INCIDENCE OF ANTIMALARIAL PRETREATMENT AND DRUG-SENSITIVITY IN-VITRO IN MULTIDRUG-RESISTANT PLASMODIUM-FALCIPARUM INFECTION IN THAILAND

Blood samples for determination of baseline antimalarial levels and se nsitivity testing in vitro were collected from 411 patients with uncom plicated multidrug-resistant Plasmodium falciparum malaria (365 males, 46 females) before starting antimalarial treatment (62 in hospital an d 349 as out-patients). Three hundred and eighty-two were successfully tested, and 110 (28.8%) and 20 (5.2%) patients, respectively, had det ectable baseline blood mefloquine and quinine levels. Thirty-nine (10. 2%), 44 (11.5%), 23 (6.0%) and 4 (1.1%) cases, respectively, had meflo quine concentrations in whole blood of <100, 100-500, >500-1000 and >1 000 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 bas eline artemether or artesunate. Sensitivity tests in vitro of pretreat ment P. falciparum isolates showed the median IC50, IC90 and IC99 valu es (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) mu M, 0 .256 (0.064-1.315), 1.10 (0.154-20.49) and 2.56 (0.64-5.12) mu M, and 0.02 (0.003-0.382), 0.112 (0.015-4.3) and 0.3 (0.03-3.0) mu M, respect ively. There was no difference in the sensitivity of P. falciparum iso lates to these antimalarial compounds, regardless of the areas where p atients had contracted the infection. Previous treatment with mefloqui ne or quinine was not statistically associated with a high incidence o f resistance to these compounds.