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.
Highlights
Introduction of drug AB or BCHuman populationNumber of malaria cases per yearMalaria transmission and immunity in a “steady state”Malaria transmission and spread of resistance to drug-sensitive and symptomatic humans receive only monotherapy (drug A)Number of patent malaria casesResistance to drug A TimeSFcigheumreat1ic diagram of the biological model through time Schematic diagram of the biological model through time
Resistance, transmission intensity and artemisininbased combination therapy (ACT) coverage Model consistency and model sensitivity are explored in four baseline scenarios (low transmission setting with low ACT coverage, low transmission setting with high ACT coverage, high transmission setting with low ACT coverage and high transmission with high ACT coverage)
The model consistency is expressed as the Coefficient of Variation (CV) i.e. the variations in the model outputs given that there are uncertainties in the input parameter estimated (Tables S9, Additional File 3)
Summary
Introduction of drug AB or BCHuman populationNumber of malaria cases per yearMalaria transmission and immunity in a “steady state”Malaria transmission and spread of resistance to drug ANumber of patent malaria casesResistance to drug A Time (years)SFcigheumreat1ic diagram of the biological model through time Schematic diagram of the biological model through time. Most malaria-endemic countries are implementing a change in anti-malarial drug policy to artemisininbased combination therapy (ACT). The World Health Organization (WHO) recommends artemisinin-based combination therapy (ACT) as first-line treatment for all falciparum malaria in endemic areas [1]. As for any combination therapy, which involves two effective drugs from different classes, both component drugs protect each other from the development of drug resistance, whilst present at effective concentrations. This should prolong their useful lifespan provided that the individual components are not widely available as monotherapies [6]
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