Project Title

Impact of RTS,S/AS01 vaccine and insecticide treated bednets on neurobehavioural impairment and school participation in children from rural Kenya

EDCTP Project Call

Career Development Fellowship (CDF)

Project Objectives

Main objective To determine the impact of impact of RTS,S/AS01 vaccination and ITBN intervention on neurobehavioural impairments and school participation. Specific objectives To compare the prevalence of neurobehavioural impairments between children previously received RTS,S/AS01 or ITBN and those who received placebo; To compare the prevalence of school participation between children previously vaccinated with RTS,S/AS01 or using ITBN and those who received placebo; To investigate the role of malaria episodes, chronic parasitaemia burden, admissions to hospital, doses of vaccine received and immunological correlates of vaccination on neurobehavioural outcomes and school participation of children vaccinated with RTS,S/AS01 or used ITBN

Study Design

Study justification Despite the recent successes in control of malaria of malaria in Africa, about half a million children still die from malaria. In addition, recent studies have ranked malaria among the top causes of DALYs (795 per 100,000) among neglected tropical diseases (Abajobir et al., 2017). Severe malaria is associated with neurobehavioural impairments, in particular acute seizures, epilepsy, behavioural/emotional problems and cognitive impairments. Repeated episodes of mild malaria and chronic parasitisation burden may also be associated with such impairments, particularly in children under 2 years of age, during the period of maximum brain growth. Recently we showed that elimination of malaria may reduce over 90% of neurobehavioural impairments attributable to malaria including seizure disorders. Since vaccination with RTS,S/AS01 was associated with over 50% efficacy against severe malaria in older children and use of ITBN prevented malaria in 44% of children, this may have averted a number of malaria episodes and burden of chronic parasitisation, preventing neurodisabilities attributable to malaria at a critical age of accerelated brain development. This would have important public health implications in that RTS,S/AS01 and ITBN will not only have prevented against malaria episodes but also improved neurobehavioural outcomes and schooling potential of children. Methodology Study participants, design and settings This will be an observation cohort study in which children who participated in RTS,S/AS01 and ITBN trial will be followed up for assessment of neurobehavioural impairments and school participation in 2018, when they will be aged 9-16 years. These cohort studies will have a primary investigational study and a secondary external validation study (Figure 1). Primary investigational study The primary investigational study will attempt to establish whether vaccination with RTS,S/AS01 and participation in the ITBN intervention is associated with

Project Summary

ome of the consequences of being ill with severe malaria include thoughts and emotional problems, learning difficulties, and convulsions including epilepsy; all of which can affect involvement in schooling. Some of these problems may be addressed by prevention of malaria through vaccination and use of bed nets, but the impact needs to be tested in research studies. We want to assess if children who received a malaria vaccine 10 years ago, and those who slept under a bed net, are at present showing fewer thoughts and emotional problems, learning difficulties, convulsions including epilepsy and non-attendance at school, compared to their peers who did not receive these malaria prevention measures. Outcomes for about 368 children who received either a phase II malaria vaccine in Kilifi or phase III malaria vaccine in Kombewa and Siaya will be compared with those who did not receive the vaccine (N=368). Similar number of children were included in the case-comparison study for the impact of use of bednets on the listed outcomes. Over the two years, the protocol for this study was submitted for ethical review in Kenya and Oxford, and permission to conduct the study granted by both committees. Community engagement about the study has been key during the study, while observing COVID-19 guidelines. Training of staff about the study procedures, and development of online tools for data collection is complete. Data collection has started, with recruitments and assessments completed for 80% of the eligible of the participants in Kilifi. From the few assessments completed so far, vaccination appears to be protective against seizure disorders and mental health scores. A review of the literature, supported by this fellowship, showed a lack of therapeutic interventions such as vaccines for improving neurobehavioural outcomes. This study is generating evidence to inform inclusion of routine evaluation of brain function into future malaria prevention interventions including vaccines. Participating in this study is helping the community to appreciate the link between malaria and brain damage, subsequently encouraging them to embrace future malaria prevention measures. Additionally, participating children are usually referred for appropriate care if medical concerns are found during clinical examination.

Host Organisation

Current Organisation

KEMRI-Wellcome Trust Research Programme

Current Job Title

Postdoctoral scientist

Biography