Ensuring the Public Health Impact of Malaria Vaccination in High-Transmission Settings.

Two vaccines against Plasmodium falciparum, RTS,S and R21, have been recommended for widespread implementation by the World Health Organization. Both vaccines displayed safety and efficacy in clinical trials, and early RTS,S pilot implementation results suggested reductions in severe disease and death. However, RTS,S efficacy was lower in higher transmission settings during trials. Between- and within-site analyses suggest that reduced efficacy was partially due to greater natural immunity development in control groups in higher transmission settings, resulting in temporary periods of negative efficacy beginning approximately three years after the primary vaccine series. Results from RTS,S pilot implementation and seasonal administration for both vaccines are promising, but study designs have thus far precluded the identification of similar periods of negative efficacy. Because we expect delayed malaria cases of unknown severity in vaccinated individuals during implementation in high-transmission settings, we recommend enhanced surveillance and interventions that supplement malaria vaccination to strengthen prevention.