MI: Opportunistic Viral Infections Flashcards
Describe some key overarching features of opportunistic viral infections.
- Occurs more frequently in immunocompromised patients
- More severe presentations that normal viral infections
- May be an absence of signs of infection (e.g. afebrile) and a lack of localising signs
- Fevers may have non-infectious causes
List some causes of immune compromise.
Metabolic/endocrine
- Alcohol abuse
- Diabetes mellitus
- Uraemia
- Malnutrition
Impaired barrier to infection
- Burns
- Haemodialysis
- IVDU
Pregnancy
Extremes of age
List some primary causes of immune compromise
- UNC93B deficiency and TLR deficiency (associated with predisposition to herpes simplex encephalitis)
- Epidermodysplasia verruciformis
- SCID
- Haemophagocytic lymphohistiocytosis in perforin deficiency
- HHV8 is associated with STIM1 mutation
NOTE: perforin deficiency is also assocaited with increased incidence of EBV
List some acquired causes of immune compromise
- Solid organ transplantation
- Bone marrow transplantation
- Immunosuppressive drugs
- Advanced HIV
- Measles can cause a prolonged immunodeficient state
Outline the natural history of HIV infection
- There is an early dramatic decline in CD4+ count accompanied by a sharp increase in viral load
- The CD4+ count then rises and viral load declines as the immune system brings it under control
- After a period of years, viral load climbs again and CD4+ count drops leading to AIDS
Describe the difference in immunosuppression with solid organ transplants compared to haematological transplants.
Solid organ transplantation - life-long immunosuppression
Haematological transplant - intense immunosuppression for a relatively short time
List the major classes of immunosuppressive drugs.
- Glucocorticoids
- Calcineurin inhibitors (cyclosporin, tacrolimus)
- Anti-proliferative agents (azathioprine, mycophenolate mofetil, sirolimus)
- Antibodies (e.g. rituximab)
- Co-stimulation blockers
List some iatrogenic causes of immunosuppression in order of increasing risk of opportunistic viral infection
- DMARDs and steroids (LOWEST RISK)
- Cytotoxic chemotherapy
- Monoclonal antibodies
- Solid organ transplant
- Advanced HIV
- Allogeneic stem cell transplant (HIGHEST RISK)
Outline the typic timeline of viral infections following solid organ transplant.
Reactive viral infections don’t tend to happen until >1 month after transplant
Early infections (<1 month) tend to be transmitted from the donor
How is the typical timeline of viral infections following solid organ transplan different from bone marrow transplants?
In bone marrow transplants, viral infections tend to to occur early (<1 month)
This is because bone marrow transplant patients receive intense immunosuppression
List some sources of infection in transplant patients.
Virus acquired from graft (e.g. HBV)
- Assessed by serology and donor risk assessment
Virus reactivated from the host (e.g. HSV)
- Tracked by monitoring serostatus, prophylaxis and pre-emptive therapy
New infection (e.g. VZV)
- Isolate, advise and vaccinate contacts and post-exposure prophylaxis
List some diseases that it is important to monitor for in post-transplant patients.
- CMV monitoring and prophylaxis
- EBV monitoring
- Adenovirus monitoring (in paediatric BMT)
- HSV prophylaxis if indicated
List the human herpes viruses
- HSV1
- HSV2
- VZV
- EBV
- CMV
- HHV6
- HHV7
- HHV8
What is the characteristic common feature of herpes viruses?
Latent infection (only a small subset of genes are expressed)
List the sites of latent infection of:
- VZV
- CMV
- EBV
- VZV = dorsal root ganglion
- CMV = monocytes
- EBV = B cells
In bone marrow transplant patients, describe the timescale in which the herpes infections tend to occur.
HSV, HHV6 and HHV7 tend to occur <1 month after transplant
CMV, VZV and EBV tend to reactive later
For herpes simplex virus, list:
- Symptoms
- Complications
- Treatment
- Symptoms
- Cold sores
- Stomatitis
- Mouth ulcers
- Recurrent genital disease
- Complications
- Cutaneous disseminated
- Oesophagitis
- Hepatitis
- Viraemia
- Treatment
- Aciclovir or valaciclovir
- Foscarnet
List some manifestations of VZV infection.
- Skin lesions
- Pneumonitis
- Encephalitis
- Hepatitis
- Purpura fulminans (neonates)
- Acute retinal necrosis
- VZV-associated vasculopathy
Describe the onset of shingles in post-transplant patients compared to HIV patients.
Shingles is an early manifestation in HIV
Shingles is a late manifestation post-transplant
Which features of zoster infection are associated with a high mortality?
Multi-dermatomal or disseminated infection
How can VZV infection be prevented post-transplant?
Aciclovir prophylaxis
Post-exposure prophylaxis with VZIG
List some manifestations of CMV infection.
- Retinitis
- Encephalitis
- Pneumonia
- Gastroenteritis
What is the pathological hallmark of CMV infection?
Owl’s eye appearance of lung pneumocytes due to the presence of inclusion bodies
How long after a transplant does CMV infection tend to occur?
Tends to develop <6 months after transplant
How is the risk of reactivation of CMV different in solid organ transplantation compared to bone marrow transplantation?
Solid organ: greatest risk is if the donor has had past CMV but the recipient is naive
Bone marrow: greatest risk is if the donor is naive and the recipient has had past CMV infection
NOTE: CMV is a destructive virus that directly threatens the graft and damaged endothelial cells
What is the main concern regarding EBV and transplants?
Post-transplant lymphoproliferative disease
Outline the main features of post-transplant lymphoproliferative disease.
Raised EBV viral load associated with widespread lymphadenopathy
How is post-transplant lymphoproliferative disease managed?
Reduce immunosuppression
Anti-CD20 antibodies (e.g. rituximab)
Which virus is Kaposi sarcoma associated with?
HHV8
Which other diseases is HHV8 associated with?
Primary effusion lymphoma
Multicentric Castleman’s disease
List the characteristic histological findings of Kaposi sarcoma
Spindle cell proliferation
Neo-angiogenesis
Inflammation and oedema
How is Kaposi sarcoma treated?
Chemotherapy
Antiretoviral therapy
What deadly condition is is JC virus associated with?
Progressive multifocal leukoencephalopathy (PML)
This is a dementing process characterised by loss of higher functions (personality change, motor deficits, focal neurological signs)
Characterised by demyelination of white matter
How is PML diagnosed?
MRI
PCR of CSF
Which specific medication is associated with an icreased risk of PML?
Natalizumab - monoclonal antibody used in the treatment of multiple sclerosis
What can a BK virus cause?
BK cystitis (post-stem cell transplant)
BK nephropathy (post-renal transplant)
NOTE: can be treated by reducing immunosuppression
In which group of patients is adenovirus a major problem?
Bone marrow transplant patients
List some manifestations of adenovirus infection in bone marrow transplant patients.
- Fever
- Encephalitis
- Pneumonitis
- Colitis
List some viral causes of pneumonia with high mortality in immunocompromised patients.
- Influenza A and B
- Parainfluenza
- RSV
- Adenovirus
- MERS
How are viral infections causing pneumonia in immunocompromised patients diagnosed?
- Nasopharyngeal aspirates
- Bronchoalveolar lavage
- Nose and throat swabs
- Multiplex PCR is the best investigation
What does parvovirus B19 cause in the immunocompromised?
Causes chronic anaemia
How is parvovirus B19 infection diagnosed in the immunocompromised?
PCR of the blood
NOTE: serology is not useful in immunocompromised patients
How is parvovirus B19 infection in the immunocompromised treated?
IVIG
Blood transfusion may be required to correct the anaemia
What is a feature of chronic hepatitis B infection on serology?
Persistant HBsAg
What are the two consequences of hepatitis B virus in the immunocompromised?
Carriers may have a flare of the disease
Those with past infection may reactivate
Which treatments particularly increase the risk of hepatitis B infection?
B-cell depleting therapies (e.g. rituximab)
How can risk of hepatitis B infection with certain treatments be prevented?
Nucleoside/nucleotide analogue prophylaxis (e.g. tenofovir)
How is hepatitis E different in developed countries compared to developing countries?
- Devloped countries - zoonosis caused by genotype 3
- Developing countries - mainly caused by genotype 1
NOTE: high mortality in pregnant women
