Malaria: Study Reveals Dramatic Reduction in Severe Cases and Deaths Among African Children

For the double-blind, randomized, controlled study, nearly 6 thousand children aged between 5 and 17 months were recruited in Burkina Faso and Mali, two countries with a high malaria burden

A randomized trial found that seasonal vaccination and the combination of preventive medications reduced hospitalizations and deaths in children from malaria by approximately 70%. The results of the phase 3 clinical trial were published in the New England Journal of Medicine. Entitled Seasonal Malaria Vaccination with or without Seasonal Malaria Chemoprevention, the study followed nearly 6000 children aged between 5 and 17 months in Burkina Faso and Mali – two countries with very high disease burden – and where seasonal chemoprophylaxis is the current therapeutic regimen.

Coordinated by researchers from the London School of Hygiene and Tropical Medicine (LSHTM) in partnership with the Institut de Recherche en Sciences de la Santé (Burkina Faso); Malaria Research and Training Center (Mali) and Bamako University of Science, Technology and Techniques (Mali), the study involving the worlds first vaccine against malaria (RTS,S/AS01) found that combined administration rather than isolated, of vaccine and anti-malarial drugs before the rainy season could substantially reduce life-threatening cases in the Sahel (large sub-Saharan strip across Africa), a region where the increase in malaria transmission is seasonal. After three years, the combination of seasonal administration of antimalarials, known as seasonal malaria chemoprophylaxis (SMC) and vaccination has reduced clinical episodes, hospital admissions with severe malaria defined by the World Health Organization (WHO), as well as deaths caused by illness. SMC is the approach currently used in Burkina Faso and Mali. “This is the first time that a combination of chemoprevention and vaccination has been shown to be synergistic in reducing the incidence of uncomplicated and severe malaria”, highlights the LSHTM professor and member of the research team and Dr. Daniel Chandramohan.

For this double-blind, randomized, controlled study, children were divided into three intervention groups, one of which received the RTS,S/AS01E vaccine alone; another received seasonal malaria chemoprevention alone, and the third group received a combination of vaccine and SMC. With this, the team found that a combination of the RTS,S/AS01E and SMC vaccine was more effective than either the vaccine or the SMC alone. The association with the vaccine reduced the incidence of cases of infection by 62%, severe malaria by 70% and death from the disease by 73%.

Dr. Chandramohan explains that the children received three doses of the vaccine before the malaria transmission season in the first year and then a booster dose before the rainy season in subsequent years. Asked whether there was any evidence that the effectiveness of the combined intervention against clinical malaria was greater in the few months after the primary series of vaccinations than after the booster doses, Dr. Chandramohan confirms and says that the effect after the primary doses of the vaccine was greater than the booster doses in year 2 and year 3. “However, the effect of the combination of vaccine and chemoprevention was significantly greater than that of SMC alone. We are following the children in the study to assess the effect of booster doses 3 and 4. The results will be available in 2022”, he adds.

For the researcher, this combination, with surprising results, has the potential to prevent malaria in large parts of Africa, where cases remain high and where the disease is transmitted seasonally. “Seasonal vaccination with seasonal chemoprevention will be a new approach to reduce the burden of malaria in areas of seasonal transmission”, he emphasizes. Also according to Dr. Chandramohan, if resistance to the drugs currently used for SMC increases, seasonal vaccination with RTS,S/AS01 could be a potential solution. “If resistance to Sulfadoxine-pyrimethamine + amodiaquine (SP + AQ) becomes high and if there is no alternative drug combination, seasonal vaccination alone is an option”, he points out.

Seasonal chemoprevention with the vaccine has a positive impact by reducing the effect of the disease on children. However, prevention activities must be a priority for international support. “Hopefully, the WHO Strategic Expert Advisory Group (SAGE)/Malaria Policy Advisory Group (MPAG) meeting in October will recommend scaling up malaria vaccination and possibly a combination of chemoprevention associated with seasonal vaccination”, he celebrates.

Finally, the professor details that the possibility of “rebound or delayed” malaria is being evaluated in his study cohort. They are also modeling and planning to conduct studies to evaluate different approaches to providing the combination of seasonal vaccination and chemoprevention. Both interventions can be delivered in Expanded Programme of Immunization (EPI) mode or in campaigns or a combination of these two approaches. In addition, a cost-benefit study is underway to estimate how many dollars were spent per child/year. “We still dont know the exact price of the vaccine per dose, but we will have an idea in a few months”, he emphasizes.

A cost-effective solution

According to the study Effectiveness of seasonal malaria chemoprevention at a scale in West and Central Africa: an observational study , treatment with SMC was associated with a protective efficacy of 88,2%, with an average economic cost of US$ 3.63 per child/year. The study entitled Cost-effectiveness of district-wide seasonal malaria chemoprevention when implemented through routine malaria control program in Kita, Mali using fixed point distribution ratifies the information.

About malaria

An acute febrile disease, malaria is caused by protozoa of the Plasmodium genus and transmitted by the bite of the Anopheles sp mosquito. The disease, which causes a range of symptoms including headaches, malaise, gastrointestinal problems, back pain, cough and neurological problems ranging from dizziness and seizures to coma, is present in 87 countries. In 2019, 229 million people were infected worldwide, and 409 thousand died from the disease. Children under the age of 5 in sub-Saharan Africa account for approximately two-thirds of these deaths. In 2000, 238 million infections were reported. To learn more, click here. There are five species of parasites that cause malaria and two of these – P. falciparum and P. vivax – are the biggest threats.

About the vaccine

RTS,S/AS01 (trade name Mosquirix) is a protein-based recombinant vaccine. Approved for use by European regulators in July 2015, it is the worlds first licensed malaria vaccine and also the first licensed for use against any human parasitic disease of any kind. RTS,S/AS01 was conceived and created in the late 80s by scientists working at the SmithKline Beecham Biologicals (now GlaxoSmithKline Vaccines) laboratories in Belgium. It was developed through a collaboration between GSK and the Walter Reed Army Research Institute and was funded in part by the PATH Malaria Vaccine Initiative and the Bill & Melinda Gates Foundation. Its effectiveness ranges from 26 to 50% in babies and young children. On October 23rd, 2015, the WHO Strategic Advisory Group on Immunization (SAGE) and the Malaria Policy Advisory Committee (MPAC) jointly recommended a pilot implementation of the vaccine in Africa. This pilot vaccination project was launched on April 23rd, 2019 in Malawi, on April 30th, 2019 in Ghana and on September 13th, 2019 in Kenya.