Inhibition of rotavirus ECwt infection in ICR suckling mice by N-acetylcysteine, peroxisome proliferator-activated receptor gamma agonists and cyclooxygenase-2 inhibitors

Live attenuated vaccines have recently been introduced for preventing rotavirus disease in children. However, alternative strategies for prevention and treatment of rotavirus infection are needed mainly in developing countries where low vaccine coverage occurs. In the present work, N-acetylcysteine (NAC), ascorbic acid (AA), some nonsteroidal anti-inflammatory drugs (NSAIDs) and peroxisome proliferator-activated receptor gamma (PPARγ) agonists were tested for their ability to interfere with rotavirus ECwt infectivity as detected by the percentage of viral antigen-positive cells of small intestinal villi isolated from ECwt-infected ICR mice. Administration of 6 mg NAC/kg every 8 h for three days following the first diarrhoeal episode reduced viral infectivity by about 90%. Administration of AA, ibuprofen, diclofenac, pioglitazone or rosiglitazone decreased viral infectivity by about 55%, 90%, 35%, 32% and 25%, respectively. ECwt infection of mice increased expression of cyclooxygenase-2, ERp57, Hsc70, NF-κB, Hsp70, protein disulphide isomerase (PDI) and PPARγ in intestinal villus cells. NAC treatment of ECwt-infected mice reduced Hsc70 and PDI expression to levels similar to those observed in villi from uninfected control mice. The present results suggest that the drugs tested in the present work could be assayed in preventing or treating rotaviral diarrhoea in children and young animals.

Rotavirus / Rotavirus

la infección por rotavirus es responsable de 125 millones de casos, de más 500.000 defunciones anuales y de 40% de la hospitalización por diarrea en menores de 5 años de edad. en países en desarrollo la tasa de infección es más alta en el grupo de edad de 3 a 11 meses, quienes presentan mayor letalidad producto de la desnutrición y de la dificultad para acceder oportunamente a los servicios de salud; se observa que al año de vida, 65-80 % de los niños han desarrollado anticuerpos contra el rotavirus y 95% a los 2 años. Actualmente se utilizan dos vacunas contra el rotavirus, las cuales han demostrado ser seguras, eficaces y poco relacionadas con invaginación intestinal. En venezuela, la vacuna monovalente-humana se introdujo en el Programa Ampliado de Inmunizaciones en abril de 2006. un estudio previo mostró que la administración masiva de dos dosis de esta vacuna contra el rotavirus es altamente costo-efectiva. cuatro años después en un estudio nacional se evaluó el impacto y se evidenció reducción de 50% de la tasa de mortalidad en los menores de 5 años, siendo mayor en el grupo de menores de 1 año con 55% y en el grupo de 1-4 años de 44%. sin embargo el seguimiento de este programa nos indica que las coberturas de inmunización contra rotavirus en venezuela siguen siendo bajas

Infection by rotavirus is responsible for 125 million cases, 500,000 annual deaths and 40% of hospitalizations for diarrhea in children under 5 years of age. In developing countries the rate of infection is higher in the group of 3 to 11 months of age, which present a higher lethality, product of undernourishment and difficulties to accede opportunely to health services. during the first year of life, 65 to 80%of children have developed antibodies against rotavirus and 95% will achieve this by the age of two. At the moment two vaccines against rotavirus are available, and have demonstrated to be safe, effective and with very low association with intestinal invagination. In venezuela, the monovalent-human vaccine was introduced in the extended Program of Immunizations in April of 2006. A previous study showed that the massive administration of two doses of this vaccine against rotavirus is highly cost-effective. Four years later, a national study showed a reduction of mortality rate of 50% in children under 5 years of age, 55% reduction in those less than one year and 44% reduction in the group of 1-4 years of age. nevertheless the follow up of this program indicates that immunization coverage against rotavirus in venezuela continues to be low

Randomized double blinded controlled trial to evaluate the efficacy and safety of Bifilac in patients with acute viral diarrhea.

OBJECTIVE: To evaluate the efficacy and safety of Bifilac on reducing the episodes (frequency) and duration of diarrhea induced by rotaviral infection and to evaluate the efficacy of Bifilac to ameliorate the associated symptoms like dehydration and duration of rotaviral shedding in faeces. METHODS: 80 children aged between 3 months and 3 years were enrolled and divided into 2 groups, one group received standard therapy + placebo, the other group received standard therapy + probiotic (Bifilac) randomly. Children assessed for frequency and duration of diarrhea. Degree of dehydration, duration and volume of oral rehydration salt [ORS] therapy, duration and volume of Intra venous fluids and duration of rotaviral shedding. RESULTS: When compared to the placebo, Bifilac showed clinical as well as statistically significant reduction in Number of episodes (frequency) of diarrhea in a day, mean duration of diarrhea (in days) degree of dehydration, duration and volume of oral rehydration salt [ORS] therapy, duration and volume of intravenous fluid [IVF] therapy, duration of rotaviral shedding (P<0.01). CONCLUSION: The synbiotic, bifilac, appears to be a safe and very effective adjuvant in the management of acute rotaviral diarrhea.