Grand Rounds: Preventing Aedes Mosquito-Borne Diseases

 

# 10,049

 

Each month the CDC holds a Grand Rounds web presentation that focuses on a single health-related issue.  In the past I’ve highlighted their broadcasts on such diverse topics as Multidrug-Resistant Gonorrhea, Childhood Emergency Preparedness, and Discovering New Diseases  . . . to name a few.

 

The CDC maintains an archive of these informative presentations – going back to 2009 – which you can access at Grand Rounds – Archives.  Highly recommended.

 

With summer almost here, and both Chikungunya and Dengue spreading extensively in the Caribbean and Central and South America, these mosquito borne diseases may be on the verge of making inroads into North America. All of which makes the timing of next week’s presentation fortuitous. 

 

First details on Tuesday’s event, then I’ll be back with more on the arbovirus disease threats to the United States.

 

Dengue and Chikungunya in Our Backyard: Preventing Aedes Mosquito-Borne Disease

 

Webcast Links

Windows Media:
http://wm.onlinevideoservice.com/CDC1

Flash:
http://www.onlinevideoservice.com/clients/CDC/?mount=CDC3

Captions are only available on the Windows Media links. The webcast links are only active during the date and time of the session, but all sessions are archived for future viewing.

Tuesday, May 19 at 1pm EDT

Aedes aegypti and Aedes albopictus mosquitoes are the primary vectors for dengue, chikungunya, yellow fever, and Zika viruses. Taken together, these viruses account for almost 100 million cases of mosquito-borne disease per year. Globally, dengue is the most important mosquito-borne viral disease. In the last 50 years, incidence has increased 30-fold by expanding into new countries and new areas. Chikungunya often occurs in large outbreaks with high infection rates, affecting more than a third of the population in areas where the virus is circulating. In 2014, more than a million cases were reported worldwide. While Chikungunya disease rarely results in death, the symptoms can be severe and disabling.

Outbreaks of mosquito-borne diseases depend on many factors and are especially difficult to predict, prevent and control. Because there are no licensed vaccines available to prevent dengue or chikungunya, controlling mosquito populations and reducing bites are currently the most effective prevention measures.

This session of Grand Rounds will highlight the importance of preventing Aedes mosquito-borne diseases and the need for improved diagnostic, prevention and control measures.

Presented By:

Marc Fischer, MD, MPH
Chief, Surveillance and Epidemiology Activity, Arboviral Diseases Branch
Division of Vector-Borne Diseases
National Center for Emerging and Zoonotic Infectious Diseases, CDC
"Dengue, Chikungunya and Other Aedes Mosquito-Borne Diseases"

Thomas W. Scott, PhD
Professor and Director, Vector-Borne Disease Laboratory
Department of Entomology and Nematology
University of California, Davis
"The Status and Frontiers of Vector Control"

Harold Margolis, MD
Branch Chief, Dengue Branch
Division of Vector-Borne Diseases
National Center for Emerging and Zoonotic Infectious Diseases, CDC
"Prevention Strategies for Aedes Mosquito-Borne Diseases"

Facilitated By:

John Iskander, MD, MPH, Scientific Director, Public Health Grand Rounds
Phoebe Thorpe, MD, MPH, Deputy Scientific Director, Public Health Grand Rounds
Susan Laird, MSN, RN, Communications Director, Public Health Grand Rounds

Although Dengue and Chikungunya now regularly arrive in the North America via infected (viremic) travelers, we’ve been lucky in that neither has had much success in entrenching itself into our local mosquito populations. 

 

How long our luck will hold is anyone’s guess.  West Nile Virus, which emerged in NYC in 1999, quickly spread across the nation and is now a perennial threat.

 

Chikungunya was introduced by viremic travelers to the Caribbean in the fall of 2013, who inadvertently `seeded’ the virus into the local mosquito population.  Over the past 18 months there have been well over 1.4 million infections in the Americas – spanning more than 3 dozen nations - and millions more will undoubtedly be infected in the years to come.  

Dengue arrived in South Florida in 2009 in a similar fashion (see MMWR: Dengue Fever In Key West), as did West Nile Virus to NYC in the late 1990s.  So far, Dengue and Chikungunya have had only very limited success spreading in the United States. Literally only a handful of cases have been reported thus far.

 

But as we’ve seen with West Nile Virus - when the right combination of multiple virus introductions, competent vectors, and favorable environmental conditions come together - formerly exotic diseases can get a foothold and even thrive here in the United States.

 

Right now, Dengue and Chikungunya are minor threats in North America, but that could change quickly. When you add in the other mosquito-borne illnesses (EEE, WNV, SLEV, etc.) it just makes sense to do whatever you can to limit your exposure.

 

Which is why the Florida State Health Department urge residents and visitors to follow the `5 D’s’:

Updating West Nile, CHKV & Dengue

 

# 8926

 

While Ebola dominates the daily news cycle, there are plenty of other public health concerns out there that are far more likely to threaten the average North American than imported cases of hemorrhagic fever.  Among those are mosquito-borne diseases like WNV, dengue, EEE, and Chikungunya.

 

Yesterday, the California Department of Public Health  announced two recent deaths from West Nile Virus, adding to a handful of deaths already reported this year in Arizona, Louisiana & Missouri.

 

CDPH Reports First Human West Nile Virus Fatalities This Summer

Date: 8/6/2014

Number: 14-069

Contact: Anita Gore - (916) 440-7259

SACRAMENTO

The first two deaths this summer due to West Nile virus infection have been confirmed by the California Department of Public Health (CDPH) it was announced today by Dr. Ron Chapman, CDPH Director and state public health officer. The first was a senior citizen from Sacramento County. The second was an adult from Shasta County.

“These unfortunate deaths remind us that we must protect ourselves from mosquito bites to prevent West Nile virus and other mosquito born infections,” said Chapman. “West Nile virus activity is greatest during the summertime.”

West Nile virus is transmitted to humans and animals by the bite of an infected mosquito. The risk of serious illness to most people is low. However, some individuals – less than one percent – can develop a serious neurologic illness such as encephalitis or meningitis. People 50 years of age and older have a higher chance of getting sick and are more likely to develop complications. Recent data also indicate that those with diabetes and/or hypertension are at greatest risk for serious illness.

To date in 2014, West Nile virus has been detected in 36 California counties.

(Continue . . . )

 

 

The least severe form of the disease – West Nile Fever - probably infects more than 100,000 Americans every year, although most are so mildly affected they have no idea the are infected.

 

Neuroinvasive cases (which present with meningitis, encephalitis, or flaccid Paralysis), while less common, are severe enough that they nearly always result in hospitalization and diagnosis, and so they are considered the best indicator of the scope of each year’s epidemic. 

 

Right now, California and Arizona lead the nation in reporting neuroinvasive cases of WNV, with a combined total of 24.

The amount of WNV activity varies considerable from year-to-year, and this year (so far, anyway) we haven’t seen a huge number of cases.  Surveillance and reporting, however, often lags several weeks behind actual events, and so we may still see a substantial number of cases this year.

 

This year we are also monitoring the arrival of locally transmitted Chikungunya in the United States, and while only 4 cases have been reported (all in Florida), we continue to see large numbers of imported cases being reported across the nation. 

Each imported case provides an opportunity for local mosquitoes to pick up, and transmit, the disease.

Florida and New York lead the nation with the number of imported CHKV cases, but as Chikungunya is not a nationally notifiable disease, surveillance is likely to under report cases. 

 

Chikungunya – while rarely fatal - can cause prolonged fever and polyarthralgias (joint pain), which in some cases can lead to permanent disability. 

 

With PAHO reporting more than 500,000 CHKV cases across the Caribbean over the past 7 months, it isn’t surprising that we are beginning to see locally transmitted cases in both Puerto Rico and the U.S. Virgin Islands.

 

Despite its rapid spread across the islands of the Caribbean, and into Central and South America, there are reasons to hope that CHKV won’t spread as rapidly as WNV has in the United States.

 

Unlike WNV, which resides in birds, CHKV doesn’t have an animal host other than humans which can aid in its spread (see WNV vs CHIKV: A Host Of Differences).  And studies have suggested that lifestyle and economic factors (ie. air conditioning, window screens, mosquito control programs) may further reduce transmission. 

 

Thus far, we haven’t seen much reporting on locally acquired Dengue this summer, with only one case reported in the Miami-Dade region of south Florida (see Florida: Miami Reports 1st Locally Acquired Dengue Case Of 2014). 

 

While now the most common mosquito-borne virus in the world (causing up to 100 million infections a year), Dengue has managed to do little more than spark a few limited outbreaks in North America, despite an abundance of the right mosquito vectors.

 

Whether our relative good luck will continue to hold with Dengue, and CHKV, remains to be seen. 

 

While the overall risk of contracting a mosquito-borne illness anywhere in the United States remains very small, with no vaccines available, and scattered cases of Dengue, West Nile Virus, EEE, SLEV, and the recent arrival of Chikungunya  - Florida’s Health departments urge people to always follow the `5 D’s’:

Wolbachia, West Nile Virus & An Unexpected Result

Credit Wikpedia

 

# 8824

 

Three years ago the mosquito-disease control world was abuzz with news of a promising new method to prevent mosquitoes from carrying, and passing on, dengue to humans. It involved infecting mosquitoes with Wolbachia, a bacterium commonly carried by a variety of insects around the world, and then releasing them into the wild.

Scientists discovered that when mosquitoes are infected with Wolbachia, their lifespan was halved and their ability to transmit dengue was greatly reduced, although the exact mechanism behind those effects wasn’t understood.

 

And given that, for mosquitoes – Wolbachia is a sexually transmitted disease – it was expected that wouldn’t take long after releasing a relatively small number of infected mozzies to start a local epidemic. We looked at some of these early trials back in 2011, with A Mosquito STD To Fight Dengue & A Sexually Transmitted Disease Cure).

 

And the early results were impressive. In early 2011 scientists in Queensland, Australia began releasing thousands of Wolbachia infected mosquitoes each week into the remote communities of Gordonvale and Yorkeys Knob, and within weeks infected mosquitoes overran the uninfected mosquito population in both test environments.

 

When an infected male mosquito mates with an uninfected female, the resultant fertilized eggs will fail to mature due to an abnormality known as cytoplasmic incompatibility (CI). Only the offspring from the union between already infected parents survive.

 

Since the Wolbachia infection is passed down from one generation to the next, that was expected to give the Wolbachia infected mosquitoes quite an evolutionary advantage.

 

And over the past couple of years hopes have even been raised that Wolbachia might be used to control malaria as well, as laboratory studies showed that infected anopheles stephensi mosquitoes developed resistance to malarial infection.

 

Wolbachia Invades Anopheles stephensi Populations and Induces Refractoriness to Plasmodium Infection

Guowu Bian¹,², Deepak Joshi¹, Yuemei Dong³, Peng Lu¹, Guoli Zhou¹, Xiaoling Pan¹, Yao Xu¹, George Dimopoulos³, Zhiyong Xi¹,⁴,*

+Wolbachia is a maternally transmitted symbiotic bacterium of insects that has been proposed as a potential agent for the control of insect-transmitted diseases. One of the major limitations preventing the development of Wolbachia for malaria control has been the inability to establish inherited infections of Wolbachia in anopheline mosquitoes. Here, we report the establishment of a stable Wolbachia infection in an important malaria vector, Anopheles stephensi. In A. stephensi, Wolbachia strain wAlbB displays both perfect maternal transmission and the ability to induce high levels of cytoplasmic incompatibility. Seeding of naturally uninfected A. stephensi populations with infected females repeatedly resulted in Wolbachia invasion of laboratory mosquito populations. Furthermore, wAlbB conferred resistance in the mosquito to the human malaria parasite Plasmodium falciparum.

 

While Wolbachia’s stock is riding high, yesterday a study published in PLoS Neglected Tropical Diseases raises a bit of an unexpected red flag. 

 

Researchers from Penn State, the University of Maryland, New York’s DOH and the State University of New York at Albany infected Culex tarsalis mosquitoes with Wolbachia and then allowed them to dine on West Nile Virus infected blood, fully expecting to see the same reduction in viral carriage as observed with dengue. 

 

Instead, they found quite the opposite:

 

Wolbachia Enhances West Nile Virus (WNV) Infection in the Mosquito Culex tarsalis

Brittany L. Dodson, Grant L. Hughes, Oluwatobi Paul, Amy C. Matacchiero, Laura D. Kramer, Jason L. Rasgon mail

Published: July 10, 2014  DOI: 10.1371/journal.pntd.0002965

Abstract

Novel strategies are required to control mosquitoes and the pathogens they transmit. One attractive approach involves maternally inherited endosymbiotic Wolbachia bacteria. After artificial infection with Wolbachia, many mosquitoes become refractory to infection and transmission of diverse pathogens. We evaluated the effects of Wolbachia (wAlbB strain) on infection, dissemination and transmission of West Nile virus (WNV) in the naturally uninfected mosquito Culex tarsalis, which is an important WNV vector in North America. After inoculation into adult female mosquitoes, Wolbachia reached high titers and disseminated widely to numerous tissues including the head, thoracic flight muscles, fat body and ovarian follicles.

Contrary to other systems, Wolbachia did not inhibit WNV in this mosquito. Rather, WNV infection rate was significantly higher in Wolbachia-infected mosquitoes compared to controls. Quantitative PCR of selected innate immune genes indicated that REL1 (the activator of the antiviral Toll immune pathway) was down regulated in Wolbachia-infected relative to control mosquitoes. This is the first observation of Wolbachia-induced enhancement of a human pathogen in mosquitoes, suggesting that caution should be applied before releasing Wolbachia-infected insects as part of a vector-borne disease control program.

Author Summary

Current methods to control mosquitoes and the pathogens they transmit are ineffective, partly due to insecticide and drug resistance. One novel control method involves exploiting naturally occurring Wolbachia bacteria in insects. Wolbachia are bacterial symbionts that are attractive candidates for mosquito-borne disease control due to their ability to inhibit pathogens infecting humans. Additionally, Wolbachia affects insect reproduction to facilitate its own transmission to offspring, which has been exploited to establish the bacterium in naturally uninfected field populations. Most Wolbachia pathogen control research has focused on Aedes and Anopheles mosquitoes, but Culex mosquitoes also transmit pathogens that affect human health.

We evaluated impacts of Wolbachia infection on West Nile virus (WNV) in the naturally uninfected mosquito Culex tarsalis. Wolbachia was able to efficiently establish infection in Cx. tarsalis but contrary to other studies, Wolbachia enhanced rather than inhibited WNV infection. Enhancement occurred in conjunction with suppression of mosquito anti-viral immune gene expression. This study indicates that Wolbachia control strategies to disrupt WNV via pathogen interference may not be feasible in Cx. tarsalis, and that caution should be used when releasing Wolbachia infected mosquitoes to control human vector-borne diseases.

 

Skipping down to the discussion section of the study, the authors write:

To our knowledge this is first study showing Wolbachia can potentially enhance a vector-borne pathogen that causes human disease. Our results, combined with other Wolbachia enhancement studies [17]–[20], [46]–[47], suggest that field deployment of Wolbachia-infected mosquitoes should proceed with caution.

Wolbachia effects on all potential pathogens in the study area should be determined. Additionally, several studies have shown that Wolbachia is capable of horizontal transfer to other insect species which could have unforeseen effects on non-target insects [52]–[54].

A lack of understanding of Wolbachia-pathogen-mosquito interactions could impact efficacy of disease control programs. Cx. tarsalis is a competent vector for many human pathogens, and further studies that assess alternative Wolbachia strains and viruses in Cx. tarsalis may elucidate the importance of host background on pathogen interference phenotypes in this medically important mosquito species.

 

None of this knocks Wolbachia out of the running as a potential control for dengue or malaria, two of the greatest impact infectious diseases in the world. This is a preliminary study, based on a single strain of Wolbachia in a single species of mosquito, and much more research is needed. 

It does, however, remind us that there are a great many more variables in the wild than can be accounted for inside the laboratory. 

 

And that when contemplating `bio-engineering’  - no matter how noble the goal - one must always consider the law of unintended consequences and proceed with caution.

Dealing With Uninvited Guests

Aedes Albopictus – Asian Tiger Mosquito

 

# 8746

 

Yesterday Dr. Jen Halverson left a highly informative comment on my PAHO Chikungunya Update blog, which describes her impressions of the outbreak in Haiti, and is deserving of additional exposure.

 

The situation is Haiti is, as you said, very badly underreported. I got chikungunya (confirmed by testing in the US) on 5/14. I was one of the first cases among my friends. The vast majority of my ex-pat friends in Port au Prince have had it. Other cities are very affected as well. The majority of my Haitian friends and colleagues have already had it. My conservative estimate for Haiti is at least a million cases so far, and probably more. We will obviously never know the true numbers. I have been working in Haiti for 16 years (I'm an ER doctor) and I've never seen anything like this.

 

My thanks to Dr. Halverson for this sobering first hand report, and for the work she does under difficult conditions.  

 

Her account is all the more concerning as the rainy season in Haiti is really just getting underway. While tropical temps abound year-round, the rainy season runs from May through October, and can be greatly exacerbated by tropical storms and hurricanes which most often arrive in August and September. 

 

It is worth noting that this first Chikungunya outbreak began in late November of last year, after the end of the traditional rainy season, and has spread with remarkable efficiency during what are considered the driest 6 months of the year.

 

As you can see by the following CDC chart for Puerto Rico, dengue (which is spread by the same types of mosquitoes as Chikungunya), usually peaks in late September, during the height of the rainy season.   

 

 

Given the Chikungunya outbreak in the Caribbean, public health departments here in Florida and around the United States, are urging people to be more diligent about removing breeding places for mosquitoes around their homes.

 

But it isn’t just outside the home where people need to check . . .  some mosquito species are perfectly capable of setting up light housekeeping inside the home as well.

 

While the Aedes aegypti has long been associated with spreading nasties such as yellow fever, dengue and Chikungunya, in 2005 a mutation in the envelope protein gene (E1-A226V) of the Chikungunya virus was credited with allowing Aedes Albopictus or `Asian tiger’ mosquito to transmit the virus efficiently (see A Single Mutation in Chikungunya Virus Affects Vector Specificity and Epidemic Potential). 

 

An important development in that the `Asian tiger’ mosquito is both well distributed around the world, and that it is a very aggressive daytime biter.  

 

While most often found outdoors, research has shown that the Ae. albopictus lives longer, may exhibit increased nighttime biting activity, and produces more offspring when living in an indoor environment (see PLoS One Indoor-Breeding of Aedes albopictus in Northern Peninsular Malaysia and Its Potential Epidemiological Implications).

 

Although this particular study was set in Malaysia, the Aedes albopictus mosquito has made extensive inroads in the rest of the world over the past 40 years, and is considered one of the top 100 worst invasive species according to the Global Invasive Species Database.

Dark Blue indicates the A. Albopictus native range, while green indicates new introductions in last 40 years.

 

Having lived aboard a sailboat in the Florida keys around the Everglades,  I can assure you that well-fitted screens are your most important barrier against indoor mosquitoes.  Yet, despite your best efforts, some may still get inside. 

 

Since mosquito larvae can grow in as little as a tablespoon of water, it is important to consider indoor potted plants, and other places where stagnant water may exist, as well as outdoor breeding places.  Aedes mosquitoes have been been found breeding in such unusual places as Waterpiks, fridge trays, and seldom used toilets (according to the Miami Herald Mosquitoes carrying dengue fever can live indoors).

Source - Mosquito Control Measures CHIK (2.0 MB PDF)

 

Given the risks posed by Chikungunya and dengue (and that of other mosquito borne diseases in the U.S., like WNV, EEE, & SLEV), it makes sense to take proactive mosquito prevention steps to protect you and your family.

 

So today would be a good day to go around and look for likely breeding places in, and around your home. This should become a weekly habit – at least during mosquito season.

 

And to help you with warding off these pests, we’ve an interactive insect repellant search engine developed by the EPA that will that will allow you to input your needs and it will spit out the best repellants to use.

(click image to go to search engine)

 

And a final note, if you live in the United States (and this presumably is valid in other places as well), and you are seeing an unusual number of mosquitoes in your neighborhood, call your local mosquito control board and report it.  Quite often they will respond to your request by dispatching inspectors to look for, and eliminate, nearby breeding places.

JAMA: The 2012 West Nile Encephalitis Epidemic in Dallas, Tx

 

 

# 7487

Although West Nile Virus (WNV) activity was high across much of the country in 2012, the hardest hit area was Dallas County, Texas, where at least 19 people died from the severe form of this mosquito borne infection called Neuroinvasive West Nile Disease.

 

Mild cases – called West Nile Fever – often go undiagnosed, with probably only 2%-3% being identified. You’ll find some of my coverage of last year’s outbreak in Texas in the following blogs:

 

CDC Telebriefing on West Nile Virus

Updating the Texas West Nile Outbreak

Dallas West Nile Update

 

Nationally, the CDC reported last May:

 

Final 2012 West Nile virus update:

In 2012, all 48 contiguous states, the District of Columbia, and Puerto Rico reported West Nile virus infections in people, birds, or mosquitoes. A total of 5,674 cases of West Nile virus disease in people, including 286 deaths, were reported to CDC. Of these, 2,873 (51%) were classified as neuroinvasive disease (such as meningitis or encephalitis) and 2,801 (49%) were classified as non-neuroinvasive disease. The numbers of neuroinvasive, non-neuroinvasive, and total West Nile virus disease cases reported in 2012 are the highest since 2003.

 

 

It is estimated that only about 20% of the people who are infected with WNV develop symptoms, and the vast majority of those only experience a mild flu-like illness. Accordingly, mild, asymptomatic, or non-neuroinvasive infections are likely vastly undercounted.

 

The more severe `neuroinvasive’ form of WNV can produce symptoms that include headache, stiff neck, confusion, coma, convulsions, and even paralysis.

 

According to the CDC’s WEST NILE SYMPTOMS Q&A page.

 

What are the symptoms of West Nile virus disease?

No symptoms in most people. Most people (70-80%) who become infected with West Nile virus do not develop any symptoms.

 

Febrile illness in some people. About 1 in 5 people who are infected will develop a fever with other symptoms such as headache, body aches, joint pains, vomiting, diarrhea, or rash. Most people with this type of West Nile virus disease recover completely, but fatigue and weakness can last for weeks or months.

 

Severe symptoms in a few people. Less than 1% of people who are infected will develop a serious neurologic illness such as encephalitis or meningitis (inflammation of the brain or surrounding tissues). The symptoms of neurologic illness can include headache, high fever, neck stiffness, disorientation, coma, tremors, seizures, or paralysis.

 

Recovery from severe disease may take several weeks or months. Some of the neurologic effects may be permanent. About 10 percent of people who develop neurologic infection due to West Nile virus will die.

 

 

Which brings us to a research article (which you can read in its entirety) that appeared in JAMA yesterday on the Dallas epidemic, that finds correlations between an unusually mild winter, the early detection of WNV bearing mosquitoes, and the likelihood of seeing a major WNV outbreak.

 

 

The 2012 West Nile Encephalitis Epidemic in Dallas, Texas FREE

Wendy M. Chung, MD, SM¹; Christen M. Buseman, PhD, MPH¹; Sibeso N. Joyner, MPH¹; Sonya M. Hughes, MPH¹; Thomas B. Fomby, PhD⁴; James P. Luby, MD²; Robert W. Haley, MD³

Conclusions and Relevance Large West Nile virus epidemics in Dallas County begin early after unusually warm winters, revisit similar geographical distributions, and are strongly predicted by the mosquito vector index. Consideration of weather patterns and historical geographical hot spots and acting on the vector index may help prevent West Nile virus–associated illness.

 

The outbreak, which reached its peak in early August, was eventually brought under control after aerial spraying began in week 32 (see chart below).

 

Despite some initial public concerns over the use of aerial insecticides, surveillance of local emergency rooms did not detect any increase in ER visits for respiratory symptoms or rashes following airborne spraying.

 

In addition to the study you’ll find a short (4 minute) video by Dr. WM Chung, lead author of the study. 

 

 

 

Although it is too early in the summer to know what kind of WNV season 2013 will bring, the CDC’s DVBID reports the following activity:

 

Preliminary Maps & Data for 2013

As of July 9, 2013, 25 states and the District of Columbia have reported West Nile virus infections in people, birds, or mosquitoes. A total of 14 cases of West Nile virus disease in people, including two deaths, have been reported to CDC. Of these, five (36%) were classified as neuroinvasive disease (such as meningitis or encephalitis) and nine (64%) were classified as non-neuroinvasive disease.

 

 

Which is why health departments across the nation urge people to follow the `5 D’s’ of mosquito protection:

Florida: An Early Case Of EEE

 

Credit FL DOH

# 7031

 

 

Although much of the rest of the country has endured a long procession of bitter winter storms, Florida has enjoyed one of its milder winters in recent years. While great for tourists and residents alike, balmy winters make a great environment for mosquitoes as well.

 

Overnight, local media has been reporting on the EEE (Eastern Equine Encephalitis) infection of an 11 year-old boy from Hillsborough County (Tampa) which began (unusually, even for Florida) in February.

 

The boy – who is now recovered - spent three days in intensive care after apparently being bitten by an infected mosquito during a field trip to a local nature preserve (see local ABC News coverage).

 

This marks the first EEE case in Hillsborough County since 2010 (see Third Florida EEE Death in July).  In January of this year, another EEE case was reported in a Levy County resident (see Florida Arbovirus Surveillance Report).

 

EEE (Triple `E’) is an often serious, but exceedingly rare illness in humans.  It is one of more than 100 kinds of arbovirus (viruses transmitted by arthropods  e.g., Mosquitoes, sandflies, midges, or ticks).

 

According to the MMWR  (here), between 1999 and 2008 there were a median of seven (range: 3--21) EEE cases (not deaths) reported in the United States each year.

 

In addition to EEE, West Nile virus (WNV), La Crosse virus (LACV), and St. Louis encephalitis virus (SLEV) also circulate at low levels in the United States.

 

While the number of yearly cases is low, the distribution of EEE in the United States far ranging. Often, the heaviest EEE activity is reported in northern states.  

 

You may recall that last October, I blogged on the surprising role that snakes play in the ecology of the EEE virus (see A Disease Detective Story: Figuring Out Where EEE Spends The Winter).

 

To keep things in perspective, on average 58 people are struck and killed by lightning each year in the United States, and Bee stings account for an additional 40 deaths each year.

 

Which isn’t to minimize EEE or any of the other arboviruses, or to suggest that people not take precautions against mosquitoes, but is simply a reminder that a lot of the diseases we talk about in this column are pretty rare.

 

Hillsborough County Health Department has issued a mosquito advisory based on this most recent case.

 

Human Case of Eastern Equine Encephalitis Confirmed Mosquito-Borne Disease Advisory Issued for Hillsborough County

For Immediate Release
March 25, 2013

 

 

Compared to Dengue and West Nile Virus, the ecology and epidemiology of EEE is fairly complicated.

 

The natural host for the EEE virus are songbirds, which can become infected generally without suffering ill effect.  The virus is spread among these birds by the blood feeding of female mosquitoes (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 contains enough virus to infect subsequent mosquitoes that feed on it.

 

Culiseta melanura, which means "curly black hairs", is the species of swamp mosquito that serves as the primary vector for this virus among birds.

 

It, however, isn’t usually predisposed to d to biting humans.

 

So it generally 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.

 

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 a `dead-end host’.

 

For more on this fascinating topic, there’s an absolutely terrific multimedia presentation on arboviruses in Florida.

 

It is a narrated slide show, by Rebecca Shultz, the Arthropod-borne Disease Surveillance Coordinator for the Florida Department of Health, and it covers EEE, SLEV, and West Nile Virus.

 

The presentation runs just over 20 minutes.   The transcript is here.  Click the image below (or this link )to go to the slide show, and turn on your speakers.

 

Highly recommended.

 

 

2012 was a near-record year for West Nile Virus across the nation as well, which resulted in at least 5,387  confirmed cases, including 243 deaths(see DVBID: Final West Nile Report For 2012).

 

 

Which is why the State Health Departments around the nation continue to urge residents and visitors to follow the `5 D’s’:

 

PLoS One: Mosquitoes Less Deterred By DEET After Previous Exposure

 

# 6954

 

 

In May of 2010 in  From the `Nature Bats Last’ Dept, we looked at a PNAS study by James Logan et al. that looked at the reasons behind the small but growing number of mosquitoes that are not repelled by DEET - or N,N-Diethyl-m-toluamide.

Among some specially bred female Aedes aegypti mosquitoes, researchers found resistance to DEET to be caused by a single dominant gene, one that could be passed down to subsequent generations even if inherited from one parent.

 

Today, these same researchers are back with a new study that finds it doesn’t require a genetic change to reduce a mosquito’s susceptibility to DEET, all it really takes is time.

 

Roughly three hours.

 

 

Aedes aegypti Mosquitoes Exhibit Decreased Repellency by DEET following Previous Exposure

Nina M. Stanczyk, John F. Y. Brookfield, Linda M. Field, James G. Logan

Abstract

DEET (N,N-Diethyl-m-toluamide) is one of the most widely used mosquito repellents. Although DEET has been shown to be extremely effective, recent studies have revealed that certain individual insects are unaffected by its presence.

 

A genetic basis for this has been shown in Aedes aegypti mosquitoes and the fruit fly Drosophila melanogaster, but, for the triatomine bug, Rhodnius prolixus, a decrease in response to DEET occurred shortly after previous exposure, indicating that non-genetic factors may also be involved in DEET “insensitivity”.

 

In this study, we examined host-seeking behaviour and electrophysiological responses of A. aegypti after pre-exposure to DEET. We found that three hours after pre-exposure the mosquitoes showed behavioural insensitivity, and electroantennography revealed this correlated with the olfactory receptor neurons responding less to DEET.

 

The change in behaviour as a result of pre-exposure to DEET has implications for the use of repellents and the ability of mosquitoes to overcome them.

 

 

Follow the link to read the entire open-access study.  How long this acquired `resistance’ lasts in an exposed mosquito has not been determined.

 

Coming off a near-record setting year for West Nile Virus infections in the United States (see DVBID: Final West Nile Report For 2012), and with the continued  global spread of Dengue, Chikungunya, Malaria, Yellow Fever and other mosquito-borne pathogens, mosquito repellants are an important disease preventative.

 

In a press release from the Public Library of Science,  lead author James Logan explains further:

 

Mosquitoes exposed to DEET once are less repelled by it a few hours later

(EXCERPT)5

"Our study shows that the effects of this exposure last up to three hours. We will be doing further research to determine how long the effect lasts", says Logan.

<SNIP>

He adds, "This doesn't mean that we should stop using repellents - on the contrary, DEET is a very good repellent, and is still recommended for use in high risk areas. However, we are keeping a close eye on how mosquitoes can overcome the repellent and ways in which we can combat this."

The Risks Of Chikungunya Outbreaks In The United States

 

Credit Wikipedia

# 6855

 

 

Chikungunya, up until about a decade ago, was a little known mosquito-borne disease first described in Tanganyika in the early 1950s. For the next five decades it was sporadically seen across eastern and central Africa.

 

That is, until 2005, when Chikungunya made a surprise jump to the Indian Ocean island of Réunion. There, it infected nearly 1/3rd of the island’s 770,000 residents (see 2006 EID article Chikungunya Disease Outbreak, Reunion Island) in just a matter of months.

 

Chikungunya typically produces a fever, severe muscle and joint pain, and headaches. The symptoms usually go away after a few weeks, but some patients can sustain permanent disability, and some deaths have been reported.

 

In the eight years since that  jump, `Chik’ has spread further across the Indian Ocean, Southeast Asia, and even briefly into northern Italy.

 

While the virus isn't normally found in Europe, the vector, the Aedes mosquito, is.  All it took was one infected traveler to arrive infected with the virus to start the chain of transmission.

 

 

I told the story several years ago in It's A Smaller World After All, but the short version is that a traveler, returning from India, brought the virus to Italy in 2007 which led to more than 290 cases reported in the province of Ravenna, which is in northeast Italy.

 

The concern is that the same sort of introduction could happen elsewhere in Europe, or here in the United States, just as we saw with West Nile Virus in 1999 (see DVBID: Final West Nile Report For 2012) and with Dengue Fever in 2010 (see MMWR: Dengue Fever In Key West)

 

The two primary mosquito vectors of Chikungunya are the Aedes aegypti and Aedes albopictus (cite WHO FAQ) both of which can be found across many regions of the Americas.

Aedes albopictus (Asian Tiger) Mosquito - Wikipedia

Dark blue: Native range
Dark green: introduced (as of December 2007)

 

The risk is considered great enough that early last year, the CDC and PAHO (Pan American Health Organization) put together a 161-page guide on preparing for the arrival of Chikungunya to the Americas (see Preparedness and Response for Chikungunya Virus Introduction in the Americas).

 

All of which serves as prelude to a report that appeared last month in PloS Neglected Tropical Diseases called:

 

Modeling Dynamic Introduction of Chikungunya Virus in the United States

Abstract (reparagraphed for readability)

Chikungunya is a mosquito-borne viral infection of humans that previously was confined to regions in central Africa. However, during this century, the virus has shown surprising potential for geographic expansion as it invaded other countries including more temperate regions.

 

With no vaccine and no specific treatment, the main control strategy for Chikungunya remains preventive control of mosquito populations. In consideration for the risk of Chikungunya introduction to the US, we developed a model for disease introduction based on virus introduction by one individual. Our study combines a climate-based mosquito population dynamics stochastic model with an epidemiological model to identify temporal windows that have epidemic risk. We ran this model with temperature data from different locations to study the geographic sensitivity of epidemic potential.

 

We found that in locations with marked seasonal variation in temperature there also was a season of epidemic risk matching the period of the year in which mosquito populations survive and grow. In these locations controlling mosquito population sizes might be an efficient strategy.

 

But, in other locations where the temperature supports mosquito development all year the epidemic risk is high and (practically) constant. In these locations, mosquito population control alone might not be an efficient disease control strategy and other approaches should be implemented to complement it.

 

Our results strongly suggest that, in the event of an introduction and establishment of Chikungunya in the US, endemic and epidemic regions would emerge initially, primarily defined by environmental factors controlling annual mosquito population cycles. These regions should be identified to plan different intervention measures.

In addition, reducing vector: human ratios can lower the probability and magnitude of outbreaks for regions with strong seasonal temperature patterns. This is the first model to consider Chikungunya risk in the US and can be applied to other vector borne diseases.

(Continue . . . )

 

More background on this modeling study is available from the Cornell University Press Office.

 

 

Chances seen rising for chikungunya outbreaks in NYC, Atlanta, Miami

ITHACA, N.Y. – Global travel and climate warming could be creating the right conditions for outbreaks of a new virus in this country, according to a new Cornell University computer model.

 

The model predicts that outbreaks of chikungunya, a painful virus transported by travelers and spread by the invasive Asian tiger mosquito, could occur in 2013 in New York City during August and September, in Atlanta from June through September, and year-round in Miami. The probability of a disease outbreak is correlated with temperature, as warmer weather allows the Asian tiger mosquito to breed faster and grow in numbers, according to the study published in the November issue of PLOS Neglected Tropical Diseases.

 

According to the simulation, there is a high probability of a chikungunya outbreak if a single infected person arrives in New York in July or August and is bitten by an Asian tiger mosquito. The risks are the same, but with wider time frames, for transmission in Atlanta and Miami, according to the paper.

 

Asian tiger mosquitoes were introduced to the United States in Texas in the 1980s; they are established up the East Coast into New Jersey and are rising in numbers in New York City. The aggressive mosquito outcompetes local varieties and transmits more than 20 pathogens, including chikungunya and dengue, said Laura Harrington, associate professor of entomology and the study’s senior author.

 

“The virus is moving in people, and resident mosquito populations are picking it up,” Harrington said.

 

The model estimates that with typical regional temperatures, a chikungunya outbreak in New York would infect about one in 5,000 people, said Diego Ruiz-Moreno, a postdoctoral associate and the paper’s lead author

 

“However, this number would increase drastically as temperatures rise due to climate change,” Ruiz-Moreno said.

(Continue . . . )

 

While this study focused on Chikungunya, much the same could be said about the potential for seeing Dengue, Malaria, or even Yellow Fever making inroads in the United States and Europe. 

 

In March of 2010 the journal  Eurosurveillance carried a series of articles on vector borne diseases and their potential to impact those living in Europe. One of the articles, Yellow fever and dengue: a threat to Europe? by P. Reiter, had these sobering comments about the future of vector-borne illnesses in Europe.

 

The history of dengue and yellow fever in Europe is evidence that conditions are already suitable for transmission. The establishment of Ae. albopictus has made this possible, and the possibility will increase as the species expands northwards, or if Ae. aegypti is re-established.

 

The epidemic of chikungunya in northern Italy in 2007 [8,49] confirms that Ae. albopictus is capable of supporting epidemic transmission, although laboratory studies indicate that the strain of virus involved was particularly adapted to this species [50,51].

 

Nevertheless, it is not unreasonable to assume that climatic conditions that permit malaria transmission will also support transmission of yellow fever and dengue, in which case transmission could extend into northern Europe [52].

 

Reason enough that if you live in - or are visiting  - a mosquito prone area, to remember to follow the `5 D’s’  (courtesy Florida Department of Health).

 

DVBID: Final West Nile Report For 2012

 

# 6779

 

While final numbers won’t be available until the spring, 2012 looks like it will go down as one of the most active West Nile Fever seasons since the virus arrived in North America in 1999.

 

The CDC’s  DVBID has released their final tally of cases for 2012 on their West Nile Update Page.  They summarize the season thusly:

 

2012 West Nile virus update: December 11

This will be the last update for 2012 until final data are available in the spring of 2013.

As of December 11, 2012, 48 states have reported West Nile virus infections in people, birds, or mosquitoes. A total of 5,387 cases of West Nile virus disease in people, including 243 deaths, have been reported to CDC. Of these, 2,734 (51%) were classified as neuroinvasive disease (such as meningitis or encephalitis) and 2,653 (49%) were classified as non-neuroinvasive disease.

 

The 5,387 cases reported thus far in 2012 is the highest number of West Nile virus disease cases reported to CDC through the second week in December since 2003. Eighty percent of the cases have been reported from 13 states (Texas, California, Louisiana, Illinois, Mississippi, South Dakota, Michigan, Oklahoma, Nebraska, Colorado, Arizona, Ohio, and New York) and a third of all cases have been reported from Texas.

 

Neuroinvasive cases (which present with meningitis, encephalitis, or flaccid Paralysis) are severe enough that they result in hospitalization and diagnosis, and so they are considered the best indicator of the scope of each year’s epidemic.

 

Mild cases – called West Nile Fever – often go undiagnosed, with probably only 2%-3% being identified.

 

Meaning that with more than 2,600 mild cases reported, the true incidence was probably in excess of 100,000 infections.

Hardest hit this year was Texas, with more than 1,700 cases and 76 deaths. Far behind, but in second place, was California with 461 cases and 16 deaths. 

 

Nevertheless, the highest incidence of neuroinvasive disease occurred along the Gulf Coast and into the upper Mid West.

 

 

Earlier this year the CDC indicated they would be taking a look at this year’s WNV season to see if any changes have occurred in the virus to account for this sudden spike in activity. 

 

While West Nile season has passed for most of the country, there are still a few areas where mosquitoes are still active.  So, if you live in, or are visiting one of these areas, the advice by many health departments to follow the `5 D’s’ remains intact. 

Dengue Update: Puerto Rico, Florida & The Americas

 

# 6702

 

While not reaching the levels we saw during their 2010 Dengue epidemic, Puerto Rico is once again seeing epidemic levels of the mosquito-borne virus, as evidenced by this latest chart from the CDC.  

 

As indicated by the red line, the number of cases over the past couple of weeks has been climbing like a homesick angel. 

 

Health Secretary Lorenzo Gonzalez of the Puerto Rico Health Department declared a Dengue epidemic on the island (PDF Link – in Spanish) in early October after six people died or the disease, two of them children.

 

This week, Florida also reported its third locally acquired Dengue case (see Another Central Florida dengue case confirmed) of 2012. This latest case was identified in Osceola County, and a fourth suspected case is being investigated.

 

While once a serious problem in Florida, through aggressive mosquito control efforts during the 1940s Dengue and Malaria were both eliminated from the Sunshine State – and remained so for nearly a half century.

 

In 2009 – for the first time in more than 50 years – we started to see a small number of locally acquired Dengue cases showing up in Key West (see MMWR: Dengue Fever In Key West), and in 2010 they totaled 65 cases in Key West and 1 each in Broward and Miami-Dade County.

 

The number of cases dropped in 2011, and have been low once again in 2012.

 

The concern is - with millions of visitors arriving each year, many from regions where these diseases are endemic – there are plenty of opportunities to re-introduce the virus.

 

The CDC’s MMWR in a report in May of 2010 on Locally Acquired Dengue in Key West, had this to say:

 

Cases of dengue in returning U.S. travelers have increased steadily during the past 20 years (8). Dengue is now the leading cause of acute febrile illness in U.S. travelers returning from the Caribbean, South America, and Asia (9).

 

Many of these travelers are still viremic upon return to the United States and potentially capable of introducing dengue virus into a community with competent mosquito vectors.

 

In truth, it may take many such introductions of Dengue or Malaria to an area before the right combination of weather, insect vectors, and ongoing transmission occur to enable it to get a foothold in a community.

 

But Florida’s latest Arbovirus Surveillance report lists more than 90 cases of Imported Dengue this year:

 

Ninety-four cases of dengue with onset in 2012 have been reported in individuals with travel history to a dengue endemic country in the two weeks prior to onset. Countries of origin were Brazil, Colombia, Cuba (21), Dominican Republic (9), Ecuador (4), El Salvador (2), Ghana, Guyana (2), Haiti (14), Honduras, India, Jamaica (17), Mexico (2), Nicaragua, Panama, Philippines, Puerto Rico (6), South Africa, Sri Lanka, St. Vincent, Suriname, Trinidad (4), and Turks & Caicos.

Counties reporting cases were Brevard (3), Broward (17), Collier, Duval (2), Hillsborough (4), Lee (2), Marion, Miami-Dade (36), Orange (12), Palm Beach (6), Pinellas (2), Polk, Sarasota (2), Seminole (3), and Volusia (2). Nine of the cases were reported in non-Florida residents.

 

The state has also reported more than 50 cases of Imported Malaria, although no locally acquired cases have been reported.

 

Fifty-three imported cases of malaria with onset in 2012 have been reported.  Countries of origin were: Afghanistan (2), Cameroon, Central African Republic, Colombia, Costa Rica, Ethiopia, Ghana (5), Guyana (2), Haiti (9), Honduras (3), India, Ivory Coast (3), Kenya, Liberia (2), Nigeria (8), Pakistan, Peru, Sierra Leone (2), South Africa, Sub Saharan Africa, Sudan, Togo, Uganda, Zambia, and multiple African countries (2).

Counties reporting cases were: Alachua, Brevard, Broward (8), Charlotte, Duval (6), Hillsborough (6), Lake (2), Leon, Manatee, Marion, Martin, Miami-Dade (7), Orange (5), Osceola (2), Palm Beach (4), Pinellas (3), Polk, Seminole, and Volusia. Five of the cases were reported in non-Florida residents.

 

A broader perspective comes from PAHO, who's Oct 31st update shows nearly 1 million cases of Dengue in the Americas this year.

 

An interactive map view of Dengue activity in the Americas, and around the world, can be seen via the CDC-Healthmap collaborative DengueMap.

 

 

Although the overall risk of contracting a mosquito-borne illness in Florida or Puerto Rico remains very small, reports of Dengue (along with West Nile, EEE, SLEV, and other rare arboviral threats) are reason enough that health departments continue to urge people to remember to follow the `5 D’s’:

 

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 

ABSTRACT

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)