Clinical Signs and Symptoms of Zika Virus Disease

Key points

  • Approximately 80% of people infected with Zika virus are asymptomatic.
  • Clinical illness is typically mild, characterized by fever, arthralgia, conjunctivitis, and maculopapular rash.
  • Complications are rare, but can include Guillain-Barré syndrome, encephalopathy, myelitis, uveitis, and thrombocytopenia.
  • Infection during pregnancy can cause congenital Zika virus infection, which can result in serious birth defects of the brain and eyes.
Posterior view of a patient’s back, captured in a clinical setting, upon presenting with this blotchy rash. After a diagnostic work-up, it was determined that the rash had been caused by the Zika virus.

Clinical features

Approximately 80% of people infected with Zika virus are asymptomatic.

The incubation period for Zika virus disease is 3 to 14 days. Characteristic clinical findings associated with Zika virus disease are acute onset of fever with maculopapular rash, arthralgia, or nonpurulent conjunctivitis. Other commonly reported symptoms include myalgia and headache. Clinical illness is usually mild with symptoms lasting for several days to a week.

Severe disease requiring hospitalization is uncommon and case fatality occurs in <1% of cases. However, cases of Guillain-Barré syndrome have occurred in patients following Zika virus infection. Rarely, encephalopathy, meningoencephalitis, myelitis, uveitis, and severe thrombocytopenia can occur.

Zika virus during pregnancy can cause a congenital infection with serious birth defects of the brain and eyes, including severe microcephaly, intracranial calcifications, cerebral or cortical atrophy, chorioretinal abnormalities, and optic nerve abnormalities. Transmission of Zika virus during pregnancy can occur regardless of symptoms in the gestational parent. Infants with congenital Zika virus infection may appear asymptomatic at birth but have neuroimaging findings or clinical sequelae (e.g., vision loss) that is only detected after birth. Fetuses and infants of people infected with Zika virus during pregnancy should be evaluated for possible congenital infection with neurologic and ocular abnormalities.

Because perinatal transmission of Zika virus from gestational parent to infant during delivery is possible, Zika virus disease should also be considered in an infant

  1. who has one or more of the following manifestations: fever, rash, conjunctivitis, and arthralgia during the first 2 weeks of life, and
  2. whose gestational parent was potentially exposed to Zika virus within approximately 2 weeks of delivery.

Arthralgia can be difficult to detect in infants and young children. It can manifest as irritability, difficulty moving or refusing to move an extremity, pain on palpation, or pain with active or passive movement of the affected joint.

Clinical assessment

Based on the typical clinical features, the differential diagnosis for Zika virus infection is broad. In addition to dengue, other considerations include leptospirosis, malaria, rubella, measles, and parvovirus, enterovirus, adenovirus, rickettsial, group A streptococcal, and alphavirus (e.g., caused by chikungunya, Mayaro, Ross River, Barmah Forest, o'nyong-nyong, and Sindbis viruses) infections.

Preliminary diagnosis is based on the patient's clinical features, places and dates of travel, and activities. Laboratory diagnosis is generally accomplished by testing whole blood, serum, or plasma to detect virus, viral nucleic acid, or virus-specific immunoglobulin M and neutralizing antibodies. For pregnant patients, testing urine to detect viral nucleic acid may also be recommended.