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Zika in Infants and Children

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A special issue of Tropical Medicine and Infectious Disease (ISSN 2414-6366). This special issue belongs to the section "Infectious Diseases".

Deadline for manuscript submissions: closed (20 August 2021) | Viewed by 41099

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Special Issue Editors

Dr. Sarah B. Mulkey

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Guest Editor

1. Prenatal Pediatrics Institute, Children’s National Hospital, Washington, DC 20010, USA
2. Department of Pediatrics, The George Washington University School of Medicine and Health Sciences, Washington, DC 20052, USA
3. Department of Neurology, The George Washington University School of Medicine and Health Sciences, Washington, DC 20052, USA
Interests: congenital Zika syndrome; congenital infections; fetal neurology; neonatal neurology; neuroimaging; child neurodevelopment

Dr. Roberta L. DeBiasi

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Guest Editor

1. Division of Pediatric Infectious Diseases, Children’s National Hospital, Washington, DC 20010, USA
2. Department of Pediatrics, The George Washington University School of Medicine and Health Sciences, Washington, DC 20052, USA
3. Department of Microbiology, Immunology and Tropical Medicine, The George Washington University School of Medicine and Health Sciences, Washington, DC 20052, USA
Interests: pediatric infectious disease; congenital Zika syndrome; congenital infections; Lyme disease; congenital cytomegalovirus infection; emerging infectious disease; SARS-CoV-2 in children

Special Issue Information

Dear Colleagues,

We are excited to introduce a very special upcoming issue in Tropical Medicine and Infectious Disease that will focus on the wealth of knowledge and experience we have gained in caring for infants and children affected by Zika virus infection. Prior to the WHO declaring Zika virus infection a major public health threat to infants in 2016, we did not know that this virus could wreak such havoc on the developing brain. During the past 4 years, our understanding of the diagnosis and limitations of testing has improved, we have learned how to evaluate pregnant women, infants, and children for neurologic and other body system abnormalities associated with Zika virus exposure, and we are now learning the range of long-term neurodevelopmental outcomes associated with prenatal Zika virus infection. In the coming years we will learn more about how the virus may impact children at school age and beyond. Despite all that we have learned, there are still many remaining gaps in our knowledge about Zika virus in infants and children. We need to better understand genetic and environmental risk factors for infection and brain injury severity, methods to improve neurodevelopment in Zika-virus-exposed infants and children, laboratory methods to diagnose congenital infection in children with developmental delay possibly owing to Zika virus exposure, and we ultimately need to prepare for a future epidemic of congenital Zika syndrome or other congenital infection which may cause serious injury to the developing brain. We invite you to join in this important effort and contribute your work to this Special Issue.

Dr. Sarah B. Mulkey
Dr. Roberta L. DeBiasi
Guest Editors

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Keywords

Congenital Zika infection
Neurodevelopment
Genetic and environmental risk factors
Neuroimaging in Zika
Zika laboratory diagnostics
Zika public health and surveillance
Zika in the older child
Lessons learned from Zika to prepare for future infectious threats to the developing infant brain
Zika and its impact on the family unit
Care of children with congenital Zika syndrome
Multi-body system effects in the Zika-exposed infant and child (i.e., audiologic, ophthalmologic, orthopedic, cardiologic, psychologic)

Published Papers (11 papers)

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Editorial

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4 pages, 193 KiB

Open AccessEditorial

New Insights into Zika in Infants and Children

by Sarah B. Mulkey and Roberta L. DeBiasi

Trop. Med. Infect. Dis. 2022, 7(8), 158; https://0-doi-org.brum.beds.ac.uk/10.3390/tropicalmed7080158 - 30 Jul 2022

Cited by 2 | Viewed by 1241

Abstract

In the original article [...] Full article

(This article belongs to the Special Issue Zika in Infants and Children)

Research

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16 pages, 365 KiB

Open AccessArticle

Pregnancy, Birth, Infant, and Early Childhood Neurodevelopmental Outcomes among a Cohort of Women with Symptoms of Zika Virus Disease during Pregnancy in Three Surveillance Sites, Project Vigilancia de Embarazadas con Zika (VEZ), Colombia, 2016–2018

by Marcela Mercado-Reyes, Suzanne M. Gilboa, Diana Valencia, Marcela Daza, Van T. Tong, Romeo R. Galang, Christina M. Winfield, Shana Godfred-Cato, Mónica Benavides, Julie M. Villanueva, Jennifer D. Thomas, Jonathan Daniels, Sherif Zaki, Sarah Reagan-Steiner, Julu Bhatnagar, Jarad Schiffer, Evelene Steward-Clark, Jessica N. Ricaldi, Johana Osorio, Christina L. Sancken, Lissethe Pardo, Sarah C. Tinker, Kayla N. Anderson, Angelica Rico, Veronica K. Burkel, Jacob Hojnacki, Miranda J. Delahoy, Maritza González, May B. Osorio, Cynthia A. Moore, Margaret A. Honein and Martha Lucia Ospina Martinez Show full author list Hide full author list

Trop. Med. Infect. Dis. 2021, 6(4), 183; https://0-doi-org.brum.beds.ac.uk/10.3390/tropicalmed6040183 - 12 Oct 2021

Cited by 9 | Viewed by 3482

Abstract

Project Vigilancia de Embarazadas con Zika (VEZ), an intensified surveillance of pregnant women with symptoms of the Zika virus disease (ZVD) in Colombia, aimed to evaluate the relationship between symptoms of ZVD during pregnancy and adverse pregnancy, birth, and infant outcomes and early childhood neurodevelopmental outcomes. During May–November 2016, pregnant women in three Colombian cities who were reported with symptoms of ZVD to the national surveillance system, or with symptoms of ZVD visiting participating clinics, were enrolled in Project VEZ. Data from maternal and pediatric (up to two years of age) medical records were abstracted. Available maternal specimens were tested for the presence of the Zika virus ribonucleic acid and/or anti-Zika virus immunoglobulin antibodies. Of 1213 enrolled pregnant women with symptoms of ZVD, 1180 had a known pregnancy outcome. Results of the Zika virus laboratory testing were available for 569 (48.2%) pregnancies with a known pregnancy outcome though testing timing varied and was often distal to the timing of symptoms; 254 (21.5% of the whole cohort; 44.6% of those with testing results) were confirmed or presumptive positive for the Zika virus infection. Of pregnancies with a known outcome, 50 (4.2%) fetuses/infants had Zika-associated brain or eye defects, which included microcephaly at birth. Early childhood adverse neurodevelopmental outcomes were more common among those with Zika-associated birth defects than among those without and more common among those with laboratory evidence of a Zika virus infection compared with the full cohort. The proportion of fetuses/infants with any Zika-associated brain or eye defect was consistent with the proportion seen in other studies. Enhancements to Colombia’s existing national surveillance enabled the assessment of adverse outcomes associated with ZVD in pregnancy. Full article

(This article belongs to the Special Issue Zika in Infants and Children)

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12 pages, 538 KiB

Open AccessArticle

Ocular Findings and Visual Function in Children Examined during the Zika Health Brigade in the US Virgin Islands, March 2018

by S. Grace Prakalapakorn, Lucas Bonafede, Linda Lawrence, Daniel Lattin, Nicola Kim, Richard D. House, Braeanna Hillman, Leah de Wilde, Cosme Harrison, Nicole Fehrenbach, Shana Godfred-Cato, Megan R. Reynolds and Esther M. Ellis

Trop. Med. Infect. Dis. 2021, 6(2), 66; https://0-doi-org.brum.beds.ac.uk/10.3390/tropicalmed6020066 - 29 Apr 2021

Cited by 4 | Viewed by 2864

Abstract

Among children born with laboratory-confirmed Zika virus (ZIKV) infection, visual impairment (VI) can occur despite normal ocular structure. The objective of this report is to describe ocular findings and visual function among children examined during the Department of Health Zika Health Brigade (ZHB) in the United States Virgin Islands in March 2018. This analysis is based on a retrospective chart review of children eligible to participate in the ZHB (i.e., part of the US Zika Pregnancy and Infant Registry) and who were examined by ophthalmologists. Eighty-eight children attended the ZHB. This report includes 81 children [48 (59.3%) males] whose charts were located [average gestational age = 37.6 weeks (range: 27.6–41.3) and average adjusted age at examination = 9.1 months (range: 0.9–21.9)]. Of those examined, 5/81 (6.2%) had microcephaly at birth, 2/81 (2.5%) had a structural eye abnormality, and 19/72 (26.4%) had VI. Among children with normal ocular structure and neurologic examination, 13/51 (25.5%) had VI. Despite a low incidence of abnormal ocular structure and microcephaly, about a quarter of children examined had VI. Our findings emphasize that ophthalmological examinations should be performed in all children with suspicion for antenatal ZIKV infection, even children with normal ocular structure and neurologic examination. Full article

(This article belongs to the Special Issue Zika in Infants and Children)

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9 pages, 1068 KiB

Open AccessArticle

Measurement of Head Circumference: Implications for Microcephaly Surveillance in Zika-Affected Areas

by Emily W. Harville, Van T. Tong, Suzanne M. Gilboa, Cynthia A. Moore, Maria Luisa Cafferata, Jackeline Alger, Luz Gibbons, Carolina Bustillo, Allison Callejas, Mario Castillo, Jenny Fúnes, Jorge García, Gustavo Hernández, Wendy López, Carlos Ochoa, Fátima Rico, Heriberto Rodríguez, Concepción Zúniga, Alvaro Ciganda, Candela Stella, Giselle Tomasso and Pierre Buekens Show full author list Hide full author list

Trop. Med. Infect. Dis. 2021, 6(1), 5; https://0-doi-org.brum.beds.ac.uk/10.3390/tropicalmed6010005 - 29 Dec 2020

Cited by 5 | Viewed by 3737

Abstract

Worldwide recognition of the Zika virus outbreak in the Americas was triggered by an unexplained increase in the frequency of microcephaly. While severe microcephaly is readily identifiable at birth, diagnosing less severe cases requires comparison of head circumference (HC) measurement to a growth chart. We examine measured values of HC and digit preference in those values, and, by extension, the prevalence of microcephaly at birth in two data sources: a research study in Honduras and routine surveillance data in Uruguay. The Zika in Pregnancy in Honduras study enrolled pregnant women prenatally and followed them until delivery. Head circumference was measured with insertion tapes (SECA 212), and instructions including consistent placement of the tape and a request to record HC to the millimeter were posted where newborns were examined. Three indicators of microcephaly were calculated: (1) HC more than 2 standard deviations (SD) below the mean, (2) HC more than 3 SD below the mean (referred to as “severe microcephaly”) and (3) HC less than the 3rd percentile for sex and gestational age, using the INTERGROWTH-21st growth standards. We compared these results from those from a previous analysis of surveillance HC data from the Uruguay Perinatal Information System (Sistema Informático Perinatal (SIP). Valid data on HC were available on 579 infants, 578 with gestational age data. Nine babies (1.56%, 95% CI 0.71–2.93) had HC < 2SD, including two (0.35%, 95% CI 0.04–1.24) with HC < 3SD, and 11 (1.9%, 95% CI, 0.79–3.02) were below the 3rd percentile. The distribution of HC showed strong digit preference: 72% of measures were to the whole centimeter (cm) and 19% to the half-cm. Training and use of insertion tapes had little effect on digit preference, nor were overall HC curves sufficient to detect an increase in microcephaly during the Zika epidemic in Honduras. When microcephaly prevalence needs to be carefully analyzed, such as during the Zika epidemic, researchers may need to interpret HC data with caution. Full article

(This article belongs to the Special Issue Zika in Infants and Children)

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6 pages, 184 KiB

Open AccessArticle

2018 Zika Health Brigade: Delivering Critical Health Screening in the U.S. Virgin Islands

by Shana Godfred-Cato, S. Nicole Fehrenbach, Megan R. Reynolds, Romeo R. Galang, Dan Schoelles, Lessely Brown-Shuler, Braeanna Hillman, Leah DeWilde, Andra Prosper, Amy Hudson, Cynthia A. Moore and Esther M. Ellis

Trop. Med. Infect. Dis. 2020, 5(4), 168; https://0-doi-org.brum.beds.ac.uk/10.3390/tropicalmed5040168 - 09 Nov 2020

Cited by 5 | Viewed by 2062

Abstract

In 2017, Hurricanes Irma and Maria caused significant damage to the United States Virgin Islands (USVI), heightening the challenges many residents faced in accessing adequate healthcare and receiving recommended Zika virus screening services. To address this challenge, the USVI Department of Health (DOH) requested technical assistance from the Centers for Disease Control and Prevention (CDC), the Health Resources and Services Administration (HRSA), and the American Academy of Pediatrics (AAP) to organize a health brigade to bring needed medical care to an underserved population. It also established the development of important partnerships between federal and private partners as well as between clinical providers and public health entities such as the Epidemiology & Disease Reporting, Maternal Child Health (MCH), and Infant and Toddlers Programs within the DOH, and local clinicians. This health brigade model could be replicated to ensure recommended evaluations are delivered to populations that may have unmet medical needs due to the complexity of the conditions and/or rural location. Full article

(This article belongs to the Special Issue Zika in Infants and Children)

18 pages, 1967 KiB

Open AccessArticle

Early Growth Parameters as Predictors of Developmental Delay among Children Conceived During the 2015–2016 Zika Virus Outbreak in Northeastern Brazil

by Charles E. Rose, Jeanne Bertolli, Jacob Elijah Attell, Cynthia A. Moore, Flavio Melo, Kim Kotzky, Nevin Krishna, Ashley Satterfield-Nash, Isabela Ornelas Pereira, Andre Pessoa, Donna Camille Smith, Ana Carolina Faria e Silva Santelli and Georgina Peacock

Trop. Med. Infect. Dis. 2020, 5(4), 155; https://0-doi-org.brum.beds.ac.uk/10.3390/tropicalmed5040155 - 01 Oct 2020

Cited by 1 | Viewed by 2375

Abstract

Background: Identifying infants with congenital infection for early intervention will likely be challenging in future Zika virus outbreaks. We investigated indicators of risk for developmental delay among children born with and without obvious manifestations of congenital Zika virus infection. Methods: We evaluated 120 children conceived during the 2015−2016 Zika virus outbreak in Paraíba, Brazil. We analyzed data from children at birth; ages 1−7 months and approximately 24 months, using medical records (i.e., anthropometric measurements diagnoses), medical evaluation (i.e., Zika/other laboratory tests, dysmorphic features), and parent report (seizures, developmental delay). We used a Bayesian modeling approach to identify predictors of developmental delay. Results: Head circumference (HC) and length at birth and rates of growth for HC and length at follow-up were consistent across domains of developmental delay; (e.g., for every 1 cm per month decrease in HC growth rate; there was a corresponding decrease in the gross motor z-score). Modeling results indicated that HC and length at birth, and follow-up HC and length rates of growth, were predictive of developmental delay. Conclusion: These findings suggest that accurate measurement and frequent monitoring of HC and length, especially in the first few months of life, may be useful for identifying children possibly congenitally exposed to Zika virus who could benefit from early intervention services. Full article

(This article belongs to the Special Issue Zika in Infants and Children)

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7 pages, 524 KiB

Open AccessCommunication

The Zika Virus Individual Participant Data Consortium: A Global Initiative to Estimate the Effects of Exposure to Zika Virus during Pregnancy on Adverse Fetal, Infant, and Child Health Outcomes

by Zika Virus Individual Participant Data Consortium

Trop. Med. Infect. Dis. 2020, 5(4), 152; https://0-doi-org.brum.beds.ac.uk/10.3390/tropicalmed5040152 - 30 Sep 2020

Cited by 11 | Viewed by 6644

Abstract

This commentary describes the creation of the Zika Virus Individual Participant Data Consortium, a global collaboration to address outstanding questions in Zika virus (ZIKV) epidemiology through conducting an individual participant data meta-analysis (IPD-MA). The aims of the IPD-MA are to (1) estimate the absolute and relative risks of miscarriage, fetal loss, and short- and long-term sequelae of fetal exposure; (2) identify and quantify the relative importance of different sources of heterogeneity (e.g., immune profiles, concurrent flavivirus infection) for the risk of adverse fetal, infant, and child outcomes among infants exposed to ZIKV in utero; and (3) develop and validate a prognostic model for the early identification of high-risk pregnancies and inform communication between health care providers and their patients and public health interventions (e.g., vector control strategies, antenatal care, and family planning programs). By leveraging data from a diversity of populations across the world, the IPD-MA will provide a more precise estimate of the risk of adverse ZIKV-related outcomes within clinically relevant subgroups and a quantitative assessment of the generalizability of these estimates across populations and settings. The ZIKV IPD Consortium effort is indicative of the growing recognition that data sharing is a central component of global health security and outbreak response. Full article

(This article belongs to the Special Issue Zika in Infants and Children)

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Review

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12 pages, 893 KiB

Open AccessReview

Clinical and Preclinical Evidence for Adverse Neurodevelopment after Postnatal Zika Virus Infection

by Jessica Raper and Ann Chahroudi

Trop. Med. Infect. Dis. 2021, 6(1), 10; https://0-doi-org.brum.beds.ac.uk/10.3390/tropicalmed6010010 - 12 Jan 2021

Cited by 11 | Viewed by 3818

Abstract

Although the Zika virus (ZIKV) typically causes mild or no symptoms in adults, during the 2015−2016 outbreak, ZIKV infection in pregnancy resulted in a spectrum of diseases in infants, including birth defects and neurodevelopmental disorders identified in childhood. While intense clinical and basic science research has focused on the neurodevelopmental outcomes of prenatal ZIKV infection, less is known about the consequences of infection during early life. Considering the neurotropism of ZIKV and the rapidly-developing postnatal brain, it is important to understand how infection during infancy may disrupt neurodevelopment. This paper reviews the current knowledge regarding early postnatal ZIKV infection. Emerging clinical evidence supports the hypothesis that ZIKV infection during infancy can result in negative neurologic consequences. However, clinical data regarding postnatal ZIKV infection in children are limited; as such, animal models play an important role in understanding the potential complications of ZIKV infection related to the vulnerable developing brain. Preclinical data provide insight into the potential behavioral, cognitive, and motor domains that clinical studies should examine in pediatric populations exposed to ZIKV during infancy. Full article

(This article belongs to the Special Issue Zika in Infants and Children)

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Other

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14 pages, 1028 KiB

Open AccessPerspective

Causes of Phenotypic Variability and Disabilities after Prenatal Viral Infections

by Youssef A. Kousa and Reafa A. Hossain

Trop. Med. Infect. Dis. 2021, 6(2), 95; https://0-doi-org.brum.beds.ac.uk/10.3390/tropicalmed6020095 - 01 Jun 2021

Cited by 3 | Viewed by 5706

Abstract

Prenatal viral infection can lead to a spectrum of neurodevelopmental disabilities or fetal demise. These can include microencephaly, global developmental delay, intellectual disability, refractory epilepsy, deafness, retinal defects, and cortical-visual impairment. Each of these clinical conditions can occur on a semi-quantitative to continuous spectrum, from mild to severe disease, and often as a collective of phenotypes. Such serious outcomes result from viruses’ overlapping neuropathology and hosts’ common neuronal and gene regulatory response to infections. The etiology of variability in clinical outcomes is not yet clear, but it may be related to viral, host, vector, and/or environmental risk and protective factors that likely interact in multiple ways. In this perspective of the literature, we work toward understanding the causes of phenotypic variability after prenatal viral infections by highlighting key aspects of the viral lifecycle that can affect human disease, with special attention to the 2015 Zika pandemic. Therefore, this work offers important insights into how viral infections and environmental teratogens affect the prenatal brain, toward our ultimate goal of preventing neurodevelopmental disabilities. Full article

(This article belongs to the Special Issue Zika in Infants and Children)

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6 pages, 409 KiB

Open AccessCase Report

Zika Virus Infection in Tourists Travelling to Thailand: Case Series Report

by Natàlia Romaní, Marie Antoinette Frick, Elena Sulleiro, Carlota Rodó, María Espiau, Diana Pou, Aroa Silgado, Anna Suy, Tomás Pumarola, Pere Soler-Palacín and Antoni Soriano-Arandes

Trop. Med. Infect. Dis. 2021, 6(1), 3; https://0-doi-org.brum.beds.ac.uk/10.3390/tropicalmed6010003 - 28 Dec 2020

Cited by 2 | Viewed by 3421

Abstract

Thailand is a popular tourist destination where Zika virus (ZIKV) transmission is currently active. To our knowledge, there are no reports of ZIKV infection imported from Thailand and affecting children. Here, we describe the clinical and microbiological findings in three cases of vector-borne ZIKV infection: An 11-year-old boy, a 2-year-old girl, and her pregnant mother, this last case leading to the prenatal exposure of her second baby to ZIKV in the second trimester of pregnancy. All patients were diagnosed after traveling to Thailand between September 2019 and January 2020. No complications were detected in any patient at follow-up, and the prenatally exposed fetus showed no abnormalities during intensive antenatal health care monitoring. On postnatal study, there were no clinical signs or microbiological findings of mother-to-child ZIKV transmission. ZIKV IgG was initially positive, but seroreversion occurred at 4 months of life. This report describes the clinical and serological evolution of vector-borne ZIKV infection occurring in dengue-naïve tourists returning from Thailand. The World Health Organization currently recommends that pre-travel advice to prevent arbovirus infection should be maintained in travelers to Southeast Asia. Full article

(This article belongs to the Special Issue Zika in Infants and Children)

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14 pages, 1890 KiB

Open AccessCase Report

Discordant Clinical Outcomes in a Monozygotic Dichorionic-Diamniotic Twin Pregnancy with Probable Zika Virus Exposure. Case Report

by Marcela Mercado, Marcela Daza, Cynthia A. Moore, Diana Valencia, Angelica Rico, Diego A. Álvarez-Diaz, Aaron C. Brault, Kelly Fitzpatrick and Sarah B. Mulkey

Trop. Med. Infect. Dis. 2020, 5(4), 188; https://0-doi-org.brum.beds.ac.uk/10.3390/tropicalmed5040188 - 19 Dec 2020

Cited by 2 | Viewed by 3502

Abstract

Prenatal exposure to Zika virus (ZIKV) is associated with congenital anomalies of the brain and the eye and neurodevelopmental sequelae. The spectrum of disease outcomes may relate to timing of infection as well as genetic and environmental factors. Congenital infections occurring in twin pregnancies can inform the clinical spectrum of these conditions and provide unique information regarding timing of infection and in utero environment with disease pathophysiology. Herein, we report a monozygotic dichorionic-diamniotic twin pregnancy with probable prenatal ZIKV exposure identified through the Colombian ZIKV disease surveillance system. Multidisciplinary clinical evaluations were provided to the twins during their first three years of life through a national program for children with in utero ZIKV exposure. Laboratory evidence of congenital infection as well as microcephaly, brain, eye, and neurodevelopmental compromise related to prenatal ZIKV infection were identified in only one infant of the twin pregnancy. This is the first report of monozygotic twins discordant for Zika-associated birth defects. The evaluation of the pathophysiology of discordance in disease outcome for congenital infections in twin pregnancies may lead to a better understanding of potential complex environmental and genetic interactions between the mother, her offspring, and an infectious exposure. Full article

(This article belongs to the Special Issue Zika in Infants and Children)

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