Opportunistic Viral Infections Flashcards
What is a major cause of morbidity in autologous STC and mortality in allogenic STC?
Viral infections- 3 weeks patient engrafting, started on cyclosporin from chemo so immunosuppressed plus immunological conflict, not immediate.
Allogenic 1 year, autologous less of a problem.
graft from donor fight against host antigens, graft vs host immunosuppressive in itself.
What are the risk factors for virus associate morbidity and mortality?
Allogenic BMT Mismatched related, match unrelated Acute or chronic graft vs host disease Immunosuppressive therapy In vitro T cell depletion Delayed cd4 cell recovery
How can HIV infected hosts affect susceptibility to viral infection?
Risk of developing opportunistic infections can be predicted from cd4 count
CMV- below 50
HSV- higher
Anti retroviral- below 350 or earlier
What are the different routes of infection in the transplant recipient?
Virus acquired from graft- hep b, CMV
Virus reactivation from host- herpes
Novel infection from infected individual- measles, parvovirus, VZV
May primarily involve the grafted organ- CMV affect kidney
What are the different disease manifestations?
Increased severity of the disease
Wider range of systems involved
Disseminated disease
Each organism gives rise to different disease manifestations in different patient group eg CMV pneumonitis in HSCT, retinitis in AIDS
Novel syndromes- EBV associated post transplant lymphoproliferative disease
What is the basic principle of treatment for opportunistic viral infection?
Difficult, requires early treatment, higher dose, longer course, sometimes drug combinations
Increased risk of antiviral drug resistance
What is preferred between serology and virus detection?
Virus detection- nucleic acid, PCR etc, antigen detection
Serology- listed diagnostic value especially in immunosuppressed patients as they may not have developed antibodies, received blood products
How can be PCR be applied in a routine diagnostic lab?
Many types of samples- blood, resp secretions (predictive value low), vesicles swab, conjunctival swab, stools, biopsies, CSF, blood collected by EDTA bottle
Use of viral load in blood (quantitative assay)- CMV, EBV, adenovirus, can be used as guide to clinical significance of infection, monitor response to treatment.
What is PCR?
Exponential replication of DNA, RNA virus reverse transcription phase first.
Real time PCR, reporter probes
Ct- cycle threshold, after 17 cycle able to detect fluoresence. More cycle for fluoresce to be detected means, more virus
Using blood sample with known conc of CMV, serial dilution, and calibrate sample, quantification of sample.
What DNA viruses are included in the HHV group?
HSV 1 and 2 VZV CMV HHV 6 EBV HHV 8
How are HHV involved when immunosurveillance is broken up?
Latent infection, only small subset of genes are expressed
Reactivation can occur leading to expression of viral genes and production of progeny virus
Leads to destruction of the host cells
Where are the sites of latency for the HHV?
HSV 1,2 and VZV- sensory nerve ganglia CMV- b lymphocyte EBV- leukocyte and epithelial cells HHV 6 A and B- t lymphocytes, epithelial cells HHV 8- epithelial cells
When are HHV reactivated in allo stem cell recipients?
HSV- early before engraftment period HHV 6,7 CMV early EBV VZV Not so much now as patients are on acyclovir prophylaxis
What is the sequlae for HSV in the immunocompromised?
Transplant setting- viral reactivation in patients tested HSV igG positive pre transplant
Reactivation common in first month post treatment
What is e clinical course for HSV reactivation and the immunocompromised?
Cold sores, stomatitis, mouth ulcers
Recurrent genital disease (HIV)
Cutaneous dissemination and visceral involvement, oesophagitis, hepatitis
HSV encephalitis not increased in frequency
How is HSV diagnosed in the immunocompromised?
PCR on swab, biopsy, on blood.
if mouth ulcers differential diagnosis is enterovirus infection
What is the sequlae for VZV and the immunocompromised?
Varicella as primary infection carries increased risk of complication
Secondary bacterial infection of rash, group a strep
Bullous or haemorrhagic skin lesions, purpura fulminans
Visceral involvement- pneumonitis and hepatitis
What happens if VZV reactivated from reactivation of endogenous virus in patients who are VZV igG positive pre transplant?
Shingles or herpes zoster, late complication more than 100 days post BMT
Dermatomal skin erruptions
Varicella like skin lesions with no dermatomal distribution, high risk of visceral involvement
VZV reactivation without skin lesions
What are the drugs most commonly used for HSV and VZV?
Acyclovir- nucleoside analogue, ACV triphosphate a potent inhibitor of HSV encoded DNA polymerase, oral or IV
Valaciclovir- valine ester prodrug of ACV, better availability
Both predominantly active against HSV and to lesser extent VZV
Risk of resistance
How can HSV VZV prevention occur?
ACV at prophylactic dose mainly to prevent HSV infection, started pre transplant, HIV patients on for years
Post exposure prophylaxis of severe varicella- VZIG
within 10 days of a significant contact with a case of chicken pox or shingles
What are the 3 sources of CMV infection after transplant?
Exogenous- primary infection, from graft, blood, persons excreting virus
Endogenous- reactivation
solid organ transplant, d+r-, carries greatest risk of reactivation
BMT, adoptive immunity, d-r+, carries greatest risk of reactivation
Exogenous re infection
