Hyperparasitaemia and low dosing are an important source of anti-malarial drug resistance

BACKGROUND: Preventing the emergence of anti-malarial drug resistance is critical for the success of current malaria elimination efforts. Prevention strategies have focused predominantly on qualitative factors, such as choice of drugs, use of combinations and deployment of multiple first-line treatments. The importance of anti-malarial treatment dosing has been underappreciated. Treatment recommendations are often for the lowest doses that produce "satisfactory" results. METHODS: The probability of de-novo resistant malaria parasites surviving and transmitting depends on the relationship between their degree of resistance and the blood concentration profiles of the anti-malarial drug to which they are exposed. The conditions required for the in-vivo selection of de-novo emergent resistant malaria parasites were examined and relative probabilities assessed. RESULTS: Recrudescence is essential for the transmission of de-novo resistance. For rapidly eliminated anti-malarials high-grade resistance can arise from a single drug exposure, but low-grade resistance can arise only from repeated inadequate treatments. Resistance to artemisinins is, therefore, unlikely to emerge with single drug exposures. Hyperparasitaemic patients are an important source of de-novo anti-malarial drug resistance. Their parasite populations are larger, their control of the infection insufficient, and their rates of recrudescence following anti-malarial treatment are high. As use of substandard drugs, poor adherence, unusual pharmacokinetics, and inadequate immune responses are host characteristics, likely to pertain to each recurrence of infection, a small subgroup of patients provides the particular circumstances conducive to de-novo resistance selection and transmission. CONCLUSION: Current dosing recommendations provide a resistance selection opportunity in those patients with low drug levels and high parasite burdens (often children or pregnant women). Patients with hyperparasitaemia who receive outpatient treatments provide the greatest risk of selecting de-novo resistant parasites. This emphasizes the importance of ensuring that only quality-assured anti-malarial combinations are used, that treatment doses are optimized on the basis of pharmacodynamic and pharmacokinetic assessments in the target populations, and that patients with heavy parasite burdens are identified and receive sufficient treatment to prevent recrudescence

The effectiveness of mathematics teaching: a cross-national investigation in primary schools in England and China

This study focuses on the effectiveness of mathematics teaching to children aged 9-10 years, applies a mixture of six methods to classroom-level data collected in England and China, correlates observable teacher behaviours with pupil mathematics performance and collects multiple perceptions that indirectly connect with the differences of teaching and learning cross-nationally. It has been found in the study that 9-to 10-year-olds (n = 343) from China outscored their English peers (n = 236) at the same age by over 20 per cent in each of two mathematics tests derived from TIMSS 2003. Structured analysis of lesson videos has revealed that Chinese mathematics teachers scored much higher than their English colleagues on an internationally validated observation instrument which focused on the quality of six dimensions of teacher behaviours. Furthermore, the quantity of teacher behaviours was also measured and the subsequent correlational analysis on pooled data indicated a positive effect of whole-class interactive teaching (r = 0.97, p < 0.01) and pupil time on task (r = 0.95, p < 0.01) and a negative impact of whole-class lecture (r = -0.91, p < 0.01), individual/group work (r=-0.81, p < 0.05) and classroom management (r = -0.77, p < 0.05) on pupils’ mathematics performance cross-nationally. Qualitative findings are connected with quantitative results to explain how teachers think, how this relates to the way they teach and how the differences of teaching result in the performance gap cross-nationally. The study replicated previous TER findings from the West across two geographically and culturally different countries, suggested possible directions for future enquiries, and recommended potential ways for practice and policy innovations