Does reservoir host mortality enhance transmission of West Nile virus?

<p>Abstract</p> <p>Background</p> <p>Since its 1999 emergence in New York City, West Nile virus (WNV) has become the most important and widespread cause of mosquito-transmitted disease in North America. Its sweeping spread from the Atlantic to the Pacific coast was accompanied by widespread mortality among wild birds, especially corvids. Only sporadic avian mortality had previously been associated with this infection in the Old World. Here, we examine the possibility that reservoir host mortality may intensify transmission, both by concentrating vector mosquitoes on remaining hosts and by preventing the accumulation of "herd immunity".</p> <p>Results</p> <p>Inspection of the Ross-Macdonald expression of the basic reproductive number (<it>R</it>₀) suggests that this quantity may increase with reservoir host mortality. Computer simulation confirms this finding and indicates that the level of virulence is positively associated with the numbers of infectious mosquitoes by the end of the epizootic. The presence of reservoir incompetent hosts in even moderate numbers largely eliminated the transmission-enhancing effect of host mortality. Local host die-off may prevent mosquitoes to "waste" infectious blood meals on immune host and may thus facilitate perpetuation and spread of transmission.</p> <p>Conclusion</p> <p>Under certain conditions, host mortality may enhance transmission of WNV and similarly maintained arboviruses and thus facilitate their emergence and spread. The validity of the assumptions upon which this argument is built need to be empirically examined.</p

Avian Host-Selection by Culex pipiens in Experimental Trials

Evidence from field studies suggests that Culex pipiens, the primary mosquito vector of West Nile virus (WNV) in the northeastern and north central United States, feeds preferentially on American robins (Turdus migratorius). To determine the contribution of innate preferences to observed preference patterns in the field, we conducted host preference trials with a known number of adult female C. pipiens in outdoor cages comparing the relative attractiveness of American robins with two common sympatric bird species, European starling, Sternus vulgaris and house sparrow, Passer domesticus. Host seeking C. pipiens were three times more likely to enter robin-baited traps when with the alternate host was a European starling (n = 4 trials; OR = 3.06; CI [1.42–6.46]) and almost twice more likely when the alternative was a house sparrow (n = 8 trials; OR = 1.80; CI = [1.22–2.90]). There was no difference in the probability of trap entry when two robins were offered (n = 8 trials). Logistic regression analysis determined that the age, sex and weight of the birds, the date of the trial, starting-time, temperature, humidity, wind-speed and age of the mosquitoes had no effect on the probability of a choosing a robin over an alternate bird. Findings indicate that preferential feeding by C. pipiens mosquitoes on certain avian hosts is likely to be inherent, and we discuss the implications innate host preferences may have on enzootic WNV transmission

The Business Case for Preconception Care: Methods and Issues

Only a limited number of economic evaluations have addressed the costs and benefits of preconception care. In order to persuade health care providers, payers, or purchasers to become actively involved in promoting preconception care, it is important to demonstrate the value of doing so through development of a “business case”. Perceived benefits in terms of organizational reputation and market share can be influential in forming a business case. In addition, it is standard to include an economic analysis of financial costs and benefits from the perspective of the provider practice, payer, or purchaser in a business case. The methods, data needs, and other issues involved with preparing an economic analysis of the likely financial return on investment in preconception care are presented here. This is accompanied by a review or case study of economic evaluations of preconception care for women with recognized diabetes. Although the data are not sufficient to draw firm conclusions, there are indications that such care may yield positive financial benefits to health care organizations through reduction in maternal and infant hospitalizations. More work is needed to establish how costs and economic benefits are distributed among different types of organizations. Also, the optimum methods of delivering preconception care for women with diabetes need to be evaluated. Similar assessments should also be conducted for other forms of preconception care, including comprehensive care

Predicting Bison Migration out of Yellowstone National Park Using Bayesian Models

Long distance migrations by ungulate species often surpass the boundaries of preservation areas where conflicts with various publics lead to management actions that can threaten populations. We chose the partially migratory bison (Bison bison) population in Yellowstone National Park as an example of integrating science into management policies to better conserve migratory ungulates. Approximately 60% of these bison have been exposed to bovine brucellosis and thousands of migrants exiting the park boundary have been culled during the past two decades to reduce the risk of disease transmission to cattle. Data were assimilated using models representing competing hypotheses of bison migration during 1990–2009 in a hierarchal Bayesian framework. Migration differed at the scale of herds, but a single unifying logistic model was useful for predicting migrations by both herds. Migration beyond the northern park boundary was affected by herd size, accumulated snow water equivalent, and aboveground dried biomass. Migration beyond the western park boundary was less influenced by these predictors and process model performance suggested an important control on recent migrations was excluded. Simulations of migrations over the next decade suggest that allowing increased numbers of bison beyond park boundaries during severe climate conditions may be the only means of avoiding episodic, large-scale reductions to the Yellowstone bison population in the foreseeable future. This research is an example of how long distance migration dynamics can be incorporated into improved management policies

Nothing a Hot Bath Won't Cure: Infection Rates of Amphibian Chytrid Fungus Correlate Negatively with Water Temperature under Natural Field Settings

Dramatic declines and extinctions of amphibian populations throughout the world have been associated with chytridiomycosis, an infectious disease caused by the pathogenic chytrid fungus Batrachochytrium dendrobatidis (Bd). Previous studies indicated that Bd prevalence correlates with cooler temperatures in the field, and laboratory experiments have demonstrated that Bd ceases growth at temperatures above 28°C. Here we investigate how small-scale variations in water temperature correlate with Bd prevalence in the wild. We sampled 221 amphibians, including 201 lowland leopard frogs (Rana [Lithobates] yavapaiensis), from 12 sites in Arizona, USA, and tested them for Bd. Amphibians were encountered in microhabitats that exhibited a wide range of water temperatures (10–50°C), including several geothermal water sources. There was a strong inverse correlation between the water temperature in which lowland leopard frogs were captured and Bd prevalence, even after taking into account the influence of year, season, and host size. In locations where Bd was known to be present, the prevalence of Bd infections dropped from 75–100% in water <15°C, to less than 10% in water >30°C. A strong inverse correlation between Bd infection status and water temperature was also observed within sites. Our findings suggest that microhabitats where water temperatures exceed 30°C provide lowland leopard frogs with significant protection from Bd, which could have important implications for disease dynamics, as well as management applications

Quantifying the effects of temperature on mosquito and parasite traits that determine the transmission potential of human malaria

Malaria transmission is known to be strongly impacted by temperature. The current understanding of how temperature affects mosquito and parasite life history traits derives from a limited number of empirical studies. These studies, some dating back to the early part of last century, are often poorly controlled, have limited replication, explore a narrow range of temperatures, and use a mixture of parasite and mosquito species. Here, we use a single pairing of the Asian mosquito vector, An. stephensi and the human malaria parasite, P. falciparum to conduct a comprehensive evaluation of the thermal performance curves of a range of mosquito and parasite traits relevant to transmission. We show that biting rate, adult mortality rate, parasite development rate, and vector competence are temperature sensitive. Importantly, we find qualitative and quantitative differences to the assumed temperature-dependent relationships. To explore the overall implications of temperature for transmission, we first use a standard model of relative vectorial capacity. This approach suggests a temperature optimum for transmission of 29°C, with minimum and maximum temperatures of 12°C and 38°C, respectively. However, the robustness of the vectorial capacity approach is challenged by the fact that the empirical data violate several of the model's simplifying assumptions. Accordingly, we present an alternative model of relative force of infection that better captures the observed biology of the vector-parasite interaction. This model suggests a temperature optimum for transmission of 26°C, with a minimum and maximum of 17°C and 35°C, respectively. The differences between the models lead to potentially divergent predictions for the potential impacts of current and future climate change on malaria transmission. The study provides a framework for more detailed, system-specific studies that are essential to develop an improved understanding on the effects of temperature on malaria transmission

Steroid Hormone Control of Cell Death and Cell Survival: Molecular Insights Using RNAi

The insect steroid hormone ecdysone triggers programmed cell death of obsolete larval tissues during metamorphosis and provides a model system for understanding steroid hormone control of cell death and cell survival. Previous genome-wide expression studies of Drosophila larval salivary glands resulted in the identification of many genes associated with ecdysone-induced cell death and cell survival, but functional verification was lacking. In this study, we test functionally 460 of these genes using RNA interference in ecdysone-treated Drosophila l(2)mbn cells. Cell viability, cell morphology, cell proliferation, and apoptosis assays confirmed the effects of known genes and additionally resulted in the identification of six new pro-death related genes, including sorting nexin-like gene SH3PX1 and Sox box protein Sox14, and 18 new pro-survival genes. Identified genes were further characterized to determine their ecdysone dependency and potential function in cell death regulation. We found that the pro-survival function of five genes (Ras85D, Cp1, CG13784, CG32016, and CG33087), was dependent on ecdysone signaling. The TUNEL assay revealed an additional two genes (Kap-α3 and Smr) with an ecdysone-dependent cell survival function that was associated with reduced cell death. In vitro, Sox14 RNAi reduced the percentage of TUNEL-positive l(2)mbn cells (p<0.05) following ecdysone treatment, and Sox14 overexpression was sufficient to induce apoptosis. In vivo analyses of Sox14-RNAi animals revealed multiple phenotypes characteristic of aberrant or reduced ecdysone signaling, including defects in larval midgut and salivary gland destruction. These studies identify Sox14 as a positive regulator of ecdysone-mediated cell death and provide new insights into the molecular mechanisms underlying the ecdysone signaling network governing cell death and cell survival

Agrarian diet and diseases of affluence – Do evolutionary novel dietary lectins cause leptin resistance?

BACKGROUND: The global pattern of varying prevalence of diseases of affluence, such as obesity, cardiovascular disease and diabetes, suggests that some environmental factor specific to agrarian societies could initiate these diseases. PRESENTATION OF THE HYPOTHESIS: We propose that a cereal-based diet could be such an environmental factor. Through previous studies in archaeology and molecular evolution we conclude that humans and the human leptin system are not specifically adapted to a cereal-based diet, and that leptin resistance associated with diseases of affluence could be a sign of insufficient adaptation to such a diet. We further propose lectins as a cereal constituent with sufficient properties to cause leptin resistance, either through effects on metabolism central to the proper functions of the leptin system, and/or directly through binding to human leptin or human leptin receptor, thereby affecting the function. TESTING THE HYPOTHESIS: Dietary interventions should compare effects of agrarian and non-agrarian diets on incidence of diseases of affluence, related risk factors and leptin resistance. A non-significant (p = 0.10) increase of cardiovascular mortality was noted in patients advised to eat more whole-grain cereals. Our lab conducted a study on 24 domestic pigs in which a cereal-free hunter-gatherer diet promoted significantly higher insulin sensitivity, lower diastolic blood pressure and lower C-reactive protein as compared to a cereal-based swine feed. Testing should also evaluate the effects of grass lectins on the leptin system in vivo by diet interventions, and in vitro in various leptin and leptin receptor models. Our group currently conducts such studies. IMPLICATIONS OF THE HYPOTHESIS: If an agrarian diet initiates diseases of affluence it should be possible to identify the responsible constituents and modify or remove them so as to make an agrarian diet healthier

A “Candidate-Interactome” Aggregate Analysis of Genome-Wide Association Data in Multiple Sclerosis

Though difficult, the study of gene-environment interactions in multifactorial diseases is crucial for interpreting the relevance of non-heritable factors and prevents from overlooking genetic associations with small but measurable effects. We propose a "candidate interactome" (i.e. a group of genes whose products are known to physically interact with environmental factors that may be relevant for disease pathogenesis) analysis of genome-wide association data in multiple sclerosis. We looked for statistical enrichment of associations among interactomes that, at the current state of knowledge, may be representative of gene-environment interactions of potential, uncertain or unlikely relevance for multiple sclerosis pathogenesis: Epstein-Barr virus, human immunodeficiency virus, hepatitis B virus, hepatitis C virus, cytomegalovirus, HHV8-Kaposi sarcoma, H1N1-influenza, JC virus, human innate immunity interactome for type I interferon, autoimmune regulator, vitamin D receptor, aryl hydrocarbon receptor and a panel of proteins targeted by 70 innate immune-modulating viral open reading frames from 30 viral species. Interactomes were either obtained from the literature or were manually curated. The P values of all single nucleotide polymorphism mapping to a given interactome were obtained from the last genome-wide association study of the International Multiple Sclerosis Genetics Consortium & the Wellcome Trust Case Control Consortium, 2. The interaction between genotype and Epstein Barr virus emerges as relevant for multiple sclerosis etiology. However, in line with recent data on the coexistence of common and unique strategies used by viruses to perturb the human molecular system, also other viruses have a similar potential, though probably less relevant in epidemiological terms