Future Vaccines
Malaria
Introduction
Human malaria is caused by a protozoan parasite of five Plasmodium species – five Plasmodium species – P. falciparum, P. ovale, P. malariae, P. knowlesi and P. vivax. Humans are the only known reservoirs of these species, except P. knowlesi whose natural hosts are the long-tailed and pig-tailed macaques.
Human malaria is established following a bite from the female anopheline mosquitoes. The incubation period ranges from 8-14 days. The infection can range from mild fever to life-threatening disease ranging from coma, respiratory distress, severe anemia or circulatory shock. In young children and non-immune adults, the clinical picture can change rapidly from a mild condition to a life-threatening illness.
There were an estimated 263 million new malaria cases and 597,000 malaria deaths globally in 2023. The WHO African Region continues to shoulder the heaviest malaria burden, comprising 94% of malaria cases and 95% of malaria deaths globally. Almost all malaria deaths are caused by Plasmodium falciparum. The risk of P. knowlesi, a simian malaria parasite, is closely tied to rapid deforestation. P. knowlesi is increasingly reported in Southeast Asia, including Malaysia, Indonesia, Thailand, Vietnam, and Myanmar, and has established transmission in Southeast Asia.
Malaysia has come a long way in the prevention and control of malaria since the introduction of the Malaria Eradication Program in 1961 in Sabah and Sarawak, and in 1967 in Peninsular Malaysia. Malaria became a mandatory notifiable disease under the Malaysian Infectious Disease Prevention and Control Act 1988. By 2012, Plasmodium vivax accounted for 50.2% of human malaria cases, followed by P. falciparum (30.7%), P. malariae (16.7%) and mixed infection (2.2%). It’s important to note that children <5 years old only accounted for 2.5% of all cases, whereas 61.9% of the infected cases were those aged 20-49 years. In 2012, Malaysia also reported that of the 61.6% of human malaria cases, 38% were caused by the zoonotic P. knowlesi. Since 2008, Malaysia had already reported >15,000 cases of P. knowlesi infection and about 50 deaths. Infections in 2017 alone totalled 3,600.
Vaccines
Malaria vaccines have been in development since the 1960s, with significant progress in the last decade. Malaria vaccines are now classified by the parasite developmental stage targeted: pre-erythrocytic vaccines, blood stage vaccines, and transmission blocking vaccines. Some vaccines may target multiple developmental stages.
Table 29.11 P. falciparum Malaria Vaccines
Table 29.12 High-Risk Groups (as recommended by WHO)
As of 2024, WHO recommends the use of malaria vaccines for the prevention of P. falciparum malaria in children living in malaria endemic areas, prioritizing areas of moderate and high transmission. Malaria vaccines should be provided as part of a comprehensive malaria control strategy.
Malaysia reports an overall malaria incidence rate of 8.6/100,000 with a mortality rate of 0.03/100,000 by the end of 2022, indicating low transmission setting. Thus, Malaysia does not currently have widespread routine malaria vaccination programmes for the general public, nor travellers. Focus is currently on chemoprophylaxis and vector control programmes for high risk areas to reduce transmission of P. knowlesi and P. falciparum.
As of 2024, WHO does not recommend the malaria vaccines for use in adults (including health workers and pregnant persons). The vaccine is not indicated for travellers, who should use chemoprophylaxis and vector control methods to prevent malaria when travelling to endemic settings.
Evidence of Safety and Effectiveness
Both vaccines are considered to be safe and well tolerated. There is a small risk of febrile seizures within 7 days (mainly within 2–3 days) of vaccination. The most commonly reported adverse reactions were fever, followed less frequently by irritability, and injection site reactions such as pain and swelling.
The two malaria vaccines have been shown to reduce clinical malaria cases by more than half during the 12 months following the initial three doses, and a fourth dose given in the second year of life prolonged efficacy. They have been shown to prevent three-quarters of malaria cases when given seasonally (prior to onset of the rainy season in areas of high seasonal transmission), where seasonal malaria chemoprevention is provided. There is no evidence one vaccine is superior to the other. Current malaria vaccines reduce uncomplicated malaria by ~40%, severe malaria by ~30%, and all-cause mortality by 13%.
References
- World Health Organization (2023). World Malaria Report. https://www.who.int/teams/global-malaria-programme/reports/world-malaria-report-2023
- World Health Organization. (2024). WHO Position paper: Malaria vaccine. Weekly Epidemiological Record. No 19, 2024, 99, 225–248. Available at https://www.who.int/publications/i/item/who-wer-9919-225-248
- World Health Organisation (2024). Malaysia country profile. Available at https://www.who.int/publications/m/item/malaria-2024-mys-country-profile
- Collins, K. A., Snaith, R., Cottingham, M. G., Gilbert, S. C., & Hill, A. (2017). Enhancing protective immunity to malaria with a highly immunogenic virus-like particle vaccine. Scientific reports, 7, 46621. https://doi.org/10.1038/srep46621
- Draper, S. J., Sack, B. K., King, C. R., et al.(2018). Malaria Vaccines: Recent Advances and New Horizons. Cell Host & Microbe, 24(1), 43–56. https://doi.org/10.1016/j.chom.2018.06.008
- Fornace, K. M., Abidin, T. R., Alexander, N., et al. (2016). Association between Landscape Factors and Spatial Patterns of Plasmodium knowlesi Infections in Sabah, Malaysia. Emerging Infectious Diseases, 22(2), 201–208. https://doi.org/10.3201/eid2202.150656
- Ishizuka, A. S., Lyke, K. E., DeZure, A., et al (2016). Protection against malaria at 1 year and immune correlates following PfSPZ vaccination. Nature Medicine, 22(6), 614–623. https://doi.org/10.1038/nm.4110
- Laurens, M.B. (2020). RTS,S/AS01 vaccine (MosquirixTM): an overview. Human Vaccines and Immunotherapeutics;16(3):480-489. Available at https://doi.org/10.1080/21645515.2019.1669415
- Barber, B. E., Rajahram, G. S., Grigg, M. J., William, T., & Anstey, N. M. (2017). World Malaria Report: time to acknowledge Plasmodium knowlesi Malaria Journal, 16(1), 135. https://doi.org/10.1186/s12936-017-1787-y
- Chin AZ, Maluda MCM, Jelip J, Jeffree MSB, Culleton R, and Ahmed K. (2020). Malaria elimination in Malaysia and the rising threat of Plasmodium knowlesi. J Physiol Anthropol ;39(1):36. https://doi.org/10.1186/s40101-020-00247-5.
- Lee, WC., Cheong, F.W., Amir, A. et al. (2022). Plasmodium knowlesi: the game changer for malaria eradication. Malaria J; 21, 140. Available at https://doi.org/10.1186/s12936-022-04131-8
- Malaysia Ministry of Health (2017). Malaria Vaccine. Report 003/2017. Malaysian Health Technology Assessment Section (MaHTAS), Medical Development Division.
- Ministry of Health Malaysia (2023, October) Malaysia Health Facts 2022. https://www.moh.gov.my/moh/resources/Penerbitan/Penerbitan%20Utama/4._Health_Facts_2023-compressed_.pdf