Randomised Comparative Study of Mefloquine, Qinghaosu, and Pyrimethamine-Sulfadoxine in Patients With Falciparum Malaria

Li, Guoqiao; Guo, Xiuping; Arnold, Keith; Jian, Hwaxiang; Fu, Lin-Chun

doi:10.1016/s0140-6736(84)92057-9

Cited by 102 publications

(60 citation statements)

References 6 publications

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“…1,16,17 With ALLQUIN treatment, none of the patients had P. vivax in peripheral blood during follow-up. It has been reported that P. vivax infection is not detectable until P. falciparum has been eradicated by treatment with quinine, 1,16,17 suggesting that a mixed infection may occur. Allopurinol has a parasiticidal effect on P. vivax.…”

Section: Discussionmentioning

confidence: 99%

Allopurinol as an additive to quinine in the treatment of acute complicated falciparum malaria.

Sarma

Mandal²,

Khamis³

1998

The American Journal of Tropical Medicine and Hygiene

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Abstract. The emergence of chloroquine resistance, and a world-wide scarcity of quinine, have resulted in a search for newer antimalarial drugs directed against falciparum malaria. Allopurinol causes virtually complete inhibition of purine biosynthesis of malaria parasites, which may prove lethal to the parasites. This study was designed to examine if allopurinol is additive to quinine in the treatment of acute falciparum malaria. Forty-seven Asian-Indian adults with acute complicated falciparum malaria were assigned to a treatment period of five days. They were randomly assigned to receive either oral allopurinol (12 mg/kg in three divided doses for five days) plus quinine (600 mg intravenously every 8 hr for two days, followed by 600 mg orally every 8 hr for three days ) (n ϭ 24), or quinine alone (600 mg intravenously every 8 hr for two days, followed by 600 mg orally every 8 hr for three days) (n ϭ 23). The responses were assessed by parasite clearance time, defervescence time, splenomegaly disappearance time, and cure rate. In the allopurinol-quinine (ALLQUIN)-treated group, all the durations were significantly shorter than those in the quinine alone (QUIN)-treated group. They were ALLQUIN versus QUIN (mean Ϯ SD ϭ 65.33 Ϯ 11.47 hr versus 76.78 Ϯ 18.20 hr; P ϭ 0.0214; 57.66 Ϯ 13.01 hr versus 82.52 Ϯ 23.55 hr, P ϭ 0.0002; 10 Ϯ 1.64 days versus 14.65 Ϯ 2.4 days; P ϭ 0.0002), respectively. The cure rate was higher in the ALLQUIN group (91.7%) than in the QUIN group (87%). However, this difference was not statistically significant. Therefore, this study indicates that allopurinol can be an additive to quinine to bring about both faster eradication of Plasmodium falciparum and clinical remission than with quinine alone.With the emergence of Plasmodium falciparum strains resistant to chloroquine and/or to sulfadoxine/pyrimethamine in almost all endemic areas, 1 quinine has remained one of the few drugs for treatment of falciparum malaria 2 and has caused a resurgence of its use. 3 Quinine administered daily for three days clears parasitemia within a few days; but after two to four weeks, parasitemia recrudesces. 4 Although, during successful antimalarial treatment, parasite clearance time in African children with severe P. falciparum infection did not usually exceed 60 hr, some parasites remained alive despite exposure to extremely high concentrations of quinine for up to 96 hr. 2 Allopurinol has a broad antiprotozoal activity. 5 Due to a lack of a de novo purine biosynthesis pathway, 6 and malaria parasite's nonspecific hypoxanthine guanine phosphoribosyl transferase, malaria parasites use allopurinol as a hypoxanthine analog. 7 Consequently, 4-aminopyrazolopyrimidine ribonucleotide triphosphate, a highly toxic analog of adenosine triphosphate is formed and incorporated into protozoal ribonucleic acid. 8 Allopurinol thus brings about virtually complete cessation of intraerythrocytic (IE) plasmodial purine biosynthesis and protein metabolism, which prove lethal to the parasites. Allopurinol (11-36 mg/kg/day) is ra...

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Section: Discussionmentioning

confidence: 99%

Allopurinol as an additive to quinine in the treatment of acute complicated falciparum malaria.

Sarma

Mandal²,

Khamis³

1998

The American Journal of Tropical Medicine and Hygiene

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“…A similar increase in parasite count over the first 16 hr following treatment initiation was also observed with mefloquine in a study by Jiang and others, 33 but not in a study by Li and others. 34 Atovaquone/proguanil exemplifies how synergism rather than just additive activity can be achieved via a combination of antimalarial agents. In vitro, the concentration of drug that inhibits parasite growth by 50% (IC 50 ) of atovaquone against various P. falciparum strains is 0.7-4.3 nM, making it consistently more potent than chloroquine, which has an IC 50 of 74-633 nM against the same strains.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of atovaquone/proguanil compared with mefloquine for treatment of acute Plasmodium falciparum malaria in Thailand.

Looareesuwan¹,

Wilairatana²,

Chalermarut³

et al. 1999

The American Journal of Tropical Medicine and Hygiene

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Abstract. The increasing frequency of therapeutic failures in falciparum malaria underscores the need for novel, rapidly effective antimalarial drugs or drug combinations. Atovaquone and proguanil are blood schizonticides that demonstrate synergistic activity against multi-drug-resistant Plasmodium falciparum in vitro. In an open-label, randomized, controlled clinical trial conducted in Thailand, adult patients with acute P. falciparum malaria were randomly assigned to treatment with atovaquone and proguanil/hydrochloride (1,000 mg and 400 mg, respectively, administered orally at 24-hr intervals for three doses) or mefloquine (750 mg administered orally, followed 6 hr later by an additional 500-mg dose). Efficacy was assessed by cure rate (the percentage of patients in whom parasitemia was eliminated and did not recur during 28 days of follow-up), parasite clearance time (PCT), and fever clearance time (FCT). Safety was assessed by sequential clinical and laboratory assessments for 28 days. Atovaquone/proguanil was significantly more effective than mefloquine (cure rate 100% [79 of 79] vs. 86% [68 of 79]; P Ͻ 0.002). The atovaquone/proguanil and mefloquine treatments did not differ with respect to PCT (mean ϭ 65 hr versus 74 hr) or FCT (mean ϭ 59 hr versus 51 hr). Adverse events were generally typical of malaria symptoms and each occurred in Ͻ 10% of the patients in either group, with the exception of increased vomiting found in the atovaquone/proguanil group. Transient elevations of liver enzyme levels occurred more frequently in patients treated with atovaquone/ proguanil than with mefloquine, but the differences were not significant and values returned to normal by day 28 in most patients. The combination of atovaquone and proguanil was well tolerated and more effective than mefloquine in the treatment of acute uncomplicated multidrug-resistant falciparum malaria in Thailand.

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“…The mechanism of action of artemisinins remains controversial [2,3] but they retain activity against parasites that have become resistant to anti-malarials such as such as chloroquine and pyrimethamine [4]. Furthermore, artemisinins can be faster acting than other drugs malarial treatments [5,6]. These impressive qualities have resulted in the World Health Organisation recommending that all anti-malarials be combined with an ART component when used in first line treatment [7].…”

Section: Artemisinin (Art) Is a Natural Trioxane That Is Isolated Fromentioning

confidence: 99%

In vitro study of the anti-cancer effects of artemisone alone or in combination with other chemotherapeutic agents

Gravett

Liu

Krishna

et al. 2010

Cancer Chemother Pharmacol

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Randomised Comparative Study of Mefloquine, Qinghaosu, and Pyrimethamine-Sulfadoxine in Patients With Falciparum Malaria

Cited by 102 publications

References 6 publications

Allopurinol as an additive to quinine in the treatment of acute complicated falciparum malaria.

Allopurinol as an additive to quinine in the treatment of acute complicated falciparum malaria.

Efficacy and safety of atovaquone/proguanil compared with mefloquine for treatment of acute Plasmodium falciparum malaria in Thailand.

In vitro study of the anti-cancer effects of artemisone alone or in combination with other chemotherapeutic agents

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