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Objective: We compared the prevalence of frailty by HIV serostatus and related biomarkers to the modified frailty phenotype among older individuals in a rural population in South Africa. Methods: Questionnaire data were from a cohort of people living with HIV (PWH) on antiretroviral therapy (ART) and HIV-uninfected people aged 50 years and older sampled from the Africa Health Research Institute Demographic Health and Surveillance area in northern KwaZulu-Natal. The prevalence of frailty was compared using five categories: (1) physical activity; (2) mobility; (3) fatigue; (4) gait speed; and (5) grip strength, and assessed for demographic, clinical, and inflammatory correlates of frailty. Results: Among 614 individuals in the study, 384 (62.5%) were women. The median age at study enrolment was 64 years [Interquartile range (IQR) (58.6-72.0)]. 292 (47.6%) were PWH. 499 (81%) were classified as either pre-frail or frail. 43 (7%) were frail and HIV positive, 185 (30%) were pre-frail and HIV positive, 57 were frail and HIV negative and 214 (35%) were pre-frail and HIV negative. Frailty was similar for HIV negative and PWH (17.7% vs 14.7%, p = 0.72). Women were more likely to be frail (18.3% vs 13.04%, p = 0.16). The prevalence of frailty increased with age for both HIV groups. In the multivariable analysis, the odds of being frail were higher in those aged 70 years and above than those aged between 50 and 59 years (p < 0.001). Females were less likely to be pre-frail than males (p < 0.001). There was no association between any of the inflammatory biomarkers and frailty and pre-frailty. Conclusion: In this population, the prevalence of frailty is similar for PWH and people without HIV, but higher for women than men. These data suggest that the odds of developing frailty is similar for PWH over the age of 50 years, who survive into older age, as for people without HIV.

Computer-aided digital chest radiograph interpretation (CAD) can facilitate high-throughput screening for tuberculosis (TB), but its use in population-based active case-finding programs has been limited. In an HIV-endemic area in rural South Africa, we used a CAD algorithm (CAD4TBv5) to interpret digital chest x-rays (CXR) as part of a mobile health screening effort. Participants with TB symptoms or CAD4TBv5 score above the triaging threshold were referred for microbiological sputum assessment. During an initial pilot phase, a low CAD4TBv5 triaging threshold of 25 was selected to maximize TB case finding. We report the performance of CAD4TBv5 in screening 9,914 participants, 99 (1.0%) of whom were found to have microbiologically proven TB. CAD4TBv5 was able to identify TB cases at the same sensitivity but lower specificity as a blinded radiologist, whereas the next generation of the algorithm (CAD4TBv6) achieved comparable sensitivity and specificity to the radiologist. The CXRs of people with microbiologically confirmed TB spanned a range of lung field abnormality, including 19 (19.2%) cases deemed normal by the radiologist. HIV serostatus did not impact CAD4TB’s performance. Notably, 78.8% of the TB cases identified during this population-based survey were asymptomatic and therefore triaged for sputum collection on the basis of CAD4TBv5 score alone. While CAD4TBv6 has the potential to replace radiologists for triaging CXRs in TB prevalence surveys, population-specific piloting is necessary to set the appropriate triaging thresholds. Further work on image analysis strategies is needed to identify radiologically subtle active TB.

Background Adolescent girls and young women (AGYW) in rural KwaZulu-Natal, South Africa are disproportionately affected by herpes simplex virus type 2 (HSV-2) and HIV. As HSV-2 infection enhances the acquisition and transmission of HIV and other STIs, broader STI control requires understanding of HSV-2 predictors. We therefore assessed how HSV-2 incidence and prevalence were associated with sexual behaviours among AGYW in this region. Methods We analysed data from a two-year (2017–2019) prospective cohort study among a random sample of 2184 AGYW aged 13–22 which was representative of the study population. Data were collected at baseline, 12 months and 24 months. We calculated HSV-2 prevalence at any study visit and incidence among those HSV-2 negative at baseline. We ran Poisson and logistic regressions to assess the association of sexual behaviours with both HSV-2 incidence and prevalence. Results HSV-2 prevalence was 26.2% among the study population, and was strongly associated with having sexual debut before the age of 16 (adjusted odds ratio (aOR) 1.52, 95% confidence interval (CI) 1.06–2.17) and having two or more sexual partners in the past 12 months (aOR 3.64, 95% CI 1.39–9.50). 307 of 1,433 baseline HSV-2 seronegative AGYW seroconverted during follow-up (incidence rate 16.5/100 person years at risk, 95% CI 14.7–18.4). Self-reported lower age of sexual debut, one or more sexual partners and inconsistent condom use were bivariately associated with HSV-2 incidence. None of these self-reported sexual behaviour measures remained associated with incident HSV-2 after adjusting for socio-demographic, social and biological variables. Conclusion The high HSV-2 rates among AGYW particularly those engaging in high-risk sexual behaviours underscores the need for HSV-2 control interventions to slow its spread and other STIs in KwaZulu-Natal. However, further research is required for more targeted interventions due to the lack of association between sexual behaviours and HSV-2 incidence.

Background Computer-aided digital chest radiograph (CXR) interpretation can facilitate high-throughput screening for tuberculosis (TB), but its use in population-based screening has been limited. We applied an automated image interpretation algorithm, CAD4TBv5, prospectively in an HIV-endemic area. Methods Participants underwent CXR and, for those with symptoms or lung field abnormality, microbiological assessment of sputum collected at a mobile camp in rural South Africa. CAD4TBv5 scored each CXR on a 0-100 scale in the field. An expert radiologist, blinded to the CAD4TBv5 score and other data, assessed CXRs for 1) lung field abnormality and 2) findings diagnostic of active TB (R+). We estimated the performance of CAD4TBv5 for triaging (identifying lung field abnormality as a criteria for sputum examination) and diagnosis (detection of active TB as defined by microbiologic (M+) or radiologic (R+) gold standards). Findings For triaging, a CAD4TBv5 threshold of 25 identified abnormal lung fields with a sensitivity of 90.3% and specificity of 48.2%. For diagnosis, CAD4TBv5 had less agreement with the microbiological reference standard (M+) used to define definite TB (AUC 0.78) than with the radiological reference standard (R+) used to define probable TB (AUC 0.96). HIV-serostatus did not impact CAD4TB9s performance. Interpretation A low CAD4TBv5 threshold was required to achieve acceptable triaging sensitivity. Low specificity at this threshold led to high rates of sputum collection despite normal lung fields. CAD4TBv5 had difficulty identifying microbiologically-confirmed TB cases with subtle radiological features but had excellent agreement with the radiologist in identifying radiologically-defined TB cases. We conclude that computer-aided CXR interpretation can be useful in population-based screening in HIV-endemic settings, but threshold selection should be guided by setting-specific piloting and priorities. CXR interpretation algorithms require refinement for the identification of radiologically-subtle early TB.

A coordinated system of disease surveillance will be critical to effectively control the coronavirus disease 2019 (Covid-19) pandemic. Such systems enable rapid detection and mapping of epidemics and inform allocation of scarce prevention and intervention resources. Although many lower- and middle-income settings lack infrastructure for optimal disease surveillance, health and demographic surveillance systems (HDSS) provide a unique opportunity for epidemic monitoring. This protocol describes a surveillance program at the Africa Health Research Institute�s Population Intervention Platform site in northern KwaZulu-Natal. The program leverages a longstanding HDSS in a rural, resource-limited setting with very high prevalence of HIV and tuberculosis to perform Covid-19 surveillance. Our primary aims include: describing the epidemiology of the Covid-19 epidemic in rural KwaZulu-Natal; determining the impact of the Covid-19 outbreak and non-pharmaceutical control interventions (NPI) on behaviour and wellbeing; determining the impact of HIV and tuberculosis on Covid-19 susceptibility; and using collected data to support the local public-sector health response. The program involves telephone-based interviews with over 20,000 households every four months, plus a sub-study calling 750 households every two weeks. Each call asks a household representative how the epidemic and NPI are affecting the household and conducts a Covid-19 risk screen for all resident members. Any individuals screening positive are invited to a clinical screen, potential test and referral to necessary care � conducted in-person near their home following careful risk minimization procedures. In this protocol we report the details of our cohort design, questionnaires, data and reporting structures, and standard operating procedures in hopes that our project can inform similar efforts elsewhere.

IntroductionA cluster randomised controlled trial (cRCT) to determine whether HIV self-testing (HIVST) delivered by peers either directly or through incentivised peer-networks, could increase the uptake of antiretroviral therapy and pre-exposure prophylaxis (PrEP) among young women (18 to 24 years) is being undertaken in an HIV hyperendemic area in KwaZulu-Natal, South Africa.Methods and analysisA three-arm cRCT started mid-March 2019, in 24 areas in rural KwaZulu-Natal. Twenty-four pairs of peer navigators working with ~12 000 young people aged 18 to 30 years over a period of 6 months were randomised to: (1) incentivised-peer-networks: peer-navigators recruited participants ‘seeds’ to distribute up to five HIVST packs and HIV prevention information to peers within their social networks. Seeds receive an incentive (20 Rand = US$1.5) for each respondent who contacts a peer-navigator for additional HIVST packs to distribute; (2) peer-navigator-distribution: peer-navigators distribute HIVST packs and information directly to young people; (3) standard of care: peer-navigators distribute referral slips and information. All arms promote sexual health information and provide barcoded clinic referral slips to facilitate linkage to HIV testing, prevention and care services. The primary outcome is the difference in linkage rate between arms, defined as the number of women (18 to 24 years) per peer-navigators month of outreach work (/pnm) who linked to clinic-based PrEP eligibility screening or started antiretroviral, based on HIV-status, within 90 days of receiving the clinic referral slip.Ethics and disseminationThis study was approved by the Institutional Review Boards at the WHO, Switzerland (Protocol ID: STAR CRT, South Africa), London School of Hygiene and Tropical Medicine, UK (Reference: 15 990–1), University of KwaZulu-Natal (BFC311/18) and the KwaZulu-Natal Department of Health (Reference: KZ_201901_012), South Africa. The findings of this trial will be disseminated at local, regional and international meetings and through peer-reviewed publications.Trial registration numberNCT03751826; Pre-results.

Background Adolescent girls and young women (AGYW) In South Africa are at high risk of HIV and early pregnancy. MTV-Shuga, a mass-media edu-drama, improved some sexual health outcomes in a randomised trial amongst young people in Nigeria. We used the national free-to-air TV screening of MTV-Shuga (the “Down South” series), concurrent with the roll-out of a large scale-up of combination HIV prevention for AGYW - to test the hypothesis that mass-media edu-drama can improve the sexual health of AGYW in a rural and resource-constrained area of KwaZulu-Natal. Methods We followed a representative population-based prospective cohort of females aged 13–23 between May 2017 and September 2018. We measured the relationship between exposure to MTV-Shuga (i.e., reporting seeing ≥1 of 24 episodes; able to recall any storyline) and: incident HSV-2; incident pregnancy; condom use at last sex; uptake of HIV-testing and contraception; and awareness of HIV Pre-Exposure Prophylaxis (PrEP). Results 2183 (85.5%) eligible participants were surveyed at baseline, of whom 1853 (86.5%) completed follow-up. MTV-Shuga exposure was low – 152 (8.2%) reported seeing ≥1 episode and 73 (3.9%) recalled any storyline – while teenage pregnancy and incident HSV-2 were high (6.4 and 11.3/100 person-years respectively). MTV-Shuga exposed AGYW were from wealthier households (p Conclusion AGYW exposure to the MTV-Shuga edu-drama was very low in a setting where AGYW remain at high risk for STI, HIV and early pregnancy. Nevertheless, there is a suggestion that those who were exposed to MTV-Shuga had better sexual health outcomes. There is a need for strategies to raise uptake of such edu-dramas, and to evaluate whether wider coverage leads to population impact. Disclosure No significant relationships.

A coordinated system of disease surveillance will be critical to effectively control the coronavirus disease 2019 (Covid-19) pandemic. Such systems enable rapid detection and mapping of epidemics and inform allocation of scarce prevention and intervention resources. Although many lower- and middle-income settings lack infrastructure for optimal disease surveillance, health and demographic surveillance systems (HDSS) provide a unique opportunity for epidemic monitoring. This protocol describes a surveillance program at the Africa Health Research Institute’s Population Intervention Platform site in northern KwaZulu-Natal. The program leverages a longstanding HDSS in a rural, resource-limited setting with very high prevalence of HIV and tuberculosis to perform Covid-19 surveillance. Our primary aims include: describing the epidemiology of the Covid-19 epidemic in rural KwaZulu-Natal; determining the impact of the Covid-19 outbreak and non-pharmaceutical control interventions (NPI) on behaviour and wellbeing; determining the impact of HIV and tuberculosis on Covid-19 susceptibility; and using collected data to support the local public-sector health response. The program involves telephone-based interviews with over 20,000 households every four months, plus a sub-study calling 750 households every two weeks. Each call asks a household representative how the epidemic and NPI are affecting the household and conducts a Covid-19 risk screen for all resident members. Any individuals screening positive are invited to a clinical screen, potential test and referral to necessary care – conducted in-person near their home following careful risk minimization procedures. In this protocol we report the details of our cohort design, questionnaires, data and reporting structures, and standard operating procedures in hopes that our project can inform similar efforts elsewhere.

Rapid diagnostic tests (RDTs) are the mainstay of HIV diagnosis in the developing world but might have poor sensitivity among individuals taking antiretroviral therapy (ART). We leveraged a home-based HIV testing program linked to clinical data to compare the sensitivity of RDTs between individuals using versus not using ART. Field workers tested 6802 individuals using 2 HIV RDTs, which were compared to a single HIV immunoassay tested on dried blood spots. Approximately 5% (371/6802) tested positive by immunoassay, of whom 157 (42%) were currently on ART. The sensitivity of the Abon RDT among those never versus currently on ART was 91.6% (95% CI 88.3–94.3) and 96.6% (95% CI 88.3–94.3), respectively, and 95.4% (95% CI 92.8–97.3) versus 99.3% (95% CI 95.2–99.7) for the Advanced Quality assay. We report similar sensitivity of RDTs in ART-naive and ART-experienced individuals, which mitigates concerns about their use among treated individuals in population-based epidemiologic surveys and those transferring care.

Background Sexually transmitted infections (STIs) and bacterial vaginosis (BV) are associated with increased transmission of HIV, and poor reproductive and sexual health. The burden of STIs/BV among young people is unknown in many high HIV prevalence settings. We conducted an acceptability, feasibility, and prevalence study of home-based sampling for STIs/BV among young men and women aged 15–24 years old in a health and demographic surveillance site (HDSS) in rural KwaZulu-Natal, South Africa. Methods and findings A total of 1,342 young people, stratified by age (15–19 and 20–24 years) and sex were selected from the HDSS sampling frame; 1,171/1,342 (87%) individuals had ≥1 attempted home visit between 4 October 2016 and 31 January 2017, of whom 790 (67%) were successfully contacted. Among the 645 who were contacted and eligible, 447 (69%) enrolled. Consenting/assenting participants were interviewed, and blood, self-collected urine (men), and vaginal swabs (women) were tested for herpes simplex virus type 2 (HSV-2), chlamydia, gonorrhoea, syphilis, trichomoniasis, and BV. Both men and women reported that sample collection was easy. Participants disagreed that sampling was painful; more than half of the participants disagreed that they felt anxious or embarrassed. The weighted prevalence of STIs/BV among men and women, respectively, was 5.3% and 11.2% for chlamydia, 1.5% and 1.8% for gonorrhoea, 0% and 0.4% for active syphilis, 0.6% and 4.6% for trichomoniasis, 16.8% and 28.7% for HSV-2, and 42.1% for BV (women only). Of the women with ≥1 curable STI, 75% reported no symptoms. Factors associated with STIs/BV included having older age, being female, and not being in school or working. Among those who participated in the 2016 HIV serosurvey, the prevalence of HIV was 5.6% among men and 19% among women. Feasibility was impacted by the short study duration and the difficulty finding men at home. Conclusions A high prevalence of STIs/BV was found in this rural setting with high HIV prevalence in South Africa. Most STIs and HIV infections were asymptomatic and would not have been identified or treated under national syndromic management guidelines. A nested STI/BV survey within a HDSS proved acceptable and feasible. This is a proof of concept for population-based STI surveillance in low- and middle-income countries that could be utilised in the evaluation of STI/HIV prevention and control programmes., Suzanna C Francis and colleagues report on acceptability, feasibility and prevalence results from home-based STI sampling among young men and women in rural KwaZulu-Natal, South Africa., Author summary Why was this study done? Adolescents and young adults are particularly vulnerable to sexually transmitted infections (STIs). The first strategic direction of the WHO Global Health Sector Strategy on Sexually Transmitted Infections 2016–2021 is to collect information on STI prevalence and incidence across representative populations. There is evidence that bacterial vaginosis (BV) is a risk factor for poor birth outcomes and STIs including HIV. The collection of BV prevalence may therefore also be important. Developing new cohorts for dedicated STI/BV prevalence studies may not be realistic, particularly in sub-Saharan Africa, where the impact of STIs/BV and their consequences may be greatest. Nesting STI/BV surveys within networks of health and demographic surveillance sites (HDSSs) would be an efficient way of providing data to better understand STI epidemiology among adolescents and young people in high HIV prevalence settings. What did the researchers do and find? We carried out a nested STI/BV survey among 1,342 adolescent and young people in an HDSS in KwaZulu-Natal, South Africa, between October 2016 and January 2017. Potential participants were contacted at home and invited to participate. Participants were interviewed, and samples were collected for STI/BV testing. We showed that this study was feasible within the 3.5-month time period: 1,171/1,342 (87%) individuals had ≥1 attempted home visit, of whom 790 (67%) were successfully contacted. The study was acceptable: among those contacted and eligible, 447/645 (69%) enrolled. Both men and women reported few problems with sample collection. We report a high burden of STIs/BV in this population, particularly of chlamydia (5% in men and 11% in women), herpes simplex virus type 2 (17% in men and 29% in women), and BV (42% in women). What do these findings mean? Nested STI/BV surveys in HDSSs can be feasible and acceptable; however, more survey time is needed to ensure that all potential participants are visited and contacted. These studies should be carried out in conjunction with studies to measure STI/BV prevalence in high-risk populations (e.g., female sex workers) to provide robust prevalence estimates. These data are essential to advocate, fund, plan, implement, and evaluate interventions for STI prevention and control among adolescents and young people. Strategies for the prevention and control of chlamydia, herpes simplex virus type 2, and BV are needed in this population.