Original Research: Parvovirus B19 infection in children with sickle cell disease in the hydroxyurea era

Abstract

Parvovirus B19 infection causes transient aplastic crisis in sickle cell disease (SCD) due to a temporary interruption in the red blood cell production. Toxicity from hydroxyurea includes anemia and reticulocytopenia, both of which also occurring during a transient aplastic crisis event. Hydroxyurea inhibits proliferation of hematopoietic cells and may be immunosuppressive. We postulated that hydroxyurea could exacerbate parvovirus B19-induced aplastic crisis and inhibit the development of specific immune responses in children with SCD. We conducted a retrospective review of parvovirus B19 infection in 330 children with SCD. Altogether there were 120 known cases of aplastic crisis attributed to parvovirus B19 infection, and 12% of children were on hydroxyurea treatment during the episode. We evaluated hematological and immune responses. Children with HbSS or HbSβ0-thalassemia treated with hydroxyurea, when compared with untreated children, required fewer transfusions and had higher Hb concentration nadir during transient aplastic crisis. Duration of hospital stays was no different between hydroxyurea-treated and untreated groups. Children tested within a week following aplastic crisis disease were positive for parvovirus-specific IgG. Immune responses lasted for the duration of the observation period, up to 13 years after transient aplastic crisis, and there were no repeat aplastic crisis episodes. The frequencies of parvovirus-specific antibodies in all children with SCD increased with age, as expected due to the increased likelihood of a parvovirus exposure, and were comparable to frequencies reported for healthy children. Approximately one-third of children had a positive parvovirus B19-specific IgG test without a documented history of transient aplastic crisis, 64% of them were treated with hydroxyurea. Hydroxyurea may reduce requirements for blood transfusions and may attenuate symptoms during transient aplastic crisis episodes caused by parvovirus B19 infections. Children with SCD, whether treated or untreated with hydroxyurea, generate sustained and protective parvovirus B19-specific immune responses.

Saccharomyces cerevisiae -derived virus-like particle parvovirus B19 vaccine elicits binding and neutralizing antibodies in a mouse model for sickle cell disease

“…[17], who showed that children with SCD respond well to an influenza virus vaccine. The animal model results are also consistent with our own observations that children with SCD respond well immunologically to parvovirus B19 antigens after a natural infection, and that parvovirus sero-prevalence is similar between children with SCD and their unaffected counterparts [18]. Importantly, we noted that IgG responses against parvovirus B19 persisted at least 13 years (the longest period of time evaluated in the study) in children with SCD; responses were not dampened by hydroxyurea, a common therapy for SCD that is known to cause myleosuppression [19]; and no child who was previously exposed to parvovirus B19 experienced a repeat occurrence of parvovirus-induced disease.…”

“…Importantly, we noted that IgG responses against parvovirus B19 persisted at least 13 years (the longest period of time evaluated in the study) in children with SCD; responses were not dampened by hydroxyurea, a common therapy for SCD that is known to cause myleosuppression [19]; and no child who was previously exposed to parvovirus B19 experienced a repeat occurrence of parvovirus-induced disease. All of these factors suggest that parvovirus B19 vaccination has the potential to confer durable protection against infection in patients with SCD [18]. In total, results encourage the rapid development and testing of a VLP candidate vaccine in individuals with SCD to protect against the morbidity and mortality caused by parvovirus B19 infections in this patient population.…”

Detection of parvovirus B19 IgM in patients with sickle cell disease in Lagos, Nigeria

“…Although the outcome of transient red cell aplasia occurrences in children with SCD is mostly non-threatening, many are treated with red cell transfusions to minimize the threat of circulatory collapse due to severe anaemia [14]. Hydroxyurea may reduce the requirements for blood transfusion and may attenuate symptoms during transient aplastic crisis episodes caused by parvovirus B19 [15]. In Nigeria, this virus is not routinely screened…”

Modeling the parvovirus B19 blood safety risk in Australia

“…The specific rate is unclear; therefore, risk was estimated for three values: 1%, 5%, and 10%. The number of red blood cells (RBCs) transfused to patients with hereditary hemolytic anemias (HHAs) per year is approximately equal to national hospital separations for these conditions with equivalent RBC use patterns to those reported in a 2011 South Australian study Transfusion‐dependent and sporadically transfused sickle cell disease (SCD) patients receive an average of 20 and 2 RBC components per year, respectively. The frequency of B19V‐attributable transient aplastic crisis (TAC) in patients with SCD is 40%, which is applicable to patients with other HHAs. …”