Clinical Manifestation and Congenital Zika Virus Infection

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The page below is a sample from the LabCE course Zika Virus: Overview and Laboratory Testing. Access the complete course and earn ASCLS P.A.C.E.-approved continuing education credits by subscribing online.

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Clinical Manifestation and Congenital Zika Virus Infection

Aside from the mild symptoms (fever, rash, joint pain, conjunctivitis, muscle pain, and headache) associated with Zika virus infection, more serious sequelae related to the central nervous system (CNS) can occur with in utero Zika virus infections, commonly called congenital Zika virus infection. The most common abnormalities appearing in fetuses associated with congenital Zika virus infections are microcephaly, ventriculomegaly, and intracranial calcifications. Although the features of this infection have been described, the full spectrum of the infection is still being investigated. The following is a brief review of the conditions associated with congenital Zika infection:

Microcephaly is a rare neurological condition in which an infant's head is significantly smaller than the heads of other children of the same age and sex. The condition can be detected at birth and is usually the result of the brain developing abnormally in the womb or not growing as it should after birth. Normally, some degree of microcephaly occurs in one in 5,000 to one in 10,000 of all births. Most children with microcephaly will often have developmental issues, however in approximately 15% of cases, a small head will have minimal if any effect on the infant.
Microcephaly can be caused by a variety of genetic and environmental factors. Generally, there is no treatment for microcephaly, but early intervention with supportive therapies (such as speech and occupational therapies) may help enhance the child's development and improve quality of life.
Based on a rapidly increasing number of observations combined with the identification of the Zika virus in the cerebrospinal fluid and serum of newborns with microcephaly, the World Health Organization (WHO), the CDC, and other scientific groups have concluded that the Zika virus can cause microcephaly. In addition, microcephaly appears to be more of a consequence of Zika infection early in pregnancy, rather than newborns infected in the third trimester.

Ventriculomegaly is a brain condition that occurs when the lateral ventricles become dilated. This abnormality occurs in about 1% of pregnancies. The enlargement of the ventricles may occur for a number of reasons, including infections; however, in many cases there is no identifiable cause. Ventriculomegaly occurs in about one in 1,000 births. Mild cases usually have no symptoms and do not require treatment. The condition only needs treatment if the child develops progressive accumulation of cerebrospinal fluid (hydrocephalus). Ventriculomegaly has been reported in some fetuses in several cases of congenital Zika virus infection.

Intracranial calcification (ICC)
ICC refers to calcifications that occur within the brain. When this condition is present in the fetus, it is called fetal ICC, which is typically detected in utero. It may be caused by in utero infections, intracranial tumors, or intracranial hemorrhage. For a large number of ICC cases, no common pathological or genetic mechanism can be identified. A significant number of fetal cases are caused by congenital infection, especially with cytomegalovirus. Symptoms may include motor function deterioration dementia, mental retardation, spastic paralysis, dysarthria (slurred speech), spasticity (continuous contraction of certain muscles), ocular (eye) problems, and involuntary writhing movements. Fetal ICC has been observed in a small percentage of fetuses associated with congenital Zika virus infections.

Other CNS and related abnormalities
Although rarer in presentation, other CNS and related abnormalities can occur as a result of congenital Zika infection, including but not limited to decreased brain parenchymal volume, cortical atrophy and malformation, hypoplasia of the cerebellum, spasticity, severe irritability, seizures, ocular abnormalities, hearing loss, and clubfoot.

Microcephaly comparison. Courtesy CDC.