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Zika Virus (ZV) Infections

By

Thomas M. Yuill

, PhD, University of Wisconsin-Madison

Last full review/revision Mar 2020| Content last modified Mar 2020
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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, avoiding travel to areas with ongoing transmission.

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 US, A. aegypti is restricted to an area that extends from the deep South along the US-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 US is unclear.

Epidemiology

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

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 US. However, Zika virus infection has been reported in travelers returning to the US 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 US 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.

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 US 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

  • Transmission through blood transfusion

  • Transmission through organ or tissue transplantation (theoretically)

  • Intrauterine transmission from mother to fetus, resulting in congenital infection

  • Transmission from an infected mother to her infant through breast milk

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 (1). A recent 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.

Transmission by blood transfusion has been reported in Brazil; however, at present, no cases of transmission by blood transfusion have been confirmed in the US (see also the Zika and Blood Transfusion).

The Zika virus, like the viruses that cause dengue, chikungunya disease, West Nile virus, and yellow fever, can be transmitted from mother to child during pregnancy. The Zika virus, like the viruses that cause dengue and West Nile virus, can be transmitted in breast milk. However, because breastfeeding has many benefits, the CDC encourages mothers to breastfeed even in areas where Zika virus transmission is ongoing.

Transmission reference

  • 1. CDC media statement: First female-to-male sexual transmission of Zika virus infection reported in New York City. July 2016.

Symptoms and Signs

Most (80%) 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.

Microcephaly and other congenital abnormalities

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: Update: Interim Guidance for the Diagnosis, Evaluation, and Management of Infants with Possible Congenital Zika Virus Infection).

In the continental US, 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. The CDC is monitoring a number of pregnant women who have Zika virus infection and who live on the US mainland or in Puerto Rico or other US territories.

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. 

Diagnosis

  • Serologic testing

  • Reverse transcriptase–polymerase chain reaction (RT-PCR) testing

Clinicians are required to notify the CDC if they identify a case of Zika virus infection. (See also CDC: Diagnostic Tests for Zika Virus.)

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, 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:

  • Serologic testing (enzyme-linked immunosorbent assay [ELISA] for IgM, the plaque reduction neutralization test [PRNT] for Zika virus antibodies)

  • RT-PCR to detect viral RNA in serum or urine.

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 measures virus-specific neutralizing antibodies and helps distinguish cross-reacting antibodies from closely related flaviviruses.

During the first week after symptom onset, the Zika virus can often be detected using RT-PCR on serum; urine samples should be collected < 14 days after symptom onset for RT-PCR testing.

In the US, emergency use authorization for the following diagnostic tests for Zika virus has been issued:

  • Zika MAC-ELISA

  • Trioplex real-time RT-PCR assay

These tests are being distributed to laboratories that are certified to perform high-complexity tests in the US (for more information about these tests, see the CDC's CDC: Diagnostic Tests for Zika Virus and CDC: Types of Zika Virus Tests).

To aid in the diagnosis and treatment of Zika virus infection, the CDC has issued interim guidelines for pregnant women and interim guidelines for infants born to mothers who traveled to or live in an area with ongoing Zika virus transmission during pregnancy.

Currently, testing men to assess risk of sexual transmission is not recommended (see also 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.

Maternal testing

For pregnant travelers returning from areas with ongoing Zika virus transmission, the CDC guidelines recommend serologic testing for all pregnant women, whether they have symptoms of Zika virus infection or not. In addition, if pregnant women may have been exposed to Zika virus, ultrasonography to assess fetal anatomy is recommended (see also CDC: Update: Interim Guidance for Health Care Providers Caring for Pregnant Women with Possible Zika Virus Exposure—US (Including US Territories), July 2017).

  • For asymptomatic pregnant women: Testing should be done 2 to 12 weeks after pregnant women return from traveling.

  • For symptomatic pregnant women: Testing should be done while they are symptomatic.

For pregnant women who live in areas with ongoing Zika virus transmission, Zika virus infection is a risk throughout pregnancy. If pregnant women develop symptoms suggesting Zika virus infection, testing should be done during the first week of illness. For asymptomatic pregnant women who live in areas with ongoing Zika virus transmission, the CDC recommends testing at the first prenatal visit and, if the results are negative, during the middle of the 2nd trimester; fetal ultrasonography should be done at 18 to 20 weeks gestation (see also CDC: Update: Interim Guidance for Health Care Providers Caring for Pregnant Women with Possible Zika Virus Exposure).

Compared with pregnant travelers, pregnant women living in areas with ongoing Zika virus transmission are more likely to have a false-positive IgM result because they are more likely to have been exposed to a related flavivirus.

Infant testing and follow-up

If the mother of an infant traveled to or lived in an area affected by Zika virus infection during pregnancy, testing should be guided by what the mother's Zika virus test results are and whether the infant has microcephaly, intracranial calcifications, eye abnormalities, or other defects consistent with congenital Zika syndrome (see also CDC: Evaluation and Testing: Congenital Zika Virus Infection).

  • If mothers have negative Zika virus test results or were not tested for Zika virus and their infant does not have microcephaly or intracranial calcifications, the infant should be given routine care. Results of studies of adverse neurodevelopmental effects in infants infected after birth are conflicting, but suggest that ongoing monitoring of these infants is prudent.

  • If mothers have positive or inconclusive Zika virus test results and their infant has microcephaly or intracranial calcifications, the CDC's Update: Interim Guidance for the Diagnosis, Evaluation, and Management of Infants with Possible Congenital Zika Virus Infection should be followed. Infants without microcephaly or ocular lesions should also be followed because in infants born with a normal head size, the Zika virus may have damaged the brain, which then may not develop normally.

  • If the infant has microcephaly or intracranial calcifications, the infant is tested for Zika virus regardless of the mother's test results.

Treatment

  • Supportive care

No specific antiviral treatment is available for Zika virus infection.

Treatment is supportive; it includes the following:

  • Rest

  • Fluids to prevent dehydration

  • Acetaminophen to relieve fever and pain

  • Avoidance of aspirin and other NSAIDs (nonsteroidal anti-inflammatory drugs)

Aspirin and other NSAIDs are not typically used during pregnancy and should specifically be avoided in all patients treated for Zika virus infection until 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.

Treatment references

Prevention

The CDC has recommended that pregnant women NOT travel to areas with ongoing Zika virus outbreaks (see also CDC: Pregnant Women). Before travel to areas with risk of Zika, the CDC recommends pregnant women talk with their physician 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

  • Infection of mosquitoes with Wolbachia bacteria that block susceptibility of the female mosquito's gut to Zika virus

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.

  • Use Environmental Protection Agency–registered insect repellents with ingredients such as DEET (diethyltoluamide) or other approved active ingredients on exposed skin surfaces.

  • Treat clothing and gear with permethrin insecticide (do not apply directly to the skin).

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 transmission via blood transfusion

In July 2018, the US Food and Drug Administration (FDA) issued revised guidance recommending that blood centers in all states and US territories screen donated whole blood and blood components with a blood screening nucleic acid test licensed for use by FDA rather than screening donors by epidemiologic factors (see FDA: Revised Recommendations for Reducing the Risk of Zika Virus Transmission by Blood and Blood Components). 

Prevention of sexual transmission

RNA of the Zika virus has been detected in semen up to 281 days after the onset of symptoms. However, detection of viral RNA does not necessarily indicate the presence of infectious virus. In a recent 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, the CDC recommends people 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 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 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.

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.

  • Treat supportively; treat fever with acetaminophen and avoid using aspirin or NSAIDs until dengue has been excluded.

  • 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.

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NOTE: This is the Professional Version. CONSUMERS: Click here for the Consumer Version

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