Opportunistic Viral Infections Flashcards
How are viruses classified?
Baltimore classification
By replicative life cycle + genetic material
What is an opportunistic infection?
Infection caused by an organism that does not normally cause disease in an immunocompetent host
or symptomatology may be altered in the immunocompromised
What are endogenous viral infections?
Latent viruses that reactivate in absence of normal immune system.
Acquired in past, prior to immune suppression e.g. Varicella Zoster.
What are exogenous viral infections?
Viruses acquired from environment.
Increased severity in immunosuppressed e.g. Influenza, SARS-CoV-2.
How do you remember which HPV is more severe?
higher number= greater severity
HPV 6+8: genital warts
HPV 16+18: cervical cancer
What is indirect detection of a virus?
Response of immune system to the virus.
Useful to see if you have EVER had the infection.
What is direct detection of a virus?
Useful to see if you have the infection NOW
- Viral proteins (lateral flow/ antigen tests).
- Viral genetic material (virus genetic material present with pt sample)
Polymerase chain reaction.
How is serology used to determine infection with a virus?
Measure levels of antibody in patients serum.
+++ IgM: Active/ Resolving infection
+++ IgG: past infection > 6w ago
Antibody levels ↓↓↓ reduced in Immunosuppressed.
Serological course may differ depending upon virus.
What does this mean?
Surface antibody declines in the future, core antibody remains high for Hep B.
Surface antibody indicates previous vaccination, core antibody is previous infection with the real thing.
Give 3 facts about direct detection with PCR
Highly sensitive + specific
Viral load can be used to monitor infection
Can remain +ve even after infection resolved
At what point does the PCR viral load tend to peak?
When most infectious + just prior to worst Sx
What approach is used for virology diagnostics in immunocompromised?
- Screen prior to immunosuppression- identify previous exposure that may reactivate + guide antiviral prophylaxis
- Monitor with PCR: identify reactivation promptly + detect infection
Which antibodies are screened in serological screening prior to immunosuppression?
HIV Ag/Ab
HBV surface antigen, core antibody + surface antibody
HCV antibody
EBV antibody
CMV antibody
HSV antibody
VZV antibody
HTLV antibody
What is monitored/prophylactically treated during immunosuppression?
CMV monitoring PCR or prophylaxis
EBV monitoring PCR
BK monitoring PCR (Renal + BMT)
Adenovirus monitoring PCR (Paediatric BMT)
HSV prophylaxis if indicated
A 51-year-old with a recent HSCT is unwell. Which is the most appropriate test? ALT = 800 IU/mL
A. EBV IgG/IgM
B. HBV sAb
C. Parvovirus PCR
D. HEV PCR
E. CMV IgG/IgM
D. HEV PCR
Immune system not functioning- unable to accurately test production of antibodies, IgM + IgG
Abnormal ALT is likely in Hepatitis E
Parvovirus more likely to cause red cell aplasia/ anaemia
What increases the risk of opportunistic infections, from highest to lowest?
Allogeneic stem cell transplant
Advanced HIV infection (CD4 dep)
Solid organ transplant
Various monoclonal antibody therapies
Cytotoxic chemotherapy
DMARDs and steroids
Describe the transplant immunosuppression timeline for haematopoeitic stem cells
- Total body irradiation/ cyclophosphamide- eradicates disease + wipes out immune system
- Transplant- no neutrophils
- Wait for transplant to take- no neutrophils
- Engraftment- neutrophils start to rise- now need ongoing immunosuppression to prevent GvHD
- If successful, eventually cease immunosuppression
Describe the transplant immunosuppression timeline for solid organs
- Induction immunosuppression- need to suppress + prevent T cell activation
- Transplant organ
- Continue maintenance immunosuppression- lifelong
What are sources of viral infection from transplants?
Acquired from graft: HBV
Reactivation from the host: HSV
Novel infection from infected individual: VZV
What can be done to reduce risk of acquiring viruses from grafts?
Check donor serostatus
Risk assessment
What can be done to reduce risk of viral reactivation in a transplant recipient?
Check recipient + donor serostatus
Monitor with PCR
Consider prophylaxis + pre-emptive therapy
What can be done to reduce risk of acquiring novel viruses in a transplant patient?
Isolation barrier nursing
Educating visitors
PEP
Vaccinate contacts
Control diet
List 5 high incidence infections pre-engraftment in HSCT recipients
CoNS
Strep Viridans
HSV
Candida
Aspergillus
List 4 high incidence infections post-engraftment in HSCT recipients
CMV
VZV
Adenovirus
Aspergillus
Which type of immunosuppression carries the greatest relative risk of developing a viral infection?
A. Steroids
B. Solid organ transplant
C. Allogeneic stem cell transplant
D. Monoclonal antibody therapies
E. Cytotoxic chemotherapy
C. Allogeneic stem cell transplant
What is symptomatic screening molecular testing?
Screen + perform molecular tests according to presenting Sx
e.g. Headache, confusion, meningism do LP + screen CSF
What 8 viruses are tested for in symptomatic screening in the CSF?
- HSV
- VZV
- Enterovirus
- EBV
- CMV
- Adenovirus
- HHV6
- JC virus
What 5 viruses are tested for in symptomatic screening in the blood?
- CMV
- EBV
- Adeno
- HHV6
- Parvo
What 9 viruses are tested for in symptomatic screening in the respiratory system?
- Flu A/B
- Paraflu 1-4
- Adenovirus
- Enterovirus
- RSV
- HMPV
- Rhinovirus
- Coronaviruses
- CMV in BAL
What 3 viruses are tested for in symptomatic screening in the gut?
- HSV
- CMV
- Adeno
Give 2 challenges of anti-viral therapy in the immunosuppressed
Increased levels of antiviral resistance
Increased toxicity of antivirals
How are viral infections different in the immunocompromised?
- Present differently
- Disseminated
- Different organs than in immunocompetent
- More severe
- Oncogenic
- Lack of immune mediated Sx.
What is shown here?
LHS: HSV in immunocompetent
RHS: HSV in immunocompromised- oesophagitis
What are 4 issues with HSV infections in immunocompromised patients?
- Increased frequency
- Increased severity/ risk of dissemination
- More organs can be involved (pneumonitis, eosophagitis, hepatitis); NB: not enceph!
- Increased risk of acyclovir resistance
What treatment should be given to HIV/AIDS patients with CD4 <200 and HSV infection?
Start ART to raise CD4 count
What is the prophylactic management of the HSV in transplant patients undergoing intense immunosuppression?
Prior to transplant: Test for HSV IgG, if detect: Aciclovir/ Valaciclovir prophylaxis
BMT: continue 1 month post engraftment
SOT: 3-6 months (+ restart this if treated for rejection)
What can varicella (chicken-pox) cause in immunocompromised patients?
- Pneumonitis
- Encephalitis
- Hepatitis
- Purpura fulminans in neonate
What is seen here?
Disseminated varicella zoster in an immunocompromised host
What is seen here?
Purpura fulminans caused by varicella infection in immunocompromised neonate
What can VZV cause in immunocompromised patients?
Zoster (shingles)
- Multi-dermatomal/disseminated
- Often late presenting immunosuppression Sx
What is the preventative approach to VZV in the immunocompromised?
Prophylaxis: Aciclovir or Valaciclovir, even post transplant- if post-BMT ~1y)
PEP: Varicella Immunoglobulin IVIg within 10d of contact
Vaccination: if no prior exposure
What is the treatment for VZV?
Varicella- chickenpox picture:
Anti-viral for 7-10d
Start IV, switch to PO once no new lesions arising
Zoster- shingles presentation:
Aciclolvir/ Valaciclovir (IV if disseminated) + analgesia
If Ramsay-Hunt: Add steroids
If Herpes zoster opthalmicus: Add topical steroids
A patient who received a stem cell transplant 2 weeks ago presents with mouth ulcers. Which of the following viruses would you test for on the mouth swab?
A. Enterovirus
B. Adenovirus
C. Herpes simplex type 1
D. Human herpesvirus 6
E. Human gammaherpesvirus 8
C. Herpes simplex type 1
What is EBV associated with?
Post-transplant lymphoproliferative disease (PTLD)
Latently infected B cells: polyclonal activation.
Predisposes to lymphoma.
Occurs in SOT or allogenic HSCT
Related to level of immunosuppression
What indicates and diagnoses EBV associated PTLD?
Suspicion on rising EBV viral load (>10^5 c/ml) + CT scan.
Confirmation with biopsy of lymph nodes.
What are complications associated with EBV in immunosuppressed?
Oncogenesis:
- B-cell latency, high turn-over
- T-cells monitor/ control this
B-cell lymphomas
PTLD
How are complications of EBV prevented in immunocompromised?
Monitor EBV levels: PCR 1-2 weekly
Ix for lymphoma as needed
What are the recommendations for treating complications of EBV in immunocompromised?
? Rituximab
Reduce immunosuppression.
What are 4 complications associated with CMV in those with HIV + CD4 <50?
Ocular (retinitis)
Polyradiculopathy
Pneumonitis
GI tract- gastroenteritis
What are 2 complications associated with CMV in those who have received a solid organ transplant ?
Allograft disease
GI tract (i.e. renal)
What is the prevention approach and management for CMV in immunocompromised?
Prophylaxis (i.e. lung transplant).
Pre-emptive tx (i.e. renal transplant / HSCT).
Treat if disease (HIV/AIDS).
Rx: Ganciclovir/ Valganciclovir
Reduce immunosuppression.
What is a concern in SOT patients e.g. renal, about latent CMV?
More worried if donor is +ve
CMV remains latent in cells
Patient exposed to CMV for first time
What is a concern in HSCT patients about latent CMV?
More worried if recipient if +ve
Wipe out recipient immune system, replace with naive donors immune system
Recipient reactivation a/w morbidity/ mortality
What is the post-transplantation prevention strategy against CMV in HSCT?
CMV viral load twice weekly
Treat if virus reactivates until suppressed (pre-emptive therapy).
What is the post-transplantation prevention strategy against CMV in Solid Organ Transplant?
Valganciclovir prophylaxis for 100 days
List 5 drugs involved in treatment of CMV and their associated side effects
Ganciclovir (IV): BM suppression
Valganciclovir (Oral)
Foscarnet (IV): Nephrotoxicity
Cidofovir: Nephrotoxicity
IVIg (with another drug for pneumonitis).
Which of these is NOT an antiviral?
A. Sotrovimab
B. Valganciclovir
C. Foscarnet
D. Rituximab
E. Tenofovir
D. Rituximab
(Monoclonal antibody)
What is JC Virus (John Cunningham)?
JC virus= polyomavirus.
Can cause Progressive multifocal leukoencephalopathy.
Effective ART drastically reduced PML incidence in HIV+ve
PML can be seen in other types of immunosuppressed:
- Those with Humanised monoclonal antibodies
- Those taking Natalizumab (for tx of MS)
What is the recommendation for patients taking Natalizumab for MS?
After 2y patients can progress PML
If at 6m test shows JC virus +ve, do 6 monthly PCR + MRI head scans
Don’t prescribe for longer than 2y
What is the treatment for JC virus?
No specific tx for JC virus
What is progressive multifocal leukoencephalopathy (PML)?
Cognitive disturbance, personality change, motor deficits, other focal neurological signs.
Demyelination of white matter → neurological deficits.
Dx: MRI + PCR on CSF
What is BK virus?
Polyomavirus with ds-DNA
Post SCT: haemorrhage cystitis- blood in catheter
BK nephropathy Post Renal Tx
What is the treatment for BK virus?
Cidifovir (nephrotic itself)
Bladder irrigation
Modulation of immunosuppression
Which patient has previously had Hepatitis B Infection?
sAg= Surface antigen cAb = core antibody sAb= Surface antibody
A. sAg+, cAb+, sAb-
B. sAg-, cAb-, sAb+
C. sAg-, cAb+, sAb-
D. sAg-, cAb-, sAb-
E. sAg+, cAb-, sAb-
C. sAg-, cAb+, sAb-
cAb MUST be +ve if previous infection
sAg indicates active infection
How are viruses classified?
Baltimore classification
By replicative life cycle + genetic material
List 5 respiratory viruses associated with increased risk of pneumonitis and high mortality in the immunocompromised
Influenza A+B
Parainfluenza 1-4
RSV
Adenovirus
SARS-CoV-2
What treatment can be given for influenza in the immunocompromised?
Oseltamivir PO for 5d
What treatment can be given for SARS-CoV-2 in the immunosuppressed?
Sotrovimab
Describe how hepatitis is more severe in the immunocompromised, and thus the preventative measures
A: More severe, vaccinate to prevent
B: increased risk of reactivation. Vaccinate/ give prophylaxis
C: increased risk of fibrosis. Give direct acting antiviral
E: causes chronic infection. No tx, reduce immunosuppression
How can Hepatitis B manifest in the immunocompromised?
- Carriers may have flare of disease
- Those who have had past infection can reactivate- increased risk with B cell depleting therapies- Rituximab, IL-6 inhibitors
What drugs are used in the prevention of hepatitis B in the immunocompromised?
Nucleoside: Lamivudine
Nucleotide: Tenofovir
Give 3 markers of hepatitis B disease
sAg+ = circulating virus
eAg+ = circulating virus
cAb+ (IgM) = acute immune response
Give 3 markers of hepatitis B immunity
sAb+: from virus or vaccine
cAb+ (IgG): from prior infection with virus
eAb+: from past viral exposure
Describe the rash in monkeypox
Plaques- Papules - Vesicles- Pustules- Crusts
May be atypical
Most commonly on genitals inc. peri-anally
Appears 1-3d after fever onset
List 4 symptoms/ signs of monkeypox
Fever
Lymphadenopathy
Headache
Myalgia
What prophylaxis is available for monkeypox?
Smallpox vaccine
Describe the management of a patient with monkeypox
Isolate
Symptomatic tx: analgesia
If severe e.g. encephalitis: Tecovirimat
Screen for other STIs
Inform UKHSA
