Dataset: 11.1K articles from the COVID-19 Open Research Dataset (PMC Open Access subset)
All articles are made available under a Creative Commons or similar license. Specific licensing information for individual articles can be found in the PMC source and CORD-19 metadata.
More datasets: Wikipedia | CORD-19
Deep Learning Technology: Sebastian Arnold, Betty van Aken, Paul Grundmann, Felix A. Gers and Alexander Löser. Learning Contextualized Document Representations for Healthcare Answer Retrieval. The Web Conference 2020 (WWW'20)
Funded by The Federal Ministry for Economic Affairs and Energy; Grant: 01MD19013D, Smart-MD Project, Digital Technologies
Environmental factors, specifically climate conditions, are the seasonal drivers that have received the most attention. This may be because they often covary with seasonal disease incidence. Environmental drivers are abiotic conditions that influence transmission via their effects on hosts and/or parasites; classic examples are temperature and rainfall, which influence a variety of infectious diseases, but other examples include seasonal nonclimatic abiotic environmental conditions, such as water salinity, which may impact water-borne pathogens. Environmental factors can impact pathogen survival during transitions between hosts. Transitions can take place during short time windows (e.g., for droplet-transmitted infections) or long time windows (e.g., for parasites with environmental life stages). In addition to their impact on pathogens, environmental drivers can also influence host susceptibility to infection or vector population dynamics.
As for host susceptibility, environmental conditions can impact the host immune response and increase cells' susceptibility to infection or pose seasonal challenges (such as food limitations) that leave hosts vulnerable to infection or pathology, which has been proposed to influence disease progression in individuals infected with HIV. For directly transmitted infections, environmental conditions can be major drivers of cycles in incidence, with influenza and cholera transmission being notable examples (e.g., see [3, 80]). The effects of climate on flu transmission have been studied using population-level data coupled with transmission models, as well as empirical animal studies, to demonstrate the effects of temperature and humidity on transmission. Although climate conditions undoubtedly play a direct role in several directly transmitted infections, they may play a more nuanced role in vector-borne disease systems in which they modulate vector population dynamics and subsequently disease transmission. For example, in the case of African sleeping sickness (Table 1), the rainy season is hypothesized to modify tsetse fly distribution, which results in changes in human–tsetse fly contact and subsequently African sleeping sickness incidence; in this case, we can classify the seasonal driver as (1) vector seasonality alone or as (2) seasonal climate influencing vector seasonality and vector seasonality having a downstream effect on seasonal exposure. Abiotic and biotic seasonal drivers are therefore interconnected and not mutually exclusive.
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
An ideal animal model for the study of a human disease is one which utilizes a route of infection that mimics the natural transmission of the pathogen; the ability to obtain disease with an infectious dose equivalent to that causing disease in humans; as well having a disease course, morbidity and mortality similar to that seen with human disease. Additionally, the animal model should have a mode(s) of transmission that mimics human cases. Factors which subsequently allow more detailed inferences about disease pathogenesis include the availability of reagents to evaluate host innate and adaptive immune responses to the pathogen, and histopathological changes in the host which result from infection or the host response to infection. These findings can then be compared to what is known of human disease. The utility of a small animal model of human disease for study of therapeutic efficacy is augmented when large numbers of animals are available for use in appropriately, well-powered studies. Even if all aspects of an animal model of disease are not completely faithful to what is known of human disease, important information regarding therapeutic efficacy can be gleaned from their use in “pre-clinical” studies.
The published literature on clinical manifestations of systemic human orthopoxvirus disease is derived from historic literature descriptions of human smallpox and more recent descriptions of human monkeypox disease. The clinical-descriptive literature on human monkeypox is expected to grow in the next five years, as data acquisition and analysis from an ongoing study in the Democratic Republic of Congo is finalized. Currently available literature is largely derived from WHO-sponsored surveillance efforts in West Africa and the Congo Basin in the 1980s, after the first recognition of human disease in these areas, and subsequent analyses of public health response data and human research studies following the introduction of West African clade virus into the U.S. in 2003. Human monkeypox, as described through the active surveillance and case ascertainment studies sponsored by WHO in the 1980s, was depicted as resembling discrete ordinary smallpox. In natural human infection, exposure leading to infection is believed to occur via a respiratory route, with subsequent progressive viremias/lymphemia, ultimately leading to seeding of the skin to generate a generalized rash. Percutaneous exposure, also leading to generalized rash formation, has also been described for both viral infections. The disease pathogenesis has been conjectured and modeled largely from animal studies; initial models were using ectromelia infection of mice; some kinetic observations of virus shedding and viremia have been made in human studies of smallpox and monkeypox. The time course of disease is generally thought to include an asymptomatic phase of 10–12 days, during which time the virus initially enters the host, replicates, seeds reticuloendothelial organs, replicates, then spreads via the bloodstream (inducing a febrile response) which is the first symptomatic hallmark of disease. The fever is usually described as occurring 10–12 days post initial exposure/infection. The range has been 7–17 days. Fever is accompanied by other symptoms, including headache, backache, myalgias, and or abdominal pain. Two to three days following the fever, rash develops—initially presenting as a macular, then papular, then vesicular and pustular eruption. Scabbing then begins. Each stage of rash lasts 1–2 days. Approximately 2–3 weeks post initial symptoms, scabs begin to separate from the skin. Death and disease severity have had some correlation with rash burden in epidemiologic studies of hospitalized smallpox patients. Severe outcomes are more frequent in unvaccinated, younger age groups; death occurs within the first week of illness in cases with hemorrhagic manifestations, and during the second or third week of illness in “ordinary” cases. In the human monkeypox cases studied in Zaire/DRC between 1981–1986, of the 33 deaths among 338 patients, all occurred in unvaccinated children less than eight years of age. Death occurred during the first week of illness in 21%, the second week in 52%, and the third week of illness in the remaining 27%.
The development of small animal models for the study of monkeypox virus (MPXV) has been quite extensive for the relatively short period of time this pathogen has been known. Initial animal models were designed to address natural history in potential or surrogate reservoir host species, as well as studies of disease in primates. Routes of exposure were designed to evaluate disease if respiratory or percutaneous exposures occurred, or in some cases to simply address whether virus would replicate in the animal model system. Factors that influence the outcome of a challenge study include the age of the animal at time of infection, inoculation route used, and the viral dosage given. Additionally, the strain of MPXV (currently delineated as belonging to Congo Basin clade or West African clade) used in the study may influence the disease severity.
The spread of infectious diseases strongly depends on how habitat characteristics shape patterns of between-host interactions,. In particular, habitat heterogeneity influences patterns of between-individual contacts and hence, disease dynamics,. For example, “habitat hotspots”, sites that attract individuals or social groups over long distances, can be visited by a large subset of a population. Around hotspots, between-individual contact rates often increase in frequency, which amplifies disease transmission. In humans, schools and working places are typical examples of hotspots and have been shown to accelerate the spread of measles, influenza and SARS,,. Thus, limiting transmission at hotspots has become a promising strategy for mitigating epidemics (e.g., influenza) although the efficiency of such strategies also depends on the role hotspots plays relative to other sources of local transmission (e.g., influenza,)
In wild animal populations, high quality feeding spots (e.g., fruit trees), breeding sites, waterholes or sleeping sites can exacerbate direct physical contacts. Empirical and theoretical studies on the epidemiological importance of habitat hotspots have mainly focused on how the spatial aggregation of animals favors disease transmission at the hotspot itself,. For example, the aggregation of wild boar at watering sites significantly increases the transmission of tuberculosis-like lesions. However, inter-individual contacts may not always significantly increase at the hotspot itself. This is for example the case of habitat hotspots that some animal species only visited occasionally, such as some mineral licks,. Also, animals present at the same time at a particularly large hotspot may not be close enough to each other to transmit infectious diseases. This is the case of large forest clearings, or large waterholes. Finally, species such as primates and ungulates might avoid defecating in hotspots of high food resources, limiting the transmission of fecal-oral parasites at hotspots,.
When disease transmission does not occur at the hotspot, it can still occur at a certain distance from the hotspot. This phenomenon has received little attention so far. Specifically, infective contacts may be observed when infectious individuals travel to the hotspot and cross the territory of susceptible individuals and, reversely, when susceptible individuals cross the territory of infectious individuals. This second type of transmission may be prominent when the disease reduces the mobility of sick individuals (i.e., sickness behavior,,). For example, in humans, sick individuals often stay home, which alters disease dynamics,. Sick wild animals also commonly reduce their rate of search for food or water. Such transmission may particularly apply to parasites that can survive in the environment (e.g., gastrointestinal parasites) for which the spatial overlap of the home ranges of sympatric hosts favors transmission.
To investigate these transmission mechanisms, we developed an agent-based model exploring patterns of disease spread in a large closed population composed of territorial social groups, in which one or more hotspots influence group movement patterns, but where direct disease transmission at the hotspot itself is negligible. Our hypothesis is that terrestrial animals necessarily cross conspecifics' home ranges on their way to a hotspot, which modifies the contact network of the population and may subsequently alter disease transmission. We assumed that between-group disease transmission can occur both between groups having neighbouring territories and between groups travelling to a hotspot and groups whose territories are crossed en route. We also assumed that only groups which territory lies within a certain distance from the hotspot (further referred as “radius of attraction”) can visit it, and that their visitation rate decreases as this distance increases.
The relationship between the radius of attraction and the disease dynamics was then investigated under two scenarios: i) when groups including sick individuals do not travel to the hotspot, and ii) when these groups still travel to the hotspot. The first scenario corresponds to the case of virulent parasites that can strongly decrease the mobility of infected individuals, such as Ebola virus in western lowland gorillas, whereas the second scenario applies to pathogens that do not strongly modify the behavior of their host, such as some gastro-intestinal macro-parasites and bacteria. Under both scenarios, we investigated the relationship between the disease attack rate and the hotspot radius of attraction, identified the groups in the population that have the highest risk of infection and explored the relationship between the number of hotspots and the magnitude of an epidemic.
An emerging infectious disease (EID) can be defined as ‘an infectious disease whose incidence is increasing following its first introduction into a new host population or whose incidence is increasing in an existing host population as a result of long-term changes in its underlying epidemiology'.1 EID events may also be caused by a pathogen expanding into an area in which it has not previously been reported, or which has significantly changed its pathological or clinical presentation.2
Mostly, infectious disease emergence in humans is caused by pathogens of animal origin, so-called zoonoses.2,3,4,5 Likewise, cross-over events may occur between non-human species including between domestic animals and wildlife, and such events also involve transmission from a reservoir population into a novel host population (spill-over).5,6,7 Emergence in a novel host, which includes spill-over/zoonoses, has been extensively studied. An elaborate framework featuring the subsequent stages in the emergence process of a species jump has already been developed, describing how an established animal pathogen, through stages of spill-over and lengthening of the transmission chain in the novel host, may evolve all the way up to an established and genetically consolidated pathogenic agent.8,9,10 However, as implied by the above broader definition of EID, other categories can be distinguished in addition to emergence in a novel host, including disease outbreaks in an existing host or the emergence of a disease complex beyond the normal geographic range.
Here, we will argue that changes in host range, in pathogen traits displayed in the same host, and the geographic distribution of a disease complex, form three distinct sets of complementary and only slightly intersecting disease emergence scenarios. Together, these scenarios present the full picture and range of possible disease emergence dynamics. Hence, we categorize EIDs into three main groups, with emergence of (i) a pathogen in a novel host; (ii) a pathogen with novel traits within the same host; and (iii) a disease complex moving into a novel geographic area. Human actions that modulate the interplay between pathogens, hosts and environment are at the basis of almost all EID events, although the exact drivers and mechanisms differ. For each of the three groups, we will argue how the emergence process is driven by specific sets of causal factors, discuss the changes in disease ecology and transmission and elaborate on the invasion dynamics and on the characteristics of pathogens that are dominant in each group. Such structuring of the myriad of EID on the basis of the changes in the interplay between pathogens, hosts and environment will assist in better understanding of specific EID events and in designing tailored measures for prevention and prediction. Moreover, the framework contributes to understanding the effects of human actions that pave the way for the three distinct emergence scenarios. We propose that the resulting framework applies not just to pathogens affecting humans and animals in agriculture and natural ecosystems; it may be usefully applied also for pest and disease emergence in aquaculture, plant production and insect rearing.
Since the earliest documented epidemics of plague, leptospirosis, viral hemorrhagic fevers, and rabies, we have known that humans and our domestic animals can become ill after contact with other animals. Most animal pathogens can infect multiple host species, and pathogen spillover from one host species to another is common. Pathogen spillover has been defined as scenarios in which disease occurrence in a focal population depends on a distinct reservoir source that maintains the pathogen indefinitely. Thus, controlling spillover diseases is complicated by the need to manage not only cases in the target population but also transmission interfaces and reservoir populations. Broadly, a disease reservoir is the source of new cases in a target population. A better understanding of the types of species that form reservoirs will therefore facilitate the management of many emerging infectious diseases.
However, what precisely constitutes a reservoir has been the subject of debate [4–6]. Haydon et al. defined a reservoir as “one or more epidemiologically connected populations or environments in which the pathogen can be permanently maintained and from which infection is transmitted to the defined target population.” Following this definition, one pathogen may cause disease in multiple target populations, and the reservoir for each target population can be different. To identify reservoirs, researchers must find evidence of natural infection and spillover. Here, we follow the Haydon et al. definition to study reservoirs of spillover pathogens.
A number of recent studies have attempted to answer the question, “Are reservoirs special?”, with the goal of identifying likely disease sources. Ungulates, carnivores, and rodents are the source of most zoonoses, yet recent outbreaks suggest that bats may be a uniquely important reservoir of human pathogens. Reservoir species with fast life history characteristics appear to have higher reservoir competence and contribute disproportionately to cases of some zoonotic diseases. In a study of reservoirs for tick-borne zoonotic diseases, the mammalian species with the fastest life history traits also exhibited the highest reservoir competence. Species with high reproductive output produce a large number of naïve host individuals that can sustain pathogens, even those that induce long-lasting host immunity. For example, the persistence of classical swine fever in pigs and wild boar has been attributed, in part, to high birth rates that maintain a large population of susceptible individuals. Further, because of trade-offs between pace of life and the immune system investment, fast-lived species may exhibit greater reservoir competence through a proneness to acquire, maintain, and transmit pathogens.
To summarize characteristics of reservoirs and determine what makes reservoirs special, we assembled and analyzed a database of pathogens, their targets, and their known reservoirs to address the following questions: 1) What are the most represented taxa among reservoirs of spillover pathogens? 2) What are the characteristics and common taxa of reservoirs for pathogens that are zoonotic “high priority” (defined below) or have epidemic potential? And 3) Are mammalian reservoir species distinct in their life history traits compared to all mammals? Given the strong research bias in favor of human and domestic animal pathogens, we expect that most known disease reservoirs will include mammals. We also hypothesize that, more often than not, reservoirs will include multiple species and wildlife. Because past studies suggested that faster-lived species may be more competent hosts, we predict that reservoir species will exhibit faster life histories.
A wide range of infectious disease drivers can be grouped under this category, including climate change, land-use patterns, global trade and travel, migration, and so on. Climate change involves mean temperature increases in many parts of the world, as well as increased likelihood of adverse or even extreme weather events (11–13). Many infectious diseases are temperature sensitive as many vectors and pathogens are dependent upon permissive ambient conditions. There is thus a substantial body of research that collectively demonstrates that warming will increase the transmission of vector-borne diseases in the geographic ranges of their distribution (14–18). Changing temperature and precipitation patterns can affect the habitats and population growth of cold-blooded disease vectors, such as mosquitoes and ticks, as well as the replication rates of infectious diseases within their hosts, and even the rates at which disease-carrying vectors bite humans (18–20).
Among the best substantiated indicators of the observed effects of climate change on infectious disease is evidence of an altitudinal increase of malaria in the highlands of Columbia and Ethiopia (21) and of the northerly expansion of the disease-transmitting tick species, Ixodes ricinus, in Sweden (22). Many modelling studies project significant shifts in the transmission of vector-borne diseases such as malaria (23, 24), dengue (25), and Chikungunya (26) under climate change scenarios, but it is important to note that the extent of observed changes will depend on the presence or absence of mitigating measures, such as vector control or socioeconomic development (27, 28). Other examples of infectious diseases in Europe anticipated to be affected by climate change include West Nile virus (29), salmonella (30), campylobacter, and cryptosporidium (31, 32).
Land-use patterns, meanwhile, are a crucial driver of infectious disease emergence. It has been estimated that more than 60% of human pathogens are zoonotic (i.e. diseases of animals that can be transmitted to humans) (33). Many human land-use activities, including agriculture, irrigation, hunting, deforestation, and urban expansion, can cause or increase the risk of zoonotic and food- and water-borne diseases (33, 34). For example, one consequence of urban sprawl and deforestation is that wildlife may increasingly need to find new habitats in urban or abandoned environments, which could lead to increased human exposures to infectious pathogens. Meanwhile, the density of human population, also associated with increasing urbanisation, has also been shown to be linked to the emergence of many infectious diseases (35).
Intensified global trade and travel, not to mention migration, render political borders irrelevant and create further possibilities for global disease transmission (36–38). There are numerous examples of the arrival, establishment, and spread of ‘exotic’ pathogens to new geographic locations, including malaria, dengue, Chikungunya, West Nile, and bluetongue in recent years, aided by shipping or other trade routes (36). This process is facilitated when the environmental conditions in different parts of the world share common characteristics (36). Meanwhile, numerous vaccine-preventable diseases, such as polio, meningitis or measles, can also be introduced or reintroduced to susceptible populations as a consequence of international travel (39).
Blood smears were stained with Diff Kwik (eosin and methylene blue) and microscopically examined at 40x and 100x (oil) magnification for cellular abnormalities and haemoparasites.
Ohio led the United States in measles cases in 2014, ostensibly and directly related to unvaccinated international air travelers (Ohio Department of Health, 2015). Researchers have validated concerns that Ohio scored lower than 43 other states in being prepared for infectious disease outbreaks (Trust in America's Health, Robert Wood Johnson Foundation, news release, Dec. 17, 2015). These researchers have urged efforts to protect Americans from “new threats such as Middle East respiratory syndrome coronavirus (MERS-CoV) and antibiotic-resistant superbugs, along with resurging diseases such as tuberculosis, whooping cough and gonorrhea.” These concerns over emergent diseases led us to review the literature of infectious diseases with adequate travel histories and to conduct a retrospective cohort study of the risk to Ohio's population including a nested case control study to explore the association between infectious disease risk and air travel. The methodological reasons for selecting malaria, seasonal influenza hospitalizations (IH), and hepatitis A (HA) among the diseases reviewed will be discussed. HA virus is highly contagious and can affect liver function. HA is transmitted frequently through contaminated food and water. The World Health Organization (WHO) estimates that there are over 1.3 million cases of acute HA every year. Influenza disease is caused by a virus that attacks the respiratory system. Symptoms include sudden onset of fever, body aches, fatigue, and cough. Pneumonia can be a complication of influenza, especially in the persons with weakened immune systems. WHO estimates that over 3 million persons are hospitalized and over 250,000 persons die each year from influenza.
External parasites were collected during physical exam of the pelage and placed in ethanol for later testing for bacterial pathogens as explained below.
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].
Two features of human behavior throughout history are striking. The first has been the domestication of numerous animals for food production, as working animals for activities such as transport, and for hunting purposes. They are also, particularly in modern times, used as a source of companionship, and in the USA alone there are estimated to be over 77 million dogs.1 The second feature is our propensity to travel. This trait has accelerated in the modern age through technical innovations such as the motor car, air travel, and international shipping.2 Human travel through migration, leisure, or business continues to increase in parallel with a population increase and the spread of affluence. This provides opportunities for pathogens to move to new areas and cause outbreaks of disease. Commercial air travel has been particularly effective at transporting pathogens such as SARS coronavirus and influenza viruses.3 It is also contributing to the spread of disease vectors and the diseases they transmit.4 As we travel, we take animals with us either through trade in livestock or in the movement of companion animals.
In Europe, the free movement of people within the continent has been enabled by the formation of the European Union (EU) and liberalization of border controls. This was formalized by the Schengen Agreement signed by member states in 1985 and implemented in 1995. This created the Schengen Area that reduced border controls between member states and allowed free movement of people between countries. Some countries, including the UK and Ireland, have in the past, agreed opt-outs that retain limitations of movement into those countries.
When humans travel, they often take their companion animals, particularly dogs, and these in turn can relocate the pathogens and vectors they harbor. Canine parvovirus emerged in 1978 as a new disease in dogs causing hemorrhagic enteritis. Retrospective serology suggested that the disease appeared in Europe in 1976 and spread throughout the world by 1978.5 The mechanism that enabled global dissemination of the virus has been attributed to contaminated footwear. There are numerous canine-associated diseases but relatively few are significant zoonoses. However, of these, a number are fatal to humans and control is essential to protect public health. Globally, the most significant is the rabies virus. Infection leads to fatal encephalitis, for which there is no treatment.6,7 Pre-exposure vaccination protects against the disease in mammals, and due to the extended incubation period between contact with a rabid animal and development of disease, often measured in months, timely post-exposure vaccination is also effective in humans.8 The dog is the most important reservoir for the virus, and contact with dogs is responsible for virtually all human cases of the disease. Where efforts have been concentrated on controlling dog rabies, the reduction in human cases of disease has been dramatic.9 Dog rabies has been virtually eliminated from Europe, although there are examples of reintroduction10,11 and cross-border movement of rabid animals.12
Alveolar echinococcosis is caused by the tapeworm Echinococcus multilocularis. It is a fatal condition that is relatively rare in Europe although there are clear areas of endemicity, resulting in human infections in an area of Europe ranging from France in the west to Austria in the east.13 The disease manifests as a tumor-like growth of cysts containing the larval stage of the parasite in organs such as the liver. Detection of cysts often occurs many years after initial infection, and without intervention such as surgery to remove the cyst(s), the disease is fatal. Dogs act as the definitive host for the adult form of the parasite and movement of infected dogs can lead to the spread of tapeworm eggs and introduction of the disease into new areas. As the adult worm is very small (less than 5 mm) and does not cause clinical signs in the definitive host, spreading of eggs and human infection can remain undetected until clinical symptoms develop.
Leishmaniasis is caused by protozoa belonging to the genus Leishmania. Two forms are recognized, ie, cutaneous leishmaniasis causing skin lesions and the more serious visceral disease involving multiple organs. Natural transmission is through the bite of phlebotomine sandflies belonging to the genera Phlebotomus in the Old World.14 Distribution of leishmaniasis is limited by the presence of the vector. In Europe, the vector is indigenous to those countries around the Mediterranean Sea. The major mammalian reservoir is the domestic dog. Estimates of autochthonous human cases in Europe are approximately 700 a year.15 Numbers of cases in Turkey are higher, with over 3,000 annually. Non-endemic countries in Europe do encounter cases of canine leishmaniasis as a result of pet movements.16
In the absence of border restrictions, it is difficult to establish the true extent of regional movement of animals either for trade or through holiday travel. Monitoring of dogs and cats entering the UK through its pet travel scheme indicated that almost 100,000 animals entered the country annually (Table 1). A similar situation is likely to exist for most EU member states. In addition to this, there is the problem of illegal movement of animals either by organized groups for commercial purposes or inadvertent contraventions of legal requirements by holidaymakers through importation of their animals. Quantification of this is by its very nature difficult, but detection of noncompliance with legislation or deliberately smuggled animals is a regular occurrence,17 and the incidence of disease often highlights this activity.
The following sections review important zoonotic diseases of pet origin and the policies currently in place to control zoonotic diseases of companion animals and their limitations, concluding with recommendations on what more could be done.
With all the probabilities calculated already, we can calculate the total probability of entry of the disease j from the country i to the European Union, taking into account all the routes of entry already evaluated(PIij).
To do this, we calculate the probability of occurrence of the opposite case, the probability of no introduction of the j disease by any of the routes of entry, using the following formula:
With the same type of formula, it is estimated the likelihood of entry of a disease j in the European Union.
A high, moderate and low risk of introduction of infectious diseases from different countries has been estimated based on a 75 and 90-percentile (P75 and P90) over the final results of probability of each route of entry. Therefore, the results that are over the 75-percentile and 90-percentile are classified as moderate and high risk of entry.
The probability of introduction of the j disease into the European Union through live animal's trade from the country i
(PIAji) is calculated as the proportion of animals that are annually transported to Europe coming from the country i multiplied by the probability of the country i being affected by the disease j
Legionnaires’ disease is a relatively rare cause of community-acquired pneumonia caused by Legionella species; however, 20%-25% of patients who are hospitalized with Legionnaires’ disease require invasive mechanical ventilation and average mortality rates for sporadic disease range from 10% to 15%. Legionnaires’ disease is caused by inhalation of Legionella species, which are intracellular, Gram-negative bacilli ubiquitously found in the environment. Host risk factors for Legionnaires’ disease include male gender, age older than 50 years, cigarette smoking, diabetes, end-stage renal failure, organ transplantation and immunosuppression, such as glucocorticoids or anti-rejection drugs following organ transplantation. Travel is an important and underappreciated risk factor associated with legionellosis in a community setting. Treatment options for Legionnaires' disease include macrolides, fluoroquinolones, or tetracycline; however, preferred therapies for immunocompromised patients with Legionnaires’ disease include levofloxacin and azithromycin. We describe an immunocompromised and severely ill patient with Legionnaires' disease and who also has allergies to both fluoroquinolones and macrolides; he was successfully treated using tigecycline, a third generation glycylcycline, indicating that tigecycline may serve as a safe and effective alternative therapeutic option for treatment of Legionnaires’ disease in select cases.
The financing, provision, and quality of healthcare systems; the availability of vaccines, antivirals, and antibiotics medicines, and appropriate compliance to treatment protocols are all important determinants of infectious disease transmission. Although the correlation between healthcare system financing and efficacy is not perfect, recent budget cuts to healthcare are an important consideration when anticipating infectious disease risk. In part related to the global economic crisis, it has been reported that many high-income governments have introduced policies to lower spending through cutting the prices of medical products and, for example, through budget restrictions and wage cuts in hospitals (54). There are many indirect and direct pathways through which budget cuts could affect disease transmission; to provide just one example, it has been estimated that 20–30% of healthcare-associated infections are preventable with intensive hygiene and control programmes2 – should investments in this area diminish, then healthcare-acquired infections could become an even more problematic issue. There are currently roughly 4.1 million healthcare-associated infections each year in the EU alone.3
A broader issue related to healthcare provision is population mobility for both healthcare professionals and patients who might increasingly seek work or healthcare in other countries – the provision of cross-border healthcare and the mitigation of cross-border health threats will necessitate collaboration across borders (55, 56) and solutions for the brain-drain of medical personnel from resource-poor countries (57). Also related to the healthcare provision and practice is the over-prescription or overuse of antibiotics. In combination with a lag in pharmaceutical innovation, rapid transmission, and poor infection control measures, this has driven resistance of organisms such as methicillin-resistant Staphylococcus aureus, or extended-spectrum beta-lactamases, and carbapenemase-producing gram-negatives such as Klebsiella pneumoniae carbapenemase (KPC) (58). Antimicrobial resistance is currently one of the major health risks facing society (59).
Food production systems remain a persistent source for human infectious diseases. Attempts are underway to estimate the global burden of food-borne disease (60), which is likely substantial. Many factors in food production affect human health. A vast range of familiar human pathogens can be acquired through the consumption of animal products and other disease drivers, such as global travel, further provoke this (61). In addition to farmed animals, the hunting and slaughtering of wild animals has led to the emergence of more exotic pathogens: SARS originated in wildlife markets and restaurants in southern China (62) and HIV and Ebola have both been linked to the hunting or slaughtering of primates and other wild animals (33, 63, 64). The density and health of livestock, meanwhile, have been linked to disease in humans (65, 66). Although inconclusive, there is some evidence to suggest that livestock production may lead to increased antibiotic resistance in human pathogens. There are certainly many pathways by which drug resistant pathogens could transmit from livestock to humans, including environmental contamination by excreted veterinary antibiotics (33, 67, 68).
The burden of viral disease is a global concern. Due to their unique properties, viruses have a particular relevance when analyzing the interaction among humans, animals, and the environment. Viruses are small compared to other pathogens, facilitating transport in the environment. Moreover, their resistance to disinfection and ability to survive for prolonged periods in water and solids make their transmission from the environment to suitable hosts likely. This is compounded by their low infectious dose, inability to be treated by antibiotics, and their proclivity for adaptive mutation. Additionally, viruses do not replicate outside their host cells, therefore detection in environmental samples can be directly related to the human or animal population that excreted these viruses.
Fig. 1 summarizes viral exposure pathways and the relevance of the One-Health approach. One-Health is a relatively new approach to the solving of global health challenges. Formally put forth by the One Health Commission in 2007, the concept is defined as “the collaborative effort of multiple disciplines – working locally, nationally, and globally – to attain optimal health for people, animals and our environment.” Consequently, a key component to the One-Health approach is the notion that human health, animal health, and environmental health are all innately interrelated. The quality and well-being of one group can directly and indirectly impact the quality of the other two groups. By taking all three aspects of health into account, solutions can be generated that not only address the health problems of a specific group but mitigate the source of those problems as well.
Much of the current work using the One-Health approach is focused upon the exposure pathway between humans and animals, while the water-related exposure pathway has not been thoroughly investigated from a One-Health perspective. The purpose of this paper is to explore water-related exposure pathways as they relate to human, animal, and environmental health, to explore the possibility of surveillance of water and wastewater systems as means of identification of endemic disease and potential outbreaks at a population level, and to develop a framework with which to apply the One-Health methodology for early detection and management of water-related viral outbreaks.
China is one of the largest and most populous countries in the world with nearly 20% of the world’s population. Over the last few decades, China has witnessed an unprecedented economic boom with its Gross Domestic Product (GDP) per capita growing from $193 in 1980 to $6092 in 2012. However, such great economic growth may have been achieved at the cost of the environment and public health programs as compared to other aspects of development including economy, education and technology. One issue is infectious diseases, which continue to impair population health in this populous country. Although infectious diseases only accounted for about 0.89%–1.06% of all deaths in China in 2011, estimates suggest that there are about 7 million cases of notified infectious diseases, such as viral hepatitis, pulmonary tuberculosis, dengue and malaria, occurring amongst the 1.3 billion population, leading to approximately 17,000 deaths each year. Tremendous efforts were made to reduce infectious diseases after 1949, but some infectious diseases have rebounded and even increased in some areas since the 1980s. Malaria, for example, has been a serious public health problem in China for many years and great efforts have been made to address the problem. Despite a remarkable decline in its incidence from about 2800 per 100,000 in 1970 to 10 per 100,000 in 1990, malaria has re-emerged in some areas since 2001, e.g., Henan, Hubei and Anhui provinces.
Prior to the outbreak of severe acute respiratory syndrome (SARS) in 2003, infectious diseases control and prevention had not been given enough attention. The SARS outbreak started in Guangdong Province in November 2012 and challenged the then Chinese infectious disease control and prevention system. After the SARS outbreak, the Chinese government invested heavily in disease control and prevention. As a result, there have been great improvements in public health infrastructure and public health workforce with new laboratories built, a surveillance system upgrade and increases in numbers of public health professionals.
The recent outbreak of Ebola virus disease in West Africa in 2014 has drawn worldwide attention, and accordingly, public health professionals in China have estimated the risk of imported cases and proposed pro-active disease control and prevention actions to minimize the risk of the transmission of the disease to China. This is partly because China has a close trade relationship with Africa involving a frequent flow of travelers. Public health authorities have been made aware of the need to continuously strengthen capacity to manage current infectious disease control systems to cope with possible emerging and re-emerging infectious diseases challenges.
China is an economically, geographically and climatologically diverse country with a huge population which may be the epicenter of new diseases and strains. However, it remains uncertain how well current disease prevention and management system can sufficiently respond to future challenges of emerging and re-emerging infectious diseases, which may be exacerbated by the rapid process of urbanization, high numbers of migrant workers, and the impacts from a changing climate. In this light, this paper aims to examine China’s capacity to manage infectious diseases in the future, especially in terms of disease surveillance and the likely impacts of two important issues affecting infectious disease trends—increasing urbanization and climate change.
Genomic information offers the opportunity for more personalized treatment and prevention in clinical practice and public health settings. Until recently, such efforts have focused largely on common, complex diseases (for example, cancers, heart disease, neurodegenerative diseases) and less common inherited diseases; examples of such efforts include risk screening, diagnostic sequencing and pharmacogenomics. Now there is growing interest in the application of genomics to the management of infectious diseases and epidemics, which are among the top global public health burdens. Rapid and large-scale sequencing of pathogen genomes, which provides stronger and more accurate evidence than was previously possible for source and contact tracing, is being applied widely for disease outbreak management - most recently and publicly in the case of the Ebola outbreak in West Africa. Additional uses include precise diagnosis of microbial infection, describing transmission patterns, understanding the genomics of emerging drug resistance and identifying targets for new therapeutics and vaccines. There is growing evidence that, as well as pathogen genetic factors, host genetic factors and the interaction between host, vector and pathogen influence variability in infection rates, immune responses, susceptibility to infection, disease progression and severity, and response to preventive or therapeutic interventions. As such, genomic research is improving our understanding of infectious disease pathogenesis and immune response and may help guide future vaccine development and treatment strategies [11–18].
While the past few years have seen substantial federal and private research funding for infectious disease genomics research, there has been little discussion of the possible ELSIs - for individuals, groups or larger society - of using genomic information in the management of infectious disease. This gap may be explained in part by the current paucity of scientific advances in genomics that have practical applications to infectious disease management. Although it may be premature, we must nevertheless anticipate the possibility of ELSI-associated challenges in the future. This Opinion aims to anticipate what some of these issues might be and under what conditions they could arise. We argue that these considerations - even as the science is still developing - should become part of the agenda of researchers, clinicians, policymakers and public health officials so that the benefits of genomic applications to infectious disease are maximized while potential harms to individuals and populations are minimized.
We begin by acknowledging the existing scholarship on ELSI issues in the genomics of non-communicable diseases, and the ethical and legal issues surrounding infectious disease management. Then we briefly describe some of the epidemiologic characteristics and recent genomic advances associated with four particular infectious diseases - Ebola, pandemic influenza, hepatitis B and tuberculosis - that have large-scale public health consequences but differ in terms of ease of transmission, chronicity, severity, preventability and treatability, factors which affect a range of ELSI issues. In this section we also consider the situations under which the use of genomic information might or might not be appropriate in the management of infectious diseases. Finally, we describe some of the major ethical, legal and social issues that arise in the context of genomics and how they may play out in the management of these four specific infectious diseases.
Understanding infectious disease patterns (i.e. space-time variations and/or changes) has always been a challenging affair. Disease diffusion can vary significantly from place to place and from time to time for a number of reasons, including heterogeneity of the hosts and pathogens, physical and social environments, and interactions across space and time. Moreover, uncertainties linked to population movement and records of infected individuals can increase the difficulty of understanding the spatiotemporal spread of an infectious disease. A number of key studies have shown that infectious disease spread depends significantly upon the spatial features of a population– whereas major benefits of spatial disease modeling include the assessment of disease intervention and control strategies (e.g., border control and quarantine). Accordingly, several models have been proposed to quantify the spatial disease features at both population and individual scales,–. Among the best-known models are the gravity, the spatial micro-simulation, and the network models,,. Most of these models focus primarily on interactions between the susceptible and infected populations across geographical locations, without considering the continuous local population dynamics of disease evolution. This is especially the case for the gravity model, where the geographical distribution and interaction patterns of populations are discretized into separated locations. Stochastic “Susceptible-Infected-Recovered” models (SIR,–) have been widely implemented to represent disease evolution of populations over time. Spatial metapopulation approaches extend SIR models to explicitly account for the local or global population movements between different geographical locations, in terms of patches or networks with deterministic or stochastic characteristics–.
The present study proposes a realistic space-time extension of a purely temporal SIR model, i.e. metapopulation model, in the context of Bayesian maximum entropy (BME) theory,. The space-time BME-SIR model has certain attractive features: (1) it represents the population dynamics of infectious diseases within and across localities; (2) it takes into consideration the composite space-time variation of disease features; (3) it accounts for observation uncertainties (e.g., in the records of infected individuals); (4) in addition to the susceptible-infected-recovered disease dynamics, it integrates different sources of knowledge (e.g., hard and soft disease data together with epidemic models and physical laws); and (5) it updates the space-time model parameters in real time.
The drivers of pathogen emergence change the overall pattern of the pathogen–host–environment interactions leading to either (i) a pathogen showing up in a novel host; (ii) a mutant pathogen with novel traits causing more frequent or more severe disease while remaining in the same host; or (iii) an invasion process involving a novel geographic area. As shown in Figure 1, disease emergence starts with an existing disease complex or pathogen–host–environment complex. While the three emergence categories are broadly speaking distinct, there are also grey areas, between existing and emerging disease events and at the interfaces of the three disease emergence categories. Taken together, these different sets of circumstances represent the full range of disease emergence. A brief introduction to the basics of this framework and the three distinct emergence categories is given in the present section. Details and examples further describing the three disease emergence categories are provided in subsequent sections.
As a first category, pathogens may enter in closer contact with novel host types, be it humans, domestic animals or wildlife. Increased pathogen spill-over may result from this mixing of species and eventually, given progressive exposure of the new host to the ‘new' pathogen, generate a ‘species jump' with sustained transmission in the novel host species. Examples of drivers comprise bush or wild meat hunting and consumption, deforestation and logging, other forms of human encroachment of forests and game reserves, and increased interspecies contacts at the wildlife/agriculture interface, between humans and their pet animals, and within food animal production systems.
Second, pathogens may develop novel traits while circulating in a given host. Key to these dynamics is that the novel trait allows the pathogen to unlock host resources that would otherwise remain unavailable. Mass rearing of animals and use of antimicrobials and vaccines may yield ‘virulence jumpers' with increased pathological or clinical presentation, pathogens acquiring antimicrobial resistance or escaping vaccine-acquired immunity.
Third, diseases may become established in new areas and landscapes, as a result of passive and/or active redistribution of pathogens, vectors and hosts. Two distinct types of geographic invasion may be further considered: pathogens increasing the extent of their geographic range (‘geographic expansion') and pathogens that become dispersed over distances with saltation, across physical barriers in the landscape (‘geographic jumps'). A key factor in the first scenario, geographic expansion, is the suitability of the landscape for the disease complex to become introduced and established. Climate and weather and also land use changes may play a role as drivers. Geographic jumps are facilitated by international travel, trade and traffic, together enhancing the level of connectivity between distinct landscapes, and their respective host, vector and pathogen communities.
In addition, there are intermediates between the three disease emergence categories (indicated by ‘i' in Figure 1). Pathogens emerging in new host species will spread geographically when the species jump is successful, and host specificity adjustment may be an integral component of pathogen invasion of a new area. The expression of new traits of a pathogen in its original host species may lead to higher incidences and more spill-over events to new host species. And new traits may lead to geographic spread of a pathogen in a new area, and geographic spread of a pathogen may lead to adjustment of the infection course.
Distinctly different from the above three disease emergence categories is the disease behavior that that normally plays at the population level. All diseases feature a certain degree of plasticity in terms of their behavior in time and space, responding to host demographic cycles, host immune status, spatial population structure, seasonality or health protection measures (Figure 1, numbers 1, 2 and 3).
Chest radiograph results were available for six of the animals. Three of them exhibited radiographic evidence of pulmonary disease. The two animals infected by the IV route (group III) had no significant change in chest radiographs, while three of four animals infected by a mucosal route (groups I and II) developed radiographic disease (
Figure 1). Two animals with radiographic disease were infected with the icSARS-CoV (both group I) and one animal (group II) was infected with wild-type virus.
Of the three animals with radiographic evidence of disease, two (292Q and 91–379) were infected by the IB/IN route (group I) and one (91–512) was infected by the CJ/IN route (group II). All developed significant airspace disease on PID 6. The group II animal had normal radiographs until PID 6, when it developed a perihilar left upper lobe infiltrate. By PID 8, there was perihilar disease in the right upper lobe as well. These findings were relatively subtle and began to resolve on PID 12. They were still evident, albeit continuing to resolve, by PID 18. The two group I animals had subtle changes on PID 2 (right mid-lower lobe for 292Q, right lower lobe for 91–379). Radiographic appearance was unchanged on PID 4 in 292Q, but 91–379 did have a slight increase in the right lower lobe opacity. On PID 6, both animals had dramatic radiographic changes, with 292Q developing increasing lower lobe disease and new right-upper lobe airspace disease and 91–379 showing a significant increase in the right lower lobe consolidation. Both 292Q and 91–379 had increasing disease on PID 8 and demonstrated slight improvement by PID 10. Changes completely resolved by PID 14 in 91–379, but mild residual and resolving changes were still evident in 292Q on PID 18.
We infected eight cynomolgus macaques with SARS-CoV in three groups: Group I (
n = 4) was infected in the nares and bronchus, group II (
n = 2) in the nares and conjunctiva and group III (
n = 2) intravenously. Basic clinical findings are summarized in
Table 1. All animals in groups I and II displayed mild to moderate symptoms of illness beginning between postinfection days (PID) 2–4. Observed symptoms included decreased activity, decreased feeding, snuffling, and mildly labored breathing. Animal activity and appearance returned to baseline by PID 12–14 in all cases. Animals infected with wild-type SARS-CoV or with icSARS-CoV both displayed clinical signs of illness. We observed no overt clinical illness in the group III animals, which were infected intravenously.
None of the animals developed a measurable fever. Continuous telemetry monitoring in four animals revealed no significant changes in temperature, heart rate, blood pressure, or left ventricular pressures (unpublished data).
Prions, which were first proposed by Dr Prusiner at the University of California, San Francisco, became a hot topic since they do not have genes, unlike bacteria or viruses, and are able to replicate, unlike toxic elements. Eventually, he scientifically answered a number of questions and suggested that these gene-less proteins can replicate in the body, induce the disease, and be subsequently transmitted to other animals; he received a Nobel Prize for his work in 1997. This type of prion-only hypothesis is recognized as a new pathogenic mechanism of neurodegenerative disorders.
The word “prion”, distinguished from virus or virion, was coined by Prusiner to refer to the scrapie pathogen in sheep; prion means a proteinaceous infectious particle. PrPSc, a scrapie form of a prion known to be pathogenic and misfolded, does not always induce clinical symptoms; therefore, the PrPSc that induces clinical symptoms is marked as a disease prion: PrPd. However, prions already exist in animals and humans in the cellular form of the protein (PrPC), which does not have any pathogenic properties. The primary amino acid sequences and the state of modification in both isoforms of PrPSc and PrPC are identical; however, they have different three-dimensional structures, which give them distinct biochemical and biophysical properties. Also, alterations in amino acid sequences change the conformation of these proteins, resulting in a thermodynamically stable protein variant (PrPSc) that can cause diseases in both animals and humans.
When PrPC comes in contact with PrPSc, PrPC changes into a thermodynamically stable PrPSc via protein folding; then, PrPSc converts PrPC into another PrPSc. After this process is repeated over time, PrPSc accumulates in the body and results in induction of TSE. Although it is not certain whether TSEs are caused by PrPSc alone or by a complex reaction with PrPSc and other factors, such as other proteins, nucleic acids, or pathogens, it is certain that the main causative agent is PrPSc. However, to explain the replication of PrPSc within the body, two thermodynamically stable PrPSc molecules must be separated and combined with other PrPCs. The animal’s genetic type and other additional factors should be considered in the process. Therefore, scientists assume that the hypothetical macromolecule—designated protein X—may play a role in the conversion from PrPC to PrPSc and continue to search for candidates. At present, dozens of proteins in the cytosol, plasma membrane, extracellular matrix, and lipid rafts are known to interact with PrPC and/or PrPSc; however, strong evidence for the identity of protein X has not been revealed yet. Identifying the existence and role of protein X, prion diseases can be prevented and/or treated. Normal PrPC, which is encoded on the gene locus PRNP in the genome of hosts, is a glyco-protein found in neuron cell membranes in animals and humans. PrPC has a ∼40% α-helical and ∼3% β-sheet conformation, whereas PrPSc has a ∼30% α-helical and ∼40% β-sheet conformation. The conformational transition from the helices and hydrophobic regions of PrPC is a major cause of the increase of β-sheet composition in PrPSc (Figure 1). Since the conformational alteration from PrPC to PrPSc is not immunogenic, the immune system of the organism can hardly distinguish the normal protein structure from the infectious prion structure, except with respect to its stability. Unlike bacteria or viruses, pathogenic PrPSc cannot be removed by regular alcohol or formalin sterilization processes, and cannot be decomposed by proteolytic enzymes. Moreover, it is resistant to heat, ultraviolet rays, and chemicals. Under three times the atmospheric pressure the materials for prion should be sterilized for more than 18 minutes at 134–138° C; surfaces should be sterilized for over an hour with 2% sodium hypochlorite and 2N sodium hydroxide at 20°C, and equipment should be sterilized for more than 12 hours with the same solution. In laboratories, materials should be disinfected for more than 4.5 hours at 132°C or for 1 hour at 134–138°Cby steam sterilization under pressure. Because it responds well to alkaline conditions, highly concentrated sodium hydroxide or phenol is used to decontaminate PrPSc.