Vol

DEPARTMENT OF PATHOLOGY
The Johns Hopkins Medical Institutions

Vol. 20, No. 32
THE JOHNS HOPKINS MICROBIOLOGY NEWSLETTER
Tuesday, August 7, 2001

A. Provided by Leslie Edwards Reger, Division of Outbreak Investigation, Maryland Department of Health and Mental Hygiene.

5 outbreaks reported during MMWR week 30 (July 22-28, 2001):

2 outbreaks of foodborne gastroenteritis associated with food-service facilities (1 in Montgomery Co, 1 in Baltimore Co.)
1 outbreak of typhoid fever in a private home (Prince George's Co.)
1 outbreak of acute respiratory disease in a nursing home (Washington Co.)
1 outbreak of gastroenteritis among persons at 2 vacation homes in the
same community (Garrett Co.)

B. The Johns Hopkins Hospital. Information provided by Robert W. Allan, M.D., Department of Pathology and Laboratory Medicine.

Case Report: The patient was a 33 year old male who received a cadaveric kidney/pancreas transplant 3 year prior to admission due to diabetes mellitus and end stage renal disease. He presented with an acute increase in creatinine from a baseline of 1.4 to 2.6mg/dl. He was immunosuppressed with cyclosporine and FK506. He had been feeling well except for some urinary frequency and urgency. He had no hematuria. He denied fever, chills, sweats, cough, fatigue or rash. He had no exposures or travel history. On examination, he was in no acute distress. He was afebrile with normal vital signs. Physical examination was unremarkable. Urinalysis revealed greater than 10⁵ colonies of Klebsiella sensitive to TMP/Sulfa. Laboratory studies were remarkable for the elevated creatinine and a borderline elevated FK506 level. A renal allograft biopsy was obtained. The biopsy specimen showed scattered renal tubular epithelial cells with enlarged, somewhat smudged basophilic nuclei and early interstitial nephritis. Immunohistochemical stains for polyoma virus (SV40 antibody) were positive. BK Human Polyoma virus interstitial nephritis Organism: Polyoma virus type BK (BK virus) is a non-enveloped, circular, double stranded DNA virus of the family Papovaviruses (Papilloma and Polyoma viruses). The polyoma viruses consist of the BK virus, JC virus and SV40 virus. The BK virus shares 69% and 75% homology with the JC and SV40 virus, respectively. BK virus was first isolated from the urine of a renal transplant patient in 1971.

Clinical Manifestations: Most primary infections with polyomaviruses occur in childhood. In fact, 60-80% of adults show serologic evidence of prior infection, most of which are subclinical. Both BK and JC viruses persist in the urine of immunocompromised individuals; BK virus being more common. In immunocompromised renal transplant recipients, reactivation of latent virus infection occurs from 2 months to 5 years post-transplantation. Rare de-novo infections have been described. Most documented infections are asymptomatic.

BK virus commonly causes asymptomatic infections in renal transplant patients. However, BK can also cause interstitial nephritis in this setting. BK virus induced interstitial nephritis coexists with or possibly contributes to episodes of acute rejection; 35% of patients with biopsy-proven interstitial nephritis experience graft loss³. Interestingly, interstitial nephritis has not been reported in recipients of heart and liver allografts and the occurrence is rare in other forms of immunodeficiency. Thus, it is possible that the local renal allograft environment may play a significant role in the activation of the virus. The virus has also been associated with hemorrhagic cystitis and ureteral stenosis.

Diagnosis: In patients who have undergone renal allograft biopsy the diagnosis can be made based on the clinical history and identifying enlarged tubular epithelial cells and interstitial nephritis. Similar appearing cells can be detected in the urine that can mimic the nuclear enlargement and atypia of urothelial carcinomas (so-called "decoy cells"); however, these cells are not diagnostic of interstitial nephritis since they may be seen in asymptomatic infections. Immunohistochemical stains are directed against the SV40 T antigen. This antibody cross-reacts with the T antigen of other polyoma virus and can be useful in discriminating polyoma virus cytopathic effects from those of CMV, adenovirus and herpes viruses. BK virus is not routinely cultured in clinical laboratories. A PCR test for BK in urine is offered at JHH. However, the clinical specificity of this assay is mitigated by positivity in asymptomatic individuals shedding BK virus in the urine. Recent reports indicate that testing the plasma for BK virus by PCR might hold promise for predicting the presence of virus-induced interstitial nephritis². PCR testing for BK virus in the plasma needs prior approval of a faculty member in microbiology (5-5077) at JHH as it is not from a validated source.

Treatment: No effective anti-viral therapy exists for BK virus. However, there are case reports citing the effectiveness of cidofovir. The mainstay of therapy usually entails lessening the immunosuppressive regimen. Unfortunately, this can often trigger episodes of rejection.

References:

1. Lui L, Fresco R, Picken M. Intranuclear inclusions in allograft kidney: human polyomavirus-associated interstitial nephritis in an allograft kidney. Archive of Pathology and Laboratory Medicine 2001: 125 (7): 973-975.

2. Nickeleit V et al. Testing for Polyomavirus Type BK DNA in plasma to identify renal-allograft recipients with viral nephropathy. New England Journal of Medicine 2000: 342 (18): 1309- 1315.

3. Randhawa PS, Demetris AJ. Nephropathy due to polyomavirus type BK. New England Journal of Medicine 2000: 342: 1361-1363.

4. Gonzalez-Fraile MI, Canizo C, Caballero D et al. Cidofovir treatment of human polyomavirus-associated acute haemorrhagic cystitis. Transpl Infect Dis 2001 Mar;3(1):44-6.

5. Held TK, Biel SS, Nitsche A et al. Treatment of BK virus-associated hemorrhagic cystitis and simultaneous CMV reactivation with cidofovir. Bone Marrow Transplant 2000 Aug;26(3):347-50.