Estimated impact of RTS,S/AS01 malaria vaccine allocation strategies in sub-Saharan Africa: a modelling study

Background: The RTS,S/AS01 vaccine against P. falciparum malaria infection completed phase 3 trials in 2014, and demonstrated efficacy against clinical malaria of approximately 36% over 4 years for a 4-dose schedule in children aged 5–17 months. Pilot vaccine implementation has recently begun in three African countries. If the pilots demonstrate both a positive health impact and resolve remaining safety concerns, wider roll-out could be recommended from 2021 onwards. Vaccine demand may however outstrip initial supply. We sought to identify where vaccine introduction should be prioritised to maximise public health impact under a range of supply constraints using mathematical modelling. Methods and Findings: Using a mathematical model of P. falciparum malaria transmission and RTS,S vaccine impact, we estimated the clinical cases and deaths averted in children aged 0–5 years in sub-Saharan Africa under two scenarios for vaccine coverage (100% and realistic) and two scenarios for other interventions (current coverage and WHO Global Technical Strategy targets). We used a prioritisation algorithm to identify potential allocative efficiency gains fromprioritising vaccine allocation among countries or administrative units to maximise cases or deaths averted. If malaria burden at introduction is similar to current levels, assuming realistic vaccine coverage and country-level prioritisation in areas with parasite prevalence >10%, we estimate 4.3 million (95% credible interval, CrI 2.8–6.8 million) malaria cases and 22,000 (95% CrI 11,000–35,000) deaths in children younger than 5 years could be averted annually at a dose constraint of 30 million. This decreases to 3.0 million (95% CrI 2.0–4.7 million) cases and14,000 (95% CrI 7,000–23,000) deaths at a dose constraint of 20 million,and increases to 6.6 million (95% CrI 4.2–10.8 million) cases and38,000 (95% CrI 18,000–61,000) deaths at a dose constraint of 60 million. At 100% vaccine coverage, these impact estimates increase to 5.2 million (95% CrI 3.5–8.2 million) cases and27,000 (95% CrI 14,000–43,000) deaths, 3.9 million (95% CrI 2.7–6.0 million) cases and 19,000 (95% CrI 10,000–30,000) deaths,and 10.0 million (95% CrI 6.7–15.7 million) cases and51,000 (95% CrI 25,000–82,000) deaths respectively. Under realistic vaccine coverage, if the vaccine is prioritised sub-nationally, 5.3 million (95% CrI 3.5–8.2 million) cases and 24,000 (95% CrI 12,000–38,000) deaths could be averted at a dose constraint of 30 million. Furthermore, sub-national prioritisation would allow introduction in almost double the number of countries compared to national prioritisation (21 versus 11). If vaccine introduction is prioritised in the three pilot countries (Ghana, Kenya and Malawi), health impact would be reduced but this effect becomes less substantial (change of