Refractory adenovirus infection after simultaneous kidney-pancreas transplantation: successful treatment with intravenous ribavirin and pooled human intravenous immunoglobulin

Emovon, Osemwegie E.; Lin, Angello; Howell, David N.; Afzal, Fuad; Baillie, Mark; Rogers, Jeffrey; Baliga, Prabhakar K.; Chavin, Kenneth D.; Nickeleit, Volker; Rajagapalan, P. R.; Self, Sally

doi:10.1093/ndt/gfg365

Cited by 49 publications

(34 citation statements)

References 8 publications

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“…The most feared sequelae in immunocompromised individuals include enteritis, hemorrhagic cystitis, nephritis, fulminant hepatitis and disseminated disease; the mortality rate can be as great as 80%. [1][2][3][4][5][6][7][8] The risk of disseminated disease has been shown to correlate positively with viral load as measured by quantitative PCR methods. [9][10][11] Cidofovir has emerged as the primary therapy for AdV infection.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of a surveillance strategy for early detection of adenovirus by PCR of peripheral blood in hematopoietic SCT recipients: incidence and outcome

Öhrmalm

Lindblom

Omar

et al. 2010

Bone Marrow Transplant

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Adenoviruses (AdV) have emerged as important causes of morbidity and mortality in patients after hematopoietic SCT (HSCT). Early diagnosis of the infection by detection of viral DNA may improve the prognosis. A surveillance strategy was evaluated for detection of AdV DNA by PCR in a prospective study of unselected allogeneic HSCT recipients. In parallel with a routine CMV surveillance program, plasma from 20 children and 77 adults was analyzed by quantitative PCR for detection of AdV DNA. In addition, in 12 unselected patients, the presence of AdV-specific T cells were analyzed by enzyme-linked immunosorbent spot (ELISPOT) at 1 to 3 months after transplantation. A total of 5 of 97 (5%) patients had detectable AdV DNA in peripheral blood. Only one patient had high titers and none developed AdV disease. BM as a source of stem cells and myelodysplastic syndrome as the indication for transplantation were independently associated with higher risk of acquiring AdV infection. AdV-specific T cells were detected in 7 (58%) of 12 patients. Although AdV DNA was found in peripheral blood by quantitative PCR in 5% of patients undergoing allogeneic HSCT, the present surveillance program did not have a significant effect on the clinical outcome.

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Section: Introductionmentioning

confidence: 99%

Evaluation of a surveillance strategy for early detection of adenovirus by PCR of peripheral blood in hematopoietic SCT recipients: incidence and outcome

Öhrmalm

Lindblom

Omar

et al. 2010

Bone Marrow Transplant

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“…Th e urinary tract predilection of this virus is noteworthy; our patient had no signs of pancreas rejection or viral infection, with euglycemia and normal pancreatic enzyme levels. Pancreatic grafts have also been spared in two other reported cases of adenovirus infection in SKP recipients (11,12).…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…However, adenovirus infection has rarely been reported in SKP recipients (11,12). Presentation beyond 1 year after SKP is extremely rare, as only one reported case of adenovirus infection 18 months after transplantation has been reported (12). Adeno virus can be detected using viral culture, antigen detection, molecular diagnosis, and/or histopathology with electron microscopy (3).…”

Section: Discussionmentioning

confidence: 99%

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Late Presentation of Adenovirus-Induced Hemorrhagic Cystitis and Ureteral Obstruction in a Kidney-Pancreas Transplant Recipient

Klein¹,

Kuperman²,

Haley³

et al. 2015

Baylor University Medical Center Proceedings

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We report a late presentation of adenovirus-induced renal allograft and bladder infection causing azotemia and hemorrhagic cystitis in a patient 5 years after simultaneous kidney-pancreas transplantation. Adenovirus has been increasingly recognized as a cause of morbidity and mortality in both solid organ and stem cell transplant recipients. We wish to emphasize the importance of early detection, as treatment options involve reduction of immunosuppression, followed by the addition of antiviral agents and supportive care.A denovirus causes 5% to 10% of all childhood febrile illnesses, and the immunocompetent host generally endures a mild, self-limited upper respiratory tract infection. Adenovirus then establishes latent infection in the lymphoepithelial tissues (1). In immunocompromised hosts, the clinical manifestations of adenovirus reactivation or de novo infection can range from asymptomatic to fatal. Adenovirus is identifi ed as a late complication of bone marrow transplantation with hemorrhagic cystitis, and it is increasingly recognized as a serious, though rare, adverse complication of solid organ transplantation. We describe a rare late presentation of hemorrhagic cystitis and signifi cant renal allograft dysfunction with ureteral obstruction in a patient who had undergone simultaneous kidney-pancreas transplantation (SKP) nearly 5 years earlier. With adenovirus detected in the urine, blood, and renal allograft, the patient was treated with reduction of immunosuppression, intravenous immunoglobulin, and cidofovir. Renal function did not improve despite treatment. Pancreas function, as in rare case reports, was preserved, suggesting tropism of the adenovirus. CASE DESCRIPTIONA 45-year-old African American woman had a past medical history of type 1 diabetes mellitus complicated by peripheral neuropathy, retinopathy, and end-stage renal disease. She underwent SKP in February 2009 and received daclizumab induction per protocol. Th e donor was a 2/6 human leukocyte antigen match, and both donor and recipient were cytomegalovirus positive. Th e transplant was complicated by cellular rejection of the kidney in March 2009 treated with Solu-Medrol and biopsy-proven pancreas rejection treated with 10 doses of muromonab-CD3. Renal function stabilized with a creatinine of 1.4 mg/dL. Maintenance immunosuppression included azathioprine 100 mg daily, prednisone 5 mg daily, and tacrolimus 4 mg twice daily.Five years after transplant, the patient presented with a 1-week history of fever, suprapubic pain, and nausea, with the development of hematuria 3 days later. She had presented to an emergency department for presumed urinary tract infection 3 days before admission and was treated with nitrofurantoin. However, she developed worsening hematuria and presented to the transplant clinic. She denied sick contacts and had been compliant with all medications. On examination, she had orthostatic hypotension and fever. She was pale and appeared acutely ill. Th e left lower quadrant and suprapubic area were tender without rebound...

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“…Special consideration should therefore be given to the development of adenovirus-specific immunoglobulin as a more convenient approach to reconstitute the patient's immune status than costly, time-consuming, and labor-intensive adoptive cellular immunotherapy strategies for transplant recipients at risk for adenovirus infections. In this context, intravenous immunoglobulin therapy is sometimes included in treatment schedules, yet with various results (9,11). Nonetheless, although pooled intravenous immunoglobulin batches are relatively low in adenovirus-specific antibody titers, it is possible that the selection of donor material containing high titers of neutralizing antibodies specific for the infectious adenovirus serotype may favorably alter the course of the infection (10).…”

Section: Discussionmentioning

confidence: 99%

Recovery of Humoral Immunity Is Critical for Successful Antiviral Therapy in Disseminated Mouse Adenovirus Type 1 Infection

Lenaerts

Kelchtermans

Geboes

et al. 2008

Antimicrob Agents Chemother

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Severe adenovirus infections in transplant recipients undergoing immunosuppressive therapy are of increasing concern. Controversy exists on the contribution of antiviral therapy and the host immune response to recovery from these infections. Here, we established a systemic mouse adenovirus type 1 (MAV-1) infection in cyclophosphamide (CyP)-treated BALB/c mice. CyP was administered at 100 mg per kg of body weight every other day for 2, 3, or 4 weeks, thereby inducing general but reversible leukopenia, with a major suppression of the B-cell numbers and functionality that was more pronounced than that seen with T cells. The outcome of MAV-1 infection was dependent on the duration of CyP therapy, as the mice with the most severe immunosuppression were the most vulnerable to MAV-1-induced hemorrhagic enteritis and mortality. The protective effect of concomitant antiviral therapy with cidofovir depended on the level of immunosuppression. The combination of cidofovir treatment with the withdrawal of immunosuppression was the most successful regimen for increasing survival rates. Survival was clearly correlated with the clearance of virus and increased titers of MAV-1-specific antibodies in sera. In addition, the passive transfer of MAV-1-specific immunoglobulin G into MAV-1-infected SCID BALB/c mice caused a marked delay in mortality, the extent of the delay being dependent on the titer of MAV-1-specific antibodies. Based on the critical role of the humoral immune response in the early defense against disseminated adenovirus infection, the concomitant use of adenovirus-specific immunoglobulins and antiviral therapy should be considered for transplant patients at risk for severe adenovirus infections.

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Refractory adenovirus infection after simultaneous kidney-pancreas transplantation: successful treatment with intravenous ribavirin and pooled human intravenous immunoglobulin

Cited by 49 publications

References 8 publications

Evaluation of a surveillance strategy for early detection of adenovirus by PCR of peripheral blood in hematopoietic SCT recipients: incidence and outcome

Evaluation of a surveillance strategy for early detection of adenovirus by PCR of peripheral blood in hematopoietic SCT recipients: incidence and outcome

Late Presentation of Adenovirus-Induced Hemorrhagic Cystitis and Ureteral Obstruction in a Kidney-Pancreas Transplant Recipient

Recovery of Humoral Immunity Is Critical for Successful Antiviral Therapy in Disseminated Mouse Adenovirus Type 1 Infection

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