Safety and Tolerability of a Novel Llama-derived Anti-rotavirus VHH Fragment in Human Volunteers (Part-I), and Its Effect on Severity and Duration of Rotavirus Diarrhoea in Children (Part II). (This Registration Only Covers Part II)

Brief Summary Study investigating the efficacy of oral administration of VHH antibody fragment derived from antibodies as found in milk of llamas and camels via a prototype food product in reducing the severity of rotavirus diarrhoea in children.

Detailed Description

Introduction Rotavirus is the leading viral enteropathogen, which is responsible for 11-71% of all diarrhoea episodes in infants and children worldwide. In developing countries, rotavirus is associated with more than 125 million episodes of diarrhoea each year (Cook et al. 1990), leading to an estimated 600,000 deaths. It is responsible for 60% of all diarrhoeal episodes, 20-60% of diarrhoeal hospitalizations, and 20% of diarrhoea-related deaths in children <5 years of age (Perez-Schael et al. 1997). In the United States of America alone, rotavirus is associated with 3% of all hospitalizations of children younger than 5 years with medical and indirect costs of over US$ 1 billion each year (Glass et al. 1991). In many localities deaths from rotavirus infections persist despite national programs to encourage the use of oral rehydration therapy.

Current management of rotavirus gastroenteritis Current management of rotavirus diarrhoea includes prevention of dehydration, or management of dehydration using oral or intravenous rehydration, as appropriate, and continued feeding. Early resumption of normal feeding is encouraged to enhance mucosal repair and to minimize nutritional consequences of infection. The children of developing countries might benefit from zinc supplementation, but its mode of delivery and cost effectiveness are yet to be decided in rotavirus diarrhoea. No specific treatment is currently available to reduce the duration or severity of this illness. Therefore, rotavirus-induced diarrhoea, which is considered to be a self-limited disease, is responsible for significant childhood deaths in the developing countries (Glass et al. 1996).

Active immunization against rotavirus infection The development, testing and eventual use of an effective, safe and inexpensive rotavirus vaccine would be the most efficient method for preventing severe disease and deaths in developing countries. Rapid progress has been made, and several candidate rotavirus vaccines have been developed and tested. Two rotavirus vaccines, Rotarix (GlaxoSmithKline Biologicals, Belgium) and RotaTeq (Merck & Co., USA) have recently entered the market in the developed world. Both vaccines appear to be safe with respect to intussusception, and are highly efficacious in preventing severe gastroenteritis due to rotavirus strains carrying predominantly serotype G1 (Cunliffe & Nakagomi 2005). Confirmation of the safety and efficacy of both vaccines in developing countries is still needed. Moreover, assessment of the ability of each vaccine to provide protection against increasingly diverse population of rotavirus strains will depend on continuous surveillance on the strain and development of newer vaccines as newer serotypes predominate in different geographical locations, which may not be easy for the developing countries. There thus is a clear need to define improved, cost effective interventions in the management of rotavirus diarrhoea until the time an effective, safe and inexpensive vaccine, affordable to the developing countries, is available.