Cases reported "Adenoviridae Infections"

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11/105. Fulminant hepatic failure secondary to adenovirus following fludarabine-based chemotherapy for non-Hodgkin's lymphoma.

    Self-limited adenoviral infections are very common with the majority of infections resolving rapidly. Fatal complications may occur in severely immunocompromised patients. We describe a case of fulminant hepatic failure due to adenovirus in a 54-year-old man treated with fludarabine and cyclophosphamide for non-Hodgkin's lymphoma. There are no previous reports of this complication in conjunction with purine nucleoside therapy.
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12/105. Intravenous ribavirin treatment for severe adenovirus disease in immunocompromised children.

    BACKGROUND: Adenovirus is an important cause of morbidity and mortality in the immunocompromised host. The incidence of severe adenovirus disease in pediatrics is increasing in association with growing numbers of immunocompromised children, where case fatality rates as high as 50% to 80% have been reported. There are no approved antiviral agents with proven efficacy for the treatment of severe adenovirus disease, nor are there any prospective randomized, controlled trials of potentially useful anti-adenovirus therapies. Apparent clinical success in the treatment of severe adenovirus disease is limited to a few case reports and small series. Experience is greatest with intravenous ribavirin and cidofovir. ribavirin, a guanosine analogue, has broad antiviral activity against both rna and dna viruses, including documented activity against adenovirus in vitro. ribavirin is licensed in aerosol form for the treatment of respiratory syncytial virus infection, and orally in combination with interferon to treat hepatitis c. Intravenous ribavirin is the treatment of choice for infection with hemorrhagic fever viruses. The most common adverse effect of intravenous ribavirin is reversible mild anemia. The use of cidofovir in severe adenovirus infection has been limited by adverse effects, the most significant of which is nephrotoxicity. OBJECTIVE: We report our experience with intravenous ribavirin therapy for severe adenovirus disease in a series of immunocompromised children and review the literature. DESIGN/methods: We retrospectively reviewed the medical records of 5 children treated with intravenous ribavirin for documented severe adenovirus disease. Two patients developed adenovirus hemorrhagic cystitis after cardiac and bone marrow transplants, respectively. The bone marrow transplant patient also received intravenous cidofovir for progressive disseminated disease. An additional 3 children developed adenovirus pneumonia; 2 were neonates, 1 of whom had partial digeorge syndrome. The remaining infant had recently undergone a cardiac transplant. Intravenous ribavirin was administered on a compassionate-use protocol. RESULTS: Complete clinical recovery followed later by viral clearance was observed in 2 children: the cardiac transplant recipient with adenovirus hemorrhagic cystitis and the immunocompetent neonate with adenovirus pneumonia. The remaining 3 children died of adenovirus disease. Intravenous ribavirin therapy was well tolerated. Use of cidofovir in 1 child was associated with progressive renal failure and neutropenia. DISCUSSION: Our series of patients is representative of the spectrum of immunocompromised children at greatest risk for severe adenovirus disease, namely solid-organ and bone marrow transplant recipients, neonates, and children with immunodeficiency. Although intravenous ribavirin was not effective for all children with severe adenovirus disease in this series or in the literature, therapy is unlikely to be of benefit if begun late in the course of the infection. Early identification, eg by polymerase chain reaction of those patients at risk of disseminated adenovirus disease may permit earlier antiviral treatment and better evaluation of therapeutic response. CONCLUSIONS: Two of 5 children with severe adenovirus disease treated with intravenous ribavirin recovered. The availability of newer rapid diagnostic techniques, such as polymerase chain reaction, may make earlier, more effective treatment of adenovirus infection possible. Given the seriousness and increasing prevalence of adenovirus disease in certain hosts, especially children, a large, multicenter clinical trial of potentially useful anti-adenoviral therapies, such as intravenous ribavirin, is clearly required to demonstrate the most effective and least toxic therapy.
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13/105. High levels of adenovirus DNA in serum correlate with fatal outcome of adenovirus infection in children after allogeneic stem-cell transplantation.

    An increase in the incidence of adenovirus (AdV) infection leading to death among children who have undergone allogeneic stem-cell transplantation has made it necessary to find new ways to monitor AdV infection. In this retrospective study, levels of AdV DNA in serum samples obtained from 36 transplant recipients with stool cultures positive for AdV were measured by polymerase chain reaction (PCR) semiquantitatively by analyzing serial dilutions of the DNA template. Six (86%) of 7 children who died of AdV infection, compared with only 2 (7%) of 29 other patients, had high serum levels of AdV DNA (detectable by PCR at a > or =100-fold dilution of the DNA template; P<.0001). High serum levels of AdV DNA were reached a mean of 18 days before death (range, 6-29 days). Quantification of adenoviral DNA in serum may prove to be a valuable tool to diagnose and monitor AdV infection and disease in immunocompromised children.
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14/105. Intravenous Cidofovir therapy for disseminated adenovirus in a pediatric liver transplant recipient.

    BACKGROUND: No definitive antiviral therapy exists for adenovirus (ADV) in immunosuppressed hosts. Cidofovir (CDV), a broad spectrum anti-DNA viral agent, has previously been shown to be of therapeutic benefit in life-threatening adenoviral disease in bone marrow stem-cell recipients. methods: A 71/2-month-old girl with a history of biliary atresia developed fevers, hematochezia, tachypnea, and laboratory evidence of hepatitis and pancreatitis 12 days after liver transplantation. A stool culture, oropharyngeal culture, blood viral culture, and blood polymerase chain reaction (PCR) confirmed ADV. Cidofovir 1 mg/kg intravenously three times per week was initiated. The patient received intravenous hydration and probenecid with the infusions to reduce the nephrotoxicity of CDV. immunosuppression was reduced to achieve tacrolimus trough levels of approximately 8 ng/mL and prednisone at 0.1 mg/kg per day. Complete blood cell count, urinalysis, and viral studies were obtained weekly. RESULTS: Detection of ADV DNA by PCR made a transition from positive to negative during CDV therapy. Blood viral cultures became negative after two CDV doses. alanine aminotransferase normalized by 5 weeks of therapy. CDV was discontinued after 7 weeks secondary to transient acidosis and proteinuria. The patient never developed azotemia, neutropenia, or ocular abnormalities. CONCLUSIONS: CDV was associated with improved clinical status, viral clearance, and minimal transient side effects in a pediatric liver transplant recipient with disseminated adenoviral disease. The current report documents clearance of disseminated ADV infection in a liver transplant recipient receiving CDV infusions.
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15/105. Use of polymerase chain reaction for diagnosis of disseminated adenovirus infection.

    We report a fatal case of disseminated adenovirus infection with fulminant hepatic failure in an 8-month-old child after peripheral blood stem cell transplantation. The virus was identified in blood, urine, respiratory aspirate and stool samples and was typed as adenovirus type 2 through PCR and sequencing of part of the hexon gene, with the use of degenerated consensus primers.
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16/105. Fatal adenovirus infection during alemtuzumab (anti-CD52 monoclonal antibody) treatment of a patient with fludarabine-refractory B-cell chronic lymphocytic leukemia.

    Alemtuzumab (Campath-1H) is a humanized CD52 monoclonal antibody that targets normal as well as malignant B- and t-lymphocytes. Alemtuzumab has significant antitumor activity in chronic lymphocytic leukemia (B-CLL) but also induces immunosuppression. We describe a case of fatal adenovirus infection in a heavily pretreated patient with fludarabine-refractory B-CLL receiving alemtuzumab therapy, drawing attention to the fact that also viruses other than cytomegalovirus (CMV) and herpes simplex (HSV) need to be considered in B-CLL patients with fever of unknown origin while on alemtuzumab treatment.
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17/105. Adenovirus type 21-associated acute flaccid paralysis during an outbreak of hand-foot-and-mouth disease in Sarawak, malaysia.

    We report the virological and clinical features of 8 children who presented with adenovirus-associated acute flaccid paralysis (AFP) during an epidemic of enterovirus type 71 (EV71)-associated hand-foot-and-mouth disease (HFMD) in Sarawak, malaysia, in 1997. neutralization tests and phylogenetic analysis revealed adenovirus type 21 (Ad21), although DNA restriction digests suggested that this virus was different from the prototype Ad21. Four children had upper-limb monoparesis, 2 had lower-limb monoparesis (one of whom had changes in the anterior spinal cord noted on magnetic resonance imaging), and 2 had flaccid paraparesis. At follow-up, 4 children were noted to have made full recoveries and 3 had residual flaccid weakness and wasting. Neurophysiological investigation revealed a mixture of axonal and demyelinating features in motor and sensory nerves, with denervation. These findings suggest that Ad21 might cause AFP by anterior horn cell damage or neuropathy of the brachial or lumbosacral plexus. The occurrence of these unusual adenovirus infections during an outbreak of EV71-associated HFMD suggests that an interaction between the 2 viruses may have occurred.
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18/105. Adenovirus infection of a renal allograft.

    One month after renal transplantation, a 60-year-old man developed acute allograft dysfunction associated with gross hematuria and dysuria. Urinary cytological examination showed viral inclusion-bearing epithelial cells. A renal transplant biopsy specimen showed granulomatous interstitial nephritis, tubular necrosis, and ground glass-like intranuclear viral inclusion bodies in tubular cells caused by an adenovirus (ADV) infection. A reduction in baseline immunosuppressive therapy resulted in rapid normalization of allograft function and ultimately viral clearance. We report this case not only to illustrate an exceptional manifestation of an ADV infection in a renal allograft, but also to highlight the beneficial effect of reduction in immunosuppressive therapy on viral replication and clinical outcome.
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19/105. Fulminant adenovirus hepatitis following bone marrow transplantation. A case report and brief review of the literature.

    Adenovirus infections are frequently encountered in immunocompromised patients and transplant recipients. However, fulminant hepatic failure due to adenovirus infection as a fatal complication in bone marrow transplant recipients is extremely rare. We report a case of fulminant adenovirus hepatitis in a 21-year-old allogeneic bone marrow transplant recipient who subsequently died of the disease. The diagnosis was established by histologic and immunohistochemical examination of a liver biopsy and was confirmed by liver tissue and blood cultures.
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20/105. Hemophagocytic syndrome associated with severe adenoviral pneumonia: usefulness of real-time polymerase chain reaction for diagnosis.

    In infection-associated hemophagocytic syndrome (HPS) the causative pathogen is often undetected, except in cases of herpes virus infections. We describe a 12-year-old girl with life-threatening pneumonia with HPS caused by an adenovirus. She was admitted with complaints of persistent fever and systemic petechiae/purpura. The day after admission the patient developed sudden dyspnea with massive infiltration of the bilateral lower lung field. She exhibited coagulopathy, hepatic dysfunction, and remarkable elevations in serum levels of cytokine, ferritin, and urinary beta2-microglobulin. A diagnosis of HPS was made, and the patient was treated with dexamethasone and cyclosporin A on the second hospital day. Her fever went down quickly, and the abnormal laboratory and chest radiographic findings returned to normal over a period of 2 weeks. Antibody analysis was not successful in identifying the pathogen responsible. However, a polymerase chain reaction (PCR) assay of lung tissue biopsied on the fifth hospital day was positive for an adenovirus (subgroup B), and quantitative adenoviral DNA analysis by real-time PCR using primers covering serotypes 3, 7,11, and 35 (all subgroup B) confirmed this initial finding (93 copies/microg DNA in the biopsied lung and no detectable adenovirus DNA in the lung tissues of control subjects).This approach may provide important clues for improving outcomes and clarifying the exact etiology in cases of often fatal, infection-associated HPS.
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