The Status of Malaria Vaccines and the Road Ahead

A persistent global threat: Malaria, a mosquito-borne parasitic infection, remains a formidable public health threat on a global scale.? According to the latest World malaria report by WHO, there were?249 million cases of malaria in 2022?compared to 244 million cases in 2021. The estimated number of malaria deaths stood at 608 000 in 2022 compared to 610 000 in 2021.

Challenges of Malaria Control: One of the major challenges in combating malaria is its intricate life cycle. Unlike many infectious diseases, the Plasmodium parasite responsible for malaria undergoes multiple developmental stages within both the mosquito vector (the Anopheles mosquito) and the human host. This complex life cycle makes it difficult to develop interventions that can effectively target the parasite at each vulnerable stage. Furthermore, the existence of five distinct Plasmodium species that infect humans adds another layer of complexity. Of these five species, Plasmodium falciparum, the deadliest, is particularly prevalent in Africa, infecting 94% of cases and 95% of fatalities concentrated on the continent. (Baer K, Klotz C, Kappe SH, et al. 2007)

Socioeconomic Factors as a Breeding Ground for Malaria: Socioeconomic factors further exacerbate the challenges of malaria control. Poverty, limited access to healthcare facilities, and inadequate housing conditions in areas with high malaria transmission create a breeding ground for the disease. These factors make it difficult to implement preventive measures like insecticide-treated bed nets and indoor residual spraying consistently and effectively.? ?

Rising Threat:? While initial progress in reducing malaria deaths was made before 2015, the last decade has seen a concerning stagnation. Global cases dropped by 29% between 2000 and 2019, but this progress stalled, with only a 2% decrease observed between 2015 and 2019. This highlights the urgent need for innovative tools to combat this devastating disease.?

The Development of Malaria Vaccines: Developing a malaria vaccine has been a complex and lengthy process, taking nearly 30 years. The parasite's complex life cycle presented a significant challenge. However, after years of research, we now have two available vaccines:?

• RTS, S/AS01: This vaccine demonstrates a 36% efficacy against clinical malaria in children aged 5-17 months. Pilot studies in Ghana, Kenya, and Malawi have already seen nearly 2 million children receive the vaccine, resulting in a promising 13% reduction in child mortality.?

• R21/Matrix-M: This newly WHO-prequalified vaccine shows even greater promise, with phase 3 results demonstrating a 75% efficacy against the first clinical malaria episode in children aged 5-36 months at seasonal transmission sites and a 68% efficacy in areas with year-round transmission (https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(24)00235-6/fulltext).?

Countries Taking Action:?

• Cameroon: Pioneered the introduction of RTS, S/AS01 into its national immunization program in January 2024.?

• Eight African Countries (as of April 2024): Have begun incorporating unspecified malaria vaccines into their childhood immunization programs.?

• At least ten more African Countries: Expected to follow suit with vaccine rollout by the end of 2024.?

WHO Recommends Malaria Vaccines for Children?

In October 2023, the World Health Organization (WHO) updated its malaria vaccine recommendation for children living in endemic areas, prioritizing those with moderate and high transmission. The recommendation applies to both RTS,S and R21 vaccines.?

Vaccination Schedule and Considerations?

• Children receive the vaccine in a 4-dose schedule starting around 5 months of age.?

• A 5th dose may be offered a year after the 4th dose in areas with high malaria risk.?

• Countries with seasonal malaria transmission may consider age-based, seasonal, or a hybrid approach for vaccination.?

• While prioritizing moderate and high transmission areas, some countries may consider vaccination in low transmission settings based on cost-effectiveness and programmatic considerations.?

• Vaccination should be integrated into comprehensive national malaria control plans.?

Challenges and the Road Ahead?

Despite these advancements, significant hurdles remain:?

• Limited Production Capacity: Both vaccines require a four-dose regimen, and current production capacity struggles to meet demand. With only 18 million initial doses of RTS,S/AS01 available for 12 countries in the next few years, ensuring widespread access is crucial.?

• Funding Shortfalls: The 2023 World Malaria Report highlighted a significant funding gap, with an estimated $7.8 billion needed to effectively combat malaria as reported by Jen (2023) [2].? Increased financial support from donors is essential to help high-burden countries afford and deliver these life-saving vaccines.?

To maximize the impact of these vaccines, a multi-pronged approach is needed:?

• Increased Vaccine Production: Scaling up production is essential to meet the high demand across Africa.?

• Improved Access Strategies: Efforts are needed to overcome logistical and financial barriers to ensure vaccine access for high-risk populations, especially in remote areas.?

• Sustained Funding: Although Gavi's initial investment of $155.7 [3] million provides a strong foundation for vaccine introduction and delivery in eligible countries but continued donor support is vital to bridge the funding gap and ensure affordability for countries disproportionately affected by malaria.?

The combined implementation of malaria vaccines alongside existing intervention and preventative strategies offers a powerful pathway towards the elimination of this ancient disease.? ?

References: ?

1. World Health Organization. (2023, April 28). Malaria [Fact Sheet]. who.int

2. Jen, J. (2023, November 30). World closer than ever to losing fight against malaria as cases rise, expert says [1]. Reuters.?

3. Gavi, the Vaccine Alliance. (2021, December 2). Gavi Board approves funding to support malaria vaccine roll-out in sub-Saharan Africa [Press release]. gavi.org?

4. Release of hepatic?Plasmodium yoelii?merozoites into the pulmonary microvasculature.?PLoS Pathogens ;(11):e171.

Author:

Farah Yeasmin

Grant and Knowledge Management Coordinator

GroupMappers , Mahidol Oxford Tropical Medicine Research Unit MORU