The significance of variation in the susceptibility of Schistosoma mansoni to the antischistosomal drug oxamniquine

Abstract

Clinical and laboratory evidence is reviewed which shows that there is a great deal of variation in the susceptibility of Schistosoma mansoni to oxamniquine. This variation occurs both among endemic regions and within endemic regions in Brazil and Kenya. It is genetically controlled. It is suggested that the parasite possesses a large capacity for developing resistance to the drug and that resistance will develop where sufficient drug pressure is maintained.

Exposure to hycanthone alters chromatin structure around specific gene functions and specific repeats in Schistosoma mansoni

“…Unfortunately, the data for the first 3–5 generations are not available but one can assume that incomplete penetrance of the phenotype was observed. These large differences in penetrance of resistance phenotypes (i.e., large dose dependency) in different isolates were also found by others (Coles et al, 1986; Kinoti, 1987) and also described in Pica-Mattoccia et al (1993). Kinoti noted important variations in the dose of oxamniquine needed to eliminate 99% of the worms (ED99), in both laboratory and clinical trials.…”

“…Kinoti noted important variations in the dose of oxamniquine needed to eliminate 99% of the worms (ED99), in both laboratory and clinical trials. For example, East African isolates needed a dose of oxamniquine 200–250% higher than Puerto-Rican isolates to reach ED99 (Kinoti, 1987). In all publications, at least 3 generations of selection were necessary to produce stable resistance, but even then, phenotypic differences between the different resistance strains and most notably an exception to the Mendelian segregation pattern were observed.…”

Altered Response of Strain of Schistosoma mansoni to Oxamniquine and Praziquantel

“…These findings support Kinoti's (1987) supposition that S. mansoni has a great capacity to develop resistance to therapeutic doses of a determined drug, especially when the parasitic population is under continuous pressure from schistosomicides (Coles & Bruce 1990).…”

Study of Schistosoma mansoni isolates from patients with failure of treatment with oxamniquine

“…Araújo et al (1980), Dias et al (1978Dias et al ( , 1982, Meang et al (1987), , emphasized similar results with Brazilian isolates from Minas Gerais. Kinoti (1987) reported variations in the suscetibility of S. mansoni to oxamniquine within certain areas of Brazil and Kenya. In our study we recovered five S. mansoni isolates from patients from Minas Gerais, Bahia and Paraíba who did not respond to the drug.…”