Eastern Equine #Encephalitis Virus [#EEEV] — Another Emergent #Arbovirus in the #US (N Engl J Med., summary)

[Source: The New England Journal of Medicine, full page: (LINK). Summary, edited.]

Eastern Equine Encephalitis Virus — Another Emergent Arbovirus in the United States

David M. Morens, M.D., Gregory K. Folkers, M.S., M.P.H., and Anthony S. Fauci, M.D.


Humans have always lived in intimate association with arthropods that transmit pathogens between humans or from animals to humans. About 700,000 deaths due to vectorborne diseases occur globally each year, according to World Health Organization estimates. In the summer and fall of 2019, nine U.S. states have reported 36 human cases (14 of them fatal) of one of the deadliest of these diseases: eastern equine encephalitis (EEE), an arthropod-borne viral (arboviral) disease transmitted by mosquitoes. In recent years, the Americas have witnessed a steady stream of other emerging or reemerging arboviruses, such as dengue, West Nile, chikungunya, Zika, and Powassan, as well as increasing numbers of travel-related cases of various other arboviral infections. This year’s EEE outbreaks may thus be a harbinger of a new era of arboviral emergences.



Disclosure forms provided by the authors are available at NEJM.org.

Author Affiliations: From the Office of the Director, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.

Keywords: Arbovirus; Alphavirus; Eastern Equine Encephalitis Virus; USA; Moquitoes.


Emergence of #Madariaga virus as a cause of acute febrile #illness in #children, #Haiti, 2015-2016 (PLoS Negl Trop Dis., abstract)

[Source: PLoS Neglected Tropical Diseases, full page: (LINK). Abstract, edited.]


Emergence of Madariaga virus as a cause of acute febrile illness in children, Haiti, 2015-2016

John A. Lednicky, Sarah K. White, Carla N. Mavian, Maha A. El Badry, Taina Telisma, Marco Salemi, Bernard A. OKech, V. Madsen Beau De Rochars, J. Glenn Morris Jr.

Published: January 10, 2019 / DOI: https://doi.org/10.1371/journal.pntd.0006972



Madariaga virus (MADV), also known as South American eastern equine encephalitis virus, has been identified in animals and humans in South and Central America, but not previously in Hispaniola or the northern Caribbean. MADV was isolated from virus cultures of plasma from an 8-year-old child in a school cohort in the Gressier/Leogane region of Haiti, who was seen in April, 2015, with acute febrile illness (AFI). The virus was subsequently cultured from an additional seven AFI case patients from this same cohort in February, April, and May 2016. Symptoms most closely resembled those seen with confirmed dengue virus infection. Sequence data were available for four isolates: all were within the same clade, with phylogenetic and molecular clock data suggesting recent introduction of the virus into Haiti from Panama sometime in the period from October 2012-January 2015. Our data document the movement of MADV into Haiti, and raise questions about the potential for further spread in the Caribbean or North America.


Author summary

Madariaga virus (MADV) is the name given to what used to be called South American eastern equine encephalitis virus (EEEV), based on recent studies suggesting that MADV is distinct genetically from the EEEV circulating in North America. Until now, MADV has been found primarily in animals in South and Central America, with a limited number of human cases reported (most of whom had encephalitis). Our group has been responsible for a series of studies assessing the etiology of acute febrile illness (AFI) among children in a school cohort in Haiti. Unexpectedly, in April, 2015, we identified MADV on viral culture of plasma from a student with AFI in this cohort; an additional seven cases were identified on culture of samples from children with AFI in this same cohort in February, April, and May 2016. On sequence analysis, all strains were very similar genetically, and appear to have come from a strain introduced into Haiti from Panama sometime in the period from October 2012- January 2015. Symptoms of children were similar to those seen with dengue; none had encephalitis. Our data indicate that this virus, which has the potential for causing serious illness, has been recently introduced into Haiti, and raises the possibility that it might move into other parts of the Caribbean or North America.


Citation: Lednicky JA, White SK, Mavian CN, El Badry MA, Telisma T, Salemi M, et al. (2019) Emergence of Madariaga virus as a cause of acute febrile illness in children, Haiti, 2015-2016. PLoS Negl Trop Dis 13(1): e0006972. https://doi.org/10.1371/journal.pntd.0006972


Received: August 7, 2018; Accepted: November 3, 2018; Published: January 10, 2019

Copyright: © 2019 Lednicky et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the manuscript and its supporting information files. Private health information for patients is excluded, and cannot be provided due to IRB restrictions.

Funding: Work was supported in part by NIH grant R01 AI126357-01S1, awarded to JGM. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

Keywords: Eastern Equine Encephalitis Virus; Madariaga Virus; Haiti.


Novel #insect-specific #Eilat virus-based chimeric #vaccine candidates provide durable, mono- and multi-valent, single dose protection against lethal #alphavirus challenge (J Virol., abstract)

[Source: Journal of Virology, full page: (LINK). Abstract, edited.]

Novel insect-specific Eilat virus-based chimeric vaccine candidates provide durable, mono- and multi-valent, single dose protection against lethal alphavirus challenge

Jesse H. Erasmus1, Robert L. Seymour1, Jason T. Kaelber2, Dal Y. Kim3, Grace Leal1, Michael B. Sherman1, Ilya Frolov3, Wah Chiu2, Scott C. Weaver1* and Farooq Nasar1,4*

Author Affiliations: 1 Institute for Human Infections and Immunity, Center for Tropical Diseases, and Department of Microbiology and Immunology, Center for Structural Biology and Molecular Biophysics, Department of Biochemistry and Molecular Biology University of Texas Medical Branch, Galveston, Texas, USA. 2 National Center for Macromolecular Imaging, Verna and Marrs McLean Department of Biochemistry and Molecular Biology, and Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA. 3 Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA; 4 Virology Division, United States Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Frederick, MD 21702, USA



Most alphaviruses are mosquito-borne and exhibit a broad host range, infecting many different vertebrates including birds, rodents, equids, humans and nonhuman primates. Recently, a host-restricted, mosquito-borne alphavirus, Eilat virus (EILV), was described with an inability to infect vertebrate cells based on defective attachment and/or entry as well as a lack of genomic RNA replication. We investigated the utilization of EILV recombinant technology as a vaccine platform against eastern (EEEV) and Venezuelan equine encephalitis viruses (VEEV), two important pathogens of humans and domesticated animals. EILV chimeras containing structural proteins of EEEV or VEEV were engineered and successfully rescued in Aedes albopictus cells. Cryo-EM reconstructions at 8 and 11 Å of EILV/VEEV and EILV/EEEV, respectively, showed virion and glycoprotein spike structures similar to VEEV-Tc83 and other alphaviruses. The chimeras were unable to replicate in vertebrate cell lines or in brains of newborn mice when injected intracranially. Histopathologic examinations of the brain tissues showed no evidence of pathologic lesions, and were indistinguishable from those of mock-infected animals. A single-dose immunization of either monovalent or multivalent EILV chimera(s) generated neutralizing antibody responses and protected animals against lethal challenge 70 days later. Lastly, a single dose of monovalent EILV chimeras generated protective responses as early as day 1 post-vaccination, and partial or complete protection by day 6. These data demonstrate the safety, immunogenicity, and efficacy of novel insect-specific EILV-based chimeras as potential EEEV and VEEV vaccines.



Mostly in the last decade, insect-specific viruses have been discovered in several arbovirus families. However, most of these viruses are not well studied and largely have been ignored. We explored use of the mosquito-specific alphavirus, Eilat virus (EILV), as an alphavirus vaccine platform in well-established disease models for eastern (EEE) and Venezuelan equine encephalitis (VEE). EILV-based chimeras replicated to high titers in a mosquito cell line, yet retained their host range restriction in vertebrates both in vitro and in vivo. In addition, the chimeras generated immune responses that were higher than other human and/or equine vaccines. These findings indicate the feasibility of producing a safe, efficacious, mono- or multi-valent vaccine against the encephalitic alphaviruses, VEEV and EEEV. Lastly, these data demonstrate how host restricted, insect-specific viruses can be engineered to develop vaccines against related pathogenic arboviruses that cause severe disease in humans and domesticated animals.



*Corresponding authors: Scott C. Weaver, Mailing address: University of Texas Medical Branch, 301 University Blvd., Galveston, TX 77555-0609., Phone: (409) 747-0758. Fax: (409) 747-2429., E-mail: sweaver@utmb.edu

*Farooq Nasar, Mailing address: United States Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Frederick, MD 21702, Phone: (301)-619-1317., Email: fanasar@icloud.com

Copyright © 2017 American Society for Microbiology. All Rights Reserved.

Keywords: Arbovirus; Alphavirus; Eilat Virus; Eastern Equine Encephalitis Virus; Venezuelan Equine Encephalitis Virus.


Seasonal #Patterns in Eastern #Equine #Encephalitis Virus #Antibody in #Songbirds in Southern #Maine (Vector Borne Zoo Dis., abstract)

[Source: Vector Borne and Zoonotic Diseases, full page: (LINK). Abstract, edited.]

Vector-Borne and Zoonotic Diseases

Seasonal Patterns in Eastern Equine Encephalitis Virus Antibody in Songbirds in Southern Maine

To cite this article: Elias Susan P., Keenan Patrick, Kenney Joan L., Morris Sara R., Covino Kristen M., Robinson Sara, Foss Kimberly A., Rand Peter W., Lubelczyk Charles, Lacombe Eleanor H., Mutebi John-Paul, Evers David, and Smith Robert P. Jr.. Vector-Borne and Zoonotic Diseases. March 2017, ahead of print. doi:10.1089/vbz.2016.2029.

Online Ahead of Print: March 13, 2017

Author information: Susan P. Elias,1 Patrick Keenan,2 Joan L. Kenney,3 Sara R. Morris,4,5 Kristen M. Covino,4,5,6 Sara Robinson,7 Kimberly A. Foss,8 Peter W. Rand,1 Charles Lubelczyk,1 Eleanor H. Lacombe,1 John-Paul Mutebi,3 David Evers,2 and Robert P. Smith Jr.1

1Vector-borne Disease Laboratory, Maine Medical Center Research Institute, Scarborough, Maine. 2Biodiversity Research Institute, Portland, Maine. 3Centers for Disease Control and Prevention, Fort Collins, Colorado. 4Department of Biology, Canisius College, Buffalo, New York. 5Shoals Marine Laboratory, Portsmouth, New Hampshire. 6Department of Biological Sciences, University of Southern Mississippi, Hattiesburg, Mississippi. 7Maine Center for Disease Control and Prevention, Augusta, Maine. 8SWAMP, Inc., Newington, New Hampshire.

Address correspondence to: Susan P. Elias, Vector-borne Disease Laboratory, Maine Medical Center Research Institute, 81 Research Drive, Scarborough, ME 04074, E-mail: eliass@mmc.org



The intent of this study was to assess passerine eastern equine encephalitis virus (EEEv) seroprevalence during the breeding season in southern Maine by testing songbird species identified in the literature as amplifying hosts of this virus. In 2013 and 2014, we collected serum samples from songbirds at a mainland site and an offshore island migratory stopover site, and screened samples for EEEv antibodies using plaque reduction neutralization tests. We compared seasonal changes in EEEv antibody seroprevalence in young (hatched in year of capture) and adult birds at the mainland site, and also compared early season seroprevalence in mainland versus offshore adult birds. EEEv seroprevalence did not differ significantly between years at either site. During the early season (May), EEEv antibody seroprevalence was substantially lower (9.6%) in the island migrant adults than in mainland adults (42.9%), 2013–2014. On the mainland, EEEv antibody seroprevalence in young birds increased from 12.9% in midseason (June–August) to 45.6% in late season (September/October), 2013–2014. Seroprevalence in adult birds did not differ between seasons (48.8% vs. 53.3%). EEEv activity in Maine has increased in the past decade as measured by increased virus detection in mosquitoes and veterinary cases. High EEEv seroprevalence in young birds—as compared to that of young birds in other studies—corresponded with two consecutive active EEEv years in Maine. We suggest that young, locally hatched songbirds be sampled as a part of long-term EEEv surveillance, and provide a list of suggested species to sample, including EEEv “superspreaders.”

Keywords: Eastern Equine Encephalitis; Wild Birds; USA; Maine.

Recombinant #Isfahan virus and #VSV #vectors provide durable, multivalent, single dose #protection against lethal #alphavirus challenge (J Virol., abstract)

[Source: Journal of Virology, full page: (LINK). Abstract, edited.]

Recombinant Isfahan virus and vesicular stomatitis virus vaccine vectors provide durable, multivalent, single dose protection against lethal alphavirus challenge

Farooq Nasar1*, Demetrius Matassov3, Robert L. Seymour1, Theresa Latham3, Rodion V. Gorchakov4, Rebecca M Nowak3, Grace Leal1, Stefan Hamm3, John H. Eldridge3, Robert B. Tesh1, David K. Clarke3 and Scott C. Weaver1*

Author Affiliations: 1Institute for Human Infections and Immunity, Center for Tropical Diseases, and Departments of Pathology and Microbiology & Immunology, University of Texas Medical Branch, Galveston, Texas, 77555, USA. 3Profectus BioSciences Inc., 777 Old Saw Mill River Road, Tarrytown, New York 10591, USA; 4Department of Pediatrics, Section of Tropical Medicine, Baylor College of Medicine, Houston, Texas 77030, USA.



The demonstrated clinical efficacy of a recombinant vesicular stomatitis virus (rVSV) vaccine vector has stimulated the investigation of additional serologically distinct Vesiculovirus vectors as therapeutic and/or prophylactic vaccine vectors to combat emerging viral diseases. Amongst these viral threats are encephalitic alphaviruses, Venezuelan and eastern equine encephalitic viruses (VEEV, EEEV), which have demonstrated potential for natural disease outbreaks, yet no licensed vaccines are available in the event of an epidemic. Here we report rescue of recombinant Isfahan virus (rISFV) from genomic cDNA as a potential new vaccine vector platform. The rISFV genome was modified to attenuate virulence and engineered to express VEEV and EEEV E2/E1 surface glycoproteins as vaccine antigens. A single dose of the rISFV vaccine vectors elicited neutralizing antibody responses and protected mice from lethal VEEV and EEEV challenge at one month post-vaccination as well as lethal VEEV challenge at eight months post-vaccination. A mixture of rISFV vectors expressing VEEV and EEEV E2/E1 glycoproteins also provided durable, single-dose protection from lethal VEEV and EEEV challenge, demonstrating the potential for a multivalent vaccine formulation. These findings were paralleled in studies with an attenuated form of rVSV expressing VEEV E2/E1 glycoproteins. Both rVSV and rISFV vectors were attenuated using an approach which has demonstrated safety in human trials of an rVSV/HIV-1 vaccine. Vaccines based on either of these vaccine vector platforms may present a safe and effective approach to prevent alphavirus induced disease in humans.



This work introduces rISFV as a novel vaccine vector platform that is serologically distinct and phylogenetically distant from VSV. The rISFV vector has been attenuated by an approach used for an rVSV vector that has demonstrated safety in clinical studies. The vaccine potential of the rISFV vector was investigated in a well-established alphavirus disease model. The findings indicate the feasibility of producing a safe, efficacious, multivalent vaccine against the encephalitic alphaviruses VEEV and EEEV, both of which can cause fatal disease. The work also demonstrates efficacy of an attenuated rVSV vector that has already demonstrated safety and immunogenicity in multiple HIV-1 Phase I clinical studies. The absence of serological cross-reactivity between rVSV and rISFV and their phylogenetic divergence within the Vesiculovirus genus indicates potential for two stand-alone vaccine vector platforms that could be used to target multiple bacterial and/or viral agents in successive immunization campaigns, or as heterologous prime-boost agents.



*Corresponding authors: Farooq Nasar, Mailing address: United States Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Frederick, MD 21702, Phone: (301)-619-1317. Email: fanasar@icloud.com;

*Scott C. Weaver, Mailing address: University of Texas Medical Branch, 301 University Blvd., Galveston, TX 77555-0610., Phone: (409) 747-0758. Fax: (409) 747-2429. 35, E-mail: sweaver@utmb.edu

Copyright © 2017 American Society for Microbiology. All Rights Reserved.

Keywords: Alphavirus; Eastern Equine Encephalitis Virus; Venezuelan Encephalitis Virus.


Locally Acquired Eastern #Equine #Encephalitis Virus Disease, #Arkansas, #USA (@CDC_EIDjournal, extract)

[Source: US Centers for Disease Control and Prevention (CDC), Emerging Infectious Diseases Journal, full page: (LINK). Extract, edited.]

Volume 22, Number 12—December 2016 / Letter

Locally Acquired Eastern Equine Encephalitis Virus Disease, Arkansas, USA


To the Editor:

Eastern equine encephalitis virus (EEEV) is an arbovirus (family Togaviridae, genus Alphavirus) transmitted to humans primarily from Aedes, Coquillettidia, and Culex mosquitoes. EEEV is maintained in a transmission cycle between Culiseta melanura mosquitoes and birds in freshwater hardwood swamps (1). Affected humans and horses are considered to be dead-end hosts; that is, they usually do not develop sufficient levels of viremia to infect mosquitoes. Although human EEEV disease is rare, it has a case-fatality rate of >30% and >50% of survivors may have permanent neurologic sequelae (2–5). Cases occur sporadically each year, primarily along the eastern and Gulf coasts of North America, but no cases have been previously reported in Arkansas (1). We report a locally acquired case of human EEEV disease in Arkansas.



Suggested citation for this article: Garlick J, Lee TJ, Shepherd P, Linam WM, Pastula DM, Weinstein S, et al. Locally acquired eastern equine encephalitis virus disease, Arkansas, USA [letter]. Emerg Infect Dis. 2016 Dec [date cited]. http://dx.doi.org/10.3201/eid2212.160844

DOI: 10.3201/eid2212.160844

Keywords: Research; Abstracts; USA; Arkansas; Eastern Equine Encephalitis; Alphavirus.


#Geography and #Timing of #Cases of Eastern Equine #Encephalitis [#EEE] in #NewYork #State from 1992 to 2012 (Vector Borne Zoo Dis., abstract)

[Source: Vector Borne and Zoonotic Diseases, full page: (LINK). Abstract, edited.]

Vector-Borne and Zoonotic Diseases

Geography and Timing of Cases of Eastern Equine Encephalitis in New York State from 1992 to 2012  [      ]

To cite this article: Oliver JoAnne, Lukacik Gary, Kramer Laura D., Backenson P. Bryon, Sherwood James A., and Howard John J.. Vector-Borne and Zoonotic Diseases. February 2016, ahead of print. doi:10.1089/vbz.2015.1864.

Online Ahead of Print: February 22, 2016




In New York State (NYS), Eastern equine encephalitis (EEE) was first reported in a human in 1971, in horses in 1970, and in pheasants in 1952.

Material and Method:

Following work for the interval from 1970 to 1991, we identified cases in vertebrates from 1992 to 2012, through a passive surveillance system involving veterinarians in clinical practice, county health departments, and the Departments of Agriculture and Markets, Environmental Conservation, and Health, of the State of New York.


During an 11-year hiatus, from 1992 to 2002, no case in any vertebrate was observed. In a re-emergence, from 2003 to 2012, disease occurred in 12 counties, including 7 counties where disease had never been documented. Vertebrate cases included 4 cases in humans and 77 nonhuman occurrences; in 58 horses, Equus ferus caballus L.; 2 deer, Odocoileus virginianus Zimmermann; 6 dogs, Canis familiaris; 10 birds; and 1 flock of pheasants, Phasianus colchicus L. These were the first reported cases in NYS in white-tailed deer, the domestic dog, and in five species of birds: American crow, Corvus brachyrhynchos Brehm; American goldfinch, Carduelis tristis L.; bald eagle, Haliaeetus leucocephalus L.; blue jay, Cyanocitta cristata (L.); and red-tailed hawk, Buteo jamaicensis Gmelin. One crow was dually infected with EEE virus and West Nile virus. The northern, southern, and southeastern borders of the state were newly affected.


The geographic area, time periods, and vertebrate species with risk of EEE disease expanded from 1992 to 2012.

Keywords: Research; Abstracts; USA; New York; Eastern Equine Encephalitis.


#Maine #CDC Announces Eastern #Equine #Encephalitis #Death (DoH, Nov. 24 ‘15)

[Source: US State of Maine Department of Health, full page: (LINK).]

Press Release /  November 24, 2015

Maine CDC Announces Eastern Equine Encephalitis Death [      ]

This is Maine’s first-ever human death due to EEE.


Maine Center for Disease Control and Prevention announced today that a mature adult (age 65 or above) from York County who died on October 17 was confirmed to have Eastern Equine Encephalitis (EEE). This marks the first death ever from EEE in Maine.

This individual became ill with encephalitis in late September and was hospitalized in New Hampshire on September 30.

Preliminary testing in early October by New Hampshire’s public health laboratory was inconclusive and the sample was sent to the federal CDC in Fort Collins, Colorado for confirmation.

Maine CDC received the positive results late last week.

“Our hearts go out to the family during this difficult time,’’ said State Epidemiologist Siiri Bennett “As this disease is transmitted through a bite from an infected mosquito it’s important for Mainers to know that there is no current risk of EEE in Maine as there are no active mosquitos.”

EEE is a deadly illness.

One in every three individuals who are infected die, though many persons infected with EEE will have no obvious symptoms.

In those persons who develop illness, symptoms range from mild flu- like illness to inflammation of the brain, coma and death.

Maine has many resources regarding mosquito-borne diseases:

–> Short videos on mosquito-borne diseases, mosquito habitat, and repellent use are available at http://www.maine.gov/dhhs/mecdc/infectious-disease/epi/videos.shtml or through Maine CDC’s YouTube channel https://www.youtube.com/user/MainePublicHealth

–> Maine CDC’s vectorborne disease website http://www.maine.gov/dhhs/mecdc/infectious-disease/epi/vector-borne/index.shtml also offers additional information.

Keywords: USA; Updates; Maine; Eastern Equine Encephalitis; Viral Encephalitis; Human.