By Gift Briton

Combining malaria vaccines with antimalarial drugs has shown dramatic reductions in Malaria cases and deaths among children below five years in settings of highly seasonal malaria transmission.

This is according to the final results of a landmark study published in The Lancet Infectious Diseases.

According to the study findings, vaccine-drug combination has reduced clinical malaria episodes, including cases of severe malaria, and deaths from malaria in young children by nearly two-thirds compared with either RTS,S vaccination or seasonal malaria chemoprevention (SMC) alone.

SMC, which involves giving antimalarial drugs sulfadoxine-pyrimethamine and amodiaquine to young children four or five times during the rainy season when malaria transmission peaks, is highly effective in preventing malaria and was recommended by WHO in 2012 for use in areas with highly seasonal transmission.

The RTS, S vaccine was approved in 2021 for use in children in regions of moderate to high malaria transmission within sub-Saharan Africa.

The authors say that this finding offers a potential new approach to malaria control in areas with seasonal malaria transmission.

The study which was conducted in Mali and Burkina Faso followed more than 5,000 children over a total of five years and confirmed that the efficacy of RTS,S in preventing malaria in highly seasonal settings was similar, or “non-inferior,” to that of SMC.

“In addition to the study’s findings—which by themselves are remarkable—we can say that children who received the RTS,S-drug combination and also used bednets likely had greater than 90% protection against malaria episodes during the study. This points to the importance of ensuring access to multiple malaria prevention tools for reducing the tremendous burden of malaria disease and death in these highly seasonal settings,” Professor Brian Greenwood, a member of the research team, said.

Professor Jean-Bosco Ouedraogo, PhD, also a member of the research team, said, “It is tremendously exciting to know that our research could benefit the health of millions of children at high risk of malaria in countries like Burkina Faso and Mali. The challenge now is to determine how best to deliver the vaccine-drug combination and to follow these highly protected children as they grow older.”

Over the full five years of the study, protective efficacy of the RTS,S-SMC combination was very similar to that seen in the first three years, with protective efficacy of the combination versus SMC alone being 57.7% and versus RTS,S alone, 59%.

Also, compared with SMC alone, the RTS,S-SMC combination reduced by two-thirds hospital admissions for WHO-defined severe malaria (66.8%), malarial anemia (65.9%), blood transfusions (68.1%), and malaria deaths (66.8%).

Professor Alassane Dicko, MD, of the Malaria Research and Training Center and a member of the research team, said, “Our study showed that administering the RTS,S vaccine seasonally every year reduces the burden of malaria drastically in children under the age of 5, who are the most affected by this disease. Rapid implementation of this new additional tool is needed to reduce the huge burden of malaria on children in our countries.”

Continued testing of a subset of children in the study found that the drugs currently used for SMC remain effective in the study areas. However, the study authors concluded that seasonal vaccination with RTS,S could be a potential solution, if resistance to the drugs increases and no alternatives are available.

“These study results come at a critical time. Nearly half of childhood deaths from malaria are in children living in areas of highly seasonal transmission. These data show the remarkable reduction in malaria that can be achieved by strategically delivering the vaccine with other effective interventions—and the potential for saving many young lives,” Mary Hamel, MD, Senior Technical Officer at the WHO Product Development Research Unit and Team Lead for Malaria Vaccines said.

“This study’s findings should be a source of hope for families in these highly malarious areas. But they also present a challenge to regulators, policymakers, and donors: how to ensure that these lifesaving interventions are available and accessible to all who need them. No child should die from malaria or have their potential sapped by repeated malaria illnesses,” said Ashley Birkett, PhD, Global Head of Malaria Vaccines and Biologics at PATH.

The study was coordinated by the London School of Hygiene & Tropical Medicine (LSHTM) with partners Institut des Sciences et Techniques and Institut de Recherche en Sciences de la Santé, Burkina Faso; the Malaria Research and Training Center, University of Sciences, Techniques and Technologies of Bamako, Mali; and PATH, Seattle, Washington, USA.