acvim medical forum 2002

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ACVIM MEDICAL FORUM 2002 The American College of Veteri- nary Internal Medicine (ACVIM) held their 20th Medical Forum May 29 to June 1, 2002, in Dallas, TX. A major topic in the equine sessions was the West Nile Virus (WNV). Three papers were presented on the subject. Since then, it has become evident that WNV will soon be endemic in the entire United States if not this year, at least by next season. WNV Disease Dr. Maureen T. Long, from the Uni- versity of Florida, described the virus and the disease. Until the outbreak in New York in 1999, WNV had been known only in Europe, Asia, Africa, and the South Pacific. In those localities in which the disease has historically oc- curred, detection of infected birds coin- cides with both human and equine cases. This has been true in the United States where the spread from New York into adjacent states has been signaled with the death of many birds found positive for the virus. As the disease has spread across the country, WNV has become endemic in many areas. Dr. Eileen N. Ostlund, from the Na- tional Veterinary Services Laboratory (NVSL), in Ames, IA, chronicled the spread of WNV since the initial out- break. WNV has overwintered twice and has significantly broadened its geo- graphic range. “During 2002, evidence of local WNV activity was found in 12 northeast- ern and mid-Atlantic states from New Hampshire and Vermont to North Caro- lina, plus the District of Columbia,” said Dr. Ostlund. “Although there were only 21 human cases of West Nile encephali- tis that year, 60 horses had confirmed cases of West Nile encephalitis. Affected horses were in seven states: Connecticut, Delaware, Massachusetts, New York, New Jersey, Pennsylvania, and Rhode Island.” She noted that by 2001, WNV posi- tive birds and/or mosquitoes were identi- fied in nearly every state in the eastern half of the country. Positive birds and/or mos- Copyright 2002, Elsevier Science (USA). All rights reserved. 0737-0806/02/2208-0004$35.00/0 doi:10.1053/jevs.2002.37106 343 Volume 22, Number 8, 2002

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Page 1: ACVIM Medical Forum 2002

ACVIM MEDICAL FORUM 2002

The American College of Veteri-nary Internal Medicine (ACVIM) heldtheir 20th Medical Forum May 29 toJune 1, 2002, in Dallas, TX. A majortopic in the equine sessions was the WestNile Virus (WNV). Three papers werepresented on the subject. Since then, ithas become evident that WNV will soonbe endemic in the entire United States ifnot this year, at least by next season.

WNV DiseaseDr. Maureen T. Long, from the Uni-

versity of Florida, described the virus

and the disease. Until the outbreak inNew York in 1999, WNV had beenknown only in Europe, Asia, Africa, andthe South Pacific. In those localities inwhich the disease has historically oc-curred, detection of infected birds coin-cides with both human and equine cases.This has been true in the United Stateswhere the spread from New York intoadjacent states has been signaled withthe death of many birds found positivefor the virus. As the disease has spreadacross the country, WNV has becomeendemic in many areas.

Dr. Eileen N. Ostlund, from the Na-tional Veterinary Services Laboratory(NVSL), in Ames, IA, chronicled thespread of WNV since the initial out-break. WNV has overwintered twice and

has significantly broadened its geo-graphic range.

“During 2002, evidence of localWNV activity was found in 12 northeast-ern and mid-Atlantic states from NewHampshire and Vermont to North Caro-lina, plus the District of Columbia,” saidDr. Ostlund. “Although there were only21 human cases of West Nile encephali-tis that year, 60 horses had confirmedcases of West Nile encephalitis. Affectedhorses were in seven states: Connecticut,Delaware, Massachusetts, New York,New Jersey, Pennsylvania, and RhodeIsland.”

She noted that by 2001, WNV posi-tive birds and/or mosquitoes were identi-fied in nearly every state in the eastern halfof the country. Positive birds and/or mos-

Copyright 2002, Elsevier Science (USA). Allrights reserved.

0737-0806/02/2208-0004$35.00/0doi:10.1053/jevs.2002.37106

343Volume 22, Number 8, 2002

Page 2: ACVIM Medical Forum 2002

quitoes were also found in Canada and theCayman Islands. In 2001, there were 58human cases of WNV and more than 600equine cases in 20 states. Dr. Ostlundnoted that over 75% of the equine casesthis year were in the 2 most recently in-fected states, Georgia and Florida.

According to Dr. Ostlund, surveil-lance data and research studies indicatethat a wide range of native US mosqui-toes and bird species support WNV rep-lication. One interesting observation isthat in other continents WNV activitywas not associated with significant ill-ness in birds. In the United States, not allspecies of birds have the same mortalityrate. The greatest die off has occurred incrows, blue jays, flamingos, cormorants,and even bald eagles, whereas manycommon US birds such as sparrows androbins were apparently not affected.

“The spread of WNV within the US,to date, closely follows north-south birdmigratory flyways,” said Dr. Ostlund.“During the past three years, equine ill-ness attributable to WNV in the north-eastern states mirrored the season ofpeak mosquito activity.”

She noted that in southern statescases of equine WNV have extended intothe winter. This suggests that in areaswith year-round mosquito activity, thereexists that potential for year-round trans-mission of WNV.

Differential DiagnosisDr. Long described several prob-

lematic trends with WNV, a flavivirusthat is antigenically related to the Japa-nese encephalitis complex, the St. Louisencephalitis, and the subtype of WNV,Kunjin. This group of viruses is en-croaching into new geographic areas, de-veloping new viral variants or subtypes,increasing in severity of both human andhorse outbreaks, and increasingly greateravian losses.

“Common among many flavivirusesis a predilection for neural tissue,” Dr.

Long said. “These viruses cause a po-lioencephalomyelitis infection of greymatter) with lesions increasing in num-ber in the diencephalon, progressingthrough the hind brain, and frequentlyincreasing in severity caudally through-out the spinal cord. This distinguishesflavivirus disease both pathologicallyand many times clinically from alphavi-ruses (eastern equine encephalitis, west-ern equine encephalitis, and Venezuelanequine encephalitis). Although alphavi-ruses also prefer neural grey matter, theseverity is ascending in nature with apredilection for the cerebral cortex. Withflavivirus encephalitis, the spinal mani-festation of clinical signs (flaccid paral-ysis in many cases) requires consider-ation as a differential diagnosis fromdiseases that present with predominatelyspinal signs. Specifically in WNV, onlybirds appear to develop a significantviremia that can serve as a reservoir fortransmission. Two reports exist in whichhorses developed a transient low-levelviremia during acute infection. This vire-mia is not thought to be high enough fortransmission.”

According to Dr. Ostlund, the clin-ical response in horses to infection withWNV can be variable, with some beingclinically unapparent. In fact, during theoutbreaks of WNV in this country overthe past 3 years only 20% to 40% of illhorses died or were euthanized.

“Although full recovery may takeseveral months,” said Dr. Ostlund,“horses that overcome West Nile en-cephalitis generally return to their pre-infection health status.”

Last year Fort Dodge AnimalHealth released a WNV vaccine underconditional United States Department ofAgriculture licensure. Only limited test-ing of the vaccine had been done, andlittle was known about the efficacy of theproduct or what effect it would have onantibody testing to WNV. The vaccine isadministered in 2 doses 3 to 6 weeksapart, with an annual booster before theonset of the mosquito season. Over amillion doses of the vaccine have beendistributed, but the impact of the vaccinewill not be known for some time.

“Like the viruses that cause east-ern equine encephalomyelitis, westernequine encephalomyelitis, and Venezu-ela equine encephalomyelitis, WNV isprimarily transmitted between birds andmosquitoes in nature,”’ Dr. Ostlund ex-plained. “Horses and humans are themammalian species most likely to man-ifest illness following WNV infectionfrom mosquito bites. However, they areconsidered dead-end hosts because nei-ther is known to develop viremia of suf-ficient magnitude or duration to enablefurther transmission to uninfected mos-quitoes.”

There are 2 described lineages ofWNV, only one of which has been asso-ciated with human and equine encepha-litis. From sequence comparison ofstrains isolated, it is suspected that theentry of WNV into the United States wasfrom Israel.

Dr. Long explained that flaviviruseshave a predilection for neural tissue,causing a polioencephalomyelitis, whichis an infection of the grey matter, de-scending caudally throughout the spinalcord. The alphaviruses (Eastern equineencephalomyelitis, Western equine en-cephalomyelitis, Venezuela equine en-cephalomyelitis) also prefer neural greymatter, but they have a predilection forthe cerebral cortex. These differences inpredilection result in somewhat differentclinical signs that are helpful in differen-tial diagnosis.

Clinical signs of 45 equine cases ofWNV at the University of Florida weredescribed by Dr. Long: “Fasciculationsof facial and neck muscles along withvarying degrees of pelvic limb ataxia andweakness were the most common clini-cal signs. Signs usually were bilateral,but could present with marked asymme-try. Not previously reported were alsoblindness and weakness of the tongue. Inmany cases, there appeared to be a re-crudescence of mild to moderate clinicalsigns 2-3 days after acute signs abated.”

The differential diagnosis includedalphaviruses, rabies, equine protozoalmyeloencephalitis, equine herpes vi-rus-1, less likely botulism, and vermin-ous meningoencephalomyelitis. Also

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various noninfectious causes shouldbe considered, such as hypocalcemia,tremorigenic toxicities, hepatoencepha-lopathy, and leukoencephalomalacia.

“In alphaviral encephalitis and ra-bies, signs of cerebral involvement arecommon,” said Dr. Long. “Change inconsciousness is characterized by behav-ioral alterations, depression, seizure, andcoma. Motor function is abnormal, char-acterized by circling, propulsive walk-ing, or head pressing. Cortical blindnesscan also be present. Cranial nerve signsare also common, including head tilt,pharyngeal/laryngeal dysfunction, andparesis of the tongue. Signs in commonwith WNV are the muscle fasciculations,hyperaesthesia, excitability, blindness,somnolence, weakness of the tongue,and progression to recumbency.”

“Confirmation of WNV infectionwith encephalitis fits the criteria recentlyestablished by the NVSL, in conjunctionwith Centers for Disease Control in At-lanta, GA. This includes probably casedefinition based on clinical signs inhorses from a county in which WNV hasbeen confirmed in the current calendaryear in mosquito, bird, human, or horses.Serologic testing has been developed byNVSL and relies on the development ofIgM and IgG responses in acute phaseserum as tested by an IgM capture en-zyme-linked immunosorbent assay andplaque neutralization test, respectively.Other means of confirmation includespostmortem detection of WNV by PCR[polymerase chain reaction], culture, andimmunohistochemistry in tissues of thecentral nervous system. Tests that rely onIgG levels will likely become less usefulgiven the widespread vaccination.”

Treatment of WNV encephalomy-

elitis is supportive and largely anecdotal,according to Dr. Long, because the sur-vival rate is high and many horses re-cover in 3 to 5 days. She recommendedprophylactic antiprotozoal medicationsuntil EPM is ruled out.

WNV EpidemiologyDr. William J.A. Saville formed an

Applied Field Epidemiology Forum inOhio in March 1999. The forum broughttogether people from government agen-cies, both state and federal, universityand industry groups to discuss animaland public health issues in Ohio. Duringthe past 2 years, the forum has producedthe Ohio West Nile Virus Work Group.As the spread of the virus approachedOhio, the work group developed a re-sponse plan for the state of Ohio, dealingwith education and communication, sur-veillance, infrastructure, training, andprevention and control.

Dr. Saville said, “Since New Yorkand Pennsylvania had already done all ofthis preparation, we at least had a base-line guide to use in our efforts. Factsheets were formatted and distributedthroughout the state. Communicationwas coordinated through various agen-cies with numerous articles sent out tolay publications, as well as, newspaper,television and radio interviews to edu-cate the public.”

The work group submitted a budgetto the Ohio legislature but received nomoney. Nevertheless surveillance sys-tems were established for humans,horses, and birds. A mosquito surveil-lance program was already in effect andWNV surveillance was already in effect,and WNV surveillance was added.

“We started with an antigen-capture

ELISA [enzyme-linked immunosorbentassay] for the mosquito pools and wereable to add RT-PCR [reverse-transcrip-tase polymerase chain reaction] by theend of 2001,” said Dr. Saville. “The sys-tem we used for the dead crow and bluejay surveillance put the onus on localhealth departments. We established aDead Bird Form where the informationcould be phoned in the Ohio Departmentof Health, or they could be faxed. Hun-dreds of phone calls later, we decidedthis information would be better col-lected on a local level, so for 200s thelocal health departments are keepingtrack of that information.”

The Ohio Department of Agriculture,Animal Disease Diagnostic Laboratory re-ceived serum and cerebrospinal fluid sam-ples from horses with clinical disease sug-gestive of WNV. The samples were thenshipped to the NVSL at Ames for the IgMcapture enzyme-linked immunosorbent as-say and plaque reduction neutralizationtest. NVSL would test only samples fromhorses with clinical signs. The Ohio Ani-mal Disease Diagnostic Laboratory is cur-rently testing Coggins samples for WNV.The Coggins samples resulted, so far, inpositive horses in 6 counties from whichthere were no positive birds or mosquitoes.

Physician reports were the basis forhuman surveillance. All cases of viralencephalitis, viral meningoencephalitis,or viral (aseptic) meningitis, either con-firmed or suspected, were tested forWNV.

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345Volume 22, Number 8, 2002