Continued Transmission of Parvovirus B19 in Plasma-Derived Factor Concentrates After the Implementation of B19 Nucleic Acid Plasma Minipool Screening,

Parvovirus B19 (B19) is a small, non-enveloped virus that causes a typically benign flu-like illness most commonly in childhood. However, B19 has been associated with arthritis and poses a hazard to the fetus of a pregnant woman. Because infection is common and viremia can occur before symptoms develop, about 1% of blood donations can be contaminated with B19 virus. The virus is resistant to current viral inactivation steps used in the manufacture of plasma-derived (P-D) anti-hemophilic factor concentrates and B19 transmission through these products has been documented. Since 2000, manufacturers have used a B19 nucleic acid test (NAT) to screen plasma pools and withhold from fractionation those with B19 DNA exceeding an established threshold. No study of populations using these products has been conducted to assess the impact of the screening on B19 transmission.

Blood specimens obtained from participants of the CDC-sponsored Universal Data Collection (UDC) surveillance system of persons with bleeding disorders conducted by specialized US bleeding disorders clinics were used in a B19 seroprevalence study. Since B19 NAT screening began in 2000, only participants born after January 1, 2001 were eligible for study. Data collected on treatment products used by participants both prior to and after enrolment in UDC were used to categorize lifetime exposure as 1) no products, 2) recombinant (recomb) products only, 3) P-D products only, or 4) both recomb and P-D products. The proportions of participants with B19 IgG antibodies were compared across age and product exposure categories to determine whether users of products were at higher risk of past infection with B19 compared to those exposed to B19 only by the usual respiratory route.

A total of 1,643 specimens from 1,043 participants aged 2 – 7 years were tested. Demographic and clinical characteristics of study participants are shown in Table 1. Compared to subjects with no exposure to products, subjects in nearly every age group exposed to either P-D products alone or to both P-D and recomb products had a higher B19 prevalence (Table 2). In a logistic regression analysis that controlled for differences in the distribution of age, sex, bleeding disorder, treatment type, number of bleeds in previous 6 months, hemophilia inhibitor status, and year specimen obtained, participants exposed to P-D products alone were 1.7 times more likely to have B19 antibodies than those unexposed to blood or factor products (p = 0.002). In addition, there was a significant overall trend of increasing B19 prevalence over time.

P-D factor products are important therapies for people with VWD, hemophilia inhibitors and rarer factor deficiencies. Although we had no data on clinical illness, these serologic data provide evidence for continued transmission of B19 through these products after implementation of B19 NAT screening. Lowering the B19 threshold for plasma pool rejection should be considered. More importantly, effective viral inactivation processes are needed to protect users of these products not only from infection with B19 but from other as yet unidentified or emerging viruses that would not be detected by B19 NAT.

Kessler:Novo Nordisk Inc.: Consultancy.