Parvovirus B19 infection after kidney transplantation

Prevalence for human parvovirus B19 infection is estimated to be between 2% and 30% in renal transplant recipients. In post-transplant settings, parvovirus B19 infection may occur either as a primary infection or a reactivation. Parvovirus transmission most commonly occurs through respiratory tract but may also result from graft or blood packs contamination. Co-infections with HHV-6 and CMV viruses are frequent. The hallmark symptom is anemia, more rarely pancytopenia and hemophagocytic syndrome. In respect to renal involvement, parvovirus B19 infection has been associated with graft dysfunction in 10% of cases. Both thrombotic microangiopathies and collapsing glomerulopathies have been reported concomitantly with parvovirus B19 infection but the causal link remains unclear. Other complications are seldomly reported, including hepatitis, encephalitis, and myocarditis. Diagnosis is based on pre and post-transplant serological status. In addition, the management of parvovirus B19 infection in immunocompromised patients requires quantitative assessment of blood viral load by PCR. The treatment relies primarily on reduction of immunosuppression combined with intravenous immunoglobulin infusions. Relapses occur in 30% of cases.     

Thrombotic microangiopathy associated with parvovirus B 19 infection after renal transplantation

Human parvovirus B19 is considered an etiologic agent of aplastic anemia in immunosuppressed patients. Microscopic vasculitis, with or without renal involvement, has recently been attributed to this viral infection in immunocompetent patients. This study describes four cases of thrombotic renal graft microangiopathy presumably secondary to B19 infection. Twelve to 50 days after transplantation, four patients presented a renal graft dysfunction with creatinine rising to 360 to 1088 micromol/L and requiring hemodialysis in three cases. Renal involvement appeared after a systemic illness characterized by fever, fatigue and arthralgia, aplastic anemia (hemoglobin ranged from 5.3 to 7.8 g/dl), and thrombocytopenia. A thrombotic microangiopathy was observed in the renal biopsies, and the parvovirus B19 genome was isolated by PCR from the specimens. All four patients also became IgM-positive for parvovirus. Three of the four renal biopsies taken at the time of transplantation (T0) from the same patients were found positive for the B19 genome. Graft function recovered, with resolution of the aplastic anemia, within 22 to 110 d. Twenty biopsies performed as routine controls or for suspected acute rejection and nine T0 biopsies of patients with no signs of B19 infection were used. The B19 genome was found in two of 20 posttransplant biopsies and in one of nine T0 biopsies. The temporal association between aplastic anemia and the onset of thrombotic graft microangiopathy, isolation of the viral genome in renal specimens, seroconversion, and endothelial tropism of the virus suggests that B19 could be the etiologic agent of thrombotic microangiopathy in these cases. The development of the disease after infection could depend on other detrimental cofactors, which make the patient more susceptible to microthrombi formation in the renal microvasculature. The renal graft could represent the route of B19 transmission.     

Parvovirus B19 Infection as a Rare Cause of Fulminant Liver Failure: A Case Report

Parvovirus B19 infection is common in childhood. The clinical presentations range from benign to life threatening. The literature shows that the clinical presentation is influenced by the patient's age and the presence of chronic disease such as chronic hemolytic disorders and immunosuppressed conditions. As the majority of patients with liver failure are diagnosed as indeterminate, knowledge about parvovirus B19 associated liver disease is limited. We examined 3 children with parvovirus B19-induced fulminant liver failure, 2 of whom underwent liver transplantation. Although the presented patients received standard corticosteroid and tacrolimus therapy as an immunosuppressive regimen, acute rejection, parvovirus B19 persistence, or any other complications due to parvovirus B19 were not observed. Physicians should be aware of the parvovirus B19 infection in association to acute liver diseases.     

Parvovirus B19-induced anemia in renal transplantation: a role for rHuEPO in resistance to classical treatment

Human parvovirus B19 (PVB 19) is responsible for pure red cell aplasia in immunocompromised patients, and particularly solid organ recipients. Intravenous immunoglobulins (IVIG) have been shown to be efficient to achieve the correction of anemia in association with the reduction of immunosuppression. We report a case of kidney transplant recipient with PVB 19-induced anemia that did not respond to recombinant human erythropoietin (rHuEPO) and to a first course of IVIG. After discontinuation of rHuEPO, a second course of IVIG was successful with the resolution of anemia. We discuss the role of rHuEPO that may facilitate PVB 19 replication in erythropoietin-sensitive human erythroid progenitor cells.     

Chronic anemia as a complication of parvovirus B19 infection in a pediatric kidney transplant patient

. This is a report of unexplained anemia that persisted for 4 months in an adolescent renal transplant patient receiving immunosuppression that included prednisone, tacrolimus, and mycophenolate mofetil. This patient required monthly blood transfusions for fatigue, palpitations, and hematocrit levels between 15% and 17%. In addition, his posttransplant course was notable for the development of insulin-dependent diabetes mellitus. While receiving low-dose prednisone, he was switched from tacrolimus to cyclosporin and tapered off insulin injections over the next 2 months. At 4.5 months post-transplantation, further diagnostic evaluation was suggestive of parvovirus B19 infection as the cause for our patient’s chronic anemia. After testing negative for serum-specific parvovirus B19 IgM and IgG antibodies, parvovirus B19 infection was detected in blood by the polymerase chain reaction. Treatment with intravenous immunoglobulin (1 g/kg per day × 2 days) resulted in normalization of both his reticulocyte count and hematocrit within 6 weeks. At 4 months after receiving the immunoglobulin infusion, he has maintained a normal hematocrit level and stable renal function without requiring further blood transfusions. Received August 23, 1996; received in revised form and accepted November 20, 1996     

Clinical implications of quantitative real time-polymerase chain reaction of parvovirus B19 in kidney transplant recipients – a prospective study

This prospective study was designed to investigate the clinically significant level of parvovirus B19 viral load using quantitative real-time (RT) polymerase-chain reaction (PCR) in kidney transplantation (KT) recipients. One hundred forty-three adult recipients who underwent their first KT between November 2003 and October 2005 were enrolled. Six blood samples (the first taken preoperatively, subsequent samples taken every 4 weeks for 20 weeks) were taken from each patient for parvovirus B19 DNA RT-PCR analysis. All recipients were diligently followed for 1 year post-transplant. One hundred sixty-eight of the 715 (23.5%) postoperative samples were positive for parvovirus B19 PCR. Eighty-four of the 143 KT recipients (58.7%) showed at least one positive PCR. Sixteen of the 143 (11.1%) KT recipients had sustained severe anemia (SSA) with hemoglobin lower than 7.0 g/dl, after 4 weeks post-transplant. The incidence of SSA in recipients with a titer higher than 1 × 10⁶ copies/5 μl whole blood was significantly higher than those with a negative or low titer ( P  <   0.001, positive predictive value 84.6%, negative predictive value 96.2%). In conclusion, a high titer of parvovirus B19 DNA higher than 1 × 10⁶ copies/5 μl whole blood in KT recipients was related with SSA after 4 weeks post-transplant.     

A nosocomial parvovirus B19 infection-induced transient aplastic crisis in a patient with chronic renal failure

A male patient aged 67 years with chronic renal failure (CRF), who had undergone hemodialysis since June 3, complained of dyspnea while walking on June 23, 1998. Rapidly progressive anemia and severe reticulocytopenia were noted. Serological tests showed that parvovirus B19- (B19) specific IgM antibody, but not IgG antibody, was present in the patient's serum. B19 DNA was detected in the patient's serum by the polymerase chain reaction (PCR). Therefore, a definite diagnosis of transient aplastic crisis induced by B19 was made. On June 10, prior to the appearance of this case, a female nurse aged 27 years working in our hemodialysis center, complained of cough, fever and arthralgia. Another female nurse, aged 35 years, developed similar symptoms on July 3. Both nurses had a positive IgM titer against B19, but were negative for IgG, indicating an acute B19 infection. These findings led us to suspect that this series of B19 infection was spread by nosocomial transmission. Although some cases of B19 infection have been reported to occur in laboratory staffs, the B19 nosocomial infection has not been described in the literature. We also suggest that a transient aplastic crisis due to B19 infection could lead to severe anemia in cases of CRF whose erythropoiesis is maintained by a recombinant human erythropoietin.     

A Cluster of Parvovirus B19 Infections in Renal Transplant Recipients: A Prospective Case Series and Review of the Literature

Up to 9% of renal transplant recipients have severe multifactorial erythropoietin-resistant anemia. Human parvovirus B19 (PVB19) infection can cause severe anemia and is likely underreported. Sparse information on epidemiology and management in this population exists. To address these issues, after our first index case, we modified our clinical practice to prospectively screen patients with persistent hemoglobin (Hb) <10 mg/dL for PVB19 infection after excluding common causes of anemia including erythropoietin resistance. Potentially infected patients were further evaluated by serology, qualitative polymerase chain reaction (quPCR) and bone marrow biopsy (BMB) for cytomegalovirus, Epstein-Barr virus, PVB19 and other etiologies. Over 3 months, 212 kidney recipients visited outpatient clinics. Of 52 recipients with anemia, 8 had an Hb <10 mg/dL with erythropoietin resistance and were screened for PVB19 infection. Three cases had PVB19 infection by quPCR and often-inconclusive serology/BMB results. Cases had immunosuppression reduced and received IVIG (0.5 gm/kg x 4 doses) with recovery from anemia, viral clearance in two cases and one recurrence. PVB19-mediated anemia occurred in up to three out of eight (38%) screened kidney recipients with Hb <10 mg/dL resistant to erythrypoietin. We recommend prospective risk stratification for this population, high indices of suspicion using at least qualitative techniques for diagnosis and treatment goal for viral eradication.     

Human parvovirus B19 in solid organ transplantation: Guidelines from the American society of transplantation infectious diseases community of practice

Clinical manifestations of human parvovirus B19 infection can vary widely and may be atypical in solid organ transplant (SOT) recipients. However, disease is apparent when there is destruction of erythrocyte progenitor cells leading to severe acute or chronic anemia with lack of an appropriate reticulocyte response in the setting of active parvovirus B19 infection. Serology may not reliably establish the diagnosis. High‐level viremia is more likely to be associated with symptomatic disease. Conversely, ongoing DNAemia after infection may not be clinically significant, if detected at low levels. Despite lack of robust data, intravenous immunoglobulin (IVIG) is frequently used for the treatment of SOT recipients with symptomatic parvovirus B19 infection. Although the optimal dosage and duration of IVIG is not known, most patients receive a total of 2 g/kg over a period of 2‐5 days. A daily dose of 1 g/kg or more seems to be associated with higher incidence of toxicity. Application of standard and droplet isolation precautions remains the cornerstone for preventing human parvovirus B19 transmission. Additional research is needed to assess the efficacy of current and novel therapies and to develop a safe and effective parvovirus B19 vaccine.     

Lung cancer with polyarthropathy due to parvovirus B19: report of a case

We reported a case of lung cancer with polyarthropathy induced by human parvovirus B19. A 60-year-old female with lung cancer was admitted to our hospital with polyarthropathy similar to rheumatoid arthritis. Although the abnormal accumulation of 99mTc-MDP in the bone scan film and rheumatoid factor positive were detected before operation, we diagnosed polyarthropathy induced by parvovirus B19 through the detection of parvovirus B19 IgM and B19 DNA. The joint pain gradually improved after surgical treatment for lung cancer.     

Incidence and clinical significance of human parvovirus B19 infection in kidney transplant recipients

Human parvovirus B19 (B19) infection has been known to cause chronic anemia, pure red cell aplasia (PRCA), glomerulopathy, and allograft dysfunction in kidney transplant (KT) recipients. The aim of this study was to evaluate the incidence and clinical significance of B19 infection in KT recipients. A total of 537 serum samples from 167 KT recipients were included in the present study. The incidence of B19 infection was based on either qualitative polymerase chain reaction (PCR) or quantitative PCR with LightCycler Parvovirus B19 Quantitation kit. Clinical significance of B19 infection was investigated by a retrospective review of hemoglobin (Hb) levels and the results of kidney and bone marrow biopsies. The overall PCR positive rate was 18.3% (98/537), and 52 of 167 (31.1%) KT recipients showed at least one positive PCR. In addition, 20 of 167 subjects (12.0%) showed PCR-positivity more than two consecutive times, and they had significantly lower Hb levels than those with negative or one positive PCR (p < 0.0001). Furthermore, two patients suffered from PRCA, which was confirmed by bone marrow biopsy. However, B19 infection did not seem to affect the graft outcome. In conclusion, the B19 infection in KT recipients was not uncommon and was associated with low Hb levels and PRCA after KT.     

Chronic parvovirus B19 infection in a pediatric lung transplanted patient

In immunocompromised patients, clinical manifestations of human parvovirus B19 (PVB19) infection are mostly reported as acute or chronic hematological disorders. Recently, PVB19 infection has been associated with nonhematological symptoms. Four years after lung transplantation, a 9-year-old girl developed a severe anemia with reticulocytopenia requiring blood transfusion. PVB19 DNA was found by polymerase chain reaction in blood. Blood marrow aspiration revealed typical features of PVB19 infection. She was successfully treated with high dose of i.v. Ig. Then, she exhibited recurrent nonregenerative anemia requiring another course of i.v. Ig. PVB19 DNA has been persisted in blood with no specific immune response. At the same time, she suffered from several lung infection syndromes with no microorganism found except PVB19 DNA. Recurrent mild renal dysfunction was noticed with no other explanation than PVB19 infection. This report indicates that pediatric transplanted patients are at risk of chronic PVB19 infection, which can be associated with lung and/or renal disorders.     

肝移植术后人类细小病毒B19感染的二代测序筛查及其相关危险因素分析

目的  总结肝移植术后人类细小病毒(HPV)B19感染的筛查方法并分析相关危险因素。方法  回顾性分析86例受者的临床资料。根据二代测序(NGS)结果  分为HPV B19感染组和对照组, 分析HPV B19感染患者的临床特点、治疗方案及预后, 采用单因素和多因素Logistic回归向前LR逐步法分析HPV B19感染的危险因素。结果86例受者中9例受者肝移植术后2周左右出现不明原因发热伴进行性贫血, NGS检测提示HPV B19阳性, 诊断为HPV B19感染引起的纯红细胞再生障碍性贫血(PRCA)。所有患者给予静脉注射用免疫球蛋白(IVIG)治疗及免疫抑制方案调整后, 血红蛋白水平明显回升。多因素分析结果显示, 患者术后7 d外周血清球蛋白水平低[比值比(OR)=0.749, P=0.040]、年轻患者(OR=0.937, P=0.038)是肝移植术后HPV B19感染的独立危险因素。结论  对于肝移植术后早期出现不明原因的血红蛋白水平下降的相对年轻患者, 需考虑HPV B19感染。NGS筛查是早期诊断HPV B19感染的有效方法。患者术后7 d外周血清球蛋白水平低和年龄(年轻患者)可能是其发生的独立危险因素。     

Resolution of Henoch-Schönlein purpura nephritis after acquired IgA deficiency

We report a case of Henoch-Schönlein purpura nephritis (HSPN) with acquired IgA deficiency due to parvovirus B19 infection. The patient was diagnosed as having Henoch-Schönlein purpura (HSP) at 6 years old, and subsequently developed macrohematuria and massive proteinuria of 7.4 g/day with decreased creatinine clearance of 70.2 ml/min/1.73 m² and significantly elevated serum IgA level of 449 mg/dl. The first kidney biopsy yielded the diagnosis of severe HSPN. After the initiation of the immunosuppressive therapy, the patient was infected with parvovirus B19 and developed virus-associated hemophagocytic syndrome (VAHS). Thereafter, the serum level of IgA selectively decreased and remained undetectable until the present time. Repeated kidney biopsies performed over a period of 14 years revealed a remarkable histological improvement in association with stabilization of the patient's kidney function. Considering the severity of initial kidney injury, persistent acquired IgA deficiency was likely to add favorable effects to the immunosuppressive therapy in this patient with HSPN.     

A case of acute erythroblastic anemia due to infection with human parvovirus B19 after coronary artery bypass grafting

A 37-year-old male developed reticulocytopenia and leukopenia with fever from the 11th patient day after coronary artery bypass grafting. Bone-marrow puncture revealed a marked decrease of erythroblasts and appearance of giant proerythroblasts. Thus, infection with human parvovirus B 19 (HPV-B 19) was suspected. At the onset of the disease, only IgM antibody was positive, but later IgG antibody also turned positive, and DNA of HPV-B19 was detected by polymerase chain reaction (PCR) from the bone marrow specimen of the patient. Then the patient was diagnosed with acute erythroblastic anemia due to infection with HPV-B19. In this case, DNA of HPV-B19 was detected by PCR from a fibrin sealant used during operation. The fibrin sealant was found to be the source of infection. Fibrin sealants are used widely in the domain of surgery. Therefore, we should perform screening of plasma and make examination of the sealants, while paying attention to infections with HPV-B 19 in the future.     

Parvovirus B19‐induced severe anemia in heart transplant recipients: Case report and review of the literature

We report a case of a 64‐year‐old woman who developed transfusion‐dependent anemia after cardiac transplantation, the etiology of which was unknown after initial comprehensive evaluation. At the suggestion of the Transplant Infectious Diseases consultant, microbial agents with red blood cell tropism pertinent to this patient such as Parvovirus B 19 (B19V) were investigated. The B19V viral load by PCR in peripheral blood was >100 000 000 copies/ml and after treatment with intravenous immunoglobulin (IVIG), her anemia resolved. Here, we summarize the clinical and virologic characteristics, treatment, and outcome of fifteen cases of B19V‐induced anemia in heart transplant recipients. Spontaneous recovery from anemia secondary to B19V has also been reported in some heart transplant recipients, possibly due to an absence of their B19V P‐antigen receptor and/or reduction in their immunosuppression. Therefore, in heart transplant patients, B19V should be suspected early as a cause of severe anemia of unknown etiology. The extent that B19V‐induced anemia is underdiagnosed in heart transplant recipients is unknown.     

Central nervous system vasculitis secondary to parvovirus B19 infection in a pediatric renal transplant patient

Central nervous system (CNS) vasculitis secondary to chronic parvovirus B19 (B19) infection presenting with recurrent neurological findings is a very rare disorder during childhood. Here we report a 12-year-old boy with a renal transplant who had chronic B19 infection with skin eruptions and recurrent episodes of encephalopathy with focal neurological deficits. B19 DNA was detected in blood, bone marrow, and skin biopsy specimens. Repeat cranial magnetic resonance (MR) imaging during each episode of encephalopathy showed variable focal findings, and MR angiography revealed vasculitic changes with narrowing of the cerebral arteries. We hypothesized that the CNS vasculitis might be associated with the chronic B19 infection. At the time of his fourth presentation with the same clinical findings, we administered intravenous immunoglobulin (IVIG) (1 g/kg per day, 2 consecutive days), which we continued for 6 months, at monthly intervals. IVIG therapy resulted in remission and has been effective not only for the clearance of B19, but also for the improvement of clinical and radiological findings of CNS vasculitis. We suggest that chronic B19 infection should be considered in immunocompromised patients with suspected CNS vasculitis. IVIG should be considered as a part of the treatment.     

Dual infection with human herpesvirus type 6 and parvovirus B19 in a renal transplant recipient

A 7-year-old boy developed intermittent fever and rashes 2 weeks after anti-lymphocyte globulin therapy for a transplant rejection episode. Dual infection with parvovirus B19 and human herpesvirus type 6 was suggested by serological tests. Neither virus has been reported previously in a symptomatic paediatric renal transplant recipient.