Parvovirus Infection

What is Parvovirus Infection?

Parvovirus infection is an acute infectious disease of predominantly childhood age caused by a parvovirus and characterized by a variety of clinical manifestations. Most often, parvovirus infection manifests itself as an infectious erythema (“fifth disease”).

In the 80s. It was found that a number of diseases, from infectious erythema and acute arthritis in otherwise healthy people to aplastic crises and chronic anemia in debilitated patients, are due to parvovirus infection. In pregnant women, it can lead to intrauterine infection, dropsy of the fetus and its death.

Many severe manifestations of parvovirus infection are associated with reproduction of parvovirus in the cells of the erythroid rostock of the bone marrow and their destruction.

Causes of Parvovirus Infection

The family of parvoviruses includes several species-specific animal viruses.
For human pathogen, only parvovirus B19, called the number of the sample of human serum, from which it was first isolated. It is a small virus with a diameter of 20-25 nm without an outer shell. The icosahedral capsid of two structural proteins surrounds one plus or minus strand of DNA. Parvovirus B19 is highly resistant: it remains viable when heated for 16 hours at 60 ° C. In cell cultures, commonly used in laboratory practice, it does not multiply and does not cause infection in laboratory animals. It can be cultivated in progenitor cells of erythrocytes obtained from human bone marrow, blood, umbilical cord or fetal liver.

Parvovirus diseases are found at any time of the year, but the most common of these, infectious erythema, often causes outbreaks in schools in the winter and spring. With such outbreaks, 20-60% of children fall ill, and many more are asymptomatic.

According to mass serological studies, antibodies to parvovirus B19 are about half of adults. The percentage of seropositive individuals quickly rises from 5 to 18 years and continues to increase further, indicating that adults are also infected. Patients are contagious in the viremia phase, when the virus is detected in swabs from the pharynx, airway secretions and serum.

Patients with aplastic crises are very infectious: an outbreak of infectious erythema among nurses has been described, in which such a patient was the undoubted source of infection. Patients with erythema infection are much less contagious.
The mechanism of transmission under natural conditions is unclear. Apparently, it is transmitted by airborne droplets or by direct contact. Infection with coagulation factor infusion drugs, even when treated with steam and dry heat, is also possible.

Pathogenesis during Parvovirus Infection

Thanks to research on volunteers, it is known that parvovirus infection has two phases.

The first phase coincides with viremia, which develops approximately 6 days after intranasal administration of the virus to susceptible (seronegative) individuals. Viremia lasts about 1 week; General symptoms (headache, malaise, myalgia, chills, fever, pruritus), reticulocytopenia are observed in the first 2-3 days. During this period, the virus is secreted with respiratory secretions. After a few days, there is a slight decrease in hemoglobin level, which lasts for 7-10 days. An examination of the bone marrow during this period reveals a significant depletion of the erythroid sprout. Sometimes there are light lymphopenia, neutropenia and thrombocytopenia.

The second phase of the disease occurs 17-18 days after infection. By this time, viremia ceases, specific IgM antibodies appear. The antibodies will disappear after a few months. A few days later, IgM IgG antibodies appear, which persist indefinitely. In this phase, the virus from the nasopharyngeal secretion disappears, the number of reticulocytes in the blood normalizes, within 2-3 days there is a maculopapular rash, for 1-2 days longer arthralgia or arthritis.

The above-mentioned studies have shown that in healthy people, parvovirus infection quickly passes without treatment. Its clinical manifestations — infectious erythema and arthritis — are almost certainly due to the formation of immune complexes. This suggestion is supported by the development of infectious erythema in patients with chronic viremia with the introduction of normal immunoglobulins.

In patients with chronic hemolytic anemia or immunodeficiency, parvovirus infection is often difficult, accompanied by extensive destruction of the erythroid germ of the bone marrow. While healthy people easily tolerate the cessation of erythropoiesis for 7-10 days, with hemolytic anemia, when compensation is achieved through enhanced erythropoiesis, the destruction of the precursor cells of erythrocytes usually leads to severe aplastic crisis. In patients with immunodeficiency viremia does not stop, severe chronic anemia develops due to the constant infection of the erythroid germ cells with the virus.

Dropsy of the fetus during intrauterine infection due to its need for a much more intense than in adults, erythropoiesis in combination with the immaturity of the immune system.

Parvovirus B19 selectively attaches to the erythrocyte membrane receptor – antigen P, which explains the tropism of this virus to the erythrocyte progenitor cells, especially to erythroblasts and normoblasts. In the few individuals who do not have antigen P, parvovirus B19 does not cause infection.

Symptoms of Parvovirus Infection

Infectious erythema (fifth disease) is the most common manifestation of parvovirus infection; it is mainly found in children and is also known as the “fifth disease”, given to her at the end of the 19th century as one of six childhood infections accompanied by a rash.

The disease proceeds easily. A bright spotted rash appears on the cheeks (slapped cheeks). Sometimes rash precedes subfebrile temperature. The rash is usually maculopapular and has a reticular, laced appearance; it spreads quickly to limbs. Occasionally, a measles-like, vesicular, hemorrhagic rash, or itching. Usually it passes in about a week, but during the following weeks transient rashes may appear, especially during anxiety, physical exertion, exposure to the sun, bathing, and changes in the surrounding temperature.

Acute arthralgia and arthritis are rare in children, but frequent manifestations of parvovirus infection in adults. Rash in adults, on the contrary, is often absent or atypical – without a characteristic erythema on the face. In most cases, arthritis symmetrically affects the peripheral joints (knee, wrist and wrist joints) and usually goes away after 3 weeks, leaving no destructive changes. However, in some patients it lasts for several months, in rare cases for several years. It is not known whether prolonged arthritis is caused by chronic infection or autoimmune reactions. Described isolated cases in which it is assumed (but not proven) relationship of parvovirus infection with idiopathic trombopitopenicheskoy purpura, hemophagocytic syndrome, pancytopenia, arthritis-like joint damage with Lyme disease, with recurrent paresthesia, fibromyalgia, lupus, systemic vasculitis (including nodular nodosa , Wegener’s granulomatosis, Kawasaki disease).

Parvovirus infection is the cause of most sudden aplastic crises in almost all chronic hemolytic anemias, including sickle cell anemia, enzymopathies, hereditary microspherocytosis, thalassemia, paroxysmal nocturnal hemoglobinuria, autoimmune hemolytic anemia. In addition, a parvovirus infection can cause an aplastic crisis in patients with acute blood loss.

Crises are accompanied by severe anemia with pallor, weakness, drowsiness. Often, a few days before the crisis, there are common symptoms. Deep reticulocytopenia lasts 7-10 days. Erythroid germ cells in the bone marrow are absent, although granulocyte-monocytic germ cells are sufficient. Hemoglobin levels can drop to a life-threatening limit, requiring urgent blood transfusions.
Unlike infectious erythema and arthritis, aplastic crisis is accompanied by viremia, and such patients are contagious.

In patients with immunodeficiency, probably due to the inability to produce enough IgG antibodies, the parvovirus B19 is not eliminated from the body. Chronic infection develops with the destruction of the precursor cells of red blood cells in the bone marrow and anemia, requiring regular blood transfusions. Such anemia has been described for HIV infection, congenital immunodeficiency, supportive chemotherapy for acute lymphoblastic leukemia in bone marrow recipients.

Chronic parvovirus infection can cause idiopathic aplasia of an erythroid sprout. Anemia due to this infection is sometimes the only manifestation of unrecognized immunodeficiency. Anemia can occur in waves; it can be cured or improved with normal immunoglobulins. The spectrum of immunodeficiencies in which there is chronic anemia caused by parvovirus B19, and the prevalence of this combination has not yet been studied.

In most cases, parvovirus infection in pregnant women does not lead to infection of the fetus and does not have a harmful effect on it. However, in almost 10% of pregnant women who have had a parvovirus infection, the fetus dies from non-immune dropsy. Fetal death occurs from severe anemia and heart failure. The virus is found in fetal tissues, especially in erythroblasts and normoblasts. Pregnant women who may become infected with parvovirus B19 need to periodically determine IgM titer and the level of alpha-fetoprotein and carry out repeated ultrasounds in order to timely detect fetal dropsy. In some cases, the fetus suffers dropsy and is born healthy or, less commonly, with congenital anemia and hypogammaglobulinemia, which is not amenable to treatment with normal immunoglobulins.

Diagnosis of Parvovirus Infection

Parvovirus infection is usually confirmed by measuring the titers of specific IgM and IgG using ready-made ELISA kits. Sometimes a virus is isolated from serum or tissues, or viral antigens and DNA are detected in them. An acute infection is indicated by a characteristic clinical picture and a high IgM titer or the isolation of the virus itself, and a long time ago – a high IgG titer.

In infectious erythema and acute arthritis, serum virus usually cannot be isolated, but IgM titer is high. In aplastic crises, in parallel with a high IgM titer in serum, a large amount of the virus or its DNA is determined. Characteristic giant erythroblasts and erythroid germ hypoplasia are found in the bone marrow. In patients with immunodeficiency, antibodies often cannot be determined, but a virus or its DNA is detected in serum.

The diagnosis of intrauterine infection is confirmed by fetal drops if viral DNA is present in the amniotic fluid or fetal blood in combination with a high specific IgM titer in a pregnant woman.

Treatment of Parvovirus Infection

Infectious erythema and arthritis in most cases do not require treatment. For severe, particularly protracted, arthritis, NSAIDs are used. In an aplastic crisis, red blood cell transfusions are usually required. For anemia, normal immunoglobulin for intravenous administration, containing antibodies to parvovirus B19, is used in patients with immunodeficiency. With its help, it is possible to achieve a cure or at least suppression of a parvovirus infection.

Prevention of Parvovirus Infection

Upon contact with parvovirus infection, the prophylactic use of this drug is indicated for patients with immunodeficiency and chronic hemolytic anemia and for pregnant women, but the effectiveness of such immunoprophylaxis, carried out immediately before or immediately after infection, has not been established.
To reduce the chance of infection, people at risk should wash their hands before eating and after contact with patients.

Patients with aplastic crisis and chronic infection caused by parvovirus B19, in contrast to patients with erythema infection and arthritis, are a source of hospital infection. They are hospitalized in separate chambers and observe contact and respiratory isolation.

A vaccine against parvovirus B19 has not yet been created, but the possibility of obtaining it with the help of an insect cell line infected with a recombinant baculovirus that expresses the capsid proteins of parvovirus B19, which does not cause disease but has immunogenic properties, is being investigated.