G: Global Health
Oral Abstract Submission
Flor M. Munoz, MD
Associate Professor of Pediatrics
Baylor College of Medicine
Disclosure: Biocryst: Grant/Research Support
CDC: Research Grant
Moderna: Other Financial or Material Support, Safety Monitoring Board Member/Chair
NIH: Research Grant
Novavax: Research Grant
UP to Date: Author and Editor - Royalties, Other Financial or Material Support
Evan J. Anderson, MD
Infectious Diseases Physician
Emory University, Atlanta VA Medical Center
Disclosure: AbbVie: Consultant
MedImmune: Scientific Research Study Investigator
Merck: Scientific Research Study Investigator
Micron Biomedical: Scientific Research Study Investigator
Novavax: Grant/Research Support
PaxVax: Scientific Research Study Investigator
Pfizer: Consultant, Grant/Research Support
Regeneron: Scientific Research Study Investigator
Sanofi Pasteur: Scientific Research Study Investigator
Background : Diagnosing ZIKV infection in children in dengue (DENV) endemic regions is challenging. The kinetics and effects of maternal Ab on infant infection responses remain unknown, as do the ND effects of ZIKV acquired in early life.
Methods : Population-based prospective cohort study in infant-mother pairs and children < 5 y in a rural DENV endemic area of Guatemala to evaluate the incidence and ND outcomes of postnatally-acquired ZIKV infection. Subjects were followed 1 year for symptoms of flavivirus-like illness (FLI), serologic and virologic evidence of ZIKV or DENV infection and ND outcomes. ZIKV and DENV neutralizing antibodies (NAb) were measured at enrollment and longitudinally. Subjects were classified as ZIKV- or DENV-infected based on NAb. Specimens from acute illnesses were tested for viral RNA by rRT-PCR. ND was assessed at enrollment and longitudinally using an adapted Mullen Scales of Early Learning (MSEL).
Results : 1,371 subjects (374 children 1-5 y, 500 infants, 497 mothers) were enrolled 06/2017-07/2018. Among 1,335 evaluable subjects, 7.6% (101) had serologic evidence of recent ZIKV infection (NAb > 500 or > 100 and DENV-neg); 13.2% (176) were DENV-pos only; 44.8% (598) were ZIKV-neg (NAb15 - < 100) or low (< 500) ZIKV and DENV NAb, suggesting prior flavivirus infection or cross reactivity. (Figs 1 and 2) ZIKV infection alone was more prevalent in children 1-5 y, while infants’ serologic pattern was similar to that of their mothers. One child ZIKV seroconverted. In 391 FLI episodes (67 children 1-5 y and 215 infants with fever, rash, myalgia and conjunctivitis; 109 mothers with fever, myalgia and joint pain), acute DENV infections, but not ZIKV, were identified by rRT-PCR. MSEL scores were similar to US norms in infants < 12 m (composite mean 94.8, SD 11.9), but lower in children 1-5 y in all domains (mean 75.1, SD 17.4, p< 0.0001) (Fig 3).
Conclusion : Serologic evidence of recent ZIKV infection, but no acute ZIKV, was documented in young children in Guatemala. Infant seroreactivity derives from prior maternal infection and DENV cross-reactivity. Observed substantial differences in ND scores between infants and children 1-5 y challenge the ability to isolate potential effects of ZIKV infection in early life. NIAID Contract HHSN272201300015I Task Order HHSN27200013. FMM & EJA Co-PIs.