herpes virus Flashcards
classification of herpes virus:
- basic features:
▪ Enveloped — viruses
▪ Make a – enzyme, which is essential for the virus to –
▪ The DNA polymerase is
inhibited by – such as –
( Electron micrograph of a herpes virus(Nottingham PHL)
* Invade human cells to cause —
* – is characteristic of herpes viruses
i.e. after primary infection, the immune system controls the virus but can’t get rid of it so the virus stays indefinitely in the body in an — state
* HSV 1 & 2 and VZV persist in – cells
* EBV & CMV persist in –
* Reactivation may be precipitated by:
– —
– —
– Other —
HERPES VIRUSES: CLASSIFICATION
1. Herpes simplex virus, type 1 (HSV1)
2. Herpes simplex virus, type 2 (HSV2)
3. Varicella-zoster virus (VZV)
4. Cytomegalovirus (CMV)
5. Epstein-Barr virus (EBV)
6. Human herpes virus 6 (HHV-6)
7. Human herpes virus 7 (HHV-7)
8. Human herpes virus 8 (HHV-8)
dna
dna polyemrase
replicate
antiviral as aciclovir
infection
latency
inactive state
nerve cells
lymphocyte
immusuppreson , stress , other infection
herpes simplex virus HSV-1+2)
* — very common
– High — ~90% by adulthood worldwide
– — over time
– Lower in — countries
* — less common
* Historically, HSV-1 infected “ – the-waist ” and HSV-2 “ — the waist” but epidemiology has changed & either can cause – or – disease
HSV-1
seroprevalence
declining
high income
HSV-2
above
below
oral n genital
herpes simplex virus 1-2 pathogenesis:
* Infect — cells
* — transmission from contact with —
* Virus causes —
‒ — (blister-like, fluid-filled) painful lesions of skin/ mucous membranes
* Virus then establishes – infection of innervating — (e.g. trigeminal ganglion)
* Reactivation occurs when immune system fails to suppress —
clinical features:
* “—” : Vesicular lesions of–/–, common
* —- whitlow: Vesicular lesion on —
* —: — now causes this more commonly than —
* — : Eye; can lead to — if scarring
* — herpeticum: — of eczema
* Encephalitis: Brain; poor outcomes, — mortality
* Disseminated disease: In —
muco epithelial
direct
vesicular fluid
cell lysis
vesicular
latent infection
neruon
viral replication
cold sores
lips and face
herpetic
fingers
genital herpes
hsv-1 more common that hsv2
heratitis
visual loss
eczema
superinfection
high
immunosuppressed
( very top to bottom aka very minor to more serious ones )
- HSV1 - oropharyngeal infection:
— infection - Majority —
- Fever, malaise, myalgia, painful
local lymphadenopathy - — can be widely
distributed
– Palate, pharynx, gingivae, buccal
mucosa, tongue - Can also get — infections
– i.e. Just – - HSV1 latency and recurrent infection:
Recurrent — infection - Induced by — fever, trauma, stress
- Usually corners of – /—
- Usually — than primary
infection - After primary infection, the
virus remains — in the
trigeminal ganglion
primary
asymptomatic
vesicular lesions
milder
just lips
( vesicles is early while crusted lesions is late)
oral
uv light aka sun
mouth n lips
milder
latent
HSV1 cutaneous infection:
— whitlow
* May occur due to —
* May be – e.g. in healthcare workers
Herpes gladiatorum
* — contact e.g. wrestling, rugby
HSV1 KERATITIS:
▪ Keratitis: inflammation of the –
▪ Mostly —
▪ Complications: Recurrent disease (≈30%)/permanent scarring/corneal damage /blindness
▪ — must not be given!
HSV1 encephalitis:
▪ Typically involves the —
▪ Often – outcomes (— mortality)
▪ Fever malaise, headache,
confusion, behavioural changes, seizures, coma
▪ Pathology: — , — , —
▪ Treatment: IV –
herpetic
auto inoculation
occupational
close
cornea
unilateral
topical steriods
fronto-temporal lobe
poor
high
haemorrhage , necrosis m oedema
iv acicilovir
herpes simplex virus 2
Clinical Manifestations:
* — herpes (sexually-transmitted)
– Historically HSV-2-associated but now more commonly caused by HSV-1
* Can also cause any of the manifestations of HSV-1 infection already discussed
characteristic of genital herpes:
* Characteristic —
* Penis in men
* Labia, vagina & or cervix in women (& urethra may be involved)
* Can also get—/— infection with HSV-2
genital herpes
vesicular lesions
rectal orpharngeal
neonatal HSV infection ( HSV1 or 2)
Acquisition
1. Via — (90%)
- 50% chance of neonatal infection if mother has primary— at delivery
2. — contact with someone with HSV
- e.g. — or —
* Most cases occur in babies of mothers who had — of HSV infection
* Because of poor — immune response in neonate, – risk of dissemination and – infection
* Consequences include:
- —
- —
- — sequelae
vaginal canal
genital infection
close contact as cold sores or herpetic whitlow
no sings
cell mediated
high risk
CNS infection
death intellectual disability and neurological
lab diagnosis of HSV 1 +2 :
Minor infections e.g. — :
* NOT required for (diagnosis based on characteristic clinical features)
Genital herpes:
* — on vesicular— used to confirm and to differentiate HSV-1 from HSV-2
Herpes simplex encephalitis:
* — on —
— HSV:
* Skin/mucosal swabs, CSF & blood for HSV DNA PCR
* Serology:
– Only — serology assay is commonly available/useful
– Can be type — e.g. HSV-1 IgG or HSV-2 IgG
– Main role = determining between — infection and— infection in pregnancy
cold sores
pcr on vesicular fluid
pcr on CSF
neonatal
IgG
specific
acute aka new and recurrent infection
varicella zoster virus VZV:
* ≥90% of adults in temperate climates are VZV — positive, indicating previous — infection
- Most people are infected in —
* — infection (chickenpox) is — contagious before & during symptoms
- Rates of infection >90% among susceptible household contacts of chickenpox ( — transmission)
* Reactivation of latent virus is known as – or —
- Occurs in ~30% over lifetime
- Risk increases with — as — immunity wanes
1- day 0: exposure by — or — with —-
2- day 14-21 fever/ irritability followed by appearance of —-
3- anytime after: reactivation ( —) especially in – or —
- incubation period is :
- infectious period is from – before rash until the skin lesions have —- which takes —
- latency in dorsal nerve root ganglia which takes —
IgG
primary infection
early childhood
primary
highly
aribone
herpes zoster or shingles
age
cell mediated
droplet inhalation or contact w vesicle fluid or fomites
vesicular lesions of chickenpox
shingles
old ppl or immuncompromised
2-3 weeks
48 hours
crusted over
few days
lifetime
VZV primary infection ( varicella/chickenpox) :
Clinical Features
– – / —
– — vesicular rash, especially on –
– — after few days, lesions –
* Most childhood varicella is —
* Complications much more likely in –
* Potential complications include:
- —- (e.g. with group —)
- —
- — manifestations: encephalitis, cerebellar ataxia
* Complicated infection requires treatment with–
- complications of varicella in pregnancy:
* High risk of complications of — in pregnant woman (pneumonia)
* Small risk of — syndrome in the baby (rare) if an expectant mother gets chicken pox in the first 20 weeks of pregnancy
* High risk of severe — in
the neonate if a mother gets — around the time of delivery
fever and irritability
genrelized
trunk
crust
itchy
not severe
adults
bacterial superinfection ( group a strep)
peumontitis
CNS
acivlovir
chicken pox
congenital vaticalla
disseminated varicella
chickenpox
VZV reactivation aka — - clinical features:
* Reactivation of latent virus from —
* Often in —/ — /patients with human —
* —- vesicular rash
* Treatment: —
* Pain precedes onset of rash & can
persist as —
* If shingles affects the ophthalmic
division of the trigeminal nerve, it
can be —
VZV lab diagnosis :
Uncomplicated primary infection in childhood / zoster:
* — diagnosis, — testing not usually
required
Other situations (e.g. infection in hospitalised patients):
* detection of VZV DNA by – in fluid from — lesions
* Detection of VZV IgG in blood is only used if evidence of — required
zoster or shingles
dorsal root ganglion
elderly immunosuppressed patient w HIV aka immunodeficiency virus
dermatomal
acivlovir
post-herpetic neuralgia
sight threatening
clinical
lab
pcr
fluid from skin lesions
previous infections
VZV prevention:
— Immunisation: 2 vaccines available
1. — vaccine (for prevention of chickenpox in children >12
months) Introduced as part of routine vaccination schedule in Ireland for children born after October 24 – 2 doses: 12 months,4/5 years
2. — vaccine (for prevention of shingles in older people)
—- Immunisation
Varicella zoster — (VZIG) - given — -exposure in high risk patients as:
– —
– —
– Neonate whose mother has — infection peri-partum
Infection Prevention and Control:
* — of hospitalised patients to prevent transmission
* Hospitalised patients with primary varicella infection should be
isolated with — precautions ( — infectious)
active
varicella
zoster
passive
imunoglobin
post exposure
preggo immunocompromised , primary infection
isolation
airborne
high
cytomegalovirus CMV:
Epidemiology: CMV seroprevalence varies widely between countries & socio-economic groups (~70% in adults inhigh-income countries)
Pathogenesis & Clinical Features:
* Primary CMV infection
– Infection acquired from most — (saliva, urine, breast milk), blood, tissue/organs ( — )
– Typically — or — especially in young children
– May uncommonly cause an infectious — syndrome
* Latent infection is in —
* Reactivation is a problem in —
patients e.g. post- organ transplan
bodily fluids
transplant
mild n asymptomatic
infectious mononucleosis-like syndrome
lymphocytes
immunocompromised
CMV congenital infection:
* Primary infection in pregnancy may lead to — CMV in the baby
* Estimated that 1% of all newborns are infected at birth
* 10-15% of these are — at birth
* – size
* Microcephaly, intra-cerebral calcifications, chorioretinitis, encephalitis
* Jaundice, hepatomegaly, rash, thrombocytopenia
* Unilateral or bilateral –
* A further 10-15% who appear – at birth present with sequelae
* Sensorineural —
* Developmental –
congenital
symptomatic
small
deafness
normal
hearing loss
delay
CMV in immunocompromised:
CMV reactivation is an important cause of complicated infection in — hosts
* – -positive patients with low – count: CMV retinitis
* — patients: CMV colitis ( — manifestation), pneumonitis etc.
Treatment:
* Reduce — (if — )
* — therapy (if — )
* — (e.g. – )
lab diagnosis of cmv:
* — for CMV – is the method of choice in immunosuppressed patients
- Blood PCR performed to detect — in immunosuppressed patients e.g. post-transplant
- — PCR (i.e. amount of virus in the blood) is used to monitor response to treatment
- Urine/ saliva PCR performed in suspected — CMV infection
* Serology (— , — )
* Histology e.g. for –
prevention of CMV:
No vaccine available at present but clinical trials are in progress
Neonatal:
* No CMV screening in—
* Neonates screened clinically at — as indicated
Transplant recipients:
CMV prevention protocols vary between centres
* Transplant donor & recipient screening, matching where possible
* Prophylactic administration of antiviral agents such as ganciclovir
immunocompromised
HIV
cd4
transplant
commonest
immunospression if transplant
antiretroviral if hiv
antivirals as ganciclovir
PCR for CMV DNA
reactivation
quantitive
congenital
IgM IgG
colitis
pregnancy
brith
epstein barr virus EBV:
* Discovered in biopsy specimens of —
~90- 95% of people are — seropositive
* Primary infection usually occurs
during – (often — )
* Primary infection in adolescents/
young adults can present as
infectious — (= —- )
Transmission:
* — , close — “Kissing disease”
Clinical Features:
* Exudative –
* —
* — (15-65%)
* —/ –
* Rash, typically after —
treatment for presumed “strep
throat”
(DDx. CMV, HIV, toxoplasmosis) ( the pathogenesis of 2,3,4 occur due to activation n proliferation of T cells )
B-cell lymphomas
IgG
childhood
asymptotic
mononucleosis
glandular fever
saliva oral contact
pharyngitis
lymphadenopathy
splenomegaly
hepatitis/hepatomegaly
ampiclin
EBV lab diagnosis of infectious mononucleosis:
Serology
* — to the virus
itself
- EBV —
- IgG to – antigen
(VCA) - for -
- IgG to — antigens (EBNA)- for –
* — antibody
(“Monospot”/ “Paul-Bunnell” test)
- Detected at the end of first
week; 10% false negative
Blood film
Atypical lymphocytes (blue
arrows) [compare with normal
lymphocyte (black arrow)]
EBV pathogensis of latent infection:
* EBV persists in —
* Stimulates B-cells in tissue culture to proliferate indefinitely
* — are essential in limiting the — of EBV-infected B-cells
* Impairment of T-cell immunity (e.g. post-organ transplant, in HIV infection) can result in —-
antibodies
IgM
viral capsid for early
nucelar antigen for late
Heterophile
b cells
T cells
proliferation
EBV-associated malignancies
complications of EBV associated malignancy:
* B- cell — as:
* — carcinoma
* –
*— disease (PTLD)
1- — refers to the poorly differentiated B-cell lymphoma of face & jaw endemic in parts of Africa
2- oral hairy leukiplakia refers to the — infection of —- causing lesions in — and it occurs in —
lymphomas as Burkitt’s lymphoma, Hodgkin’s lymphoma
nasopharyngeal
T cell lymphoma
psot transplant lymphoprolferative disease
burkitts lymphoma
opportunistic
epithelial cells
mouth
hiv
HIV 6,7:
HHV-6
* Causes—
— illness of childhood with — & — rash
May be associated with—
Most children infected by age –
* Can reactivate in — e.g. stem cell transplant/ solid organ transplant
* Integrated HHV-6 ~1% of population inherited as part of the —
HHV-7
* Roseola infantum ( – common than HHV-6)
* Not much known about its role in human disease
HHIV 8 - human herpes virus:
Causes — (HHV-8 essential but not the only factor)
– *N.B. Associated with — HIV infection *
– Different form occurs in the absence of HIV (e.g.sub-Saharan Africa, Eastern Europe and Mediterranean)
* HHV-8 mainly — transmitted, also —
transmission in children in Africa
* HHV-8 also linked to— -related body cavity lymphoma (type of non-Hodgkin’s lymphoma occurring in body cavities
e.g. pleural space/ peritoneal cavity)
roseola infantum
self limiting
high fever n maculopapular rash
febrile seizures
age 2
immunsorpssion
gremlin
less common
kaposi sacroma
advanced
sexually
horizontal
aids
summary:
virus: disease: site og latency
1- Herpes Simplex Virus 1 (HSV-1) : – : –
2-Herpes Simplex Virus 2 (HSV-2) : – : –
3-Varicella Zoster Virus (VZV)
—-
4-Cytomegalovirus (CMV) :
5-Epstein-Barr Virus (EBV) :
6-Human Herpesvirus 6 (HHV-6) :
7-Human Herpesvirus 7 (HHV-7) :
8- Human Herpesvirus 8 (HHV-8):
1- Coldsores etc. Encephalitis : Sensory nerve ganglia
2-Genital lesions etc. Neonatal herpes:
Sensory nerve ganglia
3- chickenpox Reactivation: shingles
:Sensory nerve ganglia
4- infectious mononucleosis,
Congenital infection:Lymphocytes
5- Infectious mononucleosis,
Burkitt’s lymphoma etc.:B-lymphocytes
6- Roseola infantum: CD4 T-cells
7- Roseola infantum: CD4 T-cells
8- Kaposi sarcoma: Tissue
