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Historical information as well as microbial sequencing and phylogenetic constructions make it clear that infectious diseases have been emerging and reemerging over millennia, and that such emergences are driven by numerous factors (Table 1). Notably, 60 to 80 percent of new human infections likely originated in animals, disproportionately rodents and bats, as shown by the examples of hantavirus pulmonary syndrome, Lassa fever, and Nipah virus encephalitis–. Most other emerging/reemerging diseases result from human-adapted infectious agents that genetically acquire heightened transmission and/or pathogenic characteristics. Examples of such diseases include multidrug-resistant and extensively drug-resistant (MDR and XDR) tuberculosis, toxin-producing Staphylococcus aureus causing toxic shock syndrome, and pandemic influenza–.
Although precise figures are lacking, emerging infectious diseases comprise a substantial fraction of all consequential human infections. They have caused the deadliest pandemics in recorded human history, including the Black Death pandemic (bubonic/pneumonic plague; 25–40 million deaths) in the fourteenth century, the 1918 influenza pandemic (50 million deaths), and the HIV/AIDS pandemic (35 million deaths so far),.
Two major categories of emerging infections—newly emerging and reemerging infectious diseases—can be defined, respectively, as diseases that are recognized in the human host for the first time; and diseases that historically have infected humans, but continue to appear in new locations or in drug-resistant forms, or that reappear after apparent control or elimination. Emerging/reemerging infections may exhibit successive stages of emergence. These stages include adaptation to a new host, an epidemic/pathogenic stage, an endemic stage, and a fully adapted stage in which the organism may become nonpathogenic and potentially even beneficial to the new host (e.g., the human gut microbiome) or stably integrated into the host genome (e.g., as endogenous retroviruses). Although these successive stages characterize the evolution of certain microbial agents more than others, they nevertheless can provide a useful framework for understanding many of the dynamic relationships between microorganisms, human hosts, and the environment.
It is also worth noting that the dynamic and complicated nature of many emerging infections often leaves distinctions between emerging and reemerging infections open to question, leading various experts to classify them differently. For example, we describe as “reemerging” new or more severe diseases associated with acquisition of new genes by an existing microbe, e.g., antibiotic resistance genes, even when mutations cause entirely new diseases with unique clinical epidemiologic features, e.g., Brazilian purpuric fever. Similarly, we refer to SARS as an emerging disease a decade after it disappeared, and apply the same term to the related MERS (Middle East Respiratory Syndrome) β coronavirus which appeared in Saudi Arabia in late 2012.
Throughout recorded history, infectious diseases have plagued human existence. One effective approach to limiting these diseases has been vaccination. For example, in a recent report by Roush and colleagues at the U.S. Centers for Disease Control and Prevention (CDC), ever since the introduction of vaccines the incidence of infectious diseases like diphtheria, mumps, pertussis, tetanus, hepatitis A and B, Haemophilus influenza and varicella zoster has declined by more than 80% in the U.S. Furthermore, after the introduction of vaccines, large scale transmission of measles, rubella, and polio has been eliminated in the U.S., while smallpox has been eradicated worldwide. However, new emerging infectious pathogens such as HIV (human immunodeficiency virus), SARS coronavirus (severe acute respiratory syndrome virus), and highly pathogenic avian influenza (H5N1) viruses have adapted strategies to rapidly change their genetic compositions. As the influenza pandemic of 1918 (H1N1) killed approximately 20 to 50 million people worldwide, massive disease and death is similarly feared from newly emerging pathogens. In addition, the current novel swine derived H1N1 pandemic further exemplifies the need for a rapid and effective vaccine against emerging pathogens. Thus a vaccination strategy to control emerging diseases will require a more effective and rapid response than available from conventional approaches such as live-attenuated vaccines, inactivated vaccines, or protein subunit vaccines. Plasmid DNA vaccines, as reviewed in this article, may be an option to effectively combat current emerging infectious diseases.
Globally, environmental and anthropogenic changes are impacting ecosystems, and perturbing plant and animal demographics and behaviors. These changes contribute to the increasing pace of infectious disease emergence worldwide, largely driven by increasing contacts between and among species,. Drivers of disease emergence include mobility and trade, encroachment of natural habitats and climate change, as well as intrinsic characteristics of pathogens, such as wide host range for animal pathogens and the ability of plant pathogens to hybridize.
The vast majority of emerging infectious diseases in humans are zoonotic in nature,. Often, they escape their natural wildlife reservoirs and infect captive or domestic animals and humans upon cross-species transmission. While the majority of zoonotic pathogens spread limitedly among humans, occasionally some do evolve the ability to efficiently transmit. These may cause devastating epidemics, if not pandemics, and may establish as novel human pathogens. Emerging infectious diseases of animals likewise have typically the ability to cross species barriers and invade new host species. In contrast, introduction of pathogens into new geographical areas and climate change play an essential role in the emergence of plant diseases, and the hybridization of plant pathogens that are not naturally sympatric is repeatedly reported to be involved in plant disease emergence events. The consequences of emerging pathogens in newly infected species, be it wild or domestic, or in new geographical areas, can have dire repercussions on human welfare, for example, through the disruption of ecosystem services or from large agricultural economic losses,. As such, emerging infectious diseases are One Health threats to the global community.
Despite progress in our understanding of the mechanisms and drivers of pathogen emergence and adaptation, infectious disease emergence and associated health and economic burdens remain essentially unpredictable. They continue to impose heavy burdens on the global community, as most recently painfully demonstrated by the emergence of MERS coronavirus in the Middle East and Ebola virus in West Africa. Because the nature, time and location of the next One Health threat cannot be forecasted, preparedness and responsiveness are essential to curb future emerging infectious disease burdens.
Surveillance is key to preparedness by identifying and monitoring new threats to plant, animal and human health, and raising early-warning flags upon changing epidemiology. Major global initiatives have profoundly revolutionized the scope of infectious disease surveillance in plants, animals and humans. These include the World Animal Health Information Database (WAHID) Interface of the OIE, the Global Animal Disease Information system EMPRES-i of the FAO, the situation assessments and reports of the WHO, and the internet-based Program for Monitoring Emerging Diseases (ProMED) of the International Society for Infectious Diseases.
Using the data collected from these different sources, we present the current status of major One Health threats. In this update, the current status of low pathogenic avian influenza virus (LPAIV) H7N9, highly pathogenic avian influenza viruses (HPAIVs) of the H5 subtype, MERS coronavirus and Ebola virus are summarized. The present report will be updated every three months, with newly acquired data on the diseases listed above, as well as with data on any new One Health threat that would have emerged during that period.
Thousands of different microorganisms affect the health and safety of the world's populations of humans, animals, and plants. Infectious microorganisms include species of bacteria, viruses, fungi, and protozoa. Many different medical and governmental organizations have created lists of the pathogenic microorganisms most relevant to their missions. For example, the Centers for Disease Control and Prevention (CDC) maintains an ever-changing list of notifiable diseases, the National Institute of Allergy and Infectious Disease (NIAID) lists agents with potential for use in bioterrorist attacks, and the Department of Health and Human Services (HHS) maintains a list of critical human pathogens. Unfortunately, the nomenclature for biological agents on these lists and pathogens described in the literature is imprecise. Organisms are often referred to using common names, alternative spellings, or out-dated or alternative names. Sometimes a disease rather than a particular organism is mentioned, and often there may be multiple organisms or co-infections capable of causing a particular disease. Not surprisingly, this ambiguity poses a significant hurdle to communication among the diverse communities that must deal with epidemics or bioterrorist attacks.
To facilitate comprehensive access to information on disease-causing organisms and toxins, we have developed a database known as "The Microbial Rosetta Stone" that uses a new data model and novel computational tools to manage microbiological data. This article focuses on the information in the database for pathogens that impact global public health, emerging infectious organisms, and bioterrorist threat agents. It provides a compilation of lists, taken from the database, of important and/or regulated biological agents from a number of agencies including HHS, the United States Department of Agriculture (USDA), the CDC, the World Health Organization (WHO), the NIAID, and other sources. We curated these lists to include organism names that are consistent with the National Center for Biotechnology Information (NCBI) nomenclature and to provide sequence accession numbers for genomic sequencing projects (if available). Important synonyms or previously used names that identify the organisms are also shown. We have organized the lists according to phylogenetic structure. This paper provides graphic representations of the phylogenetic relatedness of important pathogenic organisms.
The goal of the database is to provide an informative, readily accessible, single location for basic information on a broad range of important disease causing agents. The database will help users to avoid the pitfalls of confusing nomenclature and taxonomic relationships and allow access to literature on in-depth studies. The database can be accessed at .
Human microbiologic infections, known as zoonoses, are acquired directly from animals or via arthropods bites and are an increasing public health problem. More than two thirds of emerging human pathogens are of zoonotic origin, and of these, more than 70% originate from wildlife. In novel environments, viruses, particularly RNA viruses, can easily cross the species barrier by mutations, recombinations or reassortments of their genetic material, resulting in the capacity to infect novel hosts. Because of their adaptive abilities, RNA viruses represent more than 70% of the viruses that infect humans. When socio-economic and ecologic changes affect their environment, humans may encounter increased contact with emerging viruses that originate in wild or domestic animals.
Wolfe et al. in 2007 and Karesh et al. in 2012 described different stages in the switch from an animal-specific infectious agent into a human-specific pathogen. The key stage is the transition of a strictly animal-specific infectious agent (originating from wildlife or domestic animals) to exposed human populations, resulting in sporadic human infections (Figure 1). If the pathogen is able to adapt to its human host and acquire the means to accomplish an inter-human transmission, horizontal human-to-human transmission occurs and maintains the viral cycle. Sometimes, an intermediate host, such as a domestic animal, is the link between sylvatic viral circulation and human viral circulation. For example, some human infections originating from bats, such as Nipah, Hendra, SARS and Ebola viral infections, may involve intermediate amplification in hosts such as pigs, horses, civets and primates, respectively (Figure 1). Genetic, biologic, social, political or economic factors may explain a switch in viral host targets. For example, climate changes may influence the geographical repartition of vector arthropods, leading to new areas of the distribution of infectious diseases, like Aedes albopictus and Chikungunya infections in the Mediterranean. Morens et al. listed different key factors that may contribute to the emergence or re-emergence of infectious diseases, such as microbial adaptation to a new environment, biodiversity loss, ecosystem changes that lead to more frequent contact between wildlife and domestic animals or human populations, human demographics and behavior, economic development and land use, international travel and commerce, etc.. These patterns of transmission allow identifying different animals to follow in order to monitor the appearance of new or re-emerging infectious agents before its first detection in the human populations. Therefore, hematophagous arthropods, wildlife and domestic animals may serve as targets for zoonotic and arboviral disease surveillance, particularly because sampling procedures and long-term follow-up studies are more easily performed in these hosts than in humans.
Historically, classic viral detection techniques were based on the intracerebral inoculation of suckling mice or viral isolation in culture and the subsequent observation of cytopathic effects on cell lines. Later, immunologic methods, e.g., seroneutralization or hemaglutination, were used to detect viral antigens in various complex samples. These techniques were based on the isolation of viral agents. With the progresses of molecular biology, polymerase chain reaction (PCR)-based methods became the main techniques for virus discovery and allowed the detection of uncultivable viruses, but these techniques required prior knowledge of closely related viral genomes. Next-Generation Sequencing (NGS) techniques make it possible to sequence all viral genomes in a given sample without previous knowledge about their nature. These techniques, known as viral metagenomics, have allowed the discovery of completely new viral species. Because of their low cost, the use of NGS techniques is exponentially increasing.
The transmission of infections between humans occurs after a pathogen from a wild or domestic animal contacts with exposed human populations. The human exposures may or may not be mediated by the bite of bloodsucking arthropods. Surveillance programs may target wildlife, domestic animals or arthropods for emerging viruses before their adaptation to human hosts.
Each year in the United States, there are approximately 76 million cases of food-borne illness, including 325,000 hospitalizations and 5,000 deaths. In an estimated 2 to 3% of these cases, chronic sequelae develop. These sequelae include renal disease, cardiovascular diseases, gastrointestinal disorders, neural disorders, and autoimmune disease. The estimated cost of food-borne illness in the United States is $23 billion annually. Mishandling of food is believed to be responsible for 85% of all outbreaks of food-borne disease in developed nations, primarily due to a lack of education. Food-borne pathogens [see Additional File 3] are also important because they represent one of the largest sources of emerging antibiotic-resistant pathogens. This is due in part to the administration of sub-therapeutic doses of antibiotics to food-producing animals to enhance growth. For example, certain strains of Salmonella show resistance to eight or more antibiotics. Studies have shown that antibiotic resistance in Salmonella cannot be traced to antibiotic use in humans, suggesting that antibiotic use in animals is the primary cause of resistance.
While much is known about the major microbes responsible for diseases, there are still many undiagnosed cases of infectious disease. It has been estimated that as many as three-fifths of the deaths from acute gastroenteritis per year in the United States are caused by an infectious organism of unknown etiology. Four of the major causes of food-borne infections (Campylobacter jejuni, Escherichia coli O157:H7, Listeria monocytogenes, and Cyclospora cayetanensis, Figure 2) were only recently recognized as causes of food-borne illness.
LPAIV H7N9 was identified as a newly emerging zoonotic pathogen in early 2013. It has caused since then a total of 680 cases of zoonotic infection, with a case-fatality rate of about 20%, principally in adult and elderly individuals. With an incubation time of 2–8 days, H7N9 virus infection can progress from initial symptoms of high fever and other influenza-like signs to more severe lower respiratory tract infection, respiratory distress and associated complications. Exposure to infected poultry is considered the primary risk factor for human infection. A total of 556 outbreaks have been reported in domestic poultry, including chickens, ducks, geese, pigeons and pheasants, largely concurrently to zoonotic cases of infection (Table 1). A few cases were reported in wild bird species. Because of their low pathogenic nature, H7N9 viruses typically cause asymptomatic or mild infections in birds.
Most animal outbreaks and zoonotic cases of low pathogenic avian influenza H7N9 virus infection occurred in mainland China, while imported zoonotic cases were identified in Canada and Malaysia (Fig. 1). The first epidemic of H7N9 virus infection in poultry peaked in April 2013 soon after the first identification of the virus as a cause of a zoonotic case of infection. Epidemics subsequently re-occurred in winter 2014 and 2015, with the highest reported numbers of animal outbreaks and zoonotic cases of infection during the months of January–February of each year.
LPAIV H7N9, in contrast to most other avian influenza viruses, can bind to the cellular receptors used by seasonal influenza viruses,. This ability is associated with one or two specific amino-acids in the hemagglutinin glycoprotein. Because seasonal influenza viruses and LPAIV H7N9 peak coincidentally during the winter months, they may co-infect an individual and subsequently reassort. This may give rise to a transmissible variant, against which the human population has little pre-existing immunity, and may be at the origin of a new influenza pandemic. Strict monitoring and isolation measures are therefore essential to limit the risk of seasonal influenza and reassortment in individuals with zoonotic H7N9 virus infection.
It seems as though centuries have passed since we routinely experienced childhood diseases such as polio, measles, diphtheria, Haemophilus influenzae type B and rubella, and much of society cannot remember the often devastating impact of these once common infectious diseases. Rarely, if ever, do we see someone on crutches as a result of paralytic poliomyelitis or with a hearing deficiency caused by a measles infection. We owe a huge debt of gratitude to the pioneering vaccinologists of the twentieth century for their success in developing vaccines for many of the life-threatening childhood diseases, success that resulted in the US Centers for Disease Control and Prevention considering vaccines the greatest public health achievement of the twentieth century.1 Similarly, there have been comparable successes with the development of many veterinary vaccines and to date the crowning glories of the science of vaccinology are the eradication of smallpox for humans and rinderpest for cattle.2,3
Countries in the Eastern Mediterranean Region (EMR) continue to be hotspots for emerging and reemerging infectious diseases (1). Outbreaks of such diseases have a significant impact on health and economic development in the Region. At least 11 of the 22 countries in the Region have reported epidemics from emerging infectious disease over the past 10 years with the potential for global spread (2). These epidemic threats remain potentially devastating to the social and economic development of the Region, combined with the risk for international spread. The need to prevent, detect, and respond to any infectious disease that poses a persistent threat to global health security remains a national, regional, and international priority (3).
The mission of WHO Health Emergencies (WHE) Program is to build the capacity of Member States to manage health emergency risks and, when national capacities are overwhelmed, to lead and coordinate the international health response to contain outbreaks and to provide effective relief and recovery to affected populations.
The Infectious Hazard Management unit of WHE program in the EMR of World Health Organization (WHO) is responsible for establishing risk mitigation strategies and capacities for priority high-threat infectious hazards. This includes developing and supporting prevention and control strategies, tools and capacities for high-threat infectious hazards, establishing and maintaining experts’ networks to monitor, detect, understand, and manage emerging or reemerging high-threat infectious diseases in the Region.
The principal risk factors contributing to the emergence and rapid spread of epidemic diseases in the Region include acute and protracted humanitarian emergencies resulting in fragile health systems, increased population mobility (travel and displacement), rapid urbanization, climate change, weak surveillance and limited laboratory diagnostic capacity, and increased human–animal interaction (4).
By the 1970s, the human burden of infectious diseases in the developed world was substantially diminished from historical levels, largely due to improved sanitation and the development of effective vaccines and antimicrobial drugs. The emergence of a series of novel diseases in the 1970s and 1980s (e.g. toxic shock syndrome, Legionnaire's disease), culminating with the global spread of HIV/AIDS, however, led to infectious disease rising back up the health policy and political agendas. Public concern about emerging infectious diseases (EIDs) has been heightened because of the perception that infectious diseases were previously under control, because of their often rapid spread (e.g. severe acute respiratory syndrome; SARS), because they often have high case fatality rates (e.g. Ebola virus disease) and because the development of drugs and vaccines to combat some of these (e.g. HIV/AIDS) has been slow and costly. By the 1990s, authors had begun to review similarities among these diseases and identify patterns in their origins and emergence. Similarities included a skew to zoonotic pathogens originating in wildlife in tropical regions (e.g. Ebola virus), and that emergence was associated with environmental or human behavioural change and human interaction with wildlife (e.g. HIV/AIDS) or with domestic animals which had interactions with wildlife (e.g. Nipah virus) [5–7]. Emergence was found to be exacerbated by increasing volumes and rates of human travel and globalized trade.
By the end of the 1990s, the study of EIDs was a staple of most schools of public health, a key focus of national health agencies, a book topic and the title of a scientific journal. Novel diseases continued to emerge, often from unexpected reservoirs and via new pathways. For example, between 1994 and 1998, three new zoonotic viruses (Hendra, Menangle and Nipah viruses) emerged from pteropodid bats in Australia and southeast Asia. Each of these was transmitted via livestock (horses or pigs), and each belonged to the Paramyxoviridae. Around this time, emerging diseases were identified in a series of well-reported die-offs in wildlife, including canine distemper in African lions (Panthera leo) in the Serengeti, chytridiomycosis in amphibians globally, pilchard herpesvirus disease in Australasia and West Nile virus in corvids and other birds in New York [10–13]. Pathogens were also implicated for the first time in species extinctions, or near-extinctions, e.g. canine distemper in the black-footed ferret (Mustela nigripes), chytridiomycosis in the sharp-snouted day frog (Taudactylus acutirostris) and steinhausiosis in the Polynesian tree snail, Partula turgida [14–16]. Novel diseases and their emergence in people and wildlife were reviewed, and commonalities in the underlying causes of emergence discussed, in a paper published at the end of the decade. Here, we re-examine some of the key conclusions of that paper, review how the field has progressed 17 years on and identify some of the remaining challenges to understanding and mitigating the impacts of disease emergence in and from wildlife.1
The precise mechanism of the induction of immunity after pDNA vaccination is complex and multi-factorial (Figure 1).
It is thought that after immunization, transfected muscle cells may produce antigen or foreign proteins that then directly stimulate B cells of the immune system, which in turn produce antibodies. Transfected muscle cells could possibly transfer the antigen to so-called antigen presenting cells (as demonstrated by cross priming) which then transport the proteins via distinct pathways (the MHC I for CD8+T cells or MHC II for CD4+T cells) that result in the display of different processed fragments of expressed proteins (antigens). Finally, direct transfection of antigen presenting cells (such as dendritic cells) with subsequent processing and display of MHC-antigen complexes may also occur. Because the process of antigen production by host cells after DNA vaccination mimics the production of antigens during a natural infection, the resulting immune response is thought to be similar to the type induced by pathogens. Indeed, DNA vaccination generates antigens in their native form and with similar structure and function to antigens generated after natural infection.
The incidence of various emerging and reemerging infectious diseases continues to pose a substantial threat to the human health throughout the world. During the past two decades newly emerging ones, for example, severe acute respiratory syndrome (SARS), reemerging ones, for example, West Nile virus, and even deliberately disseminated infectious diseases, for example, anthrax from bioterrorism, threaten the health of the hundreds and millions of the people globally. During early nineties, there was a consensus that it was the time to close the book as the battle against infectious disease had been won. But reemergence of cholera to the Americas in 1991, the plague outbreak in India in 1994, and the emergence of SARS outbreak in 2002-2003, Swine flu (H1N1) pandemic in 2009, and most recently Zika outbreak in Brazil in 2015 eventually prove that thought wrong. Ebola virus disease (EVD) is one of the notorious emerging infectious diseases that endanger the human lives from time to time since its appearance in 1976 in Zaire (later renamed the Democratic Republic of the Congo) and Sudan in Africa continent. The recent epidemic of EVD started in Guinea in December 2013. Within a short period of time, it has spread across land borders to Sierra Leone and Liberia, by air to Nigeria and USA, and by land to Mali and Senegal. On August 8, 2014, the World Health Organization (WHO) declared the EVD outbreak in West Africa a Public Health Emergency of International Concern (PHEIC) under the International Health Regulations (2005). On March 29, 2016, PHEIC related to EVD was lifted from West Africa and on June 9, 2016, WHO declared the end of the most recent outbreak of EVD. By the end of the epidemic, total 15227 confirmed EVD cases have been reported with 11310 deaths in Guinea, Liberia, and Sierra Leone. Till date no indigenous EVD case has been reported in India. But no country is free from the threat of EVD outbreak. A precise prediction about transmission and consequences after an EVD outbreak in India will be effective for proper planning and management to combat with the situation.
Precision public health is a state-of-the-art concept in the new era of public health research and its application in health care. The concept of precision public health evolved within the last two to three years. The precision public health can be simply described as improving the ability to prevent disease, promote health, and reduce health disparities in populations by applying emerging methods and technologies for measuring disease, pathogens, exposures, behaviours, and susceptibility in populations and developing interventional policies for targeted public health programs to improve health. The emergent areas of precession public health are improving methodologies for early detection of pathogens and infectious disease outbreaks, modernizing public health surveillance, epidemiology, and information systems, and targeting health interventions to improve health and prevent diseases. Application of information technology and data science, like real time data acquisition, geospatial epidemiological modelling, big data analytics, and machine learning technology, in field of epidemiology paves the way to its transformation to digital epidemiology, which is conceptually more accurate and precise in nature [8, 9].
Geospatial epidemiological modelling, an application of geographic information system (GIS), is an important tool of precision public health to study the dynamics of disease transmission more accurately. This tool can be applied to predict the spread of an outbreak. Various interventional measures and subsequent outcome can also be studied, which will help to develop efficient and effective disease specific outbreak prevention and management strategies.
Keeping the concept of precision public health and geospatial epidemiological modelling in mind, a computer simulation based study, related to hypothetical EVD outbreak in India, was undertaken with following objectives: To simulate the spread of Ebola virus disease after a hypothetical outbreak in India on 01.01.2017 at New Delhi and to predict the number of exposed and infectious persons and deaths due to that EVD outbreak within a span of 2 years.
Emerging infectious diseases, defined as novel or known infectious diseases increasing in incidence within a specific location or population, and environmental contaminants pose global and profound threats to human, animal, and environmental health. The rise of emerging infectious diseases demonstrates the dynamic relationship among pathogens, hosts, and their environment. Over sixty percent of emerging infectious diseases are zoonotic, and over seventy percent of those zoonoses have a wildlife origin, including highly pathogenic avian influenza (HPAI), sylvatic plague, Lyme disease, anthrax, and severe acute respiratory syndrome (SARS). These diseases increase burdens on public health systems, negatively impact the world economy, cause declines and extinctions of animal species, and increase loss of ecological integrity. The potential global impact of a wildlife-associated pathogen on human health is exemplified by the over 35 million people currently infected with human immunodeficiency virus (HIV), which is reported to have originated from a simian (primate) virus. Likewise, negative effects of emerging and resurging diseases on agriculture, food safety and security, wildlife health, and human health in Southeast Asia have resulted from outbreaks of HPAI. There are also several newly described pathogens and diseases that have resulted in wildlife population declines and global extinctions. Batrachochytrium dendrobatidis, a cutaneous fungal infection of amphibians, is linked to global declines of amphibian populations, and Pseudogymnoascus destructans, the etiologic agent of white-nose syndrome, has caused precipitous declines in the abundance of North American hibernating bat species. Such large-scale losses of animal species and biodiversity subsequently jeopardize the ecosystems on which all life depends. Of particular concern are novel emerging infectious diseases of wildlife origin as they are difficult to anticipate, devastating to wildlife populations, challenging to manage, and have the potential to have ecological ripple effects. Emerging diseases and pathogens of wildlife origin are increasing globally at alarming rates, in both incidence and by geographic location, which can be largely attributed to the driving forces of globalization, an increasing human population, and climate change.
Globalization, including the rising amounts of international human travel and trade in animal- and plant-based products and other goods, potentiates the spread of pathogens. Emerging infectious diseases are also driven by socio-economic, environmental, and ecological factors, including ecological disruption, microbial adaptation, and lack of preventative measures. For example, outbreaks of HPAI in Southeast Asia present ongoing challenges to biosecurity and food safety related to trade, transport, and marketing of poultry within and between countries. The growing human population and the ensuing urban development increase interactions among people, domestic animals, and wildlife, further escalating the risk for transmitting pathogens and initiating novel disease outbreaks. Climate change can also facilitate the movement of pathogens into new geographic regions. Additionally, climate change is altering insect population dynamics and increasing the potential for spread of vector-borne diseases, which constitute twenty to thirty percent of all emerging infectious diseases.
As a demonstration of an interconnected system, bats contribute up to 50 billion USD annually to the United States of America (US) agricultural economy through their part in insect control. However, the emergence of white-nose syndrome has resulted in the death of over 6 million bats in North America resulting in a marked decrease in insect control. Additionally, while bats are critical components of world ecosystems, they are also potential reservoirs of zoonotic viruses, including rabies, Marburg virus, and Nipah virus. In today's age of dynamic changes in the emergence of infectious diseases associated with increasing interactions among humans, domestic animals, and wildlife, the need to consider these interactions fully becomes crucial for effective management that balances the needs of humans, animals, and the environment.
Such issues are not limited to infectious diseases. For example, while it has long been known that human exposure to unsafe levels of methylmercury is predominantly through dietary consumption of contaminated fish and shellfish, recent technological advances in high-resolution mass spectroscopy now provide a means to “fingerprint” the contributing mercury and determine its source. For example, many locations are impacted by both point-source releases as well as nearly ubiquitous atmospheric fallout of mercury. This new fingerprinting capability has extended the capacity to determine which mercury sources contribute to fish, wildlife, and human exposures, thereby informing environmental decision makers of the most effective means to reduce such exposures.
Severe Acute Respiratory Syndrome (SARS) was the first emerging infectious disease of the new century with epidemic potential. First recognized on 26 Feb 2003, SARS spread rapidly and resulted in 8098 reported cases and 774 deaths in close to 30 countries. While there was no endemic transmission in the majority of these countries, explosive outbreaks were observed in China, Hong Kong, Taiwan, Canada, Vietnam and Singapore. Ongoing research points to an existing animal reservoir for the virus, and future epidemics may hence sporadically emerge from this source.
A key feature in the epidemiology of SARS is the widespread variation in the number of secondary infections caused by each potentially infectious case. While multiple secondary infections were traced to single individuals in several super-spreading events, the majority of infected individuals did not cause any secondary infections.
A recent paper showed that the efficiency of outbreak control measures could be greatly enhanced if there were predictive methods for identifying infectious individuals. However, a review by Yu and Sung noted that the key risk factors for transmission remain largely unknown. While two previous papers attempted to identify risk factors for onward transmission from index patients, both studies were restricted to household contacts, and neither accounted for factors such as clinical presentation, immune status and disease severity in the index patient, all of which have been suspected to play a role in disease transmission.
In this study, we analysed epidemiological and clinical data on probable SARS patients admitted to Tan Tock Seng Hospital. We attempted to identify if any of these factors could explain if individual index patients had transmitted the disease by the time they were detected and isolated, and developed a simple model for explaining the variability in secondary transmission.
The global loss of biological diversity affects the well being of both animals and people. Human impact on ecosystems and ecological processes is well documented. Habitat destruction and species loss have led to ecosystem disruptions that include, among other impacts, the alteration of disease transmission patterns (i.e., emerging diseases), the accumulation of toxic pollutants and the invasion of alien species and pathogens. Ecological perturbations are creating a medium for new disease patterns and health manifestations. For example, in the marine environment, new variants of Vibrio cholerae have been identified within red tide algal blooms. These toxic blooms are occurring in greater frequency and size throughout the temperate coastal zones of the world. In arid zones of the southwestern United States, Brazil and Argentina, hantavirus epidemics have emerged in ecosystems that exhibit habitat degradation and climatic disturbances. These brief examples illustrate our growing awareness of the interrelationship between health and the environment. When the natural resilience of ecosystems is stressed and barriers to disease transmission are reduced the emergence, resurgence and redistribution of infectious diseases are obvious symptoms of a deteriorating planet. According to the World Health Organization, 30 new diseases have been described in people including AIDS, Legionnaire's disease, and toxic E. coli infections since the mid 1970s. Diseases like tuberculosis, temperate-zone malaria, hemorrhagic dengue fever and diphtheria are also re-emerging as threats.
Anthropogenic change can be considered the primary factor causing the emergence of infectious diseases including vector-borne diseases. Global warming, human population growth, deforestation, globalisation, wildlife trade and pollution of oceans and freshwater bodies may have an impact on the prevalence and distribution of infectious pathogens. The dynamics of disease emergence from wildlife are complex and bring human and domestic animal populations into increasing contact with wild animals potentially infecting wildlife with new pathogens causing high mortality, decline and even local extinctions. In some cases, wildlife will survive infection and will become reservoirs. As human populations continue to augment exponentially and globalisation is imminent with increased travel and trade, these anthropogenic pressures on wildlife habitat and populations also will increase. The result can be predicted as a continuing spillover of new pathogens shared among wildlife, domestic animals and humans.
Viruses can be identified by a wide range of techniques, which are mainly based on comparisons with known viruses. Historic methods include electron microscopy, cell culture, inoculation in suckling mice and serology, but these methods have limitations. For example, many viruses cannot be cultivated, excluding the use of cell line isolation and serologic techniques, and can only be characterized by molecular methods. In 2011, Bexfield summarized the different molecular techniques that identify new viruses such as microarray, subtractive hybridization-based and PCR-based methods. Although these techniques have allowed the discovery of many viruses, the prior knowledge of similar viruses is required. Recent advances in sequence-independent PCR-based methods have overcome this limitation, and Sequence-Independent Single Primer Amplification (SISPA), Degenerate Oligonucleotide Primed PCR (DOP-PCR), random PCR and Rolling Circle Amplification (RCA) methods have emerged. The end result of most of these PCR methods is amplified DNA that requires definitive identification by sequencing.
Novel DNA sequencing techniques, known as “Next-Generation Sequencing” (NGS) techniques, are new tools providing high-throughput sequence data with many possible applications in research and diagnostic settings. With the development of different NGS platforms, it is now possible to sequence all viral genomes in a given sample without previous knowledge about their nature with the use of sequence-independent amplification followed by high-throughput sequencing. This combination of techniques, known as viral metagenomics, allows the discovery of completely new viral species within a complex sample and, due to decreasing costs, are nowadays exponentially increasing.
NGS techniques are able to generate a huge number of sequences, ranging from thousands to millions of reads, in only one reaction. In order to fully benefit from this depth of sequencing to identify infectious agents present in a given environment, host DNA/RNA should previously be removed from samples. Preliminary treatments are therefore required prior to nucleic acid amplification and sequencing, mainly based on nucleases treatments and/or viral purification by ultracentrifugation on sucrose, cesium chloride or glycerol gradients. These strategies are known as “Particle-Associated nucleic acid amplification”, i.e., they try to isolate intact (i.e., infectious) viral particles from their environment, protected from the action of nucleases. Subsequent low amount of nucleic acids have required the use of Sequence-Independent Amplifications (SIA) such as SISPA, DOP-PCR, random PCR, RCA. Although these techniques allow generating enough nucleic acid material for sequencing, their main disadvantage remains that they distort quantitative analyzes by introducing bias of amplification in viral diversity studies. As a consequence, quantitative analyses of the composition of resulting viromes may not reflect the reality.
In diagnostic virology, in either human or veterinary medicine, viral metagenomics has allowed the discovery of causative viral agents of disease conditions. Virome analyses have also been conducted to describe the baseline viral diversity in healthy human conditions, as a prior knowledge before studying the viral flora of pathologic conditions.
In the same way, the use of viral metagenomics as a tool for arboviral and zoonotic disease surveillance requires prior knowledge of the viral diversity associated to hematophagous arthropods and animals in close contact with humans. This review thus summarizes our current knowledge of the diversity of viral communities associated with several arthropods, wildlife and domestic animals and present its potential applications for the surveillance of zoonotic and arboviral diseases.
Emerging infectious diseases under this category were subcategorized into 1a, 1b and 1c. Subcategory 1a covers known pathogens that occur in new ecological niches/geographical areas. A few past examples belonging to this subcategory are the introduction and spread of West Nile virus in North America; chikungunya virus of the Central/East Africa genotype in Reunion Island, the Indian subcontinent and South East Asia; and dengue virus of different serotypes in the Pacific Islands and Central and South America.18,19,20,21,22,23 Factors that contributed to the occurrence of emerging infectious diseases in this subcategory include population growth; urbanization; environmental and anthropogenic driven ecological changes; increased volume and speed of international travel and commerce with rapid, massive movement of people, animals and commodities; and deterioration of public health infrastructure. Subcategory 1b includes known and unknown infectious agents that occur in new host ‘niches'. Infectious microbes/agents placed under this subcategory are better known as ‘opportunistic' pathogens that normally do not cause disease in immunocompetent human hosts but that can lead to serious diseases in immunocompromised individuals. The increased susceptibility of human hosts to infectious agents is largely due to the HIV/acquired immune deficiency syndrome pandemic, and to a lesser extent, due to immunosuppression resulting from cancer chemotherapy, anti-rejection treatments in transplant recipients, and drugs and monoclonal antibodies that are used to treat autoimmune and immune-mediated disorders. A notable example is the increased incidence of progressive multifocal leukoencephalopathy, a demyelinating disease of the central nervous system that is caused by the polyomavirus ‘JC' following the increased use of immunomodulatory therapies for anti-rejection regimens and for the treatment of autoimmune diseases.24,25,26 Subcategory 1c includes known and unknown infectious agents causing infections associated with iatrogenic modalities. Some examples of emerging infections under this subcategory include therapeutic epidural injection of steroids that are contaminated with Exserhilum rostratum and infectious agents transmitted from donor to recipients through organ transplantation, such as rabies virus, West Nile virus, Dandenong virus or Acanthamoeba.27,28,29,30,31
Infectious diseases have affected humans since the first recorded history of man. Infectious diseases remain the second leading cause of death worldwide despite the recent rapid developments and advancements in modern medicine, science and biotechnology. Greater than 15 million (>25%) of an estimated 57 million deaths that occur throughout the world annually are directly caused by infectious diseases. Millions more deaths are due to the secondary effects of infections. Moreover, infectious diseases cause increased morbidity and a loss of work productivity as a result of compromised health and disability, accounting for approximately 30% of all disability-adjusted life years globally.1,2
Compounding the existing infectious disease burden, the world has experienced an increased incidence and transboundary spread of emerging infectious diseases due to population growth, urbanization and globalization over the past four decades.3,4,5,6,7,8 Most of these newly emerging and re-emerging pathogens are viruses, although fewer than 200 of the approximately 1400 pathogen species recognized to infect humans are viruses. On average, however, more than two new species of viruses infecting humans are reported worldwide every year,9 most of which are likely to be RNA viruses.6
Emerging novel viruses are a major public health concern with the potential of causing high health and socioeconomic impacts, as has occurred with progressive pandemic infectious diseases such as human immunodeficiency viruses (HIV), the recent pandemic caused by the novel quadruple re-assortment strain of influenza A virus (H1N1), and more transient events such as the outbreaks of Nipah virus in 1998/1999 and severe acute respiratory syndrome (SARS) coronavirus in 2003.10,11,12,13,14 In addition, other emerging infections of regional or global interest include highly pathogenic avian influenza H5N1, henipavirus, Ebola virus, expanded multidrug-resistant Mycobacterium tuberculosis and antimicrobial resistant microorganisms, as well as acute hemorrhagic diseases caused by hantaviruses, arenaviruses and dengue viruses.
To minimize the health and socioeconomic impacts of emerging epidemic infectious diseases, major challenges must be overcome in the national and international capacity for early detection, rapid and accurate etiological identification (especially those caused by novel pathogens), rapid response and effective control (Figure 1). The diagnostic laboratory plays a central role in identifying the etiological agent causing an outbreak and provides timely, accurate information required to guide control measures. This is exemplified by the epidemic of Nipah virus in Malaysia in 1998/1999, which took more than six months to effectively control as a consequence of the misdiagnosis of the etiologic agent and the resulting implementation of incorrect control measures.15,16 However, there are occasions when control measures must be based on the epidemiological features of the outbreak and pattern of disease transmission, as not all pathogens are easily identifiable in the early stage of the outbreak (Figure 1). Establishing laboratory and epidemiological capacity at the country and regional levels, therefore, is critical to minimize the impact of future emerging infectious disease epidemics. Developing such public health capacity requires commitment on the part of all countries in the region. However, to develop and establish such an effective national public health capacity, especially the laboratory component to support infectious disease surveillance, outbreak investigation and early response, a good understanding of the concepts of emerging infectious diseases and an integrated country and regional public health laboratory system in accordance with the nature and type of emerging pathogens, especially novel ones, are highly recommended.
Traditionally, emerging infectious diseases are broadly defined as infections that: (i) have newly appeared in a population; (ii) are increasing in incidence or geographic range; or (iii) whose incidence threatens to increase in the near future.6,17 Six major factors, and combinations of these factors, have been reported to contribute to disease emergence and re-emergence: (i) changes in human demographics and behavior; (ii) advances in technology and changes in industry practices; (iii) economic development and changes in land use patterns; (iv) dramatic increases in volume and speed of international travel and commerce; (v) microbial mutation and adaptation; and (vi) inadequate public health capacity.6,17
From the perspective of public health planning and preparedness for effective emerging infectious disease surveillance, outbreak investigation and early response, the above working definition of emerging infectious disease and its associated factors that contribute to infectious disease emergence are too broad and generic for more specific application and for the development of a national public health system, especially in the context of a public health laboratory system in a country. Thus, in this article, emerging infectious diseases are divided into four categories based on the nature and characteristics of pathogens or infectious agents causing the emerging infections; these categories are summarized in Table 1. The categorization is based on the patterns of infectious disease emergence and modes leading to the discovery of the causative novel pathogens. The factors or combinations of factors contributing to the emergence of these pathogens also vary within each category. Likewise, the strategic approaches and types of public health preparedness that need to be adopted, in particular with respect to the types of public health laboratories that need to be developed for optimal system performance, will also vary greatly with respect to each category of emerging infectious diseases. These four categories of emerging infectious diseases and the factors that contribute to the emergence of infectious diseases in each category are briefly described below.
Twenty years ago (1992), a landmark Institute of Medicine (IOM) report entitled “Emerging Infections: Microbial Threats to Health in the United States” underscored the important but often underappreciated concept of emerging infectious diseases (EIDs) (1). Although the IOM report was influential in thrusting the issue of EIDs squarely into scientific and public discourse, the awareness that diseases periodically emerge and reemerge actually goes back millennia (2, 3). For example, ancient Greek, Roman, and Persian writers documented the emergence of many new epidemics. During and after the 14th-century “Black Death” pandemic of bubonic/pneumonic plague, European city officials quarantined arriving ships to prevent its importation and set up quarantine stations to isolate and care for patients. In 1685, the scientist Robert Boyle presciently observed that “there are ever new forms of epidemic diseases appearing…among [them] the emergent variety of exotick and hurtful…” (4, 5).
By the mid-19th century, the discovery of microbes as causative agents of infectious diseases led to the development of preventive countermeasures such as passive immunotherapy, vaccines, and drugs against infective agents (6). These advances spurred optimistic predictions that infections would soon be conquered (7), and physicians and public health workers began to lose sight of the possibility of the emergence of new and previously unrecognized infectious diseases. To a large extent, it was the shock of the recognition of HIV/AIDS in the early 1980s, followed by the IOM report of 1992, that rekindled awareness of, and interest in, EIDs. Two decades after the IOM report, it is appropriate to ask what has been learned about EIDs, where have we succeeded or failed in our efforts to fight them, and what challenges remain.
China established the Pneumonia of Unknown Etiology (PUE) Surveillance System in 2004 for timely detection of emerging respiratory infectious diseases, and the system has played an important role in detecting human infections with novel avian influenza viruses including A(H5N1), A(H10N8), A(H9N2), and A(H5N6) [2–4]. Nevertheless, a 2007 evaluation identified persistent underutilization of the PUE surveillance system. More recently, inconsistent reporting occurred during the initial 2013 outbreak of low pathogenic avian influenza (LPAI) A(H7N9) [henceforth A(H7N9)], prompting public health authorities to allow clinicians to report cases directly without expert consultation committee approval. This change resulted in the reporting of 1118 cases in 5 weeks compared with 1016 cases in the previous 10 years. Laboratory and case investigation resources were quickly strained and reporting procedures reverted to those used prior to the outbreak. As a result, case reporting subsequently decreased. A 2015 assessment of clinician and health administrator knowledge, attitude and practices related to PUE surveillance conducted within 43 healthcare facilities revealed a willingness to report PUE cases, but identified limited awareness of the PUE system, lack of understanding of the reporting process, and failure to follow the case definition.
To evaluate these gaps, we piloted a 3-month active surveillance program in two hospitals to 1) quantify the number of cases meeting the PUE case definition and the number reported and 2) to identify ways to improve the PUE surveillance system’s detection of respiratory infections of public health significance.
An important area of infectious disease epidemiology is concerned with the planning for mitigation and control of new emerging epidemics. The importance of such planning has been highlighted during epidemics over recent decades, such as human immunodeficiency virus (HIV) around 1980, severe acute respiratory syndrome (SARS) in 2002/2003, the influenza A H1N1 pandemic in 2009 and the Ebola outbreak in West Africa, which started in 2014. A key priority is the early and rapid assessment of the transmission potential of the emerging infection. This transmission potential is often summarized by the expected number of new infections caused by a typical infected individual during the early phase of the outbreak, and is usually denoted by the basic reproduction number, R0. Another key priority is estimation of the proportion of infected individuals we should isolate before they become infectious, and thus completely prevent them from spreading the disease to any other individuals in order to break the chain of transmission. This quantity is denoted as the required control effort, vc. From a modelling perspective, vc is equivalent to the critical vaccination coverage: if a vaccine is available, then the required control effort is equal to the proportion of the population that needs to be immunized in order to stop the outbreak, if the immunized people are chosen uniformly at random. These key quantities are inferred from available observations on symptom onset dates of cases and the generation times, i.e. the typical duration between time of infection of a case and infection of its infector. The inference procedure for R0 and vc requires information on the infectious contact structure (‘who contacts whom’), information that is typically not available or hard to obtain quickly for emerging infections.
The novelty of this paper lies in that we assess the estimators for the basic reproduction number R0 and required control effort vc, which are based on usually available observations, over a wide range of assumptions about the underlying infectious contact structure. We find that most plausible contact structures result in only slightly different estimates of R0 and vc. Furthermore, we find that ignoring the infectious contact pattern, thus effectively assuming that individuals mix homogeneously, will in many cases result in a slight overestimation of these key epidemiological quantities, even if the actual contact structure is far from homogeneous. This is important good news for planning for mitigation and control of emerging infections, because the relevant contact structure is typically unknown: ignoring the contact structures results in slightly conservative estimates for R0 and vc. This is a significant justification for basing infection control policies on estimates of R0 derived for the Ebola outbreak in West Africa in, for which, although we know that transmission is mainly due to close and intimate contact with bodily fluids, it is hard to obtain data on who regularly has such contact with whom. Therefore, the data are stratified by region, without further assumptions on contact structure.
We focus on communicable diseases in a closed population (i.e. a population without births, migration and non-disease-related deaths) that follow an infection cycle where the end of the infectious period is followed by long-lasting immunity or death. In such an infection cycle, individuals are either susceptible, exposed (latently infected), infectious or removed, which means either recovered and permanently immune (or immune for the duration of the epidemic) or dead. Those dynamics can be described by the so-called stochastic SEIR epidemic model [7, ch. 3]. For ease of presentation, we use the Markov SIR epidemic as a leading example. In this special case, there is no latent period (so an individual is able to infect other individuals as soon as they are infected), the infectious period is exponentially distributed with expected length 1/γ, and infected individuals make close contacts at a constant rate λ. While infectious, an individual infects all susceptible individuals with whom he or she has close contact. The rate at which an infectious individual makes contact with other individuals depends on the contact structure in the community but it does not change over time in the Markov SIR model. The more general results for the full SEIR epidemic model are given and derived in the electronic supplementary material.
We cover a wide range of possible contact structures. For each of these, we derive estimators of the basic reproduction number and the required control effort. We start with the absence of structure, when the individuals mix homogeneously [8, ch. 1] (figure 1a). We examine three different kinds of heterogeneities in contacts: the first kind, network structure [9–12] (figure 1b), emphasizes that individuals have regular contacts with only a limited number of other individuals; the second kind, multi-type structure (figure 1c), emphasizes that individuals can be categorized into different types, such as age classes, where differences in contact behaviour with respect to disease transmission are pronounced among individuals of different type but negligible among individuals of the same type; and the third kind, household structure (figure 1d), emphasizes that individuals tend to make most contacts in small social circles, such as households, school classes or workplaces. Finally, we compare the performance of the estimators for R0 and vc against the simulated spread of an epidemic on an empirical contact network.
A “disease” is any condition that impairs the normal function of a body organ and/or system, of the psyche, or of the organism as a whole, which is associated with specific signs and symptoms. Factors that lead to organs and/or systems function impairment may be intrinsic or extrinsic. Intrinsic factors arise from within the host and may be due to the genetic features of an organism or any disorder within the host that interferes with normal functional processes of a body organ and/or system. An example is the genetic disease, sickle cell anaemia, characterized by pain leading to organ damage due to defect in haemoglobin of the red blood cell, which occurs as a result of change of a single base, thymine, to adenine in a gene responsible for encoding one of the protein chains of haemoglobin. Extrinsic factors are those that access the host's system when the host contacts an agent from outside. An example is the bite of a mosquito of Anopheles species that transmits the Plasmodium falciparum parasite, which causes malaria. A disease that occurs through the invasion of a host by a foreign agent whose activities harm or impair the normal functioning of the host's organs and/or systems is referred to as infectious disease [1–3].
Infectious diseases are generally caused by microorganisms. They derive their importance from the type and extent of damage their causative agents inflict on organs and/or systems when they gain entry into a host. Entry into host is mostly by routes such as the mouth, eyes, genital openings, nose, and the skin. Damage to tissues mainly results from the growth and metabolic processes of infectious agents intracellular or within body fluids, with the production and release of toxins or enzymes that interfere with the normal functions of organs and/or systems. These products may be distributed and cause damage in other organs and/or systems or function such that the pathogen consequently invades more organs and/or systems.
Naturally the host's elaborate defence mechanism, immune system, fights infectious agents and eliminates them. Infectious disease results or emerges in instances when the immune system fails to eliminate pathogenic infectious agents. Thus, all infectious diseases emerge at some point in time in a given population and in a given context or environment. By understanding the dynamics of disease and the means of contracting it, methods of fighting, preventing, and controlling are developed [2, 5, 6]. However, some pathogens, after apparent elimination and a period of dormancy, are able to acquire properties that enable them to reinfect their original or new hosts, usually in increasingly alarming proportions.
Understanding how once dominant diseases are reappearing is critical to controlling the damage they cause. The world is constantly faced with challenges from infectious diseases, some of which, though having pandemic potential, either receive less attention or are neglected. There is a need for constant awareness of infectious diseases and advances in control efforts to help engender appropriate public health responses [7, 8].
Please see Additional file 1 for translation of the abstract into five official working languages of the United Nations.
Emerging and re-emerging viral infections have been a major threat to public health worldwide, since their recognition in the late 20th century. These infectious diseases include those caused by newly identified viruses, previously known viruses that acquired additional virulence traits, and those showing spread to unaffected regions. In the last ten years, re-emergence has been noted for Zika, Ebola, MERS, Dengue, Chikungunya and avian influenza, while SFTS (severe fever with thrombocytopenia syndrome) was recognized to be caused by a novel virus. These diseases are free to move across national borders according to rapid human mobility via global airline network. With this background, any novel infectious disease anywhere in the world may have the potential for global spread.
Although various factors are considered to be associated with an increase of emerging/ re-emerging infectious diseases, they can be summarized as three major changes on the global level, i.e., (1) change in human/society/behavior, (2) change in environment/ecosystem, and (3) change in microorganisms. These changes are considered to synergistically increase the risks for the emergence of pathogens, transmission of pathogens, and opportunity of infection (susceptible hosts).
Factors related to humans and society are the most responsible for emergence and spread of infectious diseases. At present, global population is estimated to be 7.4 billion and growing rapidly, described as “a population explosion”. This increase is remarkable in sub-Saharan Africa and South Asia. Increase of population is a common issue in developing regions and facilitates poverty, and leads to urbanization associated with the growth of megacities (37 cities as of 2017) with a population of more than 10 million. High population and its density increase the risk for transmission of infectious pathogens via human-to-human contact, and low hygienic condition arising from undeveloped infrastructures (e.g., sewerage system). Naturally, population explosion and urbanization facilitate the expansion of residence area of humans, which promote forest development associated with environmental destruction. During the process, humans may encounter unknown viruses which have been lurking in any animal but harmful to humans. Although it has not yet been fully demonstrated, Ebola virus is suggested to reside in some species of fruit bats as potential natural host, from which this virus might have transmitted to humans, causing Ebola Virus Disease (EVD).
International tourists who traveled abroad reached over 1.1 billion in 2014, and have been constantly increasing. The development of airline networks enables infectious pathogen to spread globally in a few days. Such typical situation was evident for the outbreak of SARS (severe acute respiratory syndrome) in 2003, when the unknown pathogen, which was later revealed to be a novel coronavirus, was disseminated from China to at least 17 countries within a week via air travel of infected patients. The recent outbreak of MERS coronavirus in Korea (2015) was also caused by a returnee from the Middle East. Spread of emerging viruses is indirectly related to socioeconomic problems including civil wars, an increase of refugees, and natural disasters. These human factors always compromise human health and increase the risk for emerging/re-emerging infectious diseases.
More than 200 virus species have been known to be able to infect humans. Historically, the number of newly identified virus species/family has been constantly increasing since the 20th century, which was associated with the development of technology, from tissue culture and serological detection, to genetic identification represented by PCR and high throughput sequencing. Among more than 1000 pathogens of humans, over 50% of them were considered to have originated in animal species (vertebrates). Emerging viruses are considered more likely to be zoonotic. The number of infectious diseases outbreaks increased globally about 4 times from the 1980s to 2010, associated with an evident increase of zoonosis as well as vector-borne disease, compared with human-specific infections. Increase of zoonosis and vector-borne diseases is related to global changes in environment and ecosystem which may be caused by climate change associated with global warming. Floods, fierce heat, and drought which arise as an influence of climate variation, may cause an increase of vectors, facilitating their move from an endemic area, and a decrease of natural enemies to vectors. Phylogenetic analysis combined with chronological tracing indicated that recent global spread of Chikungunya was caused synergistically by factors of humans, environment, vectors, and viruses. In the 1980s and 1990s, illegally dumped waste tires increased due to globalized trading and industrialization. These tires provided water pool for the proliferation of mosquitos, enhancing local endemicity. Thereafter, viruses with vectors have disseminated via international airline network, associated with the occurrence of genetic diversity in viral genome. A mutation in the envelope protein conferred increased viral growth in mosquito, which facilitated spread of this vector-born disease. Thus, spread of emerging viral diseases is considered to be caused by multifactorial mechanisms.
Currently, globally important viral infectious diseases may be classified into following categories with features such as (1) high frequency worldwide (diarrhea, respiratory infections, etc.), (2) pandemic concern (EVD, etc.), (3) directed to eradication/elimination (e.g., poliomyelitis), and (4) neglected tropical diseases (e.g., rabies). These viral diseases are prone to be prevalent in developing countries, because of 1) higher population (density), 2) higher prevalence of vector/reservoir of virus pathogens, 3) shortage of medical/preventive resources against viral diseases and 4) low socioeconomic/hygienic status. Furthermore, it is difficult to predict the emergence or spread of novel viral infections, and particularly zoonosis is impossible to eradicate because wild animals/vectors carry viral pathogens. Despite such situations, scientists have a significant role to reduce the risks of emerging viral diseases. The first priority is to ensure adequate surveillance of viral diseases, i.e., to maintain epidemiological study on humans, animals, virus strains from various sources including environment, which is relevant to “One Health” approach advocated recently. Molecular epidemiology and population dynamics of viruses provide suggestions for the genetic, phenotypic, and epidemiologic trend of the viral diseases. Outcomes from those efforts are definitely essential for developing diagnostic methods, therapeutic approaches, and vaccines.