School of Mathematics and Statistics - Research Publications
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ItemNo Preview AvailableMathematical models of Plasmodium vivax transmission: A scoping review(PUBLIC LIBRARY SCIENCE, 2024-03)Plasmodium vivax is one of the most geographically widespread malaria parasites in the world, primarily found across South-East Asia, Latin America, and parts of Africa. One of the significant characteristics of the P. vivax parasite is its ability to remain dormant in the human liver as hypnozoites and subsequently reactivate after the initial infection (i.e. relapse infections). Mathematical modelling approaches have been widely applied to understand P. vivax dynamics and predict the impact of intervention outcomes. Models that capture P. vivax dynamics differ from those that capture P. falciparum dynamics, as they must account for relapses caused by the activation of hypnozoites. In this article, we provide a scoping review of mathematical models that capture P. vivax transmission dynamics published between January 1988 and May 2023. The primary objective of this work is to provide a comprehensive summary of the mathematical models and techniques used to model P. vivax dynamics. In doing so, we aim to assist researchers working on mathematical epidemiology, disease transmission, and other aspects of P. vivax malaria by highlighting best practices in currently published models and highlighting where further model development is required. We categorise P. vivax models according to whether a deterministic or agent-based approach was used. We provide an overview of the different strategies used to incorporate the parasite's biology, use of multiple scales (within-host and population-level), superinfection, immunity, and treatment interventions. In most of the published literature, the rationale for different modelling approaches was driven by the research question at hand. Some models focus on the parasites' complicated biology, while others incorporate simplified assumptions to avoid model complexity. Overall, the existing literature on mathematical models for P. vivax encompasses various aspects of the parasite's dynamics. We recommend that future research should focus on refining how key aspects of P. vivax dynamics are modelled, including spatial heterogeneity in exposure risk and heterogeneity in susceptibility to infection, the accumulation of hypnozoite variation, the interaction between P. falciparum and P. vivax, acquisition of immunity, and recovery under superinfection.
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ItemNo Preview AvailableA model for malaria treatment evaluation in the presence of multiple species(ELSEVIER, 2023-09)Plasmodium falciparum and P. vivax are the two most common causes of malaria. While the majority of deaths and severe morbidity are due to P. falciparum, P. vivax poses a greater challenge to eliminating malaria outside of Africa due to its ability to form latent liver stage parasites (hypnozoites), which can cause relapsing episodes within an individual patient. In areas where P. falciparum and P. vivax are co-endemic, individuals can carry parasites of both species simultaneously. These mixed infections complicate dynamics in several ways: treatment of mixed infections will simultaneously affect both species, P. falciparum can mask the detection of P. vivax, and it has been hypothesised that clearing P. falciparum may trigger a relapse of dormant P. vivax. When mixed infections are treated for only blood-stage parasites, patients are at risk of relapse infections due to P. vivax hypnozoites. We present a stochastic mathematical model that captures interactions between P. falciparum and P. vivax, and incorporates both standard schizonticidal treatment (which targets blood-stage parasites) and radical cure treatment (which additionally targets liver-stage parasites). We apply this model via a hypothetical simulation study to assess the implications of different treatment coverages of radical cure for mixed and P. vivax infections and a "unified radical cure" treatment strategy where P. falciparum, P. vivax, and mixed infections all receive radical cure after screening glucose-6-phosphate dehydrogenase (G6PD) normal. In addition, we investigated the impact of mass drug administration (MDA) of blood-stage treatment. We find that a unified radical cure strategy leads to a substantially lower incidence of malaria cases and deaths overall. MDA with schizonticidal treatment was found to decrease P. falciparum with little effect on P. vivax. We perform a univariate sensitivity analysis to highlight important model parameters.
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ItemNo Preview AvailableOptimal Interruption of P. vivax Malaria Transmission Using Mass Drug Administration(SPRINGER, 2023-06)Plasmodium vivax is the most geographically widespread malaria-causing parasite resulting in significant associated global morbidity and mortality. One of the factors driving this widespread phenomenon is the ability of the parasites to remain dormant in the liver. Known as 'hypnozoites', they reside in the liver following an initial exposure, before activating later to cause further infections, referred to as 'relapses'. As around 79-96% of infections are attributed to relapses from activating hypnozoites, we expect it will be highly impactful to apply treatment to target the hypnozoite reservoir (i.e. the collection of dormant parasites) to eliminate P. vivax. Treatment with radical cure, for example tafenoquine or primaquine, to target the hypnozoite reservoir is a potential tool to control and/or eliminate P. vivax. We have developed a deterministic multiscale mathematical model as a system of integro-differential equations that captures the complex dynamics of P. vivax hypnozoites and the effect of hypnozoite relapse on disease transmission. Here, we use our multiscale model to study the anticipated effect of radical cure treatment administered via a mass drug administration (MDA) program. We implement multiple rounds of MDA with a fixed interval between rounds, starting from different steady-state disease prevalences. We then construct an optimisation model with three different objective functions motivated on a public health basis to obtain the optimal MDA interval. We also incorporate mosquito seasonality in our model to study its effect on the optimal treatment regime. We find that the effect of MDA interventions is temporary and depends on the pre-intervention disease prevalence (and choice of model parameters) as well as the number of MDA rounds under consideration. The optimal interval between MDA rounds also depends on the objective (combinations of expected intervention outcomes). We find radical cure alone may not be enough to lead to P. vivax elimination under our mathematical model (and choice of model parameters) since the prevalence of infection eventually returns to pre-MDA levels.
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ItemA Multiscale Mathematical Model of Plasmodium Vivax Transmission(SPRINGER, 2022-08)Malaria is caused by Plasmodium parasites which are transmitted to humans by the bite of an infected Anopheles mosquito. Plasmodium vivax is distinct from other malaria species in its ability to remain dormant in the liver (as hypnozoites) and activate later to cause further infections (referred to as relapses). Mathematical models to describe the transmission dynamics of P. vivax have been developed, but most of them fail to capture realistic dynamics of hypnozoites. Models that do capture the complexity tend to involve many governing equations, making them difficult to extend to incorporate other important factors for P. vivax, such as treatment status, age and pregnancy. In this paper, we have developed a multiscale model (a system of integro-differential equations) that involves a minimal set of equations at the population scale, with an embedded within-host model that can capture the dynamics of the hypnozoite reservoir. In this way, we can gain key insights into dynamics of P. vivax transmission with a minimum number of equations at the population scale, making this framework readily scalable to incorporate more complexity. We performed a sensitivity analysis of our multiscale model over key parameters and found that prevalence of P. vivax blood-stage infection increases with both bite rate and number of mosquitoes but decreases with hypnozoite death rate. Since our mathematical model captures the complex dynamics of P. vivax and the hypnozoite reservoir, it has the potential to become a key tool to inform elimination strategies for P. vivax.