Authors: Drew A. Long, BS (@drewlong2232, Vanderbilt University School of Medicine, US Army) and Brit Long, MD (@long_brit, EM Chief Resident at SAUSHEC, USAF) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital)

Introduction

In January 2016, the U.S. and European Centers for Disease Control and Prevention advised that pregnant women postpone travel to any area where Zika virus transmission was currently occurring.1-3 Just a year prior, the majority of the public had never heard of Zika virus. This little-known virus currently dominates headlines and has created public fear unseen since the Ebola virus in 2014. Due to public perception of this virus and potential complications, emergency providers must know when to be concerned for this virus and what conditions to consider.

Zika virus was first discovered in the Zika Forest of Uganda in 1947.4 Until the early 2000s, it was largely confined to Africa and Asia. Since 2014, it has been reported in South America, Central America, the Caribbean, Mexico, and Puerto Rico.5 Transmission has occurred in travelers returning from the infected regions to non-endemic countries, such as the United States and Western Europe.6

Pathogenesis

Zika virus is an arthropod-borne flavivirus.6,7 The disease is related to Dengue, yellow fever, West Nile, and Japanese encephalitis viruses.6,7 The virus is spread by the bite of an Aedes mosquito,8,9 which feeds during the day and twilight, making bed-nets less effective. Of note, the Aedes mosquito also transmits Dengue and Chikungunya viruses.5-8

Zika virus RNA has been detected in blood, urine, semen, saliva, CSF, amniotic fluid, and breast milk in infected individuals.8,10-13 Risk for infection via blood transfusion and sexual activity is present,8 while transmission via breast milk has not been documented.8,14 Maternal-fetal transmission can occur, including intrapartum transmission.1,8,14,15

Clinical manifestations

The incubation period ranges from 2 to 12 days.6,9 Only 20% of people infected with the virus will exhibit any clinical signs/symptoms, 5-9 with symptoms similar to those of Dengue and Chikungunya.7,8

Table 1. Clinical Features of Zika virus compared with Dengue and Chikungunya (Adopted from Dehning M, Liu L, Phipps A, Klein K, Swienton R. Brief Clinical Practice Update: Dengue, Chikungunya, & Zika Virus. Department of Emergency Medicine, EDGH Division, UT Southwestern/Parkland Memorial Hospital. Feb 2016).

Features Zika Chikungunya Dengue Fever Low grade High grade High grade Rash Maculopapular erythematous rash Pruritic, maculopapular rash Pruritic petechiae Conjunctivitis Present Absent Absent Arthralgia Present Severe, most commonly small joints Present Other signs and symptoms Myalgia, headache, retro-orbital pain, astheniaRare: GBS Rare: myelitis, retinitis, meningoencephalitis, epistaxis, subconjunctival hemorrhage Headache, myalgia, extensive hemorrhage (in dengue hemorrhagic fever)

The disease usually results in a mild illness, with symptoms lasting for about a week.8,14,16 Chikungunya infection can lead to persistent or relapsing arthralgia lasting months or more.17 The most common symptoms include acute-onset low-grade fever, maculopapular rash (duration: 2-14 days), arthralgias (notably small joints of hands and feet, duration: 1-14 days), and conjunctivitis.7,8,17 Diagnosis and clinical illness is consistent with Zika virus disease if two or more of these symptoms are present.

Other common symptoms include myalgias, headache, retro-orbital pain, joint swelling, and asthenia.5-9 Less common symptoms include abdominal pain, nausea, diarrhea, mucus membrane ulcerations, and pruritis.18 Unfortunately, these symptoms are nonspecific, so the disease must be considered in the context of any risk factors (travel history, exposure to person with confirmed Zika virus).

Complications

The most concerning complication is microcephaly – defined as head circumference 2 standard deviations below the mean for sex and gestational age at birth.7 From March 2015 to January 2016, over 4000 cases of microcephaly was reported in newborns in Brazil born to mothers infected with Zika virus. This is a 20-fold increase in microcephaly compared with previous years.19-21 This prompted the CDC to recommend pregnant women postpone travel to any country where Zika virus transmission is occurring.1-3 According to a preliminary analysis of research from Brazilian authorities, the greatest risk of microcephaly and malformations occurs from maternal infection with Zika virus during the first trimester.22

Guillain-Barre syndrome has also been linked with the Zika virus,20 but this has less documented evidence than microcephaly.

Differential diagnosis7

This includes other infectious causes of arthralgias/fever: Dengue fever, Chikungunya, Parvovirus, Rubella, Measles, Leptospirosis, Malaria, Rickettsia, Group A strep, and other viruses (enterovirus, adenovirus, and alphaviruses).

Diagnosis

The first step is clinical suspicion. Ask about travel history in any patient with a fever or history of fever, and suspect Zika when a patient with exposure has two or more of the following: low-grade fever, maculopapular rash, arthralgia, and conjunctivitis.

Ultimately, diagnosis is made by RT-PCR for Zika viral RNA or Zika virus serology.1,15 Viremia occurs from 0 to 11 days after symptom onset,23 and RT-PCR is positive only for 3-7 days when the infected person has viremia.7 Unfortunately, negative results cannot exclude infection. Four or more days after onset of symptoms, diagnosis can be made by Zika virus serologic testing.7 Diagnosis can be complicated by potential co-infection with Dengue and Chikungunya.6-7

Importantly, rule out the more serious infectious pathogens, such as malaria, as it is present in many of the same areas as Zika virus and carries a higher fatality rate.9 Testing for malaria, Dengue, and Chikungunya is warranted. In pregnant women with Zika virus exposure, conduct ultrasonography to evaluate for presence of fetal microcephaly or intracranial calcifications.7

Treatment5-9

Currently, no vaccine and no specific treatment for Zika virus exist. Treatment is largely symptomatic: rest, fluids, and acetaminophen (for fever, myalgias, headache). NSAIDs should be avoided until Dengue infection has been ruled out, mostly due to the risk of Dengue hemorrhagic fever.

Prevention6

Protect from mosquito bites by wearing long-sleeved shirts and long pants, and utilize insect repellent if/when going outdoors.

References / Further Reading

Centers for Disease Control and Prevention. Emergency Preparedness and Response: Recognizing, Managing, and Reporting Zika Virus Infections in Travelers Returning from Central America, South America, the Caribbean, and Mexico. http://emergency.cdc.gov.proxy.library.vanderbilt.edu/han/han00385.asp Centers for Disease Control and Prevention. CDC Newsroom: CDC adds countries to interim travel guidance related to Zika virus. http://www.cdc.gov.proxy.library.vanderbilt.edu/media/releases/2016/s0122-zika-travel-guidance.html European Centre for Disease Prevention and Control. Rapid Risk Assessment: Zika virus disease epidemic: Potential association with microcephaly and Guillain-Barre syndrome (first update), 21 January 2016. ECDC, Stockholm 2016. http://ecdc.europa.eu/en/publications/Publications/rapid-risk-assessment-zika-virus-first-update-jan-2016.pdf Dick GW, Kitchen SF, Haddow AJ. Zika virus. I. Isolations and serological specificity. Trans R Soc Trop Med Hyg. 1952;46:509-20. Zika Virus. TheBMJ. February 2016. http://www.bmj.com/freezikaresources Chen LH, and Davidson HH. Zika Virus: Rapid Spread in the Western Hemisphere. Annals of Internal Medicine. 2 February 2016. Sexton DJ. Zika virus infection. UpToDate. 6 February 2016. Centers for Disease Control and Prevention. Zika Virus. 3 February 2016. http://www.cdc.gov/zika/index.html Baombe J. Breaking news: Zika virus update. Emlyn’s. 28 January 2016. Pan American Health Organization. Zika virus infection and Zika fever: Frequently asked questions. http://www.paho.org.proxy.library.vanderbilt.edu/hq/index.php?option=com_content&view=article&id=9183&Itemid=41463&lang=en 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). Gourinat AC, O-Connor O, Calvez E, et al. Detection of Zika virus in urine. Emerg Infect Dis. 2015 Jan;21(1):84-6. Musso D, Roche C, Nhan TX, et al. Detection of Zika virus in saliva. J Clin Virol. 2015 Jul;68:53-5. Hennessey M, Fischer M, Staples JE. Zika Virus Spreads to New Areas-Region of the Americas, May 2015-January 2016. MMWR Morb Mortal Wkly Rep. 2016;65:55. Petersen EE, Staples JE, Meaney-Delman D, et al. Interim Guidelines for Pregnant Women During a Zika Virus Outbreak-United States, 2016. MMWR Morb Mortal Wkly Rep. 2016;65(2):30. Duffy MR, Chen TH, Hancock WT, et al. Zika virus outbreak on Yap island, Federated States of Micronesia. N Engl J Med. 2009;360:2536-43. Hamer DH, Chen LH. Chikungunya: establishing a new home in the Western Hemisphere. Intern Med. 2014;161:827-8. Ministry of Health – Manuatu Hauora. Zika virus. http://www.health.govt.nz/our-work/diseases-and-conditions/zika-virus Pan American Health Organization. Zika Virus Infection. http://www.paho.org.proxy.library.vanderbilt.edu/hq/index.php?option=com_topics&view=article&id=427&Itemid=41484 Pan American Health Organization. Epidemiological Alert: Neurological syndrome, congenital malformations, and Zika virus infection. Implications for public health in the Americas, 1 December 2015. http://www.paho.org.proxy.library.vanderbilt.edu/hq/index.php?option=com_docman&task=doc_view&Itemid=270&gid=32405&lang=en European Centre for Disease Prevention and Control. Rapid risk assessment: Zika virus epidemic in the Americas: Potential association with microcephaly and Guillain-Barré syndrome – 10 December 2015. ECDC, Stockholm 2015. http://ecdc.europa.eu/en/publications/Publications/zika-virus-americas-association-with-microcephaly-rapid-risk-assessment.pdf Pan American Health Organization. Question and Answers: Zika and pregnancy. http://www.paho.org.proxy.library.vanderbilt.edu/hq/index.php?option=com_content&view=article&id=11552%3Aquestion-and-answers-zika-and-pregnancy&catid=3986%3Azika-virus-infection&Itemid=41672&lang=en Lanciotti RS, Kosoy OL, Laven JJ, et al. Genetic and serologic properties of Zika virus associated with an epidemic, Yap State, Micronesia, 2007. Emerg Infect Dis. 2008;14:1232-9.