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[Rotavirus infection in Brazil: epidemiology and challenges for its control].

Worldwide, rotaviruses account for 600,000 to 870,000 deaths per year among infants and young children. In Brazil, rotaviruses were first seen in 1976 by scanning electron microscopy of stool samples from diarrheic infants in Belém, Pará. Hospital-based studies have shown that rotaviruses are associated with 12-42% of cases of acute diarrhea. In addition, community-based studies yielded an average of 0.25 rotavirus-related diarrheal episodes per child per year. G types 1 to 4 account for about two-thirds of circulating strains, but the (unusual) P[8],G5 genotype has been claimed to cause over 10% of rotavirus diarrheal episodes. It has been shown that over 70% of children develop rotavirus antibodies by the age of 4-5 years. The tetravalent rhesus-human rotavirus vaccine (RRV-TV) conferred 35% protection according to a two-year follow-up study in Belém, Pará, Brazil, but reached an efficacy of 60% during the first year of life. RRV-TV was also shown to be 75% protective against very severe gastroenteritis in northern Brazil. Vaccination with RRV-TV has been suspended recently in the United States because of the detection of intussusception as a side effect. Therefore, further vaccine trials in Brazil will probably involve rotavirus candidate vaccines other than RRV-TV.

Acute Disease↗

The effects of infant feeding on rotavirus-induced gastroenteritis: a prospective study.

The relationship between feeding method and risk of rotavirus infection was studied by following a cohort of 197 infants from low income households through the winter diarrhea season of 1983-84. Fecal specimens were systematically collected and tested for the presence of rotavirus particles by electron microscopy, confirmed by ELISA. The attack rates of rotavirus gastroenteritis were similar for breast-fed and bottle-fed infants (20 per cent, 17 per cent, respectively); however, the clinical course of rotavirus gastroenteritis was quite different. Infants who were breast-fed had illnesses which were characterized by milder symptoms of shorter duration. Of the 10 breast-fed infants who acquired rotavirus gastroenteritis, nine (90 per cent) were classified as mild illnesses while of the 25 bottle-fed infants who acquired rotavirus gastroenteritis, only nine (36 per cent) were classified as having mild illnesses. These data suggest that factors associated with breast-feeding, although not affecting rotavirus infection rates, may moderate the clinical course of rotavirus gastroenteritis.

Adolescent↗

[Viraemia and extraintestinal involvement after rotavirus infection].

OBJECTIVE: To study the incidence of viraemia and extraintestinal organ damage in children with acute rotavirus (RV) gastroenteritis. METHODS: Eighty-three children with acute rotavirus gastroenteritis were hospitalized from October 2002 to March 2003, whose blood and fecal samples were obtained on admission. Rotavirus RNA (encoding the VP7 outer capsid protein) were detected in blood and fecal samples by nest reverse transcription-polymerase chain reaction (RT-PCR). According to the result of blood RV-RNA, the patients were divided into RV-RNA positive group and RV-RNA negative group. The differences between these two groups in the severity of gastroenteritis and extraintestinal organ damage were analyzed. RESULTS: Eighty-two of 83 stool samples from the children with rotavirus infection were positive for rotavirus RNA. Sixteen of 83 blood samples were positive for rotavirus RNA with a positive rate of 19.3%. The nucleotide sequence of cloned cDNAs, resembling part of the VP7 gene, was identical from paired blood and fecal samples. There were no significant differences between blood RV-RNA positive group and blood RV-RNA negative group in the rate and degree of fever, diarrhea, dehydration, metabolic acidosis, hypokalemia and myocardial damage (P>0.05); while the incidences of liver damage, rash, lower respiratory tract infection and the central nervous system involvement in the blood RV-RNA positive group were significantly higher than those in the blood RV-RNA negative group (P<0.05). CONCLUSION: Viraemia is present in the children with acute rotavirus gastroenteritis. Viraemia might be an important mechanism by which rotavirus spread to the extraintestinal sites resulting in organs damage.

Base Sequence↗

Rotavirus gastroenteritis in children: 5-year experience in a medical center.

Rotavirus infection is the leading cause of childhood gastroenteritis. We retrospectively reviewed cases of rotavirus gastroenteritis at National Taiwan University Hospital from January 1993 to December 1997. During the study period there were 429 patients with rotavirus infection with ages ranging from 1 day to 16 years with a median of 13 months. The male-to-female ratio was 1.2:1. Infection occurred before the age of 2 years old in 76% of patients. The seasonal peak occurred in the late winter and early spring during 1993 to 1996, but the case number increased in late spring and summer in 1997. The G serotype of the rotavirus was identified in 302 patients (70%). Vomiting and dehydration developed more frequently following infection with G1 rotaviruses, while an increased frequency of seizures was noted following G2 infection; the differences were not statistically significant. One patient had two episodes of infection; the first one was caused by G1 rotavirus, and the strain causing the second infection could not be typed. In conclusion, the results suggest that there is a strong seasonal variation in the incidence and characteristics of rotavirus infection in Taipei area. The infections caused by G1 and G2 rotaviruses were clinically indistinguishable.

Adolescent↗

Association between diarrhoea and shedding of group A and atypical groups B to E rotaviruses in suckling pigs.

The frequency of shedding of rotavirus in faeces of diarrhoeic piglets was studied in 2 farms. In farm I, where 82% of the litters had diarrhoea, group A rotavirus was detected in 52/117 (44%) faeces of pigs with diarrhoea while atypical groups B to E rotaviruses were detected in 2/117 (2%) faeces of diarrhoeic piglets that came from litters where group A rotavirus had also been found. In farm II where the morbidity due to diarrhoeas was lower (57% of the litters had diarrhoea), 8/141 (6%) faeces of piglets with diarrhoea had group A rotavirus and 4/141 (3%) had groups B to E atypical rotaviruses. It was concluded that group A and groups B to E rotaviruses can coexist in the same farm but group A rotavirus seems to induce more diarrhoeas in piglets.

Animals↗

Short electropherotype rotaviruses isolated longitudinally from a cohort of Mexican infants.

Stool specimens obtained longitudinally during the first year of life of a cohort of 75 rural infants were tested for the presence of rotavirus with an enzyme-linked immunosorbent assay. Thirty four infants showed the presence of rotaviruses during the first year of life. Only 41% of these episodes were associated with diarrhea. Extraction of rotavirus RNA was still possible in 12 of 34 stool samples, ten of them obtained during episodes of associated-diarrhea. Electropherotyping of these rotavirus showed that nine had a short electropherotype. One diarrheal and two asymptomatic samples had a long electropherotype. Subgrouping the viruses with monoclonal antibodies showed that five of the nine rotaviruses with short electropherotype belonged to subgroup I, and two of the three with long electropherotype belonged to subgroup II. The rest of rotaviruses could not be subgrouped. This study confirms the prevalence of only few rotavirus strains in any defined geographic region over a specific period of time, in this case, a rotavirus with a short electropherotype.

Cohort Studies↗

Rhesus Rotavirus candidate vaccine. Clinical trial in children vaccinated between 2 and 5 months of age.

Live attenuated oral rhesus Rotavirus candidate vaccine (strain MMU 18006 [lot RRV-1]) was evaluated for immunogenicity, safety, and clinical protection in a double-blind, placebo-controlled trial involving 200 infants aged 2 to 5 months when vaccinated. Vaccine-induced fourfold or greater rise of Rotavirus antibodies was seen in 62% of the infants. Febrile reactions of short duration on days 3 and/or 4 after vaccination occurred in 26% of the vaccine recipients. The clinical follow-up covered two Rotavirus seasons, in which serotypes 1 and 4 were prevalent. There were 16 cases of confirmed Rotavirus diarrhea in the placebo-treated group and 10 in the vaccine-treated group; from this a vaccine protection rate of 38% was derived. Clinical severity of Rotavirus diarrhea was assessed by a score; 13 cases in the placebo-treated group and 5 in the vaccine-treated group were regarded as severe or moderately severe, giving a vaccine protection rate of 67%. The rhesus Rotavirus vaccine induces partial protection against heterotypic Rotavirus disease, but the level of protection achieved with the present vaccine dose in this age group appears to be insufficient for a general Rotavirus vaccination.

Antibody Formation↗

[Data on the study of the epidemiology of rotavirus infection in Leningrad].

The results obtained in the study of rotavirus infection in Leningrad in 1984-1987 are presented. Enzyme immunoassay techniques were used for the examination of 4,715 children aged 0-14 years and 1,162 adults with diagnosed acute enteral infection of unknown etiology, as well as the control group of 556 of healthy children aged 0-6 years and 77 healthy adults. The rotavirus antigen was detected in 1.210 sick children (25.7%) and 133 sick adults (11.4%), as well as in 6 healthy children (1.1%), but not detected in healthy adults. The following epidemiological regularities of rotavirus infection were established: the highest sick rate among children aged 0-2 years and a low level of rotavirus carriership among healthy persons; the seasonal character of rotavirus infection, its outbreaks occurring in winter and the epidemic periods varying in their character and duration in different years; the prevailing role of rotaviruses in the development of winter rises of acute enteral infection of unknown etiology in the city among children aged 0-2 years. The problem of the respiratory syndrome in rotavirus diarrhea is discussed. The rotavirus antigen was detected in 39 out of 144 children (27%) with diagnosed acute respiratory virus diseases and in 4 out of 99 nasopharyngeal washings (4%) from diarrhea patients. Adenoviruses were shown to play an insignificant role in the etiology of diarrhea (10% of cases).

Acute Disease↗

[Rotavirus infections in pigs].

Rotaviruses were found in the study of 123 pigs and 132 fecal samples from animals with diarrhea. Employed were the method of immunofluorescence and the high concentration of virions (10(4) up to 10(9)/cm3). As high as 57.3 per cent of the fecal extracts proved positive for rotaviruses. In 14.3 per cent of the extracts a group-specific rotavirus antigen was established via the agar gel immunodiffusion, and 30.9 per cent of the intestinal cross sections were positive as demonstrated through immunofluorescence. Conditionally, the cases of rotavirus gastroenteritis are divided into two types--early and late. The first ones have been seen in sucking piglest at the age of 10-15 days, and with the growing of the epizootic wave--in 3-day-old ones, too. The second type of rotavirus gastroenteritis have been described in young pigs fifteen days after weaning, The death rate with sucking pigs was found to vary from 7 to 17 per cent, and it was 5 per cent with weaned ones. High mortality rate (82 per cent) was observed on a farm where a mixed infection with transmissive gastroenteritis was noted. The diagnosed cases of rotavirus enteritis prevailed in the cold months of the year (autumn-winter). On two farms the disease was established in the summer. The serologic examination of the blood sera of sows revealed group-specific antibodies to rotaviruses in 71 per cent of the cases. The percent of seroagents with the young sows ranged from 50 to 63.3 per cent, while with the adult ones it was 87 to 100 per cent. Discussed is the link between the low titer of natural immunity and the aspects of the epizootic process with rotavirus diarrhea.

Animals↗

Epidemiological aspects of porcine rotavirus infection in Venezuela.

The prevalence of porcine rotavirus infection in Venezuela was studied from November 1980 to November 1981. Rotaviruses were identified in 21.3 per cent of 286 diarrhoeic samples analysed by electron microscopy and in none of the 48 controls. Rotaviruses were readily detected throughout the year, which may correspond to the absence of seasonal climatic variations in a tropical country such as Venezuela. Rotavirus infection was frequently observed in pigs that were two to six weeks old and was rare in younger animals. The age distribution of rotavirus infection correlated well with the presence of circulating antibodies, as measured by the complement fixation test. Sucking pigs less than two weeks old appeared to be protected from the infection by passive immunity; no antibodies were detected in the two- to three-week-old group, coinciding with an increased susceptibility to rotavirus infection. The antigenic specificity of the rotavirus isolates was confirmed by enzyme-linked immunosorbent assay test, using antibodies directed against the group-specific antigen of human rotavirus. Polyacrylamide gel electrophoresis of viral double-stranded RNA revealed an heterogeneity on the electropherotype of selected samples obtained at different times during the study period.

Age Factors↗

A follow-up study on bovine rotavirus dissemination among calves of a large dairy herd.

Rotaviruses had previously been involved in lethal diarrhoea of newborn calves as well as non-lethal diarrhoea in calves aged 6 to 7 weeks in a closed dairy herd comprising 220 heads of cattle. Fifty calves born consecutively were thereafter tested at weekly intervals till 8 weeks old for diarrhoea by clinical judgement of their feces and for rotavirus excretion by ELISA tests. Serum antibodies against rotaviruses were sporadically determined by CF tests. Rotavirus was shown to persist in this herd in widely disseminated form, in seasonal waves, peaking during the second week of age. The first week of life and the third, in this order, ranked next in frequency of dissemination. Silent, non-clinical rotavirus excretion also occurred quite frequently in calves 1 to 3 weeks old. All calves examined possessed maternally-derived antibodies in their blood serum, which according to literature merely exert protective activity as long as present in the unabsorbed state in the gut lumen. Careful colostrum feeding during the first week postponed rotavirus excretion as compared to the earlier onset described in the United States, and milk replacer (devoid of antibody) fed from day 8 onward accounted for the peak of rotavirus infection in the second week of life. It proved impossible to assess the degree of rotavirus coetiology for diarrhoea observed at high frequency.

Animals↗

Effect of feeding human milk on nosocomial rotavirus infections in an infants ward.

Children aged 1-15 months hospitalized for different respiratory diseases (including otitis media) at an infants ward frequently developed diarrhoea during their stay in the clinic. Bacteriological examinations of stool samples were usually negative but rotavirus excretion was frequent according to ELISA tests. Children fed with human milk are assumed to be less susceptible to rotavirus infections due to the protection by maternal antibody. In view of preventive measures for avoiding rotavirus nosocomial infections a study was carried out. All children entering the infants ward and showing no sign of gastrointestinal disorders were distributed at random into two groups. The first group received a normal diet according to age, the second group received in addition 200 ml of fresh human milk per day. Serial stool samples were taken at the first day and thereafter every 3-4 days. Routine bacteriological examination and tests for rotavirus excretion were carried out. Children already excreting rotavirus at the first day were excluded from the study. Analysis of the gene segments of excreted rotavirus revealed the presence of two subspecies of rotavirus type 2 appearing at different periods during the study indicating nosocomial infections. Such infections were surprisingly frequent: 16 of 28 children started to excrete rotavirus during their stay in the ward and 8 of these 16 got diarrhoea. A statistically significant difference in the infection rate between the two groups was not observed although clinical symptoms seemed to be less severe in children fed with human milk.

Cross Infection↗

Detection and control of rotavirus infections in zoo animals.

Fecal specimens from 15 exotic animal species, with and without diarrhea, were examined for the presence of rotavirus, bacterial enteropathogens, and intestinal parasites. A commercial enzyme-linked immunosorbent assay was used to detect antigens of rotavirus. Rotavirus was detected in the feces of 20 (57%) of 35 of the animals, which included addax (Addax nasomaculatus), nyala (Tragelaphus angasi), saiga (Saiga tatarica), white-tailed gnu (Connochaetus gnou), greater kudu (Tragelaphus strepsiceros), sitatunga (Tragelaphus spekei), Grant's gazelle (Gazella granti roosevelti), sable antelope (Hippotragus niger niger), kob (Kobus kob leucotis), pygmy marmoset (Callithrix pygmaea), bush dog (Speothos venaticus), grizzly bear (Ursus arctos horribilis), and red kangaroo (Megaleia rufa). Bacterial pathogens were found in 8 animals, 5 of which had concurrent rotavirus infections. Most (60%) of the animals with rotavirus infection were less than 2 weeks old; however, rotavirus also was detected in feces from adult animals. Although most of the cases of rotavirus infection were detected in nursery-reared animals, exhibit-reared animals also were infected with rotavirus.

Animals↗

[The detection of atypical human rotaviruses and their characteristics].

The electrophoretic typing of 1,370 rotavirus strains revealed the presence of group C rotaviruses in 1.3% of cases. In the Arkhangelsk region group C rotaviruses were detected in 34.4% of cases. The detected group C rotaviruses were shown to be no different in their morphology from typical ones; they were characterized by the variability of their genome and the absence of hybridization with RNA of group A rotaviruses. Group C rotaviruses were detected in children aged 3-6 years; in this age group they caused both sporadic morbidity and an outbreak of infection. The clinical manifestations of gastroenteritis caused by group C rotaviruses were no different from typical rotavirus gastroenteritis.

Acute Disease↗

[5th day convulsions of the newborn infant in rotavirus infections].

AIM OF THE STUDY: The pathogenesis of fifth day fits in newborns has not yet been explained. From 1989-1991 we observed an epidemic occurrence of 21 cases in 1917 hospitalized newborn children. After finding rotavirus in the faeces of several cases we suspected a coincidence. METHODS: We tested the faeces of 19 fifth day fitters as well as 30 healthy newborns (4.-6. day of life) for rotavirus infection. The results of all clinically indicated rotavirus examinations in neonates of 4 to 6 days of age from 1989-1991 were analysed. In 6 rotavirus positive fifth day fitters we performed an immunologic and electron microscopic examination of cerebrospinal fluid. RESULTS: 18 of 19 examined children with fifth day fits (95%) had rotavirus in the faeces. Within the healthy control group we found 12 of 30 (40%, Chi-square 12.46, p < 0.001) and in the group of sick neonates without convulsions 98 of 202 (48.5%, Chi-square 12.44, p < 0.001). This shows a statistically significant coincidence of rotavirus positive faeces with fifth day fits. Rotavirus was not present in cerebrospinal fluid. CONCLUSIONS: We suggest a causal relation between fifth day fits and rotavirus infections. Pathogenetic details remain unclear.

Cerebrospinal Fluid↗

A molecular epidemiological study of porcine rotaviruses.

Diarrhoea in the piglet can lead to stunted growth and neonatal death, with important implications for the pig farmer. During 1993, a pilot study was initiated to monitor the epidemiology of rotavirus infection in piglets with diarrhoea. Bimonthly diarrhoeal faecal specimens were collected from scouring piglets less than 6 weeks of age on a pig farm in the Northern Transvaal. The stool specimens were examined by a commercial enzyme-linked immunosorbent assay (Rotavirus EIA, IDL, Jerusalem). In total, rotavirus antigen was detected in 24% of the litters by the ELISA, which is directed at the group A rotavirus antigen. Rotavirus was found to occur throughout the year and predominantly in piglets 4 weeks old. Polyacrylamide electrophoretic analysis of the viral RNA genomes showed the presence of four distinct strains of Group A rotaviruses circulating on this farm. This study highlights the natural diversity of rotavirus strains circulating on a single farm and may indicate the importance of rotavirus infection in piglets with diarrhoea in South Africa.

Age Factors↗

[Use of the western blot method for detecting antibodies against proteins of various rotavirus strains].

The aim of this work was to adapt the Western blot method to analyse the humoral response to proteins of rotavirus strains having various antigens. 10 serum samples from animals immunized with SA11, 18 serum samples from hospitalized children with rotavirus infections and 17 serum samples from healthy adults were examined for rotavirus antibodies using Western blot. Antibodies against all structural rotavirus proteins were detected. The examined sera reacted differently with rotavirus proteins depending on the strain used. The highest IgG reactivity was observed for Wa and SA11, while the lowest was noted for DS-1. At the same time a different level of cross-reactivity of human sera with specific proteins of antigenically varying rotaviruses was observed. The sera taken from adults showed a lower reactivity with proteins of antigens used compared with sera from children. The exception was VP6 of the Ito strain for which the reactivity of adult sera was statistically higher. Essential differences in the reactivity of children's and adult sera were found mainly in the case of VP2 and VP4 belonging to the SA11 strain and VP4 and VP7 of the Ito strain. From these investigations we can conclude that the Western blot method may be useful in assessing immune response caused by rotaviruses. The results of reactivity of some human sera with proteins of strains used indicates that the persons had previously been infected by antigenically varied rotaviruses.

Adult↗

Safety and efficacy of a pentavalent human-bovine (WC3) reassortant rotavirus vaccine.

BACKGROUND: Rotavirus is a leading cause of childhood gastroenteritis and death worldwide. METHODS: We studied healthy infants approximately 6 to 12 weeks old who were randomly assigned to receive three oral doses of live pentavalent human-bovine (WC3 strain) reassortant rotavirus vaccine containing human serotypes G1, G2, G3, G4, and P[8] or placebo at 4-to-10-week intervals in a blinded fashion. Active surveillance was used to identify subjects with serious adverse and other events. RESULTS: The 34,035 infants in the vaccine group and 34,003 in the placebo group were monitored for serious adverse events. Intussusception occurred in 12 vaccine recipients and 15 placebo recipients within one year after the first dose including six vaccine recipients and five placebo recipients within 42 days after any dose (relative risk, 1.6; 95 percent confidence interval, 0.4 to 6.4). The vaccine reduced hospitalizations and emergency department visits related to G1-G4 rotavirus gastroenteritis occurring 14 or more days after the third dose by 94.5 percent (95 percent confidence interval, 91.2 to 96.6 percent). In a nested substudy, efficacy against any G1-G4 rotavirus gastroenteritis through the first full rotavirus season after vaccination was 74.0 percent (95 percent confidence interval, 66.8 to 79.9 percent); efficacy against severe gastroenteritis was 98.0 percent (95 percent confidence interval, 88.3 to 100 percent). The vaccine reduced clinic visits for G1-G4 rotavirus gastroenteritis by 86.0 percent (95 percent confidence interval, 73.9 to 92.5 percent). CONCLUSIONS: This vaccine was efficacious in preventing rotavirus gastroenteritis, decreasing severe disease and health care contacts. The risk of intussusception was similar in vaccine and placebo recipients. (ClinicalTrials.gov number, NCT00090233.)

Administration, Oral↗