Rotavirus-induced Gastroenteritis Research Articles

Spray-dried plasma protects against rotavirus-induced gastroenteritis via regulating macrophage and T cells divergence in weanling pigs.

Infectious gastroenteritis is the major cause for diarrhea in piglets. The protection of spray-dried plasma (SDP) on viral gastroenteritis during the progression of rotavirus (RV) infection remain unclear. In this study, 64 weanling piglets were randomly assigned to control diets (n = 40) and SDP diets (n = 24) for 14 days, and then pigs were challenged with RV on day 15. Pigs were sacrificed on day 14 (normal condition), day 18 (manifestation stage), and day 21 (convalescent stage) of the trial. Prior to RV infection, SDP increased ADG, M1 macrophages and CD4+ T cells in different organs without increasing proinflammatory cytokines, indicating a more robust immunity with less inflammation. During the manifestation of infection, SDP enhanced mucosal immunity by increasing M1 macrophages, M1/M2 ratio and cytokines in mucosa and increasing intraepithelial CD8+ T cells for RV clearance. During the convalescence, SDP promoted M2 macrophage polarization and reduced pro-inflammatory cytokines to facilitate intestinal repair and prevent prolonged inflammation. Collectively, SDP enhanced mucosal immunity to promote viral clearance and maintained immune homeostasis to prevent long-lasting inflammation as a therapeutically approach for infectious gastroenteritis.

Efficacy of Lactose-Free Milk in Treating Acute Gastroenteritis in Vietnamese Children: A Randomized Controlled Trial.

Low lactase levels in Asian children appear to be genetically determined or rotavirus-induced gastroenteritis. Consuming lactose-free formula in children with acute gastroenteritis may shorten diarrhea's duration and increase weight gain. This study aims to determine whether lactose-free milk will change the duration of diarrhea and weight gain in Vietnamese children aged 2-24 months with acute gastroenteritis. A randomized control trial was performed on 66 children under 24 months of age with acute gastroenteritis at the Gastroenterology Department of Can Tho Children's Hospital. In adjunction to oral rehydration solution, they received either a lactose-free formula (n=33) or a lactose-containing formula (n=33). Diarrhea duration, weight gain, treatment failure, and days of hospitalization were all studied. A total of 66 children participated in this trial, with a mean age of 13.4 ± 5.1 months, and 38 participants (57.6%) were male. There were no significant differences between the lactose-free formula group and the lactose-containing formula group in the duration of diarrhea (2.2±0.8 days versus 2.4±0.9 days; P=0.321), percentage of weight gain (1.96 [IQR:1.35-2.36] percent vs. 2.29 [IQR:1.81-2.40] percent; P=0.131), treatment failure rate (33.3% vs. 36.4%; P= 0.796), and days of hospitalization (5.8±1.7 vs. 6.5±2.5 days; P=0.158). It may not be necessary to use lactose-free milk routinely in Vietnamese children under 24 months with acute gastroenteritis as the duration of diarrhea, weight change, treatment failure rates, and hospital stay are similar to those of children fed lactose-containing milk.

Correlates of immune protection against human rotaviruses: natural infection and vaccination.

Species A rotaviruses are the leading viral cause of acute gastroenteritis in children under 5 years of age worldwide. Despite progress in the characterization of the pathogenesis and immunology of rotavirus-induced gastroenteritis, correlates of protection (CoPs) in the course of either natural infection or vaccine-induced immunity are not fully understood. There are numerous factors such as serological responses (IgA and IgG), the presence of maternal antibodies (Abs) in breast milk, changes in the intestinal microbiome, and rotavirus structural and non-structural proteins that contribute to the outcome of the CoP. Indeed, while an intestinal IgA response and its surrogate, the serum IgA level, are suggested as the principal CoPs for oral rotavirus vaccines, the IgG level is more likely to be a CoP for parenteral non-replicating rotavirus vaccines. Integrating clinical and immunological data will be instrumental in improving rotavirus vaccine efficacy, especially in low- and middle-income countries, where vaccine efficacy is significantly lower than in high-income countries. Further knowledge on CoPs against rotavirus disease will be helpful for next-generation vaccine development. Herein, available data and literature on interacting components and proposed CoPs against human rotavirus disease are reviewed, and limitations and gaps in our knowledge in this area are discussed.

Complete Inhibition of Human Rotavirus Infection by the Aqueous Extract of Scrophularia variegata

Background: Recently, plant-based medications have been considered promising. Scrophularia has been demonstrated to have antibacterial, antifungal, antiparasitic, anticancer, and antiinflammatory effects; however, no evidence of its antiviral potency is available. Objective: This study aimed to evaluate whether the aqueous extract of Scrophularia variegata has antiviral activity against rotavirus as the leading cause of severe diarrhea and acute gastroenteritis in children. Methods: The neutral red assay was utilized to assess the cytotoxicity of the aqueous extract on the cell line. Cytopathic effect (CPE) inhibition, TCID50 (50% cell culture infectious dose), and real-time PCR assays were performed to determine the extract's impact on human rotavirus at non-toxic dilutions. Results: Cell viability was raised following treatment with the aqueous extract at all dilutions. Rotavirus- induced CPEs were considerably reduced when higher dilutions of the aqueous extract were applied to the infected cells. The most substantial inhibitory effect was observed at the highest dilution with no detectable infectious rotavirus titer using the TCID50 assay and no Ct value using the real-time PCR assay. Conclusion: Our findings show that the aqueous extract of Scrophularia Variegata may be a promising candidate for the treatment of rotavirus-induced gastroenteritis.

EPIDEMIOLOGY AND PHARMACOTHERAPY OF ROTAVIRUS AND IMPACT OF VACCINATION TO PREVENTION ITS MORTALITY

Rotavirus is a type of virus that primarily affects infants and young children, causing gastroenteritis, which is inflammation of the stomach and intestines. It is one of the leading reasons for server diarrhea worldwide,especially in developing lands. The virus is highly contagious and can spread through the fecal-oral route, primarily through contaminated food, water, and surfaces. The introduction of the rotavirus vaccines has had a significant impact on reducing the burden of rotavirus-related illnesses. Many countries have incorporated rotavirus vaccination into their national immunization programs. The vaccines havesignificantly reduced rotavirus-related hospitalizations, deaths, and overall disease burden in countries where vaccination coverage is high. Here, we will discuss the recent developments in epidemiology, diagnosis, and treatments of rotavirus-induced gastroenteritis. Moreover, suggestions to prevent incidences of infection have been elegantly discussed

Metabolites profiling and molecular docking identification of putative leads from endophytic Phyllosticta capitalensis as modulators of key druggable structural targets of rotavirus A

Rotavirus-induced gastroenteritis is a global health concern and the leading cause of death in low-income countries and children under the age of five. While rotavirus A (RVA) vaccines are available, there accessibility and efficacy remain challenging, especially in the third world countries. This has necessitated the need to develop therapeutics to manage RVA infection. This study investigated gas chromatography-mass spectrometry-derived Phyllosticta capitalensis metabolites as potential therapeutics against the key structural proteins [VP8* portion of the VP4 (spike protein), the VP7 (capsid protein), and the VP1 (RNA-dependent RNA polymerase)] of RVA using molecular docking and ADME approaches. The results revealed that four [lup-20(29)-en-one, A’-neogammacer-22(29)-ene, stigmasta-4,7,22-trien-3-α-ol, and fucosterol] of the 67 metabolites had favourable affinity for the three structural proteins and belonged to classes of metabolite of antiviral importance. Further analysis and pharmacokinetic profiling showed that the pentacyclic triterpenoids, lup-20(29)-en-one and A’-neogammacer-22(29)-ene, had the potential to be developed as antivirals against RVA infection and effort is underway in this direction.

Clinical Characteristics of Rotavirus-Induced Gastroenteritis in Infants

Abstract Rotavirus is the most common cause of acute infectious diarrhea in infants and young children up to the age of five. The disease is characterized by profuse watery diarrhea, vomiting and fever. The major complications of rotavirus gastroenteritis (RVGE) are dehydration, middle ear inflammation and upper respiratory tract infection. The basis of treatment is compensation for fluid loss and administration of probiotics. The aim of this study was to analyze the clinical characteristics of rotavirus gastroenteritis in infants. The study was conducted by the type of retrospective-prospective clinical study on infants with rotavirus gastroenteritis diagnosed on the basis of a positive Rotalex test (Orion Diagnostica Finland) and exclusion of other etiological factors at the University Children's Clinic in Belgrade, from April 2005 to December 2010. In addition to the detailed medical history and clinical examination, relevant laboratory analyzes were performed in all patients. Descriptive and analytical statistical methods were applied in the study. Among the descriptive methods, we used grouping, tabulation, graphing, calculating measures of central tendency, calculating measures of variability and calculating relative numbers. Of the analytical statistical methods, distribution normality testing, χ2 test, Mann-Whitney U test and T test were used. Statistical significance will be taken to mean p < 0.05. The average infant mortality was 6.7 ± 3.7 months. All respondents were divided into two groups according to the age. The first group consisted of infants aged 0 to 5 months (46%), the second group consisted of infants aged 6 to 12 months (54%). The incidence of aqueous diarrhea (100%), vomiting (84%) and fever (74%) in infants suffering from rotavirus gastroenteritis was analyzed. The significance of the age on the symptomatology of rotavirus gastroenteritis as well as on the importance of using probiotics has been demonstrated.

Monocyte Chemoattractant Protein (MCP)-1 in Rotavirus-Associated White Matter Injury in Newborns.

Recent reports have suggested an association between rotavirus infection and a distinctive pattern of white matter injury (WMI) in neonates with seizures; however, the connection between the two is not fully understood. To evaluate the underlying mechanism, we profiled and compared eight cytokines (IL [interleukin]-1β, IL-6, IL-8, IL-10, IFN-γ [interferon-γ ], MCP-1 [monocyte chemoattractant protein-1], MIP-1β [macrophage inflammatory protein-1β], and TNF-α [tumor necrosis factor-α]) in the cerebrospinal fluid (CSF) of 33 neonates with seizures who had no other well-known causes of seizures and 13 control patients (rotavirus-induced gastroenteritis but without seizures). Among the 33 neonates with seizures, 9 showed WMI and all were infected with rotavirus (R + W + ). Among the 24 patients without WMI, 11 were infected with rotavirus (R + W - ) and 13 were not (R - W - ).Only MCP-1 and MIP-1β were different between the groups. MCP-1 was increased in R+ W+ compared with R + W- (p < 0.01), R - W- (p < 0.01), and control (p = 0.03) patients. MIP-1β was decreased in R + W+ compared with R - W- (p < 0.01) and control (p < 0.01), but not R + W- (p = 0.23) patients. MCP-1 and MIP-1β are C-C chemokines that recruit immune cells to the site of inflammation. Our pilot study suggests MCP-1-mediated monocyte recruitment may be linked with this complication caused by rotavirus.

Cost-effectiveness estimates of vaccination against rotavirus in Piedmont, Italy.

Rotavirus-induced gastroenteritis (RVGE) represents the most frequent form of severe gastroenteritis in children. In such a scenario, the availability of an efficient anti-Rotavirus (anti-RV) vaccine represents an effective prevention tool able to prevent those complications mainly linked to the moderate-severe forms of this disease, which require hospital care. The aim of the present study is to estimate the cost effectiveness of universal routine infant RV vaccination program and its budget impact on the Regional Health Service (RHS) of Piedmont, Italy, in order to evaluate the opportunity of the implementation of a national anti-Rotavirus vaccination programme. The researchers performed a cost-effectiveness analysis comparing costs and benefits of a Rotarix two-dose vaccination versus non vaccination and a budget impact analysis (BIA), complementary to the cost-effectiveness analysis. Our results show that the mass implementation of an anti-RV vaccination in Piedmont, in addition to the expected public health benefits, also allows the RHS to save a considerable amount of money within a short period of time, due to the remarkable reduction of direct health costs associated with RVGE management. In fact, as the analysis shows, a universal vaccination against RV results in money-saving for the RHS already from the 2nd year (with a vaccination coverage of 50%). During the five year period, the active and free offer of the anti-RV vaccination would determine a total saving for RHS of about € 503.000. The cost-effectiveness analysis results showed a cost-saving ICER (incremental cost-effectiveness ratio) relevant to the RHS and equal to - €12.197/QALY. In conclusion the adoption of a universal preventive strategy for all the infants in the Piedmont Region may contribute significantly towards the control of RVGE incidence, thus allowing a noteworthy saving of economic and social resources for both the RHS and the general public.

Burden of severe rotavirus disease leading to hospitalization assessed in a prospective cohort study in Sweden

The aim of this prospective cohort study was to estimate the burden of severe disease caused by rotavirus-induced gastroenteritis in Swedish children aged < 5 y. Rotavirus-positive children admitted to hospitals serving 3 geographical regions with 155,838 children aged < 5 y, were offered inclusion in this 1-year study. Rotavirus strains identified were genotyped using multiplex PCR. Disease progression was documented through interviews and chart reviews. In total, 604 children with rotavirus-induced gastroenteritis were included in the study. Forty-nine of 604 (8.1%) fulfilled the criteria for nosocomial infection. The minimum incidence was 388 per 100,000, with significant variability between study regions, ranging from 280 to 542 per 100,000. In all regions, the peak season occurred in February-April, but the season start varied, with first cases observed in October in the eastern region and December in the northern region. Genotypes identified differed between the regions: G1[P8] was most prevalent in all regions (77%), while the most varied pattern was observed in the western region, with G1[P8] observed in 61%, G4[P8] in 13%, G9[P8] in 10%, G2[P4] in 8%, and G3[P8] in 8% of the children. The median age of hospitalized children was 14 months and the median total duration of diarrhoea was 6.9 days. Sixty-eight percent reported a temperature > 38.5°C upon admission. Complications occurred in > 10% of the children, with hypertonic dehydration (32/604) and seizures (10/604) occurring most frequently. Rotaviruses may cause severe febrile acute gastroenteritis leading to dehydration requiring acute rehydration in hospital. In addition, further complications occurred in > 10% of hospitalized children.

Three-Combination Probiotics Therapy in Children With Salmonella and Rotavirus Gastroenteritis

Quantitative Vesikari scales and qualitative severe diarrhea (Vesikari scale ≥11) assessments were used to grade the Salmonella-induced and rotavirus-induced gastroenteritis severity. A significant reduction in severe diarrhea (Vesikari score ≥11) was used to evaluate the efficacy of three-combination probiotics (BIO-THREE). Several studies have shown that rotavirus and Salmonella infections are the leading causes of infectious gastroenteritis. Although probiotics have been effective in some studies, the use of 3-combination formulation probiotics is rare. This single-center, open-label, randomized, controlled trial included 159 patients (age range, 3 mo to 14 y) hospitalized with infectious gastroenteritis between February 2009 and October 2010. Patients were grouped according to the pathogen identified (48, Salmonella; 42, rotavirus; and 69, unknown origin). The total diarrhea duration was significantly shorter for children who received BIO-THREE (P<0.0001). After BIO-THREE administration, there were significantly less intervention group patients with severe diarrhea at intervention day 3. Vesikari scale or diarrhea frequency results did not reveal significant differences between groups (except for day 5 in patients with rotavirus), and there were no significant changes in other clinical parameters or the length of hospital stay. Seven-day BIO-THREE administration demonstrated high efficacy and safety in infants and children with severe gastroenteritis. The incidence of severe gastroenteritis was significantly reduced in the rotavirus origin and BIO-THREE intervention groups.

Genetic and Antigenic Diversity of Human Rotaviruses: Potential Impact on Vaccination Programs

The successful development and implementation of rotavirus vaccines will have a significant impact on rotavirus-induced gastroenteritis in children worldwide. However, this introduction will increase the immune pressure against wild-type rotavirus strains circulating in the community, altering the forces and balances that drive rotavirus evolution. There is concern that antigenically distinct novel or rare strains may be selected and spread, decreasing vaccine efficacy. This review describes the diversity of rotavirus strains and the mechanism by which wild-type rotavirus strains can evolve, including genetic drift and genetic reassortment.

Rotavirus vaccines and pathogenesis: 2008.

Rotaviruses cause life-threatening gastroenteritis in children throughout the world. The burden of disease has resulted in the development of two live, attenuated vaccines that are now licensed in many countries. This review summarizes new data on these vaccines, their effectiveness, and remaining challenges including new data on the rotavirus enterotoxin, a potential antiviral target. Live attenuated rotavirus vaccines are used to protect infants against severe rotavirus-induced gastroenteritis and, RotaTeq, a pentavalent bovine-based vaccine, and, Rotarix, a monovalent human rotavirus, are now currently licensed in many countries. Initial results of the licensed RotaTeq vaccine have been promising in the USA and results of immunogenicity and efficacy in developing countries are expected soon. However, universal vaccine implementation is challenging due to age limitations on administration of these vaccines. Chronic rotavirus infections in immunocompromised children may remain a problem and require the development of new treatments including antiviral drugs. Increasing data on the mechanisms of action of the rotavirus enterotoxin highlight this pleiotropic protein as a good target as well as a unique calcium agonist. Rotavirus is now a commonly occurring vaccine-preventable disease among children in developed countries and hopefully this also will soon be true for developing countries. Future studies will determine whether other methods of prevention, such as nonreplicating vaccines and antiviral drugs, will be needed to treat disease in immunocompromised children.

Cost-effectiveness analysis of vaccination against rotavirus with RIX4414 in France

It is estimated that annually 300 000 cases of rotavirus-induced gastroenteritis (RVGE) occur in children aged up to 5 years in France. A two-dose vaccine against rotavirus infection (RIX4414; Rotarix, GlaxoSmithKline), has been shown to be highly effective against severe RVGE. This study evaluated the cost effectiveness of general vaccination against rotavirus using RIX4414 in France. A Markov model simulated RVGE events and the associated outcomes and costs relating to general vaccination of infants against rotavirus infection using RIX4414 (Rotarix) in a birth cohort of children aged up to 5 years in France with a combined adjustment for age distribution with the seasonality of the infection. Costs and outcomes were estimated from a limited societal perspective, including direct medical costs paid out of pocket or by third-party payers, as well as the proportion of direct medical costs reimbursed by the health authorities. Indirect costs were not included in the base-case analysis. The primary outcome measure was the incremental cost per QALY. Vaccination with RIX4414 incurred an incremental cost of 44 583 Euro per QALY at a public price of 57 Euro per vaccine dose. Univariate sensitivity analyses showed that the parameters with the largest influence on the results were the transition probabilities of severe diarrhoea, seeking medical advice and emergency visits, utility scores of diarrhoea (mild) in children and infants, and the discount rate for benefits. Probabilistic multivariate sensitivity analysis confirmed these results. The acceptability curve indicated that 94% of the results were under an informal threshold of 50 000 Euro per QALY. Comparing our results with those of a recently published study using pooled data for two rotavirus vaccine products in France, the main differences are explained by differences in model structure and in data input values. They include a different age distribution of the infection, shorter duration of the at-risk period (3 years instead of 5 years), different vaccine efficacy, different unit cost data, different disease duration, and different disutility values for the health states in the model. There is a need for agreed standards to improve comparability of results from different studies. The results demonstrate that a generalized vaccination strategy with RIX4414 would be cost effective in France from a limited societal perspective, depending on the baseline assumptions for disease progression and on utility scores selected.

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

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. 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. 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. 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.

Tetravalent rotavirus vaccine.

To review the clinical efficacy, safety, and pharmacoeconomic data about the use of rhesus-human reassortant rotavirus tetravalent vaccine (RRV-TV) in infants and children. A MEDLINE search (January 1990-December 1998) was conducted to identify all publications on the RRV-TV vaccine including pharmacology, clinical trials, adverse effects, and pharmacoeconomics in infants and children. Bibliographies of articles were also used. All randomized and placebo-controlled clinical efficacy trials were reviewed. Additionally, pharmacoeconomic studies focusing on the potential impact on healthcare costs were chosen for review. Rotavirus-induced gastroenteritis is a significant problem in developed and developing countries. Various forms of a rotavirus vaccine have been studied worldwide. The tetravalent vaccine appears to have similar efficacy in developed and developing countries. It seems to be most effective against the most severe forms of gastroenteritis, with an 80% overall efficacy rate. This vaccine is well tolerated; the most common adverse effect is fever after the first dose. Pharmacoeconomic studies indicate that although the vaccine may be only moderately effective against less severe gastroenteritis, over $1 billion annually could potentially be saved in the US with its universal use. The new rotavirus vaccine is effective in preventing and reducing the incidence of rotavirus-induced gastroenteritis. The morbidity, mortality, and healthcare costs from this disease may be reduced if this vaccine is provided to children worldwide.

Inhibition of rotavirus replication by prostaglandin A: evidence for a block of virus maturation.

Rotaviruses are recognized as the leading cause of severe viral gastroenteritis in young children and in immunocompromised patients. Cyclopentenone prostaglandins possess antiviral activity against several single-strand RNA viruses; therefore, the effect of prostaglandin A1 (PGA1) on SA-11 simian rotavirus infection was investigated in cultured cells. PGA1 potently inhibited SA-11 rotavirus replication. Whereas it did not affect virus adsorption or penetration, PGA1 partially inhibited VP4 and VP7 synthesis and selectively reduced glucosamine incorporation into the NSP4 viral enterotoxin. Electron microscopy analysis showed that, despite normal formation of cytoplasmic inclusions and budding of particles into the rough endoplasmic reticulum, virus maturation was impaired in PGA1-treated cells, with most of the virus particles remaining in the membrane-enveloped intermediate form. Because prostaglandins are used clinically as cytoprotective drugs for gastric ulcers, these observations offer new perspectives in the search for therapeutic agents for rotavirus-induced gastroenteritis.

Towards Understanding the Structural Requirements for Endogenous Transcription in Rotavirus

Abstract Rotaviruses are complex, relatively large (1000 Å) nonenveloped icosahedral viruses. They are the major causative agents of severe diarrhea in children and animals. Annually an estimated 1 million children die from rotavirus-induced gastroenteritis worldwide. Medical relevance, intriguing structural complexity, and several unique strategies in the morphogenesis and replication have provoked extensive molecular biological and structural studies on rotaviruses in recent years. Rotaviruses are double-stranded RNA (dsRNA) viruses belonging to the family Reoviridae. Each of the 11 segments codes for one protein. Of the eleven proteins encoded by the genomic RNA, six are structural and five are non-structural. Structural studies have shown that mature rotaviruses are triple-layered particles (TLPs). During the process of cell entry the outer-most layer consisting of VP7 and the spike protein VP4 is lost and the resulting double layered particles (DLPs) become transcriptionally active (Fig. 1 A). During the process of transcription, the DLPs maintain their structural Integrity.

Rotavirus-specific proteins are detected in murine macrophages in both intestinal and extraintestinal lymphoid tissues

Rotaviruses replicate in mature, villous epithelial cells of the mammalian small intestine. Although rotavirus has not been detected in plasma of infants with rotavirus-induced gastroenteritis, rotavirus particles and rotavirus genomic RNA have been detected in extraintestinal sites (e.g. cerebrospinal fluid). Using a murine rotavirus strain well adapted to growth in the small intestines of suckling mice, we found that macrophages (and to a lesser extent B cells) in gut-associated lymphoid tissue contained rotavirus-specific proteins, and that these antigen-containing cells travelled to sites distant to the intestine.

Rotavirus-specific cytotoxic T lymphocytes passively protect against gastroenteritis in suckling mice

Suckling mice are protected against murine rotavirus-induced gastroenteritis after adoptive transfer of splenic lymphocytes from immunized animals. Adoptive transfer of Thy1(+)-depleted or CD8(+)-depleted lymphocytes abrogated protection against challenge. (We previously found that depletion of Thy1+ or CD8+ lymphocytes from rotavirus-immunized mice decreased rotavirus-specific cytotoxic activity in vitro.) Protection against disease occurred in the absence of rotavirus-specific neutralizing antibodies in the sera of suckling mice. Rotavirus-specific cytotoxic T lymphocytes may be important in either amelioration of acute infection or protection against reinfection.