The perfect should not be the enemy of the good, especially when it comes to fighting a devastating disease like malaria. A new vaccine, which prevented symptomatic disease in less than half the older children who received it, is rapidly moving toward the marketplace in a field desperate for good news. Given that more than 200 million people fall ill with malaria each year, even a partially effective vaccine could spare huge numbers of people from the debilitating and sometimes fatal effects caused by a bite from a mosquito that transmits the malaria-causing parasite.
“The results are encouraging and perhaps more positive than some were expecting,” says Richard Feachem, a malaria specialist at the University of California, San Francisco (UCSF), who was not involved with the work.
The large-scale study of the vaccine, known as RTS,S (an acronym for its ingredients), began in March 2009. Preliminary results reported in 2011 suggested that the product was somewhat effective in combating malaria in children given shots between 5 and 17 months of age. Researchers running the placebo-controlled trial—which is taking place in more than 15,000 children at 11 sites in seven sub-Saharan countries—found a 56% drop in cases of “clinical,” or symptomatic, malaria in the youngsters , and a 47% reduction in “severe” disease such as anemia, neurological problems, or even death. This analysis was done 1 year after the kids received their third dose, and, because vaccine-induced immunity wanes over time, some worried that meaningful protection might soon evaporate. A subsequent report that focused on infants who received their first shot at 6 to 12 weeks old disappointingly found that the impact on clinical malaria dropped sharply to only a 31% reduction in cases .
The new study, presented today at the 6th Multilateral Initiative on Malaria Pan-African Malaria Conference in Durban, South Africa, looked at the older group of children 18 months after their last shot and discovered that the immunity had not waned as much as some had feared: There were 46% fewer clinical cases and a drop of 36% in “severe” disease. Vaccinated children in this group required 42% fewer hospitalizations than those who received the placebo. The younger infants had 27% fewer cases of clinical malaria, but rates of hospitalization were the same as unvaccinated infants in a control group.
The vaccine’s maker, GlaxoSmithKline (GSK) of Brentford, U.K., says it plans to seek regulatory approval from the European Medicines Agency (EMA) in 2014. The World Health Organization (WHO), which offers influential policy advice about vaccines, said it could recommend its use as early as 2015 if EMA determines that RTS,S is safe and effective. UCSF’s Feachem says that seeking regulatory approval now is a good idea. “The sooner we start, the more lives will be saved.”
Although the vaccine’s efficacy is far from ideal, some researchers contend that it could add a critical new tool to malaria prevention efforts. “The vaccine efficacy alone only tells part of the story of the public health impact it can have,” says David Kaslow, who heads the PATH Malaria Vaccine Initiative, which helps run the trial with substantial support from the Bill & Melinda Gates Foundation. In particular, a modestly effective vaccine combined with insecticide-treated bed nets, spraying efforts, and improved diagnostics could have an important additive effect. He notes that the trial data show there were 941 clinical malaria cases averted per 1000 vaccinated kids—many get the disease more than once—in settings in which 78% used insecticide-treated bed nets. “That’s the new and important data,” Kaslow says.
The latest analysis also shows for the first time that the vaccine worked at each of the 11 sites, cutting disease by 40% to 77% in the older kids. A fourth booster dose being given to participants at 18 months of age in the ongoing study might also bolster vaccine efficacy, notes Vasee Moorthy, the lead person for malaria vaccines at WHO. “A really important point is we don’t know what’s going to happen with the booster dose,” he says, adding that it may even increase efficacy rates in the younger group. “How those booster doses pan out is going to be critical for our policy recommendations.” Final trial results, which will include an evaluation of the booster shot, are expected by the end of 2014.
UCSF’s Feachem says that even if the vaccine clears regulatory hurdles and has a WHO endorsement, cost-effectiveness studies will have to determine where its use makes the most sense. “My hunch is that models will show adoption of the vaccine is attractive in some circumstances, but not in all,” he says. GSK has committed to selling the vaccine at cost plus about 5%, but no dollar amount has been announced. Then there’s the thorny question of who is going to pay for the vaccine in the many low-income countries that have a heavy malaria burden. Says Feachem: “That’s a very important international health decision that has to be arrived at sooner rather than later.”