Blutt Sarah E, Matson David O, Crawford Sue E, Staat Mary Allen, Azimi Parvin, Bennett Berkeley L, Piedra Pedro A, Conner Margaret E
Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, United States of America.
PLoS Med. 2007 Apr;4(4):e121. doi: 10.1371/journal.pmed.0040121.
Antigenemia 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.
Serum 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).
Most 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.
在轮状病毒感染的儿童中，抗原血症很常见。虽然已在血清中检测到轮状病毒RNA，但尚未有轮状病毒血症的确切证据。我们旨在分析特定患者群体，以确定在轮状病毒抗原血症患儿的血清中能否检测到感染性病毒。
收集了因胃肠炎住院儿童（57例粪便轮状病毒阳性和41例轮状病毒阴性）、已知（n = 58）或未知（n = 17）病毒病因的确诊细支气管炎患儿、非感染性非慢性疾病患儿（n = 17）以及健康成人（n = 28）的血清样本，通过酶免疫测定（EIA）检测轮状病毒抗原。评估血清抗原检测结果与儿童临床和免疫特征的相关性。在粪便轮状病毒阳性的儿童中，90%（51/57）检测到轮状病毒抗原血症；在无腹泻但粪便轮状病毒阳性的儿童中，89%（8/9）检测到；在无胃肠炎的病因不明的细支气管炎患儿中，12%（2/17）检测到；在患有胃肠炎但粪便轮状病毒阴性的儿童中，12%（5/41）检测到。在非感染性非慢性疾病患儿、病因已知且无胃肠炎的细支气管炎患儿或健康成人的血清中未检测到抗原血症。胃肠炎发病后八天内的年龄和血清采集时间均未显著影响抗原血症水平，且抗原血症与病毒基因型之间无相关性。然而，血清轮状病毒抗原与急性轮状病毒特异性血清IgA（r = -0.44，p = 0.025）和IgG（r = -0.40，p = 0.01）滴度呈负相关。我们使用轮状病毒结构和非结构蛋白的免疫荧光染色，在HT - 29细胞中对11份抗原阳性和9份抗原阴性血清进行了三轮盲传后，检测感染性病毒。在血清抗原阳性儿童的11/11（100%）份血清中检测到感染性病毒，在抗原阴性儿童的9份血清样本中的2份（22%）中检测到（p = 0.002）。
大多数感染轮状病毒的儿童存在病毒血症。病毒血症的存在与抗原血症的检测直接相关，且与腹泻的存在无关。抗原血症负荷与血清中抗轮状病毒抗体滴度呈负相关。血液中检测到感染性轮状病毒表明轮状病毒发病机制中存在肠道外受累；然而，轮状病毒血症对感染临床表现的影响尚不清楚。
