Biology subjects

Mideo, N.

Publications and source records attributed to Mideo, N..

8 recordsLinked to original sources

bioRxiv2026

Evaluating the estimability of within-host population dynamics models

Despite the impacts of within-host disease dynamics on disease outcomes in individual hosts and disease spread among-hosts, generic models of within-host population dynamics have received far less attention than their among-host counterparts. While a number of models have been proposed to explore theoretical eco-evolutionary dynamics, they have yet to be evaluated for estimability, raising questions about their ability to provide reliable inference when confronted with data. We evaluated the estimability of two generic within-host population dynamics models by assessing: (1) parameter estimation, our ability to recover correct values of model parameters from data, (2) the consequences of mis-assigning the underlying mechanistic model on parameter estimation, and (3) the reproduction of qualitative dynamics, or, our ability to use parameter estimates to reproduce observed dynamical behaviours. In some cases, fitting a mis-matched mechanistic model to time series data produced reasonable parameter estimates that were able to reproduce system dynamics, and that when provided the data-generating model, parameter uncertainty can produce substantial behavioural uncertainty. Our findings highlight the impacts of structural, parametric, and behavioural uncertainty on inference, and demonstrate the value of improving system-specific knowledge to prevent the use of incorrect functional forms and of measuring consequential parameters to improve estimability.

ecology↗

bioRxiv2025

Host constraints on viral recombination and emergence

Recombination (including reassortment) is a salient force in viral evolution and has been implicated in the emergence of several zoonotic pathogens in humans. Viral recombination occurs during simultaneous infection of an individual host with multiple genotypes (co-infection). Thus, processes which affect the incidence of a disease in the host population affect how often viral genotypes recombine. We investigate whether and how host traits affect the realized rate of viral recombination using a mathematical model that makes feedbacks between viral evolution and host ecology (in particular, lifespan) explicit. Our main result is that viruses of host species that are short-lived tend to recombine more frequently than those of relatively long-lived hosts. This is because of differences in population density and, thus, the prevalence of (co-)infection at equilibrium. Using highly pathogenic avian influenza sequence data, we test the prediction that recombination is elevated in short-lived hosts. In agreement with this prediction, the magnitude of statistical associations between mutations on different segments of the flu genome increases with host body size, a proxy for lifespan. Similarly, estimates of the reassortment rate from phylogenetic network analyses decrease with body size. We discuss the implications of these findings for disease emergence. Subject categoryEvolution Subject areasevolution, health and disease and epidemiology, ecology

evolutionary biology↗

bioRxiv2025

Optimal cues for transmission investment in malaria parasites

The timing of investment into reproduction is a key determinant of lifetime reproductive success (fitness). Many organisms exhibit plastic, i.e., environmentally-responsive, investment strategies, raising the questions of what environmental cues trigger responses and why organisms have evolved to respond to those particular cues. For malaria parasites (Plasmodium spp.), investment into the production of specialized transmission stages (versus stages that replicate asexually within the host) is synonymous with reproductive investment and also plastic, responding to host- and parasite-derived factors. Previous theory has identified optimal plastic transmission investment strategies for the rodent malaria parasite, Plasmodium chabaudi, as a function of the time since infection, implicitly assuming that parasites have perfect information about the within-host environment and how it is changing. We extend that theory to ask which cue(s) should parasites use? Put another way, which cue(s) maximize parasite fitness, quantified as host infectiousness during acute infection? Our results show that sensing a parasite-associated cue, e.g., the abundance of infected red blood cells or transmission stages, allows parasites to achieve fitness approaching that of the optimal time-varying strategy, but only when parasites perceive the cue non-linearly, responding more sensitively to changes at low densities. However, no single cue can recreate the best time-varying strategy or allow parasites to adopt terminal investment as the infection ends, a classic expectation for reproductive investment. Sensing two cues--log-transformed infected and uninfected red blood cell abundance--enables parasites to accurately track the progression of the infection, permits terminal investment, and recovers the fitness of the optimal time-varying investment strategy. Importantly, parasites that detect two cues more efficiently exploit hosts, resulting in higher virulence compared with those sensing only one cue. Finally, our results suggest a potential tradeoff between achieving an optimal transmission investment strategy in a given host environment and robustness in the face of environmental or developmental fluctuations.

evolutionary biology↗

bioRxiv2024

How to quantify developmental synchrony in malaria parasites

Malaria infections represent an iconic example of developmental synchrony, where periodic fevers can result when the population of parasites develops synchronously within host red blood cells. The level of synchrony appears to vary across individual hosts and across parasite species and strains, variation that--once quantified--can illuminate the ecological and evolutionary drivers of synchrony. Yet current approaches for quantifying synchrony in parasites are either biased by population dynamics or unsuitable when population growth rates vary through time, features ubiquitous to parasite populations in vitro and in vivo. Here we develop an approach to estimate synchrony that accounts for population dynamics, including changing population growth rates, and validate it with simulated time series data encompassing a range of synchrony levels in two different host-parasite systems: malaria infections of mice and human malaria parasites in vitro. This new method accurately quantifies developmental synchrony from per capita growth rates using obtainable abundance data even with realistic sampling noise, without the need to sort parasites into developmental stages. Our approach enables variability in developmental schedules to be disentangled from even extreme variation in population dynamics, providing a comparative metric of developmental synchrony.

ecology↗

bioRxiv2022

Vector diversity and malaria prevalence: global trends and local determinants

Identifying determinants of global infectious disease burden is a central goal of disease ecology. While it is widely accepted that host diversity structures parasite diversity and prevalence across large spatial scales, the influence of vector diversity on disease risk has rarely been examined despite the role of vectors as obligatory intermediate hosts for many parasites. Malaria, for instance, can be transmitted by over 70 species of mosquitoes, but the impact of this diversity on malaria risk remains unclear. Further, such relationships are likely dependent on the context in which disease transmission occurs, as arthropod life history and behavior are highly sensitive to environmental factors such as temperature. We studied the relationship between vector diversity, malaria prevalence, and environmental attributes using a unique dataset we curated by integrating several open-access sources. Globally, the association between vector species richness and malaria prevalence differed by latitude, indicating that this relationship is strongly dependent on underlying environmental conditions. Structural equation models further revealed different processes by which the environment impacts vector community assemblage and function, and subsequently disease prevalence, in different regions. In Africa, the environment exerted a top-down influence on disease through its role in shaping vector communities, whereas in Southeast Asia, disease prevalence is influenced by more complex interactions between the physical and socioeconomic environment (i.e., rainfall and GDP) and vector diversity across sites. This work highlights the key role of vector diversity in structuring disease distribution at large spatial scales and offers crucial insights to vector management and disease control. Significance statementThe global health threat from persistent and emerging vector-borne diseases continues to increase and is exacerbated by rapid environmental and societal change. Predicting how disease burden will shift in response to these changes necessitates a clear understanding of existing determinants of disease risk. We focused on an underappreciated potential source of variation in disease burden - vector diversity - and its role in structuring global malaria distribution. Our work revealed that vector diversity influences malaria prevalence and that the strength and nature of this association strongly depend on local environmental context. Extending disease transmission theory, surveillance, and control to embrace heterogeneity in vector community structure and function across space and time is an asset in the fight against vector-borne diseases.

ecology↗

bioRxiv2020

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

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. Author summaryDrug resistance in the malaria parasite, Plasmodium falciparum, presents an ongoing public health challenge, but aspects of its evolution are poorly understood. Although antimalarial resistance is common worldwide, it can typically be traced to just a handful of origins. Counterintuitively, although Sub Saharan Africa bears 90% of the global malaria burden, resistance typically originates in regions where transmission intensity is low. In high transmission regions, infections are genetically diverse, and hosts have significant standing adaptive immunity, both of which are known to suppress frequency of resistance within infections. However, interactions between immune-driven selection, transmission intensity, and resistance have not been investigated. Using a multiscale, agent-based model, we found that high transmission intensity slowed the evolution of resistance in two ways. First, it intensified competition, allowing sensitive lineages to suppress resistant lineages. Second, high population immunity selected for antigenic novelty, which interfered with selection for resistance. However, once resistance was at a high frequency, immune selection maintained it in the population at a high prevalence. Our findings provide a novel explanation for observations about the origin of resistance and demonstrate that adaptive immunity is a critical component of selection.

evolutionary biology↗

bioRxiv2020

Mosaic vaccination: how distributing different vaccines across a population could improve epidemic control

Although vaccination has been remarkably effective against some pathogens, for others, rapid antigenic evolution results in vaccination conferring only weak and/or short-lived protection. Consequently, considerable effort has been invested in developing more evolutionarily robust vaccines, either by targeting highly conserved components of the pathogen (universal vaccines) or by including multiple immunological targets within a single vaccine (multi-epitope vaccines). An unexplored third possibility is to vaccinate individuals with one of a number of qualitatively different vaccines, creating a mosaic of individual immunity in the population. Here we explore whether a mosaic vaccination strategy can deliver superior epidemiological outcomes to conventional vaccination, in which all individuals receive the same vaccine. We suppose vaccine doses can be distributed between distinct vaccine targets (e.g., different surface proteins against which an immune response can be generated) and/or immunologically-distinct variants at these targets (e.g., strains); the pathogen can undergo antigenic evolution at both targets. Using simple mathematical models, we show that mosaic vaccination often outperforms conventional vaccination, leading to fewer infected individuals, improved vaccine efficacy, and lower individual risks over the course of the epidemic.

evolutionary biology↗

bioRxiv2017

Co-evolution of virulence and immunosuppression through multiple infections

Many components of host-parasite interactions have been shown to affect the way virulence (i.e., parasite-induced harm to the host) evolves. However, coevolution of multiple parasite traits is often neglected. We explore how an immunosuppressive mechanism of parasites affects and co-evolves with virulence through multiple infections. Applying the adaptive dynamics framework to epidemiological models with coinfection, we show that immunosuppression is a double-edged-sword for the evolution of virulence. On one hand, it amplifies the adaptive benefit of virulence by increasing the abundance of coinfections through epidemiological feedbacks. On the other hand, immunosuppression hinders host recovery, prolonging the duration of infection and elevating the cost of killing the host. The balance between the cost and benefit of immunosuppression varies across different background mortality rates of hosts. In addition, we find that immunosuppression evolution is influenced considerably by the precise trade-off shape determining the effect of immunosuppression on host recovery and susceptibility to further infection. These results demonstrate that the evolution of virulence is shaped by immunosuppression while highlighting that the evolution of immune evasion mechanisms deserves further research attention.

evolutionary biology↗