Quantifying the Routes of Transmission for Pandemic Influenza

Motivated by the desire to assess nonpharmaceutical interventions for pandemic influenza, we seek in this study to quantify the routes of transmission for this disease. We construct a mathematical model of aerosol (i.e., droplet-nuclei) and contact transmission of influenza within a household containing one infected. An analysis of this model in conjunction with influenza and rhinovirus data suggests that aerosol transmission is far more dominant than contact transmission for influenza. We also consider a separate model of a close expiratory event, and find that a close cough is unlikely (≈1% probability) to generate traditional droplet transmission (i.e., direct deposition on the mucous membranes), although a close, unprotected and horizontally-directed sneeze is potent enough to cause droplet transmission. There are insufficient data on the frequency of close expiratory events to assess the relative importance of aerosol transmission and droplet transmission, and it is prudent to leave open the possibility that droplet transmission is important until proven otherwise. However, the rarity of close, unprotected and horizontally-directed sneezes—coupled with the evidence of significant aerosol and contact transmission for rhinovirus and our comparison of hazard rates for rhinovirus and influenza—leads us to suspect that aerosol transmission is the dominant mode of transmission for influenza.     

Contact transmission of Tobacco mosaic virus: a quantitative analysis of parameters relevant for virus evolution

Transmission between hosts is required for the maintenance of parasites in the host population and determines their ultimate evolutionary success. The transmission ability of parasites conditions their evolution in two ways: on one side, it affects the genetic structure of founded populations in new hosts. On the other side, parasite traits that increase transmission efficiency will be selected for. Therefore, knowledge of the factors and parameters that determine transmission efficiency is critical to predict the evolution of parasites. For plant viruses, little is known about the parameters of contact transmission, a major way of transmission of important virus genera and species. Here, we analyze the factors determining the efficiency of contact transmission of Tobacco mosaic virus (TMV) that may affect virus evolution. As it has been reported for other modes of transmission, the rate of TMV transmission by contact depended on the contact opportunities between an infected and a noninfected host. However, TMV contact transmission differed from other modes of transmission, in that a positive correlation between the virus titer in the source leaf and the rate of transmission was not found within the range of our experimental conditions. Other factors associated with the nature of the source leaf, such as leaf age and the way in which it was infected, had an effect on the rate of transmission. Importantly, contact transmission resulted in severe bottlenecks, which did not depend on the host susceptibility to infection. Interestingly, the effective number of founders initiating the infection of a new host was highly similar to that reported for aphid-transmitted plant viruses, suggesting that this trait has evolved to an optimum value.     

Persistence of Pathogens with Short Infectious Periods in Seasonal Tick Populations: The Relative Importance of Three Transmission Routes

Background

The flaviviruses causing tick-borne encephalitis (TBE) persist at low but consistent levels in tick populations, despite short infectious periods in their mammalian hosts and transmission periods constrained by distinctly seasonal tick life cycles. In addition to systemic and vertical transmission, cofeeding transmission has been proposed as an important route for the persistence of TBE-causing viruses. Because cofeeding transmission requires ticks to feed simultaneously, the timing of tick activity may be critical to pathogen persistence. Existing models of tick-borne diseases do not incorporate all transmission routes and tick seasonality. Our aim is to evaluate the influence of seasonality on the relative importance of different transmission routes by using a comprehensive mathematical model.

Methodology/Principal Findings

We developed a stage-structured population model that includes tick seasonality and evaluated the relative importance of the transmission routes for pathogens with short infectious periods, in particular Powassan virus (POWV) and the related “deer tick virus,” emergent encephalitis-causing flaviviruses in North America. We used the next generation matrix method to calculate the basic reproductive ratio and performed elasticity analyses. We confirmed that cofeeding transmission is critically important for such pathogens to persist in seasonal tick populations over the reasonable range of parameter values. At higher but still plausible rates of vertical transmission, our model suggests that vertical transmission can strongly enhance pathogen prevalence when it operates in combination with cofeeding transmission.

Conclusions/Significance

Our results demonstrate that the consistent prevalence of POWV observed in tick populations could be maintained by a combination of low vertical, intermediate cofeeding and high systemic transmission rates. When vertical transmission is weak, nymphal ticks support integral parts of the transmission cycle that are critical for maintaining the pathogen. We also extended the model to pathogens that cause chronic infections in hosts and found that cofeeding transmission could contribute to elevating prevalence even in these systems. Therefore, the common assumption that cofeeding transmission is not relevant in models of chronic host infection, such as Lyme disease, could lead to underestimating pathogen prevalence.     

Infection parameters in the sand fly vector that predict transmission of Leishmania major

To identify parameters of Leishmania infection within a population of infected sand flies that reliably predict subsequent transmission to the mammalian host, we sampled groups of infected flies and compared infection intensity and degree of metacyclogenesis with the frequency of transmission. The percentage of parasites within the midgut that were metacyclic promastigotes had the highest correlation with the frequency of transmission. Meta-analysis of multiple transmission experiments allowed us to establish a percent-metacyclic "cutoff" value that predicted transmission competence. Sand fly infections initiated with variable doses of parasites resulted in correspondingly altered percentages of metacyclic promastigotes, resulting in altered transmission frequency and disease severity. Lastly, alteration of sand fly oviposition status and environmental conditions at the time of transmission also influenced transmission frequency. These observations have implications for transmission of Leishmania by the sand fly vector in both the laboratory and in nature, including how the number of organisms acquired by the sand fly from an infection reservoir may influence the clinical outcome of infection following transmission by bite.     

Theoretical aspects of the mode of transmission in cultural inheritance.

This study investigates how evolutionary factors interact to determine the relative importance of vertical versus nonvertical mode of transmission in cultural inheritance. Simple mathematical models are provided to study the joint evolution of two cultural characters, one determining the viability and the fertility of individuals, and the other determining the vertical transmission rate of the first trait. Ordinary local stability analyses indicate that intrademic processes should lead to a greater reliance on vertical cultural transmission. On the other hand, when newly arisen variants are adaptive and favored in biased cultural transmission, interdemic processes may lead to a decrease in vertical transmission. This is because biased nonvertical transmission may effectively propagate the adaptive variants, further increasing the average growth rate of the population. These results are verified under several distinct sets of assumptions. It is also inferred that the degree and intensity of transmission bias may be the important determinants of cultural processes.     

The impact of transmission mode on the evolution of benefits provided by microbial symbionts

While past work has often examined the effects of transmission mode on virulence evolution in parasites, few studies have explored the impact of horizontal transmission on the evolution of benefits conferred by a symbiont to its host. Here, we identify three mechanisms that create a positive covariance between horizontal transmission and symbiont‐provided benefits: pleiotropy within the symbiont genome, partner choice by the host, and consumption of host waste by‐products by symbionts. We modify a susceptible‐infected model to incorporate the details of each mechanism and examine the evolution of symbiont benefits given variation in either the immigration rate of susceptible hosts or the rate of successful vertical transmission. We find conditions for each case under which greater opportunity for horizontal transmission (higher migration rate) favors the evolution of mutualism. Further, we find the surprising result that vertical transmission can inhibit the evolution of benefits provided by symbionts to hosts when horizontal transmission and symbiont‐provided benefits are positively correlated. These predictions may apply to a number of natural systems, and the results may explain why many mutualisms that rely on partner choice often lack a mechanism for vertical transmission.     

The curse of the Pharaoh revisited: evolutionary bi-stability in environmentally transmitted pathogens

It is increasingly evident that for a number of high-profile pathogens, transmission involves both direct and environmental pathways. Much of the distinguished evolutionary theory has, however, focused on each of transmission component separately. Herein, we use the framework of adaptive dynamics to study the evolutionary consequences of mixed transmission. We find that environmental transmission can select for increased virulence when direct transmission is low. Increasing the efficiency of direct transmission gives rise to an evolutionary bi-stability, with coexistence of different levels of virulence. We conclude that the overlooked contribution of environmental transmission may explain the curious appearance of high virulence in pathogens that are typically only moderately pathogenic, as observed for avian influenza viruses and cholera.     

The effect of contact heterogeneity and multiple routes of transmission on final epidemic size

Heterogeneity in the number of potentially infectious contacts amongst members of a population increases the basic reproduction ratio (R(0)) and markedly alters disease dynamics compared to traditional mean-field models. Most models describing transmission on contact networks only account for one specific route of transmission. However, for many infectious diseases multiple routes of transmission exist. The model presented here captures transmission through a well defined network of contacts, complemented by mean-field type transmission amongst the nodes of the network that accounts for alternative routes of transmission. The impact of these combined transmission mechanisms on the final epidemic size is investigated analytically. The analytic predictions for the purely mean-field case and the transmission through the network-only case are confirmed by individual-based network simulations. There is a critical transmission potential above which an increased contribution of the mean-field type transmission increases the final epidemic size while an increased contribution of the transmission through the network decreases it. Below the critical transmission potential the opposite effect is observed.     

Unidirectional Optical Transmission of a Dual Metallic Grating with Grooves

In this paper, a dual grating structure for unidirectional transmission is presented. The forward and backward transmission performances have been investigated by finite element method. To enhance the forward transmission and to suppress the backward transmission simultaneously, we suggested to cut grooves on the surfaces of one of the gratings, and the effects of the grooves on the optical transmission have been studied. The numerical simulation results reveal that the transmission contrast ratio and the optical unidirectional transmission of the structure can be improved markedly by properly arranging the size and the position of the grooves. The forward transmission can be more than 90%, while the backward transmission transmittance is less than 5%.

     

The role of HIV replicative fitness in perinatal transmission of HIV

Perinatal transmission of Human immunodeficiency virus(HIV),also called mother-to-child transmission(MTCT),accounts for 90% of infections in infants worldwide and occurs in 30%-45% of children born to untreated HIV-1 infected mothers.Among HIV-1 infected mothers,some viruses are transmitted from mothers to their infants while others are not.The relationship between virologic properties and the pathogenesis caused by HIV-1 remains unclear.Previous studies have demonstrated that one obvious source of selective pressure in the perinatal transmission of HIV-1 is maternal neutralizing antibodies.Recent studies have shown that viruses which are successfully transmitted to the child have growth advantages over those not transmitted,when those two viruses are grown together.Furthermore,the higher fitness is determined by the gp120 protein of the virus envelope.This suggests that the selective transmission of viruses with higher fitness occurred exclusively,regardless of transmission routes.There are many factors contributing to the selective transmission and HIV replicative fitness is an important one that should not be neglected.This review summarizes current knowledge of the role of HIV replicative fitness in HIV MTCT transmission and the determinants of viral fitness upon MTCT.     

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.     

Genetic control of horizontal virus transmission in the chestnut blight fungus, Cryphonectria parasitica

Vegetative incompatibility in fungi has long been known to reduce the transmission of viruses between individuals, but the barrier to transmission is incomplete. In replicated laboratory assays, we showed conclusively that the transmission of viruses between individuals of the chestnut blight fungus Cryphonectria parasitica is controlled primarily by vegetative incompatibility (vic) genes. By replicating vic genotypes in independent fungal isolates, we quantified the effect of heteroallelism at each of six vic loci on virus transmission. Transmission occurs with 100% frequency when donor and recipient isolates have the same vic genotypes, but heteroallelism at one or more vic loci generally reduces virus transmission. Transmission was variable among single heteroallelic loci. At the extremes, heteroallelism at vic4 had no effect on virus transmission, but transmission occurred in only 21% of pairings that were heteroallelic at vic2. Intermediate frequencies of transmission were observed when vic3 and vic6 were heteroallelic (76 and 32%, respectively). When vic1, vic2, and vic7 were heteroallelic, the frequency of transmission depended on which alleles were present in the donor and the recipient. The effect of heteroallelism at two vic loci was mostly additive, although small but statistically significant interactions (epistasis) were observed in four pairs of vic loci. A logistic regression model was developed to predict the probability of virus transmission between vic genotypes. Heteroallelism at vic loci, asymmetry, and epistasis were the dominant factors controlling transmission, but host genetic background also was statistically significant, indicating that vic genes alone cannot explain all the variation in virus transmission. Predictions from the logistic regression model were highly correlated to independent transmission tests with field isolates. Our model can be used to estimate horizontal transmission rates as a function of host genetics in natural populations of C. parasitica.     

Elimination of vector-borne transmission of Chagas disease

The control of the vector-borne transmission of Chagas disease in Brazil was organized as a national program in 1975, when two large entomological and sero-epidemiological surveys were conducted in the country in order to identify areas at highest risk of transmission and to guide interventions regarding the chemical treatment of domestic vectors of the disease. The authors present the baseline data gathered through these studies and compare them with more recent data. The evaluation performed shows that the transmission by Triatoma infestans is virtually interrupted and that the transmission by other native species of triatominae from different regions of the country is possibly very low. It is emphasized the need to maintain permanent actions of entomological surveillance in order to prevent recurrent transmission.     

Dispersal increases local transmission of avian malarial parasites

The relationships between dispersal and local transmission rate of parasites are essential to understanding host–parasite coevolution and the emergence and spread of novel disease threats. Here we show that year‐round transmission, as opposed to summer transmission, has repeatedly evolved in malarial parasites (genera Plasmodium and Haemoproteus) of a migratory bird. Year‐round transmission allows parasites to spread in sympatric host's wintering areas, and hence to colonize distantly located host's breeding areas connected by host‐migration movements. Widespread parasites had higher local prevalence, revealing increased transmission, than geographically restricted parasites. Our results show a positive relationship between dispersal and local transmission of malarial parasites that is apparently mediated by frequent evolutionary changes in parasite transmission dynamics, which has important implications for the ecology and evolution of infectious diseases.     

Secondary theorem of natural selection in biocultural populations.

The "Secondary Theorem of Natural Selection," an extension of Fisher's fundamental theorem, states that the rate of change in the mean of an arbitrary character in response to selection is proportional to the additive genetic covariance between the character and fitness. Here I derive an expression for the change in the mean value of a trait subject to both genetic and cultural transmission. I start with the one-locus case under generalized mating and cultural transmission from parents to offspring, then proceed to the two-locus case. My results support previous work on the effects of nongenetic inheritance by showing that (i) cultural transmission introduces a timelag in the population response to selection; (ii) with cultural transmission the effects of selection persist even after selection is relaxed; and (iii) cultural transmission can either enhance or retard phenotypic evolution relative to that obtained under purely genetic transmission.     

Timing of transmission and the evolution of virulence of an insect virus

We used the nuclear polyhedrosis virus of the gypsy moth, Lymantria dispar, to investigate whether the timing of transmission influences the evolution of virulence. In theory, early transmission should favour rapid replication and increase virulence, while late transmission should favour slower replication and reduce virulence. We tested this prediction by subjecting one set of 10 virus lineages to early transmission (Early viruses) and another set to late transmission (Late viruses). Each lineage of virus underwent nine cycles of transmission. Virulence assays on these lineages indicated that viruses transmitted early were significantly more lethal than those transmitted late. Increased exploitation of the host appears to come at a cost, however. While Early viruses initially produced more progeny, Late viruses were ultimately more productive over the entire duration of the infection. These results illustrate fitness trade-offs associated with the evolution of virulence and indicate that milder viruses can obtain a numerical advantage when mild and harmful strains tend to infect separate hosts.     

The Role of Environmental Transmission in Recurrent Avian Influenza Epidemics

Avian influenza virus (AIV) persists in North American wild waterfowl, exhibiting major outbreaks every 2–4 years. Attempts to explain the patterns of periodicity and persistence using simple direct transmission models are unsuccessful. Motivated by empirical evidence, we examine the contribution of an overlooked AIV transmission mode: environmental transmission. It is known that infectious birds shed large concentrations of virions in the environment, where virions may persist for a long time. We thus propose that, in addition to direct fecal/oral transmission, birds may become infected by ingesting virions that have long persisted in the environment. We design a new host–pathogen model that combines within-season transmission dynamics, between-season migration and reproduction, and environmental variation. Analysis of the model yields three major results. First, environmental transmission provides a persistence mechanism within small communities where epidemics cannot be sustained by direct transmission only (i.e., communities smaller than the critical community size). Second, environmental transmission offers a parsimonious explanation of the 2–4 year periodicity of avian influenza epidemics. Third, very low levels of environmental transmission (i.e., few cases per year) are sufficient for avian influenza to persist in populations where it would otherwise vanish.     

Potential versus actual contribution of vertical transmission to pathogen fitness

Theory predicts that virulent parasites cannot be maintained at high prevalence if they are only vertically transmitted. However, parasites with high rates of vertical transmission that cause severe reduction in host fitness have been reported. Atkinsonella hypoxylon is a fungal pathogen capable of both vertical and horizontal transmission that drastically reduces its host''s fitness. In contrast with theoretical predictions, field and laboratory observations suggested that the primary mechanism of transmission was vertical. Using randomly amplified polymorphic DNA markers, we investigated the effective contribution of vertical and horizontal transmission to the genetic structure of three natural populations of A. hypoxylon. We found high genotypic diversity and low linkage disequilibrium, indicating that most established genotypes are derived from horizontally transmitted, sexual spores. The low contribution of vertical transmission to the parasite''s fitness despite its high potential might be due to lower establishment of cleistogamous seeds (through which vertical transmission occurs) or lower vigour of vertically transmitted fungal genotypes. Low establishment of vertically infected hosts might explain the persistence of virulent parasites with high apparent vertical transmission. Our results suggest that caution must be taken when using the potential for vertical transmission to make predictions about the evolution of parasite virulence.     

The role of adaptations in two-strain competition for sylvatic Trypanosoma cruzi transmission

This study presents a continuous-time model for the sylvatic transmission dynamics of two strains of Trypanosoma cruzi enzootic in North America, in order to study the role that adaptations of each strain to distinct modes of transmission (classical stercorarian transmission on the one hand, and vertical and oral transmission on the other) may play in the competition between the two strains. A deterministic model incorporating contact process saturation predicts competitive exclusion, and reproductive numbers for the infection provide a framework for evaluating the competition in terms of adaptive trade-off between distinct transmission modes. Results highlight the importance of oral transmission in mediating the competition between horizontal (stercorarian) and vertical transmission; its presence as a competing contact process advantages vertical transmission even without adaptation to oral transmission, but such adaptation appears necessary to explain the persistence of (vertically-adapted) T. cruzi IV in raccoons and woodrats in the southeastern United States.