The effect of spatial heterogenity on the aggregation of ticks on white-footed mice

Parasites are often aggregated on a minority of the individuals in their host populations. Although host characteristics are commonly presumed to explain parasite aggregation on hosts, spatio-temporal aggregation of parasites during their host-seeking stages may have a dominant effect on the aggregation on hosts. We aimed to quantify, using mixed models, repeatability and autocorrelation analyses, the degree to which the aggregation of blacklegged ticks (Ixodes scapularis) on white-footed mice (Peromyscus leucopus) is influenced by spatio-temporal distributions of the host-seeking ticks and by heterogeneity among mice. Host-seeking ticks were spatially aggregated at both the larval and nymphal life-stages. However, this spatial aggregation accounted for little of the variation in larval and nymphal burdens observed on mice (3% and 0%, respectively). Conversely, mouse identity accounted for a substantial proportion of the variance in tick burdens. Mouse identity was a significant explanatory factor as the majority of ticks parasitized a consistent set of mice throughout the activity seasons. Of the characteristics associated with mouse identity investigated, only gender affected larval burdens, and body mass and home range sizes in males were correlated with nymphal burdens. These analyses suggest that aggregation of ticks on a minority of mice does not result from the distribution of host-seeking ticks but from characteristics of the hosts.     

Energy-state dependent responses of Anopheles gambiae (Diptera: Culicidae) to simulated bednet-protected hosts

In nature, Anopheles gambiae mosquitoes are found at various energy levels and such females must choose between seeking somatic energy from sugar sources and obtaining both somatic and gametic energy from blood hosts. We used a straight-tube olfactometer containing a simulated unobtainable blood host (human foot smell protected by a net) as well as a sugar source (honey odor). We assessed female probing rate and residence time at the net as a function of energy state (0, 24, 48, 72-h starved). In our trials, 0-h starved females showed low response to human odor, low probing rate, and residence time at the human odor site. By contrast, both 48 and 72-h individuals showed high response to foot odor, longer residence time, and higher probing rates. Seventy-two-h females also flew towards the honey source less often than other groups. Our findings suggest that managing sugar sources might be a viable strategy for influencing mosquito biting behavior.     

The risk of a mosquito-borne infection in a heterogeneous environment

A common assumption about malaria, dengue, and other mosquito-borne infections is that the two main components of the risk of human infection—the rate at which people are bitten (human biting rate) and the proportion of mosquitoes that are infectious—are positively correlated. In fact, these two risk factors are generated by different processes and may be negatively correlated across space and time in heterogeneous environments. Uneven distribution of blood-meal hosts and larval habitat creates a spatial mosaic of demograPhic sources and sinks. Moreover, mosquito populations fluctuate temporally, forced by environmental variables such as rainfall, temperature, and humidity. These sources of spatial and temporal heterogeneity in the distribution of mosquito populations generate variability in the human biting rate, in the proportion of mosquitoes that are infectious, and in the risk of human infection. To understand how heterogeneity affects the epidemiology of mosquito-borne infections, we developed a set of simple models that incorporate heterogeneity in a stepwise fashion. These models predict that the human biting rate is highest shortly after the mosquito densities peak, near breeding sites where adult mosquitoes emerge, and around the edges of areas where humans are aggregated. In contrast, the proportion of mosquitoes that are infectious reflects the age structure of mosquito populations; it peaks where old mosquitoes are found, far from mosquito breeding habitat, and when mosquito population density is declining. Finally, we show that estimates for the average risk of infection that are based on the average entomological inoculation rate are strongly biased in heterogeneous environments.     

The importance of environmental spatial heterogeneity and host social structure in disease transmission

[First paragraph]The spatial structure of a host population determines the spatial probability distribution of interaction between individuals, and therefore influences the spatio-temporal dynamics of disease transmission within the host population (Keeling, 1999; Gudelj and White, 2004). Nigel Barlow recognised this and included non-linear transmission in his later models (Barlow, 1991), simulating the result of spatial heterogeneity of risk in susceptible hosts. These models produced behaviour that could not be found in models with homogeneously mixed host populations: more rapid disease dynamics and a greater robustness of disease to control measures. However, in this model there was no causal mechanism driving the initial spatial heterogeneity of risk in host individuals. Environmental heterogeneity is likely to be a key factor in determining the spatial distribution of host individuals (Cronin and Reeve, 2005). We attempted to explore how environmental heterogeneity may affect disease dynamics via its influence on the spatial distribution of host individuals. We developed a spatially explicit stochastic model that incorporated spatially variable host density distributions, primarily driven by environmental heterogeneity.     

Spatial Heterogeneity,Host Movement and Mosquito-Borne Disease Transmission

Mosquito-borne diseases are a global health priority disproportionately affecting low-income populations in tropical and sub-tropical countries. These pathogens live in mosquitoes and hosts that interact in spatially heterogeneous environments where hosts move between regions of varying transmission intensity. Although there is increasing interest in the implications of spatial processes for mosquito-borne disease dynamics, most of our understanding derives from models that assume spatially homogeneous transmission. Spatial variation in contact rates can influence transmission and the risk of epidemics, yet the interaction between spatial heterogeneity and movement of hosts remains relatively unexplored. Here we explore, analytically and through numerical simulations, how human mobility connects spatially heterogeneous mosquito populations, thereby influencing disease persistence (determined by the basic reproduction number R ₀), prevalence and their relationship. We show that, when local transmission rates are highly heterogeneous, R ₀ declines asymptotically as human mobility increases, but infection prevalence peaks at low to intermediate rates of movement and decreases asymptotically after this peak. Movement can reduce heterogeneity in exposure to mosquito biting. As a result, if biting intensity is high but uneven, infection prevalence increases with mobility despite reductions in R ₀. This increase in prevalence decreases with further increase in mobility because individuals do not spend enough time in high transmission patches, hence decreasing the number of new infections and overall prevalence. These results provide a better basis for understanding the interplay between spatial transmission heterogeneity and human mobility, and their combined influence on prevalence and R ₀.     

植食性昆虫寄主植物嗅觉搜寻述介

植食性昆虫与寄主植物关系的本质是化学。植食性昆虫搜寻寄主的嗅觉媒介是植物气味即化学信息物质。在介绍植物气味构成及其扩散模型基础上,阐述了植物气味在地上植食性昆虫成虫、幼虫和地下植食性昆虫搜寻寄主过程中的嗅觉导向作用,并指出了今后相关研究需要注意的问题。从植物与环境因子的关系来看,植物气味包括构成性气味和诱发性气味两类,这两类气味的概念既相联系而又不同。构成性气味组分及构成因植物分类地位等而不同。诱发性气味组分因植食性昆虫取食、植物病原微生物、机械致伤等因子的胁迫而变化,这种变化性状随植物属和/或种、植株生长发育阶段、胁迫因子性质及其作用方式而不同。无论是哪种植物气味,其释放均具有节律性。气味扩散过程比较复杂,扩散状态可用数学模型表征。对于地上植食性昆虫成虫,植物气味对其寄主搜寻行为具有导向特异性,重点分析了这种特异性形成的两个假说;鳞翅目昆虫幼虫,能够利用植物化学信息物质趋向寄主植物或回避非寄主植物;地下植食性昆虫搜寻寄主,既与寄主植物地下组织释放或分泌的次级代谢物有关,又与一些初级代谢物有关。初级代谢物中的CO₂,起着“搜寻触发器”作用。有助于增强人们对昆虫与植...     

The unexpected importance of mosquito oviposition behaviour for malaria: non-productive larval habitats can be sources for malaria transmission

Background

Mosquitoes commute between blood-meal hosts and water. Thus, heterogeneity in human biting reflects underlying spatial heterogeneity in the distribution and suitability of larval habitat as well as inherent differences in the attractiveness, suitability and distribution of blood-meal hosts. One of the possible strategies of malaria control is to identify local vector species and then attack water bodies that contain their larvae.

Methods

Biting and host seeking, not oviposition, have been the focus of most previous studies of mosquitoes and malaria transmission. This study presents a mathematical model that incorporates mosquito oviposition behaviour.

Results

The model demonstrates that oviposition is one potential factor explaining heterogeneous biting and vector distribution in a landscape with a heterogeneous distribution of larval habitat. Adult female mosquitoes tend to aggregate around places where they oviposit, thereby increasing the risk of malaria, regardless of the suitability of the habitat for larval development. Thus, a water body may be unsuitable for adult mosquito emergence, but simultaneously, be a source for human malaria.

Conclusion

Larval density may be a misleading indicator of a habitat's importance for malaria control. Even if mosquitoes could be lured to oviposit in sprayed larval habitats, this would not necessarily mitigate – and might aggravate – the risk of malaria transmission. Forcing mosquitoes to fly away from humans in search of larval habitat may be a more efficient way to reduce the risk of malaria than killing larvae. Thus, draining, fouling, or filling standing water where mosquitoes oviposit can be more effective than applying larvicide.     

Juvenile hormone regulation of the second biting cycle in Culex pipiens

Juvenile hormone regulation of the second biting cycle was studied in Culex pipiens by allatectomizing mosquitoes at daily intervals after the first blood meal. Mosquitoes oviposited and were tested for biting 2 days later. Allatectomy on days 1 through 4 prevented biting in a high percentage of females, indicating that juvenile hormone was required for a second biting cycle. When allatectomy was delayed 6 or more days after the first blood meal, the mosquitoes took a second blood meal after oviposition even though eggs were retained at the time of allatectomy. Thus, egg retention did not prevent mosquitoes from releasing juvenile hormone for a second biting cycle. Unoperated mosquitoes also bit when they were forced to retain eggs after the first blood meal. However, these mosquitoes only fed on blood if they were confined on or near the host; they would not feed in cages where host seeking was required to locate the host. Based on these findings, it appeared that oviposition was necessary to initiate host-seeking behaviour, whereas juvenile hormone release initiated biting. These results, in conjunction with earlier work demonstrating juvenile hormone induction of the first biting cycle, indicated that alternating periods of juvenile hormone production and oviposition regulate the cyclic patterns of biting and host-seeking behaviour throughout the life of the mosquito.     

Stage-specific manipulation of a mosquito's host-seeking behavior by the malaria parasite Plasmodium gallinaceum

We present experimental evidence that different stages of themalaria parasite Plasmodium gallinaceum differentially affectthe host-seeking behavior of its mosquito vector Aedes aegypti.In uninfected mosquitoes, host-seeking behavior is continuedif mosquitoes have ingested less than a threshold volume ofblood, whereas a larger blood meal inhibits host seeking. Weinvestigated the parasite's effect on this behavior by feedinginfected and uninfected mosquitoes for variable amounts of timeand assaying 30-45 min later whether they continued their attemptsat blood-feeding. Mosquitoes infected with oocysts (which cannotbe transmitted) had a smaller threshold volume and were lesslikely to return for further probing, whereas individuals infectedwith transmissible sporozoites increased the threshold volumerequired to inhibit host-seeking behavior. We conclude thatthe stage-specific effect of the parasite on host-seeking behavioris likely to be an active manipulation by the parasite to increaseits transmission success.     

The transmission dynamics of a within-and between-hosts malaria model

In this paper, we developed a novel deterministic coupled model tying together the effects of within-host and population level dynamics on malaria transmission dynamics. We develop within-host and within-vector dynamic models, population level between-hosts models, and a nested coupled model combining these levels. The unique feature of this work is the way the coupling and feedback for the model use the various life stages of the malaria parasite both in the human host and the mosquito vector. Analysis of the coupled and the within-human host models indicate the existence of locally asymptotically stable infection- and parasite-free equilibria when the associated reproduction numbers are less than one. The population-level model, on the other hand, exhibits backward bifurcation, where the stable disease-free equilibrium co-exists with a stable endemic equilibrium. A global sensitivity analysis was carried out to measure the effects of the sensitivity and uncertainty in the various model parameters estimates. The results indicate that the most important parameters driving the pathogen level within an infected human are the production rate of the red blood cells from the bone marrow, the infection rate, the immunogenicity of the infected red blood cells, merozoites and gametocytes, and the immunosensitivity of the merozoites and gametocytes. The key parameters identified at the population level are the human recovery rate, the death rate of the mosquitoes, the recruitment rate of susceptible humans into the population, the mosquito biting rate, the transmission probabilities per contact in mosquitoes and in humans, and the parasite production and clearance rates in the mosquitoes. Defining the feedback functions as a linear function of the mosquito biting rate, numerical exploration of the coupled model reveals oscillations in the parasite populations within a human host in the presence of the host immune response. These oscillations dampen as the mosquito biting rate increases. We also observed that the oscillation and damping effect seen in the within-human host dynamics fed back into the population level dynamics; this in turn amplifies the oscillations in the parasite population within the mosquito-host.     

Determining Important Parameters in the Spread of Malaria Through the Sensitivity Analysis of a Mathematical Model

We perform sensitivity analyses on a mathematical model of malaria transmission to determine the relative importance of model parameters to disease transmission and prevalence. We compile two sets of baseline parameter values: one for areas of high transmission and one for low transmission. We compute sensitivity indices of the reproductive number (which measures initial disease transmission) and the endemic equilibrium point (which measures disease prevalence) to the parameters at the baseline values. We find that in areas of low transmission, the reproductive number and the equilibrium proportion of infectious humans are most sensitive to the mosquito biting rate. In areas of high transmission, the reproductive number is again most sensitive to the mosquito biting rate, but the equilibrium proportion of infectious humans is most sensitive to the human recovery rate. This suggests strategies that target the mosquito biting rate (such as the use of insecticide-treated bed nets and indoor residual spraying) and those that target the human recovery rate (such as the prompt diagnosis and treatment of infectious individuals) can be successful in controlling malaria.     

Modelling variability in lymphatic filariasis: macrofilarial dynamics in the Brugia pahangi--cat model.

A striking feature of lymphatic filariasis is the considerable heterogeneity in infection burden observed between hosts, which greatly complicates the analysis of the population dynamics of the disease. Here, we describe the first application of the moment closure equation approach to model the sources and the impact of this heterogeneity for macrofilarial population dynamics. The analysis is based on the closest laboratory equivalent of the life cycle and immunology of infection in humans--cats chronically infected with the filarial nematode Brugia pahangi. Two sets of long-term experiments are analysed: hosts given either single primary infections or given repeat infections. We begin by quantifying changes in the mean and aggregation of adult parasites (inversely measured by the negative binomial parameter, kappa in cohorts of hosts using generalized linear models. We then apply simple stochastic models to interpret observed patterns. The models and empirical data indicate that parasite aggregation tracks the decline in the mean burden with host age in primary infections. Conversely, in repeat infections, aggregation increases as the worm burden declines with experience of infection. The results show that the primary infection variability is consistent with heterogeneities in parasite survival between hosts. By contrast, the models indicate that the reduction in parasite variability with time in repeat infections is most likely due to the ''filtering'' effect of a strong, acquired immune response, which gradually acts to remove the initial variability generated by heterogeneities in larval mortality. We discuss this result in terms of the homogenizing effect of host immunity-driven density-dependence on macrofilarial burden in older hosts.     

A quantitative test of the relationship between parasite dose and infection probability across different host-parasite combinations

Epidemiological models generally assume that the number of susceptible individuals that become infected within a unit of time depends on the density of the hosts and the concentration of parasites (i.e. mass-action principle). However, empirical studies have found significant deviations from this assumption due to biotic and abiotic factors, such as seasonality, the spatial structure of the host population and host heterogeneity with respect to immunity and susceptibility. In this paper, we examine the effect of the dose level of the bacterial endoparasite Pasteuria ramosa on the infection rate of its host, the water flea Daphnia magna. Using seven host clones and two parasite isolates, we measure the fraction of infected hosts after exposure to eight different parasite doses to determine whether there is variation in the infection process across different host clone-parasite isolate combinations. In five combinations, a pronounced dose-dependent infection pattern was found. Using a likelihood approach, we compare the infection data of these five combinations to the fit of three mathematical models: a mass-action model, a parasite antagonism model (i.e. an increase in the parasite dose leads to an under-proportionate increase in the infection rate per host) and a heterogeneous host model. We found that the host heterogeneity model, in which we assumed the existence of non-inherited phenotypic differences in host susceptibilities to the parasite, provides the best fit. Our analysis suggests that among 5 out of the 14 host clone-parasite isolate combinations that resulted in appreciable infections, non-genetic host heterogeneity plays an important role.     

The host-seeking inhibitory peptide, Aea-HP-1, is made in the male accessory gland and transferred to the female during copulation

Male accessory glands (MAGs) of insects are responsible for the production of many of the seminal fluid proteins and peptides that elicit physiological and behavioral responses in the post-mated female. In the yellow fever mosquito, Aedes aegypti, seminal fluid components are responsible for stimulating egg production, changing female behavior away from host-seeking toward egg-laying and mating refractoriness, but hitherto no behavior-modifying molecule from the MAGs has been structurally characterized. We now show using mass spectrometry and HPLC/ELISA that the MAG is a major site of synthesis of the biologically active decapeptide, Aea-HP-1 (pERPhPSLKTRFamide) that was first characterized by Matsumoto and colleagues in 1989 from mosquito head extracts and shown to have host-seeking inhibitory properties. The peptide is localized to the anterior portion of the MAG, occurs at high concentrations in the gland and is transferred to the female reproductive tract on copulation. Aea-HP-1 has a pyroglutamic acid at the N-terminus, an amidated carboxyl at the C-terminus and an unusual 4-hydroxyproline in position 4 of the peptide. The structure of the peptide with its blocked N- and C-termini confers resistance to metabolic inactivation by MAG peptidases; however the peptide persists for less than 2h in the female reproductive tract after copulation. Aea-HP-1 is not a ligand for the mosquito sex peptide/myoinhibitory peptide receptor. A. aegypti often mate close to the host and therefore it is possible that male-derived Aea-HP-1 induces short-term changes to female host-seeking behavior to reduce potentially lethal encounters with hosts soon after insemination.     

Mosquito-mediated attraction of female mosquitoes to a host

ABSTRACT. Female mosquitoes seeking blood respond primarily to kairomones emitted by potential hosts. We now confirm, in the laboratory, field evidence showing that the presence of other female mosquitoes at the host significantly enhances the host-seeking response. Olfactometry strongly suggests that a chemical of mosquito origin is responsible. The adaptive value of this behaviour is discussed.     

Heterogeneous Feeding Patterns of the Dengue Vector,Aedes aegypti,on Individual Human Hosts in Rural Thailand

Background

Mosquito biting frequency and how bites are distributed among different people can have significant epidemiologic effects. An improved understanding of mosquito vector-human interactions would refine knowledge of the entomological processes supporting pathogen transmission and could reveal targets for minimizing risk and breaking pathogen transmission cycles.

Methodology and principal findings

We used human DNA blood meal profiling of the dengue virus (DENV) vector, Aedes aegypti, to quantify its contact with human hosts and to infer epidemiologic implications of its blood feeding behavior. We determined the number of different people bitten, biting frequency by host age, size, mosquito age, and the number of times each person was bitten. Of 3,677 engorged mosquitoes collected and 1,186 complete DNA profiles, only 420 meals matched people from the study area, indicating that Ae. aegypti feed on people moving transiently through communities to conduct daily business. 10–13% of engorged mosquitoes fed on more than one person. No biting rate differences were detected between high- and low-dengue transmission seasons. We estimate that 43–46% of engorged mosquitoes bit more than one person within each gonotrophic cycle. Most multiple meals were from residents of the mosquito collection house or neighbors. People ≤25 years old were bitten less often than older people. Some hosts were fed on frequently, with three hosts bitten nine times. Interaction networks for mosquitoes and humans revealed biologically significant blood feeding hotspots, including community marketplaces.

Conclusion and significance

High multiple-feeding rates and feeding on community visitors are likely important features in the efficient transmission and rapid spread of DENV. These results help explain why reducing vector populations alone is difficult for dengue prevention and support the argument for additional studies of mosquito feeding behavior, which when integrated with a greater understanding of human behavior will refine estimates of risk and strategies for dengue control.     

The influence of varying spatial heterogeneity on the refuge model for coexistence of specialist parasitoid assemblages

Models of host–parasitoid dynamics often assume constant levels of spatial heterogeneity in parasitoid attack rate, which tends to stabilize the interactions. Recently, authors have questioned this assumption and shown that outcomes of simple host–parasitoid models change if spatial heterogeneity is allowed to vary with parasitoid density. Here, we allow spatial heterogeneity to vary with either parasitoid density or percent parasitism in a model designed to explain specialist parasitoid coexistence on insect hosts with various levels of refuge. By examining this model we can evaluate the effect of varying spatial heterogeneity on a more complex model in which spatial heterogeneity is not considered the primary determinant of persistence. By modeling communities with one host and two parasitoid species, we show that the probability of species persistence for the competitively inferior parasitoid depends on the assumed relationship between spatial heterogeneity and both parasitoid density and percent parasitism. The probability of parasitoid coexistence is generally lower when spatial heterogeneity varies with parasitoid demographics. We conclude that the conditions for which host refuge promote specialist parasitoid coexistence are less common that proposed by the original model. Finally, we compared a model in which spatial heterogeneity varies with percent parasitism to data from laboratory trials and find a reasonable fit. We conclude that the change in spatial heterogeneity strongly influenced the outcome of the laboratory trials, and we suggest more research is necessary before researchers can assume constant spatial heterogeneity in future models.     

Effectiveness of zooprophylaxis in malaria control: a theoretical inquiry, with a model for mosquito populations with two bloodmeal hosts

A model for a vector mosquito population with two bloodmeal hosts (man and a domestic animal) was developed to study the influences of domestic animals on the frequency of mosquito bites on man and the endemicity of human malaria. The vector population model, including blood-feeding success in the adult stage (depending on host density and biting efficiency) and density-dependent regulation in the larval stage, was combined with the Ross-Macdonald malaria transmission model. Model analyses suggested that introduction of domestic animals easily fed upon by mosquitoes increases mosquito density and, in some situations, frequency of mosquito bites on man and the infection rate of malaria through increased success of blood-feeding. Extinction of malaria was predicted only when an extremely large number of easily accessible (as compared to man) domestic animals are introduced. Limitations in the concept of zooprophylaxis and problems of livestock management in malaria control are discussed.     

Effects of sublethal pyrethroid exposure on the host-seeking behavior of female mosquitoes

A common method of adult mosquito control consists of residual application on surfaces and aerial spraying often using pyrethroids. However, not all insects that contact insecticides are killed. Sublethal exposure to neurotoxic compounds can negatively affect sensory organs and reduce efficiency of host location. Flight tracks of host-seeking female Culex quinquefasciatus, Anopheles albimanus, and Aedes aegypti in a wind tunnel were video-recorded to compare activation of host-seeking and patterns of flight orientation to host odors. During host-seeking flights, all three mosquito species differed significantly in flight duration, velocity, turn angle, and angular velocity. Mosquitoes were then exposed to sublethal levels (LD(25) ) of pyrethroid insecticides to evaluate the effects of the neurotoxicants 24 hours post-exposure. Significant reductions in time of activation to flight and flight direction were observed in mosquitoes exposed to deltamethrin and permethrin. Additionally, pesticide-treated Cx. quinquefasciatus mosquitoes flew significantly slower, spent more time in flight, and turned more frequently than untreated controls.     

Diverse Host-Seeking Behaviors of Skin-Penetrating Nematodes

Skin-penetrating parasitic nematodes infect approximately one billion people worldwide and are responsible for some of the most common neglected tropical diseases. The infective larvae of skin-penetrating nematodes are thought to search for hosts using sensory cues, yet their host-seeking behavior is poorly understood. We conducted an in-depth analysis of host seeking in the skin-penetrating human parasite Strongyloides stercoralis, and compared its behavior to that of other parasitic nematodes. We found that Str. stercoralis is highly mobile relative to other parasitic nematodes and uses a cruising strategy for finding hosts. Str. stercoralis shows robust attraction to a diverse array of human skin and sweat odorants, most of which are known mosquito attractants. Olfactory preferences of Str. stercoralis vary across life stages, suggesting a mechanism by which host seeking is limited to infective larvae. A comparison of odor-driven behavior in Str. stercoralis and six other nematode species revealed that parasite olfactory preferences reflect host specificity rather than phylogeny, suggesting an important role for olfaction in host selection. Our results may enable the development of new strategies for combating harmful nematode infections.