Herpes infections Flashcards
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.
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)
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)
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
5
Q
What sort of genetic material do the neurotropic herpes viruses possess?
A
dsDNA
6
Q
Does HSV have an animal reservoir?
A
No
7
Q
How is HSV transmitted?
A
Muco-cutaneous contact
8
Q
How is VZV transmitted?
A
Droplet spread
9
Q
Which cell types undergo lytic infection by HSV?
A
Fibroblasts and epithelial cells
10
Q
In which part of the nervous system does HSV have a persistent latent phase?
A
The dorsal root ganglion
11
Q
Where in the human body does VZV replicate?
A
Initially lymph nodes followed by liver and spleen
12
Q
Describe the rash caused by VZV. How long after infection does this rash arise?
A
Vesicular
~48 hours post
13
Q
What is the incubation period for oral HSV (cold sore/Herpes labialis)?
A
2-12 days
14
Q
Describe a coldsore infection
A
Severe painful ulceration on/around the lips Tendency to coalesce Erythematous base Fever Submandibular lymphadenopathy
15
Q
What is the main differential diagnosis for herpes labialis?
A
Herpangina (caused by Coxsackie A virus)
16
Q
What is the incubation period for genital herpes?
A
4-7 days
17
Q
Describe the presenting symptoms of genital herpes
A
Fever Dysuria Malaise Inguinal lymphadenopathy Pain++ Vesicular rash
18
Q
What percentage of primary genital herpes cases are followed by herpes meningitis?
A
4-8%
Occurs 1-2 weeks after primary infection
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
20
Q
Which type of HSV causes cold sores?
A
HSV1
21
Q
Which type of HSV predominantly affects the genitals?
A
HSV2
Remember: 2 people have sex
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
23
Q
Describe the presenting features of herpetic keratitis
A
Unilateral/bilateral conjunctivitis
Pre-auricular lymph node involvement
24
Q
Without treatment, what might herpetic keratitis progress to in healthy patients?
A
Acute retinal necrosis
25
What might herpetic keratitis progress to in immunosuppressed patients?
Progressive Outer Retinal Necrosis (PORN)
26
Other than HSV, which other herpes viruses can cause Progressive Outer Retinal Necrosis (PORN)?
VZV, EBV, CMV
27
At what stage of pregnancy is a mother at risk of transmitting HSV to fetus?
3rd trimester
| Primary infection in 1st and 2nd trimesters not associated with increased risk to fetus
28
What is the treatment for maternal primary HSV infection during 3rd trimester?
Oral/IV acyclovir 6 weeks before EDD
If genital infection persists/presents close to EDD C-section is indicated
29
When is HSV most commonly transmitted from mother to child?
Most often at delivery
Postnatally via mother with cold sores kissing baby
Rarely transmitted in utero
30
How can neonatal HSV present?
- 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)
31
Which form of HSV most commonly causes encephalitis?
HSV1 in 90% cases
| remember: we have 1 brain
32
Describe the presenting features of herpetic encephalitis?
```
Flu like prodrome for 2 weeks
Focal neurology
Fever
Confusion
Behavioural change
Decreased consciousness
Seizures
Nausea and vomiting
Coma
Death
```
33
Which age group is most likely to be affected by herpetic encephalitis?
>60s (half of all cases are in this age group)
34
What is Mollaret's meningitis?
Benign recurrent aseptic meningitis usually caused by latent HSV2
35
Which lobes of the brain are affected by herpetic encephalitis?
Fronto-temporal and parietal (lesions seen on CT/MRI)
36
What CSF results would be expected in herpetic encephalitis?
Lymphocytic pleiocytosis
Cytology may be normal
Normal glucose
Raised protein
37
How is herpetic encephalitis diagnosed?
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
38
What is the treatment for herpetic encephalitis?
IV acyclovir stat
| 10mg/kg TDS then oral acyclovir for total of 2-3 weeks
39
List 6 skin infections caused by herpes viruses
```
Herpes gladitorum/scrum pox
Herpetic whitlow
Erythema multiforme
HS dermatitis
Eczema herpeticum
Zosteriform HS (painless)
```
40
How does herpes gladitorum/scrum pox present?
Often in rugby players
| Painful blisters and inguinal lymphadenopathy
41
How does herpetic whitlow present?
Painful red finger
42
How are dermatological herpes infections diagnosed?
```
Clinical impression
Culture
ELISA
Swab PCR
Blood PCR if disseminated infection
```
43
Name 4 treatments for dermatological herpes
- Acyclic nucleotide analogues: acyclovir, valacyclovir, famcyclovir
- Gancyclovir (pro-drug = valgancyclovir)
- Foscarnet (pyrophosphate analogue)
- Cidofovir
44
Which herpes virus causes chickenpox?
Varicella zoster (VZV)
45
How does chickenpox present?
Fever
Malaise
Headache
Characteristic crops of rash ("dew on a rose petal")
Lesions scab after 1 week - no longer contagious at this stage
46
When does a chickenpox infection stop being contagious?
When lesions scab over, approximately 1 week after first signs of infection
47
List 4 non-neurological potential complications of chickenpox
Scarring
Pneumonitis
Haemorrhage
Eye involvement
48
List 6 neurological potential complications of chickenpox
- 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
How can chickenpox be diagnosed?
- 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
What is congenital varicella syndrome?
Extremely rare disorder in which affected infants have distinctive abnormalities at birth due to maternal VZV infection during early pregnancy.
51
If a woman has chickenpox during pregnancy, what is the risk of her child having congenital varicella syndrome?
0.4% if
52
What are the key features of congenital varicella syndrome?
```
Scarring
Hypoplastic limbs
Cortical atrophy
Psychomotor retardation
Choreoretinitis
Cataracts
```
53
What risk is associated with maternal chickenpox +/-7 days from delivery?
Disseminated varicella infection in the neonate
| No passive immunity so infection is severe, with neonatal mortality rate ~30%
54
What are the indications for treating chickenpox?
```
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
Who requires post-exposure prophylaxis for VZV and what is given?
VZIG
Immunocompromised and pregnant women
56
If treatment for chickenpox is indicated, what is given?
Acyclovir 800mg PO TDS 7/7
OR
Valacyclovir 1g TDS
57
What does the chickenpox vaccine contain?
Attenuated Oka strain (live vaccine against varicella)
58
In which group is the chickenpox vaccine contraindicated?
Pregnant women
59
What is shingles/herpes zoster?
Reactivation of latent VZV in the dorsal root ganglion.
| Causes painful rash in a specific dermatome
60
What can cause shingles?
```
Stress
Decreased immunity (eg in immunocompromise/ people >50years)
```
61
When is treatment for shingles indicated?
Symptomatic children
| Healthy adult smokers (if 20/40
62
What is the treatment for shingles?
```
Acyclovir 800mg PO 5x daily
OR
Famcyclovir 250mg PO TDS
OR
Valacyclovir 1000mg PO TDS
```
63
What additional treatment is given for opthalmic shingles?
Topical antiviral eye drops (must be in addition to oral AVx)
64
What additional treatment may be given for shingles in immunocompromised patients?
PEP for 7-9 days
65
Name 2 epitheliotropic herpes viruses
Cytomegalovirus (CMV)(HHV5) and roseola virus (HHV6)
66
Name 2 lymphotropic herpes viruses
Epstein-Barr Virus (EBV)(HHV4) and Kaposi's sarcoma-associated herpesvirus (KSHV)(HHV-8)
67
In CMV, what does the "mega" part refer to?
Infected cells swell, increasing in size
68
What proportion of CMV infections are asymptomatic?
80%
69
How can congenital CMV present?
| list of 11!
```
IUGR
Jaundice
Hepatosplenomegally
Chorioretinitis
Encephalitis
Microencephaly
Thrombocytopaenia
Late progressove sensorineural deafness
Impaired IQ
Cytomegalic inclusion disease (13%)
Death
```
70
How does CMV mononucleosis present?
Very similar to EBV mono (glandular fever): fever, pharyngitis, lymphadenopathy
71
How can a CMV infection present in immunocompromised patients?
(list of 8)
```
Fever
Hepatitis
Colitis
Retinitis
Pneumonitis
Bone marrow suppression
Addison's disease
Radiculopathy
```
72
How is CMV likely to present in patients following a bone marrow transplant?
Pneumonitis
73
How is CMV likely to present in patients with AIDS?
Retinitis
74
Which cell types does CMV infect?
Macrophages
Endothelial cells
B and T lymphocytes
Bone marrow stem cells
75
Which investigations are used to diagnose CMV?
```
Blood PCR
Histopathology
Tissue immunofluorescence
Cell culture in human fibroblasts
Serology
Heterophile antibody test (eg Paul Bunnel/monospot)
```
76
What are "owl's eye inclusions" a sign of?
CMV - seen on cell culture in human fibroblasts
77
When is serology a useful test for CMV?
In immunocompetent patients. In the immunocompromised it is of little diagnostic value.
78
If an immunocompetent patient has CMV, what can be seen on serology?
CMV IgM and IgG
| but IgG has low avidity in a primary infection
79
If a patient is positive for CMV, what will a heterophile antibody test show?
Clumping of sheep RBCs
80
Which treatments are used for CMV?
Ganciclovir (or prodrug: valganciclovir)
Cidofovir
Foscarnet
81
Give 3 names for the disease caused by a roseola virus infection
Roseola infantum / exanthum subitum / Sixth disease
| 3 names for the same thing
82
How does roseola present?
Disease of children, usually under 2 years old
| 3 days of fever, followed by transient rash
83
Why can roseola cause a child to be mis-labelled as penicillin allergic?
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
Which virus is the most common cause of febrile convulsions?
Roseola virus
85
In which cells does roseola virus persist latently?
Monocytes and lymphocytes
86
How can roseola infection present in bone marrow transplant patients?
Pneumonitis
Hepatitis
Encephalitis
87
Which investigation diagnoses roseola?
Blood PCR
88
Which treatments are used for roseola virus?
Ganciclovir
Cidofovir
Foscarnet
89
Which of the human herpes viruses is the most mysterious? (ie least understood)
HHV7
90
Name the common disease caused by EBV
Infectious mononucleosis / Glandular fever / kissign disease
91
How does glandular fever present?
Incubation period of 4-6 weeks
Triad of fever, pharyngitis, lymphadenopathy
Maculopapular rash
92
How is EBV diagnosed?
Blood film
Monospot agglutination/Paul-Bunnel test
EBV antibodies
93
Which two cancers are associated with EBV infection?
```
Burkitt's lymphoma (Endemic/African variant)
Nasopharyngeal cancer (also more common in Africa)
```
94
What is the transplant-related disease caused by EBV?
Post-transplant lymphoproliferative disease.
Predisposes to lymphoma
95
What is the treatment for post-transplant lymphoproliferative disease?
```
Reduce immuosuppression
Give rituxumab (anti-CD20 monoclonal antibody)
```
96
Is EBV dangerous in pregnancy?
No
97
How is HHV8 transmitted?
Genitally
98
Name 3 diseases associated with HHV8
- Kaposi's sarcoma
- Primary effusion lymphoma (associated w/EBV co-infection)
- Castleman's disease (non-cancerous growth in the lymph nodes)
99
What is the treatment for HHV8?
Ganciclovir
| Foscarnet
