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August 26, 2021
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‘Remarkable’: Combining vaccination, chemoprevention significantly reduces malaria

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A combination of seasonal vaccination and chemoprevention reduced malaria episodes and deaths among children by around 70% compared with either intervention alone during a 3-year study in two African countries, researchers reported.

The vaccine, RTS,S/AS01E (GlaxoSmithKline), was the first vaccine ever shown to significantly reduce malaria in children. It is being administered in a pilot program in three African countries — Ghana, Kenya and Malawi.

Chandramohan D, et al. New Engl J Med. 2021;doi:10.1056/NEJMoa2026330
Chandramohan D, et al. New Engl J Med. 2021;doi:10.1056/NEJMoa2026330

Results of the study published this week in The New England Journal of Medicine are from a study conducted from 2017 to 2020 in Burkina Faso and Mali.

Daniel Chandramohan,

“The burden of severe malaria continues to be high in countries where seasonal malaria chemoprevention is implemented, so it is clear that we need an effective intervention in addition to seasonal malaria chemoprevention,” Daniel Chandramohan, MBBS, PhD, MSc, a professor of public health at the London School of Hygiene and Tropical Medicine, told Healio.

“It has been shown that the RTS,S malaria vaccine has good protective efficacy for at least first 6 months post-vaccination,” Chandramohan said. “This prompted our study to test the hypothesis that a combination of seasonal malaria vaccination with chemoprevention will reduce the burden of malaria in this region.”

Chandramohan and colleagues performed an individually randomized, controlled trial to assess whether seasonal vaccination with RTS,S administered with the adjuvant AS01E was noninferior to chemoprevention in preventing uncomplicated malaria and whether the interventions used together were superior to either one used alone in preventing uncomplicated malaria and severe malaria-related outcomes.

According to the study, from April through May of 2017, the researchers randomly assigned 6,861 children aged 5 to 17 months of age to receive seasonal chemoprevention with sulfadoxine-pyrimethamine and amodiaquine alone (n = 2,287), the vaccine alone (n = 2,288), and 2,286 to receive a combination of both.

A total of 1,716 children in the chemoprevention-alone group, 1,734 in the vaccine-alone group and 1,740 in the combination group received their first dose of treatment and completed follow-up through May 31, 2020.

In total, there were 305 events of uncomplicated clinical malaria per 1,000 person-years at risk in the chemoprevention-alone group, 278 in the vaccine-alone group and 113 in the combination group, the researchers reported. The calculated protective efficacy of the combination compared with chemoprevention alone was 62.8% (95% CI, 58.4-66.8) against clinical malaria, 70.5% (95% CI, 41.9-85) against hospital admission with severe malaria based on the WHO definition, and 72.9% (95% CI, 2.9-92.4) against death from malaria.

They calculated the protective efficacy of the combination compared with the vaccine alone against these outcomes to be 59.6% (95% CI, 54.7-64), 70.6% (95% CI, 42.3-85) and 75.3% (95% CI, 12.5-93), respectively.

Ashley Birkett, PhD, director of PATH’s Malaria Vaccine Initiative, called the results “remarkable.” PATH provided some funding for the study.

“This represents a potential breakthrough for how the world’s first malaria vaccine could be used in a new way to save children’s lives,” Birkett said in a press release. “The evidence from Burkina Faso and Mali suggests that in areas with highly seasonal malaria, using the RTS,S vaccine just prior to the peak transmission season in combination with current malaria control interventions, could have a major impact.”