Micro 11 - Opportunistic viral infections Flashcards
Endogenous vs exogenous viruses
o Endogenous
Latent viruses that reactivate in absence of immune system
Acquired in past prior to immune suppression e.g. VZV
o Exogenous
Viruses acquired from the environment
Increased severity in immunosuppressed e.g. Influenza, Sars-cov-2
Detection of viruses in immunocompetent vs immunocompromised
Immunocompetent
direct –> PCR
Indirect –> serology (IgM, IgG)
Immunocompromised
serology not helpful if immunocompromised
Serological screening –> serology (screen prior to immunosuppression)
monitoring/prophylaxis –> PCR
Marker of replication for HAV
Marker of replication for HBV
Marker of replication for HAV = HAV in stool
Marker of replication for HBV = HbsAg in blood
Monitoring/ prophylaxis during immunosuppression
CMV + EBV PCR
BK virus (renal + BMT) Adenovirus (paeds BMT)
Relative risk of opportunistic infection
Allogeneic stem cell transplant
Advanced HIV infection (CD4 dep)
Solid organ transplant
Various monoclonal antibody therapies
Cytotoxic chemotherapy
DMARDs and steroids
List names of calcineurin inhibitors
Cyclosporine
Tacrolimus
(sirolimus (rapamycin) is NOT a calcineurin inhibitor)
Give 2 examples of infections that happen in the pre-engraftment interval (<30d from transplant)
HSV HHV6 HHV7 Candida Respiratory and enteric viruses
Give 2 examples of infections that happen in the early post-engraftment interval (30-100 from transplant)
CMV EBV VZV Adenovirus PCP Pneumocystis jirovecii Toxoplasma gondii
Immunosuppression in HSCT vs solid organ transplant
- Haematological transplantation (HSCT) patient immunosuppressed for some time and tapered down
- Solid organ transplants (SOT) patients immunosuppressed for life
List the different HHV viruses + the time at which they infect the host after the transplant
o HHV-1, HHV-2 (HSV 1 and 2) <1 month
o HHV-3 (VZV) >1 month
o HHV-4 (EBV)
>1 month
o HHV-5 (CMV)
>1 month (~6m)
o HHV-6 (Roseolovirus) <1 month
o HHV-7 (Roseolovirus) <1 month
o HHV-8 (Kaposi’s sarcoma-associated HV)
How does infection with HHV/HSV present
Pneumonitis
Hepatitis
Oesophagitis
DOES NOT cause encephalitis
o Q/A HSV is most likely to cause pain on swallowing after a liver transplant
Prophylaxis for HSV infection
Test for HSV IgG in recipient
Solid organ transplant –> give prophylaxis for 3-6m
Bone marrow transplant –> give prophylaxis for 1 month
How does VZV present in immunocompromised
Encephalitis
Purpura fulminans in the neonate
Hepatitis
Pneumonitis
VZV mx in immunocompromised
varicella
zoster
Varicella
acyclovir 7-10d
IV until no new lesions
PO until all have crusted
Zoster
o Anti-viral (IV if disseminated) + analgesia
o If Ramsay-Hunt – add steroids
o If HZO (herpes zoster ophthalmicus)– add topical steroids
What can EBV cause
Post transplant lymphoproliferative disease (latently infected B cells - polyclonal activation)
B cell lymphoma
CMV pathognomic histological feature
Owl’s eye lung pneumocytes (inclusion bodies)
CMV risk in solid vs HSCT
SOLID (e.. renal) organ transplantation greatest risk = donor +ve past CMV; recipient -ve immunosuppressed patient gets given some CMV for the first time
HSCT / BM transplant greatest risk = donor -ve past CMV; recipient +ve patient with CMV has immune system replaced with one that hasn’t seen CMV
CMV prevention strategies post transplant
Solid organ transplant
HSCT
Solid organ transplant
valganciclovir prophylaxis for 100 days
HSCT
2x weekly CMV PCR
Treat if virus reactivates
CMV reactivation mx post transplant
HSCT Foscarnet IV (nephrotoxic)
SOT
Ganciclovir IV (BM suppression)
Valganciclovir PO
other
Cidofovir (nephrotoxicity)
IVIG with another drug for pneumonitis
What is JC virus and how do we ix it
John Cunningham virus
Polyomavirus
>12m of transplantation
causes progressive multifocal leukoencephalopathy
MRI
PCR CSF
BK virus dx + mx
BK dx - PCR/NAAT
modulation/ reduction of immunosuppression
Post HSCT –> BK haemorrhagic cystitis –> intravesical cidofovir (avoids nephrotoxicity) + bladder irrigation
Post renal Tx - BK nephropathy - IVIG
Respiratory viruses in the immunocompromised ix
Multiplex PCR of NPA, BAL, nose, throat swabs
Influenza A+B mx
Oseltamivir PO 5/7
Zanamivir (IV or inhalation) if resistance/severe/immunocompromised
Covid mx
Sotrovimab
or
Casirivimab/ imdevimab
Hepatitis virus mx
A
B
C
E
• Hep A
o More severe
o Vaccinate
• Hep B
o Re-activation
o Vaccinate/prophylaxis
• Hep C
o Increased fibrosis
o Rx – direct acting antiviral
• Hep E
o Chronic infection
o Reduce immunosuppression
Hepatitis B
chronic infection vs full recovery
chronic infection - HbsAg persist
Full recovery - loss of HbSAg
Patients at risk of HBV reacivation
B cell depleting therapies e.g. rituximab
IL-6 inhibitor
Covid
HBV sAg +
HBV cAb +
HBV sAb -
Current
https://medschool.co/images/detail/hepb.gif
HBV sAg -
HBV cAb +
HBV sAb +
Past
https://medschool.co/images/detail/hepb.gif
HBV sAg -
HBV cAb -
HBV sAb +
Vaccination
https://medschool.co/images/detail/hepb.gif
HBV prevention
o Nucleoside reverse transcriptase inhibitor (lamivudine)
o Nucleotide reverse transcriptase inhibitor (tenofovir, entecavir)
o Prophylaxis
“Preemptive therapy”
involves directing prophylaxis only toward high-risk transplantation recipients (e.g., patients in whom early replication of CMV occurs) in an attempt to prevent the progression of asymptomatic infection into CMV disease.
Biopsy of Kaposis sarcoma + mx
• Diagnosis from biopsy characteristic histological findings:
o Spindle cell proliferation
o Neo-angiogenesis
o Inflammation and oedema
• Treatment
o Chemotherapy
o Antiretroviral therapy
see menti qs
x
HBV sAg -
HBV cAb +
HBV sAb -
cAb only produced by resolved infection
post infection can also look like cAb+ and sAb+
sAb wanes after both natural infection + immunisation
in people who have had hep B the core antibody is much longer lasting than the surface antibody (therefore isolate cAb+ but sAg- have had hep B long time in the past)
HBV sAg +
HBV cAb -
HBV sAb -
E carrier – ongoing chronic activation of hep B
