Salicylic acid

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Salicylic_acid 

 

Salicylic acid

Names
Preferred IUPAC name 2-Hydroxybenzoic acid
Identifiers
CAS Number	69-72-7
3D model (JSmol)	Interactive image
ChEBI	CHEBI:16914
ChEMBL	ChEMBL424
ChemSpider	331
DrugBank	DB00936
ECHA InfoCard	100.000.648
EC Number	200-712-3
IUPHAR/BPS	4306
KEGG	D00097
PubChem CID	338
RTECS number	VO0525000
UNII	O414PZ4LPZ
CompTox Dashboard (EPA)	DTXSID7026368

InChI

SMILES
Properties
Chemical formula	C7H6O3
Molar mass	138.122 g/mol
Appearance	Colorless to white crystals
Odor	Odorless
Density	1.443 g/cm3 (20 °C)
Melting point	158.6 °C (317.5 °F; 431.8 K)
Boiling point	200 °C (392 °F; 473 K) decomposes 211 °C (412 °F; 484 K) at 20 mmHg
Sublimation conditions	Sublimes at 76 °C
Solubility in water	1.24 g/L (0 °C) 2.48 g/L (25 °C) 4.14 g/L (40 °C) 17.41 g/L (75 °C) 77.79 g/L (100 °C)
Solubility	Soluble in ether, CCl4, benzene, propanol, acetone, ethanol, oil of turpentine, toluene
Solubility in benzene	0.46 g/100 g (11.7 °C) 0.775 g/100 g (25 °C) 0.991 g/100 g (30.5 °C) 2.38 g/100 g (49.4 °C) 4.4 g/100 g (64.2 °C)
Solubility in chloroform	2.22 g/100 mL (25 °C) 2.31 g/100 mL (30.5 °C)
Solubility in methanol	40.67 g/100 g (−3 °C) 62.48 g/100 g (21 °C)
Solubility in olive oil	2.43 g/100 g (23 °C)
Solubility in acetone	39.6 g/100 g (23 °C)
log P	2.26
Vapor pressure	10.93 mPa
Acidity (pKa)	2.97 (25 °C) 13.82 (20 °C)
UV-vis (λmax)	210 nm, 234 nm, 303 nm (4 mg/dL in ethanol)
Magnetic susceptibility (χ)	−72.23·10−6 cm3/mol
Refractive index (nD)	1.565 (20 °C)
Dipole moment	2.65 D
Thermochemistry
Std enthalpy of formation (ΔfH⦵298)	−589.9 kJ/mol
Std enthalpy of combustion (ΔcH⦵298)	3.025 MJ/mol
Pharmacology
ATC code	A01AD05 (WHO) B01AC06 (WHO) D01AE12 (WHO) N02BA01 (WHO) S01BC08 (WHO)
Hazards
Safety data sheet	MSDS
GHS pictograms
GHS Signal word	Danger
GHS hazard statements	H302, H318
GHS precautionary statements	P280, P305+351+338
Eye hazard	Severe irritation
Skin hazard	Mild irritation
NFPA 704 (fire diamond)	2 1 0
Flash point	157 °C (315 °F; 430 K) closed cup
Autoignition temperature	540 °C (1,004 °F; 813 K)
Lethal dose or concentration (LD, LC):
LD50 (median dose)	480 mg/kg (mice, oral)
Related compounds
Related compounds	Methyl salicylate, Benzoic acid, Phenol, Aspirin, 4-Hydroxybenzoic acid, Magnesium salicylate, Choline salicylate, Bismuth subsalicylate, Sulfosalicylic acid
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Infobox references

Salicylic acid is an organic compound with the formula HOC₆H₄CO₂H. A colorless, bitter-tasting solid, it is a precursor to and a metabolite of aspirin (acetylsalicylic acid). It is a plant hormone. The name is from Latin salix for willow tree. It is an ingredient in some anti-acne products. Salts and esters of salicylic acid are known as salicylates.

Uses

Medicine

Main article: Medical uses of salicylic acid

 

Cotton pads soaked in salicylic acid can be used to chemically exfoliate skin.

Salicylic acid as a medication is used commonly to remove the outer layer of the skin. As such, it is used to treat warts, psoriasis, acne vulgaris, ringworm, dandruff, and ichthyosis.

Similar to other hydroxy acids, salicylic acid is an ingredient in many skincare products for the treatment of seborrhoeic dermatitis, acne, psoriasis, calluses, corns, keratosis pilaris, acanthosis nigricans, ichthyosis, and warts.

Uses in manufacturing

Salicylic acid is used in the production of other pharmaceuticals, including 4-aminosalicylic acid, sandulpiride, and landetimide (via salethamide).

Salicylic acid has long been a key starting material for making acetylsalicylic acid (aspirin). Aspirin (acetylsalicylic acid or ASA) is prepared by the esterification of the phenolic hydroxyl group of salicylic acid with the acetyl group from acetic anhydride or acetyl chloride.

Bismuth subsalicylate, a salt of bismuth and salicylic acid, is the active ingredient in stomach-relief aids such as Pepto-Bismol, is the main ingredient of Kaopectate, and "displays anti-inflammatory action (due to salicylic acid) and also acts as an antacid and mild antibiotic".

Other derivatives include methyl salicylate used as a liniment to soothe joint and muscle pain and choline salicylate used topically to relieve the pain of mouth ulcers.

Other uses

Salicylic acid is used as a food preservative, a bactericide, and an antiseptic.

Sodium salicylate is a useful phosphor in the vacuum ultraviolet spectral range, with nearly flat quantum efficiency for wavelengths between 10 and 100 nm. It fluoresces in the blue at 420 nm. It is easily prepared on a clean surface by spraying a saturated solution of the salt in methanol followed by evaporation.

Mechanism of action

Salicylic acid modulates COX1 enzymatic activity to decrease the formation of pro-inflammatory prostaglandins. Salicylate may competitively inhibit prostaglandin formation. Salicylate's antirheumatic (nonsteroidal anti-inflammatory) actions are a result of its analgesic and anti-inflammatory mechanisms.

Salicylic acid works by causing the cells of the epidermis to slough off more readily, preventing pores from clogging up, and allowing room for new cell growth. Salicylic acid inhibits the oxidation of uridine-5-diphosphoglucose (UDPG) competitively with nicotinamide adenosine dinucleotide and noncompetitively with UDPG. It also competitively inhibits the transferring of glucuronyl group of uridine-5-phosphoglucuronic acid to the phenolic acceptor.

The wound-healing retardation action of salicylates is probably due mainly to its inhibitory action on mucopolysaccharide synthesis.

Safety

If high concentrations of salicylic ointment are applied to a large percentage of body surface, high levels of salicylic acid can enter the blood, requiring hemodialysis to avoid further complications.

Production and chemical reactions

Biosynthesis

Salicylic acid is biosynthesized from the amino acid phenylalanine. In Arabidopsis thaliana, it can be synthesized via a phenylalanine-independent pathway.

Industrial synthesis

Sodium salicylate is commercially prepared by treating sodium phenolate (the sodium salt of phenol) with carbon dioxide at high pressure (100 atm) and high temperature (115 °C) – a method known as the Kolbe-Schmitt reaction. Acidification of the product with sulfuric acid gives salicylic acid:

It can also be prepared by the hydrolysis of aspirin (acetylsalicylic acid) or methyl salicylate (oil of wintergreen) with a strong acid or base.

Reactions

Upon heating, salicylic acid converts to phenyl salicylate:

2 HOC₆H₄CO₂H → C₆H₅O₂C₆H₄OH + CO₂ + H₂O

Further heating gives xanthone.

Salicylic acid as its conjugate base is a chelating agent, with an affinity for iron(III).

Salicylic acid slowly degrades to phenol and carbon dioxide at 200–230 °C:

C₆H₄OH(CO₂H) → C₆H₅OH + CO₂

History

Main article: History of aspirin

White willow (Salix alba) is a natural source of salicylic acid.

Hippocrates, Galen, Pliny the Elder, and others knew that willow bark could ease pain and reduce fevers. It was used in Europe and China to treat these conditions. This remedy is mentioned in texts from Ancient Egypt, Sumer, and Assyria. The Cherokee and other Native Americans use an infusion of the bark for fever and other medicinal purposes.

In 2014, archaeologists identified traces of salicylic acid on seventh-century pottery fragments found in east-central Colorado. The Reverend Edward Stone, a vicar from Chipping Norton, Oxfordshire, England, noted in 1763 that the bark of the willow was effective in reducing a fever.

The active extract of the bark, called salicin, after the Latin name for the white willow (Salix alba), was isolated and named by German chemist Johann Andreas Buchner in 1828. A larger amount of the substance was isolated in 1829 by Henri Leroux, a French pharmacist. Raffaele Piria, an Italian chemist, was able to convert the substance into a sugar and a second component, which on oxidation becomes salicylic acid.

Salicylic acid was also isolated from the herb meadowsweet (Filipendula ulmaria, formerly classified as Spiraea ulmaria) by German researchers in 1839. While their extract was somewhat effective, it also caused digestive problems such as gastric irritation, bleeding, diarrhea, and even death when consumed in high doses.

Dietary sources

Salicylic acid occurs in plants as free salicylic acid and its carboxylated esters and phenolic glycosides. Several studies suggest that humans metabolize salicylic acid in measurable quantities from these plants. High-salicylate beverages and foods include beer, coffee, tea, numerous fruits and vegetables, sweet potato, nuts, and olive oil. Meat, poultry, fish, eggs, dairy products, sugar, and breads and cereals have low salicylate content.

Some people with sensitivity to dietary salicylates may have symptoms of allergic reaction, such as bronchial asthma, rhinitis, gastrointestinal disorders, or diarrhea, so may need to adopt a low-salicylate diet.

Plant hormone

Salicylic acid is a phenolic phytohormone, and is found in plants with roles in plant growth and development, photosynthesis, transpiration, and ion uptake and transport. Salicylic acid is involved in endogenous signaling, mediating plant defense against pathogens. It plays a role in the resistance to pathogens (i.e. systemic acquired resistance) by inducing the production of pathogenesis-related proteins and other defensive metabolites. Exogenously, salicylic acid can aid plant development via enhanced seed germination, bud flowering, and fruit ripening, though too high of a concentration of salicylic acid can negatively regulate these developmental processes.

The volatile methyl ester of salicylic acid, methyl salicylate, can also diffuse through the air, facilitating plant-plant communication. Methyl salicylate is taken up by the stomata of the nearby plant, where it can induce an immune response after being converted back to salicylic acid.

Signal transduction

A number of proteins have been identified that interact with SA in plants, especially salicylic acid binding proteins (SABPs) and the NPR genes (Nonexpressor of pathogenesis related genes), which are putative receptors.

History

In 1979, salicylates were found to be involved in induced defenses of tobacco against tobacco mosaic virus. In 1987, salicylic acid was identified as the long-sought signal that causes thermogenic plants such as the voodoo lily, Sauromatum guttatum, to heat up.

See also

• Salsalate
• Trolamine salicylate

Biosecurity

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Biosecurity

Biosecurity refers to measures aimed at preventing the introduction and/or spread of harmful organisms (e.g. viruses, bacteria, etc.) to animals and plants in order to minimize the risk of transmission of infectious disease. In agriculture, these measures are aimed at protecting food crops and livestock from pests, invasive species, and other organisms not conducive to the welfare of the human population. The term includes biological threats to people, including those from pandemic diseases and bioterrorism. The definition has sometimes been broadened to embrace other concepts, and it is used for different purposes in different contexts.

The COVID-19 pandemic is a recent example of a threat for which biosecurity measures have been needed in all countries of the world.

Background and terminology

The term "biosecurity" has been defined differently by various disciplines. The term was first used by the agricultural and environmental communities to describe preventative measures against threats from naturally occurring diseases and pests, later expanded to introduced species. Australia and New Zealand, among other countries, had incorporated this definition within their legislation by 2010. New Zealand was the earliest adopter of a comprehensive approach with its Biosecurity Act 1993. In 2001, the US National Association of State Departments of Agriculture (NASDA) defined biosecurity as "the sum of risk management practices in defense against biological threats", and its main goal as "protect[ing] against the risk posed by disease and organisms".

In 2010, the World Health Organization (WHO) provided an information note describing biosecurity as a strategic and integrated approach to analysing and managing relevant risks to human, animal and plant life and health and associated risks for the environment. In another document, it describes the aim of biosecurity being "to enhance the ability to protect human health, agricultural production systems, and the people and industries that depend on them", with the overarching goal being "to prevent, control and/or manage risks to life and health as appropriate to the particular biosecurity sector".

Measures taken to counter biosecurity risks typically include compulsory terms of quarantine, and are put in place to minimise the risk of invasive pests or diseases arriving at a specific location that could damage crops and livestock as well as the wider environment.

In general, the term is today taken to include managing biological threats to people, industries or environment. These may be from foreign or endemic organisms, but they can also extend to pandemic diseases and the threat of bioterrorism, both of which pose threats to public health.

Laboratory biosafety and intentional harm

Main articles: Bioterrorism, Laboratory biosafety, and Biological weapons

The definition has sometimes been broadened to embrace other concepts, and it is used for different purposes in different contexts. A 2016 draft handbook on biosecurity education produced by the Bradford Disarmament Research Centre at Bradford University in the UK, where the focus is on the dangers of "dual-use" research, defines the term as meaning "successful minimising of the risks that the biological sciences will be deliberately or accidentally misused in a way which causes harm for humans, animals, plants or the environment, including through awareness and understanding of the risks".

From the late 1990s, in response to the threat of biological terrorism, the term started to include the prevention of the theft of biological materials from research laboratories, called "laboratory biosecurity" by WHO. The term laboratory biosafety refers to the measures taken "to reduce the risk of accidental release of or exposure to infectious disease agents", whereas laboratory biosecurity is usually taken to mean "a set of systems and practices employed in legitimate bioscience facilities to reduce the risk that dangerous that dangerous biological agents will be stolen and used maliciously". Joseph Kanabrocki (2017) source elaborates: "Biosafety focuses on protection of the researcher, their contacts and the environment via accidental release of a pathogen from containment, whether by direct release into the environment or by a laboratory-acquired infection. Conversely, biosecurity focuses on controlling access to pathogens of consequence and on the reliability of the scientists granted this access (thereby reducing the threat of an intentional release of a pathogen) and/or access to sensitive information related to a pathogen’s virulence, host-range, transmissibility, resistance to medical countermeasures, and environmental stability, among other things".

In the US, the National Science Advisory Board on Biosecurity was created in 2004 to provide biosecurity oversight of "dual-use research", defined as "biological research with legitimate scientific purpose that may be misused to pose a biological threat to public health and/or national security". In 2006, the National Academy of Sciences defined biosecurity as "security against the inadvertent, inappropriate, or intentional malicious or malevolent use of potentially dangerous biological agents or biotechnology, including the development, production, stockpiling, or use of biological weapons as well as outbreaks of newly emergent and epidemic disease".

A number of nations have developed biological weapons for military use, and many civilian research projects in medicine have the potential to be used in military applications (dual-use research), so biosecurity protocols are used to prevent dangerous biological materials from falling into the hands of malevolent parties.

Laboratory program

Components of a laboratory biosecurity program include:

• Physical security
• Personnel security
• Material control and accountability
• Transport security
• Information security
• Program management
• Biological Security

Animals and plants

Threats to animals and plants, in particular food crops, which may in turn threaten human health, are typically overseen by a government department of agriculture.

Animal biosecurity encompasses different means of prevention and containment of disease agents in a specific area. A critical element in animal biosecurity is biocontainment – the control of disease agents already present in a particular area and work to prevent transmission. Animal biosecurity may protect organisms from infectious agents or noninfectious agents such as toxins or pollutants, and can be executed in areas as large as a nation or as small as a local farm.

Animal biosecurity takes into account the epidemiological triad for disease occurrence: the individual host, the disease, and the environment in contributing to disease susceptibility. It aims to improve nonspecific immunity of the host to resist the introduction of an agent, or limit the risk that an agent will be sustained in an environment at adequate levels. Biocontainment works to improve specific immunity towards already present pathogens.

The aquaculture industry is also vulnerable to pathogenic organisms, including fungal, bacterial, or viral infections which can affect fish at different stages of their life cycle.

Human health

Direct threats to human health may come in the form of epidemics or pandemics, such as the 1918 Spanish flu pandemic and other influenza epidemics, MERS, SARS, or the COVID-19 pandemic, or they may be deliberate attacks (bioterrorism). The country/federal and/or state health departments are usually responsible for managing the control of outbreaks and transmission and the supply of information to the public.

Medical countermeasures

Medical countermeasures (MCMs) are products such as biologics and pharmaceutical drugs that can protect from or treat the effects of a chemical, biological, radiological, or nuclear (CBRN) attack or in the case of public health emergencies. MCMs can also be used for prevention and diagnosis of symptoms associated with CBRN attacks or threats.

In the US, the Food and Drug Administration (FDA) runs a program called the "FDA Medical Countermeasures Initiative" (MCMi), with programs funded by the federal government. It helps support "partner" agencies and organisations prepare for public health emergencies that could require MCMs.

International agreements and guidelines

Biosecurity sign for use on a farm or agricultural area experiencing swine fever (Dutch example).

Agricultural biosecurity and human health

Various international organisations, international bodies and legal instruments and agreements make up a worldwide governance framework for biosecurity.

Standard-setting organisations include the Codex Alimentarius Commission (CAC), the World Organisation for Animal Health (OIE) and the Commission on Phytosanitary Measures (CPM) develop standards pertinent to their focuses, which then become international reference points through the World Trade Organization (WTO)'s Agreement on the Application of Sanitary and Phytosanitary Measures (SPS Agreement), created in 1995. This agreement requires all members of the WTO to consider all import requests concerning agricultural products from other countries. Broadly, the measures covered by the agreement are those aimed at the protection of human, animal or plant life or health from certain risks.

Other important global and regional agreements include the International Health Regulations (IHR, 2005), the International Plant Protection Convention (IPPC), the Cartagena Protocol on Biosafety, the Codex Alimentarius, the Convention on Biological Diversity (CBD) and the General Agreement on Tariffs and Trade (GATT, 1947).

The UN Food and Agriculture Organization (FAO), the International Maritime Organization (IMO), the Organisation for Economic Co-operation and Development (OECD) and WHO are the most important organisations associated with biosecurity.

The IHR is a legally binding agreement on 196 nations, including all member states of WHO. Its purpose and scope is "to prevent, protect against, control, and provide a public health response to the international spread of disease in ways that are commensurate with and restricted to public health risks and that avoid unnecessary interference with international traffic and trade", "to help the international community prevent and respond to acute public health risks that have the potential to cross borders and threaten people worldwide".

Biological weapons

• The Biological Weapons Convention was the first multilateral disarmament treaty banning the production of an entire category of weapons, being biological weapons.
• UN Resolution 1540 (2004) "affirms that the proliferation of nuclear, chemical and biological weapons and their means of delivery constitutes a threat to international peace and security. The resolution obliges States, inter alia, to refrain from supporting by any means non-State actors from developing, acquiring, manufacturing, possessing, transporting, transferring or using nuclear, chemical or biological weapons and their means of delivery". Resolution 2325, reaffirming 1540, was adopted unanimously on 15 December 2016.

Laboratory safety

• OECD Best Practice Guidelines for Biological Resource Centres, a consensus report created in 2001 after experts from OECD countries came together, calling upon "national governments to undertake actions to bring the BRC concept into being in concert with the international scientific community". BRCs are "repositories and providers of high-quality biological materials and information".

As international security issue

For a long time, health security or biosecurity issues were not considered as an international security issue, especially in the traditional view of international relations. However, some changes in trend have contributed to the inclusion of biosecurity (health security) in discussions of security. As time progressed, there was a movement towards securitisation. Non-traditional security issues such as climate change, organised crime, terrorism, and landmines came to be included in the definition of international security. There was a general realisation that the actors in the international system not only involved nation-states but also included international organisations, institutions, and individuals, which ensured the security of various actors within each nation became an important agenda. Biosecurity is one of the issues to be securitised under this trend. On 10 January 2000, the UN Security Council convened to discuss HIV/AIDS as a security issue in Africa and designated it a threat in the following month. The UNDP Millennium Development Goals also recognise health issues as international security issue.

Several instances of epidemics such as SARS increased awareness of health security (biosecurity). Several factors have rendered biosecurity issues more severe: there is a continuing advancement of biotechnology, which increases the possibility for malevolent use, evolution of infectious diseases, and globalising force which is making the world more interdependent and more susceptible to spread of epidemics.

Controversial experiments in synthetic biology, including the synthesis of poliovirus from its genetic sequence, and the modification of flu type H5N1 for airborne transmission in mammals, led to calls for tighter controls on the materials and information used to perform similar feats. Ideas include better enforcement by national governments and private entities concerning shipments and downloads of such materials, and registration or background check requirements for anyone handling such materials.

Challenges

Diseases caused by emerging viruses are a major threat to global public health. The proliferation of high biosafety level laboratories around the world has resulted in concern about the availability of targets for those that might be interested in stealing dangerous pathogens. The growth in containment laboratories is often in response to emerging diseases, and many new containment labs' main focus is to find ways to control these diseases. By strengthening national disease surveillance, prevention, control and response systems, the labs have improved international public health.

One of the major challenges of biosecurity is that harmful technology has become more available and accessible. Biomedical advances and the globalisation of scientific and technical expertise have made it possible to greatly improve public health; however, there is also the risk that these advances can make it easier for terrorists to produce biological weapons.

Communication between the citizen and law enforcement officials is important. Indicators of agro-terrorism at a food processing plant may include persons taking notes or photos of a business, theft of employee uniforms, employees changing working hours, or persons attempting to gain information about security measures and personnel. Unusual activity is best handled if reported to law enforcement personnel promptly. Communication between policymakers and life sciences scientists is also important.

The MENA (Middle East and North Africa) region, with its socio-political unrest, diverse cultures and societies, and recent biological weapons programs, faces particular challenges.

The future

Biosecurity requires the cooperation of scientists, technicians, policy makers, security engineers, and law enforcement officials.

The emerging nature of newer biosecurity threats means that small-scale risks can blow up rapidly, which makes the development of an effective policy challenging owing to the limitations on time and resources available for analysing threats and estimating the likelihood of their occurrence. It is likely that further synergies with other disciplines, such as virology or the detection of chemical contaminants, will develop over time.

Some uncertainties about the policy implementation for biosecurity remain for future. In order to carefully plan out preventive policies, policy makers need to be able to somewhat predict the probability and assess the risks; however, as the uncertain nature of the biosecurity issue goes it is largely difficult to predict and also involves a complex process as it requires a multidisciplinary approach. The policy choices they make to address an immediate threat could pose another threat in the future, facing an unintended trade-off.

Philosopher Toby Ord, in his 2020 book The Precipice: Existential Risk and the Future of Humanity, puts into question whether the current international conventions regarding biotechnology research and development regulation, and self-regulation by biotechnology companies and the scientific community are adequate.

Role of education

The advance of the life sciences and biotechnology has the potential to bring great benefits to humankind through responding to societal challenges. However, it is also possible that such advances could be exploited for hostile purposes, something evidenced in a small number of incidents of bioterrorism, particularly by the series of large-scale offensive biological warfare programs carried out by major states in the last century. Dealing with this challenge, which has been labelled the "dual-use dilemma," requires a number of different activities. However, one way of ensuring that the life sciences continue to generate significant benefits and do not become subject to misuse for hostile purposes is a process of engagement between scientists and the security community, and the development of strong ethical and normative frameworks to complement legal and regulatory measures that are developed by states.

See also

• Biodefence
• Biological Weapons Convention
• Biorisk
• Biosecurity in Australia
• Biosecurity in New Zealand
• Biosecurity in the United States
• Biowar
• Cyberbiosecurity
• Food safety
• Global health
• Global Health Security Initiative (GHSI)
• Good Agricultural Practices
• Human security
• International Health Regulations
• Interplanetary contamination
• Public health
• Quarantine
• Select agent

 

Emergent virus

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Emergent_virus 

An emergent virus (or emerging virus) is a virus that is either newly appeared, notably increasing in incidence/geographic range or has the potential to increase in the near future. Emergent viruses are a leading cause of emerging infectious diseases and raise public health challenges globally, given their potential to cause outbreaks of disease which can lead to epidemics and pandemics. As well as causing disease, emergent viruses can also have severe economic implications. Recent examples include the SARS-related coronaviruses, which have caused the 2002-2004 outbreak of SARS (SARS-CoV-1) and the 2019–21 pandemic of COVID-19 (SARS-CoV-2). Other examples include the human immunodeficiency virus which causes HIV/AIDS; the viruses responsible for Ebola; the H5N1 influenza virus responsible for avian flu; and H1N1/09, which caused the 2009 swine flu pandemic (an earlier emergent strain of H1N1 caused the 1918 Spanish flu pandemic). Viral emergence in humans is often a consequence of zoonosis, which involves a cross-species jump of a viral disease into humans from other animals. As zoonotic viruses exist in animal reservoirs, they are much more difficult to eradicate and can therefore establish persistent infections in human populations.

Emergent viruses should not be confused with re-emerging viruses or newly detected viruses. A re-emerging virus is generally considered to be a previously appeared virus that is experiencing a resurgence, for example measles. A newly detected virus is a previously unrecognized virus that had been circulating in the species as endemic or epidemic infections. Newly detected viruses may have escaped classification because they left no distinctive clues, and/or could not be isolated or propagated in cell culture. Examples include human rhinovirus (a leading cause of common colds which was first identified in 1956), hepatitis C (eventually identified in 1989), and human metapneumovirus (first described in 2001, but thought to have been circulating since the 19th century). As the detection of such viruses is technology driven, the number reported is likely to expand.

Zoonosis

See also: Zoonosis

Given the rarity of spontaneous development of new virus species, the most frequent cause of emergent viruses in humans is zoonosis. This phenomenon is estimated to account for 73% of all emerging or re-emerging pathogens, with viruses playing a disproportionately large role. RNA viruses are particularly frequent, accounting for 37% of emerging and re-emerging pathogens. A broad range of animals - including wild birds, rodents and bats - are associated with zoonotic viruses. It is not possible to predict specific zoonotic events that may be associated with a particular animal reservoir at any given time.

Zoonotic spillover can either result in self-limited 'dead-end' infections, in which no further human-human transmission occurs (as with the rabies virus), or in infectious cases, in which the zoonotic pathogen is able to sustain human-human transmission (as with the Ebola virus). If the zoonotic virus is able to maintain successful human-human transmission, an outbreak may occur. Some spillover events can also result in the virus adapting exclusively for human infection (as occurred with the HIV virus), in which case humans become a new reservoir for the pathogen.

A successful zoonotic 'jump' depends on human contact with an animal harbouring a virus variant that is able to infect humans. In order to overcome host-range restrictions and sustain efficient human-human transmission, viruses originating from an animal reservoir will normally undergo mutation, genetic recombination and reassortment. Due to their rapid replication and high mutation rates, RNA viruses are more likely to successfully adapt for invasion of a new host population.

Examples of animal sources

Bats

Different bat species

While bats are essential members of many ecosystems, they are also frequently implicated as frequent sources of emerging virus infections. Their immune systems have evolved in such a way as to suppress any inflammatory response to viral infections, thereby allowing them to become tolerant hosts for evolving viruses, and consequently provide major reservoirs of zoonotic viruses. They are associated with more zoonotic viruses per host species than any other mammal, and molecular studies have demonstrated that they are the natural hosts for several high-profile zoonotic viruses, including severe acute respiratory syndrome-related coronaviruses and Ebola/Marburg hemorrhagic fever filoviruses. In terms of their potential for spillover events, bats have taken over the leading role previously assigned to rodents. Viruses can be transmitted from bats via several mechanisms, including bat bite, aerosolization of saliva (e.g. during echolocation) and faeces/urine.

Due to their distinct ecology/behaviour, bats are naturally more susceptible to viral infection and transmission. Several bat species (e.g. brown bats) aggregate in crowded roosts, which promotes intra- and interspecies viral transmission. Moreover, as bats are widespread in urban areas, humans occasionally encroach on their habitats which are contaminated with guano and urine. Their ability to fly and migration patterns also means that bats are able to spread disease over a large geographic area, while also acquiring new viruses. Additionally, bats experience persistent viral infections which, together with their extreme longevity (some bat species have lifespans of 35 years), helps to maintain viruses and transmit them to other species. Other bat characteristics which contribute to their potency as viral hosts include: their food choices, torpor/hibernation habits and susceptibility to reinfection.

Drivers of viral emergence

See also: Infection § Emerging diseases

Viral emergence is often a consequence of both nature and human activity. In particular, ecological changes can greatly facilitate the emergence and re-emergence of zoonotic viruses. Factors such as deforestation, reforestation, habitat fragmentation and irrigation can all impact the ways in which humans come into contact with wild animal species, and consequently promote virus emergence. Additionally, climate change can affect ecosystems and vector distribution, which in turn can affect the emergence of vector-borne viruses. Other ecological changes - for example, species introduction and predator loss - can also affect virus emergence and prevalence. Some agricultural practices, for example livestock intensification and inappropriate management/disposal of farm animal faeces, are also associated with an increased risk of zoonosis.

Viruses may also emerge due to the establishment of human populations that are vulnerable to infection. For example, a virus may emerge following loss of cross-protective immunity, which may occur due to loss of a wild virus or termination of vaccination programmes. Well-developed countries also have higher proportions of aging citizens and obesity-related disease, thus meaning that their populations may be more immunosuppressed and therefore at risk of infection. Contrastingly, poorer nations may have immunocompromised populations due to malnutrition or chronic infection; these countries are also unlikely to have stable vaccination programmes. Additionally, changes in human demographics – for example, the birth and/or migration of immunologically naïve individuals – can lead to the development of a susceptible population that enables large-scale virus infection.

Other factors which can promote viral emergence include globalisation; in particular, international trade and human travel/migration can result in the introduction of viruses into new areas. Moreover, as densely populated cities promote rapid pathogen transmission, uncontrolled urbanization (i.e. the increased movement and settling of individuals in urban areas) can promote viral emergence. Animal migration can also lead to the emergence of viruses, as was the case for the West Nile virus which was spread by migrating bird populations. Additionally, human practices regarding food production and consumption can also contribute to the risk of viral emergence. In particular, wet markets (i.e. live animal markets) are an ideal environment for virus transfer, due to the high density of people and wild/farmed animals present. Consumption of bush meat is also associated with pathogen emergence.

Prevention

Control and prevention of zoonotic diseases depends on appropriate global surveillance at various levels, including identification of novel pathogens, public health surveillance (including serological surveys), and analysis of the risks of transmission. The complexity of zoonotic events around the world predicates a multidisciplinary approach to prevention. The One Health Model has been proposed as a global strategy to help prevent the emergence of zoonotic diseases in humans, including novel viral diseases. The One Health concept aims to promote the health of animals, humans, and the environment, both locally and globally, by fostering understanding and collaboration between practitioners of different interrelated disciplines, including wildlife biology, veterinary science, medicine, agriculture, ecology, microbiology, epidemiology, and biomedical engineering.

Virulence of emergent viruses

As hosts are immunologically naïve to pathogens they have not encountered before, emergent viruses are often extremely virulent in terms of their capacity to cause disease. Their high virulence is also due to a lack of adaptation to the new host; viruses normally exert strong selection pressure on the immune systems of their natural hosts, which in turn exerts a strong selection pressure on viruses. This coevolution means that the natural host is able to manage infection. However, when the virus jumps to a new host (e.g. humans), the new host is unable to deal with infection due to a lack of coevolution, which results in mismatch between host immunoeffectors and virus immunomodulators.

Additionally, in order to maximise transmission, viruses often naturally undergo attenuation (i.e. virulence is reduced) so that infected animals can survive long enough to infect other animals more efficiently. However, as attenuation takes time to achieve, new host populations will not initially benefit from this phenomenon. Moreover, as zoonotic viruses also naturally exist in animal reservoirs, their survival is not dependent on transmission between new hosts; this means that emergent viruses are even more unlikely to attenuate for the purpose of maximal transmission, and they remain virulent.

Although emergent viruses are frequently highly virulent, they are limited by several host factors including: innate immunity, natural antibodies and receptor specificity. If the host has previously been infected by a pathogen that is similar to the emergent virus, the host may also benefit from cross-protective immunity.

Examples of emergent viruses

Influenza A

Electron micrograph of influenza virus, magnification is approximately 100,000

Influenza is a highly contagious respiratory infection, which affects approximately 9% of the global population and causes 300,000 to 500,000 deaths annually. Based on their core proteins, influenza viruses are classified into types A, B, C and D. While both influenza A and B can cause epidemics in humans, influenza A also has pandemic potential and a higher mutation rate, therefore is most significant to public health.

Influenza A viruses are further classified into subtypes, based on the combinations of the surface glycoproteins hemagglutinin (HA) and neuraminidase (NA). The primary natural reservoir for most influenza A subtypes are wild aquatic birds; however, through a series of mutations, a small subset of these viruses have adapted for infection of humans (and other animals). A key determinant of whether a particular influenza A subtype can infect humans is its binding specificity. Avian influenza A preferentially binds to cell surface receptors with a terminal α2,3‐linked sialic acid, while human influenza A preferentially binds to cell surface receptors with a terminal α2,6‐linked sialic acid. Via mutation, some avian influenza A viruses have successfully altered their binding specificity from α2,3‐ to α2,6‐linked sialic acid. However, in order to emerge in humans, avian influenza A viruses must also adapt their RNA polymerases for function in mammalian cells, as well as mutating for stability in the acidic respiratory tract of humans.

Following adaptation and host switch, influenza A viruses have the potential to cause epidemics and pandemics in humans. Minor changes in HA and NA structure (antigenic drift) occur frequently, which enables the virus to cause repetitive outbreaks (i.e. seasonal influenza) by evading immune recognition. Major changes in HA and NA structure (antigenic shift), which are caused by genetic reassortment between different influenza A subtypes (e.g. between human and animal subtypes), can instead cause large regional/global pandemics. Due to the emergence of antigenically different influenza A strains in humans, four pandemics occurred in the 20th century alone.

Additionally, although animal influenza A viruses (e.g. swine influenza) are distinct from human influenza viruses, they can still cause zoonotic infection in humans. These infections are largely acquired following direct contact with infected animals or contaminated environments, but do not result in efficient human-human transmission; examples of this include H5N1 influenza and H7N9 influenza.

SARS-CoV

Electron micrograph of SARS-CoV

In 2002, a highly pathogenic SARS-CoV (Severe Acute Respiratory Syndrome Coronavirus) strain emerged from a zoonotic reservoir; approximately 8000 people were infected worldwide, and mortality rates approached 50% or more in the elderly. As SARS-CoV is most contagious post-symptoms, the introduction of strict public health measures effectively halted the pandemic. The natural reservoir host for SARS-CoV is thought to be horseshoe bats, although the virus has also been identified in several small carnivores (e.g. palm civets and racoon dogs). The emergence of SARS-CoV is believed to have been facilitated by Chinese wet markets, in which civets positive for the virus acted as intermediate hosts and passed SARS-CoV onto humans (and other species). However, more recent analysis suggests that SARS-CoV may have directly jumped from bats to humans, with subsequent cross-transmission between humans and civets.

In order to infect cells, SARS-CoV uses the spike surface glycoprotein to recognise and bind to host ACE-2, which it uses as a cellular entry receptor; the development of this characteristic was crucial in enabling SARS-CoV to ‘jump’ from bats to other species.

MERS-CoV

Electron micrograph of MERS-CoV

First reported in 2012, MERS-CoV (Middle East Respiratory Syndrome Coronavirus) marks the second known introduction of a highly pathogenic coronavirus from a zoonotic reservoir into humans. The case mortality rate of this emergent virus is approximately 35%, with 80% of all cases reported by Saudi Arabia. Although MERS-CoV is likely to have originated in bats, dromedary camels have been implicated as probable intermediate hosts. MERS-CoV is believed to have been circulating in these mammals for over 20 years, and it is thought that novel camel farming practices drove the spillover of MERS-CoV into humans. Studies have shown that humans can be infected with MERS-CoV via direct or indirect contact within infected dromedary camels, while human-human transmission is limited.

MERS-CoV gains cellular entry by using a spike surface protein to bind to the host DPP4 surface receptor; the core subdomain of this spike surface protein shares similarities with that of SARS-CoV, but its receptor binding subdomain (RBSD) significantly differs.

Bluetongue disease

Domestic yak with Bluetongue disease - tongue is visibly swollen and cyanotic

Bluetongue disease is a non-contagious vector-borne disease caused by bluetongue virus, which affects species of ruminants (particularly sheep). Climate change has been implicated in the emergence and global spread of this disease, due to its impact on vector distribution. The natural vector of the bluetongue virus is the African midge C. imicola, which is normally limited to Africa and subtropical Asia. However, global warming has extended the geographic range of C. imicola, so that it now overlaps with a different vector (C. pulcaris or C. obsoletus) with a much more northward geographic range. This change enabled the bluetongue virus to jump vector, thus causing the northward spread of bluetongue disease into Europe.

See also

• Biosecurity
• Emerging infectious disease
• History of emerging infectious diseases
• Laboratory biosafety
• Viral quasispecies