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Transmission intensity and drug resistance in malaria population dynamics: implications for climate change.

Artzy-Randrup Y, Alonso D, Pascual M - PLoS ONE (2010)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Howard Hughes Medical Institute, Department of Ecology and Evolutionary Biology, University of Michigan, Ann Arbor, Michigan, United States of America. YArtzy@umich.edu

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, 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.

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Related in: MedlinePlus

Fraction of clinically immune individuals as a function of vectorial capacity for a two-class model scenario (the x-axis is given in log scale).Results of increasing strain diversity are plotted in escalating shades from top to bottom (gain of immunity  = 5 years,  = 10 years and  = 20 years, respectively). Threshold levels at which resistance is out competed by wild type, , are marked by horizontal gray lines (see definition of A and B in the Materials and Methods subsection, Thresholds in a two class model). For lower strain diversity, immunity is rapidly gained in the population and the threshold, , is low. Alternatively, when strain diversity is higher, immunity is gained more gradually, and the threshold is higher (Similar results are obtained for multiple classes).
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pone-0013588-g004: Fraction of clinically immune individuals as a function of vectorial capacity for a two-class model scenario (the x-axis is given in log scale).Results of increasing strain diversity are plotted in escalating shades from top to bottom (gain of immunity  = 5 years,  = 10 years and  = 20 years, respectively). Threshold levels at which resistance is out competed by wild type, , are marked by horizontal gray lines (see definition of A and B in the Materials and Methods subsection, Thresholds in a two class model). For lower strain diversity, immunity is rapidly gained in the population and the threshold, , is low. Alternatively, when strain diversity is higher, immunity is gained more gradually, and the threshold is higher (Similar results are obtained for multiple classes).

Mentions: Figure 4 illustrates the role that strain diversity may have on the establishment of anti-malarial drug resistance. The expected threshold () for a two-class model is , where A and B are positive and as defined in the Materials and Methods section (Thresholds in a two class model). Hence, when the fraction of the population in the second immunity class () is below this threshold (), the resistant parasite out-competes the sensitive one, and when the fraction is above this threshold, the sensitive parasite out-competes the resistant. For different diversity levels, we find that the lower the diversity, the lower the vectorial capacity at which the threshold is crossed. Hence, the first threshold described in our analysis (as well as in [1]) can become a moving target, shifting towards higher values of transmission intensity as diversity also increases. This would make such threshold more difficult to reach with the population remaining in a regime where drug resistance is favored as transmission intensity increases.


Transmission intensity and drug resistance in malaria population dynamics: implications for climate change.

Artzy-Randrup Y, Alonso D, Pascual M - PLoS ONE (2010)

Fraction of clinically immune individuals as a function of vectorial capacity for a two-class model scenario (the x-axis is given in log scale).Results of increasing strain diversity are plotted in escalating shades from top to bottom (gain of immunity  = 5 years,  = 10 years and  = 20 years, respectively). Threshold levels at which resistance is out competed by wild type, , are marked by horizontal gray lines (see definition of A and B in the Materials and Methods subsection, Thresholds in a two class model). For lower strain diversity, immunity is rapidly gained in the population and the threshold, , is low. Alternatively, when strain diversity is higher, immunity is gained more gradually, and the threshold is higher (Similar results are obtained for multiple classes).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2965653&req=5

pone-0013588-g004: Fraction of clinically immune individuals as a function of vectorial capacity for a two-class model scenario (the x-axis is given in log scale).Results of increasing strain diversity are plotted in escalating shades from top to bottom (gain of immunity  = 5 years,  = 10 years and  = 20 years, respectively). Threshold levels at which resistance is out competed by wild type, , are marked by horizontal gray lines (see definition of A and B in the Materials and Methods subsection, Thresholds in a two class model). For lower strain diversity, immunity is rapidly gained in the population and the threshold, , is low. Alternatively, when strain diversity is higher, immunity is gained more gradually, and the threshold is higher (Similar results are obtained for multiple classes).
Mentions: Figure 4 illustrates the role that strain diversity may have on the establishment of anti-malarial drug resistance. The expected threshold () for a two-class model is , where A and B are positive and as defined in the Materials and Methods section (Thresholds in a two class model). Hence, when the fraction of the population in the second immunity class () is below this threshold (), the resistant parasite out-competes the sensitive one, and when the fraction is above this threshold, the sensitive parasite out-competes the resistant. For different diversity levels, we find that the lower the diversity, the lower the vectorial capacity at which the threshold is crossed. Hence, the first threshold described in our analysis (as well as in [1]) can become a moving target, shifting towards higher values of transmission intensity as diversity also increases. This would make such threshold more difficult to reach with the population remaining in a regime where drug resistance is favored as transmission intensity increases.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Howard Hughes Medical Institute, Department of Ecology and Evolutionary Biology, University of Michigan, Ann Arbor, Michigan, United States of America. YArtzy@umich.edu

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, 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.

Show MeSH
Related in: MedlinePlus