Viral etiology of acute gastroenteritis in young children studied by polymerase chain reaction assay

Abstract

Using PCR assays, 1561 episodes (729 in the rhesus-human reassortant tetravalent (RRV-TV) rotavirus vaccine group and 832 in the placebo group) of acute gastroenteritis in prospectively followed children between 2 months and 2 years of age during an efficacy trial of the RRV-TV rotavirus vaccine in 1993 to 1995 were examined for rotaviruses, enteric adenoviruses (Ead), astroviruses, Norwalk-like viruses (NLV), and Sapporo-like viruses (SLV). PCR could establish a viral etiology in 60% (502/8320) of all episodes of acute gastroenteritis and in 85% of moderately severe or severe cases of acute gastroenteritis in young children in Finland. This is in contrast with the 46% rate of resolving mild cases. The detecting rate were: rotavirus 29%, NLV 20%, SLV 9.3%, astrovirus 9%, and Ead 6.3%. Rotavirus occurred in winter time and the season peaked between March and May. The epidemic season of astrovirus was similar to that of rotavirus. Ead occurred throughout the year. NLV and SLV each also had a winter epidemic season, but distinct from each other and distinct from rotavirus. The order of overall severity of the gastroenteritis episodes was rotavirus > NLV > Ead > SLV > astrovirus. For diarrhea, the order ofseverity was rotavirus > Ead > SLV > NLV > astrovirus, and for vomiting rotavirus = NLV > astrovirus = SLV = Ead. Rotavirus gastroenteritis was associated with the highest fever, with Ead second. The study demonstrated that with appropriate PCR methods, a viral etiology can be found for vast majority of clinically significant episodes of acute gastroenteritis in young children in the community. Rotaviruses and NLVs are the two most important viral causes of gastroenteritis in children under 2 years of age in Finland. Rotavirus RT-PCR detected 27% more cases than EIA, which complemented the final results of the RRV-TV rotavirus vaccine efficacy trial. The overall vaccine efficacy was reduced from 68% to 61% using rotavirus case detection by RT-PCR as an endpoint. Since most pf the 'new' cases of rotavirus gastroenteritis detected by RT-PCR were clinically mild, the vaccine efficacy for severe rotavirus disease was not changed with the addition of RT-PCR positive cases. Particularly G2 and G4 rotaviruses were more frequently detected by RT-PCR than had previously been by EIA. With the combined EIA and RT-PCR results it was also possible to conclude that the RRV-TV vaccine provided 60% protection against G2 and 62% protection against G4 rotavirus associated gastroenteritis. RRV-TV rotavirus vaccine shortened and reduced Ead diarrhea even if the vaccine did not reduce the number of cases of Ead gastroenteritis. RRV-TV rotavirus vaccine did not affect astrovirus and NLV gastroenteritis in this study. At present, there do not appear to be any other large scale studies that have looked for all of the presently known gastroenteritis viruses using PCR methods in the community. The methods used in the present study are unsuitable for routine diagnostic work, but for reseach purposes similar etiologic surneys should be conducted elsewhere.

Using PCR assays, 1561 episodes (729 in the rhesus-human reassortant tetravalent (RRV-TV) rotavirus vaccine group and 832 in the placebo group) of acute gastroenteritis in prospectively followed children between 2 months and 2 years of age during an efficacy trial of the RRV-TV rotavirus vaccine in 1993 to 1995 were examined for rotaviruses, enteric adenoviruses (Ead), astroviruses, Norwalk-like viruses (NLV), and Sapporo-like viruses (SLV). PCR could establish a viral etiology in 60% (502/8320) of all episodes of acute gastroenteritis and in 85% of moderately severe or severe cases of acute gastroenteritis in young children in Finland. This is in contrast with the 46% rate of resolving mild cases. The detecting rate were: rotavirus 29%, NLV 20%, SLV 9.3%, astrovirus 9%, and Ead 6.3%. Rotavirus occurred in winter time and the season peaked between March and May. The epidemic season of astrovirus was similar to that of rotavirus. Ead occurred throughout the year. NLV and SLV each also had a winter epidemic season, but distinct from each other and distinct from rotavirus. The order of overall severity of the gastroenteritis episodes was rotavirus > NLV > Ead > SLV > astrovirus. For diarrhea, the order ofseverity was rotavirus > Ead > SLV > NLV > astrovirus, and for vomiting rotavirus = NLV > astrovirus = SLV = Ead. Rotavirus gastroenteritis was associated with the highest fever, with Ead second. The study demonstrated that with appropriate PCR methods, a viral etiology can be found for vast majority of clinically significant episodes of acute gastroenteritis in young children in the community. Rotaviruses and NLVs are the two most important viral causes of gastroenteritis in children under 2 years of age in Finland. Rotavirus RT-PCR detected 27% more cases than EIA, which complemented the final results of the RRV-TV rotavirus vaccine efficacy trial. The overall vaccine efficacy was reduced from 68% to 61% using rotavirus case detection by RT-PCR as an endpoint. Since most pf the 'new' cases of rotavirus gastroenteritis detected by RT-PCR were clinically mild, the vaccine efficacy for severe rotavirus disease was not changed with the addition of RT-PCR positive cases. Particularly G2 and G4 rotaviruses were more frequently detected by RT-PCR than had previously been by EIA. With the combined EIA and RT-PCR results it was also possible to conclude that the RRV-TV vaccine provided 60% protection against G2 and 62% protection against G4 rotavirus associated gastroenteritis. RRV-TV rotavirus vaccine shortened and reduced Ead diarrhea even if the vaccine did not reduce the number of cases of Ead gastroenteritis. RRV-TV rotavirus vaccine did not affect astrovirus and NLV gastroenteritis in this study. At present, there do not appear to be any other large scale studies that have looked for all of the presently known gastroenteritis viruses using PCR methods in the community. The methods used in the present study are unsuitable for routine diagnostic work, but for reseach purposes similar etiologic surneys should be conducted elsewhere.