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

Abstract

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...

A novel group A rotavirus associated with acute illness and hepatic necrosis in pigeons (Columba livia), in Australia

“…In mammals, rotaviruses are generally recognised to be gastroenteric pathogens of neonates [ 26 ] although the pathogenesis of disease is incompletely understood [ 27 ]. However, there is increasing recognition that infection may be associated with viraemia [ 27 – 32 ], and disease other than enteritis has been reported in both humans and animals [ 20 , 27 , 33 ] although not yet in birds.…”

Pathophysiological analysis of five severe cases with rotavirus infection

“…Blutt et al (2007) reported that antigenaemia is predictive of viraemia and can be used as a marker of extraintestinal rotavirus involvement. Rotavirus antigen and RNA have been detected in endothelial cells (Cioc & Nuovo, 2002;Morrison et al, 2001), the central nervous system (Nakano et al, 2011), and the liver (Gilger et al, 1992;Nakano et al, 2011) of autopsy cases with fatal rotavirus infection. Because permission for autopsy was not granted in our fatal cases, we could not investigate the relationship between antigenaemia and extraintestinal involvement.…”

“…Prior to implementation of routine rotavirus immunization, rotavirus gastroenteritis annually caused an estimated 14-60 deaths among children in Europe and the USA (Parashar & Glass, 2006;Van Damme et al, 2006). Infection is mostly localized to the intestine, but severe cases can have extraintestinal involvement, including encephalopathy and sudden death (Ioi et al, 2006;Medici et al, 2011;Minato et al, 1992;Nakano et al, 2011;Salmi et al, 1978). The pathogenesis of these severe infections remains unclear.…”

N -Acetylcysteine Treatment of Rotavirus-Associated Diarrhea in Children

“…Rotavirus, a member of the Reoviridae family, is the leading cause of dehydrating diarrhea in children younger than 5 years old worldwide . Fatal encephalopathy with rotavirus systemic infection and virus replication in different organs has been recently reported . Two efficient rotavirus vaccines have been recently introduced, but the age‐restricted recommendation for vaccine administration, the low vaccine coverage, and the low on‐time immunization rates, as well as some logistical problems, are challenging the potential of these vaccines for reducing the risk of death in the poorest countries .…”

“…1 Fatal encephalopathy with rotavirus systemic infection and virus replication in different organs has been recently reported. 2 Two efficient rotavirus vaccines have been recently introduced, but the age-restricted recommendation for vaccine administration, the low vaccine coverage, and the low on-time immunization rates, as well as some logistical problems, are challenging the potential of these vaccines for reducing the risk of death in the poorest countries. 3,4 Alternative or complementary strategies for preventing or treating rotavirus-associated diarrhea are needed mainly in these countries.…”