Yasuko Matsunaga

Childhood transient erythroblastopenia complicated by thrombocytopenia and neutropenia

We report on 4 children with transient erythroblastopenia complicated by thrombocytopenia and/or neutropenia. Bone marrow examination revealed severe erythroid hypoplasia with normal granulopoiesis and thrombopoiesis. Human parvovirus B19 infection was confirmed serologically in 2 children. An in vitro study using autologous bone marrow cells after recovery demonstrated IgG‐mediated inhibition of erythropoiesis in 4 children. Additionally, antibodies directed against platelets and neutrophils were detected. These findings suggest that the IgG‐mediated mechanism may be pathogenetic for the transient pancytopenia of these children.

Pure red cell aplasia caused by parvovirus B19 infection in a renal transplant recipient

To the Editor: Human parvovirus B 19, which is the etiologic agent of transient aplastic crisis in hemolytic anemia, is known to cause chronic bone marrow failure in immunocompromised hosts (1-4). To our knowledge, there have been 2 previous case reports describing parvovirus B 19 infection in renal transplant recipients (5 ,6 ) . We report here another case of severe anemia caused by parvovirus B 19 infection in a renal transplant recipient. Although humoral immune response to the virus was absent for a while due to immunosuppressive therapy, treatment with a regimen of intravenous commercial immunoglobulin resulted in rapid elevation of the reticulocyte count and resolution of the anemia. A 48-year-old man with chronic renal failure secondary to diabetic nephropathy, who had been undergoing chronic hemodialysis and administration of recombinant human erythropoietin (rhEPO) for the treatment of renal anemia, was hospitalized to receive a cadaveric kidney transplant. On the 1st hospital day (d 0), he underwent cadaver donor kidney transplantation, and immunosuppressive therapy with cyclosporin (3 mg/kg/d), prednisolone (70 mg/d), mizoribine (200 mg/d), and antilymphocyte globulin (1000 mg/d) was started. The donor was a 52-year-old man who had died of subarachnoid hemorrhage. Laboratory examination of the recipient on admission showed a white blood cell count of 5300/mm3, a hemoglobin level of 10.6 g/dl, and a platelet count of 204 000/mm3. After transplantation, his anemia began to progress without improvement after rhEPO treatment. On d 18, his hemoglobin level dropped to 5.0 g/dl, reticulocyte count was 0.08 %, white blood cell count was 2500/mm3, and platelet count was 172000/mm3. Bone marrow aspiration revealed severe erythroid hypoplasia with the appearance of many giant proerythroblasts, suggesting the presence of parvovirus B 19 infection. Thereafter, rhEPO was discontinued and the patient was treated with a 7-d course of intravenous commercial immunoglobulin preparations ( 5 g/d) and red cell transfusion. Thereafter, the reticulocyte count increased and his anemia improved. Normal hematopoiesis was observed on bone marrow examination on d 38. The serial serum specimens during the course of illness were subjected to enzyme-linked immunosorbent assay (ELISA) for detection of virus antigen, and polymerase chain reaction (PCR) for detection of virus DNA. B19 antigen became positive on d 2, reached a peak on d 5 , and lasted 18 d. However, viral DNA was detected by PCR in the serum specimen taken just before transplantation, and was negative or faintly positive on d 48. Interestingly, the amount of viral DNA was transiently elevated on d 153 (Fig. 1). The presence of a replicative form of B 19 virus was demonstrated by Southern blot analysis in the bone marrow specimen (Fig. 2) (7). In the serum specimen from the donor, viral DNA was not detected. The assay of virusspecific antibody revealed that IgM and IgG response was not observed until d 153 while the appearance of IgG response was detected in the sample

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.

HUMAN PARVOVIRUS B19-INDUCED APLASTIC CRISIS IN AUTOIMMUNE HAEMOLYTIC ANAEMIA

0.04 x 109/1) and a platelet count of 90 x 1OY/1. He was placed in protective isolation and treated with intravenous gentamicin and piperacillin. Bone marrow examination showed an absence of red cell precursors with ‘maturation arrest’ of granulopoiesis at the early metamyelocyte stage and normal numbers of megakaryocytes. No reticulocyte counts were performed as he was transfusion dependent. He became apyrexial within 24 h and his white cell count rose to 5.1 x 10y/l (neutrophils 3.7 x 10y/l, lymphocytes 0.74 x 10y/l, eosinophils 0.15 x 10y/l, basophils 0.01 x loy/ I, monocytes 0.41 x 10y/l) with a platelet count of 3 15 x lo9/ 1 over the next 3 d. His haemoglobin increased to 12.0 g/dl after a 5 unit transfusion and he was discharged. Sputum, urine and blood cultures and throat swabs were all bacteriologically negative but a serum sample showed 100 units of anti-HPV IgM. (Reported by Dr P. Mortimer, PHLS, Colindale.) Between 30% and 60% of adults in this country have antiHPV IgG, indicating a previous infection, but the incidence of the virus in donated blood is very low, less than 1 in 50000 donations. One study by Mortimer et al (1983) showed no significant increase in anti HPV antibodies in those receiving multiple red cell transfusions ( 3 6%) over matched controls (23%) although haemophiliacs had a much higher incidence of seroconversion after receiving pooled factor concentrates (97%). The incubation period of HPV infection has been demonstrated with human volunteers to be 13-18 d (Anderson et al, 19 8 5) and in the same study IgM levels of 100 units were not achieved in less than 20 d from the onset of symptoms for HPV infection. It is therefore unlikely that the transfusion 6 d before the onset of symptoms was the origin of the HPV infection. It is likely that the presenting symptoms were not of the primary HPV infection, which may have been sub-clinical. but of an opportunistic infection secondary to the neutropenia. A fall in white count was noted in healthy volunteers infected with HPV and low white cell counts and platelet counts were seen accompanying red cell aplasia in cases of HPV infection with congenital spherocytosis reported by Saunders et a1 (1 986). Here a patient whose red cells were supplied by transfusion presents with neutropenia, a rare complication of this common infectious disease.

組換え (VP1+VP2) 粒子抗原を用いたヒトパルボウイルスB19の血清疫学

Antibody prevalence to B19 virus in Japan was previously reported with 1973 and 1984 serum collections. Since then we have had two big epidemics of erythema infectiosum in Japan: 1986-87 and 1991-92. In an attempt to estimate how much those epidemics have affected seroprevalence to B19 virus infection, we studied seroepidemiology in three separate areas using a newly developed ELISA system consisting of recombinant VP1 + VP2 particle antigen. Total of 900 sera obtained in 1993 from healthy individuals living in northern, central and southwest parts of Japan were assayed for the presence of anti B19 IgG antibody. In the first, the new assay system was compared with our conventional assay system in which native B19 virus particles were used as antigen. Of 220 serum samples tested, 212 (96.4%) gave same results in both assays. Remaining 8 samples which gave variable results were those of near cut off values. We concluded that this new ELISA system can be recommended for seroepidemiological use. Antibody prevalence rates were 10% (0-4 y), 54% (5-9 y), 59% (10-14 y), 46% (15-19 Y), 38% (20-29 y), 48% (30-39 y), 64% (40-49y) and 76% (50 y-). No gender difference was observed. Comparison of antibody prevalences in 1973, 1984 and 1993 suggested that approximately 10% (about 8 million people) of the total population under 40 years of age acquired immunity to B19 virus during one epidemic period.

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.