Week #22 Lecture outline

Togaviruses: Alphaviruses and

Flaviviruses
Rhabdovirus, Reovirus,
Poxvirus, Scrapies-like agents
 Togavirus and Flaviviruses introduction

• Enveloped, linear ssRNA

• Togaviruses: replicate in cytoplasm, bud at
plasma membrane
– Alphaviruses arborviruses, similar antigenicity
– Pestivirus & Arterivirus no human pathogens
– Rubivirus Rubella virus German measles

• Flavivirus: replicate in cytoplasm, bud at

internal membranes, serologically related
– arborviruses (West Nile Virus), HCV, HGV
Alphavirus structure
 Alpha and flavivirus pathogenesis
• discussed together because they are
arborviruses and have similar pathogenesis
and epidemiology

• pathogenic characteristics are determined by:

– 1) route of entry into host
– 2) status of infection in vector- i.e. inoculum
– 3) tissue tropism of virus
– 4) status of infection in hosts

• cause lytic infections in vertebrate hosts:

• 1) viral RNA blocks host mRNA translation
• 2) cell permeability changes affect cellular ion
conc. to favor enzymes that translate viral mRNA

• cause persistent infections in invertebrate vectors

 Arborvirus course of disease
• Virus affects vertebrate host (eg. birds)
• Female mosquitoe takes blood meal from vertebrate
host
– virus infects midgut cells and replicates must
cross basal lamina of GIT viremic spread to
salivary glands
• persistent infection, high titer- 1-2 weeks after
ingesting virus
• Female mosquitoe bites another vertebrate host
– (eg. humans, domestic animals) regurgitates virus
infected saliva into bloodstream affects target
cells monocytes, macrophages, endothelial cells
of capillaries lytic infection
» viremia
• Why use a vector?
– Humans are “dead end” accidental hosts can’t
spread back to vector- not high enough viremia
Course of disease
 Consequences of Alpha and flavivirus in host
• Virus enters bloodstream and has tropism for
target cells monocyte/ macrophage/ vascular
endothelial cells
– replication in target tissues
• 4-7 days after infection flu-like symptoms due to IFN
release: fever, backache, chills, H/A
– majority of infections stop here (99% in West Nile virus)
• rarely (1% for West Nile)
– secondary viremia affect brain (encephalitis); LV
(hepatitis), skin (rash), vasculature (haemorrhagic
fever)
• some arborviruses (especially dengue fever virus)
express Fc receptors
– increase infectivity by 200X with re-infection
 Alpha and flavivirus immunity
• Humoral and cellular immunity control
infection and prevent further infection
• viral mRNA during infection becomes ds
mRNA intermediate
– induces IFN synthesis and release into blood
• cause flu-like symptoms and limits viral replication in
blood
– NK cells, T cells and macrophages also limit viral
replication
• IgM (produced within 6 days)
– blocks viremic spread
• IgG
– prevents subsequent infection by same strain
Alpha and Flavivirus immunity cont’d
• Good • Bad
• Ab
• Ab – in subsequent
– iff neutralizing infections
limits viremia • increase uptake of
• cross-reactivity
virus in
macrophages and
prevents other cells with Fc
infection from receptors
other alpha/
flavivirus
• CMI
– inflammation can
• CMI damage tissue
• immunopathology
– helps clear • DTH, Ag/Ab complexes
infection can weaken
vasculature- leading to
• provides hemorrhagic symptoms
protection from
further infection
Alpha and Flavivirus epidemiology
• Zoonoses with broad host range
– mammals, birds, amphibians, reptiles
• Vectors mosquitoes (or ticks/ sandflies)
– restricted to persistent genus of mosquito
• must be able to establish persistent infection of
salivary glands
• Reservoirs “immunologically naïve”
birds small mammals/ reptiles/
amphibians
– persistent source of infection
• Humans- dead end hosts
– susceptible iff living near reservoir/ vectors
Alpha/ Flavivirus epidemiology cont’d
• Rural environments
– tropical forests, swamps, stagnant water
• puddles, ditches
• Urban environments
– artificial ponds, toys, trash cans

• Virus over-winters in:

– 1) arthropod larvae or eggs or in reptiles/
amphibians
– 2) migrate with birds, return in summer
 Alpha/ Flavivirus clinical syndromes
• Sporadic incidence of disease
• Infection flu-like syndrome (chills, fever,
anorexia, myalgia) becomes either:
– 1) meningitis/ encephalitis 3-10 days
after infection high fever, H/A,
decreased LOC
• eg. WEE, EEE, VEE, West Nile, St. Louis,
Japanese
– or 2) hepatitis, hemorrhagic fever,
shock, viral arthritis
• eg. dengue fever, yellow fever, Ross River
 Infection

Flu-like syndrome

Encephalitis Hepatitis

Western equine hemorrhagic fever

Eastern equine dengue/ yellow fever
Venezuelan shock
West Nile, St. Louis arthritis
 Yellow fever
• In Africa, Central and S. America, Caribbean
– monkey reservoir (jungle fever), Aedes
aegypti mosquito
• not contagious no person to person
spread
• 3-6 day incubation sudden onset of high
fever, H/A, muscular aches organ pathology
– LV jaundice, dark urine, clay colored stools
– KI proteinuria, tubular necrosis, oliguria
– HT failure, HTN, myocarditis pulmonary edema
– Blood vessels haemorrhage
– Hematemesis: “black vomit”
– Unlike other flaviruses encephalitis is rare
– Prostration/ shock
• 50% mortality during epidemics
Yellow fever endemic areas
 Dengue (break bone) fever
• S. E. Asia, Pacific, Caribbean
– quadrupled incidence since 1984, 50%
mortality if untreated
• Aedes aegypti mosquito, 4 different dengue
viruses
• Primary infection:
– 4-8 day incubation high fever (39.50C-
41.40C), n/v, rash
• back/ bone pain for 6-7 days remission for
few days
– fever returns with a maculopapular rash
» resolve in two weeks
Distribution of Aedes aegypti in 1970
and 2002
Laboratory confirmed cases of DHF in
Americas
Dengue hemorrhagic shock syndrome:

– M/C in children upon re-exposure to

related strains of virus
• Ab from previous infection promotes
uptake into macrophages/ monocytes
– memory T cells respond by releasing many
inflammatory cytokines
• hypersensitivity reactions
– weaken, rupture vasculature
» internal bleeding, epistaxis, purpura,
gum bleeding, menorrhagia, DIC, shock,
no bone pain, abdominal pain
Dengue fever hemorrhagic syndrome
Alpha/ Flavivirus lab diagnosis
• Culture:
– difficult to grow
• Serology:
– 4X increase in viral titer by
immunofluorescence
• problem: false (+) much cross-
reactivity
• RT-PCR:
– genomic/ viral mRNA in blood etc.
• ELISA/ latex agglutination
Alpha/ Flavivirus treatment/ Prevention
• Treatment:
– none, symptomatic only
• Prevention:
– avoid breeding grounds
• wear mosquito repellant (Deep woods off--DEET (not
directly to children skin, not if pregnant, not if < 2 y.o.a.)
citronella, musk-oil, skin so soft), garlic, vegetarian?
– control of mosquito
• larvicide, pesticide
– vaccines for yellow fever (live attenuated virus-
17D), EEE, WEE, Japanese, Russian Spring/
Summer, VEE
• no vaccine for Dengue fever:
– potential risk for immune enhancement upon
subsequent re-challenge
 Quote of the day
• “If you didn’t get all the things you
wanted,
• you can still be grateful for all the
things you didn’t want that you
didn’t get”

– Anonymous
 Phylogeny
• A) Picornaviridae family
– 1) enterovirus genera
• polio, coxsackie, echo virus species
– 2) rhinovirus genera
– 3) heparnavirus genera
– 4) cardiovirus genera
– 5) aphthovirus genera
 Phylogeny cont’d
• A) Togavirus family:
– Genera Alphavirus- VEE, WEE, EEE
– Genera Rubivirus--Rubella species
– Genera Arterivirus- no known human disease
• B) Flaviridae family
– Genera flaviviruses- dengue, yellow fever,
west nile, HCV, HGV, St. Louis encephalitis,
Japanese encephalitis, Ross River
– Genera pestivirus- no known human diseases
• Arborvirus grouping
– Alphavirus and flavivirus
 Phylum Arthropoda
• Subphylum Chelicerata
• Class Merostomata (horseshoe crabs, eurypterids)
• Class Pycnogonida (sea spiders)
• Class Arachnida (spiders, ticks, mites)
• Subphylum Crustacea
• Class Remipedia
• Class Cephalocarida
• Class Branchiopoda (fairy shrimp, water fleas, etc.)
• Class Maxillopoda (ostracods, copepods, barnacles)
• Class Malacostraca (isopods, amphipods, krill, crabs, shrimp,
etc.)
• Subphylum Uniramia
• Class Chilopoda (centipedes)
• Class Diplopoda (millipedes)
• Class Insecta
 West Nile Virus introduction

• Originally from Africa (Nile river), West Asia,

Middle East-(first case, 1937 in Uganda)

– 1st confirmed in U.S.A. on September 14,

1999
• captive dead pheasants and flamingos at
Bronx Zoo, crows in Central Park
– 71 confirmed deaths in U.S.A. in 2002 (6 or
7 in Canada), 88 confirmed deaths in 2004
(0 in Canada)
• also affect horses (ataxia, muscle
twitching, “apprehension”)
– Closely related to St. Louis virus in
U.S.A.
 West Nile Virus introduction

• “almost 2X as likely to be hit by lightening

than to die from West Nile virus”
– in infected areas only < 1% of
mosquitoes are infected and < 1% of
people bitten by infected mosquito get
serious health affects
• “probably at limits of range in S.E.
Ontario but still potential spread to
Maritime provinces and West Coast”
 West Nile transmission and immunity
• Vector is Culex pipens/ Culex restuans
mosquitoe (larvae can overwinter)
• No person to person transmission
– possibly breast feeding, blood products, organ
transplants, prenatal
• main reservoir is corvid birds
– Crows, magpies, ravens, jays, sparrows?
• but also can infect horses, cats, bats, chipmunks,
skunks, squirrels- chickens?
• Immunity?:
– not sure if cause chronic infection but unlikely
• assumed that immunity to re-infection is life-long but
not sure
 West Nile Virus clinical syndrome
• full clinical spectrum has not been determined
but most infections are mild or sub-clinical
– 3-14 days febrile disease of sudden onset
• malaise, anorexia, n/v, H/A, myalgia, rash, eye
pain, lymphadenopathy--lasts 3-6 days
• severe disease encephalitis
– (severe H/A, nuchal rigidity, altered LOC,
seizures, ataxia, cranial nerve abnormalities,
optic neuritis), fever, weakness, GI
symptoms, rash on neck/ trunk/ arms/ legs
• Most significant risk factor is advanced age
(immunocompromised?)
 West Nile virus diagnosis
• Unexplained encephalitis or meningitis
in adults > 50 y.o.a. in summer or early
fall
– Travel history to endemic areas
• Lab dx:
– ELISA for anti- WNV IgM in serum or CSF
within 8 days of infection
– CSF:
• lymphocystosis, elevated protein, normal
glucose
– RT- PCR for viral genome
 West Nile treatment/ control
• Treatment:
– supportive only
• hospitalization, IV fluids, respiratory support,
prevent secondary infections
• Control:
– regular mosquito protection (clothing, repellants,
avoid outside activity during evening hours),
remove outside water containers
• larvicide to standing water (contains Bacillus
sphaericus. B. thuringiensis (Bt part of GMOs?)-
larvae ingest bacteria--bacteria disrupt mosquito
gut (“will not affect other animals”)
• Altosid- XR extended residual briquette to
standing water (contains Methoprene- insect
growth regulator and pesticide)
 Rhabdovirus introduction
• Two genus:
– 1) Vesiculovirus--vesicular stomatitis viruses
– 2) Lyssavirus---rabies virus
• simple, enveloped ssRNA with bullet shaped,
helical nucleocapsid
– VAP is a glycoprotein
• internalized by endocytosis, replicate in cytoplasm,
bud at plasma membrane
– Unlike other viruses causing encephalitis--not very
cytolytic--rare inflammatory lesions
• One the most deadly viral diseases--100% mortality
Rhabdovirus structure
 Rabies transmission/ epidemiology
• Zoonoses- transmitted from animal to human
– M/C’ly bite of a rabid dog (also cats, foxes,
raccoons, coyotes, skunks, bats)
• also aerosolized--bat caves,
– also corneal transplants and body fluids
• endemic in animals worldwide except
Australia and Japan
– also major cause of death in cattle and bats?
• does not penetrate intact mucosal membranes
– Risk with health care workers
• exposed to salvia, tears, urine of infected person
Rabies transmission
 Rabies pathogenesis
• Attach to nicotinic Ach/
ganglioside receptors at
muscle/ nerve at site of
• Incubation phase
wound- local replication
– lasts for days to
months depending on
proximity to CNS,
infectious dose, host’s
age, host’s immune
status
• start to develop
protective Abs iff
actively immunized
 Rabies pathogenesis cont’d
• Prodrome • Retrograde axoplasmic flow to dorsal root
ganglia
– no detectable Abs
• hidden from immune system

• Neurologic • travel to infect brain/ encephalitis

phase – hippocampus/ limbic system
(behavioral changes), brain stem
(respiratory centers), cerebellum
(coordination)
• travel back down afferent nerves to
skin of head/ neck, salivary glands,
nasal mucosa, adrenal glands, KI,
pancreas, retina/ cornea/
conjunctiva, lactating glands and
milk
 Rabies clinical disease
• Asymptomatic
• Incubation phase – 1-12 months after
exposure
• Delay is important for
treatment

• 2-10 days of fever,

• Prodrome
malaise, H/A, pain/
paresthesia at site of
wound, GI symptoms,
fatigue, anorexia, sore
throat
 Rabies clinical disease cont’d
• 2-10 days of progressively worse:
• Neurological Hydrophobia (20-50% of those infected)
(pharnygeal spasms/ pain when drinking water,
foaming at mouth), aerophobia,
hyperactivity, aggressiveness, seizures,
delerium/ hallucinations
– “furious rabies”- death in 1 week
• like tetanus but with CNS changes

• 15- 60% just have symmetrical

ascending paralysis- “dumb rabies”
– death 2-3 weeks
• progress to death by cardiac or
respiratory arrest (only 4 known
survivors)
 Rabies diagnosis
• Once there is evidence of infection (symptoms or Abs) it is
too late for effective intervention
– Capture and observe infected animal in isolation-
• iff survive 10-14 days-unlikely to be rabies
– iff die quickly start anti-rabies treatment of infected person

• Lab dx:
– usually to confirm diagnosis
• immunofluorescent viral Ag detection by ELISA or latex
agglutination in corneal epithelium, skin biopsy (+ only > 7-10
days after) or PCR
– post-mortem Negri bodies in neurons of hippocampus
and cerebellum Purkine cells
• eosinophilic intro-cytoplasmic aggregates of nucleocapsids
Negri bodies
 Rabies treatment
• Treatment:
– aggressive post- exposure prophylaxis is only hope for
overturning clinical illness
• Treat no later than 4-5 days after wound exposure or 100%
fatal
• 1) wound management
– clean thoroughly (water, soap, detergent, iodine, 40-70% EtOH,
citricidal, thymol, oil of oregano)
• anti-rabies serum around and into wound
• 2) immunization:
– passive (human rabies immunoglobulin/ HRIG or equine anti-
rabies) and active (chemically inactivated rabies infected tissue
culture from human diploid cells or fetal rhesus lung cells)
• IM day of exposure and days 3, 7, 14, 28
• Homeopathic- ledum, arnica, hydrophobinum or lyssisinum
 Rabies control
• Vaccinate:
– domestic animals, wild animals (oral vaccine injected into
bait and parachuted into forest, other viral vectors containing
recombinant rabies glycoprotein gene), humans travelling to
endemic areas, animal workers
• active vaccination with 3 subsequent doses will give 2 years
immunity

• Vaccine
– introduced by Louis Pasteur in 1885-crude extract of
rabbit spinal cord containing virus
• hypothesized that long incubation time would allow immunity
to develop before onset of symptoms
 Reoviridae introduction
• Respiratory Enteric Orphan viruses
• Includes:
– Orbiviruses, Coltiviruses (Colorado Tick
fever),
– Orthoreoviruses (asymptomatic infections),
– Rotaviruses (#1 cause of infant diarrhea
worldwide)

• double layered protein capsid containing 1-

12 segments of dsRNA (antigenic shift like
Influenzae A)
• non-enveloped (resistant to detergents,
acidic pH, drying, repeated freezing/
thawing)
Rotavirus structure
Viral orphans
 Rotavirus pathogenesis
• Spread is fecal-oral and ?respiratory?
• Absorption to columnar epithelial cells of
villi of SI
– shorten/ blunt villi and promote mononuclear cell
infiltrate into lamina propria

• 8hrs after infection

– notice cytoplasmic inclusions and 1010
virions /gm stool
• NSP4 protein (like cholera toxin) loss of
ions (Na, Ca, glucose) into intestinal lumen
prevents absorption of H2O
 Rotavirus immunity
• Abs from mothers colostrum/ milk
– only prevents infection for 6 months
• sIgA helps prevent infection but only
temporarily (several months)

• Antigenic shift (like influenzae)

makes immunity only temporary
– always new strains

• Without neutralizing Abs even a small

number of virions (10) can cause
infection
– consider that there is 1010 virions per
gram of stool at most infectious stage!!!!
 Rotavirus epidemiology
• Ubiquitous 95% of children
worldwide are infected by age 3-5
– very contagious maximal shedding 2-5
days after start of diarrhea
• transmitted on furniture, fomites, toys,
hands
– M/C in autumn and spring
» Outbreaks in preschools, daycare,
children’s hospitals, cruise ships
• Type A:
– infants < 24 months and malnourished in
developing nations
• gastroenteritis- potential dehydration
• Type B:
– Chinese infants, older children, adults
 Rotavirus clinical
syndromes
• Gastroenteritis:
– 48hr incubation sudden onset of
severe vomiting (projectile), watery
diarrhea, fever, dehydration
• Also cough and coryza is common?
• Self-limited recovery usually
without sequelae
– Not distinguishable from other
types of gastroenteritis (Norwalk
virus, bacterial) by signs and
symptoms
• no blood or leukocytes in stool
Rotavirus prevention
 Rotavirus lab diagnosis/ treatment/
control
• Diagnosis:
– Stool samples:
• ELIZA, RIA, latex agglutination, TEM for
viral antigens
– Serology:
• 4X increase in titer
• Treatment: supportive only
• Control:
– vaccines (prepare from animal
rotaviruses--rhesus monkey, Nebraska
calf)
• share Ag determinants with humans
– previous failed vaccine that caused
intestinal defect
 Coltivirus introduction
• M/C tick borne viral disease in USA
– (compare to Lyme disease and RMSF)
• similar to other reoviruses but:
– 1) no discernible capsomeric structure
– 2) persistent viremia infects RBC
precursors
• survives in mature RBCS protected from
immune response
– 3) life cycle is vector wood tick
(Dermacenter andersoni); reservoir
squirrels/ chipmunks;
• Hosts humans
• invades vascular endothelium/ vascular
smooth muscle
 Coltivirus epidemiology/ lab
diagnosis
• Western/ Northwestern USA and
Canada
– M/C in spring/ summer/ autumn
• unlike other tick diseases, coltivirus
must enter blood stream quickly
– I.e. must remove ticks quickly before they
bite
• Lab dx:
– detect viral Ag on surfaces of RBCs of
blood smear- immunofluorescence
– Serology:
• specific IgM present for 45 days after
onset of illness
– Blood work:
• marked leukopenia (including
Colorado tick virus
 Colorado tick fever
• 3-6 day incubation
– sudden onset of fever
(biphasic), chills, H/A,
photophobia (conjunctivitis),
myalgia, arthralgia, lethargy,
• maculopapular/ petechial rash
(like RMSF)
lymphadenopathy,
hepatosplenomegaly
– Hemorrhage hypotension
shock (like dengue fever)
 Colorado tick fever
treatment/ prevention
• Treatment:
– none, supportive only

• Prevention:
– same as for other tick borne
disease (protective clothing, tick
repellents, avoid tick areas), remove
tick quickly
 Poxviridae introduction
• Orthopoxvirus: Variola (smallpox)
– Molluscipoxvirus: Molluscum
contagiosum
• one of the largest, most complex
viruses brick/ ovoid shaped linear
dsDNA virus
– unique double layered envelope
• unlike other viruses, envelope is
formed at Golgi apparatus
• entire replication cycle occurs in the
cytoplasm
– unlike other viruses
• Pox viruses contain all the necessary
Pox virus structure
 Smallpox virus history
• Historical accounts for over 2000 years
– 18th century England caused 7-12 % of
all deaths, >30% deaths in children
• 1st live vaccine in 1796
– vaccinia rubbed in sores
• in 1967 WHO mandated that in 10 years they
would vaccinate all susceptible people in the
world
– last reported case October, 1977 in
Merca, Southern Somalia (in lab in UK
1978)
– worldwide eradication declared in 1980
• “eradication is one of the greatest
triumphs in medical history”
– the “smallpox virus joined the dodo and the
 Smallpox virus today
• “One diagnosed case of the disease anywhere
in the Western hemisphere would be
perceived as a terrorist assault by the Bush
administration”
• Category A
– greatest potential threat for adverse public health
with moderate to high potential for large scale
dissemination (include anthrax, plague, botulism,
tularemia, viral hemorrhagic fevers)
• Vaccine stockpiled in U.S.A. and Russia
(spread to terrorist groups?)
– Friday, December 13, 2002 George Bush
declares plan to inoculate 11 million
military personnel and emergency
responders (mandatory for 500,000 armed
forces heading to Persian Gulf), wants to
give vaccine to all Americans by early
spring
• “The risk of the vaccine is higher than the risk of
us having a case of smallpox”.
Concern for Smallpox as bioterrorist
threat
• In 1980, when WHO declared Smallpox as
extinct “the former Soviet Union began an
aggressive campaign to stockpile vaccine
and create weapons of mass destruction to
disseminate it as biological warfare-- with
collapse of Soviet Union--some of these
stocks have fallen into the hands of
countries with known terrorist groups”
• Anthrax kills 90% of those infected but is
not spread person to person Small pox
kills only 30% but:
– is very infectious
• 50-100 people infected could spread to
thousands
– need direct and fairly prolonged face to
face contact but also fomites, body fluids
– aerosol stable, small infectious dose
– immunologically naïve population
•
 Smallpox vaccine
• (DryVax) live Vaccinia (modified
Cowpox prepared from calf lymphus)
virus injected
– enough antigenic cross- reactivity? to
protect against Variola (Smallpox)

• Side-effects include:
– swelling, tenderness, itching, fever,
fatigue, encephalitis, vaccinia necrosum,
myocarditis, photophobia
• (14-52/ 106 experience potentially life-
threatening reactions, death in 1-2 per
106 inoculated 300-600 people if
every American inoculated)
– vaccinated person potentially infectious
for 2-3 weeks after (avoid close contact)
Vaccinia necrosum
Post vaccinial
lymphadenitis
Eczema vaccinatum
 Smallpox vaccine cont’d
• can not be given to pregnant, HIV+,
immunosuppressed (CA, steroid
treatments), or skin diseases like
eczema (even if these skin conditions
occurred in the past), children >12-18
y.o.a.
– theoretically 95% effective
• 15 million still get smallpox?
– high level immunity for only 3-5
years
• life long if natural
 Smallpox
• Variola major (5 types) most serious
15-40% mortality), variola minor
milder, 1% mortality

• Variola is inhaled (4- 19 days,

asymptomatic, not contagious)
– replicates in upper respiratory tract
enters macrophages
• Lymphatics local lymph nodes cell
associated 10 viremia
• prodrome (2-4 days)
– Abrupt onset 20 intense viremia and high
fever, myalgia, vomiting, malaise etc.
spread to internal organs (SP, LV, bone
marrow)
Smallpox disease course
 Smallpox cont’d
• skin rash (most contagious)
– hemorrhage of dermal vessels
leads to rash and pox
• spread from face (tongue and mouth)/
trunk to extremities within 24 hours
small red open sores nodules
– thick opaque fluid filled center with
“belly button-like depression in
center” pustules- crusts
» infectious until all scabs fall off
(6 days) permanent scars
• unlike chicken pox, in smallpox, all
the lesions are at the same stage at
the same time
Small pox rash
Smallpox rash
 Smallpox diagnosis/
treatment
• Diagnosis:
– M/C’ ly clinical only, PCR or RFLP
• CPE:
– characteristic lesions (pocks) on
chorioallantoic membrane of
embryonated chicken eggs
• Treatment:
– Injected cidofovir (not absorbed through
GIT) new drug is HDP-cidofovir (cidofovir
linked to fatty acid molecules that are absorbed);
therefore, taken orally
– “Patients with smallpox must be isolated
and managed, if possible, in a negative-
pressure room until death or until all
Other pox viruses epidemiology
• Molluscum contagiosum and other
pox viruses are zoonoses
– spread by direct contact with diseased
animals
• eg. Cowpox/ pseudocowpox- milker’s disease
– infected udders, rodents, cats, vaccine
related disease
• Monkeypox
– monkey as food in parts of Africa (Ivory
Coast)
• Molluscum contagiosum
– STD, fomites, wrestling, rugby
• M/C in children (especially atopics)
– increasing incidence in sexually
active and HIV+
 Orf
• Caused by direct
contact with
infected sheep/
goats, soil?
– contagious
pustular
dermatitis,
painless vesicles
• progress to red,
weeping
granulomatous,
nodules
– crusting,
healing
» self limited
(25-35 days)
Ecthyma contagiosum (Orf)
 Molluscum contagiosum
• Genital tumors or
disseminated large skin
tumors
(immunocompromised) or
small benign warts,
cutaneous papules in
children/ adults
– 2-8 week incubation

– fleshy, pearl- like

umbilicated
nodules with
 Molluscum
contagiosum
Molluscum contagiosum
in immunosuppressed
Molluscum contagiosum diagnosis
and treatment

• Treatment:
– None: self-limiting 2-12 months
– curettage or liquid N2 or
podophyllin or 2% salicylic acid
• Diagnosis:
– characteristic skin lesions
– molluscum bodies on biopsy
• large eosinophilic cytoplasmic
inclusions in epithelial cells
• No culture or animal models
– only affects humans
Molluscum bodies
Molluscum bodies
Scrapies-like agent introduction
• First described over 200 years ago in
sheep/ goats in Europe cachexia,
ataxia, pruritic
– Nobel Prize 1997 (Stanley Prussner)
• infectious agents were prions
(proteinaceous infectious particles)
– filterable (size of viruses) but no DNA or
RNA
• replicate very slowly
– 5 days to 1 week doubling time
• (C. perfringens is 14 minutes)
• very resistant
– heat (boiling, 800C), chemicals (formaldehye
for years), UV irradiation
–
 Scrapies agent cont’d

• Cause of:
– Scrapie, BSE (mad cow disease),
transmissible milk encephalopathy
(mink farms), chronic wasting
disease (mule deer, elk), Kuru
(cannibals in Papa New Guinea),
sporadic Creutzfeld-Jakob disease,
variant CJD

• Associated with familial GSS and

fatal familial insomnia
 Scrapie-like illness
epidemiology
• Transmissible neurogenerative
disease to a variety of
mammals including humans,
primates, cows, sheep/ goats,
mink, hamsters, mice etc.
Scrapie like agents epidemiology
 Scrapie-like illness
pathogenesis
• Not very well known
– very closely associated with normal
human protein PrPc
• on chromosome 20, in variety of cells in CNS,
Cu binding, synaptic transmission?
– PrPSc some variation of PrPc that might
be actual infective agent
• direct interaction with PrPc in susceptible
people might spark catalytic conversion to
pathogenic PrPSc form

• get aggregates of protease resistant

hydrophobic glycoproteins in plaques/ fibrils
in CNS
– no immune response and no inflammation
• aggregate in host cell amyloid plaques
 Scrapie-like illness
diagnosis
• Mostly clinical and patient
history

• Not cultivated in lab, no Abs

produced, normal CT scan,
normal MRI, abnormal EEG

• Western blot
– confirm diagnosis
c
Scrapie-like diseases Western Blot
 Creutzfeld Jacob disease
sporadic form
• Long incubation (up to 30 years) but rapidly
fatal once symptomatic (M/C only 1 year)
– Rare incidence is 1 in 106

• rapidly progressing dementia, cerebellar

dysfunction, cortical blindness, akinetic
mutism, pyramidal and extra-pyramidal signs
(loss of muscle control/ coordination, shivering,
myoclonic jerks/ tremors)
– mutation of meth/ val at codon 129 of PrPc

» genetically susceptible person infected

with prions?
 Creutzfeld- Jacob disease
sporadic form transmission?

• Eating or in contact with BSE

contaminated food
– not proven
• Incompletely sterilized neurosurgical
stereotactic electrodes
• corneal grafts
• injection of GH prepared from pooled
human pituitary glands
– before engineered GH
• genetic susceptibility
– 10% occurs in families with mutations in
PrPc gene- spontaneous mutation or more
easily converted to pathogenic PrPSc form
after contact with prion
 Creutzfeld-Jacob disease
variant form
• 1st identified in 1996:
– by 2002 affected 125 people in UK, 6 in
France, 1 in Ireland and 1 in Italy
– meth/ meth mutation at codon 129 in PrPc
gene

• Young onset mean is 27 y.o.a.

– prolonged clinical illness (average 13
months)
• pyschiatric/ sensory symptoms
ataxia within weeks or months/
myoclonus
– dementia at final stage only
» unlike sporadic CJD
Sc
 Creutzfeld-Jacob variant
form
• Strong laboratory and epidemiological
evidence of link to BSE
– identical to BSE agent in mice, similar
Western Blot pattern, similar timing to
BSE outbreak in UK (all affected people had
multiple -year exposure in UK during 1908-1996
BSE outbreak, contaminated beef/ beef products?)-
• no BSE in U.S.A., one possible case
April 18, 2002 in Florida (22 year old
male)
• currently a donor deferral policy
– no blood collected from people that
have lived or traveled for >3
months in Europe from 1980-1996
vCJD brain tissue
 Quote of the day
• “You must not let your life run in
the ordinary way; do something
that nobody else has done,
something that will dazzle the
world. Show that God's creative
principle works in you.”

• by Paramahansa Yogananda
 Quote of the day

• A friend is someone who knows

• the song in your heart
• and can sing it back to you
• when you have forgotten the words.

• -- Unknown