Human parvoviruses: implications for transfusion medicine

HUMAN PARVOVIRUS B 19 is a single-stranded DNA virus of the genus Pmovirus. Other members of this genus include canine parvovirus, feline panleukopenia virus, and other animal parvoviruses; animal parvoviruses do not infect humans, and B19 has not been found to infect other animals. ’ Human parvovirus B19 (hereafter called B19) is the only human parvovirus that produces clinical illness. The illnesses associated with B 19 are for the most part benign. In children and young adults, erythema infectiosum, or fifth disease, a common childhood exanthem, is seen. In adults, transient rheumatic symptoms and arthritis have been reported. However, in pregnant women, patients with disorders involving increased red cell (RBC) production, and those with either acquired or congenital immunodeficiency, B 19 can cause life-threatening disease. The disease manifestations in these individuals include, respectively, hydrops fetalis, acute aplastic and hypoplastic anemia, and chronic anemia. These disorders result from the unusual propensity of B 19 to infect proliferating hematopoietic cells, of which the late erythroid progenitor cells are of greatest importance. In addition, B19 has been detected in fetal myocardial cells2 and other fetal cell lines? which suggests a further role of B19 in fetal pathology. B 19 is a heat-stable, single-stranded DNA virus of 5.5kilobase length and 18to 25-nm diameter, which lacks an envelope. It has two structural proteins, one 83-kDa minor protein (VPl) and one 58-kDa major protein (VP2), that enclose the single-stranded DNA in a capsid. The 83-kDa protein is important in eliciting virus-neutralizating antibody. There is also a 77-kDa nonstructural protein whose function is not yet defined. ’ The viral DNA contains a 5.5-kb sequence that has been cloned; certain sequences allow the DNA to fold back in hairpin turns during replication. This permits the identification of replicative B19 in tissues using in situ hybridization techniques. Studies of healthy volunteers infected with B19 permit evaluation of the normal immune response to this virus. ’ After intranasal inoculation of B 19-positive serum in five B19 IgG-seronegative volunteers, virus was deAbbrevhtlonr: B19 p o n o v l ~ s B19; BFU-E burnt-forming unlts-crythroid; CFU-E cdony-formlng unltberythroid, CSF cdoay-rtfmulatlng hctor; M V h u m lmmunodcllrkncy vW, IMC Intravcnow Immunoghbulln; PCR polymersme chah rertlon; RBC(r) red cell(r). From Tmsfusion Medicine and Hematology, Department of Labomtoy Medicine, Children’s Hospital, Washington. Dc. Received for publication March 22,1993; revision received December31, 1993,andacceptedJanuq31. 1994. tected in 6 days, peaked at 7 to 9 days, and was present for 3.4. 5, or 7 more days in four of the five individuals. ’Ihree of the five infected volunteers developed a biphasic illness that began with fever. malaise, myalgia, chills, and excretion of virus in respiratory secretions. The second phase occurred 17 to 18 days after inoculation and was characterized by maculopapular, erythematous rash, arthralgias and stiffness and swelling of the hands, knees, and ankles. Reticulocytopenia occurred on Days 7 to 10. At that time, a drop in hemoglobin, lymphopenia, neutropenia, and thrombocytopenia also occurred, but, in an otherwise normal individual, they might have been clinically inapparent. IgG-seropositive inoculated volunteers did not demonstrate any signs or symptoms of B 19 infection. Bone marrow examination of one IgG-seronegative inoculated volunteer on Day 6 after infection showed giant pronormoblasts with vacuolization. Another study subject’s bone marrow on Day 10 demonstrated a decrease of RBC precursors and large vacuolated proerythroblasts.4 These studies provided the foundation for delineation of the effect of B 19 on bone marrow precursors and the resultant anemiaAe major clinical finding in this disorder. Advances in diagnostic tests now allow documentation of acute, recent, and past infection and tissue invasion. In acute infection in the normal host, a transitory B 19-specific IgM response is followed by an IgG response. The IgM antibody response decreases rapidly and becomes nondetectable by 3 to 8 months after infection. The loss of IgM antibody indicates a recent infection. Seroconversion from IgG-seronegative to -seropositive also implies recent infection. When only one analysis is obtained, the presence of B19 IgG antibody implies past infection. Both the IgG and IgM antibody have neutralizing activity;’ the IgG antibody, however, provides lifelong immunity. It is most likely that the early response is to the 58-kDa epitope, while long-term immunity depends on antibody to the 83-kDa minor capsid protein.6 Reinfection has been documented in an individual with trace IgG antibody who developed a second rise in IgM and increased level of IgG antibodies. ‘ In an individual with pre-existing B19-specific IgG, the appearance of IgM or a rising IgG titer indicates acute or recent infection. The antibody assays are based on standard enzyme immunoassay, antigen-capture,’ and radioimmunoassay methodologies. Detection of B19 capsid antigen is less available because of the limited supply of monoclonal antibodies with