Bordetella pertussis

Bordetella pertussis

Bordetella pertussis is a bacterium of the genus Bordetella, as the causative agent of whooping cough is of great medical importance.

Morphology

It is in Bordetella pertussis small (approx. 0.8 x 0.4 microns ), coccoid non-motile, Gram-negative rods whose sole habitat are the ciliated epithelial cells of the human respiratory tract. They appear on the microscopic slide individually or stored in pairs. Colonies of B. pertussis are small, smooth and shiny with a high convexity (such as a mercury bead). The germ can be cultured on special media within 3 to 4 days at 37 ° C in an aerobic atmosphere. It grows with β - hemolysis and can be morphologically difficult to distinguish from other Bordetella parapertussis and B. bronchiseptica as B..

Pathogenesis

Bordetella pertussis overcomes the local immune mechanisms of the upper respiratory tract and can trigger in complete host health with no predisposing factors a disease. The bacterium is transmitted airborne (droplet infection). By means of various adhesins, the bacteria bind very tightly to the cells of the epithelium, and can cause a condition caused by the release of toxins. An invasion into the epithelium is rare; it comes to the (sub - ) epithelial inflammation and necrosis. Although the pathogens are generally non-invasive, i.e., not in the tissue or enter the blood stream to pass through the toxins produced but systemic effects.

In addition to the capsule, which offers protection against the pathogen inactivation by complement, can be functionally distinguish two groups of virulence factors: toxins and adhesins.

• The two most important adherence factors adherence factors that are Filamenthämagglutinin (FHA) and the pertussis toxin (PT ), which can function both as exotoxin as well as an adhesin. In addition, as has pertussis different antigenically distinct fimbriae, which are responsible for the further stabilization of the adhesion to the epithelial cells of the upper respiratory tract. Furthermore, the bacterium has at the outer membrane, the membrane proteins and pertactin 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 pertussis toxin ( PT), which consists of six subunits ( hexamer ) is constructed and has kinship to other toxins of the AB type such as cholera toxin, shiga toxin and diphtheria toxin. The actual toxic component is a monomer A which is of five different subunits which together form the oligomer B is stabilized. The monomer A is an ADP- ribosyl transferase that initiates inter alia, an altered signal transduction within the epithelial cell. The PT sensitized beyond the body for histamine, ensures enhanced Leukozytenbildung and enhances insulin secretion. Another protein, the invasive adenylate cyclase ( CyaA ), can penetrate into the host cell is there to lead to a non-physiologically high levels of cAMP.

• Endotoxins The tracheal formed from the peptidoglycan of the cell wall cytotoxin (TCT ) leads to a standstill of the ciliary.

In the outer membrane of the bacteria are lipooligosaccharides that the lipopolysaccharides of other gram -negative pathogens are similar chemically and in their effect on the host. Even if they seem to have no role in the natural infection, they are possibly for some of the unwanted side effects of the cellular vaccine (full seed vaccines) responsible.

Pathogen detection

Since, under certain circumstances, other pathogens such as Bordetella parapertussis, Bordetella bronchiseptica, Chlamydia trachomatis and adenoviruses can cause temporary symptoms similar to Bordetella pertussis, the bacteriological- serological diagnosis plays a crucial role. A definitive diagnosis is currently made ​​possible by the cultural detection of pathogens by culturing or by detection by polymerase chain reaction.

Isolation of the pathogen

On directly inoculated culture media, the isolation succeed most easily in the early stage of paroxysmal whooping cough, that is, in the first two weeks after onset of typical clinical symptoms. The sample should be, but not won with a flexible calcium alginate or Dacron swab from the posterior nasopharynx from the throat, where the swab is left about 5 to 10 seconds there. Then the immediate inoculation of the selective medium should be or will be given to the installation of the bacterial culture of the swab in a transport medium. The success rate of bacterial culture with antibiotic drops significantly ( erythromycin or trimethoprim -sulfamethoxazole ) pretreated patients and in delayed conditioning of the swab material, with long being off the onset of symptoms (more than 3 weeks) and in vaccinated patients.

Culture

Bordetella species are strict aerobes and have very simple demands on nutrient media. Only one offer to nicotinamide, cystine or cysteine ​​and other amino acids as a nitrogen source are considered growth conditions. However, can be inhibited by substances present in the soil, such as unsaturated fatty acids, metal ions, colloidal sulfur and peroxides, the growth of the culture. With a generation time of 2.5 to 5 hours, the growth is very slow. Therefore, a 3 to 4 -day incubation at 37 ° C for colony formation is necessary. Since the bacterium is very sensitive to desiccation, sufficient moisture of the medium is necessary. Before a negative finding is backed up, the nutrient media should be incubated for at least 7 days.

Determination

The final determination of the cultured bacteria Bordetella pertussis is achieved by direct immunofluorescence assay, or by agglutination with specific commercially available sera.

Biochemical Behavior

The otherwise relatively inactive biochemically bordetellae contain the enzyme catalase. However, their differentiation based on certain biochemical parameters ( motility, growth on peptone agar, pigment production, nitrate reductase activity, urea cleavage and Oxidasereduktion ) is possible.

Polymerase chain reaction

The Erregeranzüchtung of B. pertussis leads in medical practice often will not produce useful results. Only in about half the cases succeed the cultural detection of pathogens, which also only after 3-5 days results in final statements. A much more reliable and faster method is the real-time PCR ( polymerase chain reaction). A 1998 published interlaboratory comparison to 15 laboratories in Germany and Switzerland can prove the reliability of the method, which is more sensitive by about one order of magnitude than the cultivation and yet only 4% gave false-positive results.

Epidemiology

The bacterium is found globally. The human organism is a single host. Source of infection with whooping cough sufferers during the catarrhal stage, the cough up the pathogen. Healthy germ carriers do not exist. In addition, can not be excluded transmission through contaminated objects, as the pertussis bacterium can survive for several days outside the body. Because of the high contagion index in non-immune people to B. pertussis epidemic can spread in populations with niederiger seroprevalence. In regions with high vaccination rate of pertussis pathogen is endemic, because the immunity discount allowed colonization. There is no difference in the morbidity of boys and girls. Nor play season and climate for the incidence a role.

Immunity and prophylaxis

After natural infection is in the first decade after the disease a viable immunity. The most important prophylactic measure is the active immunization. Purpose, there are a whole cell vaccine (cellular vaccine ) and various acellular vaccines.

• Lysates of inactivated Bordetella pertussis cells obtained: whole cell vaccine ( whole cell vaccine )
• Acellular vaccine ( subunit vaccines ): Mixtures of Bordetella pertussis components

The currently approved drugs in both categories offer fully guided immunization scheme a very good vaccination, but neither vaccine nor disease guarantee life-long protection against infection with B. pertussis. Adults fall ill less often and less severe as children or infants. From a medical perspective vaccination rates of more than 90 % are to strive to build a cohort protection, which offers a maximum protection of infants and children in the first months of life.

History of Research

1906 was a difficult anzüchtbares bacteria are first identified by the bacteriologists, Jules Bordet and Octave Gengou as the causative agent of whooping cough. At first it was as Bordet - Gengou bacillus associated with the hemophilic bacilli. In the classification necessary later the name was chosen in honor of Bordetella pertussis Bordets. In 2002, the genome of the whooping cough agent, which consists of a total of 3800 individual genes has been decrypted after more than four years of research by an international team of researchers at the University of Cambridge.