Dataset Information

Potential effect modification of RTS,S/AS01 malaria vaccine efficacy by household socio-economic status.

ABSTRACT:

Background

In the phase III RTS,S /AS01 trial, significant heterogeneity in efficacy of the vaccine across study sites was seen. Question on whether variations in socio - economic status (SES) of participant contributed to the heterogeinity of the vaccine efficacy (VE) remains unknown.

Methods

Data from the Phase III RTS,S /AS01 trial in children aged 5-17?months in Kintampo were re-analysed. SES of each child was derived from the Kintampo Health and Demographic Surveillance System, using principal component analysis of household assets. Extended Cox regression was used to estimate the interaction between RTS,S/AS01 VE and household SES.

Results

Protective efficacy of the RTS,S/AS0 vaccine significantly varied by participant's household SES, thus increase in household SES was associated with an increase in protective efficacy (P-value?=?0.0041). Effect modification persisted after adjusting for age at first vaccination, gender, distance from community to the health facility, child's haemoglobin level, household size, place of residence and mothers' educational level.

Conclusion

Household SES may be a proxy for malaria transmission intensity. The study showed a significant modification of the RTS,S/AS01 malaria vaccine efficacy by the different levels of child's household socio - economic status.

Trial registration

Efficacy of GSK Biologicals' candidate malaria vaccine (25049) against malaria disease in infants and children in Africa. NCT00866619 prospectively registered on 20 March 2009.

SUBMITTER: Gyaase S

PROVIDER: S-EPMC7845116 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Potential effect modification of RTS,S/AS01 malaria vaccine efficacy by household socio-economic status.

Gyaase Stephaney S Asante Kwaku Poku KP Adeniji Elisha E Boahen Owusu O Cairns Matthew M Owusu-Agyei Seth S

BMC public health 20210128 1

<h4>Background</h4>In the phase III RTS,S /AS01 trial, significant heterogeneity in efficacy of the vaccine across study sites was seen. Question on whether variations in socio - economic status (SES) of participant contributed to the heterogeinity of the vaccine efficacy (VE) remains unknown.<h4>Methods</h4>Data from the Phase III RTS,S /AS01 trial in children aged 5-17 months in Kintampo were re-analysed. SES of each child was derived from the Kintampo Health and Demographic Surveillance Syste ...[more]

PMID: 33509156

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Project description:BackgroundRTS,S/AS01 is the first vaccine against malaria to undergo pilot implementation, beginning in 2019 and vaccinating 360,000 children per year in Malawi, Ghana, and Kenya. The four-dose vaccine is given as a primary three-dose series with a fourth dose given approximately 18 months later. The efficacy of RTS,S/AS01 was variable among the 11 sites participating in the 2009-2014 phase III trial (MALARIA-055, NCT00866619), possibly due to differences in transmission intensity. However, a within-site examination of environmental factors related to transmission intensity and their impact on vaccine efficacy has yet to be conducted.MethodsWe implemented the phase III RTS,S/AS01 trial at the Malawi site, which enrolled 1578 infants (6-12 weeks) and children (5-17 months) living in the Lilongwe District in Central Malawi and followed them for 3 years between 2009 and 2014. A global positioning system survey and an ecological questionnaire were conducted to collect participant household locations and characteristics, while additional data on background malaria prevalence were obtained from a concurrent Malaria Transmission Intensity (MTI) survey. Negative binomial regression models were used to assess whether the efficacy of the vaccine varied by estimated background malaria prevalence, household roof type, or amount of nearby vegetation.ResultsVaccine efficacy did not significantly vary by estimated malaria prevalence or by roof type. However, increased vegetation cover was associated with an increase in the efficacy of the three-dose primary RTS,S/AS01 series in the 18 months before the fourth dose and a decrease in the efficacy of the primary vaccine series in the second 18 months following, if the fourth dose was not given. Vegetation cover did not alter the efficacy of the fourth dose in a statistically or practically significant manner.ConclusionsVegetation coverage in this study site might be a proxy for nearness to rivers or branching, shallow wetlands called "dambos" which could serve as breeding sites for mosquitoes. We observed statistically significant modification of the efficacy of RTS,S/AS01 by forest cover, suggesting that initial vaccine efficacy and the importance of the fourth dose varies based on ecological context.Trial registrationEfficacy of GSK Biologicals' Candidate Malaria Vaccine (257049) Against Malaria Disease Caused by P. falciparum Infection in Infants and Children in Africa. NCT00866619 prospectively registered 20 March 2009.

Project description:BackgroundThe candidate malaria vaccine RTS,S/AS01 is being evaluated in order to inform a decision regarding its inclusion in routine vaccination schedules.MethodsWe conducted 7 years of follow-up in children who had been randomly assigned, at 5 to 17 months of age, to receive three doses of either the RTS,S/AS01 vaccine or a rabies (control) vaccine. The end point was clinical malaria (temperature of ≥37.5°C and infection with Plasmodium falciparum of >2500 parasites per cubic millimeter). In an analysis that was not prespecified, the malaria exposure of each child was estimated with the use of information on the prevalence of malaria among residents within a 1-km radius of the child's home. Vaccine efficacy was defined as 1 minus the hazard ratio or the incidence-rate ratio, multiplied by 100, in the RTS,S/AS01 group versus the control group.ResultsOver 7 years of follow-up, we identified 1002 episodes of clinical malaria among 223 children randomly assigned to the RTS,S/AS01 group and 992 episodes among 224 children randomly assigned to the control group. The vaccine efficacy, as assessed by negative binomial regression, was 4.4% (95% confidence interval [CI], -17.0 to 21.9; P=0.66) in the intention-to-treat analysis and 7.0% (95% CI, -14.5 to 24.6; P=0.52) in the per-protocol analysis. Vaccine efficacy waned over time (P=0.006 for the interaction between vaccination and time), including negative efficacy during the fifth year among children with higher-than-average exposure to malaria parasites (intention-to-treat analysis: -43.5%; 95% CI, -100.3 to -2.8 [P=0.03]; per-protocol analysis: -56.8%; 95% CI, -118.7 to -12.3 [P=0.008]).ConclusionsA three-dose vaccination with RTS,S/AS01 was initially protective against clinical malaria, but this result was offset by rebound in later years in areas with higher-than-average exposure to malaria parasites. (Funded by the PATH Malaria Vaccine Initiative and others; ClinicalTrials.gov number, NCT00872963.).

Project description:Malaria is a parasitic infection caused by bites from Plasmodium falciparum (P. falciparum)-infected mosquitoes with a present scale of symptoms ranging from moderate fever to neurological disorders. P. falciparum is the most lethal of the five strains of malaria, and is a major case of morbidity and mortality in endemic regions. Recent advancements in malaria diagnostic tools and prevention strategies have improved conjugation antimalarial therapies using fumigation and long-lasting insecticidal sprays, thus lowering malarial infections. Declines in the total number of infected individuals have been correlated with antimalarial drugs. Despite this, malaria remains a major health threat, affecting more than 30 million men, women, and children around the globe, and 20 percent of all children around the globe have malaria parasites in their blood. To overcome this life-threatening condition, novel therapeutic strategies, including immunization, are urgently needed to tackle this infection around the world. In line with this, the development of the RTS, S vaccine was a significant step forward in the fight against malaria. RTS, S is a vaccine for P. falciparum in which R specifies central repeat units, T the T-cell epitopes, and S indicates surface antigen. The RTS, S/AS01 malarial vaccine was synthesized and screened in several clinical trials between 2009 and 2014, involving thousands of young children in seven African countries, showing that children who received the vaccine did not suffer from severe malaria. Mosquirix™ was approved by the World Health Organization in 2021, indicating it to be safe and advocating its integration into routine immunization programs and existing malaria control measures. This paper examines the various stages of the vaccine's development, including the evaluation of its immunogenicity and efficacy on the basis of a total of 2.3 million administered doses through a routine immunization program. The protection and effectiveness provided by the vaccine are strong, and evidence shows that it can be effectively delivered through the routine child immunization platform. The economic cost of the vaccine remains to be considered.

Dataset Information

Potential effect modification of RTS,S/AS01 malaria vaccine efficacy by household socio-economic status.

Background

Methods

Results

Conclusion

Trial registration

Publications

Potential effect modification of RTS,S/AS01 malaria vaccine efficacy by household socio-economic status.

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