Opportunistic viral infection

Question 1

when do opportunistic infections in HIV start

Answer 1

CD4 <200

Question 2

what are the classes of immuno suppressive drugs

Answer 2

o	Glucocorticoids or steroids	
o	Calcineurin inhibitors (of T cell function):
	Cyclosporine
	Tacrolimus
o	Antiproliferative agents:
	Azathioprine
	Mycophenolate mofetil
	Sirolimus 
o	Antibodies:
	Depleting
	Non-depleting (anti-CD25r ABs, costimulation blockers)

Question 3

what are the 3 points of time where a transplant recipient is exposd to viruses

Answer 3

o (1) <1m = Virus acquired from grafts (i.e. HBV) –  risk with DONOR serostatus, DONOR risk assessments

o (2) 1-12m = Viral reactivation (i.e. HSV) –  risk with serostatus, monitoring, prophylaxis, pre-emptive therapy

o (3) >12m = Novel infection (i.e. VZV) –  risk with barrier nursing, advice, PEP, vaccinating contacts, diet control

Question 4

Herpes simplex virus

Answer 4

• Herpes Simplex Virus: Q/A  HSV is most likely to cause pain on swallowing after a liver transplant
o Symptoms:
 Cold sores Stomatitis
 Mouth ulcers Recurrent genital disease (HIV and adult transplant)
o Complications:
 Cutaneous dissemination Oesophagitis
 Hepatitis Viraemia
o Treatment:
 Aciclovir or valaciclovir
 Foscarnet

Question 5

What is most likely to cause pain on swallowing after a liver transplant

Answer 5

hsv

Question 6

varicella zoster

Answer 6

o Complications (primary infection):
 Pneumonitis Encephalitis
 Hepatitis Purpura fulminans in the neonate (see below)
 Immunocompromised: = DIC + coagulation in small vessels  skin necrosis
• Acute retinal necrosis (ARN)
• Progressive outer retinal necrosis (PORN)
• VZV-associated vasculopathy
o Shingles:
 Shingles is usually a late manifestation of VZV post-transplant
 Shingles can be an early manifestation of HIV
o Multi-dermatomal or disseminated zoster has a HIGH mortality
o Prevention:
 Aciclovir prophylaxis
 VZV IVIG post-exposure prophylaxis

Question 7

CMV

Answer 7

o Manifestations:
 Retinitis Encephalitis
 Pneumonia Gastroenteritis
o Pathognomonic histological feature  Owl’s eye lung pneumocytes (inclusion bodies)
o Reactivation:
 Develops within 6m of transplantation
 Risk dependent on donor/recipient pre-treatment serostatus (have they had it before?)
• SOLID organ transplantation  greatest risk = donor +ve past CMV; recipient -ve
• HSCT / BM transplant  greatest risk = donor -ve past CMV; recipient +ve
o CMV is a destructive infection that directly threatens the graft and damages endothelial cells
o Prevention strategies 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
o Treatment:
 Solid organ  Ganciclovir (IV) (bone marrow suppression) Valganciclovir: oral
 HSCT  Foscarnet (IV) (nephrotoxicity) Cidofovir (nephrotoxicity)
 IVIG (with another drug for pneumonitis)

Question 8

which patients should you never give ganciclovir to

Answer 8

post hsct as it suppresses bone marrow

Question 9

EBV

Answer 9

o Biggest concern = Post-Transplant Lymphoproliferative Disease (PTLD)
 Latent infected B cells have polyclonal activation  predispose to lymphoma
 Suspicion on rising EBV viral load (>105c/mL) and CT scan  confirm on biopsy of LN
o Management:
 Reduce immunosuppression
 Anti-CD20 monoclonal antibodies (Rituximab) - removes the B cells

Question 10

JC virus

Answer 10

• JC virus is a polyomavirus
• Associated with progressive multifocal leukoencephalopathy:
o A dementing process
o Characterised by loss of higher functions (personality change, motor deficits, focal neurological signs)
o Focal signs
• Diagnosis: MRI and PCR of CSF
o Demyelination of white matter (corresponds to area of brain affected)
• Treatment:
o Before HAART, PML occurred about 5% of AIDS patients and had a high mortality
o PML can also be seen in other types of immunocompromise
o Increased risk of PML is associated with:
 Natalizumab (monoclonal antibody used in MS)
 Rituximab
 Mycophenolate mofetil

Question 11

BK virus

Answer 11

• Polyomavirus (like JC virus); dsDNA
• Can cause:
o BK cystitis (post-HSCT)  intravesical cidofovir (direct into bladder – avoid nephrotoxicity)
o BK nephropathy (post-renal solid organ transplant)  IVIG (cidofovir is nephrotoxic)
• This can be treated by reducing immunosuppression

Question 12

adenovirus

Answer 12

• Particular problem after bone marrow transplant / HSCT
• Can occur as an exogenous infection or reactivation of persistent endogenous infection
o High mortality if disseminated infection
o Regular screening of urine, respiratory secretions, blood and stool is done on post-transplant people
• Manifestations:
o Fever (septic appearance)
o Encephalitis, Pneumonitis, Colitis

Question 13

respiratory viruses

Answer 13

• Increased risk of complications (pneumonitis) and high mortality associated with:
o Influenza A and B; treatment:
 Oseltamivir, OD, 5 days
o Parainfluenza 1, 2, 3, 4
o RSV No standard tx protocol
o Adenovirus
o MERS coronavirus
• Diagnosed by taking NPA, BAL, nose and throat swabs
• Multiplex PCR is the investigation of choice