Linkage to HIV care and early retention in HIV care among men in the 'universal test-and-treat' era in a high HIV-burdened district, KwaZulu-Natal, South Africa.

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.

Comparing PrEP initiation rates by service delivery models among high risk adolescent boys and young men in KwaZulu-Natal, South Africa: findings from a population-based prospective study.

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.

Vaccine and Non-Vaccine HPV Types Presence in Adolescents with Vertically Acquired HIV Five Years Post Gardasil Quadrivalent Vaccination: The ZIMGARD Cohort.

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.

A descriptive study of vancomycin use at Red Cross War Memorial Children's Hospital, Cape Town.

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.

Enhancing linkage to HIV care in the "Universal Test and Treat" era: Barriers and enablers to HIV care among adults in a high HIV burdened district in KwaZulu-Natal, South Africa.

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.

Low incidence of pulmonary hypertension in children with suspected obstructive sleep apnea: A prospective observational study.

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.

Healthcare provider perceptions on the implementation of the universal test-and-treat policy in South Africa: a qualitative inquiry.

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.

Service delivery models that promote linkages to PrEP for adolescent girls and young women and men in sub-Saharan Africa: a scoping review.

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.

Candida bloodstream infection among children hospitalised in three public-sector hospitals in the Metro West region of Cape Town, South Africa.

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.

Strengthening health system's capacity for linkage to HIV care for adolescent girls and young women and adolescent boys and young men in South Africa (SheS'Cap-Linkage): Protocol for a mixed methods study in KwaZulu-Natal, South Africa.

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.

Outcomes of patients undergoing lung resection for drug-resistant TB and the prognostic significance of pre-operative positron emission tomography/computed tomography (PET/CT) in predicting treatment failure.

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).

Linkage to HIV Care and Early Retention in Care Rates in the Universal Test-and-Treat Era: A Population-based Prospective Study in KwaZulu-Natal, South Africa.

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.

Barriers and Facilitating Factors to HIV Treatment Among Men in a High-HIV-Burdened District in KwaZulu-Natal, South Africa: A Qualitative Study.

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.

Service delivery models for enhancing linkage to and retention in HIV care services for adolescent girls and young women and adolescent boys and young men: a protocol for an overview of systematic reviews.

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.

Strengthening health system's capacity for pre-exposure prophylaxis for adolescent girls and young women and adolescent boys and young men in South Africa (SHeS'Cap-PrEP): Protocol for a mixed methods study in KwaZulu-Natal, South Africa.

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.

Ascaris lumbricoides and ticks associated with sensitization to galactose α1,3-galactose and elicitation of the alpha-gal syndrome.

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.

Environment-dependent alterations of immune mediators in urban and rural South African children with atopic dermatitis.

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, TNFß, IL-1α, IL-6, IL-8, IL-21, MCP-1, MIP-1α, MIP-1ß, MDC, sICAM1, sVCAM1, VEGFA, VEGFD and Tie2, suggesting a generalized microinflammation or a pattern of trained immunity without any specific TH polarization. In contrast, IL-15, IL-22, Flt1, PIGF and ßFGF 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.

Tertiary hospitals physician's knowledge and perceptions towards antibiotic use and antibiotic resistance in Cameroon.

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.