For Infant/Toddler Malaria Prevention, Vaccine Not Inferior to Drugs, but Both Are Best

By Gene Emery

August 26, 2021

NEW YORK (Reuters Health) - A malaria study comparing monthly chemoprevention, vaccination, or both among children aged 5 months to 17 months has concluded that the combination works best, and that seasonal vaccination is not inferior to daily treatment with amodiaquine, sulfadoxine and pyrimethamine.

Those receiving the vaccine RTS,S/AS01-E were not significantly more likely to develop uncomplicated malaria or have a severe malaria-related outcome compared to children given the prevention drugs during the malaria season.

Yet the children who received both treatments saw their risk of clinical malaria drop by 62.8%, their odds of hospitalization for severe malaria decline by 70.5% and their chances of death from malaria go down by 72.9% compared with children who only received the drugs. The number of all-cause deaths dropped by 53.4%.

The respective risks compared with vaccination alone declined by 59.6%, 70.6% and 75.3% respectively when both treatments were given. All of the findings were statistically significant.

Results of the randomized study, conducted from 2017 through 2019 on 6,861 children in Burkina Faso and Mali, appear in The New England Journal of Medicine. An extension study is continuing to follow the children until their fifth birthday.

"The combination of drugs and vaccine works very well in this situation of highly seasonal malaria, which is a lot of Africa," senior author Dr. Brian Greenwood, a professor of tropical medicine at the London School of Hygiene and Tropical Medicine, told Reuters Health by phone. "This is really good news."

An estimated 409,000 people died of malaria in 2019 according to the World Health Organization. Most were children.

The sulfadoxine-pyrimethamine combination and amodiaquine were given as four treatments, one per month during each malaria season. The vaccine, made by GlaxoSmithKline, sold under the brand name Mosquirix, but usually referred to as RTS,S, was given five times - in April, May and June of 2017 and then each June, just before the rainy season.

Children in the vaccine group received placebo medication. Those in the chemoprevention group received three doses of the Rabipur inactivated rabies vaccine in 2017 and injections of the Havrix hepatitis A vaccine in June of 2018 and 2019 to make it harder to determine which child has received which malaria treatment.

All of the parents were given insecticide-treated bed netting for their children at the time of enrollment, a strategy known to cut malaria risk by roughly half.

The incidence of clinical malaria was 304.8 events per 1,000 person-years at risk in the group that received the drugs but not the vaccine, 278.2 among those who got the vaccine but not the shots, and 113 in the combination group.

"The incidences of death from any causes, excluding external causes and surgery, and deaths attributable to malaria were also markedly lower in the combination group than in either single-intervention group," the researchers say.

Of the 3,955 children who received the vaccine, five had febrile seizures the day after their vaccination. All recovered with no further problems.

Dr. Greenwood said the seizures were likely an offshoot of a high fever that some children experience, but "the children do perfectly well the next day."

There were no other serious side effects attributable to the vaccine. "What we didn't find was the meningitis and more deaths in females" that had been a potential concern in earlier tests, he said.

The group is now hoping to test the effectiveness of the vaccine in older children.

The vaccine has already been given to more than 740,000 children in Ghana, Kenya and Malawi, according to Dr. Pedro Alonso, director of the World Health Organization's Global Malaria Program.

The study did not have commercial funding.

SOURCE: The New England Journal of Medicine, online Aug. 25, 2021.