Malaria Research and Treatment最新文献

Single dose pharmacokinetics study of 97/63 (IND191710, 2004), a trioxane antimalarial developed by Central Drug Research Institute, Lucknow, India, was studied in rats following intravenous and oral administration. Serum samples were analysed by HPLC-UV assay. Separation was achieved on a RP-18 column attached with a guard using acetonitrile : phosphate buffer (70 : 30% v/v) with UV detector at wavelength 244 nm. Serum samples were extracted with n-hexane. Two-compartment model without lag time and first-order elimination rate was considered to be the best fit to explain the generated oral and intravenous data. Method was sensitive with limit of quantification of 10 ng mL(-1). Recovery was >74%. Terminal half-life and area under curve (AUC) after administering single oral (72 mg kg(-1)) and intravenous (18 mg kg(-1)) doses were 10.61 h, 10.57 h, and 1268.97 ng h mL(-1), 2025.75 ng h mL(-1), respectively. After oral dose, 97/63 was rapidly absorbed attaining maximum concentration 229.24 ng mL(-1) at 1 h. Bioavailability of 97/63 was ~16%. The lower bioavailability of drug may be due to poor solubility and first-pass metabolism and can be improved by prodrug formation of 97/63.

Folic acid supplementation may potentially alter the efficacy of sulfadoxine-pyrimethamine (SP) treatment in children with malaria. However, there is lack of evidence from randomized controlled trials and effects of folic acid supplementation on clinical efficacy of SP therapy remain moderately understood among children. In a double masked, placebo-controlled trial among preschool children in Pemba Island (Tanzania), iron and folic acid supplementation (Fe/FA) showed an increased risk of hospitalizations and death. In the present paper, we evaluated if folic acid supplementation reduced the efficacy of malaria treatment and thereby contributed to observed adverse effects. During the study, 1648 children had confirmed malarial episodes and received either sulphadoxine-pyrimethamine (SP) treatment and iron folic acid or SP treatment and placebo. These children were evaluated for recovery and incidence of hospitalization during the next 15, 30, and 140 days. Two groups did not differ in malarial episode or hospitalization rate on subsequent 15, 30, and 140 days. Altered efficacy of SP by folic acid was not observed and did not contribute to adverse events in the previous trial. This trial is registered with Controlled-trials.com ISRCTN59549825.

Emergence of drugs resistant strains of Plasmodium falciparum has augmented the scourge of malaria in endemic areas. Antimalaria drugs act on different intracellular targets. The majority of them interfere with digestive vacuoles (DVs) while others affect other organelles, namely, apicoplast and mitochondria. Prevention of drug accumulation or access into the target site is one of the mechanisms that plasmodium adopts to develop resistance. Plasmodia are endowed with series of transporters that shuffle drugs away from the target site, namely, pfmdr (Plasmodium falciparum multidrug resistance transporter) and pfcrt (Plasmodium falciparum chloroquine resistance transporter) which exist in DV membrane and are considered as putative markers of CQ resistance. They are homologues to human P-glycoproteins (P-gh or multidrug resistance system) and members of drug metabolite transporter (DMT) family, respectively. The former mediates drifting of xenobiotics towards the DV while the latter chucks them outside. Resistance to drugs whose target site of action is intravacuolar develops when the transporters expel them outside the DVs and vice versa for those whose target is extravacuolar. In this review, we are going to summarize the possible pfcrt and pfmdr mutation and their role in changing plasmodium sensitivity to different anti-Plasmodium drugs.

Background. Malaria is an entrenched global health challenge particularly in the sub-Saharan African countries. However, in Ghana, little is known about the determinants of malaria prevalence among under-five children. As such, this study sought to examine the sociodemographic factors that determine malaria among under-five children in Ghana. Methods. This paper used secondary data drawn from the 2008 Ghana Demographic and Health Survey. Bivariate analysis and complementary log-log regression models were used to examine the determinants of malaria prevalence among under-five children in Ghana for the study period. Results. The results therefore revealed that region of residence, age of child, and ownership of mosquito net were the key predictors of malaria cases among under-five children in Ghana for the five-year period preceding the survey. Conclusion. It is therefore imperative that special education on prevention of malaria should be intensified by the National Malaria Control Programme in all the regions in order to reduce malaria prevalence particularly among under-five children in Ghana.

The study aimed at investigating the effects of adult uncomplicated malaria on insulin resistance. Fasting levels of blood glucose (FBG), glycosylated hemoglobin (HbA1c), and serum insulin were measured in 100 diabetics and 100 age-matched controls before and during Plasmodium falciparum malaria. Insulin resistance and beta cell function were computed by homeostatic models assessment of insulin resistance (HOMAIR) and beta cell function (HOMAB) formulae, respectively. Body mass index (BMI) was computed. At baseline, diabetics had significantly (P < 0.05) higher levels of BMI, FBG, HbA1c, and HOMAIR but lower level of HOMAB than controls. Baseline insulin levels were comparable (P > 0.05) between the two study groups. During malaria, diabetics maintained significantly (P < 0.05) higher levels of BMI, FBG, and HbA1c but lower levels of insulin and HOMAB than controls. Malaria-induced HOMAIR levels were comparable (P > 0.05) between the two study groups but higher than baseline levels. Apart from BMI and HOMAB, mean levels of all the remaining parameters increased in malaria-infected controls. In malaria-infected diabetics, significant (P < 0.05) increase was only observed for insulin and HOMAIR but not the other measured parameters. Uncomplicated malaria increased insulin resistance in diabetics and controls independent of BMI. This finding may have implications for the evolution of T2DM in malaria-endemic regions.

Chloroquine (CQ) resistance is widespread in Africa, but few data are available for Niger. Pfcrt haplotypes (aa 56-118) and ex vivo responses to CQ and amodiaquine were characterized for 26 isolates collected in South Niger from children under 15 years of age suffering from uncomplicated falciparum malaria, six years after the introduction of artemisinin-based combinations and the withdrawal of CQ. The wild-type Pfcrt haplotype CVMNK was found in 22 of the 26 isolates, with CVIET sequences observed in only three of the samples. We also describe for the first time a new CVINT haplotype. The ex vivo responses were better for CVMNK than for CVIET parasites. Pfcrt sequence data were compared with those obtained for 26 additional parasitized blood samples collected in Gabon, from an area of CQ resistance used as a control. Our findings suggest that there has been a significant decline in CQ-resistant genotypes since the previous estimates for Niger were obtained. No such decline in molecular resistance to CQ was observed in the subset of samples collected in similar conditions from Gabon. These results have important implications for public health and support the policy implemented in Niger since 2005, which aims to increase the efficacy and availability of antimalarial drugs whilst controlling the spread of resistance.

Metabolic enzymes have been known to carry out a variety of functions besides their normal housekeeping roles known as "moonlighting functions." These functionalities arise from structural changes induced by posttranslational modifications and/or binding of interacting proteins. Glycolysis is the sole source of energy generation for malaria parasite Plasmodium falciparum, hence a potential pathway for therapeutic intervention. Crystal structures of several P. falciparum glycolytic enzymes have been solved, revealing that they exhibit unique structural differences from the respective host enzymes, which could be exploited for their selective targeting. In addition, these enzymes carry out many parasite-specific functions, which could be of potential interest to control parasite development and transmission. This review focuses on the moonlighting functions of P. falciparum glycolytic enzymes and unique structural differences and functional features of the parasite enzymes, which could be exploited for therapeutic and transmission blocking interventions against malaria.

This study, conducted as part of our overall goal of regular pharmacovigilance of antimalarial medicines, reports on the quality of 132 artemisinin-based antimalarial medicines distributed in Ghana and Togo. Three methods were employed in the quality evaluation-basic (colorimetric) tests for establishing the identity of the requisite active pharmaceutical ingredients (APIs), semi-quantitative TLC assay for the identification and estimation of API content, and HPLC assay for a more accurate quantification of API content. From the basic tests, only one sample totally lacked API. The HPLC assay, however, showed that 83.7% of the ACTs and 57.9% of the artemisinin-based monotherapies failed to comply with international pharmacopoeia requirements due to insufficient API content. In most of the ACTs, the artemisinin component was usually the insufficient API. Generally, there was a good correlation between the HPLC and SQ-TLC assays. The overall failure rates for both locally manufactured (77.3%) and imported medicines (77.5%) were comparable. Similarly the unregistered medicines recorded a slightly higher overall failure rate (84.7%) than registered medicines (70.8%). Only two instances of possible cross-border exchange of medicines were observed and there was little difference between the medicine quality of collections from border towns and those from inland parts of both countries.

Submicroscopic infections account for more than 50% of all Plasmodium (P.) infections in areas with decreasing malaria prevalence and might contribute to poor pregnancy outcomes. The frequency of submicroscopic P. falciparum infections was assessed in matched peripheral and placental blood samples with microscopy negative or discordant results according to IPTp administration. Methods. P. falciparum infection was detected by nested PCR in matched blood samples collected from delivering women with a history of antimalarial drug treatment and living in Gabon. Results. Submicroscopic P. falciparum infections were detected in 87% (n = 33) of the 44 selected matched samples. Plasmodial DNA was found in 90% (n = 35/39) and 87% (n = 33/38) of microscopy negative peripheral and placental blood samples, respectively. Overall, 95% of samples obtained during the high IPTp-SP coverage period had a submicroscopic infection versus 79% among those from the low coverage period. Conclusion. Submicroscopic infections frequency is high in peripheral and placental blood samples from delivering women with a history of antimalarial treatment whatever the level of IPTp coverage. These data highlight the need of accurate diagnostic tools for a regular antenatal screening of malaria during the pregnancy in endemic areas.