PEDIATRICS Vol. 96 No. 1 July 1995, pp. 42
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PREDICTORS OF TREATMENT FAILURE IN MULTIPLE DRUG-RESISTANT FALCIPARUM MALARIA: RESULTS FROM A 42-DAY FOLLOW-UP OF 224 PATIENTS IN EASTERN THAILAND

AL Fontanet and AM Walker

Mefloquine was introduced in 1984 as a single dose treatment for uncomplicated drug-resistant falciparum malaria. Recently there are reports of patients with malaria who are resistant to treatment with mefloquine. Two major determinants of treatment failure are decreased drug susceptibility of a particular strain of malarial parasite and an insufficient level of drug concentration in the blood. However, host factors may play a part. Therefore, the authors performed the present study to elucidate the predictors of treatment failure in a more detailed fashion.

Patients seen between August and December of 1991 with uncomplicated falciparum malaria in a camp for displaced persons on the border between Thailand and Cambodia were included in this study. During the first half of this study, treatment consisted of 15 mg/kg of mefloquine in a single dose for patients weighing less than 40 kg. For patients weighing 40 kg or more, 750 mg of mefloquine was given in a single dose. For the second half of the study, only adults were eligible and were randomly assigned to receive either 15 or 25 mg/kg of mefloquine. Patients were asked to return for outpatient visits six times during the first month and once on day 42. Treatment failures were defined as any increase in asexual parasites in blood after the initial decrease during the first 3 days of treatment. For all patients, observation continued with therapy of mefloquine for 42 days or until treatment failure or loss to follow-up.

There were 224 patients and of these 113 were seen during the first half of the trial and 111 during the second half. Children were underrepresented in the study. Diarrhea and vomiting were the most common side effects of mefloquine and it occurred on day two affecting 24% and 18% of the patients, respectively. Of the 224 patients, 15 (6.7%) were lost to follow-up. The overall failure rate in the remaining patients was 16% at day 9, 46% on day 28, and 57% on day 42. When all the baseline characteristics and the recorded side effects were examined, five variables were independent and important predictors of treatment failure. They were: a young age, a low hemoglobin level (le10 g/dL) on the day of treatment, a high parasitemia count of over 100,000/µL at the time of treatment, a history of diarrhea in the first 2 days after treatment, and a history of at least three mefloquine treatments during the previous year.

One of the most important observations was the high-risk of failure in children less than 15 years of age. Between days 10 and 42 the failure rate was 0.85 with a confidence interval of 0.69 to 1.05. Because of this very high correlation between treatment failure and young age, the authors recommend that future studies on drug efficacy in the treatment of malaria should include children because this group may represent an important population for development of drug resistance.