Henle-Koch postulates
The Henle-Koch postulates , often just called Koch postulates or Koch's postulates , historically describe the cause-effect relationship between a parasite and the host for the causation ( etiology ) of an infectious disease . With the help of these postulates , the causal relationship can be experimentally checked and delimited. If they are fulfilled, a microorganism can rightly be regarded as the causative agent of a disease. However, these strict criteria set very narrow limits; in some cases, not all requirements have to be met for an etiological agent to be correctly described as a pathogen , as Koch explained in 1890. At the time it was formulated, important findings from modern infectious diseases - for example on viruses and symptom-free carriers of disease such as permanent excretors - were still unknown.
The name of the postulates derives from the preparatory work of the anatomist and pathologist Jakob Henle (1809–1885) as well as the work of the doctors and microbiologists Robert Koch (1843–1910) and Friedrich Loeffler (1852–1915).
history
The requirements of the postulates can be traced back to Henle's essay "Of the miasms and contagies and of the miasmatic-contagious diseases" from 1840, where he expressed the assumption that parasitic microorganisms are the cause of infections and formulated: "That they [the microorganisms] are really effective, could only be proven empirically if one could isolate [...] [the] contagium [and observe its effect], an attempt that one would have to do without. ”Another source is working Edwin Klebs ' from the 1870s in which he the classic three-step of isolating, culturing, inoculate , is absolutely necessary to explain formulated without this, however. Robert Koch, who had studied with Henle in Göttingen , did not write down any postulates of this kind, but gave a list of certain criteria for an infection, for example in a publication on wound infectious diseases in 1878 and in an article on tuberculosis in 1884 . Friedrich Loeffler , one of Koch's employees, was the first to designate and number the three steps as postulates in 1883. In his work on the diphtheria bacillus he formulated as follows:
If diphtheria is a disease caused by microorganisms, it must also be possible to fulfill those three postulates, the fulfillment of which is absolutely necessary for the strict proof of the parasitic nature of every such disease:
1) There must be constant diseases in the local Batches of organisms can be detected in a typical arrangement.
2) The organisms to which, according to their behavior towards the diseased parts, should be ascribed an importance for the occurrence of these changes, must be isolated and cultivated purely.
3) It must be possible to reproduce the disease experimentally with the pure cultures. "
Koch himself often varied his methodology and never spoke of postulates. Loeffler's postulates, however, reflect the methodology that both had used in their joint work on tuberculosis. Robert Koch, who also published on this in 1884, placed the problem and not the solution at the center of his remarks:
“The facts obtained in this way can possibly already provide so much evidence that only the most extreme skepticism can raise the objection that the microorganisms found are not the cause, but only a side effect of the disease. Often, however, this objection will have a certain justification, and it is therefore part of the complete demonstration that one is not content with merely establishing the coincidence of the disease and the parasites, but that these parasites are also directly proven as the actual cause of the disease. This can only be done in such a way that the parasites are completely separated from the diseased organism and freed from all products of the disease to which a disease-causing influence could be ascribed, and that by introducing the isolated parasites into the healthy organism, the disease with all of them their peculiar properties are evoked anew. "
At the 10th International Medical Congress in Berlin in 1890 , Koch gave a lecture on "Bacteriological Research". He saw the requirement of proving a causal connection not strictly bound to these postulates; Here, especially with regard to cholera, he was of the opinion:
“We are therefore already justified in claiming that if only the first two requirements of the evidence are met, that is, if the regular and exclusive occurrence of the parasite has been proven, so that the causal connection between parasite and disease is also fully proven . "
Today the postulates are no longer required in a strict form, but they are a popular historical reference in infectious studies.
Modern form of postulates
In the "golden age of microbiology" that followed the discoveries of Louis Pasteur , Koch and Loeffler, Koch's postulates were unreservedly valid. Numerous infectious diseases were discovered, therapies and vaccinations developed.
It is now known that there are also pathogens causing infectious diseases that do not fulfill all of Koch's postulates. Viruses, for example, cannot be cultivated on simple culture media, as can certain bacteria ( rickettsiae , chlamydia , treponemas ). Other pathogens act differently on animals than they do on humans, so that the third postulate is violated (e.g. in the case of the pathogen causing gonorrhea , Neisseria gonorrhoeae ). Other pathogens have only become detectable with modern molecular biological methods. It was therefore necessary to redraft the "postulates":
The first postulate concerns the regular, e.g. B. microscopic detection of the pathogen in the products of the disease in question. The second postulate deals with the purification of the pathogen outside of the diseased organism. The third postulate determines the evidence of the pathogenic properties of the pure-bred pathogen. A fourth formulated postulate added today also includes evidence of immunological pathogen-host relationships.
First postulate
Finding the natural location of the obligate pathogens corresponds to the first postulate. Each pathogen has a certain host spectrum or a certain tissue or organ affinity. Pathogenic properties of the pathogen and the sensitivity of the host are reciprocal. So one conditions the other and vice versa. The best form of mutual adaptation is symbiosis , the coexistence of pathogen and host with mutual benefit. For example, people who excrete typhoid bacteria are immune to their own germs, which are highly dangerous for non-immune people. Various transmission mechanisms guarantee the spread of certain pathogens if the host and with it the “location” dies or if the parasites succumb to the host's defenses. Other transmission mechanisms are linked to the continued existence of the site.
In short: the suspected pathogen must always be associated with the disease and must not be detected in healthy animals.
Second postulate
The fulfillment of the second postulate places special demands on the work of the culture medium for the breeding conditions. The natural environmental conditions of the pathogen should be simulated and its pathogenic properties preserved.
In short: the suspected pathogen must be grown in pure culture.
Third postulate
The third postulate is based on the proof of the pathogenic properties of the pathogen. The characteristics sought must be quantitatively verifiable using laboratory methods. Adhesion and penetration, reproductive power and pathogenicity are properties that depend on virulence , i.e. H. the number of pathogens required and the immunity, i.e. the host defense. In animal experiments, either the penetration and multiplication potential of the pathogens and / or their pathogenicity is measured. If the pathogenic effect is absent in the animal or if the factors thereof in animal experiments are different from those in humans, the comparison between the experimental infection and that of humans is doubtful.
In short: a pure culture of the suspected pathogen should trigger the disease in healthy animals.
Addition: fourth postulate
The supplementary fourth postulate deals with the immunological pathogen-host relationship. Here, the pathogen is defined in terms of its ability to stimulate the host's white blood cells ( leukocytes ) to produce antibodies after invading and multiplying . Antibodies are protein molecules that are formed by a new synthesis and release into the body fluids against the causative pathogen or are already present. Due to their specific structure, they are able to reduce or neutralize the pathogenic potency of the pathogen, its reproductive power or its pathogenicity, after binding to the pathogen or its pathogenic excretions. The presence of such antibody molecules is also an important indication of ongoing or expired contacts between the host's tissues and the pathogens.
In particular, the increase or decrease in the measurable antibody effects in the host's blood is a recognition aid if the pathogens are not or difficult to breed, if vaccinations are planned and their success is to be determined or if the state of preparedness and thus the spread of the pathogen in of the population should be examined.
In short: the organism must be re-isolated and be identical to the original pathogen.
literature
- Robert Koch: The Etiology of Tuberculosis. In: Collected works by Robert Koch. Edited by Julius Schwalbe, Volume 1, Georg Thieme, Leipzig (1884) 1912, pp. 467-565.
- Friedrich Loeffler: "Investigation of the importance of microorganisms for the development of diphtheria in humans, in pigeons and in calves" , in: Mittheilungen aus dem Imperial Health Office 2 (1884), pp. 421-499.
- K. Codell Carter: "Koch's Postulates in Relation to the Work of Jacob Henle and Edwin Klebs" , in: Medical History 29 (1985), pp. 353-375.
- Christoph Gradmann: “It's all a question of method. On the historicity of Koch's postulates 1840–2000 ” , in: Medizinhistorisches Journal 43 (2008), pp. 121–148.
See also: infection biology , infectiology
Individual evidence
- ↑ DN Fredricks, DA Relman: Sequence-based identification of microbial pathogens: a reconsideration of Koch's postulates . In: Clinical Microbiology Reviews . tape 9 , no. 1 , January 1996, ISSN 0893-8512 , p. 20 , doi : 10.1128 / CMR.9.1.18-33.1996 , PMID 8665474 , PMC 172879 (free full text).
- ^ A b Robert Koch: About bacteriological research. In: Negotiations of the Xth International Medical Congress, Berlin 1890. Volume I. Verlag August Hirschwald, Berlin 1891, p. 655. PDF
- ↑ Quoted from Werner Köhler : Kochsche Postulate. In: Werner E. Gerabek , Bernhard D. Haage, Gundolf Keil , Wolfgang Wegner (eds.): Enzyklopädie Medizingeschichte. De Gruyter, Berlin / New York 2005, ISBN 3-11-015714-4 , p. 769.
- ↑ Edwin Klebs: About the transformation of medical views in the last three decades. In: Official. Ber. 50th Assembly of German Naturalists and doctors. Munich 1877, pp. 41-45.
- ↑ Friedrich Loeffler: Investigation of the importance of microorganisms for the development of diphtheria in humans, in pigeons and in calves. In: Communications from the Imperial Health Office. 1884, p. 424. Digitized
- ↑ Robert Koch: About the etiology of tuberculosis. In: Communications from the Imperial Health Office. 1884, Volume II; P. 469f. PDF
- ↑ a b c d Bernt-Dieter Huismans: Plea for the detection of pathogens in chronic Lyme borreliosis . Munich, ISBN 978-3-638-92337-8 , pp. 5 .