Persistence of Anti-ZIKV-IgG over Time Is Not a Useful Congenital Infection Marker in Infants Born to ZIKV-Infected Mothers: The NATZIG Cohort

Confirming ZIKV congenital infection is challenging because viral RNA is infrequently detected. We compared the presence of anti-ZIKV-IgM and the persistence of anti-ZIKV-IgG antibodies over 18 months in two cohorts of infants born to ZIKV-infected mothers: Cohort one: 30 infants with typical microcephaly or major brain abnormalities (Congenital Zika Syndrome-CZS); Cohort two: 123 asymptomatic infants. Serum samples obtained within 6 months of age were tested for anti-ZIKV-IgM. Anti-ZIKV-IgG was quantified in sequential samples collected at birth, 3–6 weeks, 3, 6, 12, and 18 months. ZIKV-RNA was never detected postnatally. Anti-ZIKV-IgM antibodies were detected at least once in 15/25 (60.0%; 95%CI: 38.7–78.9) infants with CZS and in 2/115 (1.7%; 95%CI: 0.2–6.1) asymptomatic infants. Although anti-ZIKV-IgG was always positive within 3–6 weeks of age, IgG levels decreased similarly over time in both cohorts. IgG levels decreased similarly in ZIKV-IgM-positive and ZIKV-IgM-negative CZS infants. Differently from other congenital infections, IgM would fail to diagnose 40% of severely symptomatic infants, and the persistence of IgG is not a useful marker for discriminating congenital infection among infants exposed to maternal ZIKV infection.

[1]  J. Dunn,et al.  Update in Pediatric Diagnostic Microbiology. , 2020, Clinics in laboratory medicine.

[2]  C. Aranda,et al.  Immune system: development and acquisition of immunological competence , 2020, Jornal de pediatria.

[3]  Early maternal Zika infection predicts severe neonatal neurological damage: results from the prospective Natural History of Zika Virus Infection in Gestation cohort study , 2020, BJOG : an international journal of obstetrics and gynaecology.

[4]  G. Cheng,et al.  Zika virus vertical transmission in children with confirmed antenatal exposure , 2020, Nature Communications.

[5]  M. Koopmans,et al.  Performance of Zika Assays in the Context of Toxoplasma gondii, Parvovirus B19, Rubella Virus, and Cytomegalovirus (TORCH) Diagnostic Assays , 2019, Clinical Microbiology Reviews.

[6]  A. Ko,et al.  Zika Virus Infection - After the Pandemic. , 2019, The New England journal of medicine.

[7]  L. Coffey,et al.  Postnatal Zika virus infection of nonhuman primate infants born to mothers infected with homologous Brazilian Zika virus , 2019, Scientific Reports.

[8]  R. Dietze,et al.  Efficient transplacental IgG transfer in women infected with Zika virus during pregnancy , 2019, PLoS neglected tropical diseases.

[9]  S. Briolant,et al.  Performance of 2 Commercial Serologic Tests for Diagnosing Zika Virus Infection , 2019, Emerging infectious diseases.

[10]  M. Collins,et al.  Detecting Vertical Zika Transmission: Emerging Diagnostic Approaches for an Emerged Flavivirus. , 2019, ACS infectious diseases.

[11]  I. Brandi,et al.  Difficulties with laboratory confirmation of congenital Zika virus infection in a tertiary hospital in Northeastern Brazil. , 2019, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[12]  L. Rodrigues,et al.  Perinatal analyses of Zika- and dengue virus-specific neutralizing antibodies: A microcephaly case-control study in an area of high dengue endemicity in Brazil , 2019, PLoS neglected tropical diseases.

[13]  D. Rousset,et al.  Maternal-fetal transmission and adverse perinatal outcomes in pregnant women infected with Zika virus: prospective cohort study in French Guiana , 2018, British Medical Journal.

[14]  V. Wiwanitkit,et al.  Zika Virus Infection Among Pregnant Women and Their Neonates in New York City, January 2016-June 2017. , 2018, Obstetrics and Gynecology.

[15]  N. M. Vora,et al.  Zika Virus Infection Among Pregnant Women and Their Neonates in New York City, January 2016-June 2017. , 2018, Obstetrics and gynecology.

[16]  D. O’Connor,et al.  Antibody responses to Zika virus proteins in pregnant and non-pregnant macaques , 2018, bioRxiv.

[17]  A. Fomsgaard,et al.  Zika Virus IgG in Infants with Microcephaly, Guinea-Bissau, 2016 , 2018, Emerging infectious diseases.

[18]  J. Muñoz-Jordán,et al.  Persistence of Zika Virus in Body Fluids — Final Report , 2017, New England journal of medicine.

[19]  Christophe Pasquier,et al.  Kinetics of anti-ZIKV antibodies after Zika infection using two commercial enzyme-linked immunoassays. , 2018, Diagnostic microbiology and infectious disease.

[20]  R. DeBiasi,et al.  Update: Interim Guidance for the Diagnosis, Evaluation, and Management of Infants with Possible Congenital Zika Virus Infection — United States, October 2017 , 2017, MMWR. Morbidity and mortality weekly report.

[21]  R. Charrel,et al.  Variable Sensitivity in Molecular Detection of Zika Virus in European Expert Laboratories: External Quality Assessment, November 2016 , 2017, Journal of Clinical Microbiology.

[22]  F. Rovida,et al.  Antibody-based assay discriminates Zika virus infection from other flaviviruses , 2017, Proceedings of the National Academy of Sciences.

[23]  R. Césaire,et al.  Analysis of blood from Zika virus-infected fetuses: a prospective case series. , 2017, The Lancet. Infectious diseases.

[24]  S. Rasmussen,et al.  Characterizing the Pattern of Anomalies in Congenital Zika Syndrome for Pediatric Clinicians , 2017, JAMA pediatrics.

[25]  Y. Maldonado,et al.  Diagnosis, Treatment, and Prevention of Congenital Toxoplasmosis in the United States , 2017, Pediatrics.

[26]  Catherine M. Brown,et al.  Birth Defects Among Fetuses and Infants of US Women With Evidence of Possible Zika Virus Infection During Pregnancy , 2017, JAMA.

[27]  K. Aagaard,et al.  Prolonged Detection of Zika Virus in Vaginal Secretions and Whole Blood , 2017, Emerging infectious diseases.

[28]  O. Nascimento,et al.  Congenital Zika Virus Infection: Beyond Neonatal Microcephaly. , 2017, JAMA neurology.

[29]  F. Tovar-Moll,et al.  Congenital Zika Virus Infection: Beyond Neonatal Microcephaly. , 2017, JAMA neurology.

[30]  L. Pena,et al.  Results of a Zika Virus (ZIKV) Immunoglobulin M-Specific Diagnostic Assay Are Highly Correlated With Detection of Neutralizing Anti-ZIKV Antibodies in Neonates With Congenital Disease. , 2016, The Journal of infectious diseases.

[31]  D. Levine,et al.  Congenital Brain Abnormalities and Zika Virus: What the Radiologist Can Expect to See Prenatally and Postnatally. , 2016, Radiology.

[32]  M. Valença,et al.  Clinical features and neuroimaging (CT and MRI) findings in presumed Zika virus related congenital infection and microcephaly: retrospective case series study , 2016, British Medical Journal.

[33]  M. Valença,et al.  Clinical features and neuroimaging (CT and MRI) findings in presumed Zika virus related congenital infection and microcephaly: retrospective case series study , 2016, British Medical Journal.

[34]  José Villar,et al.  International standards for newborn weight, length, and head circumference by gestational age and sex: the Newborn Cross-Sectional Study of the INTERGROWTH-21st Project , 2014, The Lancet.

[35]  Cameron P Simmons,et al.  Dengue virus infections and maternal antibody decay in a prospective birth cohort study of Vietnamese infants. , 2009, The Journal of infectious diseases.

[36]  R. Lanciotti,et al.  Genetic and Serologic Properties of Zika Virus Associated with an Epidemic, Yap State, Micronesia, 2007 , 2008, Emerging infectious diseases.

[37]  A. Nisalak,et al.  Transplacentally transferred maternal-infant antibodies to dengue virus. , 2003, The American journal of tropical medicine and hygiene.