Zika Virus (ZV) Infections

The Zika virus was first isolated from monkeys in the Zika Forest of Uganda in 1947 but was not considered to be 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.

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 (1).

In 2016 and 2017, cases of locally transmitted Zika virus infection were reported in Miami-Dade County in southeastern Florida and Brownsville, Texas. Local transmission of Zika virus in the continental United States has not been reported since 2019. However, Zika virus infection has been reported in travelers returning to the United States after travel to countries where the virus is transmitted locally.

In May 2025, there are no geographic areas with an active Zika virus outbreak (1).

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.

During the first week of infection, the Zika virus is present in blood. Mosquitoes acquire the virus when they bite infected people and 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. 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 rare and limited.

Although the Zika virus is transmitted primarily by mosquitoes, other modes of transmission 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 (2, 3).

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, even when the men do not have symptoms. Zika virus persists in semen 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 (4).

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 persists in vaginal secretions after it disappears from blood and urine; female-to-male sexual transmission of Zika virus infection has been reported (4). Intermittent viral RNA shedding has been detected in vaginal secretions for up to 6 months although detection of viral RNA does not prove the 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 although cases of transmission by blood transfusion have not been confirmed in the United States (5). Laboratory-acquired Zika virus has been reported in researchers and is thought to occur through needle-stick injuries (6).

Most people who become infected have no symptoms.

Symptoms of Zika virus infection include fever, maculopapular rash, conjunctivitis, joint pain, retro-orbital pain, headache, and muscle pain. Symptoms are typically mild and last 4 to 7 days (1). 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 (2). GBS is an acute, usually rapidly progressive but self-limited inflammatory polyneuropathy thought to be caused by an autoimmune reaction.

• 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 geographic location or travel. Because 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, diagnosis of Zika virus infection requires laboratory confirmation by one of the following (1):

• 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 of symptom onset and up to 14 days in urine samples. NAAT may detect Zika virus in whole blood for up to 3 months (2).

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 (3, 4).

Routine testing for Zika virus infection is not recommended for pregnant women who do not have symptoms. 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).

For pregnant women with symptoms and 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 fetal 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 serum and urine 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 (3 and 5).

Nonpregnant patients should be tested if they have suspected Zika virus infection and severe symptoms. Testing men without symptoms to assess risk of sexual transmission is not recommended (6). 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, oral sex) 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 (3).

• 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 painAcetaminophen to relieve fever and pain

• Avoidance of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs)Avoidance of aspirin and other nonsteroidal anti-inflammatory drugs (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 Aspirin and other NSAIDs are not typically used during pregnancy and should specifically be avoided in all patients treated for Zika virus infection untildengue can be excluded 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 ultrasounds 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 (3).

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 (4, 5).

If possible, pregnant women should NOT travel to areas with ongoing Zika virus outbreaks. 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 no vaccine to prevent Zika virus infection.