MI: Opportunistic Viral Infections Pt.1 Flashcards

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1
Q

Describe some key overarching features of opportunistic viral infections.

A
  • 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
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2
Q

List some causes of immune compromise.

A

Metabolic/endocrine

  • Alcohol abuse
  • Diabetes mellitus
  • Uraemia
  • Malnutrition

Impaired barrier to infection

  • Burns
  • Haemodialysis
  • IVDU

Pregnancy

Extremes of age

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3
Q

List some primary causes of immune compromise

A
  • 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

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4
Q

List some acquired causes of immune compromise

A
  • Solid organ transplantation
  • Bone marrow transplantation
  • Immunosuppressive drugs
  • Advanced HIV
  • Measles can cause a prolonged immunodeficient state
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5
Q

Outline the natural history of HIV infection

A
  1. There is an early dramatic decline in CD4+ count accompanied by a sharp increase in viral load
  2. The CD4+ count then rises and viral load declines as the immune system brings it under control
  3. After a period of years, viral load climbs again and CD4+ count drops leading to AIDS
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6
Q

Describe the difference in immunosuppression with solid organ transplants compared to haematological transplants.

A

Solid organ transplantation - life-long immunosuppression

Haematological transplant - intense immunosuppression for a relatively short time

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7
Q

List the major classes of immunosuppressive drugs.

A
  • Glucocorticoids
  • Calcineurin inhibitors (cyclosporin, tacrolimus)
  • Anti-proliferative agents (azathioprine, mycophenolate mofetil, sirolimus)
  • Antibodies (e.g. rituximab)
  • Co-stimulation blockers
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8
Q

List some iatrogenic causes of immunosuppression in order of increasing risk of opportunistic viral infection

A
  • DMARDs and steroids (LOWEST RISK)
  • Cytotoxic chemotherapy
  • Monoclonal antibodies
  • Solid organ transplant
  • Advanced HIV
  • Allogeneic stem cell transplant (HIGHEST RISK)
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9
Q

Outline the typic timeline of viral infections following solid organ transplant.

A

Reactive viral infections don’t tend to happen until >1 month after transplant

Early infections (<1 month) tend to be transmitted from the donor

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10
Q

How is the typical timeline of viral infections following solid organ transplan different from bone marrow transplants?

A

In bone marrow transplants, viral infections tend to to occur early (<1 month)

This is because bone marrow transplant patients receive intense immunosuppression

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11
Q

List some sources of infection in transplant patients.

A

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
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12
Q

List some diseases that it is important to monitor for in post-transplant patients.

A
  • CMV monitoring and prophylaxis
  • EBV monitoring
  • Adenovirus monitoring (in paediatric BMT)
  • HSV prophylaxis if indicated
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13
Q

List the human herpes viruses

A
  • HSV1
  • HSV2
  • VZV
  • EBV
  • CMV
  • HHV6
  • HHV7
  • HHV8
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14
Q

What is the characteristic common feature of herpes viruses?

A

Latent infection (only a small subset of genes are expressed)

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15
Q

List the sites of latent infection of:

  1. VZV
  2. CMV
  3. EBV
A
  1. VZV = dorsal root ganglion
  2. CMV = monocytes
  3. EBV = B cells
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16
Q

In bone marrow transplant patients, describe the timescale in which the herpes infections tend to occur.

A

HSV, HHV6 and HHV7 tend to occur <1 month after transplant

CMV, VZV and EBV tend to reactive later

17
Q

For herpes simplex virus, list:

  1. Symptoms
  2. Complications
  3. Treatment
A
  1. Symptoms
    • Cold sores
    • Stomatitis
    • Mouth ulcers
    • Recurrent genital disease
  2. Complications
    • Cutaneous disseminated
    • Oesophagitis
    • Hepatitis
    • Viraemia
  3. Treatment
    • Aciclovir or valaciclovir
    • Foscarnet
18
Q

List some manifestations of VZV infection.

A
  • Skin lesions
  • Pneumonitis
  • Encephalitis
  • Hepatitis
  • Purpura fulminans (neonates)
  • Acute retinal necrosis
  • VZV-associated vasculopathy
19
Q

Describe the onset of shingles in post-transplant patients compared to HIV patients.

A

Shingles is an early manifestation in HIV

Shingles is a late manifestation post-transplant

20
Q

Which features of zoster infection are associated with a high mortality?

A

Multi-dermatomal or disseminated infection

21
Q

How can VZV infection be prevented post-transplant?

A

Aciclovir prophylaxis

Post-exposure prophylaxis with VZIG

22
Q

List some manifestations of CMV infection.

A
  • Retinitis
  • Encephalitis
  • Pneumonia
  • Gastroenteritis
23
Q

What is the pathological hallmark of CMV infection?

A

Owl’s eye appearance of lung pneumocytes due to the presence of inclusion bodies

24
Q

How long after a transplant does CMV infection tend to occur?

A

Tends to develop <6 months after transplant

25
Q

How is the risk of reactivation of CMV different in solid organ transplantation compared to bone marrow transplantation?

A

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