Establishment of a rotavirus-infected zebrafish model and its application in drug screening.

Rotavirus (RV) is one of the main pathogens that induce infantile diarrhea and by now no effective drugs are available for RV-induced infantile diarrhea. Thus the development of novel models is of vital importance for the pathological research of RV-induced infantile diarrhea, as well as the progress of the associated treatment strategy. Here we introduced for the first time that RV-Wa strain and RV-SA-11 strain could infect 5 dpf(day post fertilization) and 28 dpf larvae, to induce infantile diarrhea model that was highly consistent with the clinical infection of infants. RV infection significantly changed the signs, survival rate and inflammation of larvae. Some important indicators, including the levels of RV antigen VP4 and VP6, the in vivo RV tracking, and the RV particles were also analyzed, which collectively demonstrated that the model was successfully established. More importantly, we also determined the potentials of the proposed RV-infected zebrafish model for anti-viral drug assessment. In conclusion, we established a RV-infected zebrafish model with formulated relevant indicators both larvae and adult fish, which might be served as a high throughput platform for antiviral drug screening.

Bovine Colostrum in the Treatment of Acute Diarrhea in Children: A Double-Blinded Randomized Controlled Trial.

OBJECTIVES: To evaluate the effect of bovine colostrum (BC) on the treatment of children with acute diarrhea attending the outpatient clinic. METHODS: This double-blind randomized controlled trial was conducted on 160 children with diarrhea; 80 cases were randomly treated with BC group and 80 cases randomly received placebo (placebo group). All cases were investigated for bacterial causes of diarrhea (Salmonella spp, Shigella spp, diarrheagenic E. coli (DEC), Campylobacter spp., and Vibrio cholerae) as well as for Rotavirus antigen in stool. RESULTS: After 48 h, the BC group had a significantly lower frequency of vomiting, diarrhea and Vesikari scoring compared with the placebo group (p = 0.000, p = 0.000, p = 0.000, respectively), whether it was due to Rotavirus or E. coli infection. CONCLUSIONS: BC is effective in the treatment of acute diarrhea and can be considered as adjuvant therapy in both viral and bacterial diarrhea to prevent diarrhea-related complications.

Supplementation With 2'-FL and scGOS/lcFOS Ameliorates Rotavirus-Induced Diarrhea in Suckling Rats.

Rotavirus (RV) is considered to be the most common cause of gastroenteritis among infants aged less than 5 years old. Human milk bioactive compounds have the ability to modulate the diarrheic process caused by several intestinal pathogens. This study aimed to evaluate the potential protective role of a specific human milk oligosaccharide, 2'-fucosyllactose (2'-FL), a mixture of the prebiotic short-chain galacto-oligosaccharides and long-chain fructo-oligosaccharides 9:1 (GOS/FOS) and their combination (2'-FL+GOS/FOS) on RV-induced diarrhea in suckling rats. The nutritional intervention was performed from the second to the sixteenth day of life by oral gavage and on day 5 an RV strain was orally administered to induce infection. Fecal samples were scored daily to assess the clinical pattern of severity, incidence and duration of diarrhea. Blood and tissues were obtained at day 8 and 16 in order to evaluate the effects on the epithelial barrier and the mucosal and systemic immune responses. In the assessment of severity, incidence and duration of diarrhea, both 2'-FL and GOS/FOS displayed a beneficial effect in terms of amelioration. However, the mechanisms involved seemed to differ: 2'-FL displayed a direct ability to promote intestinal maturation and to enhance neonatal immune responses, while GOS/FOS induced an intestinal trophic effect and an RV-blocking action. The combination of 2'-FL and GOS/FOS showed additive effects in some variables. Therefore, it could be a good strategy to add these compounds in combination to infant formulas, to protect against human RV-induced diarrhea in children.

Cytokines in the management of rotavirus infection: A systematic review of in vivo studies.

OBJECTIVE: Rotavirus is a leading cause of childhood diarrhoea. Rotavirus vaccines are effective against severe rotavirus gastroenteritis, but have lower efficacy in low income countries in Africa. Anti-rotavirus treatment is not available. This study reviews the literature of animal studies evaluating whether cytokine mediated pathways of immune activation could improve rotavirus therapy. METHODS: We performed a systematic review of articles in English published from 2010 to 2016 reporting agents with in vivo antirotavirus activity for the management of rotavirus infection. The search was carried in PubMed, EMBASE, Scopus and Web of Science. Animal experiments where cytokines were investigated to assess the outcome of rotavirus therapy were included. RESULTS: A total of 869 publications were identified. Of these, 19 pertained the objectives of the review, and 11 articles described the effect of probiotics/commensals on rotavirus infection and immune responses in animals. Eight further in vivo studies evaluated the immunomodulating effects of herbs, secondary metabolites and food-derived products on cytokine responses of rotavirus-infected animals. Studies extensively reported the regulatory roles for T-helper (Th)1 (interferon gamma (IFN-γ), interleukin (IL)-2, IL-12) and Th2 (IL-4, IL-6, IL-10) cytokines responses to rotavirus pathogenesis and immunity, inhibiting rotavirus infection through suppression of inflammation by viral inhibition. CONCLUSION: Th1 and Th2 cytokines stimulate the immune system, inhibiting rotavirus binding and/or replication in animal models. Th1/Th2 cytokine responses have optimal immunomodulating effects to reduce rotavirus diarrhoea and enhance immune responses in experimental rotavirus infection.

Viral associated diarrhea in immunocompromised and cancer patients at a large comprehensive cancer center: a 10-year retrospective study.

BACKGROUND: Viral associated diarrhea (VAD) due to Norovirus (NV), Rotavirus (RV) and Adenovirus (AV) is common in immunocompromised and cancer patients. We sought to determine if the clinical characteristics, morbidity and seasonality of infection differed according to the type of enteric virus identified. METHODS: Cases of NV, RV and AV were identified in stool specimens submitted to the clinical microbiology laboratory between November 2005 and February 2015. Clinical characteristics of patients, potential risk factors and outcomes were compared. RESULTS: A total of 97 VAD cases were identified: NV (n = 49), RV (n = 34) and AV (n = 14). The majority of cases were in patients with leukemia and lymphoma. NV (59%), RV (74%) and AV (78%) were identified in hematopoietic stem cell transplant (HSCT) recipients; and in patients with graft versus host disease (GVHD): NV (34%), RV (46%) and AV (57%). Nine cases of NV were genotyped; all were due to genotype II. Nine of 49 (18%) cases of NV, 7 of 34 (20%) cases of RV and 2 of 14 (14%) cases of AV were considered to be health care acquired (HCA). In multivariate analysis, immunosuppression (OR 2.8 95% CI 1.26-6.60, p = .01) and neutropenia (OR 4.8 95% CI 1.27-18.5, p = .01) were identified as risk factors for NV diarrhea compared to RV and AV. CONCLUSIONS: In our study, agents responsible for VAD occurred year round but predominated in the winter time; caused prolonged illness and were frequently health care associated. Presentations were atypical in many cases without upper gastrointestinal symptoms such as nausea and vomiting.

Diarrheagenic pathogens in adults attending a hospital in Singapore.

BACKGROUND: Singapore's diarrhoeal notification system is based on specific pathogens. Official data may thus be skewed towards notifiable diseases. Limited information is available on the profiles of aetiological agents responsible for acute gastroenteritis (AGE) cases, especially among the adult population. To understand the frequency and distribution of potential causative agents of diarrheal disease in Singapore, we screened adults' stool samples collected from a large public hospital. METHODS: The stool samples were screened for 18 diarrheagenic pathogens using a combination of commercial multiplex polymerase chain reaction (PCR), in-house singleplex PCR and immunochromatographic assays. One hundred adult faecal samples that were collected from October 2013 to January 2014 for routine diagnostic purposes and submitted for culture at Tan Tock Seng Hospital, Singapore were used. RESULTS: Pathogens were detected in 32% of the samples. The predominant organisms encountered were norovirus genogroup II (11%), Aeromonas spp. (9%) and Campylobacter spp. (5%). One sample was positive for both verocytotoxigenic E. coli (VTEC) and E. coli O157:H7. Two other samples were positive for VTEC only, and one other sample was positive for E. coli O157:H7 only. Astrovirus, C. perfringens, Shigella spp. and toxigenic C. difficile were each detected in 2% of the samples. Cryptosporidium parvum, Giardia lamblia, group A rotavirus, Salmonella spp. and Vibrio spp. were each detected in 1% of the samples. No L. monocytogenes, Y. enterocolitica, enteric adenovirus, or norovirus genogroup I were detected. CONCLUSION: Our preliminary findings suggest that pathogens causing non-notifiable diseases might have contributed considerably to the adult hospitalised AGE cases. However, as the samples were from an adult hospital, the data obtained may not be representative of the whole community. Thus, a larger study to collect clinical samples and risk exposure data from primary healthcare clinics and children hospital is planned for, to gain a more holistic perspective on the epidemiology of AGE in Singapore. A larger study may also offer valuable insights for improving the approach of microbiological surveillance of food, as well as strategizing inspection efforts along the food supply chain by public health authorities.

Budget impact and cost-utility analysis of universal infant rotavirus vaccination in Spain.

Rotavirus is not included in the Spanish mass infant vaccination schedule but has also not been economically evaluated for its inclusion. We analysed cost-utility of the universal infant rotavirus vaccination using RotaTeq® versus no vaccination in Spain. We also carried out a budget impact analysis and determined the effect on results of different variables introduced in the model. A deterministic Markov model was built considering loss of quality of life for children and their parents, and introducing direct and indirect costs updated to 2011. The introduction of the vaccination using RotaTeq® as a universal infant vaccination would increase the annual health care budget in 10.43 million euro and would result in a gain of an additional Quality Adjusted Life Year at a cost of 280,338€ from the healthcare system perspective and 210,167€ from the societal perspective. The model was stable to variable modifications. To sum up, according to our model and estimates, the introduction of a universal infant rotavirus vaccination with RotaTeq® in Spain would cause a large impact on the health care budget and would not be efficient unless significant variations in vaccine price, vaccine efficacy and/or utilities took place.

Changing trend of persistent diarrhoea in young children over two decades: observations from a large diarrhoeal disease hospital in Bangladesh.

AIM: We studied the changing trend and factors associated with persistent diarrhoea (PD) in under-five children presenting to a large diarrhoeal disease hospital in urban Dhaka, Bangladesh, over the last two decades. METHODS: We used an unmatched case-control design, with a case (persistent diarrhoea; n=944) to control (acute diarrhoea; n=2832) ratio of 1:3 attending the Dhaka Hospital of icddr,b between 1991 and 2010. RESULTS: The proportion of children with PD decreased significantly from 8% in 1991 to 1% in 2010. The proportion of breastfeeding practices, measles vaccination coverage and vitamin A supplementation among 12-59 months old improved from 79% to 85%, 69% to 85% and 26% to 74%, respectively, which were significant. Although the isolation of rotavirus from stool in children with PD and acute diarrhoea increased, the isolation of Shigella spp., and Vibrio cholerae O1 decreased significantly. In a logistic regression analysis, wasting (OR=1.62), use of antibiotic before attending hospital (OR=5.94), absent clinical dehydration (OR=1.53) and bloody/mucoid stool (OR=3.33) were significantly associated with persistent diarrhoea. CONCLUSION: There, thus, is a need to integrate an appropriate and sustainable deterrent strategy to take the benefit of the significant reduction in prevalence as well as risks of PD in such population.

Enteric pathogens associated with childhood diarrhea in Tripoli-Libya.

Stool samples from children < 5 years of age with diarrhea (N = 239) were examined for enteric pathogens using a combination of culture, enzyme-immunoassay, and polymerase chain reaction methods. Pathogens were detected in 122 (51%) stool samples; single pathogens were detected in 37.2% and co-pathogens in 13.8% of samples. Norovirus, rotavirus, and diarrheagenic Escherichia coli (DEC) were the most frequently detected pathogens (15.5%, 13.4%, and 11.2%, respectively); Salmonella, adenovirus, and Aeromonas were detected less frequently (7.9%, 7.1%, and 4.2%). The most commonly detected DEC was enteroaggregative E. coli (5.4%). Resistance to ≥ 3 antimicrobials was observed in 60% (18/30) of the bacterial pathogens. Salmonella resistance to ciprofloxacin (63.1%) has become a concern. Enteric viral pathogens were the most significant causative agents of childhood diarrhea in Tripoli. Bacterial pathogens were also important contributors to pediatric diarrhea. The emergence of ciprofloxacin-resistant Salmonella represents a serious health problem that must be addressed by Libyan health authorities.

Breastfeeding and the risk of rotavirus diarrhea in hospitalized infants in Uganda: a matched case control study.

BACKGROUND: Rotavirus is responsible for over 25 million outpatient visits, over 2 million hospitalizations and 527,000 deaths annually, worldwide. It is estimated that breastfeeding in accordance with the World Health Organization recommendations would save 1.45 million children's lives each year in the developing countries. The few studies that examined the effect of breastfeeding on rotavirus diarrhea produced conflicting results. This study aimed to determine the effect of breastfeeding on rotavirus diarrhea among admitted infants in Uganda. METHODS: The study was conducted in the Pediatrics medical emergency unit of a National Referral hospital during a peak incidence time for rotavirus from February to April 2008. It was an age matched case-control study with a ratio of 1:1. We consecutively enrolled infants presenting at the study site during this period whose caretakers consented to participate in the study. A minimum sample size of 90 pairs was adequate with power of 80% to detect a 30% decrease in breastfeeding rate among the cases assuming a breastfeeding rate of 80% in the controls. The infants with rotavirus positive results were the "cases". We used the commercial enzyme immunoassay kit (DAKO IDEIA™ rotavirus EIA detection kit) to diagnose the cases. The "controls" were admitted children with no diarrhea. We compared the cases and controls for antecedent breastfeeding patterns. RESULTS: Ninety-one matched case-control age-matched pairs with an age caliper of one month were included in the analysis. Breastfeeding was not protective against rotavirus diarrhea (OR 1.08: 95% CI 0.52 - 2.25; p = 0.8) in the conditional logistic model. CONCLUSIONS: Our study findings did not reveal breastfeeding as protective against rotavirus diarrhea in infants. This suggests searching for other complementary preventive methods such as rotavirus vaccination and zinc supplementation to reduce the problem of rotavirus diarrhea in infants irrespective of their feeding practices.

Detection of rotavirus in food associated with a gastroenteritis outbreak in a mother and child sanatorium.

In the course of a rotavirus outbreak in a mother and child sanatorium 74 food samples from the sanatorium kitchen were taken and tested for rotavirus. Rotavirus particles were isolated from 25 g food samples by a simple method including ultrafiltration, originally designed for the detection of norovirus in various food matrices. Rotavirus was successfully detected in a sample of potato stew by conventional RT-seminested-PCR. Sequence comparison of the amplification products obtained from the potato stew and a stool sample from an infected child verified that the two viruses were identical.

Oral diosmectite reduces stool output and diarrhea duration in children with acute watery diarrhea.

BACKGROUND & AIMS: Diosmectite is a clay used to treat children with acute watery diarrhea. However, its effects on stool output reduction, the key outcome for pediatric antidiarrheal drugs, have not been shown. METHODS: Two parallel, double-blind studies of diosmectite efficacy on stool reduction were conducted in children 1 to 36 months old in Peru (n = 300) and Malaysia (n = 302). Inclusion criteria included 3 or more watery stools per day for less than 72 hours and weight/height ratios of 0.8 or greater. Exclusion criteria were the need for intravenous rehydration, gross blood in stools, fever higher than 39 degrees C, or current treatment with antidiarrheal or antibiotic medications. Rotavirus status was determined. Diosmectite dosage was 6 g/day (children 1-12 months old) or 12 g/day (children 13-36 months old), given for at least 3 days, followed by half doses until complete recovery. Patients were assigned randomly to groups given diosmectite or placebo, in addition to oral rehydration solution (World Health Organization). RESULTS: Children in each study had comparable average ages and weights. The frequencies of rotavirus infection were 22% in Peru and 12% in Malaysia. Similar amounts of oral rehydration solution were given to children in the diosmectite and placebo groups. Stool output was decreased significantly by diosmectite in both studies, especially among rotavirus-positive children. In pooled data, children had a mean stool output of 94.5 +/- 74.4 g/kg of body weight in the diosmectite group versus 104.1 +/- 94.2 g/kg in the placebo group (P = .002). Diarrhea duration was reduced by diosmectite, which was well tolerated. CONCLUSIONS: These results show that diosmectite significantly decreased stool output in children with acute watery diarrhea, especially those who were rotavirus-positive.

Australian Rotavirus Surveillance Program annual report, 2007/08.

The National Rotavirus Reference Centre together with collaborating laboratories Australia-wide conducts a laboratory based rotavirus surveillance program. This report describes the types of rotavirus strains responsible for the hospitalisation of children with acute gastroenteritis during the period 1 July 2007 to 30 June 2008, the first complete year of surveillance following introduction of rotavirus into the National Immunisation Program. Six hundred faecal samples from across Australia were examined using a combined approach of monoclonal antibody immunoassays and reverse transcription-polymerase chain reaction. Of the 419 confirmed as rotavirus positive, serotype G1 was the dominant serotype nationally, representing 52% of specimens, followed by serotype G2 (19.8%), serotype G9 (12.2%), and serotype G3 (11%). No serotype G4 strains were identified. All G1, G3 and G9 strains assayed for P genotype contained the P[8] genotype, while all G2 strains contained the P[4] genotype, except one G2 strain which possessed a P[8]. Uncommon rotavirus genotypes, G8 (n = 2) and P[9] (n = 2) were identified during this study period. There was no evidence of unexpected changes in serotype distribution during the first 12 months of rotavirus vaccine use in the National Immunisation Program.

Effective prophylaxis against rotavirus diarrhea using a combination of Lactobacillus rhamnosus GG and antibodies.

BACKGROUND: Rotavirus is a worldwide cause of infectious infantile diarrhea that claims over 600,000 lives annually. Recently, two new vaccine candidates have been developed but their efficacy in developing countries, still remains to be proven. Oral delivery of specific immunoglobulins provides passive immunity and is a fast acting treatment for rotavirus diarrhea. Probiotic bacteria have also gained considerable attention lately as treatment for rotavirus diarrhea. Here we report an evaluation of the therapeutic potential of different probiotics and their combination with anti - rotavirus antibodies in a mouse model of rotavirus diarrhea. RESULTS: Of the six probiotic bacteria tested, Lactobacillus rhamnosus strain GG had the strongest influence in reducing prevalence, duration and severity of diarrhea and was therefore chosen for combination treatment with immunoglobulins. The combination treatment reduced the diarrhea outcome measures significantly, prevented histopathological changes and reduced the virus load in the intestines. CONCLUSION: The advantages associated with immunoglobulins and probiotics based therapy is that the treatment provides a rapid therapeutic effect and is cost efficient. These components do not require special storage conditions and could potentially complement the rehydration therapy that is currently used.

Australian Rotavirus Surveillance Program: annual report, 2006-07.

The National Rotavirus Reference Centre, together with collaborating laboratories Australia-wide, conducts a laboratory based rotavirus surveillance program. This report describes the serotypes of rotavirus strains responsible for the hospitalisation of children with acute gastroenteritis during the period 1 July 2006 to 30 June 2007. One thousand and two faecal samples from across Australia were examined using a combined approach of monoclonal antibody immunoassays, reverse transcription-polymerase chain reaction and polyacrylamide gel analysis. Serotype G1 was the dominant serotype nationally, representing 36.7% of all strains, followed by serotype G9 (31.1%), and serotype G3 (23.3%). Serotype G2 represented less than 5% of strains, while no serotype G4 strains were identified. All G1, G3 and G9 strains assayed for P genotype contained the P[8] genotype, bar one G1 strain, which possessed a P[6]. Uncommon rotavirus genotypes, G8 (n = 1) and G12 (n = 2) were identified in children with acute gastroenteritis during this study period.

Procedure for rapid concentration and detection of enteric viruses from berries and vegetables.

Several hepatitis A virus (HAV) and norovirus (NV) outbreaks due to consumption of berries and vegetables have been reported during recent years. To facilitate the detection of enteric viruses that may be present on different fresh and frozen products, we developed a rapid and sensitive detection method for HAV, NV, and rotavirus (RV). Initial experiments focused on optimizing the composition of the elution buffer, improving the viral concentration method, and evaluating the performance of various extraction kits. Viruses were extracted from the food surface by a direct elution method in a glycine-Tris (pH 9.5) buffer containing 1% beef extract and concentrated by ultrafiltration. Occasionally, PCR inhibitors were present in the processed berry samples, which gave relatively poor detection limits. However, this problem was overcome by adding a pectinase treatment in the protocol, which markedly improved the sensitivity of the method. After optimization, this concentration method was applied in combination with real-time reverse transcription-PCR (RT-PCR) using specific primers in various types of berries and vegetables. The average detection limits were 1 50% tissue culture infective dose (TCID(50)), 54 RT-PCR units, and 0.02 TCID(50) per 15 g of food for HAV, NV, and RV, respectively. Based on our results, it is concluded that this procedure is suitable to detect and quantify enteric viruses within 6 h and can be applied for surveillance of enteric viruses in fresh and frozen products.

Biotin-psolaren labeled cDNA amplicons for genotyping rotavirus strains by dot hybridization assay.

A simple method to produce biotinylated probes by utilizing an amine-psoralen to conjugate an ester-biotin to nucleic acid molecules is described. It is simple, rapid, and well suited to label cDNA probes with any PCR-generated amplicon for hybridization assay. Its application to identify or to confirm the G and P genotypes of rotavirus-derived amplicons is described; however, it may be used to label amplicons of any origin. As an alternative or as a complementary test to either PCR-typing assay and/or sequencing, it should reduce considerably the laboratory costs required to genotype fully virus strains in large epidemiological surveys conducted in developing countries.

Anti-rotavirus antibodies in human milk: quantification and neutralizing activity.

OBJECTIVE: To analyze anti-rotavirus antibodies in human milk in order to determine their isotypes and neutralizing activity on rotavirus strains representing different viral serotypes. METHODS: One hundred seventy-three milk samples (65 colostrum, 55 transitional milk and 53 mature milk) obtained from 65 mothers were analyzed along with 49 serum samples collected just before delivery. Total immunoglobulin A (IgA) and rotavirus-specific IgA and immunoglobulins G (IgG) antibodies were determined in milk and serum by enzyme-linked immunosorbent assay. Neutralizing activity was evaluated by an immunoperoxidase focus reduction assay. Milk IgA was purified by binding to the lectin jacalin, elution and ultrafiltration. RESULTS: Total IgA antibodies were detected in all serum and milk samples analyzed. IgA levels decreased sharply during the replacement of colostrum by transitional milk, and more gradually from transitional to mature milk. These differences in IgA concentration during the 3 periods were statistically significant. Anti-rotavirus antibodies detected in human milk were exclusively of the IgA type, whereas both IgA and IgG anti-rotavirus antibodies were present in serum samples. Both milk and serum samples showed in vitro neutralization of the infectivity of rotavirus strains SA11, Wa and VA70, this activity being stronger toward the human rotavirus strain Wa. No correlation was however found between the inhibitory effect on rotavirus and the concentrations of IgA in human milk and serum samples. CONCLUSION: Anti-rotavirus antibodies are only partly responsible for the neutralizing activity detected in milk and serum. This result suggests that other components possessing suppressive activity against rotavirus must also be present.

National Rotavirus Surveillance Program annual report, 2005-06.

The National Rotavirus Reference Centre together with collaborating laboratories Australia-wide has conducted rotavirus surveillance since June 1999. This report describes the serotypes of rotavirus strains responsible for the hospitalisation of children with acute gastroenteritis during the period 1 July 2005 to 30 June 2006. Eight hundred and forty-eight faecal samples from across Australia were examined using monoclonal antibody immunoassays, reverse transcription-polymerase chain reaction and polyacrylamide gel analysis. Serotype G1 was the dominant serotype nationally, representing 40.2 per cent of all strains, followed by serotype G4 (22.6%), serotype G9 (15.1%) and serotype G3 (14.7%). Genotype G12 strains were identified for the first time in Australia. As in previous years, there was substantial geographic variation in the prevalence of rotavirus serotypes.

Supplemental dietary whey protein concentrate reduces rotavirus-induced disease symptoms in suckling mice.

Rotavirus-induced diarrhea is a common infection that results in the death of nearly 500,000 children annually. Currently, no large-scale preventative treatments or vaccines exist. Because some whey protein concentrates (WPC) were shown to contain bioactive ingredients that may activate immune cells and/or prevent infection, the current study was conducted to assess whether the proprietary WPC IMUCARE (WPC-IC) could protect against rotavirus. Suckling BALB/c mice were treated by gavage once daily with WPC-IC or with the control protein bovine serum albumin from the age of 9 to 17 d, and were infected with murine rotavirus at the age of 11 d. Disease symptoms were graded as mild, moderate, or severe, and viral shedding was measured in fecal samples during the postinfection period. Severe diarrhea occurred in 63% of control mice; this was significantly reduced to 36% in WPC-IC-fed mice. Severe diarrhea occurred for a 4-d period in the control group but only for a 2-d period in the WPC-IC group. Although the mean viral load per mouse did not differ between the groups, the proportion of mice shedding high levels of the virus in the feces postinfection was significantly lower in the WPC-IC group on d 13, 16, and 17, and significantly higher on d 14. Rotavirus-specific antibody levels in serum and gut fluid did not differ between groups. Thus, prophylactic treatment with WPC-IC may reduce rotaviral disease by decreasing the prevalence of severe diarrhea and by decreasing the time period during which severe symptoms and high viral shedding occur.