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Treatment failure in malaria is a major dilemma that health-care workers face throughout the country. True drug resistance is one of the causes after ruling out compliance and drug quality issues; the other causes being re-infection with a new strain of the parasite during the treatment period or, in the case of Plasmodium vivax, the release of hypnozoites from the liver. Since it is difficult, in the field, to identify the cause as being due to re-infection with a new strain of the parasite during the treatment period or, in the case of P. vivax, the release of hypnozoites from the liver, providing antimalarials to overcome drug resistance is the mainstay of therapy.