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Herpes infections Flashcards

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1
Q

Fun fact: where does the word herpes come from?

A

The Greek word herpein (“to creep”), referring to the latent, recurring infections typical of this group of viruses.

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2
Q

In total, how many herpes viruses can affect humans?

A

8 - confusingly named as both strains of human herpes virus (HHV) and their own name: -

           More common
HHV1   -   HSV1
HHV2  -   HSV2
HHV3  -   VZV
HHV4  -   EBV
HHV5  -   CMV
           Less common
HHV6  -   Roseolovirus
HHV7  -   ? sad no name virus :(
HHV8  -   Kaposi's sarcoma-associated herpesvirus
(KSHV)
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3
Q

Name the 5 most common species of herpes virus

A 
Herpes simplex virus 1 (HSV1)
Herpes simplex virus 2 (HSV2)
Varicella zoster virus (VZV)
Epstein-Barr virus (EBV)
Cytomegalovirus (CMV)

(HHV1-5)

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4
Q

Which 3 herpes viruses are neurotropic and what does this mean

A

HSV1, HSV2 and VZV

  • Capable of infecting nerve cells, which are also the site of latency for these 3 viruses
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5
Q

What sort of genetic material do the neurotropic herpes viruses possess?

A

dsDNA

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6
Q

Does HSV have an animal reservoir?

A

No

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7
Q

How is HSV transmitted?

A

Muco-cutaneous contact

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8
Q

How is VZV transmitted?

A

Droplet spread

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9
Q

Which cell types undergo lytic infection by HSV?

A

Fibroblasts and epithelial cells

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10
Q

In which part of the nervous system does HSV have a persistent latent phase?

A

The dorsal root ganglion

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11
Q

Where in the human body does VZV replicate?

A

Initially lymph nodes followed by liver and spleen

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12
Q

Describe the rash caused by VZV. How long after infection does this rash arise?

A

Vesicular

~48 hours post

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13
Q

What is the incubation period for oral HSV (cold sore/Herpes labialis)?

A

2-12 days

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14
Q

Describe a coldsore infection

A 
Severe painful ulceration on/around the lips
Tendency to coalesce
Erythematous base
Fever
Submandibular lymphadenopathy
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15
Q

What is the main differential diagnosis for herpes labialis?

A

Herpangina (caused by Coxsackie A virus)

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16
Q

What is the incubation period for genital herpes?

A

4-7 days

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17
Q

Describe the presenting symptoms of genital herpes

A 
Fever
Dysuria
Malaise
Inguinal lymphadenopathy
Pain++
Vesicular rash
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18
Q

What percentage of primary genital herpes cases are followed by herpes meningitis?

A

4-8%

Occurs 1-2 weeks after primary infection

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19
Q

What is sacral radiculomyelitis/radiculitis?

A

A self-limiting syndrome of acute urinary retention triggered by HSV2

AKA Elsberg syndrome

Occurs in ~5% genital herpes

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20
Q

Which type of HSV causes cold sores?

A

HSV1

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21
Q

Which type of HSV predominantly affects the genitals?

A

HSV2

Remember: 2 people have sex

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22
Q

Name the disease caused by an ocular HSV 1 infection

A

Herpetic keratitis

NB can also be caused by HSV2, but much less common

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23
Q

Describe the presenting features of herpetic keratitis

A

Unilateral/bilateral conjunctivitis

Pre-auricular lymph node involvement

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24
Q

Without treatment, what might herpetic keratitis progress to in healthy patients?

A

Acute retinal necrosis

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25
Q

What might herpetic keratitis progress to in immunosuppressed patients?

A

Progressive Outer Retinal Necrosis (PORN)

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26
Q

Other than HSV, which other herpes viruses can cause Progressive Outer Retinal Necrosis (PORN)?

A

VZV, EBV, CMV

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27
Q

At what stage of pregnancy is a mother at risk of transmitting HSV to fetus?

A

3rd trimester

Primary infection in 1st and 2nd trimesters not associated with increased risk to fetus

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28
Q

What is the treatment for maternal primary HSV infection during 3rd trimester?

A

Oral/IV acyclovir 6 weeks before EDD

If genital infection persists/presents close to EDD C-section is indicated

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29
Q

When is HSV most commonly transmitted from mother to child?

A

Most often at delivery
Postnatally via mother with cold sores kissing baby
Rarely transmitted in utero

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30
Q

How can neonatal HSV present?

A
  • Fetal loss
  • Skin, eye and mouth (SEM) lesions at 7-12 days post-partum. Long term ocular and neural sequelae
  • Disseminated disease +/- vesicles at 4-11 days post-partum. Risk of fuminant hepatitis or multi-organ failure. 80% mortality
  • Neurological disease +/- SEM at 17-18 days post-partum. 50% mortality

(In summary: it’s really bad news)

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31
Q

Which form of HSV most commonly causes encephalitis?

A

HSV1 in 90% cases

remember: we have 1 brain

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32
Q

Describe the presenting features of herpetic encephalitis?

A 
Flu like prodrome for 2 weeks
Focal neurology
Fever 
Confusion
Behavioural change
Decreased consciousness
Seizures
Nausea and vomiting
Coma
Death
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33
Q

Which age group is most likely to be affected by herpetic encephalitis?

A

> 60s (half of all cases are in this age group)

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34
Q

What is Mollaret’s meningitis?

A

Benign recurrent aseptic meningitis usually caused by latent HSV2

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35
Q

Which lobes of the brain are affected by herpetic encephalitis?

A

Fronto-temporal and parietal (lesions seen on CT/MRI)

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36
Q

What CSF results would be expected in herpetic encephalitis?

A

Lymphocytic pleiocytosis
Cytology may be normal
Normal glucose
Raised protein

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37
Q

How is herpetic encephalitis diagnosed?

A

Definitive diagnosis can only be made by PCR of CSF or brain biopsy.
PCR slow, treatment should be started on clinical suspiscion.
False negatives possible with PCR - should not exclude if negative

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38
Q

What is the treatment for herpetic encephalitis?

A

IV acyclovir stat

10mg/kg TDS then oral acyclovir for total of 2-3 weeks

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39
Q

List 6 skin infections caused by herpes viruses

A 
Herpes gladitorum/scrum pox
Herpetic whitlow
Erythema multiforme
HS dermatitis
Eczema herpeticum
Zosteriform HS (painless)
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40
Q

How does herpes gladitorum/scrum pox present?

A

Often in rugby players

Painful blisters and inguinal lymphadenopathy

41
Q

How does herpetic whitlow present?

A

Painful red finger

42
Q

How are dermatological herpes infections diagnosed?

A 
Clinical impression
Culture
ELISA
Swab PCR
Blood PCR if disseminated infection
43
Q

Name 4 treatments for dermatological herpes

A
  • Acyclic nucleotide analogues: acyclovir, valacyclovir, famcyclovir
  • Gancyclovir (pro-drug = valgancyclovir)
  • Foscarnet (pyrophosphate analogue)
  • Cidofovir
44
Q

Which herpes virus causes chickenpox?

A

Varicella zoster (VZV)

45
Q

How does chickenpox present?

A

Fever
Malaise
Headache
Characteristic crops of rash (“dew on a rose petal”)
Lesions scab after 1 week - no longer contagious at this stage

46
Q

When does a chickenpox infection stop being contagious?

A

When lesions scab over, approximately 1 week after first signs of infection

47
Q

List 4 non-neurological potential complications of chickenpox

A

Scarring
Pneumonitis
Haemorrhage
Eye involvement

48
Q

List 6 neurological potential complications of chickenpox

A
  • Reye’s syndrome (rapidly progressive encephalopathy - poss. associations with aspirin)
  • Acute cerebellar ataxia
  • Guillain Barre
  • Ramsay Hunt syndrome (Facial palsy and vesicles in ear. Geniculate ganglion of CNvii affected - hearing loss and vertigo)
  • Encephalitis (vasculopathy)
  • Post-herpetic neuralgia
49
Q

How can chickenpox be diagnosed?

A
  • Examination - characteristic rash and vesicles present
  • Cytology - scrapings for multinucleated giant cells (Tzanck cells)
  • Immunofluorescence cytology - cells from vesicles
  • PCR, esp if rash is old or CNS/eye involvement
50
Q

What is congenital varicella syndrome?

A

Extremely rare disorder in which affected infants have distinctive abnormalities at birth due to maternal VZV infection during early pregnancy.

51
Q

If a woman has chickenpox during pregnancy, what is the risk of her child having congenital varicella syndrome?

A

0.4% if

52
Q

What are the key features of congenital varicella syndrome?

A 
Scarring
Hypoplastic limbs
Cortical atrophy
Psychomotor retardation
Choreoretinitis
Cataracts
53
Q

What risk is associated with maternal chickenpox +/-7 days from delivery?

A

Disseminated varicella infection in the neonate

No passive immunity so infection is severe, with neonatal mortality rate ~30%

54
Q

What are the indications for treating chickenpox?

A 
All adults, due to higher risk of complications (but only useful if started within first 24hours of symptoms)
Neonates
Immunocompromised 
Eye involvement
All pts presenting with pain
55
Q

Who requires post-exposure prophylaxis for VZV and what is given?

A

VZIG

Immunocompromised and pregnant women

56
Q

If treatment for chickenpox is indicated, what is given?

A

Acyclovir 800mg PO TDS 7/7
OR
Valacyclovir 1g TDS

57
Q

What does the chickenpox vaccine contain?

A

Attenuated Oka strain (live vaccine against varicella)

58
Q

In which group is the chickenpox vaccine contraindicated?

A

Pregnant women

59
Q

What is shingles/herpes zoster?

A

Reactivation of latent VZV in the dorsal root ganglion.

Causes painful rash in a specific dermatome

60
Q

What can cause shingles?

A 
Stress
Decreased immunity (eg in immunocompromise/ people >50years)
61
Q

When is treatment for shingles indicated?

A

Symptomatic children

Healthy adult smokers (if 20/40

62
Q

What is the treatment for shingles?

A 
Acyclovir 800mg PO 5x daily
OR
Famcyclovir 250mg PO TDS
OR
Valacyclovir 1000mg PO TDS
63
Q

What additional treatment is given for opthalmic shingles?

A

Topical antiviral eye drops (must be in addition to oral AVx)

64
Q

What additional treatment may be given for shingles in immunocompromised patients?

A

PEP for 7-9 days

65
Q

Name 2 epitheliotropic herpes viruses

A

Cytomegalovirus (CMV)(HHV5) and roseola virus (HHV6)

66
Q

Name 2 lymphotropic herpes viruses

A

Epstein-Barr Virus (EBV)(HHV4) and Kaposi’s sarcoma-associated herpesvirus (KSHV)(HHV-8)

67
Q

In CMV, what does the “mega” part refer to?

A

Infected cells swell, increasing in size

68
Q

What proportion of CMV infections are asymptomatic?

A

80%

69
Q

How can congenital CMV present?

list of 11!

A 
IUGR
Jaundice
Hepatosplenomegally
Chorioretinitis
Encephalitis
Microencephaly
Thrombocytopaenia
Late progressove sensorineural deafness
Impaired IQ
Cytomegalic inclusion disease (13%)
Death
70
Q

How does CMV mononucleosis present?

A

Very similar to EBV mono (glandular fever): fever, pharyngitis, lymphadenopathy

71
Q

How can a CMV infection present in immunocompromised patients?

(list of 8)

A 
Fever
Hepatitis
Colitis
Retinitis
Pneumonitis
Bone marrow suppression
Addison's disease
Radiculopathy
72
Q

How is CMV likely to present in patients following a bone marrow transplant?

A

Pneumonitis

73
Q

How is CMV likely to present in patients with AIDS?

A

Retinitis

74
Q

Which cell types does CMV infect?

A

Macrophages
Endothelial cells
B and T lymphocytes
Bone marrow stem cells

75
Q

Which investigations are used to diagnose CMV?

A 
Blood PCR
Histopathology
Tissue immunofluorescence
Cell culture in human fibroblasts
Serology
Heterophile antibody test (eg Paul Bunnel/monospot)
76
Q

What are “owl’s eye inclusions” a sign of?

A

CMV - seen on cell culture in human fibroblasts

77
Q

When is serology a useful test for CMV?

A

In immunocompetent patients. In the immunocompromised it is of little diagnostic value.

78
Q

If an immunocompetent patient has CMV, what can be seen on serology?

A

CMV IgM and IgG

but IgG has low avidity in a primary infection

79
Q

If a patient is positive for CMV, what will a heterophile antibody test show?

A

Clumping of sheep RBCs

80
Q

Which treatments are used for CMV?

A

Ganciclovir (or prodrug: valganciclovir)
Cidofovir
Foscarnet

81
Q

Give 3 names for the disease caused by a roseola virus infection

A

Roseola infantum / exanthum subitum / Sixth disease

3 names for the same thing

82
Q

How does roseola present?

A

Disease of children, usually under 2 years old

3 days of fever, followed by transient rash

83
Q

Why can roseola cause a child to be mis-labelled as penicillin allergic?

A

Penicillin may be prescribed for the fever, then blamed for the rash which comes later. This is further supported by the fact that the rash doesn’t last long.

84
Q

Which virus is the most common cause of febrile convulsions?

A

Roseola virus

85
Q

In which cells does roseola virus persist latently?

A

Monocytes and lymphocytes

86
Q

How can roseola infection present in bone marrow transplant patients?

A

Pneumonitis
Hepatitis
Encephalitis

87
Q

Which investigation diagnoses roseola?

A

Blood PCR

88
Q

Which treatments are used for roseola virus?

A

Ganciclovir
Cidofovir
Foscarnet

89
Q

Which of the human herpes viruses is the most mysterious? (ie least understood)

A

HHV7

90
Q

Name the common disease caused by EBV

A

Infectious mononucleosis / Glandular fever / kissign disease

91
Q

How does glandular fever present?

A

Incubation period of 4-6 weeks
Triad of fever, pharyngitis, lymphadenopathy
Maculopapular rash

92
Q

How is EBV diagnosed?

A

Blood film
Monospot agglutination/Paul-Bunnel test
EBV antibodies

93
Q

Which two cancers are associated with EBV infection?

A 
Burkitt's lymphoma (Endemic/African variant)
Nasopharyngeal cancer (also more common in Africa)
94
Q

What is the transplant-related disease caused by EBV?

A

Post-transplant lymphoproliferative disease.

Predisposes to lymphoma

95
Q

What is the treatment for post-transplant lymphoproliferative disease?

A 
Reduce immuosuppression
Give rituxumab (anti-CD20 monoclonal antibody)
96
Q

Is EBV dangerous in pregnancy?

A

No

97
Q

How is HHV8 transmitted?

A

Genitally

98
Q

Name 3 diseases associated with HHV8

A
  • Kaposi’s sarcoma
  • Primary effusion lymphoma (associated w/EBV co-infection)
  • Castleman’s disease (non-cancerous growth in the lymph nodes)
99
Q

What is the treatment for HHV8?

A

Ganciclovir

Foscarnet

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