With malaria deaths rebounding worldwide, a pilot program testing a new and fiercely debated malaria vaccine began on Tuesday in Malawi.
Dr. Katherine O’Brien, the World Health Organization’s director of immunization, called the rollout “a historic moment in the fight against malaria,” and said the testing will soon expand to malarious regions of Ghana and Kenya.
But the vaccine, known as RTS,S, or Mosquirix, has been in development by GSK, the former GlaxoSmithKline, for more than 30 years, and it has serious drawbacks that have led some experts to argue that it does not work well enough to spend millions of dollars pursuing.
Malaria kills about 450,000 people a year, most of them young African children. Over the last 15 years, the death rate has been reduced by more than half through extensive, donor-funded efforts to hand out free mosquito nets, spray homes with insecticide and treat people with a new generation of medicines.
But deaths have increased again as money has run short, populations have grown, resistance to some new drugs has emerged and mosquitoes have expanded their ranges.
Finding new weapons is crucial, experts agree, but making a malaria vaccine has proved challenging in the extreme.
Surviving the disease does not provide lasting immunity. People who suffer numerous bouts in childhood become able to tolerate new infections, but if they leave the area for even a few years, their immunity wanes and a later infection can kill them.
The new vaccine has many weaknesses. It is inconvenient: A child must receive four injections before age 2, sometimes at intervals that do not match the routine vaccine schedules for most other diseases. And it is only partly effective. Testing in more than 10,000 African children from 2009 to 2014 showed that, even after four doses, the vaccine prevented only about 40 percent of detectable malaria infections.
The vaccine reduced the occurrence of severe malaria by about 30 percent, and the occurrence of severe anemia — a complication that often kills children — by about 60 percent. It did not protect well against parasite strains that were poor genetic matches, raising a concern that, over time, parasites could evolve resistance to the vaccine as they have to drugs.
Moreover, it is unclear how long even those relatively low levels of protection last; previous trials followed vaccinated children for four years. Experts also worry that parents whose children are vaccinated will become less vigilant about using mosquito nets, and less likely to seek medical care when their children develop fevers.
In 2015, Doctors Without Borders said it would not join any pilot projects such as those announced this week, arguing that its money and time would be better spent on proven malaria-fighting measures.
Nonetheless, the W.H.O.’s vaccine advisory group recommended that testing be expanded to 360,000 children to see how well the vaccine works in real-world situations, as part of routine immunization programs run by African health ministries, rather than within the careful confines of clinical trials.
The health organization’s Strategic Advisory Group of Experts will assess the results of each high-transmission season for at least three years, watching to see in particular whether parents bring in their children for all four doses and whether any rare but threatening side effects appear.
During earlier trials, some children developed high fevers and seizures soon after being immunized, but they recovered. A few children later developed life-threatening meningitis, but it was not clear that the vaccine was to blame.
The most important outcome will be overall survival rates, Dr. O’Brien said. If those rates increase substantially among vaccinated children, the W.H.O. may recommend rolling out the vaccine in more locations.
Very few children died in the 2009-2014 clinical trials, because they could be diagnosed and treated quickly, and hospital care with blood transfusions for severe anemia was readily available.
The current rollout will cost about $ 50 million. It is being paid for by the Global Fund to Fight AIDS, Tuberculosis and Malaria; Gavi, the Vaccine Alliance; Unitaid, and the countries involved.
The W.H.O. and Path, a nonprofit group in Seattle that has collaborated with GSK on the vaccine since 2001, will contribute expertise. Glaxo will donate 10 million doses of vaccine.
Early next year, a clinical trial of another malaria vaccine, PfSPZ, is scheduled to begin on Bioko Island, just off the western coast of central Africa.
That vaccine, made by Sanaria, a biotech company in Rockville, Md., uses whole malaria parasites that are irradiated and then removed from the mosquitoes’ salivary glands.
This vaccine, too, has limitations. It must be delivered by intravenous injection, must be stored in liquid nitrogen and requires very high doses of parasites.
Its efficacy rate has fluctuated significantly during its development. Early testing on a handful of volunteers suggested it could be 100 percent effective. But later tests showed overall efficacy rates of 55 percent, in 2016, and of 64 percent, in 2017, when used on small numbers of subjects who were “challenged” by intentional bites from infected mosquitoes.
In a 2017 trial in about 100 adults in Mali, the efficacy rate was 29 percent.
The new trial, initially in about 2,000 people, will be paid for by the government of Equatorial Guinea and three oil companies whose employees work in high-malaria areas.