Parvoviruses, members of the family Parvoviridae, are small (diameter, ∼22 nm), nonenveloped, icosahedral-shaped viruses with a linear single-strand DNA genome of ∼5000 nucleotides. These viruses are dependent on either rapidly dividing host cells or helper viruses for replication. At least four groups of parvoviruses infect humans: parvovirus B19 (B19V), dependoviruses (adeno-associated viruses; AAVs), PARV4/5 virus, and human bocaviruses (HBoVs). Human dependoviruses are nonpathogenic and will not be considered further in this chapter.
B19V is the type member of the genus Erythrovirus. On the basis of viral sequence, B19V is divided into three genotypes (designated 1, 2, and 3), but only a single B19V antigenic type has been described. Genotype 1 is predominant in most parts of the world; genotype 2 is rarely associated with active infection; and genotype 3 appears to predominate in parts of western Africa.
B19V exclusively infects humans, and infection is endemic in virtually all parts of the world. Transmission occurs predominantly via the respiratory route and is followed by the onset of rash and arthralgia. By the age of 15 years, ∼ 50% of children have detectable IgG; this figure rises to >90% among the elderly. In pregnant women, the estimated annual seroconversion rate is ∼1%. Within households, secondary infection rates approach 50%.
Detection of high-titer B19V in blood is not unusual (see “Pathogenesis,” below). Transmission can occur as a result of transfusion, most commonly of pooled components. To reduce the risk of transmission, plasma pools are screened by nucleic acid amplification technology, and high-titer pools are discarded. B19V is resistant to both heat and solvent-detergent inactivation.
B19V replicates primarily in erythroid progenitors. This specificity is due in part to the limited tissue distribution of the primary B19V receptor, blood group P antigen (globoside). Infection leads to high-titer viremia, with >1012 virus particles (or IU)/mL detectable in the blood at the apex (Fig. 184-1), and virus-induced cytotoxicity results in cessation of red cell production. In immunocompetent individuals, viremia and arrest of erythropoiesis are transient and resolve as the IgM and IgG antibody response is mounted. In individuals with normal erythropoiesis, there is only a minimal drop in hemoglobin levels; however, in those with increased erythropoiesis (especially with hemolytic anemia), this cessation of red cell production can induce a transient crisis with severe anemia (Fig. 184-1). Similarly, if an individual (or, after maternal infection, a fetus) does not mount a neutralizing antibody response and halt the lytic infection, erythroid production is compromised and chronic anemia develops (Fig. 184-1).
Schematic of the time course of parvovirus B19V infection in (A) normals (erythema infectiosum), (B) transient aplastic crisis (TAC), and (C) chronic anemia/pure red-cell aplasia (PRCA). (Reprinted with permission from Young and Brown, 2004. © 2004 Massachusetts Medical Society. All rights reserved.)
The immune-mediated phase of illness, which begins 2–3 weeks after infection as the IgM response peaks, manifests as the rash of fifth disease together with arthralgia and/or frank arthritis. Low-level B19V DNA can be detected by polymerase chain reaction (PCR) in blood and tissues for months to years after acute infection. The B19V receptor is found in a variety of other cells and tissues, including megakaryocytes, endothelial cells, placenta, myocardium, and liver. Infection of these tissues by B19V may be responsible for some of the more unusual presentations of the infection. Rare individuals who lack P antigen are naturally resistant to B19V infection.
Most B19V infections are asymptomatic or are associated with only a mild nonspecific illness. The main manifestation of symptomatic B19V infection is erythema infectiosum, also known as fifth disease or slapped-cheek disease (Fig. 184-2). Infection begins with a minor febrile prodrome ∼7–10 days after exposure, and the classic facial rash develops several days later; after 2–3 days, the erythematous macular rash may spread to the extremities in a lacy reticular pattern. However, its intensity and distribution vary, and B19V-induced rash is difficult to distinguish from other viral exanthems. Adults typically do not exhibit the “slapped-cheek” phenomenon but present with arthralgia, with or without the macular rash.
Young child with erythema infectiosum, or fifth disease, showing typical "slapped-cheek" appearance.
Although uncommon among children, arthropathy occurs in ∼50% of adults and is more common among women than among men. The distribution of the affected joints is often symmetrical, with arthralgia affecting the small joints of the hands and occasionally the ankles, knees, and wrists. Resolution usually occurs within a few weeks, but recurring symptoms can continue for months. The illness may mimic rheumatoid arthritis, and rheumatoid factor can often be detected in serum. B19V infection may trigger rheumatoid disease in some patients and has been associated with juvenile idiopathic arthritis.
Transient Aplastic Crisis
Asymptomatic transient reticulocytopenia occurs in most individuals with B19V infection. However, in patients who depend on continual rapid production of red cells, infection can cause transient aplastic crisis (TAC). Affected individuals include those with hemolytic disorders, hemoglobinopathies, red cell enzymopathies, and autoimmune hemolytic anemias. Patients present with symptoms of severe anemia (sometimes life-threatening) and a low reticulocyte count, and bone marrow examination reveals an absence of erythroid precursors and characteristic giant pronormoblasts. As its name indicates, the illness is transient, and anemia resolves with the cessation of cytopathic infection in the erythroid progenitors.
Pure Red-Cell Aplasia/Chronic Anemia
Chronic B19V infection has been reported in a wide range ...