Transmission Intensity and Drug Resistance in Malaria Population Dynamics: Implications for Climate Change

Yael Artzy-Randrup,Mercedes Pascual,David Alonso,Stephen J. Cornell

doi:10.1371/journal.pone.0013588

Yael Artzy-Randrup, Mercedes Pascual + Show 2 more

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https://doi.org/10.1371/journal.pone.0013588

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Abstract

Although the spread of drug resistance and the influence of climate change on malaria are most often considered separately, these factors have the potential to interact through altered levels of transmission intensity. The influence of transmission intensity on the evolution of drug resistance has been addressed in theoretical studies from a population genetics' perspective; less is known however on how epidemiological dynamics at the population level modulates this influence. We ask from a theoretical perspective, whether population dynamics can explain non-trivial, non-monotonic, patterns of treatment failure with transmission intensity, and, if so, under what conditions. We then address the implications of warmer temperatures in an East African highland, where, as in other similar regions at the altitudinal edge of malaria's distribution, there has been a pronounced increase of cases from the 1970s to the 1990s. Our theoretical analyses, with a transmission model that includes different levels of immunity, demonstrate that an increase in transmission beyond a threshold can lead to a decrease in drug resistance, as previously shown [1], but that a second threshold may occur and lead to the re-establishment of drug resistance. Estimates of the increase in transmission intensity from the 1970s to the 1990s for the Kenyan time series, obtained by fitting the two-stage version of the model with an explicit representation of vector dynamics, suggest that warmer temperatures are likely to have moved the system towards the first threshold, and in so doing, to have promoted the faster spread of drug resistance. Climate change and drug resistance can interact and need not be considered as alternative explanations for trends in disease incidence in this region. Non-monotonic patterns of treatment failure with transmission intensity similar to those described as the ‘valley phenomenon’ for Uganda can result from epidemiological dynamics but under poorly understood assumptions.

Highlights

Evolutionary change is one main challenge to the understanding and prediction of climate change impacts on biological systems
We end with implications of our findings in relation to empirical patterns, including the ‘valley phenomenon’ described for CQ in the Uganda highlands, where treatment failure was found to be higher in areas of low and high transmission, and at it’s lowest at intermediate transmission areas [22,23,24]
Our findings underscore that drug resistance and climate change can interact through the effects of warmer temperatures on transmission intensity

Summary

Introduction

Evolutionary change is one main challenge to the understanding and prediction of climate change impacts on biological systems. Environmental and evolutionary drivers of biological change are likely to interact in ways poorly understood. One area where this interaction has the potential to act on relatively fast time scales is the dynamics of vector-transmitted diseases. These diseases, such as malaria, are especially sensitive to changes in environmental conditions. Warmer temperatures accelerate physiological processes of the mosquito vector, leading to increased activity such as biting rate, growth, development and reproduction. Physiological processes of parasite development within the vector are affected by temperature levels in a nonlinear way [2,3,4,5]. Temperature plays a key limiting role on malaria at the edge of the altitudinal distribution of the disease, in highland regions, where the parasite is not likely to complete development during the lifetime of its vector

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