Bordetella pertussis
| Bordetella pertussis | ||||||||||||
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Bordetella pertussis |
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| Bordetella pertussis | ||||||||||||
| ( Bergey et al. 1923) Moreno-Lopez 1952 |
Bordetella pertussis is a bacterium of the genus Bordetella , which is ofgreat medical importanceas the causative agent of whooping cough .
morphology
Bordetella pertussis consists of small (approx. 0.8 × 0.4 µm), cocoid, immobile, gram-negative rods whose sole habitat is the ciliated epithelial cells of the human respiratory tract . They appear in the microscopic preparation individually or in pairs. B. pertussis colonies are small, smooth, and shiny with a high convexity (like a mercury bead). The germ can be cultivated on special media within 3 to 4 days at 37 ° C in an aerobic atmosphere . It grows with β-hemolysis and is difficult to distinguish morphologically from other Bordetella such as B. parapertussis and B. bronchiseptica . The specialty of the bacterium is that it goes through four stages of development. In the first stage it attacks the red blood cells and tissues in humans. In the fourth stage it sheds part of its capsid and is less aggressive afterwards.
Pathogenesis
Bordetella pertussis overcomes the local immune mechanisms of the upper respiratory tract and can in complete health a host without predisposing factors disease trigger. The bacterium is transmitted aerogenically ( droplet infection ). With the help of various adhesins , the bacteria bind very tightly to the cells of the ciliated epithelium and can then trigger a disease by releasing toxins . Invasion of the epithelium is rare; (sub-) epithelial inflammation and necrosis occur . Although the pathogens are usually not invasive, i. H. do not get into the tissue or bloodstream , systemic effects still occur due to the toxins produced. Since, along with other amino acids, cystine is the optimal breeding ground for the bacterium, which is produced by the E. Coli in the rectum, which are also used industrially for the production of cystine , pertussis creates intestinal problems. Since cystine is also stored in the skin, it can lead to aggressive itching of the skin and small, weeping, itchy patches of skin.
In addition to the capsule, which protects the pathogen from inactivation by complement , two groups of virulence factors can be distinguished functionally : toxins and adhesins .
- Adherence factors The two most important adherence factors are filament hemagglutinin (FHA) and pertussis toxin (PT), which can function as both an exotoxin and an adhesin . In addition, B. pertussis has different antigenetically different fimbriae , which are responsible for the further stabilization of the attachment to the epithelial cells of the upper respiratory tract . In the bacterium has at the outer membrane , the membrane proteins pertactin and brka ( Bordetella resistance to killing ) that contribute to the binding to the host cells.
- Exotoxins Of crucial importance for the pathogenesis of whooping cough is the pertussis toxin (PT), which is composed of six subunits ( hexamer ) and is related to other toxins of the AB type such as cholera toxin , shiga toxin and diphtheria toxin . The actually toxic component is monomer A, which isstabilizedby five other subunits that togetherform oligomer B. The monomer A is an ADP-ribosyltransferase which u. a. triggersan altered signal transduction within the epithelial cell. The PT also sensitizes the body to histamine , increases leukocyte production and increases insulin secretion . Another protein, the invasive adenylate cyclase (CyaA), canpenetratethe host cell to leadto an unphysiologically high cAMP level there.
- Endotoxins The tracheal cytotoxin (TCT)formedfrom the peptidoglycan in the cell wallstops the movement of the cilia.
The outer membrane of the bacteria contains lipooligosaccharides , which are chemically and in their effect on the host similar to the lipopolysaccharides of other gram-negative pathogens. Even if they do not seem to have a role in the natural infection, they are possibly responsible for some of the undesirable side effects of cellular vaccines (whole-germ vaccines ).
Pathogen detection
Since other pathogens such as Bordetella parapertussis , Bordetella bronchiseptica , Chlamydia trachomatis and adenoviruses can temporarily cause symptoms similar to Bordetella pertussis , bacteriological-serological diagnostics play a decisive role. A definitive confirmation of the diagnosis is currently possible through the cultural detection of the pathogen by means of cultivation or by detection using the polymerase chain reaction .
Isolation of the pathogen
Isolation is easiest in the early convulsive stage of whooping cough on immediately inoculated culture media . H. in the first two weeks after the onset of typical clinical symptoms . A flexible calcium alginate or Dacron swab should be used to collect the specimen from the posterior nasopharynx , not the throat , leaving the swab there for about 5 to 10 seconds. Then the immediate should inoculation of the selective medium are made or pending investment of bacterial culture of the swab is placed in a transport medium. The success rate of pathogen cultivation drops significantly in patients who have been pretreated with antibiotics ( erythromycin or trimethoprim-sulfamethoxazole ) as well as in the case of delayed creation of the smear material, if the symptoms began a long time ago (more than 3 weeks) and in vaccinated patients.
Culture
Bordetella species are strictly aerobic and have very simple requirements for culture media. Only an offer of nicotinic acid amide , cystine or cysteine and other amino acids as a nitrogen source are considered growth requirements. However, by accompanying substances in the nutrient medium, such. B. unsaturated fatty acids , metal ions , colloidal sulfur and peroxides , the growth of the culture can be inhibited. With a generation time of 2.5 to 5 hours, growth is quite slow. This is why an incubation period of 3 to 4 days at 37 ° C is necessary for colony formation. Since the bacterium is very sensitive to dehydration, sufficient moisture in the nutrient medium is necessary. Before a negative result is confirmed, the culture media must be incubated for at least 7 days.
determination
The definitive determination of the cultured bacteria as Bordetella pertussis is achieved by the direct immunofluorescence test or by agglutination with specific, commercially available sera.
Biochemical behavior
The otherwise biochemically relatively inactive Bordetellen have the enzyme catalase . However, it is possible to differentiate them on the basis of certain biochemical parameters (mobility, growth on peptone agar , pigment production, nitrate reductase activity, urea cleavage and oxidase reduction ).
Polymerase chain reaction
Cultivating the pathogen from B. pertussis often leads to less informative results in medical practice. The cultural pathogen detection is only successful in about half of the cases, and this only leads to definitive statements after 3–5 days. A much more reliable and faster method is real-time PCR ( polymerase chain reaction ). A round robin test published in 1998 at 15 laboratories in Germany and Switzerland proves the reliability of the method, which is around a power of ten more sensitive than cultivation and yet only gave 4% false positive results.
Epidemiology
The bacterium occurs globally. The human organism is the only host . Sources of infection are people with whooping cough , especially during the catarrhal stage , who cough up the pathogen. Vaccinated persons are largely protected from the disease, but can be temporarily populated with brothels and thus represent a source of infection. In addition, transmission via contaminated objects cannot be ruled out, since the pertussis bacterium is resistant to dehydration and can survive outside the organism for a few days. Because of the high contagion index in non-immune humans, B. pertussis can spread epidemically in populations with a low infection rate . But even in regions with a high vaccination rate, the pertussis pathogen remains endemic , as the decrease in immunity allows colonization. An eradication of the pathogen is not possible from today's perspective. Even herd immunity through vaccination programs is not possible. There is no difference in morbidity between boys and girls. Neither do the season and climate play a role in the incidence of the disease.
Immunity and prophylaxis
After a natural infection, there is viable immunity for the first decade after the disease . The most important prophylactic measure is vaccination (active immunization). A whole-germ vaccine (cellular vaccine ) and various acellular vaccines exist for this .
- Whole cell vaccine ( whole cell vaccine ): inactivated Bordetella pertussis cells derived lysates
- acellular vaccines ( subunit vaccines ): mixtures of Bordetella pertussis components
The currently approved preparations of both categories offer very good vaccination protection if the immunization scheme is fully carried out , but neither vaccination nor disease guarantee lifelong protection against infection with B. pertussis . Adults are less likely to get sick and are less severe than children or infants. From a medical point of view, vaccination rates of more than 90% should be aimed at in order to build up a cohort protection that offers maximum protection for newborns and children in the first months of life.
Research history
In 1906 the bacteriologists Jules Bordet and Octave Gengou identified a difficult-to-breed bacterium as the causative agent of whooping cough. Initially it was assigned to the hemophilic rod- shaped bacteria as Bordet-Gengou-Bacillus . In the later necessary classification , the name Bordetella pertussis was chosen in honor of Bordet . In 2002 the genome of the whooping cough pathogen, which consists of a total of 3800 individual genes, was deciphered by an international team of researchers at Cambridge University after more than four years of research .
Reporting requirement
In Germany, direct or indirect evidence of Bordetella pertussis must be reported by name in accordance with Section 7 of the Infection Protection Act , if the evidence indicates an acute infection. Laboratories etc. are required to report ( Section 8 IfSG).
literature
- Georg Plum: The genus Bordetella (whooping cough). In: Werner Köhler et al. (Ed.): Medical Microbiology. 8th completely revised edition. Urban & Fischer, Munich et al. 2001, ISBN 3-437-41640-5 , pp. 359–365.
- Fritz H. Kayser: Bacteria as Pathogens. In: Fritz H. Kayser et al. (Hrsg.): Medical Microbiology. Understand - Learn - Look Up. 10th completely revised edition. Thieme, Stuttgart et al. 2001, ISBN 3-13-444810-6 , pp. 239-360.
Web links
Individual evidence
- ↑ S. Swidsinski, G. Schmidt-Schläpfer, B. Schneeweiß, A. Swidsinski: Pertussis-PCR New standard in whooping cough diagnosis Evaluation of a first multicenter round-robin test in Germany and Switzerland . In: Monthly Pediatrics . 146, No. 12, 1998, pp. 1171-1175. ISSN 0026-9298 . doi : 10.1007 / s001120050375 .
- ^ Stanley A. Plotkin , Walter Orenstein, Paul A. Offit, Kathryn M. Edwards: Plotkin's Vaccines. Elsevier, 2017. ISBN 9780323393010 . P. 725.
- ↑ Vaccination against pertussis: Frequently asked questions and answers , Robert Koch Institute, online December 14, 2012, accessed September 18, 2019
- ↑ RKI guidebook whooping cough (pertussis) , online as of November 27, 2017, accessed on September 19, 2019
- ↑ Pertussis Frequently Asked Questions , [Centers for Disease Control and Prevention], online April 1, 2019, accessed September 19, 2019