“As some of you may know, I started my career as a malaria researcher, and I longed for the day that we would have an effective vaccine against this ancient and terrible disease. Today is that day, an historic day.”
- Tedros Adhanom Ghebreyesus, WHO Director General
“In many ways, the future remains hopeful for tackling malaria as long as we stay the course . . . and add new antimalarial arrows to our quiver. But no one with in-depth knowledge of this killer that once afflicted a far larger swath of our world ever said it would be easy.”
- Claire Panosian Dunavan, MD, professor of medicine and infectious diseases, David Geffen School of Medicine, UCLA
There are now 42 “malaria free” territories and nations in the world. Although the campaign to eliminate malaria is progressing, we still have a long way to go to rid the world of this scourge. Several recent developments, however, have energized the scientific and world health communities in their quest to conquer this horrific enemy. In this Germ Gems post, I summarize these recent advances as well as the formidable challenges that lie ahead.
Synopsis of malaria’s impact. The mosquito-borne parasite Plasmodium has wreaked havoc on human populations since ancient times. (I provide more information on malaria in my January 20, 2021, Germ Gems post “Microbes that Stop Malaria.”) According to the latest World malaria report, there were 247 million cases of malaria across 90 countries in 2021. That year the estimated number of malaria deaths stood at 619,000, and, tragically, most occurred in children under five years of age in sub-Saharan Africa.
First, the good news. Without question, the biggest and most exciting development in malaria research in recent memory was the roll-out in October 2021 of the “world’s first malaria vaccine”—a vaccine that was 30 years in the making. The World Health Organization declared it “A Historical Event.”
The new vaccine, produced by Oxford University and its collaborators, is called “R21/Matrix-M” (Trade Name, Mosquirix). Given in four doses, the vaccine works by stimulating a child’s immune system to thwart Plasmodium falciparum, the deadliest of five malaria pathogens, and by targeting the sporozoite (the first stage of the parasite to enter the body after a bite by an infected mosquito).
Many tropical medicine researchers herald the vaccine as the “holy grail of malaria prevention.” More than 2.3 million doses already have been administered and, so far, the vaccine is proving effective and safe in large Phase III Trials in Africa.
The R21 vaccine wasn’t the only malaria vaccine to capture attention in 2021. In the June 2021 issue of Nature, scientists reported the results of a small study of a malaria vaccine that combines live P. falciparum sporozoites with a dose of an antimalarial drug, chloroquine or pyrimethamine. The parasite and drug combo (“a one-two punch”) showed 87.5% efficacy. If the results hold up in a larger study, experts agree this would be a fantastic addition to the antimalarial armamentarium.
This past year, the New England Journal of Medicine published the results of two promising clinical trials using monoclonal antibodies. Led by researchers from the National Institutes of Health, the scientists administered a monoclonal antibody against the sporozoites of P. falciparum to healthy adults in the Western African country of Mali. Their results demonstrated a high level of efficacy and safety, providing proof of concept that monoclonal antibodies could be another strategy for preventing malaria.
Now, the more sobering news. Dating to the 17th century, when Jesuit missionaries brought quinine (“Peruvian bark”) from the New World back to Europe to treat fevers (malaria), antimalarial drugs became a mainstay of prevention and treatment. But the Plasmodium parasite has consistently proved up to the task of developing resistance to one antimalarial agent after another. Of greatest concern most recently is the emergence of artemisinin-resistant P. falciparum in East Africa. Not only is drug resistance a problem but the effectiveness of nets in controlling malaria is being compromised due to widespread resistance of mosquitoes to the chemical in insecticidal nets.
As if these challenges to malaria prevention aren’t sufficiently daunting, it appears that one species of the mosquito vector for malaria may be jumping continents. In November 2022, researchers saw evidence for the first time of an invasive, insecticide-resistant Asian mosquito, Anopheles stephensi—the primary mosquito vector of malaria in urban India—as the cause of a malaria outbreak in Ethiopia. It is hoped that lessons from treating A. stephensi in India can be applied to African countries.
Climate change poses a final challenge to the conquest of malaria. Earlier this year, a team of researchers from Georgetown University reported a link between the spread of malaria and rising temperatures suggesting some of the deadliest impacts of climate change won’t just come from floods, droughts, and other disasters, but also could involve diseases such as malaria.
A final note of optimism. It seemed that as soon as the celebration of the world’s first malaria vaccine began, new roadblocks to malaria elimination cropped up. But the history of the battle against the Plasmodium parasite and its mosquito vector is strewn not only with setbacks but also with major victories, including Nobel Prizes (most recently awarded in 2015 to Chinese professor, Yongu Tu, for her contributions to the discovery of artemisinin). So, for now, don’t underestimate human ingenuity and keep in mind the two big steps forward in the past two years—new vaccines and monoclonal antibodies.