A Shot Against Malaria

Even through a crackled cellular connection from Durban, South Africa, the optimism can be heard in Dr. David Kaslow’s mild-mannered voice. “It’s been a fairly long road. Twenty-plus years in development. There’s been a lot of twists and turns.”

Kaslow is the director of the Malaria Vaccine Initiative at the nonprofit health organization PATH, as well as vice-president of PATH’s product development. He and his Kenyan colleague, Dr. Lucas Otieno, presented the Phase III trial results at the Multilateral Initiative on Malaria Pan-African Conference, in Durban, earlier this week: the RTS,S vaccine, which was tested on over sixty-five hundred infants and nearly nine thousand children, effectively protects young children and infants from malaria up to eighteen months after vaccination. It is currently the world’s most advanced malaria vaccine.

Next year, the vaccine will be submitted for evaluation by the European Medicines Agency. If the E.M.A. gives a positive opinion, the World Health Organization could recommend the vaccine’s use as early as 2015. The implications for sub-Saharan Africa, where a child dies every minute from malaria, are staggering. Globally, the disease kills over six hundred and sixty thousand people a year, most before they reach their fifth birthday.

Of the four varieties of malaria parasites, the Plasmodium falciparum is by far the most lethal; it is the target of the vaccine, whose full name is RTS,S/AS01. The letters refer to the different components that make up the vaccine. For instance, the first “S” refers to the antigen for another disease, hepatitis B, which infects the liver like malaria. It’s used in the vaccine because scientists already know that the human body is able to mount a very strong immune response against it. The “AS01” part of the name refers to the adjuvant, which directs and strengthens the body’s immune response. Altogether, the vaccine is a one-two punch against the protozoan parasite: it amps up the response of both antibodies and disease-fighting T-cells in the human body. (The hybrid vaccine is expected to be effective in preventing hepatitis B infection as well.)

Malaria is transmitted when a female anopheles mosquito, after picking up the parasite from biting an already-infected person, goes on to bite a healthy human. The clinical manifestation of the disease happens when the parasite travels from the initial blood entry-point to the liver, where it silently camps out and multiplies. It then reënters the bloodstream, infecting red blood cells and eventually the brain. The vaccine aims to trigger the immune system to fight off the parasite at two crossroads: when it first enters the human’s bloodstream and after it infects the liver. P. falciparum is dangerous in part because it is able to replicate at a very high rate—and thus rapidly evolve resistance to drugs.

The development of RTS,S is one of the longest ongoing vaccine projects in history, dating back to 1984, as a combined venture between GlaxoSmithKline and the Walter Reed Army Institute of Research. In 2001, a public-private partnership was created with PATH, an international nonprofit organization based in Seattle that seeks to “transform global health through innovation,” using grant funding from the Bill & Melinda Gates Foundation, which Michael Specter wrote about in the magazine in 2005.

“I started my postgraduate career studying medical genetics,” said Kaslow, who has been working on a malaria vaccine for over a quarter century. “I didn’t know much about malaria, but it was clear from looking at the human genome that this parasite must have exacted a heavy toll against humans. The more I read about this wily parasite, the more it peaked my scientific curiosity. But what really wrenched my heart was the more I travelled in sub-Saharan Africa,” the more he saw “mothers sleeping in crowded, humid pediatric wards, caring for their comatose children suffering from cerebral malaria” and “languid toddlers with severe anemia, sapped of all energy to the point that staring listless is all they can do.”

Those experiences in Africa continue to motivate Kaslow’s efforts, though he is eager to credit his colleagues in eleven research centers across seven African countries for the breakthrough with RTS,S. Dr. Moncef Slaoui, the chairman of research and development and head of vaccines at GlaxoSmithKline, also emphasizes the combined efforts of hundreds—maybe thousands—of people over the years, especially his colleagues in sub-Saharan Africa. In the summer of 2004, “I was driving from Chicago to Philadelphia with my kids when I got a call from the team in Mozambique, where the first trial was being conducted in infants,” Slaoui recalled. “When I heard the positive results, I was shaking so much I couldn’t put my foot on the clutch. It took me more than an hour to be able to drive again, I was so emotional. My kids couldn’t stop making fun of me.”

According to the results of the clinical trials, the vaccine’s efficacy against clinical malaria was forty-six per cent among children and twenty-seven per cent among infants eighteen months after the initial three-dose vaccination series; the scientists project that the vaccine could prevent nine hundred and forty-one malaria cases per thousand children, and four hundred and forty-four cases per thousand infants. (The percentages don’t line up at first sight because one individual can be infected repeatedly.)

The numbers may seem low; the polio vaccine is up to ninety-five per cent effective. But both Slaoui and Kaslow caution that the data must be considered from the broader perspective of public health. “We tend in the Northern Hemisphere to discuss, ‘What was the efficacy?’ If it’s not eighty or ninety per cent, it’s not a vaccination,” Kaslow said. “That may be true if it’s not a huge disease burden. But when the disease burden is huge, even moderately successful vaccines can have a huge impact.” Slaoui added, “This isn’t perfect, but it’s very good. In sub-Saharan Africa, millions of cases of malaria could be averted.”

The next steps in the vaccine’s development include testing if a booster shot given eighteen months after the primary vaccination series would increase immunity. Until the vaccine is approved, two methods will continue to be the primary means of prevention: spraying indoor insecticide and sleeping under insecticide-treated bed nets. Experts are already concerned about how resources will be divided, given that the vaccine likely will exist alongside them, and the vaccine is expected to cost dollars, not pennies. Globally, $3.6 billion is spent each year on extant prevention methods. Implementing and scaling up a vaccination program just for African children under one year of age would add an estimated five hundred and thirty-three million dollars on top of that. GlaxoSmithKline intends to field the vaccine at-cost, plus five per cent for reinvestment in future vaccine research.

Even now, after many years of working as a doctor in Africa, it still strikes me how quickly local clinicians are able to correctly diagnose malaria in anyone with the slightest hint of anemia, and to accurately dose anti-malarial artemisinin-based combination therapy as if it was common penicillin. I will never forget walking past the funeral of a five-year-old girl who died of cerebral malaria, and seeing the readiness of her family to accept her death as simply a part of the African existence, because there, malaria routinely prematurely disrupts the circle of life. But with the promise of this anti-malarial vaccine, I hope that these stories will achromatize into “back-when-we-used-to-work-in-Africa” memories of a bygone time.

Helen Ouyang is an emergency physician at Columbia University Medical Center, where she is the associate director of the International Emergency Medicine Fellowship. She is also an affiliate faculty of the Harvard Humanitarian Initiative.

Photograph by Pascal Guyot/AFP/Getty.