Sign that says Malaria resurgence is not accepted

The World Celebrates the First Malaria Vaccine—But Don’t Expect Malaria to Disappear

On October 6, 2021, the World Health Organization (WHO) announced it was recommending the first malaria vaccine, known as RTS,S, for broad use. The next day, we entered a University of Oregon classroom to meet 20 freshmen enrolled in Malaria: Science, Ethics, History, Technology. We wanted our students to know two things about the new malaria vaccine: first, that it’s a historic scientific discovery, the culmination of a half-century of research and more than 30 years of clinical trials. We collectively whooped with joy since this is big news and will provide additional protections for children under age five in sub-Saharan Africa. But when we recovered, we pointed out the less inspiring reality: this vaccine won’t solve the world’s malaria problem. The RTS,S vaccine is only moderately effective and it’s unclear how large of an impact it will have in equatorial Africa, where malaria morbidity and mortality is highest. While we are excited about RTS,S, we’ve done too much research on the history of malaria interventions in Africa to believe that one new tool will alter everything. Nevertheless, with enough funding and support from the Global North and international agencies, this vaccine offers the opportunity for many lives to be saved.

A man in a white hazard suit and helmet pumps a spray can
Zanzibari sprayer in the Indoor Residual Spraying campaign. (©2018 Zanzibar Malaria Elimination Programme calendar)

While the vaccine is the first to be recommended by the WHO, it is still unclear if it will be a game-changer. Optimists point out that the RTS,S vaccine prevents Plasmodium falciparum, which is responsible for most malaria deaths globally; any reduction in cases will thus lead to a reduction in deaths. The malaria parasite enters the bloodstream, infects and reproduces in the liver, before reentering the bloodstream and causing symptoms, including recurrent fever, chills, and in severe cases, coma and death. The vaccine works by preventing the parasite from infecting and reproducing. Years of data collected in Phase 3 clinical trials and a Phase 4 feasibility study in sub-Saharan Africa have shown that among children who receive four doses, the vaccine reduced malaria cases by 40% and severe malaria cases (those requiring hospitalization) by 30%. It appears that efficacy wanes to close to zero by the fourth year. Optimists would be right in noting that 40% fewer malaria cases is nothing to scoff at, and pessimists are not wrong to question the overall utility of a vaccine that requires 4 doses and prevents only 30% of severe cases. Questions remain about what will happen 4 years after children receive the vaccine. Will their immune systems be mature enough to fight off malaria infections, so it becomes more a disease of sickness rather than death? Or will malaria mortality merely shift to a slightly older group of children?

While scientists have long sought an effective vaccine, this is clearly a new tool in our arsenal. Malaria is an ancient disease, and there’s evidence that it emerged from earlier parasitic infections among great apes. Long before British and Italian scientists working in colonial settings identified the parasite and the mosquito vector, or unraveled its complicated life cycle, indigenous people living in malarial areas developed methods for living with the disease. Strategies included avoiding spaces with mosquitoes and limiting human-mosquito contact, and creating salves from local plants to rub on skin or burning leaves meant to repel mosquitoes.

Since the early 1900s, a formalized and globally practiced set of tools and strategies have developed, some high-tech and some decidedly not. Because malaria is a vector-borne disease caused by a parasite spread through the bite of female Anopheles mosquitoes, control strategies have historically fallen into one of three categories: reducing the number of mosquito vectors by modifying the environment; reducing the number of parasites in humans through testing and treatment; or reducing contact between humans and mosquitoes with the use of simple barriers. These pre-1950 interventions typically relied on forms of environmental control, such as swamp drainage, land reclamation, and oiling of breeding sites. A vast majority of malaria control interventions from 1900–1950 happened in British, Belgian, French, Portuguese, and German colonial spaces and sought to protect colonial employees rather than Indigenous people.

Two men in brown uniforms and white hats spray a thatched-roof cottage with chemicals to kill mosquitoes
Indoor residual spraying (IRS) with dieldrin during the Pare Taveta Malaria Scheme.
(Photos from the Malaria Archive held at the Wellcome Unit for the History of Medicine, University of Oxford)

After World War II, building on the development of new chemicals through wartime research, there were great hopes for a quick, technological fix. The 1950s and ’60s were characterized by a desire not just for malaria control but for global eradication. In 1955, fueled by the promise of the insecticide DDT, WHO launched the Global Malaria Eradication Program (GMEP). DDT was envisioned as the singular tool (the first “silver bullet”) that would eradicate malaria-transmitting mosquito populations globally. The insecticide was highly effective when sprayed inside structures and lasted for months, and regular indoor residual spraying with DDT was the backbone of the WHO’s global campaign. Programs were launched everywhere, including in Africa, and there were some clear successes – malaria was eliminated in parts of Southern Europe and temporarily reduced in others.

But by the mid-1960s, it became clear that the silver bullet had limits. New research documented DDT’s harmful effects on the environment (such as in Rachel Carson’s well known Silent Spring, which had implications for how the pesticide was used in relation to malaria). Another more immediate concern was mosquito resistance to DDT, which WHO scientists around the globe reported. The new chemical would be sprayed and sprayed again, yet mosquitoes didn’t die. Despite the initial great hopes about this new technology and the global campaign, it became obvious that malaria would not be eradicated. The WHO suspended the GMEP in 1969, declaring a return to malaria control.

Considering the role of DDT in the WHO’s global eradication campaign is instructive when thinking about the future of the RTS,S vaccine. The GMEP’s failures gave way to a few decades of total neglect of malaria until the turn of the century, when a more integrated strategy emerged that layered together multiple techniques. In practice, this means that many countries rely on a combination of indoor residual spraying with insecticides to kill mosquitoes, mass drug administration to clear plasmodium parasites from infected people, and providing long-lasting insecticide-treated bed nets that protect people from mosquito bites at night. There’s evidence that this approach, also drawing on environmental forms of control such as integrated vector management, can control malaria even in highly endemic spaces when supported by stable funding.

One successful example comes from Zanzibar. A variety of interventions were implemented over the past two decades, including the distribution of bed nets, the use of the highly effective malaria treatment artemisinin combination therapy (ACT), and the creation of a robust case tracking system. These strategies reduced malaria incidence on parts of the island to under 1%. No single intervention can eliminate malaria; in endemic areas, success is always dependent on continued interventions. The malaria parasite and the mosquito vector have adapted and eluded every chemical scientists have developed from chloroquine and sulfadoxine/pyrimethamine to DDT and Dieldrin. We may dream of a single, technological solution to malaria, but the reality is that any reasonable approach must be multilayered and long-term.

There is a huge potential for the vaccine to save lives. It offers a degree of protection to children under age five, who are most vulnerable to dying from malaria. Yet the vaccine also has limitations. It is certainly better than nothing, but it’s not the level of protection we generally expect from vaccines adopted as part of the WHO’s Essential Programme on Immunization. When Phase 3 data was released six years ago, Médecins Sans Frontières (MSF) issued a public statement saying “RTS,S ultimately does not meet the criteria needed to provide adequate protection for those who need it most” and that their organization would not be administering the vaccine. They felt the actual and logistical costs of deploying the vaccine were too great to make it worthwhile. In the unfair calculus of global health, where priorities are many and funding is scarce, MSF judged they could make a bigger impact by focusing on other malaria control interventions, prevention, and treatments.

It remains unclear how health officials will navigate the myriad practical, logistical, and financial hurdles that RTS,S will face. WHO approval doesn’t mean African countries will feel comfortable adopting it (similar issues have arisen with polio vaccines in Northern Nigeria and COVID vaccines in Tanzania); it doesn’t mean that patent-holder GlaxoSmithKlein will make the vaccine available at an affordable price; and it doesn’t mean that organizations like GAVI or UNICEF will allocate or have enough funds for purchasing the vaccine. This sets aside entirely how people receiving it might understand the vaccine, or whether they choose to adopt it. The malaria vaccine has the potential to save lives and the world should be excited about the WHO’s recommendation, but this vaccine won’t solve malaria. It’s just another tool – a much-needed one – in our malaria fighting toolkit.

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