virology 2 Flashcards
1
Q
describe the measles and mumps in terms of the structure of the virus and their nucleic acid content
A
paramyxovirusesRNAsingle strandednegative senseenvelopedhelical
2
Q
do paramyxoviruses have to carry RNA polymerase?
A
yes
3
Q
are measles and mumps capable of radical antigenic shifts?
A
no- paramyxoviruses only contain one strand of RNA
4
Q
how does the type of infection dictate the incubation period and subsequent immunity for measles and mumps?
A
they travel through the blood as viremia and cause systemic infections. thus:1 incubation time is longer2 IgG provides life long immunity
5
Q
how many serotypes of mumps are there?
A
1
6
Q
how many other animals act as resevoirs for mumps?
A
just humans
7
Q
what is the normal incubation period for mumps?
A
3 weeks
8
Q
what are the symptoms of mumps?
A
after 3 weeks, prodromal symptoms will developfever, malaise, anorexiafollowed shortly by asymmetrical parotiditis and potentially orchitis post puberty. parotiditis is the presenting symptom.aspetic meningitis is also common
9
Q
describe transmission of mumps
A
occurs usually via respiratory exposure to saliva droplets containing virionviremia spread from the parotids to the salivary glands, where virions produced there enter the mouth and spread via coughs and sneezes
10
Q
describe antiviral therapy for mumps
A
none
11
Q
describe the vaccine used for mumps
A
live-attenuatedparted of the MMR vaccine given twice
12
Q
explain the occurrence of 3 year cycles of epidemics for measles
A
measles is the most contagious disease known. an outbreak would result in herd immunity, but as years go by and new people are born, the proportion of immune people decreases to a critical point where herd immunity is no longer effective, causing a new epidemic
13
Q
describe measles transmissoin
A
transmitted through respiratory droplets (coughs/sneezes) and infects respiratory tract.it multiplies in the lymph and respiratory epithelium
14
Q
describe measles symptoms
A
prodromal symptoms occur first:fever, cold-like symptoms, runny nose, red eyes, coughing, sneezing, photophobiafollowed by Koplik spots (bright red lesions w white central spot inside mouth)- predicts measles rashrash begins after 14 days. maculopapular erythematous rash generated at least partially by immune system
15
Q
describe measles virus excretion
A
excreted from respiratory tract and in tears and urine in the days before and after rash
16
Q
measles incubation period
A
14 days
17
Q
measles complications
A
- pneumonia2. otitis media3. acute encephalitisdeath in 1/1000complications more common in kids under 5, people over 20, and immunocompromisedgiant cell pneumonia- sometimes pneumonia results w/o measles rash d/t suppression of cell mediated immunity
18
Q
measles treatment
A
nonetreatment with vitamin A in developing countries has helped reduce mortality- death often occurs w/ measles and malnutrition
19
Q
does mumps or measles cause syncitia
A
measles
20
Q
describe what measles does to cell mediated immunity
A
suppresses it, causes anergy
21
Q
how many serotypes of measles are there?
A
1
22
Q
how many animals act as a resevoir for measles?
A
just humans
23
Q
describe measles immunization
A
live attenuatedgiven twice in MMRlife long protection
24
Q
“slow viruses”
A
- long incubation period (years)2. relentless course leading to death3. genetic predisposition4. re-emerge from latency b/c of immune suppressionexamples: HIV, JC, BK neuropathy
25
JC virus
papovaviruscauses progressive multifocal leukoencephalopathy (PML)PML is a progressive demyelinating disease of the brain (affects oligodendroglia) w/o inflammationoccurs w/ immunosuppressionprogression includes blindness, dementia, and death
26
SSPE
subacute sclerosing panencephalitisonset of intellectual deterioration, psychological disturbance, blindness and terminal paralysisassociated w/ measles- - high Ab to measles- CNS contains measle antigendistinct inclusion bodies. relation to measles unclear. does occur after vaccination (one in a million)
27
prion characteristics
1 long incubation period2. slow relentless course to death3 confined to CNS4 produce spongiform encephalopathy5. genetic predisposition
28
what are prions?
theorized to be infectious proteins w/o nucleic acid
29
what are the 5 spongiform encephalopathies caused by prions?
KURUCDJ Cretzfeld-Jacob diseasevariant CDJ mad cowGSS- gerstmann straussler scheinker syndromefatal familial insomnia
30
scarpie
chronic progressive CNS disorder in adult sheepgenetic predisposition indicatedincubation period of less than a yearprion disease- no nucleic acids
31
KURU
progressive degenerative disorder of the CNS, especially the cerebellumlimited to small tribe in new gunieano environmental factors- partially geneticcould be transmitted to apes by eating the human brains
32
CDJ
most common human prionmost are the result of a mutation, w/ obvious cause. risk increases w/ agesome reported cases were iatrogenic- caused by physicians using contaminated surgical equipmentsome variants are linked to families fCDJsome are sporadic sCDJ
33
mad cow
variant CDJcaused an epidemic in great britain as a result of using brains/bone marrow of cows to feed other cows, which became infected, and when consumed, infected other people
34
describe the structure of a herpes virus
DNA, double strand, enveloped, icos
35
describe the herpes life cycle
adsorption and fusion w/ hostnucleocapsid releases viral DNA into nucleusDNA becomes circularmRNA, viral protein synthesis inside nucleusprogeny nucleocapsids assemble in nucleus causing inclusion bodiesviral glycoproteins are inserted into membrane (can cause syncitia)progeny bud out from membrane**needs nucleus
36
describe how herpes is eliminated from the body
herpes is not eliminated from the body, even upon asymptomatic recovery. instead, herpes becomes latent. even in asymptomatic latency, pts may sporadically create infectious virions
37
describe the subclassifications of herpes virus and some examples
alphaherpesvirus- HSV1- wide host range, latency in neuronsbetaherpesvirus- CMV- narrow host range, latency in monocytesgammaherpesvirus- EBV- narrow host range, latency in B lymphocytes
38
latency
all herpes viruses can become latent:non destructivelifelongpersistence of viral genome in non infectious statepotential to be reactivated
39
is latency active or static?
active-creating gene products that prevent apoptosis, but opens the virus to immune recognitionalso have asymptomatic shedding
40
why could herpes be good for you?
chronic stimulation of immunity by non-lethal pathogens could be beneficial
41
HSV1- primary and recurrent infection mechanisms
"cold sores"primary infection often subclinical and most commonly causes stomatitis virions produced at the site of initial infection travel up sensory neurons to nearest ganglion (often trigeminal ganglia) and establish latent infectionrecurrent infection occurs when viral multiplication resumes and virions are tranported down axons to cutaneous site of primary infection- results in cold sores
42
what % of the population has HSV1?
> 80%
43
what is the incubation period for HSV 1
1-2 weeks
44
what factors can aggravate latency, causing a recurrent infection?
UV lightfeveremotion
45
HSV1 vaccine
none
46
HSV2
"genital herpes"primary infection of genital mucosa, virus follows sensory neurons back to ganglia and establishes latency (sacral ganglia)
47
HSV2 incubation period
1-2 weeks
48
what % of the population has HSV2?
20%
49
describe the complications of HSV2 and perinatal infection
virions released by vaginal secretions can cause systemic disease in newborns ~6 days after birthdisease is often fatal, with destruction of liver and adrenalmost dangerous scenario is when mother has just gotten primary infection and has no AbHSV2 shedding before deliver is indication for C-section
50
HSV1 and 2 also cause what in addition to skin lesions
encephalitisocular disease
51
herpes simplex encephalitis
most common cause of sporadic encephalitis- usually HSV1causes high fever, confusion, lymphocytes in CSF, lesions on MRIoften death w/o early recognition
52
treatment for herpes simplex encephalitis
acyclovir
53
herpes simplex keratitis
herpes simplex infection of eyeunilateral red eyecan cause blindness if untreated
54
does herpes simplex cross placenta
no
55
how do you diagnose herpes simplex?
isolation and cultureELISADNA PCR of CSFserology (IgM in primary infection)
56
HSV2 vaccine
none
57
what are the treatments for herpes simplex
acyclovir- gold standardherpes thymidine kinase will phosphorylate ACV, which can then be subsequently be phosphorylated by host and incorporated into DNA, which halts synthesis and causes death in infected cells
58
varicella zoster virus
chickenpox/shinglesprimary infection causes chickenpox- infection through respiratory tract- causes viremia. then spreads to the skin andcauses small itchy vesicles (rash) and fever. then travels retrograde to sensory neuronsoften fatal to immunosuppressed
59
varicella zoster virus transmission
aerosolspread from mucosa in skin lesions to the respiratory tract. vesicles in respiratory tract may also rupture and spread disease
60
treatment for varicella zoster virus
can get IgG- VZIG or acyclovir
61
congenital varicella syndrome
fetal infection from a pregnant mothercauses limb atrophy and scarring of the skin
62
zoster
shingles- more common w/ agereactivation in a sensory ganglia that results in pain distributed along a specific dermatome, followed by lesionscan be followed by post-herpetic neuralgia- residual painmore
63
zoster treatment
acyclovir
64
vaccinations to varicella zoster virus
vaccines to both varicella (live attenuated, requires boosting) and zoster
65
CMV
causes enlarged cells w/ "owl eye" inclusion bodiescauses retinits, colitis, heterophile negative monoleading cause of congenital abnormalities- from infection in 1st trimester- can go through placenta
66
CMV immune evasion
has 6 genes to evade T cell activation via disrupting antigen presentation
67
CMV transmission
blood/ bodily secretions (urine)
68
CMV infects what
epithelia- moves to ganglia- infects monocytes
69
easiest way to test for CMV in neonates
CMV in urine
70
CMV vaccine
none
71
CMV treatment
ganciclovir or foscarnet
72
CMV findings in newborns
retinal inflammationjaundicelarge spleen and liverlow weightmineral deposits in brainrashseizuressmall headretardationdeafness
73
EBV
causes heterophile positive mono and cancersubclinical infections in kids, but more prevalent post puberty1st symptom is sore throatalso: fever, sore throat, lethargy
74
EBV transmission
salvia or oral contactseen in college aged peopleinfects mucosal epithelia before spreading to B lymphocytes. can become latent w/ these b lymphocytesseen in people post puberty
75
EBV vaccine
none
76
EBV incubation period
2-4 weeks
77
% of population with EBV
90%
78
describe the immune response to EBV
CTLs develop to clear infected B cells, causing abnormal cellular phenotype in blooddevelop Abs that cross react w/ sheep RBCs, creating a diagnostic test
79
diagnostic tests for EBV
look for CTLs or test for agglutination with sheep RBCsIg to viral capsid
80
EBV treatment
no treatment
81
HHV6
most prevalent herpes virus > 90%genome can integrate w/ human genome and becomes heritablecauses: roseola infantum and exanthm subitum (rashes) w/ high fever
82
HHV7
causes infections but w/o symptoms
83
HHV8
Kaposis Herpesvirusnot seen in 1980s b/c of AIDS.common in sexually transmitted HIVforms spindle epidermal cellsalso in GI and lungsrarely seen in US b/c of antivirals tumor virus
84
HHV8 treatments or vaccines
none
85
B virus
infection of rhesus macaques (benign in monkeys, not in humans)very rare- seen in people who work in animal facilitiescaueses encephalitis, serious neurological squelae, and death
86
B virus treatment
acyclovir
87
triflurodine
useful in treating keratitis simplex infections causes nucleotide form of triflurodine to be incorporated into DNA and to halt DNA synthesis.cells in cornea replicate slowly enough that only infected cells will die off
88
adenine arabinoside
analogue of deoxyadenosine that gets phosphorylated by host enzymes an incorporated into DNA, halting DNA synthesis
89
foscarnet
inhibits DNA polymerase of herpes virus selectivelyalternative to ganciclovir in CMV
90
what does transformation mean?
cell can grow indefinitely and growth cannot be arrested. it requires less serum, does not exhibit contact inhibition, and is anchorage independentis "tumorigenic"
91
what is the mechanism by which viruses cause tumors
two ways:RNA viruses will introduce, upregulate, or mutate proto-oncogenesDNA viruses will degrade or sequester tumor suppressor genes
92
how can you detect oncogenic viruses in tumors?
1. take cell free extract and inject into animal model/cells to see if tumors form2 use fluorescent Abs, western blot, ELISA, etc. to look for viral proteins3 use PCR, northern blotting, southern blotting, etc. to look for nucleic acids
93
describe how the morphology of cancer cells differs from regular cells in vitro
regular cells grow flat, in an ordered waycancer cells grow rounded, disordered
94
describe the biochemical differences between cancer cells and regular cells in vitro
cancer cells have higher rates of glycolysis and glucose transport. they have lots of proteinases, but reduced fibronectin and actin
95
papovirus characteristics
DNA, double stranded (circular), naked, icosahedralproduces 10 genes, all of which are essential for tumor growth
96
what are some examples of papoviruses?
papilloma virus- infects humanspolyoma virus- rodentsSV40- monkeys
97
describe papovirus replication. how is this related to its tumorgenic properties?
replication divided into early and late stagesearly replication involves host RNA polymerase transcribing the T-antigenT-antigen binds the origin of replication. host DNA poly recognizes and binds the T-antigen, beginning replication.following replication, late replication starts and transcribe the viral capsidsviral capsids self assemble and cause lytic burst of cellin addition to binding origin of replication, T antigen also binds and inactivates p53 and Rb tumor suppressors
98
what cells does HPV infect?
epithelial cells- no viremia- grows locally,
99
what does HPV cause
warts and condylomas (genital warts)6 and 1 1- most common cause of condylomas16 and 18- cause cervical cancer
100
which strands of HPV cause cervical cancer? how?
16 and 18- they have oncogenes E6 and E7, which bind p53 and Rb respectively, targeting them for destruction and thus inactivating them
101
what is another large cofactor for developing cervical cancer when infected w/ HPV
cigarette smoking
102
describe the gardisil vaccine
protects against 6, 11, 16, and 18dead virusgiven in 3 doses over 6 months to people 9-26
103
describe the cervarix vaccine
protects against 6 and 11 onlydead virus3 doses over 6 months
104
do adenoviruses cause cancer in humans?
no- cause cancer in rats
105
how do adenoviruses cause cancer?
two important proteins: E1A binds and inactivates Rb, p300, and CBPalso binds to transcription factors to initiate S phaseE1B upregulates E1A
106
describe herpes virus characteristics?
DNA, double stranded, enveloped, icosahedral
107
what herpes viruses cause cancer?
EBV and Kaposis sarcoma virus (HHV8)
108
EBV cancer
causes burkitts lymphoma- a B cell lymphomacauses tumors in jaw, heart, abdomen, but does respond to chemo(can also cause nasopharyngeal carcinoma in Asia but mechanisms not understood)
109
how does EBV cause cancer
extrachromosomal EBV genomes always found in b-cellsinfection is latent, and integration is not required for transformationtranslocation puts c-myc proto-oncogen under transcriptional control of an Ig- over expressionT-cell normally controls these B-cell except under immunosuppression or in immunocompromised individuals
110
what are two important EBV genes that cause transformation
EBNA-2 transcriptional activatorLMP-1- CD40 analogoue
111
where is Burkitts lymphoma found
equitorial africa- coincidence w/ AIDS and malaria
112
Kapsois Sarcoma herpes virus cancer mechanisms
Kapsois sarcoma most common cancer w/ AIDS, but is uncommon w/o immunosuppresiontumors present w/ multiple, pigmented, high vascular skin nodules. tumor cells express VGEFviral genes: GPCR (VGEF) and LANA (cell growth)
113
retrovirus characteristics
RNA, single stranded, positive sense, enveloped, helical
114
essential retrovirus genes
gag- nucleocapsid proteinspol- reverse transcriptase and integraseenv- envelop glycolipids
115
retrovirus classification
divided into oncoviruses and lentiviruses (no cancer)oncoviruses have 3 classifications:transducing- have captured an onco-gene and insert it directly. transformation is short. usually cannot replicatenon-transducing- don't have an oncogene, instead cellular oncogene is activated by provirus. replication intact. intermediate transformation timenon-transducing, long latency- long transformation. viral protein influencing transcription
116
provirus
retroviruses are positive sense single strande RNARNA transcriptase converts the RNA into double stranded DNA and integrates it into host genome. this serves to make mRNA for future progeny and is called a provirus
117
long tandem repeats
Reverse transcriptase adds regulatory elements to the ends of the DNA it creates
118
describe retrovirus replication
enters cytoplasm. reverse transcriptase begins at primer tRNA, creating a RNA-DNA hybrid. RNase H degrades the viral RNA, and reverse transcriptase finishes the DNA.DNA is longer because of LTRs. it moves into the nucleus and integrates, becoming a provirushost DNA polymerase and replication machinary create and translate mRNA and viral proteins, eventually creating entire viral genome copies that can then leave
119
RSV
rous sarcoma virus- transducing virus- transforms w/in 24 hours of introduction to chickenencodes src oncogene (tyrosine kinase)
120
what types of proteins make good protooncogenes
growth factorsgrowth factor receptorskinasesG proteinsproteins that regulate transcription and regulation
121
how do acute transforming viruses replicate?
they cannot replicate themselves because one of their 3 essential genes has been replaced with an oncogene. if they are to grow, they need a helper retrovirus to coinfect the cell and provide the missing proteins
122
what are the human carcinogenic retroviruses?
HTLV 1 and 2. they do not have oncogenes
123
how is HTLV transmitted
blood, semen, perinatal (bodily fluid)
124
where does HTLV infect?
mucous membranes- viremia- t-lymphocytes
125
what does HTLV 1 cause?
adult t cell leukemia (.1% of infected, everyone else is usually asymptomatic. takes years)
126
hepatitis B cancer
5% of hep b cases become chronic. 5% of those cases get liver cancer.cause unknown, but hep viral genome integrates w/ host.theories: inserts near proto-oncogenehas an oncogenedestruction and redevelopment of liver provides opportunities for errors
127
what are the differences in how hepatitis b and retroviruses use reverse transcriptase
retrovirus is an RNA virus, and uses it to create DNA provirus that can integrate into the nucleushep B is a DNA virus. it creates mRNA copies of itself, which are then put into the capsid, and reverse transcriptase then generate the proper DNA format at the end of the lifecycle
128
hep C cancer
20% of people with chronic hep C develop cancer. there is no oncogene and integration does not occur.
129
arbovirus characteristics
RNA, single stranded, plus stranded, enveloped, icosahedral
130
how are arboviruses transmitted?
via blood sucking arthropod hosts (mosquitos and ticks)
131
difference between intrinsic incubation and extrinsic incubation
intrinsic- incubation in humans- usually 1 weekextrinsic- inside the arthropod, virus is not infectious until 14 days. arthropod is then infected for life
132
in the USA, what is the only serious disease concern stemming from arboviruses?
encephalitis
133
can you get human to human transmission?
not really- not unless blood transfusions
134
describe the progression of arboviral encephalitis
incubation is 1 weekviremia occurs quickly. virus multiplies in vascular endothelium.causes febrile malaise followed by encephalitis, paralysiss, coma and death
135
what is the treatment for arboviral encephalitis?
none
136
describe eastern equine encephalitis (EEE) and western equine encephalitis
togavirus- RNA, ss, +, enveloped, icosassociated w/ focal outbreaks in summer months, usually near swamps or after rainy seasonshorses and humans are dead-end hosts- usually die before can infect mosquitosinstead, the virus is maintained in nature via transmissions between mosquitos and birds, neither of which develop symptoms
137
west nile virus
flavivirusRNA, ss, +, enveloped, icosmost common cause of arbovirus in US. imported from egypt recently, now in every state.maintained by bird-mosquito cycles. humans are dead end hosts. most fatal cases are in elderly
138
st louis encephalitis
flavivirusRNA, ss, +, enveloped, icosantigenically related to west nile, native to US. most fatal cases in elderly
139
dengue fever
arbovirus- flavivirusRNA, ss, +, enveloped, icos4 typesincubation period 1 week- humans are not dead-end hostsfever, severe headache, muscle and joint pains, rash
140
what are the symptoms of dengue fever
fever, severe headache, muscle and joint pains, rash
141
dengue hemorrhagic fever
more severe form, notable for hemorrhage, vomiting blood, and shockcaused w/ sequential infections of cross reacting dengue fevers result in excessive inflammation and vascular permeability
142
yellow fever
arbovirus- flavivirusRNA, ss, +, enveloped, icoscauses fever, nausea, jaundice, hemorrhageextensive multiplication in liver, spleen, and kidneys
143
how are yellow fever and dengue transmitted?
human-mosquito-human-mosquitoin the jungle, monkeys can also become infected w/ yellow fever and serve as a resevoir from which we can get infected
144
yellow fever vaccine
live attenuated
145
zika
arbovirus, flavivirusRNA, ss, +, enveloped, icoscauses a mild form of dengue, may cause microcephaly
146
what defenses does a fetus have against viral infection?
placentamaternal IgGfetal IgMinterferoncell mediated immunity?
147
parvovirus B-19 characteristics
DNA, single stranded, unenveloped, icos
148
how is parvovirus transmitted?
through respiratory tract or transplacental
149
what is the parvovirus incubation period?
14 days
150
what are the symptoms of parvovirus?
asymptomatic orfever, malaise, erythema infectiosum (slapped cheek), transient athritis
151
where does parvovirus replicate?
RBC precursors- causes lack of new RBCs for a week, which is tolerated fine normallytransient aplasic crisis- person w/ anemia infected with parvovirus has severe deficit in O2 carrying ability
152
hydrops fetalis
transplacental infection during first or second trimester can cause death w/ severe swelling
153
rubella characteristics
togavirus- NOT ARBOVIRUSRNA, ss, +, enveloped, icos
154
rubella incubation
18 days
155
rubella transmission
respiratory aersols
156
rubella multiplication
respiratory epithelium followed by viremia
157
rubella symptoms
skin rash (3 days), fever, lymphadenopathy, transient arthritis
158
rubella vaccine
live attenuatedpurpose is to prevent congenital rubella
159
congenital rubella syndrome
virus crossing the placenta in the first trimester can have a variety of effects including:cataractsheart defectsdeafnessretardationspontaneous abortion
160
describe poxvirus characteristics
DNA, double stranded, asymmetric capsid, both enveloped and uneveloped
161
what characteristics of poxvirus distinguish it from other viruses?
it has an asymmetrical capsid and can be infectious enveloped or unenveloped
162
does the virion require host RNA polymerases?
no, it carries its own.poxviruses are the only viruses that carry a DNA dependent RNA polymerase with them
163
where do poxviruses form their inclusion bodies?
cytoplasm
164
what do inclusion bodies indicate
they indicate sites of virion or nucleocapsid assembly.can be used to help distinguish viruses
165
molluscum contagiosum
poxvirus transmitted by intimate cutaneous contactcauses white skin papules- bumps on the skinmuch worse in immunosuppressedresolves on its own w/ t-cell immunityharmless
166
how is molluscum contagiosum transmitted?
intimate cutaneous contact
167
how long is the incubation period for molluscum contagiosum?
2-8 weeks
168
why can it be difficult to diagnose molluscum contagiosum
grows poorly in culture
169
smallpox characteristics
DNA, double stranded, asymmetric, both enveloped and nonenveloped
170
smallpox transmission
respiratory
171
describe smallpox infection
infects respiratory mucosa and lymph, establishes viremia that attacks lungs, liver, spleensecond viremia infects skin
172
what is the clinical presentation of smallpox
papules, vesicles, pustules.lesions in oral mucosa are the main source of new infection
173
smallpox virus vaccine
live- vaccinia virus
174
how many serotypes of smallpox are there?
1
175
how many other animals act as resevoirs for smallpox?
0- just humans
176
complications of smallpox vaccinations
encephalitisvaccinia necrosum- spreading necrosis at site of infection d/t t-cell immunityeczema vaccinatum- pread of lesion in pre-exisitng eczemageneralized vaccinia- spread of lesions in the absence of eczemaheart infection
177
when is the smallpox vaccination useful?
prior to infection or w/in 4 days of infection
178
what other treatments work for small pox
passive immunization w/ IgG
179
rhabdovirus characteristics
RNA, single stranded, minus strand, enveloped, helicalrabies
180
rabies transmission
bite from infected animal
181
rabies infection
no viremia- tropism for nervous systemreplicates into salivary glands
182
incubation period of rabies
week to months
183
rabies prognosis untreated?
human and canines- fatal
184
rabies symptoms
fever, anorexiaLater: hydrophobia (d/t swallowing pain), paralysis, coma, death
185
rabies diagnosis
negri bodies- cytoplasmic inclusions in nerve cellsuses fluorescent Abs to confirm
186
where are herpes inclusion bodies?
nucleus
187
rabies vaccine
killed vaccinecan be given any time during the incubation period, but once CNS symptoms begin, will not stop death
188
rabies treatment
combination of passive and activeIgG given to delay symptoms and then killed vaccine used to activate active immunityused in all cases of unknown bites or prophylactically w/ vets
189
how does transmission usually occur in the US?
bites from wild animals' (bats, foxes, racoons, etc.)dogs are not a big source (except near mexican border) b/c of vaccination requirements
