Hard choices: Ethical challenges in phase 1 of COVID-19 vaccine roll-out in South Africa.

Access to COVID-19 vaccines has raised concerns globally. Despite calls for solidarity and social justice during the pandemic, vaccine nationalism, stockpiling of limited vaccine supplies by high-income countries and profit-driven strategies of global pharmaceutical manufacturers have brought into sharp focus global health inequities and the plight of low- and middle-income countries (LMICs) as they wait in line for restricted tranches of vaccines. Even in high-income countries that received vaccine supplies first, vaccine roll-out globally has been fraught with logistic and ethical challenges. South Africa (SA) is no exception. Flawed global institutional strategies for vaccine distribution and delivery have undermined public procurement platforms, leaving LMICs facing disproportionate shortages necessitating strict criteria for vaccine prioritisation. In anticipation of our first consignment of vaccines, deliberations around phase 1 roll-out were intense and contentious. Although the first phase focuses on healthcare personnel (HCP), the devil is in the detail. Navigating the granularity of prioritising different categories of risk in healthcare sectors in SA is complicated by definitions of risk in personal and occupational contexts. The inequitable public-private divide that characterises the SA health system adds another layer of complexity. Unlike other therapeutic or preventive interventions that are procured independently by the private health sector, COVID-19 vaccine procurement is currently limited to the SA government only, leaving HCP in the private sector dependent on central government allocation. Fair distribution among tertiary, secondary and primary levels of care is another consideration. Taking all these complexities into account, procedural and substantive ethical principles supporting a prioritisation approach are outlined. Within the constraints of suboptimal global health governance, LMICs must optimise progressive distribution of scarce vaccines to HCP at highest risk.

Tracking progress on the health status and service delivery outcomes for neonates and children in the Metro West geographic service area of the Cape Metropole, 2010 - 2015

Background. Monitoring the health status of populations of children is one of the building blocks of the health system. The provision of an indicator dashboard with disaggregated data that are collected over time can be used to gauge the performance of the health system, guide the allocation of resources and prioritise health interventions within districts.Objectives. To determine neonatal and child mortality, morbidity and health service outcomes over a 6-year period in the Metro West geographic service area (GSA) of the Cape Town metropole.Methods. A dashboard with key indicators was developed using existing data.Results. From 2010 to 2015, there was a decrease in the perinatal mortality rate from 31.7 to 24.8 per 1 000 deliveries, and the early neonatal and neonatal mortality rates from 7.8 and 8.6 to 7.0 and 8.2 per 1 000 live births, respectively. The main obstetric causes of early neonatal deaths were antepartum haemorrhage (22 - 24%) and unexplained intrauterine death (13 - 16%); the main neonatal causes were immaturity (17 - 34%), congenital abnormalities (23 - 29%) and hypoxia (23 - 26%). Under-five mortality decreased in 2013 from 25 to 22 per 1 000 live births, with the main causes being neonatal conditions (32%), pneumonia (25%), congenital abnormalities (9%), injuries (8%) and diarrhoea (8%). Fifty percent of child deaths were out of hospital, with pneumonia and diarrhoea accounting for more than half of these. There was an improvement in health service coverage rates in 2015: immunisation <1 year old (99%); measles second dose (85%), pneumococcal third dose (100%) and rotavirus second dose (100%); maternal antiretroviral coverage (90%); HIV testing in mothers (93%); HIV DNA polymerase chain reaction testing in babies (97%); and a decrease in HIV transmission (2%). Exclusive breastfeeding coverage rates at 14 weeks, and vitamin A supplementation at 12 - 59 months, were only 30% and 44%,respectively, across the GSA.Conclusion. There was a decrease in perinatal, early neonatal, infant and under-five mortality in Metro West over the 6 years. Further reductions in under-five mortality will require focusing on interventions to reduce neonatal and out-of-hospital deaths across the service delivery platform. Home visits to at-risk mothers and infants by community health workers could prevent out-of-hospital deaths and improve exclusive breastfeeding and vitamin A coverage. This will require increasing the number of community health workers and broadening their scope of practice

Key issues in the clinical development and implementation of TB vaccines in South Africa.

Significant progress has been made in advancing the development pipeline for a new and more effective TB vaccine with some candidate vaccines now in late stage clinical evaluation. However, progress has been hampered by an incomplete understanding of the components of a protective immune response and limited animal models, rendering the field unable to reliably predict vaccine efficacy earlier in preclinical development, including by evaluation in animal models, and limiting the predictive utility of comparing immunogenic effects across vaccine candidates in phase I/II studies. Consequently, new candidate vaccines have to be evaluated for efficacy in large-scale phase II/III trials using clinical endpoints. Apart from the technical challenges of characterising TB incidence in target populations at high risk of acquiring TB disease and standardising case definitions in order to improve both the sensitivity and more importantly the specificity of trial endpoints, there is an urgency in expanding and supporting the considerable trial infrastructure that will be required to evaluate and ultimately license a new TB vaccine. In the longer term, implementation strategies are dependent on what policy makers most value. Economic analyses will be essential to guide policy and implementation. This paper outlines the gaps and challenges and identifies solutions for effectively developing and efficiently introducing a new TB vaccine.

Tuberculosis case finding for vaccine trials in young children in high-incidence settings: a randomised trial.

SETTING: A high tuberculosis (TB) burden rural area in South Africa. OBJECTIVE: To compare TB case yield and disease profile among bacille Calmette-Guérin (BCG) vaccinated children using two case-finding strategies from birth until 2 years of age. DESIGN: BCG-vaccinated infants were enrolled within 2 weeks of birth and randomised to 3-monthly home visits for questionnaire-based TB screening plus record surveillance of TB registers, hospital admission and X-ray lists at health facilities for TB suspects and cases (Group 1), or record surveillance (as above) only (Group 2). Both groups received a close-out visit after 2 years. Participants were evaluated for suspected TB disease using standardised investigations. RESULTS: A total of 4786 infants were enrolled: 2392 were randomised to Group 1 and 2394 to Group 2. The case-finding rate was significantly greater in Group 1 (2.2/100 py) than in Group 2 (0.8/100 py), with a case-finding rate ratio of 2.6 (95%CI 1.8-4.0, P < 0.001). Although the proportion of cases with bacteriological confirmation was lower in Group 1, this difference did not reach statistical significance. There was also no significant difference in the proportions with TB symptoms and signs. CONCLUSION: Home visits combined with record surveillance detected significantly more cases than record surveillance with a single study-end visit. The TB case profile did not differ significantly between the two groups.

Tuberculin skin test and QuantiFERON® assay in young children investigated for tuberculosis in South Africa.

SETTING: Although the literature on interferon-gamma release assays on tuberculosis (TB) in children has increased, data pertaining to young children remain relatively limited. OBJECTIVE: To compare results from the tuberculin skin test (TST) and the QuantiFERON®-TB Gold In-Tube assay (QFT) in children aged <3 years investigated for TB disease. DESIGN: TB suspects were evaluated by medical history and examination, TST, QFT, chest radiography, induced sputum and gastric washings for smear and culture for Mycobacterium tuberculosis. RESULTS: A total of 400 children were enrolled. Among 397 children with both test results, 68 (17%) were QFT-positive and 72 (18%) were TST-positive (≥10 mm). Agreement between the tests was excellent (94%, κ = 0.79, 95%CI 0.69-0.89). TB disease was diagnosed in 52/397 (13%) participants: 3 definite, 35 probable and 14 possible TB. QFT sensitivity and specificity for TB disease were respectively 38% and 81%. TST sensitivity and specificity were respectively 35% and 84%. CONCLUSION: While TST and QFT had excellent concordance in this population, both tests had much lower sensitivity for TB disease than has been reported for other age groups. Our results suggested equivalent performance of QFT and TST in the diagnosis of TB disease in young children in a high-burden setting.

Age-related tuberculosis incidence and severity in children under 5 years of age in Cape Town, South Africa.

SETTING: Limited data are available on the characteristics of tuberculosis (TB) disease in young children, especially in high-burden countries. OBJECTIVE: To assess the incidence and severity of TB in children aged <5 years. METHODS: TB records and chest radiographs of children born in Cape Town in 1999 and diagnosed with TB between 1999 and 2004 were reviewed retrospectively. RESULTS: A total of 1607 cases were registered. The cumulative incidence of definite (bacteriologically confirmed) and probable (radiological evidence and > or =1 TB clinical feature) TB in children aged <5 years was 2.9% and was highest between the ages of 12 and 23 months. Of 1233 children with definite or probable TB, 506 (41%) had severe disease (dissemination, cavities or >1 lobe involved). The under 5 years incidence of disseminated TB was 0.33%. Of 239 (15%) cases that were bacteriologically confirmed, clinical features typical of TB disease were individually present in <60%. The most common combined symptoms were cough for >2 weeks and weight loss, occurring in 43/239 (18%). CONCLUSION: TB incidence was high, and peaked in children aged 12-23 months. Many children experienced severe disease. A fifth of children with microbiologically confirmed disease presented with only one feature typically associated with TB.