Published: Aug 5, 2014
By Michael Smith, North American Correspondent, MedPage Today
A monthly pill appears to protect infants against malaria in regions where the mosquito-borne disease is transmitted year round, researchers reported.
In a randomized open-label trial,dihydroartemisinin-piperaquine (Duo-Cotecxin) had a protective efficacy of 58% compared with no medication, according to Grant Dorsey, MD, of the University of California San Francisco, and colleagues.
The drug combination -- known as DP in the trial -- also outperformed other antimalaria drugs in protecting infants, Dorsey and colleagues reported online in PLOS Medicine.
The DP combination might actually have worked better than the 58% figure would suggest, the researchers reported, since there was evidence of nonadherence in about half of the children diagnosed with malaria who were supposed to be taking the drug.
Chemoprevention "offers a promising strategy" to prevent malaria in African children, the authors noted, but it's not clear exactly how to do that in regions where transmission occurs year round and the disease is resistant to many antimalarial drugs.
To help clarify the issue, Dorsey and colleagues conducted a randomized trial comparing no chemoprevention to three medication arms -- monthly dihydroartemisinin-piperaquine (DP), monthly sulfadoxine-pyrimethamine (SP), and daily trimethoprim-sulfamethoxazole (TS).
Children were enrolled at 6 months and received study medication until they were 2. The researchers then followed them for another year. The primary endpoint of the study was efficacy in preventing malaria during the intervention period, compared with no chemoprevention.
During the intervention, the incidence of malaria in the no chemoprevention arm was 6.95 episodes per person-year at risk, compared with 6.73 in the SP arm, 5.21 in the TS arm, and 3.02 in the DP arm.
Compared with no prevention, the protective efficacy was 7% for SP, 28% for TS, and 58% for DP, the researchers reported, although only the latter two reached statistical significance.
Protection was better in the first 6 months of the trial and declined in the following 12 months. Specifically:
For the DP combination, malaria incidence in the first 6 months was 1.49 per person-year at risk, compared with 3.88 in the 12 months following. Those rates yielded respective protective efficacies of 78% and 45%, both significant (P<0.001) compared with no chemoprevention.
For the daily TS combination, incidence in the first 6 months was 3.27 per person-year at risk, compared with 6.32 in the following year, yielding efficacy rates of 51% and 11% compared with no chemoprevention. Only the first was statistically significant.
For the monthly SP duo, incidence was 5.51 per person-year at risk in the first 6 months and 7.41 thereafter. Neither was significantly different from no chemoprevention.
Based on diaries completed by primary caregivers, more than 98% of the assigned doses of the study drugs was administered, Dorsey and colleagues reported.
But an analysis of blood among children assigned to the DP combination drug who were diagnosed with malaria told a different story: 52% of them had no detectable piperaquine, suggesting "frequent nonadherence."
All told 2,487 treatments were given for malaria during the intervention period, including 21 for complicated malaria and nine for severe malaria.
There were no significant differences in complicated malaria, hospital admission, diarrhea, or respiratory tract infections between the intervention arms and the control arm.
On the other hand, moderate to severe anemia, defined as hemoglobin less than 8 grams per deciliter, was significantly higher in the SP arm and lower in the DP arm than in the no chemoprevention arm.
As well, the researchers reported, the incidence of elevated temperature, anemia, and thrombocytopenia was significantly lower in the DP arm, but not the other two medication arms, compared with no chemoprevention.
In the year after the intervention, the incidence of malaria in the no chemoprevention arm was 10.85 cases per person-year at risk, not significantly different from any of the chemoprevention arms.
Dorsey and colleagues cautioned that parents or caregivers gave study drugs at home and administration was not directly observed. As well, they noted, multiple comparisons mean that a finding of statistical significance should be interpreted cautiously.
And, they noted, the study took place in an area of high transmission intensity, and widespread resistance to antifolate drugs so the results might not apply elsewhere.
AMSA at UC Merced is where student idealism is transformed into meaningful public service, innovation and institutional change. We hope to provide students with the insight and support necessary to evoke change within their respective avenues of medical advocacy and the achievement of their dreams in each of their medical careers.