From Pasteur to genomics: progress and challenges in infectious diseases

Over the past decade, microbiology and infectious disease research have undergone the most profound revolution since the times of Pasteur. Genomic sequencing has revealed the much-awaited blueprint of most pathogens. Screening blood for the nucleic acids of infectious agents has blunted the spread of pathogens by transfusion, the field of antiviral therapeutics has exploded and technologies for the development of novel and safer vaccines have become available. The quantum jump in our ability to detect, prevent and treat infectious diseases resulting from improved technologies and genomics was moderated during this period by the greatest emergence of new infectious agents ever recorded and a worrisome increase in resistance to existing therapies. Dozens of new infectious diseases are expected to emerge in the coming decades. Controlling these diseases will require a better understanding of the worldwide threat and economic burden of infectious diseases and a global agenda.     

Neanderthal genomics suggests a pleistocene time frame for the first epidemiologic transition

High quality Altai Neanderthal and Denisovan genomes are revealing which regions of archaic hominin DNA have persisted in the modern human genome. A number of these regions are associated with response to infection and immunity, with a suggestion that derived Neanderthal alleles found in modern Europeans and East Asians may be associated with autoimmunity. As such Neanderthal genomes are an independent line of evidence of which infectious diseases Neanderthals were genetically adapted to. Sympathetically, human genome adaptive introgression is an independent line of evidence of which infectious diseases were important for AMH coming in to Eurasia and interacting with Neanderthals. The Neanderthals and Denisovans present interesting cases of hominin hunter‐gatherers adapted to a Eurasian rather than African infectious disease package. Independent sources of DNA‐based evidence allow a re‐evaluation of the first epidemiologic transition and how infectious disease affected Pleistocene hominins. By combining skeletal, archaeological and genetic evidence from modern humans and extinct Eurasian hominins, we question whether the first epidemiologic transition in Eurasia featured a new package of infectious diseases or a change in the impact of existing pathogens. Coupled with pathogen genomics, this approach supports the view that many infectious diseases are pre‐Neolithic, and the list continues to expand. The transfer of pathogens between hominin populations, including the expansion of pathogens from Africa, may also have played a role in the extinction of the Neanderthals and offers an important mechanism to understand hominin–hominin interactions well back beyond the current limits for aDNA extraction from fossils alone. Am J Phys Anthropol 160:379–388, 2016. © 2016 Wiley Periodicals, Inc.     

CD22 regulates time course of both B cell division and antibody response

Because pathogens induce infectious symptoms in a time-dependent manner, a rapid immune response is beneficial for defending hosts from pathogens, especially those inducing acute infectious diseases. However, it is largely unknown how the time course of immune responses is regulated. In this study, we demonstrate that B cells deficient in the inhibitory coreceptor CD22 undergo accelerated cell division after Ag stimulation, resulting in rapid generation of plasma cells and Ab production. This finding indicates that CD22 regulates the time course of B cell responses and suggests that CD22 is a good target to shorten the time required for Ab production, thereby augmenting host defense against acute infectious diseases as "universal vaccination."     

Emerging and Reemerging Infectious Diseases: Biocomplexity as an Interdisciplinary Paradigm

Understanding factors responsible for reemergence of diseases believed to have been controlled and outbreaks of previously unknown infectious diseases is one of the most difficult scientific problems facing society today. Significant knowledge gaps exist for even the most studied emerging infectious diseases. Coupled with failures in the response to the resurgence of infectious diseases, this lack of information is embedded in a simplistic view of pathogens and disconnected from a social and ecological context, and assumes a linear response of pathogens to environmental change. In fact, the natural reservoirs and transmission rates of most emerging infectious diseases primarily are affected by environmental factors, such as seasonality or meteorological events, typically producing nonlinear responses that are inherently unpredictable. A more realistic view of emerging infectious diseases requires a holistic perspective that incorporates social as well as physical, chemical, and biological dimensions of our planet’s systems. The notion of biocomplexity captures this depth and richness, and most importantly, the interactions of human and natural systems. This article provides a brief review and a synthesis of interdisciplinary approaches and insights employing the biocomplexity paradigm and offers a social–ecological approach for addressing and garnering an improved understanding of emerging infectious diseases. Drawing on findings from studies of cholera and other examples of emerging waterborne, zoonotic, and vectorborne diseases, a “blueprint” for the proposed interdisciplinary research framework is offered which integrates biological processes from the molecular level to that of communities and regional systems, incorporating public health infrastructure and climate aspects.     

Plant‐based oral vaccines against zoonotic and non‐zoonotic diseases

The shared diseases between animals and humans are known as zoonotic diseases and spread infectious diseases among humans. Zoonotic diseases are not only a major burden to livestock industry but also threaten humans accounting for >60% cases of human illness. About 75% of emerging infectious diseases in humans have been reported to originate from zoonotic pathogens. Because antibiotics are frequently used to protect livestock from bacterial diseases, the development of antibiotic‐resistant strains of epidemic and zoonotic pathogens is now a major concern. Live attenuated and killed vaccines are the only option to control these infectious diseases and this approach has been used since 1890. However, major problems with this approach include high cost and injectable vaccines is impractical for >20 billion poultry animals or fish in aquaculture. Plants offer an attractive and affordable platform for vaccines against animal diseases because of their low cost, and they are free of attenuated pathogens and cold chain requirement. Therefore, several plant‐based vaccines against human and animals diseases have been developed recently that undergo clinical and regulatory approval. Plant‐based vaccines serve as ideal booster vaccines that could eliminate multiple boosters of attenuated bacteria or viruses, but requirement of injectable priming with adjuvant is a current limitation. So, new approaches like oral vaccines are needed to overcome this challenge. In this review, we discuss the progress made in plant‐based vaccines against zoonotic or other animal diseases and future challenges in advancing this field.     

Recommendations for control of pathogens and infectious diseases in fish research facilities

Concerns about infectious diseases in fish used for research have risen along with the dramatic increase in the use of fish as models in biomedical research. In addition to acute diseases causing severe morbidity and mortality, underlying chronic conditions that cause low-grade or subclinical infections may confound research results. Here we present recommendations and strategies to avoid or minimize the impacts of infectious agents in fishes maintained in the research setting. There are distinct differences in strategies for control of pathogens in fish used for research compared to fishes reared as pets or in aquaculture. Also, much can be learned from strategies and protocols for control of diseases in rodents used in research, but there are differences. This is due, in part, the unique aquatic environment that is modified by the source and quality of the water provided and the design of facilities. The process of control of pathogens and infectious diseases in fish research facilities is relatively new, and will be an evolving process over time. Nevertheless, the goal of documenting, detecting, and excluding pathogens in fish is just as important as in mammalian research models.     

Interleukin-18 (IL-18) and infectious diseases, with special emphasis on diseases induced by intracellular pathogens

Interleukin-18 (IL-18) is a novel cytokine mainly produced by activated macrophages. IL-18 was originally called interferon-gamma inducing factor, due to its action in inducing IFN-gamma secretion from Th1 cells, NK cells and NKT cells. It has been reported that IL-18 may play important roles in various diseases including cancer and infectious diseases. This review deals with the roles of IL-18 in infectious diseases, with special emphasis on IL-18 in infectious diseases caused by intracellular pathogens including Mycobacterium tuberculosis, Mycobacterium leprae, Listeria monocytogenes and Salmonella typhimurium.     

The effects of environmental stress on outbreaks of infectious diseases of fishes*

Infectious diseases of fishes occur when susceptible fishes are exposed to virulent pathogens under certain environmental stress conditions. Very little research has been carried out to show the effect of pollution on outbreaks of infectious diseases of fishes. Therefore, examples taken from the literature were selected and reviewed to show the coincidence of infectious diseases with stress caused by temperature, eutrophication, sewage, metabolic products of fishes, industrial pollution, and pesticides.     

Evolution of airborne infectious diseases according to changes in characteristics of the host population

The authors predicted evolutionary changes in airborne infectious diseases according to changes in the characteristics of the host population. The predictions were based upon a mathematical model of infectious diseases and the validity of the predictions was verified against the history of man and pathogens. The feature of this model is that it involves a density of pathogens in the environment as an additional variable which can be regarded as more suitable to airborne infectious diseases. In spite of this modification, this study reached a similar conclusion to the threshold density theory: that is, susceptible host density in the absence of the pathogen must be larger than that in the presence of the pathogen, for the pathogen to be persistent. Moreover the authors concluded that one type of pathogen cannot be replaced by another type of pathogen as long as the susceptible host density of the former type is the mininum one. The predictions were considered to be valid for a wide range of infectous diseases. Making use of these principles, the authors predicted that the variety of infectious diseases should increase as host density increases and that pathogens should evolve to be less virulent as the host life-span increases. The finalidea discussed is whether or nor the history of man and pathogen can be verified by the predictions.     

Shoe soles as a potential vector for pathogen transmission: a systematic review

Shoe soles are possible vectors for infectious diseases. Although studies have been performed to assess the prevalence of infectious pathogens on shoe soles and decontamination techniques, no systematic review has ever occurred. The aim of this study was to perform a systematic review of the literature to determine the prevalence of infectious agents on shoe bottoms and possible decontamination strategies. Three electronic bibliographic databases were searched using a predefined search strategy evaluating prevalence of infectious pathogens on shoe bottoms and decontamination strategies. Quality assessment was performed independently by two reviews with disagreements resolved by consensus. Thirteen studies were identified that supported the hypothesis that shoe soles are a vector for infectious pathogens. Methicillin‐resistant Staphylococcus aureus, Clostridium difficile and multidrug‐resistant Gram‐negative species among other pathogens were documented on shoe bottoms in the health care setting, in the community and among food workers. Fifteen studies were identified that investigated decontamination strategies for shoe soles. A number of decontamination strategies have been studied of which none have been shown to be consistently successful at disinfecting shoe soles. In conclusion, a high prevalence of microbiological pathogens was identified from shoe soles studied in the health care, community and animal worker setting. An effective decontamination strategy for shoe soles was not identified. Studies are needed to assess the potential for contaminated shoes to contribute to the transmission of infectious pathogens.     

宏基因组测序在中枢神经系统感染性疾病诊断中的应用及研究进展

中枢神经系统(central nervous system,CNS)感染是指由病毒、细菌或真菌等侵染中枢神经系统引起的急性或慢性炎症性(或非炎症性)疾病,致死率高,易引发严重后遗症。由于检测通量及灵敏度的限制,一半以上的中枢神经系统感染患者无法通过常规检测方法确定病原体。宏基因组测序是一种新兴的病原检测技术,能够极大地提升病原检出率。当前部分临床医生及相关从业人员对宏基因组测序的认识存在不足,限制了其在临床诊疗中的快速推广和应用。本文系统介绍了宏基因组测序整体流程,综述了该技术在中枢神经系统感染性疾病诊疗中的发展历程和最新研究进展,希望为中枢神经系统感染性疾病的诊断和治疗提供参考。     

感染性疾病动物模型-观点与思考

感染性疾病动物模型是以导致感染性疾病的病原感染动物,或人工导入病原遗传物质,使动物发生和人类相同疾病、类似疾病、部分疾病改变或机体对病原产生反应,为疾病系统研究、比较医学研究以及抗病原药物和疫苗等研制、筛选和评价提供的模式动物。目前,国内外没有严格的感染性疾病模型的分类标准,但是,感染性病原动物模型的分类明显不同于一般动物模型的分类,因此,本文建议将感染性疾病动物模型按照病原种类特性以及疾病表现程度进行分类,便于规范化应用。     

线粒体自噬在感染性疾病中的作用机制研究进展

线粒体自噬作为一种选择性自噬方式是近年研究的热点。细胞通过自噬机制选择性清除受损伤或不必需的线粒体,从而维持其功能稳态。近年来,越来越多的研究聚焦于病原体通过胁迫线粒体自噬在机体感染过程中调节先天免疫信号通路,从而影响感染性疾病的进程。本文分别从线粒体自噬在病毒、细菌和真菌感染性疾病中的作用机制研究进展进行综述,以期为感染性疾病的防治提供新的指导策略。     

Epidemiological study of zoonoses derived from humans in captive chimpanzees

Emerging infectious diseases (EIDs) in wildlife are major threats both to human health and to biodiversity conservation. An estimated 71.8 % of zoonotic EID events are caused by pathogens in wildlife and the incidence of such diseases is increasing significantly in humans. In addition, human diseases are starting to infect wildlife, especially non-human primates. The chimpanzee is an endangered species that is threatened by human activity such as deforestation, poaching, and human disease transmission. Recently, several respiratory disease outbreaks that are suspected of having been transmitted by humans have been reported in wild chimpanzees. Therefore, we need to study zoonotic pathogens that can threaten captive chimpanzees in primate research institutes. Serological surveillance is one of several methods used to reveal infection history. We examined serum from 14 captive chimpanzees in Japanese primate research institutes for antibodies against 62 human pathogens and 1 chimpanzee-borne infectious disease. Antibodies tested positive against 29 pathogens at high or low prevalence in the chimpanzees. These results suggest that the proportions of human-borne infections may reflect the chimpanzee’s history, management system in the institute, or regional epidemics. Furthermore, captive chimpanzees are highly susceptible to human pathogens, and their induced antibodies reveal not only their history of infection, but also the possibility of protection against human pathogens.     

Why should cell biologists study microbial pathogens?

One quarter of all deaths worldwide each year result from infectious diseases caused by microbial pathogens. Pathogens infect and cause disease by producing virulence factors that target host cell molecules. Studying how virulence factors target host cells has revealed fundamental principles of cell biology. These include important advances in our understanding of the cytoskeleton, organelles and membrane-trafficking intermediates, signal transduction pathways, cell cycle regulators, the organelle/protein recycling machinery, and cell-death pathways. Such studies have also revealed cellular pathways crucial for the immune response. Discoveries from basic research on the cell biology of pathogenesis are actively being translated into the development of host-targeted therapies to treat infectious diseases. Thus there are many reasons for cell biologists to incorporate the study of microbial pathogens into their research programs.     

Systematics and emerging infectious diseases: from management to solution

The crisis of emerging infectious disease stems from the absence of comprehensive taxonomic inventories of the world's parasites, which includes the world's pathogens. Recent technological developments raise hopes that the global inventory of species, including potential pathogens, can be accomplished in a timely and cost-effective manner. The phylogenetics revolution initiated by systematists provides a means by which information about pathogen transmission dynamics can be placed in a predictive framework. Increasingly, that information is widely available in digital form on the Internet. Systematic biology is well positioned to play a crucial role in efforts to be proactive in the arena of emerging parasitic and infectious diseases.     

Unraveling the role of membrane microdomains during microbial infections

Infectious diseases pose major socioeconomic and health-related threats to millions of people across the globe. Strategies to combat infectious diseases derive from our understanding of the complex interactions between the host and specific bacterial, viral, and fungal pathogens. Lipid rafts are membrane microdomains that play important role in life cycle of microbes. Interaction of microbial pathogens with host membrane rafts influences not only their initial colonization but also their spread and the induction of inflammation. Therefore, intervention strategies aimed at modulating the assembly of membrane rafts and/or regulating raft-directed signaling pathways are attractive approaches for the. management of infectious diseases. The current review discusses the latest advances in terms of techniques used to study the role of membrane microdomains in various pathological conditions and provides updated information regarding the role of membrane rafts during bacterial, viral and fungal infections.     

A Quantitative Prioritisation of Human and Domestic Animal Pathogens in Europe

Disease or pathogen risk prioritisations aid understanding of infectious agent impact within surveillance or mitigation and biosecurity work, but take significant development. Previous work has shown the H-(Hirsch-)index as an alternative proxy. We present a weighted risk analysis describing infectious pathogen impact for human health (human pathogens) and well-being (domestic animal pathogens) using an objective, evidence-based, repeatable approach; the H-index. This study established the highest H-index European pathogens. Commonalities amongst pathogens not included in previous surveillance or risk analyses were examined. Differences between host types (humans/animals/zoonotic) in pathogen H-indices were explored as a One Health impact indicator. Finally, the acceptability of the H-index proxy for animal pathogen impact was examined by comparison with other measures. 57 pathogens appeared solely in the top 100 highest H-indices (1) human or (2) animal pathogens list, and 43 occurred in both. Of human pathogens, 66 were zoonotic and 67 were emerging, compared to 67 and 57 for animals. There were statistically significant differences between H-indices for host types (humans, animal, zoonotic), and there was limited evidence that H-indices are a reasonable proxy for animal pathogen impact. This work addresses measures outlined by the European Commission to strengthen climate change resilience and biosecurity for infectious diseases. The results include a quantitative evaluation of infectious pathogen impact, and suggest greater impacts of human-only compared to zoonotic pathogens or scientific under-representation of zoonoses. The outputs separate high and low impact pathogens, and should be combined with other risk assessment methods relying on expert opinion or qualitative data for priority setting, or could be used to prioritise diseases for which formal risk assessments are not possible because of data gaps.     

DNA microarrays in the clinic: infectious diseases

We argue that the most-promising area of clinical application of microarrays in the foreseeable future is the diagnostics and monitoring of infectious diseases. Microarrays for the detection and characterization of human pathogens have already found their way into clinical practice in some countries. After discussing the persistent, yet often underestimated, importance of infectious diseases for public health, we consider the technologies that are best suited for the detection and clinical investigation of pathogens. Clinical application of microarray technologies for the detection of mycobacteria, Bacillus anthracis, HIV, hepatitis and influenza viruses, and other major pathogens, as well as the analysis of their drug-resistance patterns, illustrate our main thesis.