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Review
. 2016 Mar 2;10(3):e0004530.
doi: 10.1371/journal.pntd.0004530. eCollection 2016 Mar.

Zika Virus: Medical Countermeasure Development Challenges

Robert W Malone  1   2 , Jane Homan  3 , Michael V Callahan  4 , Jill Glasspool-Malone  1   2 , Lambodhar Damodaran  5 , Adriano De Bernardi Schneider  5 , Rebecca Zimler  6 , James Talton  7 , Ronald R Cobb  7 , Ivan Ruzic  8 , Julie Smith-Gagen  9 , Daniel Janies  5 , James Wilson  10 ; Zika Response Working Group
Affiliations
Review

Zika Virus: Medical Countermeasure Development Challenges

Robert W Malone et al. PLoS Negl Trop Dis. .

Abstract

Introduction: Reports of high rates of primary microcephaly and Guillain-Barré syndrome associated with Zika virus infection in French Polynesia and Brazil have raised concerns that the virus circulating in these regions is a rapidly developing neuropathic, teratogenic, emerging infectious public health threat. There are no licensed medical countermeasures (vaccines, therapies or preventive drugs) available for Zika virus infection and disease. The Pan American Health Organization (PAHO) predicts that Zika virus will continue to spread and eventually reach all countries and territories in the Americas with endemic Aedes mosquitoes. This paper reviews the status of the Zika virus outbreak, including medical countermeasure options, with a focus on how the epidemiology, insect vectors, neuropathology, virology and immunology inform options and strategies available for medical countermeasure development and deployment.

Methods: Multiple information sources were employed to support the review. These included publically available literature, patents, official communications, English and Lusophone lay press. Online surveys were distributed to physicians in the US, Mexico and Argentina and responses analyzed. Computational epitope analysis as well as infectious disease outbreak modeling and forecasting were implemented. Field observations in Brazil were compiled and interviews conducted with public health officials.

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Conflict of interest statement

I have read the journal's policy and the authors of this manuscript have the following competing interests: RWM and JGM are employees and equity holders in RW Malone MD LLC. JH is an employee and equity holder in ioGenetics LLC. JT is an employee and equity holder in Nanotherapeutics, Inc. RRC is an employee of Nanotherapeutics, Inc.

Figures

Fig 1
Fig 1. Phylogeographic analyses illustrating the lineage of the Zika virus currently circulating in Brazil.
Phylogeographic analysis based on the envelope gene of Zika virus. This analysis illustrates the path of travel of Zika virus from Africa, Asia, and across the Pacific to South America. This analysis was created with Supramap [68]. Yellow circles and branches are associated with common ancestors. Red pins and black lines are associated with observed viral isolates. The root of the tree is indicated with a green circle. Data analyzed included all envelope variants of Zika virus available in the public domain as of January 18, 2016. Nucleotide sequence data were aligned using MAFFT v7.215 under default settings. A dataset for the envelope gene was created resulting in a matrix of 56 taxa and 753 aligned positions. A phylogenetic tree search was conducted for each dataset using RAxML v8.1.16 for 100 replicates under the GTRCAT model of nucleotide substitution. The outgroup was set to HQ234498. Supramap to project the phylogenetic tree into the earth [68].
Fig 2
Fig 2. Zika virus, past and current distribution.
Source: Centers for Disease Control and Prevention [83].
Fig 3
Fig 3. States in Brazil investigating microcephaly cases for association with Zika virus infection (above), and with confirmed circulation of Zika virus (below).
After [99]. Information sources include Brazilian Health Ministry (Ministério da Saúde);WHO (World Health Organization); PAHO (Pan American Health Organization).
See this image and copyright information in PMC

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