August 25, 2014

Drug Prevents Malaria in High-Risk Region

At a Glance

  • A combination drug treatment substantially reduced the incidence of malaria in young children without causing serious side effects.
  • The treatment could help reduce the burden of malaria among those most at risk, such as young children living in Africa.
Mosquito. A female Anopheles gambiae mosquito feeding on a human.CDC, James Gathany

Malaria is caused by the Plasmodium parasite, which is transmitted to people through mosquitoes. More than 40% of the world’s population lives in at-risk regions. Malaria affects about 300-500 million people each year. Most cases can be successfully treated, but nearly 1 million still die of the disease every year, including about 800,000 children under age 5 in Sub-Saharan Africa.

Researchers have been developing vaccines and other preventive strategies to combat malaria. In addition to insecticide-treated bed nets, certain drugs can help prevent malaria in infants during the rainy season. However, they aren’t recommended in areas with a high risk of malaria year round and with high rates of drug resistance.

A team at the University of California, San Francisco, led by Dr. Grant Dorsey and colleagues in Kampala, Uganda, compared drugs to prevent infant malaria in areas with a high risk year round and high rates of drug resistance. The effort was funded by NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD).

The team enrolled 400 infants in eastern Uganda. At 6 months of age, the children were randomly divided into 4 groups. They received either current preventative treatments—the antifolate drugs sulfadoxine-pyrimethamine (SP) monthly or trimethoprim-sulfamethoxozole (TS) daily, or a new combination drug called dihydroartemisinin-piperaquine (DP) once daily for 3 consecutive days each month. A fourth control group received the current standard of care, with no preventive drugs.

The drugs were administered by the families and recorded in a diary. Infants were routinely monitored at clinics. Families were also encouraged to take the children to the clinic any time they were ill. All families were given insecticide-treated bed nets and encouraged to use them. Treatments stopped at 24 months of age, and most children (340) were followed until age 3. Results appeared on August 5, 2014, in PLOS Medicine.

The researchers found that DP provided the most protection, with children in the DP group 58% less likely to develop malaria than those in the control group. TS treatment was moderately protective (28%), but SP treatment wasn't significantly different from the non-treatment group (7%).There were 3.02 malaria episodes per person year in the DP group, 5.21 for the TS group, 6.73 for the SP group, and 6.95 for the control group. There were no significant side effects from the drugs. In addition, after the interventions stopped, the rates of malaria in the groups were similar over the next year.

Notably, tests performed on the day malaria was diagnosed suggested that a complete dose of DP hadn’t been given to the infant in the previous month in half the malaria cases. These findings suggest that DP is a promising long-term preventative treatment for malaria in infants. However, ensuring proper dosing may be a challenge. Further studies will also be needed to clarify the long-term safety and efficacy of DP treatment.

“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,” Dorsey says. “We believe that this treatment regimen will be of substantial benefit in many parts of the world in need of improved malaria control measures.”

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Reference: Protective efficacy and safety of three antimalarial regimens for the prevention of malariain young ugandan children: a randomized controlled trial. Bigira V, Kapisi J, Clark TD, Kinara S, Mwangwa F, Muhindo MK, Osterbauer B, Aweeka FT, Huang L, Achan J, Havlir DV, Rosenthal PJ, Kamya MR, Dorsey G. PLoS Med. 2014 Aug 5;11(8):e1001689. doi: 10.1371/journal.pmed.1001689. eCollection 2014 Aug. PMID: 25093754.

Funding: NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD).