Healthcare costs of congenital cytomegalovirus (cCMV) disease in infants during the first two years of life: a retrospective German claims database analysis.

BACKGROUND: Congenital cytomegalovirus (cCMV) infection can cause severe neurological damage, growth retardation, hearing loss, and microcephaly in infants. We aimed at assessing healthcare costs of infants with recorded cCMV diagnosis in an administrative claims database in the first 2 years of life. METHODS: We conducted a retrospective, controlled cohort study using German claims data from the Institute for Applied Health Research Berlin (InGef) database. Incremental healthcare costs during the first and second year of life were assessed by matching (1:60) infants with cCMV diagnoses ≤ 90 days after birth (cCMV90 cohort) to infants without cCMV diagnosis ("representative" controls) and infants with cCMV diagnoses ≤ 21 days after birth plus specific symptoms (cCMV21-S) to infants without cCMV and any ICD-10-GM records (besides Z00-Z99) until 4th preventive health check-up ("healthy" controls). Due to missing data, mean imputation was applied for aids and remedies costs. RESULTS: We identified 54 and 24 infants born 2014-2018 for the cCMV90 and cCMV21-S cohorts, respectively. During the first year, mean (median) healthcare costs were significantly higher in cCMV90 cases vs. "representative" controls (€22,737 (€9759) vs. €3091 (€863), p < 0.001), with 87.2% inpatient costs. Healthcare costs for cCMV21-S cases compared to "healthy" controls were €34,498 (€20,924) vs. €680 (€569), p < 0.001. Differences decreased for both comparisons in the second year but remained statistically significant. CONCLUSIONS: cCMV comprises a considerable economic burden for the German healthcare system (€19,646 to €33,818 higher mean costs for infants with recorded cCMV diagnosis in the first year of life). Attempts should be made to reduce this burden.

Structure of Parvovirus B19 Decorated by Fabs from a Human Antibody.

Parvovirus B19, one of the most common human pathogens, is a small DNA virus that belongs to the Parvoviridae As a result of previous infections, antibodies to B19 are present in most adults. B19 has a strong tropism to erythroid progenitor cells and is able to cause a series of medical conditions, including fifth disease, arthritis, myocarditis, hydrops fetalis, and aplastic crisis. No approved vaccine is currently available for B19, and there is a lack of structural characterization of any B19 epitopes. Here we present the first cryo-electron microscopy (cryo-EM) structure of a B19 virus-like particle (VLP) complexed with the antigen-binding fragment (Fab) of a human neutralizing antibody, 860-55D. A model was built into the 3.2-Å-resolution map, and the antigenic residues on the surface of the B19 capsid were identified. Antibody 860-55D bridges the capsid of B19 by binding to a quaternary structure epitope formed by residues from three neighboring VP2 capsid proteins.IMPORTANCE Parvovirus B19 is a common human pathogen and a particular threat to children, pregnant women, and patients with sickle cell disease or AIDS. Currently, neutralizing antibody is the most efficient treatment for acute B19 infections. Research on the antigenic properties of B19 will guide the usage of these antibodies and facilitate vaccine development. We have determined and report here the high-resolution structure of B19 virus-like particles (VLPs) complexed with the Fab of a human neutralizing antibody. The structure shows a quaternary structure epitope formed by three VP2 proteins and provides details on host recognition of human B19 virus.

Persistent pure red cell aplasia in dicygotic twins with persistent congenital parvovirus B19 infection-remission following high dose intravenous immunoglobulin.

UNLABELLED: We report the course of dicygotic twins born preterm after 29 (4)/7 weeks of gestation due to congenital Parvovirus B19 infection causing fetal hydrops with severe anemia in one infant in whom intrauterine transfusion was impossible to perform and high levels of viremia in both infants. After being discharged, they were readmitted at 3 months of age with critical aplastic crisis. Therapy with intravenous immunoglobulin infusion resulted in decreasing viremia followed by stable hemoglobin levels in both infants. CONCLUSION: Intravenous immunoglobulin treatment of congenital pure red cell aplasia due to Parvovirus B19 infection in preterm infants seems to be effective to introduce viral remission and to normalize erythropoiesis.

Burden of sequelae and healthcare resource utilization in the first year of life in infants born with congenital cytomegalovirus (cCMV) infection in Germany: A retrospective statutory health insurance claims database analysis.

BACKGROUND: Congenital cytomegalovirus (cCMV) infection can have a broad range of manifestations. This study aimed to assess cCMV-associated sequelae and healthcare resource utilization (HCRU) in infants during the first year of life in Germany. METHODS: A retrospective, controlled cohort study using German claims data from the Institute for Applied Health Research Berlin (InGef) database was conducted. cCMV-associated sequelae and HCRU during the first year of life were assessed by matching (1:60) infants with at least one inpatient/outpatient cCMV diagnosis (ICD-10-GM: P35.1) ≤90 days after birth (cCMV90 cohort) and infants with at least one inpatient cCMV diagnosis plus specific sequelae ≤21 days after birth (cCMV21-S) to infants without cCMV or CMV (ICD-10-GM: B25) diagnosis (control group), respectively. Outcomes were analyzed during the first 365 days of life. RESULTS: Between 2014-2018, we identified 54 newborns for cCMV90 and 24 newborns for cCMV21-S cohort. Compared to the 3,240 and 1,440 controls, respectively, more cCMV90 infants (83.3% vs. 41.9%, p<0.01) presented with at least one sequela during the first year of life, including intrauterine growth retardation (42.6% vs. 5.3%, p<0.01), sensorineural hearing loss (SNHL) to deafness (38.9% vs. 2.2%, p<0.01), and motor development disorders (33.3% vs. 10.9%, p<0.01). Further, 13.0% of cCMV90 infants (vs. 2.3%, p<0.01) suffered from visual impairment. In cCMV21-S cohort, intrauterine growth retardation (79.2% vs. 6.0%, p<0.01), prematurity (54.2% vs. 7.3%, p<0.01), and motor development disorders (50.0% vs. 11.0%, p<0.01) were the most frequent sequelae. Infants in the cCMV90 and cCMV21-S cohort had, on average, 7.3 times and 9.5 times more hospitalizations and 2.0 times and 2.1 times more outpatient physician visits than their respective controls (p<0.01). Hospitalized infants with cCMV stayed, on average, significantly longer in hospital compared to their controls (cCMV90 cohort: 30.3 days vs. 9.0 days, p<0.01; cCMV21-S cohort: 46.5 days vs. 9.3 days, p<0.01). CONCLUSIONS: cCMV-infection shows a considerable disease and healthcare burden during the first year of life. More than 80% of the identified newborns with cCMV suffered from at least one associated sequela during the first year of life, including long-term sequelae such as SNHL (40%) and visual impairment (13%). Additional steps for prevention of cCMV infection and associated sequelae as well as a comprehensive monitoring of disease burden are needed.

Congenital Cytomegalovirus Infection: A Narrative Review of the Issues in Screening and Management From a Panel of European Experts.

Maternal primary and non-primary cytomegalovirus (CMV) infection during pregnancy can result in in utero transmission to the developing fetus. Congenital CMV (cCMV) can result in significant morbidity, mortality or long-term sequelae, including sensorineural hearing loss, the most common sequela. As a leading cause of congenital infections worldwide, cCMV infection meets many of the criteria for screening. However, currently there are no universal programs that offer maternal or neonatal screening to identify infected mothers and infants, no vaccines to prevent infection, and no efficacious and safe therapies available for the treatment of maternal or fetal CMV infection. Data has shown that there are several maternal and neonatal screening strategies, and diagnostic methodologies, that allow the identification of those at risk of developing sequelae and adequately detect cCMV. Nevertheless, many questions remain unanswered in this field. Well-designed clinical trials to address several facets of CMV treatment (in pregnant women, CMV-infected fetuses and both symptomatic and asymptomatic neonates and children) are required. Prevention (vaccines), biology and transmission factors associated with non-primary CMV, and the cost-effectiveness of universal screening, all demand further exploration to fully realize the ultimate goal of preventing cCMV. In the meantime, prevention of primary infection during pregnancy should be championed to all by means of hygiene education.

Prevalence of parvovirus B19 and human bocavirus DNA in the heart of patients with no evidence of dilated cardiomyopathy or myocarditis.

BACKGROUND: Although the DNA of parvovirus B19 (B19V) is frequently detected in patients with dilated cardiomyopathy or myocarditis, whether the parvovirus causes disease is questionable, since even in healthy individuals the virus persists in various tissues. The same question applies to human bocavirus (HBoV). We have determined the prevalence and quantity of B19V and HBoV DNA in heart tissue of patients who were not experiencing virus-related heart diseases and analyzed whether the seroprevalence corresponded to DNA prevalence in the heart. METHODS: Samples of left-atrium heart tissue and serum were obtained from 100 patients who underwent open-heart surgery. Serum immunoglobulin (Ig) G and IgM against proteins encoded by B19V and HBoV were detected by enzyme-linked immunoabsorption assay and immunoblotting. B19V and HBoV DNA concentrations were determined by quantitative real-time polymerase chain reaction (PCR) in heart tissue and serum samples. Nested PCRs for VP1, K71, and GT3 identified the B19V genotypes. RESULTS: The prevalences of serum IgG specific for B19V and HBoV were 85% and 96%, respectively. Of all the patients, 85% had B19V DNA detected in heart tissues, and 4% displayed low-level B19V viremia, whereas only 5% of heart tissue samples and none of the serum samples demonstrated HBoV DNA. The sensitivity of B19V serological testing for B19V DNA in heart samples was 0.96 (95% confidence interval, 0.92-1.0). Specificity was 0.8 (95% confidence interval, 0.6-1.0), and the positive predictive value was 0.96 (95% confidence interval, 0.92-1.0). B19V genotypes 1 and 2 were present in 11% and 89% of heart tissues samples, respectively. B19V genotype 3 was not detected in any of the samples. CONCLUSIONS: Our data suggest that B19V but not HBoV demonstrates a lifelong persistence in the heart. The detection of B19V DNA in heart tissue showed no correlation with clinical symptoms. We strongly recommend that serological testing become a standardized procedure for future studies, to obtain representative data concerning the prevalence of B19V in the heart.

Visualization of the externalized VP2 N termini of infectious human parvovirus B19.

The structures of infectious human parvovirus B19 and empty wild-type particles were determined by cryoelectron microscopy (cryoEM) to 7.5-A and 11.3-A resolution, respectively, assuming icosahedral symmetry. Both of these, DNA filled and empty, wild-type particles contain a few copies of the minor capsid protein VP1. Comparison of wild-type B19 with the crystal structure and cryoEM reconstruction of recombinant B19 particles consisting of only the major capsid protein VP2 showed structural differences in the vicinity of the icosahedral fivefold axes. Although the unique N-terminal region of VP1 could not be visualized in the icosahedrally averaged maps, the N terminus of VP2 was shown to be exposed on the viral surface adjacent to the fivefold beta-cylinder. The conserved glycine-rich region is positioned between two neighboring, fivefold-symmetrically related VP subunits and not in the fivefold channel as observed for other parvoviruses.

Adaptive immune responses against parvovirus B19 in patients with myocardial disease.

BACKGROUND: Parvovirus B19 (B19V)-DNA is frequently detected in endomyocardial biopsies (EMBs) from patients with acute myocarditis (AMC) and dilated cardiomyopathy (DCM), but also in various healthy tissues. The clinical relevance of this DNA-persistence is unclear. OBJECTIVES: To investigate potential pathogenic influences of B19V-DNA in EMBs, we analyzed B19V-specific adaptive immune responses in AMC/DCM patients and healthy controls. STUDY DESIGN: 15 AMC/DCM patients with detectable B19V-DNA in EMBs and 51 controls were analyzed for signs of acute B19V-infections and virus-specific immune responses by PCR, ELISA, Western line, and ELISpot-assays. RESULTS: Productive B19V-infection was determined in three patients. Slightly lower levels of B19V-specific T-cells were observed in patients as compared to the controls, no differences were observed in virus-specific serology. Viral DNA-load in EMBs could not be correlated to the number of B19V-specific T-cells. No differences in T-cell response, viremia and/or serological markers indicative for viral pathogenesis were observed in patients with inflammatory cardiomyopathy. CONCLUSIONS: Discrepancies in B19V-specific adaptive immunity were not observed in AMC/DCM patients as compared to controls. The data indicate that the exclusive detection of B19V-DNA in EMBs is not sufficient to associate B19V with AMC/DCM but should be complemented with additional virological and immunological parameters in further studies.

Generation of multifunctional murine monoclonal antibodies specifically directed to the VP1unique region protein of human parvovirus B19.

Little is known about the VP1unique region (VP1u), a part of one major capsid protein of human parvovirus B19 (B19), concerning its involvement in viral replication and infection cycle. Showing a phospholipase A2 (PLA2)-like activity, which is discussed to be necessary for viral release from host cell, its precise function remains unclear. The purpose of this study was to generate multifunctional monoclonal antibodies (mabs) for different applications that may be useful in investigating VP1u's relevance. To establish antiVP1u antibodies, spleen cells from Balb/c mice immunized with purified recombinant viral protein were used for generating antibody-producing hybridoma cell lines. Usability of the antibodies was tested in enzyme-linked immunosorbent assay (ELISA), Western-blot analysis, immunofluorescence and an inhibition assay of enzymatic activity of PLA2. Three hybridoma cell lines secreting mab's specifically directed against the VP1u protein of B19 could be generated and functioned in every screening method used in this study. These antibodies are helpful tools for investigations in B19 research and diagnosis. Furthermore, the antibodies could help in gaining a deeper understanding of VP1u's role in viral replication and infection especially in the importance of its constitutive PLA2-like activity.

Clinical and epidemiological aspects of human bocavirus infection.

Human bocavirus was recently described as a novel member of the Parvoviridae to infect humans. Based on accumulating clinical and epidemiological data the virus is currently being associated with respiratory infections in young children and infants and is furthermore discussed as causative agent of gastrointestinal illness.

Human bocavirus--a novel parvovirus to infect humans.

For almost three decades parvovirus B19 has been described as the only member of the Parvoviridae to infect and cause illness in humans. This statement was correct until 2005 when a group of Swedish scientists identified a previously uncharacterized virus in pools of human nasopharyngeal aspirates obtained from individuals suffering from diseases of the respiratory tract. Comprehensive sequence and phylogenetic analysis allowed the identification of the new virus as a member of the Parvoviridae. Based on its close relation to the minute virus of canines and the bovine parvovirus, it was named human bocavirus (HBoV). Since the identification of HBoV, viral genomes have been frequently detected worldwide in nasopharyngeal swabs, serum and fecal samples almost exclusively derived from young children with various symptoms of the respiratory or the gastrointestinal tract. The detection of HBoV genomes tends to be associated with elevated rates of coinfections with further respiratory viruses, e.g. respiratory syncytial virus or metapneumovirus. First studies on virus-specific immune responses have described the presence of ubiquitous humoral and cellular immune reactions against HBoV in adults and adolescents, indicating a high seroprevalence of this new virus in humans.

Parvovirus B19 profiles in patients presenting with acute myocarditis and chronic dilated cardiomyopathy.

BACKGROUND: Parvovirus B19 (B19V) is the most prevalent cardiotropic virus in endomyocardial biopsies (EMBs) from patients presenting with acute myocarditis (AMC) and chronic dilated cardiomyopathy (DCM). We elucidated the role of B19V specific IgG and IgM antibodies against native VP2-capsids and denatured VP1-, VP2- and NS1-proteins, which discriminate disease acuity in other B19V related diseases, in patients presenting with clinically suspected AMC and DCM for the determination of the viral infection stage. MATERIAL/METHODS: n=62 prospectively enrolled AMC (n=33) and DCM (n=29) patients were investigated. B19V genomes were amplified in EMBs by nested PCR (nPCR). B19V-specific IgG and IgM were investigated by recomLine blots in the sera. RESULTS: B19V genomes were detectable by nPCR with comparable frequencies in AMC (63.6%) and DCM patients (51.7%), respectively. IgM antibodies were detectable in 18.1% of the AMC, but not in DCM patients. In patients with myocardial B19V infection, antibody profiles indicating recent infections were more frequent in AMC (47.6%) compared with DCM patients (6.7%), while persistent/reactivating profiles were significantly more prevalent in DCM (20.0%) compared with AMC (0%) patients (p<0.05). CONCLUSIONS: IgM B19V antibodies can be detected primarily in AMC, but not in DCM patients. The discrimination of the B19V specific IgG antibodies using recomLine blots may be suitable to distinguish acute versus chronic, and persistent/reactivating infection status in patients with myocardial B19V infection.

Different patterns of disease manifestations of parvovirus B19-associated reactive juvenile arthritis and the induction of antiphospholipid-antibodies.

Children with rheumatic oligo- and polyarthritis frequently establish persistent parvovirus B19 infections, which may be associated with the production of antiphospholipid antibodies. Reported in this paper are the data of five girls with polyarticular rheumatic diseases of different types and persistent parvovirus B19 infection associated in four cases with the presence of antibodies against phospholipids. Clinical parameters, virus load, and antiphospholipid-IgG levels were determined during an observation period up to 92 months. In two patients, erythema infectiosum preceded the development of arthritis and B19 viremia persisted. Two other girls showed antibodies against parvoviral structural proteins at time of the manifestation of the rheumatic disease. Subsequent samples also revealed persistent B19 infection. In the fifth patient, parvovirus B19-specific IgG antibodies were detected for the first time after 120 months of progressing disease at an age of 11 1/2 years. Five years later, quantitative polymerase chain reaction (PCR) revealed viral DNA. In a synovial tissue specimen subsequently obtained, parvovirus B19 structural proteins could be detected by immunohistochemistry. Three of five patients recovered completely without severe sequels. One patient is in remission under immunosuppressive therapy. The fifth patient suffers from progressive erosions despite intensive therapeutical efforts. In consequence, parvovirus B 19 should generally be taken into consideration as a trigger of various forms of juvenile arthritis and persistence of infection should be evaluated.

Human parvovirus B19 infection and antiphospholipid antibodies.

Erythema infectiosum is the main manifestation of human parvovirus B19 infections. Further B19-related diseases commonly associated with the acute infection are flue-like symptoms, transient aplastic crisis, transient arthralgias, leukopenia and thrombocytopenia, spontaneous abortion and hydrops fetalis in pregnant women. Hepatitis, myocarditis, meningitis, encephalitis as well as pure red cell anemia may occur occasionally. In addition parvovirus B19 infections have been frequently described as cause or trigger of various forms of autoimmune diseases affecting all blood cell lines, joints, connective tissue, uvea, large and small vessels. Molecular mimicry may be one major contribution to the appearance of autoimmune antibodies, f.e. antiphospholipid and antineutrophil cytoplasmic antibodies as well as antinuclear antigens. These mechanisms implicated in the pathogenesis of parvovirus B19 triggered autoimmune diseases, especially focused on the development of antiphospholipid antibodies will be discussed in this short review.

Are antiphospholipid antibodies an essential requirement for an effective immune response to infections?

Antiphospholipid antibodies show a close association to a variety of infections. Recent data implicate that parvovirus B19 may be used as a model-system for studying the interaction of viral infection and the development of these autoantibodies. B19-related diseases commonly associated with the acute infection show flu-like symptoms, transient arthralgias, leukopenia and thrombocytopenia, and, in pregnant women, spontaneous abortion and hydrops fetalis. Hepatitis, myocarditis, meningitis, encephalitis, as well as pure red cell anemia may occur occasionally. In addition, parvovirus B19 infections have been frequently described as the cause or trigger of various forms of autoimmune diseases affecting all blood cell lines, joints, connective tissue, uvea, and large and small vessels. Molecular mimicry may be one major contribution to the appearance of autoimmune antibodies, for example, antiphospholipid and antineutrophil cytoplasmic antibodies as well as antinuclear antigens. These mechanisms implicated in the pathogenesis of parvovirus B19-triggered autoimmune diseases, especially focused on the development of antiphospholipid antibodies, will be discussed in this mini review.

Impact of Parvovirus B19 Viremia in Liver Transplanted Children on Anemia: A Retrospective Study.

Acute parvovirus B19 (B19V) infection in immunocompromised patients may lead to severe anemia. However, in adult transplant recipients, B19V reactivations without anemia and low-level viremia are common. The impact of B19V in pediatric transplant patients, with high risk of primary infection, is investigated here. In a six-month period, 159 blood samples of 54 pediatric liver transplant recipients were tested for B19V DNA by quantitative real-time PCR. Viremia was correlated with anemia and immunosuppression and compared with rates in adult transplant recipients. B19V DNA was detected in 5/54 patients. Primary B19V infections were observed in four patients prior to and in one patient after transplantation. Rates of viremia were significantly higher in pediatric recipients than in adults. Prolonged virus shedding after primary infection prior to transplantation accounts for most viremic cases. Anemia was significantly more frequent in samples from viremic patients, but remained mild. In 15% of anemic samples, B19V DNA was detected. Therefore, in anemic pediatric transplant recipients, diagnostics for B19V seem reasonable.

Parvovirus B19 infection and autoimmune disease.

Human parvovirus B19 infections may cause a widespread benign and self-limiting disease in children and adults, known as erythema infectiosum or fifth disease. A variety of further manifestations are associated with the infection such as arthralgias, arthritis, leukopenia and thrombocytopenia, anemia and vasculitis, spontaneous abortion and hydrops fetalis in pregnant women. Both in children and adults parvovirus B19 infections have been frequently implicated as a cause or trigger of various forms of autoimmune diseases affecting joints, connective tissue and large and small vessels. In addition, autoimmune neutropenia, thrombocytopenia and hemolytic anemia are known as sequelae of B19 infection. The molecular basis of the autoimmune phenomena and resultant pathogenesis is unclear. The involvement of molecular mimicry between cellular and viral proteins, the induction of enhanced cytokine production via the viral transactivator protein NS1 and the phospholipase A2-like activity of the capsid protein VP1 may contribute to the induction of autoimmune reactions. All the known data and the potential mechanisms involved in the pathogenesis will be discussed in this review.

Long-term parvovirus B19 viraemia associated with pure red cell aplasia after allogeneic bone marrow transplantation.

BACKGROUND: Parvovirus B19 infection is associated with a variety of symptoms like erythema infectiosum, anaemia and arthritis. In immunocompetent persons, viraemia is usually cleared a few weeks after infection. OBJECTIVE: An immunocompromised adult female patient was persistently infected with B19 after allogenic bone marrow transplantation (BMT) and developed chronic anaemia. STUDY DESIGN: B19-specific antibodies were determined by ELISA and viral load was assessed using a quantitative real time B19 PCR. The patient was evaluated clinically. RESULTS: Two years after successful BMT, the patient received intensified immunosuppressive treatment, erythropoetin and erythrocyte concentrates due to chronic graft-versus-host disease with renal failure. Despite of this treatment, the aplastic anaemia worsened. PCR revealed B19 viraemia with 10(12) geq/ml serum. After 7 months of repeated applications of immunoglobulins and reduction of immunosuppressive treatment, reticulocyte counts and haemoglobin levels normalized and the viral load finally dropped to 10(3) geq/ml serum. One of the back-up samples of the erythrocyte concentrates tested positive, the respective transfusion had been applied 2 months after the beginning of viraemia. CONCLUSIONS: The source of the primary infection remained unclear, but at least re-infection by blood transfusion is likely. Treatment did not result in virus elimination from peripheral blood but in resolvement of symptoms.

Chronic human parvovirus B19 infection in rheumatic disease of childhood and adolescence.

Parvovirus B19 causes erythema infectiosum in children, but the virus is associated with an increasing range of different diseases. About 20% of infections are associated with delayed virus elimination and viremia persisting over several months or years. These persistent B19-infections are characterised by the presence of IgG against the non-structural protein NS1. This study aimed to find further evidence for an association of parvovirus B19 persistence with VP1/2- and NS1-specific IgG-antibodies in children suffering from rheumatic diseases of childhood. Forty-eight children and adolescents with joint complaints lasting longer than 1 year including patients with juvenile systemic sclerosis and juvenile dermatomyositis showed antibodies against the viral NS1-protein. Laboratory markers of inflammation, humoral immune response against parvovirus B19 proteins and the presence of viral genomes in patients' sera as well as in 124 healthy children were investigated. Almost 50% of the patients showed laboratory signs of chronic inflammation. B19-DNA was amplified in 31% of patients' sera and 7% of the controls (P<0.0001). VP2-specific IgM was detectable in 50% of the patients' and 6% of control sera. NS1-specific immune reactions were linked to persistent B19-infection as indicated by the presence of viral genomes in the peripheral blood and of VP2-specific IgM years after disease onset. To estimate the severity of the disease and the clinical course, the number of affected and functionally impaired joints were noted and compared with the records from patients' initial visit in the hospital. Disease related complications were registered. Impairment of activities of daily living was assessed by Childhood Health Assessment Questionnaire (CHAQ)- and Munich Quality of Life Questionnaire (KINDL)-tests. During observation the clinical state of four patients worsened, 27 improved, the others remained stable. Twenty-four children were restricted in their daily activities.

Low-level DNAemia of parvovirus B19 (genotypes 1-3) in adult transplant recipients is not associated with anaemia.

BACKGROUND: After acute parvovirus B19 (B19V) infection of immunocompetent individuals, viral genomes persist lifelong in various tissues. In immunocompromized patients, acute B19V infection may be associated with severe anaemia. It is unclear whether reactivation of latent B19V DNA may contribute to persistent viraemia and anaemia in transplant recipients. OBJECTIVE AND STUDY DESIGN: We retrospectively analysed the impact of B19V infection in 371 adult transplant recipients (kidney, liver, heart, bone marrow). The patients' pre-transplantation serostatus was determined. 1431 sera or plasmas obtained in monthly intervals during six months following transplantation were analysed for the presence of B19V DNA by quantitative PCR which allows discrimination between B19V genotypes 1-3. RESULTS: Overall, 82% of the patients were seropositive. B19V DNA (<600-1100 geq/ml) was detected in 4.0% of patients and classified as genotype 1 in 12, genotype 2 in one and genotype 3 in two patients. Whereas 5.5%, 6.7% and 5.7% of liver, heart and bone marrow recipients displayed DNAemia, viral genomes were detected only in 1.4% of kidney recipients. Haemoglobin levels and reticulocyte counts showed no differences between DNAemic and non-DNAemic patients. In a control group of 120 healthy subjects, 78% were seropositive and 2.5% displayed DNAemia. CONCLUSIONS: Prevalence and level of B19V DNAemia in adult transplant recipients was comparable to that observed in healthy individuals, but with a distinct accumulation within the first weeks post-transplantation. The presence of low-level DNAemia in transplant recipients was not associated with anaemia.