Environmental disease: environmental alteration and infectious disease

Humans have changed their environment to survive and to achieve a safer and more comfortable life. For example, drinking water and wastewater infrastructures are indispensable for civilized societies to flourish and to prevent water-borne infectious diseases. However, excessive loading on environments might disturb microbial ecosystems, resulting in outbreaks of pathogenic microbes and the expansion of infectious diseases. Clarifying the relationship between environmental alterations and changes in microbial ecosystems is thus important to prevent further outbreaks of infectious diseases. The present study aims to understand the links between the following factors: environmental alterations; ecosystem disturbance and the occurrence of infectious disease; and impact on society. We focus on legionellosis and nontuberculous mycobacterial diseases from the viewpoint of their environmental linkage. While Legionella spp. are ubiquitous in aquatic environments, Legionella pneumophila often increases in anthropogenic environments, such as cooling towers or spas, and can cause outbreaks of legionellosis. Recently, travel-associated Legionnaires’ disease has caused concern in many countries. The numbers of patients infected with nontuberculous Mycobacteria (NTM) have increased worldwide since the 1990s. Disturbances to microbial ecosystems caused by changes in water usage might be one cause of NTM diseases. Clarifying the dynamics of Legionella pneumophila and NTM in aquatic environments should help prevent outbreaks of diseases associated with these bacteria.     

Seasonal infectious disease epidemiology

Seasonal change in the incidence of infectious diseases is a common phenomenon in both temperate and tropical climates. However, the mechanisms responsible for seasonal disease incidence, and the epidemiological consequences of seasonality, are poorly understood with rare exception. Standard epidemiological theory and concepts such as the basic reproductive number R0 no longer apply, and the implications for interventions that themselves may be periodic, such as pulse vaccination, have not been formally examined. This paper examines the causes and consequences of seasonality, and in so doing derives several new results concerning vaccination strategy and the interpretation of disease outbreak data. It begins with a brief review of published scientific studies in support of different causes of seasonality in infectious diseases of humans, identifying four principal mechanisms and their association with different routes of transmission. It then describes the consequences of seasonality for R0, disease outbreaks, endemic dynamics and persistence. Finally, a mathematical analysis of routine and pulse vaccination programmes for seasonal infections is presented. The synthesis of seasonal infectious disease epidemiology attempted by this paper highlights the need for further empirical and theoretical work.     

Glycosaminoglycans in infectious disease

Glycosaminoglycans (GAGs) are complex carbohydrates that are ubiquitously present on the cell surface and in the extracellular matrix. Interactions between GAGs and pathogens represent the first line of contact between pathogen and host cell and are crucial to a pathogen's invasive potential. Their complexity and structural diversity allow GAGs to control a wide array of biological interactions influencing many physiological and pathological processes, including adhesion, cell‐to‐cell communication, biochemical cascades, and the immune response. In recent years, increasing evidence indicates an extraordinary role for GAGs in the pathogenesis of viruses, bacteria and parasites. Herein, we examine the interface between GAGs and different pathogens, and address the divergent biological functions of GAGs in infectious disease. We consider approaches to use this understanding to design novel therapeutic strategies addressing new challenges in the treatment of infectious diseases.     

Bacterial DNA topology and infectious disease

The Gram-negative bacterium Escherichia coli and its close relative Salmonella enterica have made important contributions historically to our understanding of how bacteria control DNA supercoiling and of how supercoiling influences gene expression and vice versa. Now they are contributing again by providing examples where changes in DNA supercoiling affect the expression of virulence traits that are important for infectious disease. Available examples encompass both the earliest stages of pathogen–host interactions and the more intimate relationships in which the bacteria invade and proliferate within host cells. A key insight concerns the link between the physiological state of the bacterium and the activity of DNA gyrase, with downstream effects on the expression of genes with promoters that sense changes in DNA supercoiling. Thus the expression of virulence traits by a pathogen can be interpreted partly as a response to its own changing physiology. Knowledge of the molecular connections between physiology, DNA topology and gene expression offers new opportunities to fight infection.     

Global mapping of infectious disease

The primary aim of this review was to evaluate the state of knowledge of the geographical distribution of all infectious diseases of clinical significance to humans. A systematic review was conducted to enumerate cartographic progress, with respect to the data available for mapping and the methods currently applied. The results helped define the minimum information requirements for mapping infectious disease occurrence, and a quantitative framework for assessing the mapping opportunities for all infectious diseases. This revealed that of 355 infectious diseases identified, 174 (49%) have a strong rationale for mapping and of these only 7 (4%) had been comprehensively mapped. A variety of ambitions, such as the quantification of the global burden of infectious disease, international biosurveillance, assessing the likelihood of infectious disease outbreaks and exploring the propensity for infectious disease evolution and emergence, are limited by these omissions. An overview of the factors hindering progress in disease cartography is provided. It is argued that rapid improvement in the landscape of infectious diseases mapping can be made by embracing non-conventional data sources, automation of geo-positioning and mapping procedures enabled by machine learning and information technology, respectively, in addition to harnessing labour of the volunteer ‘cognitive surplus’ through crowdsourcing.     

Genetic susceptibility to infectious disease

Our understanding of the variation in individual clinical responses to pathogens has become increasingly relevant, particularly in the face of new emerging epidemics as well as the increasing number of multi-drug-resistant organisms. An effective immune response to infection has contributed to the development of host genetic diversity through selective pressure, with an increasing number of studies characterizing the role that host genetics plays in disease susceptibility. Knowledge of the role host mechanisms play in the pathogenesis of infectious disease can contribute to the design of new therapeutic strategies. Rapid advances in the field of human genomics offer great opportunities for adopting this approach to find new insights into pathogenesis.     

Persister cells, dormancy and infectious disease

Several well-recognized puzzles in microbiology have remained unsolved for decades. These include latent bacterial infections, unculturable microorganisms, persister cells and biofilm multidrug tolerance. Accumulating evidence suggests that these seemingly disparate phenomena result from the ability of bacteria to enter into a dormant (non-dividing) state. The molecular mechanisms that underlie the formation of dormant persister cells are now being unravelled and are the focus of this Review.     

Bacterial population genomics and infectious disease diagnostics

New sequencing technologies have made the production of bacterial genome sequences increasingly easy, and it can be confidently forecasted that vast genomic databases will be generated in the next few years. Here, we detail how collections of bacterial genomes from a particular species (population genomics libraries) have already been used to improve the design of several diagnostic assays for bacterial pathogens. Genome sequencing itself is also becoming more commonly used for epidemiological, forensic and clinical investigations. There is an opportunity for the further development of bioinformatic tools to bring even further value to bacterial diagnostic genomics.     

Serendipity and new drugs for infectious disease

Serendipity, in various shades of semantic legitimacy, is abundantly evident in the history of the chemotherapy of infectious disease. We may be on the threshold of a new era of rational drug design, but most medications for infectious diseases have arisen, and continue to arise, from chance observation, clinical experience, and the empirical search for substances active against pathogens. Chance does not produce drugs; but where chance has played a pivotal role in drug discovery, the event may be considered serendipitous to a greater or lesser degree. In a deliberate search for new drugs, it is often difficult to assess the degree to which any resulting discovery is serendipitous, and the usefulness of the term becomes debatable. Many therapeutic advances emerge from research involving animals, and a triggering "happy accident" may reside in the most basic aspects of animal care or in the most arcane knowledge of animals. The examples discussed in this article deal mostly with parasitic disease and the use of animal models in the discovery of antiparasitic agents. In this area, as in others, chance has laid the groundwork for scientific advancement and practical benefit. Although the applicability of the word serendipity to drug discovery may often be uncertain, the role played by chance should be recognized and welcomed.     

Public health surveillance and infectious disease detection

Emerging infectious diseases, such as HIV/AIDS, SARS, and pandemic influenza, and the anthrax attacks of 2001, have demonstrated that we remain vulnerable to health threats caused by infectious diseases. The importance of strengthening global public health surveillance to provide early warning has been the primary recommendation of expert groups for at least the past 2 decades. However, despite improvements in the past decade, public health surveillance capabilities remain limited and fragmented, with uneven global coverage. Recent initiatives provide hope of addressing this issue, and new technological and conceptual advances could, for the first time, place capability for global surveillance within reach. Such advances include the revised International Health Regulations (IHR 2005) and the use of new data sources and methods to improve global coverage, sensitivity, and timeliness, which show promise for providing capabilities to extend and complement the existing infrastructure. One example is syndromic surveillance, using nontraditional and often automated data sources. Over the past 20 years, other initiatives, including ProMED-mail, GPHIN, and HealthMap, have demonstrated new mechanisms for acquiring surveillance data. In 2009 the U.S. Agency for International Development (USAID) began the Emerging Pandemic Threats (EPT) program, which includes the PREDICT project, to build global capacity for surveillance of novel infections that have pandemic potential (originating in wildlife and at the animal-human interface) and to develop a framework for risk assessment. Improved understanding of factors driving infectious disease emergence and new technological capabilities in modeling, diagnostics and pathogen identification, and communications, such as using the increasing global coverage of cellphones for public health surveillance, can further enhance global surveillance.     

Catecholamine activity and infectious disease episodes.

The profile of 3-hydroxy-4-methoxy mandelic acid (VMA) excretion was studied in relation to reported acute infectious disease episodes. Daily VMA excretion levels and symptom reports were analyzed for a group of 47 volunteers over a four-week period. Results showed a tendency for elevated VMA levels to occur with greater frequency within three days prior to the onset of symptoms. These findings are interpreted as suggesting that elevated levels of catecholamine activity may increase susceptibility to disease by interfering with the immune response, and in the presence of an agent lead to an infectious disease episode.