Impacts of heat exposure in utero on long-term health and social outcomes: a systematic review.

BACKGROUND: Climate change, particularly global warming, is amongst the greatest threats to human health. While short-term effects of heat exposure in pregnancy, such as preterm birth, are well documented, long-term effects have received less attention. This review aims to systematically assess evidence on the long-term impacts on the foetus of heat exposure in utero. METHODS: A search was conducted in August 2019 and updated in April 2023 in MEDLINE(PubMed). We included studies on the relationship of environmental heat exposure during pregnancy and any long-term outcomes. Risk of bias was assessed using tools developed by the Joanna-Briggs Institute, and the evidence was appraised using the GRADE approach. Synthesis without Meta-Analysis (SWiM) guidelines were used. RESULTS: Eighteen thousand six hundred twenty one records were screened, with 29 studies included across six outcome groups. Studies were mostly conducted in high-income countries (n = 16/25), in cooler climates. All studies were observational, with 17 cohort, 5 case-control and 8 cross-sectional studies. The timeline of the data is from 1913 to 2019, and individuals ranged in age from neonates to adults, and the elderly. Increasing heat exposure during pregnancy was associated with decreased earnings and lower educational attainment (n = 4/6), as well as worsened cardiovascular (n = 3/6), respiratory (n = 3/3), psychiatric (n = 7/12) and anthropometric (n = 2/2) outcomes, possibly culminating in increased overall mortality (n = 2/3). The effect on female infants was greater than on males in 8 of 9 studies differentiating by sex. The quality of evidence was low in respiratory and longevity outcome groups to very low in all others. CONCLUSIONS: Increasing heat exposure was associated with a multitude of detrimental outcomes across diverse body systems. The biological pathways involved are yet to be elucidated, but could include epigenetic and developmental perturbations, through interactions with the placenta and inflammation. This highlights the need for further research into the long-term effects of heat exposure, biological pathways, and possible adaptation strategies in studies, particularly in neglected regions. Heat exposure in-utero has the potential to compound existing health and social inequalities. Poor study design of the included studies constrains the conclusions of this review, with heterogenous exposure measures and outcomes rendering comparisons across contexts/studies difficult. TRIAL REGISTRATION: PROSPERO CRD 42019140136.

A WHO-led global strategy to control greenhouse gas emissions: a call for action.

BACKGROUND: Climate change, driven by anthropogenic greenhouse gas emissions, is among the greatest threats to human health. The World Health Organisation (WHO), has led global efforts to respond to emerging public health threats including the control of hazardous substances such as tobacco, alcohol, lead and asbestos, with remarkable health gains. BODY: Despite WHO's clear messaging on the enormous and growing health risks of climate change, greenhouse gases are not yet classified as hazardous substances, requiring control through a global strategy or framework. Additionally, WHO has not classified disease attributable to climate change as a result of the promulgation of these hazards as a Public Health Emergency of International Concern (PHEIC), despite the serious and preventable health risks it poses globally. Several historical precedents set the stage for WHO to declare excess greenhouse gases as health hazards, including the control of ozone-depleting substances and breast-milk substitutes where the public benefit of control exceeded the potential benefit of their promulgation. In addition, WHO's undertaking within the International Health Regulations to protect global health, providing imperative to declare climate change a PHEIC, with Tedros Adhanom Ghebreyesus, director-general of WHO, declaring: "The climate crisis is a health crisis, fuelling outbreaks, contributing to higher rates of noncommunicable diseases, and threatening to overwhelm our health workforce and health infrastructure". Importantly, the health sector, perhaps more than other sectors, has successfully overcome formidable, vested interests in combatting these threats to health. CONCLUSION: It is thus imperative that WHO make full use of their credibility and influence to establish a global framework for the control of greenhouse gases through the declaration of excess greenhouse gas emissions as a hazardous substance, and declaring climate change a PHEIC. Who else is better placed to drive the considerable societal transformation needed to secure a liveable future?

COVID-19 in Africa: care and protection for frontline healthcare workers.

Medical staff caring for COVID-19 patients face mental stress, physical exhaustion, separation from families, stigma, and the pain of losing patients and colleagues. Many of them have acquired SARS-CoV-2 and some have died. In Africa, where the pandemic is escalating, there are major gaps in response capacity, especially in human resources and protective equipment. We examine these challenges and propose interventions to protect healthcare workers on the continent, drawing on articles identified on Medline (Pubmed) in a search on 24 March 2020. Global jostling means that supplies of personal protective equipment are limited in Africa. Even low-cost interventions such as facemasks for patients with a cough and water supplies for handwashing may be challenging, as is 'physical distancing' in overcrowded primary health care clinics. Without adequate protection, COVID-19 mortality may be high among healthcare workers and their family in Africa given limited critical care beds and difficulties in transporting ill healthcare workers from rural to urban care centres. Much can be done to protect healthcare workers, however. The continent has learnt invaluable lessons from Ebola and HIV control. HIV counselors and community healthcare workers are key resources, and could promote social distancing and related interventions, dispel myths, support healthcare workers, perform symptom screening and trace contacts. Staff motivation and retention may be enhanced through carefully managed risk 'allowances' or compensation. International support with personnel and protective equipment, especially from China, could turn the pandemic's trajectory in Africa around. Telemedicine holds promise as it rationalises human resources and reduces patient contact and thus infection risks. Importantly, healthcare workers, using their authoritative voice, can promote effective COVID-19 policies and prioritization of their safety. Prioritizing healthcare workers for SARS-CoV-2 testing, hospital beds and targeted research, as well as ensuring that public figures and the population acknowledge the commitment of healthcare workers may help to maintain morale. Clearly there are multiple ways that international support and national commitment could help safeguard healthcare workers in Africa, essential for limiting the pandemic's potentially devastating heath, socio-economic and security impacts on the continent.

Field Performance and Diagnostic Accuracy of a Low-Cost Instrument-Free Point-of-Care CD4 Test (Visitect CD4) Performed by Different Health Worker Cadres among Pregnant Women.

Measuring CD4 counts remains an important component of HIV care. The Visitect CD4 is the first instrument-free low-cost point-of-care CD4 test with results interpreted visually after 40 min, providing a result of ≥350 CD4 cells/mm3 The field performance and diagnostic accuracy of the test was assessed among HIV-infected pregnant women in South Africa. A nurse performed testing at the point-of-care using both venous and finger-prick blood, and a counselor and laboratory staff tested venous blood in the clinic laboratory (four Visitect CD4 tests/participant). Performance was compared to the mean CD4 count from duplicate flow cytometry tests on venous blood (FACSCalibur Trucount). In 2017, 156 patients were enrolled, providing a total of 624 Visitect CD4 tests (468 venous and 156 finger-prick samples). Of 624 tests, 28 (4.5%) were inconclusive. Generalized linear mixed modeling showed better performance of the test on venous blood (sensitivity = 81.7%; 95% confidence interval [CI] = 72.3 to 91.1]; specificity = 82.6%, 95% CI = 77.1 to 88.1) than on finger-prick specimens (sensitivity = 60.7%; 95% CI = 45.0 to 76.3; specificity = 89.5%, 95% CI = 83.2 to 95.8; P = 0.001). No difference in performance was detected by cadre of health worker (P = 0.113) or between point-of-care versus laboratory-based testing (P = 0.108). Adequate performance of Visitect CD4 with different operators and at the point of care, with no need of electricity or instrument, shows the potential utility of this device, especially for facilitating decentralization of CD4 testing services in rural areas.

Incidence, Persistence, Clearance, and Correlates of Genital Human Papillomavirus Infection and Anogenital Warts in a Cohort of Men Living With Human Immunodeficiency Virus in South Africa.

OBJECTIVE: To estimate the incidence; persistence and correlates of human papillomavirus (HPV) infection and anogenital warts (AGW) among men living with human immunodeficiency virus (MLHIV). METHODS: Overall, 304 MLHIV 18 years or older were enrolled and attended follow-up visits at 6, 12, and 18 months. Clinicians examined for AGW, collected blood, and penile swabs for HPV testing (Roche Linear Array) at each visit. Time to AGW incidence or clearance was estimated by Kaplan-Meier method. Factors associated with persistent HPV infection and AGW clearance were evaluated with generalized estimating equations and Cox regression, respectively. RESULTS: Mean age of participants was 38 years (standard deviation, 8 years); 25% reported more than 1 sexual partner in the past 3 months. Most (65%) participants were on antiretroviral treatment (ART) with a median CD4 count of 445 cells/µL (interquartile range, 328-567). Prevalence of HPV infection and AGW at enrolment were 79% (224 of 283) and 12% (36 of 304), respectively. Two hundred fifty-nine men were followed up for a median (interquartile range) 1.4 years (0.5-1.7 years). Incidence of any-genital HPV infection was 2.9 (95% confidence interval, 1.5-5.5) per 100 person-years. Persistence of any-genital HPV infection was 35% (68 of 192) and was higher among MLHIV with low CD4 count (adjusted odds ratio, 3.54; 95% confidence interval, 2.07-6.05). Incidence of AGW was 1.4 per 100 person-years. Men living with human immunodeficiency virus with high CD4 count were more likely to clear AGW than those with low CD4 count (adjusted hazard ratio, 3.69; 95% confidence interval, 1.44-9.47). No associations were observed between persistent genital HPV infection, AGW clearance with enrolment ART status or duration. CONCLUSIONS: Human immunodeficiency virus-positive men have a high burden of genital HPV infection and AGW. The ART and HPV vaccine could reduce this burden.

Type-Specific Human Papillomavirus Prevalence, Incident Cases, Persistence, and Associated Pregnancy Outcomes Among HIV-Infected Women in Kenya.

BACKGROUND: Persistent infection with high-risk types of human papillomavirus (HPV) is the preeminent factor driving the development of cervical cancer. There are large gaps in knowledge about both the role of pregnancy in the natural history of HPV infection and the impact of HPV on pregnancy outcomes. METHODS: This single-site prospective cohort substudy, nested within an international multisite randomized controlled trial, assessed prevalence, incident cases, and persistence of type-specific HPV infection, and the association between persistence of high-risk HPV infection with pregnancy outcomes among HIV-infected pregnant women in Kenya, including HIV transmission to infants. Type-specific HPV was assessed using a line probe assay in pregnancy and again at 3 months after delivery. HIV status of children was determined using polymerase chain reaction at 6 weeks. RESULTS: In total, 84.1% (206/245) of women had a high-risk HPV infection at enrollment. Three quarters (157/206) of these infections persisted postpartum. Persistence of HPV16 and/or HPV18 types was observed in more than half (53.4%; 39/73) of women with this infection at enrollment. Almost two-thirds had an incident high-risk HPV infection postpartum, which was not present in pregnancy (62.5%), most commonly HPV52 (19.0%). After adjustments, no association was detected between persistent high-risk HPV and preterm birth. All mothers of the 7 cases of infant HIV infection had persistent high-risk HPV infection (P = 0.044). CONCLUSIONS: High levels of high-risk HPV infection and type-specific persistence were documented, heightening the urgency of mass role out of HPV vaccination. The association between HPV persistence and HIV transmission is a novel finding, warranting further study.

Climate change adaptation in South Africa: a case study on the role of the health sector.

BACKGROUND: Globally, the response to climate change is gradually gaining momentum as the impacts of climate change unfold. In South Africa, it is increasingly apparent that delays in responding to climate change over the past decades have jeopardized human life and livelihoods. While slow progress with mitigation, especially in the energy sector, has garnered much attention, focus is now shifting to developing plans and systems to adapt to the impacts of climate change. METHODS: We applied systematic review methods to assess progress with climate change adaptation in the health sector in South Africa. This case study provides useful lessons which could be applied in other countries in the African region, or globally. We reviewed the literature indexed in PubMed and Web of Science, together with relevant grey literature. We included articles describing adaptation interventions to reduce the impact of climate change on health in South Africa. All study designs were eligible. Data from included articles and grey literature were summed thematically. RESULTS: Of the 820 publications screened, 21 were included, together with an additional xx papers. Very few studies presented findings of an intervention or used high-quality research designs. Several policy frameworks for climate change have been developed at national and local government levels. These, however, pay little attention to health concerns and the specific needs of vulnerable groups. Systems for forecasting extreme weather, and tracking malaria and other infections appear well established. Yet, there is little evidence about the country's preparedness for extreme weather events, or the ability of the already strained health system to respond to these events. Seemingly, few adaptation measures have taken place in occupational and other settings. To date, little attention has been given to climate change in training curricula for health workers. CONCLUSIONS: Overall, the volume and quality of research is disappointing, and disproportionate to the threat posed by climate change in South Africa. This is surprising given that the requisite expertise for policy advocacy, identifying effective interventions and implementing systems-based approaches rests within the health sector. More effective use of data, a traditional strength of health professionals, could support adaptation and promote accountability of the state. With increased health-sector leadership, climate change could be reframed as predominately a health issue, one necessitating an urgent, adequately-resourced response. Such a shift in South Africa, but also beyond the country, may play a key role in accelerating climate change adaptation and mitigation.

Qualitative assessment of South African healthcare worker perspectives on an instrument-free rapid CD4 test.

BACKGROUND: Accurate measurement of CD4 cell counts remains an important tenet of clinical care for people living with HIV. We assessed an instrument-free point-of-care CD4 test (VISITECT® CD4) based on a lateral flow principle, which gives visual results after 40 min. The test involves five steps and categorises CD4 counts as above or below 350 cells/µL. As one component of a performance evaluation of the test, this qualitative study explored the views of healthcare workers in a large women and children's hospital on the acceptability and feasibility of the test. METHODS: Perspectives on the VISITECT® CD4 test were elicited through in-depth interviews with eight healthcare workers involved in the performance evaluation at an antenatal care facility in Johannesburg, South Africa. Audio recordings were transcribed in full and analysed thematically. RESULTS: Healthcare providers recognised the on-going relevance of CD4 testing. All eight perceived the VISITECT® CD4 test to be predominantly user-friendly, although some felt that the need for precision and optimal concentration in performing test procedures made it more challenging to use. The greatest strength of the test was perceived to be its quick turn-around of results. There were mixed views on the semi-quantitative nature of the test results and how best to integrate this test into existing health services. Participants believed that patients in this setting would likely accept the test, given their general familiarity with other point-of-care tests. CONCLUSIONS: Overall, the VISITECT® CD4 test was acceptable to healthcare workers and those interviewed were supportive of scale-up and implementation in other antenatal care settings. Both health workers and patients will need to be oriented to the semi-quantitative nature of the test and how to interpret the results of tests.

Lipid levels, insulin resistance and cardiovascular risk over 96 weeks of antiretroviral therapy: a randomised controlled trial comparing low-dose stavudine and tenofovir.

BACKGROUND: HIV infection and antiretroviral treatment are associated with changes in lipid levels, insulin resistance and risk of cardiovascular disease (CVD). We investigated these changes in the first 96 weeks of treatment with low-dose stavudine or tenofovir regimens. METHODS: This is a secondary analysis of a double blind, randomised controlled trial performed in South-Africa, Uganda and India comparing low-dose stavudine (20 mg twice daily) with tenofovir in combination with efavirenz and lamivudine in antiretroviral-naïve adults (n = 1067) (Clinicaltrials.gov, NCT02670772). Over 96 weeks, data were collected on fasting lipids, glucose and insulin. Insulin resistance was assessed with the HOMA-IR index and 10-year CVD risk with the Framingham risk score (FRS). A generalized linear mixed model was used to estimate trends over time. RESULTS: Participants were on average 35.3 years old, 57.6% female and 91.8% Black African. All lipid levels increased following treatment initiation, with the sharpest increase in the first 24 weeks of treatment. The increase in all lipid subcomponents over 96 weeks was higher among those in the stavudine than the tenofovir group. Insulin resistance increased steadily with no difference detected between study groups. FRS rose from 1.90% (1.84-1.98%) at baseline to 2.06 (1.98-2.15%) at week 96 for the total group, with no difference between treatment arms (p = 0.144). Lipid changes were more marked in Indian than African participants. CONCLUSION: Lipid levels increased in both groups, with low-dose stavudine resulting in a worse lipid profile compared to tenofovir. Insulin resistance increased, with no difference between regimens. CVD risk increased over time and tended to increase more in the group on stavudine. The low CVD risk across both arms argues against routine lipid and glucose monitoring in the absence of other CVD risk factors. In high risk patients, monitoring may only be appropriate at least a year after treatment initiation.

Social health insurance contributes to universal coverage in South Africa, but generates inequities: survey among members of a government employee insurance scheme.

BACKGROUND: Many low- and middle-income countries are reforming their health financing mechanisms as part of broader strategies to achieve universal health coverage (UHC). Voluntary social health insurance, despite evidence of resulting inequities, is attractive to policy makers as it generates additional funds for health, and provides access to a greater range of benefits for the formally employed. The South African government introduced a voluntary health insurance scheme (GEMS) for government employees in 2005 with the aim of improving access to care and extending health coverage. In this paper we ask whether the new scheme has assisted in efforts to move towards UHC. METHODS: Using a cross-sectional survey across four of South Africa's nine provinces, we interviewed 1329 government employees, from the education and health sectors. Data were collected on socio-demographics, insurance coverage, health status and utilisation of health care. Multivariate logistic regression was used to determine if service utilisation was associated with insurance status. RESULTS: A quarter of respondents remained uninsured, even higher among 20-29 year olds (46%) and lower-skilled employees (58%). In multivariate analysis, the odds of an outpatient visit and hospital admission for the uninsured was 0.3 fold that of the insured. Cross-subsidisation within the scheme has provided lower-paid civil servants with improved access to outpatient care at private facilities and chronic medication, where their outpatient (0.54 visits/month) and inpatient utilisation (10.1%/year) approximates that of the overall population (29.4/month and 12.2% respectively). The scheme, however, generated inequities in utilisation among its members due to its differential benefit packages, with, for example, those with the most benefits having 1.0 outpatient visits/month compared to 0.6/month with lowest benefits. CONCLUSIONS: By introducing the scheme, the government chose to prioritise access to private sector care for government employees, over improving the availability and quality of public sector services available to all. Government has recently regained its focus on achieving UHC through the public system, but is unlikely to discontinue GEMS, which is now firmly established. The inequities generated by the scheme have thus been institutionalised within the country's financing system, and warrant attention. Raising scheme uptake and reducing differentials between benefit packages will ameliorate inequities within civil servants, but not across the country as a whole.

Advancing STI priorities in the SDG era: priorities for action.

The Sustainable Development Goals present an opportunity to reimagine and then reconfigure the approach to controlling sexually transmitted infections (STIs). The predilection of STIs for women and for vulnerable populations means that services that ameliorate STIs, by their nature, enhance equity, a key focus of the goals. Given the considerable breadth and depth of the goals, it is important to locate points of convergence between the SDGs and STIs, further craft synergies with HIV and select a few population groups and settings to prioritise. There are many opportunities for STI aficionados in this era to advance the field and global control of these infections.

Priority gaps and promising areas in maternal health research in low- and middle-income countries: summary findings of a mapping of 2292 publications between 2000 and 2012.

This commentary sums the findings of a series of papers on a study that mapped the global research agenda for maternal health. The mapping reviewed published interventional research across low- and middle-income countries (LMICs) from 2000 to 2012, specifically focusing on investigating the topics covered by this research, the methodologies applied, the funding landscape and trends in authorship attribution.The overarching aim underpinning the mapping activities was to evaluate whether research and funding align with causes of maternal mortality, and thereby highlight gaps in research priorities and governance. Fifteen reviewers from 8 countries screened 35,078 titles and abstracts, and extracted data from 2292 full-text articles.Over the period reviewed, the volume of publications rose several-fold, especially from 2004 to 2007. The methodologies broadened, increasingly encompassing qualitative research and systematic review. Malaria and HIV research dominated over other topics, while sexually-transmitted infection research progressively diminished. Health systems and health promotion research increased rapidly, but were less frequently evaluated in trials or published in high-impact journals. Relative to disease burden, hypertension had double the publications of haemorrhage. Many Latin American countries, China and Russia had relatively few papers per billion US dollars Gross Domestic Product. Total LMIC lead authorships rose substantially, but only a quarter of countries had a local first author lead on >75% of their research, with levels lowest in sub-Saharan Africa. The median Impact Factor of high-income country led papers was 3.1 and LMIC-led 1.8. The NIH, USAID and Gates Foundation constituted 40% of funder acknowledgements, and addressed similar topics and countries.The commentary notes that increases in outputs and broadening of methodologies suggest research capacity has expanded considerably, allowing for more nuanced, systems-based and context-specific studies. However, funders seemingly duplicate efforts, with topics and countries either receiving excessive or little attention. Better coordinated funding might reduce duplication and allow researchers to develop highly-specialised expertise. Repeated scrutiny of research agendas and funding may foment shifts in priorities. Building leadership capacity in LMICs and reconsidering authorship guidelines is needed.

Attendance at antenatal clinics in inner-city Johannesburg, South Africa and its associations with birth outcomes: analysis of data from birth registers at three facilities.

BACKGROUND: Antenatal care (ANC) clinics serve as key gateways to screening and treatment interventions that improve pregnancy outcomes, and are especially important for HIV-infected women. By disaggregating data on access to ANC, we aimed to identify variation in ANC attendance by level of care and across vulnerable groups in inner-city Johannesburg, and document the impact of non-attendance on birth outcomes. METHODS: This record review of routine health service data involved manual extraction of 2 years of data from birth registers at a primary-, secondary- and tertiary-level facility within inner-city Johannesburg. Information was gathered on ANC attendance, HIV testing and status, pregnancy duration, delivery mode and birth outcomes. Women with an unknown attendance status were considered as not having attended clinic, but effects of this assumption were tested in sensitivity analyses. Multiple logistic regression was used to identify associations between ANC attendance and birth outcomes. RESULTS: Of 31,179 women who delivered, 88.7% (27,651) had attended ANC (95% CI = 88.3-89.0). Attendance was only 77% at primary care (5813/7543), compared to 89% at secondary (3661/4113) and 93% at tertiary level (18,177/19,523). Adolescents had lower ANC attendance than adults (85%, 1951/2295 versus 89%, 22,039/24,771). Only 37% of women not attending ANC had an HIV test (1308/3528), compared with 93% of ANC attenders (25,756/27,651). Caesarean section rates were considerably higher in women who had attended ANC (40%, 10,866/27,344) than non-attenders (13%, 422/3360). Compared to those who had attended ANC, non-attenders were 1.6 fold more likely to have a preterm delivery (95% CI adjusted odds ratio [aOR] = 1.4-1.8) and 1.4 fold more likely to have a stillbirth (aOR 95% CI = 1.1-1.9). Similar results were seen in analyses where missing data on ANC attendance was classified in different ways. CONCLUSION: Inner-city Johannesburg has an almost 5% lower ANC attendance rate than national levels. Attendance is particularly concerning in the primary care clinic that serves a predominantly migrant population. Adolescents had especially low rates, perhaps owing to stigma when seeking care. Interventions to raise ANC attendance, especially among adolescents, may help improve birth outcomes and HIV testing rates, bringing the country closer to achieving maternal and child health targets and eliminating HIV in children.

Alcohol use and sexual risk behaviour among men and women in inner-city Johannesburg, South Africa.

BACKGROUND: Alcohol misuse is a key factor underlying the remarkable vulnerability to HIV infection among men and women in sub-Saharan Africa, especially within urban settings. Its effects, however, vary by type of drinking, population group and are modified by socio-cultural co-factors. METHODS: We interviewed a random sample of 1465 men living in single-sex hostels and 1008 women in adjacent informal settlements in inner-city, Johannesburg, South Africa. Being drunk in the past week was used as an indicator of heavy episodic drinking, and frequency of drinking and number of alcohol units/week used as measures of volume. Associations between dimensions of alcohol use (current drinking, volume of alcohol consumed and heavy episodic drinking patterns) and sexual behaviours were assessed using multivariate logistic regression. RESULTS: Most participants were internal migrants from KwaZulu Natal province. About half of men were current drinkers, as were 13% of women. Of current male drinkers, 18% drank daily and 23% were drunk in the past week (women: 14% and 29% respectively). Among men, associations between heavy episodic drinking and sexual behaviour were especially pronounced. Compared with non-drinkers, episodic ones were 2.6 fold more likely to have transactional sex (95%CI = 1.7-4.1) and 2.2 fold more likely to have a concurrent partner (95%CI = 1.5-3.2). Alcohol use in men, regardless of measure, was strongly associated with having used physical force to have sex. Overall effects of alcohol on sexual behaviour were larger in women than men, and associations were detected between all alcohol measures in women, and concurrency, transactional sex and having been forced to have sex. CONCLUSIONS: Alcohol use and sexual behaviours are strongly linked among male and female migrant populations in inner-city Johannesburg. More rigorous interventions at both local and macro level are needed to alleviate alcohol harms and mitigate the alcohol-HIV nexus, especially among already vulnerable groups. These should target the specific dimensions of alcohol use that are harmful, assist women who drink to do so more safely and address the linkages between alcohol and sexual violence.

Is laboratory screening prior to antiretroviral treatment useful in Johannesburg, South Africa? Baseline findings of a clinical trial.

BACKGROUND: Screening for renal, hepatic and haematological disorders complicates the initiation of current first-line antiretroviral therapy (ART). Each additional test done adds substantial costs, both through direct laboratory expenses, but also by increasing the burden on health workers and patients. Evaluating the prevalence of clinically relevant abnormalities in different population groups could guide decisions about what tests to recommend in national guidelines, or in local adaptations of these. METHODS: As part of enrolment procedures in a clinical trial, 771 HIV-positive adults, predominantly from inner-city primary health care clinics, underwent laboratory screening prior to ART. Participants had to be eligible for ART, based on the then CD4 eligibility threshold of 350 cells/µL, antiretroviral naïve and have no symptoms of peripheral neuropathy. RESULTS: Participants were mostly female (57%) and a mean 34 years old. Creatinine clearance rates were almost all above 50 mL/min (99%), although 5% had microalbuminuria. Hepatitis B antigenaemia was common (8% of participants), of whom 40% had a raised AST/ALT, though only 2 had transaminase levels above 200 IU/L. Only 2% of participants had severe anaemia (haemoglobin <8 g/dl) and 1% neutropaenia (neutrophils <0.75 × 10^9/L). Costs per case detected of hepatitis B infection was USD135, but more than USD800 for a raised creatinine. CONCLUSIONS: Hepatitis B continues to be a common co-infection in HIV-infected adults, and adds complexity to management of ART switches involving tenofovir. Routine renal and haematological screening prior to ART detected few abnormalities. The use of these screening tests should be assessed among patients with higher CD4 counts, who may even have fewer abnormalities. Formal evaluation of cost-effectiveness of laboratory screening prior to ART is warranted.

'Leaving no one behind': reflections on the design of community-based HIV prevention for migrants in Johannesburg's inner-city hostels and informal settlements.

BACKGROUND: Unmanaged urban growth in southern and eastern Africa has led to a growth of informal housing in cities, which are home to poor, marginalised populations, and associated with the highest HIV prevalence in urban areas. This article describes and reflects on the authors' experiences in designing and implementing an HIV intervention originally intended for migrant men living in single-sex hostels of inner-city Johannesburg. It shows how formative research findings were incorporated into project design, substantially shifting the scope of the original project. METHODS: Formative research activities were undertaken to better understand the demand- and supply-side barriers to delivering HIV prevention activities within this community. These included community mapping, a baseline survey (n = 1458) and client-simulation exercise in local public sector clinics. The intervention was designed and implemented in the study setting over a period of 18 months. Implementation was assessed by way of a process evaluation of selected project components. RESULTS: The project scope expanded to include women living in adjacent informal settlements. Concurrent sexual partnerships between these women and male hostel residents were common, and HIV prevalence was higher among women (56%) than men (24%). Overwhelmingly, hostel residents were internal migrants from another province, and most felt 'alienated' from the rest of the city. While men prioritised the need for jobs, women were more concerned about water, sanitation, housing and poverty alleviation. Most women (70%) regarded their community as unsafe (cf. 47% of men). In the final intervention, project objectives were modified and HIV prevention activities were embedded within a broader health and development focus. 'Community health clubs' were established to build residents' capacity to promote health and longer term well-being, and to initiate and sustain change within their communities. CONCLUSIONS: To improve efforts to address HIV in urban informal settings, intervention designers must acknowledge and engage with the priorities set by the marginalised communities that live here, which may well encompass more pressing issues associated with daily survival.

Using surrogate vaccines to assess feasibility and acceptability of future HIV vaccine trials in men: a randomised trial in inner-city Johannesburg, South Africa.

BACKGROUND: Developing an effective HIV vaccine is the overriding priority for HIV prevention research. Enrolling and maintaining cohorts of men into HIV vaccine efficacy trials is a necessary prerequisite for the development and licensure of a safe and efficacious vaccine. METHODS: One hundred-fifty consenting HIV-negative men were enrolled into a pilot 1:1 randomised controlled trial of immediate vaccination with a three-dose hepatitis B vaccine compared to deferred vaccination (at 12 months) to investigate feasibility and acceptability of a future HIV vaccine trial in this population. Adverse events, changes in risk behaviour, acceptability of trial procedures and motivations for participation in future trials were assessed. RESULTS: Men were a median 25 years old (inter-quartile range = 23-29), 53% were employed, 90% secondary school educated and 67% uncircumcised. Of the 900 scheduled study visits, 90% were completed in the immediate vaccination arm (405/450) and 88% (396/450) in the delayed arm (P = 0.338). Acceptability of trial procedures and services was very high overall. However, only 65% of the deferred group strongly liked being randomised compared to 90% in the immediate group (P = 0.001). Informed consent processes were viewed favourably by 92% of the delayed and 82% of the immediate group (P = 0.080). Good quality health services, especially if provided by a male nurse, were rated highly. Even though almost all participants had some concern about the safety of a future HIV vaccine (98%), the majority were willing to participate in a future trial. Future trial participation would be motivated mainly by the potential for accessing an effective vaccine (81%) and altruism (75%), rather than by reimbursement incentives (2%). CONCLUSIONS: Recruitment and retention of men into vaccine trials is feasible and acceptable in our setting. Findings from this surrogate vaccine trial show a high willingness to participate in future HIV vaccine trials. While access to potentially effective vaccines is important, quality health services are an equally compelling incentive for enrolment.

Intersections between polyvictimisation and mental health among adolescents in five urban disadvantaged settings: the role of gender.

BACKGROUND: Polyvictimisation (PV) - exposure to violence across multiple contexts - causes considerable morbidity and mortality among adolescents. Despite high levels of violence in urban disadvantaged settings, gender differences in associations between PV and mental health have not been well established. METHODS: We analysed data from a survey with 2393 adolescents aged 15-19 years, recruited using respondent-driven sampling from urban disadvantaged settings in Baltimore (USA), Delhi (India), Ibadan (Nigeria), Johannesburg (South Africa) and Shanghai (China). PV was defined as exposure to two or more types of violence in the past 12 months with family, peers, in the community, or from intimate partners and non-partner sexual violence. Weighted logistic regression models are presented by gender to evaluate whether PV is associated with posttraumatic stress, depression, suicidal thoughts and perceived health status. RESULTS: PV was extremely common overall, but ranged widely, from 74.5% of boys and 82.0% of girls in Johannesburg, to 25.8 and 23.9% respectively in Shanghai. Community violence was the predominant violence type, affecting 72.8-93.7% across the sites. More than half of girls (53.7%) and 45.9% of boys had at least one adverse mental health outcome. Compared to those that did not report violence, boys exposed to PV had 11.4 higher odds of having a negative perception of health (95%CI adjusted OR = 2.45-53.2), whilst this figure was 2.58 times in girls (95%CI = 1.62-4.12). Among girls, PV was associated with suicidal thoughts (adjusted OR = 4.68; 95%CI = 2.29-9.54), posttraumatic stress (aOR = 4.53; 95%CI = 2.44-8.41) and depression (aOR = 2.65; 95%CI = 1.25-5.63). Among boys, an association was only detected between PV and depression (aOR = 1.82; 95%CI = 1.00-3.33). CONCLUSION: The findings demonstrate that PV is common among both sexes in urban disadvantaged settings across the world, and that it is associated with poor mental health outcomes in girls, and with poor health status in both girls and boys. Clearly, prevention interventions are failing to address violence exposure across multiple contexts, but especially within community settings and in Johannesburg. Interventions are needed to identify adolescents exposed to PV and link them to care, with services targeting a range of mental health conditions among girls and perhaps focusing on depression among boys.

Prevalence of anogenital HPV infection, related disease and risk factors among HIV-infected men in inner-city Johannesburg, South Africa: baseline findings from a cohort study.

BACKGROUND: Persistent high-risk human papillomavirus (HR-HPV) infection is associated with the development of anogenital cancers, particularly in men living with HIV (MLWH). We describe the prevalence of anogenital HPV infection, abnormal anal cytology and anogenital warts (AGWs) in MLWH in Johannesburg, and explore whether HPV infection and receipt of antiretroviral treatment is associated with detection of abnormal anal cytology and AGWs. METHODS: We enrolled a cohort of 304 sexually-active MLWH ≥18 years, who completed a questionnaire and physical examination. Genital swabs were collected from all men and intra-anal swabs from 250 (82%). Swabs were tested for HPV DNA and genotypes, and anal smears graded using the Bethesda classification. Factors associated with anogenital disease were assessed by logistic regression models. RESULTS: Two thirds were receiving antiretroviral treatment, for a median 33 months (IQR = 15-58) and 54% were HIV-virologically suppressed. Only 5% reported ever having sex with men. Among 283 genital swabs with valid results, 79% had any HPV, 52% had HR-HPV and 27% had >1 HR-HPV infection. By comparison, 39% of the 227 valid intra-anal swabs had detectable HPV, 25% had any HR-HPV and 7% >1 HR infection. While most anal smears were normal (51%), 20% had ASCUS and 29% were LSIL. No cases had HSIL or cancer. Infection with >1 HR type (adjusted OR [aOR] = 2.39; 95%CI = 1.02-5.58) and alpha-9 types (aOR = 3.98; 95%CI = 1.42-11.16) were associated with having abnormal cytology. Prevalence of AGWs was 12%. Infection with any LR type (aOR = 41.28; 95%CI = 13.57-125.62), >1 LR type (aOR = 4.14; 95%CI = 1.60-10.69), being <6 months on antiretroviral treatment (aOR = 6.90; 95%CI = 1.63-29.20) and having a CD4+ count <200 cells/µL (aOR = 5.48; 95%CI: 1.60-18.78) were associated with having AGWs. CONCLUSIONS: In this population, anogenital HR-HPV infection and associated low-grade disease is common, but severe anal dysplasia was not detected. Findings reinforce the need for HPV vaccination in men for preventing both AGWs and HR-HPV infection. Given the absence of anal HSILs, however, the findings do not support the use of anal screening programmes in this population.

Local and foreign authorship of maternal health interventional research in low- and middle-income countries: systematic mapping of publications 2000-2012.

BACKGROUND: Researchers in low- and middle-income countries (LMICs) are under-represented in scientific literature. Mapping of authorship of articles can provide an assessment of data ownership and research capacity in LMICs over time and identify variations between different settings. METHODS: Systematic mapping of maternal health interventional research in LMICs from 2000 to 2012, comparing country of study and of affiliation of first authors. Studies on health systems or promotion; community-based activities; and haemorrhage, hypertension, HIV/STIs and malaria were included. Following review of 35,078 titles and abstracts, 2292 full-text publications were included. Data ownership was measured by the proportion of articles with an LMIC lead author (author affiliated with an LMIC institution). RESULTS: The total number of papers led by an LMIC author rose from 45.0/year in 2000-2003 to 98.0/year in 2004-2007, but increased only slightly thereafter to 113.1/year in 2008-2012. In the same periods, the proportion of papers led by a local author was 58.4 %, 60.8 % and 60.1 %, respectively. Data ownership varies markedly between countries. A quarter of countries led more than 75 % of their research; while in 10 countries, under 25 % of publications had a local first author. Researchers at LMIC institutions led 56.6 % (1297) of all papers, but only 26.8 % of systematic reviews (65/243), 29.9 % of modelling studies (44/147), and 33.2 % of articles in journals with an Impact Factor ≥5 (61/184). Sub-Saharan Africa authors led 54.2 % (538/993) of studies in the region, while 73.4 % did in Latin America and the Caribbean (223/304). Authors affiliated with United States (561) and United Kingdom (207) institutions together account for a third of publications. Around two thirds of USAID and European Union funded studies had high-income country leads, twice as many as that of Wellcome Trust and Rockefeller Foundation. CONCLUSIONS: There are marked gaps in data ownership and these have not diminished over time. Increased locally-led publications, however, does suggest a growing capacity in LMIC institutions to analyse and articulate research findings. Differences in author attribution between funders might signal important variations in funders' expectations of authorship and discrepancies in how funders understand collaboration. More stringent authorship oversight and reconsideration of authorship guidelines could facilitate growth in LMIC leadership. Left unaddressed, deficiencies in research ownership will continue to hinder alignment between the research undertaken and knowledge needs of LMICs.