Parvovirus B19 infection transmitted by transfusion of red blood cells confirmed by molecular analysis of linked donor and recipient samples

Abstract

Background: Extremely high viremic levels of parvovirus B19 (B19V) can be found in acutely infected, but asymptomatic donors. However, reports of transmission by single-donor blood components are rare. In this prospective study, paired donor-recipient samples were used to investigate the transfusion risk.

Study design and methods: Posttransfusion plasma or blood samples from recipients were tested for B19V DNA by polymerase chain reaction, generally at 4 and 8 weeks, and for anti-B19V immunoglobulin (Ig)G by enzyme immunoassay, at 12 and 24 weeks. To rule out infection unrelated to transfusion, pretransfusion samples and linked donor's samples for each B19V DNA-positive recipient were assayed for B19V DNA and anti-B19V IgG and IgM. To confirm transmission, sequencing and phylogenetic analysis were performed.

Results: A total of 14 of 869 (1.6%) recipients were B19V DNA positive, but only 1 of 869 (0.12%; 95% confidence interval, 0.0029%-0.6409%) was negative for B19V DNA and anti-B19V IgG before transfusion and seroconverted posttransfusion. This newly infected patient received 5 × 10(10) IU B19V DNA in one red blood cell (RBC) unit from an acutely infected anti-B19V-negative donor in addition to RBCs from three other donors that cumulatively contained 1320 IU of anti-B19V IgG. DNA sequencing and phylogenetic analysis showed that sequences from the linked donor and recipient were identical (Genotype 1), thus establishing transfusion transmission.

Conclusions: The 0.12% transmission rate documented here, although low, could nonetheless result in hundreds or thousands of infections annually in the United States based on calculated confidence limits. Although most would be asymptomatic, some could have severe clinical outcomes, especially in neonates and those with immunocompromised or hemolytic states.

Fig. 1

(A) B19 nucleotide sequence alignments within the VP1-unique region (Nucleotides 2465–3124) and a portion of the N-terminal VP2 region (Nucleotides 3125–3174). All sequences obtained for Nucleotides 2465 to 2520, 2581 to 2730, and 2791 to 3174 were identical and therefore are not shown. Nucleotide numbering of the sequence is based on the published B19 Au strain (M13178). Sequences were determined directly from purified PCR-amplified products derived from the patient’s 2-and 8-week plasma samples and from plasma and WB samples from Donor 4 (Table 3). As the positive control, the WHO B19V DNA standard was similarly sequenced. (B) Phylogenetic comparison of the above-mentioned B19 sequences (Nucleotides 2465–3174; 710 nucleotides) along with other corresponding published B19 sequences in the GenBank, that is, Genotype 1 = M13178 (Au), AF162273, AY386330, and AY504945; Genotype 2 = AY064476 (A6) and AY044266 (Lali); and a Genotype 3 = AY083234 (D91.1). Evolutionary distances are in units of the number of base substitutions per site (0.01 unit shown).