MICRO: Opportunistic viral infections Flashcards
What are ‘endogenous’ vs ‘exogenous’ viruses?
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
How are viruses classified?
Baltimore classification
List some AIDS defining illnesses with viral causes (opportunistic viral infections).
- Cervical cancer, invasive
- CMV disease
- CMV retinitis
- Encephalopathy HIV related
- HSV chronic ulcers, bronchitis, pneumonitis, oesophagitis
- Kaposi sarcoma
- Lymphoma, Burkitt’s
- Progressive multifocal leukoencephalopathy
What classification system is used for all viruses?
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.
How do we detect viruses?
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
What is the problem with using antibody levels to measure infection in the immunosuppressed?
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
How can you overcome challenges with diagnostic virology in immunocompromise?
- Screen prior to immunocompromise - to identify previous viral exposire and guide antiviral prophylaxis
- Monitor using PCR - usually done monthly to detect infection and reactivation promptly so that
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
- Allogeneic stem cell transplant - HIGHEST RISK
- Advanced HIV infection (CD4 dep)
- Solid organ transplant
- Various monoclonal antibody therapies
- Cytotoxic chemotherapy
- DMARDs and steroids - LOWEST RISK
What are the sources of viral infections in transplant recipients?
- Viruses acquired from graft e.g. HBV
- Viral reactivation from host e.g. HSV
- Novel infection from infected infividual e.g. VZV
What are the steps to prevent viral infection at each of these stages in transplant patients?
- Viruses acquired from graft
- Viral reactivation from host
- Novel infection from infected individual
- Viruses acquired from graft
- serostatus risk assessment
- Viral reactivation from host
- serostatus monitoring
- prophylaxis
- pre-emptive therapy
- Novel infection from infected infividual
- isolation-brrier nursing
- advice for visitors
- vaccination of contacts
- control of diet
- post-exposure prophylaxis
Chronology of HSCT infections
What are the challenges with anti-viral therapy in the immunocompromised?
- Increased doses
- Longer duration
- Combination therapy
- ↑ Opportunity antiviral resistance
- ↑ Toxicity of antivirals
How are viral infections different in the immunocompromised?
- Present differently
- Disseminated
- Different organs
- More severe
- Oncogenic
- Lack of immune mediated symptoms
What are the issues with HSV 1 and 2 in immunocompromised?
- Increased frequency severity with risk of dissemination
- More organs can be involved e.g. pneumonitis, oesophagiis, hepatitis but NOT encephalitis
- Risk of acyclovir resistance
What is the management of HSV1/2 in immunocompromised?
Give prophylaxis
- BM - 1 month (until enlargement)
- Solid organ - 3-6 months and if treated for rejection
Test for HSV IgG
What are the clinical features of VZV infection in the immunocompromised?
Chicken-pox - pneumonitis, encephalitis, hepatitis, purpura fulminans in neonate
Shingles - multi-dermatomal; often late presenting immunosuppression
What is the mangement of VZV in immunocompromise? (prevention + treatment)
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
What complications of Zoster may require addition of steroids to the treatment?
Ramsay-Hunt - add steroids
HZO - add topical steroids
What is the biggest concern with EBV infection in immunocompromise? When should you suspect it?
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.
How do you confirm EBV PTLD?
Rising EBV viral load
CT
Confirmed with biopsy of lymph nodes.
What is the management of EBV in immunocompromise?
- Monitor EBV levels
- Ix for lymphoma as needed
- ? rituximab
- Reduce immunosuppression
What are the issues with CMV infection in immunocompromised?
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)
What is the management of CMV in immunocompromise? When would you give it prophylactically vs treating disease?
- Prophylaxis (in lung transplantation)
- Pre-emptive treatment (in renal transplant/HSCT)
- Treat if disease (in HIV/AIDS)
Management:
- Ganciclovir/valganciclovir
- Reduce immunosuppression
What pathognomonic feature of CMV infection is shown below?
Owl’s eye lung pneumocytes (inclusion bodies)
What are the manifestations of CMV in the immunosuppressed?
In HIV/AIDS it causes:
- Retinitis
- Encephalitis
- Pneumointis
- Gastroenteritis
In SOT it can cause allograft disease and affect the GI tract (i.e. renal)
What are the CMV prevention strategies post-transplant (solid organ vs HSCT)?
HSCT: CMV viral load twice weekly - treat if virus reactivates, until suppressed (pre-emptive therapy)
Solid organ transplant: Valganciclovir prophylaxis for 100 days
What are the treatment options for CMV? What are the differences between them?
Ganciclovir (IV): bone marrow suppression
Valganciclovir: oral
Foscarnet (IV) (nephrotoxicity)
Cidofovir (nephrotoxicity)
IVIg (with another drug for pneumonitis)
What type of virus is JC virus? What disease does it cause?
JC virus is a polyomavirus
–> Progressive multifocal leukoencephalopathy (PML)
Apart from HIV, what other condition has PML been found in?
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)
What are the clinical features of PML? How is it diagnosed?
Clinical features:
- Cognitive disturbance
- Personality change
- Motor deficits
- Other focal neurological signs
Diagnosis:
- MRI (Demyelination of white matter → neurological deficits)
- PCR on CSF
What is another example of a polyoma virus? Is it DNA/RNA double/single stranded?
BK virus
Double stranded DNA
What types of transplant is BK infection most common in? What manifestations does it cause?
- BK cystitis post SCT
- BK nephropathy post renal Tx
(renal and SCT)
What is the management of BK virus?
- Bladder irrigation
- Modulation of immunosuppression
- Cidofovir - this is nephrotoxic itself though
Which opportunistic viral respiratory infections occur in the immunocompromised?
- Influenza A and B
- Parainfluenza 1, 2, 3 and 4
- Respiratory Syncytial Virus (RSV) Adenovirus
- SARS-CoV-2
What is the management of Influenza A/B in oseltamavir?
Oseltamivir (oral drug) for 5 days
If resistance/severe/immunosuppressed → zanamivir (inhalation or IV)
What medication can be used for the treatment of SARS-CoV-2 in the immunosuppressed?
Sotrovimab
or Casirivimab/imdevimab
How does the course of HAV present in immunosuppression compared to normal?
More severe infection
How does HBV present in immunosuppression compared to normal?
- Carriers may have flare of disease.
- Those who have had past infection can reactivate
What drug is HBV reactivation more common in in the immunosuppressed?
Reactivation ↑ B-cell depleting therapies (i.e Rituximab)
IL-6 inhibitor use in COVID also a risk
What is the preventative treatment for HBV?
Nucleoside (lamivudine) or nucleotide (tenofovir, entecavir) reverse transcriptase inhibitors
What do these markers in HBV tell us?
sAg+, cAb+, eAg+
- sAg+ - circulating virus
- cAb+ - acute immune response
- eAg+ - circulating virus, infectivity marker
What do these markers of immunity tell us in HBV?
sAb, cAb, eAb
sAb+ -either generated from virus or vaccine
cAb+ (IgG/total)- generated from cAg (virus) meaning prior infection
eAb+ - generated from eAg (virus)
Risk of HBV reactivation:
In presence of HBsAg: highest with chemotherapy, anti-CD20 or anti-CD56 treatment and combination of these with steroids
How does the course of HCV present in immunosuppression compared to normal?
- Increased fibrosis
- Treat with direct-acting antiviral
How does the course of HEV present in immunosuppression compared to normal?
Chornic infection, needs reduction in immunosuppression
Menti:
D
Antibody tests are not good for infection now.
Menti:
Allogeneic stem cell transplant
Menti:
HSV (type 1 is probably most common)
Menti
Answer is D (mAb)
- A - targets COVID*
- B - CMV*
- C - HSV*
- E - HBV*
Menti:
Answer - C
- A - acute active*
- B - vaccinated*
- D - never seen HBV*
- E - only SAg so carrier with chronic infection*
- F -unreliable serology*
