[Intestinal rotavirus infections (HRV - human Rotavirus)].
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The purpose of this study was to determine the role of intestinal specific rotavirus IgA antibody in protection against diarrhoea due to rotavirus infection. Stool from children aged below 5 years with diarrhoea who reported to the Paediatric Observation Ward, Kenyatta National Hospital were examined for micro-organisms and IgA antibody. Specific rotavirus IgA antibody and antigen were determined using enzyme linked immunosorbent assay technique. Out of 153 stool specimens, 22% (34/153) were positive for rotavirus antigen and 15% (23/153) had IgA specific antibody to rotavirus. Children with specific IgA to rotavirus had no rotavirus except in two cases (p < 0.05). There was no difference in levels of specific IgA antibody between normal and malnourished children (p = 0.4). It is probable that intestinal specific IgA to rotavirus protects children against rotavirus diarrhoea.
Rotavirus is the most common cause of acute watery diarrhea in young Korean children. Rotavirus vaccine will soon be available, and information is urgently required about the serotype distribution of recent epidemics and clinical characteristics of rotavirus infection in Korean children before the implementation of a vaccination program against rotavirus. We reviewed published studies of the past 20 years, carried out on Korean children with rotavirus gastroenteritis. Rotavirus was estimated to be responsible for 46% of 4668 hospitalized Korean children with acute gastroenteritis. Rotavirus gastroenteritis was most prevalent among children aged 6-24 months, which accounted for 84% of all cases. Asymptomatic rotavirus infection was common. Rotavirus was one of the most commonly identified enteric pathogens in nosocomial diarrhea. Vomiting, respiratory symptoms and fever were prominent symptoms in rotavirus gastroenteritis. Transient elevation of liver enzymes, pulmonic infiltration and rarely afebrile convulsion were also observed. The epidemic peak, which occurred in November of the last 15 years, has been moving toward late winter and early spring in recent years. No apparent cause has been found to explain this alteration of peak seasonality. All serotyping studies in Korea for the past 10 years until 1997 revealed that G1 was most prevalent (45-81%). Interestingly, the predominant G serotype of the recent outbreaks in 1998 and 1999 was not G1 but G4. Approximately 95% of rotavirus isolates in recent outbreaks belonged to serotype G1, 2, 3 or 4.
Rotavirus infection is the most common cause of acute diarrhoea in children worldwide. The structural and functional consequences of mammalian rotavirus infection in the small intestine have been incompletely studied and the mechanism of enterocyte damage poorly defined. This study used a neonatal rat model of group B rotavirus infection to study the natural history, clinical features, and the structural and functional consequences of infection in the small intestine. Group B rotavirus infection in eight day old neonatal rats produced diarrhoea by 24-36 hours, which was accompanied by weight loss during the early stages of infection. By seven days the diarrhoea had ceased and body weight was similar to noninfected controls. Rotavirus could be recovered in faeces from 24-72 hours. Light microscopy and morphometry confirmed reduction in villous height in both jejunum and ileum, with a reduction in total mucosal thickness indicating true flat mucosa. Increase in crypt depth followed villous shortening and continued as villous height progressively increased between 96-168 hours. Steady state perfusion of the entire small intestine with a plasma electrolyte solution confirmed the presence of a net secretory state for water between 12-48 hours, with a parallel reduction in sodium absorption. Group B rotavirus infection produces a self limiting acute diarrhoeal illness in neonatal rats similar to human rotavirus infection. Infection causes a reversible flat mucosa resulting from enterocyte loss associated with a net secretory state for water and impaired sodium absorption as a functional correlate. These findings may have relevance for the pathogenesis of human rotavirus infection.
The characteristics of rotavirus infection in 23 children with a variety of primary immunodeficiency diseases were studied. Stools and sera were tested for rotavirus by means of the enzyme-linked immunosorbent assay and the enzyme-linked fluorescent assay, respectively. Four immunodeficient patients had diarrhea during the study period and all had rotavirus infection; rotavirus was not detected in the stools of the 19 asymptomatic immunodeficient patients. Forty-six control children with diarrhea were tested and 22 had rotavirus infection; rotavirus was not detected in 39 asymptomatic control children. One immunodeficient patient with X-linked agammaglobulinemia and one with severe combined immunodeficiency had chronic, symptomatic rotavirus infection with rotavirus excretion lasting more than six weeks. The other two immunodeficient patients and eight control children eliminated the rotavirus from their stools in periods ranging from two to 12 days. Rotavirus antigen was detected in the sera of three of the four immunodeficient patients; none of the 14 control infants tested had rotavirus antigen detected in their sera. This study indicates that rotavirus may produce a chronic infection in immunodeficient children.
AIM: To determine the severity and clinical characteristics of human astrovirus (HAstV) infections among hospitalized children and compare them with children infected by rotavirus. METHODS: Retrospective, case-control study of astrovirus-infected and rotavirus-infected children. Astroviruses were detected in stool samples by enzyme immunoassay and/or reverse transcriptase-polymerase chain reaction. All stool samples were tested for rotavirus and bacterial pathogens, and all negative samples were further tested for human astrovirus. Children with astrovirus-positive stool samples and complete clinical data were included in this study. RESULTS: Astrovirus was detected in 29 (1.8%) children, and 63 rotavirus-infected children were included as controls. Astrovirus-infected children had shorter duration of diarrhea than rotavirus-infected children (median 4 and 6 d, respectively; p<0.05), and 79% of the astrovirus infections were associated with a short duration of vomiting (median 1 and 4 d, respectively; p<0.0001). Rotavirus-infected children had longer hospitalization (p<0.050) than astrovirus-infected children. CONCLUSION: HAstV-infected children had similar symptoms to those occurring in rotavirus infection. However, astrovirus-infected patients had a significantly shorter duration of diarrhea and vomiting, and they required a shorter hospitalization. On the basis of the clinical data and severity scores, children with rotavirus infection had more severe illness.
Rotavirus infection and associated symptoms were studied prospectively from 1976 through 1981 in a 10% sample of families in Tecumseh, Michigan. Infection was determined using an antibody enzyme-linked immunosorbent assay (ELISA) method designed for use with large numbers of sera collected semiannually. Illness was identified from symptoms ascertained weekly by telephone. Risks of infection during a rotavirus season varied from 4.8% in 1978 to 9.2% in 1980. Risks were 20.6% in the under two years age group and decreased progressively with age to 3.6% in individuals aged 45 years or over. Preschool children accounted for less than 20% of the infections in the population of reference. Infection was associated with diarrhea in the first two years of life and with both diarrhea and vomiting later in life. There was no evidence for association of rotavirus infection with a gastrointestinal-respiratory syndrome. The pathogenicity of infection, the protectiveness of antibody, and the socioeconomic correlates of infection showed marked changes from year to year. In 1978, there was a dramatically higher pathogenicity and a greater protectiveness of ELISA measured antibody than in other years. There was also a dramatic reversal in the socioeconomic relations of infection from 1977 to 1978. Taken together, these findings suggest that different rotaviruses might have predominated in these years.
BACKGROUND: Rotavirus is the most common cause of severe diarrhea in children. Morbidity and mortality related to rotavirus infection is not well known in temperate countries in general, and in France in particular. OBJECTIVES: The aim of this study was estimate the morbidity, mortality, and cost related to the rotavirus infection in France, in order to assess the potential impact of a vaccination program. METHODS: A birth cohort was followed until 5 years of age using a decision tree model. Rotavirus infection incidence rates were modeled according to age, seasons, and breast-feeding status. RESULTS: Based on estimates from a decision model, we found that in France, rotavirus infection was responsible for 300,000 annual episodes of acute diarrhea, 138,000 visits to general practitioners, 18,000 hospitalizations, and 9 deaths. The annual direct cost related to rotavirus infection care was estimated at 28 million euros. CONCLUSION: This study demonstrates the high morbidity and cost of care associated with rotavirus infection in France. The decision tree model developed in this study could be used in the future to estimate the potential effectiveness, cost and cost-effectiveness of childhood vaccination strategies using new rotavirus vaccines.
Rotavirus is a major cause of acute severe diarrhea in children worldwide and an important cause of death among young children in developing countries. Group A rotaviruses are antigenically complex and multiple serotypes infect humans. Reassortant rotavirus vaccines are now available which offer protection against severe illness caused by rotavirus serotypes G1-4. Before vaccines are introduced into target populations, it is necessary to establish the baseline data of the epidemiology of rotavirus infection in those countries. The purpose of the present study is to provide information related to the epidemiology of rotavirus infection in Thailand. All rotavirus studies performed in Thailand were found through Medline and Thai Index Medicus searches. A total of 26 of the most relevant studies published in international and national journals are reviewed. Most studies reported that the prevalence of rotavirus infection in Thailand was 27-34%, although a few studies have reported a prevalence above this range. The peak seasonal distribution of rotavirus infection among children hospitalized with diarrhea in Thailand was seen in the dry cool seasons: October to February. The prevalence of rotavirus infection was most frequently found in children aged 6-11 months up to 2 years. G1 was the most prevalent serotype in Thailand, followed by G2, G4 and G3, respectively. At least three G serotypes, mostly G1, G2 and G4, are seen to coexist in Thailand each epidemic year and in some studies all four G-serotypes were reported in the same epidemics. In a 1996-1997 study, G9 was the third prevailing serotype after G1 and G2, respectively. These results indicate that rotavirus epidemics occur in Thailand every year and children are the most affected population. In Thailand, although G1-G4 have been reported, G1 is the most prevalent serotype in each epidemic and G9 is becoming increasingly common.
Recognition of rotaviruses as a major aetiological agent of acute gastroenteritis in infants and young children has prompted the investigation of their epidemiology by molecular techniques. Genome analysis by electrophoretic separation of the RNA segments has been widely used to distinguish virus isolates and to monitor patterns of virus transmission. Examination of virus isolates from different epidemics has clearly demonstrated the existance of extensive genomic variation in viruses circulating in large communities; with the co-circulation of a number of viruses of differing electrophoretype. Preliminary studies using the more advanced techniques of oligonucleotide mapping and hybridization analysis have suggested that variation among the viruses may occur by processes involving both "drift" and "shift". Because of their ease and specificity the new hybridization analysis techniques should greatly facilitate both the rapid diagnosis of rotavirus infections, and the solution of many epidemiological and evolutionary questions. Continued and expanded use of molecular techniques for the study of the epidemiology of rotavirus infections will be required to manage future outbreaks and to effect long term control measures.
The epidemiological features of rotavirus infection may be quite relevant for evaluation of the performance of a rotavirus vaccine in different settings, as well as for monitoring its impact during vaccination under routine conditions. This article describes some important issues regarding rotavirus epidemiology in Venezuela, where major field trials of rotavirus vaccine have been carried out. Rotaviruses was significantly more frequently observed in inpatient (43%) than in outpatient (21%) consultations for diarrhea in infants and young children. There was a high prevalence of rotavirus illness, regardless of socioeconomic conditions, but the risk of dehydration was greater among the lower socioeconomic groups. Rotavirus disease occurs year-round, with a slight seasonal pattern. Eighty-five percent of rotavirus-positive diarrheal episodes, as well as 86% of cases of dehydration due to rotavirus, occurred during the first year of life. However, rotavirus illnesses occur less commonly during the first months of life (0-2 months), which may be a result of protection by transplacental antibodies. The pattern of acquisition of rotavirus antibody was consistent with this age distribution of disease and with optimal age for vaccination. Thus, regional epidemiological characteristics of rotavirus infection may affect optimal performance of rotavirus vaccine.
The pathophysiological mechanisms behind rotavirus-induced diarrhoea still remain incomplete. Current views suggest that the non-structural protein 4 (NSP4) of rotavirus and the enteric nervous system (ENS) participate in water secretion and diarrhoea. In the present work the role of nitric oxide (NO) in rotavirus infection and disease has been studied in vitro, mice and humans. Incubation of human intestinal epithelial cells (HT-29) with purified NSP4 but not with infectious virus produced NO2/NO3 accumulation in the incubation media. The NSP4-induced release of NO metabolites occurred within the first minutes after the addition of the toxin. Mice infected with murine rotavirus (strain EDIM) accumulated NO2/NO3 in the urine at the onset for diarrhoea. Following rotavirus infection, inducible nitric oxide synthetase (iNOS) mRNA was upregulated in ileum, but not in duodenum or jejunum of newborn pups within 5 days post-infection. A prospective clinical study including 46 children with acute rotavirus infection and age-matched controls concluded that rotavirus infection stimulates NO production during the course of the disease (P < 0.001). These observations identify NO as an important mediator of host responses during rotavirus infection.
Rotavirus-seronegative mice were orally inoculated with murine rotavirus in order to study the kinetics of rotavirus replication and the relationship of viral replication to immunity and disease and to assess the effects of local and systemic antibodies on viral clearance and disease resolution.
During three months after a family outbreak of diarrhoeal disease, rotavirus-specific immunoglobulins of the IgA, IgG and IgM classes were measured by enzyme-linked immunosorbent assay in faecal extracts from the four people involved. Shortly afterwards, sequential extracts were obtained from another infant after a proven rotavirus infection. Rotavirus infection was diagnosed by electron microscopy in three of the patients from whom acute-phase faecal samples were obtained, and all five patients developed a transient specific-antibody response. Antirotaviral IgA, IgM and IgG all reached peak titres between two and four weeks after infection, then dropped back to undetectable levels after two months. If these findings are confirmed in larger numbers of cases, they will provide the basis for simple diagnosis of recent rotavirus infections, without the need of even a single sample of serum.
Among etiologic agents, rotavirus is the major cause of severe dehydration diarrhea in infant mammals. In vitro and in vivo studies have indicated that the human milk-fat globule protein lactadherin inhibits rotavirus binding and protects breast-fed children against symptomatic rotavirus infection. The present work was conducted to evaluate the effect of lactadherin, along with some other milk proteins and fractions, on rotavirus infections in MA104 and Caco-2 cell lines. It is shown that human, and not bovine, lactadherin inhibits Wa rotavirus infection in vitro. Human lactadherin seems to act through a mechanism involving protein-virus interactions. The reason for the activity of human lactadherin is not clear, but it might lie within differences in the protein structure or the attached oligosaccharides. Likewise, in our hands, bovine lactoferrin did not show any suppressive activity against rotavirus. In contrast, MUC1 from bovine milk inhibits the neuraminidase-sensitive rotavirus RRV strain efficiently, whereas it has no effect on the neuraminidase-resistant Wa strain. Finally, a bovine macromolecular whey protein fraction turned out to have an efficient and versatile inhibitory activity against rotavirus.
Rotavirus induced diarrhoea was investigated in neonatal mice. Assessment of oxidative/antioxidative profile was the mechanistic approach to study the nature of injury. Neonatal mice (NMRI strain) were infected orally with the homologous strain of (EB) rotavirus (serotype 3). The peak severity of rotavirus infection was attained on the third day post infection. The whole small intestine of neonatal mice on day 3 post infection was homogenized and analysed for oxidative/antioxidative profile. Glutathione and related thiols were significantly declined in rotavirus infected group. Superoxide dismutase, glutathione peroxidase and glutathione-S-transferase (1-chloro 2, 4 dinitrobenzene) activities were also decreased in the rotavirus infected group. The activities of glutathione reductase and glutathione-S-transferase (ethacrynic acid) however were elevated with rotavirus infection in comparison to the control group. Similarly, ADP-FeCI3, NADPH induced lipid peroxidation was elevated with rotavirus infection. Thus the altered oxidative/antioxidative profile indicated the presence of oxidative stress in the rotavirus infected group and can be postulated to have a prominent role in the pathogenesis of the disease.
We have characterized the neutralizing antibody immune response to six human rotavirus serotypes (G1 to G4, G8, and G9) in Brazilian children with primary and secondary rotavirus infections and correlated the response with the G serotype of the infecting rotavirus strain. Twenty-five children were studied: 17 had a single rotavirus infection, 4 were reinfected once, and 4 experienced three infections. Two of the reinfections were by non-group A rotaviruses. Among the 25 primary infections, we observed homotypic as well as heterotypic responses; the serotype G1 viruses, which accounted for 13 of these infections, induced mostly a homotypic response, while infections by serotype G2 and G4 viruses induced, in addition to the homotypic, a heterotypic response directed primarily to serotype G1. Two of the primary infections induced heterotypic antibodies to 69M, a serotype G8 virus that by RNA electrophoresis analysis was found not to circulate in the population during the time of the study. The specificity of the neutralizing antibody immune response induced by a virus of a given serotype was the same in primary as well as secondary infections. These results indicate that the heterotypic immune response induced in a primary rotavirus infection is an intrinsic property of the virus strain, and although there seem to be general patterns of serotype-specific seroconversion, these may vary from serotype to serotype and from strain to strain within a serotype.
A human rotavirus complement-fixing (CF) antigen, prepared by purification of large volumes of fluid feces collected from children with winter diarrhea, was used to study the development and persistence of antibody in children with diarrhea and the prevalence of rotavirus antibody in Melbourne. In children with diarrhea, antibody rises were detectable within 4 to 6 weeks of the onset of illness, and the titers usually remained elevated for the next 1 to 2 years. CF antibody did not develop in two children with proven rotavirus infection aged less than 6 months, an age at which poor CF responses to other viruses have also been observed. A study of CF antibody levels in the general community showed that in Melbourne, most children have been infected with human rotavirus by the age of 3 years.