Oxamniquine resistance

Cioli, D., Pica-Mattoccia, L. and Moroni, R. (1992) Schistosoma mansoni hycanthone/oxamniquine resistance is controlled by a single autosomal recessive gene. Experimental Parasitology 75, 425 432. 

Strains of S mansoni in different parts of the world vary in susceptibility. Oxamniquine has been effective in instances of praziquantel resistance. 

The definition of resistance provided by Prichard et al. (1 980) is suitable for trematodes and cestodes. Resistance is present when there is a greater frequency of individuals within a population able to tolerate doses of compound than in a normal population of the same species and is heritable. The definition has been refined for Schistosoma sp. to stress the difference between tolerance and resistance. Tolerance is when a drug has never worked against a parasite, e.g. oxamniquine and S. japonicum. Genes for resistance are present if an isolate of a parasite is significantly less susceptible than the most susceptible isolate of the same species (Coles and Kinoti, 1997). 

Dias, L.C., Pedro, R.J. and Debelardini, E.R. (1982) Use of praziquantel in patients with schistosomiasis mansoni previously treated with oxamniquine and/or hycanthone resistance of Schistosoma mansoni to schistosomicidal agents. Transactions of the Royal Society of Tropical Medicine and Hygiene 76, 652-659. 

Fallon, P.G. and Doenhoff, M.J. (1 994) Drug-resistant schistosomiasis resistance to praziquantel and oxamniquine induced in Schistosoma mansoni in mice is drug specific. American journal of Tropical Medicine and Hygiene 51, 83-88. 

Cuimaraes, R.X., Tchakerian, A., Dias, L.C., de Almeida, F.M., Vilela, M.P., Cabeca, M. and Takeda, A.K. (1979) Resistance to hycanthone and oxamniquine in patients with a clinical hepato-intestinal form of schistosomiasis. AMB Revista da Associaco Medica Brasileira 25, 48-50. 

Oxamniquine is active against mature and immature forms of Schistosoma mansoni (but not other schistosomes), though resistance can occur. The initial use of the drug was presumably based on identification of the parasite ova in stools, this drug s ease of administration (it is orally effective), and— perhaps—its availability. Adverse effects of oxamniquine include dizziness, headache, drowsiness, gastrointestinal irritation, and pruritus. Effects probably due... 

Oxamniquine is activated via esterification to a biological ester that spontaneously dissociates to an electrophile, which alkylates the helminth DNA, leading to irreversible inhibition of nucleic acid metabolism (Fig. 39.20) (72). Resistant helminths do not esterify oxamniquine therefore, activation does not occur. Other metabolic reactions consist of oxidative reactions, leading to inactivation (Fig. 39.20). The metabolites are excreted primarily in the urine. 

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