opportunistic viral infections

Question 1

What’s the definition of opportunities infections and categories

Answer 1

An infection of a niche, not available in healthy people.
Endogenous - latent viruses, acquired prior to immuno-compromised
Exogenous (environment, Iatrogenic,from graft)- increased severity in Immuno-suppressed.

Question 2

What drugs can induce immunocompromise? (5 types)

Answer 2

Steroids
Calcineurin inhibitors - cyclosporine, tacrolimus
Antiproliferative agents- (DMARDs) Azathioprine, mycophenolate mofetil-organ transplabt, sirolimus
Antibodies - depleting/ non eg anti CD25r ABs,
Co-stimulation blockers

Question 3

How are viruses detected - investigations

Answer 3

Indirection - immune response (not useful in immunocomp pts) Serology - IgM Active or resolving infection. IgG - past infection >6 weeks
Direct -Viral proteins, genetic material (eg NATs, PCR)

Question 4

How do you monitor infections in immunocompromised patients

Answer 4

Screen prior to immunosuppression - HIV Ag/Ab, HBV surface ag, core, surface ab, HCV ab, EBV ab, CMV ab, HSVab, VZVab, HTLVab guides prophylaxis
Monitor using PCR - reactivation and new infection.
CMV, EBV, BK, adenovirus (paeds BMT), HSV prophylaxis

Question 5

What is the order of risk for opportunistic infections (groups of pts)

Answer 5

Worst
Allogenic stem cell
Advance HIV
Solid-organ transplant
monoclonal abs
cytotoxic chemo
DMARDs and steroids

Question 6

What investigations would you do in a symptomatic immunocompromised patient.
Throat swab
Bloods
CSF
Gut biopsy

Answer 6

.
Resp- Flu-A/B, paraflu 1-4, adenovirus, enterovirus, RSV, HMPV, rhinovirus, coronavirus, CMV (on BAL)
Blood- CMV, EBV, Adeno, HHV6, parvo.
CSF- HSV,VZV, enterovirus, EBV, CMV, adenovirus, HHv6, JC virus
Gut biopsy- HSV, CMV, adeno

Question 7

How does the treatment of viral infections differ in immunocompromised patients

Answer 7

Pre-emptive + prophylaxis
^dosage and duration (increased toxicity)
Combination therapy (increased resistance)

Question 8

How are patients receiving transplants immunosuppressed

Answer 8

Total Body irradiation, cyclophosphamide
Haematological - suppressed for a while after the transplant but will be tapered and return to normal following transplant.

Solid organs - will remain on immunosuppressants forever

Question 9

What infections are commonly opportunistic viral and fungal

Answer 9

Viral
-CMV, EBV, HSV, VZV, HHV8
-JC and BK
-Influenza A and B, Parainfluenza 1,2,3,4, RSV, Adeno, coronaviruses
Fungi
-Candida, cryptococcal, Aspergillus, dermatophytes, mucormycosi

Question 10

When does each Flu strain peak

ignore for now

Answer 10

A - H1 - peaks in early January
B H1N1- end of December
B - March

Question 11

Which infections are most likely following HSCT - <30 days, 30-100 >100

Answer 11

<30
Coagulase negative staph, virdians Step, HSV, Candida, Aspergillus, Gram negatives.

30-100 -
Adeno, CMV, VZV, Aspergillus+ some rarer eg Pneumocystis and toxoplasmagondi

> 100
CMV, VZV, Aspergillus

Question 12

How do viral infections present differently in immunocompromised patients

Answer 12

May be more severe- disseminated, oncogenic
, may be infections not seen in immuno competent individuals, May be asymptomatic/ non-specific due to a lack of immune response.

Question 13

How does HSV present differently in immunocompromised patients and how is its management different?

Answer 13

Dissemination - oral, oesophageal, pneumonitis, hepatitis.
Aciclovir resistance
eg HIV maintain CD4<200
Prophylaxisis + regular IgG test if BM or organ transplant

Question 14

How is VZV different in immunocompromised pts

Answer 14

Dissemination - Varicella - pneumonitis, encephalitis, hepatitis, Purpura fulminans (neonates)
Shingles - multi-dermatomal

Question 15

VZV management in immunocomp

Answer 15

Prophylaxis (BM), Vaccination

Tx- Chicken pos - antiviral 7-10, IV until no new lesions then PO until crusted
Zoster - IV if disseminated +/- steroids

Question 16

What is PTLD

Answer 16

Post-transplant lymphoproliferative disease
- Induced by EBV- have suspicion on rising viral load.
Latently infect B cell-> polyclonal activation -> RF for lymphoma.
Confirm with lymph node biopsy

Question 17

Management of CMV in immunocompromised patients?

Answer 17

Reassurance if immunocompetent

Prophylaxis ( pre transplant- solid organ) /Pre-emptive (check CMV viral load HSCT 
Ganciclovir - IV 1st line
Valganciclovir oral step down
Foscarnet- IV
Cidofovir
IVIg
or reduce immunosuppresants

Question 18

What immunosuppression is JC virus associated with?

Answer 18

HIV, ( antiretrovirals have reduced this)

Monoclonal Abs eg Natalizumab (for MS)

Question 19

What are the signs and symptoms of progressive mutifocal leukoencephalopathy?

Answer 19

Cognitive disturbance + focal neurology (caused by neuronal demyelination- seen on MRI)

Question 20

How do you manage viral hepatiis in immunocompromised pts? Each type

Answer 20

A - (more severe) Vaccinate
B- (Re-activation)- Vaccinate/ prophylaxis (lamivudine, tenofovir, entecavir)
C- direct-acting antiviral
E- chronic infection - reduce immunosuppression

Question 21

Explain the serology of Hepatitis B

Answer 21

surface antigen - cirrculating virus
Core antibody- Current / previous infection - IgG acute, igG/total can show prior, depending on sAg
Surface antibody - from vaccine or virus