Cases reported "Viremia"

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1/27. Quantitative dna analysis of low-level hepatitis B viremia in two patients with serologically negative chronic hepatitis B.

    Low-level viremia due to hepatitis b virus (HBV) was demonstrated in the sera of two patients diagnosed previously as having non-B, non-C chronic hepatitis. Both patients had a "silent" HBV infection, because they were negative for both hepatitis B surface antigen (HBsAg) and anti-hepatitis B core antibody. The TaqMan chemistry polymerase chain reaction (PCR) amplified the HBV dna, enabling quantitation of the virus in their sera. Their serum HBV dna concentrations were low: the amount of each HBV S or X gene amplified showed there were approximately 10(3) copies/ml and HBV dna was detected occasionally during clinical follow-up. Positive HBsAg staining in liver tissues was demonstrated by an immunoperoxidase technique. Vertical transmission of silent HBV from one patient to her daughter was confirmed. Direct nucleotide sequencing of the amplified HBV X region revealed several mutations, suggesting reduced viral replication. One patient had a T-to-C mutation at the extreme 5'-terminus of the direct repeat 2 region and the other exhibited a coexisting X region with a 155-nucleotide deletion. These findings suggest that HBV replication is suppressed considerably in patients with silent hepatitis B.
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2/27. Ultrastructural changes in peripheral blood neutrophils in a patient receiving ganciclovir for CMV pneumonitis following allogenic bone marrow transplantation.

    A 13-year-old splenectomized, multitransfused beta-thalassemia major, male patient received an allogenic BMT from his HLA-compatible brother after suffering grade III regimen-related pulmonary toxicity. He developed features of CMV pneumonitis with positive pp65 CMV antigenemia involving 2.5% peripheral blood neutrophils from day 46. The patient received intravenous immunoglobulin and ganciclovir 5 mg/kg intravenously twice daily. His neutrophil count was maintained above 1 x 10(9)/l by G-CSF 5 microg/kg subcutaneously as and when required. From day 7 onwards following twice daily ganciclovir his peripheral blood smear started showing isolated cytoplasmic inclusions, 1-3 per neutrophil, 3-5 mu in diameter, involving 2-3% of the neutrophils and occasional monocytes. Transmission election microscopy of peripheral blood neutrophils showed type I and type II intranuclear inclusions. These inclusions disappeared within 48 h of stopping ganciclovir. Inclusions were not seen in three patients who were given prophylactic ganciclovir 5 mg/kg once daily for 5 days every week following allogenic BMT after the same conditioning regimen. These patients were also negative for CMV antigenemia. Development of type I and type II intranuclear inclusions in blood neutrophils in patients receiving ganciclovir therapy has not been reported previously, and the striking light microscopic changes provide simple morphological evidence of the toxic effect of this drug on blood neutrophils.
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3/27. cytomegalovirus as a cause of very late interstitial pneumonia after bone marrow transplantation.

    cytomegalovirus (CMV) infection is an important cause of morbidity and mortality after allogeneic transplant. Interstitial pneumonia (IP) is the most common manifestation of CMV in BMT patients, with a 30-48% mortality rate despite adequate treatment. Most CMV infection occurs in the first 100 days. However, prolonged ganciclovir (GCV) prophylaxis has favored the occurrence of late CMV IP, probably by inhibition of the development of CMV-specific T cell lymphocyte responses. We report the case of a patient treated with an allogeneic BMT who received pre-emptive GCV until day 100 because of CMV-positive antigenemia. He developed a CMV IP on day 811 post BMT, which responded to treatment. We intend to alert clinicians that even at long-term (>1 year) post-BMT, CMV is a possible cause of IP in high-risk patients.
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4/27. lamivudine as an alternative therapy for interferon-resistant chronic hepatitis B and the characteristics of hepatitis b virus: a case report.

    A 27-year-old man who had been diagnosed as having chronic hepatitis B suffered disease exacerbation with marked reactivation of hepatitis b virus (HBV). Treatment with interferon (IFN) did not improve his condition, and his serum HBV dna level increased to over 10 000 pg/ml during IFN administration. Following replacement with lamivudine, there was a substantial reduction in HBV dna to an undetectable level, and liver function parameters subsequently improved to within the normal range. Quantitative analysis of the precore mutant HBV dna, which is a variant that cannot express hepatitis B e antigen due to a G-to-A point mutation in the precore region of the viral genome, revealed that the amount present was greater than for the precore wild-type HBV dna in the serum taken before IFN treatment. This case suggests that lamivudine would be an appropriate alternative to IFN, particularly in patients infected with HBV containing an excess of precore mutants resistant to IFN therapy.
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5/27. Bone marrow failure associated with human herpesvirus 8 infection after transplantation.

    BACKGROUND: Human herpesvirus 8 (HHV-8) infection has been linked to the development of Kaposi's sarcoma and to rare lymphoproliferative disorders. methods: We used molecular methods, serologic methods, in situ hybridization, and immunohistochemical analyses to study HHV-8 infection in association with nonmalignant illnesses in three patients after transplantation. RESULTS: Primary HHV-8 infections developed in two patients four months after each received a kidney from the same HHV-8-seropositive cadaveric donor. Seroconversion and viremia occurred coincidentally with disseminated Kaposi's sarcoma in one patient and with an acute syndrome of fever, splenomegaly, cytopenia, and marrow failure with plasmacytosis in the other patient. HHV-8 latent nuclear antigen was present in immature progenitor cells from the aplastic marrow of the latter patient. Identification of the highly variable K1 gene sequence of the HHV-8 genome in both the donor's peripheral-blood cells and the recipients' serum confirmed that transmission had occurred. HHV-8 viremia also occurred after autologous peripheral-blood stem-cell transplantation in an HHV-8-seropositive patient with non-Hodgkin's lymphoma. Reactivation of the infection was associated with the development of fever and marrow aplasia with plasmacytosis; there was no evidence of other infections. HHV-8 transcripts and latent nuclear antigen were expressed in the aplastic marrow but not in two normal marrow samples obtained before transplantation. CONCLUSIONS: Primary HHV-8 infection and reactivation of infection may be associated with nonneoplastic complications in immunosuppressed patients.
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6/27. Severe pancytopenia and hemophagocytosis after HHV-8 primary infection in a renal transplant patient successfully treated with foscarnet.

    We report the occurrence of human herpesvirus (HHV)-8 primary infection in an adult male kidney recipient. Four months after transplantation, the patient developed visceral Kaposi sarcoma, and 1 month later he presented with progressive and severe peripheral cytopenia, in the presence of a normocellular or hypercellular bone marrow (BM) with hemophagocytosis. HHV-8 was the sole pathogen detected by polymerase chain reaction either in the serum or in the BM. HHV-8 latent nuclear antigen was detected in immature progenitor cells from the BM. Immunosuppressive therapy was reduced, and the patient was treated with foscarnet for 2 weeks, leading to a dramatic normalization of blood cell counts, concomitantly with the disappearance of HHV-8 viremia. At the end of antiviral therapy, the patient received chemotherapy, and Kaposi sarcoma regressed in 2 months. Severe peripheral cytopenia may be a posttransplant complication after HHV-8 infection, for which treatment with foscarnet seems appropriate.
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7/27. Fatal disseminated herpes simplex virus infection in a previously healthy pregnant woman. A case report.

    BACKGROUND: In contrast to the frequent occurrence of localized herpes simplex virus (HSV) infections during pregnancy, disseminated disease has rarely been reported. CASE: A 21-year-old woman in the 27th week of gestation developed a catastrophic illness characterized by fever, progressive pneumonia, respiratory failure, leukopenia, disseminated intravascular coagulation (DIC), anicteric hepatitis, septic shock and acute renal failure. Initial studies for an infectious etiology were negative. In spite of empiric broad-spectrum antimicrobial therapy, her condition continued to deteriorate. Sparse vesicular skin lesions suggestive of HSV infection subsequently appeared. Despite initiation of acyclovir therapy, the patient died. HSV type 2 was cultured from a skin vesicle, and at autopsy there was extensive necrosis of the liver and lung with immunohistochemical stains positive for HSV antigen. CONCLUSION: In the third trimester of pregnancy, HSV can occasionally disseminate in immunocompetent women. A clinical syndrome of unexplained fever, pneumonia, anicteric hepatitis, leukopenia and DIC without mucocutaneous lesions should prompt investigation and possible treatment for disseminated HSV infection.
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8/27. Transmission of west nile virus from an organ donor to four transplant recipients.

    BACKGROUND: In August 2002, fever and mental-status changes developed in recipients of organs from a common donor. Transmission of west nile virus through organ transplantation was suspected. methods: We reviewed medical records, conducted interviews, and collected blood and tissue samples for testing with a variety of assays. persons who donated blood to the organ donor and associated blood components were identified and tested for west nile virus. RESULTS: We identified west nile virus infection in the organ donor and in all four organ recipients. encephalitis developed in three of the organ recipients, and febrile illness developed in one. Three recipients became seropositive for west nile virus IgM antibody; the fourth recipient had brain tissue that was positive for west nile virus by isolation and nucleic acid and antigen assays. serum specimens obtained from the organ donor before and immediately after blood transfusions showed no evidence of west nile virus; however, serum and plasma samples obtained at the time of organ recovery were positive on viral nucleic acid testing and viral culture. The organ donor had received blood transfusions from 63 donors. A review of blood donors and follow-up testing identified one donor who had viremia at the time of donation and who became seropositive for west nile virus IgM antibodies during the next two months. CONCLUSIONS: Our investigation of this cluster documents the transmission of west nile virus by organ transplantation. Organ recipients receiving immunosuppressive drugs may be at high risk for severe disease after west nile virus infection. blood transfusion was the probable source of the west nile virus viremia in the organ donor.
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9/27. Serological response and detection of viraemia in acute hepatitis c virus infection.

    The serological response during acute hepatitis c virus (HCV) infection was examined by enzyme-linked immunosorbent assay (ELISA) in sequential serum samples from 13 haemophiliacs following their first exposure to factor viii concentrates contaminated with HCV. The commercially available C100-3 peptide and a new 22 kDa recombinant protein (p22) encoded by the nucleocapsid region of the viral genome were used for antibody detection, whilst a nested polymerase chain reaction (PCR) method was used for the detection of viraemia. In addition, eight sporadic cases of acute HCV infection were studied. The results in haemophiliacs demonstrated that seroconversion to the C100-3 antigen occurred in only one-third of the patients within 12 weeks of disease onset, but all of the patients had a diagnostic serological response to p22 during this phase of the disease. The new test was positive in all the sporadic cases at a time when the commercially available test was negative. Although PCR offers a sensitive method for the detection of recent HCV infection, the complex methodology makes it unsuitable for diagnostic laboratories. The new ELISA test with p22 may therefore have a useful diagnostic role in acute disease.
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10/27. Hepatitis B surface antigen escape mutant in a first time blood donor potentially missed by a routine screening assay.

    Mutant forms of hepatitis B surface antigen have developed from a matter of academic interest into a real threat due to the fact that they may remain undetected by certain commercial immunoassays. The risk is especially high when hepatitis B surface antigen is the only strategy to detect an asymptomatic HBV carrier in blood donor screening. Surface antigen escape mutants arise in individuals under medically or naturally induced selective immune pressure and certain mutations are known to be stable and horizontally transmittable. Currently, only one case report has been published from a blood donor carrying an escape mutant. We herewith present a further case of a blood donor with a mutation so far undescribed that alters the common 'a' determinant of HBsAg in such a way that several immunoassays fail to detect this hepatitis b virus infected patient. We conclude that it is absolutely necessary to use HBsAg assays with a high sensitivity for mutant forms in blood donor screening.
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