Vaccines for preventing malaria (pre-erythrocytic).
BACKGROUND
Vaccines against all stages of the malaria parasite are in development, mainly for Plasmodium falciparum, which causes the most serious form of malaria. Pre-erythrocytic vaccines act to prevent or delay a malaria attack by attacking the sporozoite and liver stages before the parasite reaches the bloodstream.


OBJECTIVE
To assess the efficacy and safety of pre-erythrocytic malaria vaccines against any type of human malaria.


METHODS
In March 2006, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (The Cochrane Library 2006, Issue 1), MEDLINE, EMBASE, LILACS, and the Science Citation Index. We also searched conference proceedings and reference lists of articles, and contacted organizations and researchers in the field.


METHODS
Randomized controlled trials comparing pre-erythrocytic vaccines with placebo, control vaccine, or routine antimalarial control measures in people of any age receiving an artificial challenge or natural exposure to malaria infection.


METHODS
Both authors independently assessed trial quality and extracted data. Results of meta-analyses were expressed as relative risks with 95% confidence intervals (CI) using an intention-to-treat analysis.


RESULTS
Nine safety and efficacy trials, and two safety trials, with over 3000 participants were included. In semi-immune children, RTS,S vaccine reduced clinical episodes of malaria by 26% (95% CI 13% to 37%) and severe malaria by 58% (95% CI 15% to 79%) for up to 18 months. Prevalence of parasitaemia was also reduced by 26% (95% CI 11% to 38%) at six months after immunization. RTS,S also reduced clinical malaria episodes by 63% (95% CI 18% to 83%) in semi-immune adult men in the second year of follow up after a booster dose. No severe adverse events were judged to be related to RTS,S vaccine, although the frequencies of injection site pain, swelling, arm motion limitation, headache, and malaise were increased in the vaccine groups. There was no evidence for effect of the CS-NANP vaccines (307 participants, 3 trials), CS102 peptide vaccine (14 participants, 1 trial), or the ME-TRAP vaccine (372 participants, 1 trial).


CONCLUSIONS
RTS,S vaccine was effective in preventing a significant number of clinical malaria episodes, including good protection against severe malaria in children for 18 months. No severe adverse events were attributable to the vaccine. Progression of this vaccine towards licensing is justified while efforts to increase its efficacy continue. The other vaccines do not look promising and further research is a priority.
Graves
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EpiVec Consulting, 606 Kimberly Lane NE, Atlanta, GA 30306, USA. epivec@comcast.net
Gelband
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D000328:Adult; D000953:Antigens, Protozoan / Q000276:immunology; D002648:Child; D006801:Humans; D008288:Malaria / Q000517:prevention & control*; D017780:Malaria Vaccines / Q000627:therapeutic use*; D015800:Protozoan Proteins / Q000276:immunology; D019444:Vaccines, DNA / Q000627:therapeutic use
D000953:Antigens, Protozoan; D017780:Malaria Vaccines; D015800:Protozoan Proteins; D019444:Vaccines, DNA; C041595:circumsporozoite protein, Protozoan