Children in Uganda

Credit: Malayaka house

Year-round prophylaxis with a newer antimalaria treatment can reduce the risk of malaria in young children without posing a risk of serious adverse events, according to a study published in PLOS Medicine.

The researchers found that dihydroartemisinin-piperaquine (DP), an artemisinin-based combination therapy, was the most effective of 3 treatments at reducing malaria risk in children aged 6 months to 24 months.

The other 2 treatments, the antifolates sulfadoxine-pyrimethamine (SP) and trimethoprim-sulfamethoxazole (TS), have been in use longer than DP. And, in many locations, the malaria parasite has developed a resistance to them.

The researchers conducted this study to determine if the benefits of malaria prophylaxis outweighed the potential risk of anemia and other side effects from the drugs.

And they found the benefits did outweigh the risks. There was no significant increase in grade 3/4 adverse events with any of the treatments when compared to a control group.

The researchers also wanted to look specifically at the effects of year-round treatment. They noted that most previous studies of malaria prophylaxis have been limited to areas where there is only a seasonal risk of the disease. But this study took place in Uganda, where the risk persists throughout the year.

“Our study showed that preventive drug treatment can greatly reduce malaria in young children in areas where there are year-round high rates of transmission,” said study author Grant Dorsey, MD, of the University of California, San Francisco.

To make this discovery, the researchers studied 393 children from Tororo, Uganda. Beginning at 6 months of age, the children were randomized to 1 of 4 groups: monthly DP, monthly SP, daily TS, or a group that didn’t receive any prophylaxis, which is the standard medical practice in the area.

Treatments were given at home without supervision. Piperaquine levels were used as a measure of compliance in the DP arm.

All of the families involved in the study received insecticide-treated bed nets to put over the children when they slept. By 24 months of age, 352 children were still taking part in the study.

There were 3.02 malaria episodes per person-year in the DP group, 5.21 in the TS group, 6.73 in the SP group, and 6.95 in the control group. Protective efficacy measured 58% for the DP group, 28% for the TS group, and 7% for the SP group.

Piperaquine levels were below the detection limit 52% of the time when malaria was diagnosed in the DP group, which suggests non-adherence to treatment.

Between the groups, there was no significant difference in the rate of grade 3/4 adverse events related to treatment. There were 8 such events in the SP group, 8 in the TS group, and 3 in the DP group. Events included elevated temperature, anemia, neutropenia, thrombocytopenia, and elevated ALT/AST.

Considering all grade 3/4 adverse events regardless of their relationship to treatment, the researchers found the overall incidence was significantly lower in the DP group, but not the SP or TS groups, compared to the control group. The same was true for the incidence of elevated temperature, anemia, and thrombocytopenia.

After discontinuing the children’s treatment at 24 months of age, the researchers followed the children until age 3 and found no difference in malaria rates between the groups.

The team said these results suggest monthly administration of DP is a safe and effective option for reducing malaria among infants in regions with year-round transmission and high resistance to antifolates.

The findings also help to allay any concerns that continuous treatment might interfere with the children’s ability to develop an immune response against malaria, thereby making them more likely to contract the disease after treatment stops.

The researchers noted, however, that additional research is needed to evaluate the preventive efficacy of DP in other areas, maintain surveillance for potential selection of drug-resistant parasites, and evaluate the role of preventative treatment in the context of other malaria control interventions.

Malaria prophylaxis appears safe, effective in kids