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Rotavirus (RV) epidemiology presents differences between developing and developed countries among which are seasonality age at first infection variability of strain in circulation and severity of disease. Since in Venezuela we have distinct seasonal patterns of RV occurrence we examined the epidemiological profile of RV disease associated to these differences by analyzing data from previous studies conducted in Venezuela. Data were collected from children

The efficacy of a rhesus rotavirus vaccine (MMU 18006, serotype 3) against infantile diarrhea was evaluated by active home surveillance of a group of 320 children 1-10 months of age in Caracas, Venezuela. During a 1 year period following oral administration of vaccine or placebo under a double-masked code, over 600 diarrheal episodes were detected. Etiologic studies revealed that heat-stable toxin (ST) producing enterotoxigenic E. coli (ETEC) was the most common diarrheal agent detected (34%) followed by enteropathogenic E. coli (EPEC, 10.9%), heat-labile toxin (LT) producing ETEC (7.6%), rotavirus (6.9%), Cryptosporidium (4.8%) and Campylobacter (1.3%). ST-producing ETEC were also recovered from over 20% of control stool specimens obtained during diarrhea-free periods, whereas EPEC, rotavirus, Cryptosporidium, and Campylobacter were rarely detected in such control specimens. Rotavirus was responsible for about one-half of the more severe cases of diarrhea. Twenty-two of 151 infants who received placebo (14.6%) and eight of 151 receiving a 10(4) PFU dose of vaccine (5.3%) had rotavirus diarrhea during the follow-up period for an efficacy level of 64% against any rotavirus diarrhea. However, vaccine efficacy reached 90% against the more severe cases of rotavirus diarrhea and was noticeably high in the 1-4 month age group. Serotypic analysis of the rotaviruses detected suggests that the resistance induced by the vaccine was type specific since significant protection was only evident against serotype 3 rotaviruses. A 10(3) PFU dose tested initially in 18 children did not appear to protect against rotavirus diarrhea.

To directly compare serum rotavirus specific IgA as a marker of protection in children vaccinated with the RRV-TV (Rotashield) vaccine and in naturally infected children, we studied pre-existing rotavirus IgA antibodies by ELISA assays in these groups of children within the first 5 days after the onset of a diarrhea episode, due or not to rotavirus. In immunized children, rotavirus IgA titers were similar between infected and non-RV infected children. In non-immunized children, the proportion with rotavirus IgA titers was significantly greater in non-RV infected children (58%) than in infected children (31%). Additionally, a titer >/=1:800 was associated with 68% protection. Thus, in this study serum rotavirus IgA showed a good correlation with protection in children pre-exposed to natural infection but not in those immunized with the RRV-TV vaccine.

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.

Some aspects of rotavirus humoral immunity were assessed on the basis of distinguishing serotype-specific specificities (VP4/VP7) by using rotavirus reassortants, human and animal strains in neutralization assays in serum samples obtained during the acute phase, and 1, 6 and 12 months after primary natural infection. In this study, all the infecting virus strains were characterized as G type and some also as P type. Primary natural infection induces a significantly greater homotypic neutralization response than heterotypic response. In addition, there was no significant difference in the number of homotypic or heterotypic responses following reinfection. Transplacentally acquired homotypic antibodies were associated with protection against dehydration during rotavirus gastroenteritis.

The temporal distribution and clinical severity of rotavirus VP7 serotypes 1, 2, 3, and 4 recovered from 427 Venezuelan children with acute gastroenteritis over a period of 11 years were studied. Rotavirus VP7 serotype was established by ELISA serotyping in 298 (69.78%) of the specimens while the serotype of the remaining 129 (30.21%) samples could not be determined. Of the specimens typed, 85 (19.90% of the total) were serotype 1, 43 (10.07%) were serotype 2, 105 (24.59%) were serotype 3, and 65 (15.22%) were serotype 4. Yearly changes in the frequency of individual serotypes were observed. The predominance of a single serotype with minor contribution from others was noted every year. In this study, serotype 1 appears to induce a less severe illness in comparison with serotypes 2, 3, and 4. No apparent association between the proportion of each serotype and the children's age were found.

The genetic relatedness of 81 clinical rotavirus isolates to the human rotavirus prototype strains Wa (subgroup 2, serotype 1) and DS-1 (subgroup 1, serotype 2) was examined by RNA hybridization techniques. Labeled single-stranded (+) transcripts of Wa or DS-1 virus were incubated with denatured genomic rotaviral RNAs, and the resulting hybrids were subjected to gel electrophoresis and autoradiography. Nineteen of the specimens contained subgroup 1 rotavirus with a "short" RNA migration pattern. These viruses were found to be closely related to the DS-1 strain and were associated with illness of short duration. The remaining 62 isolates belonged to subgroup 2 and exhibited a "long" RNA migration pattern. Fifty-four of these isolates exhibited significant hybridization with the Wa strain probe. Four isolates yielded multiple hybrid bands with the Wa probe but also possessed at least one gene segment homologous to the DS-1 strain. The remaining four subgroup 2 rotaviruses did not exhibit significant homology in the form of labeled hybrid bands when tested with either the Wa or DS-1 probe. These findings suggest that most clinical rotavirus isolates belong to one of two human rotavirus "families" defined as Wa-like or DS-1-like. Our observations also suggest that reassortment occurs in vivo between rotaviruses belonging to the two human rotavirus "families" and that there are one or more additional families of human rotavirus.