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Continuing Education for Health Professionals

Zika Virus (ZIKV)

Module 2

Transmission of Zika Virus

ZIKV is a single-stranded RNA virus of the Flaviviridae family, genus Flavivirus, closely related to Dengue. It is an arthropod-borne virus* (arbovirus), transmitted to humans primarily through the bite of an infected Aedes species mosquito, especially Aedes aegypti, which is the main vector worldwide. In forested areas of Africa, Asia, and South America ZIKV is maintained in enzootic transmission cycles, a cycle that involves mostly wild animals such as birds, rodents, and non-human primates as the reservoirs, usually in a limited region or area.

*Arthropod-borne viruses (arboviruses) are transmitted to humans primarily through the bites of infected mosquitoes and ticks. Most arboviruses are maintained in transmission cycles between arthropods and vertebrate hosts (typically birds or small mammals). Human arboviral cases with laboratory evidence of recent infection are classified as neuroinvasive disease (causing encephalitis, meningitis, or acute flaccid paralysis) or non-neuroinvasive disease.

In urban and suburban areas, the virus is transmitted between people who have been bitten by Aedes mosquitoes. Aedes aegypti mosquitoes have a high vectorial capacity (effectiveness of virus transmission in nature) (CDC, 2016b).

 

In the United States, People Serve as Primary Vertebrate Hosts

image: people as primary vertebrate hosts

Source: CDC, 2016c.

 

Unlike the Culex mosquitoes that carry West Nile virus—which are active from dusk to dawn—Aedes mosquitoes are aggressive daytime biters and feed both indoors and outdoors near dwellings. They are most active 2 hours after dawn and 2 hours before dusk but can bite throughout the day. Non-human and human primates are likely the main reservoirs of the virus, and anthroponotic (human-to-vector-to-human) transmission occurs during outbreaks (CDC, 2016a).

Aedes mosquitoes typically breed in domestic water-holding containers and thrive in urban environments where small pools of water and moist soil are readily available. They are able to find people using several complex sensory systems. Dark colors, body heat, and smells from body chemicals, such as carbon dioxide and lactic acid, all attract mosquitoes; they can smell carbon dioxide from 75 feet away. Both male and female mosquitoes feed on plant nectar for their own nourishment but only females feed on blood so they can make eggs (NIAID, 2015).

 

Female Aedes aegypti Mosquito

image: female aedes aegypti mosquito

This 2006 photograph depicts a female Aedes aegypti mosquito in the process of acquiring a blood meal from her human host. The feeding apparatus consists of a sharp, orange-colored fascicle that is covered in a soft, pliant sheath called the labellum while not feeding. The labellum is shown here retracted as the sharp stylets contained within pierce the host’s skin surface, allowing the insect to obtain its blood meal. The orange color of the fascicle is due to the red color of the blood as it migrated up the thin, sharp translucent tube. Note the distended abdominal exoskeleton which, being translucent, allowed the color of the ingested blood meal to be visible. Photo credit: James Gathany, CDC, Public Health Image Library.

Through Mosquito Bites

Zika virus is transmitted to people primarily through the bite of an infected Aedes species mosquito (A. aegypti and A. albopictus). Primates, including humans, are the best-documented Zika virus animal reservoir, with transmission to humans primarily by mosquito vectors. Based on serology, but not verified by viral isolation, many other species may support Zika virus infection, including forest-dwelling birds, horses, goats, cattle, ducks and bats. Zika virus is also present in the saliva of infected patients (Malone et al., 2016).  

Mother-to-Child Transmission

Prior to the current outbreak of Zika viral infection in Brazil, no cases of transmission of ZIKV from mother to fetus had been reported (Oliveira Melo et al., 2016). Perinatal transmission was documented in French Polynesia during the 2013–2014 outbreak where Zika virus sequences were identified in breast milk by polymerase chain reaction (PCR), but reports from that outbreak did not indicate microcephaly as a complication (Malone et al., 2016).

Maternal-fetal transmission of Zika virus has now been documented throughout pregnancy in the recent Brazilian outbreak (Petersen et al., 2016) and Zika virus RNA has been detected in the pathologic specimens of fetal losses. Zika virus infections have been confirmed in infants with microcephaly in the current outbreak in Brazil (Petersen et al., 2016).

On December 2, 2015, Brazilian health officials released a statement providing guidance on Zika virus and breastfeeding. The document states that there is insufficient evidence to modify current breastfeeding practices (ECDC, 2015). Although Zika virus RNA has been detected in breast milk, transmission of Zika infection through breastfeeding has not been documented (CDC, 2016a).

On June 21, 2016 the U.S. National Institutes of Health and Fundacao Oswaldo Cruz-Fiocruz (Fiocruz), a national scientific research organization linked to the Brazilian Ministry of Health, announced they have begun a multi-country study to evaluate the magnitude of health risks that Zika virus infection poses to pregnant women and their developing fetuses and infants. The study is opening in Puerto Rico and will expand to several locations in Brazil, Colombia and other areas that are experiencing active local transmission of the virus (NIH, 2016).

The incidence of Zika virus infection in pregnant women is not currently known and data on pregnant women infected with Zika virus are limited. No evidence exists to suggest that pregnant women are more susceptible to Zika virus infection or experience more severe disease during pregnancy (Staples and Meaney-Delman et al., 2016).

In the United States, As of June 16, 2016, laboratory evidence of possible ZIKV infection has been found in 265 pregnant women in the U.S. and the District of Columbia and 216 pregnant women in Puerto Rico. Of these, 4 infants were born with birth defects and 4 pregnancy losses were reported. In the live births, defects included microcephaly, calcium deposits in the brain indicating possible brain damage, excess fluid in the brain cavities and surrounding the brain, absent or poorly formed brain structures, abnormal eye development, or other problems resulting from damage to the brain that affects nerves, muscles and bones, such as clubfoot or inflexible joints. The pregnancy losses included miscarriage, stillbirths, and terminations with evidence of the birth defects already mentioned (CDC, 2016a). 

CDC has developed interim guidelines for healthcare providers in the United States who are caring for pregnant women during a Zika virus outbreak. These guidelines include recommendations for pregnant women who are considering travel to an area with Zika virus transmission, and recommendations for screening, testing, and management of returning pregnant travelers. Updates on areas with ongoing Zika virus transmission are available online (http://wwwnc.cdc.gov/travel/notices/) (Staples and Meaney-Delman et al., 2016).

Healthcare providers should ask all pregnant women about recent travel. Pregnant women with a history of travel to an area with Zika virus transmission and who report two or more symptoms consistent with Zika virus disease (acute onset of fever, maculopapular rash, arthralgia, or conjunctivitis) during or within two weeks of travel, or who have ultrasound findings of fetal microcephaly or intracranial calcifications, should be tested for Zika virus infection. Testing is not indicated for women without a travel history to an area with Zika virus transmission (Staples and Meaney-Delman et al., 2016).

In pregnant women with laboratory evidence of Zika virus infection, serial ultrasound examination should be considered to monitor fetal growth and anatomy, and referral to a maternal­–fetal medicine or infectious disease specialist with expertise in pregnancy management is recommended. There is no specific antiviral treatment for Zika virus; supportive care is recommended (Staples and Meaney-Delman et al., 2016).

Sexual Transmission

Zika can be passed through sex from a person who has Zika to his or her partners even if the infected person does not have symptoms at the time. Potential sexual exposure to Zika virus includes having had sex with a person who has traveled to or lives in an area with active Zika virus transmission when the sexual contact did not include a barrier to protect against infection. Such barriers include male or female condoms for vaginal or anal sex and other barriers for oral sex. Sexual exposure includes vaginal sex, anal sex, oral sex, or other activities that might expose a sex partner to genital secretions (MMWR, 2016, July 29).

Zika virus infection is of particular concern during pregnancy. Pregnant women with sex partners (male or female) who live in or who have traveled to an area with active Zika virus transmission should consistently and correctly use barriers against infection during sex or abstain from sex for the duration of the pregnancy. This reduces the risk for sexual transmission of Zika virus during pregnancy. Pregnant women should discuss with their healthcare provider their own and their sex partner’s history of having been in areas with active Zika virus transmission and history of illness consistent with Zika virus disease; providers can consult CDC’s guidance for evaluation and testing of pregnant women (MMWR, 2016, July 29).

Men and women who want to reduce the risk for sexual transmission of Zika virus should use barrier methods against infection consistently and correctly during sex or abstain from sex when one sex partner has traveled to or lives in an area with active Zika virus transmission. Based on expert opinion and on limited but evolving information about the sexual transmission of Zika virus, the recommended duration of consistent use of a barrier method against infection or abstinence from sex depends on whether the sex partner has confirmed infection or clinical illness consistent with Zika virus disease and whether the sex partner is male or female (MMWR, 2016, July 29).

As of July 20, 2016, 15 cases of Zika virus infection transmitted by sexual contact had been reported in the United States. Sexually transmitted Zika virus infection has also been reported in other countries. In published reports, the longest interval after symptom onset that sexual transmission from a man might have occurred was 32–41 days. Using real-time reverse transcription–polymerase chain reaction (rRT-PCR), Zika virus RNA has been detected in semen up to 93 days after symptom onset. In addition, one report describes an asymptomatically infected man with Zika virus RNA detected by rRT-PCR in his semen 39 days following departure from a Zika virus-affected area and who might have sexually transmitted Zika virus to his partner. In most cases, serial semen specimens were not collected until Zika virus RNA was no longer detectable so that the precise duration and pattern of infectious Zika virus in semen remain unknown (MMWR, 2016, July 29). 

Zika virus also has been transmitted from a symptomatically infected woman to a male sex partner, and Zika virus RNA has been detected in vaginal fluids 3 days after symptom onset and in cervical mucus up to 11 days after symptom onset. For sex partners of infected women, Zika virus might be transmitted through exposure to vaginal secretions or menstrual blood. Sexual transmission of infections, including those caused by other viruses, is reduced by consistent and correct use of barriers to protect against infection (MMWR, 2016, July 29).

On September 30, 2016, CDC updated its interim guidance for persons with possible Zika virus exposure who are planning to conceive and interim guidance to prevent transmission of Zika virus through sexual contact, now combined into a single document. CDC now recommends that men with possible Zika virus exposure, regardless of symptom status, wait at least 6 months from symptom onset (if symptomatic) or last possible exposure (if asymptomatic) before attempting conception with their partner. They should also wait at least 6 months before having condomless sex to minimize their risk for sexual transmission of Zika virus to partners. The updated guidelines are available from Morbidity and Mortality Weekly Report, 2016, October 7.

Blood

During the first week of infection, Zika virus in the blood of an infected person can be passed through a mosquito bite to another mosquito. An infected mosquito can then spread the virus to other people. Zika virus RNA has been identified in asymptomatic blood donors during an ongoing outbreak and transfusion-transmission events have been reported (CDC, 2016a).

During the 2014 French Polynesian outbreak, 2.8% of blood donors tested positive for Zika and in previous outbreaks, the virus has been found in blood donors (CDC, 2016a). Because the vast majority (80%) of people infected with the Zika virus are asymptomatic, many blood donors may not know they have been infected.
 
In February 2016, the Food and Drug Administration issued industry recommendations to reduce the risk of transfusion-transmission of the Zika virus. They state that the Zika virus is likely cleared by the existing viral inactivation and removal methods that are currently used to clear viruses in the manufacturing processes for plasma-derived products. This includes pasteurization, solvent/detergent treatment, and incubation at low pH. Although highly effective for plasma-derived products, these methods are not generally applicable for use in blood and blood components intended for transfusion (FDA, 2016).

The risk of transmission of ZIKV by blood transfusion is considered likely based on the following evidence:
  • two possible cases of transfusion-transmission in Campinas, Brazil;
  • there have been documented transfusion-transmissions of other flaviviruses such as West Nile virus, Dengue virus and Yellow Fever vaccine virus, all of which have been shown to produce detectable viremia (the presence of virus in the blood) during asymptomatic and symptomatic infections; 
  • ZIKV infection produces viremia that may last up to (and possibly beyond) 14 days, with varying reports of viremia from 2 days before to 11 days after onset of symptoms;
  • the pre-symptomatic period for ZIKV infection varies (if symptoms develop) from 3 to 12 days, during which viremia may occur;
  • an estimated 80% of ZIKV infections remain asymptomatic;
  • perinatal transmission of ZIKV, most likely by transplacental transmission or during delivery, has been reported; and,
  • blood donations positive for ZIKV viral RNA by nucleic acid testing (NAT) were detected during the French Polynesia outbreak in 2013-2014 (FDA, 2016).  

Urine

Other flaviviruses, such as Dengue and West Nile can be detected in urine samples for a longer time than in serum samples. A 2015 study at the Institut Pasteur in New Caledonia (a subtropical island west of Australia and north of New Zealand) detected strongly positive results for ZIKV RNA in the urine of 6 Zika patients. ZIKV RNA was detected ≤15 days (range 10 days to >20 days) after onset of symptoms, which was >7 days after it was no longer detected in serum samples (Gourinat et al., 2015).

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