smallpox, rabies Flashcards
what viruses are in the poxviruses family?
smallpox/variola vaccinia molluscum contagiosum (MCV)
what is the only disease to have been completely eradicated?
smallpox
how was smallpox eradicated?
vaccine
possible because there’s only one, stable serotype
what is the genome structure of poxviruses?
linear double-stranded DNA
are poxviruses enveloped?
yes, they have a lipoprotein envelope
do poxviruses contain a polymerase?
yes, a DNA-dependent RNA polymerase
where do poxviruses replicate? what are the implications for this in terms of what the virus must have?
in the cytoplasm (unusual for a DNA virus)
needs it’s own polymerase
how many serotypes of smallpox are there?
just one
how many reservoirs for smallpox are there?
just one, humans
describe the replication cycle of smallpox
1: penetration of cell
2: uncoating
3: virion DNA-dependent RNA polymerase synthesizes early mRNA
4: early mRNA translated into early, nonstructural proteins, esp enzymes required for subsequent steps in viral replication
5: viral DNA replicated
6: late, structural proteins synthesized
7: virions assembled
8: attain envelope by budding from cell membrane
how is smallpox transmitted?
via respiratory aerosol or by direct contact with virus either in the skin lesions or on fomites such as bedding
where does smallpox initially infect?
upper respiratory tract and local lymph nodes
what organs and tissue types are infected by smallpox and in what order? at what point during the illness do these event occur?
initially upper respiratory tract and local lymph nodes
spread via viremia to blood
infects internal organs
renters blood and spreads to skin
all occurs during incubation period when patient is still well
why does smallpox cause a rash?
due to virus replicating in the skin and then damage due to cytotoxic T cells attacking virus-infected cells
how long is immunity to smallpox virus? how long is immunity after vaccination?
immunity is lifelong after disease, about 10 years after vaccination
what is the incubation period of smallpox?
7 to 14 days
what are the prodromal symptoms of smallpox?
fever and malaise appear suddenly after incubation period
what is the clinical presentation of the rash due to smallpox infection?
much worse on face and extremities than on the trunk
evolves through stages from macules to papules, vesicles, pustules, and finally crusts after 2-3 weeks
how is smallpox diagnosed? (laboratory diagnosis)
either grow virus in cell culture or chick embryos or detect viral antigens in vesicular fluid using immunofluorescence
what kind of vaccine is the smallpox vaccine?
live attenuated vaccinia virus
what are the critical factors that allowed for the smallpox vaccine to be sucessful? (5)
1: smallpox has a single, stable serotype
2: there is no animal reservoir and humans are the only hosts
3: the antibody response is prompt and therefore exposed persons can be protected
4: the disease is easily recognized clinically and therefore exposed persons can be immunized promptly
5: there is no carrier state or subclinial infection
why are people no longer routinely vaccinated for smallpox?
side effects such as encephalitis, generalized vaccinia and vaccinia gangrenosa exceeded the incidence of smallpox
military personel and first responders are still vaccinated
how is smallpox vaccine applied? how can you tell that it worked?
applied intradermally, where virus replication occurs
formation of a vesicle is indication of a “take” (success)
what is ring vaccination?
based on fact that an individual exposed to smallpox can be immunized as long as 4 days after exposure and be protected
so if smallpox was used in a terrorist attack, can vaccinate people after the fact
will immunize people known to be exposed, and then their direct contacts, and then the contacts of those contacts in an expanding ring
how can you treat complications of smallpox vaccination?
vaccinia immune globulins (VIG) - have high titer of antibodies against vaccinia virus
methisazone has also been used
what does rifampin do to smallpox?
inhibits viral DNA-dependent RNA polymerase, but not used clinically against smallpox
what is the clinical presentation of MCV (colluscum contagiosum)?
small, flesh-colored papule on the skin or mucous membrane that is painless, nonpruritic and not inflamed
have characteristic cup-shaped crater with a white core
what is in the lesions seen with MCV infection?
hyperplastic epithelial cells within which a cytoplastic inclusion body can been seen - inclusion body contains progeny MCV
how is MCV transmitted?
close personal contact, including sexually
where would you expect to see lesions due to MCV?
in children, around the eyes and on the trunk
in adults, in the genital area
how long do the lesions from MCV last?
self-limited but may last for months
how is the diagnosis of MCV made?
clinically since virus is not isolated in the clinical laboratory and antibody titers are not helpful
how are MCV lesions treated?
lesions removed by curettage or with liquid nitrogen
no established antiviral therapy but cidofovir may be useful in immunocompromised patients
antiretroviral therapy in AIDS patients
what class of virus is rabies?
rhabdovirus
what is the genome structure of rabies virus?
single-stranded RNA, negative
what is the capsid structure of rabies?
bullet-shaped
is rabies virus enveloped?
yes
does rabies have a polymerase?
yes, since it’s negative stranded it carries an RNA-dependent RNA polymerase
in general, which viruses can we expect to carry polymerases?
ones that replicate in the cytoplasm and ones that carry negative stranded RNA
how many antigenic types of rabies virus are there?
only one - antigenicity resides in envelope glycoprotein spikes
what is the host range for rabies virus?
broad - can infect all mammals
describe the replicative cycle of rabies virus
1: attaches to acetylcholine receptor on cell surface
2: enters cell
3: virion RNA polymerase synthesizes five mRNAs that code for viral proteins
4: genome viral RNA replicated by virus-encoded RNA polymerase
5: progeny RNA is assembled with virion proteins to make nucelocapsid
6: virion buds through membrane and acquires envelope
how is rabies virus transmitted?
by the bite of a rabid animal
in the US, usually from the bite from a skunk, racoon and bats - cats and dogs frequently immunized so rarely source of infection
bats most common source in recent years
rodents and rabbits don’t transmit it
aerosols of bat secretions can also transmit it = nonbite exposures
can also be transmitted during corneal transplant
why do rabid animals bite?
the viral encephalitis caused by rabies virus manifests aggressive, biting behavior
how many cases of rabies are seen in the US per year? in developing countries?
fewer than 10, and most are imported
can be hundreds in developing countries, mostly due to rabid dogs
where does the rabies virus multiply? where does it spread?
starts by multiplying locally at the bite site
infects sensory neurons
moves by axonal transport to the CNS
multiplies in CNS
travels down peripheral nerves to salivary glands and other organs
enters saliva from salivary glands to allow it to be transmitted via bite
why is there little immune response to rabies virus?
it’s transported within the nervous system, which shelters it from an immune response
does rabies have a viremic stage?
no
what are the clinical consequences of rabies virus infection?
encephalitis - death of neurons and demylenation
what histologic characteristics would you look for in neurons infected with rabies virus?
eosinophilic cytoplasmic inclusion called negri body
what is the incubation period of rabies virus?
2 weeks to 16 weeks, depending on the location of the bite (shorter if bites on head)
what are the clincial symptoms of rabies infection?
fever, anorexia, changes in sensation at the bite site
confusion, lethargy and increased salivation after a few days
painful spasm of throat muscles on swallowing resulting in hydrophobia (aversion to swallowing water)
seizures, paralysis and coma within several days
death
how is rabies virus diagnosed? (laboratory diagnosis)?
in animals: examination of brain tissue either by PCR, fluorescent antibody to rabies virus or histologic staining of negri bodies in cytoplasm of hippocampal neruons
can be isolated from animal brain by growth in culture - but takes too long to use in diagnosis
in humans: PCR assay or fluorescent antibody staining of biopsy specimen from skin of neck at hairline
isolate virus from sources like saliva, spinal fluid, and brian tissue
or look for rise in antibody titer
negri bodies in corneal scrapings and in autopsy specimens
how is rabies virus treated?
no antiviral therapy
only supportive treatment available
how is rabies virus prevented preexposure?
immunization with rabies vaccine to high-risk groups (vets, zookeepers, etc.) and people going to area of hyperepidemics (peach corps members)
how many doses are needed for the rabies vaccine?
three doses given on days 0, 7, and 21 or 28
booster doses given as needed to maintain antibody titer of 1:5
how is rabies virus prevented postexposure?
use vaccine
since has long incubation time, vaccine can induce protective immunity in time
also give human rabies immune globulin (RIG; obtained from hyperimmunized persons) - give only once with first dose of vaccine into bite site if possible
also immediately clean wound
also consider tetanus immunization
what is in the rabies vaccine in the US? (for humans and for pets)
inactivated virus grown in human diploid cells
in animal vaccine, inactivated rabies virus - can also use alternative vaccine for live canarypox virus genetically engineered to contain gene for envelope protein of rabies virus
how do you decide whether to give post-exposure immunization to rabies?
1: type of animal (give for all wild animal attacks)
2: whether attach by a domestic animal was provoked, whether animal was immunized, whether animal is available to be observed
3: whether rabies is epidemic in the area
seek advice of local public health officials
