Zika virusThe Zika virus outbreak has recently been put on “Level 1” activation status by the Emergency Operations Center at the U.S. Centers for Disease Control and Prevention (CDC). If you haven’t already thought about this affecting your emergency department, you should starting now. A Level 1 status has been triggered only 3 times in the recent years: Ebola (2014), H1N1 (2009), Hurricane Katrina (2005). The following are some key facts and resources.

Historical Background

Zika virus was first isolated from a macque in 1947 in the Zika forest of Uganda.1 The first human case was reported in Nigeria in 1954.2 Since then, human disease was sporadic and limited mostly to Africa. The first large epidemic of Zika virus infection occurred on Yap Island, Federated States of Micronesia in 2007.3 Zika Virus arrived in Brazil in May 2015,4 and has spread throughout the Americas in a very short period of time. The first case in the United States was reported on January 13, 2016 in a patient who had returned to Houston, TX after traveling to Latin America.5,6

What are the classic symptoms and time course?

  • The Zika virus causes a mild acute illness. In fact, approximately 80% of patients are asymptomatic.7
  • Symptoms include fever, rash, joint pain, and conjunctivitis typically beginning 2 to 7 days after being bitten by an infected mosquito.

Why is there all this talk about pregnancy and Zika virus?

  • Recent evidence suggests a possible epidemiologic association between maternal Zika virus infection and adverse fetal outcomes, such as congenital microcephaly.8,9 Specifically, there has been a spike in the reported frequency of microcephaly in northeastern Brazil. This spike began after Zika virus arrived in the region. Zika virus RNA has also been detected in brain tissue of 2 infants born with microcepahly and fetal tissue from 2 miscarriages in women with first-trimester Zika virus infection.10 It is important to note, however, that debate is ongoing about the true magnitude of the reported rates of microcephaly, owing to likely reporting bias and changing definitions of microcephaly.11
  • Possible association with Guillain-Barré syndrome 7,12  as also been reported.

How is Zika virus transmitted?

  • Primarily transmitted to humans through bites from Aedes mosquitoes (which also are also responsible for transmission of dengue and chikungunya viruses)
  • Perinatal transmission is also possible and there have been rare case reports of sexual transmission and transmission through blood transfusion. 12–15

What travel history should be a red flag?

This is an evolving answer. See the CDC’s Zika Travel Information web page for updated travel notices.Regions with active transmission as of February 2016 include: 4,16

  • Africa: Cape Verde
  • Caribbean: Barbados; Curaçao; Dominican Republic; Guadeloupe; Haiti; Jamaica; Martinique; the Commonwealth of Puerto Rico, a U.S. territory; Saint Martin; U.S. Virgin Islands
  • Central America: Guatemala, Honduras, El Salvador, Nicaragua, Costa Rica, Panama
  • Mexico
  • Oceania/Pacific Islands: Fiji, American Samoa, Samoa, Tonga
  • South America: Brazil (where Zika-associated micocephaly was first reported), Bolivia, Colombia, Ecuador, French Guiana, Guyana, Paraguay, Suriname, Venezuela

What is the treatment?

  • There is no specific treatment or antidote for Zika virus disease.
  • Because the patient’s signs and symptoms are mild and self-limited, the treatment is mainly supportive, which includes hydration and antipyretics.
  • Avoid NSAIDs given the presence of dengue and chikungunya virus in endemic areas of Zika virus, until dengue can be excluded to avoid risk of hemorrhage.1

Can one be tested for Zika virus infection?

  • As an arboviral disease, Zika virus is a nationally notifiable condition per the CDC’s National Notifiable Diseases Surveillance System (NNDSS) site.
  • There are no commercially available diagnostic tests for Zika virus.
  • Contact your local health department to coordinate testing and care.
  • If necessary, Zika virus testing (RT-PCR and IgM antibody assays) is performed at the CDC Arbovirus Diagnostic Laboratory and a few state or local health departments.
  • Cross-reaction with related flaviviruses (dengue and yellow fever) is common in serological testing. 16

Who should you test for Zika virus infection?

  • Testing can be considered in any person who has travelled to an endemic areas within the past 2 weeks who presents with an acute onset illness and any of the following symptoms:
    • Fever
    • Maculopapular rash
    • Arthralgia
    • Conjunctivitis
  • All pregnant women with recent travel to a Zika virus endemic area who have ≥2 of the following symptoms of acute infection during or within 2 weeks of travel.
    • Acute onset of fever
    • Maculopapular rash
    • Arthralgia
    • Conjunctivitis
  • Asymptomatic pregnant women who have traveled to any Zika virus endemic area should be offered testing within 2-12 weeks of return to the U.S.
  • Infants with microcephaly or intracranial calcifications born to women who traveled to or resided in an area with Zika virus transmission while pregnant; or infants born to mothers with positive or inconclusive test results for Zika virus infection.12

What advice should you provide your patient?

  • Advise pregnant women (or women who want to become pregnant) to avoid travel to areas with active transmission.
  • Men, who have traveled from an area with circulating Zika virus and who have a pregnant partner, should abstain entirely from sexual intercourse or use condoms consistently for the remainder of the pregnancy.12
  • If traveling to areas with active transmission, avoid mosquito bites by wearing long sleeves and tucked pant legs, sleeping under a mosquito net, and using effective insect repellents.
  • Pregnant women who test positive for Zika virus should be referred to maternal fetal medicine specialists for serial fetal ultrasounds and possible fetal testing.
DICK G, KITCHEN S, HADDOW A. Zika virus.  I.  Isolations and serological specificity. Trans R Soc Trop Med Hyg. 1952;46(5):509-520. [PubMed]
Gatherer D, Kohl A. Zika virus: a previously slow pandemic spreads rapidly through the Americas. J Gen Virol. 2016;97(2):269-273. [PubMed]
Duffy M, Chen T, Hancock W, et al. Zika virus outbreak on Yap Island, Federated States of Micronesia. N Engl J Med. 2009;360(24):2536-2543. [PubMed]
Zika virus infection. Pan American Health Organization / World Health Organization. http://www.paho.org/hq/index.php?option=com_content&view=article&id=11585&Itemid=41688&lang=en. [Source]
Tetro J. Zika and microcephaly: causation, correlation, or coincidence? Microbes Infect. 2016;18(3):167-168. [PubMed]
Faccini-Martínez Á, Botero-García C, Benítez-Baracaldo F, Pérez-Díaz C. With regard about the case of Dengue, Chikungunya and Zika co-infection in a patient from Colombia. J Infect Public Health. 2016;9(5):687-688. [PubMed]
Zika Virus for Healthcare Providers. CDC. http://www.cdc.gov/zika/hc-providers/preparing-for-zika/clinicalevaluationdisease.html. Published August 31, 2016.
Oliveira M, Malinger G, Ximenes R, Szejnfeld P, Alves S, Bispo de. Zika virus intrauterine infection causes fetal brain abnormality and microcephaly: tip of the iceberg? Ultrasound Obstet Gynecol. 2016;47(1):6-7. [PubMed]
Zika virus epidemic in the Americas: potential association with microcephaly and Guillain-Barré syndrome. European Centre for Disease Prevention and Control. http://ecdc.europa.eu/en/publications/Publications/zika-virus-americas-association-with-microcephaly-rapid-risk-assessment.pdf. Published December 10, 2015.
Notes from the Field: Evidence of Zika Virus Infection in Brain and Placental Tissues from Two Congenitally Infected Newborns and Two Fetal Losses. CDC.gov. http://www.cdc.gov/mmwr/volumes/65/wr/mm6506e1.htm.
Victora C, Schuler-Faccini L, Matijasevich A, Ribeiro E, Pessoa A, Barros F. Microcephaly in Brazil: how to interpret reported numbers? Lancet. 2016;387(10019):621-624. [PubMed]
Update: Interim Guidance for the Evaluation and Management of Infants with Possible Congenital Zika Virus Infection. CDC.gov. http://www.cdc.gov/mmwr/volumes/65/wr/mm6533e2.htm?s_cid=mm6533e2_w. [Source]
Musso D, Nhan T, Robin E, et al. Potential for Zika virus transmission through blood transfusion demonstrated during an outbreak in French Polynesia, November 2013 to February 2014. Euro Surveill. 2014;19(14). [PubMed]
Hayes EB. Zika virus outside Africa. Emerg Infect Dis [serial on the Internet]. 2009 Sep [date cited]. Available from http://wwwnc.cdc.gov/eid/article/15/9/09-0442.
Musso D, Roche C, Robin E, Nhan T, Teissier A, Cao-Lormeau V. Potential sexual transmission of Zika virus. Emerg Infect Dis. 2015;21(2):359-361. [PubMed]
Zika Virus – Diagnostic Testing. CDC. http://www.cdc.gov/zika/hc-providers/testing-for-zikavirus.html. Published October 13, 2016.
Lauren Pike, MD

Lauren Pike, MD

Emergency Medicine resident
Stanford-Kaiser EM residency program
Lauren Pike, MD

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Julian Villar, MD MPH

Julian Villar, MD MPH

Clinical Fellow, Critical Care Medicine
Stanford University;
Emergency Physician,
San Francisco Veterans Affairs Medical Center and
Mercy Medical Center, Merced CA