Human Parvoviruses (Parvovirus B19 and Bocavirus)

Microbiology and Pathogenesis

The single-stranded DNA genome encodes one major nonstructural protein, which mediates cytotoxicity, and two capsid proteins—VP1 and VP2—which self-assemble to form virus-like particles in vitro. Based on the viral sequence, B19V can be divided into three distinct genotypes (genotypes 1, 2, and 3), but all cause similar disease patterns, and there is serologic cross-reactivity—and thus a single serotype has been described.

B19V is highly erythrotropic with efficient viral replication only occurring in late erythroid precursor cells. Virus-induced cytotoxicity, therefore, results in arrest of red cell production and reticulocytopenia. In patients who have increased erythropoiesis, such as those with sickle cell or hemolytic anemia, B19V infection may induce a transient aplastic crisis. In patients who are immunosuppressed and unable to mount an appropriate neutralizing antibody response, B19V infection can cause pure red cell aplasia and chronic anemia.

The erythroid specificity is in part due to the tissue distribution of the receptor for B19V, the blood group P antigen, also known as globoside . This antigen is found in the erythrocyte precursors in bone marrow as well as in a variety of other tissues, including megakaryocytes, endothelial cells, placenta, fetal myocardium, and fetal liver. Rare individuals who lack blood group P antigen are naturally resistant to parvovirus B19 infection. Some of the clinical consequences of B19V infection, including the rash, are immune mediated.

After infection there is a brisk viremia, which peaks at >10 ¹² virus particles (international units)/mL of blood ( Fig. 214.1 ). Viremia often is accompanied by a nonspecific febrile illness. In immunocompetent individuals, an immunoglobulin M (IgM) and IgG antibody response is mounted, and the concentration of virus in blood drops. The second, immune-mediated phase of illness coincides with the antibody response ( Fig. 214.1 ). Typical manifestations of this phase of the illness are the rash of fifth disease, arthralgia, and arthritis. In normal immunocompetent hosts, infection resolves, although low levels of B19V DNA can be detected by polymerase chain reaction (PCR) in blood and tissues for months to years after acute infection. Chronic, high-level viremia can occur in immunocompromised individuals who do not make neutralizing antibody ( Fig. 214.1 ).

Epidemiology

Parvovirus B19 infection is a common illness of childhood; by 15 years of age, approximately 50% of children have detectable IgG antibodies.

In temperate climates, most infections occur in the spring, with mini epidemics occurring at regular intervals several years apart. ^, The highest risks for transmission are between close contact within households and schools, and secondary infection rates approach 50% in households. Transmission is predominantly through the respiratory route—probably by droplet spread—and is highest at the time of viremia, before the onset of rash or arthralgia.

Persons who have hemolytic anemias or decreased red cell production are at increased risk for severe anemia or transient aplastic crisis when infected with B19V. Globally, many children have severe anemia due to malaria, chronic parasitic infections (e.g., hookworm), and nutritional deficiencies (e.g., iron, vitamin A, vitamin B ₁₂ ). Studies investigating the relationship between parvovirus B19 and these conditions indicate that B19V infection may be an important contributor to severe anemia, especially in malaria endemic regions.

B19V infections also can occur as a result of transfusion of blood or blood products. Most reported cases of transfusion-related infection are due to pooled components, especially factors VIII and IX concentrate, rather than individual units. B19V is resistant to solvent-detergent inactivation and relatively resistant to heat inactivation at high titer. In July 2009, the US Food and Drug Administration issued a guidance for nucleic acid testing of blood to reduce the risk for transmission of B19V by plasma-derived products. Other countries have similar policies.

Clinical Manifestations

Most infections caused by B19V are asymptomatic or mild. When infection is associated with symptoms, a variety of disease manifestations, depending on the immune status of the host, can be observed ( Table 214.1 ).