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The Emergence of Zika Virus: A Narrative ReviewThe Emergence of Zika Virus

Kathryn B. Anderson, MD, PhD; Stephen J. Thomas, MD; and Timothy P. Endy, MD, MPH
[+] Article, Author, and Disclosure Information

This article was published at www.annals.org on 3 May 2016.

From the University of Minnesota, Minneapolis, Minnesota; U.S. Army Medical Directorate–Armed Forces Research Institute of Medical Sciences of the Walter Reed Army Institute of Research, Bangkok, Thailand; Walter Reed Army Institute of Research, Silver Spring, Maryland; and State University of New York, Upstate Medical University, Syracuse, New York.

Note: Dr. Anderson accepts the final responsibility for the decision to submit the manuscript.

Disclaimer: The opinions or assertions contained herein are the private views of the authors and are not to be construed as reflecting the official views of the U.S. Army or the U.S. Department of Defense.

Disclosures: Dr. Anderson has disclosed no conflicts of interest. Dr. Thomas reports that he is an inventor on a provisional invention disclosure for an inactivated ZIKV vaccine and for a combined flavivirus vaccine with a ZIKV component pending, with all rights assigned to the U.S. government. Dr. Endy reports grants from the National Institutes of Health outside the submitted work; personal fees from Sanofi Pasteur, Merck, and Veristat outside the submitted work; and a pending patent on a ZIKV vaccine. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M16-0617.

Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that she has no financial relationships or interests to disclose. Darren B. Taichman, MD, PhD, Executive Deputy Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer and Johnson & Johnson.

Requests for Single Reprints: Kathryn B. Anderson, MD, PhD, Department of Medicine, University of Minnesota, MMC 741, Mayo Building, Minneapolis, MN 55455; e-mail, ande7622@umn.edu.

Current Author Addresses: Dr. Anderson: Department of Medicine, University of Minnesota, MMC 741, Mayo Building, Minneapolis, MN 55455.

Dr. Thomas: Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910.

Dr. Endy: Division of Infectious Diseases, State University of New York, Upstate Medical University, 750 East Adams Street, CPOB Suite 304, Syracuse, NY 13210.

Author Contributions: Conception and design: K.B. Anderson, T.P. Endy.

Analysis and interpretation of the data: K.B. Anderson, S.J. Thomas.

Drafting of the article: K.B. Anderson, S.J. Thomas, T.P. Endy.

Critical revision of the article for important intellectual content: K.B. Anderson, T.P. Endy.

Final approval of the article: K.B. Anderson, S.J. Thomas, T.P. Endy.

Administrative, technical, or logistic support: K.B. Anderson.

Collection and assembly of data: S.J. Thomas, T.P. Endy.

Ann Intern Med. 2016;165(3):175-183. doi:10.7326/M16-0617
© 2016 American College of Physicians
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Zika virus (ZIKV) is yet another arbovirus that is rapidly emerging on a global scale, on the heels of a chikungunya epidemic in the Americas that began in 2013. A ZIKV epidemic that began in Brazil in 2015 has now spread rapidly to more than 30 countries in the Americas and the Caribbean, infecting more than 2 million inhabitants. This epidemic currently continues unabated. The explosive nature of recent outbreaks and concerning links to Guillain–Barré syndrome and microcephaly are incompletely understood. Also unknown is the relative importance of sexual transmission of ZIKV and asymptomatic ZIKV infections to the overall burden of transmission. The limited understanding of ZIKV presents an enormous challenge for responses to this rapidly emerging threat to human health. This article reviews the existing literature on ZIKV and proposes critical questions for vaccine development and other areas of needed research.


Grahic Jump Location
Figure 1.

Predicted risk for local Zika transmission, based on final destinations for travelers departing Brazil and incorporating ecological niche information for Aedes aegypti and A albopictus.

Reproduced with permission from reference 39.

Grahic Jump Location
Grahic Jump Location
Figure 2.

Lineages of Zika virus isolates based on envelope gene sequences.

Reproduced with permission from reference 41.

Grahic Jump Location




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Submit a Comment/Letter
Strain differences vs other factors
Posted on May 4, 2016
Stuart C. Ray, M.D., FACP, FIDSA
Johns Hopkins University School of Medicine
Conflict of Interest: None Declared
In this excellent article the authors note, "All 3 recent epidemics have been linked to expansion of the Asian lineage of ZIKV (Figure 2) (22, 41). It is not known whether strains of ZIKV are associated with an increased risk for neurologic disease or whether mutations have facilitated the explosive spread of ZIKV in recent years."

The second sentence in that quotation could be interpreted as suggesting that these are alternatives, or that they are inclusive. Of course, they are not - and I infer that was not the authors' intent.

It is an intriguing possibility that mutations, which collectively contribute to the evolution of distinct strains, are determinants of severity but (as the authors suggest) that remains an unknown.
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