WNV Horse Vaccine

<x-flowed iso-8859-1>WNV sickened more than 400 horses in 2001, according to the tally of
the USDA Animal and Plant Health Inspection Service (APHIS). In a
recent Press Release, Pennsylvania's Department of Agriculture put
the numbers much higher: "More than 700 equine cases were reported
[in 2001], with at least 156 deaths; the total number of fatalities
is probably much higher, but many of the equine case outcomes were
not reported." Whichever statistic is the more accurate, WNV is
seen as a serious equine disease, but one that now may be preventable
by a vaccine.

In response to questions received about the vaccine, I've compiled
the following DRAFT summary about it and other measures to protect
horses from WNV. The summary draws from USDA and state Dept of
Agriculture press releases, prior postings on WestNileVirus-L and
ProMed-mail, and personal correspondences. Please send
additions/corrections to me or post to this listserv.

(1) Vaccine Background, Licensing, Use, Efficacy and Adverse Effects
(2) Links to additional information
(3) USDA APHIS EMERGENCY MANAGEMENT NOTICE, August 1, 2001: West Nile
Virus, Issuance of a Conditional License for Equine Vaccine, Killed
Virus
(4) USDA PRESS RELEASE, August 1, 2001

(1) WEST NILE VIRUS, HORSES, HORSE VACCINE

BACKGROUND

On August 1, 2001, the USDA announced its issuance of a one-year
conditional license to Fort Dodge Laboratories, Inc. [previously a
division of American Home Products, Inc.; now a division of Wyeth
(NYSE:WYE)] for development, manufacture and distribution of a
vaccine intended to aid in the prevention of WNV in horses. The
product--identified by USDA APHIS as West Nile Virus Vaccine, Killed
Virus--is restricted to use by a veterinarian in those states where
use of the product has been approved by the appropriate state
regulatory authorities.

According to the USDA, "[WNV] infection in horses may include both
central nervous system and peripheral nervous system signs. Although
horses can be infected by the virus, there is no documentation that
infected horses can spread the virus to uninfected horses or other
animals.... The most common signs of [WNV] infection in US horses
have been stumbling or incoordination, weakness of limbs, partial
paralysis, muscle twitching and death. Fever has been detected in
less than one-quarter of all confirmed cases." (Full news release
pasted below or at http://www.usda.gov/news/releases/2001/08/0130.htm
).

The USDA comment re: the marginal role of horses in the WNV
transmission cycle is supported by research reported in the current
issue of the journal Emerging Infectious Diseases (Experimental
Infection of Horses with West Nile Virus. Bunning et al. April 2002)
: "horses infected with WNV develop viremias of low magnitude and
short duration and ... infected horses are unlikely to serve as
important amplifying hosts for WNV in nature." [LCL note: I.e.,
mosquitoes fed on the infected horses did not become infected with
the virus.]
(Full text: http://www.cdc.gov/ncidod/EID/vol8no4/01-0239.htm )

VACCINE LICENSING: The WNV equine vaccine is a "veterinary
biological product." As such it is regulated under the
Virus-Serum-Toxin Act. To be licensed under this Act, a product must
be shown to be pure, safe, potent, and efficacious. Regulations
provide that a conditional license may be issued to meet special
circumstances--such as presented by West Nile Virus--if the product
is pure and safe, and has reasonable expectation of efficacy.

The conditional license for WNV equine vaccine was issued on the
basis that the manufacturer had demonstrated reasonable expectation
of efficacy and that no significant safety concerns had been noted in
preliminary results from field safety trials. USDA APHIS continues to
evaluate potency and efficacy data throughout the 1-year conditional
licensure period (Aug 1, 2001-Aug 1 2002). At the end of the
conditional license period, data obtained in support of the product's
efficacy, potency, and product performance are evaluated to determine
if the conditional license should be renewed or if a regular product
license may be issued.

VACCINE DOSE & ADMINISTRATION: The product is restricted to use by a
veterinarian in those states where its use has been approved by the
appropriate state regulatory authorities. The vaccine is
administered intramuscularly to healthy horses. Two doses are
required, with the first at least 6 weeks prior to expected mosquito
activity in the area.

A single dose of vaccine is not likely to protect a horse from
infection. Horses bitten by an infected mosquito before receiving the
second dose of vaccine may become infected and ill. This suggests
that it is vital to adhere to the recommended protocol of 2 (1 ml)
intramuscular (IM) doses 3 to 6 weeks apart. The second dose should
be given at least 3 weeks before mosquito activity is expected in
your area, if possible. An annual booster is recommended.

INTERNATIONAL TRAVEL: Horse owners planning to ship their animals to
other countries should be aware that vaccinated animals may not meet
import requirements for those countries because the horses will have
WNV antibodies in their bloodstream. It is apparently impossible to
identify naturally infected horses from vaccinated horses with
current laboratory tests.

VACCINE ADVERSE EFFECTS: (Information from personal communication
between John H. Tuttle DVM, of Fort Dodge laboratories and
K.S.)--Approximately 1.2 million doses of West Nile vaccine has been
used since it's release in August 2001. Unfiltered adverse events
reported to professional services number approximately 0.007%, or 7
reports per 100,000 doses used. Unfiltered reports include
incidences, when investigated, which are proven not to be associated
with the use of the WNV vaccine. We [Fort Dodge labs], however, are
not allowed to eliminate those reports from our database, as these
are reported to the USDA. Therefore, in all reality, the reporting
events would be closer to 0.003%, or 3 reports per 100,000 doses
used. This is an extremely low incidence, by any standard. No
deaths have been attributed with the use of the vaccine.

-------------------------------
(2) LINKS TO ADDITIONAL INFORMATION

           USDA APHIS (Animal and Plant Health Inspection Services):
             http://www.aphis.usda.gov/oa/wnv/index.html

           Fort Dodge Animal Health’ Professional Services Dept: 1-800-533-8536,
             http://www.wyeth.com/divisions/fort_dodge.asp
             (At the time the conditional license was issued, the
manufacturer, Fort Dodge
             Laboratories, Inc. was a division of American Home
Products, Inc.; it is now a
             division of Wyeth (NYSE:WYE).

          West Nile Virus and Horses (ERAP annotated bibliography):
             http://www.cfe.cornell.edu/erap/WNV/WNVPublicRefs.cfm#SectionVI

          Your State Department of Health--ERAP's West Nile Virus
weblinks for contact
             information: http://www.cfe.cornell.edu/erap/WNV/WNVWeblinks.cfm

           ProMed-Mail searchable archives re: infectious diseases:
             http://www.promedmail.org.

----------------------------
(3) USDA APHIS, CENTER for VETERINARY BIOLOGICS Notice 01-09, August
1, 2001, EMERGENCY MANAGEMENT NOTICE 1:

WEST NILE VIRUS, ISSUANCE of a CONDITIONAL LICENSE for EQUINE
VACCINE, KILLED VIRUS

The Animal and Plant Health Inspection Service (APHIS) has issued a
conditional United States Veterinary Biological Product License to
American Home Products, Inc., Establishment No. 112, Fort Dodge,
Iowa, for the manufacture and distribution of West Nile Virus
Vaccine, Killed Virus.

A veterinary biological product regulated under the Virus-Serum-Toxin
Act must be shown to be pure, safe, potent, and efficacious before a
veterinary biological product license may be issued. The regulations
in 9 CFR Part 102 regarding the licensing of biological products
provide that a conditional veterinary biological product license may
be issued to meet an emergency situation, limited market, local
situation, or special circumstance. The special circumstance
addressed here is the need for a product to aid in the prevention of
disease caused by the West Nile virus in horses. Conditionally
licensed products are required to be pure and safe, and have a
reasonable expectation of efficacy.

  The conditional license was issued on the basis that American Home
Products, Inc., has demonstrated that the product has a reasonable
expectation of efficacy. No significant safety concerns have been
noted in preliminary results from field safety trials. APHIS will
continue to evaluate potency and efficacy data throughout the
conditional licensure period. The conditional license will expire in
one year.

The product is for intramuscular use in horses. Two doses are
required, given 3 to 6 weeks apart. (Source:
http://www.aphis.usda.gov/oa/wnv/wnvemn1.html)

------------------------------------
(4) USDA PRESS RELEASE AUGUST 1, 2001:

USDA ISSUES CONDITIONAL LICENSE FOR WEST NILE VIRUS VACCINE FOR HORSES

WASHINGTON, Aug. 1, 2001-The U.S. Department of Agriculture today
announced that it has issued a conditional license to Fort Dodge
Laboratories, Inc., of Fort Dodge, Iowa, a division of American Home
Products, Inc. for a vaccine intended to aid in the prevention of
disease in horses caused by West Nile virus.

USDA's Animal and Plant Health Inspection Service issues conditional
licenses for veterinary biologics products to meet an emergency
situation, limited market, local situation, or special circumstance.
The special circumstance addressed here is the need for a product to
aid in the prevention of disease caused by West Nile virus.

Under these regulations, a product that is shown to be pure and safe
and demonstrates a reasonable expectation of efficacy may be licensed
while data to establish efficacy and potency are still being
obtained.

West Nile virus is a mosquito-borne virus that was first detected in
the United States in 1999. The virus, which can cause encephalitis,
or inflammation of the brain in animals and in some cases, humans,
has been found in Africa, western Asia, the Middle East, the
Mediterranean region of Europe, and most recently in various parts of
the eastern United States.

West Nile virus infection in horses may include both central nervous
system and peripheral nervous system signs. Although horses can be
infected by the virus, there is no documentation that infected horses
can spread the virus to uninfected horses or other animals. In 1999
and 2000, 85 horses were infected with the virus, and 32 of these
cases resulted in death.

The most common signs of West Nile virus infection in U.S. horses
have been stumbling or incoordination, weakness of limbs, partial
paralysis, muscle twitching and death. Fever has been detected in
less than one-quarter of all confirmed cases.

  Conditional licenses are generally issued with restrictions and for
a limited period of time. At the end of the conditional license
period, data obtained in support of the product's efficacy, potency,
and product performance are evaluated to determine if the conditional
license should be renewed or if a regular product license may be
issued.

In keeping with these regulations, the product described above has
been issued a conditional license for one year. The product is
restricted to use by a veterinarian in those states where use of the
product has been approved by the appropriate state regulatory
authorities.

Horse owners planning to ship their animals to other countries should
be aware that vaccinated animals may not meet the import requirements
of those countries due to the presence of certain antibodies in their
blood. While the presence of this antibody is not permanent, it
could lead to complications in shipping the horse.

--
Lois Levitan, PhD       Program Leader
Environmental Risk Analysis Program
Center for the Environment
213 Rice Hall, Cornell University
Ithaca, New York USA 14853-5601
Phone:   (607) 255-4765     Fax: (607) 255-0238
Email:  LCL3@cornell.edu
Program Email: envrisk@cornell.edu
Web:http://www.cfe.cornell.edu/ERAP
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WESTNILEVIRUS-L is an email discussion group for communication
and discussion about West Nile Virus, particularly regarding policy,
risk reduction and public education issues. It is moderated by
Dr. Lois Levitan at Cornell University's Center for the Environment.
To subscribe (or unsubscribe), send an email request to <envrisk@cornell.edu>.
Subscribers can post to the group by sending an email to:
WESTNILEVIRUS-L@cornell.edu.  Archives  are posted at:
http://www.cfe.cornell.edu/erap/WNV/WNV-L_ArchiveIndex.html
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