Gregory D. Hussey

Background: Robust evidence that is contextual, relevant, and timely is crucial to the effective functioning of National Immunization Technical Advisory Groups (NITAGs). These groups provide independent advice to their Ministry of Health on issues related to immunization and vaccines, based on evidence and the national context. Similarly, evidence generation is a major hallmark of academic institutions. To ensure national immunization policies benefits from local and contextual evidence, there should be a strong linkage between academic institutions and NITAGs. This study investigated NITAGs and local academic linkage strategies and ways to strengthen such linkages. Methods: The WHO’s quick guide manual on “Performing a landscape analysis: Understanding health product research and development” was adapted and utilized for this landscape analysis which was conducted in two broad phases. The first phase involved the review of published literature, while the second phase entailed key informant interviews (KIIs) with NITAG members and other identified stakeholders in the study countries of Ethiopia and Zambia. The transcripts were transcribed and thematically analyzed. Results: The landscape analysis highlights the paucity of materials focused on documenting the linkage between NITAGs and local academic institutions. The main cross-cutting theme identified from the analysis of the KIIs is the informal and ‘ad hoc’ nature of the linkage, which interviewees described as “working”; was sub-optimal. Conclusion: The overwhelming recommendation calls for the formalization and official recognition of the relationship.

The World Health Organization (WHO) recommends the consideration of introducing routine hepatitis A vaccination into national immunization schedules for children ≥ 1 years old in countries with intermediate HAV endemicity. Recent data suggest that South Africa is transitioning from high to intermediate HAV endemicity, thus it is important to consider the impact and cost of potential routine hepatitis A vaccination strategies in the country. An age-structured compartmental model of hepatitis A transmission was calibrated with available data from South Africa, incorporating direct costs of hepatitis A treatment and vaccination. We used the calibrated model to evaluate the impact and costs of several childhood hepatitis A vaccination scenarios from 2023 to 2030. We assessed how each scenario impacted the burden of hepatitis A (symptomatic hepatitis A cases and mortality) as well as calculated the incremental cost per DALY averted as compared to the South African cost-effectiveness threshold. All costs and outcomes were discounted at 5%. For the modelled scenarios, the median estimated cost of the different vaccination strategies ranged from USD 1.71 billion to USD 2.85 billion over the period of 2023 to 2030, with the cost increasing for each successive scenario and approximately 39–52% of costs being due to vaccination. Scenario 1, which represented the administration of one dose of the hepatitis A vaccine in children < 2 years old, requires approximately 5.3 million vaccine doses over 2023–2030 and is projected to avert a total of 136,042 symptomatic cases [IQR: 88,842–221,483] and 31,106 [IQR: 22,975–36,742] deaths due to hepatitis A over the period of 2023 to 2030. The model projects that Scenario 1 would avert 8741 DALYs over the period of 2023 to 2030; however, it is not cost-effective against the South African cost-effectiveness threshold with an ICER per DALY averted of USD 21,006. While Scenario 3 and 4 included the administration of more vaccine doses and averted more symptomatic cases of hepatitis A, these scenarios were absolutely dominated owing to the population being infected before vaccination through the mass campaigns at older ages. The model was highly sensitive to variation of access to liver transplant in South Africa. When increasing the access to liver transplant to 100% for the baseline and Scenario 1, the ICER for Scenario 1 becomes cost-effective against the CET (ICER = USD 2425). Given these findings, we recommend further research is conducted to understand the access to liver transplants in South Africa and better estimate the cost of liver transplant care for hepatitis A patients. The modelling presented in this paper has been used to develop a user-friendly application for vaccine policy makers to further interrogate the model outcomes and consider the costs and benefits of introducing routine hepatitis A vaccination in South Africa.

Immune activation is associated with increased risk of tuberculosis (TB) disease in infants. We performed a case-control analysis to identify drivers of immune activation and disease risk. Among 49 infants who developed TB disease over the first 2 years of life, and 129 healthy matched controls, we found the cytomegalovirus-stimulated (CMV-stimulated) IFN-γ response to be associated with CD8 ⁺ T cell activation (Spearman’s rho, P = 6 × 10 ^–8 ). A CMV-specific IFN-γ response was also associated with increased risk of developing TB disease (conditional logistic regression; P = 0.043; OR, 2.2; 95% CI, 1.02–4.83) and shorter time to TB diagnosis (Log Rank Mantel-Cox, P = 0.037). CMV ⁺ infants who developed TB disease had lower expression of NK cell–associated gene signatures and a lower frequency of CD3 ^– CD4 ^– CD8 ^– lymphocytes. We identified transcriptional signatures predictive of TB disease risk among CMV ELISpot–positive (area under the receiver operating characteristic [AUROC], 0.98, accuracy, 92.57%) and –negative (AUROC, 0.9; accuracy, 79.3%) infants; the CMV ^– signature was validated in an independent infant study (AUROC, 0.71; accuracy, 63.9%). A 16-gene signature that previously identified adolescents at risk of developing TB disease did not accurately classify case and control infants in this study. Understanding the microbial drivers of T cell activation, such as CMV, could guide new strategies for prevention of TB disease in infants.

Hepatitis A, caused by the hepatitis A virus (HAV), is a vaccine preventable disease. In Low and Middle-Income Countries (LMICs), poor hygiene and sanitation conditions are the main risk factors contributing to HAV infection. There have been, however, notable improvements in hygiene and sanitation conditions in many LMICs. As a result, there are studies showing a possible transition of some LMICs from high to intermediate HAV endemicity. The World Health Organization (WHO) recommends that countries should routinely collect, analyse and review local factors (including disease burden) to guide the development of hepatitis A vaccination programs. Up-to-date information on hepatitis A burden is, therefore, critical in aiding the development of country-specific recommendations on hepatitis A vaccination. We conducted a systematic review to present an up-to-date, comprehensive synthesis of hepatitis A epidemiological data in Africa. The main results of this review include: 1) the reported HAV seroprevalence data suggests that Africa, as a whole, should not be considered as a high HAV endemic region; 2) the IgM anti-HAV seroprevalence data showed similar risk of acute hepatitis A infection among all age-groups; 3) South Africa could be experiencing a possible transition from high to intermediate HAV endemicity. The results of this review should be interpreted with caution as the reported data represents research work with significant sociocultural, economic and environmental diversity from 13 out of 54 African countries. Our findings show that priority should be given to collecting HAV seroprevalence data and re-assessing the current hepatitis A control strategies in Africa to prevent future disease outbreaks.

Varicella zoster virus (VZV) causes varicella and herpes zoster. These vaccine preventable diseases are common globally. Most available data on VZV epidemiology are from industrialised temperate countries and cannot be used to guide decisions on the immunization policy against VZV in Africa. This systematic review aims to review the published data on VZV morbidity and mortality in Africa. All published studies conducted in Africa from 1974 to 2015 were eligible. Eligible studies must have reported any VZV epidemiological measure (incidence, prevalence, hospitalization rate and mortality rate). For inclusion in the review, studies must have used a defined VZV case definition, be it clinical or laboratory-based. Twenty articles from 13 African countries were included in the review. Most included studies were cross-sectional, conducted on hospitalized patients, and half of the studies used varying serological methods for diagnosis. VZV seroprevalence was very high among adults. Limited data on VZV seroprevalence in children showed very low seropositivity to anti-VZV antibodies. Co-morbidity with VZV was common. There is lack of quality data that could be used to develop VZV control programmes, including vaccination, in Africa. PROSPERO 2015: CRD42015026144 .

Africa is considered an area of high endemicity for hepatitis A virus infection. However, in the past two decades, tremendous progress has been made in improving water sources and sanitation which are risk factors for hepatitis A virus infection. Recent studies suggest that several African countries could be in epidemiological transitions due to the evident socio-economic development. As a result, there may be a decrease in the exposure to and infection with hepatitis A virus at an early age. Understanding and mapping the shifting epidemiology is vital in developing control measures against the disease. We are conducting a comprehensive systematic review study to document the current burden of hepatitis A virus infection in Africa. Our population of interest is children between 1 and 10 years in any African country. We will select cross-sectional, case-control, and cohort studies that have tested hepatitis A virus infection by serological confirmation of antibodies against the virus. We will search for eligible studies published without language restrictions from PubMed, Scopus, Africa-wide, Web of Science, and WHOLIS as well as the reference lists of the relevant articles. Two authors will independently review the search outputs, select eligible articles, and extract pre-defined study outcomes. Inconsistencies will be resolved by discussion and consensus among the authors. Data will be extracted using a standardised data collection form. Trends in the prevalence and/or incidence will be evaluated by urban and rural setting if sufficient data is available. Where there is sufficient homogeneity between studies, meta-analysis will also be conducted, otherwise the results will be presented in a narrative format. The systematic review will generate up-to-date information on the current burden of hepatitis A virus in Africa. This information may have implications on policy for hepatitis A vaccination on individual African countries. CRD42015023764