Clinical symptoms
Zika virus and pregnancy
Guidelines for clinicians
The U.S. Centers for Disease Control (CDC) has issued guidelines for healthcare providers managing pregnant women at risk of exposure to the Zika virus during the current pandemic (Petersen et al. MMWR Morb Mortal Wkly Rep 2016;65:30-33; free full text at http://dx.doi.org/10.15585/mmwr.mm6502e1).
An estimated 2-3 million people may be exposed to the virus over the next 12 months, according to Dr. Sylvain Aldighieri of the Pan American Health Organization, in an interview with the New York Times. Of concern is the high number of cases of microcephaly in infants born during the recent Zika virus outbreak in Brazil. There have been over 4,000 cases of microcephaly in Brazil since October 2015, compared to a prior rate of 150 cases per year (Tavernise S. NY Times, January 28, 2016).
Zika virus was isolated in 1947 in the Zika Valley, Uganda. The first published report was in 1952 (Dick et al. Trans R Soc Trop Med Hyg 1952;46:509-520). Zika is classified as a Flavivirus, a genus that includes yellow fever virus, dengue virus, West Nile virus, and Japanese encephalitis virus. Cross-reactivity with dengue and yellow fever is common with antibody testing. Reverse-transcription polymerase chain reaction (RT-PCR) testing of blood, urine or saliva may be employed (Gourinat et al. Emerg Infect Dis 2015;21:84-86. Musso et al. J Clin Virol 2015;68:53-55).
Zika is described as an Arbovirus, one of a variety of predominantly RNA viruses transmitted by mosquitoes and ticks. The main vectors are Aedes africanus and Ae. aegypti, but other Aedes species (e.g. Ae. albopictus, Ae. hensilli) have also been reported to transmit the virus (Grard et al. PLoS Negl Trop Dis 2014;8:e268. Ledermann et al. PLoS Negl Trop Dis 2014;8:e3188). An emerging issue is the wider distribution of Ae. albopictus, which is found in over one-half of the states in the U.S (Fauci & Morens. N Engl J Med 2016; epublished January 13, 2015). Viral infection through sexual intercourse and blood transfusion have also been reported (Musso et al. Emerg Infect Dis 2015;21:359-361. Musso et al. Euro Surveill 2014;19. pii: 20761).
Locally-acquired Zika infections have been reported in Mexico, South America, Africa, Southeast Asia and the Pacific Islands (Fauci 2016). At present, there does not appear to be a risk of acquiring the virus in Canada due to the limited range of the vector. The first case of Zika viral infection in Canada was reported in 2014 in a patient returning from Thailand (Fonseca et al. Am J Trop Med Hyg 2014;91:1035-1038), and three additional cases have been recorded in the current outbreak in travellers returning from El Salvador and Columbia (CBC News, January 28, 2016).
Back to top
Clinical symptoms
An estimated 80% of Zika viral infections are asymptomatic (Duffy et al. N Engl J Med 2009;360:2536-2543). Symptoms may include maculopapular rash, low-grade fever, headache, arthritis, arthralgia, myalgia, conjunctivitis, retro-orbital pain, edema and vomiting. Symptoms generally persist for up to one week. Severe disease is uncommon. Co-infection with dengue virus has been described (Dupont-Rouzeyrol et al. Emerg Infect Dis 2015;21:381-382). A case of Zika virus infection complicated by Guillain-Barre syndrome has also been reported (Oehler et al. Euro Surveill 2014;19. pii: 20720).
Zika virus and pregnancy
The CDC reports that pregnant women can be infected with Zika virus in any trimester, and maternal-fetal viral transmission can occur at any time during pregnancy. There is no evidence that pregnant women are more susceptible to infection.
It has not yet been established that Zika virus infection causes fetal loss. There has been a marked increase in the number of cases of microcephaly in Brazil coincident with the current Zika outbreak, but causality has not been determined. The role of other potential contributory factors needs further investigation.
A report of two cases of microcephaly from the Brazil cluster has been published (Oliveira Melo et al. Ultrasound Obstet Gynecol 2016;47:6-7). In one case, head circumference was 246 mm (2.6 SD below expected) at 30 weeks’ gestation. Brain anomalies included atrophy, coarse calcifications involving the white matter of the frontal lobes, dysgenesis of the corpus callosum, and enlarged cisterna magna. In the second case, head circumference was 229 mm (3.1 SD below expected) at 29 weeks’ gestation. There was marked asymmetry of the cerebral hemispheres, displacement of the midline, thinning of the parenchyma, failure to visualize the corpus callosum and thalami, and the pons and brainstem were thin. Both women presented with symptoms suggestive of Zika virus infection but had negative blood test results. Amniocentesis and RT-PCR were subsequently positive for Zika virus.
Guidelines for clinicians
The CDC recommends that clinicians advise all pregnant women to postpone any travel to areas where Zika viral transmission is ongoing. If a pregnant woman does travel to an affected area, she should be advised to avoid mosquito bites by wearing long-sleeved shirts and long pants, using insect repellents, and sleeping in a screened or air-conditioned room.
Clinicians should ask all pregnant women about recent travel. Women who have visited a country with ongoing Zika transmission should be evaluated for signs and symptoms of infection. Women reporting symptoms consistent with Zika virus infection should be tested for infection. Recommended tests are RT-PCR for patients with onset of symptoms within the previous week; or IgM and neutralizing antibody testing for specimens collected >4 days after symptom onset. Testing should not be performed in asymptomatic pregnant women with no abnormalities on fetal ultrasound. There is no commercially available test specific for Zika virus.
Fetal ultrasound should be performed on symptomatic and asymptomatic women with possible Zika virus exposure to detect microcephaly and/or intracranial calcifications. If either abnormality is found, amniocentesis for Zika virus testing may be offered. Symptomatic patients should also be evaluated for dengue and chikungunya virus infection.
For babies born with evidence of fetal or maternal Zika virus infection, the recommended tests are histopathologic examination of the placenta and umbilical cord; testing of frozen placental tissue and cord tissue for Zika virus RNA; and testing of cord serum for Zika and dengue virus IgM and neutralizing antibodies. If there is laboratory evidence of Zika virus in serum or amniotic fluid, ultrasounds should be considered every 3-4 weeks to monitor fetal growth and anatomy. Referral to a specialist in obstetrics or infectious disease is recommended.
In cases of fetal loss where there is suspected viral exposure, Zika virus RT-PCR and immunohistochemical staining should be performed on fetal tissues, including umbilical cord and placenta.
There is no antiviral treatment specific to Zika virus. Management includes rest, fluids, use of analgesics and antipyretics. ASA and NSAIDS should be avoided until dengue has been ruled out due to the risk of hemorrhage.