The content of African diets is adequate to achieve optimal efficacy with fixed-dose artemether-lumefantrine: a review of the evidence

A fixed-dose combination of artemether-lumefantrine (AL, Coartem®) has shown high efficacy, good tolerability and cost-effectiveness in adults and children with uncomplicated malaria caused by Plasmodium falciparum. Lumefantrine bioavailability is enhanced by food, particularly fat

Similar efficacy and safety of artemether-lumefantrine (Coartem®) in African infants and children with uncomplicated falciparum malaria across different body weight ranges

<p>Abstract</p> <p>Background</p> <p>Artemisinin-based combination therapy, including artemether-lumefantrine (AL), is currently recommended for the treatment of uncomplicated <it>Plasmodium falciparum </it>malaria. The objectives of the current analysis were to compare the efficacy and safety of AL across different body weight ranges in African children, and to examine the age and body weight relationship in this population.</p> <p>Methods</p> <p>Efficacy, safety and pharmacokinetic data from a randomized, investigator-blinded, multicentre trial of AL for treatment of acute uncomplicated <it>P. falciparum </it>malaria in infants and children in Africa were analysed according to body weight group.</p> <p>Results</p> <p>The trial included 899 patients (intent-to-treat population 886). The modified intent-to-treat (ITT) population (n = 812) comprised 143 children 5 to < 10 kg, 334 children 10 to < 15 kg, 277 children 15 to < 25 kg, and 58 children 25 to < 35 kg. The 28-day PCR cure rate, the primary endpoint, was comparable across all four body weight groups (97.2%, 98.9%, 97.8% and 98.3%, respectively). There were no clinically relevant differences in safety or tolerability between body weight groups. In the three AL body weight dosing groups (5 to < 15 kg, 15 to < 25 kg and 25 to < 35 kg), 80% of patients were aged 10-50 months, 46-100 months and 90-147 months, respectively.</p> <p>Conclusion</p> <p>Efficacy of AL in uncomplicated falciparum malaria is similar across body weight dosing groups as currently recommended in the label with no clinically relevant differences in safety or tolerability. AL dosing based on body weight remains advisable.</p

Knowledge of caregivers of febrile children about fever, paracetamol use and paracetamol induced hepatic toxicity in Lagos Nigeria. 1 1

ABSTRACT Background: Fever is as a result of immune response to many pathogens. Paracetamol is widely and irrationally used at home for treatment of fever in children before presentation at the health facility but it is not clear whether caregivers are aware of the toxicity that can result from non-rational use of paracetamol

Toxicological evaluation of a polyherbal formulation on biochemical parameters in Spraque-Dawley rats

Background: Alomo bitters is an alcoholic polyherbal formulation consumedorally in Nigeria for its anti-pile and libido enhancing effects.Objective: This study was designed to evaluate the toxicity of the alcoholic herbal formulation of subchronic oral administration in laboratory rats.Methods: The oral LD50 was determined using the Miller and Tainter method. For the subchronic study, rats of both sexes were administered 0.12, 0.25 and 0.5 mL/kg of alomo bitters daily for 40 days while control rats were administered 5 mL/kg distilled water. At the end of the study, animals were sacrificed by cervical dislocation and blood samples collected for hematological and biochemical analysis.Results: The LD50 oral was found to be 1.74mL/kg. There was progressive increase in mean weight gain of treated rats at 0.25 and 0.5 mL/kg respectively compared to control. For the biochemical assay, a dose dependent significant (p&lt; 0.05) increase was observed in the level of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), creatinine, total cholesterol, triglycerides and low density lipoprotein (LDL) with a corresponding significant decrease in high density lipoprotein (HDL) at 0.25 and 0.5 mL/kg respectively compared to the controls.In the hematological assay, there was significant (p &lt; 0.05) reduction in PCV and RBC at 0.25 and 0.5 mL/kg. Conversely, WBC was significantly (p&lt; 0.05) increased at 0.25 and 0.5 mL/kg respectively.Conclusion: The alcoholic herbal formulation investigated in this study can be considered relatively safe for consumption at lower doses within a short period of time. However, long term consumption of the herbal drink and at high doses poses a significant risk and damaging effect hence, could compromise human health.Keywords: Polyherbal, subchronic, hematological, biochemica

Effect of riboceine on neuropsychiatric symptoms and oxidative stress parameters in hippocampus and frontal lobe of 4-vinylcyclohexene diepoxide induced perimenopausal rats

Memory impairment and anxiety are common perimenopausal symptoms with pathophysiologic mechanisms linked to oxidative stress. The study investigated the effect of Riboceine (CGVT ), an antioxidant on memory impairment and anxiety during perimenopausal transition in rats.Immature female Sprague-Dawley rats were divided into 2 groups; PREMP injected with corn oil (2.5μl/g BW); VCD injected with 4-vinylcyclohexene diepoxide (160 mg/kg BW) in corn oil for 15 days. A 3rd group of older and matured female rats (AGING) at 90 days of age was left to age naturally till 200 days. Fourteen weeks after VCD/corn oil administrations, and 200 days in Aged group, rats were administered Riboceine (200mg/kg BW) and distilled water for additional 30 days. At 150–165 days in PREMP and VCD groups, 215–230 days in AGING group on diestrus morning, animals were subjected to cognitive Y maze and anxiety tests. The animals were humanely sacrificed, brains isolated, weighed and homogenized for measurement of GSH, SOD, catalase and MDA. There was no significant difference in percentage correct alternation in VCD PRM and AGING PRM groups on CGVT compared to distilled water. The closed versus open arm ratio was significantly higher in VCD PRM and AGING PRM groups compared to the PREMP group. Riboceine significantly reduced (p &lt; 0.05) SOD and catalase activities in both frontal lobe and hippocampus of perimenopausal rats. It significantly reduced (p &lt; 0.05) MDAlevels in frontal lobe of premenopausal and perimenopausal rats and had opposing effect in the hippocampus. Our results suggest that Riboceine at supra-therapeutic dose had no effect on memory and anxiety in the perimenopausal rats. AbstraitLes troubles de la mémoire et l'anxiété sont des symptômes courants de la périménopause avec des mécanismes physiopathologiques liés au stress oxydatif. L'étude a examiné l'effet de Riboceine® (CGVT), un antioxydant sur les troubles de la mémoire et l'anxiété pendant la transition périménopausique chez le rat. Les rats femelles immatures Sprague-Dawley ont été divisés en 2 groupes; PREMP injecté avec de l'huile de maïs (2,5 μl / g BW); VCD injecté avec du diépoxyde de 4-vinylcyclohexène (160 mg / kg pc) dans de l'huile de maïs pendant 15 jours. Un troisième groupe de rats femelles âgés et matures (VIEILLISSEMENT) à 90 jours a été laissé vieillir naturellement jusqu'à 200 jours. Quatorze semaines après l'administration de VCD / huile de maïs et 200 jours dans le groupe âgé, on a administré à des rats Riboceine® (200 mg / kg de poids corporel) et de l'eau distillée pendant 30 jours supplémentaires. À 150–165 jours dans les groupes PREMP et VCD, 215–230 jours dans le groupe AGING le matin du diestrus, les animaux ont été soumis à des tests de labyrinthe cognitif en Y et d'anxiété. Les animaux ont été sacrifiés sans cruauté, les cerveaux isolés, pesés et homogénéisés pour la mesure de GSH, SOD, catalase et MDA. Il n'y avait pas de différence significative dans le pourcentage d'alternance correcte dans les groupes VCD PRM et AGING PRM sur CGVT par rapport à l';eau distillée. Le ratio bras fermé / bras ouvert était significativement plus élevé dans les groupes VCD PRM et AGING PRM que dans le groupe PREMP. La riboceine® a réduit de manière significative (p &amp;lt;0,05) les activités de SOD et de catalase dans le lobe frontal et l'hippocampe de rats en périménopause. Il a significativement réduit (p &amp;lt;0,05) les taux de MDAdans le lobe frontal des rats préménopausiques et périménopausiques et a eu un effet opposé dans l'hippocampe. Nos résultats suggèrent que Riboceine® à dose supra-thérapeutique n'a eu aucun effet sur la mémoire et l'anxiété chez les rats périménopausiques

The content of African diets is adequate to achieve optimal efficacy with fixed-dose artemether-lumefantrine: a review of the evidence

Abstract A fixed-dose combination of artemether-lumefantrine (AL, Coartem®) has shown high efficacy, good tolerability and cost-effectiveness in adults and children with uncomplicated malaria caused by Plasmodium falciparum. Lumefantrine bioavailability is enhanced by food, particularly fat. As the fat content of sub-Saharan African meals is approximately a third that of Western countries, it raises the question of whether fat consumption by African patients is sufficient for good efficacy. Data from healthy volunteers have indicated that drinking 36 mL soya milk (containing only 1.2 g of fat) results in 90% of the lumefantrine absorption obtained with 500 mL milk (16 g fat). African diets are typically based on a carbohydrate staple (starchy root vegetables, fruit [plantain] or cereals) supplemented by soups, relishes and sauces derived from vegetables, pulses, nuts or fish. The most important sources of dietary fat in African countries are oil crops (e.g. peanuts, soya beans) and cooking oils as red palm, peanut, coconut and sesame oils. Total fat intake in the majority of subSaharan countries is estimated to be in the range 30–60 g/person/day across the whole population (average 43 g/person/day). Breast-feeding of infants up to two years of age is standard, with one study estimating a fat intake of 15–30 g fat/day from breast milk up to the age of 18 months. Weaning foods typically contain low levels of fat, and the transition from breast milk to complete weaning is associated with a marked reduction in dietary fat. Nevertheless, fat intake >10 g/day has been reported in young children post-weaning. A randomized trial in Uganda reported no difference in the efficacy of AL between patients receiving supervised meals with a fixed fat content (~23 g fat) or taking AL unsupervised, suggesting that fat intake at home was sufficient for optimal efficacy. Moreover, randomized trials in African children aged 5–59 months have shown similar high cure rates to those observed in older populations, indicating that food consumption is adequate post-weaning. In conclusion, it appears that only a very small amount of dietary fat is necessary to ensure optimal efficacy with AL and that the fat content of standard meals or breast milk in sub-Saharan Africa is adequate.</p