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HSV Flashcards

1
Q

Management of patient who delivers at term with primary HSV in 1st/2nd trimester

A

Aciclovir 400mg TDS from 32/40 then vaginal delivery

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2
Q

Management of patient who delivers at term with primary HSV in 3rd trimester but no vesicles at birth

A

Aciclovir 400mg TDS from diagnosis or 32/40 and C section

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3
Q

Management of patient who presents at term with primary HSV diagnosed at presentation for delivery

A

C section, consider intrapartum aciclovir, high risk neonate

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4
Q

Baby born to mum by SVD. Mum develops primary HSV 2 weeks following birth. Investigation and management of child?

A

Highest risk - send Blood, swabs (skin, conjunctivae, nose, rectum, mouth) and CSF. Treat empirically. 10 days negative results (14 days SEM, 21 days CNS/disseminated)

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5
Q

Management of patient who has HSV infection prior to pregnancy. No lesions in pregnancy or at time of delivery.

A

Prophylactic aciclovir from 32/40 and SVD.

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6
Q

Management of patient with non primary HSV who is felt to represent a high risk of pre term delivery.

A

Prophylactic aciclovir 400md BD from “at risk” period until 32/40 then 400mg TDS. normal SVD.

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7
Q

Proportion of neonatal HSV infections that are postnatal?

A

10-25%

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8
Q

3 presentations of neonatal HSV and proportions

A

1/3 each
- SEM (skin, eyes, mouth)
- CNS
- Disseminated

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9
Q

Highest risk neonate for HSV infection, investigations and management.

A

Criteria
- Symptomatic HSV
- Pos HSV testing
- SVD and primary HSV infection at time of birth
- Postpartum infection of mum up to 4/52

Investigation
- Swabs - conjunctivae, mouth, skin, rectum
- Blood PCR
- CSF PCR

Mgmt
- Empiric - 10 days
- SEM - 14 days
- CNS/disseminated - 21 days with CSF/bood recheck at end of Rx. If Pos then continue 1 more week.

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10
Q

High risk neonate criteria, investigation and mgmt.

A

Criteria
- Primary HSV in the 6 weeks prior to delivery regardless of delivery method

Investigation
- Swabs - conjunctivae, mouth, skin, rectum
- Blood PCR
- CSF PCR

Mgmt
- Empiric - 10 days
- SEM - 14 days
- CNS/disseminated - 21 days with CSF/bood recheck at end of Rx. If Pos then continue 1 more week.

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11
Q

Low risk neonate criteria, investigation, mgmt

A

Criteria
- Asymptomatic baby born by any method to mum with non-primary HSV lesions at delivery
- Asymptomatic babies born at<37 weeks by any delivery method with no active lesions at delivery and a history of HSV infection more than 6 weeks previously

Investigation
- Swabs - conjunctivae, mouth, skin, rectum
- Blood PCR
- Note CSF not routinely recommended.

Mgmt
- monitor. If any evidence HSV then manage as per symptomatic (highest risk)

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12
Q

Lowest risk neonate criteria, investigation, mgmt

A

Criteria
- Asymptomatic babies born at >37 weeks by any delivery method with with no active lesions in birthing woman or person at delivery AND a history of HSV infection more than 6 weeks previously

Investigation
- no empiric investigations

Mgmt
-monitor for 24h then home

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13
Q

Treatment of patient who delivers via SVD at term with primary HSV diagnosed at delivery

A

intrapartum aciclovir. Neonate represents highest risk

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14
Q

HSV
- Baltimore class
- Enveloped/non enveloped

A

Linear dsDNA - Class 1
Enveloepd

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15
Q

HSV presentations - immunocompotent adults

A
  • Skin - coldsore, genital, exzema herpeticum, herpetic whitlow
  • eyes - dendritic ulcer
  • meningitis - mainly HSV2
  • Encephalitis - Mainly HSV1
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16
Q

Diagnosis - recurrent HSV 2 meningitis

A

Mollaret’s meningitis

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17
Q

Factors associated with worse outcomes in neonatal HSV infection

A

HSV2
Premature (no transplacental AB transfer)
Disseminated disease
Delay in treatment

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18
Q

Management of patient who has HSV infection prior to pregnancy and who is found to have lesions at presentation for delivery at term.

A

SVD. Baby represents low risk. No empiric ix. Monitor for 24h

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19
Q

Where is HSV latent?

A

HSV-1 most commonly in the trigeminal ganglion

HSV-2 most commonly in the sacral ganglia

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20
Q

What causes HSV reactivation?

A

Stress (acute, episodic acute, or chronic), fever, UV light, heat can cause reactivation by activating the glucocorticoid receptor

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21
Q

Why does HSV-2 infection increase risk of HIV transmission?

A

It causes upregulation of CCR5 receptors

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22
Q

Clinical spectrum of HSV disease

A

Orolabial and genital lesions
Neonatal infection
Encephalitis and meningitis
Hepatitis
Keratitis/dendritic ulcer
HSV pneumonitis

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23
Q

What is the clinical implication of HSV DNA detection in blood?

A

Viraemia (or DNAemia) can be present during benign disease (20% viraemia detected in patients with coldsores) but severe disseminated disease is rare

Interpret results with clinical picture and how strong the positive is

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24
Q

Which patients are most at risk of HSV hepatitis?

What are the common features?

Are lesions present?

What is often the outcome?

A

SOT and pregnant women in third trimester

Fever, very high aminotransferases, leukopenia, thrombocytopenia, encephalopathy, coagulopathy, and acute renal failure - non-specific presentation and often mis/undiagnosed

Mucocutaneous lesions not present in >50% cases

Acute liver failure. Transplant may be required

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25
What is the implication of HSV detected in the URT/LRT of critically ill patients?
Can just be bystander. Up to 50-60% of ventilated patients are positive in both URT and LRT samples Consider pneumonitis
26
In which SOT is HSV pneumonitis most commonly observed?
Heart-lung
27
What are symptoms of HSV pneumonitis? Which patients does this occur in? What is the mortality rate?
Prodrome with rapidly worsening respiratory failure. Upper airway manifestations (gingivostomatitis and pharyngitis are common) HSV pneumonia/pneumonitis is extremely rare, but can occur in both immunosuppressed and immunocompetent patients (mostly with extended ventilation) 60% mortality
28
Term for recurrent benign lymphocytic meningitis? What is this? What is the most common cause?
Mollaret's meningitis Rare clinical disorder characterized by at least three recurrent episodes of meningitis associated with spontaneous recovery HSV-2 most common cause
29
Which HSV is most commonly associated with meningitis and what clinical syndrome is often associated?
HSV-2 Most commonly associated with genital herpes (symptomatic or not)
30
Differentials of HSV encephalitis
Other viral encephalitis (VZV, entero, CMV, EBV, adeno, flu, vector borne), autoimmune, vascular events, CNS malignancies, brain abscess
31
Symptoms of HSV encephalitis
Usually acute onset (although some subacute) Headache, fever, neurological findings eg cranial nerve deficit, hemiparesis, dysphasia, aphasia, ataxia, altered mental state, personality changes and reduced consciousness Olfactory hallucinations occur during prodrome
32
What % of HSV encephalitis is caused by: HSV-1 vs HSV-2 Primary vs reactivation Immunocompetent vs immunocompromised
HSV-1 = 90%, HSV-2 = 10% 30% caused by primary infection, 70% due to reactivation No increased risk in immunocompromise (but may have atypical presentation)
33
What is seen in the brain during HSV encephalitis?
Necrotising encephalitis involving temporal lobe, inferior-frontal lobe, and /or insular cortex Imaging is unilateral (later in disease bilateral) Histology show Cowdry type A bodies
34
What procedure significantly increases the risk of HSV encephalitis?
Brain radiotherapy
35
What is the pathophysiology in HSV encephalitis?
CNS pathology includes cytolytic viral replication and immune mediated mechanisms (inflammatory cytokine production) Pathogenesis incompletely understood, possibilities include: >Primary/reactivation of oropharynx with direct infection of CSF via olfactory system >Haematogenous spread to CNS >Reactivation directly in CNS from latent HSV in brain
36
What features would you see in CSF in HSV encephalitis?
Elevated protein (50-200 mg), Leucocytosis (5-500 cells), predominantly lymphocytes, glucose normal PCR is usually positive within 24 h of symptom onset but may be falsely negative in early infection (<72 h)
37
What is the PPV of MRI in HSV encephalitis?
MRI can be negative early on but after 3 days 95% should have abnormal MRI
38
When is intrathecal Ab used for diagnosis of HSV encephalitis?
Intrathecal Ab testing can be used if diagnosis occurs >10 days post symptom onset DNA should be detectable prior to this, and PCR usually positive for at least 1 week if acyclovir treatment received
39
What is seen on EEG in HSV encephalitis?
EEG is abnormal in 80%, typically intermittent high amplitude slow waves
40
Stopping rules for aciclovir in suspected HSV encephalitis?
Empirical aciclovir can be stopped if: 1) Alternative diagnosis made 2) PCR negative 2x 24-48 h apart AND normal MRI 3) PCR negative >72 h after symptoms AND normal MRI AND normal cell count
41
Treatment for HSV encephalitis? How does treatment effect mortality rate?
IV acyclovir 10 mg/kg TDS 14 days � if immunosuppressed or <12 then 21 d (dose 3m-12y 500 mg/m2 TDS) Treatment reduces mortality from 75% to 10-25%
42
What mimics HSV encephalitis, especially in older patients with renal dysfunction? How can you investigate this?
Aciclvoir induced encephalitis Test for ACV and CMMG (9-carboxymethoxymethylguanine) levels in blood, urine, CSF. Rapid regression of symptoms on cessation of aciclovir. If toxicity occures force diuresis and if severe then dialyse patient
43
In rare cases of aciclovir resistant HSV in encephalitis, what is the alternative treatment?
Foscarnet
44
How many patients have relapsing symptoms after HSV encephalitis? What is the most common cause? When does this most often occur? What is the treatment?
10-25% of patients Most neurological relapse occurring after resolution of HSV encephalitis is due to NMDA-R encephalitis, CSF is PCR negative but Ab to NMDA-R high Occurs on average at 50 days Treat with IVIG and methylpred True virological relapse is rare, late relapse >3 months to decades can occur
45
What should you consider in unwell patients with sepsis like illness or worsening liver function?
Disseminated HSV
46
Treatment for genital HSV?
Within 5 days of lesions 400 mg aciclovir TDS for 5 days
47
Differential diagnosis for genital lesions?
HSV VZV Mpox Syphilis
48
What proportion of patients experience symptoms after initial infection with HSV-2?
1/3 of patients have genital symptoms, however systemic symptoms are common in primary infection
49
When should pregnant women with previous HSV infection receive prophylactic aciclovir? What is the dose? What is the rationale?
400 mg BD from 22-31 weeks if at risk of preterm delivery 400 mg TDS from 32 weeks in all patients Risk of transmission is 41% with primary infection in third trimester. This was previosuly 36 weeks but chnaged to 32 weeks as 23% of neonatal HSV occured before 36 w
50
Actions for pregnant women presenting with first episode of genital herpes
Type specific serology Treat with aciclovir if appropriate and then give prophylactic aciclovir Avoid sex in the last trimester unless Ab to both types
51
When can patient with genital herpes have vaginal birth?
If infected prior to third trimester
52
When should a patient with genital herpes have C-section?
If infected less than 6 weeks previously or if infected in third trimester (esp if within last 6 weeks)
53
Risk of neonatal HSV if vaginal birth in: First episode at onset of labour First episode at onset of labour but infected previously with other HSV type Recurrent genital herpes
41% 25% 0-3%
54
Definition of neonate born to mother with genital herpes in: a) Lowest b) Low c) High d) Highest risk infant
a) asymptomatic, >37 w, any mode of delivery, no active lesions in mum, history of HSV >6 w pre delivery b) asymptomatic, any mode of delivery, with lesions in in mum and >37 w, or <37 weeks without lesions, history of HSV >6 w pre delivery c) primary HSV within 6 weeks, asymptomatic, vaginal delivery or C-section if PROM d) all symptomatic neonates or testing HSV positive. Babies born by vaginal delivery with active lesions, mother systemically unwell at delivery, HSV in mum up to 4 weeks post birth. Pre-term infant with PROM
55
Investigations and prophylaxis of: a) Lowest b) Low c) High d) Highest risk infant
In all cases - inform neonatal team a) No investigations b) At 24 hours throat, nose, conjunctival, rectal swab and blood - no prophylaxis c) At 24 hours throat, nose, conjunctival, rectal swab, blood and CSF - 20 mg/kg IV aciclovir for 10 days d) At 24 hours throat, nose, conjunctival, rectal swab, blood, lesions and CSF - 20 mg/kg IV aciclovir for 10 days. Isolate.
56
Additional non-virology investigations for neonates at high and highest risk of HSV
FBC, LFTs, Coag screen CSF - protein, glucose, micro Ophthalmic review for highest risk
57
Additional requirement if mum presents in labour with primary genital herpes?
IV aciclovir 5 mg/kg - give if vaginal birth and consider if C-section esp if membranes ruptured
58
Most common source of postnatal HSV? When does this most commonly occur? What % of neonatal HSV is due to postnatal infection?
Cold sores of herpetic whitlow in family or carers First 6 weeks 10-25%
59
Can mum breastfeed with HSV lesions on breast?
No (breastmilk not a source of infection) No breastfeeding or expressing until lesions crusted
60
Additional considerations for HSV discordant couples
Consider type specific Ab testing Avoid sexual contact from 2 weeks before 3rd trimester Antiviral suppression for partner
61
Treatment options for neonatal HSV in aciclovir shortage?
Ganciclovir 6 mg/kg IV BD Foscarnet 60 mg/kg IV BD Oral aciclovir can be considered for SEM
62
Median presentation of neonatal HSV, mortality and sequalae: SEM CNS Disseminated
SEM = 8 days, death is uncommon CNS = 14 days, 50% mortality without treatment, 15% with treatment, '64% neurological morbidity Disseminated = 6 days, 85% mortality without treatmnet 66% with treatment, 41% long term morbidity
63
Dose and duration of aciclovir treatment in neonates for: High risk infant no symptoms SEM CNS Disseminated
20 mg/kg TDS for all Prophylaxis = 10 d SEM = 14 d CNS or disseminated = 21 d Re-LP around day 18 for CNS and give another 7 d if still positive For CNS or disseminated disease after treatment babies should receive 6 months of suppressive ACV
64
What is required after treatment of CNS or disseminated neonatal HSV treatment?
After parenteral treatment neonates should receive 6 months of suppressive aciclovir (300 mg/m2 TDS)
65
Can donor derived HSV infect recipients in SOT?
Yes - been described in liver, kidney and other transplants However most HSV disease in SOT is from reactivation in R+
66
When does HSV most often occur in SOT and how does this present?
Within the first month post transplant Multiple localised painful lesions
67
Dose and duration of aciclovir treatment in limited mucocutaneous HSV in SOT?
400 mg 5x day for 5 days
68
Who should receive HSV prophylaxis in SOT? What is the drug of choice and dose?
D-/R+, D+/R+, D+/R- No prophylaxis required if patients are on ganciclovir prophylaxis for CMV 2-400 mg aciclovir QDS
69
Can deceased donors donate organs if HSV positive with: Disseminated disease CNS disease
Contraindicated in disseminated disease Can consider in CNS disease if recipient given prophylaxis
70
Who should receive HSV prophylaxis in HSCT? What is the drug of choice and dose?
R+ 400 mg aciclovir QDS
71
Which haematology patients are at risk groups for HSV reactivation?
Autografts to D30 Allografts to D100 Alemtuzumab (Campath) recipients CD4<0.4 Acute Leukaemia Neutrophil <1.0 x 109/L Chemotherapy recipients with high incidence of previous coldsores/genital herpes
72
Name two topical treatments for HSV
Imiquimod Docosonol
73
What are the three mechanisms of HSV TK resistance in aciclovir and what proportion of each occur?
TK-mutations TK negative mutants (lack TK activity) TK-low producer mutants (expressed reduced levels of TK) TK-altered mutants (TK does not phosphorylate ACV specifically) <5%
74
What are the two genes in HSV that confer aciclovir resistance? Which is more common and why?
UL23 gene (encoding thymidine kinase) (95% of cases) UL30 gene (viral DNA polymerase) (5% of cases) UL23 mutations more common as TK is dispensable but pol is an absolute requirement for replication
75
What is the most common mechanism of HSV aciclovir resistance?
50% resistance due to deletions/additions in UL23 particularly in homopolymer repeats of Gs or Cs which are considered resistance hot spots (so don't need to remember specific resistance mutations?)
76
Name two resistance mutations in HSV UL30 which confer resistance to ACV and FOS and decreased sensitivity to CDV
S724N and L778M
77
When to suspect HSV aciclovir resistance?
If no improvement after 7 days of treatment
78
Why is HSV aciclovir resistance more common in immunosuppressed patients?
More common in immunocompromised host due to extended virus replication and reduced host responses allowing less pathogenic viruses to replicate
79
What has pritelevir been used to treat?
Genital herpes caused by HSV-2 Reduced shedding and longer time between recurrences
80
How would you treat aciclovir resistant genital herpes?
Imiquimod
81
Gold standard method for HSV resistance testing
Gold standard phenotypic testing is plaque reduction assay, after growing virus in Vero cells in the presence of different concentrations of the antiviral Genotypic assays can detect known mutations but do not detect novel mutations
82
Treatment for HSV keratitis?
Usually self resolving but treatment can resolve sooner/reduce long term damage. Oral aciclovir and/or topical trifluorodine/ganciclovir

Part 2 Revision (57 decks)

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