Venezuelan Equine Encephalitis Virus in Mexico Paul R' Earl Facultad de Ciencias Biologicas Universi

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Venezuelan Equine Encephalitis Virus
in MexicoPaul R. Earl Facultad de
Ciencias BiologicasUniversidad Autónomo de Nuevo
LeónSan Nicolás, NL, Mexico
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Venezuelan equine encephalitis (VEE) is a
mosquito-borne acute viral disease characterized
by fever, chills, headache, back pain, myalgias,
prostration and possibly nausea, often
progressing to encephalitis. Crashing into the
stall walls, a fence or a tree is typical of
horses and can occur in humans. An equine
pressing its head against something solid is
parallel to a man holding his head with both
hands. VEE is much more dangerous for equines
(horses, mules and donkeys) than for man. The VEE
strains most involved are IAB, AC and most
importantly IE.
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In Mexico, over 200,000 equines died in 1971.
This was reported. However, that enormous
Culex-transmitted epidemic was from 1969 to 1975.
Far far more deaths occurred, certainly way over
2 million. Also, more than one virus species was
involved, e. g., St Louis Encephalitis virus
(SLE).
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Why so misreported ?
FIRST Do not know.
SECOND Did not dutifully observe, count and
record.
THIRD Hiding the facts is often a routine of
public health.
FOURTH No index of suspicion therefore no VEE
diagnosis in people. 3 includes the bearer of
bad tidingsthe innocent reporter of bad news is
unpopular.
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A very important fact is that in Mexico the
Sectretaria de Salud is completely separated from
Patología Animal, which is part of the Secretaría
de Agricultura. Patología Animal has over 100
laboratories throughout the country, but contacts
between medical and veterinary interests are rare
indeed. In the 70s, laboratories had only
vaccine. They did not made viral identifications.
They did not have sentinels, chicks or hamsters.
They did not have mosquito light traps. The same
impoverished laboratory conditions prevail in
2004.
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How many deaths ? No one knows.We can sayat
leastthat in 1969-74 in Mexicoin all 32 states
there were 200,000-2,000,000 plus equine deaths
and some human deaths. This lecturer was
vaccinating horses in Puebla and Veracruz in
1971-74. The encephalitis virus status has not
changed in 30 years, true also for tropical
diseases.
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A VEE vaccination campaign was used.All efforts
were then placed on vaccinating equines. Some
cattle of many infected died of VEE also. The
order of encephalitis virus may have been 1/
VEEV, 2/ STLV, 3/ EEEV then 4/ WEEV. However,
the encephalitis is usually considered as caused
by VEE only. Why do you suppose that is ? A
vaccine failure may be then caused by some other
virus.
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HistoryDuring the 1930s, 3
distinct but antigenically related viruses were
recovered from sick horses and were shown to be
previously unrecognized agents of severe equine
encephalitis. Western equine encephalitis (WEE)
virus was isolated in the an Joaquin Valley in
California in 1930, Eastern equine encephalitis
(EEE) virus in Virginia and New Jersey in 1933,
and Venezuelan equine encephalitis (VEE) virus in
the Guajira peninsula of Venezuela in 1938.
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Biological WarfareVEE, like EEE, is a
potential biowarfare weapon, even without genetic
engineering, that could intensify its lethality.
An aerosol spray released from a single airplane
would infect thousands of people in thousands of
squared kilometers.Alphaviruses, especially the
equine encephalomyelitis viruses, lend themselves
very well to warefare. Although other
encephalitic viruses could be considered as
potential weapons, few possess as many
characteristics for strategic weapons development
as the alphaviruses.
10
These viruses can be produced in large amounts in
inexpensive and unsophisticated systems. They are
stable and infectious for humans as aerosols.
Strains are available that produce either
incapacitating or lethal infections, having of
multiple serotypes of VEE and EEE viruses.Just
as they have little vector or host specificity in
nature, the alphaviruses replicate readily at
very high titers in a wide range of cell types
and culture conditions in vitro. The same is true
for Flavididae viruses. Virus titers of 1 billion
infectious units/ml are reached.
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Togaviridae are close to Flaviviridae.Clinical
symptoms are similar to those of many other
viral zoonoses that cause fever and headache
caused by a Flavivirus. VEE is caused by an
enveloped single-stranded RNA virus of the
Togaviridae family, Alphavirus genus. Formerly,
this was group A arboviruses. The VEE RNA is
enveloped in an icosahedral coat structure,
having a diameter of over 60 nm. Surface spikes
are recognized by host receptors. Six subtypes
(I, II, III, IV, V and VI) have been identified.
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The core is enveloped by a lipid bilayer that is
penetrated by 80 glycoprotein spikes, arranged as
an icosahedral surface lattice. These spikes are
also arranged in a T4 lattice that is in
register with the internal nucleocapsid. Each
spike is a trimer of heterodimers that extends to
a viral radius of 345 Å with a on its globular
extremity. The heterodimer consists of 2
glycoproteins, E1 and E2, whose C-terminal ends
protrude on the cytoplasmic side of the membrane
by 2 aminoacids and between 31 and 33 aminoacids,
respectively.
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Alphaviruses are small enveloped viruses that
package an 11.5-kb, positive-sense,
single-stranded RNA genome. The viral genome
encodes 4 nonstructural (nsP1, nsP2, nsP3, and
nsP4) and 5 structural (capsid, E1, E2, E3 and
6k) proteins. This simple protein composition
makes alphaviruses model systems ideal for
studying enveloped virus assembly and structural
electron cryomicroscopy. Image reconstruction of
Sindbis, Semliki Forest, Ross River and Aura
viruses show that the envelope glycoproteins are
arranged on the outer surface of the virus as 80
trimers in a T4 icosahedral lattice.
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How do the encephalitis virus spread? The
devastating outbreak in Mexican equines was from
1969 to 1975 involving the deaths of millions of
equines. Epizootic control was obtained by a
large-scale national equine immunization program.
Mexico, Central America and Panama had subtype
IE. VEE reached Texas in 1971. ). The original
epizootic VEE viral isolate made in Venezuela in
1937 was caused by a strain of variant I-A/B,
which was also responsible for the 1969-72 plus
epizootics in Ecuador, Central America, Mexico
and Texas. Epizootics during the 1960's and
1970's, and in 1992-3 and 1995 in Colombia and
Venezuela were caused by variant I-C.
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The main sources of VEE for Mexico, e. g., IE ,
are Ecuador Colombia by mosquitoes via East
Pacific hurricanes. Still, an Atlantic hurricane
in the Caribbean can move mosquitoes west off
Venezuela into Mexico, but most of the Atlantic
hurricanes6 in the first half of 2004go
straight north, often along the Gulf coast into
the US.
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VEE seems somewhat restricted to
horsemosquitohorse, and even manmosquitoman
rather than invoving birds, rodents, etc.,
although they are like mice infectible. Then
suppose a new outbreak is imported into Mexico by
wind-borne mosquitoes from northern South
America, not generated endemically. The new
epidemic may be coming from the Eastern Pacific
Hurricane Center. An epidemic jump at hurricane
speeds from Colombia or Venezuela is easy to
visualize into Oaxaca or straight north into Baja
California, Mexico and through into
Arizona-to-California, US. The same sources might
produce winds on another occasion that can reach
Hawaii !
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Hurricane season influencesThe transmission
of VEE and other viruses via mosquitoes is
dominated by the Eastern Pacific hurricanes,
although of course controlled often by the
Atlantic hurricane winds.BOTH Pacific and
Atlantic hurricanes travel north along the
Veracruz coast into Texas and some into the other
US Gulf states and of course some reach Florida.
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The viral epidemiology CHANGES EXACTLY (!) as
the rainfall does. The main influence is the
AtlanticPacific hurricane winds changing their
directions and forces. Let us IMAGINE an
unlikely (?) strong hurricane from Colombia going
due north. It would hit La Paz, of course. It
would cover the Gulf of California and western
Sonora. It would reach California, Nevada and
Arizona in the US. COULD such a viral
epidemiology occur, or not? What was the season?
What is the time schedule? What were the wind
speeds? How long did Imagine last? How far did
it reach? What micro- and macroorganisms was it
carrying? Did Colombian mosquitoes breed in
Mexico or in the US?
19
The Alameda EEE episodeIn June, 1996,
Eastern Encephalitis Virus (EEV) arrived in
Oaxaca, Mexico from Colombia apparently. It was
in Veracruz by July and Tamaulipas (Tamps) by
September, carried by mosquitoes in hurricane
winds from the Pacific. Mexican veterinarian had
to send samples to the US National Disease
Laboratory, Ames, Iowa to be identified, because
of lack of virus facilities. This epidemic became
selflimiting in October at Alameda, Tamps.
Veterinarians in Tamps had tried to stop this
outbreak by vaccinating a ring of horses with the
old vaccine that missed completely. What was
really lost? Time. Why?
20
The Colombian EEE virus entered Oaxaca in June
and smouldered out in Tamps in October. The rainy
season was over. Did the Gulf winds reverse?
There were July August equine deaths in
Veracruz, yet no human deaths were recognized.
Signs for Vaccinate your horse were up on
Veracruz highways. Of course, that would have
been a wrongway vaccine !Was there time for
Colombian EEE culicines to breed in Mexico? Is it
really the lack of time for a sexual cycle, and
the onset of autumn drought that did stop the EEE
outbreak. Were these mosquitoes possibly 5-6
months old?
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More virus reference labs in both human and
veterinary medicine, and sharing facilities are
needed in Mexico. Sentinels might be permanently
maintained in the cities of Merida, Yucatán,
Oaxaca, Oaxaca, Tapachula, Chiapas and La Paz,
Baja California del Sur. Virus installations have
high maintenance costs and require expert
technicians. The bacterial techniques and
standard equipment may not be present in some
clinics. Veterinarian laboratories should have
improved communications with medical
laboratories. Upgrading for better human and
animal health seems needed despite the high costs
of modern laboratories and reagents.
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More than equine encephalites is involved in
improving rural life. VEE is a highlight of
tropical medicine, though primarily a veterinary
topic. Hoof-and-mouth disease in cattle in 1953
was the rural tragedy before VEE. NOW
LONG-STANDING AND IMPOVERISHED CHAGAS DISEASE IS
A RURAL TRAGEDY, HOWEVER HIDDEN IT MAY BE. Will
the next EEE episode kill people ?What might
the next DISASTER be? An interesting question
because it also asks How much MONEY will be
spent on surveillance and vector control?