Herpes Virus Flashcards
General Properties - structure (size, shape, envelope), 4 features
Herpesviridae - 95-105 nm, “fried egg”, enveloped dsDNA, 8 viruses (HHV)
- large family of viruses infection almost every species
- cross species infection is very rare - Ubiquitous, no geographic restriction, efficient transmission usually in early childhood
- Latency - persist in host for life and can be reactivated
- stimulus e.g. stress, UV light, immunosuppression - Oncogenic property e.g. HHV4 i.e. EBV associated NPC or Burkett’s lymphoma, HHV8 associated Kaposi’s sarcoma
Specific characteristics of Herpes viruses (3)
All have high prevalence (>90%) except HHV-2, 8
Neuro-latency: all except HHV-4,5,8
Lympho-latency: all except HHV-1,2,3
Dermatotropic: all except HHV4,5
HHV-1/ HSV-1: primary infection (route, symptoms, duration), latency (site), reactivation (stimulus, symptoms)
Primary infection
- early childhood, affecting >95% population
- transmitted by kissing (virus shed in saliva of parents)
- may be initially asymptomatic then progress to symptomatic
- symptoms (above waist): gingivostomatitis (painful blister-like ulcers on oral mucosa); pharyngitis and tonsilitis in older children
- other symptoms? herpes keratitis (lid swelling) and encephalitis
- duration: 2-3 weeks
Latency: local sensory dorsal root ganglion; trigeminal ganglia – reactivation possible in brain
Reactivation
- stress, UV light, injury to innervated tissue, immunosuppression
- activate at ganglion and virus travels down to nerve ending
- 40-50% have herpes labialis (cold sores)
- herpes simplex encephalitis
HHV-2/ HSV-2: primary infection (route, symptoms, associations, duration), neonatal herpes, latency (site), reactivation (frequency, symptoms, duration)
Primary infection
- sexual transmission (1-10%)
- genital infection causing vesicular lesions over genitalia (herpes genitalis)
- symptoms: fever, pain, dysuria (proctitis)
- associated with aseptic meningitis and radiculomyelitis (usually self-limiting)
- duration: 3 weeks (more severe than HSV1)
- may cause neonatal herpes (infected during vaginal delivery due to high viral load contact) –> mucosa infected, dissemination, encephalitis with high mortality (more details elsewhere)
Latency: local sensory dorsal root ganglion; sacral ganglia – reactivation impossible in the brain
Reactivation
- more frequent than oral infection (few episodes/yr)
- fewer vesicles, less painful
- 1-2 weeks
Other herpes infections by direct contact or auto-inoculation (3)
Herpes keratitis
- lid swelling (conjunctiva has lots of nutrients for pathogens to use)
- e.g. poor hand hygiene in nurses
Herpetic whitlow
- infection on the fingers of dentists due to patient shedding virus onto any open wounds
Eczema herpeticum
- atopic eczema causing break in natural barrier (skin) so virus can invade
HHV-3/ VZV: primary infection (route, symptoms, complications in adults), latency (site), reactivation (risk, symptoms, duration, complications - 2), other outcomes (3)
Primary infection : CHICKENPOX
- airborne transmission - highly infectious
- very common childhood infection (decreasing now due to universal vaccination)
- clear vesicular rash spreading from face to trunk to limbs (sequence important in diagnosis); may have pus due to bacterial infection
- more complications if in adults e.g. pneumonitis, encephalitis
Latency: dorsal root ganglia e.g. trigeminal, thoracic etc.
Reactivation: ZOSTER
- higher risk in >60 yrs
- shingles - pain/numbness followed by rash and scabs in area of nerve supply
- usually lasting 1 week
- post-herpetic neuralgia in 15% (40% of >60yrs old) = persistent pain >4 wks after healing due to nerve damage
Complications:
- Ramsay Hunt Syndrome = facial nerve palsy due to reactivation in geniculate ganglion
- Ophthalmic zoster (distinguish by involvement of nose in lesions) = poor prognosis due to eye lesions (iritis, keratitis, retinitis)
Other outcomes of VZV:
- disseminated zoster in immunocompromised
- congenital varicella syndrome (congenital infection in 1st 20 wks) - skin scarring, extremity atrophy, neurological and eye problems
- neonatal infection (5 days before-2 days after birth)
VZV prevention and protocol for healthcare workers
Vaccine:
- live attenuated
- Chickenpox: primary primary infection (universal immunisation)
- Zoster: prevent reactivation (>60 yrs old)
Immunoglobulin: HNIG, VZIG
- Post-exposure prophylaxis for high risk patients: susceptible pregnant women/ immunocompromised/ neonate
Healthcare workers:
- check VZV IgG immune status
- 2 doses of vaccine for susceptible
- approx 10% adults in HK are VZV IgG-ve
Diagnosis of HSV and VZV: sample, method, why not other methods?
Typical clinical presentations, seldom need lab investigation
CSF sample: viral nucleic acid detection by PCR (sensitive and specific)
Skin scrape sample: viral antigen detection by IF (rapid and sensitive if good samples)
Vesicular fluid: PCR and virus isolation (HSV easy to grow but takes a few days, not sensitive for VZV and takes 1 wk)
Others:
- serology not useful – cross reaction between HSV and VZV, can’t distinguish primary and secondary infection
- EM – rapid but poor sensitivity, unable to differentiate between HSV and VZV
HHV-4/ EBV: primary infection (route, symptoms in young children and teenagers), persistence and latency (site), reactivation (symptoms)
Primary infection: Young children
- common within 1st few years
- transmission by kissing
- most ASYMPTOMATIC
- occasionally infectious mononucleosis (fever, cervical LN, sore throat)
- rarely X linked lymphoproliferative syndrome (severe infection as can’t clear virus)
Primary infection: Teenagers
- escaped childhood infection
- transmission by kissing, sexual behaviour
- 1/4 have pharyngitis, tonsillitis or infectious mononucleosis
Persistence and Latency: B lymphocytes; frequent shedding in oropharynx
(Transmit through saliva and genital secretions, >90% adults infected)
Reactivation:
- Immunocompromised: lymphoproliferative disorder
- Malignancy: NPC, Burkett’s lymphoma, CA stomach, Hodgkin and Non-Hodgkin lymphoma
EBV Diagnosis in IM, lymphoproliferative disease and NPC
IM in primary infection:
- IgM against EBV VCA (viral capsid Ag)
- Monospot (heterophile Ab produced due to B cell mitogenesis)
Lymphoproliferative disease:
- histology (definitive)
- EBV DNA viral load as adjunct test
NPC:
- histology (definitive)
- IgA against EBV VCA and EA (early Ag) used as screening in high risk population
- plasma EBV DNA?
HHV-5/ CMV: primary infection (route, symptoms in different age groups - 4), persistence and latency (site), reactivation (risk, symptoms)
Primary infection:
- premature infants – hepatomegaly, pneumonitis, hepatitis etc
- infants (very common) – always asymptomatic; transmission during contact at vaginal delivery, breast milk, saliva, urine
- adults (% susceptible varies) – mostly asymptomatic, IM occasionally
In utero infection from mother – cytomegalic inclusion disease (asymptomatic/ blindness, hearing impairment/ multi organ…) - outcome depends on whether primary infection or reactivation in mother
Persistence: frequent shedding from salivary glands and kidneys (transmission)
Latency: Haematopoietic progenitors
Reactivation:
- opportunistic infection in immunocompromised e.g. AIDS, transplant recipients, immune-suppressive therapy
- –> severe disease: CMV retinitis, pneumonitis, hepatitis, enteritis
CMV status mismatch in transplant/ transfusion
Due to latency in haematopoietic progenitors –> transmission possibly in blood transfusion and organ transplant
CMV IgG +ve donor –> CMV IgG -ve recipient can cause severe primary infection in immunosuppressed patients
Use leukocyte depleted blood
Check and match CMV IgG status of organ. marrow donors/ recipients
CMV diagnosis difficulties
Infection vs Disease
- CMV virus shedding in urine and saliva is common in all ages –> isolation of CMV does not necessarily mean suffering disease (need further evidence)
- detection of virus e.g. Owl’s eye, from tissue with pathology gives better etiological correlation but still not definitive
Primary vs Secondary
- no reliable test to distinguish
- primary more severe in pregnant women and immunosuppressed
- CMV IgM and 4 fold rise in Ab occurs in both
- to confirm primary infection: need prior serum with CMV IgG-ve
Treatment of CMV is quite toxic hence need good evidence to support infection before starting!
HHV-6: primary infection (route, symptoms, associations), latency (site), reactivation (risk, symptoms)
Primary infection
- 90% infected from 6mths-2yrs (not <6 mths since there is maternal Ab)
- transmitted by kissing
- exanthem subitem (roseola infantum): HIGH FEVER THEN RASH
- a/w febrile convulsion, hepatitis, lymphadenitis
Latency: T lymphocytes, brain
Transmission: saliva
Reactivation:
- HSCT patient - encephalitis, rash
- ? possible a/w chronic fatigue syndrome and multiple sclerosis
HHV-7 clinical picture
Similar to clinical picture to HHV-6 but:
- later infection
- symptomatic primary infection less frequent
- reactivation disease unclear
