Modelling the impact and cost-effectiveness of upcoming Zika virus vaccines on congenital Zika syndrome

Background: Zika virus (ZIKV) continues to circulate in Southeast Asia following the 2015-2016 global epidemic, posing an ongoing risk of importation and disease spread for Singapore, a tropical city-state in the region. The virus remains a threat to pregnant women and their fetuses due to the risk of Congenital Zika Syndrome (CZS). Vaccines currently in development offer hope for reducing ZIKV infections and CZS cases.

Methods: We developed an agent-based compartmental model, incorporating Singapore's demographic dynamics, to simulate ZIKV epidemic trajectories and project the national disease burden of CZS over the next decade. We proposed eight vaccination strategies targeting females of child-bearing age and evaluated their cost-effectiveness-in terms of the incremental cost-effectiveness ratio (ICER)-across scenarios with varying vaccine efficacy, protection duration, coverage rate, vaccination cost, and pre-existing immunity levels in the population.

Results: Continuous high importation of ZIKV could lead to multiple small outbreaks in the next decade. Total CZS case numbers over the next decade were projected to be 68 (95 % confidence interval [CI]: 66-70), 51 (95 % CI: 49-52), and 32 (95 % CI: 31-33) under scenarios of 0 %, 2 %, and 5 % pre-existing immunity, respectively. While mass vaccination for females would avert up to 66 (95 % CI: 64-69), 49 (95 % CI: 48-50), and 31 (95 % CI: 30-31) CZS cases, respectively, the cost-effectiveness of these strategies should be evaluated on a case-by-case basis. The pre-pregnancy vaccination strategy demonstrated consistent cost-effectiveness regardless of vaccine protection duration, vaccine efficacy, vaccine price, or pre-existing immunity level in the population.

Conclusions: Localised outbreaks driven by importation are likely to persist in Singapore. The pre-pregnancy vaccination strategy is consistently cost-effective and should be considered. Mass vaccination may also be viable with the availability of a low-cost vaccine providing long-term protection.