Zika virus vaccine(Takeda Pharmaceutical Co., Ltd.)

Since the emergence of the Zika virus epidemic in 2014 and the associated novel sequalae that emerged, much has been learned about the effects of antenatal exposure to Zika virus. Zika virus in pregnancy carries severe teratogenic potential to the fetus, ranging from congenital Zika syndrome to milder neurodevelopmental sequelae. Congenital Zika syndrome is associated with a spectrum of alterations that can affect cognitive, language, and motor development. Among children with congenital Zika syndrome, dysphagia and seizures are common, as are hospitalisations for pneumonia and urinary tract infections; overall, morbidity and mortality are extremely high. Children without congenital Zika syndrome but exposed to Zika virus antenatally are also at risk of developmental disorders. In addition, in utero exposure to Zika virus does not lead to the production of neutralising antibodies. Although the epidemic has subsided, Zika virus remains endemic in many countries and continues to affect families. Maternal associations have been fundamental in advocating for health care for children with congenital Zika syndrome and economic support for families. Gaps in scientific knowledge include the absence of data on long-term outcomes among school-age children. Future research and investments are needed to improve diagnostics, restart the stalled development of Zika virus vaccines, and evaluate antiviral treatments.

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.

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.

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.

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.