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?

Too hot to thrive: a qualitative inquiry of community perspectives on the effect of high ambient temperature on postpartum women and neonates in Kilifi, Kenya.

OBJECTIVE: To understand community perspectives on the effects of high ambient temperature on the health and wellbeing of neonates, and impacts on post-partum women and infant care in Kilifi. DESIGN: Qualitative study using key informant interviews, in-depth interviews and focus group discussions with pregnant and postpartum women (n = 22), mothers-in-law (n = 19), male spouses (n = 20), community health volunteers (CHVs) (n = 22) and stakeholders from health and government ministries (n = 16). SETTINGS: We conducted our research in Kilifi County in Kenya's Coast Province. The area is largely rural and during summer, air temperatures can reach 37˚C and rarely go below 23˚C. DATA ANALYSIS: Data were analyzed in NVivo 12, using both inductive and deductive approaches. RESULTS: High ambient temperature is perceived by community members to have direct and indirect health pathways in pregnancy and postpartum periods, including on the neonates. The direct impacts include injuries on the neonate's skin and in the mouth, leading to discomfort and affecting breastfeeding and sleeping. Participants described babies as "having no peace". Heat effects were perceived to be amplified by indoor air pollution and heat from indoor cooking fires. Community members believed that exclusive breastfeeding was not practical in conditions of extreme heat because it lowered breast milk production, which was, in turn, linked to a low scarcity of food and time spend by mothers away from their neonates performing household chores. Kangaroo Mother Care (KMC) was also negatively affected. Participants reported that postpartum women took longer to heal in the heat, were exhausted most of the time and tended not to attend postnatal care. CONCLUSIONS: High ambient temperatures affect postpartum women and their neonates through direct and indirect pathways. Discomfort makes it difficult for the mother to care for the baby. Multi-sectoral policies and programs are required to mitigate the negative impacts of high ambient temperatures on maternal and neonatal health in rural Kilifi and similar settings.

Dolutegravir plus Two Different Prodrugs of Tenofovir to Treat HIV.

BACKGROUND: Two drugs under consideration for inclusion in antiretroviral therapy (ART) regimens for human immunodeficiency virus (HIV) infection are dolutegravir (DTG) and tenofovir alafenamide fumarate (TAF). There are limited data on their use in low- and middle-income countries. METHODS: We conducted a 96-week, phase 3, investigator-led, open-label, randomized trial in South Africa, in which we compared a triple-therapy combination of emtricitabine (FTC) and DTG plus either of two tenofovir prodrugs - TAF (TAF-based group) or tenofovir disoproxil fumarate (TDF) (TDF-based group) - against the local standard-of-care regimen of TDF-FTC-efavirenz (standard-care group). Inclusion criteria included an age of 12 years or older, no receipt of ART in the previous 6 months, a creatinine clearance of more than 60 ml per minute (>80 ml per minute in patients younger than 19 years of age), and an HIV type 1 (HIV-1) RNA level of 500 copies or more per milliliter. The primary end point was the percentage of patients with a 48-week HIV-1 RNA level of less than 50 copies per milliliter (as determined with the Snapshot algorithm from the Food and Drug Administration; noninferiority margin, -10 percentage points). We report the primary (48-week) efficacy and safety data. RESULTS: A total of 1053 patients underwent randomization from February 2017 through May 2018. More than 99% of the patients were black, and 59% were female. The mean age was 32 years, and the mean CD4 count was 337 cells per cubic millimeter. At week 48, the percentage of patients with an HIV-1 RNA level of less than 50 copies per milliliter was 84% in the TAF-based group, 85% in the TDF-based group, and 79% in the standard-care group, findings that indicate that the DTG-containing regimens were noninferior to the standard-care regimen. The number of patients who discontinued the trial regimen was higher in the standard-care group than in the other two groups. In the per-protocol population, the standard-care regimen had equivalent potency to the other two regimens. The TAF-based regimen had less effect on bone density and renal function than the other regimens. Weight increase (both lean and fat mass) was greatest in the TAF-based group and among female patients (mean increase, 6.4 kg in the TAF-based group, 3.2 kg in the TDF-based group, and 1.7 kg in the standard-care group). No resistance to integrase inhibitors was identified in patients receiving the DTG-containing regimens. CONCLUSIONS: Treatment with DTG combined with either of two tenofovir prodrugs (TAF and TDF) showed noninferior efficacy to treatment with the standard-care regimen. There was significantly more weight gain with the DTG-containing regimens, especially in combination with TAF, than with the standard-care regimen. (ADVANCE ClinicalTrials.gov number, NCT03122262.).

Ambient temperature during pregnancy and risk of maternal hypertensive disorders: A time-to-event study in Johannesburg, South Africa.

Hypertensive disorders in pregnancy are a leading cause of maternal and perinatal mortality and morbidity. We evaluate the effects of ambient temperature on risk of maternal hypertensive disorders throughout pregnancy. We used birth register data for all singleton births (22-43 weeks' gestation) recorded at a tertiary-level hospital in Johannesburg, South Africa, between July 2017-June 2018. Time-to-event analysis was combined with distributed lag non-linear models to examine the effects of mean weekly temperature, from conception to birth, on risk of (i) high blood pressure, hypertension, or gestational hypertension, and (ii) pre-eclampsia, eclampsia, or HELLP (hemolysis, elevated liver enzymes, low platelets). Low and high temperatures were defined as the 5th and 95th percentiles of daily mean temperature, respectively. Of 7986 women included, 844 (10.6%) had a hypertensive disorder of which 432 (51.2%) had high blood pressure/hypertension/gestational hypertension and 412 (48.8%) had pre-eclampsia/eclampsia/HELLP. High temperature in early pregnancy was associated with an increased risk of pre-eclampsia/eclampsia/HELLP. High temperature (23 °C vs 18 °C) in the third and fourth weeks of pregnancy posed the greatest risk, with hazard ratios of 1.76 (95% CI 1.12-2.78) and 1.79 (95% CI 1.19-2.71), respectively. Whereas, high temperatures in mid-late pregnancy tended to protect against pre-eclampsia/eclampsia/HELLP. Low temperature (11°) during the third trimester (from 29 weeks' gestation) was associated with an increased risk of high blood pressure/hypertension/gestational hypertension, however the strength and statistical significance of low temperature effects were reduced with model adjustments. Our findings support the hypothesis that high temperatures in early pregnancy increase risk of severe hypertensive disorders, likely through an effect on placental development. This highlights the need for greater awareness around the impacts of moderately high temperatures in early pregnancy through targeted advice, and for increased monitoring of pregnant women who conceive during periods of hot weather.

Associations between ambient temperature and risk of preterm birth in Sweden: A comparison of analytical approaches.

BACKGROUND: Evidence indicates that high temperatures are a risk factor for preterm birth. Increasing heat exposures due to climate change are therefore a concern for pregnant women. However, the large heterogeneity of study designs and statistical methods across previous studies complicate interpretation and comparisons. We investigated associations of short-term exposure to high ambient temperature with preterm birth in Sweden, applying three complementary analytical approaches. METHODS: We included 560,615 singleton live births between 2014 and 2019, identified in the Swedish Pregnancy Register. We estimated weekly mean temperatures at 1-km2 spatial resolution using a spatiotemporal machine learning methodology, and assigned them at the residential addresses of the study participants. The main outcomes of the study were gestational age in weeks and subcategories of preterm birth (<37 weeks): extremely preterm birth (<28 weeks), very preterm birth (from week 28 to <32), and moderately preterm birth (from week 32 to<37). Case-crossover, quantile regression and time-to-event analyses were applied to estimate the effects of short-term exposure to increased ambient temperature during the week before birth on preterm births. Furthermore, distributed lag nonlinear models (DLNM) were applied to identify susceptibility windows of exposures throughout pregnancy in relation to preterm birth. RESULTS: A total of 1924 births were extremely preterm (0.4%), 2636 very preterm (0.5%), and 23,664 moderately preterm (4.2%). Consistent across all three analytical approaches (case-crossover, quantile regression and time-to-event analyses), higher ambient temperature (95th vs 50th percentile) demonstrated increased risk of extremely preterm birth, but associations did not reach statistical significance. In DLNM models, we observed no evidence to suggest an increased effect of high temperature on preterm birth risk. Even so, a suggested trend was observed in both the quantile regression and time-to-event analyses of a higher risk of extremely preterm birth with higher temperature during the last week before birth. CONCLUSIONS: In Sweden, with high quality data on exposure and outcome, a temperate climate and good quality ante-natal health care, we did not find an association between high ambient temperatures and preterm births. Results were consistent across three complementary analytical approaches.

Physiological mechanisms of the impact of heat during pregnancy and the clinical implications: review of the evidence from an expert group meeting.

Many populations experience high seasonal temperatures. Pregnant women are considered vulnerable to extreme heat because ambient heat exposure has been linked to pregnancy complications including preterm birth and low birthweight. The physiological mechanisms that underpin these associations are poorly understood. We reviewed the existing research evidence to clarify the mechanisms that lead to adverse pregnancy outcomes in order to inform public health actions. A multi-disciplinary expert group met to review the existing evidence base and formulate a consensus regarding the physiological mechanisms that mediate the effect of high ambient temperature on pregnancy. A literature search was conducted in advance of the meeting to identify existing hypotheses and develop a series of questions and themes for discussion. Numerous hypotheses have been generated based on animal models and limited observational studies. There is growing evidence that pregnant women are able to appropriately thermoregulate; however, when exposed to extreme heat, there are a number of processes that may occur which could harm the mother or fetus including a reduction in placental blood flow, dehydration, and an inflammatory response that may trigger preterm birth. There is a lack of substantial evidence regarding the processes that cause heat exposure to harm pregnant women. Research is urgently needed to identify what causes the adverse outcomes in pregnancy related to high ambient temperatures so that the impact of climate change on pregnant women can be mitigated.

Maternal and newborn health risks of climate change: A call for awareness and global action.

Climate change represents one of the largest global health threats of the 21st century with immediate and long-term consequences for the most vulnerable populations, especially in the poorest countries with the least capacity to adapt to climate change. Pregnant women and newborns are increasingly being recognized as vulnerable populations in the context of climate change. The effects can be direct or indirect through heat stress, extreme weather events and air pollution, potentially impacting both the immediate and long-term health of pregnant women and newborns through a broad range of mechanisms. In 2008, the World Health Organization passed a resolution during the 61st World Health Assembly, recognizing the need for research to identify strategies and health-system strengthening to mitigate the effects of climate change on health. Climate adaptation plans need to consider vulnerable populations such as pregnant women and neonates and a broad multisectoral approach to improve overall resilience of societies.

One Health, "Disease X" & the challenge of "Unknown" Unknowns.

The emergence of SARS-CoV-2 and its rapid spread globally emphasizes the ever-present threat of emerging and re-emerging infectious diseases. In this review, the pathogen pyramid framework was utilized to identify the "unknown unknowns" associated with the emergence and rapid transmission of novel infectious disease agents. Given that the evolutionary origin of most of the emerging infectious disease agents can be traced to an animal source, we argue the need to integrate the "One Health" approach as a part of surveillance activities. The need for focusing on undertaking global and regional mapping activities to identify novel pathogens is discussed, given that there are an estimated 1.67 million unknown viruses, of which around 631,000 to 827,000 unknown viruses have the capacity to infect human beings. The emerging risks due to the ever-expanding interface between human, animals, both domestic and wildlife, and the environment are highlighted, these are largely driven by the need for safe habitation, growing food, developing infrastructure to support the increasing human population and desire for economic growth. The One Health approach provides a holistic way to address these cross-sectoral issues, by bridging institutional gaps, enumerating priority risk areas and pathogens, and highlighting putative risk factors for subsequent spillover events involving emerging and re-emerging infectious disease pathogens at the human-animal-environment interface.

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.

Integrating Cervical Cancer Screening Into Safer Conception Services to Improve Women's Health Outcomes: A Pilot Study at a Primary Care Clinic in South Africa.

BACKGROUND: Sub-optimal cervical cancer screening in low- and middle-income countries contributes to preventable cervical cancer deaths, particularly among human immunodeficiency virus (HIV)-positive women. We assessed feasibility and outcomes of integrating cervical cancer screening into safer conception services for HIV-affected women. METHODS: At a safer conception service in Johannesburg, South Africa, HIV-affected women desiring pregnancy received a standard package of care designed to minimize HIV transmission risks while optimizing prepregnancy health. All eligible women were offered Papanicolaou smear, and those with significant pathology were referred for colposcopy before attempting pregnancy. Multivariable analyses identified associations between patient characteristics and abnormal pathology. RESULTS: In total, 454 women were enrolled between June 2015 and April 2017. At enrolment, 91% were HIV-positive, 92% were on antiretroviral therapy (ART) and 82% virally suppressed. Eighty-three percent (376 of 454) of clients were eligible for cervical cancer screening and 85% (321 of 376) of these completed screening. More than half had abnormal cervical pathology (185 of 321) and 20% required colposcopy for possible high-grade or persistently atypical lesions (64 of 321). Compared with HIV-negative women, abnormal pathology was more likely among HIV-positive women, both those on ART <2 years (adjusted prevalence ratio, 2.5; 95% confidence interval, 1.2-5.0) and those on ART 2 years or longer (adjusted prevalence ratio, 2.1; 95% confidence interval, 1.0-4.2). CONCLUSIONS: Integrating cervical cancer screening into safer conception care was feasible with high coverage, including for HIV-positive women. Significant pathology, requiring colposcopy, was common, even among healthy women on ART. Safer conception services present an opportunity for integration of cervical cancer screening to avert preventable cancer-related deaths among HIV-affected women planning pregnancy.

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.

Effect of a 'diagonal' intervention on uptake of HIV and reproductive health services by female sex workers in three sub-Saharan African cities.

OBJECTIVES: To enhance uptake of sexual and reproductive health (SRH) services by female sex workers (FSWs), we conducted an implementation study in which we piloted and tested context-specific 'diagonal' interventions, combining vertical, targeted interventions with horizontally improved access to the general health services, in three cities in sub-Saharan Africa. METHODS: We collected indicators of SRH service uptake through face-to-face interviews with approximately 400 FSWs, pre- and post-intervention, in Durban, South Africa; Tete, Mozambique; and Mombasa, Kenya, recruited by respondent-driven sampling. Changes in uptake were tested for their statistical significance using multivariate logistic regression models. RESULTS: In all cities, overall uptake of services increased. Having used all services for contraception, STI care, HIV testing, HIV care, cervical cancer screening and sexual violence, if needed, increased from 12.5% to 41.5% in Durban, 25.0% to 40.1% in Tete and 44.9% to 69.1% in Mombasa. Across cities, the effect was greatest in having been tested for HIV in the past six months which increased from 40.9% to 83.2% in Durban, 56.0% to 76.6% in Tete and 70.9% to 87.6% in Mombasa. In Tete and Mombasa, rise in SRH service use was almost entirely due to a greater uptake of targeted services. Only in Durban was there additionally an increase in the utilisation of general health services. CONCLUSION: SRH service utilisation improved in the short-term in three different sub-Saharan African contexts, primarily through vertical, targeted components. The long-term effectiveness of diagonal approaches, in particular on the use of general, horizontal health services, needs further investigation.

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.