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.
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
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.
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.
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.
- Dick GW, Kitchen SF, Haddow AJ. Zika virus. I. Isolations and serological specificity. Trans R Soc Trop Med Hyg. 1952;46(5):509–520. doi:10.1016/0035-9203(52)90042-4 [CrossRef]
- MacNamara FN. Zika virus: a report on three cases of human infection during an epidemic of jaundice in Nigeria. Trans R Soc Trop Med Hyg. 1954;48(2):139–145. doi:10.1016/0035-9203(54)90006-1 [CrossRef]
- World Health Organization (WHO). Epidemiological alert: neurological syndrome, congenital malformations, and Zika virus infection. Implications for public health in the Americas. Available at: http://www.paho.org/hq/index.php?option=com_docman&task=doc_view&Itemid=270&gid=32405&lang=en. Accessed August 24, 2016.
- 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.
- Centers for Disease Control and Prevention (CDC). Zika virus: case counts in the US. Last update August24, 2016. http://www.cdc.gov/zika/geo/united-states.html. Accessed August 25, 2016.
- World Health Organization (WHO). WHO director-general summarizes the outcome of the emergency committee regarding clusters of microcephaly and Guillain-Barré syndrome. http://www.who.int/mediacentre/news/statements/2016/emergency-committee-zika-microcephaly/en/. Accessed March 10, 2016.
- Centers for Disease Control and Prevention (CDC). Zika virus. http://www.cdc.gov/zika/index.html. Accessed August 1, 2016.
- Florida State Government. Gov. Scott: With likely mosquito-borne zika cases, states will use full resources to protect Floridians. Published online July29, 2016. http://www.flgov.com/2016/07/29/gov-scott-with-likely-mosquito-borne-zika-cases-state-will-use-full-resources-to-protect-floridians/. Accessed August 20, 2016.
- 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]
- Ventura CV, Maia M, Ventura BV, et al. Ophthalmologic assessment of ten infants with microcephaly and presumable intra-uterus zika virus infection. Arq Bras Oftalmol. 2016;79(1)1–3. doi:10.5935/0004-2749.20160002 [CrossRef]
- 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]
- Miranda HA 2nd, Costa MC, Frazão MA, Simão N, Franchischini S, Moshfeghi DM. Expanded spectrum of congenital ocular findings in microcephaly with presumed Zika infection. Ophthalmology. 2016;123(8):1788–1794. doi:10.1016/j.ophtha.2016.05.001 [CrossRef]
- De Fatima Vasco Aragao M, van der Linden V, Brainer-Lima AM, et al. Clinical features and neuroimaging (CT and MRI) findings in presumed Zika virus related congenital infection and microcephaly: retrospective case series study. BMJ. 2016;353:i901.
- 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]
- Van der Linden V, Filho ELR, Lins OG, et al. Congenital Zika syndrome with arthrogryposis: retrospective case series study. BMJ. 2016;354:i3899. doi:10.1136/bmj.i3899 [CrossRef]
- Ventura CV, Maia M, Dias N, Ventura LO, Belfort R Jr, . Zika: neurological and ocular findings in infant without microcephaly. Lancet. 2016;387(10037):2502. doi:10.1016/S0140-6736(16)30776-0 [CrossRef]
Zika Virus and Dengue Fever Virus Workup in Newborn With Congenital Zika Syndrome
|Umbilical Cord Blood Zika PCR||Negative|
|Umbilical Cord Blood Zika IgM||Positive|
|Serum Zika PCR||Negative|
|Serum Zika IgM||Positive|
|CSF Zika PCR||Negative|
|CSF Zika IgM||Positive|
|Urine PCR Zika||Negative|
|Dengue IgM Cord Blood||Negative|
|Dengue IgM Serum||Negative|
|Urine Viral Culture||Negative|