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At least 973 records · Page 54Linked to original sources
PubMed2006

Effect of nitazoxanide for treatment of severe rotavirus diarrhoea: randomised double-blind placebo-controlled trial.

BACKGROUND: Rotavirus is a leading cause of morbidity and mortality in children younger than 5 years, but there is no effective treatment. We assessed the activity of nitazoxanide, a broad-spectrum anti-infective drug, against rotavirus in cell culture and in a clinical trial in paediatric patients hospitalised with severe rotavirus diarrhoea. METHODS: We did a randomised double-blind placebo-controlled trial in 50 children admitted to the Cairo University Children's Hospital between June 15 and Aug 23, 2005, with severe rotavirus diarrhoea. 38 children aged 5 months to 7 years (median age 11 months) with rotavirus as the sole identified cause of gastroenteritis were enrolled in the clinical study. Patients were randomly assigned either 7.5 mg/kg nitazoxanide as an oral suspension or placebo twice a day for 3 days, and all remained in hospital for 7 days after start of treatment. The primary endpoint was time from first dose to resolution of illness, and analysis was by modified intention-to-treat. This study is registered with ClinicalTrials.gov, number NCT00302640. FINDINGS: Survival analysis showed that the median time to resolution of illness was 31 h (IQR 22-73) for the nitazoxanide-treated group compared with 75 h (51-124) for the placebo group (p=0.0137). No significant adverse events were reported. INTERPRETATION: A 3-day course of nitazoxanide significantly reduced the duration of rotavirus disease in hospitalised paediatric patients. These results are encouraging, and might lead us to think about new approaches to managing rotavirus disease in children.

Anti-Infective Agents↗
PubMed2001

Immune responses and protection obtained with rotavirus VP6 DNA vaccines given by intramuscular injection.

Intramuscular (i.m.) injection of murine VP6 DNA vaccines raised high titers of rotavirus-specific serum IgG and IgA antibodies in BALB/c mice. A Th1-like antibody response was generated based on the ratio of serum IgG2a to IgG1 antibodies. Rotavirus-specific serum IgA but not fecal IgA was detected in mice prior to rotavirus challenge. Partial protection against rotavirus challenge was achieved as measured by reduction of rotavirus antigen shedding in feces. A similar level of protection was found with a bovine rotavirus VP6 DNA vaccine against a murine rotavirus challenge, suggesting that heterologous protection can be obtained by immunizing with VP6 DNA vaccines. We did not directly test for cytotoxic T lymphocyte (CTL) activity, but in vivo depletion of CD8+ T cells in mice immunized with a murine VP6 DNA vaccine did not significantly change the duration of virus shedding or the pattern of protection obtained. This finding suggested that CD8+ CTL activity was not essential for the partial protection we obtained by i.m. immunization of mice with VP6 DNA vaccines.

Animals↗
PubMed2001

Nasal immunisation with Salmonella typhimurium producing rotavirus VP2 and VP6 antigens stimulates specific antibody response in serum and milk but fails to protect offspring.

Rotavirus specifically infects the small intestine of young infants resulting in severe diarrhoea. Mucosal antibody responses are required to cure the infection, and mucosal administration of rotavirus-like particles induces protective immunity without requiring a mucosal adjuvant such as cholera toxin. In addition, the rotavirus protein VP6 has been defined as a protective antigen in an adult mouse rotavirus infection model. Salmonella typhimurium is an epithelium-invasive bacterium that induces specific immune responses in mucosal tissues against itself and carried antigens. In this work, we investigated the capacity of a live recombinant S. typhimurium vaccine to stimulate antibody responses against rotavirus. We constructed an attenuated S. typhimurium strain simultaneously producing VP6 and VP2 rotavirus proteins in the cytoplasm. In contrast to expression in eukaryotic cells, VP6 and VP2 did not form virus-like particles in our bacterial system. After nasal administration of female mice, the live recombinant Salmonella were able to elicit an antibody response specific to both VP2 and VP6 in serum and milk. However, these antibodies failed to passively protect the offspring against rotavirus-induced diarrhoea.

Administration, Intranasal↗
PubMed1996

A major rearrangement of the VP6 gene of a strain of rotavirus provides replication advantage.

During coinfection of BSC-1 cells with bovine rotavirus B223 and human rotavirus 69M and subsequent serial passages at low multiplicity of infection (0.1 m.o.i.), a reassortant virus (BMR) with a rearranged VP6 gene became the predominant strain. At passage 24 virus extracted from 50 of 51 plaques (98%) contained the rearranged gene 6, which had been first observed in passage 19. The analyses of the clones obtained from passages before the appearance of the rearranged VP6 gene (passage 15) and after (passage 20) indicated that the B223 VP6 gene was the origin of the rearranged VP6 gene. To test whether the rearranged VP6 gene was responsible for the selection advantage observed, reassortant C11 was generated with BMR and WA rotavirus, containing the rearranged VP6 gene and the other 10 genes from WA. Coinfection of WA rotavirus and reassortant C11 and subsequent serial passages at low m.o.i. resulted in 100% of virus from clones extracted at passage 18 being identical to reassortant C11; demonstrating that the rearranged VP6 gene was once again selected over the normal VP6 gene. The selection advantage of the rearranged VP6 gene could not be explained by comparison of the growth curves of the viruses, as there was no significant difference between the growth cycles of rotavirus B223 and reassortant BMR, nor between rotavirus Wa and reassortant C11. However, the plaque and electropherotype analysis at passage 1 of Wa and C11 coinfection revealed that 85% of the progeny viruses contained the rearranged gene 6. These data show that the gene 6 rearrangement resulted in selection of the relevant reassortant, possibly by suppression of competitive strains, and may indicate a new mechanism for the evolution of rotavirus.

Animals↗
PubMed1998

Infection with group C rotavirus in a suburban community in Brazil.

Group C rotaviruses are associated with sporadic outbreaks of gastroenteritis worldwide. Age-specific seroprevalence of group C rotavirus antibodies was investigated in sera, randomly collected and representative of a suburban community in Brazil which had previously been screened for group A rotavirus antibodies. Antibody prevalence to group C rotavirus was low in children under 5 years and increased slowly with age to 36% seropositivity in adults, reflecting continuous exposure to primary infection in all age groups. This suggests a higher incidence of infection than disease might predict. Adult antibody prevalence was similar to that in other geographical settings. No obvious patterns of infection with group A and group C rotavirus were found within individuals, which suggests independent transmission. However, further epidemiological studies are required to understand group C rotavirus dynamics and possible interactions with group A rotavirus transmission and immunity.

Adolescent↗
PubMed2000

Child rotavirus infection in association with acute gastroenteritis in two Chinese sentinel hospitals.

Rotavirus gastroenteritis is an important pediatric disease in China. In a survey of rotavirus infection at two sentinel hospitals in China (Beijing Friendship Hospital and Changchun Children's Hospital), 296 cases were detected. A total of 283 (95.6%) cases of rotavirus infection occurred in children under 5 years of age. Serotype G1 (62%) was most prevalent followed by G2 (28.5%), G3 (5%) and G4 (2%). Mixed infections (n = 8, 3%) were rate, and 16 isolates (5.5%) remained non-typeable. A consistent epidemic occurred during the winter. Rotavirus was responsible for about 61.8% of diarrhea-related hospitalizations in children under 5 years of age, with a mean hospital stay of 5.6 days (1.0-21 days). The estimated rate of rotavirus-attributed hospitalizations was 16/1000 children under 5 years of age per year. Rotavirus-related death is rare in Changchun and Beijing. The present findings suggest that a rotavirus vaccine for the prevention of severe disease and a reduction of treatment costs would be of significant benefit to China.

Child, Preschool↗
PubMed2002

Incidence of nosocomial rotavirus infections, symptomatic and asymptomatic, in breast-fed and non-breast-fed infants.

Rotavirus is one of the most important aetiological agents of nosocomial infections in childhood. We studied the incidence of nosocomial rotavirus infections in 420 patients (age range 1-18 months) consecutively admitted from 1 December 1999 to 31 May 2000 to the infant ward of the Department of Paediatrics, University of Turin. We also evaluated the protective effect of breast feeding. Faecal specimens were collected from every child (whether developing diarrhoeic symptoms or not) and tested for rotavirus during hospitalization and 72 h after discharge. The incidence of rotavirus nosocomial infections was 27.7%. The incidence of symptomatic nosocomial infections was 16.8%, and the incidence of asymptomatic infections was 10.9%. The attack rate of the infections that occurred during hospitalization was 11.8%, while for those occurring after discharge, it was 15.9%. Rotavirus infection, on average, prolonged hospital stay from 5.2 to 6.4 days. 10.6% of breast-fed infants and 32.4% of non-breast-fed infants contracted rotavirus infection (P<0.005). None of the breast-fed infants who contracted rotavirus infection developed diarrhoeic symptoms.

Breast Feeding↗
PubMed1999

Immunity to rotavirus infection in mice.

Recent findings from our laboratory regarding the immune response of mice to rotavirus (a mucosal pathogen) show that although in most situations an acquired (T or B cell or both) response is necessary for elimination of primary rotavirus infection, unidentified innate mechanisms can also play a role in some mouse strains. Similar to what is seen with many other viruses, CD8+ T cells appear to provide the first but not the exclusive mechanism that mediates clearance of a primary rotavirus infection. Antibodies are the critical mediators of prevention against rotavirus reinfection. Nonneutralizing IgA monoclonal antibodies directed against VP6 (an internal structural rotavirus protein) can mediate immunity against rotaviruses in vivo. Rotavirus-specific CD8+ T cells can mediate their antiviral effect in the absence of perforin, fas, or interferon-gamma and are preferentially represented in the subset that expresses high levels of the enteric mucosal homing receptor alpha4beta7.

Animals↗
PubMed2005

Incidence and burden of rotavirus gastroenteritis in Japan, as estimated from a prospective sentinel hospital study.

We assessed the burden of rotavirus infection-related disease, in terms of hospitalization and associated costs, at 3 sentinel hospitals in Akita prefecture, Japan. From January 2001 through December 2002, a total of 443 children <5 years of age were hospitalized for acute gastroenteritis. Of 422 stool specimens collected, 244 (58%) tested positive for rotavirus. Only 7.8% of the rotavirus disease-associated hospitalizations involved infants <6 months of age, whereas most cases of disease (39%) were reported in the second year of life, and 89% of cases had occurred by 36 months of age. The mean severity score for rotavirus gastroenteritis resulting in hospitalization was 16.5, according to the modified 20-point severity scoring system. The average associated direct medical cost was 136,000 yen (1236 US dollars) per case and was similar among the 3 hospitals. The estimated incidence of rotavirus disease-associated hospitalizations among children <5 years of age was 7.9-17.6 hospitalizations/1000 person-years, and the estimated cumulative incidence by 5 years of age was 6.6%. Thus, approximately 1 in 15 children will require hospitalization due to rotavirus diarrhea by their fifth year of life. In Japan, this would mean that 78,000 children <5 years of age would be hospitalized each year, resulting in a direct medical cost of 10 billion yen (96 US dollars million). The burden associated with rotavirus gastroenteritis in Japan is substantial and might be reduced through the introduction of vaccines.

Child, Preschool↗
PubMed2006

Production of rotavirus-like particles in tomato (Lycopersicon esculentum L.) fruit by expression of capsid proteins VP2 and VP6 and immunological studies.

A number of different antigens have been successfully expressed in transgenic plants, and some are currently being evaluated as orally delivered vaccines. Here we report the successful expression of rotavirus capsid proteins VP2 and VP6 in fruits of transgenic tomato plants. By western blot analysis, using specific antibodies, we determined that the VP2 and VP6 produced in plants have molecular weights similar to those found in native rotavirus. The plant-synthesized VP6 protein retained the capacity to form trimers. We were able to recover rotavirus virus-like particles from tomato fruit (i.e., tomatoes) by centrifugation on a sucrose cushion and to visualize them by electron microscopy. This result indicated that VP2/VP6 can self-assemble into virus-like particles (VLPs) in plant cells, even though only a small proportion of VP2/VP6 assembled into VLPs. To investigate immunogenicity, adult mice were immunized intraperitoneally (i.p.) three times with a protein extract from a transgenic tomatoes in adjuvant. We found that the transgenic tomato extract induced detectable levels of anti-rotavirus antibodies in serum; however, we did not determine the contribution of either the free rotavirus proteins or the VLPs to the induction of the antibody response. These results suggest the potential of plant-based rotavirus VLPs for the development of a vaccine against rotavirus infection.

Animals↗
PubMed1982

Carbohydrate malabsorption in infants with rotavirus diarrhea.

We studied a group of patients with rotavirus diarrhea to determine the association of carbohydrate malabsorption during diarrhea with the degree of acidosis and severity of purging. Unlike enterotoxigenic diarrhea in which the metabolic acidosis is due to loss of bicarbonate in an alkaline stool, patients with rotavirus develop a metabolic acidosis while passing an acid stool with little detectable bicarbonate. Also unlike enterotoxigenic diarrhea, rotavirus stool contains large quantities of reducing substances suggesting significant carbohydrate malabsorption. Our findings are consistent with the hypothesis that carbohydrate malabsorption is an important secondary pathophysiological mechanism in the rotavirus diarrhea syndrome. This model for rotavirus diarrhea helps to explain the electrolyte and acid-base pattern of the rotavirus stool and stresses the importance of further nutrition balance studies to determine the optimal dietary management of patients with rotavirus diarrhea.

Acidosis↗
PubMed1978

A long-term survey of rotavirus infection in Japanese children with acute gastroenteritis.

Human rotavirus was detected by electron microscopic examination of the stools of 320 (63%) of 506 infants and young children hospitalized with acute gastroenteritis between December 1974 and March 1977. Serologic responses to infection with the rotavirus were revealed by the complement-fixation test in 130 (70%) of 185 patients examined. During the study period three epidemics of human rotavirus infection occurred during the winter months. The peak incidences occurred in January 1975 (88% of patients positive by serologic analysis or electron microscopy of stools), January 1976 (92%), and February 1977 (96%). Rotavirus was detected in the stools of 288 (79%) of 365 patients tested during the cooler months (December to March) and 35 (25%) of 141 during the rest of the year. In the summer (June to August), rotavirus infection occurred rarely. The frequency of human rotavirus infection was highest among patients aged six to 11 months. These results indicate that human rotavirus can be regarded as a major etiologic agent of acute gastroenteritis in infants and young children, of which wintertime epidemics are common in Japan.

Acute Disease↗
PubMed2000

Lactulose-mannitol intestinal permeability test in children with diarrhea caused by rotavirus and cryptosporidium. Diarrhea Working Group, Peru.

BACKGROUND: The relationship between intestinal permeability and acute secretory diarrheal syndromes caused by rotavirus and Cryptosporidium parvum in infants less than 36 months of age was studied using the lactulose-mannitol excretion assay. METHODS: An oral solution containing 0.4 g/kg lactulose and 0.1 g/kg mannitol was administered to 15 infants with rotavirus, 7 with Cryptosporidium infection and a control group of 7 with secretory diarrhea admitted to the Oral Rehydration Unit of the National Children's Hospital in Lima, Peru. Urinary sugar excretion was measured using an enzymatic spectrophotometric method. The ratio of urinary excretion of lactulose to mannitol was used to measure intestinal mucosal permeability, with higher ratios indicative of increased intestinal permeability. Infants in all three groups were retested 20 days after the initial test. RESULTS: The (mean +/- SE) lactulose:mannitol (L:M) excretion ratios during the acute phase (day 1) of diarrhea in infants with rotavirus or Cryptosporidium and control infants were 0.67 +/- 0.1, 0.76 +/- 0.16, and 0.26 +/- 0.04, respectively. In the convalescent phase (day 20) the ratios were 0.19 +/- 0.02, 0.28 +/- 0.05, and 0.29 +/- 0.07, respectively. Significant reductions in L:M ratios were noted in rotavirus patients between days 1 and 20 (paired t-test; P < 0.01), Cryptosporidium patients between days 1 and 20 (paired t-test; P < 0.05), and between control subjects on day 1 and rotavirus patients on day 1 and Cryptosporidium patients on day 1 (unpaired t-tests; P < 0.05 for both). There were no significant differences in control subjects between days 1 and 20, control subjects and rotavirus patients on day 20, or control subjects and Cryptosporidium patients on day 20. CONCLUSIONS: The results indicate that increased intestinal permeability caused by rotavirus or cryptosporidium infections in Peruvian infants less than 36 months of age is a significant but reversible phenomenon. The temporal relationship observed in the current study and the contribution of such alterations in intestinal mucosal integrity to the burden of diarrheal disease and the development of malnutrition in developing countries is discussed.

Animals↗
PubMed1988

Cross-neutralizing antibodies induced by single serotype vaccination of cows with rotavirus.

Single serotype vaccination of mature cows with nine different strains of bovine, simian and human rotaviruses induced heterotypic milk and serum neutralizing antibodies against two bovine and four human rotavirus serotypes. Immunization with single-shelled simian rotavirus SA11 increased milk and serum neutralization titres fivefold over those of control cows, without inducing antibodies to outer shell polypeptides of rotavirus. Vaccination with double-shelled SA11 virions also elicited cross-reacting antibodies to the outer shell proteins VP3 and/or VP7 which neutralized rotavirus seven times more efficiently than antisera to single-shelled SA11 virus. A related rotavirus similar to simian rotavirus SA11, but from a different host, might thus be an attractive vaccine for immunization of pregnant cows to confer passive immunity to calves.

Animals↗
PubMed2000

Growth of rotaviruses in continuous human and monkey cell lines that vary in their expression of integrins.

Rotavirus replication occurs in vivo in intestinal epithelial cells. Cell lines fully permissive to rotavirus include kidney epithelial (MA104), colonic (Caco-2) and hepatic (HepG2) types. Previously, it has been shown that cellular integrins alpha 2 beta 1, alpha 4 beta 1 and alpha X beta 2 are involved in rotavirus cell entry. As receptor usage is a major determinant of virus tropism, the levels of cell surface expression of these integrins have now been investigated by flow cytometry on cell lines of human (Caco-2, HepG2, RD, K562) and monkey (MA104, COS-7) origin in relation to cellular susceptibility to infection with monkey and human rotaviruses. Cells supporting any replication of human rotaviruses (RD, HepG2, Caco-2, COS-7 and MA104) expressed alpha 2 beta 1 and (when tested) alpha X beta 2, whereas the non-permissive K562 cells did not express alpha 2 beta 1, alpha 4 beta 1 or alpha X beta 2. Only RD cells expressed alpha 4 beta 1. Although SA11 grew to higher titres in RD, HepG2, Caco-2, COS-7 and MA104 cells, this virus still replicated at a low level in K562 cells. In all cell lines tested, SA11 replicated to higher titres than did human strains, consistent with the ability of SA11 to use sialic acids as alternative receptors. Levels of cell surface alpha 2 integrin correlated with levels of rotavirus growth. The alpha 2 integrin relative linear median fluorescence intensity on K562, RD, COS-7, MA104 and Caco-2 cells correlated linearly with the titre of SA11 produced in these cells at 20 h after infection at a multiplicity of 0.1, and the data best fitted a sigmoidal dose-response curve (r(2)=1.00, P=0.005). Thus, growth of rotaviruses in these cell lines correlates with their surface expression of alpha 2 beta 1 integrin and is consistent with their expression of alpha X beta 2 and alpha 4 beta 1 integrins.

Animals↗
PubMed1989

Prospective study of nosocomial rotavirus infection in a paediatric hospital.

Hospital-acquired enteric infections, particularly those due to rotavirus, were investigated by studying 220 patients under 3 years of age who were admitted without gastroenteritis to two paediatric general medical wards during a 10 month period. Faecal specimens were collected within 48 h of admission and then daily until the patients were discharged. Samples were also collected after discharge if patients developed enteric symptoms within 2 days of discharge. Fourteen per cent (31 of 220) of patients acquired rotavirus infections while in hospital, 23% (seven of 30) excreted rotavirus only after discharge; 29% of patients infected with rotavirus were asymptomatic (nine of 31). Acquisition of rotavirus infection was most prevalent during the months May-August, with a prevalence of 34% (12 of 35) in May. Hospitalization was prolonged in those patients who acquired rotavirus (11.1 days compared with 8.0 days, P less than 0.05). This study highlights the importance of rotavirus as a cause of hospital cross-infection, particularly in the very young patient, and emphasizes the need for further assessment of factors involved in its acquisition. In order to determine correctly the incidence of hospital-acquired illness, it is essential to follow patients after discharge from hospital. This study reinforces the importance of developing preventive measures in order to reduce the frequency of this illness.

Australia↗
PubMed1999

Cost effectiveness of rotavirus vaccination in Australia.

OBJECTIVE: Rotavirus gastroenteritis causes substantial morbidity, including hospital admission, in young children. In the context of recent vaccine developments, this study aimed to estimate the cost-effectiveness of a rotavirus vaccination program in Australia. METHOD: Standard methods of health economic evaluation were used to assess the total cost of rotavirus immunisation (as the difference between estimated vaccination program costs and the cost of disease that would be avoided by immunisation) and relate this to the number of cases of disease that would be prevented. Estimates were made from both societal and health care systems perspectives. RESULTS: Based on Australian data on disease incidence and cost of hospitalisation, the current annual cost of rotavirus disease is about $26.0 million. Using conservative vaccine efficacy estimates, current immunization uptake rates and a cost of $30 per dose of vaccine, rotavirus immunisation would incur a net societal cost of $2.9 million ($11 per child), at a gross program cost of $21.6 million. These estimates are sensitive to two sources of uncertainty in the estimation of program delivery costs: vaccine price and whether separate immunization visits would be required. CONCLUSION: A rotavirus immunisation program would be cost-neutral to Australian society at a vaccine price of $26 per dose (or $19 when health care system costs only are considered). IMPLICATIONS: Rotavirus immunization may be cost-effective in Australia, but considerable uncertainty remains. Policy decisions will depend heavily on pricing of the vaccine and may also need to consider intangible costs not accounted for in this analysis.

Child, Preschool↗
PubMed1981

Quantitative aspects of rotavirus excretion in childhood diarrhoea.

The amount of rotavirus (antigen) in diarrhoeal stools was determined from serially diluted faecal specimens using a solid phase radioimmunoassay (RIA) method. The acute stage RIA titres for rotavirus antigen ranged from 1:200 to 1:200 000 with a mean titre of 1:2 936 in a group of 16 infants with age range 2 to 14 months and 1:4 703 in a group of 12 children aged 25 to 94 months. In the younger age-group the diarrhoea lasted longer (mean 7.8 days) than in the older children (mean 5.4 days) despite the fact that the quantity of rotavirus was similar. In most of the younger infants there was either no demonstrable rotavirus present at the time of cessation of diarrhoea, or the amount of virus was on the decrease. In contrast, among the older children there were cases with a high titre of rotavirus in the stools a few days after the diarrhoea had ceased. These children were considered as potential spreaders of rotavirus infection in the community. However, none of the long-term follow-up stool specimens, collected 28 to 47 days after the onset of diarrhoea, were positive for rotavirus RIA.

Antigens, Viral↗