History
In most cases, Zika virus (ZIKV) infection causes a mild, self-limited illness. The incubation period likely is 3-12 days. [1] Owing to the mild nature of the disease, more than 80% of Zika virus infection cases likely go unnoticed. [1] The spectrum of Zika virus disease overlaps with other that of arboviral infections, but rash (maculopapular and likely immune-mediated) typically predominates. [1]
The rash in Zika virus infection usually is a fine maculopapular rash that is diffusely distributed. It can involve the face, trunk, and extremities, including palms and soles. Occasionally, the rash may be pruritic. The rash, along with other symptoms, usually occurs within 2 weeks after travel to a Zika virus–affected area. Zika virus rash usually occurs within the first week of illness, with the illness itself lasting from several days to weeks.




Aside from rash, the most common symptoms of Zika virus infection include fever, arthralgia (involving the small joints of the hands and feet), retroocular headache, and conjunctivitis. [2, 4, 21] Symptoms last from 2-7 days. [1]
In rare cases, Zika virus infection is complicated by Guillain-Barré syndrome. [1, 21] A case of probable Zika virus-related hypertensive iridocyclitis was reported in an otherwise healthy young physician. [13]
More commonly, patients recover quickly and fully. In a review of 49 confirmed and 59 probable cases of Zika virus infection occurring in a 2007 outbreak on Yap Island, Micronesia, no hospitalizations, hemorrhagic complications, or deaths were attributed to the infection. [4]
Microcephaly and Other Congenital Malformations
Although Zika virus infection generally is well-tolerated, great concern is emerging over congenital malformations due to transplacental transmission of Zika virus. Six months after an outbreak of Zika virus infection began in Brazil, the incidence of microcephaly increased twenty-fold. Whereas the historical prevalence of microcephaly was 2 cases per 10,000 live births, 1248 new suspected cases of microcephaly were reported in 2015, [14, 15] and, as of January 2016, the number of suspected microcephaly cases increased to 4810, of which 270 were confirmed and 462 rejected as false diagnoses of microcephaly. [15]
Infants born with congenital microcephaly and suspected vertical acquisition of Zika virus have been found to have various ophthalmologic abnormalities, including loss of foveal reflex, macular pigment mottling, chorioretinal macular atrophy, optic nerve head hypoplasia, and optic nerve double-ring sign. [14]
Of note, causality has not been definitively proven, and concerns exist over the accuracy of the historical incidence of microcephaly and potential increased diagnoses in the past year leading to a false perception of increased incidence. [15]
A study of 35 infants with microcephaly (defined as head circumference ≥2 standard deviations below the mean for sex and gestational age) born between August and October 2015 in various states throughout Brazil found that the mothers of all 35 had lived in or visited Zika virus–affected areas during pregnancy. [16] Twenty-seven of these infants had severe microcephaly, and test results were negative for other congenital infections in all cases. Zika virus RNA also has been detected in amniotic fluid and placental and fetal tissue in several cases of nervous-system malformations amid the Brazilian outbreak. [15]
Physical Examination
The WHO recommends that newborns born to mothers with Zika virus infection undergo head circumference measurement between 1 and 7 days after birth. A head circumference of more than 2 standard deviations below the mean is considered microcephaly; a circumference of more than 3 standard deviations below the mean is classified as severe microcephaly, which should prompt neuroimaging. [30]
Complications
Serious complications have been reported in some cases of Zika virus infection, including Guillain-Barré syndrome. [1, 21] In addition, there is great concern over congenital malformations due to transplacental transmission of Zika virus, including microcephaly and various ophthalmologic abnormalities. [14, 15]
In March 2016, a 15-year-old patient diagnosed with acute myelitis on the French Caribbean island of Guadeloupe was found to have high levels of Zika virus in her cerebrospinal fluid, urine, and blood, suggesting that Zika virus may be neurotropic. Thus, Zika virus infection should be considered among individuals with acute myelitis who live in or travel from areas endemic for Zika virus. [31]
For more details, see History.
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Rash in a patient with Zika virus infection. Courtesy of Carolina O Barbosa, MD, and Antonio C Bandeira, MD, Salvador, Brazil.
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Rash in a patient with Zika virus infection. Courtesy of Carolina O Barbosa, MD, and Antonio C Bandeira, MD, Salvador, Brazil.
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Rash in a patient with Zika virus infection. Courtesy of Carolina O Barbosa, MD, and Antonio C Bandeira, MD, Salvador, Brazil.
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Rash in a patient with Zika virus infection. Courtesy of Carolina O Barbosa, MD, and Antonio C Bandeira, MD, Salvador, Brazil.
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Laboratory-confirmed symptomatic Zika virus disease cases reported to ArboNET by states and territories - United States, 2017. Courtesy of the Centers for Disease Control and Prevention (CDC).
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World map of areas with color-coded risk for Zika based on current or previously reported Zika cases, as of November 4, 2019. Courtesy of the Centers for Disease Control and Prevention (CDC).
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Diagnostic testing to interpret infection from Dengue and Zika virus. Courtesy of the Centers for Disease Control and Prevention (CDC).
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Dengue and Zika virus diagnostic testing interpretation in nonpregnant and pregnant patients. Courtesy of the Centers for Disease Control and Prevention (CDC).
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Testing algorithm for pregnant women with a clinically compatible illness and risk for Zika and Dengue virus. Courtesy of the Centers for Disease Control and Prevention (CDC).
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Dengue and Zika virus testing recommendations for nonpregnant persons with a clinically compatible illness and risk for infection with both viruses. Courtesy of the Centers for Disease Control and Prevention (CDC).
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Interpretation of results of laboratory testing of infant’s blood, urine, and/or cerebrospinal fluid for evidence of congenital Zika virus infection. Courtesy of the Centers for Disease Control and Prevention (CDC).
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Recommendations for the evaluation of infants with possible congenital Zika virus infection based on infant clinical findings, maternal testing results, and infant testing results - United States, October 2017. Courtesy of the Centers for Disease Control and Prevention (CDC).
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Consultations for infants with clinical findings consistent with congenital Zika syndrome - United States, October 2017. Courtesy of the Centers for Disease Control and Prevention (CDC).