Parvovirus and Increasing Danger in Pregnancy and Sickle Cell Disease
By Stan Deresinski, MD, FACP, FIDSA
Synopsis: The incidence of human parvovirus B19 infection is increasing in the United States, putting vulnerable groups at risk of serious complications.
Sources: Alfego D, Hernandez-Romieu AC, Briggs-Hagen M, et al. Detection of increased activity of human parvovirus B19 using commercial laboratory testing of clinical samples and source plasma donor pools — United States, 2024. MMWR Morb Mortal Wkly Rep. 2024;73(47):1076-1081.
Contag S, Dufort EM, Lim S, et al. Notes from the Field: Human parvovirus B19 infections among pregnant persons — Minnesota, January-September 2024. MMWR Morb Mortal Wkly Rep. 2024;73(47):1087-1089.
Yee MEM, Kalmus GG, Patel AP, et al. Notes from the Field: Increase in diagnoses of human parvovirus B19-associated aplastic crises in children and adolescents with sickle cell disease — Atlanta, Georgia, December 14, 2023-September 30, 2024. MMWR Morb Mortal Wky Rep. 2024;73(47):1090-1091.
Surveillance of human parvovirus B19 infection in Europe using clinical, laboratory, and blood donation screening data identified significant increased incidences in late 2023 and 2024.1 This surge has now been demonstrated to affect the United States and raises particular concern for vulnerable groups who are at risk of serious complications.
Alfego and colleagues addressed the rising incidence in the United States by reviewing parvovirus B19 immune globulin M (IgM) antibody test results on specimens submitted to a U.S. reference laboratory by physicians. They also examined the results in the same laboratory of screening nucleic acid amplification testing (NAAT) performed on pooled donor source plasma (512 donations per pool) by the same laboratory. IgM antibody testing was performed on 399,098 specimens from 359,445 adults; 92.6% were from adults and, of these, 87.7% were from women.
While < 1.5% of IgM tests were positive in 2020-2023, this proportion increased, reaching 9.9% in the second quarter of 2024. This level was higher than in second quarter peaks in 2018 (3.8%) and 2019 (5.1%). While < 2% of donor pools were NAAT-positive during 2020-2023, 20% were positive in June 2024 — significantly higher than previous peaks in 2018 (6.7%) and 2019 (7.3%).
Other data demonstrated an increase in adverse outcomes of infections in vulnerable groups. Contag and colleagues reported that the Minnesota Department of Public Health investigated five unrelated cases of parvovirus B19 infection in pregnant women aged 20-40 years that had been reported to them during May-August 2024. Four of the five had children in the household, while the fifth woman apparently was exposed while working at a childcare facility. The infection occurred at 13-20 weeks of gestation in all five cases and was confirmed by IgM antibody testing or polymerase chain reaction (PCR) (including PCR testing of amniotic fluid in three cases). None of the patients had immunocompromise or hematologic disorders.
One of the five patients developed fetal hydrops with fetal demise, while another with severe fetal anemia and hydrops received two fetal transfusions and survived. Two others with severe anemia also were transfused. Four infants were delivered at full term without complications either at the time or during the neonatal period.
Yee and colleagues described their experience with parvovirus B19 infection in children with sickle cell disease (SCD). Initially, a 10-year-old child with SCD who died unexpectedly was found to have a hematocrit of < 15%. Testing for parvovirus B19 was not performed, but six days later, a 14-year-old sibling with SCD developed an aplastic crisis, and laboratory testing confirmed the presence of parvovirus B19 infection. The sibling was given blood transfusions and recovered.
Review of the Sickle Cell Database of Children’s Healthcare of Atlanta (CHOA) was performed to examine trends in parvovirus B19 infection. All children at CHOA with SCD who experience a > 1 g/dL decrease in hemoglobin level together with reticulocytopenia are tested for the presence of parvovirus B19 infection. A total of 55 cases of B19 infection with aplastic anemia were identified from December 2023 through September 2024. The incidence (35.6 per 1,000 patient-years) was 3.8 times higher than during the period 2010-2023.
Commentary
While most cases go undiagnosed, human parvovirus B19 infection is a frequent occurrence, with approximately 50% of the population being seropositive by age 20 years, with a further increase to approximately 70% at 40 years of age. In immunocompetent people who are symptomatic, the most common manifestations are flu-like systemic symptoms, skin rash (erythema infectiosum — “slapped cheek disease”), and arthralgias. The virus infects erythrocyte precursors, which results in reduced production as reflected by anemia and reticulocytopenia and, in some patients such as those with chronic hemolytic states, potentially life-threatening aplastic anemia. In fetal infection, this may result in hydrops fetalis. An inability to mount an effective response because of immunocompromise also may result in the development of aplastic anemia. Rare cases of encephalitis also have occurred.
The increased incidence of infection identified in both Europe and the United States has been attributed to a “COVID immunity gap” — an increased non-immune population resulting from reduced infections as a consequence of pandemic-related isolation practices. It is imperative that clinicians be aware of the manifestations and risks of this infection and that precautions be taken to reduce the risk of transmission of respiratory infections.
The findings highlight the need to be familiar with all the manifestations of parvovirus B19 infection, paying particular attention regarding people with the greatest risk of adverse consequences from the infection, including pregnant people and their fetuses, people with severe immunocompromise, and people with chronic hemolytic blood disorders.1
Stan Deresinski, MD, FACP, FIDSA, is Clinical Professor of Medicine, Stanford University.
Reference
1. Deresinski S. In the Literature. Human parvovirus B19 infection surging in Europe; Risk in pregnancy. Clin Infect Dis 2024;79:i-ii. https://doi.org/10.1093/cid/ciae457