Background

Zika virus (ZIKV) belongs to the Flavivirus genus; like other flaviviruses.  In most cases, Zika virus infection causes a mild, self-limited illness. The incubation period is likely 3-12 days.[2] Owing to the mild nature of the disease, more than 80% of Zika virus infection cases likely go unnoticed.[2] The spectrum of Zika virus disease overlaps with other that of arboviral infections, but rash (maculopapular and likely immune-mediated) typically predominates.[2]

Centers for Disease Control and Prevention (CDC) warned that the risk of Zika virus infection in the United States may have been previously underestimated, citing the increased range of the mosquito vectors (now in 30 US states, up from 12 as previously thought) and the travel risks associated with the 2016 Olympics in Brazil.[3]

Zika virus was first described in a febrile rhesus monkey in the Zika forest of Entebbe, Uganda, and was reported in a human field worker shortly thereafter.[1]Currently, Zika virus is known to be widely distributed outside of Africa. Outbreaks have been described previously in Micronesia and French Polynesia.[4, 5]

Pathophysiology

Zika virus is transmitted by Aedes  mosquito, including Aedes aegypti,Aedes africanus, Aedes luteocephalus, Aedes albopictus, Aedes vittatus, Aedes furcifer, Aedes hensilli, andAedesapicoargenteus.[1, 5, 6, 2] Sexual transmission among humans has also been described.[1, 7]

Epidemiology

The global prevalence of Zika virus infection has not been widely reported owing to asymptomatic clinical course, clinical resemblance to other infection with other flaviviruses (dengue, chikungunya), and difficulty in confirming diagnosis.

In May 2015, Brazil reported the first outbreak of Zika virus infection in the Americas. The Brazil Ministry of Health estimated around 440,000-1,300,000 suspected cases of Zika virus infection in December 2015.[13]

Since then, the infection has spread rapidly to several other countries, becoming a pandemic. The association of Zika virus infection with Guillain-Barré syndrome(GBS) and congenital birth defects (particularly microcephaly) amid the ongoing outbreak of Zika virus infection in Brazil is still under investigation.[13, 14]

In March 2016, the WHO reported that Zika virus was actively circulating in 38 countries

Prognosis

Most cases of Zika virus infection are mild and self-limited. Owing to the mild nature of the disease, more than 80% of Zika virus infection cases likely go unnoticed.[2] However, serious complications have been reported in rare cases, including Guillain-Barré syndrome.[2, 9] In addition, great concern is emerging over congenital malformations due to transplacental transmission of Zika virus, including microcephaly and various ophthalmologic abnormalities.[11, 12]

Patient Education

Certain patients should be educated concerning travel risks associated with Zika virus and prevention of mosquito bites and mosquito-control measures.

The World Health Organization (WHO) and CDC recommend that mothers with Zika virus infection still breastfeed their infants, including those born with microcephaly. Zika virus transmission via breast milk has not been documented, although more research is needed for confirmation.[17]

History

In most cases, Zika virus (ZIKV) infection causes a mild, self-limited illness. The incubation period is likely 3-12 days.[2] Owing to the mild nature of the disease, more than 80% of Zika virus infection cases likely go unnoticed.[2] The spectrum of Zika virus disease overlaps with other that of arboviral infections, but rash (maculopapular and likely immune-mediated) typically predominates.[2]

The rash in Zika virus infection is usually 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.[1, 5, 9] Symptoms last from 2-7 days.[2]

In rare cases, Zika virus infection is complicated by Guillain-Barré syndrome.[2, 9] A case of probable Zika virus-related hypertensive iridocyclitis was reported in an otherwise healthy young physician.[10]

More commonly, patients recover quickly and fully.

Microcephaly and Other Congenital Malformations

While Zika virus infection is generally 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.

Infants born with congenital microcephaly and suspected vertical acquisition of Zika virus have also 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.[11]

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.[12]

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.

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.[18]

Complications have been reported in some cases of Zika virus infection, including Guillain-Barré syndrome.
 
Diagnostic Considerations

Signs and symptoms of Zika virus (ZIKV) infection are nonspecific and mimic other infections. Among them, dengue virus infection is the most serious and may be life-threatening. Other etiologies include chikungunya virus, yellow fever virus,parvovirus, enterovirus, Ross River virus, plasmodia (malaria), and rickettsia.