Rotavirus Antigenemia in Children Is Associated with Viremia

Abstract

BackgroundAntigenemia is commonly detected in rotavirus-infected children. Although rotavirus RNA has been detected in serum, definitive proof of rotavirus viremia has not been shown. We aimed to analyze a defined patient population to determine if infectious virus could be detected in sera from children with rotavirus antigenemia.Methods and FindingsSerum samples obtained upon hospitalization from children with gastroenteritis (57 stool rotavirus-positive and 41 rotavirus-negative), children with diagnosed bronchiolitis of known (n = 58) or unknown (n = 17) viral etiology, children with noninfectious, nonchronic conditions (n = 17), and healthy adults (n = 28) were tested for rotavirus antigen by enzyme immunoassay (EIA). Results of serum antigen testing were assessed for association with clinical and immunological attributes of the children. Rotavirus antigenemia was detected in 90% (51/57) of children with rotavirus-positive stools, in 89% (8/9) of children without diarrhea but with rotavirus-positive stools, in 12% (2/17) of children with bronchiolitis of unknown etiology without gastroenteritis, and in 12% (5/41) of children with gastroenteritis but with rotavirus-negative stools. Antigenemia was not detected in sera from children with noninfectious nonchronic conditions, children with bronchiolitis of known etiology and no gastroenteritis, or healthy adults. Neither age nor timing of serum collection within eight days after onset of gastroenteritis significantly affected levels of antigenemia, and there was no correlation between antigenemia and viral genotype. However, there was a negative correlation between serum rotavirus antigen and acute rotavirus-specific serum IgA (r = −0.44, p = 0.025) and IgG (r = −0.40, p = 0.01) titers. We examined 11 antigen-positive and nine antigen-negative sera for infectious virus after three blind serial passages in HT-29 cells using immunofluorescence staining for rotavirus structural and nonstructural proteins. Infectious virus was detected in 11/11 (100%) sera from serum antigen-positive children and in two out of nine (22%) sera samples from antigen-negative children (p = 0.002).ConclusionsMost children infected with rotavirus are viremic. The presence of viremia is directly related to the detection of antigenemia and is independent of the presence of diarrhea. Antigenemia load is inversely related to the titer of antirotavirus antibody in the serum. The finding of infectious rotavirus in the blood suggests extraintestinal involvement in rotavirus pathogenesis; however, the impact of rotavirus viremia on clinical manifestations of infection is unknown.

Rotavirus Differentially Infects and Polyclonally Stimulates Human B Cells Depending on Their Differentiation State and Tissue of Origin

“…In addition, a significant antigenemia and viremia is seen in most acutely infected children (8,9). In particular, we have shown the in vivo replication of homologous and heterologous RV strains in B220 ϩ cells (a marker expressed by B cells or plasmacytoid dendritic cells [pDC]) obtained from murine mesenteric lymph node (24), and recently we also demonstrated that approximately 10% of primary human circulating B cells (CBC) are targets of RV infection in vitro (49).…”

Sudden Death from Systemic Rotavirus Infection and Detection of Nonstructural Rotavirus Proteins

“…Rotavirus is a common cause of gastroenteritis in infants and children. Recent studies have shown that rotavirus infection is commonly associated with antigenemia and can occasionally spread beyond the gastrointestinal tract, causing systemic infection (1,4,12). This report highlights encephalopathy due to systemic rotavirus infection and reports novel findings relating to the characteristics of this disease.…”

“…In this case, rotavirus antigen was detected in the serum of a patient who presented with a high fever. Blutt et al reported that antigenemia is predictive of viremia and can be used as a marker for the presence of extraintestinal rotavirus (1). Fever has been correlated with the severity of rotavirus antigenemia (12).…”

Vaccination Against Rotavirus Infection: 10-Year Global Experience of Successful Use

“…Кроме того, в 2007 г. Blutt и соавт. [76] сумели выде-лить антигены вирусной РНК ротавируса в образцах крови детей с РВГЭ, а также в других органах и тканях, в результате чего предположительно и могут развивать-ся внекишечные проявления РВИ. Например, исследо-ватели из Турции приводят результаты наблюдения за 353 детьми, перенесшими РВГЭ [77].…”