Polyomavirus

 

There are two important viruses in this group- JC virus and BK virus.

It is found worldwide and the seroprevalance is above 80 %.

Primary infection is common in childhood between the age of 2 and 5 years.

 

Transmission may be through saliva exchange

Reactivation is common in immunocompromised patients, pregnant women and HIV infected patients.

 

Clinical Presentations

 

 

Primary infection is usually asymptomatic and in some it causes symptomatic illness such as mild upper respiratory tract infections.

Fever may be observed.

 

BK virus

In immunocompromised patients reactivation is common.

It is associated with nephritis and cystitis (haematuria)

In Immunocompromised patients, it is associated with hemorrhagic cystitis, ureteral stricture, encephalitis and pneumonitis.

 

JC virus

JC virus is associated with Progressive Multifocal Leukoencephalopathy (PML)- demyelinating disease

 

 

Investigation

 

Specific tests

A specific test is not required in an immunocompetent patient as infection is mainly asymptomatic.

There are serological tests for IgM and IgG however the clinical benefit is not well established.

Blood in EDTA and urine sample can be used to monitor kidney transplant patients for nephritis and other complication associated with BK. 

 

Management

 

Most are asymptomatic and treatment is not required.

Generally the management involves reducing the level of immunosuppression. Immunoreconstitution with HAART may be beneficial for HIV infected patients who have PML. 

Stem cell transplant patients with pneumonitis, hepatitis and encephalitis secondary to BK virus  may be treated by Cidofovir if they do not respond to low level of immunosuppressive agents.

Cidofovir 0.25-1.0 mg/kg every 2-3 weeks may be used.

 

Prevention

 

There is no vaccine.

At present, screening before transplantation is not recommended.  BK IgG can be done but in older patient the IgG level may be low and may not be detected by routine EIA tests.

The benefit of BK surveillance in immunocompromised patients has not been evaluated. As reactivation is the commonest causes of infection in symptomatic patients, specific preventive measures for exogenous infections are not required.

 

 

 

 

 

Text Box:   BK virus in Kidney transplant patients   Reactivation of BK virus is common in kidney transplant patient. Transmission with organ transplant may occur in susceptible recipient. Risk of transmission is high in Allogenic transplant patient Patients on treatment for GVHD on potent immunosuppressive agents   Clinical presentation Renal failure Nephritis may present with oligouria, and increase in creatinin levels. Ureteral stricture Disseminated vasculopathy Hemorrhagic cystitis   Investigations Urinary analysis- RFT- creatinine and urea level Graft biopsy- definitive diagnosis is made only on histological finding. Ultrasound examination to look for signs of ureteral stricture.   Specific tests Specimens- urine and blood (EDTA) Electron microscopy- the urine can be examined for Polyomavirus particles however the sensitivity of this test is low (detect only concentrated viral particle i.e. more than a million viral particle per ml). Cytology- “decoy cell” ground glass intranuclear inclusion in tubular epithelial cells. Decoy cells are not specific for BK viral infection however the negative predictive value of this method is almost 100 %. Decoy cells are mostly seen in symptomatic patients. PCR- can be done on urine and blood. Subsequent measurement of viral load in the blood may be useful to monitor response. Viral load in the urine may be 1000 fold higher than the blood level. Monitoring of urinary BK viral load is useless as the viral load will be affected by the urinary output. Hemorrhagic cystitis is not associated with viremia and BK viral DNA may not be detected in the blood.   Management Primarily reducing the immunosuppressive agents is effective in controlling viral replication. Care should be taken to differentiate nephritis caused by BK reactivation, and GVHD as they may present with the same clinical problems.   Antivirals Cidofovir may be effective in some patients but care should be taken as cidofovir is nephrotoxic and may aggravate renal failure. Cidofovir 0.25-1.0 mg/kg iv every 2 to 3 weeks with or without Probenecid may be beneficial. Side effect with this dose is uncommon. Nephrectomy may be done in unresponsive patients, and re-transplantation may be considered after BK clearance. Treatment of hemorrhagic cystitis may involve increasing fluid intake, bladder irrigation and occasionally surgical intervention in the bladder or uretera.   Prevention There is no prophylaxis. Pre-emptive surveillance is required in kidney transplant patients in the first 3 months, particularly in patients with Allogenic transplant,  mismatch transplant, or patients on treatment for GVHD.   Surveillance can be done with Urinary specimens Clue cells- cytology Electron microscopy may be useful to detect urinary Qualitative PCR could also be used Blood in EDTA-quantitative PCR can be done to monitor the viral load. There is a correlation between viral load and clinical problems. There is no consensus on the peak viral load for intervention. Other markers like creatinin and urea level should be considered as well.     Pathogenesis and Management of Polyomavirus infection in Transplant recipients. Kwak EJ et al . Clinical Infectious disease 2002: 35: 1081-87  

 

 

Text Box:   Polyomavirus infection in HIV patients Progressive Multifocal Leukoencephalopathy (PML) Reactivation of JC virus is common in HIV infected patients   Clinical presentation PML is seen mostly in patients with CD4 counts below 200/ml. Rapidly progressive. May present with Subacute onset of hemiparesis, visual field deficit, ataxia; Personality changes; and Cognitive changes and dementia   It is associated with fatality within a few months and it is considered to be AIDS defining illness.   Good Prognosis CD 4 >100/ml Starting HAART at the time of PML diagnosis Immune reconstitution associated PML    PML may be seen in       Organ transplant patients       Stem cell transplant patients       Patients on chemotherapy       Patients with hematological malignancy   Investigation MRI- asymmetric areas of increased T2 signal is strongly suggestive and CT scan- abnormality restricted to white matter EEG CSF   Specific tests CSF- PCR Definitive diagnosis is made on histopathological findings on the brain biopsy (demyelination). PCR on  biopsy material can be done however interpretation is difficult as JC virus DNA can be detected in 30 % of asymptomatic HIV infected patients. Negative PCR does not rule out PML Monitoring of viral load in CSF is not required. Electron microscopy is not useful  Management Prognosis was poor before HAART was introduced. At present HAART is the treatment of choice in HIV infected patients. Cidofovir has been tried and there are anecdotal reports suggesting good response. In transplant patients, reducing level of immunosuppression may control viral replication. Cytosin arabinoside may have little benefit except for HIV infected patients where the response rate for HAART is excellent. The drug is known to cause bone marrow toxicity.  Prevention HAART may prevent JC virus reactivation. Reconstitutions of the immune system may be crucial to control viral replication. Primary infection in HIV infected patient is uncommon.