On the transmission of HIV with self-protective behavior and preferred mixing

An epidemic model of HIV transmission with self-protective behavior and preferred mixing is presented. Individuals in the model are assumed to choose their levels of risk behavior by comparing the costs and benefits of self-protective actions. Unlike in models which treat individual risk behavior as exogenously given and fixed, the condition under which an endemic steady state equilibrium exists does not depend on the extent of assortative mixing in the population. Specifically, a unique endemic equilibrium exists when the basic reproductive number of the disease, which is given in the model by the expected number of secondary infections caused by an infected individual in the absence of any self-protection, is strictly greater than one. Otherwise, the disease-free equilibrium is the only steady state equilibrium. With respect to changes in contact patterns, it is shown that, if the degree of preferred mixing is increased, the disease prevalence can decrease in the high-risk subpopulation consisting of individuals who are more likely to engage in unsafe practices. The situation is reversed for the low-risk subpopulation, which is composed of individuals who are less willing to engage in risky practices, so that increasing the likelihood of mixing with members of one's own group may increase the prevalence level within the low-risk subpopulation.     

Rational behavioral response and the transmission of STDs

The susceptible-infected (SI) model is extended by allowing for individual optimal choices of self-protective actions against infection, where agents differ with respect to preferences and costs of self-protection. It is shown that a unique endemic equilibrium prevalence exists when the basic reproductive number of a STD is strictly greater than unity, and that the disease-free equilibrium is the unique steady state equilibrium when the basic reproductive number is less than or equal to one. Unlike in models that take individual behavior as given and fixed, the endemic equilibrium prevalence need not vary monotonically with respect to the basic reproductive number. Specifically, with endogenously determined self-protective behavior, a reduction in the basic reproductive number may in fact increase the endemic equilibrium prevalence. The global stability of the endemic steady state is established for the case of a homogeneous population by showing that, for any non-zero initial disease prevalence, there exists an equilibrium path which converges to the endemic steady state.     

Modeling the effect of information quality on risk behavior change and the transmission of infectious diseases

How the quality of information about the prevalence of an infectious disease affects individuals’ incentives to adopt self-protective actions to reduce the risk of infection is studied using an economic/game-theoretic model of epidemics. In the model, agents make inferences regarding the current prevalence of a disease by observing the health status of a subset of the population. Therefore, the higher the number of agents whose infection status can be observed, the better one’s information about the current prevalence is. In particular, it is assumed that an agent’s estimate of the current prevalence depends on observations of the current health status of other agents and on the agent’s estimate of past prevalence, and that the agent places more weight on the current observations in forming an estimate of the prevailing prevalence when the number of observations increases. It is shown that the likelihood of eradicating an infectious disease through behavioral changes depends critically on the amount of information that individuals have access to, which also determines whether prevalence will be relatively stable or will exhibit cyclical patterns over time. Increasing the amount of information that individuals possess may lower the likelihood of eradication.     

Transmission and Control of Plasmodium knowlesi: A Mathematical Modelling Study

Introduction

Plasmodium knowlesi is now recognised as a leading cause of malaria in Malaysia. As humans come into increasing contact with the reservoir host (long-tailed macaques) as a consequence of deforestation, assessing the potential for a shift from zoonotic to sustained P. knowlesi transmission between humans is critical.

Methods

A multi-host, multi-site transmission model was developed, taking into account the three areas (forest, farm, and village) where transmission is thought to occur. Latin hypercube sampling of model parameters was used to identify parameter sets consistent with possible prevalence in macaques and humans inferred from observed data. We then explore the consequences of increasing human-macaque contact in the farm, the likely impact of rapid treatment, and the use of long-lasting insecticide-treated nets (LLINs) in preventing wider spread of this emerging infection.

Results

Identified model parameters were consistent with transmission being sustained by the macaques with spill over infections into the human population and with high overall basic reproduction numbers (up to 2267). The extent to which macaques forage in the farms had a non-linear relationship with human infection prevalence, the highest prevalence occurring when macaques forage in the farms but return frequently to the forest where they experience higher contact with vectors and hence sustain transmission. Only one of 1,046 parameter sets was consistent with sustained human-to-human transmission in the absence of macaques, although with a low human reproduction number (R_0H = 1.04). Simulations showed LLINs and rapid treatment provide personal protection to humans with maximal estimated reductions in human prevalence of 42% and 95%, respectively.

Conclusion

This model simulates conditions where P. knowlesi transmission may occur and the potential impact of control measures. Predictions suggest that conventional control measures are sufficient at reducing the risk of infection in humans, but they must be actively implemented if P. knowlesi is to be controlled.     

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.     

Comparing apples and oranges--model-based assessment of different tsetse-transmitted trypanosomosis control strategies

The current control strategies for tsetse-transmitted trypanosomosis in cattle (trypanocidal drugs, tsetse control and trypanotolerant cattle) are briefly reviewed and their adoption rates in different geographic regions of sub-Saharan Africa are presented. The impact of these control strategies and the potential use of vaccines, should they be developed, on trypanosomosis transmission were compared using a mathematical model. The relative trypanosomosis prevalence compared with no control was estimated across a range of control coverages (from none to complete control coverage) by varying the change in specific model parameters influenced by individual control measures. Based on this comparison, the relative rankings of the effect of control strategies on reducing disease prevalence were: vector control, vaccination, and drug use, in that order. In this model, trypanotolerance was assumed to decrease disease prevalence, but not to influence transmission. Differences in the predicted impact of control measures on the transmission of human sleeping sickness are discussed. Finally, the role of transmission model outputs as inputs for economic models to guide investment decisions for trypanosomosis control is emphasised.     

Multiple Stable States of Disease Occurrence: A Note on the Implications for the Anthropological Study of Human Disease

Ecologists model human disease using predator-prey models, with humans as the prey and the pathogen as the predator. Use of these models permits the identification of stable equilibria and stable states of disease prevalence for human host-parasite systems. May (1977) has described the possibility of the presence of multiple stable states of disease prevalence for human disease systems. The model of multiple stable states implies that historical circumstances are important in determining the occurrence of disease. This model offers a theoretical framework in which to examine the occurrence of epidemics in human populations and to develop a more complete understanding of disease processes.     

A Mathematical Model of Sickle Cell Genome Frequency in Response to Selective Pressure from Malaria

Because of the relative prevalence of hereditary sickle cell disease and the auxiliary role of the sickle cell gene in reducing the mortality of malaria, it is believed that P. falciparum has exerted selection pressure on human populations to increase the prevalence of this otherwise detrimental gene. A model incorporating three genotypes and two age cohorts is used to test the hypothesis that higher death rates due to malaria can exert selective pressure to increase the prevalence of the sickle cell gene. The model displays selection pressure for the carrier gene in the presence of increasing malaria death rates for either adults or children, showing both higher final frequencies of the gene as well as shortened time to reach these frequencies.     

Distribution and ecology of campylobacters in coastal plain streams (Georgia, United States of America)

Campylobacter is the leading cause of bacterium-associated diarrhea in the United States and most developed countries. While this disease is considered a food-borne disease, many clinical cases cannot be linked to a food source. In rural and agrarian areas environmental transmission may be an important factor contributing to case loads. Here we investigated the waterborne prevalence of campylobacters in a mixed-use rural watershed in the coastal plain of southern Georgia (United States). Six sites representing various degrees of agricultural and human influence were surveyed biweekly to monthly for 1 year for the presence of culturable thermophilic campylobacters and other measures of water quality. Campylobacters were frequently present in agriculture- and sewage-impacted stretches of streams. The mean campylobacter counts and overall prevalence were highest downstream from a wastewater treatment plant that handled both human and poultry slaughterhouse waste (相似文献   

Drug resistance in tuberculosis--a reinfection model

There is increasing recognition that reinfection is an important component of TB transmission. Moreover, it has been shown that partial immunity has significant epidemiological consequences, particularly in what concerns disease prevalence and effectiveness of control measures. We address the problem of drug resistance as a competition between two types of strains of Mycobacterium tuberculosis: those that are sensitive to anti-tuberculosis drugs and those that are resistant. Our objective is to characterise the role of reinfection in the transmission of drug-resistant tuberculosis. The long-term behaviour of our model reflects how reinfection modifies the conditions for coexistence of sensitive and resistant strains. This sets the scene for discussing how strain prevalence is affected by different control strategies. It is shown that intervention effectiveness is highly sensitive to the baseline epidemiological setting.     

A Mathematical Model of Rift Valley Fever with Human Host

Rift Valley Fever is a vector-borne disease mainly transmitted by mosquito. To gain some quantitative insights into its dynamics, a deterministic model with mosquito, livestock, and human host is formulated as a system of nonlinear ordinary differential equations and analyzed. The disease threshold [Formula: see text] is computed and used to investigate the local stability of the equilibria. A sensitivity analysis is performed and the most sensitive model parameters to the measure of initial disease transmission [Formula: see text] and the endemic equilibrium are determined. Both [Formula: see text] and the disease prevalence in mosquitoes are more sensitive to the natural mosquito death rate, d(m). The disease prevalence in livestock and humans are more sensitive to livestock and human recruitment rates, [Formula: see text] and [Formula: see text], respectively, suggesting isolation of livestock from humans is a viable preventive strategy during an outbreak. Numerical simulations support the analytical results in further exploring theoretically the long-term dynamics of the disease at the population level.     

Genetic basis of human testicular germ cell cancer: insights from the fruitfly and mouse

The prevalence of tumours of the germ line is increasing in the male population. This complex disease has a complex aetiology. We examine the contribution of genetic mutations to the development of germ line tumours in this review. In particular, we concentrate on fly and mouse experimental systems in order to demonstrate that mutations in some conserved genes cause pathologies typical of certain human germ cell tumours, whereas other mutations elicit phenotypes that are unique to the experimental model. Despite these experimental systems being imperfect, we show that they are useful models of human testicular germ cell tumourigenesis.     

A mathematical model for the transmission of Schistosoma japonicum in consideration of seasonal water level fluctuations of Poyang Lake in Jiangxi,China

BackgroundPoyang Lake, the largest fresh water lake in China, is the major transmission site of Schistosoma japonicum in China. Epidemics of schistosomiasis japonica have threatened the health of residents and stunted social–economic development there.ObjectiveThis article aims at evaluating the effect of various control measures against schistosomiasis: selective mass treatment (ST), targeted mass treatment (TT), mass treatment for animal reservoirs (MT), and health education (HE), on reduction of the prevalence through simulations based on a mathematical model.MethodsWe proposed a mathematical model, which is a system of ordinary differential equations for the transmission of S. japonicum among humans, bovines, and snails. The model takes into account the seasonal variation of the water level of Poyang Lake that is caused by the backflow of the Yangtze River and inflow from five small rivers, which influences the transmission of S. japonicum. For the purpose of dealing with the age-specific prevalence and intensity of infection, the human population was classified into four age categories in the model. We carried out several simulations resulting from the execution of ST and TT for elementary school children (E Sch), and combinations of ST, MT, and HE.ResultsThe simulations indicated that all of the control measures only for humans had a trend of revival after interruption, and a combination of ST and MT has a significant effect on reducing human infection. Although TT and HE had a significant effect on the prevalence in the E Sch group, it had little effect on the overall human population.ConclusionThe simulations indicate that measures targeted to bovines such as chemotherapy besides humans will be vital to eliminate the transmission of S. japonicum in the Poyang Lake region. Moreover, it is desirable to improve health education for fishermen and herdsmen.     

The role of lizards in the ecology of Lyme disease in two endemic zones of the northeastern United States

We examined the role of lizards in the ecology of Lyme disease in New York and Maryland. We collected data on vector tick infestations, measured lizard "realized" reservoir competence for the Lyme disease spirochete Borrelia burgdorferi, and estimated lizard population density. These data were incorporated into a model that predicts a host's ability to influence the prevalence of B. burgdorferi in the tick population, a primary risk factor in the epidemiology of Lyme disease. Published data on other northeastern hosts were included in the model to provide a reference for interpreting the importance of lizards as hosts. The model results indicate that 5-lined skinks (Eumeces fasciatus) are dilution hosts, capable of reducing infection prevalence in the tick population by 10.7-51.5 percentage points, whereas eastern fence lizards (Sceloporus undulatus) are not dilution hosts in the areas studied. Owing to moderate burdens of larval ticks, relatively high population densities, and reservoir incompetence, E. fasciatus may play an important role in the ecology of Lyme disease by reducing vector infection prevalence and associated human risk of infection.     

A global view on fungal infections in humans and animals: opportunistic infections and microsporidioses

After cardiovascular diseases, infectious diseases are the second most common cause of death worldwide. Although these infections are caused mainly by viruses or bacteria, a systematically growing prevalence of human and animal opportunistic fungal infections is noticeable worldwide. More attention is being paid to this problem, especially due to the growing frequency of recalcitrant and recurrent mycoses. The latter are classically divided into superficial, which are the most common type, subcutaneous, and systemic. This work discusses opportunistic fungal pathogens without proven horizontal transmission between different animal species including humans and microsporidia as spore-forming unicellular parasites related to fungi; however, with a yet undetermined taxonomic position. The review also mentions aetiological agents, risk factors, epidemiology, geographical distribution, and finally symptoms characteristic for individual disease entities. This paper provides insight into fungal infections from a global perspective and simultaneously draws attention to emerging pathogens, whose prevalence is continuously increasing. Finally, this work also takes into consideration the correct nomenclature of fungal disease entities and the importance of secondary metabolites in the pathogenesis of fungal infections.     

Predicting the impact of long-term temperature changes on the epidemiology and control of schistosomiasis: a mechanistic model

Background

Many parasites of medical and veterinary importance are transmitted by cold-blooded intermediate hosts or vectors, the abundance of which will vary with ambient temperatures, potentially altering disease prevalence. In particular, if global climate change will increase mean ambient temperature in a region endemic with a human pathogen then it is possible that the incidence of disease will similarly increase. Here we examine this possibility by using a mathematical model to explore the effects of increasing long-term mean ambient temperature on the prevalence and abundance of the parasite Schistosoma mansoni, the causative agent of schistosomiasis in humans.

Principal Findings

The model showed that the impact of temperature on disease prevalence and abundance is not straightforward; the mean infection burden in humans increases up to 30°C, but then crashes at 35°C, primarily due to increased mortalities of the snail intermediate host. In addition, increased temperatures changed the dynamics of disease from stable, endemic infection to unstable, epidemic cycles at 35°C. However, the prevalence of infection was largely unchanged by increasing temperatures. Temperature increases also affected the response of the model to changes in each parameter, indicating certain control strategies may become less effective with local temperature changes. At lower temperatures, the most effective single control strategy is to target the adult parasites through chemotherapy. However, as temperatures increase, targeting the snail intermediate hosts, for example through molluscicide use, becomes more effective.

Conclusions

These results show that S. mansoni will not respond to increased temperatures in a linear fashion, and the optimal control strategy is likely to change as temperatures change. It is only through a mechanistic approach, incorporating the combined effects of temperature on all stages of the life-cycle, that we can begin to predict the consequences of climate change on the incidence and severity of such diseases.     

Distribution and Ecology of Campylobacters in Coastal Plain Streams (Georgia, United States of America)

Campylobacter is the leading cause of bacterium-associated diarrhea in the United States and most developed countries. While this disease is considered a food-borne disease, many clinical cases cannot be linked to a food source. In rural and agrarian areas environmental transmission may be an important factor contributing to case loads. Here we investigated the waterborne prevalence of campylobacters in a mixed-use rural watershed in the coastal plain of southern Georgia (United States). Six sites representing various degrees of agricultural and human influence were surveyed biweekly to monthly for 1 year for the presence of culturable thermophilic campylobacters and other measures of water quality. Campylobacters were frequently present in agriculture- and sewage-impacted stretches of streams. The mean campylobacter counts and overall prevalence were highest downstream from a wastewater treatment plant that handled both human and poultry slaughterhouse waste (≤595 CFU ml⁻¹; 100% positive); the concentrations were significantly higher than those for the four upstream sites (P < 0.05). The counts were significantly correlated with the number of fecal coliform bacteria, conductivity, pH, and concentrations of nutrients (NO₃⁻, PO₄³⁻, and NH₃). Campylobacters were isolated more frequently and larger numbers were present during the summer months, similar to the occurrence of clinical cases of campylobacteriosis in this region. A multivariate model showed that the levels were significantly influenced by increasing precipitation, which also peaked in the summer. The results indicate that loading from both human and domestic animal waste may be high in the watershed studied during the summer months. Mixed-use watersheds supporting agriculture production, human populations, and wildlife may be at risk for contamination by campylobacters and may be an important route for human exposure.     

Assessing the potential impact of Salmonella vaccines in an endemically infected dairy herd

Salmonella spp. in cattle contribute to bacterial foodborne disease for humans. Reduction of Salmonella prevalence in herds is important to prevent human Salmonella infections. Typical control measures are culling of infectious animals, vaccination, and improved hygiene management. Vaccines have been developed for controlling Salmonella transmission in dairy herds; however, these vaccines are imperfect and a variety of vaccine effects on susceptibility, infectiousness, Salmonella shedding level, and duration of infectious period were reported. To assess the potential impact of imperfect Salmonella vaccines on prevalence over time and the eradication criterion, we developed a deterministic compartmental model with both replacement (cohort) and lifetime (continuous) vaccination strategies, and applied it to a Salmonella Cerro infection in a dairy farm. To understand the uncertainty of prevalence and identify key model parameters, global parameter uncertainty and sensitivity analyses were performed. The results show that imperfect Salmonella vaccines reduce the prevalence of Salmonella Cerro. Among three vaccine effects that were being considered, decreasing the length of the infectious period is most effective in reducing the endemic prevalence. Analyses of contour lines of prevalence or the critical reproduction ratio illustrate that, reducing prevalence to a certain level or zero can be achieved by choosing vaccines that have either a single vaccine effect at relatively high effectiveness, or two or more vaccine effects at relatively low effectiveness. Parameter sensitivity analysis suggests that effective control measures through applying Salmonella vaccines should be adjusted at different stages of infection. In addition, lifetime (continuous) vaccination is more effective than replacement (cohort) vaccination. The potential application of the developed vaccination model to other Salmonella serotypes related to foodborne diseases was also discussed. The presented study may be used as a tool for guiding the development of Salmonella vaccines.     

Expected behavior of conditional linkage disequilibrium.

The ubiquitousness of RFLPs in the human genome has greatly helped the mapping of human disease genes, and it has been suggested that population measures of association between disease and marker loci could help with this mapping. For rare diseases, random samples are taken from within disease genotypes in order to obtain reasonable sample sizes, but this sampling strategy requires a modification of the usual measures of association. We present theoretical predictions for the mean and variance of such a modified measure, under the assumption that the disease gene is maintained at a constant low frequency in the population. The coefficient of variation of this modified measure is large enough that caution is needed in using the measure to locate disease genes, and, furthermore, the coefficient of variation cannot be made arbitrarily small by increasing sample size. The modified association measure is calculated for recently published data on cystic fibrosis.     

Analysis of rabies in China: transmission dynamics and control

Human rabies is one of the major public-health problems in China. The number of human rabies cases has increased dramatically in the last 15 years, partially due to the poor understanding of the transmission dynamics of rabies and the lack of effective control measures of the disease. In this article, in order to explore effective control and prevention measures we propose a deterministic model to study the transmission dynamics of rabies in China. The model consists of susceptible, exposed, infectious, and recovered subpopulations of both dogs and humans and describes the spread of rabies among dogs and from infectious dogs to humans. The model simulations agree with the human rabies data reported by the Chinese Ministry of Health. We estimate that the basic reproduction number for the rabies transmission in China and predict that the number of the human rabies is decreasing but may reach another peak around 2030. We also perform some sensitivity analysis of in terms of the model parameters and compare the effects of culling and immunization of dogs. Our study demonstrates that (i) reducing dog birth rate and increasing dog immunization coverage rate are the most effective methods for controlling rabies in China; and (ii) large scale culling of susceptible dogs can be replaced by immunization of them.