Thursday, October 04, 2012

A Disease Detective Story: Figuring Out Where EEE Spends The Winter



# 6606



While West Nile Virus infections are far more common (see DVBID: West Nile Infections Continue Record Pace), the Eastern Equine Encephalitis (EEE) virus elicits considerable concern because of its high fatality rate (30%+) and the large number of survivors who suffer ongoing neurological impairment.


Most years, only about 6 cases (range: 3—21) of human EEE are reported in the United States.


But this year – just as we’ve seen with WNV – is an unusually active year, and thus far the USGS is reporting 12 cases of EEE.




Given the devastating effects of infection in humans, and the fact that there is no vaccine available for humans to prevent it, learning about the ecology of the EEE virus is of particular importance.


We know that the natural hosts for the EEE virus are songbirds, which can become infected usually without suffering ill effect. The primary vector that spreads the virus among birds is the female Culiseta melanura mosquito (males don’t bite).




After an infected mosquito feeds on a bird, the bird becomes infected and the virus begins reproducing. After a few days - and for only a few days - the bird’s bloodstream amplifies the virus enough to infect subsequent mosquitoes that feed on it.


Culiseta melanura, however, isn’t usually attracted to bite humans.


So it requires a secondary type of mosquito - one that isn’t quite as picky a feeder - such as the Aedes albopictus or  Coquillettidia perturbans  `salt and pepper’ mosquito, to bite an infected bird in order to move it into the equine or human population.


The Transmission cycle is illustrated by the following graphic from the CDC.



Humans and horses don’t develop a high enough viral EEE titer in their bloodstream to pass on the virus if they are subsequently bitten by a mosquito, so they are considered to be `dead-end hosts’.


This explains the transmission cycle of the virus, but for one rather conspicuous hole in the equation.


Since birds are only viremic for a few days after being bitten, and since mosquitoes die out for several months during the winter  . . . . how does the virus manage to return each spring and summer?


For years scientists have suspected there had to be another host in the wild that could provide the EEE virus a safe place to overwinter.


But it would have to be one that could carry a high enough viral titer throughout the winter in order to reseed the virus in mosquito populations the following spring.


All of which brings us to some fascinating research that points to snakes – cottonmouths and copperheads, in particular – as being the winter residence of the EEE virus. 



Cottonmouth – Credit Wikipedia


This new study, which appears in the American Journal of Tropical Medicine and Hygiene, provides strong support for the idea that hibernating snakes serve as a bridge for the EEE virus to make it from one year to the next.


Detection of Eastern Equine Encephalomyelitis Virus RNA in North American Snakes

Andrea M. Bingham, Sean P. Graham, Nathan D. Burkett-Cadena, Gregory S. White, and Thomas R. Unnasch 


The role of non-avian vertebrates in the ecology of eastern equine encephalomyelitis virus (EEEV) is
unresolved, but mounting evidence supports a potential role for snakes in the EEEV transmission cycle, especially as over-wintering hosts.


To determine rates of exposure and infection, we examined serum samples from wild snakes at a focus of EEEV in Alabama for viral RNA using quantitative reverse transcription polymerase chain reaction.


Two species of vipers, the copperhead (Agkistrodon contortrix) and the cottonmouth (Agkistrodon piscivorus), were found to be positive for EEEV RNA by using this assay. Prevalence of EEEV RNA was more frequent in seropositive snakes than seronegative snakes. Positivity for the quantitative reverse transcription polymerase chain reaction in cottonmouths peaked in April and September. Body size and sex ratios were not significantly different between infected and uninfected snakes.


These results support the hypothesis that snakes are involved in the ecology of EEEV in North America, possibly as over-wintering hosts for the virus.

(Continue . . . )


The entire article is available online, and is a fascinating disease detective story . . . well worth reading in its entirety.


While probably not the preferred target for hungry mosquitoes - during the early spring and late fall when other blood meal sources may be in short supply - mosquitoes do feed on snakes.


They bite – not through their tough skin – but through the soft membranes around the snake’s eyes.  


Beyond discovering antibodies to the EEE virus in 35% of the cottonmouths sampled, the also found a number of snakes positive (via qRT-PCR) for the EEE virus.


This, they believe, is the first time that the active EEE virus has been documented in wild-caught snakes.


Previous tests had showed that snakes experimentally infected with the EEE virus remain viremic only for 7 to 10 days before they clear the infection – not enough time for the virus to overwinter.  


But now it appears that when a snake hibernates, it can carry the virus over the winter, and can likely reintroduce it to mosquitoes the following spring.


All of which introduces an interesting notion regarding control of the virus. Normally spraying for mosquitoes doesn’t begin until EEE starts showing up in mosquito surveillance traps, horses, or worse . . . humans.

If spraying were conducted during the early spring in swampy areas where mosquitoes and snakes are likely to meet - it might be possible to interrupt this annual cycle - and thus thwart the virus’s reintroduction to the mosquito and bird population.



As the abstract states, this study supports the hypothesis that snakes are the `bridge’ host for the EEE virus, but there is still more research needed. 


For more on this story Maggie Fox of NBC News has a good report, along with some comments from the lead author of the study; Dr. Thomas Unnasch of the University of South Florida.


Snakes may harbor deadly virus


And for more on the EEE virus, you may wish to revisit some of these earlier blogs.


MMWR: Arboviral Disease Surveillance – 2010
ASTMH: Dengue and Insect-Borne EIDs In The US
Eastern Equine Encephalitis (EEE)

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