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Malaria — A Potential Vaccine and New Treatments

The treatment of children with malaria must be based on knowledge of the specific organism and local resistance patterns.

Malaria kills an estimated 800,000 children annually worldwide and infects hundreds of millions of other children. Three studies provide information on the efficacy and safety of malaria vaccines and treatments in infants and children.

In one industry-sponsored, double-blind, randomized trial, 894 infants (age range, 5–17 months) in Kenya and Tanzania received three doses (1 per month) of either RTS,S/AS01E malaria vaccine or rabies vaccine. At a mean follow-up of 8 months, the cumulative incidence of the first or only episode of Plasmodium falciparum infection was significantly lower in the malaria-vaccine group than in the rabies-vaccine group (8% vs. 16%). The rate of serious side effects was lower in the malaria-vaccine group (11% vs. 18%).

In another trial, 340 infants in Tanzania received three doses (at 8, 12, and 16 weeks of age) of either RTS,S/AS02D malaria vaccine or hepatitis B vaccine. All infants also received diphtheria, tetanus, and pertussis with Haemophilus influenzae type b (DTPw/Hib) vaccine. At 1 month, antibody responses to each component of the DTPw/Hib vaccine were similar in the two vaccine groups, indicating that coadministration of the malaria and DTPw/Hib vaccines did not interfere with antibody development. At 6 months, the malaria vaccine significantly reduced the incidence of first P. falciparum malaria infection (adjusted efficacy rate, 65%). The rate of serious adverse events was similar in the two groups.

In Papua New Guinea, where resistance to standard antimalarial drugs has emerged, researchers randomized 482 children (age range, 6 months to 5 years) with P. falciparum malaria and 195 with P. vivax malaria to receive chloroquine-sulfadoxine-pyrimethamine or one of three artemisinin-based combination therapies. In P. falciparum-infected children, aremether-lumefantrine was associated with the highest rate of adequate clinical and parasitologic response (95%), followed by dihydroartemisinin-piperaquine (88%), artesunate-sulfadoxine-pyrimethamine (85%), and chloroquine-sulfadoxine-pyrimethamine (82%). In P. vivax-infected children, the rate of adequate clinical and parasitologic response in the dihydroartemisinin-piperaquine group (69%) was more than twice the rate of that in the other groups.

Comment: The RTS,S vaccine is the first candidate vaccine to show significant protection against clinical malaria and to reach phase 3 trials (beginning in 2009). Hopefully, widespread use will begin in the near future. The treatment of children with malaria must be based on knowledge of the specific organism and local resistance patterns. Although P. vivax can be distinguished from P. falciparum malaria based on laboratory examination, data on resistance often are not known by providers who are instituting treatment. Hence, the World Health Organization recommendations for treatment of malaria are important.

— Howard Bauchner, MD

Published in Journal Watch Pediatrics and Adolescent Medicine December 10, 2008

Citation(s):

Bejon P et al. Efficacy of RTS,S/AS01E vaccine against malaria in children 5 to 17 months of age. N Engl J Med 2008 Dec 11; 359:2521.

• Original article (Subscription may be required)
• Medline abstract (Free)

Abdulla S et al. Safety and immunogenicity of RTS,S/AS02D malaria vaccine in infants. N Engl J Med 2008 Dec 11; 359:2533.

• Original article (Subscription may be required)
• Medline abstract (Free)

Karunajeewa HA et al. A trial of combination antimalarial therapies in children from Papua New Guinea. N Engl J Med 2008 Dec 11; 359:2545.

• Original article (Subscription may be required)
• Medline abstract (Free)