Estimating the effects of variation in viremia on mosquito susceptibility, infectiousness, and R0 of Zika in Aedes aegypti.

Blanka Tesla,Matthew H Bonds,Melinda A Brindley,Courtney C Murdock,Erin A Mordecai,Hannah S Packiam,Américo D Rodríguez,Leah R Demakovsky,Robert C Reiner

doi:10.1371/journal.pntd.0006733

Abstract

Zika virus (ZIKV) is an arbovirus primarily transmitted by Aedes mosquitoes. Like most viral infections, ZIKV viremia varies over several orders of magnitude, with unknown consequences for transmission. To determine the effect of viral concentration on ZIKV transmission risk, we exposed field-derived Ae. aegypti mosquitoes to four doses (103, 104, 105, 106 PFU/mL) representative of potential variation in the field. We demonstrate that increasing ZIKV dose in the blood-meal significantly increases the probability of mosquitoes becoming infected, and consequently disseminating virus and becoming infectious. Additionally, we observed significant interactions between dose and days post-infection on dissemination and overall transmission efficiency, suggesting that variation in ZIKV dose affects the rates of midgut escape and salivary gland invasion. We did not find significant effects of dose on mosquito mortality. We also demonstrate that detecting virus using RT-qPCR approaches rather than plaque assays potentially over-estimates key transmission parameters, including the time at which mosquitoes become infectious and viral burden. Finally, using these data to parameterize an R0 model, we showed that increasing viremia from 104 to 106 PFU/mL increased relative R0 3.8-fold, demonstrating that variation in viremia substantially affects transmission risk.

Highlights

Discovered in 1947 [1], Zika virus (ZIKV) has recently become a public health concern due to its rapid spread and newly identified teratogenic effects [2]
We demonstrated that increased concentration of ZIKV in the blood significantly increases the probability and the rate at which mosquitoes become infectious, which increases the risk of ZIKV transmission
More than 4 days were required for ZIKV to disseminate into the head (Fig 2B) and more than 8 days to be present in the saliva (Fig 2C)

Summary

Introduction

Discovered in 1947 [1], Zika virus (ZIKV) has recently become a public health concern due to its rapid spread and newly identified teratogenic effects [2]. After isolation from a rhesus macaque in Uganda, the virus caused several mild infections in humans [3, 4]. The virus further spread across the Pacific, where it was first associated with GuillainBarresyndrome during the 2014 French Polynesian outbreak [6]. In 2015, transmission was confirmed in Brazil [7], after which the virus spread rapidly across the Americas [8]. ZIKV was declared a “public health emergency of international concern” by WHO in 2016 due to rapid spread and increases in complications associated with congenital Zika virus syndrome [9]

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Discussion

Conclusion