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- Classifications systems
- Classifications of animal pathogens
The great majority of micro-organisms are harmless and many are beneficial. Some of the properties of non-pathogenic micro-organisms have for instance been used in biotechnology to produce metabolites or enzymes. Non-pathogenic micro-organisms have also been used as inoculum to protect from diseases (biocontrol and biofertilizers in agriculture, probiotics), to restore contaminated sites (bioremediation) or for fermentation in food processes.
Pathogenic micro-organisms, although they represent only a small part in the total microbial world, receive much attention because they represent a threat for the human or animal health, or for the agriculture. They can cause diseases of plague dimensions with serious economic and environmental consequences. New viruses are also emerging each year to threaten the lives of both humans and animals.
From a practical perspective, pathogenicity or virulence is the capacity of some micro-organisms to cause disease. However, microbiologists recognize that pathogenicity represents a form of versatility and specialization that enables certain micro-organisms to replicate within a specific host (infectivity) and damage host cells. Although cellular damage is not clinically apparent in many cases, a significant proportion of infected hosts shows signs of disease or eventually dies.
The outcome of the infection is dependent on the properties of the pathogen (virulence, invasiveness, toxic or allergenic effects) but also upon the host immunity status. From this point of view, pathogens fall into two basic types: primary pathogens that cause disease among at least a portion of normal individuals, and opportunistic pathogens that cause disease only in individuals who are compromised in either their innate or humoral immune defences.
The etiological agents have been extensively cultured and studied since the end of the last century (isolation of pure cultures). One of the unfortunate consequences of working with etiological agents is the potential for acquiring a laboratory-associated-infection (LAI). History has shown that such infections occur (documented as early as the 1890s) and that laboratory workers are clearly at higher risk for infection with certain agents (i.e. Mycobacterium tuberculosis, Brucella, hepatitis B virus) than the general population.
However, compared with the health hazards of the early use of chemical and radioactive substances, work with etiological agents has been relatively free of disasters.
Nevertheless, biological hazards differ from all other kinds of safety hazards in one major significant way: biological agents can grow and multiply in the host organism. Moreover, secondary infections in non-laboratory workers can occur, depending on the communicability of the infectious agent.
Examples of etiological agents typically used in research or biomedical laboratories include the full range of micro-organisms: bacteria, viruses, fungi, protozoa and multi-cellular parasites.
Biological safety is a relative newcomer to the field of occupational safety. The concerns aroused by recent developments in genetic engineering and by the epidemics of acquired immunodifiency syndrome (AIDS) have influenced those involved in biological and biomedical research by increasing their awareness of the safety aspects of their work. These aspects relate not only to human health, but also to the potential for environmental damage (animals and plants). This chapter does not deal with plant disease agents that pose no risk for human or animal health.
- Sewell D. L. Laboratory-Associated Infections and Biosafety. Clinical Microbiology Reviews. 8, 389-405, 1995.
- Harding L., Liberman D. F. Epidemiology of laboratory-associated infections. In: Fleming D. O., Richardson J. H., Tulis J. J. and Vesley D. (ed.): Laboratory Safety. Principles and Practices, 2nd ed., pp 7-15. ASM Press, Washington, D.C., 1995.
- Collins C. H. and Kennedy D. A. Laboratory-Acquired Infections. 4th ed. Butterworth-Heinemann Ltd., Oxford, 1999.
Because investigations into LAI showed that certain micro-organisms were more likely to be involved than the others, several attempts have been made to classify human and animal pathogens according to the risks they present to the health of laboratory workers and to the human and animal community should they escape from the laboratory. Such categorization of risk would lead to the formulation of appropriate sets of safety precautions, called risk management.
Reference lists for risk classification of micro-organisms have been published in the Regional Decrees regulating contained use activities involving pathogen and/or genetically modified organisms.
›››› See relevant chapter for more information
The European Parliament and the Council have published in 2000 Directive 2000/54/EC on the protection of workers from risks related to exposure to biological agents at work. This Directive refers to biological agents instead of micro-organisms, and includes those which have been genetically modified, cell cultures and human endoparasites, which may be able to provoke any infection, allergy or toxicity. Although toxicity and allergenicity are included in the definition of biological agents, the four risk groups are based on the level of risk of infection (definitions according to the Directive in textbox below).
Annex III of the Directive gives a list of biological agents which are known to infect humans. Where appropriate, indicators are given of the toxic and allergic potential of these agents. Animal and plant pathogens which are known not to affect man are excluded.
This Directive has been implemented by the Members States and lists of human pathogens have been produced by the different countries. Some of these lists are available on Internet (see above).
UK was the first country in Europe to propose a classification. It was revised several times from 1975 to 1978 to finally end up with three categories A, B and C. This system, which was never very satisfactory, was superseded in 1984 by a numerical classification (Advisory Committee on Dangerous Pathogens) which parallels that of the USA.
=> Advisory Committee on Dangerous Pathogens. 2013. “The Approved List of biological agents” 3rd Edition. Health and Safety Executive
Central Committee on Biological Safety (ZKBS) - "Datenbank zu sicherheitsbewerteten Organismen" (2013)
Federal Office for the Environment (FOEN) - Lists of natural microorganisms (bacteria, viruses, parasites and fungi) and the risk groups to which they have been assigned (2013)
The first attempt to establish a classification for pathogenic micro-organisms was devised in the USA by the United States Public Health Service. They published in 1969 and 1974 a description of four classes of etiological agents (bacteria, fungi and viruses) ranking from those that pose no or minimal hazard (class 1) to those responsible for very serious diseases (class 4) (Centers for Disease Control, Office of Biosafety. Classification of Etiological Agents on the Basis of Hazard, 4th edition. United States Department of Health, Education and Welfare, Public Health Service).
The current classification uses Risk Groups (Rgs) instead of Risk Classes and agents are classified according to their relative pathogenicity for healthy adult humans. The definitions of the four Risk Groups are given in the NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules (click here to jump to the definitions). These guidelines also include an appendix listing the biological agents known to infect humans as well as selected animal agents that may pose theoretical risks if inoculated into humans. This list is subject to annual reviewing by a special committee of the American Society for Microbiology.
Information on risk assessment for specific etiological agents may be found in the Agent Summary Statements of the CDC/NIH publication, Biosafety in Microbiological and Biomedical Laboratories.
Risk Groups, Containment Levels, and Risk Assessments (2013). In Canadian Biosafety Standards (1st ed.). Government of Canada
The most important development with an international impact was initiated in 1979 by the World Health Organisation (WHO), which set up a Working Group within a special programme on safety measures in microbiology. This group formulated a set of minimum standards for laboratory safety compiled in a Laboratory Biosafety Manual. This Manual has been revised periodicaly, the last version having been published in 2003. The Manual includes the definition (see textbox below) of four risk groups based on the relative hazard of infective micro-organisms to the laboratory workers, the community, the livestock and the environment.
Although no list of infective agents is supplied, WHO recommends to each country to draw up their own classification by risk group of the agents encountered in that country based on the following factors:
- Pathogenicity of the agent.
- Mode of transmission and host range of the agent. These may be influenced by existing levels of immunity, density and movement of the host population, presence of appropriate vectors and standards of environmental hygiene.
- Availability of effective preventive measures. Such measures may include: prophylaxis by vaccination or antisera; sanitary measures, e.g., food and water hygiene; the control of animal reservoirs or arthropod vectors; the movement of people or animals; and the importation of infected animals or animal products.
- Availability of effective treatment. This includes passive immunization and postexposure vaccination, antibiotics, and chemotherapeutic agents, taking into consideration the possibility of emergence of resistant strains.
WHO also points out the necessity, when assessing the various criteria for classification, to take into account conditions prevailing in the geographical area in which the micro-organisms are handled. Individual governments should also decide to prohibit certain pathogens from being imported or handled other than for urgent diagnostic purposes (quarantine organisms).
The Working Party on Safety in Biotechnology of the European Federation of Biotechnology also worked on the classification of micro-organisms and produced a system that is directed towards the use of micro-organisms in the industry.
The Working Party kept the categorization of micro-organisms within four classes of risk for the laboratory worker and for the population, but introduced a new group, called Group E, gathering micro-organisms that present a more severe threat for the environment than for man (see definitions in textbox below). This new group includes plant pathogens, and some animal pathogens which pose no hazard for man and that can be responsible for heavy economic losses (e.g. Foot and mouth disease viruses, Ralstonia solanacearum).
- Frommer W., The WP Safety in Biotechnology of the European Federation Biotechnology, Safe Biotechnology - 3. Safety precautions for handling micro-organisms of different risk classes Appl. Microbiol. Biotechnol. 30, 541-552, 1989.
- Lelieveld H.L.M., The WP Safety in Biotechnology of the European Federation Biotechnology, Safe Biotechnology. Part 7. Classification of microorganisms on the basis of hazard. Appl. Microbiol. Biotechnol. 45, 723-729, 1996.
- Küenzi M., The WP Safety in Biotechnology of the European Federation Biotechnology, Safe Biotechnology -1. Safe biotechnology. General considerations. Appl. Microbiol. Biotechnol. 21, 1-6, 1985.
- Küenzi M., The WP Safety in Biotechnology of the European Federation Biotechnology, Safe Biotechnology - 2. The classification of microorganisms causing diseases in plants. Appl. Microbiol. Biotechnol. 27, 105, 1987.
Independently from the regulatory point of view, the classifications of pathogenic micro-organisms has only retained little attention from the international scientific community, but surprisingly, the classifications of pathogenic fungi have been thoroughly reviewed and discussed.
- Lister P. Classification of biological hazards. Vet. Rec. 131, 494, 1992.
- Burge, H. A. Classification of the fungi. Clin. Rev. Allergy 10, 153-163, 1992.
- de Hoog G.S. Risk assessment of fungi reported from humans and animals. Mycoses 39, 407-417, 1996. [Table 1. List of species with proposed risk categories]
- Meinhof W., et al. [Health risks in connection with fungi: a contribution to the assessment of fungi in the risk potential of safety provisions. German]. Mycoses. 39 Suppl 1, 48-50, 1996.
- Padhye A. A, et al. Biosafety considerations in handling medically important fungi. Med Mycol. 36 Suppl 1, 258-265, 1998.
- Vollekova, A., et al. [Classification of microscopic fungi from the aspect of risk of infection in laboratory personnel. Slovak.]. Epidemiol. Mikrobiol. Imunol. 47,154-158, 1998.
Lists of animal pathogens that necessitate quarantine or sanitary measures have been developed on a national basis, but all are inspired from the lists produced by the "Office International des Epizooties" (OIE), World Organization of Animal Health. OIE periodically releases lists (Lists A and B, see textbox below) of pathogenic micro-organisms that cause diseases in animal, some of them being also zoonotic pathogens (such as Mycobacterium bovis, rabies virus, Japanese encephalitis virus). These lists have evolved since the 1920s and diseases were sometimes added, sometimes removed. The lists can be accessed on the OIE website. All these diseases are notifiable to the OIE.
Belgium has also issued an official classification of animal pathogens. It is part of the reference lists for risk classification of micro-organisms that have been published in the Regional Decrees regulating contained use activities involving pathogen and/or genetically modified organisms. This classification, mainly based on the definitions published by the "Association Française de Normalisation" (AFNOR: NF X-42-075 Biotechnology : Guide to good practice microbiological analysis and research in the field of animal health), takes into account the importance of the disease, its communicability and the maximal risk of exposure in healthy animals. The risk group of each micro-organisms are based on the pathogenicity mechanisms, host range, epidemiological criteria, and availability of an effective therapy.
›››› See relevant page for more information
A comparison of the different lists of animal pathogens issued in the different European Member States was made by the European Committee for Standardization (European Committee for Standardization,Technical Committee 233 - Biotechnology, Working group 1. Micro-organisms - Examination of various existing lists of animal pathogens and production of a report. CR 12894, 1997). They concluded that a wide consensus exists, except for the United Kingdom where four hazard groups of animal pathogens, in addition to the harmless micro-organisms, are distinguished by the Ministry of Agriculture, Fisheries and Food (MAFF).
There seems to have a worldwide agreement on the four-group classification system. Examination of the vast majority of classifications of biological agents performed by various national committees of experts shows a uniform result. However some disagreements exist between, and even within individual states to allocate agents to one hazard or risk group. One of the problem in allocation of risk group arises obviously from the geographic and climatic distribution of the micro-organisms, their reservoir and vectors, especially when animal or plant pathogens are concerned. Sometimes political or economical considerations have also been overriding.
A comparison of the different existing lists of human pathogens has been made by the European Federation of Biotechnology (Frommer W., The WP Safety in Biotechnology of the European Federation Biotechnology, Safe Biotechnology - 3. Safety precautions for handling micro-organisms of different risk classes Appl. Microbiol. Biotechnol. 30, 541-552, 1989), the European Committee for Standardization (European Committee for Standardization,Technical Committee 233 - Biotechnology, Working group 1. Micro-organisms - Further examination of organisms in support of the classification carried out under directive 90/679/EEC. CR 12250, 1996), and the American Biological Safety Association.
Because of the variability of agent characteristics, the work conditions (diagnostic, research or production), host models and systems, and other factors, it is recommended that these classification tables should be used only as a guide for the comparison of the relative hazard levels of the agents.