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Venezuelan Equine
Encephalitis Virus
in Mexico
Paul R. Earl
Facultad de Ciencias Biologicas
Universidad Autónomo de Nuevo León
San Nicolás, NL, Mexico
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.
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).
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 tidings—
the innocent reporter of bad news is
unpopular.
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.
How many deaths ? No one knows.
We can say—at least—that in 1969-74
in Mexico—in 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.
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.
History
During 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.
Biological Warfare
VEE, 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.
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.
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.
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 T=4
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.
Alphaviruses are small enveloped viruses that
package an ~11.5-kb, positive-sense, singlestranded 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 T=4 icosahedral lattice.
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.
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 hurricanes—6 in the first
half of 2004—go straight north, often
along the Gulf coast into the US.
VEE seems “somewhat” restricted to horse—
mosquito—horse, and even man—mosquito—
man 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 !
Hurricane season influences
The 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.
The viral epidemiology CHANGES EXACTLY (!)
as the rainfall does. The main influence is the
Atlantic—Pacific 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?
The Alameda EEE episode
In 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?
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?
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.
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 LONGSTANDING 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?”