Early transmission of sensitive strain slows down emergence of drug resistance in Plasmodium vivax

Ayala, Mario J. C.; Villela, Daniel A. M.

doi:10.1371/journal.pcbi.1007945

Cited by 5 publications

(14 citation statements)

References 79 publications

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“…While mathematical and computational models have been extraordinarily useful for investigating the processes driving patterns of resistance evolution in malaria parasites [36,37,[40][41][42][43][44][45][46][47][48][49], as far as we are aware, none have explored the potential for interactions between selection for antigenic novelty and selection for drug resistance. Additionally, many have necessarily made simplifying assumptions, such as simulating homogeneous host populations, introducing mutations at a relatively high frequency, or using deterministic models of evolutionary dynamics.…”

Section: Introductionmentioning

confidence: 99%

Immune selection suppresses the emergence of drug resistance in malaria parasites but facilitates its spread

2021

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Although drug resistance in Plasmodium falciparum typically evolves in regions of low transmission, resistance spreads readily following introduction to regions with a heavier disease burden. This suggests that the origin and the spread of resistance are governed by different processes, and that high transmission intensity specifically impedes the origin. Factors associated with high transmission, such as highly immune hosts and competition within genetically diverse infections, are associated with suppression of resistant lineages within hosts. However, interactions between these factors have rarely been investigated and the specific relationship between adaptive immunity and selection for resistance has not been explored. Here, we developed a multiscale, agent-based model of Plasmodium parasites, hosts, and vectors to examine how host and parasite dynamics shape the evolution of resistance in populations with different transmission intensities. We found that selection for antigenic novelty (“immune selection”) suppressed the evolution of resistance in high transmission settings. We show that high levels of population immunity increased the strength of immune selection relative to selection for resistance. As a result, immune selection delayed the evolution of resistance in high transmission populations by allowing novel, sensitive lineages to remain in circulation at the expense of the spread of a resistant lineage. In contrast, in low transmission settings, we observed that resistant strains were able to sweep to high population prevalence without interference. Additionally, we found that the relationship between immune selection and resistance changed when resistance was widespread. Once resistance was common enough to be found on many antigenic backgrounds, immune selection stably maintained resistant parasites in the population by allowing them to proliferate, even in untreated hosts, when resistance was linked to a novel epitope. Our results suggest that immune selection plays a role in the global pattern of resistance evolution.

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Section: Introductionmentioning

confidence: 99%

Immune selection suppresses the emergence of drug resistance in malaria parasites but facilitates its spread

2021

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“…Finally, functions of climate variables are applied to parameters in a mathematical model to describe transmission in municipalities of this region. Our study then connects the impacts of wavelet and coherence analysis into the mathematical modeling through a compartmental model, extending a very recent model [19] capable of differentiating sensitive and resistant strains of malaria.…”

Section: Introductionmentioning

confidence: 90%

“…The model used in this work to assess P. vivax notification data is derived from the model of Ayala and Villela (2020) [19], which considers the impact of pharmaceutical interventions in their modeling. The modification relies on assuming that some parameters can be modeled as a function of temperature, namely the biting rate, the adult mosquito death ratio, the daily survivorship of larvae, the duration of the larvae stage, and the egg daily deposition rate.…”

Section: Modelingmentioning

confidence: 99%

Disentangling the seasonality effects of malaria transmission in the Brazilian Amazon Basin

Valiati

Villela

2022

Preprint

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The current evidence of seasonality effects in the malaria epidemiology of the Brazilian Amazon Basin indicates the need for a rigorous examination in such a large geographical area. Furthermore, as seasonal effects are related to climate variables, malaria models should incorporate these effects. This study applies wavelet analysis over incidence data in the SIVEP-malaria surveillance database. A mathematical model with climate-dependent parameterization is proposed to study counts of malaria cases over time based on notification data, temperature, and rainfall. The wavelet analysis reveals marked seasonality in states such as Amazonas and Pará, whereas not so clear in recent years for states such as Acre and Pará. The wavelet cross-power analysis indicates a strong association between incidence and temperature, especially for cities Macapá and Manaus, and a similar association for rainfall. The mathematical model replicates temporal trends observed in incidences of these two cities. Studies on climate-dependent mathematical models provide a good assessment of the baseline epidemiology of malaria. In addition, the knowledge of seasonality effects and the application of models have great potential as tools for studying interventions for malaria control.

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Section: Introductionmentioning

confidence: 99%

“…While mathematical and computational models have been extraordinarily useful for investigating the processes driving patterns of resistance evolution in malaria parasites [19,21,36,37,40–47], as far as we are aware, none have explored the potential for interactions between selection for antigenic novelty and selection for drug resistance. Additionally, many have necessarily made simplifying assumptions, such as simulating homogeneous host populations, introducing mutations at a relatively high frequency, or using deterministic models of evolutionary dynamics.…”

Section: Introductionmentioning

confidence: 99%

Immune selection suppresses the emergence of drug resistance in malaria parasites but facilitates its spread

Whitlock

Juliano

Mideo

2020

Preprint

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Although drug resistance in Plasmodium falciparum typically evolves in regions of low transmission, resistance spreads readily following introduction to regions with a heavier disease burden. This suggests that the origin and the spread of resistance are governed by different processes, and that high transmission intensity specifically impedes the origin. Factors associated with high transmission, such as highly immune hosts and competition within genetically diverse infections, are associated with suppression of resistant lineages within hosts. However, interactions between these factors have rarely been investigated and the specific relationship between adaptive immunity and selection for resistance has not been explored. Here, we developed a multiscale, agent-based model of Plasmodium parasites, hosts, and vectors to examine how host and parasite dynamics shape the evolution of resistance in populations with different transmission intensities. We found that selection for antigenic novelty (“immune selection”) and within-host competition both suppressed the evolution of resistance in high transmission settings. We show that high levels of population immunity increased the strength of immune selection relative to selection for resistance. As a result, immune selection delayed the evolution of resistance in high transmission populations by allowing novel, sensitive lineages to remain in circulation at the expense of common, resistant lineages. In contrast, in low transmission populations, we observed that common, resistant strains were able to sweep to high population prevalence without interference. Additionally, we found that the relationship between immune selection and resistance changed when resistance was widespread in the population. Once resistance was common enough to be found on many antigenic backgrounds, immune selection stably maintained resistance in the population because resistance was able to proliferate, even in untreated hosts, when it was linked to a novel epitope. The results of our simulations demonstrate that immune selection plays a major role in observed dynamics of resistance evolution.

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Early transmission of sensitive strain slows down emergence of drug resistance in Plasmodium vivax

Cited by 5 publications

References 79 publications

Immune selection suppresses the emergence of drug resistance in malaria parasites but facilitates its spread

Immune selection suppresses the emergence of drug resistance in malaria parasites but facilitates its spread

Disentangling the seasonality effects of malaria transmission in the Brazilian Amazon Basin

Immune selection suppresses the emergence of drug resistance in malaria parasites but facilitates its spread

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