Choice of disease: Malaria
Research question: What is the cost-utility and the budget impact of scaling up RTS, S/AS01 malaria vaccination of children across different malaria transmission settings relative to scaling up other malaria interventions in Kenya

Study population: Malaria endemic regions in Kenya

Rationale/significance of the research:
There have been a lot of efforts in malaria control from all fronts. These include interventions such as insecticide-treated nets (ITN), indoor residual spraying (IRS), larviciding, chemoprevention, and intermittent preventive treatment (IPT) of pregnant women and infants. Despite all the efforts and evidence of a decrease in malaria cases, malaria is still endemic in sub-Saharan Africa. The progress on elimination is slowing and innovations are needed (Sauboin et al, Kaslow et al). To accelerate this goal, there have to be increased innovations for public health interventions that reduce mortality and morbidity (Alonso et al). Immunization is one of these preventive interventions, with both health and economic benefits to a country (Fullman et al). So far, only one malaria vaccine candidate- RTS, S/AS01 has passed the Phase III trial stage and has been approved for widespread use. RTS, S is a circumsporozoite protein (CSP) subunit vaccine that has been under development for the last three decades by GlaxoSmithKline (GSK) in collaboration with Walter Reed Army Institute of Research (WRAIR) since 1984. R represents the central repeat region, T is the T-lymphocyte epitopes, and S is the surface portion of the Hepatitis B antigen that acts as the carrier matrix for the central repeat region. The other S represents the unfused portion of the Hepatitis B surface antigen that fuses to the RTS. AS01 is the adjuvant portion that improves the RTS, S immunogenicity (Laurens et al). Despite its considerably modest efficacy (Partnerships SCT), it received a positive opinion from the European Medicines Agency following a scientific evaluation by the Committee for Medicinal Products for Human Use in 2015. Subsequently, in 2015 RTS, S/AS01 malaria vaccine got WHO clearance for pilot implementation in three countries in Sub-Saharan Africa- Ghana, Kenya, and Malawi. The implementation in these countries started in 2019 (WHO). In October 2021, WHO recommended widespread use of the RTS, S/AS01 malaria vaccine to prevent Plasmodium falciparum malaria in children living in regions with moderate to high malaria transmission intensity

RTS, S/AS01 malaria vaccine has been ongoing in three countries in Sub-Saharan Africa since 2019 (18). WHO’s recommendation for large-scale implementation of RTS, S mostly focuses on uncertainties around the feasibility of delivering a four-dose schedule that includes new immunization visits in LMIC with already existing immunization coverage challenges (WHO, Asante et al). Additionally, the possibility of a rapidly decreasing protection remains a major disadvantage of this vaccine, coupled with safety concerns of unexplained excess meningitis cases and greater sex differences in all-cause mortality in girls. Countries have considered scaling up malaria treatment and vector control programs as more cost-effective than introducing the malaria vaccine at the current status quos (Mahmoudi et al).

Healthcare systems policy and decision-makers are increasingly adopting results from economic evaluations, such as cost-effectiveness analysis (CEA) and economic impact of health products and technologies including vaccines to support decisions on allocation of healthcare resources (Sara et al). Economic evaluations of RTS,S/AS01 malaria vaccine are still limited in resource-constrained countries- low-income countries (LICs) and lower middle-income countries (LMICs) owing to a lack of both country-specific cost data, clinical effectiveness data and the research capacity (Galactionova et al; Marie et al).
Given that the cost-effectiveness of malaria vaccination varies by different factors such as malaria transmission intensity and country income level, there is a need for country-specific evidence to ensure the efficient allocation of funding toward optimal implementation strategies for malaria vaccination especially when budget is constrained. I aim to conduct a CUA of the malaria vaccine and determine the budget impact of the malaria vaccine scale-up in Kenya.

Modeling can play a crucial role in answering various research questions related to developing and deploying the RTS/ S/AS01 malaria vaccine. These may include:

1. Efficacy Assessment: What is the expected efficacy of a malaria vaccine candidate under different scenarios (e.g., different transmission intensities, population demographics, and vaccine coverage levels)?

2. Impact on Transmission: How will the introduction of a malaria vaccine affect the transmission dynamics of the disease in endemic regions? What is the potential for herd immunity?

3. Optimal Deployment Strategies: What are the most cost-effective and efficient strategies for deploying a malaria vaccine in terms of target populations, timing, and coverage levels?

4. Long-Term Durability: What is the expected duration of protection provided by the malaria vaccine, and how does this impact the overall effectiveness of vaccination programs?

5. Impact on Severe Disease and Mortality: How does vaccination impact the incidence of severe malaria cases and malaria-related deaths? Can modeling estimate the potential reduction in mortality?

6. Integration with Other Interventions: How should malaria vaccination be integrated with other malaria control interventions, such as bed nets, insecticide spraying, or antimalarial drug distribution, to maximize its impact?

Modeling will help to address these questions by simulating different scenarios, estimating outcomes, and optimizing vaccination strategies to inform decision-makers and stakeholders in the fight against malaria in Kenya.