Pharmacokinetics of mefloquine administered with artesunate in patients with uncomplicated falciparum malaria from the Brazilian Amazon basin.

BACKGROUND: A fixed-dose combination of mefloquine with artesunate was evaluated in cases of falciparum malaria in the Brazilian Amazon basin with acceptable efficacy, safety and tolerability. However, there are no data on the pharmacokinetics of mefloquine in this coformulation in Brazil, which is valuable to evaluate whether Plasmodium is exposed to an effective concentration of the drug. METHODS: A prospective, single-arm study was conducted in male patients with slide-confirmed infection by Plasmodium falciparum using two tablets of a fixed-dose combination of artesunate (100 mg) and mefloquine base (200 mg) once daily and over 3 consecutive days. Serial blood samples were collected at admission and throughout 672 h post-administration of the drugs. Mefloquine was measured in each blood sample by high-performance liquid chromatography. The pharmacokinetic parameters were determined by non-compartmental analysis. RESULTS: A total of 61 patients were enrolled in the study and 450 whole blood samples were collected for mefloquine measurement. The mefloquine half-life was 10.25 days, the maximum concentration (Cmax) was 2.53 µg/ml, the area-under-the-curve (AUC0-∞) was 359 µg/ml h, the observed clearance (Cl/f) was 0.045 l/kg/h and the volume of distribution (V/f) was 14.6 l/kg. Mefloquine concentrations above 0.5 µg/ml were sustained for a mean time of 9.2 days. CONCLUSION: The pharmacokinetic parameters of mefloquine determined in the study suggest an adequate exposure of parasite to mefloquine in the multiple oral dose regimen of the fixed dose combination of mefloquine and artesunate.

Association between anthropometry-based nutritional status and malaria: a systematic review of observational studies.

BACKGROUND: Multiple studies in various parts of the world have analysed the association of nutritional status on malaria using anthropometric measures, but results differ due to the heterogeneity of the study population, species of the parasite, and other factors involved in the host and parasite relationship. The aim of this study was to perform a systematic review on the inter-relationship of nutritional status based on anthropometry and malarial infection. METHODS: Two independent reviewers accessed the MEDLINE and LILACS databases using the same search terms related to malaria and anthropometry. Prospective studies associating anthropometry and malaria (incidence or severity) were selected. References from the included studies and reviews were used to increase the review sensitivity. Data were extracted using a standardized form and the quality of the prospective studies was assessed. Selected articles were grouped based on exposures and outcomes. RESULTS: The search identified a total of 1688 studies: 1629 from MEDLINE and 59 from LILACS. A total of 23 met the inclusion criteria. Five additional studies were detected by reading the references of the 23 included studies and reviews, totaling 28 studies included. The mean sample size was 662.1 people, ranging from 57 to 5620. The mean follow-up was 365.8 days, ranging from 14 days to 1 year and 9 months, and nine studies did not report the follow-up period. Prospective studies assessing the relationship between malaria and malnutrition were mostly carried out in Africa. Of the 20 studies with malarial outcomes, fifteen had high and five had average quality, with an average score of 80.5 %. Most anthropometric parameters had no association with malaria incidence (47/52; 90.4 %) or parasite density (20/25; 80 %). However, the impact of malnutrition was noted in malaria mortality and severity (7/17; 41.2 %). Regarding the effects of malaria on malnutrition, malaria was associated with very few anthropometric parameters (8/39; 20.6 %). CONCLUSIONS: This systematic review found that most of the evidence associating malaria and malnutrition comes from P. falciparum endemic areas, with a significant heterogeneity in studies' design. Apparently malnutrition has not a great impact on malaria morbidity, but could have a negative impact on malaria mortality and severity. Most studies show no association between malaria and subsequent malnutrition in P. falciparum areas. In Plasmodium vivax endemic areas, malaria was associated with malnutrition in children. A discussion among experts in the field is needed to standardize future studies to increase external validity and accuracy.