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Zika Virus (ZV) Infections

By Matthew E. Levison, MD, Drexel University College of Medicine;Drexel University

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Patient Education

The Zika virus is a flavivirus that is similar to the viruses that cause dengue, yellow fever, and West Nile fever. 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) and eye abnormalities. Diagnosis is with enzyme-linked immunosorbent assay or reverse transcriptase–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 the deep South, but A. albopictus, which better adapted to colder climates, is present across a large part of the southeast. A. aegypti is considered to be the main vector for epidemic Zika virus infection; A. albopictus is thought to be a significant 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.

Currently, ongoing local transmission of Zika virus has been reported in the following regions:

  • South America

  • Central America

  • Caribbean Islands

  • Pacific Islands

  • Cape Verde (a nation of islands off the northwest coast of Africa)

  • Southeast Asia (sporadic cases)

The US CDC has issued travel alerts for many countries in these regions.

At present, no locally transmitted Zika virus cases have been reported in the continental US. However, Zika virus infection has been reported in travelers returning to the US.

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 in Texas, Florida, and Hawaii; chikungunya has been locally acquired in Florida. 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

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, local transmission of Zika virus is possible. However, because contact between Aedesmosquitoes and people is infrequent in most of the continental US and Hawaii (because of mosquito control and people living and working 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

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). 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 also persists in vaginal secretions after it disappears from blood and urine; female-to-male sexual transmission of Zika virus infection has recently been reported ( 1).

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 CDC: About Zika Virus Disease ).

The Zika virus, like the viruses that cause dengue, chikungunya disease, West Nile fever, and yellow fever, can be transmitted from mother to child during pregnancy. The viruses that cause dengue and West Nile fever can be transmitted in breast milk. At present, there have been no reports of Zika virus transmission via breastfeeding, and 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 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. 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

Zika virus infection during pregnancy can cause microcephaly (a congenital disorder involving incomplete brain development and small head size) and other severe fetal brain defects (see also the CDC: Clinical Guidance for Healthcare Providers Caring for Infants and Children ).

In the 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; these women contracted the virus through travel or an infected partner.

Diagnosis

  • Serologic testing

  • Reverse transcriptase-PCR (RT-PCR) testing

Clinicians are required to notify the CDC if they identify a case of Zika virus infection.

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

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 Zika Virus: Diagnostic Testing and Zika Virus: Information for State and Local Public Health Laboratories ).

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 the 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 the Zika Virus: Clinical Guidance for Healthcare Providers Caring for Pregnant Women ).

  • For asymptomatic pregnant women: Testing should be done 2 to 12 wk 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 wk gestation (see also Interim Guidance for Health Care Providers Caring for Women of Reproductive Age with Possible Zika Virus Exposure — United States, 2016 ).

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 infants have possible congenital Zika virus infection and their mother 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, or eye abnormalities.

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

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 or amniotic fluid, serial ultrasonography every 3 to 4 wk 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.

Treatment references

Prevention

Until more is known, the CDC has recommended that pregnant women consider postponing travel to areas with ongoing Zika virus transmission (see also CDC: For Pregnant Women ). If women decide to go, they should 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.

To prevent mosquito bites, the following precautions should be taken (see also the CDC's Protection against Mosquitoes and Zika virus: Prevention ):

  • 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 repellants 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 mo.

  • Do not use products containing oil of lemon eucalyptus (para-menthane-diol) on children < 3 yr.

  • 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

Even though the risk of Zika virus transmission through blood transfusions is considered extremely low, the FDA has recommended that blood donors wait 28 days if they are at risk of Zika virus infection for any of the following reasons (see the CDC: Zika and Blood Transfusion ):

  • Travel to or residence in an area with ongoing Zika virus transmission

  • History of Zika virus infection (waiting for 4 wk after symptoms resolve before donating)

  • Symptoms of Zika virus infection within 2 wk of travel to an area with ongoing Zika virus transmission

  • Sexual contact with a man who has been diagnosed with Zika virus infection

  • Sexual contact with a man who traveled to or lived in an area with ongoing Zika virus transmission in the 3 mo before the sexual contact

If donors give blood and subsequently develop symptoms of Zika virus infection, the Red Cross asks to be notified so that it can quarantine possibly affected donations.

Prevention of sexual transmission

Because Zika virus can be transmitted via semen, men who live in or have traveled to an area of ongoing Zika virus transmission should abstain from sexual activity or consistently and correctly use condoms during sex (vaginal intercourse, anal intercourse, fellatio) while their partner is pregnant. This recommendation applies whether men have symptoms or not because most Zika virus infections are asymptomatic, and when symptoms do develop, they are usually mild.

RNA of the Zika virus has been detected in semen up to 62 days after the onset of symptoms. The CDC has therefore made the following specific recommendations:

For men who have been diagnosed with Zika virus infection or who have or have had symptoms:

  • They should consider using condoms or not having sex for ≥ 6 mo.

For couples with a male partner who has traveled to an area with ongoing Zika virus transmission:

  • If the male partner has been diagnosed with Zika virus infection or has (or had) symptoms, the couple should consider using condoms or not having sex for ≥ 6 mo after symptom onset.

  • If the male partner does not develop symptoms, the couple should consider using condoms or not having sex for ≥ 8 wk after the man returns.

For couples with a male partner living in an area with ongoing Zika virus transmission:

  • If the male partner has been diagnosed with Zika virus infection or has (or had) symptoms, the couple should consider using condoms or not having sex for ≥ 6 mo after symptom onset.

  • If the male partner has never developed symptoms, the couple should consider using condoms or not having sex as long as Zika is in the area.

There has been one case of female-to-male sexual transmission. Although no cases of woman-to-woman sexual transmission have been reported, the CDC now recommends that all pregnant women who have a sex partner (male or female) who has traveled to or resides in an area with Zika use barrier methods every time they have sex or they should not have sex during the pregnancy ( 1). The CDC is continuing to update their recommendations for sexually active people.

If a female partner is not pregnant and lives in or has traveled to an area with ongoing Zika virus transmission, the couple can consider using condoms or not having sex (see also CDC: Zika and Sexual Transmission ).

Prevention reference

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

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.

  • 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 reverse transcriptase–PCR.

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

  • Pregnant women should be advised to consider postponing travel to areas with ongoing Zika virus transmission.

  • 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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* This is the Professional Version. *