Toyoko Nakagomi

Incidence and Burden of Rotavirus Gastroenteritis in Japan, as Estimated from a Prospective Sentinel Hospital Study

We assessed the burden of rotavirus infection-related disease, in terms of hospitalization and associated costs, at 3 sentinel hospitals in Akita prefecture, Japan. From January 2001 through December 2002, a total of 443 children <5 years of age were hospitalized for acute gastroenteritis. Of 422 stool specimens collected, 244 (58%) tested positive for rotavirus. Only 7.8% of the rotavirus disease-associated hospitalizations involved infants <6 months of age, whereas most cases of disease (39%) were reported in the second year of life, and 89% of cases had occurred by 36 months of age. The mean severity score for rotavirus gastroenteritis resulting in hospitalization was 16.5, according to the modified 20-point severity scoring system. The average associated direct medical cost was 136,000 yen (1236 US dollars) per case and was similar among the 3 hospitals. The estimated incidence of rotavirus disease-associated hospitalizations among children <5 years of age was 7.9-17.6 hospitalizations/1000 person-years, and the estimated cumulative incidence by 5 years of age was 6.6%. Thus, approximately 1 in 15 children will require hospitalization due to rotavirus diarrhea by their fifth year of life. In Japan, this would mean that 78,000 children <5 years of age would be hospitalized each year, resulting in a direct medical cost of 10 billion yen (96 US dollars million). The burden associated with rotavirus gastroenteritis in Japan is substantial and might be reduced through the introduction of vaccines.

Healthcare-associated Viral Gastroenteritis among Children in a Large Pediatric Hospital, United Kingdom

Enteric viruses introduced from the community are major causes of these illnesses.

Genetic diversity and similarity among mammalian rotaviruses in relation to interspecies transmission of rotavirus

SummaryTo address the question whether there was any molecular evidence for interspecies transmission of rotaviruses from one animal species to another, genetic relationships among human and animal rotaviruses were examined by a series of hybridization experiments in which genomic RNAs from 14 rotavirus strains derived from seven different host species were hybridized with the [32P]-labelled transcription probes prepared from 11 strains representing rotaviruses from those seven host species. In general, higher level of homology among most, if not all, of the cognate gene segments that allowed classification into the same genogroup was shared among rotaviruses recovered from the same animal species but this level of homology was not found among rotavirus strains derived from different host species. However, such a high level of homology that was usually found among rotaviruses recovered from the same animal species was detected between feline rotavirus strain Cat97 and canine rotavirus strain K9 as well as between human rotavirus strain AU-1 and feline rotavirus strain FRV-1. The sharing of closely related genetic constellation of most of the 11 gene segments (genogroup) by rotaviruses recovered from different animal species provided molecular evidence that interspecies transmission of rotaviruses occurred in nature at least recently in the evolutionary history.

The Relative Frequencies of G Serotypes of Rotaviruses Recovered from Hospitalized Children with Diarrhea: A 10‐Year Survey (1987–1996) in Japan with a Review of Globally Collected Data

Since rotavirus vaccines aim to protect children from severe diarrhea, knowledge of the prevailing G serotypes among rotaviruses from hospitalized children is essential. Thus, we determined the G serotypes of rotaviruses collected from children with acute diarrhea in a local referral hospital in Akita, Japan, over the 10‐year period between January 1987 and December 1996. Based on the assumption that rotaviruses with an identical electropherotype possess the same G serotype, the G serotypes of 488 rotavirus‐positive specimens that were classified into 63 electropherotypes were determined by enzyme‐linked immunosorbent assay with a supplementary use of G typing by reverse transcription‐PCR. The relative frequencies over the 10‐year period were 77.0 (G1), 14.5 (G2), 2.7 (G3) and 5.3% (G4), leaving the possibility that only 0.4% had G serotypes uncommon to human rotaviruses. Of 24,050 rotaviruses extracted by reviewing 63 serotyping studies in literature, the relative frequencies of the four major G serotypes were 50.6 (G1), 9.3 (G2), 7.2 (G3) and 11.6% (G4). As to uncommon G serotypes, only 0.9% were described as serotypes other than G1–4, and our estimate for potential uncommon serotypes were at most 8.1%. Thus, both this long‐term study focusing on the rotaviruses only from severe cases in a single hospital in Japan and the global review of G serotypes published to date indicate that the primary target of any rotavirus vaccines should be rotaviruses possessing serotypes G1–4.

Rotavirus antigenemia in children with encephalopathy accompanied by rotavirus gastroenteritis

Summary.Rotavirus antigen was detected in acute phase sera from 5 of 8 children with rotavirus-associated encephalopathy, confirming antigenemia. However, antigen was not detected in cerebrospinal fluid, failing to provide added evidence of invasion to the brain.

Winter seasonality and rotavirus diarrhoea in adults

We investigated the aetiological role of group A rotavirus in adults with acute diarrhoea in a 4-year prospective study. Of 683 patients with acute diarrhoea, 97 (14%) shed rotavirus as a sole agent, whereas six (5%) of 115 patients without diarrhoea shed rotavirus. Half of patients with rotavirus diarrhoea required admission to hospital. Unlike rotavirus diarrhoea in children, the occurrence of rotavirus-positive cases did not show a significant winter seasonality. Rotavirus infection should be included in the differential diagnosis of diarrhoeal diseases in adults.

Molecular evidence for naturally occurring single VP7 gene substitution reassortant between human rotaviruses belonging to two different genogroups

SummaryTwenty four stool rotaviruses that comprised 22 distinct electropherotypes were selected for genome analysis from the collection of diarrheal specimens obtained over an eight-year period. These 22 electropherotypes were found in 46% of the total electropherotypes identified during the previous studies and represented 328 (64%) of rotavirus specimens in the collection. When genomic RNAs from these stool rotaviruses were hybridized to the32P-labeled transcription probes prepared from prototypes representing three human rotavirus genogroups, Wa, DS-1, and AU-1, any one of the isolates showed a high degree of homology only with one of the three probes, which data confirmed and extended our previous observation on the existence of three distinct genogroups among human rotaviruses. Two stool rotaviruses which had an unusual combination of serotype (G1), subgroup (I) and RNA pattern (an identical short electropherotype), however, yielded the hybridization pattern indicative of an intergenogroupic single VP7 gene substitution reassortant. When they were cell culture adapted and analyzed by RNA-RNA hybridization, molecular evidence was obtained indicating that their VP7 gene derived from viruses belonging to the Wa genogroup whereas the remaining 10 genes hybridized with viruses belonging to the DS-1 genogroup. Interestingly, these natural reassortants emerged in the midst of the rotavirus season in which G1 strains predominated.

Isolation and molecular characterization of a serotype 9 human rotavirus strain.

A human rotavirus strain, designated AU32, that belongs to serotype 9 was isolated and was compared by RNA‐RNA hybridization with recently established two serotype 9 strains (WI61 and F45) as well as other prototype human strains. These three strains exhibited a very high degree of homology with one another and shared a high degree of homology with strains belonging to the Wa genogroup but not with strains belonging to either the DS‐1 or AU‐1 genogroup. These results suggest that genetic constellation of the serotype 9 strains is similar to that of the commonest human rotavirus despite the recent recognition of this serotype.

Direct evidence for genome segment reassortment between concurrently-circulating human rotavirus strains

Summary. Extensive heterogeneity in electropherotypes observed among group A human rotaviruses has been considered as a result of two major mechanisms; i.e., the accumulation of point mutations and genetic reassortment between concur-rently-circulating strains. However, no evidence was reported thus far indicating that any one of field isolates of rotavirus was formed by direct reassortment of concurrently circulating two parental strains. Comparison of the genome of human rotavirus specimens collected over a six year period by electropherotyping and by the sequencing of selected gene segments identified two reassortants that were generated in nature between strains circulating co-dominantly in the same epidemic season. This is the first report directly showing that at least some part of electrophoretic diversity observed among rotavirus strains was explained by genetic reassortment between strains concurrently circulating in the human population. This supports the hypothesis that genetic reassortment among co-circulating strains operates as a key mechanism for the genetic variability of rotaviruses in nature.

Rotavirus Infection and Intussusception:A View from Retrospect

A live orally‐administrable rhesus rotavirus (RRV) tetravalent (TV) vaccine, licensed in the U.S.A. and the European Union, was recalled from the market because it was suspected to increase the risk of intussusception during the week following immunization. In contrast, natural rotavirus infection is generally believed not to cause intussusception. Because my experience contributed to the first paper that linked intussusception with rotavirus infection, I have re‐examined our own data published 22 years ago and other studies on this issue. I also made a case study of adenovirus and intussusception as a paradigm to establish an etiological association of viral infection and intussusception. My hypothesis postulated in this review is that natural infection of susceptible (or predisposed) infants with some rotavirus strains, probably serotype G3 rotaviruses, will result in an appreciable fraction of idiopathic intussusception. Thus, the number of rotavirus‐induced intussusception cases may change reflecting the relative frequency of G3 strains, which I believe was much higher in the 70s than during the last two decades. The epidemiological data indicate that the RRV‐TV vaccine triggers intussusception at a rate significantly higher than the background incidence rate following the week of vaccination, particularly after the first dose. In contrast, the data do not suggest that the cumulative incidence among the vaccine recipients increases accordingly, implicating that the risk of intussusception attributable to the RRV‐TV vaccine may be minimal.