Academic journal article Bulletin of the World Health Organization

Falciparum Malaria in Eastern Thailand: A Randomized Trial of the Efficacy of a Single Dose of Mefloquine

Academic journal article Bulletin of the World Health Organization

Falciparum Malaria in Eastern Thailand: A Randomized Trial of the Efficacy of a Single Dose of Mefloquine

Article excerpt

Introduction

Mefloquine has been used since 1984 to treat uncomplicated falciparum malaria in Thailand. To delay the development of mefloquine resistance in Plasmodium falciparum strains, mefloquine was at first given in a triple combination with sulfadoxine and pyrimethamine. At a dose of 15 mg per kg body weight, mefloquine produced cure rates close to 100% in field trials (1--4). However, because of the low susceptibility of P. falciparum strains to sulfadoxine and pyrimethamine, treatment centres serving Khmer displaced persons along the eastern border of Thailand changed in July 1990 from the triple combination to mefloquine alone. A year later, an in vivo test of mefloquine efficacy in a Khmer displaced persons camp reported a cure rate of only 41% (5). Since it had been reported in an area adjacent to the Cambodian border that patients who received 25 mg of mefloquine per kg body weight had a higher maximum plasma mefloquine concentration than patients treated with 15 mg/kg (6), we initiated a clinical trial to compare the in vivo outcomes of patients treated with a single dose of 15 mg/kg or 25 mg/kg of mefloquine.

Patients and methods

Study site

The study was carried out in Site 8, a Khmer displaced persons camp on the border between Thailand and Cambodia. The camp had a population of 45 000, 40% of whom were children under the age of 10 years; it was also used as a referral hospital for patients from Cambodia. Malaria is the leading cause of morbidity and mortality in the camp, according to data from the outpatient department and the hospital. The monthly malaria incidence typically varies between 50 and 2000 cases, depending on the season. Most cases are due to P. falciparum (90%), the remainder being P. vivax infections. Uncomplicated falciparum malaria cases are treated with 15 mg/kg body weight of mefloquine (Lariam, Roche) in a single dose. Severe cases are treated with intraveneous quinine for up to 7 days, which is replaced by orally administered quinine and tetracycline when the patient is able to swallow tablets.

Mosquito collections made over the period 1983--85 show that areas close to the camp were heavily infested with both of the region's malaria vectors, Anopheles dirus and A. minimus.

Study procedure

Between September and November 1991, patients diagnosed with uncomplicated falciparum malaria at the outpatient department were treated with the camp's usual regimen of a single dose of 15 mg/kg of mefloquine. The following were contraindications for mefloquine treatment: cerebral symptoms, haemoglobin level <7 g/dl, high parasitaemia, and pregnancy.

Immediately after this first dose, adults with no history of treatment with quinine or mefloquine during the previous month were recruited for the study if they were willing to be randomized to receive a further dose of 10 mg/kg of mefloquine and if they were willing to remain available for follow-up for 42 days. The informed consent to participate in the study was obtained from the patients through the help of a translator, and the dose of 10 mg/kg of mefloquine was given to patients chosen using a table of random numbers. The interval between the first and the second dose never exceeded 15 minutes. Routine clinical information was collected using a standard form while the patients remained under observation for one hour after treatment in order to record whether or not they vomited within this period.

All thick smears were subsequently reviewed by an expert microscopist from the Thai Malaria Division. The number of parasites was calculated against 100 leukocytes (assuming a leukocyte count of 8.0 x [10.sup.9] per litre). Patients were retained for the study if they had >1600 asexual forms of P. falciparum per [micro]l of blood and no mixed P. flaciparum/P. vivax infections.

Patients were asked to return to the outpatient department for a thick smear on days 2, 7, 14, 21, 28, 42 and if they experienced any fever or symptoms of malaria outside the regular days of follow-up. …

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