Spread of anti-malarial drug resistance: Mathematical model with implications for ACT drug policiesReport as inadecuate




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Malaria Journal

, 7:229

First Online: 02 November 2008Received: 14 July 2008Accepted: 02 November 2008

Abstract

BackgroundMost malaria-endemic countries are implementing a change in anti-malarial drug policy to artemisinin-based combination therapy ACT. The impact of different drug choices and implementation strategies is uncertain. Data from many epidemiological studies in different levels of malaria endemicity and in areas with the highest prevalence of drug resistance like borders of Thailand are certainly valuable. Formulating an appropriate dynamic data-driven model is a powerful predictive tool for exploring the impact of these strategies quantitatively.

MethodsA comprehensive model was constructed incorporating important epidemiological and biological factors of human, mosquito, parasite and treatment. The iterative process of developing the model, identifying data needed, and parameterization has been taken to strongly link the model to the empirical evidence. The model provides quantitative measures of outcomes, such as malaria prevalence-incidence and treatment failure, and illustrates the spread of resistance in low and high transmission settings. The model was used to evaluate different anti-malarial policy options focusing on ACT deployment.

ResultsThe model predicts robustly that in low transmission settings drug resistance spreads faster than in high transmission settings, and treatment failure is the main force driving the spread of drug resistance. In low transmission settings, ACT slows the spread of drug resistance to a partner drug, especially at high coverage rates. This effect decreases exponentially with increasing delay in deploying the ACT and decreasing rates of coverage. In the high transmission settings, however, drug resistance is driven by the proportion of the human population with a residual drug level, which gives resistant parasites some survival advantage. The spread of drug resistance could be slowed down by controlling presumptive drug use and avoiding the use of combination therapies containing drugs with mismatched half-lives, together with reducing malaria transmission through vector control measures.

ConclusionThis paper has demonstrated the use of a comprehensive mathematical model to describe malaria transmission and the spread of drug resistance. The model is strongly linked to the empirical evidence obtained from extensive data available from various sources. This model can be a useful tool to inform the design of treatment policies, particularly at a time when ACT has been endorsed by WHO as first-line treatment for falciparum malaria worldwide.

AbbreviationsSPsulphadoxine – pyrimethamine

ACTartemisinin combination therapy

GSRgametocyte switching rate, proportion of asexual parasites committing to sexual stage differentiation

EIRentomological inoculation rate

VCvectorial capacity

AICthe Akaike information criterion

AUCgamarea under the curve of time versus blood gametocyte density

PRRparasite reduction ratio, fractional reduction in parasitaemia per asexual cycle

LHSLatin hypercube sampling

CVcoefficient of variation

PRCCpartial rank correlation coefficient

ITNinsecticide-treated bednet.

Electronic supplementary materialThe online version of this article doi:10.1186-1475-2875-7-229 contains supplementary material, which is available to authorized users.

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Author: Wirichada Pongtavornpinyo - Shunmay Yeung - Ian M Hastings - Arjen M Dondorp - Nicholas PJ Day - Nicholas J White

Source: https://link.springer.com/



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