Table 1

Summary of points supporting and not supporting each criterion of the Wilson and Jungner screening framework, with additional recommendations for futher research and/or public health actions

CriteriaPoints supporting the criterionPoints not supporting the criterionRecommendations for further public health action(s) and/or research
1. The condition sought should be an important health problem
  • ZIKV infection during pregnancy may lead to cases of CZS, which can pose a significant burden at the individual, family, and societal level.

  • ZIKV infection during pregnancy occurs at a lower frequency between outbreaks in areas with arbovirus circulation.

  • Public health surveillance for ZIKV epidemics to inform the timing and type of prenatal ZIKV screening programme.

  • Research on the long-term health, social and economic impacts of CZS on affected children, families, and communities.

2. There should be a suitable test or examination
  • Validated and acceptable molecular and serological tests for detecting ZIKV infections during pregnancy are currently available.

  • Molecular tests have narrow windows of detection.

  • Serological tests are subject to immunological cross-reactivity with other flaviviruses.

  • Combining highly specific molecular tests and highly sensitive serological tests to allow for more accurate identification of ZIKV infections.

  • Research to develop diagnostic tests with enhanced sensitivity and specificity.

  • Research to evaluate performance of tests in settings with endemic flavivirus circulation.

3. The natural history of the condition, including development from latent to declared disease, should be adequately understood
  • Children with CZS who survive infancy are expected to have a prognosis comparable with children who have other conditions associated with microcephaly, epilepsy, and intellectual disability.

  • Significant heterogeneity remains in the risk estimates of adverse outcomes associated with prenatal ZIKV exposure, in part due to inconsistencies in the range of outcomes assessed.

  • The prognosis of children with prenatal ZIKV exposure remains uncertain beyond 5 years of age.

  • Expansion of infrastructure and governance policies for sustained data sharing between Zika cohort studies.

  • Research using individual participant data meta-analyses of pregancy and paediatric cohorts and standardised outcomes to improve the precision of risk estimates.

  • Research using paediatric cohort studies and linked electronic health records to follow up children with prenatal ZIKV exposure born with or without apparent manifestations of CZS.

4. There should be a recognisable latent or early symptomatic stage
  • Sensitive and specific laboratory diagnostic assays have the potential to detect maternal ZIKV infections before the onset of severe fetal anomalies.

  • Antivirals for impeding vertical transmission of ZIKV are not currently available.

  • Prenatal and postnatal testing to identify offspring who may be ZIKV-exposed but uninfected remains limited.

  • A large portion of ZIKV infections are asymptomatic.

  • Public health efforts to improve antenatal care attendance.

  • Monitoring of children with prenatal ZIKV exposure who present asymptomatically at birth for developmental delays and late-onset sequelae of congenital infections.

  • Research to develop antiviral treatments to block vertical transmission.

  • Research to improve the safety and effectiveness of testing for offspring infection status (eg, via amniocentesis or neonatal serum/urine testing).

5. The test should be acceptable to the population
  • Non-invasive prenatal screening tests for STORCH agents are generally well accepted.

  • There is limited research on the attitudes towards prenatal screening tests for ZIKV.

  • Public health education and communication on risks of prenatal ZIKV infections and screening methods.

  • Research on attitudes of expectant families in ZIKV-endemic settings.

6. There should be an agreed policy on whom to treat as patients
  • Both the pregnant person and offspring would be considered as patients due to the potential for vertical transmission of ZIKV infection during pregnancy.

  • Local policies may differ with regards to the rights of pregnant persons and their offspring (eg, with respect to pregnancy terminations).

  • Prenatal counselling following positive screening test result.

  • Postnatal clinical and social support for children with prenatal exposure to ZIKV and their families.

  • Research to evaluate indirect effects of CZS on caregivers’ mental health, social support, and lived experiences.

7. There should be an accepted treatment for patients with recognised disease
  • Anticipatory guidance to caregivers and early referrals to appropriate specialists and early intervention programmes for the affected child and family is well accepted.

  • There are no available vaccines or antiviral treatments.

  • Access to unrestricted legal abortion remains rare in many settings where ZIKV is endemic.

  • Expanded access to specialised treatment programmes for children with CZS.

  • Research to develop vaccines to prevent ZIKV infection during pregnancy.

  • Research to develop antiviral treatments to prevent vertical transmission.

8. Facilities for diagnosis and treatment should be available
  • Diagnostics and expertise developed during the last ZIKV epidemic exist.

  • Utilisation of existing ZIKV diagnostic assays require significant resources.

  • Follow-up care for CZS patients and their families requires long-term financial commitment from health systems.

  • Public health efforts to improve accessibility and affordability of tests.

  • Research to develop rapid, low-cost, point-of-care testing.

  • Research into effectiveness of interventions in clinically relevant subgroups to inform targeted treatment.

9. The cost of case finding should be economically balanced in relation to possible expenditure on medical care as a whole
  • Screening is likely to be most cost-effective during an outbreak situation.

  • In non-outbreak situations, screening may not be cost-effective, as screening costs could be more than the preventable costs.

  • Enhancing capacity to rapidly integrate ZIKV screening into existing prenatal testing platforms during outbreak situations.

  • Research to develop multiplex prenatal screening assays, including ZIKV testing.

10. Case finding should be a continuing process and not as a once-and-for-all project
  • Ultrasound may be used with or in lieu of laboratory testing to detect cases of CZS.

  • Routine paediatric evaluations and developmental screening may be used to detect CZS-related anomalies at a later stage.

  • Maternal ZIKV infections may be asymptomatic, and ZIKV-exposed infants may present without typical CZS features.

  • Increased monitoring of pregnancies during an outbreak situation.

  • Continued monitoring of symptomatic and asymptomatic children with prenatal ZIKV exposure for developmental delays and late-onset sequelae of congenital infections.

  • Research evaluating paired mother-offspring testing to detect congenital infections postnatally.

  • CZS, Congenital Zika Syndrome; STORCH, (syphilis, toxoplasmosis, others (eg, human immunodeficiency virus, varicella-zoster virus, parvovirus B19), rubella, cytomegalovirus, and herpes simplex virus); ZIKV, Zika virus.