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Testing for Zika virus infection in pregnancy: key concepts to deal with an emerging epidemic.
Am J Obstet Gynecol. 2017 03; 216(3):209-225.AJ

Abstract

Zika virus is an emerging mosquito-borne (Aedes genus) arbovirus of the Flaviviridae family. Following epidemics in Micronesia and French Polynesia during the past decade, more recent Zika virus infection outbreaks were first reported in South America as early as May 2013 and spread to now 50 countries throughout the Americas. Although no other flavivirus has previously been known to cause major fetal malformations following perinatal infection, reports of a causal link between Zika virus and microcephaly, brain and ocular malformations, and fetal loss emerged from hard-hit regions of Brazil by October 2015. Among the minority of infected women with symptoms, clinical manifestations of Zika virus infection may include fever, headache, arthralgia, myalgia, and maculopapular rash; however, only 1 of every 4-5 people who are infected have any symptoms. Thus, clinical symptom reporting is an ineffective screening tool for the relative risk assessment of Zika virus infection in the majority of patients. As previously occurred with other largely asymptomatic viral infections posing perinatal transmission risk (such as HIV or cytomegalovirus), we must develop and implement rapid, sensitive, and specific screening and diagnostic testing for both viral detection and estimation of timing of exposure. Unfortunately, despite an unprecedented surge in attempts to rapidly advance perinatal clinical testing for a previously obscure arbovirus, there are several ongoing hindrances to molecular- and sonographic-based screening and diagnosis of congenital Zika virus infection. These include the following: (1) difficulty in estimating the timing of exposure for women living in endemic areas and thus limited interpretability of immunoglobulin M serologies; (2) cross-reaction of immunoglobulin serologies with other endemic flaviruses, such as dengue; (3) persistent viremia and viruria in pregnancy weeks to months after primary exposure; and (4) fetal brain malformations and anomalies preceding the sonographic detection of microcephaly. In this commentary, we discuss screening and diagnostic considerations that are grounded not only in the realities of current obstetrical practice in a largely global population but also in basic immunology and virology. We review recent epidemiological data pertaining to the risk of congenital Zika virus malformations based on trimester of exposure and consider side by side with emerging data demonstrating replication of Zika virus in placental and fetal tissue throughout gestation. We discuss limitations to ultrasound based strategies that rely largely or solely on the detection of microcephaly and provide alternative neurosonographic approaches for the detection of malformations that may precede or occur independent of a small head circumference. This expert review provides information that is of value for the following: (1) obstetrician, maternal-fetal medicine specialist, midwife, patient, and family in cases of suspected Zika virus infection; (2) review of the methodology for laboratory testing to explore the presence of the virus and the immune response; (3) ultrasound-based assessment of the fetus suspected to be exposed to Zika virus with particular emphasis on the central nervous system; and (4) identification of areas ready for development.

Authors+Show Affiliations

Departments of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Baylor College of Medicine, Houston, TX; Departments of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Texas Children's Hospital, Houston, TX.Departments of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Baylor College of Medicine, Houston, TX; Departments of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Texas Children's Hospital, Houston, TX.Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX; Department of Pathology and Immunology, Texas Children's Hospital, Houston, TX.Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX; National School for Tropical Medicine, Baylor College of Medicine, Houston, TX; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX; Department of Pathology and Immunology, Texas Children's Hospital, Houston, TX; Department of Pediatrics, Texas Children's Hospital, Houston, TX.National School for Tropical Medicine, Baylor College of Medicine, Houston, TX; Department of Pediatrics, Texas Children's Hospital, Houston, TX.Departments of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Baylor College of Medicine, Houston, TX; Departments of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Texas Children's Hospital, Houston, TX.Departments of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Baylor College of Medicine, Houston, TX; Departments of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Texas Children's Hospital, Houston, TX.Departments of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Baylor College of Medicine, Houston, TX; Departments of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Texas Children's Hospital, Houston, TX.Departments of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Baylor College of Medicine, Houston, TX; Departments of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Texas Children's Hospital, Houston, TX.Departments of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Baylor College of Medicine, Houston, TX; Departments of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Texas Children's Hospital, Houston, TX.National School for Tropical Medicine, Baylor College of Medicine, Houston, TX; Department of Pediatrics, Texas Children's Hospital, Houston, TX.Departments of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Baylor College of Medicine, Houston, TX; Departments of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Texas Children's Hospital, Houston, TX.Departments of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Baylor College of Medicine, Houston, TX; Departments of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Texas Children's Hospital, Houston, TX.Departments of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Baylor College of Medicine, Houston, TX; National School for Tropical Medicine, Baylor College of Medicine, Houston, TX; Departments of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Texas Children's Hospital, Houston, TX.Departments of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Baylor College of Medicine, Houston, TX; National School for Tropical Medicine, Baylor College of Medicine, Houston, TX; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX; Departments of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Texas Children's Hospital, Houston, TX. Electronic address: aagaardt@bcm.edu.

Pub Type(s)

Journal Article
Review
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28126366

Citation

Eppes, Catherine, et al. "Testing for Zika Virus Infection in Pregnancy: Key Concepts to Deal With an Emerging Epidemic." American Journal of Obstetrics and Gynecology, vol. 216, no. 3, 2017, pp. 209-225.
Eppes C, Rac M, Dunn J, et al. Testing for Zika virus infection in pregnancy: key concepts to deal with an emerging epidemic. Am J Obstet Gynecol. 2017;216(3):209-225.
Eppes, C., Rac, M., Dunn, J., Versalovic, J., Murray, K. O., Suter, M. A., Sanz Cortes, M., Espinoza, J., Seferovic, M. D., Lee, W., Hotez, P., Mastrobattista, J., Clark, S. L., Belfort, M. A., & Aagaard, K. M. (2017). Testing for Zika virus infection in pregnancy: key concepts to deal with an emerging epidemic. American Journal of Obstetrics and Gynecology, 216(3), 209-225. https://doi.org/10.1016/j.ajog.2017.01.020
Eppes C, et al. Testing for Zika Virus Infection in Pregnancy: Key Concepts to Deal With an Emerging Epidemic. Am J Obstet Gynecol. 2017;216(3):209-225. PubMed PMID: 28126366.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Testing for Zika virus infection in pregnancy: key concepts to deal with an emerging epidemic. AU - Eppes,Catherine, AU - Rac,Martha, AU - Dunn,James, AU - Versalovic,James, AU - Murray,Kristy O, AU - Suter,Melissa A, AU - Sanz Cortes,Magda, AU - Espinoza,Jimmy, AU - Seferovic,Maxim D, AU - Lee,Wesley, AU - Hotez,Peter, AU - Mastrobattista,Joan, AU - Clark,Steven L, AU - Belfort,Michael A, AU - Aagaard,Kjersti M, Y1 - 2017/01/23/ PY - 2016/12/18/received PY - 2017/01/05/revised PY - 2017/01/17/accepted PY - 2017/1/28/pubmed PY - 2017/6/8/medline PY - 2017/1/28/entrez KW - Centers for Disease Control and Prevention recommendations KW - Dengue virus KW - Food and Drug Administration regulations KW - Zika virus KW - Zika virus in pregnancy KW - amniotic fluid analysis KW - counseling of the patient at risk KW - epidemiology KW - fetal magnetic resonance imaging KW - flaviviridae family KW - head circumference KW - immunoglobulin M serology KW - microcephaly KW - neurosonography KW - perinatal viral infection KW - plaque reduction neutralization test KW - reverse transcriptase–polymerase chain reaction KW - transplacental transmission of viruses KW - viral culture KW - viral detection with polymerase chain reaction KW - viral detection with real-time reverse transcriptase–polymerase chain reaction SP - 209 EP - 225 JF - American journal of obstetrics and gynecology JO - Am J Obstet Gynecol VL - 216 IS - 3 N2 - Zika virus is an emerging mosquito-borne (Aedes genus) arbovirus of the Flaviviridae family. Following epidemics in Micronesia and French Polynesia during the past decade, more recent Zika virus infection outbreaks were first reported in South America as early as May 2013 and spread to now 50 countries throughout the Americas. Although no other flavivirus has previously been known to cause major fetal malformations following perinatal infection, reports of a causal link between Zika virus and microcephaly, brain and ocular malformations, and fetal loss emerged from hard-hit regions of Brazil by October 2015. Among the minority of infected women with symptoms, clinical manifestations of Zika virus infection may include fever, headache, arthralgia, myalgia, and maculopapular rash; however, only 1 of every 4-5 people who are infected have any symptoms. Thus, clinical symptom reporting is an ineffective screening tool for the relative risk assessment of Zika virus infection in the majority of patients. As previously occurred with other largely asymptomatic viral infections posing perinatal transmission risk (such as HIV or cytomegalovirus), we must develop and implement rapid, sensitive, and specific screening and diagnostic testing for both viral detection and estimation of timing of exposure. Unfortunately, despite an unprecedented surge in attempts to rapidly advance perinatal clinical testing for a previously obscure arbovirus, there are several ongoing hindrances to molecular- and sonographic-based screening and diagnosis of congenital Zika virus infection. These include the following: (1) difficulty in estimating the timing of exposure for women living in endemic areas and thus limited interpretability of immunoglobulin M serologies; (2) cross-reaction of immunoglobulin serologies with other endemic flaviruses, such as dengue; (3) persistent viremia and viruria in pregnancy weeks to months after primary exposure; and (4) fetal brain malformations and anomalies preceding the sonographic detection of microcephaly. In this commentary, we discuss screening and diagnostic considerations that are grounded not only in the realities of current obstetrical practice in a largely global population but also in basic immunology and virology. We review recent epidemiological data pertaining to the risk of congenital Zika virus malformations based on trimester of exposure and consider side by side with emerging data demonstrating replication of Zika virus in placental and fetal tissue throughout gestation. We discuss limitations to ultrasound based strategies that rely largely or solely on the detection of microcephaly and provide alternative neurosonographic approaches for the detection of malformations that may precede or occur independent of a small head circumference. This expert review provides information that is of value for the following: (1) obstetrician, maternal-fetal medicine specialist, midwife, patient, and family in cases of suspected Zika virus infection; (2) review of the methodology for laboratory testing to explore the presence of the virus and the immune response; (3) ultrasound-based assessment of the fetus suspected to be exposed to Zika virus with particular emphasis on the central nervous system; and (4) identification of areas ready for development. SN - 1097-6868 UR - https://www.unboundmedicine.com/medline/citation/28126366/Testing_for_Zika_virus_infection_in_pregnancy:_key_concepts_to_deal_with_an_emerging_epidemic_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0002-9378(17)30127-8 DB - PRIME DP - Unbound Medicine ER -