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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