Aims: To investigate the association of acute parvovirus B19 infection with new onset of acute lymphoblastic and myeloblastic leukaemia. Methods: Cerebrospinal fluid (CSF) samples from patients with acute myelogenous leukaemia (AML) at diagnosis (n = 2) and acute lymphoblastic leukaemia (ALL) at diagnosis (n = 14) were analysed for parvovirus B19 DNA by means of nested polymerase chain reaction. In addition, samples from patients with benign intracranial hypertension (BIH) (n = 10) and hydrocephalus (n = 13) were tested as controls.Results: Four leukaemia cases were positive-common ALL (n = 2), null cell ALL (n = 1), and M7 AML (n = 1)-whereas all controls were negative (Yates corrected x 2 value, 3.97; p = 0.046; odds ratio, 16.92; confidence interval, 1.03 to 77.18). All four patients were significantly anaemic, but none was encephalitic or had evidence of central nervous system leukaemia. In three of these patients, serum tumour necrosis a, interferon c, interleukin 6, granulocyte-macrophage colony stimulating factor (range, 34.93-3800.06 pg/ml), and macrophage chemoattractant protein 1 were detectable. All of these four patients carried at least one of the HLA-DRB1 alleles, which have been associated with symptomatic parvovirus B19 infection. Conclusion: Erythroid suppression and immune cell proliferation are both associated with B19 infection and may also be important in the pathogenesis of acute leukaemia. P arvovirus B19 is the aetiological agent of erythema infectiosum, transient bone marrow aplastic crises, arthritis, non-immune hydrops fetalis, and chronic pure red cell aplasia in immunocompromised persons. More than 20 reports describe an association between acute lymphoblastic leukaemia (ALL) and persistent B19 infection which, until recently, has been assumed to represent an opportunistic infection, the chronicity of which results from immunosuppression. However, several reports describe B19 infection preceding and mimicking ALL.

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.

Antibodies to parvovirus B19 NS1 protein are associated with chronic but not with acute arthritis after B19 infection.

Three cases of chronic fatigue syndrome (CFS) that followed acute parvovirus B19 infection were treated with a 5-day course of intravenous immunoglobulin (IVIG; 400 mg/kg per day), the only specific treatment for parvovirus B19 infection. We examined the influence of IVIG treatment on the production of cytokines and chemokines in individuals with CFS due to parvovirus B19. IVIG therapy led to clearance of parvovirus B19 viremia, resolution of symptoms, and improvement in physical and functional ability in all patients, as well as resolution of cytokine dysregulation.