R21/Matrix-M & relevance of malaria vaccines in Asia Pacific

Administering the R21/Matrix-M vaccine. Credit: University of Oxford, Tom Wilkinson 2022

The World Health Organization (WHO) recently endorsed the R21/Matrix-M vaccine, marking a pivotal step in the fight against malaria. This new vaccine primarily acts against P. falciparum and prevents malaria infection in children. This is the second malaria vaccine to be recommended by WHO after the RTS,S/AS01 vaccine in 2021. Both vaccines have demonstrated safety and effectiveness with a focus on safeguarding children in hard-to-reach and high transmission areas, particularly in sub-Saharan Africa.

As a malaria researcher, I used to dream of the day we would have a safe and effective vaccine against malaria. Now we have two. Demand for the RTS,S vaccine far exceeds supply, so this second vaccine is a vital additional tool to protect more children faster, and to bring us closer to our vision of a malaria-free future. Dr Tedros Adhanom Ghebreyesus, WHO Director-General

The introduction of the R21/Matrix-M vaccine prompts the question on its relevance in Asia Pacific. While further research is required, there are clear benefits and limitations to current tools and innovations.

Continuing the status quo is not an option

Based on the 2022 World Malaria Report and national programme data, 95% of global malaria cases continue to be from the African region. While the Asia Pacific region contributed only around 1% to the global total, there has been an alarming recent rise.

In 2022, there were 1.76 million additional cases, with Pakistan experiencing a dramatic increase from 400,000 in 2021 to 1.6 million malaria cases in 2022 -- due in part to climate-related emergencies. Thailand also saw a spike in cases, particularly along the border with Myanmar. Likely due to migrant influx from conflict-stricken Myanmar, cases rose from 3,000 in 2021 to 15,000 by mid-2023 in Thailand. Notably, 92-95% of these were P. vivax cases, which shows possibility of further increases in the future. Among the E-2025 Asia Pacific nations: Bhutan, Malaysia, and Timor-Leste reported zero cases in 2022, while countries like Thailand, Vanuatu, South Korea, and Nepal observed an uptick in indigenous cases.

While the region has made commendable strides towards malaria elimination, achieving the 2030 regional target requires an inclusive approach, ensuring no community is left vulnerable. National programmes and partners possess effective strategies, yet it is crucial to innovate, introduce novel tools to accelerate and sustain efforts, and embrace a science of delivery.

Malaria diversity must be addressed

Five Plasmodium parasite species infect humans with malaria, but P. falciparum and P. vivax are the most threatening. P. falciparum, the deadliest parasite, dominates in Africa with a prevalence of 99.1%. If P. falciparum isn't treated promptly, it can lead to severe illness and death within a day. Tragically, it's responsible for the deaths of 80% of African children under the age of five years.

In the Asia Pacific, species distribution contrasts starkly with Africa. The region records about 48% P. vivax, 32.3% P. falciparum, 19% mixed, and 0.3% other infections. There is also diversity in the prevalence of these species across countries. For instance, P. falciparum rates vary from 4.5% in Afghanistan to 78.5% in the Philippines, while P. vivax ranges between 27% in Papua New Guinea and 95% in Afghanistan. Notably, the Asia Pacific region sees a higher incidence of infections among adults, unlike Africa where children are predominantly affected.

Given the prevalence of P. vivax infections in the region, there is an urgent need to fast-track the development of P. vivax vaccines like Montanide ISA 51, which is currently under clinical trial. The milder symptoms of this infection might seem less threatening, but P. vivax comes with unique challenges, including relapses and extended treatment periods.

Asia Pacific countries require tailored interventions

While countries across the region are at varied elimination stages, all grapple with unique epidemiological, socio-demographic, and resource challenges.

Nations like China, Sri Lanka, and the Maldives have achieved malaria elimination without a vaccine, relying on established strategies like early diagnosis, treatment, and vector control using tools like bivalent RDTs, ACTs, IRS, and LLINs.

However, certain nations do not follow the general trend and bear the highest burden. For instance, Solomon Islands and Papua New Guinea (PNG) report 118 and 65 malaria cases per 1,000 people, with Sandaun province in PNG reaching 209 per 1,000. Nearby, the Indonesian province of Papua holds 88% of the country's disease.

In places where limited accessibility hinders regular surveillance and vector control, vaccines could be another critical tool. In PNG, reaching the nearest health facility can take over eight hours. A province like Milne Bay, with many P. falciparum cases, remote locations, and significant paediatric cases, stands out as a potential site for the new malaria vaccine's validation.

The future of malaria elimination

Despite malaria’s longstanding global impact, vaccine development for malaria has lagged. In contrast, COVID-19 vaccines were rapidly produced within a year, leading to the question: Why the delay for malaria? The challenge lies not just in tackling a formidable parasite but also in the chronic underfunding and lack of urgency for malaria vaccine research and deployment both globally and in Asia Pacific.

To be certain, the R21/Matrix-M vaccine is another landmark achievement. Together, let us help countries in Asia Pacific leverage this historic milestone and encourage region-specific vaccine solutions on the path to malaria elimination. While no one tool will be a silver bullet, vaccines are vital weapons in our arsenal as we seek to end the fight against the world’s oldest fever.

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