Hantavirus as important emerging agents in South America

The dawning of the 20th century was marked by the emergence of new infectious disease agents and the appearance of others previously thought controlled. Both phenomena were possibly connected with ecological disturbances that led to the recognition of a dramatic climate change, of which the effects are only now becoming noticeable. Among the variety of agents to be considered, the many new viruses stand out, not only for their numerical proliferation, but also for their genetic versatility. It is this quality that provides them dexterity for evolving new strategies and adaptations to changing environmental conditions. Recently, some of the most ubiquitous and well-publicized viral agents in the American continents have been the rodent-borne viruses, and among these are the hantaviruses, etiological agents of pulmonary syndromes. Approximately 18 hantaviruses (belonging to the family Bunyaviridae), have been discovered in South America during the last 20 years, and although most of them cause persistent infections and subclinical infections in wild rodents (particularly members of the subfamily Sigmodontinae) and humans respectively; some others might also be highly lethal for humans. The goal herein is to review the state of the art regarding general aspects of hantaviruses and the diseases they cause around the world, highlighting the most recent findings in Colombia. Finally, the many unanswered questions will be recognized and highlighted concerning clinical importance and socio-economic impact of these agents on quality of public health in Colombia.     

What's hot in animal biosafety?

In recent years, the emergence or re-emergence of critical issues in infectious disease and public health has presented new challenges and opportunities for laboratory animal care professionals. The re-emergence of bioterrorism as a threat activity of individuals or small groups has caused a heightened awareness of biosecurity and improved biosafety. The need for animal work involving high-risk or high-consequence pathogens and for arthropod-borne diseases has stimulated renewed interest in animal biosafety matters, particularly for work in containment. Application of these principles to animals retained in outdoor environments has been a consequence of disease eradication programs. The anticipated global eradication of wild poliovirus has prompted the promulgation of new biosafety guidelines for future laboratory and animal work. Increased concern regarding the use of biologically derived toxins and hazardous chemicals has stimulated a new categorization of facility containment based on risk assessment. Recognition that prion disease agents and other high-consequence pathogens require safe handling and thorough destruction during terminal decontamination treatment has led to the development of new biosafety guidelines and technologies. The implementation of these guidelines and technologies will promote state-of-the-art research while minimizing risk to laboratory animals, researchers, and the environment.     

Detection, eradication, and research implications of Helicobacter infections in laboratory rodents

Researchers first isolated and characterized Helicobacter hepaticus in 1994 as a cause of hepatitis that progressed to hepatocellular carcinoma in A/JCr mice. During the past decade, isolation and characterization of additional novel helicobacters from rodents has continued. In addition to causing overt disease, rodent helicobacter infections are important because intercurrent disease in select models will confound research data. Emerging evidence suggests that inflammatory responses to enterohepatic helicobacter infections may alter host responses to other experimental stimuli in unanticipated ways. Additionally, scientists have experimentally infected a variety of inbred mouse strains and genetically engineered mice with a variety of Helicobacter spp. isolated from rodents, birds, and higher mammals (including humans) to develop animal models of gastrointestinal diseases as well as idiopathic human disease syndromes. This review highlights current information about helicobacter infections in laboratory rodents and provides recommendations for the detection and eradication of these infections. The authors discuss the impact of subclinical and clinical disease and offer recommendations for managing helicobacter-free rodent colonies.     

The impact of infection on population health: results of the ontario burden of infectious diseases study

Background

Evidence-based priority setting is increasingly important for rationally distributing scarce health resources and for guiding future health research. We sought to quantify the contribution of a wide range of infectious diseases to the overall infectious disease burden in a high-income setting.

Methodology/Principal Findings

We used health-adjusted life years (HALYs), a composite measure comprising premature mortality and reduced functioning due to disease, to estimate the burden of 51 infectious diseases and associated syndromes in Ontario using 2005–2007 data. Deaths were estimated from vital statistics data and disease incidence was estimated from reportable disease, healthcare utilization, and cancer registry data, supplemented by local modeling studies and national and international epidemiologic studies. The 51 infectious agents and associated syndromes accounted for 729 lost HALYs, 44.2 deaths, and 58,987 incident cases per 100,000 population annually. The most burdensome infectious agents were: hepatitis C virus, Streptococcus pneumoniae, Escherichia coli, human papillomavirus, hepatitis B virus, human immunodeficiency virus, Staphylococcus aureus, influenza virus, Clostridium difficile, and rhinovirus. The top five, ten, and 20 pathogens accounted for 46%, 67%, and 75% of the total infectious disease burden, respectively. Marked sex-specific differences in disease burden were observed for some pathogens. The main limitations of this study were the exclusion of certain infectious diseases due to data availability issues, not considering the impact of co-infections and co-morbidity, and the inability to assess the burden of milder infections that do not result in healthcare utilization.

Conclusions/Significance

Infectious diseases continue to cause a substantial health burden in high-income settings such as Ontario. Most of this burden is attributable to a relatively small number of infectious agents, for which many effective interventions have been previously identified. Therefore, these findings should be used to guide public health policy, planning, and research.     

Pathogen genomic surveillance elucidates the origins,transmission and evolution of emerging viral agents in China

In the past twenty years, numerous novel zoonotic viral agents with pandemic potential have emerged in China, such as the severe acute respiratory syndrome (SARS) coronavirus and, more recently, the avian-origin influenza A/H7N9 virus, which have caused outbreaks among humans with high morbidity and mortality. In addition, several emerging and re-emerging viral pathogens have also been imported into China from travelers, e.g. the Middle East respiratory syndrome (MERS) coronavirus and Zika virus (ZIKV). Herein, we review these emerging viral pathogens in China and focus on how surveillance by pathogen genomics has been employed to discover and annotate novel pathogenic agents, identify natural reservoirs, monitor the transmission events and delineate their evolution and adaption to the human host. We also highlight the application of genomic sequencing in the recent Ebola epidemics in Western Africa. In summary, genomic sequencing has become a standard research tool in the field of emerging infectious diseases which has been proven invaluable in containing these viral infections and reducing burden of disease in humans and animals. Genomic surveillance of pathogenic agents will serve as a key epidemiological and research tool in the modern era of precision infectious diseases and in the future studies of virosphere.     

Virus evolution and transmission in an ever more connected world

The frequency and global impact of infectious disease outbreaks, particularly those caused by emerging viruses, demonstrate the need for a better understanding of how spatial ecology and pathogen evolution jointly shape epidemic dynamics. Advances in computational techniques and the increasing availability of genetic and geospatial data are helping to address this problem, particularly when both information sources are combined. Here, we review research at the intersection of evolutionary biology, human geography and epidemiology that is working towards an integrated view of spatial incidence, host mobility and viral genetic diversity. We first discuss how empirical studies have combined viral spatial and genetic data, focusing particularly on the contribution of evolutionary analyses to epidemiology and disease control. Second, we explore the interplay between virus evolution and global dispersal in more depth for two pathogens: human influenza A virus and chikungunya virus. We discuss the opportunities for future research arising from new analyses of human transportation and trade networks, as well as the associated challenges in accessing and sharing relevant spatial and genetic data.     

Development of Veterinary Laboratory Networks for Avian Influenza and Other Emerging Infectious Disease Control: The Southeast Asian Experience

The outbreak of highly pathogenic H5N1 avian influenza, with its international spread, confirmed that emerging infectious disease control must be underpinned by effective laboratory services. Laboratory results are the essential data underpinning effective surveillance, case diagnosis, or monitoring of responses. Importantly, laboratories are best managed within national and international networks of technological support rather than in isolation. A well planned laboratory network can deliver both a geographical spread of testing capacity and also a cost effective hierarchy of capability. Hence in the international context regional networks can be particularly effective. Laboratories are an integral part of a country’s veterinary services and their role and function should be clearly defined in the national animal health strategy and supporting government policies. Not every laboratory should be expected to deliver every possible service, and integration into regional and broader international networks should be a part of the overall strategy. The outputs required of each laboratory should be defined and then ensured through accredited quality assurance. The political and scientific environment in which laboratories operate changes continuously, not only through evolving national and regional animal health priorities but also through new test technologies and enhancements to existing technologies. Active networks help individual laboratories to monitor, evaluate, and respond to such challenges and opportunities. The end result is enhanced emerging infectious disease preparedness across the region.     

Old enemies, still with us after all these years

Although some previously common infections, such as Sendai virus and Mycoplasma pulmonis, have become rare in laboratory rodents in North American research facilities, others continue to plague researchers and those responsible for providing biomedical scientists with animals free of adventitious disease. Long-recognized agents that remain in research facilities in the 21st century include parvoviruses of rats and mice, mouse rotavirus, Theilers murine encephalomyelitis virus (TMEV), mouse hepatitis virus (MHV), and pinworms. The reasons for their persistence vary with the agent. The resilience of parvoviruses, for example, is due to their resistance to inactivation, their prolonged shedding, and difficulties with detection, especially in C57BL/6 mice. Rotavirus also has marked environmental resistance, but periodic reintroduction into facilities, possibly on bags of feed, bedding, or other supplies or equipment, also seems likely. TMEV is characterized by resistance to inactivation, periodic reintroduction, and relatively long shedding periods. Although MHV remains active in the environment at most a few days, currently prevalent strains are shed in massive quantities and likely transmitted by fomites. Pinworm infestations continue because of prolonged infections, inefficient diagnosis, and the survivability of eggs of some species in the environment. For all of these agents, increases in both interinstitutional shipping and the use of immunodeficient or genetically modified rodents of unknown immune status may contribute to the problem, as might incursions by wild or feral rodents. Elimination of these old enemies will require improved detection, strict adherence to protocols designed to limit the spread of infections, and comprehensive eradication programs.     

Impact of toxic agents or adverse conditions on thermoregulatory function in awake rodents

(1) In response to exposure to toxic xenobiotic agents, rodents demonstrate significant acute and subacute decreases in important indices of thermoregulatory and cardiovascular function. (2) This response has been observed in a number of studies in our laboratory and appears remarkably consistent, despite the variety of agents and exposure routes tested. (3) Animals with cardiopulmonary disease exhibit a potentiated response and may be at increased risk for adverse arrhythmic events and lethality. (4) Epidemiological studies have shown a strong association between human exposure to particulate matter (PM) and increased morbidity and mortality, particularly in cardiopulmonary-compromised individuals. (5) We have previously reported that various surrogate PM induce a robust hypothermia in rats, along with significant decreases in cardiac function, leading to arrhythmogenesis and lethality. (6) The present studies extend this research by assessing the contribution of the primary metallic constituents of PM towards the observed toxic effects.     

Individual and Population-Level Impacts of an Emerging Poxvirus Disease in a Wild Population of Great Tits

Emerging infectious diseases of wildlife can have severe effects on host populations and constitute a pressing problem for biodiversity conservation. Paridae pox is an unusually severe form of avipoxvirus infection that has recently been identified as an emerging infectious disease particularly affecting an abundant songbird, the great tit (Parus major), in Great Britain. In this study, we study the invasion and establishment of Paridae pox in a long-term monitored population of wild great tits to (i) quantify the impact of this novel pathogen on host fitness and (ii) determine the potential threat it poses to population persistence. We show that Paridae pox significantly reduces the reproductive output of great tits by reducing the ability of parents to fledge young successfully and rear those young to independence. Our results also suggested that pathogen transmission from diseased parents to their offspring was possible, and that disease entails severe mortality costs for affected chicks. Application of multistate mark-recapture modelling showed that Paridae pox causes significant reductions to host survival, with particularly large effects observed for juvenile survival. Using an age-structured population model, we demonstrate that Paridae pox has the potential to reduce population growth rate, primarily through negative impacts on host survival rates. However, at currently observed prevalence, significant disease-induced population decline seems unlikely, although pox prevalence may be underestimated if capture probability of diseased individuals is low. Despite this, because pox-affected model populations exhibited lower average growth rates, this emerging infectious disease has the potential to reduce the resilience of populations to other environmental factors that reduce population size.     

Microbial considerations in genetically engineered mouse research

Microbial infections have long been of concern to scientists using laboratory rodents because of their potential to confound and invalidate research. With the explosion of genetically engineered mice (GEM), new concerns over the impact of microbial agents have emerged because these rodents in many cases are more susceptible to disease than their inbred or outbred counterparts. Moreover, interaction between microbe and host and the resulting manifestation of disease conceivably differ between GEM and their inbred and outbred counterparts. As a result, infections may alter the GEM phenotype and confound interpretation of results and conclusions about mutated gene function. In addition, because GEM are expensive to produce and maintain, contamination by pathogens or opportunists has severe economic consequences. This review addresses how microbial infections may influence phenotype, how immunomodulation of the host as the result of induced mutations may modify host susceptibility to microbial infections, how novel host:microbe interactions have led to the development of new animal models for disease, how phenotype changes have led to the discovery of new pathogens, and new challenges associated with prevention and control of microbial infections in GEM. Although the focus is on naturally occurring infections, extensive literature on the use of GEM in studies of microbial pathogenesis also exists, and the reader is referred to this literature if microbial infection is a suspected culprit in phenotype alteration.     

Role of housing modalities on management and surveillance strategies for adventitious agents of rodents

Specific pathogen-free (SPF) rodents for modern biomedical research need to be free of pathogens and other infectious agents that may not produce disease but nevertheless cause research interference. To meet this need, rodents have been rederived to eliminate adventitious agents and then housed in room- to cage-level barrier systems to exclude microbial contaminants. Because barriers can and do fail, routine health monitoring (HM) is necessary to verify the SPF status of colonies. Testing without strict adherence to biosecurity practices, however, can lead to the inadvertent transfer of unrecognized, inapparent agents among institutions and colonies. Microisolation caging systems have become popular for housing SPF rodents because they are versatile and provide a highly effective cage-level barrier to the entry and spread of adventitious agents. But when a microisolation-caged colony is contaminated, the cage-level barrier impedes the spread of infection and so the prevalence of infection is often low, which increases the chance of missing a contamination and complicates the corroboration of unexpected positive findings. The expanding production of genetically engineered mutant (GEM) rodent strains at research institutions, where biosecurity practices vary and the risk of microbial contamination can be high, underscores the importance of accurate HM results in mitigating the risk of the introduction and spread of microbial contaminants with the exchange of mutant rodent strains among investigators and institutions.     

Metagenomic Detection of Viral Pathogens in Spanish Honeybees: Co-Infection by Aphid Lethal Paralysis,Israel Acute Paralysis and Lake Sinai Viruses

The situation in Europe concerning honeybees has in recent years become increasingly aggravated with steady decline in populations and/or catastrophic winter losses. This has largely been attributed to the occurrence of a variety of known and “unknown”, emerging novel diseases. Previous studies have demonstrated that colonies often can harbour more than one pathogen, making identification of etiological agents with classical methods difficult. By employing an unbiased metagenomic approach, which allows the detection of both unexpected and previously unknown infectious agents, the detection of three viruses, Aphid Lethal Paralysis Virus (ALPV), Israel Acute Paralysis Virus (IAPV), and Lake Sinai Virus (LSV), in honeybees from Spain is reported in this article. The existence of a subgroup of ALPV with the ability to infect bees was only recently reported and this is the first identification of such a strain in Europe. Similarly, LSV appear to be a still unclassified group of viruses with unclear impact on colony health and these viruses have not previously been identified outside of the United States. Furthermore, our study also reveals that these bees carried a plant virus, Turnip Ringspot Virus (TuRSV), potentially serving as important vector organisms. Taken together, these results demonstrate the new possibilities opened up by high-throughput sequencing and metagenomic analysis to study emerging new diseases in domestic and wild animal populations, including honeybees.     

Bacteriophage and their lysins for elimination of infectious bacteria

When phages were originally identified, the possibility of using them as antibacterial agents against pathogens was immediately recognized and put into practise based on the knowledge available at the time. However, with the advent of antibiotics a decline in the use of phage as therapeutics followed. Phages did, however, become more useful in the study of fundamental aspects of molecular biology and in the diagnostic laboratory for the identification of pathogenic bacteria. More recently, the original application of phage as therapeutics to treat human and animal infections has been rekindled, particularly in an era where antibiotic resistance has become so problematic/commonplace. Phage lysins have also been studied and utilized in their own right as potential therapeutics for the treatment of bacterial infections. Indeed the past decade has seen a considerable amount of research worldwide focused on the engineering of phages as antibacterial agents in a wide range of applications. Furthermore, the US Food and Drug Administration and/or the US Department of Agriculture have recently approved commercial phage preparations to prevent bacterial contamination of livestock, food crops, meat and other foods. Such developments have prompted this review into the status of phage research as it pertains to the control of infectious bacteria.     

White-nose syndrome: is this emerging disease a threat to European bats?

White-nose syndrome (WNS) is a newly emergent disease that potentially threatens all temperate bat species. A recently identified fungus, Geomyces destructans, is the most likely causative agent of this disease. Until 2009, WNS and G. destructans were exclusively known from North America, but recent studies have confirmed this fungus is also present in Europe. We assembled an international WNS consortium of 67 scientists from 29 countries and identified the most important research and conservation priorities to assess the risk of WNS to European bats. Here, we review what is known about WNS and G. destructans and detail the conservation and research recommendations aimed at understanding and containing this emerging infectious disease.     

Emerging and re-emerging bacterial diseases in India

There has been a remarkable progress in the prevention, control and even eradication of infectious diseases with improved hygiene and development of antimicrobials and vaccines. However, infectious diseases still remain a leading cause of global disease burden with high morbidity and mortality especially in the developing world. Furthermore, there have been threats of new diseases during the past three decades due to the evolution and adaptation of microbes and the re-emergence of old diseases due to the development of antimicrobial resistance and the capacity to spread to new geographic areas. The impact of the emerging and re-emerging diseases in India has been tremendous at socioeconomic and public health levels. Their control requires continuing surveillance, research and training, better diagnostic facilities and improved public health system. Emerging and reemerging zoonotic diseases, foodborne and waterborne diseases and diseases caused by multiresistant organisms constitute the major threats in India. This review of bacterial emerging and re-emerging diseases should be of critical importance to microbiologists, clinicians, public health personnel and policy makers in India.     

实验用生物样品的啮齿类微生物污染的检测管理

实验用生物样品在生物医学研究中有着广泛的应用.生物样品的微生物污染可危及实验动物设施的生物安全以及对动物实验研究造成负面影响.因此在将生物样品接种到啮齿类动物之前,要对其进行检测以确保无啮齿类动物传染性病原体的污染.因为检测技术和经济上的限制和局限性,不可能对所有的啮齿类动物传染性病原都进行检测.本文依据科学文献、笔者的经验以及专家的意见,尝试着去阐述如何建立一个有效可行的生物样品微生物污染检测计划.笔者建议对一些重要的微生物进行检测,并简要综述了选取这些微生物的理由即它们对科研、实验动物生物安全以及职业健康安全的影响.     

Murine norovirus, a recently discovered and highly prevalent viral agent of mice

Murine norovirus (MNV), a recently discovered viral agent of laboratory mice, is closely related to human norovirus, a contagious pathogen known to cause gastroenteritis. The prototype strain of MNV (MNV-1) was first isolated and characterized in 2003 as a sporadic, lethal pathogen in certain strains of immunocompromised knockout mice. Serological surveillance data from mouse colonies throughout the US and Canada have since shown that MNV is highly prevalent. Because MNV is unique among norovirus strains in its ability to replicate in cell culture, it serves as the most accessible model to elucidate the mechanisms of infection and replication of human norovirus. The author discusses the genetic diversity of MNV, its prevalence, pathology and potential research implications, as well as techniques for detection and eradication of this virus.     

Significance and role of early-lesions in experimental colorectal carcinogenesis

Preneoplastic or precancerous lesions in the large bowel have attracted much attention, and aberrant crypt foci (ACF) topographically identified in the colonic mucosa have found application as effective endpoint lesions for detection of chemopreventive agents as well as carcinogenic risk assessment of environmental agents. While many ACF are regarded as hyperplastic in nature, lacking the potential lesion to give rise to neoplasia, a subset termed dysplastic ACF, or newly identified "mucin depleted foci (MDF)", and "beta-catenin accumulated crypts (BCAC)" are suggested to be more reliably related to colorectal tumorigenesis in rodents. ACF and MDF can be visualized on the surface of colonic mucosa and BCAC were recently identified by our laboratory in rodents en face in cross sections. In particular, BCAC having a similar pattern of beta-catenin gene mutation to that observed in colonic carcinomas appear to be direct precursors. This review provides a review and discussion of the relevant literature relative to early lesions in colorectal carcinogenesis.     

The role of laboratory diagnostics in emerging viral infections: the example of the Middle East respiratory syndrome epidemic

Rapidly emerging infectious disease outbreaks place a great strain on laboratories to develop and implement sensitive and specific diagnostic tests for patient management and infection control in a timely manner. Furthermore, laboratories also play a role in real-time zoonotic, environmental, and epidemiological investigations to identify the ultimate source of the epidemic, facilitating measures to eventually control the outbreak. Each assay modality has unique pros and cons; therefore, incorporation of a battery of tests using traditional culture-based, molecular and serological diagnostics into diagnostic algorithms is often required. As such, laboratories face challenges in assay development, test evaluation, and subsequent quality assurance. In this review, we describe the different testing modalities available for the ongoing Middle East respiratory syndrome (MERS) epidemic including cell culture, nucleic acid amplification, antigen detection, and antibody detection assays. Applications of such tests in both acute clinical and epidemiological investigation settings are highlighted. Using the MERS epidemic as an example, we illustrate the various challenges faced by laboratories in test development and implementation in the setting of a rapidly emerging infectious disease. Future directions in the diagnosis of MERS and other emerging infectious disease investigations are also highlighted.