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review micro > MI: Opportunistic Viral Infections > Flashcards

MI: Opportunistic Viral Infections Flashcards

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

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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
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18
Q

List some manifestations of VZV infection.

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

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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

26
Q

What is the main concern regarding EBV and transplants?

A

Post-transplant lymphoproliferative disease

27
Q

Outline the main features of post-transplant lymphoproliferative disease.

A

Raised EBV viral load associated with widespread lymphadenopathy

28
Q

How is post-transplant lymphoproliferative disease managed?

A

Reduce immunosuppression

Anti-CD20 antibodies (e.g. rituximab)

29
Q

Which virus is Kaposi sarcoma associated with?

A

HHV8

30
Q

Which other diseases is HHV8 associated with?

A

Primary effusion lymphoma

Multicentric Castleman’s disease

31
Q

List the characteristic histological findings of Kaposi sarcoma

A

Spindle cell proliferation

Neo-angiogenesis

Inflammation and oedema

32
Q

How is Kaposi sarcoma treated?

A

Chemotherapy

Antiretoviral therapy

33
Q

What deadly condition is is JC virus associated with?

A

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

34
Q

How is PML diagnosed?

A

MRI

PCR of CSF

35
Q

Which specific medication is associated with an icreased risk of PML?

A

Natalizumab - monoclonal antibody used in the treatment of multiple sclerosis

36
Q

What can a BK virus cause?

A

BK cystitis (post-stem cell transplant)

BK nephropathy (post-renal transplant)

NOTE: can be treated by reducing immunosuppression

37
Q

In which group of patients is adenovirus a major problem?

A

Bone marrow transplant patients

38
Q

List some manifestations of adenovirus infection in bone marrow transplant patients.

A
  • Fever
  • Encephalitis
  • Pneumonitis
  • Colitis
39
Q

List some viral causes of pneumonia with high mortality in immunocompromised patients.

A
  • Influenza A and B
  • Parainfluenza
  • RSV
  • Adenovirus
  • MERS
40
Q

How are viral infections causing pneumonia in immunocompromised patients diagnosed?

A
  • Nasopharyngeal aspirates
  • Bronchoalveolar lavage
  • Nose and throat swabs
  • Multiplex PCR is the best investigation
41
Q

What does parvovirus B19 cause in the immunocompromised?

A

Causes chronic anaemia

42
Q

How is parvovirus B19 infection diagnosed in the immunocompromised?

A

PCR of the blood

NOTE: serology is not useful in immunocompromised patients

43
Q

How is parvovirus B19 infection in the immunocompromised treated?

A

IVIG

Blood transfusion may be required to correct the anaemia

44
Q

What is a feature of chronic hepatitis B infection on serology?

A

Persistant HBsAg

45
Q

What are the two consequences of hepatitis B virus in the immunocompromised?

A

Carriers may have a flare of the disease

Those with past infection may reactivate

46
Q

Which treatments particularly increase the risk of hepatitis B infection?

A

B-cell depleting therapies (e.g. rituximab)

47
Q

How can risk of hepatitis B infection with certain treatments be prevented?

A

Nucleoside/nucleotide analogue prophylaxis (e.g. tenofovir)

48
Q

How is hepatitis E different in developed countries compared to developing countries?

A
  • Devloped countries - zoonosis caused by genotype 3
  • Developing countries - mainly caused by genotype 1

NOTE: high mortality in pregnant women

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