A study by the Duke Clinical Research Institute comparing three treatment methods of preventing malaria in children with sickle cell anemia (SCA) found one method reduces common complications of the disease.
EPiTOMISE: Enhancing Preventive Therapy Of Malaria in Children with Sickle cell anemia in East Africa, was conducted among children with SCA in Homa Bay, Kenya, where malaria is common. It evaluated the effects of a monthly combination of sulfadoxine-pyrimethamine with amodiaquine (SP-AQ) or a monthly combination of dihydroartemisinin-piperaquine (DP) against the standard of care in Kenya, Proguanil.
Although the study found no statistically significant differences in the rates of malaria, researchers were encouraged to learn that DP reduced rates of infection by Plasmodium falciparum parasites and of dactylitis, a common complication of SCA, compared with Proguanil.
Malaria also diminished in the region, but not as a result of this trial. Instead, the researchers found that a concurrent government-sponsored program to spray area homes with insecticide had already made significant progress in the fight against malaria in the region.
“Despite the fact that there were about 95% fewer cases of malaria than we expected, owing to the fact that they killed nearly all the mosquitoes, we still found that one of these drug regimens reduced episodes of dactylitis, which is a sickle cell complication — pain in the fingers and toes — by more than 50%,” said Steve Taylor, MD, MPH, principal investigator of the study and an Infectious Disease faculty member in the Duke School of Medicine. “That same drug regimen reduced the likelihood that you would be infected by malaria parasites at all by about 80%.”
All the medications tested in the study are readily available at medicine shops in the region, with or without a prescription.
Although it did not reach the threshold of statistical significance in the study, mortality was higher among the group of children treated with SP-AQ, an important consideration for evaluating its potential for future use.
Researchers paused the trial and adjusted the protocol as a result of deaths in the SP-AQ arm of the trial, then noticed that mortality leveled out among the study’s other arms. Due to a lack of available data on mortality in children with sickle cell in the area, the researchers were not able to determine whether the deaths were associated with the drug regimen.
“One of the difficulties in assessing that observation was that we generally didn’t know what the expected background of likelihood of children of this age with sickle cell anemia in Kenya dying was, simply because there’s no clinical information systems to allow us to estimate that risk,” Taylor said. “It’s just such an understudied population that we just didn’t know what the background rate was and whether we were observing a normal rate in the (SP-AQ) arm, and a reduced rate in the other two arms.”
“SP-AQ is used for malaria prevention on a monthly basis, in a fairly unmonitored fashion, for tens of millions of children in West Africa, and in those studies, it was found to be quite safe,” Taylor said, noting that any mortality differences in this trial could be due to differences in the patient population or the duration of the drug regimen.
Taylor said he would be hesitant to recommend SP-AQ as malaria prevention in children with SCA following this trial, but that the DP regimen warrants further study and consideration.
“I think there is a place for testing DP in higher transmission settings, and I also think it would be valuable to do so in a more pragmatic design,” he said.
The study was a collaboration among the DCRI, the Duke Global Health Institute, and Moi University in Eldoret, Kenya, through its Academic Model Providing Access to Healthcare (AMPATH) research network. Key Kenya-based collaborators were site coordinator Sarah Korwa, program manager Joseph Kipkoech Kirui, and Kenya primary investigator Dr. Festus Njuguna, a lecturer in the Department of Child Health and Paediatrics at Moi University and the Head of the Paediatric Haemato-Oncology Unit at Moi Teaching and Referral Hospital in Eldoret. Other Duke-based contributors included Angie Wu, Cynthia Green, and Sheila Clapp of DCRI and Betsy Freedman and Wendy P. O’Meara of the School of Medicine and DGHI.