A monthly dose of dihydroartemisinin-piperaquine was safe and effective in reducing young Ugandan children’s risk for malaria, according to study findings in PLoS Medicine.
Victor Bigira, MBChB, of the Infectious Diseases Research Collaboration in Kampala, Uganda, and colleagues randomized 393 children to receive monthly sulfadoxine-pyrimethamine (SP) (Kamsidar, Kampala Pharmaceutical Industries), daily trimethoprim-sulfamethoxazole (TMP-SMX) (co-trimoxazole, Kampala Pharmaceutical Industries), monthly dihydroartemisinin-piperaquine (DHAPQ) (Duo-Cotexin, Beijing Holley-Cotec Pharmaceuticals) or no chemoprevention from age 6 months to 24 months. Treatment was administered at home. SP was administered in a single monthly dose; TMP-SMX was a single dose daily; and DHAPQ was administered once daily for 3 consecutive days each month. Study participants were given insecticide-treated bednets and caregivers were encouraged to bring their child to a study clinic in the event of illness.
Of the 393 children enrolled at age 6 months, 89.6% were followed up to age 24 months and 85.6% were followed up to age 36 months.
During intervention, malaria incidence among the no chemoprevention group was 6.95 episodes per person-year at risk. Compared with the no chemoprevention group, monthly SP provided no significant protection against malaria (P=.57); daily TMP-SMX provided moderate protection (P=.01); and monthly DHAPQ provided the most protection (P<.001). Adjusting for household wealth index, primary caregiver’s education level, if the child was parasitemic at enrollment, town or village residence, nutritional status at enrollment, and type of materials used in house construction did not alter protection results.
For all treatment groups, malaria incidence increased with age. All three intervention treatments had the highest protective efficacy when children were aged 6 to 11 months vs. 12 to 24 months.
The protective efficacy of monthly DHAPQ was 41% higher than daily TMP-SMX (P<.001).
During intervention, severe adverse events, including elevated temperature, anemia and thrombocytopenia, were less common among children who received DHAPQ compared with children who received no chemoprevention. This observation was not true for children who received SP or TMP-SMX vs. no chemoprevention.
Nineteen of the 424 severe adverse events were considered possibly related to study drugs, according to researchers. There were no significant differences in the incidence of serious adverse events between the no chemoprevention and intervention groups, although the incidence of severe adverse events was significantly lower among the DHAPQ group.
During the year after intervention was stopped, the malaria incidence was 10.85 episodes per person-year at risk among the no chemoprevention group. This incidence continued to increase with age. There were no significant differences in malaria incidence between the no chemoprevention and intervention groups during the year after intervention stopped.
“This study has identified an effective measure for reducing the incidence of malaria in children living in an area with high rates of the disease… It’s better to try to prevent a potentially fatal illness than it is to wait until the child gets the illness and is at increased risk for dying,” study researcher Lynne Mofenson, MD, chief of the Maternal and Pediatric Infectious Disease Branch at NIH, said in a press release.
For more information:
ClinicalTrials.gov Identifier: NCT00948896.
Disclosure: The study was funded by NIH. The researchers report no relevant financial disclosures.