Infectious Diseases

Parvovirus

OVERVIEW: What every clinician needs to know

Pathogen name and classification

Human parvovirus B19 is a member of the Parvoviridae family and the genus Erythrovirus. Its only known host is humans, and it replicates in erythroid cells.

What is the best treatment?

  • Most infections are asymptomatic or only cause mild disease, so in the majority of cases no treatment is needed.

  • For moderate to severe arthritis, nonsteroidal anti-inflammatory drugs can be used.

  • In patients with transient aplastic crisis, supportive red blood cell (RBC) transfusions are needed until the immune system clears the infection and RBC production resumes

  • In chronic infection, which usually occurs in immunocompromised patients, intravenous immunoglobulin (IVIG) in doses ranging from 0.4g/kg/day for 5 days up to 2g/kg/day in human immunodeficiency virus (HIV)-infected patients with RBC aplasia may be needed.

  • Some patients then need maintenance IVIG of 0.4mg/kg/day every 4 weeks.

  • Resolution of the immunosuppression, if possible, often clears the infection.

  • For hydrops fetalis, intrauterine RBC transfusion may be indicated between 18 to 35 weeks gestation.

How do patients contract this infection, and how do I prevent spread to other patients?

  • Epidemiology-

    • Infection occurs worldwide.

    • Transmission is primarily person to person via respiratory secretions, although vertical transmission can occur as well as transmission from blood transfusions.

    • In temperate regions, respiratory transmission is increased in the winter months.

    • Most individuals become infected during early school years, and 50% of children in the United States have a detectable level of immunoglobulin (Ig) G by age 15 years.

    • Similar seropositivity is seen in other developed countries, and developing countries have a somewhat higher seroprevalence.

    • Approximately 70% of adults have measurable antibody.

    • Among pregnant women, approximately 30% do not have a measurable level of IgG and are susceptible to infection (see information about perinatal risk later in this chapter).

    • Susceptible pregnant women with young school-age children are at particular risk for pregnancy complications.

    • Arthralgia or arthritis is more common in females than in males.

    • Household transmission is highly efficient, and nosocomial outbreaks can also occur with patient to patient transmission, patient to staff or staff to patient transmission, and between staff.

  • Infection control issues-

    • Standard infection control practices, such as handwashing, decrease the risk of transmission.

    • Patients with transient aplastic crisis should be placed on droplet isolation precautions for 7 days.

    • Immunodeficient patients with chronic infection should have these precautions for the duration of hospitalization.

    • Immune competent patients are not considered infectious after the onset of rash, arthritis, or arthralgias, as immune clearance would have reduced the viral load by that time.

    • There is no specific vaccine or antiviral prophylaxis available.

What host factors protect against this infection?

  • Patients with intact immune systems generally have asymptomatic or self-limited acute disease and do not develop severe manifestations, such as transient aplastic crisis or chronic infection.

  • Virus-specific IgM and IgG levels peak at days 8 to 9 following exposure in healthy volunteers.

  • Measureable IgA levels confer resistance infection via the nasopharynx.

  • Immune response to the major viral capsid protein VP1 is necessary for clearance; many patients with chronic infection demonstrate only VP2 antibodies.

  • The role of the cellular immune system is less understood in clearing infection.

  • Infection of a susceptible woman in pregnancy, particularly before 20 weeks gestation, is associated with intrauterine fetal demise.

What are the clinical manifestations of infection with this organism?

  • The majority of infections in immunocompetent hosts are asymptomatic or mild.

  • Erythema infectiosum or "fifth disease" primarily occurs in children, although adults can also develop it.

  • A nonspecific viral prodrome with malaise, fever, headache, nausea, and diarrhea is followed 2 to 5 days later by a classic erythematous malar rash (slapped cheek rash) with circumoral pallor. The rash is thought to be immune mediated and the prior viremia (during the prodrome) is cleared by the time it appears. In some patients, the rash can reappear for months afterward if triggered by stress, sunlight, exercise, or temperature change. 75% of patients will develop a rash, but not commonly the slapped cheeks rash of erythema infectiosum.

  • Arthralgia or arthritis can occur and is more common in females than in males. Distribution is symmetric, with the small joints of the hands, wrists, and feet most commonly affected. Symptoms usually resolve in 2 to 3 weeks, although some may persist longer. No joint destruction occurs.

  • Transient aplastic crisis is more common in individuals with underlying hematologic abnormalities, including sickle cell disease and iron deficiency anemia.

  • Patients present with severe fatigue, pallor, and in rare cases congestive heart failure or stroke. Rash is absent in the majority.

  • There is an absence of reticulocytes in the peripheral blood, and bone marrow biopsy shows pure RBC aplasia. This is usually self limited as the immune system clears the virus, and usually does not recur.

  • In immunocompromised patients, in contrast, similar RBC aplasia can occur but may become chronic as the infection is not cleared. These patients should be treated with IVIG, and may require repeated treatment for relapses. Reversal of the underlying immune disorder (eg. highly active antiretroviral therapy in HIV-infected patients) can clear the infection and reverse the anemia.

  • Parvovirus B19 has also been associated with myocarditis and dilated cardiomyopathy, and has been documented by endomyocardial biopsy, but some studies suggest that other combined factors are involved in these disease outcomes.

  • Nonimmune hydrops fetalis and intrauterine fetal death are possible outcomes of infection in pregnant women and are thought to be related to severe B19-associated fetal anemia. The risk of intrauterine fetal death is greatest in susceptible women infected before the 20th week of gestation. Similarly, the risk of anemia and hydrops fetalis is greatest with infection in the first half of pregnancy. Some cases spontaneously regress, while others require fetal transfusion. Human congenital abnormalities have NOT been associated with B19 infection.

What common complications are associated with infection with this pathogen?

  • Transient aplastic crisis is more common in individuals with underlying hematologic abnormalities including sickle cell disease or iron deficiency anemia.

  • Congestive heart failure or cerebrovascular accident can be rare complications.

  • Nonimmune hydrops fetalis and intrauterine fetal death are possible outcomes of infection in pregnant women and are thought to be related to severe B19-associated fetal anemia.

  • Infants delivered with hydrops fetalis require intensive specialty management in the immediate postdelivery period, and most should be delivered at tertiary care centers.

How should I identify parvovirus infection?

  • Determination of immune status varies by stage of infection.

  • In acute infection, IgG and IgM (using an enzyme immunoassay) makes the diagnosis in immunocompetent patients. In the immunocompromised, nucleic acid amplification (NAAT) should be used, as antibody response may be absent.

  • IgM assay protocols may require an additional step to improve sensitivity by removing IgG that may "swamp" the signal.

  • Prior infection is diagnosed with assays for IgG.

  • Antigen detection is done using NAAT, and is of most use in individuals who may not have developed an immune response (immunocompromised persons, neonates).

  • In pregnant women who may have been exposed to B19, IgM and IgG antibodies should be checked. The presence of both indicates prior infection and the fetus is protected.

  • IgM alone indicates recent infection. In pregnant women prior to 20 week gestation, counseling should be given that fetal loss is a possibility and that intrauterine transfusions might be necessary starting at 20 weeks (the earliest this is feasible from a technical standpoint). In those at more than 20 weeks gestation, some advise serial ultrasounds to monitor for hydrops fetalis, but there are no data that this improves outcomes.

  • If the assay is negative for both IgM and IgG and recent exposure, screening the serum via NAAT for B19 deoxyribonucleic acid may give additional information and the serology should be repeated in 3 to 4 weeks.

  • Immunohistological methods can detect B19 in tissues.

  • Viral culture is generally reserved for research settings.

How does this organism cause disease?

  • Parvovirus B19 is tropic for differentiated erythrocytes through the receptor blood group P antigen.

  • Those individuals who lack P antigen are resistant to B19 infection.

  • The virus is cytotoxic to erythrocytes.

  • It also induces interleukin-6 which may contribute to the arthropathy and autoimmune antibody production.

WHAT’S THE EVIDENCE for specific management and treatment recommendations?

Chauvet, A, Dewilde, A, Thomas, D, Joriot, S, Vaast, P, Houfflin-Debarge, V, Subtil, D. "Ultrasound diagnosis, management and prognosis in a consecutive series of 27 cases of fetal hydrops following maternal parvovirus B19 infection". Fetal Diagn Ther. vol. 30. 2011. pp. 41-7.

(Discusses management of the complications of perinatal infection.)

de Jong, EP, Walther, FJ, Kroes, AC, Oepkes, D. "Parvovirus B19 infection in pregnancy: new insights and management". Prenat Diagn. vol. 31. 2011. pp. 419-25.

(Good review of the management of Parvovirus B19 infection in the pregnant patient.)

Slavov, SN, Kashima, S, Pinto, AC, Covas, DT. "Human parvovirus B19: general considerations and impact on patients with sickle-cell disease and thalassemia and on blood transfusions". FEMS Immunol Med Microbiol. vol. 62. 2011. pp. 247-62.

(Article provides an overview of the clinical interaction between parvovirus B19 infection and red blood cell diseases.)

Florea, AV, Ionescu, DN, Melhem, MF. "Parvovirus B19 infection in the immunocompromised host". Arch Pathol Lab Med. vol. 131. 2007. pp. 799-804.

(Overview of the considerations in diagnosing and treating parvovirus B19 infection in immunocompromised patients.)
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