A Virology 10 Systemic

Front 1

VZV Clinical Features

Back 1

origionaly thought it was 2 diff viruses
1)1o, varicella or "chickenpox"
– systemic / disseminated viral disease
2)reactivated, zoster or "shingles"
- localized viral disease w/ neuronal spread to an affected dermatome

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VZV Chickenpox characteristics

Back 2

- mild febrile illness of kids
- disseminated vesicular rash of clear blisters w/ irregular red margin
– resolved in a few wks(no scar)
Lesion form: macules -> papules -> vesicles -> pustules -> scabs
headache and malaise: -> pruritic(itching) rash -> low fever/irritability

Front 3

VZV chickenpox complications

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1) 2o infections of lesions, w/ risk of subsequent septicemia
2) post-infectious encephalomyelitis(self limiting, fine in immunocompetent kids)
3) pneumonia if immunocompromised, high mortality(more b/c immunosupp therapy)
4) Varicella pneumonia-1o inf in adults, serious b/c cell to cell spread via Fusion
5) Reye’s syndrome-acute encephalopathy (aspirin)

Front 4

VZV Shingles characteristics

Back 4

- reactivation of latent VZV
- like chicken pox, but larger lesions on the dermatome innervated by infected sensory nerve
- may be very painful
- usually develops when immunosuppresed (so odds increase w/ age)

Front 5

VZV shingles complications

Back 5

post-herpetic neuralgia(70% of patients)
a)hypersensitive to touch and T extremes
b)may persist for months(episodic or constant)
mild to severe

Front 6

VZV Properties of the Virus

Back 6

- like herpes simplex virus(same struct/replic)
- enveloped - so easily inactivated(heat, detergents, organic solvents)
- rapid replication and ease of transmission so hard to exploit enviro fragility

Front 7

Pathogenesis of Primary Varicella-Zoster Infection

Back 7

- non-specific binding in the nasopharynx
- initial replication in resp epi -> regional LNs -> viremia to liver and spleen
- 2o viremia mediated by PBMCs -> transports virus to cutaneous epi(rash) and resp mucosal sites(spreads to other non-imune host)
- w/ hematogenous and neural spread -> latent state in the sensory nerve ganglia following 1o inf
- asymptomatically shed throughout the host’s life

Front 8

VZV Epidemiology and Transmission

Back 8

- universal childhood infection
- spread by resp droplet
- shed prior to symptoms(avoidance=difficult)
- both are non-seasonal and non-epidemic
- maternal protection for first six months
- immunity primarily cell-mediated
- 1o disease confers lifetime immunity to 1o
- but shingles(2o) may develop if immunocomp (age-80yr=50% risk fo shingles)
– then protected from shingles

Front 9

VZV Diagnosis

Back 9

- based on presentation and contact history
LAB TESTS:
1) Tzanck smear from vesicles- syncytia, intranuclear inclusion bodies
2) fluorescent Ab detect virus in lesions
- culture provides the definitive diagnosis but is difficult(growth in vitro is poor)

Front 10

VZV Prevention and Treatment

Back 10

- kids over 1 yr get one attenuated vaccine
- Acyclovir (or penciclovir) may terminate the viremia, reduce shedding, lessen severity
- Zoster immune globulin given to exposed non-immunes
- testing, live-attenuated, varicella "booster" vaccine for people >60 to stop shingles
- US('95-'00)drop in varicella in all age groups b/c of increased vaccine coverage

Front 11

Cytomegalovirus (HCMV) Clinical Features

Back 11

Presents differently among:
- normal immunocompetent
- fetuses
- immunosuppressed

Front 12

HCMV Immunocompetent inf

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- 1o = unremarkable, usually in childhood, subclinical
- most adults seropositive
- in (-) adults, 1o often from children shedding in urine, saliva and feces, or intimate contact w/ shedding adult
- adult 1o -> mild pharyngitis or EBV-like mono(fever,lymphocytosis), Mild hepatitis
- after 1o, symptoms cease; viral shedding falls but may recur
-Latent in Lymphocytes, heart, Kidneys

Front 13

Cytomegalovirus Congenital Infection

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- if infected for the first time in pregnancy, may transmit to fetus
- in 1st trimester -> severe birth defects
- if later; rarely-> congenital abnormalities
- (+) women w/ recurrent infection rarely transmit it, if they do, infants=less affected
- Affected babies may appear normal, but have progressive damage to NS, esp hearing
- most common congenital viral inf, leading cause of NS abnormalities

Front 14

Cytomegalovirus Immunosuppressed

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- may develop severe disease after 1o or re-act infection:
1)interstitial pneumonia
2)retinitis
3)enteritis
4)disseminated disease
- AIDS:
1)a high % of AIDS patients shed
2) ½ have infection at somepoint
- primary post-transplant infection, esp bone marow

Front 15

Cytomegalovirus Properties of the Virus

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- like herpes (HHV-5)
- largest herpesviruses genome
- it has a restricted host range
- it is sensitive to heat, low pH, lipid solvents (envelope)

Front 16

Cytomegalovirus Pathogenesis and Immunity

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- outcome determined by host immunity
- 1o inf in salivary gland epi -> asymptomatic viremia and shedding(in immunocompetent)

Front 17

Cytomegalovirus Epidemiology and Transmission

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- ubiquitous everywhere, more in urbar areas(b/c of need for close contact to spread)
- humans only reservoir
- in all body fluids->all types of close contact transmits
- (+) can shed for years
Sources:
a) often in transfused blood
b) daycare kids
c) immunocomp shedding more
d) (+) moms milk(maybe highest mode of transmition)

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Cytomegalovirus Diagnosis

Back 18

- hard to say it's a cause b/c it's everywhere
- subclinical in most
- misdiagnosed as EBV.
- likely the cause of mono if EBV heterophile antigen test is negative
1)found in WBCs by immunofluorescence.
2)shell vial assay detects w/in within 24 hours.
3a)in immunocomp - serology for IgM and IgG
3b)in congenital - culture infant’s urine and saliva
3c)in immunosup - culture a biopsy

Front 19

Cytomegalovirus Prevention and Treatment

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- no good treatment
- no viral TK, so no acyclovir or penciclovir
- ganciclovir(dG analog) works, b/c a viral protien kinase will phosphorylate it
a)GCV much more toxic and expensive than ACV/penciclovir

Front 20

Poxviruses Clinical Diseases

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- Smallpox(variola major/minor)
- Vacinnia
- Molluscum contagiosum
- Zoonotic poxviruses

Front 21

Poxviruses Clinical Disease Smallpox

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- eradication in 1977
- presented as either variola major or minor(less virulent form)
- rash began as macules -> papules -> vesicles -> pustules -> crusts
- loss of scabs=severe scarring/pockmarks
- major form of had 10 - 30% mortality, partly due to disruption in food production(starvation)
- Monkeypox in African is transmissible to human(clinical features=identical to smallpox)

Front 22

Poxviruses Clinical Features Vaccinia

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- Less-virulent relative of variola(used as propylaxis of variola for 200yrs)
- following subcutaneous inoculation->papule at site
- lesion has same pattern as smallpox w/out spreading(w/ scab and characteristc vaccination scar)
- Rarely->sequelae(e.g. auto-inoculation of cornea, systemic vaccinia in immuno-incompetent

Front 23

Poxviruses Clinical Features Molluscum contagiosum

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- self-limiting infection of the skin
- small umbilicated nodules w/ small white cores
- may last from months to years(spontaneously resolving)
- increased severity in AIDS
- increasing frequency in genital infections->heightened awareness

Front 24

Poxviruses Clinical Features Zoonotic poxviruses

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- transmitted by direct contact to humans
- occupational hazard
- self-limiting lesions on hands or face
- orf virus of sheep or goats
- cowpox, bovine pustular stomatitis and pseudocowpox of cattle(cowpox=cats too)

Front 25

Poxviruses Properties

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- large, dsDNA
- brick-shape virion of complex structure
- replication, transcription and prot synth occur in the cytoplasm
- have DNA-dependent RNA poly in nucleocapsids

Front 26

Poxviruses Pathogenesis

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- inhalation of variola ->replication in URT, LRT -> infection of Macs -> Macs migrate to regional LNs where virus replicates -> 1o cell-associated viremia (still asymptomatic and non-infectious)
- replication in the spleen and bone marrow -> 2o viremia and replication in small vessels of dermis
- migration of inf Macs to epidermis -> characteristic symptoms
- inf of Oropharyngeal epi -> spread to other hosts

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Poxviruses Epidemiology and Transmission

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- variola virus only shed during acute infection
- outbreaks in rural area got all age groups
- in urban = only kids(b/c frequent exposure)
- monkeypox is relatively rare and less transmissible('97 outbreak in Congo had high human-human transmition), but just as serious

Front 28

Poxviruses Diagnosis

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- not part of differential diagnosis of vesicular rash
- most related viruses ass. w/ animals or travel, take careful history

Front 29

Poxviruses Prevention and Treatment

Back 29

- vaccination for lab workers handling it
- eradication worked b/c:
1) humans only reservoir
2) 1 serotype
3) all = symptomatic
4) predictable epidemics
5) recovered patients recognized by lesions
6) vaccine very stable when dried
7) vaccinees marked by vaccination scar
- encodes a (TK) that does not Phosphorylate ACV so ACV not effective

Front 30

Poxvirus immunity

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- development of humoral immunity = important in recovery and protection from re-infection
- natural variola inf -> lifetime immunity