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In vitro susceptibility of Plasmodium falciparum to quinine: relation to parasite density and drug distribution in culture fractions
Author(s) -
Mapaba Erasto,
Ericsson Örjan,
Hellgren Urban,
Rombo Lars
Publication year - 1996
Publication title -
tropical medicine and international health
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.056
H-Index - 114
eISSN - 1365-3156
pISSN - 1360-2276
DOI - 10.1111/j.1365-3156.1996.tb00114.x
Subject(s) - schizogony , quinine , parasite hosting , plasmodium falciparum , in vitro , biology , malaria , chemistry , immunology , biochemistry , world wide web , computer science
Summary We have studied the importance of parasite density (2, 0·2, 0·02 and 0·002%) for the in vitro susceptibility of Plasmodium falciparum (F32 strain) to quinine. Shorter exposures (48 hours) only briefly inhibited parasites in wells with the highest initial density. Parasites reappeared after 3–5.5 days in wells with intermediate (0·2 and 0·02%) and lowest density (0·002%). Longer exposures (72 hours), however, inhibited them for much longer periods and parasites did not reappear in most of the wells with the lowest density during the 28 days of follow‐up. The mean multiplication rate following reappearance was tenfold per parasite schizogony cycle. The mean elimination rate per schizogony cycle was calculated to be 99·91%. The elimination and multiplication rates were not correlated to initial parasite density. The mean ratio between quinine concentrations in erythrocytes and medium was 3·6 regardless of quinine concentrations and presence of parasites. Mean quinine‐free fractions of 36 and 67% were found from total concentrations of 0·33 and 10·4 µmol/1. We conclude that initial parasite density determines the time to reappearance of parasites following quinine exposure while the elimination and multiplication rates are independent of the initial parasite density, and that quinine protein binding is concentration‐dependent in vitro and lower than during treatment.