The most widely used antimalarial therapy may not fully treat some children and pregnant women, according to a new study.
These patients’ bloodstreams contained lower concentrations of one active ingredient compared to adults who aren’t pregnant.
The research may explain why standard doses of artemether-lumefantrine combination therapy (ACT) sometimes fail to cure these sensitive groups. It suggests a change in the treatment regimen may help raise cure rates and prevent resistance.
But experts say this study alone is not enough to warrant changing treatment recommendations.
Malaria cases have fallen by 60 percent since 2000, thanks to an intensive, multibillion-dollar global campaign of prevention and treatment. But the disease still claims more than 400,000 lives per year, mostly young children in sub-Saharan Africa.
Pills combining artemether and lumefantrine are the most commonly used antimalarial treatment worldwide. The 3-day treatment is generally safe and effective.
However, most drug trials have not included children and pregnant women, who may absorb or metabolize drugs differently than others.
Some studies have found they are more likely than others to contract malaria again within weeks of ACT treatment. Results vary, but some research found failure rates as high as 20 percent.
Lower blood levels
Writing in the journal PLOS Medicine, researchers combined data from 31 studies including more than 4,000 patients. They looked at concentrations of lumefantrine in the blood seven days after treatment began.
Lumefantrine is the longer-lasting part of the drug combination. It is intended to prevent relapses.
The study found lumefantrine levels were 20 percent lower than average in pregnant women’s blood, and 15 to 25 percent less in children.
“This is pretty important,” said lead author Frank Kloprogge at University College London. Drug levels that far below average “can really make a difference.”
Treatment failure is not the only risk. Malaria parasites exposed to lower levels of the drug may survive treatment and produce resistant strains. “And this is, of course, a longer term, potentially, really big problem,” he said.
The scientists developed a model that suggests taking the pills for 5 days would be more effective than the current 3-day schedule.
More information needed
The study is “very well done and important,” said Andrea Bosman, Malaria Prevention, Diagnosis and Treatment Coordinator at the World Health Organization.
However, Bosman added, “it is still a modeling study, and we do not generally make recommendations based on modeling studies alone. We require clinical data.”
Changing therapies is complicated, he notes. The longer treatment lasts, the less people stick to it. That, too, raises the risk that treatment will fail and resistance will develop.
Also, he adds, the bigger issue is poor-quality drugs, which are widespread in much of the malaria-prone world.
Opinions are split over how big a problem the reports of treatment failure in children and pregnant women are.
Earlier this year, the U.S. Centers for Disease Control and Prevention analyzed 21 studies. “They thought we should keep the regime exactly where it is,” noted molecular biologist Brian Grimberg at Case Western Reserve University School of Medicine.
Scientists are still debating why treatment fails. The parasites may have developed resistance, or they may be what Grimberg calls “sleepy parasites.”
“They’re not resistant to the drug. They just go to sleep,” he said. “If it’s true that they’re sleepy, then maybe a longer duration of the treatment regime would be helpful.”
Kloprogge and colleagues are applying for funding to conduct a clinical trial of the 5-day treatment schedule. It will be several years before results are available.