Epidemiological studies have also confirmed the association of CQ resistance with a mutation in the transporter gene pfcrt. The amino acid substitution at pfcrt codon 76 (K to T) have shown a determinant association with the resistant phenotype (Lopes et al.1993, Babiker et al. 2001). The transporter for CQ resistance is located in the membrane of the food vacuoles where CQ is suggested to act by binding to hematin, a toxic by-product from the digestion of hemoglobin, thereby preventing synthesis of non-toxic hemozoin (Fitch et al. 1998, Bray et al. 1998).
To overcome the problem of CQ drug resistance, sulphadoxine-pyrimethamine (SP) combination was recommended by the National Programme in the country (National antimalarial programme, 1982). SP acts by interfering with two enzymes in the biosynthesis of folate. Sulphadoxine(SDX) is analogous to p-amino benzoic acid and competitively inhibits dihydropteroate synthase (DHPS) while pyrimethamine (PYR) is a competitive inhibitor of dihydrofolate reductase (DHFR). The inhibition of these two key enzymes affects the synthesis of tetrahydrofolate, which is needed in the production of dTTP and amino acids methionine and glycine (Sibley et al. 2001). As a result the parasites get killed because of impaired synthesis of DNA and amino acids.
Regretfully, resistance to SP developed rapidly in Southeast Asia even before the wide use of the drug (Wangsrpchanalai et al. 2002). Several factors contributed to the fast development of resistance to SP, one of which is long elimination half life of 10 and 4 days for SDX and PYR respectively.
Use of antimalarial treatment for febrile episodes and self-treatment are common in high malaria-endemic areas (Nwanyanwu et al.1996, Mahomva et al. 1996). Irrational treatment practices by the clinicians and also self treatment with antimalarials have been reported in the past (Nsimba et al. 2005). Uncontrolled and unnecessary use of antimalarials may increase drug pressure on the parasites and encourage parasite resistance. A number of important questions concerning factors related to self-treatment, full dose and adherence to self-treatment and the role of self-treatment in malaria morbidity or mortality remain challenge (Mccombie 2002, H