Comparison of artemether and quinine in the treatment of severe falciparum malaria in south-east Thailand

Karbwang, Juntra; Takać, Tin; Rimchala, W.; Sukontason, Kom; Namsiripongpun, V.; Thanavibul, A; Na‐Bangchang, Kesara; Laothavorn, Prasart; Bunnag, D; Harinasuta, T

doi:10.1016/0035-9203(95)90437-9

Cited by 41 publications

(37 citation statements)

References 11 publications

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“…19 Trials using clinically safe doses of artemether for the treatment of severe falciparum malaria have generally demonstrated no dysrythmia or significant changes in ECG tracings. [20][21][22] The major exception was a clinical study of 2,638 patients with uncomplicated falciparum malaria in which Ribeiro and Olliaro reported moderate lengthening of the QTc interval in 1.1% of the cases. 23 However, that study failed to take into account the effects of hydration status and potential ionic disorders.…”

Section: Discussionmentioning

confidence: 99%

The effects of antimalarial drugs on ventricular repolarization.

Touze¹,

Héno²,

Fourcade³

et al. 2002

Am J Trop Med Hyg

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Abstract. Cardiotoxicity has become a major concern during treatment with antimalarial drugs. Lengthening of the QTc and severe cardiac arrhythmia have been observed, particularly after treatment with halofantrine for chloroquineresistant Plasmodium falciparum malaria. The purpose of this prospective study was to evaluate whether antimalarial agents alter dispersion of the QTc and ventricular repolarization dynamicity. Sixty patients with uncomplicated falciparum malaria were randomly allocated in four groups of 15 patients and treated with quinine, mefloquine, artemether, or halofantrine at recommended doses. Patients in treatment groups were compared with a group including 15 healthy controls with no history of malaria and/or febrile illness within the last month. QTc dispersion was measured on surface electrocardiograms. Repolarization dynamicity was analyzed from Holter recordings, which allow automatic beat-tobeat measurement of QT and RR intervals. Plasma drug concentration was determined by reversed-phase highperformance liquid chromatography. No change in QTc dispersion was observed after treatment with quinine, mefloquine, or artemether. Treatment with halofantrine was followed by a significant increase in QTc dispersion at 9 hours (P < 0.0001) and 24 hours (P < 0.01). Assessment of QT heart rate variability by QT/RR nychtohemeral regression slope demonstrated no significant difference between the artemether (mean ± SEM ‫ס‬ 0.170 ± 0.048), mefloquine (0.145 ± 0.044), and the control groups (0.172 ± 0.039). A significant decrease in the Q-eT/RR slope was observed in the quinine group compared with the control and artemether groups (0.135 ± 0.057; P < 0.04). With halofantrine, a significant increase in the QT/RR regression slope (0.289 ± 0.118) was observed (P < 0.0002). QTc interval, QT dispersion, and QT regression slope were significantly correlated with halofantrine and quinine plasma concentration. Mefloquine and artemether did not alter ventricular repolarization. Quinine induced a significant decrease in QT/RR slope of the same order of magnitude as those previously observed with quinidine. Both QTc dispersion and QT/RR slope were significantly modified by halofantrine. These repolarization changes were related to a class-III antiarrhythmic drug effect and may explain the occurrence of ventricular arrhythmia and/or sudden deaths reported after halofantrine intake.

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Section: Discussionmentioning

confidence: 99%

The effects of antimalarial drugs on ventricular repolarization.

Touze¹,

Héno²,

Fourcade³

et al. 2002

Am J Trop Med Hyg

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“…3 Artemether (an oilsoluble artemisinin derivative) has shown effectiveness against chloroquine-resistant strains of P. falciparum in China and Thailand. 4,5 However, little information is available concerning the in vitro activity of artemisinin and its derivatives against isolates of P. falciparum from Africa other than reference strains. 6,7 The two-fold aim of this in vitro study was to evaluate the activity of artemether against fresh isolates of P. falciparum from Senegal, and to analyze cross-susceptibility between artemether, chloroquine, quinine, mefloquine, and halofantrine.…”

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confidence: 99%

In vitro activity of artemether against African isolates (Senegal) of Plasmodium falciparum in comparison with standard antimalarial drugs.

Pradines

Rogier²,

Fusaı̈³

et al. 1998

The American Journal of Tropical Medicine and Hygiene

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Abstract. The in vitro activity of artemether against 56 African isolates of Plasmodium falciparum from Senegal was evaluated using an isotope-based drug susceptibility semi-microtest. The 50% inhibitory concentration (IC 50 ) values for artemether were in a narrow range from 0.8 to 15.2 nM (mean IC 50 ϭ 3.43 nM) and the 95% confidence interval (CI) was 2.50-4.36 nM. Artemether was equally effective on chloroquine-sensitive and chloroquine-resistant isolates (mean IC 50 ϭ 346 nM, 95% CI ϭ 2.08-4.84 nM versus mean IC 50 ϭ 2.80 nM, 95% CI ϭ 2.00-3.60 nM). There was a significant positive correlation between responses to artemether and mefloquine (r 2 ϭ 0.36, P Ͻ 0.001), artemether and quinine (r 2 ϭ 0.085, P Ͻ 0.05), artemether and halofantrine (r 2 ϭ 0.075, P Ͻ 0.05), quinine and mefloquine (r 2 ϭ 0.205, P Ͻ 0.01), quinine and halofantrine (r 2 ϭ 0.124, P Ͻ 0.05), and mefloquine and halofantrine (r 2 ϭ 0.801, P Ͻ 0.001). A positive correlation between these drugs suggests in vitro cross-resistance or at least in vitro cross-susceptibility.In the absence of effective and practical preventive measures, the only current options for reducing the morbidity and mortality of malaria especially in Africa are chemoprophylaxis and chemotherapy. For this reason, the increasing prevalence of strains of Plasmodium falciparum resistant to chloroquine and other antimalarial drugs poses a serious problem for control of malaria. 1 There is an urgent need to find and develop alternative drugs against chloroquine-resistant P. falciparum.One group of alternative antimalarial drugs comprises artemisinin (qinghaosu) and its derivatives. Artemisinin is a traditional Chinese medicinal herb derived from Artemisia annua. It has a sesquiterpene lactone with a peroxide bridge and antimalarial activity has been attributed to the peroxide moiety 2 by a mechanism involving production of free radicals that damage the parasite membrane. 3 Artemether (an oilsoluble artemisinin derivative) has shown effectiveness against chloroquine-resistant strains of P. falciparum in China and Thailand. 4,5 However, little information is available concerning the in vitro activity of artemisinin and its derivatives against isolates of P. falciparum from Africa other than reference strains. 6,7 The two-fold aim of this in vitro study was to evaluate the activity of artemether against fresh isolates of P. falciparum from Senegal, and to analyze cross-susceptibility between artemether, chloroquine, quinine, mefloquine, and halofantrine. MATERIALS AND METHODSIsolates of P. falciparum. All programs were reviewed and approved by the Conseil de Perfectionnement of the Institut de Dakar, which is presided over by the Senegalese Health Secretary. Informed oral consent was obtained from the patients and/or their parents before collection of blood samples. Only oral consent was obtained because only 5% of the people in Dielmo, Ndiop, and Toubakouta can read and write. Between October 1995 and January 1996, 56 fresh P. falciparum isolates were prepared from samples obtaine...

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“…The χ 2 value was 2.35 which was statistically (P >0.2) not significant. Karbwang et al [9] found mean fever defervescence time to be 79 hrs and 84 hrs in artemisinin derivative and quinine treated patients respectively.…”

Section: Discussionmentioning

confidence: 99%

Complicated Malaria - A Randomized Control Study Comparing the Efficacy of Quinine and Artesunate in Its Management in Western Rajasthan, India

Goyal¹

2015

JPNC

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Comparison of artemether and quinine in the treatment of severe falciparum malaria in south-east Thailand

Cited by 41 publications

References 11 publications

The effects of antimalarial drugs on ventricular repolarization.

The effects of antimalarial drugs on ventricular repolarization.

In vitro activity of artemether against African isolates (Senegal) of Plasmodium falciparum in comparison with standard antimalarial drugs.

Complicated Malaria - A Randomized Control Study Comparing the Efficacy of Quinine and Artesunate in Its Management in Western Rajasthan, India

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