Tooru Kudoh

Human parvovirus B19 infection associated with acute hepatitis

BACKGROUND Human parvovirus (HPV) B19 infection produces a range of clinical manifestations including erythema infectiosum in children. Here we describe seven children who had acute hepatitis with HPV B19 infection. METHODS Hepatic dysfunction was noted in three children referred to our hospital during the course of erythema infectiosum caused by HPV B19 infection diagnosed by ELISA and PCR. The role of HPV B19 in the pathogenesis of hepatic involvement was investigated retrospectively by PCR assay of stored serum samples from 773 patients admitted to our hospital. FINDINGS 15 patients admitted to our hospital from January, 1991, to June, 1992, were HPV B19 DNA positive, of whom four had acute hepatitis of unknown origin. These four patients were aged between 7 months and 5 years. Of the seven patients, infection with hepatitis A, B, or C viruses or Epstein-Barr virus was ruled out in six by virological examinations. INTERPRETATION Epidemiological evidence suggests that HPV B19 can be the cause of acute hepatitis.

Incidence of human parvovirus B19 DNA detection in blood donors.

Summary. 1000 serum samples from blood donors were tested for human parvovirus B19 (B19) DNA by a nested PCR assay: six samples were positive for B19 DNA. The frequency was 1/167 (0‐6%), considerably higher than previous surveys (0‐004‐0‐03%). Five of the six samples were also positive for anti‐B19 IgM, indicating an acute phase of infection. It is recommended to screen for B19 DNA in blood products to prevent transfusion mediated viral infection for those susceptible such as immunocompromised patients and pregnant women.

Retrospective Study on the Influence of Human Parvovirus B19 Infection among Children with Malignant Diseases

Human parvovirus B19 (B19) is a known cause of erythema infectiosum (fifth disease) and aplastic crisis in patients with hemolytic anemias. When patients with malignant diseases are infected by B19 during chemotherapy, erythroid suppression of bone marrow sometimes occurs. We performed a retrospective investigation of B19 infection among 95 children with malignant diseases in our hospital during the past 14 years. By the method of dot blot hybridization, 9 of 95 patients were found to be positive for B19 DNA during chemotherapy. All 9 patients had reticulocytopenia at the time B19 DNA was detected in their serum samples. Neutropenia and thrombocytopenia were not found. Seven of them had only transient reticulocytopenia. Serum samples from 2 other patients were positive for B19 DNA for a longer time. They suffered from persistent anemia for about 2 and 13 month, respectively. The years when B19 DNA was detected from the 9 patients corresponded to the prevalence of erythema infectiosum in Japan.

Outcome of childhood acute lymphoblastic leukemia with induction failure treated by the Japan Association of Childhood Leukemia study (JACLS) ALL F-protocol.

Children with acute lymphoblastic leukemia (ALL) who fail to achieve complete remission (CR) after induction therapy (induction failure: IF) have a poor prognosis; however, there have been few prospective studies in patients with IF.

Pneumomediastinum, subcutaneous emphysema, and pulmonary fibrosis in a patient with idiopathic pneumonia syndrome after bone marrow transplantation.

An adolescent female underwent bone marrow transplantation for relapsed leukemia and developed acute and chronic graft-versus-host disease and idiopathic pneumonia syndrome. Her lung disease responded to large doses of methylprednisolone but evolved to pulmonary fibrosis and pneumomediastinum and subcutaneous emphysema in the convalescent period. Pulmonary function tests revealed a restrictive pattern. Pneumomediastinum and subcutaneous emphysema are complications not only of obstructive but also of restrictive lung disease and vary with respect to time of onset.

CMV retinitis after cessation of ganciclovir therapy for CMV antigenemia in an unrelated BMT recipient

An 11-year-old boy with severe aplastic anemia underwent unrelated BMT following TBI, antithymocyte globulin and CY. On day +23, CMV antigenemia was detected which resolved with ganciclovir. Eight days after discontinuing ganciclovir, he complained of impaired visual acuity. Ophthalmologic findings and a positive PCR study using anterior chamber fluid from the right eye confirmed the presumptive diagnosis of CMV retinitis, although CMV antigenemia and PCR studies using PBMC were then negative. He was successfully re-treated with ganciclovir. CMV retinitis should be considered even when CMV antigenemia is not present or PCR using PBMC is negative.

Efficacy and safety of micafungin for febrile neutropenia in pediatric patients with hematological malignancies: a multicenter prospective study.

Background: Invasive fungal infections are a major cause of infectious mortality in neutropenic patients receiving chemotherapy or hematopoietic stem cell transplantation. However, little is known about the efficacy and safety of micafungin (MCFG), an echinocandin antifungal agent, in pediatric patients with febrile neutropenia (FN). Procedure: This study was conducted as a prospective multicenter trial to evaluate the efficacy and safety of MCFG for FN in pediatric patients with hematological diseases. Efficacy was assessed based on the response to the 5 composite endpoints established by Walsh and colleagues in addition to body temperature and C-reactive protein values. Results: Thirty episodes of FN were enrolled in the study. The median dose and duration of MCFG treatment were 3.0 mg/kg/d and 13.5 days, respectively. Using the criteria of Walsh and colleagues, MCFG was effective in 56.7% of the patients. No breakthrough invasive fungal infection occurred during MCFG treatment. Body temperatures on the last day of neutropenia during administration of MCFG and on the last day of MCFG therapy and C-reactive protein values after administration of MCFG were significantly lower than on the day MCFG therapy was started. Adverse effects in the form of mild liver dysfunction were seen in only 2 patients. Conclusions: MCFG is a very effective and safe antifungal drug for FN in children. Physicians should administer MCFG early in febrile episode in patients in whom first-line antibiotics are not effective in treating FN.

Successful induction of immune tolerance in a patient with haemophilia B with inhibitor

We describe successful induction of immune tolerance (IT) in a 10‐month‐old boy with severe haemophilia B. Urticaria developed soon after starting prophylactic treatment and was associated with an inhibitor at 7 Bethesda units mL−1. Initially, we tried low dose factor IX therapy to induce IT with only a transient effect. The patient experienced an intracranial haemorrhage. A simple bolus dose of FIX eradicated the inhibitor. Thereafter he has been free from inhibitor and nephrotic syndrome for more than 5 years, although he receives FIX three times a week.

Human parvovirus B19‐induced aplastic crisis in iron deficiency anemia

Human parvovirus B19 (HPVB19) infects and replicates in erythroid progenitor cells. Its specific cytotoxic effect on these cells results in aplastic crises in patients with congenital hemolytic anemias. Aplastic crisis due to HPVB19 infection in a healthy girl revealed occult iron deficiency anemia. The condition is characterized by a high serum iron level in the aplastic phase and rapid recovery after administration of iron. Temporary HPVB19‐induced red blood cell aplasia could occur in patients with other anemias, particularly those with non‐inherited form of hemolysis.

Minocycline‐induced hemolytic anemia

A case of drug‐induced immune hemolytic anemia is described. A 2 year old boy exhibited sudden anemia and hemoglobinuria after administration of minocycline (MINO). The specific immunoglobulin G antibody against MINO was demonstrated in the patients serum by western blotting. This is a rare example where anti‐minocycline immune complex‐mediated hemolysis was responsible for an intravascular hemolytic process.