Integrating malaria vaccines into Southeast Asian elimination strategies: A cautious path forward

Malaria, a mosquito-borne parasitic disease transmitted by the Plasmodium species, is as old as humanity.[1] Traditional control methods, such as quinine treatment and insecticide-treated bed nets, have demonstrably reduced malaria burden historically. However, their ultimate effectiveness is limited by the emergence of drug resistance and logistical challenges in delivering interventions to remote populations. Climate change adds another layer of complexity, with the potential to alter mosquito breeding patterns and transmission dynamics in unpredictable ways across different regions.[2] While further research is crucial to understand these nuances,[3] one undeniable consequence is the transformation of malaria into a persistent global threat demanding a renewed and unified international response.

In 2022, 85 endemic countries reported 249 million malaria cases.[3] The urgency of the situation is underscored by the ambitious yet concerning progress toward the malaria elimination targets outlined in UN Sustainable Development Goal 3.3. This target called for a 90% reduction in both malaria incidence and mortality by 2030, alongside the elimination of the disease in at least 35 endemic countries. However, data from the World Health Organization’s (WHO) Global Technical Strategy for Malaria 2016–2030 paint a concerning picture. Progress toward critical malaria control targets, particularly in high-burden countries, has stalled.[4] It highlights the urgent need for renewed global efforts and innovative strategies to achieve malaria elimination.

Emerging biotechnologies like genetically modified mosquitoes and parasite gene drives hold promise for future malaria control; they are still under development and require extensive safety and efficacy testing.[5] Therefore, a multipronged approach, including continued research on existing methods, exploration of novel technologies, and the strategic use of the recently developed malaria vaccine with its moderate protective effect, is increasingly being considered to achieve malaria elimination.[6]

Two WHO-approved malaria vaccines offer a crucial tool in the fight against the disease. The first, RTS,S/AS01 (Mosquirix), received WHO recommendation in October 2021, followed by R21/Matrix-M prequalification in December 2023.[7] Both vaccines require a four-dose regimen starting around 5 months of age. However, despite this progress, the picture in Southeast Asia (SEA) regarding vaccine’s national approvals remains concerning. The Philippines stands out as the sole SEA nation to approve RTS,S/AS01, while India has approved R21/Matrix-M, developed by the University of Oxford and manufactured by the Serum Institute of India. Notably, the WHO Global Malaria Programme Operational Strategy 2024–2030, while outlining four strategic objectives, appears to have limited discussion on the specific integration strategies for these novel vaccines.[8]

The limited national-level approvals for these vaccines in SEA, a region entirely comprised of malaria-endemic nations, present a significant barrier to widespread deployment. Cost also remains a major concern, especially for resource-constrained Low- and Middle-Income Countries (LMICs). While the exact cost of the vaccines and delivery infrastructure remains under evaluation, estimates suggest a per-person cost of $20–40 for the four-dose regimen that questions affordability. Another challenge lies in the current age limitations of these vaccines (children aged 5–17 months). It leaves adults and older children, who also contribute significantly to the malaria reservoir, inadequately protected.

Furthermore, the moderate efficacy of the vaccines, ranging from 25% to 77% with waning immunity over time, raises questions about their practicality within existing, often overburdened, childhood immunization programs that typically include 10–15 vaccines. Finally, the potential for adverse effects also warrants careful consideration. Early trials of RTS,S/AS01 suggested a slight increase in meningitis and febrile seizure risks in some populations,[9] though further studies are required to establish definitive causal links.

While increased global advocacy efforts from the vaccine development community is welcoming to encourage broader program inclusion, rollout of vaccines in endemic countries, especially SEA regions needs serious consideration. India’s low malaria transmission setting as a determinant to prioritize vaccine rollout may serve as a case study.[10] Similar to India, epidemiological assessments in other endemic countries are paramount before national vaccine deployment decisions are made. This ensures a data-driven approach that prioritizes interventions with the greatest potential impact.

Transparency and clear communication regarding potential side effects and ongoing vaccine safety evaluations are crucial for maintaining public trust in vaccination programs. Premature vaccine introduction, disregarding sociocultural considerations and lacking complete safety data, can have cascading negative effects.[9,11] These consequences extend beyond the specific malaria vaccines in question, potentially eroding trust in broader regional vaccination programs.

Finally, cost-effectiveness analyses that consider both short-term costs and long-term economic benefits associated with reduced malaria transmission are essential to inform decision-making. Further research on cost-effectiveness, innovative financing mechanisms for LMICs (e.g., GAVI, the Vaccine Alliance), and efficient delivery models tailored to specific contexts is essential to ensure equitable access for populations most in need. Continued research efforts, increased vaccine accessibility through strategic partnerships, and unwavering commitment from the global health community and religious leaderships are all necessary to overcome these hurdles and achieve significant progress toward malaria elimination.

Ethical clearance

The study do not require ethical approval.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.