The Zika virus is a mosquito-borne flavivirus that is antigenically and structurally similar to the viruses that cause dengue, yellow fever, and West Nile virus. Zika virus infection is typically asymptomatic but can cause fever, rash, joint pain, or conjunctivitis; Zika virus infection during pregnancy can cause microcephaly (a serious birth defect), eye abnormalities, and a number of developmental impairments termed congenital Zika syndrome. Diagnosis is with enzyme-linked immunosorbent assay or reverse transcriptase–polymerase chain reaction (RT-PCR). Treatment is supportive. Prevention involves avoiding mosquito bites, avoiding unprotected sex with a partner at risk of having Zika virus infection, and, for pregnant women and their partners, avoiding travel to areas with ongoing transmission.
(See also Overview of Arbovirus, Arenavirus, and Filovirus Infections.)
Zika virus (ZV), like the viruses that cause dengue, yellow fever, and chikungunya disease, is transmitted by Aedes mosquitoes, which breed in areas of stagnant water. These mosquitoes prefer to bite people and live near people, indoors and outdoors; they bite aggressively during the day. They also bite at night.
The main vectors are A. aegypti and A. albopictus. In the United States, A. aegypti is restricted to an area that extends from the deep South along the United States-Mexican border to southern California. A. albopictus, which better adapted to colder climates, is present in a large part of the southeast up through the Upper Midwest and in southern California. A. aegypti is considered to be the main vector for epidemic Zika virus infection; A. albopictus is thought to be a secondary vector of epidemic Zika virus infection in the tropics, but whether it would do so in the more temperate climate of the United States is unclear. Although A. aegypti feeds almost exclusively on humans, A. albopictus feeds on humans as well as variety of other animals that are not susceptible to the virus and are not involved in transmission chains.
Epidemiology of Zika Virus Infections
In 1947, the Zika virus was first isolated from monkeys in the Zika Forest of Uganda but was not considered an important human pathogen until the first large-scale outbreaks in the South Pacific islands in 2007. In May 2015, local transmission was first reported in South America, then in Central America and in the Caribbean, reaching Mexico by late November 2015.
Local transmission of Zika virus has been reported in the following regions:
South America
Central America and Mexico
Caribbean Islands (including Puerto Rico and the US Virgin Islands)
Pacific Islands
Cape Verde (a nation of islands off the northwest coast of Africa)
South and Southeast Asia (sporadic cases)
Africa
Florida and Texas
The Centers for Disease Control and Prevention (CDC) issues travel alerts for countries in these regions when outbreaks occur. Although as of December 2019, there were no areas with CDC travel precautions due to Zika outbreaks, in early 2020 there were thousands of cases in some areas of Brazil and hundreds of cases in Colombia.
In 2016 and 2017, cases of locally transmitted Zika virus infection were reported in Miami-Dade County in southeastern Florida and Brownsville, Texas. According to the CDC website, there is no current local transmission of Zika virus in the continental United States. However, Zika virus infection has been reported in travelers returning to the United States after travel to countries where the virus is transmitted locally.
Predicting where the Zika virus will spread is difficult. However, because the same mosquito that transmits Zika also transmits dengue and chikungunya, local transmission of Zika virus can be expected wherever dengue or chikungunya has been transmitted. Dengue has been locally acquired most recently in Texas, Florida, and Hawaii; chikungunya has been locally acquired in Florida, Puerto Rico, and the US Virgin Islands. Similarly, in areas of the United States where dengue is now endemic (Puerto Rico and the US Virgin Islands in the Caribbean; American Samoa, Guam, and the Northern Mariana Islands in the Pacific Ocean), Zika virus infection may also become endemic. There was some serological evidence of Zika virus infection in nonhuman primates in Brazil at the end of the major outbreak in humans there. However, it is unclear whether the virus is routinely sustained in animal populations the way that yellow fever virus is.
Transmission of Zika Virus
During the first week of infection, the Zika virus is present in blood. Mosquitoes can acquire the virus when they bite infected people; the mosquitoes can then transmit the virus to other people through bites. Travelers from areas of ongoing Zika virus transmission may have Zika virus in their blood when they return home, and if mosquito vectors are present locally, transmission of Zika virus is possible there. However, because contact between Aedes mosquitoes and people is infrequent in most of the continental United States and Hawaii (because of mosquito control and people living and working in screened and in air-conditioned environments), local transmission of Zika virus is expected to be rare and limited.
Although the Zika virus is transmitted primarily by mosquitoes, other modes of transmission are possible. They include
Sexual transmission (including vaginal, anal, and oral sex)
Intrauterine transmission from mother to fetus, resulting in congenital infection
Blood transfusion
Organ or tissue transplantation (theoretically)
The Zika virus, like the viruses that cause dengue, chikungunya disease, and West Nile virus, can be transmitted from mother to child during pregnancy. The Zika virus, like the virus that causes dengue, has been detected in breast milk, but it is uncertain whether infants can acquire the infection through breastfeeding (1). However, because breastfeeding has many benefits, the CDC encourages mothers to breastfeed even in areas where Zika virus transmission is ongoing (see CDC: Zika Transmission and World Health Organization [WHO]: Guideline: infant feeding in areas of Zika virus transmission, 2nd edition).
Zika virus is present in semen and can be transmitted by men to their sex partners through sexual intercourse, including vaginal and anal sex and probably oral sex (fellatio), even when the men do not have symptoms. Zika virus persists in semen much longer than in blood, vaginal fluids, and other body fluids. Both male-to-female and male-to-male transmission during unprotected sexual activity (no condoms) has occurred (see also the CDC: Clinical Guidance for Healthcare Providers for Prevention of Sexual Transmission of Zika Virus).
Zika virus may also be transmitted by men or women to their sex partners when sex toys are shared, even when infected people have no symptoms.
Zika virus also persists in vaginal secretions after it disappears from blood and urine; female-to-male sexual transmission of Zika virus infection has been reported (2). A study in Guatemala reported viral RNA shedding in vaginal secretions intermittently for up to 6 months. However, detection of viral RNA does not prove presence of infectious virus, because polymerase chain reaction may detect one or more gene fragments, not necessarily infectious virus.
Transmission by blood transfusion has been reported in Brazil; however, at present, no cases of transmission by blood transfusion have been confirmed in the United States (see also the Zika and Blood & Tissue Safety).
Transmission references
1. Colt S, Garcia-Casal MN, Peña-Rosas JP, et al: Transmission of Zika virus through breast milk and other breastfeeding-related bodily-fluids: A systematic review. PLoS Negl Trop Dis 11(4):e0005528. 2017. Published 2017 Apr 10. doi:10.1371/journal.pntd.0005528
2. CDC media statement: First female-to-male sexual transmission of Zika virus infection reported in New York City. July 2016.
Symptoms and Signs of Zika Virus Infections
Most people who become infected have no symptoms.
Symptoms of Zika virus infection include fever, maculopapular rash, conjunctivitis (pinkeye), joint pain, retro-orbital pain, headache, and muscle pain. Symptoms last 4 to 7 days. Most infections are mild. Severe infection requiring hospitalization is uncommon. Rarely, Zika virus infection has caused encephalopathy in adults. Death due to Zika virus infection is rare.
Very uncommonly, Guillain-Barré syndrome (GBS) develops after a Zika virus infection. GBS is an acute, usually rapidly progressive but self-limited inflammatory polyneuropathy thought to be caused by an autoimmune reaction. GBS has also developed after dengue and chikungunya disease.
Congenital Zika virus infection
Zika virus infection during pregnancy can cause microcephaly (a congenital disorder involving incomplete brain development and small head size), other severe fetal brain, ocular, and other defects that, together are termed congenital Zika syndrome (see also the CDC: Congenital Zika Syndrome & Other Birth Defects).
In the continental United States, several cases of microcephaly have been linked to the Zika virus; the mothers of these infants probably contracted the infection through travel to a country with endemic infection. Cases are being monitored by the CDC and WHO (see CDC: Zika cases in the United States; WHO: Countries and territories with current or previous Zika virus transmission).
Infants infected in utero, whether they have microcephaly or not, may have ocular lesions or congenital contractures (eg, clubfoot). Infants infected in utero and born without congenital Zika syndrome are at risk for neurodevelopmental delay. Children with in utero Zika virus exposure without congenital Zika syndrome may demonstrate emerging differences in executive function, mood, and adaptive mobility that require continued evaluation.
Diagnosis of Zika Virus Infections
Serologic testing
Nucleic acid amplification tests (NAAT) with reverse transcriptase–polymerase chain reaction (RT-PCR) testing
Zika virus infection is suspected based on symptoms and on places and dates of travel. However, clinical manifestations of Zika virus infection resemble those of many febrile tropical diseases (eg, dengue, malaria, leptospirosis, other arbovirus infections), and its geographic distribution resembles that of other arboviruses. Thus, diagnosis of Zika virus infection requires laboratory confirmation by one of the following (see CDC: Dengue and Zika Virus Diagnostic Testing for Patients with a Clinically Compatible Illness and Risk for Infection with Both Viruses):
NAAT to detect viral RNA in serum or urine
Serologic testing (enzyme-linked immunosorbent assay [ELISA] for IgM, the plaque reduction neutralization test [PRNT] for Zika virus antibodies)
Zika virus can often be detected with NAAT in serum within 1 week after symptom onset and up to 14 days in urine samples. NAAT may detect Zika virus in whole blood for up to 3 months (1).
In the United States, emergency use authorization has been issued for the Trioplex real-time RT-PCR, which is a multiplex PCR assay that can detect the RNA of dengue, chikungunya, and Zika viruses in serum, blood, and cerebrospinal fluid, and can detect Zika virus RNA in urine and amniotic fluid.
Virus-specific IgM and neutralizing antibodies typically develop toward the end of the first week of illness, but cross-reaction with related flaviviruses (eg, dengue and yellow fever viruses) is common. The PRNT with acute and convalescent serum pairs measures virus-specific neutralizing antibodies and helps distinguish cross-reacting antibodies from closely related flaviviruses. A fourfold or greater rise in PRNT antibodies is diagnostic.
Diagnosis with IgM testing is limited, because IgM can persist for months after infection. Therefore, IgM test results cannot always reliably distinguish between an infection that occurred during a current pregnancy and one that occurred before a current pregnancy, particularly for women with possible Zika virus exposure before the current pregnancy.
Recommendations for Zika virus testing vary by patient population and by medical organization (see CDC: Zika and Dengue Testing Guidance; WHO: Laboratory testing for Zika virus and dengue virus infections: interim guidance).
Routine testing for Zika virus infection is not recommended for asymptomatic pregnant women. However, for those in or with recent travel to areas with high levels of epidemic transmission or who have had sex with someone with a high risk of exposure, RT-PCR testing may be considered (up to 12 weeks after exposure per CDC guidelines).
For symptomatic pregnant women with recent exposure to Zika:
CDC: < 12 weeks after symptom onset, Zika virus RT-PCR of blood and urine (if test is positive, repeat on newly extracted RNA from the same specimen); IgM antibody testing is not recommended
WHO: ≤ 14 days after symptom onset, Zika virus RT-PCR of blood and urine and, if negative, IgM testing; > 14 days, IgM testing
For pregnant women with a fetus with prenatal ultrasound findings consistent with congenital Zika virus infection who live in or traveled to areas with a risk of Zika during pregnancy, the CDC recommends both RT-PCR and IgM testing. If RT-PCR is negative and IgM is positive, confirmatory PRNTs should be performed. Zika virus RT-PCR testing of amniocentesis specimens and testing of placental and fetal tissues may also be considered. Neonates with suspected Zika virus syndrome should be tested (see CDC: Infants and Children: Evaluation & Testing for Zika Virus and CDC: Zika: Caring for Infants & Children).
Nonpregnant patients should be tested if they have suspected Zika virus infection and severe symptoms. Testing asymptomatic men to assess risk of sexual transmission is not recommended (see CDC: Clinical Guidance for Healthcare Providers for Prevention of Sexual Transmission of Zika Virus). Men who reside in or have traveled to an area of active Zika virus transmission and who have a pregnant partner should abstain from sexual activity or consistently and correctly use condoms during sex (ie, vaginal intercourse, anal intercourse, fellatio) for the duration of the pregnancy.
Clinicians in the United States are required to notify the CDC if they identify a case of Zika virus infection. (See also CDC: Diagnostic Tests for Zika Virus.)
Diagnosis reference
1. Stone M, Bakkour S, Lanteri MC, et al: Zika virus RNA and IgM persistence in blood compartments and body fluids: a prospective observational study. Lancet Infect Dis 20(12):1446-1456, 2020. doi:10.1016/S1473-3099(19)30708-X
Treatment of Zika Virus Infections
Supportive care
No specific antiviral treatment is available for Zika virus infection.
Treatment is supportive; it includes the following:
Rest
Fluids to prevent dehydration
dengue can be ruled out because hemorrhage is a risk. Also, death and severe infection due to Zika virus has been related to immune thrombocytopenia and bleeding (1, 2).
If pregnant women have laboratory evidence of Zika virus in serum, urine or amniotic fluid, serial ultrasonography every 3 to 4 weeks should be considered to monitor fetal anatomy and growth. Referral to a maternal-fetal medicine or infectious disease specialist with expertise in pregnancy management is recommended.
Brain development should be monitored for ≥ 2 years in all infants born to mothers infected with Zika virus, whether or not the infants have microcephaly, ocular lesions, or other manifestations suggestive of congenital Zika syndrome. The CDC has extensive information about testing and care for infants affected by Zika (see CDC: Care for Babies Affected by Zika).
Treatment references
1. Sharp TM, Muñoz-Jordán J, Perez-Padilla J, et al: Zika virus infection associated with severe thrombocytopenia. Clin Infect Dis 63 (9):1198–1201, 2016. doi: 10.1093/cid/ciw476
2. Karimi O, Goorhuis A, Schinkel J, et al: Thrombocytopenia and subcutaneous bleedings in a patient with Zika virus infection. The Lancet 387 (10022):939–940, 2016. doi: 10.1016/S0140-6736(16)00502-X
Prevention of Zika Virus Infections
If possible, pregnant women should NOT travel to areas with ongoing Zika virus outbreaks (see also CDC: Pregnant Women and Zika). If traveling to such areas, pregnant women should talk with their obstetric clinician about risks of Zika virus infection and precautions to be taken to avoid mosquito bites during the trip.
There is currently no vaccine to prevent Zika virus infection.
Prevention of transmission via mosquitoes
Prevention of Zika virus infection depends on control of Aedes mosquitoes and prevention of mosquito bites when traveling to countries with ongoing Zika virus transmission. Control of A. aegypti has been very difficult; however, 2 approaches are being field-tested currently:
Release of genetically altered males or sterilized males that mate with wild females whose larval offspring then do not mature or whose eggs are infertile
Release of female A. aegypti mosquitoes infected with Wolbachia bacteria that block susceptibility to Zika virus in the infected mosquitoes and their offspring
To prevent mosquito bites, the following precautions should be taken (see also the CDC's Protection against Mosquitoes and Zika virus: Prevention and Transmission):
Wear long-sleeved shirts and long pants.
Stay in places that have air conditioning or that use window and door screens to keep mosquitoes out.
Sleep under a mosquito bed net in places that are not adequately screened or air-conditioned.
For children, the following precautions are recommended:
Do not use insect repellent on infants < 2 months.
Do not use products containing oil of lemon eucalyptus (para-menthane-diol) on children < 3 years.
For older children, adults should spray repellent on their hands and then apply it to the children's skin.
Dress children in clothing that covers their arms and legs, or cover the crib, stroller, or baby carrier with mosquito netting.
Do not apply insect repellent to the hands, eyes, mouth, or cut or irritated skin of children.
Prevention of sexual transmission
RNA of the Zika virus has been detected in semen up to 281 days after the onset of symptoms (1). However, detection of viral RNA does not necessarily indicate the presence of infectious virus. In one study, infectious virus was detected in a few individuals 30 days after illness onset but, in general, shedding of infectious Zika virus appeared to become much less common with time and was limited mainly to the first few weeks after illness onset; however, there is still a possibility of later transmission. Because Zika virus can be transmitted via semen, people should use condoms or practice abstinence if one or both partners live in or have traveled to an area with current or past Zika virus transmission. This recommendation applies whether or not people have symptoms because most Zika virus infections are asymptomatic, and when symptoms do develop, they are usually mild.
Man with pregnant partner: Abstain from sexual activity, or use condoms and avoid sharing sex toys for the duration of the pregnancy
Man who traveled to area at risk of Zika with or without female partner: Abstain from sexual activity or use condoms for 3 months after return (or the start of symptoms)
Woman who traveled to area at risk of Zika without male partner: Abstain from sexual activity or use condoms for 2 months after return (or the start of symptoms)
If using condoms, they should be used from start to finish every time during vaginal, anal, and oral sex.
Although no cases of woman-to-woman sexual transmission have been reported, the CDC recommends that all pregnant women who have a female sex partner who has traveled to or resides in an area with Zika use barrier methods every time during vaginal, anal, and oral sex, or abstain from sex during the pregnancy, and avoid sharing sex toys.
See also CDC: Zika: People Trying to Conceive.
Prevention reference
1. Mead PS, Duggal NK, Hook SA, et al: Zika Virus Shedding in Semen of Symptomatic Infected Men. N Engl J Med 378(15):1377-1385, 2018. doi:10.1056/NEJMoa1711038
Key Points
The Zika virus is transmitted primarily by Aedes mosquitoes.
Most Zika virus infections are asymptomatic; symptomatic infections are usually mild, causing fever, a maculopapular rash, conjunctivitis, joint pain, retro-orbital pain, headache, and muscle pain (myalgia).
Zika virus infection during pregnancy can cause a serious birth defect called microcephaly, ocular and other lesions within the congenital Zika syndrome spectrum.
Monitor brain development in all infants born to mothers infected with Zika virus, whether infants have microcephaly or ocular lesions or not, for ≥ 2 years.
Test pregnant women for Zika virus if they have traveled to or live in areas of ongoing Zika virus transmission using serologic testing (enzyme-linked immunosorbent assay for IgM, the plaque reduction neutralization test) or RT-PCR.
Pregnant women should NOT travel to areas with ongoing Zika virus outbreaks.
Prevention of Zika virus infection depends on controlling Aedes mosquitoes and avoiding mosquito bites.
Because Zika virus can be transmitted sexually, men and women who live in or have traveled to an area of ongoing Zika virus transmission should abstain from sexual activity or consistently and correctly use barrier methods during sex while their partner is pregnant.
More Information
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