Herpes Viruses Flashcards
1
Q
Structure of herpes viruses
A
- ether-sensitive envelope
- regular icosahedral capsid composed of 162 capsomeres
- ds DNA
2
Q
Features of herpes viruses
A
- tissue culture - produces pocks on chorio-allantoic membrane
- produces characteristic giant cells & eosinophilic intranuclear inclusion bodies (except EBV)
- viral envelope binds to cell receptors - fuses w cell memb - virus uncoats - within the nucleus, viral DNA replicates - transcribed - capsid protein - viral DNA packaged into capsids - glycoproteins incorporated into nuclear membrane to form viral envelope - virions bud out through nucleus - released at cell surface
- latency: pri inf - quiescent - reactivation - recurrent inf
3
Q
Examples of herpes viruses
A
- Herpes Simplex Virus
- HSV 1 - HHV1
- HSV2 - HHV2 - Varicella-Zoster Virus - HHV3
- Cytomegalovirus - HHV5
- Epstein-Barr Virus - HHV4
- Human Herpesvirus 6
- Human Herpes virus 7
- Human Herpesvirus 8
4
Q
Symptoms of HSV (2)
A
- Vesicular eruption - blister, raised lesion on skin w clear/serous fluids
- virus proliferates in infected cells - ballooning degeneration - lyses to fill vesicle w fluid of cytoplasmic & viral content - acidophilic intranuclear inclusions - Encephalitis - infection of brain tissue - meningitis, perivascular infiltration, neuronal degeneration
5
Q
Features of HSV
A
- early inclusion - Cowdry type A inclusion body
- pri infection - mostly subclinical or severe w rash lasting 3-4 wks
- non-immune - HSV travels along sensory nerves to sensory ganglia, persists lifelong in a latent state
- reactivation - virus travels down nerve fibres - lesions
6
Q
Clinical presentations of HSV1 (8)
A
- Acute Herpetic Gingivostomatitis - vesicles on buccal mucosa, gums ulcerate w grey slough, fever, lymphadenopathy, commonest pri disease, spread by kissing
- Herpes Labialis - cold sores, herpes febrilis, commonly reactivation in trigeminal ganglion, crop of vesicles at mucocutaneous junction of lips/near nose - painful ulcers
- Herpetic Whitlow - fingers - lesions w serous exudate, hands of HCW in contact w oral secretions
- Eczema Herpeticum - Kaposi’s varicelliform eruption, superinfection of chronic eczematous skin w extensive vesiculation, fever, mortality
- Keratoconjunctivitis - edema & vesicles of eyelids, cornea - dendritic keratitis, ulcers, opacification, blindness
- Aseptic Meningitis
- Acute Necrotising Encephalitis - rare but severe, sudden fever, confusion, headache, temporal lobe necrosis, increased morbidity with neurodeficits, CSF, PCR, brain biopsy - IF, isolation
- Disseminated Herpes - immunocompromised
7
Q
Clinical presentations of HSV2 (3)
A
- Herpes Progenitalis
- sexually transmitted vesiculoulcerative lesions of genitalia, fever, malaise, lymphadenopathy, recurrent lesions from reactivation in lumbar/sacral ganglia - Neonatal Herpes
- subclinical to severe, acquired from infected birth canal of mother (do caesarean), jaundice, hepatosplenomegaly, thrombocytopaenia, large cutaneous vesicles - Cervical & Vulvular Carcinoma
- stronger association with HPV
8
Q
Immunology of HSV
A
- Newborns: passive maternal Abs lasting 6m
- HSV1 inf: acquired early in life, most have Abs by adulthood
- HSV2: acquired aft puberty, ~20% of sexually active adults have Abs
- neutralising Abs formed after pri inf do not prevent reactivation
9
Q
Diagnosis of HSV (2)
A
- Virus isolation
- specimens - vesicle fluid, skin swab, saliva, tears, corneal scraping, brain biopsy
- inoculation of cell cultures - CPE of rounded cells in 48-72h, NT/IF
- scrapings - multinucleated giant cells, Tzanck cell microscopy - Serology
- pri HSV inf - neutralising HSV IgM Ab
- significant rise in Ab titre 2-4 weeks after pri inf
- recurrent inf - high levels of existing Ab, no rise in titre
10
Q
Treatment of HSV (4)
A
- Acyclovir
- herpes encephalitis/generalised herpes (IV), genital herpes (oral/IV/topical), dendritic ulcers, cold sores, prophylaxis for immunocompromised
- little value for recurrent disease, give early in pri inf - Valaciclovir (valtrex) - greater bioavailability than acyclovir
- Idoxuridine, Trifluridine, Vidarabine (herpetic keratitis)
- Control - avoid infected sources/sites, vaccines still experimental
11
Q
Epidemiology & transmission of HSV
A
- infection most common in childhood, often asymptomatic
- transmission by close contact - HSV1 - kissing, HSV2 - sexually & perinatally
12
Q
Presentation of varicella-zoster virus
A
VZV causes
- Varicella (chicken pox) - primary illness
- Zoster (shingles) - recurrent manifestation of infection
13
Q
Symptoms of varicella
A
- incubation period 2-3weeks
- fever, crops of vesicles - pustules in waves, centripetal distribution (trunk>extremities)
- more severe in adults
- congenital varicella - transplacental, in neonates born to mothers w varicella in early preg
- neonatal varicella - child contracts from mother near time of delivery - little/no protection from maternal Abs, high mortality in severe disease
- previous infection - lifelong immunity to varicella, not zoster
14
Q
Complications of varicella (8)
A
- Skin superinfection (staph/strep - skin flora enters vesicles)
- Aspetic meningitis
- Neurological syndrome
- Post infectious encephalomyelitis (1 wk after rash)
- Pneumonia (cough, dyspnea, hypoxia, diffuse nodular infiltrate, pulm calcifiaction)
- Haemorrhagic (fulminating varicella) - thrombocytopenia, DIVC
- Arthritis
- Overwhelming varicella in immunosuppressed
15
Q
Treatment of varicella (5)
A
- Symptomatic - anti pyretic, anti pruritic
- VZIG prophylaxis in exposed immunocompromised
- Acyclovir - severe varicella pneumonia/haemorrhagic varicella
- Barrier nursing & isolation of immunosuppressed
- Live attenuated vaccine
16
Q
Transmission of varicella
A
- highly infectious
- epidemic via nose & mouth by droplet infection from saliva & contact w skin lesions
17
Q
Features of zoster
A
- recurrent disease occurring in dermatome of sensory (dorsal/cranial) nerve ganglion due to reactivation of latent VZV
- usually long after childhood varicella
- freq in old age/immunocomp
- mainly adults, not acq by contact with zoster, occasionally gives rise to varicella outbreaks
18
Q
Symptoms of zoster (3)
A
- Painful vesicular eruptions morphologically similar to varicella - skin lesions in corresponding sensory ganglia, dermatomal distribution
- thoracic 50%, cervical 20%, lumbar 20%, trigeminal nerve 15% - involvement of ophthalmic division - iridocyclitis, keratitis, corneal ulceration
- geniculate ganglion - Ramsay Hunt syndrome - vesicles in ext auditory canal, tympanic membrane, ant tongue, facial nerve palsy
19
Q
Complications of zoster (3)
A
- Encephalomyelitis, lymphocytic pleocytosis in CSF
- Post-herpetic neuralgia, often in elderly
- Disseminated zoster - vesicles outside involved dermatomes (in immunosuppressed)
20
Q
Treatment of zoster
A
Acyclovir IV - limit progression of zoster, trigeminal nerve zoster, disseminated zoster
21
Q
Diagnosis of VZV (3)
A
- Sample: vesicles
- stained smears of scrapings of swabs from base - multinucleated giant cells
- IF - intracellular viral Ags
- EM to distinguish from pox viruses
- PCR - Virus isolation
- in human fibroblast cultures - focal CPE - cell associated virus
- IF, NT of isolate w specific antisera - Serology
- IgM in varicella & zoster
- rise in Ab titre
- high levels of neut Ab (zoster)
22
Q
Transmission of CMV (4)
A
- Close contact
- Blood transfusion
- Organ transplantation
- Transplacental
- usually asymptomatic in healthy hosts, subclinical - latent
- viral shedding in saliva, tears, urine, semen, cervical secretions, breast milk
23
Q
Symptoms of CMV (6)
A
- Congenital CMV infection
- fetal infection following maternal viraemia in pregnancy
- pri maternal inf usually asymptomatic - Cytomegalic inclusion disease
- severe generalised CMV inf of infants
- intrauterine/perinatal infection
- jaundice, hepatosplenomegaly, interstitial pneumonitis, thrombocytopenia, hemolytic anemia, neurological (microcephaly, periventricular calcification, chorioretinitis, optic atrophy, mental retardation, spasticity, epilepsy)
- enlarged cells w large intranuclear owl’s eyes inclusions - Post natal hepatitis
- hepatomegaly, abnormal liver fn test, +/- jaundice - Infectious mononucleosis syndrome
- spontaneous in otherwise healthy young adults
- post perfusion syndrome/after surgery
- clinically similar to glandular fever, but less pharyngitis & lymphadenopathy
- mild hepatitis, circulating atypical lymphocytes (CMV mononucleosis), CMVuria - Infection in immunocompromised host
- pri inf w organ transplant/blood transfusion
- recrudescence following reactivation of latent inf
- CMV pneumonitis, hepatitis
- disseminated CMV - fever, leukopenia, pneumonitis, hepatitis, colitis, retinitis - Guillain-Barre syndrome
24
Q
Diagnosis of CMV (3)
A
- Virus isolation - from urine, throat swab - swollen cells, intranuclear “owls eye” inclusions after 2-3wks
- Viral detection
- desquamated cells in urinary sediment, owl’s eye inclusions
- EM, viral antigen, DNA - Serology - IgM & IgG
25
Treatment of CMV (5)
1. Ganciclovir - life threatening CMV infections eg retinitis, colitis, pneumonitis in immunocomp
2. Isolation of newborns w severe CMV
3. Screen organ & blood donors & recipients
4. CMVIG prophylaxis in CMV-seronegative organ recipients receiving organs from seropositive donors
5. Live CMV vaccines (trials)
26
Transmission of EBV
close contact - "kissing disease"
27
Features of EBV
- replicates in B lymphocytes, stimulating polyclonal growth & lymphoid hyperplasia
- EBV infection of normal human lymphocytes results in immortalisation of nuclear neoantigens
- ubiquitous in healthy adults who shed the virus in pharyngeal secretions
28
Symptoms of EBV
Infectious mononucleosis
- glandular fever
- incubation period 4-7 wks
- lethargy, anorexia, fever, pharyngitis, exudative tonsillitis, lymphadenopathy, hepatosplenomegaly, rash exacerbated by ampicillin
- most prevalent in seronegative children & young adults
29
Complications of EBV (9)
1. Hepatitis - jaundice, abnormal LFT
2. Pneumonitis
3. Neurological - aseptic meningitis, encephalitis, myelitis, optic neuritis, acute cerebellar ataxia, Guillain-Barre syndrome, peripheral neuropathy, Bells palsy
4. Haemolytic anemia, thrombocytopaenia, splenic rupture
5. Myocarditis, pericarditis
6. Burkitt's lymphoma
7. NPC
8. Immunoblastic lymphoma
9. Chronic fatigue syndrome
30
Diagnosis of EBV (2)
1. Microscopy
- atypical lymphocytosis, atypical mononuclear cells, at least 10%
2. Serology
- heterophile antibodies (Paul-Bunnell test) - haemagglutinating Abs to sheep RBCs, Abs removed by adsorption w ox RBC but not w guinea pig kidney
- 90% of healthy adults have EBV Ab
- EBV IgM - high - recent inf mononucleosis
- antibodies to EBV antigens - Anti-VCA, Anti EBNA, Anti-EA/D, Anti-EA/R
31
Treatment of EBV (2)
1. Symptomatic, avoid ampicillin (causes rash in infectious mononucleosis)
2. Vaccine - undergoing clinical trial
32
Clinical presentation of HHV6
- Exanthem subitum (roseola infantum)
- mild disease of children 6m-3y
- incubation 1-2wks
- abrupt onset, high pyrexia/febrile fits, convulsions (can cause brain damage), lymphadenopathy
- rubelliform rash (disappears after fever) except face
- leukpenia & relative lymphocytosis
33
Treatment of HHV6
- spontaneous recovery
| - Antipyretic agents to control fever
34
Diagnosis of HHV6
HHV6 in serum & throat washings during pyrexia
35
Features of HHV7
- isolated from CD4 positive T cells
- persists in saliva of 75% of normal adults
- no association with human disease so far
36
Features of HHV8
- Kaposi's sarcoma-associated herpes virus (KSHV)
- KS in AIDS - malignancy of vascular endothelial cells - purple lesions in skin, oral cavity, GIT, lungs
- Transmission: sexual, transplantation
- no antiviral/vaccine
