Of the estimated 500 million people worldwide infected with Entamoeba histolytica, only 10% develop disease. Whether virulence is a function of host or parasite factors has long been debated. Evidence has mounted over the last decade that there are distinct nonpathogenic and pathogenic strains (classified into 'zymodemes' based on isoenzyme electrophoretic patterns) of E. histolytica. However, there is also evidence of nonpathogenic zymodemes converting to pathogenic zymodemes. The long range goal of the research is to understand the molecular basis of pathogenesis of E. histolytica, and in particular, whether all or only some strains can cause disease. To address this, we will develop, validate, and apply strain specific probes and immunodiagnostic methods to an epidemiologic study of amebiasis in Mexico City. In preliminary studies, probes to two genes, M17, which encodes an immuonodominant surface antigen, and the 16S rRNA gene, were able to differentiate strains with pathogenic from those with nonpathogenic zymodemes. These probes will be tested against clinical isolates, and the results compared with zymodeme analysis and clinical symptoms, to determine their utility as diagnostic tools for the epidemiologic study. M17 fusion peptides have been synthesized and will be used to develop immunodiagnostic assays to measure total serum immunoglobulin and secretory IgA production. The assays will be used to monitor the gastrointestinal and serologic immune response to infection by different strains. In the epidemiologic study strain type will be correlated with symptoms and host immune response to determine whether only some strains are associated with disease, or whether a single strain can convert from nonpathogenic to pathogenic phenotype. The answers to these questions are important in developing treatment guidelines for asymptomatic carriers.