Ophthalmic Surgery, Lasers and Imaging Retina

Case Report 

First Travel-Associated Congenital Zika Syndrome in the US: Ocular and Neurological Findings in the Absence of Microcephaly

Camila V. Ventura, MD; Maria Paula Fernandez, MD; Ivan A. Gonzalez, MD; Delia M. Rivera-Hernandez, MD; Roberto Lopez-Alberola, MD; Maria Peinado, MD; Angelica A. Floren, MD; Patricia A. Rodriguez, MD; Basil K. Williams Jr., MD; Gabriela de la Vega Muns, MD; Ana J. Rodriguez, RN; Catherin Negron, BA; Brenda Fallas; Audina M. Berrocal, MD

Abstract

A 6-day-old female baby with known diagnosis of congenital Zika infection was referred for ophthalmologic examination. The mother (37 years old) was referred for a pruritic rash, conjunctival hyperemia, and malaise at 12 weeks of gestation while still living in Venezuela. Upon arrival to Miami, Zika virus (ZIKV) exposure was confirmed during prenatal screening. At birth, due to the known exposure, a complete congenital ZIKV workup was performed, including brain ultrasound and MRI, which disclosed calcifications in the frontal lobe. Fundus examination revealed a hypopigmented retinal lesion in the left eye that was documented with retinal imaging.

[Ophthalmic Surg Lasers Imaging Retina. 2016;47:952–955.]

Abstract

A 6-day-old female baby with known diagnosis of congenital Zika infection was referred for ophthalmologic examination. The mother (37 years old) was referred for a pruritic rash, conjunctival hyperemia, and malaise at 12 weeks of gestation while still living in Venezuela. Upon arrival to Miami, Zika virus (ZIKV) exposure was confirmed during prenatal screening. At birth, due to the known exposure, a complete congenital ZIKV workup was performed, including brain ultrasound and MRI, which disclosed calcifications in the frontal lobe. Fundus examination revealed a hypopigmented retinal lesion in the left eye that was documented with retinal imaging.

[Ophthalmic Surg Lasers Imaging Retina. 2016;47:952–955.]

Introduction

Zika virus (ZIKV), a neurotropic flavivirus, is mainly spread to humans by the Aedes aegypti mosquitoes.1 Despite being discovered more than 60 years ago, only recently ZIKV raised world concern due to an alarming emergence of microcephaly in babies born to mothers infected with the virus in the Northeast of Brazil.2,3 The ZIKV outbreak that began in Brazil has affected other parts of Latin America and the Caribbean, and ultimately has now reached the United States.4,5 Although travel-associated ZIKV infection has been identified in the U.S., a case of congenital Zika syndrome (CZS) has not been previously reported.5 Herein, we describe the first travel-associated CZS case born in the U.S.

Case Report

A 6-day-old female baby born to a 37-year-old Venezuelan mother at 40 weeks' gestational age via vaginal delivery was referred for ophthalmologic consultation after being diagnosed with brain calcifications and a known intrauterine infection of ZIKV. At 12 weeks of gestation, while living in Venezuela, the mother developed a pruritic rash followed by bilateral nonpurulent conjunctivitis and fever that resolved in a few days. Routine fetal ultrasound performed in Venezuela did not show any abnormalities.

After arriving in Miami, the mother underwent her third trimester prenatal screening and was found to be immunoglobulin M (IgM)-positive for ZIKV. At birth, the baby's head circumference measured 34 cm (23rd percentile) and her weight was 3,690 grams (59th percentile). After being admitted to the neonatal intensive care unit, a full congenital infection workup was performed, including ZIKV investigation. Toxoplasmosis, rubella, cytomegalovirus, syphilis, human immunodeficiency virus, and Dengue fever virus were ruled out. Real-time reverse transcription polymerase chain reaction for ZIKV was negative in the cord blood, serum, urine, and cerebrospinal fluid (CSF). IgM antibodies for ZIKV were identified in the CSF, umbilical cord blood, and serum (Table).


Zika Virus and Dengue Fever Virus Workup in Newborn With Congenital Zika Syndrome

Table:

Zika Virus and Dengue Fever Virus Workup in Newborn With Congenital Zika Syndrome

The encephalogram through the anterior fontanel revealed tubular calcifications at the grey-white matter junction. The brain MRI demonstrated intraparenchymal calcification in the left subcortical white matter of the frontal lobe. A smooth appearance of the right frontal and anterior temporal lobes suggested mild neuronal migration anomaly (Figure 1A and 1B).


MRI of the brain of a baby with congenital Zika infection showing (A) an area of tubular increased T1 signal in the left subcortical white matter of the frontal lobe, suggesting intraparenchymal calcification, and (B) right cortical abnormality compared to contralateral hemisphere, with smooth appearance of the frontal and anterior superior temporal lobes.

Figure 1.

MRI of the brain of a baby with congenital Zika infection showing (A) an area of tubular increased T1 signal in the left subcortical white matter of the frontal lobe, suggesting intraparenchymal calcification, and (B) right cortical abnormality compared to contralateral hemisphere, with smooth appearance of the frontal and anterior superior temporal lobes.

Ophthalmic examination was performed 6 days after delivery and a circular hypopigmented lesion superior to the optic nerve was observed on fundus examination in the left eye (Figure 2). The remaining ophthalmologic exam was unremarkable in both eyes.


Fundus image of the left eye of a baby with congenital Zika infection showing a hypopigmented lesion located in the superior quadrant.

Figure 2.

Fundus image of the left eye of a baby with congenital Zika infection showing a hypopigmented lesion located in the superior quadrant.

Discussion

The ZIKV outbreak that began in the Northeast of Brazil has already affected 47 countries and territories of the U.S.3,4 The virus' rapid spread brought tremendous fear due to the clinical manifestations and consequences in babies. As a result, the World Health Organization declared ZIKV disease a Public Health Emergency of International Concern.6

The Centers of Disease Control (CDC) established recommendations in an attempt to reduce spread of the virus. The CDC advises people, especially pregnant women, to avoid travel to countries with active ZIKV and to protect themselves from mosquito and sexual transmission.7

Despite the recommendations, the virus continued to spread, and travel-transmitted cases have been reported in the U.S. and its local territories. The most-affected U.S. territory, with 8,746 documented cases, is Puerto Rico, an island only 1,000 miles away from Florida.5 Florida's Department of Health reported the first ZIKV cases originating in Miami on July 29, 2016.8 Although ZIKV infection has been reported in the U.S., to the best of our knowledge, this is the first reported case of travel-related CZS born in the U.S.

Congenital ZIKV infection has been associated with a broad spectrum of findings, including neurological, ocular, audiological, and skeletal alterations, which characterizes a new entity called CZS.9–16 Although microcephaly is the main neurological finding encountered in babies with CZS, this is not universal. In addition to the current case, there is a similar report from Brazil.17

The main ocular findings of CZS described in the literature include optic nerve, retinal, and retinal vasculature abnormalities.10–13 Previously documented retinal alterations include chorioretinal scars and pigment dispersion, which are different from the unilateral hypopigmented retinal lesion presented in the current case.10–13

Although this patient is currently achieving all developmental milestones for her age, uncertainties regarding mid- and long-term consequences of CZS still remain. Continued monitoring for seizures with routine electroencephalograms will be needed, as the cerebral calcifications put her at risk to develop epilepsy. This case report highlights the importance of neuroimaging even in the absence of microcephaly in patients from epidemic areas or with possible exposure to ZIKV. Therefore, complete screening for CZS including neuroimaging, fundus examination with digital imaging, and audiology testing should be performed in high-risk babies.

References

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  4. Centers for Disease Control and Prevention (CDC). All countries & territories with active Zika virus transmission. Last update August22, 2016. http://www.cdc.gov/zika/geo/active-countries.html. Accessed August 24, 2016.
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  9. Miranda-Filho Dde B, Martelli CM, Ximenes RA, et al. Initial description of the presumed congenital zika syndrome. Am J Public Health. 2016;106(4):598–600. doi:10.2105/AJPH.2016.303115 [CrossRef]
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  11. de Paula Freitas B, de Oliveira Dias JR, Prazeres J, et al. Ocular findings in infants with microcephaly associated with presumed zika virus congenital infection in Salvador, Brazil. JAMA Ophthalmol. 2016;134(5):529–535. doi:10.1001/jamaophthalmol.2016.0267 [CrossRef]
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  14. Leal MC, Muniz LF, Caldas Neto SS, Van der Linden V, Ramos RC. Sensorineural hearing loss in a case of congenital Zika virus. Braz J Otorhinolaryngol. 2016. pii:S1808-8694(16)30127–6. doi:10.1016/j.bjorl.2016.06.001 [CrossRef]
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Zika Virus and Dengue Fever Virus Workup in Newborn With Congenital Zika Syndrome

TestResult
Umbilical Cord Blood Zika PCRNegative
Umbilical Cord Blood Zika IgMPositive
Serum Zika PCRNegative
Serum Zika IgMPositive
CSF Zika PCRNegative
CSF Zika IgMPositive
Urine PCR ZikaNegative
Dengue IgM Cord BloodNegative
Dengue IgM SerumNegative
Urine Viral CultureNegative
Authors

From the Department of Ophthalmology, Bascom Palmer Eye Institute, Miller School of Medicine, University of Miami, Miami (CVV, MPF, BKW, CN, BF, AMB); the Altino Ventura Foundation, Recife, Brazil (CVV); the Department of Ophthalmology and Visual Sciences, Paulista School of Medicine, Federal University of São Paulo, São Paulo, Brazil (CVV); the Department of Pediatrics, Division of Pediatric Infectious Diseases, Jackson Memorial Hospital, Miller School of Medicine, University of Miami, Miami (IAG, DR, PAR); the Department of Neurology, Jackson Memorial Hospital, Miller School of Medicine, University of Miami, Miami (RL); the Department of Pediatrics, Jackson Memorial Hospital, Miller School of Medicine, University of Miami, Miami (MP, AAF, AJR); and the Department of Neuroradiology, Jackson Memorial Hospital, Miller School of Medicine, University of Miami, Miami (GD).

The authors report no relevant financial disclosures.

Address correspondence to Audina M Berrocal, MD, Bascom Palmer Eye Institute, 900 NW 17th Avenue, Miami, FL 33136; email: aberrocal@med.miami.edu.

Received: August 28, 2016
Accepted: September 13, 2016

10.3928/23258160-20161004-09

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