Safety evaluation of the single-dose Ad26.COV2.S vaccine among healthcare workers in the Sisonke study in South Africa: A phase 3b implementation trial.

BACKGROUND: Real-world evaluation of the safety profile of vaccines after licensure is crucial to accurately characterise safety beyond clinical trials, support continued use, and thereby improve public confidence. The Sisonke study aimed to assess the safety and effectiveness of the Janssen Ad26.COV2.S vaccine among healthcare workers (HCWs) in South Africa. Here, we present the safety data. METHODS AND FINDINGS: In this open-label phase 3b implementation study among all eligible HCWs in South Africa registered in the national Electronic Vaccination Data System (EVDS), we monitored adverse events (AEs) at vaccination sites through self-reporting triggered by text messages after vaccination, healthcare provider reports, and active case finding. The frequency and incidence rate of non-serious and serious AEs were evaluated from the day of first vaccination (17 February 2021) until 28 days after the final vaccination in the study (15 June 2021). COVID-19 breakthrough infections, hospitalisations, and deaths were ascertained via linkage of the electronic vaccination register with existing national databases. Among 477,234 participants, 10,279 AEs were reported, of which 138 (1.3%) were serious AEs (SAEs) or AEs of special interest. Women reported more AEs than men (2.3% versus 1.6%). AE reports decreased with increasing age (3.2% for age 18-30 years, 2.1% for age 31-45 years, 1.8% for age 46-55 years, and 1.5% for age > 55 years). Participants with previous COVID-19 infection reported slightly more AEs (2.6% versus 2.1%). The most common reactogenicity events were headache (n = 4,923) and body aches (n = 4,483), followed by injection site pain (n = 2,767) and fever (n = 2,731), and most occurred within 48 hours of vaccination. Two cases of thrombosis with thrombocytopenia syndrome and 4 cases of Guillain-Barré Syndrome were reported post-vaccination. Most SAEs and AEs of special interest (n = 138) occurred at lower than the expected population rates. Vascular (n = 37; 39.1/100,000 person-years) and nervous system disorders (n = 31; 31.7/100,000 person-years), immune system disorders (n = 24; 24.3/100,000 person-years), and infections and infestations (n = 19; 20.1/100,000 person-years) were the most common reported SAE categories. A limitation of the study was the single-arm design, with limited routinely collected morbidity comparator data in the study setting. CONCLUSIONS: We observed similar patterns of AEs as in phase 3 trials. AEs were mostly expected reactogenicity signs and symptoms. Furthermore, most SAEs occurred below expected rates. The single-dose Ad26.COV2.S vaccine demonstrated an acceptable safety profile, supporting the continued use of this vaccine in this setting. TRIAL REGISTRATION: ClinicalTrials.gov NCT04838795; Pan African Clinical Trials Registry PACTR202102855526180.

Estimating the impact of antiretroviral treatment on adult mortality trends in South Africa: A mathematical modelling study.

BACKGROUND: Substantial reductions in adult mortality have been observed in South Africa since the mid-2000s, but there has been no formal evaluation of how much of this decline is attributable to the scale-up of antiretroviral treatment (ART), as previous models have not been calibrated to vital registration data. We developed a deterministic mathematical model to simulate the mortality trends that would have been expected in the absence of ART, and with earlier introduction of ART. METHODS AND FINDINGS: Model estimates of mortality rates in ART patients were obtained from the International Epidemiology Databases to Evaluate AIDS-Southern Africa (IeDEA-SA) collaboration. The model was calibrated to HIV prevalence data (1997-2013) and mortality data from the South African vital registration system (1997-2014), using a Bayesian approach. In the 1985-2014 period, 2.70 million adult HIV-related deaths occurred in South Africa. Adult HIV deaths peaked at 231,000 per annum in 2006 and declined to 95,000 in 2014, a reduction of 74.7% (95% CI: 73.3%-76.1%) compared to the scenario without ART. However, HIV mortality in 2014 was estimated to be 69% (95% CI: 46%-97%) higher in 2014 (161,000) if the model was calibrated only to HIV prevalence data. In the 2000-2014 period, the South African ART programme is estimated to have reduced the cumulative number of HIV deaths in adults by 1.72 million (95% CI: 1.58 million-1.84 million) and to have saved 6.15 million life years in adults (95% CI: 5.52 million-6.69 million). This compares with a potential saving of 8.80 million (95% CI: 7.90 million-9.59 million) life years that might have been achieved if South Africa had moved swiftly to implement WHO guidelines (2004-2013) and had achieved high levels of ART uptake in HIV-diagnosed individuals from 2004 onwards. The model is limited by its reliance on all-cause mortality data, given the lack of reliable cause-of-death reporting, and also does not allow for changes over time in tuberculosis control programmes and ART effectiveness. CONCLUSIONS: ART has had a dramatic impact on adult mortality in South Africa, but delays in the rollout of ART, especially in the early stages of the ART programme, have contributed to substantial loss of life. This is the first study to our knowledge to calibrate a model of ART impact to population-level recorded death data in Africa; models that are not calibrated to population-level death data may overestimate HIV-related mortality.

Global, regional, and national levels of neonatal, infant, and under-5 mortality during 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013.

BACKGROUND: Remarkable financial and political efforts have been focused on the reduction of child mortality during the past few decades. Timely measurements of levels and trends in under-5 mortality are important to assess progress towards the Millennium Development Goal 4 (MDG 4) target of reduction of child mortality by two thirds from 1990 to 2015, and to identify models of success. METHODS: We generated updated estimates of child mortality in early neonatal (age 0-6 days), late neonatal (7-28 days), postneonatal (29-364 days), childhood (1-4 years), and under-5 (0-4 years) age groups for 188 countries from 1970 to 2013, with more than 29,000 survey, census, vital registration, and sample registration datapoints. We used Gaussian process regression with adjustments for bias and non-sampling error to synthesise the data for under-5 mortality for each country, and a separate model to estimate mortality for more detailed age groups. We used explanatory mixed effects regression models to assess the association between under-5 mortality and income per person, maternal education, HIV child death rates, secular shifts, and other factors. To quantify the contribution of these different factors and birth numbers to the change in numbers of deaths in under-5 age groups from 1990 to 2013, we used Shapley decomposition. We used estimated rates of change between 2000 and 2013 to construct under-5 mortality rate scenarios out to 2030. FINDINGS: We estimated that 6·3 million (95% UI 6·0-6·6) children under-5 died in 2013, a 64% reduction from 17·6 million (17·1-18·1) in 1970. In 2013, child mortality rates ranged from 152·5 per 1000 livebirths (130·6-177·4) in Guinea-Bissau to 2·3 (1·8-2·9) per 1000 in Singapore. The annualised rates of change from 1990 to 2013 ranged from -6·8% to 0·1%. 99 of 188 countries, including 43 of 48 countries in sub-Saharan Africa, had faster decreases in child mortality during 2000-13 than during 1990-2000. In 2013, neonatal deaths accounted for 41·6% of under-5 deaths compared with 37·4% in 1990. Compared with 1990, in 2013, rising numbers of births, especially in sub-Saharan Africa, led to 1·4 million more child deaths, and rising income per person and maternal education led to 0·9 million and 2·2 million fewer deaths, respectively. Changes in secular trends led to 4·2 million fewer deaths. Unexplained factors accounted for only -1% of the change in child deaths. In 30 developing countries, decreases since 2000 have been faster than predicted attributable to income, education, and secular shift alone. INTERPRETATION: Only 27 developing countries are expected to achieve MDG 4. Decreases since 2000 in under-5 mortality rates are accelerating in many developing countries, especially in sub-Saharan Africa. The Millennium Declaration and increased development assistance for health might have been a factor in faster decreases in some developing countries. Without further accelerated progress, many countries in west and central Africa will still have high levels of under-5 mortality in 2030. FUNDING: Bill & Melinda Gates Foundation, US Agency for International Development.

Life expectancies of South African adults starting antiretroviral treatment: collaborative analysis of cohort studies.

BACKGROUND: Few estimates exist of the life expectancy of HIV-positive adults receiving antiretroviral treatment (ART) in low- and middle-income countries. We aimed to estimate the life expectancy of patients starting ART in South Africa and compare it with that of HIV-negative adults. METHODS AND FINDINGS: Data were collected from six South African ART cohorts. Analysis was restricted to 37,740 HIV-positive adults starting ART for the first time. Estimates of mortality were obtained by linking patient records to the national population register. Relative survival models were used to estimate the excess mortality attributable to HIV by age, for different baseline CD4 categories and different durations. Non-HIV mortality was estimated using a South African demographic model. The average life expectancy of men starting ART varied between 27.6 y (95% CI: 25.2-30.2) at age 20 y and 10.1 y (95% CI: 9.3-10.8) at age 60 y, while estimates for women at the same ages were substantially higher, at 36.8 y (95% CI: 34.0-39.7) and 14.4 y (95% CI: 13.3-15.3), respectively. The life expectancy of a 20-y-old woman was 43.1 y (95% CI: 40.1-46.0) if her baseline CD4 count was ≥ 200 cells/µl, compared to 29.5 y (95% CI: 26.2-33.0) if her baseline CD4 count was <50 cells/µl. Life expectancies of patients with baseline CD4 counts ≥ 200 cells/µl were between 70% and 86% of those in HIV-negative adults of the same age and sex, and life expectancies were increased by 15%-20% in patients who had survived 2 y after starting ART. However, the analysis was limited by a lack of mortality data at longer durations. CONCLUSIONS: South African HIV-positive adults can have a near-normal life expectancy, provided that they start ART before their CD4 count drops below 200 cells/µl. These findings demonstrate that the near-normal life expectancies of HIV-positive individuals receiving ART in high-income countries can apply to low- and middle-income countries as well. Please see later in the article for the Editors' Summary.

The impact of child mortality on fertility in South Africa: Do child support grants and antiretroviral treatment matter?

This paper investigates the effect of under-five mortality, child support grant (CSG) coverage and the rollout of antiretroviral therapy (ART) on fertility in South Africa. The study employs the quality-quantity trade-off framework to analyse the direct and indirect factors affecting fertility using the two stage least squares fixed effects instrumental variable approach. The analysis uses balanced panel data covering nine provinces from 2001-2016. This period was characterised by significant increases in the child support grant coverage and ART coverage. Furthermore, this period was characterised by a significant decline in the under-five mortality rate. We find no evidence to support the hypothesis that increases in the CSG coverage are associated with an increase in fertility. This finding aligns with previous literature suggesting that there are no perverse incentives for childbearing associated with the child support grant. On the other hand, results indicate that an increase in ART coverage is associated with an increase in fertility. Results also show that a decrease in under-five mortality is associated with a decline in fertility over the sample period. HIV prevalence, education, real GDP per capita, marriage prevalence and contraceptive prevalence are also important determinants of fertility in South Africa. Although the scale up of ART has improved health outcomes, it also appears to have increased fertility in HIV-positive women. The ART programme should therefore be linked with further family planning initiatives to minimise unintended pregnancies.

The role of sexually transmitted infections in the evolution of the South African HIV epidemic.

OBJECTIVES: To assess the extent to which sexually transmitted infections (STIs) have contributed to the spread of HIV in South Africa and to estimate the extent to which improvements in STI treatment have reduced HIV incidence. METHODS: A mathematical model was used to simulate interactions between HIV and six other STIs (genital herpes, syphilis, chancroid, gonorrhoea, chlamydial infection and trichomoniasis) as well as bacterial vaginosis and vaginal candidiasis. The effects of STIs on HIV transmission probabilities were assumed to be consistent with meta-analytic reviews of observational studies, and the model was fitted to South African HIV prevalence data. RESULTS: The proportion of new HIV infections in adults that were attributable to curable STIs reduced from 39% (uncertainty range: 24-50%) in 1990 to 14% (8-18%) in 2010, while the proportion of new infections attributable to genital herpes increased. Syndromic management programmes are estimated to have reduced adult HIV incidence by 6.6% (3.3-10.3%) between 1994 and 2004, by which time syndromic management coverage was 52%. Had syndromic management been introduced in 1986, with immediate achievement of 100% coverage and a doubling of the rate of health seeking, HIV incidence would have reduced by 64% (36-82%) over the next decade, but had the same intervention been delayed until 2004, HIV incidence would have reduced by only 5.5% (2.8-9.0%). CONCLUSIONS: Sexually transmitted infections have contributed significantly to the spread of HIV in South Africa, but STI control efforts have had limited impact on HIV incidence because of their late introduction and suboptimal coverage.

The Effect of HIV Programs in South Africa on National HIV Incidence Trends, 2000-2019.

BACKGROUND: Recent studies have shown HIV incidence declines at a population level in several African countries. However, these studies have not directly quantified the extent to which incidence declines are attributable to different HIV programs. METHODS: We calibrated a mathematical model of the South African HIV epidemic to age- and sex-specific data from antenatal surveys, household surveys, and death registration, using a Bayesian approach. The model was also parameterized using data on self-reported condom use, voluntary medical male circumcision (VMMC), HIV testing, and antiretroviral treatment (ART). Model estimates of HIV incidence were compared against the incidence rates that would have been expected had each program not been implemented. RESULTS: The model estimated incidence in 15-49 year olds of 0.84% (95% CI: 0.75% to 0.96%) at the start of 2019. This represents a 62% reduction (95% CI: 55% to 66%) relative to 2000, a 47% reduction (95% CI: 42% to 51%) relative to 2010, and a 73% reduction (95% CI: 68% to 77%) relative to the incidence that would have been expected in 2019 in the absence of any interventions. The reduction in incidence in 2019 because of interventions was greatest for ART and condom promotion, with VMMC and behavior change after HIV testing having relatively modest impacts. HIV program impacts differed significantly by age and sex, with condoms and VMMC having greatest impact in youth, and overall incidence reductions being greater in men than in women. CONCLUSIONS: HIV incidence in South Africa has declined substantially since 2000, with ART and condom promotion contributing most significantly to this decline.

Modelling of HIV prevention and treatment progress in five South African metropolitan districts.

Globally, large proportions of HIV-positive populations live in cities. The Fast-Track cities project aims to advance progress toward elimination of HIV as a public health threat by accelerating the response in cities across the world. This study applies a well-established HIV transmission model to provide key HIV estimates for the five largest metropolitan districts in South Africa (SA): Cape Town, Ekurhuleni, eThekwini, Johannesburg and Tshwane. We calibrate the model to metro-specific data sources and estimate progress toward the 90-90-90 targets set by UNAIDS (90% of people living with HIV (PLHIV) diagnosed, 90% of those diagnosed on antiretroviral therapy (ART) and viral suppression in 90% of those on ART). We use the model to predict progress towards similarly defined 95-95-95 targets in 2030. In SA, 90.5% of PLHIV were diagnosed in 2018, with metro estimates ranging from 86% in Johannesburg to 92% in eThekwini. However, only 68.4% of HIV-diagnosed individuals nationally were on ART in 2018, with the proportion ranging from 56% in Tshwane to 73% in eThekwini. Fractions of ART users who were virally suppressed ranged from 77% in Ekurhuleni to 91% in eThekwini, compared to 86% in the whole country. All five metros are making good progress to reach diagnosis targets and all (with the exception of Ekurhuleni) are expected to reach viral suppression targets in 2020. However, the metros and South Africa face severe challenges in reaching the 90% ART treatment target.

Rapid mortality surveillance using a national population register to monitor excess deaths during SARS-CoV-2 pandemic in South Africa.

This paper describes how an up-to-date national population register recording deaths by age and sex, whether deaths were due to natural or unnatural causes, and the offices at which the deaths were recorded can be used to monitor excess death during the SARS-CoV-2 pandemic, both nationally, and sub-nationally, in a country with a vital registration system that is neither up to date nor complete. Apart from suggesting an approach for estimating completeness of reporting at a sub-national level, the application produces estimates of the number of deaths in excess of those expected in the absence of the SARS-CoV-2 epidemic that are highly correlated with the confirmed number of COVID-19 deaths over time, but at a level 2.5 to 3 times higher than the official numbers of COVID-19 deaths. Apportioning the observed excess deaths more precisely to COVID, COVID-related and collateral deaths, and non-COVID deaths averted by interventions with reduced mobility and gatherings, etc., requires access to real-time cause-of-death information. It is suggested that the transition from ICD-10 to ICD-11 should be used as an opportunity to change from a paper-based system to electronic capture of the medical cause-of-death information.

A Bayesian approach to uncertainty analysis of sexually transmitted infection models.

OBJECTIVES: To propose a Bayesian approach to uncertainty analysis of sexually transmitted infection (STI) models, which can be used to quantify uncertainty in model assessments of policy options, estimate regional STI prevalence from sentinel surveillance data and make inferences about STI transmission and natural history parameters. METHODS: Prior distributions are specified to represent uncertainty regarding STI parameters. A likelihood function is defined using a hierarchical approach that takes account of variation between study populations, variation in diagnostic accuracy as well as random binomial variation. The method is illustrated using a model of syphilis, gonorrhoea, chlamydial infection and trichomoniasis in South Africa. RESULTS: Model estimates of STI prevalence are in good agreement with observations. Out-of-sample projections and cross-validations also show that the model is reasonably well calibrated. Model predictions of the impact of interventions are subject to significant uncertainty: the predicted reductions in the prevalence of syphilis by 2020, as a result of doubling the rate of health seeking, increasing the proportion of private practitioners using syndromic management protocols and screening all pregnant women for syphilis, are 43% (95% CI 3% to 77%), 9% (95% CI 1% to 19%) and 6% (95% CI 4% to 7%), respectively. CONCLUSIONS: This study extends uncertainty analysis techniques for fitted HIV/AIDS models to models that are fitted to other STI prevalence data. There is significant uncertainty regarding the relative effectiveness of different STI control strategies. The proposed technique is reasonable for estimating uncertainty in past STI prevalence levels and for projections of future STI prevalence.

Steep Declines in Pediatric AIDS Mortality in South Africa, Despite Poor Progress Toward Pediatric Diagnosis and Treatment Targets.

BACKGROUND: Few attempts have been made to monitor progress toward HIV diagnosis and antiretroviral treatment (ART) coverage targets in children, and the impact that ART and prevention of mother-to-child transmission (PMTCT) programs have had on pediatric HIV incidence and mortality. METHODS: A multiparameter evidence synthesis approach was adopted to integrate South African pediatric HIV data sources. A previously developed model of HIV in South Africa was calibrated to household survey HIV prevalence data, routine antibody testing data, data on numbers and ages of children on ART, vital registration data and data on HIV diagnosis at death. The impact of ART and PMTCT was estimated by comparing validated model outputs against model predictions of the trends that would have been expected in the absence of ART and PMTCT. RESULTS: By mid-2018, the model estimated that 75.2% (95% CI: 73.9%-76.8%) of HIV-positive children were diagnosed, substantially lower than the corresponding estimates in HIV-positive adults (91.0%). ART coverage in children in 2018 (51.2%, 95% CI: 49.4%-52.7%) was also lower than that in adults (62.0%). In 2017-2018, the numbers of new cases of mother-to-child transmission and pediatric AIDS deaths were reduced by 84% and 94%, respectively, relative to what would have been expected in the absence of interventions, but reductions in mortality were driven largely by PMTCT. CONCLUSIONS: Although levels of AIDS mortality in children have declined dramatically in South Africa, this has mostly been due to successful PMTCT programs, and progress toward the 90-90-90 targets appears relatively poor when compared with that in adults.

Progress towards the 2020 targets for HIV diagnosis and antiretroviral treatment in South Africa.

BACKGROUND: The UNAIDS targets for 2020 are to achieve a 90% rate of diagnosis in HIV-positive individuals, to provide antiretroviral treatment (ART) to 90% of HIV-diagnosed individuals and to achieve virological suppression in 90% of ART patients. OBJECTIVES: To assess South Africa's progress towards the 2020 targets and variations in performance by province. METHODS: A mathematical model was fitted to HIV data for each of South Africa's provinces, and for the country as a whole. Numbers of HIV tests performed in each province were estimated from routine data over the 2002-2015 period, and numbers of patients receiving ART in each province were estimated by fitting models to reported public and private ART enrolment statistics. RESULTS: By the middle of 2015, 85.5% (95% CI: 84.5% - 86.5%) of HIV-positive South African adults had been diagnosed, with little variation between provinces. However, only 56.9% (95% CI: 55.3% - 58.7%) of HIV-diagnosed adults were on ART, with this proportion varying between 50.8% in North West and 72.7% in Northern Cape. In addition, 78.4% of adults on ART were virally suppressed, with rates ranging from 69.7% in Limpopo to 85.9% in Western Cape. Overall, 3.39 million (95% CI: 3.26-3.52 million) South Africans were on ART by mid-2015, equivalent to 48.6% (95% CI: 46.0% - 51.2%) of the HIV-positive population. ART coverage varied between 43.0% in Gauteng and 63.0% in Northern Cape. CONCLUSION: Although South Africa is well on its way to reaching the 90% HIV diagnosis target, most provinces face challenges in reaching the remaining two 90% targets.

HIV epidemic drivers in South Africa: A model-based evaluation of factors accounting for inter-provincial differences in HIV prevalence and incidence trends.

BACKGROUND: HIV prevalence differs substantially between South Africa's provinces, but the factors accounting for this difference are poorly understood. OBJECTIVES: To estimate HIV prevalence and incidence trends by province, and to identify the epidemiological factors that account for most of the variation between provinces. METHODS: A mathematical model of the South African HIV epidemic was applied to each of the nine provinces, allowing for provincial differences in demography, sexual behaviour, male circumcision, interventions and epidemic timing. The model was calibrated to HIV prevalence data from antenatal and household surveys using a Bayesian approach. Parameters estimated for each province were substituted into the national model to assess sensitivity to provincial variations. RESULTS: HIV incidence in 15-49-year-olds peaked between 1997 and 2003 and has since declined steadily. By mid-2013, HIV prevalence in 15-49-year-olds varied between 9.4% (95% CI: 8.5%-10.2%) in Western Cape and 26.8% (95% CI: 25.8%-27.6%) in KwaZulu-Natal. When standardising parameters across provinces, this prevalence was sensitive to provincial differences in the prevalence of male circumcision (range 12.3%-21.4%) and the level of non-marital sexual activity (range 9.5%-24.1%), but not to provincial differences in condom use (range 17.7%-21.2%), sexual mixing (range 15.9%-19.2%), marriage (range 18.2%-19.4%) or assumed HIV prevalence in 1985 (range 17.0%-19.1%). CONCLUSION: The provinces of South Africa differ in the timing and magnitude of their HIV epidemics. Most of the heterogeneity in HIV prevalence between South Africa's provinces is attributable to differences in the prevalence of male circumcision and the frequency of non-marital sexual activity.

Prospects for HIV control in South Africa: a model-based analysis.

BACKGROUND: The goal of virtual elimination of horizontal and mother-to-child HIV transmission in South Africa (SA) has been proposed, but there have been few systematic investigations of which interventions are likely to be most critical to reducing HIV incidence. OBJECTIVE: This study aims to evaluate SA's potential to achieve virtual elimination targets and to identify which interventions will be most critical to achieving HIV incidence reductions. DESIGN: A mathematical model was developed to simulate the population-level impact of different HIV interventions in SA. Probability distributions were specified to represent uncertainty around 32 epidemiological parameters that could be influenced by interventions, and correlation coefficients (r) were calculated to assess the sensitivity of the adult HIV incidence rates and mother-to-child transmission rates (2015-2035) to each epidemiological parameter. RESULTS: HIV incidence in SA adults (ages 15-49) is expected to decline from 1.4% in 2011-2012 to 0.29% by 2035 (95% CI: 0.10-0.62%). The parameters most strongly correlated with future adult HIV incidence are the rate of viral suppression after initiating antiretroviral treatment (ART) (r=-0.56), the level of condom use in non-marital relationships (r=-0.40), the phase-in of intensified risk-reduction counselling for HIV-positive adults (r=0.29), the uptake of medical male circumcision (r=-0.24) and the phase-in of universal ART eligibility (r=0.22). The paediatric HIV parameters most strongly associated with mother-to-child transmission rates are the relative risk of transmission through breastfeeding when the mother is receiving ART (r=0.70) and the rate of ART initiation during pregnancy (r=-0.16). CONCLUSIONS: The virtual elimination target of a 0.1% incidence rate in adults will be difficult to achieve. Interventions that address the infectiousness of patients after ART initiation will be particularly critical to achieving long-term HIV incidence declines in South Africa.

Persistent burden from non-communicable diseases in South Africa needs strong action.

Continued effort and politcal will must be directed towards preventing, delaying the onset of and managing non-communicable diseases in South Africa.

Emerging trends in non-communicable disease mortality in South Africa, 1997 - 2010.

OBJECTIVES: National trends in age-standardised death rates (ASDRs) for non-communicable diseases (NCDs) in South Africa (SA) were identified between 1997 and 2010. METHODS: As part of the second National Burden of Disease Study, vital registration data were used after validity checks, proportional redistribution of missing age, sex and population group, demographic adjustments for registration incompleteness, and identification of misclassified AIDS deaths. Garbage codes were redistributed proportionally to specified codes by age, sex and population group. ASDRs were calculated using mid-year population estimates and the World Health Organization world standard. RESULTS: Of 594 071 deaths in 2010, 38.9% were due to NCDs (42.6% females). ASDRs were 287/100 000 for cardiovascular diseases (CVDs), 114/100 000 for cancers (malignant neoplasms), 58/100 000 for chronic respiratory conditions and 52/100 000 for diabetes mellitus. An overall annual decrease of 0.4% was observed resulting from declines in stroke, ischaemic heart disease, oesophageal and lung cancer, asthma and chronic respiratory disease, while increases were observed for diabetes, renal disease, endocrine and nutritional disorders, and breast and prostate cancers. Stroke was the leading NCD cause of death, accounting for 17.5% of total NCD deaths. Compared with those for whites, NCD mortality rates for other population groups were higher at 1.3 for black Africans, 1.4 for Indians and 1.4 for coloureds, but varied by condition. CONCLUSIONS: NCDs contribute to premature mortality in SA, threatening socioeconomic development. While NCD mortality rates have decreased slightly, it is necessary to strengthen prevention and healthcare provision and monitor emerging trends in cause-specific mortality to inform these strategies if the target of 2% annual decline is to be achieved.

Mortality trends and differentials in South Africa from 1997 to 2012: second National Burden of Disease Study.

BACKGROUND: The poor health of South Africans is known to be associated with a quadruple disease burden. In the second National Burden of Disease (NBD) study, we aimed to analyse cause of death data for 1997-2012 and develop national, population group, and provincial estimates of the levels and causes of mortality. METHOD: We used underlying cause of death data from death notifications for 1997-2012 obtained from Statistics South Africa. These data were adjusted for completeness using indirect demographic techniques for adults and comparison with survey and census estimates for child mortality. A regression approach was used to estimate misclassified HIV/AIDS deaths and so-called garbage codes were proportionally redistributed by age, sex, and population group population group (black African, Indian or Asian descent, white [European descent], and coloured [of mixed ancestry according to the preceding categories]). Injury deaths were estimated from additional data sources. Age-standardised death rates were calculated with mid-year population estimates and the WHO age standard. Institute of Health Metrics and Evaluation Global Burden of Disease (IHME GBD) estimates for South Africa were obtained from the IHME GHDx website for comparison. FINDINGS: All-cause age-standardised death rates increased rapidly since 1997, peaked in 2006 and then declined, driven by changes in HIV/AIDS. Mortality from tuberculosis, non-communicable diseases, and injuries decreased slightly. In 2012, HIV/AIDS caused the most deaths (29·1%) followed by cerebrovascular disease (7·5%) and lower respiratory infections (4·9%). All-cause age-standardised death rates were 1·7 times higher in the province with the highest death rate compared to the province with the lowest death rate, 2·2 times higher in black Africans compared to whites, and 1·4 times higher in males compared with females. Comparison with the IHME GBD estimates for South Africa revealed substantial differences for estimated deaths from all causes, particularly HIV/AIDS and interpersonal violence. INTERPRETATION: This study shows the reversal of HIV/AIDS, non-communicable disease, and injury mortality trends in South Africa during the study period. Mortality differentials show the importance of social determinants, raise concerns about the quality of health services, and provide relevant information to policy makers for addressing inequalities. Differences between GBD estimates for South Africa and this study emphasise the need for more careful calibration of global models with local data. FUNDING: South African Medical Research Council's Flagships Awards Project.