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BackgroundThe fifth Millennium Development Goal (MDG 5) established the goal of a 75% reduction in the maternal mortality ratio (MMR; number of maternal deaths per 100,000 livebirths) between 1990 and 2015. We aimed to measure levels and track trends in maternal mortality, the key causes contributing to maternal death, and timing of maternal death with respect to delivery.MethodsWe used robust statistical methods including the Cause of Death Ensemble model (CODEm) to analyse a database of data for 7065 site-years and estimate the number of maternal deaths from all causes in 188 countries between 1990 and 2013. We estimated the number of pregnancy-related deaths caused by HIV on the basis of a systematic review of the relative risk of dying during pregnancy for HIV-positive women compared with HIV-negative women. We also estimated the fraction of these deaths aggravated by pregnancy on the basis of a systematic review. To estimate the numbers of maternal deaths due to nine different causes, we identified 61 sources from a systematic review and 943 site-years of vital registration data. We also did a systematic review of reports about the timing of maternal death, identifying 142 sources to use in our analysis. We developed estimates for each country for 1990-2013 using Bayesian meta-regression. We estimated 95% uncertainty intervals (UIs) for all values.Findings292,982 (95% UI 261,017-327,792) maternal deaths occurred in 2013, compared with 376,034 (343,483-407,574) in 1990. The global annual rate of change in the MMR was -0·3% (-1·1 to 0·6) from 1990 to 2003, and -2·7% (-3·9 to -1·5) from 2003 to 2013, with evidence of continued acceleration. MMRs reduced consistently in south, east, and southeast Asia between 1990 and 2013, but maternal deaths increased in much of sub-Saharan Africa during the 1990s. 2070 (1290-2866) maternal deaths were related to HIV in 2013, 0·4% (0·2-0·6) of the global total. MMR was highest in the oldest age groups in both 1990 and 2013. In 2013, most deaths occurred intrapartum or postpartum. Causes varied by region and between 1990 and 2013. We recorded substantial variation in the MMR by country in 2013, from 956·8 (685·1-1262·8) in South Sudan to 2·4 (1·6-3·6) in Iceland.InterpretationGlobal rates of change suggest that only 16 countries will achieve the MDG 5 target by 2015. Accelerated reductions since the Millennium Declaration in 2000 coincide with increased development assistance for maternal, newborn, and child health. Setting of targets and associated interventions for after 2015 will need careful consideration of regions that are making slow progress, such as west and central Africa.FundingBill & Melinda Gates Foundation.

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., Author(s): Leigh F. Johnson 1,*, Margaret T. May 2, Rob E. Dorrington 3, Morna Cornell 1, Andrew Boulle 1, Matthias Egger 1,4, Mary-Ann Davies 1 Introduction Substantial declines in adult [...]

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. Saimbarashe Takuva, Azwi Takalani, and colleagues investigate the frequency and incidence of adverse events reported after receipt of a single dose of the Ad26.COV2.S COVID-19 vaccine among health care workers in South Africa. Author summary: Why was this study done?: While the safety of the Ad26.COV2.S vaccine was established in phase 3 clinical trials, continuous evaluation of safety in expanded populations is crucial. The Sisonke phase 3b implementation study enrolled almost half a million healthcare workers, providing an opportunity to further evaluate the safety of the single-dose Ad26.COV2.S vaccine. What did the researchers do and find?: A total of 477,234 healthcare workers across all South African provinces received the Ad26.COV2.S vaccine between 17 February 2021 and 17 May 2021. Through self-reports and active case finding, adverse events, serious adverse events, and adverse events of special interest were identified. Overall occurrence of adverse events was low. The majority of adverse events reported were common reactogenicity signs and symptoms. Most serious adverse events and adverse events of special interest, including vascular events, immune system disorders, and deaths, occurred at lower than the expected population rates. What do these findings mean?: The single-dose Ad26.COV2.S vaccine had an acceptable safety profile. This supports continued use of this vaccine in large rollout programmes. [ABSTRACT FROM AUTHOR]

Introduction: There is uncertainty regarding the completeness of death recording by civil registration and by health centres in South Africa. This paper aims to compare death recording by the two systems, in cohorts of South African patients receiving antiretroviral treatment (ART). Methods: Completeness of death recording was estimated using a capture-recapture approach. Six ART programmes linked their patient record systems to the vital registration system using civil identity document (ID) numbers and provided data comparing the outcomes recorded in patient files and in the vital registration. Patients were excluded if they had missing/invalid IDs or had transferred to other ART programmes. Results: After exclusions, 91,548 patient records were included. Of deaths recorded in patients files after 2003, 94.0% (95% CI: 93.3-94.6%) were recorded by civil registration, with completeness being significantly higher in urban areas, older adults and females. Of deaths recorded by civil registration after 2003, only 35.0% (95% CI: 34.2-35.8%) were recorded in patient files, with this proportion dropping from 60% in 2004-2005 to 30% in 2010 and subsequent years. Recording of deaths in patient files was significantly higher in children and in locations within 50 km of the health centre. When the information from the two systems was combined, an estimated 96.2% of all deaths were recorded (93.5% in children and 96.2% in adults). Conclusions: South Africa's civil registration system has achieved a high level of completeness in the recording of mortality. However, the fraction of deaths recorded by health centres is low and information from patient records is insufficient by itself to evaluate levels and predictors of ART patient mortality. Previously documented improvements in ART mortality over time may be biased if based only on data from patient records. Keywords: antiretroviral therapy; HIV; vital statistics registration; South Africa. To access the supplementary material to this article please see Supplementary Files under Article Tools online., Introduction Antiretroviral treatment (ART) has had a significant impact on AIDS mortality in developing countries [1-4]. However, most of what is known regarding mortality after ART initiation in developing countries [...]

Differences between estimates of maternal mortality from different research groups have been much debated. (1-3) The data that are included or omitted and the choice of models have been discussed, [...]

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 [greater than or equal to] 200 cells/µl, compared to 29.5 y (95% CI: 26.2-33.0) if her baseline CD4 count was 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., Introduction Estimates of life expectancies of HIV-infected individuals are important in providing information to patients about their long-term prognosis, in projecting the future costs of HIV-related care, and in forecasting [...]

Background. The paucity of quality data on maternal deaths and possible mis-specification of models have resulted in a range of estimates of the maternal mortality ratio (MMR) for South Africa. Objectives. This paper contrasts the estimates from multi-country models for estimating the MMR with the South African data from vital registration. Method. A literature review was undertaken to identify estimates of the MMR for South Africa and methodologies used. In addition, cause of death data from Statistics SA were analysed for trends. Results. In contrast to prediction models used by international agencies, the Health Data Advisory and Co-ordinating Committee (HDACC) recommended the use of the vital registration data adjusted for under-registration and misclassification of causes to monitor maternal mortality. HDACC also recommended that, as is done by the Maternal Mortality Estimation Interagency Group (MMEIG), the number of maternal deaths identified be scaled up by 50% to account for the general under-reporting of maternal deaths. Based on this approach, the baseline MMR in 2008 was estimated to be 310 per 100 000 live births. From vital statistics, the indications are that by 2009, South Africa had not yet managed to reverse the upward trend in MMR. The increase is largely a result of an increase in the number of maternal deaths from indirect causes, as might be expected in the context of the HIV pandemic. However, the number of indirect maternal deaths increased markedly only since 2003, a few years later than the rapid increase in AIDS mortality. Conclusions. There are opportunities to improve monitoring maternal mortality, including strengthening the information systems (vital registration, the confidential enquiry and the routine health information system) and exploring opportunities for linking data from different sources. Better data on the role of HIV in maternal mortality are needed. [ABSTRACT FROM AUTHOR]

The article discusses a study which examined global trends in neonatal, infant and under-5 mortality from 1990 to 2013. Topics discussed include a reduction in child mortality rate, an increase in the number of child births in 2013 as compared to 1990, and developing countries expected to achieve the Millennium Development Goal 4 (MDG 4).

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., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)