INTRODUCTION — Human parvovirus B19 infections are common. They are usually mild or asymptomatic, and do not require treatment. In some cases, however, infection is associated with sufficiently severe complications that treatment is indicated and may be lifesaving.
The major clinical manifestations that can occur with parvovirus B19 infection include:
●Erythema infectiosum
●Arthritis or arthralgia
●Transient aplastic crisis
●Fetal hydrops
●Chronic infection with or without anemia
The major issues related to the treatment of symptomatic parvovirus B19 infection and to prevention of infection will be reviewed here. The epidemiology, transmission, clinical syndromes, diagnosis, and management of parvovirus B19 infection in pregnancy are discussed in detail separately. (See "Clinical manifestations and diagnosis of parvovirus B19 infection" and "Virology, epidemiology, and pathogenesis of parvovirus B19 infection" and "Parvovirus B19 infection during pregnancy".)
TREATMENT — Management of parvovirus B19 infection is primarily symptomatic and varies with the clinical manifestation (table 1) [1].
There is no specific antiviral drug available for the treatment of parvovirus B19 infection. In vitro studies that demonstrate inhibition of parvovirus B19 replication with brincidofovir (a lipid conjugated form of cidofovir) at a concentration achievable in vivo, with hydroxyurea, or with a coumarin derivative, warrant further evaluation [2-6]. Another in vitro study in CD36+ cells demonstrated that flavonoids, which are known to have antiviral properties, inhibited the endonuclease activity of the B19 NS1 protein and thus B19 deoxyribonucleic acid (DNA) replication [7].
Erythema infectiosum — Erythema infectiosum ("fifth" disease) is a self-limited, mild illness most often occurring in children. There is no specific therapy and usually no indication for symptomatic treatment. In some patients, symptomatic therapy for arthralgias, arthritis, or pruritus may be indicated [8].
Arthritis or arthralgia — Arthritis or arthralgia are most often reported in adult females but can occur in either sex and at any age. The joint symptoms usually last one to two weeks, but can persist for weeks, months, and even years [9].
Nonsteroidal anti-inflammatory drugs can provide symptomatic relief. Intravenous immune globulin (IVIG) has been given to two patients with presumed chronic parvovirus B19 infection and chronic arthritis [10]. The arthritis was not cured, but there may have been a short-term decrease in symptoms. These limited data do not support the use of IVIG treatment for parvovirus B19-associated arthropathy.
Transient aplastic crisis — Acute parvovirus B19 is a cause of transient aplastic crisis (TAC) in patients with certain underlying hematologic abnormalities, in which the interruption of red cell production in this setting rapidly leads to a severe anemia.
The anemia is often sufficiently severe (hemoglobin levels below 6 g/dL with few or no reticulocytes) to require transfusion until the patient's immune response eliminates the infection and red cell production returns. As an example, in a series of 62 sickle cell patients with TAC, 54 (87 percent) required blood transfusions, 39 (63 percent) were hospitalized, and one (1.6 percent) died [11]. The one death illustrates the importance of prompt diagnosis and treatment with transfusion therapy if indicated by the patient's condition.
The usual course of parvovirus associated-anemia is spontaneous resolution within a few days to weeks. Beyond supportive red blood cell transfusion, more aggressive therapy with IVIG is generally limited to patients with chronic parvovirus B19 infection and chronic anemia (see below).
Chronic infection — Chronic infection also can occur, producing anemia or other signs or symptoms.
Chronic infection with anemia — Most patients with chronic parvovirus B19 infection and anemia have received immunosuppressive therapy for cancer, leukemia, or tissue transplantation, have a congenital immunodeficiency, or have human immunodeficiency virus (HIV)-associated immunodeficiency. Reports of pure red cell aplasia have occurred in patients with HIV who have advanced immunosuppression [12,13]. Most of these reports have occurred prior to the availability of potent antiretroviral therapy (ART). (See "Clinical manifestations and diagnosis of parvovirus B19 infection", section on 'Chronic infection in immunosuppressed hosts'.)
In the setting of chronic infection with anemia in immunosuppressed patients, including those with HIV, we suggest IVIG with reduction of immunosuppression if possible. This is consistent with guidelines from the American Society of Transplantation for the treatment of symptomatic parvovirus B19 infection in solid organ transplant recipients [14]. In persons with HIV, ART should be initiated or maintained.
●In patients with solid organ transplant or other non-HIV causes of immunosuppression, we suggest 400 mg/kg/day of IVIG for five consecutive days, along with reducing immunosuppressive therapy, if possible [14].
●For persons with HIV, several different dosing regimens have been described, and the optimal one is unknown. Reported IVIG regimens include 1 g/kg/day for 2 days or 0.4 g/kg/day for 5 to 10 days [12,13,15]. One patient with HIV, chronic parvovirus B19 infection, and anemia apparently responded to treatment with 5 mL of intramuscular immune globulin [16]. We agree with other authors who suggest maintenance IVIG at doses of 0.4 g/kg/day every four weeks following the initial IVIG treatment dose to prevent relapse in patients with low CD4 cell counts (eg, <100 cells/microL) [13].
Recurrence of anemia and reappearance or increases in parvovirus B19 DNA in serum have usually responded to additional courses of IVIG treatment. Furthermore, if the immunodeficiency improves (eg, after discontinuation of immunosuppressive therapy or with the initiation of ART for HIV), chronic infection and anemia may resolve spontaneously [17-19].
Support for IVIG in these populations comes mainly from retrospective studies. In a retrospective study of 10 patients with pure red cell aplasia and proven parvovirus B19 infection who were treated with IVIG, anemia resolved in 9 of 10 within a mean of 80 days [20]. Patients received a mean of 2.7 IVIG courses at an average dose of 1.3 ± 0.5 g/kg per course. The only patient who did not respond to IVIG had underlying myelodysplasia. Among the seven patients with available follow-up blood parvovirus B19 polymerase chain reaction (PCR) results, five had negative PCR results within a mean of 97 days (range 35 to 159 days). None of the 9 responders had a relapse during 12 months of follow-up. In a review of published studies that was part of the same report, hemoglobin level was corrected after the first IVIG course in 124 of 133 patients (93 percent) with pure red cell aplasia caused by parvovirus B19 infection, but disease relapsed in 42 (34 percent) at a mean of 4.3 months.
For patients with refractory anemia despite IVIG, foscarnet may be an option. In a study of kidney transplant recipients with refractory anemia despite IVIG therapy and with good allograft function (estimated glomerular filtration rate >45mL/minute), foscarnet 6 g/day for 5 to 14 consecutive days successfully treated 91 percent of patients (10 out of 11) without any recurrence [21].
Chronic infection without anemia — Chronic parvovirus B19 infection has been demonstrated in patients without anemia or underlying immunodeficiency [22-25]. It is not clear if IVIG treatment is helpful in this setting. One such patient with thrombocytopenia received IVIG without an obvious response [23], while two patients with presumed chronic infection and arthritis had no virologic but possibly a transient clinical response [10]. In comparison, three patients with systemic vasculitis had an apparent clinical and virologic response after IVIG therapy [22]. Further study is needed to determine the role of IVIG in these patients.
Fetal infection — The management of fetal anemia and hydrops secondary to parvovirus B19 infection is discussed elsewhere. (See "Parvovirus B19 infection during pregnancy", section on 'Management of anemia and hydrops'.)
PREVENTION — The best measures currently available to prevent parvovirus B19 infection are those designed to interrupt transmission by personal infection control practices, such as good hand hygiene, covering the face when sneezing or coughing, not touching the eyes, mouth, or nose, avoiding close contact with sick individuals, and remaining home when ill. Immunoprophylactic therapy has been considered in some instances, but insufficient data are available to determine if it is efficacious.
Preventing transmission — Attention to good infection control practices should reduce the risk of transmitting parvovirus B19. Studies of rhinoviruses and enteroviruses, which are also spread by person-to-person contact, fomites, and large droplet aerosol, and are stable in the environment, suggest that hand washing and not sharing food or drinks is likely to prevent, at least partially, spread of parvovirus B19 in a variety of settings. One report of parvovirus B19 infections in a hospital suggested that good hygienic practices by staff may have decreased their risk of acquiring infection [26]. Staff who reported washing their hands rarely or only occasionally after contact with patients had a higher infection rate (p = 0.07).
The United States Centers for Disease Control and Prevention (CDC) recommends that patients with TAC be placed on standard and droplet isolation precautions for seven days and that immunodeficient patients with chronic infection be placed on droplet precautions for the duration of their hospitalization [27]. In comparison, patients with normal immune systems are probably not infectious after the onset of parvovirus B19-associated rash, arthralgias, or arthritis, when a robust antibody response would take place and dramatically reduce the patient's viral load.
Modes of transmission are discussed elsewhere. (See "Virology, epidemiology, and pathogenesis of parvovirus B19 infection", section on 'Transmission and risk factors for infection'.)
Groups or persons that might benefit from infection control measures — Good infection control practices in the home, workplace, and hospital should be emphasized to decrease the risk of transmission to persons with compromised immune systems, those with a need for increased production of red cells (eg, sickle cell disease [SCD]), and pregnant women.
The possibility of fetal hydrops and death has generated considerable concern, especially during community outbreaks of parvovirus B19. As noted above, there is no specific prevention available. Frequently, during parvovirus B19 outbreaks, supervisors, health care workers, pregnant women, and others will ask whether avoiding the workplace or outbreak settings such as schools or child care centers will decrease the risk to the fetus. The CDC recommends that pregnant women be informed about the risks of infection and make their own decision after consultation with health care workers, public health officials, and family members [28].
Understanding the risk is essential to making this decision. The primary risk is fetal death, and this risk is given by the following equation [28]:
Rate of fetal death = (rate of susceptibility x rate of infection from the exposure) ÷ (rate of fetal death with infection)
Estimates for each of these factors are available:
●For women in their childbearing years, between 40 and 60 percent, depending on the community and antibody detection assay used, will test positive for parvovirus B19 immunoglobulin (Ig)G antibodies and are presumably not susceptible to infection [29,30]. IgG antibodies against the VP1-unique region offer lifelong protection against parvovirus B19 reinfection [31].
●The risk of fetal death with maternal infection is less than 10 percent and probably between 2 and 5 percent [28,32,33].
If we assume the risk of fetal death with infection is between 2 and 5 percent and the rate of susceptibility is 50 percent, then the risk of fetal death associated with the following settings can be estimated:
●Between 0.5 percent and 1.25 percent for a household exposure, assuming a 50 percent infection rate
●Between 0.2 and 0.5 percent from working in a school with an erythema infectiosum outbreak, assuming a 20 percent infection rate
●Between 0.06 and 0.15 percent from living in a community with an erythema infectiosum outbreak, assuming a 6 percent infection rate
The available data suggest that parvovirus B19 uncommonly, if ever, causes congenital anomalies [34].
Candidate vaccines — Studies of candidate vaccines against parvovirus B19 have been hindered by potential side effects. Further developments of an initially promising recombinant human parvovirus B19 vaccine [35] and a viral-like particle vaccine [36] were suspended because of vaccine-associated adverse events. The reactogenicity with the previous vaccine candidates was found to be related to insect cell contaminants from insect cells used to produce the virus-like particles (VLPs) and to the phospholipase A2 activity from the VP1 protein in the VLPs.
Subsequent efforts in developing a parvovirus B19 vaccine candidate are focused on expressing VP1 and VP2 proteins in Saccharomyces cerevisiae to produce VLPs. The VP1-coding region contains a point mutation, which inactivates the phospholipase A2 activity [37]. One S. cerevisiae-derived parvovirus B19 vaccine containing both VP1 and VP2 capsid antigens and co-administered with the adjuvant MF59 appeared promising in a preclinical mouse model [38].
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics". The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topic (see "Patient education: Erythema infectiosum (fifth disease) (The Basics)")
SUMMARY AND RECOMMENDATIONS
●Overview of treatment – Parvovirus B19 infections are common, usually mild or asymptomatic, and generally require no or only symptomatic therapy. However, some uncommon severe complications of infection may warrant specific treatment (table 1). There is no specific antiviral drug available for the treatment of parvovirus B19 infection. (See 'Introduction' above and 'Erythema infectiosum' above and 'Arthritis or arthralgia' above.)
●Treatment of transient aplastic crisis – Transient aplastic crisis can occur when parvovirus B19 infection occurs in patients with underlying hematologic abnormalities, such as sickle cell disease, thalassemia, and hereditary spherocytosis, and causes severe anemia. The anemia is typically severe enough to warrant red blood cell transfusion but usually resolves spontaneously within a few days to weeks. (See 'Transient aplastic crisis' above.)
●Treatment of chronic infection – For immunocompromised patients with chronic parvovirus B19 infection and anemia, we suggest intravenous immune globulin (IVIG), in addition to decreasing immunosuppression, if possible (Grade 2C). It is unclear if IVIG is beneficial in the setting of chronic parvovirus B19 infection without anemia. (See 'Chronic infection' above.)
●Parvovirus B19 infection during pregnancy – The management of fetal anemia and hydrops is discussed elsewhere. (See "Parvovirus B19 infection during pregnancy", section on 'Management of anemia and hydrops'.)
●Prevention
•Prevention of parvovirus B19 infection depends on good infection control practices targeted towards the various modes of transmission. As parvovirus B19 is likely spread in the community through close contact (eg, person to person, through fomites, or through large droplets), adequate hand washing practices and not sharing food or drink is likely to help prevent spread of parvovirus B19 in a variety of settings. (See 'Prevention' above.)
•Good hygiene and infection control practices should be emphasized for patients with compromised immune systems, those with underlying hematologic abnormalities, and pregnant women. Because of the risk of fetal death in the setting of maternal infection, pregnant women should understand the risk of infection during parvovirus B19 outbreaks or exposures. (See 'Groups or persons that might benefit from infection control measures' above and "Parvovirus B19 infection during pregnancy".)
•Nosocomial transmission of parvovirus B19 can occur between patients and staff but can be difficult to distinguish from infection acquired in the community during outbreaks. Droplet precautions are indicated for seven days for patients with transient aplastic crisis and for the duration of the hospitalization for immunodeficient patients with chronic infection. (See 'Preventing transmission' above.)
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