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PubMed1998

Extended excretion of rotavirus after severe diarrhoea in young children.

BACKGROUND: Rotaviruses are the major cause of severe childhood diarrhoea. Knowledge of the natural history of infection, including duration of intestinal virus shedding, is important in the understanding of transmission, sources of infection, and immune responses. METHODS: We carried out a study of rotavirus excretion in 37 children admitted to hospital with severe rotavirus diarrhoea. Sequential faecal specimens were collected from each child during 100 days of surveillance, and screened for rotavirus by EIA and by amplification of genome double-stranded RNA by reverse-transcription PCR. IgA coproantibody was estimated by EIA. FINDINGS: Duration of rotavirus excretion ranged from 4 to 57 days after onset of diarrhoea. Excretion ceased within 10 days in 16 (43%) children, and within 20 days in 26 (70%) children. Extended excretion was detected for 25-57 days in the remaining 11 (30%) children owing mainly to continued excretion of the primary infecting strain. Extended excretion was significantly associated with antirotavirus IgA coproantibody boosts during 100 days of surveillance (p=0.001, log-rank test), and with recurrence of mild diarrhoea symptoms during convalescence (p=0.006, Fisher's exact test). INTERPRETATION: Severe rotavirus disease in young children may be followed by extended excretion of rotavirus. The risk of transmission to others may be greater than previously believed. Extended excretion could also explain some cases of the postgastroenteritis syndrome.

Antibodies, Viral↗

PubMed1999

Heterotypic protection from rotavirus infection in mice vaccinated with virus-like particles.

Virus-like particles (VLPs) composed of rotavirus VP2, VP6, and VP7 of G1 or G3 serotype specificity were produced in insect cells coinfected with recombinant baculoviruses expressing single rotavirus genes. The VLPs were purified and subsequently evaluated for immunogenicity and protection in the adult mouse model of rotavirus infection. Mice were vaccinated twice intramuscularly with G1 VLPs formulated with Quillaja saponaria (QS-21) or adsorbed to aluminium hydroxide (AlOH), or with G1 VLPs alone. G3 VLPs, G1 plus G3 VLPs, inactivated SA11 virions formulated with QS-21, or adjuvants were similarly inoculated as controls. Mice were examined for serum and fecal antibody responses by ELISA or microneutralization assays. Protective efficacy of the VLP vaccine formulations against oral challenge with the G3 murine ECwt rotavirus was assessed by comparing the antigen shed in stool of the VLP-vaccinated mice to that of the adjuvant-immunized mice. G1 VLPs in QS-21 induced significantly higher serum and intestinal antibody titers than G1 VLPs in AlOH or G1 VLPs alone. QS-21 also heightened serum and fecal antibody responses to G3 VLPs. These QS-21-augmented antibody responses were further characterized by equivalent IgG1 and IgG2a titers in sera, suggesting that G1 or G3 VLPs in QS-21 induced a balanced Th1/Th2 response. G1 VLPs in QS-21 induced partial protection (88%) against oral challenge with the heterotypic ECwt virus, whereas G3 VLPs in QS-21 induced complete protection (100%). In contrast, G1 VLPs when formulated with AlOH induced a predominant Th2 response and did not protect (1%) mice from virus challenge. Our results indicate that the type of adjuvant used clearly influences both antibody responses to rotavirus VLPs and the protective efficacy against rotavirus infections. These data have important implications for the development of parenteral vaccines to ameliorate rotavirus disease.

Adjuvants, Immunologic↗

PubMed2003

Detection of a mammalian-like group A rotavirus in diarrhoeic chicken.

The present investigation describes detection of a mammalian-like electropherogroup A rotavirus in chicken with diarrhoea. This also records the first detection of a rotavirus in an avian species from India. During the investigation 75 diarrhoeic faecal samples collected from adult chicken were screened for the presence of group A rotavirus antigen by sandwich ELISA. All three samples positive for rotavirus antigen revealed 11 bands of RNA in polyacrylamide gel electrophoresis (PAGE). In contrast to avian group A rotavirus, segment 5 was found to migrate closer to 6 as is the case with mammalian group A rotaviruses. Segments 7, 8 and 9 were found to migrate as a tight triplet, which is characteristic of group A rotavirus.

Animals↗

PubMed2004

Vitamin A deficiency aggravates rotavirus infection in CD-1 mice through extensive involvement of the gut.

Rotavirus (RV) is one of the leading causes of life-threatening viral gastroenteritis in infants and animals. More than 100 million children live in endemic areas where they are at risk of rotavirus infection. In the western world, rotavirus is usually a self-limiting disease that involves no major sequelae; however, in the developing world it often leads to morbidity and mortality. One of the major components influencing the prognosis of rotavirus-infected children is their nutritional status. The prevalence of vitamin A deficiency in developing countries, where RV infection can be fatal, encompasses up to 40% of preschool children. We hypothesized, therefore, that vitamin A deficiency in an animal model would aggravate the course of rotavirus disease. CD-1 mice were infected with RV and fed either vitamin A-sufficient or vitamin A-deficient diets. Histological components of the small intestine and colon, stool samples from which rotavirus was recovered, and vitamin A levels were examined. Flattening of the villi along the duodenum was observed in both rotavirus-infected and non-infected vitamin A-deficient mice. Maximal effect was obtained with a combination of vitamin A deficiency and RV infection. The colon of vitamin A-deficient, infected mice displayed a significantly (p < 0.05) smaller glandular area and higher level of mucin, and viral excretion in the stool became significantly (p < 0.01) increased and lasted longer than in controls. We conclude that vitamin A deficiency aggravates the course of RV infection through both small intestinal and colonic damage.

Animals↗

PubMed2005

Rotavirus as a significant cause of prolonged diarrhoeal illness and morbidity following allogeneic bone marrow transplantation.

Infective diarrhoea is common among allogeneic stem cell transplant (SCT) recipients, frequently caused by viruses and may be difficult to differentiate from acute graft-versus-host disease (GVHD). Viral pathogens may directly or indirectly impact upon transplant-related mortality. Rotavirus is one of the most common causes of diarrhoea worldwide, but one of the least studied causes of diarrhoea post SCT. In this retrospective study we describe 21 cases of confirmed rotavirus infection in allogeneic SCT recipients. Most of these cases may occur in clusters during the winter and spring period. Symptoms of rotaviral infection were diarrhoea (95%), vomiting (62%), abdominal pain (38%), weight loss and loss of appetite in 38 and 29% of the cases, respectively. Possible extraintestinal manifestations of rotavirus infection were observed. The duration of the symptoms in this series ranged from 4 days to 4 months with median of 15 days. Patients with rotavirus infection were invariably lymphopenic and/or on immunosuppression for GVHD. Of the patients diagnosed with rotavirus, 86% required hospitalisation. In 57% of the cases, other viral pathogens were isolated near to the rotavirus infection period. Rotavirus infection is an important cause of prolonged diarrhoea post SCT, causing significant morbidity and frequently requiring hospitalisation.

Adolescent↗

PubMed2000

Development of a simple and rapid latex test for rotavirus in stool samples.

In the fields of infectious diseases, a variety of immunoassay methods has been reported. More simple, rapid and cost-effective manual tests for infectious diseases are needed. For the purpose of simple diagnosis of rotavirus infection, a rapid test against human rotavirus was developed. As for the preparation of the reagent, clinically isolated human rotavirus was cultured using MA-104 cells. Then, the cultured virus was purified by an ultracentrifugation method. The purified virus was inactivated with formaldehyde for use as antigen for immunization of rabbits. The antibody was purified and applied to sensitize the surface of latex particles to react with rotavirus in diarrheal stools. The latex agglutination test showed that the sensitivity was 98.2% and the specificity was 94.8%, in comparison with electron microscopy as the gold standard. Furthermore, to measure the virus concentration in stool samples, an automated latex photometric immunoassay system (LPIA) was used, which has been developed for quantitative measurement of agglutination. The range of the reactive viruses detected by the LPIA system was 3 x 10(7)-10(9) virions/mL. The rotavirus-positive and rotavirus-negative subjects were clearly discriminated. The results were in good accordance with electron microscope results. Those results showed that the latex agglutination test is a good tool for the simple and rapid detection of rotavirus in stool samples.

Animals↗

PubMed2006

Importance of rotavirus as a cause of gastroenteritis in Jordan: a hospital based study.

Rotavirus is recognized to be a very important cause of GE in younger children in both developed as well as developing countries, but causes most of the mortality and morbidity in the latter. The recent introduction of a rotavirus vaccine in some parts of the world makes it necessary for us to determine the impact of this organism in our population with the aim of determining the need for the vaccine. In order to determine this, a study was conducted at the JUH and 3 other private hospitals. At the JUH, 64/256 (25%) of children with GE had rotavirus in 1995. The proportions of cases attributed to rotavirus in the other 3 y were 70/199 (35.2%), 69/279 (24.7%) and 76/294 (25.8%) for 2002, 2003 and 2004, respectively. The cumulative proportion of cases attributable to rotavirus gastroenteritis in all the y was 27.14%. With regard to the 3 private hospitals, rotavirus accounted for 38/225 (16.9%), 140/664 (21%) and 668/1496 (44.6%) at the Khalidy, Jordan and Islamic hospitals, respectively. It is concluded that rotavirus is a significant cause of GE in Jordanian children regardless of their social background, and attempt at controlling this infection may be warranted.

Child↗

PubMed1984

Acute diarrhoea and rotavirus infections in young children in Kuwait.

The role of rotavirus infections in acute diarrhoea in young children was studied over a period of one year. Rotavirus was detected by electron microscopy and enzyme immunoassay methods in 40.2% of faecal specimens from 343 children with acute diarrhoea and in 4.7% of 86 controls. The infections were most common in children aged 2-12 months (42.3%). Twelve per cent of the rotavirus infected children were also infected with bacterial enteropathogens (Salmonellae, Shigellae and enteropathogenic Escherichia coli). The incidence of rotavirus infections was not related to sex, socio-economic or nutritional status of children. Rotavirus-associated diarrhoea differed in several clinical parameters from bacterial associated and nonspecific diarrhoea. Rotavirus was detected throughout the year but was most frequent during months with little rainfall and low humidity (March-May). Our results suggest that in Kuwait, rotavirus infection is a major cause of childhood diarrhoea.

Acute Disease↗

PubMed2002

Outbreaks of adult gastroenteritis traced to a single genotype of rotavirus.

Between November 1998 and December 2000, the Centers for Disease Control and Prevention screened samples from 263 outbreaks of gastroenteritis in the United States and identified 3 that were associated with rotavirus among adults. Rotaviruses from each outbreak were further characterized by reverse-transcription polymerase chain reaction. Surprisingly, all specimens were of serotype G2, a strain that is, as determined by high-stringency hybridization analysis, genetically distinct in all 11 gene segments from the other common rotavirus strains in circulation. The unusual coincidence of identification of only G2 strains in these 3 outbreaks of rotavirus gastroenteritis among adults is similar to results from other studies, in which G2 strains were found in association with more-severe disease in children than other rotavirus serotypes and in association with outbreaks of diarrhea among adults in Japan. Although rotavirus infections in adults are relatively uncommon, which indicates that good overall protective immunity exists, the predominance of G2 strains in outbreaks that have occurred in adults suggests that natural immunity to more common strains does not always provide adequate heterotypic immunity to G2 strains. For the rotavirus vaccines under development, special attention may need to be paid to protection against G2 strains.

Adult↗

PubMed2002

Protective immunity after natural rotavirus infection: a community cohort study of newborn children in Guinea-Bissau, west Africa.

To study the natural history of rotavirus infection and to determine the protection it confers against reinfection and diarrhea, 200 newborns in Guinea-Bissau were prospectively followed for up to 2 years. Rotavirus was detected in stool specimens collected weekly. By age 2 years, the incidence of primary rotavirus infection was 74%. In the first 3 months of life, 17% of the infections were diarrhea associated, compared with 60% at 9-11 months; after age 18 months, all infections were asymptomatic. A primary infection conferred 52% (95% confidence interval [CI], 16% to 73%) and 70% (95% CI, 29% to 87%) protection against subsequent rotavirus infection and rotavirus diarrhea, respectively. The protection was 66% (95% CI, 24% to 85%) against reinfection within the same epidemic, compared with 34% (95% CI, -29% to 67%) against reinfection in any subsequent epidemic. The high level of protection against symptomatic rotavirus infection provides an important incentive for development of a rotavirus vaccine.

Cohort Studies↗

PubMed2003

Rotavirus nonstructural protein NSP4 induces heterotypic antibody responses during natural infection in children.

Seroconversion of immunoglobulin A (IgA) and immunoglobulin G (IgG) (> or =4-fold rise) to rotavirus nonstructural protein 4 (NSP4) was determined, by use of enzyme-linked immunosorbent assay with fusion proteins glutathione S-transferase (GST)-NSP4 from strains SA11 (A), 116E (B), and RRV (C), in 40 children with acute rotavirus gastroenteritis and in 30 with the same disease due to other pathogens. The IgG seroconversion rates in the rotavirus group were 67.5%, 70%, and 60% when recombinant (r) NSP4A, -B, and -C, respectively, were used as antigen in the assay, and, for rotavirus-uninfected children, rates were 10%, 13%, and 7%. IgA seroconversion occurred in 57%, 70%, and 50%, respectively, of children with rotavirus gastroenteritis; in rotavirus-uninfected children, 1 child each seroconverted to the different rNSP4s. Among 9 children infected with strain NSP4A, 7, 6, and 5 children showed IgG seroconversion, and, among 18 infected with NSP4A, -B, and -C, 16, 17, and 15, respectively, showed IgG seroconversion. Between NSP4A-infected and NSP4B-infected children, IgA responses were similar to IgG responses. In conclusion, significant NSP4-specific antibody response occurs in natural rotavirus infection, and the antibody response appears to be broad and heterotypic in nature.

Antibodies, Viral↗

PubMed1985

Maternal antibody-mediated protection against gastroenteritis due to rotavirus in newborn mice is dependent on both serotype and titer of antibody.

In order to evaluate the role of passively acquired, rotavirus-specific antibodies in protection against diarrhea, we inoculated mouse dams with rotaviruses of various serotypes, and their newborns were orally challenged with a primate rotavirus (simian SA-11). Dams were immunized by using a regimen that included repeated inoculations administered either orally or intraperitoneally with adjuvant. The serum antibody response detected in dams by radioimmunoassay and plaque-reduction neutralization after parenteral immunization was approximately 15-fold and 80-fold greater, respectively, than that found after oral "hyperimmunization." Parenteral immunization with rotavirus serotypes either homotypic or heterotypic to the challenge virus protected suckling mice against diarrhea; protection was closely correlated with the in vitro neutralizing activity of maternal serum against the challenge virus. Oral immunization with only rotavirus strains homotypic to the challenge virus afforded protection; the lower immune response after oral immunization with rotaviruses heterotypic to the challenge virus resulted in a titer of neutralizing antibody to the challenge virus below the protective threshold. From our current studies it appears that antibody-mediated passive protection against rotavirus challenge is dependent on both serotype and titer of antibody.

Animals↗

PubMed1992

Detection of rotaviruses in the day care environment by reverse transcriptase polymerase chain reaction.

Group A rotavirus is an important cause of morbidity among infants and toddlers in day care centers. Transmission by the fecal-oral route is well established, but fomites and environmental surfaces may also play an important role in transmission. A highly sensitive polymerase chain reaction (PCR) assay was used to detect rotavirus RNA in day care environments. Areas sampled included floors, diaper change areas, toy balls, and other surfaces. In two centers undergoing outbreaks of rotavirus, 7 (39%) of 18 toy balls had detectable rotavirus as did 8 (21%) of 39 swabs from environmental surfaces. By comparison, only 1 (5%) of 21 toy balls and 1 (2%) of 44 environmental surface swabs had detectable rotavirus in centers without rotavirus outbreaks (P = .0001). Thus, rotaviruses are highly prevalent in day care centers during outbreaks of diarrhea. The monitoring of environments by sensitive nucleic acid amplification techniques may lead to strategies for the diminution of disease transmission within the day care environment.

Base Sequence↗

PubMed1996

Molecular determinants of immunity and pathogenicity of rotavirus infection in the mouse model.

Rotavirus-induced diarrhea is responsible for the death of approximately 800,000 children per year. Jennerian and modified Jennerian anti-rotavirus vaccines currently being tested have a moderate protective effect against rotavirus disease. Optimization of these vaccines, development of more efficient rationally designed vaccines, and identification of other strategies to prevent or treat rotavirus disease will rely on a thorough understanding of the host-virus relationship and especially on the immune mechanisms developed by the host against rotavirus. Recent advances in our understanding of the mouse model of rotavirus infection will enhance the understanding of human rotavirus disease.

Animals↗

PubMedDate not supplied

Aerosol transmission of experimental rotavirus infection.

Several aspects of the epidemiology of rotavirus suggest the possibility that transmission may occur by nonenteral routes. We utilized the mouse model of rotavirus infection to investigate the experimental transmission of rotavirus infection by respiratory droplets. Following exposure to a defined dose of aerosolized rotavirus, the kinetics of viral replication within the lung and gastrointestinal tract was studied using a double antibody enzyme immunoassay and indirect immunofluorescence. These studies documented the efficient transmission of rotavirus infection by means of aerosol in all exposed animals. Rotavirus antigen was detected as early as 12 hours after infection in the pulmonary and gastrointestinal tracts of the infected animals and antigen remained detectable in both sites for at least 8 days following infection. Gastrointestinal illness was clearly demonstrable in the animals while pulmonary pathology was not evident. These studies document that rotavirus infection can be transmitted by aerosol droplets under experimental conditions.

Aerosols↗

PubMed1988

Nosocomial transmission of rotavirus infection.

Children admitted to the infant ward between November 30, 1983, and May 5, 1984, were sampled for rotavirus antigen at admission and at 4-day intervals during subsequent hospitalization. Rotavirus was detected in 51 of 315 infants, 24 at the initial sampling and 27 after 72 hours of hospitalization (nosocomial cases). Forty-one of the cases were symptomatic and 10 were asymptomatic. Nosocomial rotavirus was detected in 5, 13 and 24% of children in the hospital for 4 to 8, 9 to 13 and greater than 13 days, respectively. Attending physicians clinically entertained the diagnosis of rotavirus infection in 58% of community-acquired cases but in only 22% of nosocomial cases. Subgrouping of 24 of the rotavirus isolates with monoclonal antibodies indicated that two-thirds of the isolates were Subgroup II, and the remainder were a mixed subgroup, with similar prevalences in the nosocomial and community-acquired cases. Only 11 of 27 instances of nosocomial rotavirus acquisition were epidemiologically associated with a rotazyme-positive roommate and in 4 of these instances different subgroups were present in the 2 roommates. These data suggest that infected roommates appear not to be a major source for direct transmission of nosocomial rotavirus infection.

Antigens, Viral↗

PubMed1993

Passive immunization for prevention of rotavirus illness in healthy infants.

Infant formula supplemented with bovine antibody (BCIg) to human rotavirus has been reported to prevent or modify rotavirus infection and illness. The purpose of this field trial was to determine the safety and feasibility of passive immunization with bovine antibody for the prevention of rotavirus infection and illness in healthy infants. Sixty-four infants, 31 of whom received BCIg and 33 placebo, participated in the study. Rotavirus infection was detected in 11 (35%) and 14 (42%) infants in the 2 groups, respectively. Symptomatic rotavirus infection was documented in 1 (3%) of the infants receiving BCIg and in 6 (18%) of the infants who received the placebo (P > 0.05). The number of days with diarrhea/1000 days of observation was significantly less in the BCIg group, 4.2, than in the placebo group, 16.8 (P < 0.01). Similarly the number of days with rotavirus-associated diarrhea/1000 days was less in the BCIg group, 1.0, than in the placebo group, 13 (P < 0.01). This study establishes the feasibility of providing passive immunity for the prevention of rotavirus illness in healthy infants.

Antibodies, Viral↗

PubMed2004

Rotavirus strain surveillance in Latin America: a review of the last nine years.

BACKGROUND: Latin America will likely be the first area in the developing world where rotavirus vaccine will be introduced into the routine childhood immunization schedule. In anticipation of that goal, we reviewed the distribution of group A rotavirus genotypes in Latin America to understand the diversity of strains to be targeted by vaccines and to identify novel strains that may pose challenges for vaccines. METHODS: We reviewed studies characterizing rotavirus strains in Latin America (published in English since 1995) that used molecular methods to type genes encoding the G and P outer capsid proteins, VP7 and VP4, and that reported data on >50 specimens. RESULTS: Fifteen studies from 5 countries met our criteria. In total, 1989 samples were characterized; 12% (233) were mixed rotavirus infections with more than 1 strain, and 20% (402) were not fully typable. Of the remaining 1354 samples that were fully typed, 83% represented the 4 common strains: P[8],G1 (40%); P[4],G2 (30%); P[8],G3 (6%); P[8],G4 (7%). The unusual strains provide interesting insights into virus evolution: some strains (G5) were regionally common; the emerging G9 strains were widely distributed; many animal-human reassortants were present; and some common serotypes (G3 and G4) were of animal origin. Also an unusual G12 serotype was recently detected in Argentina. CONCLUSIONS: The common rotavirus serotypes should remain the prime targets for vaccine development. However, the changing profile of rare strains, animal-human reassortants and nontypable strains suggest that rotavirus is constantly evolving. Laboratory surveillance is needed to monitor rotavirus strains now in circulation and to detect those that might escape the immunity induced by vaccines or represent vaccine strains entering the environment.

Capsid Proteins↗