Incidence of antimalarial pretreatment and drug sensitivity in vitro in multidrug-resistant Plasmodium falciparum infection in Thailand

Abstract

Blood samples for determination of baseline antimalarial levels and sensitivity testing in vitro were collected from 411 patients with uncomplicated multidrug-resistant Plasmodium falciparum malaria (365 males, 46 females) before starting antimalarial treatment (62 in hospital and 349 as out-patients). Three hundred and eighty-two were successfully tested, and 110 (28.8%) and 20 (5.2%) patients, respectively, had detectable baseline blood mefloquine and quinine levels. Thirty-nine (10.2%), 44 (11.5%), 23 (6.0%) and 4 (1.1%) cases, respectively, had mefloquine concentrations in whole blood of < 100, 100-500, > 500-1000 and > 1000 ng/mL; the corresponding values for baseline plasma quinine levels were 0 (0%), 9 (2.4%), 3 (0.8%) and 9 (2.4%). None had detectable baseline artemether or artesunate. Sensitivity tests in vitro of pretreatment P. falciparum isolates showed the median IC50, IC90and IC99values (ranges in parentheses) for mefloquine, quinine and artemisinin to be 0.121 (0.046-0.715), 0.333 (0.085-3.0) and 0.64 (0.16-1.28) μM, 0.256 (0.064-1.315), 1.10 (0.154-2.049) and 2.56 (0.64-5.12) μM, and 0.02 (0.003-0.382), 0.112 (0.015-4.3) and 0.3 (0.03-3.0) μM, respectively. There was no difference in the sensitivity of P. falciparum isolates to these antimalarial compounds, regardless of the areas where patients had contracted the infection. Previous treatment with mefloquine or quinine was not statistically associated with a high incidence of resistance to these compounds.