Download Assessment 11

Arboviruses
Epi & Basic Characteristics
Symptoms/Dx.
Treatment/Prevention
Remember that Rubella is a Togavirus
also.
Headache, Fever, Nuchal Rigidity, Altered mental status=viral meningitis
All the above + focal neurological signs, seizures, altered consciousness, behavioral/speech
problems=viral encephalitis
Supportive for all, if bacterial
meningitis is suspectedAbx
Think of Paul Bunyon wearing a toga,
bitten by a mosquito b/c of good flavor.
Alphaviruses (Togaviridae)
Specific viruses are listed below the
underlined genus
Category B
(think alpha males wear togas)
Dx. Of arboviruses CSF/CT then LP
WBC of CSF 50->1000 x 109/L, normal glucose, slightly elevated protein
Bioterrorism
Eastern Equine Encephalitis
(EEE)
Eastern and Gulf Coast
Caribbean and south America
Western Equine Encephalitis
(WEE)
Venezuelan Equine Encephalitis
(VEE)
Western USA
Flavivirus (Latin Flavus = Yellow,
Found world wide
Mosquito and Tick Transmission
Yellow Virus)—Correlate this with Yellow
Fever (also HCV is in this category—
yellow bc of jaundice)
SW USA South& Central Americas
Worst prognosis of the alphaviruses (fulminant ds. w/ high mortality)
High incidence of neurological problems
Dx. IgM Ab Capture ELISA
Lower incidence of neurological problems
Dx. IgM Ab Capture ELISA
Mild disease, rare neurological problems
Dx. IgM Ab Capture ELISA
Supportive for all, if bacterial
meningitis is suspectedAbx
Africa, Middle East, Russia, India.
Outbreak in NYC in ’99.
Culex, Anopheles, Aedes mosquito
vectors.
Severe muscle weakness
Erythematous maculopapular rash (neck, trunk, arms legs)
St. Louis Encephalitis
August-October outbreaks
Dx. IgM Ab Capture ELISA
Dengue Virus
Most important arbovirus in humans
West Nile Virus
WHO: 4 Criteria for Dx.
Fever, Hemorrhage, Circulatory failure,
Hepatomegaly
Yellow Fever
JBEV Encephalitis
Bunyviruses (negative sense
RNA)
LaCrosse Encephalitis
Hantavirus
Rabies (Rhabdoviridae)
(negative sense RNA)
Mosquito Borne . Formerly in Memphis.
Endemic in Africa and South America.
Sylvatic (mosquitoanimalhuman)
and urban (mosquitohuman)
transmission cycles.
Most common flavivirus.
Found in Asia and south pacific
Monitor birds and mosquitos
Dx. IgM Ab Capture ELISA

Dengue Fever, after fever breaks can get Dengue hemorrhagic fever (can have neurologic
sequelae; prior infection of one serotype of dengue virus increases risk of DHF) or
Dengue shock syndrome, strange metallic taste

Dengue fever has centrifugal maculopapular rash and “Break bone disease” (extremely
painful diffuse body pain)

Fever, Hemorrhage, Circulatory failure, Hepatomegaly

Dx. Serologic, Virus isolation (CPE), or RT-PCR genome detection
Hemorrhage, hepatic failure, proteinuria, renal failure, death
Lumbosacral myalgia
Black Vomit (from hemorrhage of stomach lining)
Vaccine Available
Dx. Serologic, Virus isolation (CPE), or RT-PCR genome detection
Vaccine available
Supportive for all, if bacterial
meningitis is suspectedAbx
Most common
Seizures and focal neurological signs
Rodent borne infection (aerosolized
excreta).
Four corners area of USA (Sin Nombre
Hantavirus is predominant form in US)
Carnivorous animals and bats.
Virus pathway:
Bitemusclesensory nervesSpinal
ganglialimbic system in brain
Hantavirus pulmonary syndrome (HPS)
Abdominal discomfort, myalgia involving large muscles of thigh and lower back
Tetrad: thrombocytopenia, leukocytosis, elevated Hct, immunoblasts in peripheral blood smear
Dx. RT-PCR, IgM and IgG titers via ELISA
Uniformly fatal if not treated (respiratory arrest)
Prodrome (malaise, chills, aches, headache, itching around bite)neurologic phase (acute) has
paralysis w/hydrophobia, autonomic instability, hyperactivity “furious rabies” or paralysis “dumb
rabies” coma (eventual respiratory arrest)
Dx. Based on history, serology is not useful
Negri bodies (eosinophilic inclusion bodies in cytoplasm of neurons).
No treatment, only supportive.
Avoid rodent contact
Post exposure: HRIG
Post infection vaccination
(three possible inactivated
vaccines: HDCV,RVA,PCEC)
Wound cleansing.
Must treat before acute phase
Bacteria
Epi & Basic Characteristics
Symptoms/Dx.
Treatment/Prevention
Obligate intracellular (utilizes hosts ATP)
Tick (dog ticks) defecates and fecal
material is scratched into a
woundBlood vesselsmultiplies in
endothelial cells and smooth muscle
layer of small blood vessels
Microthrombosis, perivascular hemorrhage,edema
RMSF (A vasculitis w/ inflammation, microthrombi, edema responsible for rash and headache)
Hallmark Features: Severe headache, high fever, maculopapular rash (starts on ankles/wrist and
spreads as petechial rash to palms/soles and trunk so is centripetal/inward spreading), history of
tick bite
Must treat immediately if you
suspect RMSF
Tickborne Bacterial Zoonosis
All are intracellular parasites
Rickettsia rickettsii
Treat adults and children with
doxycycline
Highest from NC to OK including TN (not
much in Rocky Mountain area). Also in
Wyoming.
Don’t memorize this picture.
Differential for rash on palms/soles of
feet: Coxsackie A (hand,foot,mouth
disease), RMSF, or Syphilis. Drive CARS
with palms/soles
Ehrlichia & Ananplasma
HME (human monocytic
ehrlichiosis): E. chaffeensis
HGA (human granulocytic
anaplasmosis): Anaplasma
Can’t culture
Most common form of death in tickborne infections
Obligate intracellular (infect WBC’s)
Human Monocytic Ehrlichia (HME)
Human granulocytic anaplasmosis (HGA)
Tick transmission (different tick than
RMSF ticks so different geographic area)
Flu like symptoms early, followed by rash (3-5days after symptoms), as rash spread the symptoms
become systemic and can involve CNS (meningitis)
Can effect heart: Myocarditis, or lung (pneumonitis)
Dx. Low platelets (thrombocytopenia), low RBC count, renal failure, blood and protein in urine,
hyponatremia
Dx.Cross reacts with various proteus strains (OX Strains) and get agglutination which is the basis for
the Weil-Felix test/reaction that is non-specific but still used. Confirm Weil-Felix with a specific
serological rickettsial test (only positive until several weeks after a tick bite)
Symptoms overlap with RMSF (close relative), can’t distinguish w/o RMSF rash
Milder than RMSF typically and rash is less common (rash very rare with HGA)
No Weil Felix rxn!!!
HME: Has intracellular inclusions called morulae in monocytes. HGA: has morulae in granulocytes.
Can’t culture
Collectively referred to as Ehrlichia
Coxiella burnetii
Not on test
Category B Bioterrorism
Bartonella
(Think of Bart Simpson singing Cat
Scratch Fever)
Can’t culture. Obligate intracellular
parasite.
Related to Legionella.
Cow, Sheep, Goat reservoir.
Transmitted by aerosol, handling viscera.
(aminotic fluid, raw milk, sometimes
ticks).
Spore form permits distribution by wind
(Cat. B Bioterrorism).
Pediatric patients
HME
Flu like illness (Q Fever)
Atypical pneumo.
Maculopapular rash, chronic infections can lead to endocarditis
Dx. Serological
HGA
Cat Scratch Disease
Swollen lymph glands near site of scratch or bite (no symptoms in cats and dogs though)
Flu like symptoms in adults
Can cause disseminated disease in immunocompromised
Dx. Clinical mainly (history of cat bite/scratch), not routinely cultured
Treat with Doxycycline
Borrelia burgdorferi
Spirochete, transmited from Ixodes Tick
BAKE a key lyme pie: Bell’s palsy,
arthritis, cardiac problems, erythema
chronicum migrans
Think: New England (named after Lyme,
CT)
Seen by direct light microscopy. Surface proteins undergo Ag variationrelapsing fever, humoral
and CMI response get rid of bug, untreated pt. can develop chronic Lyme Disease (see below).
Hosts cellular immune response controls infection but is responsible for pathology.
LD has a tropism for: skin, CNS, heart, joints, and eyes
“Bull’s eye rash” (Erythema Chronica Migrans): Outer red border with inner clearing, rash expands
over time and can have additional new ones show up.
Life cycle involves mice and white tailed
deer
Early: Doxycycline or
amoxicillin in children
Chronic: Prolonged IV
cephalosporins (inneffective rx.
With HLA-D4 pt.)
Prevention: Pull off tick within
24h and can entirely avoid
disease
NO Vaccine in USA (pulled off
market)
Occurs when ticks are active (May
through October)
Most common tick-borne disease in US
Initial symptoms: Nonspecific Flu Like Symptoms (Fever, headache, lethargy, muscle pain, stiff neck,
joint inflammation, lymphadenopathy)
Late manifestions:
Nervous System: Facial nerve (Bell’s) Palsy (CN VII)
Heart: Arrythmia, myocarditis, Pericarditis, AV block
Joints: Erosive, painful arthritis of large joints (immune complexes, migratory arthritis), think of
Osteoarthritis of the Knee
Dx. ELISA/indirect IFA , then must confirm with western blot (serodiagnosis produces lots of FN—
since most of these pt. are seen by Rheumatologists)
Relapsing Fever (comes and goes)—ag variation
Dx. Is serological. Also large spirochete can be seen in Wright-Giemsa-stained blood smear
Borrelia hermsii (tick)
Borrelia recurrentis (louse)
Not on Test
Leptospira interrogans
Not on Test
Spirochete, thin with hooks (question
mark shaped, hence name)
Seen by direct light microscopy, but usually DF microscopy is used
Doxycycline or Penicillin
Swineherd’s ds, swamp or mud fever, flu like illness, can progress to hepatitis if not treated
Prevention: Vaccination of
domestic livestock and pet’s
Symptoms: flu-like symptoms to jaundice, nephritis, meningitis
Water contaminated w/animal urine (Jet
skiier’s, Hawaii has the highest
incidence, triathlon contestants, etc.)
R. prowazekii
Not on Test
Category B Bioterrorism
Not transmitted by an arthropod!
Human-human spread by lice, associated
with close quarters (military)
Typhus, symptoms similar to RMSF (fever, headache, rash) but rash moves from trunk to periphery.
Think RMSF starts near wrists while Typhus starts near trunk.
Category B Bioterrorism Agent
Murine Typhus (R. Typhi): Mild version of typhus on texas gulf coast
Bacteria (Bioterrorism)
Epi & Basic Characteristics
Symptoms/Dx.
Treatment/Prevention
Bacillus anthracis (Anthrax)
Domesticated farm animals are reservoir
Potential Bioweapon
Dx. Cluster of flu like illnesses (mail handlers), papular to pustular skin lesion that develops into an
eschar (cutaneous form), dry non productive cough, Widened mediastinum (inhalation anthrax) on
XR
Use ciprofloxacin IV or Doxy IV
and at least one other Abx (to
cross BBB)
Category “A” Agent
G+ Aerobic spore former (spore must be
finely milled for bioterrorism to be
infectious)
Large Boxcar G+ chains
Post –exposure prevention:
40 days of ciprofloxacin
prophylaxis since there is a
long incubation period of the
spores
Phases of inhalation anthrax: Flu like symptoms followed by severe fever, shortness of breath, and
chest pain (infection of lymph nodes rather than a pneumonia) (more N/V less rhinorrhea to diff.
from influenza. Key symptoms of inhalational anthrax: infection of hilar/mediastinal lymph nodes
(not a true pneumonia) and mediastinal widening on xray
Vaccine exists for military
Virulence factor: Antiphagocytic non-antigenic capsule containing p-glutamic acid, AB toxin that
contributes to symptoms
AB Toxin:
B=Binding component and is the protective antigen (PA) allows binding to host receptor and
facilitates endocytosis and entry of A
A= Active subunit, two A subunits: Edema Factor (EF) is a calmodulin-activated adenylate cyclase
(responsible for mediastinal edema), Lethal Factor (LF) is a metalloprotease that cleaves MAP
kinases and disrupts immune response
Spore is infectious form, spores germinate and become encapsulated forming vegetative cells that
release toxin (swelling, sepsis, necrosis)
Yersinia pestis (Plague)
Transmission via flea from ground
rodents
Dx. Rapid flu test to rule out flu, culture of blood and CSF, Gram stain , IF Ab stain of CSF and blood to
see G+ boxcars
Cause of Bubonic Plague,
Secondary and primary plague pneumonia (primary is expected in bioterrorism attack)
Category “A” Agent
New Mexico and adjoining states
Bubonic: Infection from flea bite, swollen lymph node (Buboes), w/ fever, chills, headache, etc.
Gentamicin
Use Streptomycin if available
No response to B-lactams nor
macrolides
Chubby gram negative rods with bipolar
inclusion bodies (“safety pins”)
(same as Tularemia)
West of Mississippi river
Septicemic: w/ and w/o buboes, rapid progression and general organ failure w/vomiting diarrhea
(petechiae to extreme DIC)
Pneumonic:
Secondary pneumonic plague (disseminates from primary infection), very contagious and requires
isolation of pt. and prophylaxis for all exposed individuals sputum is more bloody and watery than
purulent (productive cough).
Primary pneuomic plague (due to direct inhalation) respiratory symptoms are same but precede
septicemia. Would be seen in terrorist attack.
Keys to Dx. are history, large swollen nodes
Dx. By serology to Abs to F1 surface Ag (confirmatory), gram stains of buboes may reveal safety pin
rods, culture, IF, and RADT can be used
Francisella tularensis
Category “A” Agent
High incidence in Arkansas
Direct contact with infected animals (tick
and deer fly)
Most common reservoir is rabbit
Small g- coccus hard to see in gram stain
No human human transmission
Tularemia: “Rabbit Fever”
Very infectious with only 10-100 organisms required (only specialized labs culture due to danger!)
Keys to Dx. History, papules, regional lymphadenopathy, atypical pneumonia, failure to respond to
beta lactams and macrolides
Symptoms:
Ulceroglandular: Most common form. Maculopapular, pustular, rash at site of entry, swollen painful
lymph nodes, fever
Systemic: Most lethal form. Toxicity (septicemia), swollen glands
Pneumonic: non productive cough, patchy infiltrates on XR, hilar lymphadenopathy, atypical
pneumonia, dyspnea, pleuritic chest pain,
Gentamicin
Use Streptomycin if available
No response to B-lactams nor
macrolides
Dx. Culture of blood and sputum (specialized lab), serological, RADT
Brucella
abortus (cows)
suis (pigs)
melitensis (sheep and goats)
Category “B” Agent
G-aerobic coccobacillus
Undulant Fever
Facultative intracellular parasite of RES,
Symptoms: slow moving chronic infection, relapsing fever w/ night sweats, weakness, back ache
(can infect vertebrae), wt. loss, fatigue, typical biopsy of lesion shows a granuloma
Animal reservoir is cow, sheep, pig, and
wild animal reservoir
Prolonged Abx
Control of pasteurization,
vaccine for cattle, destroy
infected herds
Differential: TB
Transmission: Contact and consumption
of raw milk or unpasteurized cheese.
No human-human transmission
Lab Dx. Serological, can be cultured on rich medium (may take a week)
Seen in recent immigrants from
Mediterranean area and Mexico
Prions (Proteinaceous Infectious Particle)
Disease
Characteristics
Transmissable Spongiform
Encephalopathies (Human)
-Spongiform changes
Kuru
-Ritual Cannabilism in Papa New Guinea
-This is a pic of the cannibal tribe (fun
fact only)
Molecular Biology & Clinical Symptoms
-Single exon on chromosome 20 encodes a protein highly expressed in neurons
-209 Amino Acid Glycoprotein produced from this codon
-Normal form is PrPc
Disease form is PrPSc Resistant to proteases, nucleases, radiation, formalin,etc.
-the normal protein is not crucial for survival, but is needed in order to have any of the pathology Improper folding causes aggregates (β pleated sheets) in neuronsapoptosis by unknown
mechanism
-Mechanism: PrPc is required, some mutation happens and PrPSc accumulatescauses binding to
PrP* intermediate which leads to more and more PrPScchain reaction produces tons of PrPSc
-Species barrier exists (probably due to varying homology of proteins between species)
-Very rare to get the mutation (which is why it happens later in life)
-Also explains why seeding of prions has a much quicker effect
-Template prion and not amino acid sequence dictates final conformation
-He will eat you and get Kuru
Treatment
Generally none, genetic
counseling and prophylactically
managing cattle/blood
transfusions, etc.
Creutzfeldt-Jakob Disease
(don’t memorize this picture)
Gerstmann-Straussler-Scheinker
Disease (GSS)
Fatal Familial Insomnia (FFI)
Variant CJD (vCJD)
Transmissable Spongiform
Encephalopathies (Animal)
Scrapie
Bovine spongiform
encephalopathy (BSE)
-Most common TSE
-Average age of onset is 60 years,
accounts for 85% of CJD
-Sporadic (Chance) and iatrogenic forms
-Iatrogenic (dural grafts, corneal grafts,
etc. present quicker due to location near
CNS)
-Familial form (AD pattern)—associated
with specific mutations (age of onset is
earlier, less rapid deterioration in
familial)
-Rapidly progressing Dementia/Myoclonus are main signs
-Cerebellar ataxia, akinetic mutism also
-Sporadic CJD has periodic complexes in an EEG, KNOW THIS
-AD pattern of inheritance
-Associated with a mutation at codon
102 of prion protein
-Average age of onset is 48, 5 year mean
time to death
-numerous amyloid plaques in addition
to spongiform changes
-AD inheritance, mutation at codon 129
and 178
-Gait abnormalities and ataxia, dementia is less common but there is NO characteristic EEG
-Same as Mad Cow Disease
-Transmission is from contaminated beef
but can also be from blood transfusions
-Homozygous for codon 129 mutation
(met), KNOW(He said in class this is the
one we want to know)
-Higher level of infection in periphery than in classical CJD
-anxiety, depression, visual problems
-Atypical EEG, prion positive tonsil biopsy
-“Florid plaques and spongiform changes in basal ganglia”
-Sleep disturbances and autonomic dysfunction
-Ataxia of sheep and goats
-Alimentary tract transmission
-Found in lymphatic tissue at 1 yr
-Mad Cow Disease
Infected Cow
Chronic Wasting disease
-was not elaborated on
-No treatment, dead within a
year (2-4 in familial form)
-None, average age of onset is
29 with a 14 month survival
time