Ian Hastings

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..Formulating an appropriate dynamic data-driven model is a powerful predictive tool for exploring the impact of these strategies quantitatively...

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..This study examined the relationship between climate and malaria incidence in Kagera with the aim of determining whether seasonal forecasts may assist in predicting malaria epidemics...

..For example a person with four malaria clones may contain both mutant and wildtype forms of a marker but it is not possible to distinguish the relative frequencies of the mutant and wildtypes i.e. 1:3, 2:2 or 3:1...

..This intermediate stage between fully sensitive and fully resistant parasites has far-reaching implications for the evolution of drug-resistant malaria...

..This explanation is novel and the results are equally applicable to other parasitic species where multiple infections of the same host are common...

..This seems dubious from a population genetics perspective, where intuition would lead to the opposite conclusion. The objective was to reconcile these differing views...

..e. failures not caused by the mutation), to mutation prevalence, and to the genetic background in which the marker occurs. Extreme care should therefore be taken in the construction and interpretation of these indices...

..We show that parasitological failure is the most sensitive and timely indicator, which allows around 2-3 years for drug policy change to be implemented, so as to prevent the most rapid rise in malaria-related mortality...

..In contrast, effective family planning may rapidly increase both mutation frequency and disease incidence...

..We discuss the assumptions made in such modeling approaches and how similar approaches may be refined in future work...

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..Parasites incur periodic mutations which must ultimately be eliminated to maintain their genetic integrity...

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..It is essential to account for genotyping missing minor clones; ignoring this phenomenon resulted in a 2-fold underestimation of SNPs and haplotypes present at low frequencies...

..Consequently, strategies to slow the spread of resistance need to be designed on regional, rather than national, considerations...

..The model is also applicable to the evolution of antibiotic resistance in bacteria: in particular, the need for these models to incorporate drug pharmacokinetics to avoid potentially large errors in their predictions...

..We review several lines of evidence suggesting that such costs do occur, that they may be relatively large, and review their likely impact on the evolution of drug resistance in the malaria parasite Plasmodium falciparum...

..16 and a dominance coefficient of 0.25. Our data show that strong, recent positive selective events, such as those caused by insecticide resistance, can be identified in wild insect populations...

..falciparum to be a sexual organism whose genomes are in linkage equilibrium, which acts to slow the emergence of drug resistance and vaccine insensitivity, extending the likely useful therapeutic lifespan of drugs and vaccines...

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..Our findings indicate that African urban poor are seriously affected by malaria and that irrigated agriculture may increase this risk...

..The efflux of CQ in CQR lines is not directly coupled to the energy supply, consistent with a model in which mutant PfCRT functions as a gated channel or pore, allowing charged CQ species to leak out of the DV...

..Additionally, we highlight the lack of appropriate drug disposition data in pregnancy and suggest mechanisms that can be used to capture data on risk after drug treatment in pregnancy...

..This commentary reflects the discussions held during the meeting and aims to inform researchers and policy makers of the potential for containing and reversing the emerging problem of urban malaria...

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..CONCLUSIONS: Surveillance of birthweight differences between primigravidae and multigravidae is a useful indicator of malaria exposure...

..Our findings have important implications for malaria control because increasing drug resistance has a substantial impact on mortality...