Nearly a decade ago, Bill and Melinda Gates stunned, and in some quarters irritated, the global health community by calling for the eradication of malaria, one of the world’s biggest killers.
“Any goal short of eradicating malaria is accepting malaria,” Melinda Gates said at the time. Bill Gates added that, “We should … because we can.” Many malaria experts at the Seattle meeting thought this call to action in October 2007 highly ambitious, if not downright irresponsible. Why set us all up by calling for the impossible?
But last week, to not much notice beyond this one excellent story by NPR, preliminary findings from a huge project under way in a section of central Africa known as the Sahel show a bold new strategy that might just nudge malaria eradication a bit closer toward reality.
The strategy is known as seasonal malaria chemoprevention – perhaps an intentionally boring moniker aimed at avoiding the controversy that accompanied a similar approach taken years earlier simply called mass drug administration.
It’s controversial because earlier initiatives taking this approach didn’t work and led to drug-resistant malaria.
The world has made great progress already in reducing the malaria disease burden worldwide, through distribution of bednets, insecticide use and expansion to treatment.
Yet most, including the Bill & Melinda Gates Foundation, have pinned their hopes for complete eradication on finding an effective malaria vaccine. Only a single human infectious disease, smallpox, has been eradicated so far and that success was partly due to the fact that the smallpox virus only infects humans, and the smallpox vaccine was amazingly effective, working to kill the virus even if administered soon after infection.
Malaria is a much more genetically complex parasite that infects other animals and efforts to develop a vaccine have not achieved much success. There is one malaria vaccine being tested in Africa, but most believe its low efficacy and technical requirements (multiple doses) make it a poor candidate for use in poor countries with high burdens of malaria.
Seasonal malaria chemoprevention (SMC) is, in fact, a form of mass drug administration in that both techniques distribute antimalarials to a population at risk for malaria without first diagnosing if the recipient is infected. Since many with the malaria parasite show no symptoms, the idea is to attack the parasite circulating within the population in general rather than just chase down those with the disease.
David Brandling-Bennett
“Seasonal malaria chemoprevention is intended for prevention. It’s not intended to eliminate malaria from the entire population,” emphasized David Brandling-Bennett, a medical epidemiologist and former malaria program manager at the Gates Foundation, in an interview with Humanosphere. But it’s power to greatly reduce the circulating parasite within the general population could be an essential step to elimination, Brandling-Bennett said.
Attempts to use mass drug administration (MDA) to fight malaria date as far back as the 1930s. However, without consistent and repeated administration to the entire population, MDA historically left little long-term impact. Even worse, lower concentrations of antimalarials were later added to salt, which created drug resistance in the parasite. Use of a single drug, instead of drug combinations as recommended today, also increased resistance.
The idea behind the project under way in the Sahel region of Africa is to do antimalarial mass drug administration on a seasonal basis only, to reduce the risk of drug resistance.
The Sahel
During the arid region’s four rainy months when transmission rates are highest, health workers are administering four doses of affordable antimalarials to children under the age of five, regardless of whether or not they are exhibiting symptoms. After seeing malaria cases drop as sharply as 83 percent, health officials scaled up the technique to 11 countries this summer.
“Essentially what it does is it uses seasonality as a natural barrier to malaria,” said Martin Edlund, CEO of Malaria No More. Unlike the malaria heartland, he said, “In the Sahel, you only have a few months where there’s continuous malaria transmission.”
Because they have not developed immunity to the disease yet, children under five are most vulnerable. According to the World Health Organization (WHO), which began recommending SMC in 2012, malaria killed about 306,000 children under five globally in 2015. Of those, 292,000 were in the African region, where 90 percent of all deaths from malaria in 2015 occurred.
In Mali, 40 percent of all hospital and clinic visits are due to malaria, but researchers say SMC is the first intervention to show significant impact in the country since the mass distribution of bed nets. In Senegal, malaria deaths among under-fives dropped 79 percent from 2013 to 2014. In just one hospital in Niger, mortality rates dropped from 16 percent in 2012 to 6 percent in 2016.
“I think these results also point the way to one of the exciting next potential uses of treatment, which is to again use seasonality to not only treat children, but to treat the whole population with drugs that are going to really knock out the parasite,“ Edlund told Humanosphere.
Treating every kid and adult before rainy season hits can keep parasite levels low for when the mosquitoes begin to circulate, according to Edlund. Transmission rates would consequently be much lower than that of a usual rainy season.
Martin Edlund
“It’s a really exciting prospect,” Edlund said. “It’s potentially one of the critical strategies for actually moving countries to elimination, and we’re starting to see some exciting evidence of it from places like southern Zambia, where they’re doing these campaigns now.”
“Mass drug administration needs to be used in combination with other methods to control, prevent and eliminate malaria, particularly vector control measures. And that’s indeed how even seasonal malaria chemoprevention can be used,” Brandling-Bennett said.
“We want children to be sleeping under bed nets or in rooms with walls that have been sprayed with indoor residual sprays to kill the mosquitoes and prevent exposure to malaria. In that way, it makes the approach more effective, and it lessens the likelihood that resistance is going to develop to the drugs,” he said.
Every success story in the global fight against malaria is a reminder of how critical it is to consistently attack the disease on every front. Unfortunately, so is every setback.
Earlier this month, Doctors Without Borders (MSF) announced that after a significant decline in malaria cases over the last three years in Niger – down more than 70 percent in 2014 – the disease is making an “alarming resurgence.” The number of cases more than doubled in 2016 compared to the same period in 2015.
MSF is still determining what factors led to this resurgence, but MSF contends the incorrect administration of seasonal malaria chemoprevention is one possible culprit.
Carol Bottger
“Perhaps there was some slackening after the success of the first prevention campaigns, but there are many factors that can cause an unexpected increase in transmission,” Carol Bottger, MSF medical coordinator in Niger, said in the update. Bottger also suspected earlier and heavier rains that helped spread the disease as well as drug resistance.
Medicines for Malaria Venture, a partner of the Gates Foundation, is currently developing a new antimalarial drug to skirt resistance, Deputy Director of Malaria at the Gates Foundation Bruno Moonen told Humanosphere. The foundation also supported initial studies that provided evidence to the WHO of seasonal malaria chemoprevention’s efficacy.
“I think it’s quite interesting that the African investigators and public health specialists in the affected countries … were the ones who were involved in doing these studies and pushed for them and actually pushed the WHO quite hard to recommend seasonal malaria chemoprevention,” Brandling-Bennett said.
Whatever challenges and setbacks, the overall success of seasonal malaria chemoprevention is a testament to the malaria community’s ability to refine methods and develop new tools to attain a dream they didn’t dare utter before the Gateses did in 2007.
“It’s no exaggeration to say that we would not be talking about the prospect of ending this disease in our lifetimes if it weren’t for Bill and Melinda Gates,” Edlund said. “Now, we’re talking about a disease that’s over 20 million years old that we can end within the next 25 years.”
