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The COVID-19 pandemic has already claimed considerable lives. There are major concerns in Africa due to existing high prevalence rates for both infectious and non-infectious diseases and limited resources in terms of personnel, beds and equipment. Alongside this, concerns that lockdown and other measures will have on prevention and management of other infectious diseases and non-communicable diseases (NCDs). NCDs are an increasing issue with rising morbidity and mortality rates. The World Health Organization (WHO) warns that a lack of nets and treatment could result in up to 18 million additional cases of malaria and up to 30,000 additional deaths in sub-Saharan Africa. Document current prevalence and mortality rates from COVID-19 alongside economic and other measures to reduce its spread and impact across Africa. In addition, suggested ways forward among all key stakeholder groups. Contextualise the findings from a wide range of publications including internet-based publications coupled with input from senior-level personnel. Prevalence and mortality rates are currently lower in Africa than among several Western countries and the USA. This could be due to a number of factors including early instigation of lockdown and border closures, the younger age of the population, lack of robust reporting systems and as yet unidentified genetic and other factors. Innovation is accelerating to address concerns with available equipment. There are ongoing steps to address the level of misinformation and its consequences including fines. There are also ongoing initiatives across Africa to start addressing the unintended consequences of COVID-19 activities including lockdown measures and their impact on NCDs including the likely rise in mental health disorders, exacerbated by increasing stigma associated with COVID-19. Strategies include extending prescription lengths, telemedicine and encouraging vaccination. However, these need to be accelerated to prevent increased morbidity and mortality. There are multiple activities across Africa to reduce the spread of COVID-19 and address misinformation, which can have catastrophic consequences, assisted by the WHO and others, which appear to be working in a number of countries. Research is ongoing to clarify the unintended consequences given ongoing concerns to guide future activities. Countries are learning from each other.

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.

COVID-19 vaccine effectiveness estimates from Africa are limited. These data can guide decisions on selecting priority groups in vaccine programs. This study estimated VE for BNT162b2 and Ad26.COV2.S against COVID-19-related hospitalisation, stratified by age group, time since vaccination, and HIV-infection status for three SARS-CoV-2 surges in South Africa. We applied a test-negative case-control design to hospitalisations for acute respiratory infections amongst members of a medical insurance plan during the delta (9 May 2021–18 September 2021), omicron BA.1 (28 November 2021–5 February 2022), and BA.4/5 (17 April 2022–28 May 2022) variant periods. All data, including vaccination history, were extracted from insurance plan claims. Logistic regression models adjusted for age, comorbidities, time since vaccination, income level and documentation of previous SARS-CoV-2 infection, were used to calculate VE. BNT162b2 was protective against COVID-19-related hospitalisation for all variant periods (VE 89.3 % (95 % CI, 85.9–91.9) for delta, reduced to 31.4 % (95 % CI, 19.1–41.9) and 22.7 % (95 % CI, 2.2–38.9) for omicron BA.1, and BA.4/5 respectively). VE estimates for Ad26.COV2·S, although lower than BNT162b2, were protective for all periods (48.8 % (95 % CI, 39.6–56.5), 19.8 % (95 % CI, 5.8–31.6), and 45.0 % (95 % CI, 29.8–57.0) for delta, omicron BA.1, and BA.4/5 respectively). Protection against severe infection was shown in those ≥60 years and younger age groups, as well as in people living with HIV (PLWH) and HIV-uninfected individuals. Vaccination offered significant protection against COVID-19-related hospitalisation in PLWH and the elderly, and is therefore an effective means of reducing severe outcomes in these high-risk populations in South Africa. VE against BA.4/5 waned with time since vaccination suggesting boosters may be necessary. •BNT162b2 and Ad26.COV2.S were protective against COVID-19-related hospitalisation for all variant periods.•Protection was shown in the ≥60 year age group for BNT162b2 (all variant periods) and for Ad.COV2.S (BA.4/5 period).•Protection was shown in the <60 year age group for BNT162b2 (delta, BA.1 periods) and for Ad.COV2.S (delta, BA.4/5 periods).•Protection was shown in HIV-uninfected individuals for BNT162b2 (all variant periods) and Ad.COV2.S (delta, BA.4/5).•In people living with HIV (PLWH), protection was shown for BNT162b2 (delta period) and Ad.COV2.S (delta, BA.1 periods).•Vaccination is effective in reducing severe outcomes in high-risk populations in South Africa.

COVID-19 vaccine effectiveness estimates from Africa are limited. These data can guide decisions on selecting priority groups in vaccine programs. This study estimated VE for BNT162b2 and Ad26.COV2·S against COVID-19-related hospitalisation, stratified by age group, time since vaccination, and HIV-infection status for three SARS-CoV-2 surges in South Africa. We applied a test-negative case-control design to hospitalisations for acute respiratory infections amongst members of a medical insurance plan during the delta (9 May 2021-18 September 2021), omicron BA.1 (28 November 2021-5 February 2022), and BA.4/5 (17 April 2022-28 May 2022) variant periods. All data, including vaccination history, were extracted from insurance plan claims. Logistic regression models adjusted for age, comorbidities, time since vaccination, income level and documentation of previous SARS-CoV-2 infection, were used to calculate VE. BNT162b2 was protective against COVID-19-related hospitalisation for all variant periods (VE 89.3 % (95 % CI, 85.9-91.9) for delta, reduced to 31.4 % (95 % CI, 19.1-41.9) and 22.7 % (95 % CI, 2.2-38.9) for omicron BA.1, and BA.4/5 respectively). VE estimates for Ad26.COV2·S, although lower than BNT162b2, were protective for all periods (48.8 % (95 % CI, 39.6-56.5), 19.8 % (95 % CI, 5.8-31.6), and 45.0 % (95 % CI, 29.8-57.0) for delta, omicron BA.1, and BA.4/5 respectively). Protection against severe infection was shown in those ≥60 years and younger age groups, as well as in people living with HIV (PLWH) and HIV-uninfected individuals. Vaccination offered significant protection against COVID-19-related hospitalisation in PLWH and the elderly, and is therefore an effective means of reducing severe outcomes in these high-risk populations in South Africa. VE against BA.4/5 waned with time since vaccination suggesting boosters may be necessary.

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.

Introduction: One of the aims of the re-engineering of primary health care in South Africa is to strengthen the health system and improve accessibility of health services through ward based outreach teams (WBOTs) comprising of nurses and community health workers.Aim: To evaluate the implementation of WBOTs against national guidelines and identify Community Health Worker (CHW) characteristics that influence adherence to guidelines regarding the referral and follow up of maternal and child health clients.Methodology: This cross-sectional study was conducted during 2013. All 9 WBOTs at the time were included in the study. Data were collected through: a questionnaire survey; key informant interviews and a review of records of pregnant, post-natal women and unimmunized children under five. A process evaluation was conducted to describe inputs (training, team composition, resources, and knowledge); processes (service delivery, referral linkages, support and supervision) and outputs (number of clients referred and followed up). Logistic regression was performed to identify CHW characteristics (Age, education, experience, training, and knowledge) associated with adherence to national guidelines.Results:WBOT had sufficient numbers of CHWs within the team; however lacked sufficient knowledge and resources required to conduct household visits. CHWs adhered to the guidelines regarding the follow up of maternal clients with 85% of CHW having conducted the required number of follow up visits for pregnant and postnatal women. However, only 29% of unimmunized children were appropriately followed up. Challenges identified included: lack of supervision, limited resources, and poor knowledge. There was no statistically significant association between CHW characteristics and adherence to guidelines.Conclusion and recommendations: This study highlights the challenges that need to be addressed around the WBOT implementation. It is recommended that there is improvement in resource availability, CHW supervision, capacity and training to improve the implementation process of future teams.

SignificanceOur regional-scale geochemical dataset (3He/4He) resolves the geometry of the continental collision between India and Asia. Geophysical images have led to contradictory interpretations that India directly underthrusts Tibet as a horizontal plate or India subducts steeply into the mantle. Helium transits from mantle depths to the surface within a few millennia, such that the ratio of mantle-derived 3He to dominantly crust-derived 4He provides a snapshot of the subsurface. 3He/4He data from 225 geothermal springs across a >1,000-km-wide region of southern Tibet define a sharp boundary subparallel to the surface suture between India and Asia, just north of the Himalaya, delineating the northern limit of India at ∼80-km depth. The India–Asia collision resembles oceanic subduction with an asthenospheric mantle wedge. During continent–continent collision, does the downgoing continental plate underplate far inboard of the collisional boundary or does it subduct steeply into the mantle, and how is this geometry manifested in the mantle flow field? We test conflicting models for these questions for Earth’s archetypal continental collision forming the Himalaya and Tibetan Plateau. Air-corrected helium isotope data (3He/4He) from 225 geothermal springs (196 from our group, 29 from the literature) delineate a boundary separating a Himalayan domain of only crustal helium from a Tibetan domain with significant mantle helium. This 1,000-km-long boundary is located close to the Yarlung-Zangbo Suture (YZS) in southern Tibet from 80 to 92°E and is interpreted to overlie the “mantle suture” where cold underplated Indian lithosphere is juxtaposed at >80 km depth against a sub-Tibetan incipiently molten asthenospheric mantle wedge. In southeastern Tibet, the mantle suture lies 100 km south of the YZS, implying delamination of the mantle lithosphere from the Indian crust. This helium-isotopic boundary helps resolve multiple, mutually conflicting seismological interpretations. Our synthesis of the combined data locates the northern limit of Indian underplating beneath Tibet, where the Indian plate bends to steeper dips or breaks off beneath a (likely thin) asthenospheric wedge below Tibetan crust, thereby defining limited underthrusting for the Tibetan continental collision.

In this open, randomized, multicenter trial involving extremely-low-birth-weight preterm infants, the use of a higher hemoglobin threshold for red-cell transfusion did not improve survival without neurodevelopmental impairment at 22 to 26 months of age, corrected for prematurity.

Background An increasing number of sporting bodies report unacceptably high levels of false-positive ECGs when undertaking pre-participation cardiac screening. To address this issue, modified ECG interpretation criteria have become available for use within athletes. Objective This study assessed the accuracy of the new 2014 ‘Refined Criteria’ against the 2013 Seattle Criteria and the 2010 European Society of Cardiology (ESC) recommendations in a cohort of Arabic, black and Caucasian athletes. Methods 2491 male athletes (1367 Arabic, 748 black and 376 Caucasian) undertook pre-participation screening including a 12-lead ECG, with further investigation(s) upon indication. Results Ten athletes (0.4%) were identified with cardiac pathology; seven with hypertrophic cardiomyopathy (HCM; five black and two Arabic) and three Arabs with Wolff–Parkinson–White syndrome (WPW). All three ECG criteria were 100% sensitive identifying all cases of HCM and WPW. The 2014 Refined Criteria reduced (p<0.0001) the prevalence of an abnormal ECG to 5.3% vs 11.6% (Seattle Criteria) and 22.3% (2010 ESC recommendations). The 2014 Refined Criteria significantly (p<0.0001) improved specificity (94.0%) across all ethnicities compared with the Seattle Criteria (87.5%) and ESC recommendations (76.6%). Black athletes continue to present a higher prevalence (p<0.0001) of abnormal ECGs compared with Arabic and Caucasian athletes (10% vs 3.6% and 2.1%). Conclusions The 2014 Refined Criteria for athlete ECG interpretation outperformed both the 2013 Seattle Criteria and the 2010 ESC recommendations by significantly reducing the number of false-positive ECGs in Arabic, black and Caucasian athletes while maintaining 100% sensitivity for serious cardiac pathologies.

During continent–continent collision, does the downgoing continental plate underplate far inboard of the collisional boundary or does it subduct steeply into the mantle, and how is this geometry manifested in the mantle flow field? We test conflicting models for these questions for Earth’s archetypal continental collision forming the Himalaya and Tibetan Plateau. Air-corrected helium isotope data (³He/⁴He) from 225 geothermal springs (196 from our group, 29 from the literature) delineate a boundary separating a Himalayan domain of only crustal helium from a Tibetan domain with significant mantle helium. This 1,000-km-long boundary is located close to the Yarlung-Zangbo Suture (YZS) in southern Tibet from 80 to 92°E and is interpreted to overlie the “mantle suture” where cold underplated Indian lithosphere is juxtaposed at >80 km depth against a sub-Tibetan incipiently molten asthenospheric mantle wedge. In southeastern Tibet, the mantle suture lies 100 km south of the YZS, implying delamination of the mantle lithosphere from the Indian crust. This helium-isotopic boundary helps resolve multiple, mutually conflicting seismological interpretations. Our synthesis of the combined data locates the northern limit of Indian underplating beneath Tibet, where the Indian plate bends to steeper dips or breaks off beneath a (likely thin) asthenospheric wedge below Tibetan crust, thereby defining limited underthrusting for the Tibetan continental collision.