Development of pure red cell aplasia by transmission and persistent infection of parvovirus B19 through a kidney allograft

We report a case of pure red cell aplasia (PRCA) caused by parvovirus B19 (PVB19) infection, which was transmitted through a kidney allograft. The patient underwent a living‐donor kidney transplant from his wife at the age of 60. Despite successful engraftment with a normal creatinine level, he developed severe anemia that required frequent blood transfusions 2 months after transplantation. Renal anemia was unlikely as his serum erythropoietin level was extremely high. A bone marrow aspiration test demonstrated the existence of large proerythroblasts. Although anti‐PVB19 IgM antibody levels were not increased, polymerase chain reaction (PCR) detected PVB19 DNA in his serum. Thus, he was diagnosed as having PRCA induced by PVB19 infection. PCR analysis of total DNA isolated from 0‐hour biopsy sections showed the existence of PVB19 DNA. Furthermore, PVB19 proteins was detected on renal tubules of 0‐hour allograft by immunoperoxidase staining. Thus, transmission of PVB19 through the allograft was confirmed. A single course of intravenous immunoglobulin (IVIG) therapy resulted in substantial improvement; however, the effect was limited, and severe anemia relapsed after 5‐6 months. Several courses of IVIG with adjustment of immunosuppressive drugs resulted in long‐term remission. Our case demonstrates that donor‐transmitted PVB19 infection should be suspected in kidney transplant recipients who develop refractory anemia during the early post‐operative phase.     

Parvovirus B19-related anaemia after renal transplantation

We describe here the case of a renal transplant recipient treated by sirolimus based immunosuppresive therapy, who developed severe and unusual pancytopenia 2 months after renal transplantation. Parvovirus B19 primo-infection was diagnosed. The first course of intravenous immunoglobulin failed. Bone marrow aspiration confirmed megaloblastic anaemia associated with parvovirus B19. Finally, this infection was succesfully treated by the reduction of immunosuppression combined with a second course of intravenous immunoglobulin.     

Parvovirus B19 transmitted by bone marrow

We describe a case of symptomatic parvovirus B19 infection transmitted by bone marrow (BM). The infection caused prolonged anaemia, thrombocytopenia, arthralgia and erythema infectiosum in a 16-year-old girl with acute myeloid leukaemia receiving a BM transplant (BMT). The BM donor was a 19-year-old asymptomatic brother who had parvovirus B19 viraemia at the time of BM harvest. Sequencing of the VP2 gene from the patient and the donor showed a perfect match of DNA sequences, confirming the mode of transmission. Parvovirus B19 represents a potential complicating factor in patients undergoing BMT, but screening by polymerase chain reaction (PCR) of donor BM may reduce the risk of infection.     

Acute Parvovirus B19 Infection Leading to Severe Aplastic Anemia in a Previously Healthy Adult Female

Human Parvovirus B19 has been linked to a variety of diseases. One of the most common complications is transient aplastic crisis in patients with chronic hemolytic anemia. Very few case reports have implicated this virus as a putative etiology behind hepatitis and severe aplastic anemia in immuno competent individuals. We report a case of severe aplastic anemia in a previously healthy adult female due to acute parvovirus B19 infection. Laboratory examination showed pancytopenia in peripheral blood and severe hypoplastic bone marrow on biopsy. Serological analysis (ELISA) revealed acute Parvovirus B19 infection. In the face of unavailable HLA matched bone marrow donor, immuno-supressive therapy was contemplated, but could not be given because of financial constraints. Pancytopenia persists till date, 4 months after the diagnosis, with the patient requiring repeated packed red cell and irradiated platelet transfusions. Thus, acute infection with this virus must be considered a cause of acquired aplastic anemia even in individuals without underlying disease.     

Human parvovirus B19 in patients with aplastic anemia

Aplastic anemia is characterized by pancytopenia with hypoplastic bone marrow. Various factors including viral infections have been implicated as the precipitating factors. Human parvovirus B19 has been associated with red-cell aplasia, leukopenia, and thrombocytopenia. The present study was carried out to determine the role of parvovirus B19 in aplastic anemia patients. Twenty-seven aplastic anemia patients and 20 healthy controls were tested for the presence of parvovirus B19 infection by detecting parvovirus B19-specific IgM by ELISA and viral DNA by PCR. Parvovirus B19 IgM and viral DNA were detected in significantly higher numbers of patients in comparison to the controls (40.7% vs. 5%, P < 0.01; 37% vs. 0%, P < 0.001, respectively). The presence of parvovirus DNA in aplastic anemia patients indicates active or recent infection. However, more studies are needed to explore the mechanism of bone-marrow aplasia due to human parvovirus B19 infection.     

Successful re‐transplantation in patient with recurrent parvovirus B19 pure red cell aplasia

Impaired cell‐mediated, as well as antibody‐mediated immunity predisposes a renal transplant recipient to a wide variety of atypical infection. With an increasing number of re‐transplant, the balance between immunosuppression and the risk of recurrent disease poses a clinical and therapeutic challenge. Here, we report a successful re‐transplantation in a case of parvovirus B19 infection leading to anaemia and collapsing glomerulopathy in the allograft managed with intravenous immunoglobulin (IVIG) and reduction of immunosuppression. This case emphasizes re‐consideration to renal transplant after clearance of the virus in a previous renal allograft lost to PVB19 infection.     

A case of persistent anemia in a renal transplant recipient: association with parvovirus B19 infection

We report an unexplained anemia that persisted for 4 months in a renal transplant patient who was receiving immunosuppression therapy that included prednisolone, tacrolimus and azathioprine. A bone marrow biopsy demonstrated pure erythroid hypoplasia and occasional giant pronormoblasts with intranuclear inclusions, characteristic of a parvovirus B19 infection. Both the serum and bone marrow cells were positive by parvovirus B19 DNA PCR. The anemia resolved 6 weeks after the administration of intravenous immunoglobulin (IVIG). Four months later, anemia redeveloped and IVIG was infused again. Hemoglobin levels were, however, still subnormal after 1 month of treatment and tacrolimus was then switched to cyclosporin A, resulting in a clear improvement. A parvovirus B19 infection should be included in the differential diagnosis of renal transplant recipients who present with anemia associated with a low reticulocyte count. Tacrolimus may possibly impair the clearance of a parvovirus B19 infection.     

Effects of Parvovirus B19 Infection in Renal Transplant Recipients: A Retrospective Review of Three Cases

Parvovirus B19 (PVB19) is a DNA virus which causes clinically relevant infection in renal transplant recipients (RTR) leading to significant morbidity. Manifestations include erythropoietin resistant anemia, proteinuria, and glomerulosclerosis in the allograft. Severe infection may require administration of intravenous immunoglobulin, reduction in immunosuppression and transfusions. The major challenge in managing and preventing the infection in RTR involves the act of balancing the decreased level of immunosuppression and the risk of rejection. The objective of this article is to understand the importance of PVB19 infection and its outcome in RTR. We reviewed the medical records of three RTR with confirmed PVB19 infection and recorded patient information including demographics, clinical and laboratory data, management, and outcome. The average time of occurrence of PVB19 infection as transplant was 8.6 weeks and they presented with symptomatic anemia. Elevated creatinine values were noted in two of them. Following treatment, anemia improved and creatinine values returned to baseline. One of them developed an early relapse and had to be treated once again similarly. We emphasize the importance of maintaining a high index of suspicion for PVB19 infection in patients with anemia in the posttransplant phase, especially in patients on higher doses of immunosuppressants. Early and proper treatment can prevent worsening clinical condition and possible effects on the allograft.     

Parvovirus B19 infection in HIV-1 infected patients with anemia

Summary Serum samples were analysed for IgM and IgG antibodies to parvovirus by ELISA and for parvovirus B19 DNA by polymerase chain reaction (PCR) in 69 HIV-1 infected Swedish patients with anemia and in 37 HIV-1 infected subjects without anemia. In 5/69 anemic patients, parvovirus B19 DNA was detected despite the lack of IgM antibody activity to the virus. The detection of parvovirus B19 DNA was significantly correlated to the degree of anemia in the anemic patients. In two patients who had a chronic anemia, a persistent parvovirus infection was detected by PCR, but not by serology, for 1 and 1.5 years, respectively. The results suggest that persistent parvovirus infection is a rare cause of anemia, but important to identify, since the infection is potentially treatable with intravenous immunoglobulin.

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Parvovirus B19 Infektion bei HIV-infizierten Patienten mit Anämie

Zusammenfassung Serumproben von 69 HIV-infizierten schwedischen Patienten mit Anämie und von 37 HIV-Infizierten ohne Anämie wurden mittels ELISA auf IgM- und IgG-Antikörper gegen Parvovirus B19 untersucht, auch wurde mittels Polymerasekettenreaktion (PCR) das Vorliegen von Parvovirus B19 DNA geprüft. Bei 5/69 anämischen Patienten war Parvovirus B19 DNA nachzuweisen, obwohl keine IgM-Antikörperreaktion gegen das Virus vorlag. Zwischen dem Nachweis von Parvovirus B19 DNA und dem Schweregrad der Anämie bestand bei den anämischen Patienten eine signifikante Korrelation. Bei zwei Patienten mit seit 1 beziehungsweise 1 1/2 Jahren bestehender chronischer Anämie konnte unter Anwendung der PCR eine persistierende Parvovirus-Infektion festgestellt werden, für die serologisch kein Hinweis vorlag. Die Ergebnisse lassen annehmen, daß die persistierende Parvovirus-Infektion eine seltene Ursache für eine Anämie darstellt, ihr Nachweis jedoch wegen der möglichen Behandlung mit intravenösem Immunglobulin von klinischer Relevanz ist.

     

Pure red cell aplasia in a lung transplant patient

Aplastic anemia secondary to infection by parvovirus B19 is normally an extremely rare problem in patients with no prior history. However, the presence of certain risks, such as receiving chronic immunosuppressant therapy, may facilitate its appearance. Very few cases have been published concerning red cell aplasia due to parvovirus B19 infection in patients receiving a transplanted lung. We report the case of a 24-year-old woman with cystic fibrosis who had received a double lung transplant. The patient developed red cell aplasia secondary to parvovirus B19 infection; severe anemia requiring multiple transfusions. Five days of intravenous immunoglobulin therapy resolved the anemia. We discuss the difficulty of serological diagnosis in such cases, the importance of using techniques that identify the virus and taking measures that may prevent recurrence.     

Successful Bone Marrow Transplantation for Severe Aplastic Anemia in a Patient with Persistent Human Parvovirus B19 Infection

Persistent infection with human parvovirus B19 (B19) is primarily associated with chronic bone marrow failure in immunocompromised patients, but occasionally this organism may also affect immunocompetent hosts. B19 is also suggested as a causative agent of organ failure during bone marrow transplantation (BMT).We herein report the case of a 9-year-old girl with no previous history of immunodeficiency who developed severe aplastic anemia concurrent with B19 persistent infection. Both immunoglobulin (Ig)M antibody to B19 and B19 DNA identified by real-time polymerase chain reaction were found in the patient's serum at time of diagnosis of aplastic anemia. No giant proerythroblasts were found in her bone marrow at diagnosis. Although intravenous administration of Ig (IVIg) reduced serum B19 DNA, the aplastic status of her bone marrow did not improve. Both aplastic anemia and persistent B19 viremia were successfully treated by BMT from an HLA-identical sibling donor. Serum B19 DNA increased temporarily after BMT; however, neither organ nor marrow failure was observed. B19 DNA disappeared from the serum 2 months after BMT, suggesting that a normal immune response was restored by BMT and terminated the B19 viremia. During BMT, use of high-titer IVIg for B19 might prevent B19-associated organ failure.     

Life-threatening human parvovirus B19 infection transmitted by intravenous immune globulin

Infection of human parvovirus B19 (B19) is usually a self-limiting febrile illness, but can sometimes be life-threatening under certain circumstances, such as aplastic crisis in patients with haemolytic anaemia, hydrops fetalis in pregnant women and fulminant hepatitis. B19 can be transmitted through respiratory secretions, transplacentally and by transfusion of blood or blood products. In the present case, administration of intravenous immune globulin (i.v.Ig) transmitted B19 infection and consequently caused pure red cell aplasia and aggravation of hepatitis to fulminant hepatitis. Our case may raise important questions as to the safety of i.v.Ig and possible contamination by B19.     

Severe aplastic anemia associated with human parvovirus B19 infection in a patient without underlying disease

 Human parvovirus B19 (B19 virus) infection is known to induce aplastic crisis in patients with hemolytic anemia. In healthy subjects, B19 infection may sometimes cause mild pancytopenia, but these changes are transient and recovery is spontaneous. We report the first case of aplastic anemia in a previously healthy boy without any underlying diseases, following asymptomatic infection with the B19 virus. Laboratory examination initially showed thrombocytopenia, mild leukopenia in the peripheral blood, and severe hypoplastic bone marrow. Since pancytopenia developed and worsened progressively, immunosuppressive therapy was given, resulting in a complete remission. Despite the lack of an infectious prodrome, serological and histological analysis revealed an underlying infection with the B19 virus. Thus, B19 virus infection must be considered one of the causes of aplastic anemia in patients without underlying hemolytic anemia and an apparent episode of the viral infection. Received: August 28, 1998 / Accepted: November 18, 1998     

Human Parvovirus B19: Prevalence of Viral DNA in Volunteer Blood Donors and Clinical Outcomes of Transfusion Recipients

Background and Objectives: Blood donor units are not screened for human parvovirus B19 (B19) even though it can be acquired via blood products. We estimated the prevalence of B19 in a US volunteer blood donor population and determined the clinical outcomes of transfusion recipients. Materials and Methods: Donor units were screened for B19 DNA by PCR, and positive units analyzed by EIA for B19 Ig. Unit usage was determined and recipient chart review conducted. Results: B19 DNA was detected in 11/9, 568 allogeneic units (0.1%), of which 3 had no measurable B19 Ig. One individual developed anemia consistent with B19 infection after receiving a DNA+ unit lacking B19 Ig. Conclusions: The apparent low incidence of disease in patients transfused with B19 DNA+ components may be due to coexistence of neutralizing antibodies in donors and/or recipients.     

Successful treatment of persistent erythroid aplasia caused by parvovirus B19 infection in a patient with common variable immunodeficiency with low-dose immunoglobulin

Parvovirus B19 causes persistent erythroid aplasia in immunocompromised hosts. From April through July 1996, we encountered five adult patients presenting with reticulocytopenia and fever caused by parvovirus B19 infection. The reticulocyte count of four patients with normal immunity recovered within two weeks after the onset of fever. However, in the one remaining patient with common variable immunodeficiency (CVI), reticulocytopenia, and other symptoms including fever and the elevation of lactate dehydrogenase (LDH) levels persisted beyond 16 days of onset. Although the DNA of parvovirus B19 was detected in the peripheral blood of the CVI patient, neither immunoglobulin Ig-G nor Ig-M antibodies specific to the virus were detectable. We administered 50 mg/kg of Ig to the CVI patient for six days. The reticulocyte count recovered promptly on the sixth day of the treatment and parvovirus B19 DNA was not detectable 30 days after therapy. This indicates that although patients with CVI may be susceptible to persistent erythroid aplasia during an endemic of parvovirus B19, the complication can be treated successfully with relatively low-dose Ig.     

Parvovirus B19 infection-induced anemia and leukocytopenia after myomectomy

A 38-year woman was hospitalized because of myoma uteri. She underwent myomectomy on September 30, 1997 with 2,000 ml blood loss. No blood transfusion was required, but she received a plasma protein product. On the 14th postoperative day, a complete blood count revealed anemia (Hb 9.3 g/dl) and leukocytopenia (1,600/ul). But it did not reveal anemia before the operation. Bone marrow smears showed erythroblastopenia with giant proerythroblasts. Anti-parvovirus B19 IgM antibody were positive in the serum and parvovirus B19 DNA was detected in the bone marrow cells by polymerase chain reaction. From the results, the patient was diagnosed as the anemia and leukocytopenia secondary to parvovirus B19 infection. Parvovirus B19 was not detected in the samples of the plasma protein product received on the myomectomy. The reticulocyte gradually decreased to 1/1000 on the 20th postoperative day. The anemia and leukocytopenia gradually improved. This case shows that parvovirus B19 infection could cause hematological disorders in the normal person under acute blood loss. This report warns that a careful observation is necessary for the patients who have received operations with acute blood loss.     

Phase I-II trial of foscarnet for prevention of cytomegalovirus infection in autologous and allogeneic marrow transplant recipients.

The safety and efficacy of foscarnet for prevention of cytomegalovirus (CMV) infection was evaluated in 19 CMV-seropositive bone marrow transplant (BMT) recipients. All patients received intermittent intravenous (iv) foscarnet: 40 mg/kg every 8 h from 7 days before to day 30 after BMT, then 60 mg/kg once a day until day 75. The main toxicity was transient renal dysfunction, with a greater than 50 mumol/L increase in serum creatinine above baseline in 5 of the 7 autograft recipients and in 6 of the 12 allograft recipients. Only 4 allograft recipients developed CMV infection during foscarnet prophylaxis, and no patient showed evidence of CMV disease. Because 3 allograft recipients receiving concomitant iv amphotericin B showed rapid impairment of renal function, foscarnet prophylaxis should not be given to allograft recipients requiring amphotericin B; otherwise, foscarnet prophylaxis at this dose appears safe after BMT.     

Lack of known hepatitis virus in hepatitis-associated aplastic anemia and outcome after bone marrow transplantation

Viral infection has been shown to induce aplastic anemia, unidentified types of hepatitis being the most common cause for aplastic anemia-associated viral hepatitis. The survival rate for this group of patients after bone marrow transplantation with stem cells from an HLA-matched sibling is not well known. The aim of this study was to determine the prevalence of hepatitis G virus (HGV) and transfusion transmitted virus (TTV) infection in non-A, non-B, non-C hepatitis associated-aplastic anemia (HAAA) patients, and to define the role of bone marrow transplantation (BMT) as a therapeutic modality for this disease. Sixty-eight patients (43 males and 25 females) with aplastic anemia, underwent allogeneic BMT at the Hadassah University Hospital between 1981 and 1997. Onset of hepatitis was defined as jaundice and elevated alanine aminotransaminase (ALT) levels. Onset of aplastic anemia was defined as the first date on which varying degrees of pancytopenia occurred: hemoglobin level below 10 g/dl, WBC below 2 x 10(9)/l and low platelet count 10 x 10(10)/l. Serial serum samples from HAAA patients were assayed for virological and/or serological markers of hepatitis A, B, C, D, E, G viruses, TTV and parvovirus B19. Seventeen of the 68 patients with aplastic anemia (25%) suffered from hepatitis, 12 males and five females, ages 5 to 36 years. The mean interval between onset of hepatitis and first indication of aplastic anemia was 62 days (range 14-225 days). The development of aplastic anemia was unrelated to age, sex or severity of hepatitis. Ten of the 17 patients (59%) achieved complete ALT recovery prior to the diagnosis of aplastic anemia. Serum samples were available for 15 patients; none had evidence of acute or active hepatitis A, B, C, D, E, G and TTV virus infection at the time of diagnosis. Parvovirus B19 DNA sequences were not detectable in 10 of 12 tested cases; two positive results were detected in serum samples obtained after blood transfusion, making the analysis of these positive results difficult. All 17 patients underwent BMT. The mean post-BMT follow-up period was 38 months (range 1 day-123 months), five patients (30%) died 1 to 160 days post BMT, and 12 (70%) are alive 31 to 123 months after BMT. Relapsing hepatitis was not observed in any of the patients. In conclusion, HAAA is a disease of the young and the etiologic agent associated with HAAA remains unknown. HGV, TTV and parvovirus B19 sequences were not detected in any of the HAAA cases. The survival rate after BMT with stem cells from an HLA-matched sibling is similar to that for patients with non-hepatitis-associated aplastic anemia.     

Infection humaine par le parvovirus B19. Mise au point

Pathogenicity of parvovirus B 9 has been demonstrated. The spectrum of clinical manifestations varies according to the age and immune status of affected patients. Parvovirus B 9 is the aetiologic agent of erythema infectiosum in children. In normal adults, it is responsible for acute, bilateral and symmetrical arthritis, although chronic arthritis can develop. Parvovirus B 9 has a particular tropism for erythroid precursors: in patients with underlying hemolysis, it induces transient aplastic crisis; in immunosuppressed patients the virus can lead to chronic pure red cell aplasia. Hydrops fetalis is one of the most severe manifestation of the infection. Diagnosis of recent parvovirus B 9 infection is based upon serology and PCR, especially in immunosuppressed patients in whom polyvalent intravenous immunoglobulins must be started. The link between parvovirus B 9 and systemic vasculitis is questionned.