Plasmodium falciparum: increased proportion of severe resistance (RII and RIII) to chloroquine and high rate of resistance to sulfadoxine-pyrimethamine in peninsular Malaysia after two decades

Abstract

Uncomplicated falciparum malaria patients were randomly assigned to receive either 25 mg/kg chloroquine (CHL) over 3 d or a statim dose of 25 mg/kg sulfadoxine (SDX) plus 1.25 mg/kg pyrimethamine (PYR). Patients were followed up for 28 d and the parasite response graded according to World Health Organization criteria. Overall resistance to CHL was 63.3% and 47.4% to SDX/PYR. RI, RII and RIII rates were 9.1%, 42.4% and 12.1% for CHL and 10.5%, 21.1% and 15.8% for SDX/PYR, respectively. Degree and rates of resistance to CHL were significantly correlated with pre-treatment parasite density, but not those to SDX/PYR. Plasma CHL and SDX/PYR levels were within the reported ranges and were not significantly different in patients with sensitive and resistant responses.

Mutational analysis of Plasmodium falciparum dihydrofolate reductase and dihydropteroate synthase genes in the interior division of Sabah, Malaysia

“…A large-scale study on the clinical efficacy of P. falciparum malaria to SDX/PYR in Peninsular Malaysia conducted in mid 1990s, reported 47% of the study isolates were resistant to SDX/PYR [8]. A subsequent molecular study reported 87% of P. falciparum had triple mutations in pfdhfr and all isolates having point mutation at codon A437G of pfdhps as indication of drug pressure, accompanied by 81% point mutation at codon A581G indicating reduced in vitro responsiveness of SDX [4].…”

The detection of pfcrt and pfmdr1 point mutations as molecular markers of chloroquine drug resistance, Pahang, Malaysia

“…A previous in vivo study followed by a molecular detection of resistance markers has been conducted in Sarawak and showed that CQ resistance occurred widely and therefore, CQ was replaced by sulphadoxine/pyrimethamine (SDX/PYR), and later by artemisinin combination therapy, as the drug of choice for treating uncomplicated falciparum malaria infections in East Malaysia [15]. In West Malaysia, CQ is still used as the first-line drug in the treatment policy of uncomplicated malaria caused by P. falciparum , although a previous in vivo study reported a CQ resistance rate of 63.6% among uncomplicated falciparum malaria patients [16]. Data on the molecular markers of CQ resistance in Peninsular Malaysia is not available.…”

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“…Resistance to chloroquine, an effective and safe anti-malarial that formed the first line of treatment, emerged more than 30 years ago [1], and since then malaria parasites have developed resistance against most of the widely used anti-malarials, including sulfadoxine-pyrimethamine [2,3], mefloquine [4] and quinine [5]. Indeed, it is now generally believed that the widespread use of a new drug will inevitably be followed by the appearance of resistance in the parasite population.…”