From current vaccine recommendations to everyday practices: An analysis in five sub-Saharan African countries

AbstractBackgroundEstimates of WHO and UNICEF vaccination coverage may provide little insight into the extent to which vaccinations are administered on time. Yet, lack of adherence to the recommended age to receive a specific vaccination may have detrimental health consequences. For example, delays in receiving vaccination will prolong the risk of lack of protection, often when disease risk is highest, such as during early infancy. We estimated the reported age at vaccination, and vaccine coverage at different ages in children from five sub-Saharan African countries.MethodsWe analyzed data from the latest Demographic and Health Programme databases available for Burkina Faso 2010 (n=15,044 observations), Ghana 2008 (n=2992), Kenya 2008–9 (n=6079), Senegal 2010–11 (n=12,326), and Tanzania 2010 (n=8023). We assessed, amongst vaccinees, the exact age when vaccine was administered for the three infant doses of pentavalent vaccine (DTP) and the first dose of measles-containing-vaccine (MCV), as well as the proportion of children immunized with these antigens by a certain age. Vitamin A supplementation (VAS) coverage was evaluated as a potential contact visit for vaccine introduction.ResultsFor all DTP doses, the median intervals between recommended and actual ages of receiving vaccination ranged from 12, 17 and 23 days in Kenya, to 22, 33 and 45 days in Senegal. MCV was mostly given during the recommended age of 9 months. In each country, there was a large discrepancy in the median age at DTP vaccination between regions. VAS coverage in young children ranged from 30.3% in Kenya to 78.4% in Senegal, with large variations observed between areas within each study country.ConclusionIn the context of new vaccine introduction, age of children at vaccination should be monitored to interpret data on vaccine-preventable disease burden, vaccine effectiveness, and vaccine safety, and to adapt targeted interventions and messages

Assessing the safety, impact and effectiveness of RTS,S/AS01E malaria vaccine following its introduction in three sub-Saharan African countries: methodological approaches and study set-up

Background Following a 30-year development process, RTS,S/AS01E (GSK, Belgium) is the first malaria vaccine to reach Phase IV assessments. The World Health Organization-commissioned Malaria Vaccine Implementation Programme (MVIP) is coordinating the delivery of RTS,S/AS01E through routine national immunization programmes in areas of 3 countries in sub-Saharan Africa. The first doses were given in the participating MVIP areas in Malawi on 23 April, Ghana on 30 April, and Kenya on 13 September 2019. The countries participating in the MVIP have little or no baseline incidence data on rare diseases, some of which may be associated with immunization, a deficit that could compromise the interpretation of possible adverse events reported following the introduction of a new vaccine in the paediatric population. Further, effects of vaccination on malaria transmission, existing malaria control strategies, and possible vaccine-mediated selective pressure on Plasmodium falciparum variants, could also impact long-term malaria control. To address this data gap and as part of its post-approval commitments, GSK has developed a post-approval plan comprising of 4 complementary Phase IV studies that will evaluate safety, effectiveness and impact of RTS,S/AS01E through active participant follow-up in the context of its real-life implementation. Methods EPI-MAL-002 (NCT02374450) is a pre-implementation safety surveillance study that is establishing the background incidence rates of protocol-defined adverse events of special interest. EPI-MAL-003 (NCT03855995) is an identically designed post-implementation safety and vaccine impact study. EPI-MAL-005 (NCT02251704) is a cross-sectional pre- and post-implementation study to measure malaria transmission intensity and monitor the use of other malaria control interventions in the study areas, and EPI-MAL-010 (EUPAS42948) will evaluate the P. falciparum genetic diversity in the periods before and after vaccine implementation. Conclusion GSK’s post-approval plan has been designed to address important knowledge gaps in RTS,S/AS01E vaccine safety, effectiveness and impact. The studies are currently being conducted in the MVIP areas. Their implementation has provided opportunities and posed challenges linked to conducting large studies in regions where healthcare infrastructure is limited. The results from these studies will support ongoing evaluation of RTS,S/AS01E’s benefit-risk and inform decision-making for its potential wider implementation across sub-Saharan Africa

Longitudinal estimation of Plasmodium falciparum prevalence in relation to malaria prevention measures in six sub-Saharan African countries.

BACKGROUND: Plasmodium falciparum prevalence (PfPR) is a widely used metric for assessing malaria transmission intensity. This study was carried out concurrently with the RTS,S/AS01 candidate malaria vaccine Phase III trial and estimated PfPR over ≤ 4 standardized cross-sectional surveys. METHODS: This epidemiology study (NCT01190202) was conducted in 8 sites from 6 countries (Burkina Faso, Gabon, Ghana, Kenya, Malawi, and Tanzania), between March 2011 and December 2013. Participants were enrolled in a 2:1:1 ratio according to age category: 6 months-4 years, 5-19 years, and ≥ 20 years, respectively, per year and per centre. All sites carried out surveys 1-3 while survey 4 was conducted only in 3 sites. Surveys were usually performed during the peak malaria parasite transmission season, in one home visit, when medical history and malaria risk factors/prevention measures were collected, and a blood sample taken for rapid diagnostic test, microscopy, and haemoglobin measurement. PfPR was estimated by site and age category. RESULTS: Overall, 6401 (survey 1), 6411 (survey 2), 6400 (survey 3), and 2399 (survey 4) individuals were included in the analyses. In the 6 months-4 years age group, the lowest prevalence (assessed using microscopy) was observed in 2 Tanzanian centres (4.6% for Korogwe and 9.95% for Bagamoyo) and Lambaréné, Gabon (6.0%), while the highest PfPR was recorded for Nanoro, Burkina Faso (52.5%). PfPR significantly decreased over the 3 years in Agogo (Ghana), Kombewa (Kenya), Lilongwe (Malawi), and Bagamoyo (Tanzania), and a trend for increased PfPR was observed over the 4 surveys for Kintampo, Ghana. Over the 4 surveys, for all sites, PfPR was predominantly higher in the 5-19 years group than in the other age categories. Occurrence of fever and anaemia was associated with high P. falciparum parasitaemia. Univariate analyses showed a significant association of anti-malarial treatment in 4 surveys (odds ratios [ORs]: 0.52, 0.52, 0.68, 0.41) and bed net use in 2 surveys (ORs: 0.63, 0.68, 1.03, 1.78) with lower risk of malaria infection. CONCLUSION: Local PfPR differed substantially between sites and age groups. In children 6 months-4 years old, a significant decrease in prevalence over the 3 years was observed in 4 out of the 8 study sites. Trial registration Clinical Trials.gov identifier: NCT01190202:NCT. GSK Study ID numbers: 114001

Role of the Uteroplacental Renin–Angiotensin System in Placental Development and Function, and Its Implication in the Preeclampsia Pathogenesis

Placental development and function implicate important morphological and physiological adaptations to thereby ensure efficient maternal–fetal exchanges, as well as pregnancy-specific hormone secretion and immune modulation. Incorrect placental development can lead to severe pregnancy disorders, such as preeclampsia (PE), which endangers both the mother and the infant. The implication of the systemic renin–angiotensin system (RAS) in the pregnancy-related physiological changes is now well established. However, despite the fact that the local uteroplacental RAS has been described for several decades, its role in placental development and function seems to have been underestimated. In this review, we provide an overview of the multiple roles of the uteroplacental RAS in several cellular processes of placental development, its implication in the regulation of placental function during pregnancy, and the consequences of its dysregulation in PE pathogenesis

Predicted outcomes 2025–2060 of eight vaccine introduction scenarios in 2025.

<p>(i) prevention efficacy 0.0, viral load efficacy 0.0 log₁₀, (ii) prevention efficacy 30%, viral load efficacy 0.0 log₁₀, (iii) prevention efficacy 50%, viral load efficacy 0.0 log₁₀, (iv) prevention efficacy 90%, viral load efficacy 0.0 log₁₀, (v) prevention efficacy 0.0, viral load efficacy 1.0 log₁₀, (vi) prevention efficacy 0.0, viral load efficacy 2.0 log₁₀, (vii) prevention efficacy 50%, viral load efficacy 1.0 log₁₀, (viii) prevention efficacy 90%, viral load efficacy 2.0 log₁₀. All in the context of vaccination at 15, with a rate of vaccination per 3 months of 0.3 amongst those age 15–17 (and a 5 year catch-up program amongst adults age 18–30 covering 50% of the population of that age), with a maximum coverage (in 15–17 year olds) of 70%, and with regular boosters every 5 years (the assumed duration of vaccine effect) with 80% of people being adherent to these boosts.</p

Summary of key variables and main influences in model.

<p>Effects of vaccine are illustrated in grey.</p

Multivariable uncertainty analysis based on 500 runs.

<p>Variation in effect of vaccine on HIV incidence under parameter variation, sampling from distributions of parameter values given in Supplementary Methods and Results in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0107214#pone.0107214.s001" target="_blank">File S1</a>.</p><p>Multivariable uncertainty analysis based on 500 runs.</p

Mean over 2040–2060 of the following outcomes: HIV incidence (per 1000 person years), prevalence (%), % of whole population on ART (not only HIV infected), death rate (in whole population; per 100 person years), % of population age 15–65 with on-going vaccine effect (i.e. vaccinated and up to date with boosters), 2040–2060, for base implementation characteristics.

<p>Base scenario: Coverage 70%, boosting to age 50, with 80% completion rates to boosters, no tapering in effect over time, and with an adult catch-up program in 18–30 years covering 50% of the population of that age, rate vaccination  = 0.3/3mths, vaccine effect on VL in 100% of people, duration of vaccine effect 5 years, age of introduction 15. 95% CI shown in italics.</p>+<p>of entire population, including HIV uninfected.</p><p>Mean over 2040–2060 of the following outcomes: HIV incidence (per 1000 person years), prevalence (%), % of whole population on ART (not only HIV infected), death rate (in whole population; per 100 person years), % of population age 15–65 with on-going vaccine effect (i.e. vaccinated and up to date with boosters), 2040–2060, for base implementation characteristics.</p