WHO’s rollout of malaria vaccine in Africa: can safety questions be answered after only 24 months?

Key messages

• Phase III trials of the RTS,S malaria vaccine identified three safety concerns: higher risks of meningitis, cerebral malaria, and doubled female mortality

• These safety concerns are now being investigated in pilot implementation studies with 720 000 participating children in Ghana, Kenya, and Malawi, planned to last 4-5 years

• Owing to the urgency of improving malaria control, the World Health Organization intends to decide on extending the vaccine to other African countries after only 24 months using the prevention of “severe malaria” as a surrogate marker for overall mortality

• Severe malaria is not a good marker for all cause mortality; it is not even a good marker for malaria mortality, as data indicate that case fatality from severe malaria might be higher in the malaria vaccine group

• An early decision after 24 months might be biased in favour of the vaccine, which was more efficacious in the first year of follow-up in the phase III trials; the relative risks of both cerebral malaria and female mortality increased after the booster dose at 20 months

• We recommend that the pilot studies use “overall mortality” to assess vaccine performance and that study populations are followed for the full 4-5 years of the study before a decision on rollout is made