Prospective study of rotavirus infections in Belém, Pará, Brazil: clinical and epidemiological features

A prospective study of acute diarrhoeal diseases was carried out from April 1990 to September 1992 with the purpose of assessing the immunogenicity, safety and efficacy of a Rhesus-human reassortant rotavirus ("RRV-TV") vaccine, involving 540 children living in Belém, Pará, Brazil. As half of the children received placebo, this trial provided the opportunity of broadening the knowledge on both clinical and epidemiological aspects of rotavirus infection in the Amazon region. There were 2,789 diarrhoeal episodes during the above mentioned period, of which 86 (3.1%) associated with rotavirus; serotype 1 was the more prevalent, accounting for 67.9% of serotyped strains. Rates of 5.9 and 0.2 episodes of diarrhoea per child/year were noted for all cases and the rotavirus-related ones, respectively. This agent was the only pathogen found in 70.9% of the 86 rotavirus-related episodes of acute diarrhoea, whereas the most frequent associations involved Giardia intestinalis and enteropathogenic Escherichia coli, accounting for 7.0% and 11.6% of mixed infections,respectively. The monthly rates of rotavirus-related episodes of diarrhoea ranged from 0.8% to 9.6%, reaching the highest peaks during the dry months of the year. Means of clinical severity scores of 9.4 and 5.3 were recorded for the rotavirus-related episodes of diarrhoea and those of other aetiology, respectively.     

Rotavirus vaccines: an update

PURPOSE OF REVIEW: Rotavirus infection is the most common cause of severe diarrhea disease in infants and young children worldwide and has a major global impact on childhood morbidity and mortality. Vaccination is the only control measure likely to have a significant impact on the incidence of severe dehydrating rotavirus disease. RECENT FINDINGS: Rotavirus disease prevention efforts suffered a great setback in 1999 with the withdrawal of the RRV-TV vaccine less than a year after its introduction. Several new rotavirus vaccine candidates have now been developed and are undergoing clinical trials. SUMMARY: New safe and effective rotavirus vaccines offer the best hope of reducing the toll of acute rotavirus gastroenteritis in both developed and developing countries.     

Overview of rotavirus infections in Korea

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.     

Immunogenicity of tetravalent rhesus rotavirus vaccine administered with buffer and oral polio vaccine.

Between January and November 1989, we studied 174 infants aged 6 to 16 weeks in a randomized clinical trial to (1) determine the immunogenicity of a single dose of tetravalent rhesus rotavirus vaccine (RRV-TV) when administered with three different buffer regimens: no antacid buffer and small-volume (2.5-mL) and large-volume (30-mL) antacid buffer; and (2) examine the potential interference of RRV-TV on the immune response to oral polio vaccine. Immunogenicity of RRV-TV, measured as a fourfold rise in antibody titers to rotavirus, was similar in the groups receiving small- and large-dose buffer (45% and 49%, respectively) and significantly less in the group that received RRV-TV alone (23%). Administration of RRV-TV with oral polio vaccine did not significantly interfere with the neutralization response of oral polio vaccine poliovirus serotypes 1, 2, or 3, and overall, 29%, 87%, and 24% of the infants had a fourfold rise in titer to each serotype, respectively.     

A prospective study of acute diarrhoea in Finnish children from birth to 2 1/2 years of age

To determine the incidence, clinical significance and etiology of acute diarrhoea in early childhood, a cohort of 336 children were followed from birth to the age of 24-32 (mean 26) months. More than half (55%) of the children had no diarrhoea, 26% had one episode and 19% had two or more episodes of diarrhoea during follow-up; altogether 248 episodes of diarrhoea were detected. Rotavirus was by far the most common (26%) identified pathogen; adenoviruses were detected in 4% and bacterial pathogens (EPEC, Salmonellae, Yersiniae) in 4% of the cases. Two thirds of the episodes remained etiologically unresolved. Rotavirus diarrhoea was significantly more severe than diarrhoea due to other causes; 75% of severe episodes of diarrhoea were associated with rotavirus. About two thirds of the infants were breast-fed over 6 months; breast-feeding for less than 6 months was associated with a higher incidence of rotavirus diarrhoea between 7-12 months of age but not thereafter. About three quarters of the children were cared for at home beyond 12 months of age; those at home had a lower rate of rotavirus diarrhoea than those at day-care centers.     

A Prospective Study of Acute Diarrhoea in Finnish Children from Birth to 2 1/2 Years of Age

ABSTRACT. To determine the incidence, clinical significance and etiology of acute diarrhoea in early childhood, a cohort of 336 children were followed from birth to the age of 24–32 (mean 26) months. More than half (55%) of the children had no diarrhoea, 26% had one episode and 19% had two or more episodes of diarrhoea during follow-up; altogether 248 episodes of diarrhoea were detected. Rotavirus was by far the most common (26%) identified pathogen; adenoviruses were detected in 4 % and bacterial pathogens (EPEC, Salmonellae, Yersiniae) in 4% of the cases. Two thirds of the episodes remained etiologically unresolved. Rotavirus diarrhoea was significantly more severe than diarrhoea due to other causes; 75% of severe episodes of diarrhoea were associated with rotavirus. About two thirds of the infants were breast-fed over 6 months; breast-feeding for less than 6 months was associated with a higher incidence of rotavirus diarrhoea between 7–12 months of age but not thereafter. About three quarters of the children were cared for at home beyond 12 months of age; those at home had a lower rate of rotavirus diarrhoea than those at day-care centers.     

Epidemiology and impact of rotavirus diarrhoea in Poland

Hospital and laboratory data were analysed in three hospitals to estimate rotavirus disease burden in 1994-96. Community acquired gastroenteritis was diagnosed in 757 children of whom 41% tested positive for rotavirus. A total of 196 children had rotavirus nosocomial infections (39% of all rotavirus community-acquired and nosocomial cases) Infants less than 24 months old and children less than 3 months old comprised 74% and 11.9% of admissions for rotavirus, respectively. Almost 94% of children with rotavirus infection had severe gastroenteritis (score 11). The annual rate of rotavirus associated hospitalization in Poland in 1996 was 3.1/1000 children under the age of 60 months and 5.2/1000 infants under 24 months of age. The mean hospital stay was 9.5 d (±9.8 d). We estimated that 8918 children under 60 months of age were hospitalized for rotavirus gastroenteritis in 1996; they accounted for 84899 inpatient days. We conclude that rotavirus is a leading aetiological agent of severe gastroenteritis in young children in Poland and that the Burden of this infection is significant. Rotavirus vaccine could significantly decrease the hospitalization rate and the financial impact of rotavirus Gastroenteritis in Poland. □ Acute diarrhoea, disease burden, epidemiology, gastroenteritis, rotavirus     

Reappraisal of the Peruvian and Brazilian lower titer tetravalent rhesus-human reassortant rotavirus vaccine efficacy trials: analysis by severity of diarrhea

OBJECTIVES AND METHODS: With the purpose of better understanding the efficacy of the lower titer [4 x 10(4) plaque-forming units (pfu)] tetravalent rhesus-human reassortant rotavirus vaccine (RRV-TV) against diarrheal episodes of different severities, the Peruvian and Brazilian efficacy data were reanalyzed with a 20-point scoring system. Mild, moderate/severe and very severe rotavirus diarrhea were scored as 0 to 8, 9 to 14 and >14, respectively. RESULTS: In the Peruvian study one dose of vaccine yielded 64% (P = 0.04) protection against pure cases of rotavirus disease (i.e. those in which no other enteropathogen was found) with clinical scores ranging from 9 to 14. Protective efficacy against very severe rotavirus gastroenteritis could not be assessed because of the small number of cases. In Brazil there was a trend in preventing "all" and "pure" cases of rotavirus diarrhea scored 9 to 14 (44%, P = 0.06, and 45%, P = 0.08, respectively) and the vaccine was 75% (P = 0.02) protective against pure rotavirus diarrhea scored >14. No protection was observed for mild rotavirus diarrhea (scores <9). These data were compared with those from trials in Venezuela (4 x 10(5) pfu/dose), US (4 x 10(4) pfu/dose and 4 x 10(5) pfu/dose) and Finland (4 x 10(5) pfu/dose). Combining the Peruvian (one dose, pure cases) and Brazilian studies together, the levels of protection against 9- to 14-scored rotavirus diarrhea are comparable with those from the Venezuelan (47%) and American (57, 57 and 65%) efficacy trials. In Brazil the level of protection (75%) against pure, >14-scored rotavirus diarrhea is similar to the efficacy rates yielded in the three US trials (82, 80 and 69%) and the Finnish trial (100%) for episodes of the same severity. CONCLUSIONS: Our reanalysis provides evidence that, at least against moderate/severe rotavirus gastroenteritis, RRV-TV, 4 x 10(4) pfu/dose is potentially as efficacious as RRV-TV, 4 x 10(5) pfu/dose, even in settings with very high rotavirus disease burden. The reanalysis of the Peruvian data suggests that one and three vaccine doses may yield similar efficacy rates. It is also suggested that vaccine efficacy against most severe episodes in Peru and Brazil was not evident because of the trial design used in those studies (i.e. prospective, active home surveillance rather than a catchment trial), resulting in too few cases of severe disease even in the placebo group. To confirm these findings, future trials with this vaccine are necessary in developing countries with high diarrhea morbidity rates. These trials should use catchment designs and focus on the evaluation of the efficacy of one or three doses of RRV-TV against moderate to severe/very severe rotavirus diarrhea.     

Hospitalization for acute community-acquired rotavirus gastroenteritis: a 4-year survey]

OBJECTIVE: To evaluate the number of hospitalizations due to community-acquired rotavirus acute gastroenteritis in a general pediatric unit during a four-year survey. RESULTS: From January 1997 to December 2000, 725 patients were admitted for acute gastro-enteritis to the general paediatric unit of a Parisian children hospital (nosocomial diarrhoea excluded) and 706 (97.5%) of these patients had had a stool microbiologic examination. Diarrhoea was caused by rotavirus in 359 patients (50.89%) and Salmonella sp in 61 (8.6%). Children and infants hospitalized for rotavirus acute gastroenteritis were younger (26% had three months or less, and 50.03% had six months or less) than in other European studies. CONCLUSION: This study is the first in France reporting a systematic survey of hospitalized gastroenteritis during four years. More than half of hospitalized community-acquired gastroenteritis were due to rotavirus in this Parisian area. The young age of patients should be investigated in other French areas, searching for risk factors and rotavirus strains.     

Concurrent administration of rhesus rotavirus tetravalent (RRV-TV) vaccine with pentavalent diphtheria-pertussis-tetanus–Haemophilus influenzae b-inactivated polio and hepatitis B vaccines

To investigate the incorporation of oral rhesus-human reassortant rotavirus tetravalent (RRV-TV) vaccine into a routine immunization programme, RRV-TV or oral placebo was coadministered with a pentavalent diphtheria-tetanus-whole-cell pertussis-Haemophilus influenzae b (Hib)-inactivated polio vaccine and hepatitis B vaccine following a 3-4-5-mo schedule in a double-blind trial involving 249 infants. Seroconversion rates after 3 doses of rotavirus vaccine were 80% for rotavirus immunoglobulin A (IgA) and 93% for RRV neutralizing antibodies. Rotavirus vaccine did not interfere with the immune responses to diphtheria, tetanus, pertussis, Hib, poliovirus 1, 2 and 3, or hepatitis B. Following the first, second and third doses of vaccine, fever >38 degrees C on the day of vaccination was seen in 31%, 24% and 24%, respectively, with no difference between RRV-TV- and placebo-vaccinated children. This fever was presumably due to the whole-cell pertussis vaccine. Those vaccinees who received concomitant RRV-TV vaccine had another peak of fever around d 4 after the first dose, when 25% of them had fever >38 degrees C and 3% >39 degrees C. It is concluded that RRV-TV rotavirus vaccine can be given concurrently with other childhood immunizations following a 3-4-5-mo vaccination schedule. However, febrile reactions to RRV-TV rotavirus vaccine are common when the first dose is given at the age of 3 mo.     

Rotavirus gastroenteritis among children under five years of age in Izmir, Turkey

Little is known about the epidemiology of rotavirus infection in Turkey. The aim of the study was to determine the incidence and clinical significance of rotavirus gastroenteritis, in view of the potentially available prevention by rotavirus vaccination. The study also sought to determine possible risk factors for rotavirus gastroenteritis. Therefore, 920 children under five years of age with acute gastroenteritis admitted to three pediatric hospitals in Izmir were studied. Rotavirus was identified in 39.8% of the children. Most children with rotavirus gastroenteritis (80.7%) were younger than two years of age. Marked seasonality of rotavirus gastroenteritis was observed, with a peak incidence from January to March. A total of 91% of rotavirus strains that were typed were of serotypes G 1-4. There was no significant difference among rotavirus-positive and rotavirus-negative patients with regard to family income. Compared with children who were exclusively breast-fed, those who were not exclusively breast-fed were at a two-fold greater risk of rotavirus diarrhea. Rotavirus gastroenteritis was significantly more severe than non-rotavirus gastroenteritis; 69% of children with rotavirus infection had severe gastroenteritis (score > or = 11). In conclusion, rotavirus is the most common cause of severe gastroenteritis among children under five years of age in Izmir. A new potent rotavirus vaccine, when available, will provide effective protection against severe rotavirus infection. Promotion of breast-feeding would augment the impact of rotavirus vaccines in preventing severe childhood diarrhea.     

Astrovirus,adenovirus, and rotavirus in hospitalized children: prevalence and association with gastroenteritis

BACKGROUND: Agents of viral gastroenteritis such as astrovirus, rotavirus, and adenovirus are common pediatric pathogens accounting for many physician visits, hospital admissions, and nosocomial infections. Previous hospital-based prevalence studies have examined mainly symptomatic children. PURPOSE: To evaluate the prevalence of astrovirus, rotavirus, and adenovirus infections among hospitalized children less than 6 years of age, regardless of symptoms, and determine association with gastroenteritis. METHODS: From September 1998 to June 2000, stool specimens were collected twice weekly from children less than five years of age admitted to two wards in a tertiary-care children's hospital. A total of 480 samples were obtained from 309 hospitalizations. Stools were examined using antibody-based ELISA for astrovirus, rotavirus, and adenovirus. Clinical data was abstracted from patient records. RESULTS: Twenty one percent of the children had gastroenteritis symptoms at some point during their hospitalizations (43% were hospital acquired). Astrovirus was detected in 5.2% of all children compared to 6.8% with rotavirus and 0.8% with adenovirus serotypes 40 or 41. Nosocomial acquisition was common. Seventy five percent of astrovirus infections and 90% rotavirus infections were symptomatic. Astrovirus infections were significantly more likely to occur in younger infants and in children with compromised immunity. Rotavirus infections were significantly more likely to cause dehydration. In a three-year passive surveillance of gastroenteritis at the hospital, astrovirus and rotavirus infections peaked simultaneously in winter months. CONCLUSIONS: Rotavirus and astrovirus are common symptomatic infections on pediatric wards and contribute greatly to inpatient morbidity. Adenoviruses played a limited role in gastroenteritis in hospitalized children in this study.     

Neonatal rotavirus vaccination with RIT 4237 bovine rotavirus vaccine: a preliminary report

We vaccinated 244 newborn infants orally with RIT 4237 bovine rotavirus vaccine or placebo and followed them serologically and clinically for 16 months. Initially 39 of the 119 (33%) vaccine recipients compared with 1 of the 120 placebo recipients seroconverted by enzyme-linked immunosorbent assay-immunoglobulin M. After the first winter rotavirus season, at 7 months of age 55% of the vaccinated infants and 37% of the unvaccinated infants were rotavirus-seropositive by enzyme-linked immunosorbent assay-immunoglobulin G (P less than 0.01, chi square test). At 12 months of age, after a low rotavirus prevalence season, 34% of the vaccinated children and 23% of the unvaccinated children remained seropositive. There were 14 confirmed episodes of rotavirus gastroenteritis in the vaccine group and 10 episodes in the placebo group during the first 16 months. However, only 1 of the episodes in the vaccine group was severe, 4 were moderately severe and 9 were mild, whereas 7 episodes in the placebo group were severe and 3 were moderately severe (P less than 0.001 between groups, Fisher's exact test). There was no clear correlation between vaccine-induced clinical protection and initial serologic response (enzyme-linked immunosorbent assay-immunoglobulin M) to vaccination, but during follow-up severe rotavirus gastroenteritis was more likely to occur in children with no serum rotavirus immunoglobulin G antibody at the time of infection. We conclude at the present stage that neonatal rotavirus vaccination with RIT 4237 vaccine gives no protection against rotavirus infection but appears to modify the severity of gastroenteritis.     

Rotavirus and not age determines gastroenteritis severity in children: a hospital-based study

Background The severity of childhood gastroenteritis is generally believed to be age-related rather than aetiology-related. Rotavirus-induced gastroenteritis is more severe than gastroenteritis caused by other enteric pathogens and is also age-related. We thus addressed the question of whether the increased severity of rotavirus-induced gastroenteritis is related to age or to features intrinsic to the agent. Study design In this multicentre, hospital-based, prospective survey, we evaluated the severity of diarrhoea in rotavirus-positive and rotavirus-negative children up to 4 years of age. Severity was assessed with a score in four groups of age-matched children. Results Rotavirus was detected in 381 of 911 children. Disease severity was evaluated in 589 cases for which clinical data were complete. The rotavirus-positive and rotavirus-negative groups differed with regards to diarrhoea duration, hospital stay, degree of dehydration and the number of episodes of vomiting. Gastroenteritis was more severe in rotavirus-positive than in rotavirus-negative children. In contrast, none of the main severity parameters differed in the four age groups, irrespective of the presence of rotavirus. Conclusions These data provide the evidence that aetiology and not age determines diarrhoeal severity. The demonstration that diarrhoea was more severe in rotavirus-positive children supports the need for a rotavirus vaccine and for studies that address the duration of vaccine protection.     

An efficacy trial of the rhesus rotavirus vaccine in Maryland. The Clinical Study Group

A double-blind, placebo-controlled trial of oral rhesus rotavirus vaccine at a dose of 10(4) plaque-forming units was performed in 114 young infants in Maryland. Significantly more vaccinees than controls had fever and vomiting during the week after vaccination, but these reactions were mild. Of the vaccinees, 83% had a fourfold or greater rise in neutralizing antibody to rhesus rotavirus vaccine and 69% shed vaccine virus. Seventeen percent of the vaccinees and 24% of controls had rotavirus-positive diarrhea during the 2 years of surveillance. Vaccine efficacy was therefore 29% (95% confidence limits, -31% to +66%). Stools from 12 of 13 episodes containing sufficient antigen to type were serotype 1. We conclude that rhesus rotavirus vaccine was infective, immunogenic, and probably acceptably attenuated but that this serotype 3 vaccine provided little heterotypic protection during serotype 1 outbreaks in the community.     

Acute gastroenteritis in children attending day-care centres with special reference to rotavirus infections. II. Clinical manifestations

In a prospective study of a cohort of 214 children (aged 6 months-7 years) attending day-care centres, a total of 197 episodes of acute gastroenteritis (GE) occurred in 109 children (i.e. 51% of the participants) during a 12-month observation period. Rotavirus, pathogenic bacteria and Giardia lamblia caused GE in 24%, 6% and 2% of the cases, respectively. The aetiology of the remaining 68% was not discovered. Generally, the symptoms of GE were light and only two episodes led to hospitalization. Thirty-two rotavirus infections were asymptomatic. Two rotavirus GE reinfections occurred. They showed less severe symptoms than the primary infections. The older children (greater than 1.5 years) with rotavirus GE had lighter symptoms than the younger ones (less than or equal to 1.5 years). Compared with children with non-rotavirus GE, those with rotavirus GE showed the following clinical features: (1) Age between 6 months and 2 years. (2) Occurrence of rotavirus GE almost exclusively during the rotavirus season, i.e. January to April (winter). (3) High frequency of vomiting, the onset of which often preceded that of diarrhoea. However, these signs did not form a safe basis for the clinical diagnosis of rotavirus GE. One or more upper respiratory manifestations (URM) were observed in 39% of the children with rotavirus GE and in 36% of those with non-rotavirus GE. The occurrence of URM was age-related being highest in children less than 2 years. Consequently, the existence of a rotavirus syndrome is questioned. It is argued that URM in children with rotavirus GE may be due to a co-infection of the upper respiratory tract by a different micro-organism.