Micro - Opportunistic Viral Infections Flashcards
How are viruses classified
Baltimore classification, which classifies via the replicative life cycle and characteristics (dsDNA, ssDNA, RNA etc.)
Define opportunistic infections
An infection caused by an organism that does not normally cause disease in an immunocompetent host OR symptomatology may be altered in the immunocompromised compared to immunocompetent
What are endogenous opportunistic infections and give an example
Latent viruses that reactivate in the absence of a normal immune system
Acquired in the past prior to immune suppression
e.g. Varicella Zoster (VZV)
What are exogenous opportunistic infections and give an example
Viruses which are acquired from the environment
Increased severity in the immunocompromised
e.g. influenza, SARS-CoV-2
Give examples of AIDS defining illnesses and the viruses they are associated with
Cervical cancer – HPV
CMV
Encephalitis – HIV related
Chronic ulcers - HSV
Kaposi’s sarcoma – HHV-8
Lymphoma/Burkitt’s – infection of B-cell lymphocytes with EBV
PML – JC virus
What is the difference between indirect and direct detection of viruses
Indirect detection
- Useful to see whether you have ever had the infection
- Response of the immune system to the virus
Direct detection
- Useful to see whether you currently have the infection
- Viral proteins (lateral flow/antigen tests)
- Viral genetic material (virus genetic material is present with patient sample)
- Polymerase Chain Reaction, PCR
How is serology used for virus detection and what is the disadvantage of serology
Measure levels of antibody in patients serum
+++ IgM indicate Active or Resolving infection
+++ IgG indicates past infection > 6 weeks ago
BUT Antibody levels are reduced in Immunosuppressed (so this would not work in those with immunsuppression)
What are the advantages and disadvantages of PCR for virus detection
Detect viral genome in samples via amplification
Highly sensitive and specific
Performed on many different sample types
Viral load can be used to monitor infection
Tends to peak when most infectious
However, may remain positive after infection resolved
how are viruses screened for in those who are immunocompromised
- Screen prior to immunosuppression
- Identify previous viral exposure that may reactivate
- Can be done pre-transplant etc.
- Guide the use of antiviral prophylaxis
- E.g. HIV, HBV, HCV, EBV, CMV, HSV, VZV, HTLV - Monitor using PCR
- Identify viral reactivation promptly → Rx
- Detect infection
E.g. CMV, EBV, BK, Adenovirus, HSV
Which therapies carry a high risk of immunosuppression and therefore opportunistic infection (most likely first)
Allogeneic stem cell transplant
Advanced HIV infection
Solid organ transplant
Monoclonal antibody therapies
Cytotoxic chemotherapy
DMARDs and steroids
What is the difference in immunosuppression treatment for patients with a haematopoeitic stem cell transplant compared to those with a solid organ transplant
HSTC - Conditioning regimen - wiping out a disease completely (results in a very weakened immune system i.e. no neutrophils)
Ongoing immunosuppression as neutrophils start to be produced to prevent graft versus host prophylaxis → Can come off immunosuppresion
In a SOLID organ transplant - induction immunosuppression, rather than a conditioning regimen, is carried out to prevent rejection → Lifelong immunosuppression
How do you prevent infection in immunosuppressed patients who received a graft
Serostatus
Risk assessment
How do you prevent infection in immunosuppressed patients at risk of reactivation
Serostatus
Monitoring
Prophylaxis
Pre-emptive therapy
How do you prevent infection in immunosuppressed patients at risk of novel infection
Isolation-barrier nursing
Advice for family/contacts
Post-exposure prophylaxis
Vaccinating contacts
Control of diet
Which viruses are screened for in immunosuppressed patients who have a CNS infection
HSV
VZV
Enterovirus
EBV
CMV
Adenovirus
HHV6
JC virus
Which viruses are screened for in immunosuppressed patients who have a respiratory infection
Influenza A/B
Parainfluenza 1-4
Adenovirus
Enterovirus
RSV
HMPV
Rhinovirus
Coronavirus
CMV in BAL
Which viruses are screened for in immunosuppressed patients who have a haematological infection
CMV
EBV
Adenovirus
HHV6
Parvovirus
Which viruses are screened for in immunosuppressed patients who have a gastrointestinal infection
HSV
CMV
Adenovirus
Describe anti-viral therapy in immunosuppressed aptients
Therapeutically challenging
Pre-emptive treatment
Prophylaxis
Increased doses
Longer duration
Combination therapy
↑ Opportunity antiviral resistance
↑ Toxicity of antivirals
What are the symptoms of Herpes simplex virus (normal and immunosuppressed specific)
Normal: cold sores, stomatitis, mouth ulcers
Immunosuppressed specific:
- Recurrent genital disease
- Pain on swallowing
- Increased infection frequency and severity/risk of dissemination
What are the complications of herpes simplex virus
Cutaneous dissemination
Oesophagitis
Hepatitis
Viraemia
What is the management for herpes simplex virus
Treatment:
- Aciclovir or valaciclovir
- Foscarnet
Prophylaxis with Aciclovir or valaciclovir
- Test for HSV IgG
- Bone marrow
1 month (until engraftment)
- Solid organ
3-6 months and if treated for rejection
What are the symptoms of varicella and zoster
Varicella:
- Pneumonitis
- Encephalitis
- Hepatitis
- Purpura fulminans in the neonate (see below)
Zoster
- Multi-dermatomal / disseminated - has a HIGH mortality
- Often a late presenting immunosuppression
What are the complications of varicella zoster infection
Acute retinal necrosis (ARN)
Progressive outer retinal necrosis (PORN)
VZV-associated vasculopathy
DIC + coagulation in small vessels → skin necrosis
What is the management for varicella and zoster
Varicella
- Anti-viral for 7-10 days
- IV until no new lesions; PO until all crusted
Zoster
- Anti-viral (IV if disseminated) + analgesia
- If Ramsay-Hunt: add steroids
- If HZO: add topical steroids
how is varicella zoster prevented
Aciclovir prophylaxis
VZV IVIG post-exposure prophylaxis
PEP (post-exposure prophylaxis)
What are the complications of EBV in immunosuppressed patients
Oncogenesis
- B cell latency, high turn-over
- T-cells monitor/control this
- B-cell lymphomas
- PTLD (post-transplant lympho-proliferative disorder)
Describe Post-transplant lymphoproliferative disease (PTLD)
Latent infected B cells have polyclonal activation → predispose to lymphoma
Occurs in solid organ or allogenic haematopoietic cell transplants
Related to the level of immunosuppression
Suspicion on rising EBV viral load (>105c/mL) and CT scan → confirm on biopsy of LN
What is the management for EBV infection
Monitor EBV levels
Reduce immunosuppression
Anti-CD20 monoclonal antibodies (Rituximab) - removes the B cells
What are the manifestations of CMV in immunosuppressed patients
Retinitis
Encephalitis
Pneumonia
Gastroenteritis e.g. severe diarrhoea - often confused with GvH disease
What is the histological feature of CMV
Owl’s eye lung pneumocytes (inclusion bodies)
What increases the risk of CMV reactivation
Develops within 6m of transplantation
Risk dependent on donor/recipient pre-treatment serostatus
SOLID organ transplantation: donor +ve, recipient -ve
HSCT / BM transplant: donor -ve, recipient +ve
What are the preventative measures against CMV post-transplant
Haematological transplant → CMV viral load twice weekly, treat only if virus reactivates
Solid organ transplant → valganciclovir prophylaxis for 100 days regardless of state
What is the management for CMV infection post-transplant
Solid organ:
- Ganciclovir (IV) (bone marrow suppression)
- Valganciclovir: oral
HSCT:
- Foscarnet (IV) (nephrotoxicity)
- Cidofovir (nephrotoxicity)
- IVIG (with another drug for pneumonitis)
Describe JC virus
Polyomavirus
Can cause Progressive multifocal leukoencephalopathy (PML)
Effective antiretroviral therapy has drastically reduced PML incidence in HIV+ve patient
Causes demyelination of white matter
What are the symptoms of JC virus
Cognitive disturbance
Personality change
Motor deficits
other focal neurological signs
What investigations should be done for JC virus
MRI and PCR on CSF
Describe BK virus
Polyomavirus
Double stranded DNA
Can cause:
- BK haemorrhagic cystitis (post-HSCT) (Sign: haematuria) → intravesical cidofovir (direct into bladder – avoid nephrotoxicity)
- BK nephropathy (post-renal solid organ transplant) → IVIG (cidofovir is nephrotoxic)
This can be treated by reducing immunosuppression
Which respiratory infections are associated with immunosuppression
Influenza A and B
Parainfluenza 1,2,3 and 4
RSV
Adenovirus
SARS-CoV-2
What is the management for influenza A and B
Oral oseltamivir for 5 days
Severe resistance → zanamivir
What is the management for viral hepatitis in those who are immunosuppressed
A: vaccinate
B: vaccinate/prophylaxis
C: Direct-acting antiviral
E: reduce immunosuppression
What is the presentation of monkeypox
Atypical rash
Lesions most commonly on genitals (including perianaly)
86% systemic illness - most commonly fever, LNs, myalgia
Pain
Complications: penile oedema, secondary bacterial infection, rectal perforation
What is the management for monkeypox
Prophylaxis – smallpox vaccine (but no doses left just now)
Symptomatic treatment – analgesia
If very severe - tecovirimat (developed for smallpox, hard to access, expensive ++)
Screen for other sexually transmitted infections including HIV
Support when self-isolating
Consider psychosocial impact
Inform UKHSA
