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<jats:p>Artemisinin (QHS) and its derivatives are new antimalarials which are effective against <jats:italic>Plasmodium falciparum</jats:italic> parasites resistant to chloroquine (CQ). As these drugs are introduced it is imperative that resistance is monitored. In this paper we demonstrate that the inoculum size used in <jats:italic>in vitro</jats:italic> testing influences the measured <jats:italic>in vitro</jats:italic> susceptibility to QHS and its derivative dihydroartemisinin (DHA) and to mefloquine (MEF) and CQ over the range of parasitaemias routinely used in testing with the WHO <jats:italic>in vitro</jats:italic> microtest. An increase in parasitaemia and/or haematocrit was accompanied by a decrease in the measured sensitivity of 2 laboratory lines. In the context of a field study testing <jats:italic>in vitro</jats:italic> susceptibility of parasite isolates from patients with uncomplicated malaria in Fajara, The Gambia we demonstrate that failure to control for inoculum size significantly overestimates the level of resistance to QHS and DHA as well as MEF, halofantrine (HAL) and quinine (QUIN). When controlling for the inoculum effect, cross-resistance was observed between QHS, MEF and HAL suggesting the presence of a multidrug resistance-like mechanism. These studies underline the importance of inoculum size in <jats:italic>in vitro</jats:italic> susceptibility testing.</jats:p>

Original publication

DOI

10.1017/s0031182099004953

Type

Journal article

Journal

Parasitology

Publisher

Cambridge University Press (CUP)

Publication Date

11/1999

Volume

119

Pages

435 - 440