Zika virus: What pediatricians need to know

February 2, 2016

Zika virus outbreaks in South and Central America mean that it could only be a matter of time before the virus is endemic in the United States.

Pediatricians should be on alert to screen for cases of congenital Zika infection in infants of symptomatic women who have lived in or traveled to areas where the virus is endemic, according to a new directive from the Centers for Disease Control and Prevention (CDC).

The Zika virus was first identified in a monkey in Uganda in 1947 and has typically been found since then along the equator throughout Africa and Asia. It is spread by the yellow fever mosquito (Aedes aegypti) and the Asian tiger mosquito (Aedes albopictus), which also transmit dengue and chikungunya viruses.

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About a decade ago, cases started appearing throughout the Pacific Islands, and the case in the Americas was reported in Brazil in mid-2015. Since then, the mosquito-borne disease has spread to 22 other countries and regions in the Americas, according to the World Health Organization, and may have been the cause of at least 4000 cases of microencephaly since summer 2015.

There have also been about 30 documented cases across 12 states in the United States, as well as 19 confirmed cases in Puerto Rico and 1 in the US Virgin Islands. The states where cases have been reported to local health departments include Arkansas, California, Florida, Hawaii, Illinois, Massachusetts, Minnesota, New Jersey, New York, Oregon, Texas, Virginia, and the District of Columbia.

The CDC has created a map to track Zika outbreaks, and doesn’t believe that any cases have been contracted locally, but rather during recent travel. Still, local infections may not be far off, says CDC.

“With the recent outbreaks, the number of Zika cases among travelers visiting or returning to the United States will likely increase,” says CDC. “These imported cases could result in local spread of the virus in some areas of the United States.”

H Cody Meissner, MD, FAAP, a member of the American Academy of Pediatrics Committee on Infectious Disease and chief of the division of pediatric infectious disease at Tufts Medical Center in Boston, Massachusetts says he expects Zika virus to be endemic in the United States by summer 2016, as temperatures rise across the majority of the nation.

About 20% of individuals infected with the Zika virus develop symptoms, which can include high fever, joint pain, rash, conjunctivitis, muscle pain, and headache.

The CDC says it doesn’t know the incubation period for the virus, but it is most likely between a few days and a week. The illness is usually mild, with severe illness resulting in hospitalization and death occurring rarely. No medications or treatments are available aside from comfort care such as rest, hydration, and pain relief. However, the larger risk is to the unborn children of pregnant women.

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Children born to women who are infected with Zika virus are believed to suffer from a congenital infection of the virus, which can result in serious, irreversible birth defects.

What’s uncertain, Meissner says, is whether congenital infection occurs in all cases of maternal infection, or only when the mother is symptomatic.

“Eighty percent of mothers who are infected do not develop any signs of the disease,” Meissner says. “We don’t know how efficiently the virus is transmitted to the baby. We don’t know how high the risk is.”

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Zika has been documented to occur through intrauterine transmission in viremic mothers, says CDC. Although Zika RNA has also been found in breast milk, there are no documented cases of Zika virus transmission through breastfeeding.

“We know so little about this,” Meissner says. “The important issue is for women who have been in an endemic area while they’re pregnant to have studies done.”

The CDC is recommending that only mothers who have symptoms be tested for Zika virus, rather than all mothers who have traveled to endemic areas, Meissner says, partly due to the risk of having a false positive result.

“If mother has positive serology, it could scare her and there’s nothing to do,” Meissner says. “There’s nothing to do for it. There’s no drug, there’s no treatment that can be used, and the only assist you can give a mother is the very sad news her baby is not normal.”

Meissner says most US mothers have an ultrasound in late pregnancy that would reveal any abnormalities in the baby without previous testing.

Pediatricians are advised to work closely with obstetrics providers to identify cases in which mothers may have potentially been infected with the virus during pregnancy based on their travel history or where they live, says CDC.

Fetal ultrasounds and maternal blood testing for the virus can be helpful in making a diagnosis, although the maternal blood test can easily yield false positives. The CDC recommends that Zika testing be performed on any infant with microcephaly or intracranial calcifications born to women to live in or have traveled to an area where Zika is endemic, and also on infants whose mothers had positive or inconclusive test results for Zika. When infants who are born with microcephaly or intracranial calcifications, the infant and mother should both be tested for Zika infection. The infant should also receive an ophthalmologic evaluation within the first month of life, and a hearing screen at 6 months even if the initial hearing screen was normal.

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Zika diagnoses can be made through molecular and serologic testing including reverse transcription-polymerase chain reaction (RT-PCR) for viral RNA, and immunoglobulin M ELISA and plaque reduction neutralization test for Zika virus antibodies.

“Because it is currently not known which type of testing most reliably establishes the diagnosis of congenital infection, CDC recommends both molecular and serologic testing of infants who are being evaluated for evidence of a congenital Zika virus infection,” says CDC. “No commercial tests for Zika virus are available; Zika virus testing is performed at CDC and some state and territorial health departments.”

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Zika RT-PCR tests should be performed on serum specimens collected from the umbilical cord or from the infant within 2 days of birth, CDC says, and cerebrospinal fluid and frozen and fixed placenta obtained at delivery should be tested by RT-PCR.

Immunoglobulin M ELISA is also recommended, but can yield false positives as a result of cross-reacting antibodies. Immunohistochemical staining to detect Zika virus antigen on fixed placenta and umbilical cord tissues can be performed, says CDC.

The CDC considers an infant to be congenitally infected if Zika virus RNA or viral antigen is found in any of the samples tested.

When evaluating for possible congenital Zika virus infection, the CDC defines microcephaly as an occipitofrontal circumference of less than the third percentile based on standard growth charts.

“For a diagnosis of microcephaly to be made, the occipitofrontal circumference should be disproportionately small in comparison with the length of the infant and not explained by other etiologies,” says CDC. “If an infant’s occipitofrontal circumference is equal to or greater than the third percentile but is notably disproportionate to the length of the infant, or if the infant has deficits that are related to the central nervous system, additional evaluation for Zika virus infection might be considered.”

Healthcare providers must report any cases of Zika virus to their local health departments, says CDC.

There is no vaccine against the Zika virus, and treatment is supportive only, says CDC.

As far as continued damage from the virus, Meissner says experts aren’t sure whether damage ends after the initial infection, or whether it can continue to harm the baby.

“We think once the damage is done, the virus may be done, but we don’t know,” Meissner says, adding that there is little that could be done if the infection persisted anyway.

“It’s not as though we have options of what we can do,” he says.

Meissner says experts are also uncertain of when in the pregnancy infection with the Zika virus poses the most damage. The most basic systems are already developed by the end of the first trimester, so that may be the period of greatest risk, Meissner says, but there is no guarantee that a fetus couldn’t be affected in later stages of pregnancy.