in agricultural areas are likely to be exposed to mixtures of pesticides during their daily activities, which may impair their neurodevelopment. We investigated various such activities in relation to headache severity and neurodevelopment of school-children living in rural agricultural areas in the Western Cape of South Africa., Method: We used baseline date from 1001 school-children of the Child Health Agricultural Pesticide Cohort Study in South Africa (CapSA) aged 9-16 from seven schools and three agriculture areas in the Western Cape. Questionnaires were administrated to assess activities related to pesticide exposure and health symptoms addressing four types of activities: 1) child farm activities related to pesticide handling, 2) eating crops directly from the field, 3) contact with surface water around the field, and 4) seen and smelt pesticide spraying activities. Neurocognitive performance across three domains of attention, memory and processing speed were assessed by means of an iPad-based cognitive assessment tool, Cambridge Automated NeuroPsychological Battery (CANTAB). Headache severity was enquired using a standard Headache Impact Test (HIT-6) tool. Cross-sectional regression analysis was performed., Results: About 50% of the cohort report to have ever been engaged in activities related to pesticide exposure including farm activities, eating crops directly from the field and leisure activities. Headache severity score was consistently increased in relation to pesticide-related farm activities (score increase of 1.99; 95% CI: 0.86, 3.12), eating crops (1.52; 0.41, 2.67) and leisure activities of playing, swimming or bathing in nearby water (1.25; 0.18, 2.33). For neurocognitive outcomes, an overall negative trend with pesticide exposure-related activities was observed. Among others, involvement in pesticide-related farm activities was associated with a lower multi-tasking accuracy score (-2.74; -5.19, -0.29), while lower strategy in spatial working memory (-0.29; -0.56; -0.03) and lower paired associated learning (-0.88; -1.60, -0.17) was observed for those who pick crops off the field compared to those who do not pick crops off the field. Eating fruits directly from the vineyard or orchard was associated with a lower motor screening speed (-0.06; -0.11, -0.01) and lower rapid visual processing accuracy score (-0.02; -0.03, 0.00)., Conclusions: Children who indicate activities related to pesticide exposure may be at higher risk for developing headaches and lower cognitive performance in the domains of attention, memory and processing speed. However, self-reported data and cross-sectional design are a limitation. Future research in CapSA will consider pesticide exposure estimations via urinary biomarkers and longitudinal assessment of cognitive functions., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Vascular calcification is a major risk factor for cardiovascular morbidity and mortality in patients with end-stage renal disease (ESRD). In Western countries, Blacks appear to have lesser degrees of vascular calcification compared to non-Blacks. However, there is no published data from sub-Saharan Africa., Materials and Methods: This study assessed the 5-year change in vascular calcification and mortality in a previously published cohort of patients with ESRD. Vascular calcification was assessed by abdominal aortic calcification score and vascular stiffness by pulse wave velocity (PWV)., Results: 66 of the original 74 participants studied at baseline were identified. The median age was 46.6 years (37.6 - 59.2), and 57.6% were women. Abdominal aortic calcification showed no progression among Blacks (baseline range 0 - 5, follow-up range 0 - 8 (p = 1.00)), but a trend to progression among non-Blacks (baseline range 0 - 19, follow up range 0 - 22 (p = 0.066)). Black participants did not display a survival advantage (p = 0.870). Non-Blacks had higher parathyroidectomy rates than Blacks with 9/30 cases compared to 2/36 (p = 0.036). After adjustment for parathyroidectomy at follow-up, the odds ratio of having abdominal vascular calcification score of ≥ 1 amongst non-Blacks was 8.6-fold greater compared to Blacks (p = 0.03). A positive correlation (r = 0.5) was observed between PWV and abdominal aortic calcification (p = 0.047). Elevated baseline coronary artery calcification score and FGF-23 level at baseline were not associated with a difference in mortality., Conclusion: There was no significant progression in vascular calcification among Blacks. After adjusting for increased parathyroidectomy rates, there was a greater progression of vascular calcification amongst non-Blacks compared to Blacks.

Objectives: To investigate the prevalence of high-risk (HR) human papillomavirus (HPV) and factors associated with HR-HPV infection among women from rural Eastern Cape, South Africa., Methods: HPV prevalence was determined by Hybrid Capture 2 assay in cervical specimens from 417 women aged ≥30 years (median 46 years) recruited from the community health clinic in the Eastern Cape., Results: HR-HPV prevalence was 28.5% (119/417), and HIV-positive women had significantly higher HR-HPV prevalence than HIV-negative women (40.6%, 63/155 vs 21.4%, 56/262, respectively; p = 0.001). HIV-positive status (odds ratio (OR) 2.52, 95% confidence interval (CI) 1.63-3.90), having ≥3 lifetime sexual partners (OR 2.12, 95% CI 1.16-3.89), having ≥1 sexual partner in the last month (OR 1.89, 95% CI 1.21-2.92), ≥4 times frequency of vaginal sex in the past 1 month (OR 2.40, 95% CI 1.32-4.35), and having a vaginal discharge currently/in the previous week (OR 2.13, 95% CI 1.18-3.85) increased the risk of HR-HPV infection. In the multivariate analysis, HIV positivity remained strongly associated with HR-HPV infection (OR 1.94, 95% CI 1.17-3.22)., Conclusions: Risk factors related to sexual behaviors play a significant role in HR-HPV infection in this population. This report will inform health policymakers on HPV prevalence and contribute to discussions on the use of HPV testing as the primary cervical cancer screening test in South Africa., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Electronic media use is increasing in low- and middle-income countries, thus we aim to investigate the prevalence of different aspects of e-media use and its association to symptoms and neurocognitive outcomes in rural South Africa., Methods: In the cohort study, "Child health Agricultural Pesticide study in South Africa (CapSA)", of 1001 children and adolescents, aged 9-16 years, we enquired at baseline about the following aspects of e-media use: (1) call duration (2) total screen time (3) night-time awakenings from mobile phone use, and (4) Mobile Phone Problematic Use. Four health outcomes were included: sleep disturbance, health related quality of life (HRQoL), headaches and cognitive performance, assessed through six tests on domains of attention, memory and processing speed, using the iPad-based software, CAmbridge Neuropsychological Test Automated Battery (CANTAB). Linear regression analysis adjusted for relevant confounders was conducted with categorized exposure variables low, medium and high use., Results: One third of the cohort (31.8%) are mobile phone users reporting average duration of calls per day up to 75 min (mean = 2.5 mins; SD = 8.9 mins). Amongst 46% of the cohort who report e-media device use, total screen time ranged from 1 min to 441 min (mean = 28.3; SD = 53.0). Findings Amongst those reporting regular night-time awakenings (≥1 times per week) from mobile phones, HRQol declined by 2.9 (95% CI: -6.1, 0.3), the sleep disturbance score increased by 2.0 (1.1, 2.9) units and headache impact score significantly increased by 5.4 (2.6; 8.2) units compared to non-exposed. Cognitive performance scores tended to be slightly improved mostly in moderate e-media users. The reaction response speed was consistently improved amongst all four exposure groups compared to non-users., Conclusion: These results are among the first from Africa on benefits and risks associated with e-media use. Our findings imply that with regard to the education of adolescents, a vigilant balance is needed to profit from the beneficial effects of moderate e-media use on cognition, while preventing the negative side effects for HRQoL, sleep disturbance and headache severity., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests in this study., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: The prevalence of allergic diseases differs in urban and rural populations., Objective: We sought to assess associations between environmental and dietary factors with allergic diseases in urban and rural South African children., Methods: Toddlers aged 12 to 36 months were assessed for food allergen and aeroallergen sensitization, atopic dermatitis, allergic rhinitis, asthma, and challenge-proved food allergy. Information was collected on family history of allergic diseases, household size, socioeconomic status, delivery mode, antibiotic and probiotic use, exposure to fermented and unpasteurized milk, antihelminth treatment, sunlight exposure, pet and farm animal exposure, cigarette smoke, and household cooking and heating fuels. Antenatal exposures to pets, livestock, and cigarette smoke were assessed. A subsection completed questions on consumption of fruits and vegetables, fast foods, soft drinks/fruit juices, and fried/microwaved meat., Results: Risk and protective factors differed between urban and rural settings. Exposure to farm animals in infants and their mothers during pregnancy was protective against allergic outcomes in the rural population. Consumption of unpasteurized milk is uncommon in this group of rural children and is unlikely to be an important factor in rural protection. In urban children birth by cesarean section is associated with food allergy, and consumption of fermented milk products is associated with reduced asthma and atopic dermatitis. In both cohorts antenatal maternal smoking and environmental smoking exposure were predominantly associated with asthma, and consumption of fast foods and fried meats were associated with allergy., Conclusion: In this rural environment exposure to livestock is the strongest protective factor. In urban communities, where animal contact is rare, risk factors include cesarian section, and protective factors include consumption of fermented milk products. Modifiable risk factors urgently require interventions to prevent increasing allergy rates in countries undergoing rapid urbanization., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

HIV-associated distal sensory polyneuropathy (DSP), with or without neuropathic symptoms, can develop after anti-retroviral therapy (ART). Symptoms frequently involve small fibres but reports on autonomic dysfunction in HIV-DSP are sparse. We studied an HIV-infected cohort after 5 years of ART, and report on the frequency and severity of autonomic symptoms and the impact of DSP on everyday function. This cross-sectional study comprised of participants from a community-based South African HIV-clinic. The Brief Peripheral Neuropathy Screen and reduced Total Neuropathy Score evaluated neuropathic symptoms/signs. DSP was defined as ≥2 symmetrical DSP-signs, and symptomatic DSP when accompanied by neuropathic symptoms. Autonomic symptoms questionnaires, heart rate variability and postural blood pressure changes were assessed. The Lower Extremity Functional Scale (LEFS) was completed. The 67 participants had a median age of 42 years and median ART exposure of 7 years with viral suppression in 84%. Most (81%) met our criteria for DSP and 36% had additional neuropathic symptoms. Autonomic symptoms and signs (above normative values) were present in 15% and more likely in those with symptomatic DSP (P < .001). Participants with DSP, even without symptoms, had lower LEFS scores (P ≤ .039) than those without. HIV-DSP is prevalent and impacts on daily living., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Infective endocarditis is a microbial infection of the endothelial surface of the heart, predominantly the heart valves, that is associated with high mortality and morbidity. Few contemporary data exist regarding affected children in our context., Aims and Objectives: We aimed to describe the profile and treatment outcomes of infant and childhood endocarditis at our facilities., Methods: This is a retrospective analysis of infants and children with endocarditis at two public sector hospitals in the Western Cape Province of South Africa over a 5-year period. Patients with "definite" and "possible" endocarditis according to Modified Duke Criteria were included in the review., Results: Forty-nine patients were identified for inclusion; 29 had congenital heart disease as a predisposing condition; 64% of patients met "definite" and 36% "possible" criteria. The in-hospital mortality rate was 20%; 53% of patients underwent surgery with a post-operative mortality rate of 7.7%. The median interval from diagnosis to surgery was 20 days (interquartile range, 9-47 days). Valve replacement occurred in 28% and valve repair in 58%. There was a significant reduction in valvular dysfunction in patients undergoing surgery and only a marginal improvement in patients treated medically. Overall, 43% of patients had some degree of residual valvular dysfunction., Conclusion: Endocarditis is a serious disease with a high in-hospital mortality and presents challenges in making an accurate diagnosis. Despite a significant reduction in valvular dysfunction, a portion of patients had residual valvular dysfunction. Early surgery is associated with a lower mortality rate, but a higher rate of valve replacement compared with delayed surgery.

This study describes and compares allergic diseases and sensitization in urban and rural children in the SAFFA study cohort as well as infant feeding patterns and nutritional status. We assessed the relationship between nutritional status, breastfeeding, complementary feeding patterns, and atopic diseases including aeroallergen and food allergen sensitization, self-reported atopic dermatitis, allergic rhinitis, asthma, and challenge-proven food allergy (FA)., Methodology: A total of 1185 urban and 398 rural toddlers aged 12-36 months were screened for food sensitization (FS) and FA using skin prick testing and oral food challenges. Of these, 535 and 347, respectively, were additionally screened for aeroallergen sensitization. Information was collected on infant feeding practices, and anthropometric measurements and clinical signs for atopy were documented., Results: Markedly higher rates of allergy (asthma 9.0% vs 1.0%, eczema 25.6% vs 2.0%, rhinitis 25.3% vs 3.3%, and FA 2.5% vs 0.5%) exist in urban vs rural children. 13.1% unselected urban South African children were sensitized to aeroallergens compared to 3.8% of their rural counterparts and 9.0% to any food compared to 0.5%. Exclusive breastfeeding duration was longer, and there was a later introduction of allergenic foods in rural communities. Obesity rates were similar between the two groups, but rural children were more likely to be stunted. Being overweight was associated with asthma in urban but not rural settings. In the urban cohort, children with FS and allergy were thinner than their peers., Conclusion: Allergy and sensitization rates are significantly higher in unselected urban South African toddlers than their rural counterparts. Risk and protective factors for allergy and atopy may differ between urban and rural settings., (© 2019 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: Food sensitization and challenge-proved food allergy (FA) have not been compared in urban and rural settings., Objective: We sought to determine and compare the prevalence of food sensitization and challenge-proved IgE-mediated FA in urban and rural South African toddlers aged 12 to 36 months., Methods: This cross-sectional study of unselected children included 1185 participants in urban Cape Town and 398 in the rural Eastern Cape. All participants completed a questionnaire and underwent skin prick tests (SPTs) to egg, peanut, cow's milk, fish, soya, wheat, and hazelnut. Participants with SPT responses of 1 mm or greater to 1 or more foods and not tolerant on history underwent an open oral food challenge., Result: The prevalence of FA was 2.5% (95% CI, 1.6% to 3.3%) in urban children, most commonly to raw egg white (1.9%), followed by cooked egg (0.8%), peanut (0.8%), cow's milk (0.1%), and fish (0.1%). Urban sensitization (SPT response ≥1 mm) to any food was 11.4% (95% CI, 9.6% to 13.3%) and 9.0% (95% CI, 7.5% to 10.8%) at an SPT response of 3 mm or greater. Sensitization in rural cohorts was significantly lower than in the urban cohort (1-mm SPT response, 4.5% [95% CI, 2.5% to 6.6%]; 3-mm SPT response, 2.8% [95% CI, 1.4% to 4.9%]; P < .01). In the rural black African cohort 0.5% (95% CI, 0.1% to 1.8%) of children had food allergy, all to egg. This is significantly lower than the prevalence of the urban cohort overall (2.5%) and urban black African participants (2.9%; 95% CI, 1.5% to 4.3%; P = .006)., Conclusion: FA prevalence in Cape Town is comparable with rates in industrialized middle-income countries and is significantly greater than in rural areas. Further analysis will describe and compare environmental exposures and other risk factors in this cohort., (Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Severe meat allergy with anaphylaxis may be caused by sensitization to alpha-gal. Levels of alpha-gal sensitization that correlate with high risk of meat allergy are currently unknown. We have identified an area with a high prevalence of reported red meat allergy which offered the opportunity to evaluate the diagnostic value of IgE antibody tests., Methods: To determine levels of alpha-gal IgE and alpha-gal:total IgE ratio in a large cohort of subjects with challenge-proven meat allergy compared with control subjects from the same environment, we conducted fieldwork assessing 131 participants who reported adverse reactions to meat, and 26 control subjects, by questionnaires, IgE sensitization to alpha-gal and oral food challenge to beef sausage., Results: Eighty-four participants were diagnosed with alpha-gal allergy. Alpha-gal IgE ranged between 0.7 and 344.5 kU/L. Alpha-gal:total IgE ratio ranged from 0.1% to 67.6%. Logistic regression analysis showed both alpha-gal IgE and alpha-gal:total IgE ratio strongly correlated with meat allergy, with AUC of 0.95. The values giving the best correct classification were IgE of 2.00 kU/L and ratio of 0.75%. The value above which there is a 95% probability of meat allergy is IgE>5.5 kU/L and ratio of 2.12%., Conclusion: Alpha-gal allergy in a population with a high prevalence of reported red meat allergy showed a more rapid onset of symptoms than previously described and a high prevalence of isolated subjective gastrointestinal manifestations. Cutoff values are described for levels of sensitization to alpha-gal IgE and alpha-gal:total IgE ratio that are highly likely to result in clinically significant meat allergy., (© 2018 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: Research on reproductive health effects on children from low-level, long-term exposure to pesticides currently used in the agricultural industry is limited and those on neurobehavioral effects have produced conflicting evidence. We aim at investigating the association between pesticide exposure on the reproductive health and neurobehavior of children in South Africa, by including potential relevant co-exposures from the use of electronic media and maternal alcohol consumption., Methods: The design entails a prospective cohort study with a follow-up duration of 2 years starting in 2017, including 1000 school going children between the ages of 9 to 16 years old. Children are enrolled with equal distribution in sex and residence on farms and non-farms in three different agricultural areas (mainly apple, table grapes and wheat farming systems) in the Western Cape, South Africa. The neurobehavior primary health outcome of cognitive functioning was measured through the iPad-based CAmbridge Neuropsychological Test Automated Battery (CANTAB) including domains for attention, memory, and processing speed. The reproductive health outcomes include testicular size in boys and breast size in girls assessed in a physical examination, and blood samples to detect hormone levels and anthropometric measurements. Information on pesticide exposure, co-exposures and relevant confounders are obtained through structured questionnaire interviews with the children and their guardians. Environmental occurrence of pesticides will be determined while using a structured interview with farm owners and review of spraying records and collection of passive water and air samples in all three areas. Pesticide metabolites will be analysed in urine and hair samples collected from the study subjects every 4 months starting at baseline., Discussion: The inclusion of three different agricultural areas will yield a wide range of pesticide exposure situations. The prospective longitudinal design is a further strength of this study to evaluate the reproductive and neurobehavioural effects of different pesticides on children. This research will inform relevant policies and regulatory bodies to improve the health, safety and learning environments for children and families in agricultural settings.