Rotavirus antigenemia is frequently observed in a patient's serum during the acute phase, and viral antigen levels change dramatically during the acute phase of the illness. Because patients with fever had higher rotavirus antigen levels, antigenemia severity might contribute to fever. The host immune response plays an important role in controlling antigenemia levels.

Systemic rotavirus infection, such as rotavirus antigenemia, has been found in immunocompetent rotavirus gastroenteritis patients. However, the pathogenesis of rotavirus infection in immunocompromised transplant recipients remains unclear. Enzyme-linked immunosorbent assay was used to measure rotavirus antigen levels in serially collected serum samples obtained from 62 pediatric patients receiving allogeneic hematopoietic stem cell transplants (HSCT). Rotavirus antigen was detected in 43 (6.8%) of 633 serum samples (8 of 62 patients). The duration of rotavirus antigenemia ranged between 1 and 10 weeks, and diarrhea was concurrent with rotavirus antigenemia in Cases 3, 6, 7, and 8. The level of viral antigen in the transplant recipients (0.19 ± 0.20) was significantly lower than that observed in serum samples collected from immunocompetent patients on either day 1 (0.49 ± 0.18, P = 0.0011) or day 3 (0.63 ± 0.09, P = 0.0005). A patient who received a graft from a human leukocyte antigen (HLA)-mismatched donor was at significant risk for rotavirus antigenemia (P = 0.024; odds ratio = 9.44) in comparison to patients who received grafts from HLA-matched donors. Although the duration of antigenemia was clearly longer in HSCT patients than in immunocompetent rotavirus gastroenteritis patients, the levels of viral antigen were not as high. Therefore, mismatched HLA may be a risk factor for rotavirus antigenemia after HSCT.

A 2.5-year-old girl died suddenly during the course of rotavirus gastroenteritis. The autopsy showed encephalopathy with rotavirus systemic infection. Here, we provide evidence of rotavirus replication in multiple organs. Our findings clarify that rotavirus infection in children can extend beyond the intestinal tract through viremia. CASE REPORTA previously healthy 2.5-year-old girl presented to our hospital following two febrile seizures. She had a 2-day history of diarrhea due to rotavirus gastroenteritis, which had been diagnosed before admission by a positive rotavirus antigen test of her stool. The seizures were generalized tonic-clonic seizures lasting 1 to 5 min each and occurred within 5 h of each other.On examination, she was alert with a temperature of 39.3°C. Examination showed normal pupillary light reflexes, normal muscle tone, and normal patellar and Achilles tendon reflexes. The heart and lung sounds were also normal.Laboratory analysis of blood obtained while in the emergency room showed the following: white blood cell count, 23,800/l (97% neutrophils); hemoglobin, 11.9 g/dl; platelet count, 366,000/l; erythrocyte sedimentation rate, 11 mm/h; C-reactive protein, 0.79 mg/dl; blood sugar, 121 mg/dl; serum ammonia, 22 mg/dl; sodium, 131 meq/liter; potassium, 4.1 meq/ liter; chloride, 99 meq/liter; aspartate aminotransferase (AST), 50 IU/liter; alanine aminotransferase (ALT), 32 IU/liter; lactate dehydrogenase, 317 IU/liter; and creatinine phosphokinase, 420 IU/liter. Immune function testing revealed a low IgG level, at 384 mg/dl (normal range for age 2 years, 649 to 1,306 mg/dl) but normal IgG subclass analysis. the IgA level was 31 mg/dl, and the IgM level was 74 mg/dl. Coagulation tests were not performed. A blood culture yielded no bacterial growth.An hour after arrival at the hospital, the patient experienced two more seizures. The fourth and final seizure developed into status epilepticus and was treated with intravenous diazepam. As the seizure gradually ended, the electrocardiogram monitor showed a brief period of ventricular fibrillation followed by asystole. Immediate resuscitation attempts were unsuccessful.An autopsy was undertaken 12 h after the patient died. Cardiac tissues were submitted to the National Cardiovascular Center (Japan) for pathological analysis.Analysis of the cerebrospinal fluid (CSF) obtained at autopsy revealed a leukocyte level of 240/mm 3 and a protein level of 288 mg/dl. Rotavirus RNA was detected in the CSF by reverse transcription-PCR (RT-PCR). Serum diluted 1:16 showed a positive enzyme-linked immunosorbent assay (ELISA) reaction using an anti-VP6 mouse monoclonal antibody (YO-156) to detect antigenemia (12). The optical density at 492 nm obtained with the patient's serum was 0.932, compared with 0.035 for the negative control.The autopsy revealed brain edema but no cerebral herniation. Although there was focal inflammatory cell infiltration in parts of the subarachnoid space, this was not indicative of encephalitis or meningitis. There was concentric cardiac hyp...

Rotavirus (RV) antigenemia has been reported in patients with gastroenteritis; however, the exact mechanism remains unclear. In order to elucidate the mechanism of RV antigenemia, an association between RV antigenemia and matrix metalloproteinase (MMP) were analyzed. The object of this study was to elucidate the role of MMPs and tissue inhibitors of metalloproteinases (TIMPs) in the pathogenesis of RV antigenemia. Forty children admitted to hospital with RV gastroenteritis were enrolled in this study. Paired serum samples were collected at the time of admission and discharge. Enzyme-linked immunosorbent assays (ELISA) were used to detect serum concentrations of viral antigens, MMP-1, -2, -9, -13, TIMP -1, and -2. Cytokines were measured using flow cytometric beads array. RV antigens were significantly higher in serum collected at the time of admission than discharge (P < 0.001). MMP-9 concentrations were significantly higher in serum collected at the time of admission than discharge (P < 0.001). MMP-2 concentrations were significantly lower in serum collected at the time of admission than discharge (P < 0.001). A weak but a significantly positive association (P = 0.034) was observed between RV antigen and MMP-9 in serum collected at the time of admission, and inverse association was observed between RV antigen and MMP-2. In addition, a weak but significantly positive association (P = 0.002) was observed between IL-6 and MMP-9. These data suggest that MMPs may contribute to the pathogenesis of RV antigenemia.

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