classification schemes for micro-organisms based on their
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.
compared with the health hazards of the early use of chemical
and radioactive substances, work with etiological
agents has been relatively free of disasters.
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.
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.
lists for risk classification of micro-organisms
have been published in the Regional Decrees regulating
contained use activities involving pathogen and/or genetically
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.
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.
- Liste der durch die ZKBS sicherheitsbewerteten
Organismen, Stand: Dezember 1997. [http://www.rki.de/GENTEC/ZKBS/ZKBS.HTM]
Federal Coordination Centre for Biotechnology, Switzerland. Classification of Organisms according to the Risk presented to People and the Environment. Bacteria [http://www.buwal.ch/stobobio/biotechnologie/e/bacteries.htm]
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 on Recombinant DNA and Gene Transfer, Section
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
special committee of the American
Society for Microbiology.
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 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:
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.
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.
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) 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.
also issued an official classification of animal pathogens.
is part of the reference lists for risk classification of
micro-organisms that have been published in the Regional
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
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.
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 -
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.