Symptomatic Parvovirus B19 Infection Research Articles

The impact of Parvovirus B19 on hereditary haemolytic anaemias.

The impact of Parvovirus B19 on hereditary haemolytic anaemias.

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 2g/kg over a period of 2-5days. A daily dose of 1g/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.

Réactivation d’une infection à parvovirus B19 chez une patiente infectée par le VIH

IntroductionInfection by human parvovirus B19 (erythrovirus B19) is common and usually asymptomatic during childhood conferring lasting protection against a new infection. Parvovirus B19 infection may cause erythema infectiosum (5th disease) and aplastic crisis. Secondary symptomatic parvovirus B19 infection in the same patient is rare and its physiopathology is not always clear. Case reportA 48-year-old HIV-infected female patient presented within 5years two acute episodes of parvovirus B19 infection although her CD4 cells count was above 500/mm3. Absence of specific antibodies production after the first episode and persisting parvovirus viremia suggested viral reactivation rather than re-infection. During the second episode, specific antibodies were produced. ConclusionSimilarly to most DNA viruses, parvovirus B19 reactivation is possible in HIV-infected patients while effectively treated by antiretroviral therapy.

Symptomatic parvovirus B19 infection caused by blood component transfusion

Although a risk of transfusion-transmitted human parvovirus B19V (TT-B19V) infection has been a concern, there have been very few reports of clinically relevant TT-B19V caused by the transfusion of a B19V-containing blood component. It has therefore been a matter of debate whether a universal B19V screening with an appropriate sensitivity is required. Through the Japanese Red Cross hemovigilance system, clinical reports on possible TT-B19V were collected from 1999 to 2008, during which B19V donor screening (sensitivity, 10(10) IU/mL) was conducted and repository blood samples from donors were available. Eight patients with TT-B19V caused by component transfusion have been identified. Four patients developed sustained anemia and pure red blood cell (RBC) aplasia and one patient developed pancytopenia. The underlying diseases in these five patients were either hematologic malignancy or hemolytic diseases. The viral loads of the responsible components for these cases ranged from 10(3) to 10(8) IU/mL. Two patients who underwent surgical treatment without any hematologic disorder exhibited only moderate symptoms. The B19V DNA sequence identity between a patient and the linked blood donor was confirmed in five of the eight patients. All of the components responsible for the eight cases were positive for anti-B19V immunoglobulin (Ig)M. Vulnerability to serious B19V-related hematologic disorders depended on the patient's underlying disease state of an enhanced erythropoiesis, not on the viral load of the component transfused. To prevent clinically relevant TT-B19V, a strategy is suggested in which patients at risk of acquiring RBC aplasia or pancytopenia are targeted.

Symptomatic, prolonged Parvovirus B19 infection and accompanying illness in otherwise healthy adults

Results In a 21-month period, 11 patients (7 females and 4 males), with a mean age of 36.9 (range 27-46) years with a symptomatic Parvovirus B19 infection were recorded and followed-up. Intrafamiliar exposure and occupational (health care) exposure were identified in two cases each. Clinical signs and symptoms included fever (100% of cases), polyarthralgia (90%), followed by headache (80%), anemia (70%), and rash. A mild-tomoderate myelosuppression of all hematological lines characterized 8 cases of 11 (72.7%), while increased serum transaminases were associated in 63.6% of patients. Three patients of ours deserved hospitalization (mean 10.8 days of admission), and five more cases were followed on Day-Hospital basis (for a median 75-day period); in four patients a treatment with i.v. highdosage human immunoglobulins was performed. Elevated levels of specific serum anti-Parvovirus B19 IgM antibodies were detected in all cases. In a 33-year-old female a severe anemia and a persisting headache, vomiting, and neck stiffness, led to RBC transfusion and a diagnosis of meningoencephalitis, with positive search of IgM antibodies and Parvovirus B19 viremia (detected by RT-PCR) in the cerebrospional fluid which lasted up to three months, despite treatment with i.v. serum immunoglobulins.

Symptomatic, long-term Parvovirus B19 infection in otherwise healthy adults

Background: Parvoviridae are part of air-, parenteral- and perinatal-transmitted ubiquitous viruses, whose associated signs and symptoms strongly depend on patient's age and immune defence. Methods: All cases of symptomatic Parvovirus B19 infection in otherwise healthy adults which came to our attention since spring 2006 were prospectively investigated and followedup. Results: In a 21-month period, 11 patients (7 females and 4 males), with a mean age of 36.9 (range 27-46) years with a symptomatic Parvovirus B19 infection were recorded and followed-up. Intrafamiliar exposure and occupational (health care) exposure were identified in two cases each. Clinical signs and symptoms included fever (100% of cases), polyarthralgia (90%), followed by headache (80%), anemia (70%), and rash. A mild-to-moderate myelosuppression of all hematological lines characterized 8 cases of 11 (72.7%), while increased serum transaminases were associated in 63.6% of patients. Three patients of ours deserved hospitalization (mean 10.8 days of admission), and five more cases were followed on Day-Hospital basis (for a median 75-day period); in four patients a treatment with i.v. highdosage human immunoglobulins was performed. Elevated levels of specific serum anti-Parvovirus B19 IgM antibodies were detected in all cases. In a 33-year-old female a severe anemia and a persisting headache, vomiting, and neck stiffness, led to RBC transfusion and a diagnosis of meningoencephalitis, with positive search of IgM antibodies and Parvovirus B19 viremia (detected by RT-PCR) in the cerebrospional fluid which lasted up to three months, despite treatment with i.v. serum immunoglobulins. Conclusion: Parvovirus B19 infection may play a significant role also in adult, immunocompetent subjects, and the disease sometimes is not mild and self-limiting, requiring admission and/or frequent outpatient interventions in a significant number of cases. The causes supporting a persistant infection in immunocompetent subjects have not been investigated to date, as well as the pathogenesis of myelosuppression and severe polyartrhalgia. Symptomatic Parvovirus B19 infection is still an underestimated clinical condition, and therapeutic perspectives are extremely limited until now. Abstracts for SupplementInternational Journal of Infectious DiseasesVol. 14Preview Full-Text PDF Open Archive

Parvovirus B19 in Solid Organ Transplant Recipients

Parvovirus B19 is a common, ubiquitous human pathogen.It is a small, single-stranded linear, nonenveloped DNAvirus classified into three different genotypes (genotype1, Au and Wi strains; genotype 2, LaLi and A6 strains; andgenotype 3, V9 strains). Its worldwide genetic variability islow, and there is no clear correlation between genotypeand distinctive clinical manifestation. Parvovirus B19 repli-cates most efficiently and preferentially in human erythro-cyte precursors; thus, the virus is classified as a memberof the Erythrovirus genus of the Parvoviridae family. Mostpeople are infected between the ages of 5 and 15 years;by adulthood, up to 80% are seropositive (1). Infection ap-pears to confer lifelong immunity to immunocompetenthosts, but reinfection is possible in a minority of cases(2). It has been hypothesized that Parvovirus B19 can per-sist in the bone marrow and other tissues (3), support-ing possible reactivation rather than reinfection in certainseropositive patients. Parvovirus B19 infection can be ei-ther symptomatic or asymptomatic, depending on the age,hematologic and immunologic status of the host. Whilemostpatientsrecollectonlynonspecificflu-likesymptoms,distinctive clinical entities have been associated with Par-vovirus B19 infection in both immunocompetent hosts (4)and solid organ transplant (SOT) recipients (5). The mostcommonclinicalmanifestationsofParvovirusB19aresum-marizedinTable1.Although large, prospective surveillance studies are lack-ing, earlier studies reported an incidence of Parvovirus B19disease of

Preexisting Psychological Stress Predicts Acute and Chronic Fatigue and Arthritis following Symptomatic Parvovirus B19 Infection

Psychological stress is thought to be an important factor in the pathogenesis of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). Therefore, we sought to examine this relationship in the context of parvovirus B19 infection. Thirty-nine patients with laboratory-documented acute parvovirus B19 infection were asked to complete questionnaires on negative life events, perceived stress, and negative affect relevant to the time of onset of parvovirus infection and during the preceding 12 months. These scores were combined into an overall stress index, which was then examined for associations with particular parvovirus-associated symptoms at acute infection and during the ensuing 1-3 years. Additional characteristics monitored included presence of parvovirus antibodies and nucleic acid, cortisol level, dehydroepiandrosterone level, autoantibodies, levels of a range of serum cytokines, and human leukocyte antigen class I and II alleles. Stress index was significantly associated with development of fatigue during the acute phase of parvovirus B19 infection and also with chronic fatigue and arthritis occurring 1-3 years following acute parvovirus B19 infection. Logistic regression that included all clinical variables indicated that a high stress index at the time of onset of infection was the primary predictor of CFS/ME 1-3 years following acute parvovirus B19 infection (odds ratio, 25.7; 95% confidence interval, 1.7-121.9; P=.005). We report a highly significant association between psychological stress and development of acute and chronic fatigue and arthritis several years following laboratory-documented acute parvovirus B19 infection.

Pathogenesis of Parvovirus B19 Infection: Host Gene Variability, and Possible Means and Effects of Virus Persistence

Since conducting follow-up studies of patients with acute symptomatic parvovirus B19 infection which showed that a significant proportion of patients develop prolonged arthritis and chronic fatigue syndrome (CFS), we have become interested in the mechanisms of this phenomenon. We showed that these cases have high levels of pro-inflammatory cytokines in their circulation and that this correlates with the symptoms. However, the underlying mechanisms were not apparent, and we have used various approaches to begin studying this phenomenon. DNA polymorphisms were looked for and several were shown to be more common in these subjects compared with controls; these occur within genes of both the immune response [human leucocyte antigen (HLA)-DRB1, HLA-B, transforming growth factor (TGF)-beta1] and those involved in several other cellular functions (predominantly the cytoskeleton and cell adhesion). Interestingly, one particular single-nucleotide polymorphism (SNP) which is associated with symptomatic B19 infection occurs in the Ku80 gene which has recently been shown to be a B19 co-receptor. B19 persistence is probably the key to this phenomenon, and some new data are presented on short regions of sequence homology (17-26 bp) between human, mouse and rat parvoviruses and their respective hosts which occur in many host genes. This homology may provide a foothold for virus persistence and may also play a role in the genesis of disease through gene disruption. Finally, we used microarrays and TaqMan real-time polymerase chain reaction in 108 normal persons to study human gene expression in persons who are B19-seropositive versus B19-seronegative (age- and sex-matched) to examine the hypothesis that gene regulation may be altered in subjects harbouring the B19 virus DNA. Six genes were found to be differentially expressed with roles in the cytoskeleton (SKIP, MACF1, SPAG7, FLOT1), integrin signalling (FLOT1, RASSF5), HLA class III (c6orf48), and tumour suppression (RASSF5). These results have implications not only for B19 but also for other persistent viruses as well and confirmation is required. In conclusion, these disparate findings contribute to our understanding of the pathogenesis of B19 disease. We are using these studies as a starting point to study the phenomenon of chronic immune activation following B19 infection.

Circulating cytokines and chemokines in acute symptomatic parvovirus B19 infection: negative association between levels of pro-inflammatory cytokines and development of B19-associated arthritis.

The aim of the study was to characterise the profile and clinical correlates (arthritis, rash, and fatigue) of cytokines, chemokines, and other mediators in symptomatic acute parvovirus B19 infection. Serum was examined from cases of acute B19 infection (as defined by serum anti-B19 IgM positivity) (n = 84), and in normal persons (n = 43) for B19 markers (serum B19 antibodies and DNA), rheumatoid factor (RF), and antinuclear antibody (ANA). A panel of cytokines/chemokines was measured in duplicate using the Bioplex Protein Array system (BioRad Hemel Hempstead, UK). These included interleukin-1 beta (IL-1 beta), IL-4, IL-5, IL-6, IL-8, IL-13, tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), macrophage chemoattractant protein-1 (MCP-1), granulocyte-monocyte colony stimulating factor (GM-CSF), transforming growth factor-beta1 (TGF-beta 1), endothelin-1 (ET-1), and neopterin. Acute symptomatic infection was characterised by specific IgG positivity (83%), serum B19 DNA positivity (96%), and raised levels of IL-4, IL-6, IL-8, TNF-alpha, IFN-gamma, MCP-1, GM-CSF, TGF-beta 1, and ET-1. Patients with acute B19-associated arthritis were found to have lower levels of IL-6, TNF-alpha, and GM-CSF than patients without arthritis, while those with rash had lower levels of TGF-beta 1. It is concluded that cytokine levels following acute symptomatic infection with parvovirus B19 indicate a state of immune activation. The profile of circulating mediators may provide insights into the possible pathogenesis of particular clinical manifestations of this infection.

Cytokine gene polymorphisms associated with symptomatic parvovirus B19 infection

Background: The immune system has been implicated in the pathogenesis of certain clinical manifestations of parvovirus B19 infection, including rash and arthralgia. Cytokines feature in the pathogenesis of parvovirus B19...

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.

Transmission of symptomatic parvovirus B19 infection by fibrin sealant used during surgery: M. Hino, O. Ishiko, K. Honda, et al. Br J Haematol 108:194–195, 2000

Transmission of symptomatic parvovirus B19 infection by fibrin sealant used during surgery: M. Hino, O. Ishiko, K. Honda, et al. Br J Haematol 108:194–195, 2000

Transmission of symptomatic parvovirus B19 infection by fibrin sealant used during surgery.

Human parvovirus B19 infection has been shown to be transmissible by blood and blood products and to result in transient aplastic crisis in patients with rapid red cell turnover. We report three cases of iatrogenic parvovirus B19 infection resulting from the use of the same batch of fibrin sealant under operation. Fibrin sealant, which is a typical haemostatic agent produced from blood, has been used during surgery. Human parvovirus is resistant to existing virus-inactivating techniques, suggesting that infection may occur from blood products contaminated with it. Use of recombinant products for these proteins may thus be necessary.

Symptomatic parvovirus B19 infection of one fetus in a twin pregnancy.

Twin pregnancies complicated by infection due to parvovirus B19 are uncommon. We report a case in which only one fetus developed a symptomatic infection, which presented at first as ascites and pleural effusion; later, meconium peritonitis developed. Hydrops spontaneously resolved, and at birth meconium peritonitis was successfully treated with surgery. However, even with the positive outcome of this pregnancy, a long-term follow-up is needed to exclude damage other than injury to the erythropoietic system.