Low Transmission Probability Research Articles

Controlling infectious disease through the targeted manipulation of contact network structure

Individuals in human and animal populations are linked through dynamic contact networks with characteristic structural features that drive the epidemiology of directly transmissible infectious diseases. Using animal movement data from the British cattle industry as an example, this analysis explores whether disease dynamics can be altered by placing targeted restrictions on contact formation to reconfigure network topology. This was accomplished using a simple network generation algorithm that combined configuration wiring with stochastic block modelling techniques to preserve the weighted in- and out-degree of individual nodes (farms) as well as key demographic characteristics of the individual network connections (movement date, livestock market, and animal production type). We then tested a control strategy based on introducing additional constraints into the network generation algorithm to prevent farms with a high in-degree from selling cattle to farms with a high out-degree as these particular network connections are predicted to have a disproportionately strong role in spreading disease. Results from simple dynamic disease simulation models predicted significantly lower endemic disease prevalences on the trade restricted networks compared to the baseline generated networks. As expected, the relative magnitude of the predicted changes in endemic prevalence was greater for diseases with short infectious periods and low transmission probabilities. Overall, our study findings demonstrate that there is significant potential for controlling multiple infectious diseases simultaneously by manipulating networks to have more epidemiologically favourable topological configurations. Further research is needed to determine whether the economic and social benefits of controlling disease can justify the costs of restricting contact formation.

The influence of boron micro-inhomogeneities on neutron transmission

Boron alloyed steels and boron-polyethylene have been investigated by applying neutron transmission analysis. A high degree of boron homogeneity has been confirmed in these materials. However, the neutron transmission through thick and strong absorbing steel sheets is slightly enhanced due to boron micro-inhomogeneities. Although such micro-structure remains invisible in neutron images they reveal themselves by the enhanced neutron transmission, especially in the low transmission probability rates of 10−2 and below. The transmission data have been analyzed by applying different models of micro-inhomogeneities in MCNPX, (in the range of 20μm) all of them yielding an elevated transmission compared to the homogeneous case. It will be shown that, including the micro-structure in the analysis, provides a more suitable modeling of neutron transmission through strong absorbing materials.

Tools for the selection of the transmission probability in the cluster formation phase for Event-Driven Wireless Sensor Networks

In the literature, it is common to find studies on Wireless Sensor Networks (WSNs) that consider the Carrier Sense Multiple Access (CSMA) protocol with a fixed transmission probability for means of the random access strategy. This is especially true for event-driven applications for clusteredbased architectures. However, due to the highly variable environment in these networks in terms of the number of nodes attempting a transmission (at the beginning of the cluster formation all nodes in the network contend for the channel, while at the end only a few nodes attempt a transmission), a fixed transmission probability may not entail an adequate performance. Specifically, the energy consumption may be too high by considering a fixed transmission strategy, because the use of a low transmission probability at the beginning of the cluster formation reduces the collision probability, but at the end entails long idle periods. In view of this, the effects of three different transmission probability strategies for event-driven WSNs are studied. Based on the obtained results, it is shown that a careful selection of the transmission probability is required in order to prolong the network lifetime.

Mapping the zoonotic niche of Ebola virus disease in Africa.

Ebola virus disease (EVD) is a complex zoonosis that is highly virulent in humans. The largest recorded outbreak of EVD is ongoing in West Africa, outside of its previously reported and predicted niche. We assembled location data on all recorded zoonotic transmission to humans and Ebola virus infection in bats and primates (1976-2014). Using species distribution models, these occurrence data were paired with environmental covariates to predict a zoonotic transmission niche covering 22 countries across Central and West Africa. Vegetation, elevation, temperature, evapotranspiration, and suspected reservoir bat distributions define this relationship. At-risk areas are inhabited by 22 million people; however, the rarity of human outbreaks emphasises the very low probability of transmission to humans. Increasing population sizes and international connectivity by air since the first detection of EVD in 1976 suggest that the dynamics of human-to-human secondary transmission in contemporary outbreaks will be very different to those of the past.

HIV-1 vaginal transmission: cell-free or cell-associated virus?

The vast majority of new HIV infections in male-to-female transmission occurs through semen, where HIV-1 is present in two different forms: as free and as cell-associated virus. In the female lower genital tract, semen mixes with female genital secretions that contain various factors, some of which facilitate or inhibit HIV-1 transmission. Next, HIV-1 crosses the genital epithelia, reaches the regional lymph nodes, and disseminates through the female host. Cervico-vaginal mucosa contains multiple barriers, resulting in a low probability of vaginal transmission. However, in some cases, HIV-1 is able to break these barriers. Although the exact mechanisms of how these barriers function remain unclear, their levels of efficiency against cell-free and cell-associated HIV-1 are different, and both cell-free and cell-associated virions seem to use different strategies to overcome these barriers. Understanding the basic mechanisms of HIV-1 vaginal transmission is required for the development of new antiviral strategies to contain HIV-1 epidemics.

Biophysically based computational models of astrocyte ~ neuron coupling and their functional significance

EDITORIAL article Front. Comput. Neurosci., 07 May 2013 https://doi.org/10.3389/fncom.2013.00044

Herpes simplex virus type 2 infection as a biomarker for sexual debut among young people in sub-Saharan Africa: a literature review

Biological markers are needed in order to provide objective measures to validate self-reported sexual behaviour and interpret prevention trial data. In this review, we evaluated herpes simplex type 2 virus (HSV-2), one of the most prevalent sexually transmitted infections in sub-Saharan Africa as a biological marker of sexual debut. Based on our findings, we do not recommend using HSV-2 as a biomarker for sexual debut due to its low transmission probabilities and the fact that HSV-2 prevalence is not 100% among potential sexual partners. We recommend that the validation of alternative biological measures should be prioritized, and included in future studies and trials of interventions to reduce sexual health risk.

A prospective survey of percutaneous injuries in dental post graduates during periodontal procedures.

Abstract: Occupational exposures to blood borne pathogens can occur as a result of percutaneous injuries during periodontal procedures. Detailed attention to the pattern of injuries could help in developing improved strategies to further minimize their incidence.We surveyed 12 residents enrolled in the MDS course for one year to find out how many percutaneous injuries occurred during periodontal procedures .Survey questionnaire inquired in detail about the circumstances, site and the nature of injury. We also noted the risk status of patient and device which caused the injury.A total of 48 percutaneous injuries (7.84%) were received in 612 periodontal procedures in the 1 year survey. The injury rate was 4/year/resident and individual residents suffered from 2-7 injuries during the study. The difference in number of percutaneous injuries sustained in surgical periodontal procedures (41/265) was highly significant statistically (p<0.0001) when compared to those in non surgical interventions (7/670).Most injuries occurred from suture needle followed by Castroviejo and injection needle. There is a low probability of occupational transmission of blood borne diseases in periodontal procedures. The findings of this study could possibly contribute further in efforts to reduce the incidence of percutaneous injuries during periodontal procedures.

Self-repair in a bidirectionally coupled astrocyte-neuron (AN) system based on retrograde signaling.

In this paper we demonstrate that retrograde signaling via astrocytes may underpin self-repair in the brain. Faults manifest themselves in silent or near silent neurons caused by low transmission probability (PR) synapses; the enhancement of the transmission PR of a healthy neighboring synapse by retrograde signaling can enhance the transmission PR of the “faulty” synapse (repair). Our model of self-repair is based on recent research showing that retrograde signaling via astrocytes can increase the PR of neurotransmitter release at damaged or low transmission PR synapses. The model demonstrates that astrocytes are capable of bidirectional communication with neurons which leads to modulation of synaptic activity, and that indirect signaling through retrograde messengers such as endocannabinoids leads to modulation of synaptic transmission PR. Although our model operates at the level of cells, it provides a new research direction on brain-like self-repair which can be extended to networks of astrocytes and neurons. It also provides a biologically inspired basis for developing highly adaptive, distributed computing systems that can, at fine levels of granularity, fault detect, diagnose and self-repair autonomously, without the traditional constraint of a central fault detect/repair unit.

Geographic Variation in Life Cycle Strategies of a Progenetic Trematode

Numerous parasite species have evolved complex life cycles with multiple, subsequent hosts. In trematodes, each transmission event in multi-host life cycles selects for various adaptations, one of which is facultative life cycle abbreviation. This typically occurs through progenesis, i.e., precocious maturity and reproduction via self-fertilization within the second intermediate host. Progenesis eliminates the need for the definitive host and facilitates life cycle completion. Adopting a progenetic cycle may be a conditional strategy in response to environmental cues related to low probability of transmission to the definitive host. Here, the effects of environmental factors on the reproductive strategy of the progenetic trematode Stegodexamene anguillae were investigated using comparisons among populations. In the 3-host life cycle, S. anguillae sexually reproduces within eel definitive hosts, whereas in the progenetic life cycle, S. anguillae reproduces by selfing within the metacercaria cyst in tissues of small fish intermediate hosts. Geographic variation was found in the frequency of progenesis, independent of eel abundance. Progenesis was affected by abundance and length of the second intermediate fish host as well as encystment site within the host. The present study is the first to compare life cycle strategies among parasite populations, providing insight into the often unrecognized plasticity in parasite developmental strategies and transmission.

Effect of variable transmission rate on the dynamics of HIV in sub-Saharan Africa

BackgroundThe cause of the high HIV prevalence in sub-Saharan Africa is incompletely understood, with heterosexual penile-vaginal transmission proposed as the main mechanism. Heterosexual HIV transmission has been estimated to have a very low probability; but effects of cofactors that vary in space and time may substantially alter this pattern.MethodsTo test the effect of individual variation in the HIV infectiousness generated by co-infection, we developed and analyzed a mathematical sexual network model that simulates the behavioral components of a population from Malawi, as well as the dynamics of HIV and the co-infection effect caused by other infectious diseases, including herpes simplex virus type-2, gonorrhea, syphilis and malaria.ResultsThe analysis shows that without the amplification effect caused by co-infection, no epidemic is generated, and HIV prevalence decreases to extinction. But the model indicates that an epidemic can be generated by the amplification effect on HIV transmission caused by co-infection.ConclusionThe simulated sexual network demonstrated that a single value for HIV infectivity fails to describe the dynamics of the epidemic. Regardless of the low probability of heterosexual transmission per sexual contact, the inclusion of individual variation generated by transient but repeated increases in HIV viral load associated with co-infections may provide a biological basis for the accelerated spread of HIV in sub-Saharan Africa. Moreover, our work raises the possibility that the natural history of HIV in sub-Saharan Africa cannot be fully understood if individual variation in infectiousness is neglected.

P1-S5.41 Quantifying the contribution of re-infection within partnerships to persistent spread of Chlamydia

Background Many studies show that people testing positive and treated for genital chlamydia infection are at high risk of a repeat infection in the first year after treatment. Repeat infection can come from treatment failure, a new partner, or from within an existing partnership if the partner was not treated. Partnerships can therefore form a reservoir of chlamydia infections that might affect the effectiveness of population screening programs. It is not known how much reinfection within partnerships contributes to the persistent spread of chlamydia in heterosexual populations. Methods We derive an expression for the basic reproduction number of an SIS infection in a population with long term monogamous partnerships. The basic reproduction number contains an explicit term quantifying the contribution of re-infection within partnerships to the overall reproduction number. The derivation is then extended to include partner notification and treatment. Finally, the model is extended to include two types of partnerships with differing average duration. Results For small recovery rates and low transmission probabilities reinfection plays a minor role in sustaining chlamydia transmission. However, there is an optimal combination of duration of infection and transmission probability for which reinfection contributes substantially to keeping chlamydia endemic in a population. We discuss the functional dependency of the basic reproduction number on these parameters. Using a more complex model numerical scenarios were simulated showing that partner notification prevents a large proportion of re-infections. Conclusions The effect of screening depends, in part, on whether or not it succeeds in moving the basic reproduction number away from the transmission optimum via reinfection. This can be achieved either by choice of the screening interval or by rescreening those individuals who tested positive in a first screening test. There is an optimal time interval for retesting that minimises the basic reproduction number. The precise numerical value depends on partnership durations and transmission probabilities.

Life cycle truncation in a trematode: Does higher temperature indicate shorter host longevity?

The typical three-host life cycle of most trematodes creates transmission challenges for which a variety of adaptations have evolved to increase the probability of transmission. Some species can abbreviate their life cycle via progenesis, the precocious maturation of the parasite in the second intermediate host resulting in the production of eggs through self-fertilisation without requiring a definitive host. Adoption of the progenetic life cycle may be a conditional strategy in response to different environmental cues related to low probability of transmission to the definitive host. Using high water temperature and/or limited diet as experimental stressors, we tested the effect of body condition and life span of the fish second intermediate host on facultative truncation of the typical three-host life cycle by progenesis in Stegodexamene anguillae. The results suggest that environmental cues, such as temperature and encystment site, may signal transmission opportunities to the parasite so that it may adjust its developmental strategy accordingly. Indeed, a greater proportion of worms became progenetic at higher temperatures, and progenesis was more common among worms encysted in the gonads or body cavity of their fish hosts than among those in other host tissues. These findings highlight the often unrecognised plasticity in parasite developmental and transmission strategies.

Models of epidemics: when contact repetition and clustering should be included

Background: The spread of infectious disease is determined by biological factors, e.g. the duration of the infectious period, and social factors, e.g. the arrangement of potentially contagious contacts. Repetitiveness and clustering of contacts are known to be relevant factors influencing the transmission of droplet or contact transmitted diseases. Yet unknown is however how these factors are included at best in models of disease spread. Methods: We compare two different types of individual-based models: One assumes random mixing without repetition of contacts, whereas the other assumes that the same contacts repeat day-by-day. The latter exists in two variants, with and without clustering. We systematically test and compare how the total size of an outbreak differs between these model types depending on the key parameters transmission probability, number of contacts per day, duration of the infectious period, different levels of clustering and varying proportions of repetitive contacts. Results: The difference between both model types is highest for low numbers of contacts per day and low transmission probabilities. The number of contacts and the transmission probability have a higher influence on this difference than the duration of the infectious period. Even when only minor parts of the daily contacts are repetitive and clustered can there be relevant differences compared to a purely random mixing model. Conclusion: We show that random mixing models provide acceptable estimates of the total outbreak size if the number of contacts per day is high or if the per-contact transmission probability is high, as in measles. In the case of very short infectious periods, as in Norovirus, models assuming repeating contacts will also behave similarly as random mixing models. If the number of daily contacts or the transmission probability is low, particular consideration should be given to the actual structure of potentially contagious contacts when designing the model.

Models of epidemics: when contact repetition and clustering should be included.

BackgroundThe spread of infectious disease is determined by biological factors, e.g. the duration of the infectious period, and social factors, e.g. the arrangement of potentially contagious contacts. Repetitiveness and clustering of contacts are known to be relevant factors influencing the transmission of droplet or contact transmitted diseases. However, we do not yet completely know under what conditions repetitiveness and clustering should be included for realistically modelling disease spread.MethodsWe compare two different types of individual-based models: One assumes random mixing without repetition of contacts, whereas the other assumes that the same contacts repeat day-by-day. The latter exists in two variants, with and without clustering. We systematically test and compare how the total size of an outbreak differs between these model types depending on the key parameters transmission probability, number of contacts per day, duration of the infectious period, different levels of clustering and varying proportions of repetitive contacts.ResultsThe simulation runs under different parameter constellations provide the following results: The difference between both model types is highest for low numbers of contacts per day and low transmission probabilities. The number of contacts and the transmission probability have a higher influence on this difference than the duration of the infectious period. Even when only minor parts of the daily contacts are repetitive and clustered can there be relevant differences compared to a purely random mixing model.ConclusionWe show that random mixing models provide acceptable estimates of the total outbreak size if the number of contacts per day is high or if the per-contact transmission probability is high, as seen in typical childhood diseases such as measles. In the case of very short infectious periods, for instance, as in Norovirus, models assuming repeating contacts will also behave similarly as random mixing models. If the number of daily contacts or the transmission probability is low, as assumed for MRSA or Ebola, particular consideration should be given to the actual structure of potentially contagious contacts when designing the model.

Functional Specificity of Mossy Fiber Innervation of GABAergic Cells in the Hippocampus

One million mossy fibers in the rat provide individually sparse but functionally important synaptic connections between the dentate gyrus and hippocampus. Although the majority of mossy fiber targets are GABAergic cells, the functional organization of the feedforward GABAergic machinery modulating the interactions of granule cells and CA3 pyramidal cells are not yet understood. We used mossy fiber bouton to GABA neuron paired recordings in the CA3 to demonstrate that mossy fibers provide cell type-specific innervation to distinct GABAergic neurons with specialized intra- and extrahippocampal outputs. Our results show that mossy fibers contact the perisomatically projecting fast-spiking and regular-spiking basket cells, in addition to the dendritically projecting ivy cells, and the septum-projecting spiny stratum lucidum cells. Monosynaptic mossy fiber inputs to fast-spiking basket cells and spiny stratum lucidum cells were found to be numerous, but they were small in amplitude and displayed low transmission probabilities. In contrast, regular-spiking basket cells and ivy cells were less likely to be innervated by mossy fibers, but the amplitudes of mossy fiber EPSCs were large and the transmission probabilities were high. The dependence of the numbers and strengths of the mossy fiber inputs to CA3 GABAergic cells on the postsynaptic cell type was correlated with the frequency of the background synaptic events, so that cells with weak but numerous mossy fiber inputs received high rates of spontaneous synaptic events. Together, these results reveal the diverse components and high degree of functional specificity of the GABAergic cellular machinery underlying the dentate gyrus-CA3 interface.

Updated Annual HIV Transmission Rates in the United States, 1977-2006

Updated Annual HIV Transmission Rates in the United States, 1977-2006

Disease dynamics over very different time-scales: foot-and-mouth disease and scrapie on the network of livestock movements in the UK.

We analyse the relationship between the network of livestock movements in the UK and the dynamics of two diseases: foot-and-mouth disease (FMD), which has an incubation period of days, and scrapie, which incubates over years. For FMD, the time-scale of expected epidemics is similar to the time-scale of the evolution of the network. We argue that, under appropriate conditions, a static network analysis can be an appropriate tool for gaining insights into disease dynamics even when the relevant time-scales are similar, as with FMD. We show that a subclass of ‘linkage moves’ maintains the network structure, and so removing these links has a dramatic effect on the number of potentially infected farms, an effect corroborated by simulations. In contrast, because scrapie has a low probability of transmission per contact and a long incubation period, a static network representation is probably appropriate; however, the signature of the network in the pattern of transmission is likely to be faint. Scrapie-notifying farms were more likely to be associated with each other via trading at markets than were control farms; however, network community structure proves to be less representative of prevalence patterns than geographical region. These contradictory indicators emphasize that appropriate observation time frames and good discrimination among types of potentially infectious contacts are vital in order for network analysis to be a valuable epidemiological tool.

The canine distemper epidemic in Serengeti: are lions victims of a new highly virulent canine distemper virus strain, or is pathogen circulation stochasticity to blame?

In the year 1994, the Serengeti lion population was decimated by a canine distemper disease outbreak. Retrospective investigations showed that this host population had already been in contact with the pathogen in 1981 without any detected sign of disease. As an alternative to the virus mutation hypothesis to explain this difference in virulences observed in 1981 and 1994, we propose a novel mechanism of disease emergence based on variation in population immunity. We use a stochastic model to show that stochastic fluctuations in pathogen circulation, owing to a low probability of virus transmission from its reservoir to the target host and thereby resulting in variations in the global immunity level of the target host population, can explain the observations made in Serengeti. This mechanism may also be involved in other infectious disease emergences or re-emergences.

Preclinical Assessment of HIV Vaccines and Microbicides by Repeated Low-Dose Virus Challenges

BackgroundTrials in macaque models play an essential role in the evaluation of biomedical interventions that aim to prevent HIV infection, such as vaccines, microbicides, and systemic chemoprophylaxis. These trials are usually conducted with very high virus challenge doses that result in infection with certainty. However, these high challenge doses do not realistically reflect the low probability of HIV transmission in humans, and thus may rule out preventive interventions that could protect against “real life” exposures. The belief that experiments involving realistically low challenge doses require large numbers of animals has so far prevented the development of alternatives to using high challenge doses.Methods and FindingsUsing statistical power analysis, we investigate how many animals would be needed to conduct preclinical trials using low virus challenge doses. We show that experimental designs in which animals are repeatedly challenged with low doses do not require unfeasibly large numbers of animals to assess vaccine or microbicide success.ConclusionPreclinical trials using repeated low-dose challenges represent a promising alternative approach to identify potential preventive interventions.