Viral infections in the immunocompromised Flashcards
Define humoral immunity
Immunity mediated by antibodies produced by B cells
Define cell mediated immunity
Immunity mediated by phagocyes, T lymphocytes etc.
What consequences may viral infections have on immunocompromised hosts?
1) May develop severe acute infections
2) May reactive latent infections
3) May develop unusual manifestation of the disease
Is active hepatitis cell mediated or humoral in HBV. HCV
Cell mediated
State 3 types of immunocompromisation
1) Congenital
2) Acquired
3) Iatrogenic
State 4 classes of virus that commonly infect patients with cell mediated immune deficiency
1- Herpesviruses
2- Paramyxoviruses
3- Papillomaviruses
4- Polyomamaviruses
What is the purpose of drugs used in solid organ transplants
To prevent graft rejection
What drugs are used to solid organ transplants?
1) Calcineurin inhibitors
2) Antimetabolites
3) Steroids
What drugs are used in haemopoietic stem cell transplants?
Preventing graft v host disease
Name 5 drugs used in haemopoietic stem cell transplants?
- Lymphocyte depleting drugs such as alemtuzumab
- Methotrexate
- MMF
- Calcineurin inhibitors
- Steroids
Which infections commonly occur within the month of a solid organ transplant?
- MRSA
- C. Diff
- Donor derived infection (uncommon)- HSV, LCMV, rhabdovirus
Which infections commonly occur within 1-6 months of solid organ transplant?
C diff colitis HCV Adenovirus, influenza TB Pneumocystitis Herpes virus
Which infections commonly occur >6 months after a solid organ transplant?
CAP
UTI
CMV
Hepatitis
Which strand of Herpes Simplex virus causes cold sores
1
Which strand of herpes simplex virus causes genital warts
2 mainly (1 can too)
Describe the features of the primary infection of HSV
Frequently asymptomatic.
- Pharyngitis
- Fever
- Ulceration
Describe the features of a recurrence of HSV
Prodromal tingling followed by localised painful blisters that resolve in a week
How is herpes simplex virus spread
By direct contact
How is herpes simplex virus treated
Aciclovir
What % of the UK population will have had past exposure to herpes simplex
90%
Describe the features of the primary infection of varicella zoster virus
Fever and generalised vesicular rash (chickenpox)
When is varicella zoster virus most infectious
1- 2 days prior to rash onset
What happens with varicella zoster virus reactivates
It reactivates as shingles
What complications can arise should an immunocompromised individual come into contact with varicella zoster virus
- Shingles can be multidermatolmal
- Encephalitis
- Severe disease with pneumonitis and disseminated infection
Until when is varicella zoster virus infectious?
Until it has crusted over
How should you treat VAZ pneumonitis, encephalitis of eye disease
IV treatment
Name 3 viruses that are a major hazard for allogenic HSCT and certain solid organ transplants
‘ACE’ viruses:
- Adenovirus
- Cytomegalovirus
- Epstein Barr Virus
What is CMV secreted in?
Saliva, urine and breast milk
Is CMV usually serious in children?
No- few symptoms and self limiting
What is the prevelance by age of CMV
15% of cases in under 5s
85% of cases in over 65s
Where does CMV remain latent? When does it reactivate?
Blood and bone marrow
Reactivates in immunosuppression
Describe 3 ways that CMV manifests in the immunocompromised?
- Penumonitis (esp in HSCT)
- Oesophagitis (transplant and HIV)
- Retinitis (HIV)
When is a donor recipient at a high risk of primary CMV infection
- CMV donor status positive
- CMV recepient status negative
When is a donor recipient at a high risk of uncontrolled reactivation of CMV
- CMV donor status negative
- CMV recepient status positive
How do you diagnose a CMV infection?
- Pre transplant serology
- Post transplant monitoring of CMV viraemia
How is CMV disease different to CMV infection
There is evidence of end organ damage specific to CMV in disease
Infection is laboratory evidence of virus activity
What pre-emptive therapy is available for CMV post transplant?
Monitoring of CMV activity after transplant and begin anti-viral therapy at first indication of active CMV replication
What prophylactic management is available for CMV post transplant?
Antiviral use post transplant to bridge the period with highest risk for CMV disease
What is the rationale behind pre-emptive treatment for CMV
- Reduced exposure to anti-viral
Who should have pre-emptive therapy for CMV
Bone marrow and SCT
Who should have CMV prophylaxis?
D+ R-
Pancreas, renal, liver, heart and lung transplant patients
What anti-viral is on offer for CMV
Ganciclovir
How is Epstein Barr virus spread
Saliva
What are the 2 main concerns of an immunocompromised individual contracting EBV
1- Post transplant lymphoproliferative disorder (PTLD)
2- Lymphoma
When does PTLD usually occur
First year post tranplant
Which types of transplant carry higher risks for PTLD
Small Bowel
Heart/ lung, lung, pancreato-renal
State some risk factors for the development of PTLD
- Children <5
- Associated with prior infection
- Anti-rejectin therapy
State the symptoms of PTLD
- Fever
- GI upset
- Lymphadenopathy (often retroperitoneal)
- Tonsillar hypertrophy
- Hepatosplenomegaly
- Anaemia
Which common anti-viral is not effective in treating CMV and EBV in the immunosuppressed
Aciclovir
Which drug should be used to treat CMV in transplant recipients
Ganciclovir
What main 3 syndromes are seen in adenovirus when a healthy person is infected?
- Resp disease
- Keratoconjunctivitis
- Gastroenteritis
How does adenovirus manifest in the immunosupressed
Pneumonia Hepatitis Haemorrhagic cystitis Enterocolitis Encephalitis
Are children or adults more at risk of post transplant adenovirus?
Children
Which transplants are at a higher risk for adenovirus
Heart
Multivisceral solid organ transplant
How do you screen for adenovirus
Blood and urine PCR
If positive, go to other sites such as stool
How do you manage adenovirus in the immunosuppressed?
- Limited antiviral options: some weak evidence for cidofovir
- Reduction in immune suppression beneficial
- Adoptive virus- specific CTL most promising
What are the 2 major human polyomaviruses
JC virus and BK virus
How are polyomarivues shed
Via urine
What happens during the initial infection with polomavirus
- Initial viraemia and seeding of the kidney
- Latency
What happens (briefly) when polyomavirus is reactivated
Viruria
Viraemia
End- organ disease
Name the 3 main polyomavirus syndromes described
- BK Virus associated haemorrhagic cystitis
- BK virus associated nephropathy
- JC-PML
What patients is BK virus associated haemorrhagic cystitis seen
Allogenic HSCT Recipients
