PARVOVIRUS B19 INFECTIONS
Parvoviruses are very small (18 to 26 nm), naked virions that contain a linear single-stranded DNA molecule. Diseases caused by parvoviruses have been recognized among nonhuman hosts for a number of years. Notable among these are canine parvovirus and feline panleukopenia virus, which produce particularly severe infections among puppies and kittens, respectively. These do not appear to cross species barriers. The human par-vovirus B19 has been well described, but its origin is not yet known.
Parvovirus B19 encodes three capsid proteins (VP1, VP2, and VP3). The virus can be grown in primary cultures of human bone marrow cells, fetal liver cells, hematopoietic progenitor cells generated from peripheral blood, and a megakaryocytic leukemia cell line. The major cellular receptor for the virus is globoside (also known as blood group P antigen, which is commonly found on erythroid progenitors, erythroblasts, megakary-ocytes, and endothelial cells). All represent potential targets for disease production. A pri-mary site of replication appears to be the nucleus of an immature cell in the erythrocyte lineage. Such infected cells then cease to proliferate, resulting in an impairment of nor-mal erythrocyte development.
The clinical consequences of this effect on erythrocytes are generally trivial, unless patients are already compromised by a chronic hemolytic process, such as sickle cell disease or thalassemia, in which maximal erythropoiesis is continually needed to coun-terbalance increased destruction of circulating erythrocytes. Primary infection by parvovirus B19 in such individuals often produces an acute, severe, sometimes fatal anemia manifested as a rapid fall in red blood cell counts and hemoglobin. Patients may present initially with no clinical symptoms other than fever, and is commonly re-ferred to as aplastic crisis. Immunocompromised patients such as those with acquired immunodeficiency syndrome sometimes have difficulty clearing the virus and develop persistent anemia with reticulocytopenia. Parvovirus B19 has also been occasionally implicated as a cause of persistent bone marrow failure and an acute hemophagocytic syndrome.
Erythema infectiosum (also referred to as fifth disease or academy rash) is a morecommon disease that is clearly attributable to parvovirus B19. After an incubation period of 4 to 12 days, a mild illness appears, characterized by fever, malaise, headache, myalgia, and itching in varying degrees. A confluent, indurated rash appears on the face, giving a “slapped-cheek” appearance. The rash spreads in a day or two to other areas, particularly exposed surfaces such as the arms and legs, where it is usually macular and reticular (lace-like). During the acute phase, generalized lymphadenopathy or splenomegaly may be seen, along with a mild leukopenia and anemia.
The illness lasts 1 to 2 weeks, but rash may recur for periods of 2 to 4 weeks there-after, exacerbated by heat, sunlight, exercise, or emotional stress. Arthralgia sometimes persists or recurs for weeks to months, particularly in adolescent or adult females. Overt arthritis or vasculitis have also been reported in some individuals. Serious complications, such as hepatitis, thrombocytopenia, nephritis or encephalitis are rare. However, like rubella, active transplacental transmission of parvovirus B19 can occur during primary in-fections in the first 20 weeks of pregnancy, sometimes resulting in stillbirth of fetuses that are profoundly anemic. The progress can be so severe that hypoxic damage to the heart, liver, and other tissues leads to extensive edema (hydrops fetalis). The frequency of such adverse outcomes is as yet undetermined.
It is important to be aware that erythema infectiosum is extremely variable in its clinical manifestations; even the “classic” presentation can be mimicked by other agents, such as rubella and echoviruses. Before a firm diagnosis is made on clinical grounds, especially during outbreaks, it is wise to exclude the possibility of atypical rubella infection.
Epidemiologic evidence suggests that spread of the virus is primarily by the respira-tory route, and high transmission rates occur in households. Outbreaks tend to be small and localized, particularly during the spring months, with the highest rates among chil-dren and young adults. Seroepidemiologic studies have demonstrated evidence of past in-fection in 30 to 60% of adults. Viremia usually lasts 7 to 12 days but can persist for months in some individuals. It can be detected by specific DNA probe or polymerase chain reaction (PCR) methods. Alternatively, the presence of IgM-specific antibody late in the acute phase or during convalescence strongly supports the diagnosis.
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