Opportunistic Viral Infections Flashcards
What are the different types of immunodeficiency found in a host? (2)
Primary immunodeficiency.
Acquired immunodeficiency.
What is an example of a primary immunodeficiency?
UNC93B deficiency and TLR3 deficiency predisposes to herpes simplex encephalitis, epidermodysplasia verruciformis, SCID.
What are some examples of acquired immunodeficiencies? (4)
Solid organ transplantation.
Bone marrow transplantation.
Immunosuppressive drugs.
Advanced HIV infection.
In HIV, what can be used to predict the risk of developing specific opportunistic infections?
CD4 count.
What are some AIDS-defining illnesses? (8)
Invasive cervical carcinoma.
CMV disease (other than liver, spleen, or nodes)
CMV retinitis (with loss of vision)
HIV related encephalitis.
Herpes simplex: chronic ulcers, or bronchitis, pneumonitis or oesophagitis.
Kaposi’s sarcoma.
Burkitt’s lymphoma.
Progressive multifocal leukoencephalopathy.
What are some major classes of immunosuppressive agents (5)
Glucocorticoids or steroids.
Calcineurin inhibitors (T-cell function) (cyclosporine, tacrolimus).
Antiproliferative agents (azathioprine, mycophenolate mofetil (MMF) or mycophenolic acid (MPA), sirolimus)
Antibodies (depleting, and non-depleting)
Co-stimulation blockers.
What immunosuppressive state puts you at the greatest risk of acquiring an opportunistic viral infection?
Allogeneic stem cell transplant.
Advanced HIV infection.
Solid organ transplant.
What are the three points in time that a transplant patient can catch a viral infection.
Viruses acquired from graft e.g. HBV.
Viruses reactivated from host e.g. HSV.
Novel infection from infected individual e.g. VZV
How can you reduce the risk of virus acquisition from grafts? (2)
Serostatus.
Risk assessment.
How can you reduce the risk of viral reactivation from host following transplant? (4)
Serostatus.
Monitoring.
Prophylaxis.
Pre-emptive therapy.
How can you reduce the risk of novel infection from infected individuals infecting patients with organ transplants (5)
Isolation barrier nursing. Advice for family/contacts Post-exposure prophylaxis. Vaccinating contacts. Control of diet.
What organisms are screened for in pre-transplant serology (8)
HIV HBV HCV EBV CMV HSV VZV HTLV
What organisms are continuously monitored for post-transplant until discharge/recovery. (4)
CMV monitoring or prophylaxis.
EBV monitoring.
Adenovirus monitoring (paeds bone marrow transfusion - BMT)
HSV prophylaxis if indicated.
What organisms are detected in CSF (8)
HSV VZV Enterovirus EBV CMV Adenovirus HHV6 JC virus.
What organisms are detectable in the blood (5)
CMV EBV Adenovirus HHV6 Parvovirus
What organisms are detected in sputum (9)
Flu A/B Paraflu 1-4 Adenovirus Enterovirus RSV HMPV Rhinovirus Coronaviruses CMV in BAL
What organisms can be detected from stool samples (3)
HSV
CMV
Adenovirus
What is the challenge with treating opportunistic infections
They are often more difficult to treat
What is required when treating opportunistic infections (4)
Early treatment
Higher doses required
Longer courses of antibiotics required
Sometimes drug combinations are required
What is an increased risk of treating opportunistic viral infections
Increased risk of antiviral drug resistance
What viruses form part of the family of human herpes viruses (6)
Herpes simplex virus (HSV) 1 and 2. Varicella zoster virus (VZV) Cytomegalovirus (CMV) HHV6 (human herpes virus 6) Epstein Barr Virus (EBV)
What kind of viruses are human herpes viruses
DNA viruses
What is the danger of human herpes virus infections.
The virus establishes a latent infection that persists for the life of the host.
In the latent state only a small subset of the viral genes are expressed.
Reactivation with expression of viral proteins and production of new virus particles may occur at intervals to produce recurrent infections.
Post allo stem cell transplant, what is the first latent infection to recur
HSV
What is the most common presentation for herpes simplex virus (2)
Cold sores, stomatitis, mouth ulcers.
Recurrent genital disease (particularly in HIV and adult transplant)
What are the serious complications of herpes simplex infection (4)
Cutaneous dissemination
Oesophagitis
Hepatitis
Viraemia
What is the treatment for herpes simplex infection (3)
Aciclovir or valaviclovir.
Foscarnet.
(Ganciclovir sensitive also)
When does HSV infection occur post-transplantation
Reactivation in the pre-engrafement period (usually less than 1 month post-transplant)
How is HSV reactivation prevented post-transplantation
Aciclovir prophylaxis until CD4 count increases above a certain threshold or for a specific time period.
What are the risk of primary varicella zoster infection in the immunocompromised (4)
Pneumonitis
Encephalitis
Hepatitis
Purpura fulminans in neonates
What is a late complication of VZV in the immunocompromised
Shingles
What can shingles in a young person be indicative of
HIV infection
What form of VZV is associated with higher mortality
Multidermatomal or disseminated shingles
What are some late complications of shingles in the immunocompromised (3)
Acute retinal necrosis (ARN)
Progressive outer retinal necrosis (PORN)
VZV-associated vasculopathy
How can VZV be prevented in the immunocompromised (2)
Aciclovir prophylaxis provides some protection.
Post-exposure prophylaxis of varicella with VZIg.
What is the first line treatment for VZV infection
Aciclovir
Valciclovir
Foscarnet sensitive
Ganciclovir sensitive
What are the manifestations of CMV infection (4)
Brain (encephalitis)
Eye (retinitis)
Lung (pneumonia)
Stomach and intestines (gastroenteritis)
What is risk of CMV infection post-transplant related to
Relates to pre-transplant serostatus
In solid organ transplant, what serotype carries the greatest risk of reactivation fo CMV
D+/R-
In bone marrow transplant (adoptive immunity) what serotype carries the greatest risk of reactivation
D-/R+
How can CMV be prevented post-transplant (2)
CMV viral load twice weekly, treat if virus reactivates until suppressed (pre-emptive therapy)
Valganciclovir prophylaxis for 100 days.
What is the treatment of CMV (9)
Ganciclovir (IV) bone marrow suppression. Valganciclovir - oral. Foscarnet IV (nephrotoxicity) Cidofovir (nephrotoxicity). IVIg (with another drug for pneumonitis) Letermovir Maribavir Brincidofovir Fomiversin
What are the clinical phases of EBV infection
Acute phase.
After the acute phase.
What occurs during the acute phase of EBV infection (3)
Febrile illness.
Lymphadenopathy.
Moderate hepatitis.
What occurs after the acute phase in EBV infection
Lifelong, latent, subclinical infection of B cells.
Intermittent attempts at viral replication kept in check by immunosurveillance.
EBV stimulates host cells to divide - also kept in check.
What does EBV cause post-transplant
PTLD (post transplant lymphoproliferative disease)
What is PTLD?
Post transplant lymphoproliferative disease.
Latently infected B cells - polyclonal activation
What does PTLD predispose to
Lymphoma
What increases the suspicion of lymphoma in PTLD
Rising EBV viral load (>10^5c/ml) and CT scan
What confirms lymphoma in a patient with PTLD
Biopsy of lymph nodes
How is PTLD managed (2)
Reduce immunosuppression (regression in less than 50%) Anti-CD20 monoclonal antibody therapy (B cell marker - rituximab)
What is kaposi’s sarcoma?
A cutaneous or visceral lesion, which presents as a brownish/purplish vascular lesion.
What are the characteristics of kaposi’s sarcoma? (3)
Spindle cell proliferation.
Neo-angiogenesis.
Inflammation and oedema.
How is the diagnosis of kaposi’s sarcoma made?
Biopsy.
How is kaposi’s sarcoma treated? (2)
Chemotherapy.
Initiation of antiretroviral therapy.
What is human herpesvirus 8 associated with? (3)
Kaposi’s sarcoma.
Primary effusion lymphoma (PEL)
Multicentric Castleman disease.
What are the stages in JCV infection? (4)
Primary infection.
Sites of latency.
Reactivation.
Neuroinvasion.
What is the pathogenesis of JCV infection (4)
Primary infection: infection is thought to occur following inhalation of virus – primarily in tonsillar tissue.
Sites of latency: latency is established in the kidneys and bone marrow. JCV gene rearrangements are found in patients with PML.
Reactivation: immunosuppression facilitates reactivation of JCV. Virus detected in blood is predominantly cell-associated.
Neuroinvasion: the JC virus is though to be transported across the BBB within B cells, subsequently, JCV can establish productive infection of oligodendroglia.
What is a sequale of JCV infection
Progressive multifocal leukoencephalopathy. (PML)
What kind of virus is JC
Polymavirus
What percentage of patients with AIDS would develop PML prior to the introduction of effective antiretroviral therapy
5%, with a high mortality.
What groups of people are at risk of PML? (2)
AIDS Multiple Sclerosis (due to natalizumab).
What are the clinical signs of PML (4)
Cognitive disturbance
Personality change
Motor deficits
Other focal neurological signs
What is the main pathological features of PML
Demyelination of white matter with neurological deficits corresponding to the areas of the brain affected
How is PML diagnosed (2)
MRI
PCR on CSF
What is the standard monitoring method for patients on natalizumab for JCV
Yearly brain MRI (regardless of risk index)
What does BK virus cause
BK cystitis
Who is at risk of BK virus infection
Post-transplanation patients (renal transplant)
How is BK virus diagnosed
PCR/NAAT
What are the clinical signs of BK virus (2)
Fever
Cystitis
How is BK virus treated (2)
Bladder irrigation
Modulation of immunosuppressive treatment
What group of immunosuppressed patients is adenovirus a particular risk to
Post-bone marrow transplant (particularly in children)
What are the two pathogeneses of adenovirus infection in immunosuppressed patients
Exogenous infection or reactivation of persistent endogenous infection
What are the clinical signs of adenovirus infection (4)
Fever
Encephalitis
Pneumonitis
Colitis
What can cause a high mortality with adenovirus infection
Disseminated infection
How are post-transplant paediatric patients screened for adenovirus infection
Weekly blood monitoring
How are post-transplant adult patients screened for adenovirus infection
Symptomatic screening only - urine, respiratory, stool and staging for disseminated disease to include blood if any of these are positive
How is adenovirus infection treated in immunosuppressed patients
Cidofovir + hyperhydration + probenecid 3 times a week until viral load <400cp/mL twice.
Taper off the immunosuppressive drugs if possible
What is the largest risk of respiratory viral infections in the immunocompromised
Pneumonitis and high mortality
What respiratory viruses pose a high mortality risk in the immunocompromised (5)
Influenza A and B Parainfluenze 1, 2, 3 and 4 Respiratory syncitial virus (RSV) infection Adenovirus Novel coronavirus: MERS coronavirus
How are respiratory viruses diagnosed in the immunocompromised (4)
Naso-pharyngeal aspirates (paeds)
Bronchio-alveolar lavage
Nose and throat swabs
Multiplex PCR is the investigation of choice
How is influenza A and B treated in the immunocompromised (2)
Oseltamivir (oral drug) for 5 days.
If severe immunocompromised, risk of oseltamivir resistance so use zanamivir (inhalation or IV) as an alternative.
How can influenza infection be prevented in the immunocompromised (4)
Influenza vaccination (life-long for organ/BMT recipients)
Influenza vaccination for close contacts.
Oseltamivir prophylaxis if significant contact with a case of influenza.
Infection control: handwashing, protective clothing, limit visitors, isolate immunocompromised patients, cohort nursing.
What can human parvovirus B19 cause in the immunocompromised
Chronic anaemia
How is human parvovirus B19 diagnosed (2)
Serology (IgM) not useful in the immunocompromised
PCR on blood
How is human parvovirus B19 treated in the immunocompromised (2)
Human normal immunoglobulin
May require blood transfusion.
What are you considered to have chronic hepatitis B infection
After 6 months if the virus has not been cleared
What does the following serology indicate:
HBV sAg +
HBV core Ab +
HBV sAb -
Current Hepatitis B infection
What does the following serology indicate:
HBV sAg -
HBV core Ab +
HBV sAb +
Past Hepatitis B infection
What does the following serology indicate:
HBV sAg -
HBV core Ab -
HBV sAb +
Vaccination against Hepatitis B
What are the risks of hepatitis B in the immunocompromised (2)
Carriers may have flares of the disease
Those who have had a past infection can reactivate
In the immunocompromised, when is the risk of hepatitis B reactivation particularly significant
In patients on B-cell depleating therapies (e.g. rituximab)
How can hepatitis B infection/reactivation be prevented in the immunocompromosed
Nucleoside/nucleotide analogues (lamivudine, tenofovir, entecavir) prophylaxis
What is a major cause of enterically transmitted viral hepatitis in the UK and Europe
Hepatitis E
What is the predominant genotype of Hepatitis E in developed countries
A zoonosis caused by genotype 3 virus
What is the predominant genotype of hepatitis E in developing countries
Mainly genotype 1 virus
How is hepatitis E transmitted (3)
Mainly through undercooked pork. Blood transfusions (uncommon). Possibly through organ donation
