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  1. Free, publicly-accessible full text available August 1, 2024
  2. Successful infectious disease interventions can result in large reductions in parasite prevalence. Such demographic change has fitness implications for individual parasites and may shift the parasite’s optimal life history strategy. Here, we explore whether declining infection rates can alter Plasmodium falciparum ’s investment in sexual versus asexual growth. Using a multiscale mathematical model, we demonstrate how the proportion of polyclonal infections, which decreases as parasite prevalence declines, affects the optimal sexual development strategy: Within-host competition in multiclone infections favors a greater investment in asexual growth whereas single-clone infections benefit from higher conversion to sexual forms. At the same time, drug treatment also imposes selection pressure on sexual development by shortening infection length and reducing within-host competition. We assess these models using 148 P. falciparum parasite genomes sampled in French Guiana over an 18-y period of intensive intervention (1998 to 2015). During this time frame, multiple public health measures, including the introduction of new drugs and expanded rapid diagnostic testing, were implemented, reducing P. falciparum malaria cases by an order of magnitude. Consistent with this prevalence decline, we see an increase in the relatedness among parasites, but no single clonal background grew to dominate the population. Analyzing individual allele frequency trajectories, we identify genes that likely experienced selective sweeps. Supporting our model predictions, genes showing the strongest signatures of selection include transcription factors involved in the development of P. falciparum ’s sexual gametocyte form. These results highlight how public health interventions impose wide-ranging selection pressures that affect basic parasite life history traits. 
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  3. null (Ed.)
    Abstract Background Mosquitoes are vectors for diseases such as dengue, malaria and La Crosse virus that significantly impact the human population. When multiple mosquito species are present, the competition between species may alter population dynamics as well as disease spread. Two mosquito species, Aedes albopictus and Aedes triseriatus , both inhabit areas where La Crosse virus is found. Infection of Aedes albopictus by the parasite Ascogregarina taiwanensis and Aedes triseriatus by the parasite Ascogregarina barretti can decrease a mosquito’s fitness, respectively. In particular, the decrease in fitness of Aedes albopictus occurs through the impact of Ascogregarina taiwanensis on female fecundity, larval development rate, and larval mortality and may impact its initial competitive advantage over Aedes triseriatus during invasion. Methods We examine the effects of parasitism of gregarine parasites on Aedes albopictus and triseriatus population dynamics and competition with a focus on when Aedes albopictus is new to an area. We build a compartmental model including competition between Aedes albopictus and triseriatus while under parasitism of the gregarine parasites. Using parameters based on the literature, we simulate the dynamics and analyze the equilibrium population proportion of the two species. We consider the presence of both parasites and potential dilution effects. Results We show that increased levels of parasitism in Aedes albopictus will decrease the initial competitive advantage of the species over Aedes triseriatus and increase the survivorship of Aedes triseriatus . We find Aedes albopictus is better able to invade when there is more extreme parasitism of Aedes triseriatus . Furthermore, although the transient dynamics differ, dilution of the parasite density through uptake by both species does not alter the equilibrium population sizes of either species. Conclusions Mosquito population dynamics are affected by many factors, such as abiotic factors (e.g. temperature and humidity) and competition between mosquito species. This is especially true when multiple mosquito species are vying to live in the same area. Knowledge of how population dynamics are affected by gregarine parasites among competing species can inform future mosquito control efforts and help prevent the spread of vector-borne disease. 
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  4. Perkins, Alex (Ed.)
    Mosquitoes vector harmful pathogens that infect millions of people every year, and developing approaches to effectively control mosquitoes is a topic of great interest. However, the success of many control measures is highly dependent upon ecological, physiological, and life history traits of mosquito species. The behavior of mosquitoes and their potential to vector pathogens can also be impacted by these traits. One trait of interest is mosquito body mass, which depends upon many factors associated with the environment in which juvenile mosquitoes develop. Our experiments examined the impact of larval density on the body mass of Aedes aegypti mosquitoes, which are important vectors of dengue, Zika, yellow fever, and other pathogens. To investigate the interactions between the larval environment and mosquito body mass, we built a discrete time mathematical model that incorporates body mass, larval density, and food availability and fit the model to our experimental data. We considered three categories of model complexity informed by data, and selected the best model within each category using Akaike’s Information Criterion. We found that the larval environment is an important determinant of the body mass of mosquitoes upon emergence. Furthermore, we found that larval density has greater impact on body mass of adults at emergence than on development time, and that inclusion of density dependence in the survival of female aquatic stages in models is important. We discuss the implications of our results for the control of Aedes mosquitoes and on their potential to spread disease. 
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  5. Some infectious diseases produce lifelong immunity while others only produce temporary immunity. In the case of short-lived immunity, the level of protection wanes over time and may be boosted upon re-exposure, via infection or vaccination. Previous work developed a simple model capturing waning and boosting immunity, known as the Susceptible-Infectious-Recovered-Waned-Susceptible (SIRWS) model, which exhibits rich dynamical behavior including supercritical and subcritical Hopf bifurcations among other structures. Here, we extend the bifurcation analyses of the SIRWS model to examine the influence of all parameters on these bifurcation structures. We show that the bistable region, involving both a stable fixed point and a stable limit cycle, exists only for a small region of biologically realistic parameter space. Furthermore, we contrast the SIRWS model with a modified version, where immune boosting may involve the occurrence of a secondary infection. Analysis of this extended model shows that oscillations and bistability, as found in the SIRWS model, depend on strong assumptions about infectivity and recovery rate from secondary infection. Understanding the dynamics of models of waning and boosting immunity is important for accurately assessing epidemiological data. 
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  6. Billker, Oliver (Ed.)
    Many mosquito species, including the major malaria vector Anopheles gambiae , naturally undergo multiple reproductive cycles of blood feeding, egg development and egg laying in their lifespan. Such complex mosquito behavior is regularly overlooked when mosquitoes are experimentally infected with malaria parasites, limiting our ability to accurately describe potential effects on transmission. Here, we examine how Plasmodium falciparum development and transmission potential is impacted when infected mosquitoes feed an additional time. We measured P . falciparum oocyst size and performed sporozoite time course analyses to determine the parasite’s extrinsic incubation period (EIP), i.e. the time required by parasites to reach infectious sporozoite stages, in An . gambiae females blood fed either once or twice. An additional blood feed at 3 days post infection drastically accelerates oocyst growth rates, causing earlier sporozoite accumulation in the salivary glands, thereby shortening the EIP (reduction of 2.3 ± 0.4 days). Moreover, parasite growth is further accelerated in transgenic mosquitoes with reduced reproductive capacity, which mimic genetic modifications currently proposed in population suppression gene drives. We incorporate our shortened EIP values into a measure of transmission potential, the basic reproduction number R 0 , and find the average R 0 is higher (range: 10.1%–12.1% increase) across sub-Saharan Africa than when using traditional EIP measurements. These data suggest that malaria elimination may be substantially more challenging and that younger mosquitoes or those with reduced reproductive ability may provide a larger contribution to infection than currently believed. Our findings have profound implications for current and future mosquito control interventions. 
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  7. null (Ed.)
    Mosquito-borne diseases, in particular malaria, have a significant burden worldwide leading to nearly half a million deaths each year. The malaria parasite requires a vertebrate host, such as a human, and a vector host, the Anopheles mosquito, to complete its full life cycle. Here, we focus on the parasite dynamics within the vector to examine the first appearance of sporozoites in the salivary glands, which indicates a first time of infectiousness of mosquitoes. The timing of this period of pathogen development in the mosquito until transmissibility, known as the extrinsic incubation period, remains poorly understood. We develop compartmental models of within-mosquito parasite dynamics fitted with experimental data on oocyst and sporozoite counts. We find that only a fraction of oocysts burst to release sporozoites and bursting must be delayed either via a time-dependent function or a gamma-distributed set of compartments. We use Bayesian inference to estimate distributions of parameters and determine that bursting rate is a key epidemiological parameter. A better understanding of the factors impacting the extrinsic incubation period will aid in the development of interventions to slow or stop the spread of malaria. 
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