COVID-19 and all-cause mortality in South Africa – the hidden deaths in the first four waves

Accurate statistics are essential for policy guidance and decisions. However, the reported number of cases and COVID-19 deaths are known to be biased due to under-ascertainment of SARS-CoV-2 and incomplete reporting of deaths. Making use of death data from the National Population Register has made it possible to track in near-real time the number of excess deaths experienced in South Africa. These data reveal considerable provincial differences in the impact of COVID-19, likely associated with differences in population age structure and density, patterns of social mixing, and differences in the prevalence of known comorbidities such as diabetes, hypertension, and obesity. As the waves unfolded, levels of natural immunity together with vaccination began to reduce levels of mortality. Mortality rates during the second (Beta) wave were much higher than mortality in the third (Delta) wave, which were higher than in either the first or the fourth (Omicron) waves. However, the cumulative death toll during the second (Beta) wave was of a similar order of magnitude as that during the third (Delta) wave due to the longer duration of the Delta wave. Near-real time monitoring of all-cause deaths should be refined to provide more granular-level information to enable district-level policy support. In the meanwhile, there is an urgent need to re-engineer the civil registration and vital statistics system to enable more timely access to cause of death information for public health actions.Significance:This study highlights that in South Africa there were about three times the number of excess deaths from natural causes during 2020 and 2021 than reported COVID-19 deaths. Although the cause of death remains unknown, the strong temporal correlation between excess deaths and reported COVID-19 deaths within each province indicates that the majority of excess deaths were associated with COVID-19. Many countries have found it difficult to estimate excess deaths, or to identify and report COVID-19 deaths accurately, demonstrating the value of near-real time monitoring of mortality through the use and demographic analysis of data obtained from the country’s National Population Register

HIV/AIDS mortality trends pre and post ART for 1997 - 2012 in South Africa – have we turned the tide?

Background. South Africa (SA) has one of the largest HIV/AIDS epidemics in the world and the most extensive antiretroviral therapy (ART) programme globally, which was rolled out from 2004. This paper reports the trends in HIV/AIDS mortality pre and post ART rollout in SA. Methods. Vital registration cause-of-death data from Statistics South Africa were adjusted for under-reporting of deaths using demographic methods. Misattributed HIV/AIDS deaths were identified by regressing excess mortality on a lagged indicator HIV antenatal clinic prevalence for causes found to be associated with HIV/AIDS. Background trends in the source-cause mortality rates were estimated from the trend in cause-specific mortality experienced among 75 - 84-year-olds. Mortality rates were calculated using mid-year population estimates and the World Health Organization world standard age-weights. Results. We estimated over 3 189 000 HIV/AIDS deaths for 1997 - 2012. In 1997, 60 336 (14.5%) of deaths were attributed to HIV/AIDS; this number peaked in 2006 at 283 564 (41.9%) and decreased to 153 661 (29.1%) by 2012; female mortality rates peaked in 2005 and those of males in 2006. Men aged 35 years and older had higher mortality rates than did women. While the rates at ages below 65 years in 2012 were lower than those in 2006, rates of those age 65 years and older remained unchanged. Conclusion. The number of HIV/AIDS deaths has almost halved since the ART rollout. Of concern is the high mortality in men 45 years and older and the high mortality of men compared with women in the older ages by 2012; this gap has increased with age. Treatment and prevention programmes should strategise how to target men

Ovine wet carcass syndrome of unknown aetiology

No Abstract

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

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

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.Funding for the Sisonke Study was provided by: The National Department of Health through baseline funding to the South African Medical Research Council; the Solidarity Response Fund NPC; The Michael & Susan Dell Foundation; the ELMA Vaccines and Immunization Foundation; the ELMA Vaccines and Immunization Foundation; and the Bill & Melinda Gates Foundation.https://journals.plos.org/plosmedicinedm2022Paediatrics and Child HealthSchool of Health Systems and Public Health (SHSPH

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.

BACKGROUND: A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. METHODS: This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. FINDINGS: Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0-75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4-97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8-80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3-4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. INTERPRETATION: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D'Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK

Background A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. Methods This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. Findings Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8–80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3–4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. Interpretation ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials

COVID-19 and all-cause mortality in South Africa – the hidden deaths in the first four waves

Accurate statistics are essential for policy guidance and decisions. However, the reported number of cases and COVID-19 deaths are known to be biased due to under-ascertainment of SARS-CoV-2 and incomplete reporting of deaths. Making use of death data from the National Population Register has made it possible to track in near-real time the number of excess deaths experienced in South Africa. These data reveal considerable provincial differences in the impact of COVID-19, likely associated with differences in population age structure and density, patterns of social mixing, and differences in the prevalence of known comorbidities such as diabetes, hypertension, and obesity. As the waves unfolded, levels of natural immunity together with vaccination began to reduce levels of mortality. Mortality rates during the second (Beta) wave were much higher than mortality in the third (Delta) wave, which were higher than in either the first or the fourth (Omicron) waves. However, the cumulative death toll during the second (Beta) wave was of a similar order of magnitude as that during the third (Delta) wave due to the longer duration of the Delta wave. Near-real time monitoring of all-cause deaths should be refined to provide more granular level information to enable district-level policy support. In the meanwhile, there is an urgent need to re-engineer the civil registration and vital statistics system to enable more timely access to cause of death information for public health actions. Significance: This study highlights that in South Africa there were about three times the number of excess deaths from natural causes during 2020 and 2021 than reported COVID-19 deaths. Although the cause of death remains unknown, the strong temporal correlation between excess deaths and reported COVID-19 deaths within each province indicates that the majority of excess deaths were associated with COVID-19. Many countries have found it difficult to estimate excess deaths, or to identify and report COVID-19 deaths accurately, demonstrating the value of near-real time monitoring of mortality through the use and demographic analysis of data obtained from the country’s National Population Register. Open data set: https://www.samrc.ac.za/sites/default/files/files/2022-02-09/Estimated%20deaths%20for%20SA%2007%20Feb%202022%20with%20adj2.xls