The taeniid genus Echinococcus includes cestodes of 4 species, of which 3 (E. granulosus (Batsch, 1/86), E. multilocularis Leuckart, 1863, and E. vogeli Rausch and Bernstein, 1972) in the larval stage cause severe to fatal disease in man. E. granulosus, with 2 major strains, nearly cosmopolitan in occurrence, is significant cause of morbidity in indigeneous peoples in Alaska and Canada. One strain also causes severe economic losses in livestock-raising countries. E. multilocularis, the most pathogenic, is widespread in Alaska and, since 1964, has become endemic in 8 of the contiguous states and 3 adjacent Canadian provinces. E. vogeli occurs widely in South- and Central America. The objective of the proposed work is to continue investigations, in progress by principal investigator since 1949, that would: 1) Define the mechanism of proliferation in the larval E. vogeli, a process unique for the genus, with reference to pathogenesis in man; this would involve microscopic and histological examination of developmental stages in experimentally infected rodents. 2) Define development of strobilar stage of E. multilocularis with respect to release of gravid segments, survival-time, and pathogenicity in the final host, based on materials from experimentally infected dogs and other carnivores. 3) Compare rates and characteristics of development to infectivity in larval stages of northern and European strains of E. granulosus, with respect to pathogenicity in intermediate hosts; materials from wild and experimentally infected ungulates to be used. 4) Utilize Giemsa-banding for chromosomal comparisons to define fundamental cytogenetic characteristics of taeniid cestodes and to establish taxonomic value of karyotypic differences in these cestodes; previously established methods would be applied. 5) Define effects of mebendazole on tissues of larval cestodes (E. multilocularis and E. vogeli), in conjunction with clinical trials involving inoperable human cases of alveolar hydatid disease in progress since 1974 at Alaska Native Medical Center, with emphasis on effective serum-levels of the drug; sera from both experimental animals and patients would be available. 6) Define similarities or dissimilarities of polypeptides in tissues of Echinococcus spp. and possibly other taeniid cestodes; compare their antigenicity, and characterize immune response to them in man and experimental animals. Past experience has demonstrated that concurrent pursuit of several interrelated studies is most productive.
