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West Nile Virus Encephalitis Paul R. Earl Facultad de Ciencias Biolgicas Universidad Autnoma de Nuev

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Title: West Nile Virus Encephalitis Paul R. Earl Facultad de Ciencias Biolgicas Universidad Autnoma de Nuev


1
West Nile Virus EncephalitisPaul R. Earl
Facultad de Ciencias BiológicasUniversidad
Autónoma de Nuevo LeónSan Nicolás, NL 66451,
Mexico
2
In North America since 1999, West Nile Virus
(WNV) has joined the other major viruses like
dengue that cause various encephalites. WNV as
new is clinically little known and its role in
public health (PH), epidemiology, surveilance and
vector (mosquito) control is still illdefined.
WNV is one more PH cost. Costs range from
hospital bed time and clinical labor, loss of
work hours and school time to other costs like
reagents for immunological diagnosis. Birds
(especially crows), horses and man are the most
noteworthy in a very wide range of WNV hosts.
During 1999-2002, WNV was detected in 36
mosquito species in the US.
3
WNV is a member of the family Flaviviridae which
seems very close to Togaviridae. Serologically,
it is a member of the Japanese encephalitis virus
antigenic complex, which includes St. Louis,
Japanese, Kunjin and Murray Valley encephalitis
viruses. WNV was first isolated in Uganda in
1937.The 2002 WNV epidemic and epizootic
resulted in reports of 4,156 reported human cases
of this disease (including 2,942
meningoencephalitis cases and 284 deaths), 16,741
dead birds, 6,604 infected mosquito pools and
14,571 equine cases.
4
The central problem is morbidity and mortality by
encephalites in man, domestic and wild animals
caused by different mosquito-borne viruses
throughout the Americas.
5
It is much more important to deal with the entire
group of encephalitis viruses and dengue than it
is to dwell on WNV. There SHOULD BE much
better PH orientation to the geographies and
seasonalities of all these viruses from local to
continental levels. Medical and veterinary forces
need better mutual understanding and interaction.
Climate, vector control and surveillance are
often neglected topics. Cyclonic winds have
strong yet little known epidemiologic effects.
What is the risk of infection? Of what or whom?
By what !! ?What are the public sentiments ?
6
Somehow, there is a feeling of professional
NEGLECT. Neglect relates to ignorance. Much of
the public has been hardened by its previous
disease experiences. In its turn, this relates to
POLITICAL WILL. In the end or in many situations,
the public must DEMAND PROTECTION in order to get
it. Of course, the public best understand the
RISK so that it will pay the taxes needed to
reduce the risk. Where do your tax dollars go ?
If you replied, Into vector control, that would
be a reasonably good joke.
7
So we have more than WNV. We have a group of
viruses with much in common that are clinically
little known. Let us say that the index of
suspicion is close to zero. What is it that we
need to know ? The risk. Then pay taxes in PH
terms to reduce the risk. This is the old erratic
and encephalitic risk that WNV is increasing.
People will pay willingly for mosquito control if
they understand the risks to their health. The
community MUST REALIZE that it MUST DUMP all
standing water ! Public education for awareness
of arboviruses and other agents is desired at the
primary school level.
8
Encephalites of various causes and knowing the
riskWhat are these virusus?They are 1/ WNV, 2/
dengue (DEN), 3/ Venezuelan Equine
Encephalitis Virus (VEEV), 4/ St Louis
Encephalitis Virus (SLEV), 5/ Western Equine
Encephalitis (WEEV) and 6/ Eastern Equine
Encephalitis (EEEV). Yellow Fever and Powassan
encephalitis/ meningitis and the California
serogroup viral encephalitis/meningitis,
including infections with the following viruses
La Crosse, Jamestown Canyon, Snowshoe Hare,
Trivittatus, Keystone and the California
encephalitis viruses
9
We have come a long wayperhapsfrom WNV, because
it is part of an international problem, not the
problem itself. The problem involves the costs
and methods of MOSQUITO CONTROL. It ACUTELY
involves the public recognition of disease
transmission. Many citizens do know that these
diseases are insect-transmitted, but what percent
of people, where, etc. is of course not known.
They do not know the symptoms, meaning that they
do not recognize the disease. Questionaires dont
seem to be used. Do we
want to know WHEN the risk becomes
intolerable and how to control it?
10
International surveillanceOn the surface
it seems like a good idea to coordinate insect
surveillance among Canada, USA Mexico, partly
because territories from the equator to
northern Canada are involved. However, its a
long way from good, because financing at all
levels will raise conflicts. Is the risk great
enough to demand international surveillance?
Probably not. Many inland disease outbreaks are
local ones. Mexico is almost singular, because it
absorbs shocks from both the Eastern Pacific
Atlantic Hurricane Centers. Some of these 2 winds
running over 100 km/hr mix in the Gulf of Mexico
and go straight north into Texas and Louisiana.
11
Research objectivesAs given by CDC,
these include a) Current and Future Geographic
Distribution of WNV, b) Bird Migration as a
Mechanism of WNV Dispersal, c)
Vector and Vertebrate Host Relationships
and Range, d) Virus Persistence Mechanisms,
e) Mosquito Biology, Behavior,
Vector Competence, Surveillance, and Control,
f) Development and
Evaluation of Prevention Strategies, g)
Laboratory Diagnosis, h) Clinical Spectrum of
Disease and Longterm Prognosis in Humans, i) Risk
Factor Studies, j) Detailed Clinical Descriptions
and Outcome in Human Cases, k) Viral
Pathogenesis, l) Genetic Relationships and
Molecular Basis of Virulence,
12
WNV factsORIGINS WNV has been
found in humans, horses, birds and other animals,
typically in Africa, Eastern Europe and the
Middle East. In 1999, WNV was detected in the US
(NY, NJ) for the first time, and since then it
has spread across North America, including
Mexico.
13
TRANSMISSION WNV exists in nature
through a transmission cycle involving
mosquitoes, birds and horses. Mosquitoes become
infected with WNV when they feed on infected
birds, which may carry the virus in their blood
for a few days. Infected mosquitoes can then
transmit this new virus to humans and animals.
when biting to take a blood meal. In rarest
instances, WNW may be transmitted from human to
human through organ donation or blood transfusion
or from pregnant mother to fetus.
14
SYMPTOMOLOGY Most individuals
infected with WNV will not have any symptoms or
signs of illness. People who do develop illness
may experience mild symptoms such as fever,
headache and body aches. Occasionally a skin rash
and swollen lymph glands may occur. These
symptoms generally appear 3-14 days following the
bite of an infected mosquito. Less than 1 of
persons infected with the virus will develop more
severe disease with symptoms such as high fever,
neck stiffness, stupor, disorientation, coma,
tremors, convulsions, muscle weakness, paralysis
and, most rarely, death.
15
LABORATORY FINDINGSa) Total
leukocyte counts in peripheral blood were mostly
normal or elevated, with lymphocytopenia and
anemia also occurring, b) Hyponatremia was
sometimes present, particularly among patients
with encephalitis, c) Examination of the
cerebrospinal fluid (CSF) showed pleocytosis,
usually with a predominance of lymphocytes, d)
Protein was universally elevated, e) Glucose was
normal, f) Computed tomographic scans of the
brain mostly did not show evidence of acute
disease, but in about 1/3 of patients,
g) magnetic resonance
imaging showed enhancement of the leptomeninges,
the periventricular areas or both.
16
RISK REDUCTIONReducing risk is
avoiding mosquitoes. 1/
Dump all standing water to inhibit mosquitoes
from breeding, 2/ Stay indoors at dawn or early
in the evening, 3/ Wear long-sleeved shirts and
long pants when going outdoors, 4/ Spray clothing
with repellents containing permethrin or DEET (N,
N-diethyl-meta-toluamide), 5/ Apply insect
repellent sparingly to exposed skin and following
all packageinstructions. 6/ Ensure that all
window screens in your home or business are
intact and do notcontain holes. Repair any
damaged screens.
17
The Fort Dodge Animal Health West Nile Virus
Vaccine approved by the US Department of
Agriculture (USDA) is safe. Millions of vaccine
doses have been used since the USDA approved its
use in 2001. The Center for Veterinary Biologics
within USDA's Animal and Plant Health Inspection
Service maintains a tollfree telephone hotline
(800-752-6255) and a mailbox on its Web site
(www.aphis.usda.gov/vs/cvb) and encourages
veterinarians and other vaccine consumers to
report problems with vaccines.
18
Does the WNV vaccine also have DEN1-4 and VEE
?Of course not. Does it include SLEV and EEEV?
Of course not. What proteins of the envelope
genes of these similar viruses are used now in
vaccines? What is a plasmid ?The objective would
be to produce a protective vaccine against 1/
WNV, 2/ VEEV, 3/ EEEV, 4/SLEV and the 4 serotypes
of dengue (DEN1-4). This is technically possible
with plasmids and can solve many very expensive
epidemiologic problems. Such outbreaks are
EXPENSIVE to owners by animal loss.
19
One aspect of biotechnologyor industryis that a
pharmaceutical company will not do research or
produce a vaccine in order to lose money. WNV
vaccine is produced in the US. VEE vaccine is not
produced in Mexico. This reflects the horse
owners willingness and ability to pay. We want
this multivaccination to go through one month
before victims of a future epidemic begin to
show, butincrediblywill accept a weeks time.
The organizational effort needed to stop an
ongoing viral epidemicwith properly identified
virusesis likely too slow.
20
Mosquito controlStandard mosquito
control measures for city populations such as one
plagued by dengue may have to be vastly expanded
in the countryside if the aim is to restrict an
epidemic. Note that as epidemic applies to
people, epizootic applies to animals, but that
epidemic is often also used for animals. Still,
the point here is that huge rural areas are not
like civic ones, especially when mountains are
involved. Regardless, fast streams with banks
unimpeded by brush may not be too difficult to
control chemically over rather great distances in
the hundreds of km.
21
SurveillanceAdvantages of
mosquito-based surveillance include the
following 1/ The virus invader can be
identified. 2/ It may provide the
earliest evidence of transmission in an area. 3/
It helps establish information on potential
mosquito vector species. 4/ It provides an
estimate of vector species abundance. 5/ It gives
quantifiable information on virus infection rates
in different mosquito species. 6/ It provides
quantifiable information on potential risk to
humans and animals. 7/ It provides baseline data
that can be used to guide emergency control
operations. 8/ It allows evaluation of control
methods.
22
Surveillance is a warning system that can often
save both human and animal lives. An ounce of
prevention is worth a pound of cure !See
www.cdc.gov/epo/dphsi/casedef/
encephalitiscurrent.htm
23
Surveillance is UNPOPULAR via its costs. What are
the costs with and without surveillance with or
without chemical control? They are UNKNOWN and
most difficult to estimate. We ASSUME that
vigilance pays without even an approach to
controling some future epidemic that cannot be
defined. This is a typical undefined problem of
preventive medicine. If the problem were
profitably solved, of course, the solution would
be APPLIED, but this is not the case. Finally,
one is reminded of the huge populations in
millions that cover these vast territories.
Obviously, the magnitude of the viral
encephelitis problem might result in an
equivalent surveillance cost.
24
New and little knownAlthough the
invasion of New York City by WNV in 1999 was a
new epidemic therefore not then known,
encephalitis-causing viruses are wellknown and
most are worldwide. The PH steps to be taken
remain irresolute, and what is taught in the
classroom is unsettled. What relevent information
is the 10th grader getting? The public
appreciates WNV as a new threat via TV, but not
its inner workings. What is still lacking is the
empirical experience in epidemics, and the
detailed data of epidemic progress.
25
The control of a virus outbreak is far from
simple, often having local unknowns. The
encephalitis virus result is often 1/ dead or 2/
immune. At this conjuncture, the epidemic is
over. For Part 2, either natural or arificial
immunization serves. Of course, the difficulty is
correctly attributing the cessation of the
epidemic. Having too few mosquitoes (Choice 3)
canmost obviouslystop the outbreak, leaving
susceptibles. Choice 3 might be a larvicide
campaign, reducing the number of mosquitoes.
Again, we have cost and risk. It may take some
deep thinking to work these things out.
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