Mefloquine in infants and young children.

In an area where multi-drug resistance in Plasmodium falciparum is a particular problem, more than 500 children under 5 years of age weighing > 5 kg were treated with mefloquine, either alone or combined with an artemisinin derivative, and followed up for a minimum of 28 days. The principal adverse effect was vomiting and this was associated with reduced efficacy of treatment (even when treatment was repeated). Later adverse effects occurred less frequently than in adults.

Comparative bioavailability of oral, rectal, and intramuscular artemether in healthy subjects: use of simultaneous measurement by high performance liquid chromatography and bioassay.

1. The pharmacokinetic and effect kinetic properties of oral (p.o.

Randomised double-blind placebo-controlled trial of SPf66 malaria vaccine in children in northwestern Thailand. Shoklo SPf66 Malaria Vaccine Trial Group.

Background: Previous efficacy trials of SPf66 malaria vaccine have produced conflicting results in different populations. We report a randomised double-blind trial of the SPf66 vaccine conducted in Karen children aged 2-15 living in a malarious region of northwestern Thailand. Recombinant hepatitis B vaccine was used as a comparator.

Effects of artemisinin derivatives on malaria transmissibility.

Background: On the western border of Thailand the efficacy of mefloquine in the treatment of falciparum malaria has declined while gametocyte carriage rates have increased, which suggests increased transmissibility of these resistant infections. We compared the following antimalarial drugs in relation to subsequent Plasmodium falciparum gametocyte carriage: mefloquine, halofantrine, quinine, and the artemisinin derivatives.

Methods: Between 1990 and 1995 we assessed gametocytaemia in a series of prospective studies of antimalarial drug treatment in 5193 adults and children with acute uncomplicated falciparum malaria in an area of malarious hill forest on the western border of Thailand.

Electrocardiographic monitoring in severe falciparum malaria.

Electrocardiographic monitoring over 24 h was performed with 53 patients with severe Plasmodium falciparum malaria (11 adults and 42 children) to assess the frequency of unrecognized cardiac arrhythmias. Nine patients (17%) died, 5 during the monitoring period and 4 afterwards. Pauses lasting 2-3 s were observed in 3 children, a single couplet in one, and a further child experienced frequent supraventricular ectopic beats which had not been detected clinically.

The epidemiology of malaria in a Karen population on the western border of Thailand.

From November 1991 to November 1992 a prospective, descriptive study of malaria epidemiology was conducted in a Karen population on the western border of Thailand. Two study groups were selected at random and more than 80% of the subjects were followed for one year. In Group 1, comprising 249 schoolchildren (aged 4-15 years), daily surveillance for illness was combined with fortnightly malaria surveys.

Predictors of mefloquine treatment failure: a prospective study of 1590 patients with uncomplicated falciparum malaria.

The factors which identify patients at risk of treatment failure were characterized in 1590 children and adults with uncomplicated falciparum malaria treated with 15 or 25 mg/kg of mefloquine on the borders of Thailand. Six independent predictors of failure were identified using multiple logistic regression. Age < or = 2 years (odds ratio [OR] 4.

Oral artesunate in the treatment of uncomplicated hyperparasitemic falciparum malaria.

Patients with uncomplicated hyperparasitemic falciparum malaria are usually given parenteral antimalarial treatment to prevent a progression to vital organ dysfunction and death. Since the oral artemisinin derivatives are more rapidly effective than other antimalarial drugs, we compared oral artesunate (4 mg/kg/day for three days with mefloquine 25 mg/kg on the second day) with an intravenous quinine loading dose (20 mg of salt/kg initially then 10 mg/kg every 8 hr, followed by mefloquine 25 mg/kg) in an open paired randomized trial in 60 patients with acute falciparum malaria and greater than 4% parasitemia, but no evidence of vital organ dysfunction. There were no deaths and none of the patients progressed to develop severe malaria.

Artesunate versus artemether in combination with mefloquine for the treatment of multidrug-resistant falciparum malaria.

To compare the therapeutic efficacy of oral artesunate and artemether in combination with mefloquine for the treatment of multidrug resistant malaria, a trial was conducted in 540 adults and children on the Thai-Myanmar border. Three regimens were compared: artesunate (4 mg/kg/d for 3 d), artemether (4 mg/kg/d for 3 d), both in combination with mefloquine (25 mg/kg), and a single dose of mefloquine (25 mg/kg). The artesunate and artemether regimens gave very similar clinical and parasitological responses, and were both very well tolerated.

Clinical features and outcome of severe malaria in Gambian children.

The clinical and laboratory features of severe falciparum malaria in 180 Gambian children were studied between 1985 and 1989. Of the 180 children, 118 (66%) presented with seizures, 77 (43%) had cerebral malaria, 35 (20%) had witnessed seizures after admission, 29 (16%) were hypoglycemic, and 27 (15%) died. Respiratory distress was a common harbinger of a fatal outcome.

Non specific resistance against malaria pre-erythrocytic stages: involvement of acute phase proteins.

Levels of different acute phase proteins were compared in sera from parasitaemic and non-parasitaemic women living in a Plasmodium falciparum endemic area of Thailand. The ability of their sera to interfere with hepatic stage development of the parasite was examined. Correlations were found between levels of alpha-1 antitrypsin, alpha-2 macroglobulin, hemopexin and the potential of sera to block hepatocyte invasion by the sporozoite.

New antimalarials. A risk-benefit analysis.

Although more than 40% of the world's population live in malaria endemic areas, there are only 6 available antimalarial drugs for the treatment of Plasmodium falciparum infections. Three of these have been developed in the last 20 years and are discussed in this review. Mefloquine is relatively well tolerated and has the advantage of a single day regimen.

Mefloquine treatment of acute falciparum malaria: a prospective study of non-serious adverse effects in 3673 patients.

Between 1990 and 1994, a series of prospective studies were conducted to optimize the treatment of multidrug-resistant falciparum malaria on the borders of Thailand. The tolerance of various treatment regimens containing either mefloquine 15 mg/kg (M15) or 25 mg/kg (M25) was evaluated in 3673 patients aged between 6 months and 88 years. Early vomiting (within 1 hour) is an important determinant of treatment outcome in these areas, despite re-administration of the dose.

Field trials of an asexual blood stage malaria vaccine: studies of the synthetic peptide polymer SPf66 in Thailand and the analytic plan for a phase IIb efficacy study.

Several years ago the Walter Reed Army Institute of Research (WRAIR) initiated an independent analysis of the candidate malaria blood stage vaccine SPf66. WRAIR contracted for the synthesis and formulation of SPf66 in United States Food and Drug Administration (FDA) inspected laboratories within the U.S.

Comparison of capillary whole blood, venous whole blood, and plasma concentrations of mefloquine, halofantrine, and desbutyl-halofantrine measured by high-performance liquid chromatography.

Whole blood mefloquine, halofantrine, and desbutyl-halofantrine concentrations were measured by high-performance liquid chromatography in capillary blood, venous blood, and venous plasma samples from patients along the Thai/Burmese border with falciparum malaria who were treated with either mefloquine (25 mg/kg) or halofantrine (24 mg/kg or 72 mg/kg). The limits of detection for mefloquine, halofantrine, and desbutyl-halofantrine were 50, 15, and 10 ng/ml, respectively, with 200 microliters whole blood samples. There was a good linear correlation (r > 0.

Treatment of multidrug-resistant Plasmodium falciparum malaria with 3-day artesunate-mefloquine combination.

Studies of 652 adults and children with acute uncomplicated falciparum malaria were done to determine the optimum treatment of multidrug-resistant Plasmodium falciparum malaria on the Thai-Burmese border. Single-dose artesunate (4 mg/kg) plus mefloquine (25 mg of base/kg) gave more rapid symptomatic and parasitologic responses than high-dose mefloquine alone but did not improve cure rates. Three days of artesunate (total dose, 10 mg/kg) plus mefloquine was 98% effective compared with a 28-day failure rate of 31% with high-dose mefloquine alone (relative risk [RR], 0.

Artemisinin: large community studies.

Prospective randomized trials with oral artemisinin derivatives have been conducted in over 1000 patients to determine the optimum treatment of multi-drug resistant falciparum malaria on the Thai-Burmese border. These drugs have proved valuable in 3 settings. (i) Primary treatment of uncomplicated malaria in combination with mefloquine, when they accelerate the rate of recovery, eliminate the risk of dangerous early failures, and if given for 3 d or more improve overall cure rates; (ii) treatment of recrudescent infections, which otherwise have a high failure rate; and (iii) oral treatment of patients with high parasitaemias (> or = 4%) but no clinical evidence of severity (a group who would usually receive parenteral quinine).

Mefloquine prophylaxis prevents malaria during pregnancy: a double-blind, placebo-controlled study.

A double-blind, placebo-controlled study of mefloquine antimalarial prophylaxis in pregnancy (> 20 weeks of gestation) was conducted in 339 Karen women living in an area of multidrug-resistant malaria transmission on the Thai-Burmese border. Mefloquine gave > or = 86% (95% confidence interval [CI], 59%-94%) protection against Plasmodium falciparum and complete protection against Plasmodium vivax infections. Mefloquine prophylaxis was well tolerated; use of an initial loading dose (10 mg/kg) was associated with transient dizziness, but there were no other significant adverse effects on the mother, the pregnancy, or infant survival or development (followed for 2 years).

Single day mefloquine-artesunate combination in the treatment of multi-drug resistant falciparum malaria.

The therapeutic efficacy and toxicity of a combination of low dose mefloquine (15 mg/kg) plus artesunate 10 mg/kg in one day (MA) was compared with the currently used regimen of high dose mefloquine (25 mg/kg) (MQ) in 552 patients with uncomplicated falciparum malaria in an area of multi-drug resistance on the Thai-Burmese border. MA gave faster clinical and parasitological responses and prevented early treatment failure; 15 patients in the MQ group (6%) were early failures (< 9 d) compared with none receiving MA (P = 0.0001).

Lactic acidosis and hypoglycaemia in children with severe malaria: pathophysiological and prognostic significance.

Serial clinical and metabolic changes were monitored in 115 Gambian children (1.5-12 years old) with severe malaria. Fifty-three children (46%) had cerebral malaria (coma score < or = 2) and 21 (18%) died.

Bed nets for the prevention of malaria and anaemia in pregnancy.

A prospective comparison of the antimalarial efficacy of bed nets was conducted with 341 pregnant women living in a mesoendemic malarious area of the Thai-Burmese border. Women in 3 adjacent study sites were allocated at random to receive either a single size permethrin-impregnated bed net (PIB), a non-impregnated bed net (NIB), or to a control group who used either their own family size non-impregnated bed net (FNIB) or no net. In one study site, but not the other 2, PIB significantly reduced parasite densities and, together with FNIB, reduced the incidence of malaria in pregnancy from 56% to 33% (relative risk = 1.