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YR5 Microbiology > Opportunistic Viral Infections > Flashcards

Opportunistic Viral Infections Flashcards

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1
Q

How are viruses classified?

A

Baltimore classification

By replicative life cycle + genetic material

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2
Q

What is an opportunistic infection?

A

Infection caused by an organism that does not normally cause disease in an immunocompetent host

or symptomatology may be altered in the immunocompromised

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3
Q

What are endogenous viral infections?

A

Latent viruses that reactivate in absence of normal immune system.

Acquired in past, prior to immune suppression e.g. Varicella Zoster.

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4
Q

What are exogenous viral infections?

A

Viruses acquired from environment.

Increased severity in immunosuppressed e.g. Influenza, SARS-CoV-2.

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5
Q

How do you remember which HPV is more severe?

A

higher number= greater severity

HPV 6+8: genital warts

HPV 16+18: cervical cancer

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6
Q

What is indirect detection of a virus?

A

Response of immune system to the virus.

Useful to see if you have EVER had the infection.

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7
Q

What is direct detection of a virus?

A

Useful to see if you have the infection NOW

  • Viral proteins (lateral flow/ antigen tests).
  • Viral genetic material (virus genetic material present with pt sample)

Polymerase chain reaction.

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8
Q

How is serology used to determine infection with a virus?

A

Measure levels of antibody in patients serum.

+++ IgM: Active/ Resolving infection

+++ IgG: past infection > 6w ago

Antibody levels ↓↓↓ reduced in Immunosuppressed.

Serological course may differ depending upon virus.

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9
Q

What does this mean?

A

Surface antibody declines in the future, core antibody remains high for Hep B.

Surface antibody indicates previous vaccination, core antibody is previous infection with the real thing.

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10
Q

Give 3 facts about direct detection with PCR

A

Highly sensitive + specific

Viral load can be used to monitor infection

Can remain +ve even after infection resolved

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11
Q

At what point does the PCR viral load tend to peak?

A

When most infectious + just prior to worst Sx

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12
Q

What approach is used for virology diagnostics in immunocompromised?

A
  1. Screen prior to immunosuppression- identify previous exposure that may reactivate + guide antiviral prophylaxis
  2. Monitor with PCR: identify reactivation promptly + detect infection
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13
Q

Which antibodies are screened in serological screening prior to immunosuppression?

A

HIV Ag/Ab

HBV surface antigen, core antibody + surface antibody

HCV antibody

EBV antibody

CMV antibody

HSV antibody

VZV antibody

HTLV antibody

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14
Q

What is monitored/prophylactically treated during immunosuppression?

A

CMV monitoring PCR or prophylaxis

EBV monitoring PCR

BK monitoring PCR (Renal + BMT)

Adenovirus monitoring PCR (Paediatric BMT)

HSV prophylaxis if indicated

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15
Q

A 51-year-old with a recent HSCT is unwell. Which is the most appropriate test? ALT = 800 IU/mL

A. EBV IgG/IgM

B. HBV sAb

C. Parvovirus PCR

D. HEV PCR

E. CMV IgG/IgM

A

D. HEV PCR

Immune system not functioning- unable to accurately test production of antibodies, IgM + IgG

Abnormal ALT is likely in Hepatitis E

Parvovirus more likely to cause red cell aplasia/ anaemia

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16
Q

What increases the risk of opportunistic infections, from highest to lowest?

A

Allogeneic stem cell transplant

Advanced HIV infection (CD4 dep)

Solid organ transplant

Various monoclonal antibody therapies

Cytotoxic chemotherapy

DMARDs and steroids

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17
Q

Describe the transplant immunosuppression timeline for haematopoeitic stem cells

A
  1. Total body irradiation/ cyclophosphamide- eradicates disease + wipes out immune system
  2. Transplant- no neutrophils
  3. Wait for transplant to take- no neutrophils
  4. Engraftment- neutrophils start to rise- now need ongoing immunosuppression to prevent GvHD
  5. If successful, eventually cease immunosuppression
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18
Q

Describe the transplant immunosuppression timeline for solid organs

A
  1. Induction immunosuppression- need to suppress + prevent T cell activation
  2. Transplant organ
  3. Continue maintenance immunosuppression- lifelong
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19
Q

What are sources of viral infection from transplants?

A

Acquired from graft: HBV

Reactivation from the host: HSV

Novel infection from infected individual: VZV

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20
Q

What can be done to reduce risk of acquiring viruses from grafts?

A

Check donor serostatus

Risk assessment

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21
Q

What can be done to reduce risk of viral reactivation in a transplant recipient?

A

Check recipient + donor serostatus

Monitor with PCR

Consider prophylaxis + pre-emptive therapy

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22
Q

What can be done to reduce risk of acquiring novel viruses in a transplant patient?

A

Isolation barrier nursing

Educating visitors

PEP

Vaccinate contacts

Control diet

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23
Q

List 5 high incidence infections pre-engraftment in HSCT recipients

A

CoNS

Strep Viridans

HSV

Candida

Aspergillus

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24
Q

List 4 high incidence infections post-engraftment in HSCT recipients

A

CMV

VZV

Adenovirus

Aspergillus

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25
Q

Which type of immunosuppression carries the greatest relative risk of developing a viral infection?

A. Steroids

B. Solid organ transplant

C. Allogeneic stem cell transplant

D. Monoclonal antibody therapies

E. Cytotoxic chemotherapy

A

C. Allogeneic stem cell transplant

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26
Q

What is symptomatic screening molecular testing?

A

Screen + perform molecular tests according to presenting Sx

e.g. Headache, confusion, meningism do LP + screen CSF

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27
Q

What 8 viruses are tested for in symptomatic screening in the CSF?

A
  • HSV
  • VZV
  • Enterovirus
  • EBV
  • CMV
  • Adenovirus
  • HHV6
  • JC virus
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28
Q

What 5 viruses are tested for in symptomatic screening in the blood?

A
  • CMV
  • EBV
  • Adeno
  • HHV6
  • Parvo
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29
Q

What 9 viruses are tested for in symptomatic screening in the respiratory system?

A
  • Flu A/B
  • Paraflu 1-4
  • Adenovirus
  • Enterovirus
  • RSV
  • HMPV
  • Rhinovirus
  • Coronaviruses
  • CMV in BAL
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30
Q

What 3 viruses are tested for in symptomatic screening in the gut?

A
  • HSV
  • CMV
  • Adeno
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31
Q

Give 2 challenges of anti-viral therapy in the immunosuppressed

A

Increased levels of antiviral resistance

Increased toxicity of antivirals

32
Q

How are viral infections different in the immunocompromised?

A
  • Present differently
  • Disseminated
  • Different organs than in immunocompetent
  • More severe
  • Oncogenic
  • Lack of immune mediated Sx.
33
Q

What is shown here?

A

LHS: HSV in immunocompetent

RHS: HSV in immunocompromised- oesophagitis

34
Q

What are 4 issues with HSV infections in immunocompromised patients?

A
  • Increased frequency
  • Increased severity/ risk of dissemination
  • More organs can be involved (pneumonitis, eosophagitis, hepatitis); NB: not enceph!
  • Increased risk of acyclovir resistance
35
Q

What treatment should be given to HIV/AIDS patients with CD4 <200 and HSV infection?

A

Start ART to raise CD4 count

36
Q

What is the prophylactic management of the HSV in transplant patients undergoing intense immunosuppression?

A

Prior to transplant: Test for HSV IgG, if detect: Aciclovir/ Valaciclovir prophylaxis

BMT: continue 1 month post engraftment

SOT: 3-6 months (+ restart this if treated for rejection)

37
Q

What can varicella (chicken-pox) cause in immunocompromised patients?

A
  • Pneumonitis
  • Encephalitis
  • Hepatitis
  • Purpura fulminans in neonate
38
Q

What is seen here?

A

Disseminated varicella zoster in an immunocompromised host

39
Q

What is seen here?

A

Purpura fulminans caused by varicella infection in immunocompromised neonate

40
Q

What can VZV cause in immunocompromised patients?

A

Zoster (shingles)

  • Multi-dermatomal/disseminated
  • Often late presenting immunosuppression Sx
41
Q

What is the preventative approach to VZV in the immunocompromised?

A

Prophylaxis: Aciclovir or Valaciclovir, even post transplant- if post-BMT ~1y)

PEP: Varicella Immunoglobulin IVIg within 10d of contact

Vaccination: if no prior exposure

42
Q

What is the treatment for VZV?

A

Varicella- chickenpox picture:

Anti-viral for 7-10d

Start IV, switch to PO once no new lesions arising

Zoster- shingles presentation:

Aciclolvir/ Valaciclovir (IV if disseminated) + analgesia

If Ramsay-Hunt: Add steroids

If Herpes zoster opthalmicus: Add topical steroids

43
Q

A patient who received a stem cell transplant 2 weeks ago presents with mouth ulcers. Which of the following viruses would you test for on the mouth swab?

A. Enterovirus

B. Adenovirus

C. Herpes simplex type 1

D. Human herpesvirus 6

E. Human gammaherpesvirus 8

A

C. Herpes simplex type 1

44
Q

What is EBV associated with?

A

Post-transplant lymphoproliferative disease (PTLD)

Latently infected B cells: polyclonal activation.

Predisposes to lymphoma.

Occurs in SOT or allogenic HSCT

Related to level of immunosuppression

45
Q

What indicates and diagnoses EBV associated PTLD?

A

Suspicion on rising EBV viral load (>10^5 c/ml) + CT scan.

Confirmation with biopsy of lymph nodes.

46
Q

What are complications associated with EBV in immunosuppressed?

A

Oncogenesis:

  • B-cell latency, high turn-over
  • T-cells monitor/ control this

B-cell lymphomas

PTLD

47
Q

How are complications of EBV prevented in immunocompromised?

A

Monitor EBV levels: PCR 1-2 weekly

Ix for lymphoma as needed

48
Q

What are the recommendations for treating complications of EBV in immunocompromised?

A

? Rituximab

Reduce immunosuppression.

49
Q

What are 4 complications associated with CMV in those with HIV + CD4 <50?

A

Ocular (retinitis)

Polyradiculopathy

Pneumonitis

GI tract- gastroenteritis

50
Q

What are 2 complications associated with CMV in those who have received a solid organ transplant ?

A

Allograft disease

GI tract (i.e. renal)

51
Q

What is the prevention approach and management for CMV in immunocompromised?

A

Prophylaxis (i.e. lung transplant).

Pre-emptive tx (i.e. renal transplant / HSCT).

Treat if disease (HIV/AIDS).

Rx: Ganciclovir/ Valganciclovir

Reduce immunosuppression.

52
Q

What is a concern in SOT patients e.g. renal, about latent CMV?

A

More worried if donor is +ve

CMV remains latent in cells

Patient exposed to CMV for first time

53
Q

What is a concern in HSCT patients about latent CMV?

A

More worried if recipient if +ve

Wipe out recipient immune system, replace with naive donors immune system

Recipient reactivation a/w morbidity/ mortality

54
Q

What is the post-transplantation prevention strategy against CMV in HSCT?

A

CMV viral load twice weekly

Treat if virus reactivates until suppressed (pre-emptive therapy).

55
Q

What is the post-transplantation prevention strategy against CMV in Solid Organ Transplant?

A

Valganciclovir prophylaxis for 100 days

56
Q

List 5 drugs involved in treatment of CMV and their associated side effects

A

Ganciclovir (IV): BM suppression

Valganciclovir (Oral)

Foscarnet (IV): Nephrotoxicity

Cidofovir: Nephrotoxicity

IVIg (with another drug for pneumonitis).

57
Q

Which of these is NOT an antiviral?

A. Sotrovimab

B. Valganciclovir

C. Foscarnet

D. Rituximab

E. Tenofovir

A

D. Rituximab

(Monoclonal antibody)

58
Q

What is JC Virus (John Cunningham)?

A

JC virus= polyomavirus.

Can cause Progressive multifocal leukoencephalopathy.

Effective ART drastically reduced PML incidence in HIV+ve

PML can be seen in other types of immunosuppressed:

  • Those with Humanised monoclonal antibodies
  • Those taking Natalizumab (for tx of MS)
59
Q

What is the recommendation for patients taking Natalizumab for MS?

A

After 2y patients can progress PML

If at 6m test shows JC virus +ve, do 6 monthly PCR + MRI head scans

Don’t prescribe for longer than 2y

60
Q

What is the treatment for JC virus?

A

No specific tx for JC virus

61
Q

What is progressive multifocal leukoencephalopathy (PML)?

A

Cognitive disturbance, personality change, motor deficits, other focal neurological signs.

Demyelination of white matter → neurological deficits.

Dx: MRI + PCR on CSF

62
Q

What is BK virus?

A

Polyomavirus with ds-DNA

Post SCT: haemorrhage cystitis- blood in catheter

BK nephropathy Post Renal Tx

63
Q

What is the treatment for BK virus?

A

Cidifovir (nephrotic itself)

Bladder irrigation

Modulation of immunosuppression

64
Q

Which patient has previously had Hepatitis B Infection?

sAg= Surface antigen cAb = core antibody sAb= Surface antibody

A. sAg+, cAb+, sAb-

B. sAg-, cAb-, sAb+

C. sAg-, cAb+, sAb-

D. sAg-, cAb-, sAb-

E. sAg+, cAb-, sAb-

A

C. sAg-, cAb+, sAb-

cAb MUST be +ve if previous infection

sAg indicates active infection

65
Q

How are viruses classified?

A

Baltimore classification

By replicative life cycle + genetic material

66
Q

List 5 respiratory viruses associated with increased risk of pneumonitis and high mortality in the immunocompromised

A

Influenza A+B

Parainfluenza 1-4

RSV
Adenovirus

SARS-CoV-2

67
Q

What treatment can be given for influenza in the immunocompromised?

A

Oseltamivir PO for 5d

68
Q

What treatment can be given for SARS-CoV-2 in the immunosuppressed?

A

Sotrovimab

69
Q

Describe how hepatitis is more severe in the immunocompromised, and thus the preventative measures

A

A: More severe, vaccinate to prevent

B: increased risk of reactivation. Vaccinate/ give prophylaxis

C: increased risk of fibrosis. Give direct acting antiviral

E: causes chronic infection. No tx, reduce immunosuppression

70
Q

How can Hepatitis B manifest in the immunocompromised?

A
  1. Carriers may have flare of disease
  2. Those who have had past infection can reactivate- increased risk with B cell depleting therapies- Rituximab, IL-6 inhibitors
71
Q

What drugs are used in the prevention of hepatitis B in the immunocompromised?

A

Nucleoside: Lamivudine

Nucleotide: Tenofovir

72
Q

Give 3 markers of hepatitis B disease

A

sAg+ = circulating virus

eAg+ = circulating virus

cAb+ (IgM) = acute immune response

73
Q

Give 3 markers of hepatitis B immunity

A

sAb+: from virus or vaccine

cAb+ (IgG): from prior infection with virus

eAb+: from past viral exposure

74
Q

Describe the rash in monkeypox

A

Plaques- Papules - Vesicles- Pustules- Crusts

May be atypical

Most commonly on genitals inc. peri-anally

Appears 1-3d after fever onset

75
Q

List 4 symptoms/ signs of monkeypox

A

Fever

Lymphadenopathy

Headache

Myalgia

76
Q

What prophylaxis is available for monkeypox?

A

Smallpox vaccine

77
Q

Describe the management of a patient with monkeypox

A

Isolate

Symptomatic tx: analgesia

If severe e.g. encephalitis: Tecovirimat

Screen for other STIs

Inform UKHSA

YR5 Microbiology (23 decks)

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