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what type of DNA do herpesviruses have?
dsDNA
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under electron microscopy, what do herpes look like? how can you tell between the different viruses?
- fried egg
- cannot distinguish between the viruses
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how long do herpesvirus stay for?
persist life long in an infected host
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what does latency period of the virus mean?
no viral replication or production of infectious virus
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how many human herpesviruses are they? and how are they divided? list all within their groups
- 8 human herpesviruses
- 3 alpha, 3 beta and 2 gamma
- 3 alpha: HSV1, HSV2, VZV
- 3 beta: CMV, HHV-6, HHV-7
- 2 gamma: EBV, HHV-8
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how does a primary HSV infection start?
- viral replication in epithelial cells at a mucocutaneous site
- which produces vesicles
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once HSV does viral replication at a specific site, what does it do?
virus travels RETROGRADE to the dorsal root ganglia and here establishes latency
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what is recurrence of HSV infection also known as?
reactivation
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what are the stimuli for reactivation of HSV?
- physical and emotional stress
- fever
- exposure to UV light
- tissue damage
- immunosuppression
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what are the 3 types of HSV infection?
- primary infection
- recurrent infection
- initial infection
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who does primary infection happen in?
in susceptible persons with no antibodies to HSV-1 or HSV-2
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what is an initial infection of HSV?
when a person with pre-existing antibodies to one type of HSV experiences a primary infection with the other type
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where does HSV1 generally infect and where is it latent?
- oropharynx
- latent in trigeminal ganglion
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where does HSV2 generally infect and where is it latent?
- HSV2 infects genital, peri-genital or anal sites
- latency in sacral ganglia
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what affects seroconversion in HSV1 infection?
- developing country
- low SEC
- both make seroconversion earlier in life
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when does infection with HSV1 commonly occur?
after intimate contact with an individual shedding the virus eg kissing
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how is HSV2 usually acquired?
sexual contact
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what does HSV2 genital ulcers increase the risk of?
HIV infection
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what are the 2 main infections of the oropharynx?
- 1. gingivostomatitis: symptomatic primary infection - vesicles on buccal and gingival mucosa, lymphadenopathy, malaise, sore throat
- 2. herpes labials: cluster of small fluid filled vesicles around lips, RECURRENT infection. cold sore
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how does primary genital herpes manifest?
- as macules (change in colour non palpable) and papules (elevation <1cm)
- then vesicles (<1cm), pustules (small elevation of skin containing pus) and ulcers (discontinuity of skin, loss of epidermis)
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what is primary genital herpes virus associated with?
fever, dysuria, inguinal lymphadenopathy, malaise
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who is HSV2 more severe in?
women often causing meningitis
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which HSV causes neonatal herpes?
2 > 1
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what 3 types of infection can neonates who are infected at birth get?
- 1. disease localised to skin, eye, mouth
- 2. encephalitis with or without skin involvement (and get fits)
- 3. disseminated infection
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why does timing of maternal HSV infection affect neonate HSV infection?
- if maternal infection was previous or chronic the her HSV Abs will cross to neonate
- but if mum gets infection near birth time then no time for Abs to cross to baby and baby wont be able to fight infection at all
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what Ix done for neonatal HSV?
test vesicle fluid, any swabs and CSF for viral nucleic acid on PCR
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what is Rx for neonatal HSV, how is it different from adult?
20mg/kg tds for 3 weeks (higher dose)
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what is the most common sporadic fatal encephalitis?
HSV encephalitis
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what are symptoms of HSV encephalitis?
- primary focal encephalitis
- fever, altered consciousness, bizarre behaviour, disordered mentation, seizures, localised neurological findings
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what is mortality of HSV encephalitis if not treated with aciclovir?
70%
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how is HSV encephalitis diagnosed?
PCR on CSF
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what is treatment for HSV encephalitis?
- iv aciclovir 10mg/kg/tds for 3 weeks
- treat asap, even if just suspect it
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what is done to prevent HSV infection?
- prevent HSV2 use condoms
- C-section to prevent transmission to neonate
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what is MOA of aciclovir?
- nucleoside analogue
- inhibits HSV DNA polymerase
- is a chain terminator
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What 2 diseases does VZV cause?
- Varicella (Chickenpox)
- Zoster (shingles)
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What is the difference between chickenpox and shingles: when, where etc
- Chickenpox: PRIMARY infection which becomes LATENT in dorsal root ganglia (children)
- Shingles: latent virus RE-ACTIVATES and returns from ganglion to infection skin (adults)
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Prior to eradication what was the way to distinguish chickenpox from smallpox
In Chickenpox you get new and old lesions in the same area whereas in smallpox you don't. ie in chickenpox maturity of vesicles in the same area varies
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What is the incubation period of VZV?
2 weeks (10-21 days)
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What are symptoms of chickenpox?
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How do you describe the rash in chickenpox? How long last and where more concentrated
- GENERALISED - widepsread
- Vesicular
- Pruritic
- Lasts 5 days
- Trunk and head concentrated
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Name 2 complications of varicella and 2 rare ones
- 1. Bacterial superinfection of the skin
- 2. Cerebellar ataxia
- 3. RARE Pneumonia
- 4. RARE encephalitis
- How is varicella different in immunocompromised people?
- Severe, can be fatal
- PROGRESSIVE with development of new vesicular lesions
- Haemorrhagic chickenpox
- Pneumonia
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What are consequences of varicella in pregnancy to the mum?
Varicella pneumonitis
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Name 4 symptoms of fetal varicella syndrome
- LENS
- Limb hypoplasia
- Eye defect
- Neuro abnormalities
- Skin scarring in DERMATOMAL distribution
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How does timing of varicella in pregnancy affect consequences to the fetus?
- 1st, 2nd trimester (up to 20 wks): congenital varicella syndrome
- 2nd/3rd trimester: zoster in infancy
- Around delivery: risk of neonatal varicella
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What is risk of shingles in pregnancy to fetus?
- No risk
- Unless immunosuppressed or shingles is disseminated
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How is diagnosis of chickenpox made in pregnant women and post natal babies?
- Typical rash
- Culture, EM, VZV NAT
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How is diagnosis of chickenpox made in fetus?
- Ultrasound
- VZV NAT in amniotic fluid?
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How long is infectious period if you are infected with VZV?
10 days, 2 days before rash and 8 days after
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How would you describe the rash in shingles (zoster)?
- Unilateral
- Dermatomal
- Vesicles are CONFLUENT
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How long do vesicles take to heal?
2 weeks
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What is the 2 types of pain associated with shingles?
- 1. Zoster associated
- 2. Post herpetic neuralgia – esp in older people, get protracted (means lasting for long time) pain
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What are risk factors for developing shingles?
- 1. Increased age
- 2. After drugs: steroids, cancer chemotherapy, irradiation and post transplant – may get disseminated zoster
- What is the main difference between varicella and zoster in pathogenesis?
- Primary infection with VZV gives varicella ie chickenpox
- Reactivation of latent virus from sensory ganglia many years after varicella gives shingles – zoster
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What is the main difference between varicella and zoster in susceptibility to disease?
- If seronegative for VZV virus IgG then more susceptible to varicella
- If seropositive for VZV IgG then more susceptible to zoster
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What is the main difference between varicella and zoster in getting the disease?
- Varicella: contact acquisition
- Zoster: not contact acquired
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What is the main difference between varicella and zoster in terms of where the virus is present?
- Varicella: respiratory secretions from 48hours before the rash and vesicle fluid
- Zoster: vesicle fluid
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What is the main difference between varicella and zoster in infectiousness?
- Varicella: highly communicable
- Zoster: low rate of transmission
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What is the main difference between varicella and zoster in incidence? Ie age
- Varicella: highest in children
- Zoster: elderly and immunocompromised
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What is the main difference between varicella and zoster in timing of the year?
- Varicella: late winter and spring
- Shingles: sporadic
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How is VZV diagnosed usually?
Clinically
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What is the differential diagnosis for VZV?
Disseminated HSV infection
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If diagnosis of VZV is not obvious, what is used to detect it?
- 1. Detection of VZV nucleic acid in skin scrappings, vesicle fluid of CSF
- 2. Detect VZV-specific Abs: IgM or IgG seroconversion useful only for retrospective diagnosis of varicella (NOT zoster) in the immunocompetent
- 3. VZV IgG to determine susceptibility to varicella (if seroneg then high for varicella)
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How is VZV prevented?
- Live attenuated vaccine is now liscenced in the UK
- It is an active virus.
- Given to seronegative health care workers
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Who gets passive immunisation and when and what is used?
- Give VZIG to modify disease
- Give up to 10 days after EXPOSURE (remember exposure is 2 days before rash comes)
- Given to prevent severe varicella in: neonates, immunocompromised, pregnant with close exposure to chickenpox or shingles
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When does acyclovir need to be given in VZV infection? And what dose
- When there is actual chickenpox to:
- Immunocompromised – whenever the vesicles are present: 10 mg/kg tds
- Pregnant and adults – within 3 days of rash give 800mg for 5 days; or if get pneumonitis 10mg/kg tds iv
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If an adult gets chickenpox, what do you warn them?
If they get respiratory symptoms to come to hospital as may be pneumonitis and need ACV
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how are most CMV acquired?
- asymptomatically
- childhood
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what congenital infections can CMV cause?
- cytomegalic inclusion disease
- sensorineural hearing loss
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what is incidence of CMV seropositive in developed and developing countries?
- developed: 40-60%
- developing: 90-100%
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what happens after primary infection of CMV?
latency
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how is CMV transmitted?
- intimate contact with an infected person: contact with saliva, nasopharyngeal secretions from careers
- blood transfusions
- transplant
- breast milk
- sexual activity
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what type of CMV infection affects adolescent? and what is its main feature
- CMV mononucleiosis
- fever in 100%
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give 5 ways CMV can manifest in an immunocompromised host? (think down body)
- 1. FEBRILE ILLNESS: with lymphopenia or pancytopeni
- 2. CMV pneumonitis: can be life threatening especially in transplant recipients
- 3. HEPATITIS: after liver transplant can lead to liver failure
- 4. GI DISEASE: haemorrhages, ulcerations, perforations, acute pancreatitis, cholecystitis
- 5. CMV RETINITIS
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how is CMV diagnosed?
- lab diagnosis: PCR for nucleic acid from blood urine or throat swab
- serum: antiCMV Abs (IgM or IgG) in IMMUNOCOMPETENT patients eg pregnancy
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what are the 3 drugs used to treat CMV infection, and who gets it?
- immunocompromised patients
- gangiclovir
- forcarnet
- cidofovir
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how does primary infection of EBV usually present?
asymptomatic
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how is EBV spread?
contact with saliva from an INFECTED individual who is asymptomatically shedding the virus
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in the UK what is acquisition of the virus like?
- biphasic
- young children and adolescents
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after primary infection what happens to the virus?
remains latent in memory B cells
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what are the 5 EBV-assocaited malignancies?
- 1. endemic Burkitt's lymphoma: most common childhood malignancy in tropical Africa and new guinea (B cells, t(8:14))
- 2. nasopharyngeal carcinoma: rare but one of most common in south china
- 3. hodgkin lymphoma: subset are assoc with EBV (older and paeds cases)
- 4. post transplant lymphoproliferative disorders and non-hodgkin lymphomas in AIDS (due to immunosuppression)
- 5. x-linked lymphoproliferative syndrome (Duncan's syndrome): inherited in males and inability to control EBV infection
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what virus is assoc with kaposis?
HHV8
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what is route of transmission in HHV8?
saliva
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what type of tumour is kaposis?
vascular tumour
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what are the 4 clinical manifestations of KS?
- 1. classic KS: multifocal skin lesions, HYPERPIGMENTED nodules, rare
- 2. endemic KS: equatorial africa
- 3. iatrogenic KS: post transplant. seen in immunosupp organ transplant. may go away after reducing immunosuppressive therapy
- 4. AIDS associated KS: noted first 1981,
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