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RTS,S/AS01 Vaccine Reduces Malaria Incidence by Half

Initial results from a phase III trial show protection against clinical and severe malaria during the 12 months after vaccination in children aged 5 to 17 months.

Early trials of the RTS,S/AS01 malaria vaccine have shown approximately 50% efficacy (JW Infect Dis Oct 19 2011). Now, this vaccine is being evaluated in a manufacturer-sponsored, double-blind, multicenter, phase III trial in Africa, among children in two age groups: 6 to 12 weeks and 5 to 17 months.

Children at 11 centers in seven African countries (6537 in the younger age group; 8923 in the older group) were randomized to receive three intramuscular doses of RTS,S/AS01 or a comparator vaccine at monthly intervals. In the younger children, the comparator vaccine was meningococcal C conjugate vaccine; in the older group, it was rabies vaccine.

In an interim (12-month) efficacy analysis conducted among the first 6000 children enrolled in the older age group, vaccine efficacy against clinical malaria was 50.4% in the intent-to-treat population and 55.8% in the per-protocol population. Efficacy against severe malaria was 45.1% and 47.3%, respectively. (Efficacy against severe malaria in the 2 age groups combined was lower — 34.8% — during an average follow-up of 11 months.)

In the interim safety analysis, meningitis was significantly more common in the RTS,S/AS01 group than in the control group for both age categories. In the older age category, 10 children in the RTS,S/AS01 group had at least one vaccine-related serious adverse event, including seven seizures (rate, 1.04 per 1000 doses), compared with only 1 child in the control group (who also had a seizure). The proportions of children dying and the causes of death were similar between the RTS,S/AS01 and control groups in the 5–17 month category.

Comment: Overall, these results support the findings of earlier studies. Contrary to expectations, however, no reduction was observed in malaria-related or all-cause mortality in the RTS,S/AS01 group. The authors attribute this finding to a very low rate of malaria-specific mortality in the overall study population during the course of the trial. Continued monitoring of meningitis is needed to assess whether the increase in the RTS,S/AS01 group persists. Other key questions (including duration of protection and cost) also remain unanswered. Nonetheless, as noted by an editorialist, the WHO has already indicated that it could recommend vaccine use in some areas as early as 2015 — after the full results from this trial (available in 2014) have been analyzed. Although reductions in malaria episodes and deaths have been achieved through current interventions, the addition of an effective malaria vaccine to available tools could hasten control and would be especially valuable if resistance to current first-line drugs increases.

— Mary E. Wilson, MD

Published in Journal Watch Infectious Diseases October 20, 2011

Citation(s):

The RTS,S Clinical Trials Partnership. First results of phase 3 trial of RTS,S/AS01 malaria vaccine in African children. N Engl J Med 2011 Oct 18; [e-pub ahead of print]. (http://dx.doi.org/10.1056/NEJMoa1102287)

White NJ. A vaccine for malaria. N Engl J Med 2011 Oct 18; [e-pub ahead of print]. (http://dx.doi.org/10.1056/NEJMe1111777)

Reader Remarks:

Review and add to remarks on this article

• Mortality
  Md. Shahidul Islam, Stockholm, 2 Nov 2011 1:30 PM EST
  Specialty: Internal Medicine
  Han any malaria vaccine so far reduced MORTALITY in those who are infected by malaria?

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