MICRO: Opportunistic viral infections

Question 1

What are ‘endogenous’ vs ‘exogenous’ viruses?

Answer 1

Endogenous - latent viruses that reactivate in the absence of immune sysytem; acquired in past prior to immune suppression e.g. VZV

Exogenous - viruses acquired from environment; increased severity in immunosuppressed e.g. influenza, SARS-COV-2

Question 2

How are viruses classified?

Answer 2

Baltimore classification

Question 3

List some AIDS defining illnesses with viral causes (opportunistic viral infections).

Answer 3

• Cervical cancer, invasive
• CMV disease
• CMV retinitis
• Encephalopathy HIV related
• HSV chronic ulcers, bronchitis, pneumonitis, oesophagitis
• Kaposi sarcoma
• Lymphoma, Burkitt’s
• Progressive multifocal leukoencephalopathy

Question 4

What classification system is used for all viruses?

Answer 4

Baltimore classification

Consists of 7 groups that take into consideration whether the viral genome is made DNA or RNA, whether the genome is single- or double-stranded, and whether the sense of a single-stranded RNA genome is positive or negative.

Question 5

How do we detect viruses?

Answer 5

Not grown - this requires human cell lines and is dangerous. So instead we look for indirect or direct evidence of their presence.

Indirect detection - immune system response to the virus e.g. antibody tests = PAST infection

Direct detection - fragments of the actual viruses e.g. viral proteins (LFTs), viral genetic material (PCR) = infection NOW

Question 6

What is the problem with using antibody levels to measure infection in the immunosuppressed?

Answer 6

Detection of antibody levels is generally used

• IgG = gone >6 weeks
• IgM = active/resolving infection

BUT antibodies will be lower in the immunosuppressed and serological courses may differ with different viruses

Question 7

Answer 7

Question 8

How can you overcome challenges with diagnostic virology in immunocompromise?

Answer 8

1. Screen prior to immunocompromise - to identify previous viral exposire and guide antiviral prophylaxis
2. Monitor using PCR - usually done monthly to detect infection and reactivation promptly so that

Question 9

Put these in order of highest risk of opportunistic viral infection.

• Various monoclonal antibody therapies
• DMARDs and steroids
• Allogeneic stem cell transplant
• Advanced HIV infection (CD4 dep)
• Solid organ transplant
• Cytotoxic chemotherapy

Answer 9

1. Allogeneic stem cell transplant - HIGHEST RISK
2. Advanced HIV infection (CD4 dep)
3. Solid organ transplant
4. Various monoclonal antibody therapies
5. Cytotoxic chemotherapy
6. DMARDs and steroids - LOWEST RISK

Question 10

What are the sources of viral infections in transplant recipients?

Answer 10

1. Viruses acquired from graft e.g. HBV
2. Viral reactivation from host e.g. HSV
3. Novel infection from infected infividual e.g. VZV

Question 11

What are the steps to prevent viral infection at each of these stages in transplant patients?

1. Viruses acquired from graft
2. Viral reactivation from host
3. Novel infection from infected individual

Answer 11

1. Viruses acquired from graft
   
   • serostatus risk assessment
2. Viral reactivation from host
   
   • serostatus monitoring
   • prophylaxis
   • pre-emptive therapy
3. Novel infection from infected infividual
   
   • isolation-brrier nursing
   • advice for visitors
   • vaccination of contacts
   • control of diet
   • post-exposure prophylaxis

Question 12

Chronology of HSCT infections

Question 13

What are the challenges with anti-viral therapy in the immunocompromised?

Answer 13

• Increased doses
• Longer duration
• Combination therapy
• ↑ Opportunity antiviral resistance
• ↑ Toxicity of antivirals

Question 14

How are viral infections different in the immunocompromised?

Answer 14

• Present differently
• Disseminated
• Different organs
• More severe
• Oncogenic
• Lack of immune mediated symptoms

Question 15

What are the issues with HSV 1 and 2 in immunocompromised?

Answer 15

• Increased frequency severity with risk of dissemination
• More organs can be involved e.g. pneumonitis, oesophagiis, hepatitis but NOT encephalitis
• Risk of acyclovir resistance

Question 16

What is the management of HSV1/2 in immunocompromised?

Answer 16

Give prophylaxis

• BM - 1 month (until enlargement)
• Solid organ - 3-6 months and if treated for rejection

Test for HSV IgG

Question 17

What are the clinical features of VZV infection in the immunocompromised?

Answer 17

Chicken-pox - pneumonitis, encephalitis, hepatitis, purpura fulminans in neonate

Shingles - multi-dermatomal; often late presenting immunosuppression

Question 18

What is the mangement of VZV in immunocompromise? (prevention + treatment)

Answer 18

Prevention:

• Prophylaxis medication
• PEP
• Vaccination

Treatment:

• Chickenpox (varicella) - antiviral for 10 days IV until no new lesions AND PO until all crusted
• Shinges (zoster) - antiviral (IV if disseminated) + analgesia

Question 19

What complications of Zoster may require addition of steroids to the treatment?

Answer 19

Ramsay-Hunt - add steroids

HZO - add topical steroids

Question 20

What is the biggest concern with EBV infection in immunocompromise? When should you suspect it?

Answer 20

Post-transplant lymphoproliferative disease (PTLD) - latently infected B cells (polyclonal activation) which predisposes to lymphoma

Suspect in rising EBV load (>10⁵c/ml) and CT scan. Confirmed with biopsy of lymph nodes.

Question 21

How do you confirm EBV PTLD?

Answer 21

Rising EBV viral load

CT

Confirmed with biopsy of lymph nodes.

Question 22

What is the management of EBV in immunocompromise?

Answer 22

1. Monitor EBV levels
2. Ix for lymphoma as needed
3. ? rituximab
4. Reduce immunosuppression

Question 23

What are the issues with CMV infection in immunocompromised?

Answer 23

In HIV/AIDS with CD4 <50 can cause:

• Retinitis
• Polyradiculopathy
• Pneumonititis
• GI tract e.g. gastroenteritis

Solid organ transplant can cause:

• Allograft disease
• GI tract (i.e. renal)

Question 24

What is the management of CMV in immunocompromise? When would you give it prophylactically vs treating disease?

Answer 24

1. Prophylaxis (in lung transplantation)
2. Pre-emptive treatment (in renal transplant/HSCT)
3. Treat if disease (in HIV/AIDS)

Management:

• Ganciclovir/valganciclovir
• Reduce immunosuppression

Question 25

What pathognomonic feature of CMV infection is shown below?

Answer 25

Owl's eye lung pneumocytes **(inclusion bodies)**

Question 26

What are the manifestations of CMV in the immunosuppressed?

Answer 26

In HIV/AIDS it causes: * Retinitis * Encephalitis * Pneumointis * Gastroenteritis In SOT it can cause allograft disease and affect the GI tract (i.e. renal)

Question 27

What are the CMV prevention strategies post-transplant (solid organ vs HSCT)?

Answer 27

**HSCT**: CMV viral load twice weekly - treat if virus reactivates, until suppressed (pre-emptive therapy) **Solid organ transplant**: Valganciclovir prophylaxis for 100 days

Question 28

What are the treatment options for CMV? What are the differences between them?

Answer 28

**Ganciclovir** (IV): bone marrow suppression **Valganciclovir**: oral **Foscarnet** (IV) (nephrotoxicity) **Cidofovir** (nephrotoxicity) **IVIg** (with another drug for pneumonitis)

Question 29

What type of virus is JC virus? What disease does it cause?

Answer 29

JC virus is a **polyomavirus** --\> Progressive multifocal leukoencephalopathy (PML)

Question 30

Apart from HIV, what other condition has PML been found in?

Answer 30

Effective antiretroviral therapy has drastically reduced PML incidence in HIV+ve patients PML can also be seen in: * Humanised monoclonal antibody use * Natalizumab use (for treatment of multiple sclerosis)

Question 31

What are the clinical features of PML? How is it diagnosed?

Answer 31

Clinical features: * Cognitive disturbance * Personality change * Motor deficits * Other focal neurological signs **Diagnosis**: * MRI (Demyelination of white matter → neurological deficits) * PCR on CSF

Question 32

What is another example of a polyoma virus? Is it DNA/RNA double/single stranded?

Answer 32

BK virus Double stranded DNA

Question 33

What types of transplant is BK infection most common in? What manifestations does it cause?

Answer 33

* BK cystitis **post SCT** * BK nephropathy **post renal Tx** *(renal and SCT)*

Question 34

What is the management of BK virus?

Answer 34

1. Bladder irrigation 2. Modulation of immunosuppression 3. Cidofovir - t*his is nephrotoxic itself though*

Question 35

Which opportunistic viral respiratory infections occur in the immunocompromised?

Answer 35

* Influenza A and B * Parainfluenza 1, 2, 3 and 4 * Respiratory Syncytial Virus (RSV) Adenovirus * SARS-CoV-2

Question 36

What is the management of Influenza A/B in oseltamavir?

Answer 36

**Oseltamivir** (oral drug) for 5 days If resistance/severe/immunosuppressed → **zanamivir** (inhalation or IV)

Question 37

What medication can be used for the treatment of SARS-CoV-2 in the immunosuppressed?

Answer 37

**Sotrovimab** or **Casirivimab/imdevimab**

Question 38

How does the course of HAV present in immunosuppression compared to normal?

Answer 38

More severe infection

Question 39

How does HBV present in immunosuppression compared to normal?

Answer 39

1. Carriers may have flare of disease. 2. Those who have had past infection can reactivate

Question 40

What drug is HBV reactivation more common in in the immunosuppressed?

Answer 40

Reactivation ↑ B-cell depleting therapies (i.e Rituximab) IL-6 inhibitor use in COVID also a risk

Question 41

What is the preventative treatment for HBV?

Answer 41

Nucleoside (lamivudine) or nucleotide (tenofovir, entecavir) reverse transcriptase inhibitors

Question 42

What do these markers in HBV tell us? sAg+, cAb+, eAg+

Answer 42

* sAg+ - circulating virus * cAb+ - acute immune response * eAg+ - circulating virus, infectivity marker

Question 43

What do these markers of immunity tell us in HBV? sAb, cAb, eAb

Answer 43

**sAb+** -either generated from virus or vaccine **cAb+** (IgG/total)- generated from cAg (virus) meaning **prior infection** **eAb+** - generated from eAg (virus)

Question 44

Risk of HBV reactivation:

Answer 44

In presence of HBsAg: highest with chemotherapy, anti-CD20 or anti-CD56 treatment and combination of these with steroids

Question 45

How does the course of HCV present in immunosuppression compared to normal?

Answer 45

* Increased fibrosis * Treat with direct-acting antiviral

Question 46

How does the course of HEV present in immunosuppression compared to normal?

Answer 46

Chornic infection, needs reduction in immunosuppression

Question 47

Menti:

Answer 47

D Antibody tests are not good for infection now.

Question 48

Menti:

Answer 48

Allogeneic stem cell transplant

Question 49

Menti:

Answer 49

HSV (type 1 is probably most common)

Question 50

Menti

Answer 50

Answer is D (mAb) ## Footnote * A - targets COVID* * B - CMV* * C - HSV* * E - HBV*

Question 51

Menti:

Answer 51

Answer - C ## Footnote * A - acute active* * B - vaccinated* * D - never seen HBV* * E - only SAg so carrier with chronic infection* * F -unreliable serology*