Viruses: Aerosol & Contact Transmission Of Japanese Encephalitis Virus In Experimentally Infected Mice

Credit CDC

#13,800


As our investigative methods become more precise, and more data is acquired and analyzed, we occasionally find that long held scientific beliefs need to be questioned - and sometimes revised.

Over the past two decades, we've looked at many examples in the infectious disease world where new evidence has forced conventional wisdom to change.

A few recent examples include:

• Prior to 2003 and the outbreak and spread of SARS,  coronaviruses were thought to be relatively mild in humans, and incapable of causing a pandemic.  Since then, between the emergence of MERS-CoV in the Middle East, and the discovery of other virulent coronaviruses in bats, that perception has changed. 
• Until the West African outbreak 4 years ago, Ebola was thought simply too debilitating, too lethal, and too remote to spread efficiently. Those infected were considered `too sick to travel’, and small outbreaks would inevitably `burn themselves out’ in relatively short order. 
• Until a couple of years ago, many scientists were still questioning the role of migratory birds in the spread of Highly Pathogenic Avian Influenza (HPAI) viruses.  After the 2016/2017 European epizootic and H5N8's spread into the Middle East & Africa, that debate has about ended (see Migratory Birds & The Spread Of Highly Pathogenic Avian Flu).
• The 2016 Zika epidemic in the Americas taught us that mosquito borne viruses - like Zika - can not only cause birth defects (see NEJM: CDC Concludes Zika Causes Microcephaly & Other Birth Defects, they can be sexually transmitted as well.  Neither of which were considered serious threats before.
• Despite years of assurances that `Legionellosis does not spread person to person', in 2016 in NEJM: Probable Person-to-Person Transmission Of Legionnaires’ Disease, we saw an epidemiological investigation following the 2014 outbreak in Portugal that strongly suggests that - while very rare - it is possible. 

The point being, our perceptions and understanding of how things work are often forced to change as new evidence is uncovered.  

While it is too soon to re-write the textbooks, we've a new study (published today in the journal Viruses) which presents evidence that the Japanese encephalitis virus (JEV) - which until now as been viewed as a vector borne virus - can be transmitted via direct contact and aerosols among experimentally infected mice. 

How often this occurs in the real world, or whether it has a tangible impact on outbreaks, remains to be seen. But it is a fascinating finding, and one that reminds us the importance of looking past conventional wisdom for a more complete truth.

I've only included a few excerpts from a much longer, open-access, study. Follow the link to read it in its entirety.

Viruses 2019, 11(1), 87; doi: 10.3390/v11010087
Article

Aerosol and Contact Transmission Following Intranasal Infection of Mice with Japanese Encephalitis Virus 

Chunxia Chai 1,†, Rachel Palinski 2,†, Yixuan Xu 1,†, Qiao Wang 1, Sanjie Cao 1, Yi Geng 3, Qin Zhao 1, Yiping Wen 1, Xiaobo Huang 1, Qiguai Yan 1, Xiaoping Ma 1, Xintian Wen 1, Yong Huang 1, Xinfeng Han 1, Wenjun Ma 2,* and Rui Wu 1,3,*

Received: 25 October 2018 / Accepted: 18 January 2019 / Published: 21 January 2019 

Abstract: 

The Japanese encephalitis virus (JEV), a causative agent of severe viral encephalitis in humans, has a biological cycle fluctuating between transmission in mosquitoes and avian species and amplification in pigs. Contact transmission of JEV was recently shown in pigs in the absence of arthropod vectors. 

Here, we show JEV transmission between infected and contact mice and further demonstrate that JEV transmission occurs between animals via aerosols, as both viral RNA and infectious JEV were detected in direct contact- and aerosol-exposed contact animals. The results of this study change our understanding of JEV transmission in densely populated regions and may help to explain JEV outbreaks without the presence of arthropod vectors.

      (SNIP)

Introduction

Japanese encephalitis (JE) is a zoonotic vector-borne viral disease, causing the encephalitis most frequently associated with fatal or severe outcomes in humans [1]. It is currently present in Asia and Australia with 50,000–175,000 cases occurring annually [2,3]. Human cases generally occur in rural areas or at the edges of cities following heavy rains or monsoons [1]. In these cases, less than 1% of patients develop encephalitis; however, 20–30% of encephalitic patients succumb to the disease. Most notably, ~50% of patients surviving encephalitis suffer neurologic or psychologic sequelae [4]. 

Japanese encephalitis virus (JEV), the causative agent of JE, is a mosquito-borne member of the genus Flavivirus, family Flaviviridae. Culex mosquitoes are the main vector for JEV, while wild water birds represent the reservoirs of the virus [5]. Swine are highly susceptible to JEV infection, although the clinical signs generally remain subclinical, and this species serves as amplifying hosts during human epidemics [5,6,7,8]. Neurotropic disease occurs relatively rarely in the virus’ natural hosts, although abortion has been noted in pregnant sows [1]. In contrast, humans and horses are considered dead-end hosts, as they may develop fatal disease but do not develop a viremia capable of transmitting the virus.

Despite the previously established vector–host cycle of JEV, no virus was isolated from locally collected mosquitoes during or prior to recent epidemics [9,10]. Furthermore, transfusion-related JEV transmission has been reported in patients in Hong Kong [11]. Together, these facts suggest that JEV is capable of vector-free transmission. 

In 2016, the vector-free transmission and viral persistence of JEV was experimentally confirmed in pigs. Pigs were not only susceptible to oronasal infection, but the virus was shown to persist in the tonsils for 25 days despite the detection of high titers of neutralizing antibodies. JEV RNA was detected in oral fluids for up to 14 days following infection in swine, and it seems to be the route of viral exit and entry for pigs [12,13]. The high susceptibility of infection coupled with a low infectious dose suggests vector-free transmission is important to natural infection cycles and prompts the examination of other routes of vector-free transmission [14].

        (SNIP)

4. Discussion

JEV has been thought to transmit solely through mosquito vectors. The Culex species has been implicated as the main contributors to the spread of the disease. The concept that mosquitoes are the sole contributors to JEV outbreaks and disease has been questioned recently because epidemiological and virologic data on outbreaks in non-tropical regions suggests that other factors also play a role in the spread of the disease.

In 2016, Ricklin et al. proved the contact transmission of JEV in experimentally infected pigs; the results of the study suggest contact transmission plays a more important role in viral dissemination in large, dense populations of animals [14]. Utilizing mice in this study is advantageous, as human and mouse JEV infections result in similar physiopathological markers and clinical signs of disease [23,24].

In this study, we not only confirm that contact transmission is possible but also demonstrate that aerosol transmission may occur in the mouse model. The results of these studies add to our understanding of JEV transmission within populations of susceptible species without the presence of mosquito vectors.

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