Last-come,best served? Mosquito biting order and Plasmodium transmission

A pervasive characteristic of parasite infections is their tendency to be overdispersed. Understanding the mechanisms underlying this overdispersed distribution is of key importance as it may impact the transmission dynamics of the pathogen. Although multiple factors ranging from environmental stochasticity to inter-individual heterogeneity may explain parasite overdispersion, parasite infection is also overdispersed in an inbred host population maintained under laboratory conditions, suggesting that other mechanisms are at play. Here, we show that the aggregated distribution of malaria parasites within mosquito vectors is partially explained by a temporal heterogeneity in parasite infectivity triggered by the bites of mosquitoes. Parasite transmission tripled between the mosquito''s first and last blood feed in a period of only 3 h. Surprisingly, the increase in transmission is not associated with an increase in parasite investment in production of the transmissible stage. Overall, we highlight that Plasmodium is capable of responding to the bites of mosquitoes to increase its own transmission at a much faster pace than initially thought and that this is partly responsible for overdispersed distribution of infection. We discuss the underlying mechanisms as well as the broader implications of this plastic response for the epidemiology of malaria.     

On the interpretation of host-parasite ecology: Heligmosomoides polygyrus (Nematoda) in wild wood mouse (Apodemus sylvaticus) populations

This paper describes epidemiological and seasonal patterns in the interaction between wood mice, Apodemus sylvaticus and Heligmosomoides polygyrus. Data used in the analysis were collected by C. S. Elton and co-workers at Bagley Wood, Oxfordshire in the late 1920s. Heligmosomoides polygyrus was by far the most common helminth parasite with 70% of all wood mice infected and average intensity around 12 worms per mouse. Male and female mice were shown to harbour similar parasite burdens. Parasite numbers per host were highly overdispersed and were well described by the negative binomial distribution. There was little evidence for convexity in age (= weight)-intensity curves, either within or across sexes.
Host and parasite numbers showed predictable seasonal patterns, with mouse populations at their largest at the end of the breeding season, in August and September, and parasite populations at their largest in the late spring, around May. Results are discussed in relation to the ecology of H. polygyrus in wood and laboratory mice, and tentative comparison is made with human helminth infection. The interpretation of epidemiological patterns in these data was problematic. Of particular importance was the statistical distribution of parasites within the host population, and possible differences between mouse sexes in relation to growth, survival and trapping. Such difficulties are relevant to a range of similar field data.     

Genetics of host-parasite interactions

The evolution of host susceptibility or resistance to parasites has important consequences for the evolution of parasite virulence, host sexual selection, population dynamics of both host and parasite populations, and programs of biological control. The general observation of a fraction of Individuals within a population that is not parasitized, and/or the variability in parasite intensity among hosts, may reflect several phenomena acting at different levels of ecological organization. Yet, host-parasite coevolution requires host susceptibility and parasite virulence to be genetically variable. In spite of evolutionary and epidemiological implications of genetic heterogeneities in host-parasite systems, evidence concerning natural populations is still scarce. Here, we wish to emphasize why we need a better knowledge of the genetics of host-parasite interaction in natural populations and to review the evidence concerning the heritability of host susceptibility or resistance to parasites in natural populations of animals.     

Linking predator–prey interactions with exposure to a trophically transmitted parasite using PCR‐based analyses

Parasite transmission is determined by the rate of contact between a susceptible host and an infective stage and susceptibility to infection given an exposure event. Attempts to measure levels of variation in exposure in natural populations can be especially challenging. The level of exposure to a major class of parasites, trophically transmitted parasites, can be estimated by investigating the host's feeding behaviour. Since the parasites rely on the ingestion of infective intermediate hosts for transmission, the potential for exposure to infection is inherently linked to the definitive host's feeding ecology. Here, we combined epidemiological data and molecular analyses (polymerase chain reaction) of the diet of the definitive host, the white‐footed mouse (Peromyscus leucopus), to investigate temporal and individual heterogeneities in exposure to infection. Our results show that the consumption of cricket intermediate hosts accounted for much of the variation in infection; mice that had consumed crickets were four times more likely to become infected than animals that tested negative for cricket DNA. In particular, pregnant female hosts were three times more likely to consume crickets, which corresponded to a threefold increase in infection compared with nonpregnant females. Interestingly, males in breeding condition had a higher rate of infection even though breeding males were just as likely to test positive for cricket consumption as nonbreeding males. These results suggest that while heterogeneity in host diet served as a strong predictor of exposure risk, differential susceptibility to infection may also play a key role, particularly among male hosts. By combining PCR analyses with epidemiological data, we revealed temporal variation in exposure through prey consumption and identified potentially important individual heterogeneities in parasite transmission.     

Microbial (co)infections: Powerful immune influencers

It is well established that by modulating various immune functions, host infection may alter the course of concomitant inflammatory diseases, of both infectious and autoimmune etiologies. Beyond the major impact of commensal microbiota on the immune status, host exposure to viral, bacterial, and/or parasitic microorganisms also dramatically influences inflammatory diseases in the host, in a beneficial or harmful manner. Moreover, by modifying pathogen control and host tolerance to tissue damage, a coinfection can profoundly affect the development of a concomitant infectious disease. Here, we review the diverse mechanisms that underlie the impact of (co)infections on inflammatory disorders. We discuss epidemiological studies in the context of the hygiene hypothesis and shed light on the sometimes dual impact of germ exposure on human susceptibility to inflammatory disease. We then summarize the immunomodulatory mechanisms at play, which can involve pleiotropic effects of immune players and discuss the possibility to harness pathogen-derived compounds to the host benefit.     

A review of the biology and transmission ecology of African bovine species of the genus Schistosoma

The present paper reviews the information available concerning the biology and transmission ecology of the African bovine species Schistosoma bovis, S. mattheei, S. margrebowiei and S. leiperi. Criteria for species identification (egg morphology, intermediate host spectra, definitive host-parasite relationships, etc.) are listed and the geographical distribution of the four species and factors determining the relative occurrence within their overall distributional ranges are described. S bovis and S. mattheei occur north and south of 10 degrees S, respectively, and S. margrebowiei occurs mainly, and S. leiperi only, in southern central Africa. Definitive host-related factors (susceptibility, water contact pattern, ect.) providing the background for being a primary definitive host and the primary definitive host spectra for the four schistosome species are described. The primary definitive host spectrum for S. margrebowiei and S. leiperi comprise lechwe, puku and waterbuck, for S. mattheei lechwe, puku, waterbuck plus cattle, and for S. bovis cattle and possibly also some of the listed antelope species. In addition, wild bovines and cattle may provide a reservoir of S. mattheei and S. margrebowiei in humans, but wild bovines and domestic stock play no major role in the transmission of other human species of schistosomes. The intermediate snail host spectra of S. mattheei and S. leiperi only comprise members of the Bulinus africanus species complex; S. bovis is transmitted by members of the B. truncatus, B. africanus and B. forskalii species groups, and S. margrebowiei is transmitted by members of the B. forskalii species group and possibly also by members of the B. tropicus and B. truncatus species groups. Factors determining the transmission ecology of the four schistosome species, and thereby the epidemiology of bovine schistosomiasis, are discussed. Influential factors comprise environmental conditions mediated via the effect of these on the size of the snail host population and on the rate of the intramolluscan development, behavioural patterns of the definitive host population and the course of the infection in the definitive host as related to aspects of susceptibility and level of endemicity. The epidemiological pattern (prevalence and intensity of infection, seasonality of transmission, etc.) is described and exemplified, and it is finally concluded that the increasing water conservation and changing methods of husbandry may result in bovine schistosomiasis becoming a major veterinary problem in Africa.     

Waterborne Escherichia coli O157

The waterborne route of Vero cytotoxin-producing E. coli (VTEC) O157 infection was first suggested in two unconnected human cases in 1985. Since then, waterborne VTEC O157 has been identified in sporadic cases and in outbreaks of illness. Recreational waters, private and municipal supplies have been implicated from microbiological, environmental and epidemiological studies of cases. In addition, a research cohort study of farm workers identified exposure to private water supplies as a risk factor for having antibodies to E. coli O157. Sources of contamination are thought to be animal and human faeces or sewage. The presence of low numbers of target organisms in water makes microbiological confirmation difficult, therefore epidemiological evidence has been essential in outbreak investigations. Despite the potential for contamination of water with VTEC O157, waterborne infection is relatively rare largely due to the susceptibility of the organism to water treatment processes. This paper presents the evidence for waterborne VTEC O157 infection, considering current microbiological, environmental and particularly epidemiological information.     

Environmental endocrine disruptors: New diabetogens?

The prevalence of type-2 diabetes has dramatically increased worldwide during the last few decades. While lifestyle factors (sedentariness, noxious food), together with genetic susceptibility, are well-known actors, there is accumulating evidence suggesting that endocrine disrupting chemicals (EDCs) may also play a pathophysiological role in the occurrence of metabolic diseases. Both experimental and epidemiological evidence support a role for early and chronic exposure to low doses of chemical pollutants with endocrine and metabolic disrupting effects. Most are present in the food chain and accumulate in the fat mass after absorption. In rodents, bisphenol A stimulates synthesis and secretion of pancreatic β cells and disturbs insulin signaling in liver, muscle and adipose tissue through epigenetic changes leading to insulin resistance and β cell impairment. In humans, epidemiological reports show statistical link between exposure to pesticides, polychlorinated bisphenyls, bisphenol A, phthalates, dioxins or aromatic polycyclic hydrocarbides or heavy metals and DT2 after acute accidental releases or early in life and/or chronic, low doses exposure. More prospective, longitudinal studies are needed to determine the importance of such environmental risk factors.     

Cervical cancer risk: is there a genetic component?

Human papilloma virus (HPV) is a major risk factor for the development of cervical cancer. As only some infected women develop cancer, other factors must be important for disease development. Genetic epidemiological studies show that genetic factors contribute significantly to disease risk. Genetic susceptibility to HPV exposure and/or infection appears to be important in determining the individual risk to develop this virally induced cancer.     

Interaction between breeding habitat and elevation affects prevalence but not infection intensity of Batrachochytrium dendrobatidis in Brazilian anuran assemblages

Chytridiomycosis, an infectious disease of amphibians, is caused by the fungus Batrachochytrium dendrobatidis (Bd) and has been linked to declining amphibian populations worldwide. The susceptibility of amphibians to chytridiomycosis-induced population declines is potentially influenced by many factors, including environmental characteristics, differences among host species and the growth of the pathogen itself. We investigated the effects of elevation and breeding habitat on Bd prevalence and individual infection intensity (zoospore loads) in 3 anuran assemblages of the Atlantic Coastal Forest of Brazil. Bd infection intensity was strongly influenced by elevation and breeding habitat, but we found no evidence of an interaction between those 2 variables in explaining the number of zoospores sampled from individual frogs. In contrast, Bd infection odds were predicted by elevation and by an interaction between elevation and breeding habitat, such that frogs had a higher probability of Bd infection in lotic habitats at low elevations. Our results indicate that Bd persists across a wide variety of habitats and elevations in the Atlantic Coastal Forest. Prevalence and infection intensity of Bd are highest at high elevations where overall environmental conditions for Bd are most favorable. In addition, at low elevations amphibian host habitat choice is also an important determinant of infection. Our study highlights the need to investigate interacting variables of host ecology and the environment simultaneously.     

The abundance and distribution of Diphyllobothrium dendriticum (Nitzsch) and D. ditremum (Creplin) in the char Salvelinus alpinus (L.) in Sweden

A total of 654 char, Salvelinus alpinus (L.) and 33 brown trout, Salmo trutta L., were examined for the plerocercoids of Diphyllobothrium dendriticum (Nitzsch, 1824) and D. ditremum (Creplin, 1825). Only char were found to be infected. Both parasitic species were abundant. The incidence and mean intensity of infection for D. dendriticum were 83.2% and 8.8, respectively; for D. ditremum 93.7% and 45.0. There was no variation in the intensity of infection between different parts of the lake. The incidence and intensity of infection increased with the age of the fish to age 8+ for both species. From this age the intensity of infection leveled off or decreased. No differences in intensity of infection between the sexes were found. The frequency distribution of parasite counts were overdispersed and fitted the negative binomial distribution even within single age-groups. The two parasite species showed a high positive correlation in intensity of infection, D. ditremum was concentrated in the stomach and pyloric caeca. D. dendriticum was more widely distributed within the host and was supposed to kill heavily infected fish.     

The Role of Exposure History on HIV Acquisition: Insights from Repeated Low-dose Challenge Studies

To assess the efficacy of HIV vaccine candidates or preventive treatment, many research groups have started to challenge monkeys repeatedly with low doses of the virus. Such challenge data provide a unique opportunity to assess the importance of exposure history for the acquisition of the infection. I developed stochastic models to analyze previously published challenge data. In the mathematical models, I allowed for variation of the animals'' susceptibility to infection across challenge repeats, or across animals. In none of the studies I analyzed, I found evidence for an immunizing effect of non-infecting challenges, and in most studies, there is no evidence for variation in the susceptibilities to the challenges across animals. A notable exception was a challenge experiment by Letvin et al. Sci Translat Med (2011) conducted with the strain SIVsmE660. The challenge data of this experiment showed significant susceptibility variation from animal-to-animal, which is consistent with previously established genetic differences between the involved animals. For the studies which did not show significant immunizing effects and susceptibility differences, I conducted a power analysis and could thus exclude a very strong immunization effect for some of the studies. These findings validate the assumption that non-infecting challenges do not immunize an animal — an assumption that is central in the argument that repeated low-dose challenge experiments increase the statistical power of preclinical HIV vaccine trials. They are also relevant for our understanding of the role of exposure history for HIV acquisition and forecasting the epidemiological spread of HIV.     

Variation in host susceptibility among and within populations ofPlantago lanceolata L. infected by the fungusPhomopsis subordinaria (Desm.) Trav.

Summary Susceptibility toPhomopsis stalk disease ofPlantago lanceolata genotypes, sampled in three different populations with a variable degree of infection by the fungusPhomopsis subordinaria, was determined under greenhouse conditions. Susceptibility of the host varied within, but not among populations. No relationship between the intensity of the disease in the field and the mean susceptibility of the host genotypes sampled at those locations could be established. Host susceptibility appeared to be composed of the host genotypes sampled at those locations could be established. Host susceptibility appeared to be composed of different (uncorrelated) plant characteristics. Determining whether host genotypes are highly or slightly susceptible can only be achieved by field trials, where the plants are exposed to the whole set of disease inducing factors. The relevance of host susceptibility to the intensity of disease in the field is discussed in relation to the variation in pathogenicity of the fungus and the variation in environmental factors prevailing inP. lanceolata populations underP. subordinaria pathogen pressure. Grassland Species Research Group Number 123     

Environmental triggers of multiple sclerosis

Multiple sclerosis is a chronic immune-mediated disease of the central nervous system that develops in young adults with a complex genetic predisposition. Similar to other autoimmune disease, HLA-DR and -DQ alleles within the HLA class II region on chromosome 6p21 are by far the strongest risk-conferring genes. Less robust susceptibility effects have been reported for non-MHC related genetic variants. Improvements in the design of epidemiological studies helped to identify consistent environmental risk-associations such as the increased susceptibility for MS in individuals with a history of infectious mononucleosis, a symptomatic primary infection with the human γ-herpesvirus Epstein-Barr virus (EBV). Sun exposure and serum vitamin D levels are emerging non-infectious environmental risk factors that may have independent roles. The analysis of environmental effects will likely expand in the next few years and will allow for the generation of testable hypotheses as to how environmental insults interact with genetic factors to jointly determine the susceptibility to MS. Insights gained from these studies might facilitate the development of prevention strategies and more effective treatments for MS.     

Sidestream Smoke Exposure Increases the Susceptibility of Airway Epithelia to Adenoviral Infection

Background

Although significant epidemiological evidence indicates that cigarette smoke exposure increases the incidence and severity of viral infection, the molecular mechanisms behind the increased susceptibility of the respiratory tract to viral pathogens are unclear. Adenoviruses are non-enveloped DNA viruses and important causative agents of acute respiratory disease. The Coxsackievirus and adenovirus receptor (CAR) is the primary receptor for many adenoviruses. We hypothesized that cigarette smoke exposure increases epithelial susceptibility to adenovirus infection by increasing the abundance of apical CAR.

Methodology and Findings

Cultured human airway epithelial cells (CaLu-3) were used as a model to investigate the effect of sidestream cigarette smoke (SSS), mainstream cigarette smoke (MSS), or control air exposure on the susceptibility of polarized respiratory epithelia to adenoviral infection. Using a Cultex air-liquid interface exposure system, we have discovered novel differences in epithelial susceptibility between SSS and MSS exposures. SSS exposure upregulates an eight-exon isoform of CAR and increases adenoviral entry from the apical surface whilst MSS exposure is similar to control air exposure. Additionally, the level of cellular glycogen synthase kinase 3β (GSK3β) is downregulated by SSS exposure and treatment with a specific GSK3β inhibitor recapitulates the effects of SSS exposure on CAR expression and viral infection.

Conclusions

This is the first time that SSS exposure has been shown to directly enhance the susceptibility of a polarized epithelium to infection by a common respiratory viral pathogen. This work provides a novel understanding of the impact of SSS on the burden of respiratory viral infections and may lead to new strategies to alter viral infections. Moreover, since GSK3β inhibitors are under intense clinical investigation as therapeutics for a diverse range of diseases, studies such as these might provide insight to extend the use of clinically relevant therapeutics and increase the understanding of potential side effects.     

Acanthocephalus tumescens (Acanthocephala, Echinorhynchidae) in Galaxias maculatus (Pisces, Galaxiidae) of Lake Gutiérrez, Patagonia, Argentina

The seasonal distribution of Acanthocephalus tumescens (Acanthocephala : Echinorhynchidae) among Galaxias maculatus (Pisces : Galaxiidae) in Lake Gutiérrez was studied from March 1994 to June 1996. Acanthocephalus tumescens always occurs in the intestine, has an overdispersed frequency distribution, a similar proportion of sexes, and females are larger than males. Mean intensity and prevalence are low and increase with host length. The pattern of the infection shows seasonality, with recruitment in winter and a reproductive period during spring-summer.     

Age-dependent epidemiological patterns and strain diversity in helminth parasites

Field studies of schistosomes and the major intestinal nematodes Trichuris trichiura and Ascaris lumbricoides repeatedly demonstrate that the intensity and prevalence of infection exhibit marked dependency on host age. Peak levels of infection typically occur in hosts aged between 10 and 14 yr in endemically infected communities. It has widely been assumed that the slow acquisition of resistance in adults is caused by repeated exposure to the same antigenic repertoire of a single parasite strain. Consequently, these empirical patterns have previously been taken to suggest that human immunity to helminth parasites confers poor protection against reinfection. Here, an alternative explanation is suggested on the basis of results from a simplified model of helminth transmission. It is proposed that the empirical observations can be attributed to the circulation of multiple helminth strains that each elicit highly protective immunity. If this hypothesis is correct, estimates of epidemiological parameters from field data and the potential for control of helminth diseases might require reevaluation.     

Early onset of virus infection and up-regulation of cytokines in mice treated with cadmium and manganese

A substantial database indicates that a large number of environmental pollutants, chemicals and therapeutic agents to which organisms are exposed cause immunotoxicity. The suppression of immune functions may cause increased susceptibility of the host to a variety of microbial pathogens potentially resulting in a life-threatening state. Evaluation of the immunotoxic potential of chemical xenobiotics is of great concern and, therefore, we have investigated the impact of exposure of inorganic metals, specifically cadmium (Cd) and manganese (Mn) on Encephalomyocarditis virus (EMCV), Semliki Forest virus (SFV), and Venezuelan Equine Encephalitis virus (VEEV) infection. Pretreatment with a single, oral dose of Cd or Mn increased the susceptibility of mice to a sub-lethal infection of these viruses as observed by increased severity of symptoms and mortality compared to untreated controls. An early onset of virus infection was found in brains of Cd and Mn treated animals. Histopathological observations of the brain indicate evidence of inflammation and greater tissue pathology in Cd-or Mn-exposed mice compared to control animals. Meningitis and vascular congestion was seen in virus infected mice in all the metal treated groups, and further, the perivascular inflammation appeared earlier in treated mice compared to control. Encephalitis was maximum in Cd pretreated mice. Widespread environmental contamination of metals and the potential for their exposure and subsequent infection of humans or animals is indicative that further studies of these and all other metals are important to understand the effect of environmental pollution on human health.     

Costs of resistance and infection by a generalist pathogen

Pathogen infection is typically costly to hosts, resulting in reduced fitness. However, pathogen exposure may also come at a cost even if the host does not become infected. These fitness reductions, referred to as “resistance costs”, are inducible physiological costs expressed as a result of a trade‐off between resistance to a pathogen and aspects of host fitness (e.g., reproduction). Here, we examine resistance and infection costs of a generalist fungal pathogen (Metschnikowia bicuspidata) capable of infecting a number of host species. Costs were quantified as reductions in host lifespan, total reproduction, and mean clutch size as a function of pathogen exposure (resistance cost) or infection (infection cost). We provide empirical support for infection costs and modest support for resistance costs for five Daphnia host species. Specifically, only one host species examined incurred a significant cost of resistance. This species was the least susceptible to infection, suggesting the possibility that host susceptibility to infection is associated with the detectability and size of resistance cost. Host age at the time of pathogen exposure did not influence the magnitude of resistance or infection cost. Lastly, resistant hosts had fitness values intermediate between unexposed control hosts and infected hosts. Although not statistically significant, this could suggest that pathogen exposure does come at some marginal cost. Taken together, our findings suggest that infection is costly, resistance costs may simply be difficult to detect, and the magnitude of resistance cost may vary among host species as a result of host life history or susceptibility.