Malaria Study Shows Remarkable 70% Reduction in Severe Disease and Death

Judy Stone, MD

August 30, 2021

A new study from Africa shows a remarkable 70% reduction in malaria if two treatments — a vaccine and an antimalarial medication — are combined instead of giving them individually.

Malaria is endemic in the tropics. The World Health Organization (WHO) reports that in 2019, there were 229 million cases and 409,000 deaths from this parasitic infection. Most of the burden (94%) occurs in Africa, and children younger than age 5 account for 67% of the deaths.

In the Sahel region of Africa, a broad, sub-Saharan band that stretches across the continent, high malaria transmission is seasonal. Children in some countries there are treated with monthly courses of sulfadoxine-pyrimethamine and amodiaquine chemoprophylaxis during the 4 higher-risk months. Such seasonal malaria chemoprophylaxis (SMC) has been shown to reduce infections by up to 88% and costs an average of $3.43 per child per year.

This double-blind, randomized controlled trial enrolled young children (5-17 months old) in Burkina Faso and Mali, where SMC is the current treatment regimen. Nearly 6000 children received either chemoprophylaxis, the RTS,S/AS01E malaria vaccine (RTS,S), or both treatments. The study, led by investigators at the London School of Hygiene and Tropical Medicine (LSHTM) in the UK, was reported in the New England Journal of Medicine .

Co-lead investigator Daniel Chandramohan, MBBS, PhD, MSc, professor of public health at LSHTM, told Medscape Medical News that SMC administration is quite labor-intensive and that "we thought we can replace these four cycles of seasonal cure prevention with one seasonal vaccination like the flu vaccine…and that there might be some additive benefit."

Dr Daniel Chandramohan

Instead, the study found the combination reduces the incidence of malaria by 62% against clinical malaria infection, 70% against severe malaria, and 73% against death from malaria compared with SMC alone. "Not in our wildest dreams would I have hypothesized that this is a possibility," Chandramohan said. He continued that this was unlikely a "freak result" because the findings are "consistent between both countries. Two, it is consistent across the years. Three, all the malaria outcomes…are consistently showing the protective effect at the same level."

To maintain the blinded study design, children received injections of rabies vaccine and hepatitis A vaccine instead of a placebo for RTS,S. Both were chosen to provide additional benefits by protecting children against those infections.

With so many children followed over years, accuracy in providing the correct treatment for each study arm can be difficult. Each child was given a QR code and picture identification to facilitate drug distribution each year in this study.

Miriam Laufer, MD, professor and associate director for malaria research at the University of Maryland, who was not involved in the study, told Medscape, "This is a spectacular result, you know, decreasing disease by 60%-70% using interventions that we already have."

RTS,S is not a new vaccine; it was developed in 2001 by GlaxoSmithKline with Path’s Malaria Vaccine Initiative, then manufactured by GSK. The Gates Foundation has supported production. Chandramohan said GSK has transferred the technology to Bharat, in India, and that it will take 2-3 years to ramp up production. Until then, only enough vaccine is available to supply Kenya, Malawi, and Ghana, where the pilot studies are currently being done.

Dr Miriam Laufer

Laufer stressed that the "group that got RTS,S did as well as the group that received SMC." She noted that the use of SMC is limited to specific areas of sub-Sahel with a brief transmission period. In other areas of Africa where malaria has a longer transmission period, SMC isn’t as effective. "RTS,S vaccine could really have an impact" there, she added.

Asked if RTS,S might be substituted for SMC to reduce the likelihood of resistance emerging, Laufer said, "Giving RTS,S vaccine is as good as using repeated treatment of malaria drugs during the malaria season. And that's important for two reasons. One is that the advantage of a vaccine is that you're not producing pressure of drugs that would enable drug resistance to emerge and spread. So maybe your vaccine efficacy could last longer than drug efficacy. We don't know the answer to that."

Hypothesizing about the unexpectedly good trial results, Laufer explained, "We know that RTS,S decreases the number of parasites that make it into the blood when a child is bitten by an infected mosquito. When drugs like sulfadoxine-pyrimethamine and amodiaquine that have moderate efficacy only have to kill off a small number of parasites, they can work better. Maybe that explains why the combination of RTS,S and SMC created such a positive outcome."

Laufer echoed Chandramohan, saying, "Results were much more dramatic than anybody — certainly than I anticipated." Both physicians anticipate that WHO will give full approval for this combination this fall.

Chandramohan and Laufer have disclosed no relevant financial relationships.

New Engl J Med. Published online August 25, 2021. Full text

Judy Stone, MD, is an infectious disease specialist and author of Resilience: One Family's Story of Hope and Triumph Over Evil and of Conducting Clinical Research , the essential guide to the topic. You can find her at or on Twitter @drjudystone .

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