11. Opportunistic viral infections Flashcards
What percentage of fevers following organ transplant are non-infectious?
22%
What are causes of immunocompromise?
Metabolic/endocrine such as alcohol abuse, diabetes mellitus, uraemia, malnutrition. Impaired barrier to infection such as burns, haemodialysis, IVDU. Pregnancy. Extremes of age.
What are examples of primary immunocomprise?
UNC93B deficiency, TLR3 deficiency, epidermodysplasia verruciformis, SCID, hameophagocytic lymphohistiocytosis perforin deficiency, HHV8 associated with STIM1 mutation
What is UNC93B deficiency and TLR3 deficiency associated with?
Predisposition to herpes simplex encephalitis
What is perforin deficiency associated with?
An increased incidence of EBV
What are examples of acquired immunocompromise?
Solid organ transplantation, bone marrow transplantation, immunosuppressive drugs, advanced HIV infection. (NOTE: measles also causes a prolonged immunodeficient state after the infection)
How does HIV infection occur?
It is a lentivirus and has a long incubation period. It directly targets CD4+ T cells. Through the loss of CD4+ T cells, you get an increase in the risk of opportunistic infections. Early on in disease you will get a dramatic decline in CD4 count. Then, the CD4+ count will recover but then decline more slowly. As CD4+ count decreases, the risk of opportunistic infection increases
What are major classes of immunosuppressive drugs?
Glucocorticoids or steroids, calcineurin inhibitors, antiproliferative agents, antibodies and co-stimulation blockers
What are examples of calcineurin inhibitors (T cell function)?
Cyclosporine, tacrolimus
What are examples of antiproliferative agents?
Azathioprine, mycophenolate mofetil (MMF) or mycophenolic acid (MPA), sirolimus
What are examples of antibodies immunosuppressive drugs?
Depleting, and non depleting (anti CD25 receptor antibodies, costimulation blockers and belatacept)
Relative risk of opportunistic viral infection, from lowest to highest:
DMARDs and steroids, cytotoxic chemotherapy, various monoclonal antibody therapies, solid organ transplant, advanced HIV infection (CD4 dep), allogeneic stem cell transplant.
What factors should be considered in immunosuppression?
Immunosuppressive treatment (type, timing, intensity), prior treatment (antimicrobial use, chemotherapy), muco-cutaneous integrity (catheters, lines and drains), surgical complications (collections), metabolic conditions (uraemia, alcoholism, DM, age), viral infection (Herpes viruses, HBV, HCV, HIV, RSV, respiratory virus)
When do recipients tend to have reactive viral infections after their transplant?
They do NOT tend to reactive viral infections until over a month after their transplant
What doe early infections in the recipient suggest?
Early infections (< 1 month) tend to be those that are transmitted from the donor. This can be controlled adequately by testing the donor.
When do viral infections tend to occur in bone marrow transplantation?
Early, within 1 month. This is because bone marrow transplant patients will receive intensive immunosuppression
What are sources of infection?
Viruses acquired from the graft e.g. HBV, viral reactivation from the host (e.g. HSV), novel infection from infected individual (e.g. VZV).
How can we prevent viruses from the graft?
Assessed via serology and risk assessment of the donor
How can we prevent virus reactivation in the host?
This can be tackled by looking at the patient’s serostatus, monitoring, prophylaxis and pre-emptive therapy
How can we prevent novel infection from infected individual?
Isolation, advice for family and contacts, post-exposure prophylaxis, and vaccinating contacts.
What are diagnostic protocols in transplant?
Do a pre-transplant serology. CMV monitoring or prophylaxis, EBV monitoring, adeno monitoring (paeds BMT), HSV prophylaxis if indicated
What can be tested for in CSF?
HSV, VZV, enterovirus, EBV, CMV, adenovirus, HHV6, JC virus
What can be tested for in the blood?
CMV, EBV, adenovirus, HHV6, parvovirus
What can respiratory viruses can be tested for?
Flu A/B, paraflu 1-4, adenovirus, enterovirus, RSV, HMPV, rhinovirus, coronaviruses, CMV in BAL
What can be tested in gut biopsy?
HSV, CMV, adenovirus
What does treatment of opportunistic viral infections require?
Often difficult to treat and requires: early treatment, higher dose, longer course, sometimes drug combinations. Increased risk of antiviral drug resistance.
What are types of Human Herpes Viruses?
HSV1 and 2, VZV, CMV, HHV6, EBV, HHV8
Human Herpes Viruses are latent infections (defining feature). What is the site of latent infection for VZV?
Dorsal root ganglion
Human Herpes Viruses are latent infections (defining feature). What is the site of latent infection for CMV?
Monocytes
Human Herpes Viruses are latent infections (defining feature). What is the site of latent infection for EBV?
B cells
In bone marrow transplants, when do HSV, HHV6 and HHV7 infections tend to occur?
Within a month of transplant
Herpes simplex virus symptoms
Cold sores, stomatitis, mouth ulcers, recurrent genital disease (HIV and adult transplant)
What are complications of herpes simplex virus?
cutaneous dissemination, oesophagitis, hepatitis, viraemia
What is treatment for herpes simplex virus?
Aciclovir, valaciclovir, foscarnet
What are manifestations of varicella zoster virus?
Skin lesions, pneumonitis, encephalitis, hepatitis, purpura fulminans in the neonate, acute retinal necrosis, progressive outer retinal necrosis, VZV-associated vasculopathy
What is a late manifestation of VZV post-transplant?
Shingles
What can shingles be an early manifestation of?
HIV
What is the mortality in multidermatomal or disseminated zoster?
High
How can we prevent VZV infection in an immunocompromised person?
Aciclovir prophylaxis provides some protection, post-exposure prophylaxis with VZV immunoglobulin
What are manifestations of CMV?
Retinitis, encephalitis, pneumonia, gastroenteritis
What is a pathognomonic histological feature of CMV infection?
Owl’s eye appearance of the lung pneumocytes caused by inclusion bodies
When does CMV tend to develop after transplantation?
Within 6 months of transplantation
What is the greatest risk of reactivation of CMV?
- In SOLID organ transplantation: the greatest risk of reactivation is when the donor has had past CMV infection but the recipient is naïve.
- In BONE MARROW transplantation: the greatest risk of reactivation occurs when the recipient has had past CMV infection but the donor is naïve
- CMV is a destructive infection that directly threatens the graft and damages endothelial cells
What is most concerning about with EBV?
Development of malignancy
What disease can EBV lead to?
Post-transplant lymphoproliferative disease (PTLD)
What raises a suspicion of PTLD and what confirms it?
Rising EBV viral load associated with widespread lymphadenopathy raises suspicion of PTLD. Confirmed by biopsy of the lymph nodes.
What is management for EBV?
Reduce immunosuppression, anti-CD20 monoclonal antibodies (Rituximab) - removes the B cells
What is Kaposi sarcoma associated with?
HHV8
What is HHV8 associated with?
Kaposi sarcoma, primary effusion lymphoma (PEL), multicentric castleman disease
How does Kaposi sarcoma present?
Presents with brownish/purplish vascular lesions that can be cutaneous or visceral
What are characteristic histological findings?
Spindle cell proliferation, neo-angiogenesis, inflammation and oedema
How do you diagnose Kaposi sarcoma?
Biopsy
How do you treat Kaposi sarcoma?
Chemotherapy, antiretroviral therapy
What type of virus is a JC virus?
polyomavirus
What is JC virus associated with?
Progressive multifocal leukoencephalopathy
What is JC virus characterised by?
This is a dementing process that is characterised by loss of higher functions (personality change, motor deficits, focal neurological signs)
What is the main pathological feature of JC virus?
Demyelination of white matter
How is JC virus diagnosed?
MRI and PCR of CSF
Who did progressive multifocal leukoencephalopathy occur in?
Before HAART, PML occurred about 5% of AIDS patients and had a high mortality
What is an increased risk of PML seen in?
Increased risk of PML is associated with the use of Natalizumab (monoclonal antibody used in MS)
What type of virus is BK virus?
Polyomavirus, dsDNA
What can BK virus cause?
BK cystitis (post-stem cell transplantation) and BK nephropathy (post-renal transplant)
How can we treat BK virus?
By reducing immunosuppression
When is adenovirus particularly a problem?
Particular problem after bone marrow transplant
How does adenovirus occur?
Can occur as an exogenous infection or reactivation of persistent endogenous infection
What are manifestations of adenovirus?
Manifestations: Fever (septic appearance), encephalitis, pneumonitis, colitis, HIGH MORTALITY in disseminated infection
Adenovirus has a high mortality, therefore what measures should we take in post-transplant patients?
Therefore, regular screening of urine, respiratory secretions, blood and stools to check for disseminated disease in post-transplant patients
Which respiratory viruses have an increased risk of complications (pneumonitis) and high mortality?
Influenza A and B, parainfluenza, RSV, adenovirus, MERS
How are respiratory viruses in immunocompromised patients diagnosed?
Diagnosed by taking nasopharyngeal aspirates, bronchioalveolar lavage, nose and throat swabs. Multiplex PCR is the investigation of choice
What can Human Parvovirus B19 cause in immunocompromised patients?
Chronic anaemia
How is Human Parvovirus B19 diagnosed?
PCR of blood. Serology (IgM) is NOT useful in immunocompromised patients.
What is the treatment for Human Parvovirus B19?
IVIG - may require blood transfusion
What is the serological course of hepatitis B like?
If you have been infected, you will develop antibodies against core antigen and surface antigen. If an acute infection progresses to become chronic, the HBsAg will persist.
What would HBV serology of someone with current infection look like?
HBV sAg +, HBV core Ab +, HBV s Ab -
What would HBV serology of someone with a past infection look like?
HBV sAg -, HBV core Ab +, HBV sAb +
What would HBV serology of someone with a vaccination look like?
HBV sAg -, HBV core Ab -, HBV sAb +
What are the TWO consequences of HBV in immunocompromised patients?
Carriers may have a flare of the disease. Those with a past infection may reactivate.
Who is the risk of reactivation of HBV particularly important in?
In patients on B-cell depleting therapies (Rituximab)
How can we prevent HBV infection?
Nucleoside/nucleotide analogue prophylaxis(e.g. lamivudine, tenofovir)
How is hepatitis E virus present in the UK?
Endemic
What is a major cause of enterically transmitted viral hepatitis?
Hepatitis E virus
In developed countries, what is Hepatitis E caused by?
It is a zoonosis caused by genotype 3 virus
In developing countries, what is Hepatitis E caused by?
Mainly caused by genotype 1 virus
Amongst who is hepatitis E associated with a high mortality?
Pregnant women
