University of Virginia Health System

Email Address: wap3g@virginia.edu

No vaccine is available to prevent the estimated 50 million illnesses and 100,000 annual deaths from amebiasis. Amebiasis is caused by the Biodefense Category B agent Entamoeba histolytica, a protozoan parasite that destroys host cells via contact-dependent cytolysis. Our laboratory is studying at a molecular level the parasite's mechanisms of adherence and invasion through the colonic epithelium. This basic investigation is complemented by clinical investigation in a refugee camp in Bangladesh. The unifying theme is the study of the parasite galactose-binding lectin that mediates adherence and cytotoxicity. We have identified, cloned and expressed this cell surface lectin. DNA transformation methods developed by his lab have been used to interfere with lectin function by inducible expression of dominant negative mutants, confirming the lectin's role for in vivo virulence. Additional work is underway to understand the function of the lectin in adherence and cytolysis. Complete protection from amebic colitis by immunization with the lectin has been demonstrated using a mouse model of amebiasis in our lab. The first FDA-approved diagnostic tests specific for pathogenic E. histolytica have been developed and applied to observational studies of preschool children in Bangladesh. Entamoeba histolytica infections have been detected in 55% of the children during the first 2 years of observation, with 11% of the infections resulting in diarrhea, and 2% in dysentery. Children with mucosal IgA that neutralized the lectin active site had a 70% lower incidence of new E. histolytica infection. Identification of acquired immunity to amebiasis coupled with continued clinical and basic investigation offers the promise of a vaccine for one of the deadly tropical diseases of children.