A linked donor-recipient study to evaluate parvovirus B19 transmission by blood component transfusion

Abstract

Parvovirus B19V infection can be a serious infection for hematology patients with underlying hemolysis or compromised erythropoiesis syndromes. Although case reports of B19V transmission by blood component transfusion (as contrasted to manufactured plasma derivatives) are rare, no studies have systematically determined a rate of transmission to recipients transfused with B19V DNA-positive components. We used a linked donor and recipient repository and a sensitive, quantitative B19V DNA polymerase chain reaction (PCR) assay to assess such transmission in B19V-susceptible (ie, anti-B19V immunoglobulin G [IgG] negative) recipients. We assessed 112 B19V DNA-positive components from 105 donors (of 12 529 tested donations) transfused into a population of surgical patients with a pretransfusion B19V IgG seroprevalence of 78%. We found no transmission to 24 susceptible recipients from transfusion of components with B19V DNA at concentrations less than 10 6 IU/mL (upper 95% confidence interval, 11.7%). We found an anamnestic IgG response in one pretransfusion seropositive recipient transfused with a component containing greater than 10 10 IU/mL B19V DNA. These findings show either that transmission from components with less than 10 6 IU/mL does not occur, or, if it does, it is an uncommon event. These data do not support the need to routinely screen blood donations with a sensitive B19V DNA nucleic acid assay. (Blood. 2009;114:3677-3683) IntroductionThere have been multiple reports of parvovirus B19 (B19V) transmission by pooled plasma products, including factor VIII concentrate and solvent-detergent-treated pooled plasma, documented by recipient seroconversion in asymptomatic cases or, less frequently, by clinical diagnosis of B19V-related disease in association with positive B19V test results. [1][2][3][4][5] These cases, combined with the potential for very high B19V DNA concentrations (up to 10 12 IU/mL) in plasma donations 4 and the relative resistance of B19V to inactivation methods, 4,6 have led to B19V DNA testing of plasma donations to ensure that manufacturing plasma pools destined for plasma derivatives have a B19V DNA concentration less than or equal to 10 4 IU/mL, a limit proposed by the Food and Drug Administration (FDA). 7-9 The same limit for this so-called "in process testing" is a European regulatory requirement for anti-D immunoglobulin (Ig) preparations and plasma treated for virus inactivation. 10 To achieve this B19V DNA concentration in the final plasma pool, B19V DNA screening of the plasma donations used to make the pool is performed using assays (applied in minipool format) with the ability to detect approximately 10 6 IU/mL in an input unit of plasma. 8 To date, no B19V transmissions from pooled plasma products have been documented when less than 10 3 to 10 4 IU/mL B19V DNA is present in an infused product. 3,4,[11][12][13] The reason for this lack of infectivity is not completely understood. It may be due to an inadequate amount of infused infectious virions, a neutralization effect from B19V ...

Investigation of the Prevalence of Human Parvovirus B19 DNA in Korean Plasmapheresis Donors

“…In our study, the prevalence of B19V DNA in healthy Korean plasmapheresis donors was 0.1%, which was not high compared with that of other countries such as United States (0.83-0.88%), and Germany and Austria (0.27%) [7,15].…”

Parvovirus B19 Infections and Blood Counts in Blood Donors

“…In a donor-recipient-linked study, Klein-man et al [4] showed that TT-B19V infections through blood products from donors with lower DNA concentrations (< 10 6 IU/ml B19V-DNA) are uncommon: the amount of infectious B19V is either insufficient or high titers of protective, neutralizing antibodies are existent. Although we have not traced the recipients of our B19V DNA-positive blood products so far, our data endorse at least the last assumption: in samples with B19V DNA of <10 5 IU/ml, more anti-B19V IgG was present (fig.…”

“…Infections with B19V are widespread in human populations and usually occur by droplet transmission via the upper respiratory tract. However, B19V is also a common transfusion-transmissible agent, in particular through pooled plasma derivatives [1,2] but also by cellular blood components [3,4,5]. …”

Parvovirus B19 Achievements and Challenges

“…Given both the reported frequencies of high-titer viremic blood units and seroprevalence rates in the population, the probability of infection by exposure to single blood or blood components units is low [336,337]. Very few case reports describe symptomatic infections, while linked donor-recipient studies indicate that this situation is infrequent and in most cases clinically irrelevant [338]. Single-donor screenings are therefore unjustified in terms of costs; however, high-risk patients with hematological disorders, immune deficiencies or pregnant women would benefit from the availability of dedicated donations, proven to be free from B19V.…”