Zika Virus: Background, Pathophysiology, Epidemiology http://emedicine.medscape.

com/article/2500035-overview#showall

News & Perspective

Drugs & Diseases
CME & Education
Specialty:
Edition: ENGLISH
DEUTSCH
ESPAOL
FRANAIS
PORTUGUS
Log In
Sign Up It's Free!
Edition: ENGLISH DEUTSCH ESPAOL FRANAIS PORTUGUS
Register Log In

1 of 10 10/15/2016 12:44 AM
Zika Virus: Background, Pathophysiology, Epidemiology http://emedicine.medscape.com/article/2500035-overview#showall

2 of 10 10/15/2016 12:44 AM
Zika Virus: Background, Pathophysiology, Epidemiology http://emedicine.medscape.com/article/2500035-overview#showall

3 of 10 10/15/2016 12:44 AM
Zika Virus: Background, Pathophysiology, Epidemiology http://emedicine.medscape.com/article/2500035-overview#showall

No Results

4 of 10 10/15/2016 12:44 AM
Zika Virus: Background, Pathophysiology, Epidemiology http://emedicine.medscape.com/article/2500035-overview#showall

No Results

News & Perspective Drugs & Diseases CME & Education

close
Please confirm that you would like to log out of Medscape. If you log out, you will be required to enter your username and
password the next time you visit. Log out Cancel

Zika Virus
Author: Bhagyashri D Navalkele, MD, MBBS; Chief Editor: Michael Stuart Bronze, MD more...

Updated: Jun 01, 2016

Background

5 of 10 10/15/2016 12:44 AM
Zika Virus: Background, Pathophysiology, Epidemiology http://emedicine.medscape.com/article/2500035-overview#showall

Zika virus (ZIKV) belongs to the Flavivirus genus; like other flaviviruses, Zika virus is
an icosahedral, enveloped, single-stranded RNA virus.[1] The lipid envelope is
covered with dense projections that consist of a membrane and envelope
glycoproteins.[1]

In most cases, Zika virus infection causes a mild, self-limited illness. The incubation
period is likely 3-12 days.[2] Owing to the mild nature of the disease, more than 80%
of Zika virus infection cases likely go unnoticed.[2] The spectrum of Zika virus disease
overlaps with other that of arboviral infections, but rash (maculopapular and likely
immune-mediated) typically predominates.[2]

In April 2016, a deputy director at the Centers for Disease Control and Prevention
(CDC) warned that the risk of Zika virus infection in the United States may have been
previously underestimated, citing the increased range of the mosquito vectors (now in
30 US states, up from 12 as previously thought) and the travel risks associated with
the 2016 Olympics in Brazil.[3]

Zika virus was first described in a febrile rhesus monkey in the Zika forest of Entebbe,
Uganda, and was reported in a human field worker shortly thereafter.[1] Currently, Zika
virus is known to be widely distributed outside of Africa. Outbreaks have been
described previously in Micronesia and French Polynesia.[4, 5]

The Centers for Disease Control and Prevention (CDC) currently lists the following
countries as areas of active virus transmission: Aruba, Barbados, Bolivia, Bonaire,
Brazil, Colombia, Commonwealth of Puerto Rico (US territory), Costa Rica, Cuba,
Curacao, Dominica, Dominican Republic, Ecuador, El Salvador, French Guiana,
Guadeloupe, Guatemala, Guyana, Haiti, Honduras, Jamaica, Martinique, Mexico,
Nicaragua, Panama, Paraguay, Saint Martin, Saint Vincent and the Grenadines, Sint
Maarten, Suriname, Trinidad and Tobago, US Virgin Islands, Venezuela, American
Samoa, Fiji, Kosrae (Federated States of Micronesia), Marshall Islands, New
Caledonia, Samoa, Tonga, and Cape Verde.

Zika virus infection is among the nationally notifiable diseases in the United States.
State and local health departments should be informed by healthcare professionals of
suspected cases of Zika virus infection to facilitate diagnosis and to reduce the risk of
local transmission.

The CDC has released a map of potential Zika virus spread in the United States
based on the estimated range of Aedes aegypti and Aedes albopictus mosquitoes.
The maps can be found at http://www.cdc.gov/zika/pdfs/zika-mosquito-maps.pdf.

For the latest information concerning Zika virus, see also Medscapes Zika Virus
Resource Center.

Pathophysiology
Like many other flaviviruses, Zika virus is transmitted by an arthropod: the Aedes
mosquito, including Aedes aegypti,Aedes africanus, Aedes luteocephalus, Aedes
albopictus, Aedes vittatus, Aedes furcifer, Aedes hensilli, and
Aedesapicoargenteus.[1, 5, 6, 2] Sexual transmission among humans has also been
described.[1, 7]

Zika virus is well-adapted to grow in various hosts, ranging from arthropods to

vertebrates. Viral attachment to unidentified cellular receptors is mediated by the E
(envelope) glycoprotein. This is followed by endocytic uptake and then uncoating of
the nucleocapsid and release of viral RNA into the cytoplasm. A viral polyprotein is
produced and modified by the endoplasmic reticulum. Immature virions collect both in
the endoplasmic reticulum and in secretory vesicles before being released.[1]

Sirohi et al described the structure of mature Zika virus based on cryoelectron

microscopy. The virus resembles other known flavivirus structures with the exception
of approximately 10 amino acids surrounding the Asn154 glycosylation site in each of
the 180 envelope glycoproteins comprising the icosahedral shell, the carbohydrate
moiety of which may be the attachment site of the virus to host cells.[8]

Epidemiology
The global prevalence of Zika virus infection has not been widely reported owing to
asymptomatic clinical course, clinical resemblance to other infection with other
flaviviruses (dengue, chikungunya), and difficulty in confirming diagnosis.

Based on sporadic case reports, entomological surveys, and seroprevalence

surveys, Zika virus infection had been reported in various hosts, including humans,
primates, and mosquitoes, in 14 countries across Africa, Asia, and Oceania, as of
2014.[9] The prevalence of Zika virus infection in Uganda was 6.1% in 1952 among a
population of 99 residents.[10] The prevalence of Zika virus infection was 7.1% in
Java, Indonesia, from 1977-1978 among patients who were hospitalized for fever.[11]
Since Zika virus was first isolated in 1947, the disease has spread outside of Africa,
mainly into Southeast Asia. Until 2007, sporadic cases of Zika virus illness in humans
were reported. In 2007, Yap Island in Micronesia reported an outbreak of Zika virus
infection transmitted via Aedes hensilli.[5] Subsequently, in 2013 and 2014,
epidemics of Zika virus infection occurred in French Polynesia, New Caledonia, Cook

6 of 10 10/15/2016 12:44 AM
Zika Virus: Background, Pathophysiology, Epidemiology http://emedicine.medscape.com/article/2500035-overview#showall

Islands, and Easter Islands.[12]

In May 2015, Brazil reported the first outbreak of Zika virus infection in the Americas.
The Brazil Ministry of Health estimated around 440,000-1,300,000 suspected cases
of Zika virus infection in December 2015.[13] Aedes aegypti and Aedes albopictus
were recognized as vectors for transmission of Zika virus. Since then, the infection
has spread rapidly to several other countries, becoming a pandemic. The association
of Zika virus infection with Guillain-Barr syndrome (GBS) and congenital birth defects
(particularly microcephaly) amid the ongoing outbreak of Zika virus infection in Brazil is
still under investigation.[13, 14]

In March 2016, the WHO reported that Zika virus was actively circulating in 38
countries and territories, 12 of which have reported an increase in GBS cases or
laboratory evidence of Zika virus among patients with GBS.[15]

As of June 2016, a total of 591 laboratory-confirmed travel-associated Zika virus

infections have been reported in the United States, with none acquired via local
vector-borne transmission. Eleven cases have been transmitted sexually, and one
case of associated Guillain-Barr syndrome has been reported.[16] US territories such
as Puerto Rico and the US Virgin Islands have 935 laboratory-confirmed local cases
of Zika virus infection, and 4 cases have been attributed to travel.[16] Five cases of
associated Guillain-Barr syndrome have been reported. See the images below.

Laboratory-confirmed Zika virus disease cases reported to ArboNET by state or territory United
States, 20152016 (as of May 25, 2016). Courtesy of the CDC.

All countries and territories with active Zika virus transmission. Courtesy of the CDC.

Prognosis
Most cases of Zika virus infection are mild and self-limited. Owing to the mild nature
of the disease, more than 80% of Zika virus infection cases likely go unnoticed.[2]
However, serious complications have been reported in rare cases, including
Guillain-Barr syndrome.[2, 9] In addition, great concern is emerging over congenital
malformations due to transplacental transmission of Zika virus, including microcephaly
and various ophthalmologic abnormalities.[11, 12]

For more details, see History.

Patient Education
Certain patients should be educated concerning travel risks associated with Zika virus
and prevention of mosquito bites and mosquito-control measures.

The World Health Organization (WHO) and CDC recommend that mothers with Zika
virus infection still breastfeed their infants, including those born with microcephaly.
Zika virus transmission via breast milk has not been documented, although more
research is needed for confirmation.[17]

For more details, see Prevention.

Clinical Presentation

Contributor Information and Disclosures

Author

7 of 10 10/15/2016 12:44 AM
Zika Virus: Background, Pathophysiology, Epidemiology http://emedicine.medscape.com/article/2500035-overview#showall

Bhagyashri D Navalkele, MD, MBBS Fellow, Department of Internal Medicine, Division of Infectious Diseases,
Detroit Medical Center, Harper University Hospital, Wayne State University School of Medicine

Bhagyashri D Navalkele, MD, MBBS is a member of the following medical societies: American College of
Physicians, Infectious Diseases Society of America, Medical Council of India, Society of Healthcare Epidemiology
of America

Disclosure: Nothing to disclose.

Coauthor(s)
Pranatharthi Haran Chandrasekar, MBBS, MD Professor, Chief of Infectious Disease, Program Director of
Infectious Disease Fellowship, Department of Internal Medicine, Wayne State University School of Medicine

Pranatharthi Haran Chandrasekar, MBBS, MD is a member of the following medical societies: American College of
Physicians, American Society for Microbiology, International Immunocompromised Host Society, Infectious
Diseases Society of America

Disclosure: Nothing to disclose.

Miriam T Levine, MD Fellow, Department of Medicine, Division of Infectious Diseases, Detroit Medical Center,
Wayne State University School of Medicine

Miriam T Levine, MD is a member of the following medical societies: American College of Physicians, American
Society for Microbiology, Infectious Diseases Society of America, Society of General Internal Medicine

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of
Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Chief Editor
Michael Stuart Bronze, MD David Ross Boyd Professor and Chairman, Department of Medicine, Stewart G Wolf
Endowed Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center;
Master of the American College of Physicians; Fellow, Infectious Diseases Society of America

Michael Stuart Bronze, MD is a member of the following medical societies: Alpha Omega Alpha, American Medical
Association, Oklahoma State Medical Association, Southern Society for Clinical Investigation, Association of
Professors of Medicine, American College of Physicians, Infectious Diseases Society of America

Disclosure: Nothing to disclose.

References

1. Bennett JE, Dolin R, Blaser MJ. Mandell, Douglas, and Bennett's Principles and Practice of Infectious
Diseases. 8th ed. Philadelphia, PA: Elsevier/Saunders; 2015. Vol 2:

2. Petersen E, Wilson ME, Touch S, McCloskey B, Mwaba P, Bates M, et al. Rapid Spread of Zika Virus in The
Americas - Implications for Public Health Preparedness for Mass Gatherings at the 2016 Brazil Olympic
Games. Int J Infect Dis. 2016 Feb 4. 44:11-15. [Medline].

3. Gardner T, Mason J. U.S. officials warn Zika 'scarier' than initially thought. Reuters. Available at
http://www.reuters.com/article/us-health-zika-whitehouse-idUSKCN0X825A. April 11, 2016; Accessed: April
12, 2016.

4. Besnard M, Lastere S, Teissier A, Cao-Lormeau V, Musso D. Evidence of perinatal transmission of Zika virus,
French Polynesia, December 2013 and February 2014. Euro Surveill. 2014 Apr 3. 19 (13):[Medline].

5. Duffy MR, Chen TH, Hancock WT, Powers AM, Kool JL, Lanciotti RS, et al. Zika virus outbreak on Yap Island,
Federated States of Micronesia. N Engl J Med. 2009 Jun 11. 360 (24):2536-43. [Medline].

6. Marchette NJ, Garcia R, Rudnick A. Isolation of Zika virus from Aedes aegypti mosquitoes in Malaysia. Am J
Trop Med Hyg. 1969 May. 18 (3):411-5. [Medline].

7. Foy BD, Kobylinski KC, Chilson Foy JL, Blitvich BJ, Travassos da Rosa A, Haddow AD, et al. Probable
non-vector-borne transmission of Zika virus, Colorado, USA. Emerg Infect Dis. 2011 May. 17 (5):880-2.
[Medline].

8. Sirohi D, Chen Z, Sun L, Klose T, Pierson TC, Rossmann MG, et al. The 3.8 resolution cryo-EM structure of
Zika virus. Science. 2016 Mar 31. [Medline].

9. Ioos S, Mallet HP, Leparc Goffart I, Gauthier V, Cardoso T, Herida M. Current Zika virus epidemiology and
recent epidemics. Med Mal Infect. 2014 Jul. 44 (7):302-7. [Medline].

10. Dick GW. Epidemiological notes on some viruses isolated in Uganda; Yellow fever, Rift Valley fever, Bwamba
fever, West Nile, Mengo, Semliki forest, Bunyamwera, Ntaya, Uganda S and Zika viruses. Trans R Soc Trop
Med Hyg. 1953 Jan. 47 (1):13-48. [Medline].

11. Olson JG, Ksiazek TG, Suhandiman, Triwibowo. Zika virus, a cause of fever in Central Java, Indonesia. Trans
R Soc Trop Med Hyg. 1981. 75 (3):389-93. [Medline].

12. Roth A, Mercier A, Lepers C, Hoy D, Duituturaga S, Benyon E, et al. Concurrent outbreaks of dengue,

8 of 10 10/15/2016 12:44 AM
Zika Virus: Background, Pathophysiology, Epidemiology http://emedicine.medscape.com/article/2500035-overview#showall

chikungunya and Zika virus infections - an unprecedented epidemic wave of mosquito-borne viruses in the
Pacific 2012-2014. Euro Surveill. 2014 Oct 16. 19 (41):[Medline].

13. European Centre for Disease Prevention and Control, Stockholm. Zika virus disease epidemic: potential
association with microcephaly and Guillain-Barr syndrome (first update). Available at http://ecdc.europa.eu
/en/publications/Publications/rapid-risk-assessment-zika-virus-first-update-jan-2016.pdf. January 21, 2016;

14. Mlakar J, Korva M, Tul N, Popovi M, Poljak-Prijatelj M, Mraz J, et al. Zika Virus Associated with
Microcephaly. N Engl J Med. 2016 Feb 10. [Medline].

15. World Health Organization. WHO Director-General briefs the media on the Zika situation. World Health
Organization. Available at http://www.who.int/mediacentre/news/statements/2016/zika-update-3-16/en/. March
22, 2016; Accessed: April 12, 2016.

16. Centers for Disease Control and Prevention. Zika virus disease in the United States, 20152016. Centers for
Disease Control and Prevention. Available at http://www.cdc.gov/zika/geo/united-states.html. May 25, 2016;
Accessed: June 1, 2016.

17. [Guideline] World Health Organization. Breastfeeding in the context of Zika virus: Interim guidance. World
Health Organization. Available at http://apps.who.int/iris/bitstream/10665/204473
/1/WHO_ZIKV_MOC_16.5_eng.pdf. February 25, 2016; Accessed: March 18, 2016.

18. [Guideline] World Health Organization. Assessment of infants with microcephaly in the context of Zika virus:
Interim guidance. World Health Organization. Available at http://apps.who.int/iris/bitstream/10665/204475
/1/WHO_ZIKV_MOC_16.3_eng.pdf?ua=1. March 4, 2016; Accessed: March 18, 2016.

19. Mcharles S, Herrmann C, Poullain P, Tran TH, Deschamps N, Mathon G, et al. Acute myelitis due to Zika
virus infection. Lancet. 2016 Mar 3. [Medline].

20. [Guideline] CDC. Interim Guidance for Zika Virus Testing of Urine - United States, 2016. MMWR Morb Mortal
Wkly Rep. 2016 May 13. 65 (18):474. [Medline]. [Full Text].

21. [Guideline] Petersen EE, Staples JE, Meaney-Delman D, Fischer M, Ellington SR, Callaghan WM, et al.
Interim Guidelines for Pregnant Women During a Zika Virus Outbreak - United States, 2016. MMWR Morb
Mortal Wkly Rep. 2016 Jan 22. 65 (2):30-3. [Medline]. [Full Text].

22. [Guideline] World Health Organization. Identification and management of Guillain-Barr syndrome in the
context of Zika virus: Interim guidance. World Health Organization. Available at http://apps.who.int
/iris/bitstream/10665/204474/1/WHO_ZIKV_MOC_16.4_eng.pdf?ua=1. February 25, 2016; Accessed:
March 18, 2016.

23. [Guideline] Rabe IB, Staples JE, Villanueva J, Hummel KB, Johnson JA, Rose L, et al. Interim Guidance for
Interpretation of Zika Virus Antibody Test Results. MMWR Morb Mortal Wkly Rep. 2016 Jun 3. 65
(21):543-6. [Medline]. [Full Text].

24. [Guideline] Brooks JT, Friedman A, Kachur RE, LaFlam M, Peters PJ, Jamieson DJ. Update: Interim
Guidance for Prevention of Sexual Transmission of Zika Virus - United States, July 2016. MMWR Morb
Mortal Wkly Rep. 2016 Jul 25. 65 (29):745-7. [Medline]. [Full Text].

25. Marano G, Pupella S, Vaglio S, Liumbruno GM, Grazzini G. Zika virus and the never-ending story of emerging
pathogens and transfusion medicine. Blood Transfus. 2015 Nov 5. 1-6. [Medline].

26. [Guideline] Petersen EE, Polen KN, Meaney-Delman D, et al. Update: Interim Guidance for Health Care
Providers Caring for Women of Reproductive Age with Possible Zika Virus Exposure - United States, 2016.
MMWR Morb Mortal Wkly Rep. 2016 Apr 1. 65 (12):315-22. [Medline]. [Full Text].

27. Cetron M. Revision to CDC's Zika Travel Notices: Minimal Likelihood for Mosquito-Borne Zika Virus
Transmission at Elevations Above 2,000 Meters. MMWR Morb Mortal Wkly Rep. 2016 Mar 18. 65
(10):267-8. [Medline].

28. The White House. FACT SHEET: Preparing for and Responding to the Zika Virus at Home and Abroad. The
White House. Available at https://www.whitehouse.gov/the-press-office/2016/02/08/fact-sheet-preparing-
and-responding-zika-virus-home-and-abroad. February 8, 2016;

29. [Guideline] Centers for Disease Control and Prevention. Guidelines for Travelers Visiting Friends and Family
in Areas with Chikungunya, Dengue, or Zika. Centers for Disease Control and Prevention. Available at
http://wwwnc.cdc.gov/travel/page/travelers-vfr-chikungunya-dengue-zika. August 08, 2016; Accessed: August
27, 2016.

30. [Guideline] U.S. Food and Drug Administration. Revised Recommendations for Reducing the Risk of Zika
Virus Transmission by Blood and Blood Components. U.S. Food and Drug Administration. Available at
http://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation
/Guidances/Blood/UCM518213.pdf. August 26, 2016; Accessed: August 27, 2016.

31. [Guideline] Russell K, Oliver SE, Lewis L, et al. Update: Interim Guidance for the Evaluation and Management
of Infants with Possible Congenital Zika Virus Infection - United States, August 2016. MMWR Morb Mortal
Wkly Rep. 2016 Aug 26. 65 (33):870-878. [Medline]. [Full Text].

32. Gourinat AC, O'Connor O, Calvez E, Goarant C, Dupont-Rouzeyrol M. Detection of Zika virus in urine. Emerg
Infect Dis. 2015 Jan. 21 (1):84-6. [Medline].

33. Oehler E, Watrin L, Larre P, Leparc-Goffart I, Lastere S, Valour F, et al. Zika virus infection complicated by
Guillain-Barre syndrome--case report, French Polynesia, December 2013. Euro Surveill. 2014 Mar 6. 19
(9):[Medline].

34. Fontes BM. Zika virus-related hypertensive iridocyclitis. Arq Bras Oftalmol. 2016 Feb. 79 (1):63. [Medline].

9 of 10 10/15/2016 12:44 AM
Zika Virus: Background, Pathophysiology, Epidemiology http://emedicine.medscape.com/article/2500035-overview#showall

35. Ventura CV, Maia M, Ventura BV, Linden VV, Arajo EB, Ramos RC, et al. Ophthalmological findings in infants
with microcephaly and presumable intra-uterus Zika virus infection. Arq Bras Oftalmol. 2016 Feb. 79 (1):1-3.
[Medline].

36. Butler D. Zika virus: Brazil's surge in small-headed babies questioned by report. Nature. 2016 Feb 4. 530
(7588):13-4. [Medline].

37. Schuler-Faccini L, Ribeiro EM, Feitosa IM, Horovitz DD, Cavalcanti DP, Pessoa A, et al. Possible Association
Between Zika Virus Infection and Microcephaly - Brazil, 2015. MMWR Morb Mortal Wkly Rep. 2016 Jan 29.
65 (3):59-62. [Medline].

Medscape Reference 2011 WebMD, LLC

10 of 10 10/15/2016 12:44 AM