Academic journal article Bulletin of the World Health Organization

Comparison of Oral Artesunate and Quinine Plus Tetracycline in Acute Uncomplicated Falciparum Malaria

Academic journal article Bulletin of the World Health Organization

Comparison of Oral Artesunate and Quinine Plus Tetracycline in Acute Uncomplicated Falciparum Malaria

Article excerpt

Introduction

In Thailand, multiple-drug-resistant strains of falciparum malaria are increasing and spreading (1, 2). Mefloquine is used as the first-line drug for uncomplicated falciparum malaria in Thailand; however, the efficacy of this drug has dropped dramatically in the country to less than 60% (3). The combination quinine tetracycline improves the cure rate from 75% to 95-100% compared with the use of quinine alone (2). This combination is therefore being used as a second-line drug treatment for uncomplicated malaria. However, the compliance of patients limits its use for home treatment. Cinchonism would be expected in practically all patients on this combined regimen. Alternative drugs that are better or equally as effective and which have fewer adverse effects therefore need to be studied.

Artesunate is a derivative of artemisinin and clears parasitaemia as rapidly as artemether (another derivative of artemisinin) (3-6). The parasite clearance rate of artesunate is faster than that of any other antimalarial (3, 7, 8). The potency of artesunate has been shown in several clinical trials in China and Thailand, and the adverse effects reported are very mild and transient (9-13). In China, the recommended total dose of artesunate has been 600 mg given over 5 days (14). However, recent studies in Thailand have shown that at this dosage the cure rate with uncomplicated falciparum malaria was only 72-90% when administered orally (10-13). The proper dosage regimen of artesunate for the treatment of multiple-drug-resistant falciparum malaria remains to be decided. Based on the efficacy of oral artesunate reported in recent studies (9-13), the duration of the treatment should be at least 5 days and the dose needs to be >600 mg to achieve a cure rate that approaches 100%. It is therefore interesting to assess the efficacy of a higher dose of artesunate in patients with multiple-drug-resistant falciparum malaria compared with that of the second-line drug treatment, quinine-tetracycline.

Patients and methods

A total of 64 adult Thai, male patients with acute uncomplicated falciparum malaria (asexual-forth parasitaemia, <5%), aged 15-35 years, and of weight range 43-65 kg were recruited into the study. We excluded patients who had a history of liver or kidney disease, and patients who had received antimalarial treatment for their current episode of illness. Patients with severe manifestations of malaria were also excluded (15). The written, informed consent for participation in the study was obtained from all the patients. The study was approved by the Ethics Committee of the Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.

Prior to receiving the treatment, blood smears were collected from each patient for malaria parasite identification and 3 ml of venous blood was drawn to determine the baseline drug concentrations of mefloquine and quinine. Patients who had previously received these two drugs were excluded from the study. All patients were admitted to the Bangkok Hospital for Tropical Diseases for 28 days.

The patients were randomly allocated (open randomization) to receive one of the two drug regimens, i.e., artesunate or the combination quinine-tetracycline as follows:

-- 200 mg of artesunate as an initial dose, followed

by 100 mg 12 hours later, and 100 mg daily for

another 4 days (total dose: 700 mg);

-- 600 mg of quinine sulfate at 8-hour intervals plus

250 mg of tetracycline at 6-hour intervals for 7

days.

Both regimens were administered orally with a glass of water under supervision. Based on previous data, the sample sizes chosen for the study were designed to detect a 35% faster parasite clearance rate from artesunate than from quinine-tetracycline (at a 95% confidence level).

Patients who failed to respond to either regimen were treated with 600 mg of quinine sulfate at 8-hour intervals plus 250 mg of tetracycline at 6-hour intervals, for 7 days. …

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