CS7 Bunya Virology Case Study Group _7 Final Version (3)

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Bunyavirus:
La Crosse Encephalitis Virus
Group #7
Randall Chan
Kamal Hamouda
General Overview Of Bunyaviruses
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Negative-sense RNA virus-Class V
Enveloped, spherical
80-100 nm in diameter
Genome, composed of 3 RNA segments, Large,
Medium and Small (L,M,S respectively)
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L encodes RNA Dependent RNA-pol
M encodes for viral glycoproteins, to attach to host cell
S encodes for nucleocapsid protein
ssRNA helical structure, L and M are negative sense
Ambisense in phlebovirus
Mode of Transmission for Bunyavirus
• Usually found in arthropods or rodents, but
some do infect humans, and rarely plants.
• Generally a vector-borne virus.
• Transmission occurs via arthropod, with
hantavirus through deer mice feces.
• Closely follows vector activity, such as more in
the summer.
• Has high levels of morbidity and mortality, BSL
4.
Genera of Bunyaviruses
• Bunyavirus: includes Akabane and California
encephalitis
• Phlebovirus: includes Rift Valley fever virus,
• Nairovirus: includes Nairobi sheep disease and
crimean-congo hemorrhagic fever viruses
• Uukuvirus: does not contain pathogenic viruses
• Hantavirus: infects rodents and causes hemorrhagic
fever with renal syndrome in humans.
▫ Assoc. with fever, lung edema and pulmonary failure
• Orthobunyaviruses, includes Bunymwera virus
Symptoms of Bunyaviruses
Congo-Hemmorhaggic Fever
Hantaviruses
Dengue
History of La Crosse Virus
• La Crosse virus was discovered in La Crosse,
Wisconsin in 1963.
• Occurs in the Appalachian/Midwestern regions
of the United States.
• Recent cases have also occurred in the South
East of the United States.
• Suspected to have broader distribution and
higher incidence in Eastern United States, but is
under-reported.
Mode of Transmission for La Crosse Virus:
• Mosquito Vector:
▫ Virus is maintained during the winter by
“transovarial transmission” in mosquito eggs.
▫ Zoonotic pathogen: Primarily found in infected
treehole mosquito Aedes triseriatus, but can also
be found in Aedes canadensis, Aedes sollicitans,
and Aedes vexans.
▫ The virus is maintained and amplified in treehole
mosquito species through transovarial and
venereal transmission.
La Crosse Virus Mode of Transmission:
• Other Mode of Transmission:
▫ Amplification can also occur in chipmunks and
squirrels by mosquito infection.
▫ Humans are dead-end hosts for the virus:
 Do not circulate enough La Crosse virus in the
bloodstream to infect mosquito.
 The infection cannot be spread from person to
person.
La Crosse Virus Transmission Cycle:
Pathogenesis of La Crosse Virus
• The gut of the vector
is infected initially,
and after a few
days/weeks the
virus appears in the
saliva.
• The mosquito is
infected, but is not
ill.
• Through mosquito
bite, the infected
saliva enters the
small capillaries or
lymphatics of the
human or other
vertebrate host.
Pathogenesis of La Crosse Virus
•An incubation period of a
few days ensues, after
which the vertebrate host
enters the bloodstream.
•The infection is generally
inapparent, but in some
circumstances can cause
host to become febrile.
•Unless the virus spreads
to the target organ,
humoral antibody is able
to stop the spread of the
virus and host recovers.
•The target organ for La
Crosse virus is the brain.
Symptoms & Disease Caused by La Crosse
Virus:
• Takes 5 to 15 days after the bite of an infected
mosquito to develop symptoms of La Crosse virus
disease.
• Symptoms for mild cases:
• Nausea
• Headache
• Vomiting
• Symptoms for severe cases:
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Seizures
Coma
Paralysis
Permanent brain damage
Symptoms & Disease Caused by La Crosse
Virus:
• La Crosse encephalitis occurs as a nonspecific
summertime illness.
• Severe disease generally occurs in children under
the age of 16.
• Death from La Crosse encephalitis is often rare;
occurring in less than 1% of clinical cases.
Group #7-Case Study:
• A 15 year-old summer camp counselor in Ohio
suddenly complained of a headache, nausea, and
vomiting; she had a fever and experienced a stiff
neck. She was admitted to the hospital, where a
spinal tap and examination of cerebrospinal
fluid revealed inflammatory cells. She became
lethargic over the next day but became alert
again after 4 to 5 days.
Case Study Questions:
1.
The physician suspected La Crosse encephalitis
virus as the agent. What clues pointed to La Crosse
virus?
2. What other agents would also be considered in the
differential diagnosis?
3. How was the patient infected?
4. How would the transmission of this agent be
prevented?
5. How could the local Public Health Department
determine the prevalence of La Crosse virus in the
environment of the summer camp? What samples
would they obtain, and how would they test them?
1. The physician suspected La Crosse encephalitis virus
as the agent. What clues pointed to La Crosse virus?
• Symptoms
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Headaches, vomiting, fever, neck stiffness
Inflammatory cells in CSF
-General Encephalitis
4-5 days of incubation
• Location
▫ Forested Area in the summertime
• Patient fits the category
▫ Usually found in younger cohorts
2. What other agents would also be considered in the
differential diagnosis?
• Meningitis distinguishes it from other viral,
fungal or bacterial agents
▫ Cannot be distinguished from other tick-borne
encephalitis
• Other bunyaviruses are fairly rare in the United
States
▫ Others could include Dengue, Eastern Equine
Encephalitis
• Midwestern United States
▫ Most likely La Crosse Virus
3. How was the patient infected?
• Patient was infected through the bite of the
vector, mosquito
▫ Maintained in nature through vertical
transmission in trans-ovarial transmission
▫ Can be horizontally transmitted to other
vertebrates who act as amplifiers
▫ Humans are considered dead-end hosts
• Mosquito most likely belongs to Aedes
triseriatus
4. How would the transmission of
this agent be prevented?
• No vaccination or preventative
medication discovered for La Crosse virus
infection.
• Supportive therapy: includes hospitalization,
respiratory support, IV fluids, and prevention
from other infections.
• Preventative measures: greatly reduces
infection of La Crosse virus.
Preventative Measures:
• Insect repellent: applying Deet, picaridin,
IR3535 or oil of lemon eucalyptus (PMD) on
exposed skin or clothing.
• Clothing: wearing long sleeves, thick pants, and
socks will also reduce the chances of a mosquito
bite.
▫ Can be problematic because of infecting cycle of
La Crosse virus occurs during spring/summer.
Preventative Measures:
• Eliminating mosquito breeding site:
▫ Aedes triseriatus are tree hole breeding
mosquitoes that live in woodland habitat.
▫ Prevent these mosquitoes breeding site by
emptying water from containers, barrels, flower
pots, etc…
▫ Mosquito breeding sites are generally tree holes,
filling the tree holes around the environment of
breeding sites with soil.
5. How could the local Public Health
Department determine the prevalence of
La Crosse virus in the environment of the
summer camp? What samples would they
obtain, and how would they test them?
Prevalence of La Crosse Virus:
• Collect samples of possible carriers or hosts
(mosquitoes, chipmunks/tree squirrels,
humans) of the La Crosse virus in the summer
camp environment.
• Samples should be obtained as either CSF
(cerebral spinal fluid) or serum.
Prevalence of La Crosse Virus:
• Reverse transcriptase polymerase chain
reaction (RT-PCR):
▫ Can be used if virus is isolated.
• Serological Tests Includes:
▫ Complement fixation test
▫ Immunofluorescent antibody tests
▫ The enzyme-linked immunosorbent assay
(ELISA)
▫ Hemagglutination inhibition test
▫ Neutralization test
Prevalence of La Crosse Virus:
• Serological tests allow detection of either virusspecified antibody or antigen to the virus in the
samples.
• Testing for immunoglobulin M antibodies (IgM)
and neutralizing antibodies to La Crosse virus
and many other viruses with similar
classification is necessary in order to find out if
La Crosse virus is the causative agent.
Prevalence of La Crosse Virus:
• Samples that are tested positive for LACV should
be sent to the Centers for Disease Control and
Prevention (CDC) in order to affirm that the
samples contain LACV.
• The samples should indicate whether there is a
high or low prevalence of the surrounding
summer camp environment.
• Local Public Health Department can take the
appropriate actions depending on the prevalence
of La Crosse virus in that environment.
References
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Shope RE. Bunyaviruses. In: Baron S, editor. Medical Microbiology. 4th edition. Galveston (TX):
University of Texas Medical Branch at Galveston; 1996. Chapter 56. Available from:
http://www.ncbi.nlm.nih.gov/books/NBK8004/
La Crosse Encephalitis Virus Disease. Ohio Department of Health Fact Sheet[Internet]. 2012 Jan
[cited 2012 Oct 27] Available from: http://www.odh.ohio.gov/pdf/idcm/lac.pdf
“La Crosse Encephalitis.”Centers for Disease Control and Prevention. Centers for Disease Control
and Prevention, 16 Oct. 2009. 27 Oct. 2012. http://www.cdc.gov/lac/gen/qa.html
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