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Story Publication logo July 2, 2014

Malaria Prevention, with Both Reward and Risk


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Several African countries are preemptively treating children for malaria after trials found the...

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A health worker in the Koutiala region of Mali gave a child a dose of malaria drugs in September. Image by Amy Maxmen. Mail, 2013.

Alassane Dicko shivered and sweated through part of his childhood. Sick with frequent bouts of malaria, he often missed school. His older brother died of malaria, and so did his best friend. This disease can be cured with a pill, yet it claims about 1,700 lives each day — mainly children in sub-Saharan Africa who don't take this medicine within a week of falling sick. Even when kids survive, some remain disabled or irrecoverably behind in school. That's why Dicko, now a malaria researcher at the University of Bamako in Mali, took matters into his own hands when he became a father.

Dicko gives malaria medicine to his children before they get the disease during the rainy season — the period when the mosquito-borne illness peaks in Mali. Tourists do something similar by taking malaria drugs prophylactically on trips to Africa, but for decades, health officials have said that Africans should not do so, because the widespread use of a drug eventually renders that drug ineffective. However, Dicko, who studies malaria prevention, has come to believe that the immediate health benefits are worth that risk.

After a decade of clinical trials demonstrated that the preventive measure reduces malaria cases by 75 percent, medical authorities reversed their position against it, in areas where it's most effective. They decided that the number of lives saved outweighs the cost of losing these drugs eventually. "For every drug you give, you will increase the risk of drug resistance," Dicko says. "But these drugs are efficacious right now, so why don't we use them and save thousands of lives?"

For the first time last year, Dicko's children were far from alone when they swallowed a combination of three old malaria drugs (sulphadoxine, pyrimethamine and amodiaquine). In countries across West and Central Africa, 1.2 million children took these pills for a few months during the rainy season to prevent the disease. This year, several African governments — with financial support largely from the United States and the United Nations fund for children, UNICEF — will treat nearly two million children. Next year the intervention, called seasonal malaria chemoprevention, is slated to reach more than eight million kids with additional funds from other international organizations.

This admittedly short-term solution may come as a shock to Americans, given the recent alarm sounded over antibiotic resistance. Yet doctors have always known that antibiotics would be overcome as people took the drugs to clear infections.

"For many years I was a practicing physician, and I can tell you, we were complacent about the threat of resistance because new antibiotics continuously came onto the market in the '50s, '60s, '70s and even the '80s," says Steve Solomon, the director of the office of antimicrobial resistance at the Centers for Disease Control and Prevention. One antibiotic was simply replaced by another. "We didn't worry," he says, "because there was always another option."

But now those options are running out for antibiotics, and only one malaria drug (based on artemisinin) remains highly effective around the world. Resistance to any given antibiotic or malaria medicine develops rapidly when the drug is misused. But resistance also spreads when people take the drug as prescribed because a small number of bacteria or malaria parasites inevitably have mutations that allow them to overcome the drug. The proportion of these resistant bugs gradually increases over time when a large number of people take the medicine, and kill off sensitive versions.

Drug resistance after widespread drug use mars the history of malaria treatment, with waves of death following the loss of one malaria medicine after the next.

The intervention that African governments and health workers are now rolling out in West and Central Africa does not threaten the leading ingredient in malaria drugs today, artemisinin, since healthy children are being given older malaria medicines. That's why the World Health Organization felt safe in recommending this specific strategy in 2012 to countries with seasonal malaria. Still, the intervention does risk these cheaper alternatives.

I wanted to know how mothers, scientists, and doctors in West Africa felt about seasonal malaria chemoprevention,so I traveled to Mali and Senegal to speak with them. While there, I saw how arduous it was to deliver drugs to people in far-flung places. Once each month during the rainy season, thousands of community-elected health workers collect the pills at central locations, return to their respective villages, dissolve the pills in water, and hand the milky solutions to children to swallow.

To my surprise, everyone seemed to endorse the intervention. In southeastern Mali, nurses bragged about empty pediatric wards, which usually overflow with young malaria patients soon after the first rains fall.

One health worker, Miriam Cisse from the N'tarla village, told me, "Mothers are so excited" for the intervention. "Before this, I always saw children dying from malaria, but we have less death now and our children have better health." She shrugs off concerns about pending drug resistance because these are old malaria drugs, and she hasn't witnessed any severe drug side effects. In contrast, visions of children on the verge of death are very real in Mali, where malaria steals more lives than violence, AIDS, pneumonia or cancer.

Estrella Lasry, the technical adviser for the interventions supported by the humanitarian group Doctors Without Borders in Mali, Chad and Niger, stands firmly on the side of saving lives now despite pending resistance. She says, "If you have something to prevent kids from being sick, it would verge on the unethical not to use it."

In addition, it's cheaper to prevent malaria than cure severe cases in which children become anemic. These cost about $198 per child per year (including the nurse, hospital stay and intravenous fluids), Lasry says, while the intervention costs $6 per child per year (including the pills and the cost of delivery).

This year, 10 African countries sought funds from international donors to help them roll out seasonal malaria chemoprevention. However, some countries still lack the resources to start the program, and others only have enough money to reach a subset of the children who live in regions where chemoprevention works. In Ghana, for example, just 101,000 of 704,000 children are taking preventive medication this year.

Next year looks more promising. An initiative financed by fees on airline tickets, UNITAID, recently announced a $67 million grant toward chemoprevention for 2015 and 2016. Additional 2015 funds may come from the Global Fund to Fight AIDS, Tuberculosis and Malaria. And the two groups that foot much of the bill for chemoprevention at the moment — the United Nations' fund for children, UNICEF and the U.S. Agency for International Development — will continue their support. These funds came a decade after Dicko and his colleagues began to show that chemoprevention cuts malaria cases more than any malaria vaccine tested to date.

Health officials are taking a number of steps to prolong the use of this intervention. They're combining three old malaria drugs rather than one, so that a parasite won't survive unless it acquires several mutations that allow it to overcome each of these medicines individually. And because treatments are restricted to three or four months during the rainy season, drug-sensitive parasites should have a chance to bounce back during dryer months.

Which is not to say that resistance won't develop. In fact, a recent study detected subtle signs of drug resistance in malaria parasites after three months of chemoprevention in Burkina Faso. The report went on to recommend a backup drug combination that may work when the current one loses its efficacy. Meanwhile, some researchers are pushing for prevention with a drug combination that includes the key malaria drug, artemisinin, in places where the parasite no longer responds to older medicines.

Keeping track of malaria cases, deaths, and drug resistance is essential so that interventions can be halted if they aren't effective. However, it's one thing to recommend surveillance and quite another to do it in poor countries that lack the infrastructure required for nationwide record-keeping. That's why Ramanan Laxminarayan, director of the Center for Disease Dynamics, Economics and Policy in Washington, suggests that monitoring should be included in the cost of the intervention.

"We need a robust system to track resistance around the world," he says, "and maybe this is the opportunity to set that up." If drug resistance had been detected earlier in the U.S., alarms would not be sounding. Laxminarayan says, "Antibiotics are finally getting attention because antibiotic resistance is starting to kill people."

However, funds for surveillance remain scarce. "Many of the funders who can help implement the strategy just don't have enough money left to fund evaluations," Dicko says. He and his colleagues will test parasites for genetic signs of resistance in the coming years, and he's currently working on a grant to solicit funds for evaluation from a different set of donors so that monitoring can be more widespread.

With a limited lifetime, chemoprevention is not an ideal solution for malaria. But the situation is desperate. Malaria remains the No. 1 killer in several countries, and a vaccine that reliably and permanently prevents the disease may be more than a decade away from the market. In the meantime, some malaria parasites in Cambodia no longer respond to artemisinin, and the mosquitoes that spread the parasites are becoming resistant to the insecticides used to kill them.

Despite its flaws, chemoprevention could prevent 8.8 million cases of malaria and 80,000 deaths annually — but right now, it lacks the political support to fund and carry it out to the full extent.

"You don't want kids to be sick all the time, you want them to be healthy so that they can go to school and to work," Dicko says. "We have these drugs, so we need to focus on the best use of the drugs, and keep in mind their weaknesses. For me, that's straightforward thinking."


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