Chloroquine is grossly under dosed in young children with malaria : implications for drug resistance

Background: Plasmodium falciparum malaria is treated with 25 mg/kg of chloroquine (CQ) irrespective of age. Theoretically, CQ should be dosed according to body surface area (BSA). The effect of dosing CQ according to BSA has not been determined but doubling the dose per kg doubled the efficacy of CQ in children aged <15 years infected with P. falciparum carrying CQ resistance causing genes typical for Africa. The study aim was to determine the effect of age on CQ concentrations. Methods and Findings: Day 7 whole blood CQ concentrations were determined in 150 and 302 children treated with 25 and 50 mg/kg, respectively, in previously conducted clinical trials. CQ concentrations normalised for the dose taken in mg/kg of CQ decreased with decreasing age (p<0.001). CQ concentrations normalised for dose taken in mg/m(2) were unaffected by age. The median CQ concentration in children aged <2 years taking 50 mg/kg and in children aged 10-14 years taking 25 mg/kg were 825 (95% confidence interval [CI] 662-988) and 758 (95% CI 640-876) nmol/l, respectively (p = 0.67). The median CQ concentration in children aged 10-14 taking 50 mg/kg and children aged 0-2 taking 25 mg/kg were 1521 and 549 nmol/l. Adverse events were not age/concentration dependent. Conclusions: CQ is under-dosed in children and should ideally be dosed according to BSA. Children aged <2 years need approximately double the dose per kg to attain CQ concentrations found in children aged 10-14 years. Clinical trials assessing the efficacy of CQ in Africa are typically performed in children aged <5 years. Thus the efficacy of CQ is typically assessed in children in whom CQ is under dosed. Approximately 3 fold higher drug concentrations can probably be safely given to the youngest children. As CQ resistance is concentration dependent an alternative dosing of CQ may overcome resistance in Africa.

Population pharmacokinetics and pharmacodynamics of lumefantrine in young Ugandan children treated with artemether-lumefantrine for uncomplicated malaria

Background. The pharmacokinetics and pharmacodynamics of lumefantrine, a component of the most widely used treatment for malaria, artemether-lumefantrine, has not been adequately characterized in young children. Methods. Capillary whole-blood lumefantrine concentration and treatment outcomes were determined in 105 Ugandan children, ages 6 months to 2 years, who were treated for 249 episodes of Plasmodium falciparum malaria with artemether-lumefantrine. Results. Population pharmacokinetics for lumefantrine used a 2-compartment open model with first-order absorption. Age had a significant positive correlation with bioavailability in a model that included allometric scaling. Children not receiving trimethoprim-sulfamethoxazole with capillary whole blood concentrations <200 ng/mL had a 3-fold higher hazard of 28-day recurrent parasitemia, compared with those with concentrations >200 ng/mL (P =. 0007). However, for children receiving trimethoprim-sulfamethoxazole, the risk of recurrent parasitemia did not differ significantly on the basis of this threshold. Day 3 concentrations were a stronger predictor of 28-day recurrence than day 7 concentrations. Conclusions. We demonstrate that age, in addition to weight, is a determinant of lumefantrine exposure, and in the absence of trimethoprim-sulfamethoxazole, lumefantrine exposure is a determinant of recurrent parasitemia. Exposure levels in children aged 6 months to 2 years was generally lower than levels published for older children and adults. Further refinement of artemether-lumefantrine dosing to improve exposure in infants and very young children may be warranted. © 2016 The Author.

Science is Primary - Children Thinking and Learning in theChemistry Laboratory

The goal of primary science education is to foster children’s interest, develop positive science attitudes and promote science process skills development. Learning by playing and discovering provides several opportunities for children to inquiry and understand science based on the first–hand experience. The current research was conducted in the children’s laboratory in Heureka, the Finnish science centre. Young children (aged 7 years) which came from 4 international schools did a set of chemistry experiments in the laboratory. From the results of the cognitive test, the pre-test, the post-test, supported by observation and interview, we could make the conclusion that children enjoyed studying in the laboratory. Chemistry science was interesting and fascinating for young children; no major gender differences were found between boys and girls learning in the science laboratory. Lab work not only encouraged children to explore and investigate science, but also stimulated children’s cognitive development.

Big Data Analysis in Social Networks : Extracting Food Preferences of Vegans from Twitter

Market research is often conducted through conventional methods such as surveys, focus groups and interviews. But the drawbacks of these methods are that they can be costly and timeconsuming. This study develops a new method, based on a combination of standard techniques like sentiment analysis and normalisation, to conduct market research in a manner that is free and quick. The method can be used in many application-areas, but this study focuses mainly on the veganism market to identify vegan food preferences in the form of a profile. Several food words are identified, along with their distribution between positive and negative sentiments in the profile. Surprisingly, non-vegan foods such as cheese, cake, milk, pizza and chicken dominate the profile, indicating that there is a significant market for vegan-suitable alternatives for such foods. Meanwhile, vegan-suitable foods such as coconut, potato, blueberries, kale and tofu also make strong appearances in the profile. Validation is performed by using the method on Volkswagen vehicle data to identify positive and negative sentiment across five car models. Some results were found to be consistent with sales figures and expert reviews, while others were inconsistent. The reliability of the method is therefore questionable, so the results should be used with caution.