Contact tracing in stochastic and deterministic epidemic models

We consider a simple unstructured individual based stochastic epidemic model with contact tracing. Even in the onset of the epidemic, contact tracing implies that infected individuals do not act independent of each other. Nevertheless, it is possible to analyze the embedded non-stationary Galton-Watson process. Based upon this analysis, threshold theorems and also the probability for major outbreaks can be derived. Furthermore, it is possible to obtain a deterministic model that approximates the stochastic process, and in this way, to determine the prevalence of disease in the quasi-stationary state and to investigate the dynamics of the epidemic.     

Contact switching as a control strategy for epidemic outbreaks

We study the effects of switching social contacts as a strategy to control epidemic outbreaks. Connections between susceptible and infective individuals can be broken by either individual, and then reconnected to a randomly chosen member of the population. It is assumed that the reconnecting individual has no previous information on the epidemiological condition of the new contact. We show that reconnection can completely suppress the disease, both by continuous and discontinuous transitions between the endemic and the infection-free states. For diseases with an asymptomatic phase, we analyze the conditions for the suppression of the disease, and show that—even when these conditions are not met—the increase of the endemic infection level is usually rather small. We conclude that, within some simple epidemiological models, contact switching is a quite robust and effective control strategy. This suggests that it may also be an efficient method in more complex situations.     

Lineage tracing

Lineage tracing is the identification of all progeny of a single cell. Although its origins date back to developmental biology of invertebrates in the 19(th) century, lineage tracing is now an essential tool for studying stem cell properties in adult mammalian tissues. Lineage tracing provides a powerful means of understanding tissue development, homeostasis, and disease, especially when it is combined with experimental manipulation of signals regulating cell-fate decisions. Recently, the combination of inducible recombinases, multicolor reporter constructs, and live-cell imaging has provided unprecedented insights into stem cell biology. Here we discuss the different experimental strategies currently available for lineage tracing, their associated caveats, and new opportunities to integrate lineage tracing with the monitoring of intracellular signaling pathways.     

Multiline varieties and disease control

Summary A general model for the evolution of pathogen populations on mixtures or multilines is developed. This model is used to extend previous analyses of the effects of the widespread cultivation of multilines on the evolution of virulence in obligate parasites to mixtures of lines carrying different numbers of resistance genes. It is concluded that the composition of an equilibrium pathogen population growing on a multiline may vary within wide limits and the prinicipal determinant of its composition is the number of components in the multiline and the resistance genes they carry. Other factors of importance are (i) the relative contribution made by each host class (with different numbers of resistance genes) to the pathogen spore pool each generation; (ii) the levels of stabilizing selection against unnecessary virulence genes; and (iii) the way in which unnecessary genes for virulence combine to reduce pathogen fitness. Conditions for the fixation of avirulent biotypes in the pathogen population and the evolution of a pathogen superrace are given for multilines of various compositions.Paper No. 9246 of the Journal Series of the North Carolina Agricultural Research Service, Raleigh, North Carolina. This investigation was supported in part by NIH Research Grant No. GM 11546 from the National Institute of General Medical Sciences     

Cost-effective control of chronic viral diseases: Finding the optimal level of screening and contact tracing

Chronic viral diseases such as human immunodeficiency virus (HIV) and hepatitis B virus (HBV) afflict millions of people worldwide. A key public health challenge in managing such diseases is identifying infected, asymptomatic individuals so that they can receive antiviral treatment. Such treatment can benefit both the treated individual (by improving quality and length of life) and the population as a whole (through reduced transmission). We develop a compartmental model of a chronic, treatable infectious disease and use it to evaluate the cost and effectiveness of different levels of screening and contact tracing. We show that: (1) the optimal strategy is to get infected individuals into treatment at the maximal rate until the incremental health benefits balance the incremental cost of controlling the disease; (2) as one reduces the disease prevalence by moving people into treatment (which decreases the chance that they will infect others), one should increase the level of contact tracing to compensate for the decreased effectiveness of screening; (3) as the disease becomes less prevalent, it is optimal to spend more per case identified; and (4) the relative mix of screening and contact tracing at any level of disease prevalence is such that the marginal efficiency of contact tracing (cost per infected person found) equals that of screening if possible (e.g., when capacity limitations are not binding). We also show how to determine the cost-effective equilibrium level of disease prevalence (among untreated individuals), and we develop an approximation of the path of the optimal prevalence over time. Using this, one can obtain a close approximation of the optimal solution without having to solve an optimal control problem. We apply our methods to an example of hepatitis B virus.     

Infectious animal disease and its control

The control of infectious diseases in the main food-producing animals is considered and the main factors involved in the epizootiology of disease are presented. The properties of infectious agents and their natural history together with factors that influence the spread and development of disease are summarized. The factors in intensive animal husbandry that affect the occurrence of infectious disease and its control are considered. These include population density, population movement, management, hygiene and genetic constitution of the host. They encourage the appearance of new diseases, changes in the character of established diseases and the development of pathogenicity in infectious agents that were previously of no importance. Intensive animal husbandry has also increased the importance of multifactorial disease, which includes diseases that require more than one infectious agent or one or more infectious agents plus other factors for their cause. The methods of control of infectious disease currently available are described and the success and difficulties of their control on a global, national and local (farm or enterprise) basis are considered. Examples of diseases of global importance where national and world programmes of control and eradication have been of varying success are described. Examples of diseases that are enzootic throughout the world and the procedures used for their control are also described. The technological opportunities for the improvement of the control of infectious disease in the future are discussed. It is considered that developments in molecular biology and immunology will provide improvements in diagnostic tools and will revolutionize the development of animal resistance to disease and the production and use of vaccines.     

Antimicrobial peptides and plant disease control

Several diseases caused by viruses, bacteria and fungi affect plant crops, resulting in losses and decreasing the quality and safety of agricultural products. Plant disease control relies mainly on chemical pesticides that are currently subject to strong restrictions and regulatory requirements. Antimicrobial peptides are interesting compounds in plant health because there is a need for new products in plant protection that fit into the new regulations. Living organisms secrete a wide range of antimicrobial peptides produced through ribosomal (defensins and small bacteriocins) or non-ribosomal synthesis (peptaibols, cyclopeptides and pseudopeptides). Several antimicrobial peptides are the basis for the design of new synthetic analogues, have been expressed in transgenic plants to confer disease protection or are secreted by microorganisms that are active ingredients of commercial biopesticides.     

Foot-and-mouth disease virus: biology and prospects for disease control

Foot-and-mouth disease virus (FMDV) is the causative agent of a disease that constitutes one of the main animal health concerns, as evidenced by the devastating outbreaks that occurred in different areas of the world over the last few years. In this review, we summarise important features of FMDV, aspects of its interactions with cells and hosts as well as current and new strategies for FMD control by vaccination.     

Bacteriological risks: detection and tracing

Advances in molecular taxonomy of bacteria have generated many tools allowing identification of any bacteria, whether culturable or not. In addition to taxonomic identification, growing knowledge on pathogenicity mechanisms allows the detection of bacteria with given virulence genes. The problem is in asking the proper questions so that the most appropriate tools can be chosen. Some rapid identification tools (gene amplification, in situ hybridisation) require a starting hypothesis. Other tools (rrs gene amplification and sequencing) can be used without prior hypothesis, but take longer. To face the bioterrorist threat, particular attention should be given to laboratory and strain dispatch (within- and between-laboratory) organisation.