Modelling the impact of antimalarial quality on the transmission of sulfadoxine-pyrimethamine resistance in Plasmodium falciparum

Brock, Aleisha R.; Ross, Joshua V.; Greenhalgh, Scott; Durham, David P.; Galvani, Alison P.; Parikh, Sunil; Esterman, Adrian

doi:10.1016/j.idm.2017.04.001

Cited by 4 publications

(20 citation statements)

References 45 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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“…The authors simulated that using only quality-assured ACTs resulted in a 72.7% decrease in cases. 12 One-way sensitivity analysis showed mosquito parameters (such as ratio of mosquitos to humans, rate of mosquito maturity, probability of sporozoite transmission) to be especially important, as well as the rate of gametocyte clearance of infections treated with good quality ACTs.…”

Section: Models Examining Substandard and Falsified Medicinesmentioning

confidence: 99%

“…Only one model estimated the health impact of substandard and falsified medicines on drug resistance. Brock et al (2017) modeled the transmission dynamics of resistant infections using mathematical models of humans and mosquitos. 12 The model incorporated patient care-seeking, medicine use, and prevalence of substandard and falsified medicines from the literature.…”

Section: Models Examining Substandard and Falsified Medicinesmentioning

confidence: 99%

“…Brock et al (2017) modeled the transmission dynamics of resistant infections using mathematical models of humans and mosquitos. 12 The model incorporated patient care-seeking, medicine use, and prevalence of substandard and falsified medicines from the literature. Half doses of sulfadoxine/pyrimethamine (SP) were used to represent poorquality antimalarials, which resulted in longer duration of infectivity and higher malaria transmission.…”

Section: Models Examining Substandard and Falsified Medicinesmentioning

confidence: 99%

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Modeling the Health and Economic Impact of Substandard and Falsified Medicines: A Review of Existing Models and Approaches

Ozawa

Higgins

Nwokike

et al. 2022

The American Journal of Tropical Medicine and Hygiene

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ABSTRACT. Substandard and falsified medicines are harmful to patients, causing prolonged illness, side effects, and preventable deaths. Moreover, they have an impact on the health system and society more broadly by leading to additional care, higher disease burden, productivity losses and loss of trust in health care. Models that estimate the health and economic impacts of substandard and falsified medicines can be useful for regulators to contextualize the problem and to make an economic case for solutions. Yet these models have not been systematically catalogued to date. We reviewed existing models that estimate the health and economic impact of substandard and falsified medicines to describe the varying modeling approaches and gaps in knowledge. We compared model characteristics, data sources, assumptions, and limitations. Seven models were identified. The models assessed the impact of antimalarial (n = 5) or antibiotic (n = 2) quality at a national (n = 4), regional (n = 2), or global (n = 1) level. Most models conducted uncertainty analysis and provided ranges around potential outcomes. We found that models are lacking for other medicines, few countries’ data have been analyzed, and capturing population heterogeneity remains a challenge. Providing the best estimates of the impact of substandard and falsified medicines on a level that is actionable for decision-makers is important. To enable this, research on the impact of substandard and falsified medicines should be expanded to more medicine types and classes and tailored to more countries that are affected, with greater specificity.

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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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Modelling the impact of antimalarial quality on the transmission of sulfadoxine-pyrimethamine resistance in Plasmodium falciparum

Cited by 4 publications

References 45 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

Modeling the Health and Economic Impact of Substandard and Falsified Medicines: A Review of Existing Models and Approaches

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

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