Zika virus (ZIKV) is a mosquito-borne flavivirus, a member of the Spondweni serocomplex, whose natural transmission cycle involves mainly vectors from the Aedes genus (A. furcifer, A. taylori, A. luteocephalus and A. africanus) and monkeys, while humans are occasional hosts. Clinical pictures range from asymptomatic cases to an influenza-like syndrome associated to fever, headache, malaise and cutaneous rash. Likewise, direct contact is also considered a potential route of transmission among humans during sexual intercourse.
ZIKV emerged in Uganda around 1920, most probably between 1892 and 1943. This inference is in line with the first known Zika virus isolation in Uganda in 1947 from the blood of a sentinel Rhesus monkey, stationed in the Zika forest, near the Lake Victoria in Uganda, and in 1948 Zika virus was also isolated in the same forest from a pool of A. africanus mosquitoes. Thereafter, serological and entomological data indicated ZIKV infections in the African continent and in Asia were reported.
Although Zika virus was repeatedly isolated, only 14 human cases were reported before April 2007, when a Zika fever (ZF) epidemic occurred in Yap island in Micronesia, where 49 confirmed cases and 73% of the residents older than 3 years provided serologic evidence for recent ZIKV infection. This outbreak showcased the potential of Zika fever (ZF) as an emerging disease, which could be misdiagnosed as dengue fever, as happened during the beginning of the Micronesian outbreak.
The ZIKV genome consists of a single-stranded positive sense RNA molecule with 10794 kb of length and a single long open reading frame encoding a polyprotein: 59-C-prM-E-NS1-NS2A-NS2BNS3-NS4A-NS4B-NS5-39, that is cleaved into capsid (C), precursor of membrane (prM), envelope (E) and seven non-structural proteins (NS). The Envelope (<53 kDa) is the major virion surface protein involved in various aspects of the viral cycle, mediating binding and membrane fusion.
While there are scarce resources describing ZIKV pathogenesis exclusively, the general consensus is that mosquito-borne flaviviruses replicate initially in the dendritic cells at the site of infection where it then spreads to other areas of the body via the bloodstream and lymphatic system. Viral replication typically occurs in the cytoplasm of infected cells, but there is a study that shows ZIKV antigens can also be found in the nuclei of infected host cells.
Zika virus is a single-stranded RNA virus of the Flaviviridae family, genus Flavivirus. Zika virus is transmitted to humans primarily through the bite of an infected Aedes species mosquito. The mosquito vectors typically breed in domestic water-holding containers; they are aggressive daytime biters and feed both indoors and outdoors near dwellings. Nonhuman and human primates are likely the main reservoirs of the virus, and anthroponotic (human-to-vector-to-human) transmission occurs during outbreaks.
Perinatal, in utero, and possible sexual and transfusion transmission events have also been reported. ZIKV RNA has been identified in asymptomatic blood donors during an ongoing outbreak.
In May 2015, the Pan American Health Organization (PAHO) issued an alert regarding the first confirmed Zika virus infection in Brazil. The outbreak in Brazil led to reports of Guillain-Barré syndrome and pregnant women giving birth to babies with birth defects and poor pregnancy outcomes.
In response, CDC has issued a travel alert (Level 2-Practice Enhanced Precautions) for people traveling to regions and certain countries where Zika virus transmission is ongoing.
Clinical Signs and Symptoms
About 1 in 5 people infected with ZIKV become symptomatic. Characteristic clinical findings are acute onset of fever with maculopapular rash, arthralgia, or 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 is low. However, there have been cases of Guillain-Barre syndrome reported in patients following suspected Zika virus infection. The Brazil Ministry of Health is also investigating the possible association between Zika virus and a reported increase in the number of babies born with microcephaly. Due to concerns of microcephaly associated with maternal Zika virus infection, fetuses and infants of women infected with Zika virus during pregnancy should be evaluated for possible congenital infection and neurologic abnormalities.
Based on the typical clinical features, the differential diagnosis for Zika virus infection is broad. In addition to dengue, other considerations include leptospirosis, malaria, rickettsia, group A streptococcus, rubella, measles, and parvovirus, enterovirus, adenovirus, and alphavirus infections (e.g., Chikungunya, Mayaro, Ross River, Barmah Forest, O’nyong-nyong, and Sindbis viruses).
Preliminary diagnosis is based on the patient’s clinical features, places and dates of travel, and activities. Laboratory diagnosis is generally accomplished by testing serum or plasma to detect virus, viral nucleic acid, or virus-specific immunoglobulin M and neutralizing antibodies. During the first week after onset of symptoms, ZIKV disease can often be diagnosed by performing reverse transcriptase-polymerase chain reaction (RT-PCR) on serum. Virus-specific IgM and neutralizing antibodies typically develop toward the end of the first week of illness; cross-reaction with related flaviviruses (e.g., dengue and yellow fever viruses) is common and may be difficult to discern. Plaque-reduction neutralization testing can be performed to measure virus-specific neutralizing antibodies and discriminate between cross-reacting antibodies in primary flavivirus infections.
The CDC advises pediatric healthcare providers to work with obstetric providers to identify infants whose mothers were potentially infected with ZIKV during pregnancy (based on travel to or residence in an area with Zika virus transmission) and to review fetal ultrasounds and maternal testing for Zika virus infection.
The guidelines recommend Zika virus testing for infants with microcephaly or intracranial calcifications who were born to women who traveled to or resided in an area with ZIKV transmission while pregnant and for infants born to mothers with positive or inconclusive test results for Zika virus infection
No specific antiviral treatment is available for Zika virus disease. Treatment is generally supportive and can include rest, fluids, and use of analgesics and antipyretics. Because of similar geographic distribution and symptoms, patients with suspected ZIKV infections also should be evaluated and managed for possible dengue or chikungunya virus infection. Aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) should be avoided until dengue can be ruled out to reduce the risk of hemorrhage. People infected with Zika, chikungunya, or dengue virus should be protected from further mosquito exposure during the first few days of illness to prevent other mosquitoes from becoming infected and reduce the risk of local transmission.