Bordetella pertussis

Bordetella was first described and cultivated in 1906 by the Belgian researchers Jules Bordet and Octave Gengou.

Bordetella pertussis is the classic pathogen of whooping cough. It is present worldwide. Less frequently, infections with B. parapertussis or B. holmesii can also lead to a whooping cough-like clinical picture, but the course is usually milder and shorter than with an infection by B. pertussis. In 2015-2018, 3-4% of transmitted pertussis illnesses were caused by B. parapertussis; in 2019, this proportion increased to 9% (RKI data).

The bacterium is a small gram-negative, immobile, encapsulated, coccoid, aerobic rod. It produces a variety of toxins and virulence factors. On the surface of the bacterium are outer membrane proteins, fimbriae, and lipopolysaccharides.

Route of infection: Pertussis is highly contagious. Transmission occurs by droplet infection. While persistent carriage of bordetella in the nasopharynx has not been described, B. pertussis has occasionally been detected in the nasopharynx of persons in the vicinity of outbreaks, including those vaccinated against pertussis. Adolescents and adults play an important role as carriers to infants. Bordetellae multiply on the ciliary epithelium of the respiratory mucosa. There they cause local destruction of the mucosa. Some of the toxins also locally impair the immune system and cause tissue damage.

Pertussis occurs year-round, with a slightly higher incidence in autumn and winter than in the rest of the year. Similar to other Western countries, despite high vaccination rates among younger children - in 2018, the vaccination rate of school beginners was approximately 93% - cyclical increases in pertussis continue to be observed in Germany at intervals of 4 to 6 years (RKI). Since the introduction of the nationwide pertussis reporting requirement in 2013, between 11 and 20 cases (Erkr.) per 100,000 inhabitants (Einw.) per year have been reported to the RKI nationwide according to the Infection Protection Act (Infektionsschutzgesetz, IfSG). Infants are most affected in epidemic years, with incidences of more than 100 ill./100,000 inhabitants, and often require hospital treatment. Therefore, the STIKO 2020 has recommended pertussis vaccination for women during pregnancy (see below). Due to a rapid decline in immune protection after vaccination, pertussis illnesses also occur in older children and adolescents. Although the incidence is lower in adults,approximately 60% of all cases now occur in persons ≥ 18 years of age. This is due to insufficient implementation of the recommended booster vaccinations, especially in adolescents and adults.

Virulence factors of Bordetella pertussis:

• Bordetella pertussis produces a variety of toxins and virulence factors, such as.
• Pertussis toxin (PT; lymphocytosis promoting-factor )
• Filamentous haemagglutinin (FHA): adhesion protein on the cell surface.
• Tracheacytotoxin: intoxication of effector cells, by increased intracellular cAMP
• Pertactin:proteins of the outer membrane (adhesion factor)
• Heat-labile toxin: (proteotoxin, presumably smooth muscle spasm (Hof et al. 2019)
• Adenylate cyclase hemolysin.
• Lipooligosaccharide: endotxin-like,pyrogenic, cytotin release.
• Fimbriae: adhesionpili, adhesion factor, classification of serotypes.

Reservoir: Humans are the only reservoir for B. pertussis and B. holmesii. B. parapertussis is found in humans and sheep. Duration of contagiousness: Contagiousness begins at the end of the incubation period, peaks during the first two weeks of illness and may last up to three weeks after the onset of stage convulsivum (see below). When antibiotic therapy is administered, the duration of contagiousness is shortened to about three to seven days after initiation of therapy, depending on the antibiotic used (Srinivasan R et al. 2005). For clarithromycin and erythromycin, complete microbiological eradication has been demonstrated 7 days after initiation of therapy (Lebel MH et al 2001). The elimination of microorganisms plays a particularly important role in people who have close contact with high-risk patients (infants, health care workers, pregnant women in the last month before birth).

Incubation period: Usually 9-10 days (range: 6-20 days) (Hof H et al.).

Duration of infection: Pertussis can last several weeks to months. The typical initial infection in the unvaccinated progresses in three stages:

• Stage catarrhale (duration 1-2 weeks; interval 5-21 days): It is characterized by cold-like symptoms, such as rhinitis and mild cough, but usually no or only moderate fever. Only in this stage the cultural detection of Bordetella pertussis is successful (best by means of a deep calcium alginate swab from the nose; Note: special medium - e.g. Regan-Lowe medium).
• Stage convulsivum (duration 4-6 weeks): In this stage, there are the classic symptoms of seizure-like coughing jerks (cough staccato) followed by convulsive inspiratory dragging. The typical wheezing results from sudden inspiration against a closed glottis at the end of the attack. The coughing attacks are often accompanied by regurgitation of viscous mucus followed by vomiting. Attacks may be numerous and occur more frequently at night in some patients. Fever is still absent or low; higher temperatures may be due to secondary bacterial infection.
• Stage decrementi (duration 6-10 weeks): Gradual resolution of the coughing episodes occurs. In adolescents and adults, as well as in many vaccinated children, pertussis often presents merely as a prolonged cough without the classic accompanying symptoms, such as spasmodic cough, inspiratory stridor, or vomiting.

In infants, too, the course of the disease is often atypical, with apnea often in the foreground as a symptom. Infants also have the highest risk of serious complications. Accordingly, a high proportion of all hospitalizations and almost all deaths involve young, unvaccinated infants under 6 months of age.

Complication: The most common complication is pneumonia, usually caused by superinfection with other bacterial pathogens, especially pneumococcus or unencapsulated Haemophilus influenzae. Pneumonia affects up to 10% of ill infants and the elderly, and is less common in older children and younger adults (Hof H et al.2019). Other complications: otitidis, sinusitis, incontinence, hernia, rib fracture, and subconjunctival hemorrhage have been reported (De Serres G et al.2000; Heininger U et al. 1997).

Rare neurologic complications may include cerebral seizures and encephalopathies. The cause of death in infants is often hyperleukocytosis with up to 100,000/mm3, resulting in severe hypoxemia and pulmonary hypertension (Liese JG et al 2013).

Since pertussis often does not present with the classic symptoms, particularly in adults, but also in older children and adolescents, laboratory diagnostics are crucial for making the diagnosis.

The type of laboratory diagnosis depends on the stage of disease, i.e., in the first 2 to 3 weeks after the onset of cough, detection of B. pertussis and B. parapertussis from deep nasopharyngeal swabs, nasopharyngeal secretions, or material obtained during aspiration by culture or nucleic acid amplification technique (NAT), usually PCR, is strongly recommended. Rayon, nylon or polyester swabs on flexible aluminium wire should be used, but not calcium alginate or cotton swabs, as these cannot be used for PCR. Swabs should be shipped to the laboratory either dry (for PCR studies) or in Amies medium (allows culture and PCR) in sterile tubes.B. pertussis takes three to seven days to grow and B. parapertussis takes at least two days.

Serodiagnosis is unsuitable for early diagnosis of pertussis disease because specific antibodies in serum are not detectable until about 3 weeks after the onset of coughing (De Serres G et al.(2000). In infants, direct detection should always be aimed for, as serological diagnostics are not conclusive due to the possible presence of maternal antibodies.

The method of choice for serological diagnostics is the performance of an enzyme-linked immunosorbent assay (ELISA) for the detection of IgG antibodies against PT. IgG antibody detections against PT are best validated for pertussis diagnosis.

IgA antibodies can be used to confirm an IgG PT antibody finding in the gray area.

IgM antibodies to pertussis are not informative.

The ECDC and the European Laboratory Network for Pertussis have issued recommendations for the performance of serological diagnostics (European Centre for Disease Prevention and Control. Guidance and Protocol for the serological diagnosis of human infection with Bordetella pertussis. Stockholm2012; Guiso N et al. 2011). The following threshold values are recommended for serological diagnosis in Germany:

• Indication of recent pathogen contact: PT IgG antibodies ≥ 100 IU/ml (based on a WHO reference preparation).
• No indication of recent pathogen contact: IgG-PT < 40 IU/ml
• Ensure specificity: IgG-PT antibodies ≥ 40 IU/ml but < 100 IU/ml (examination of a second sample or additional presence of significantly elevated IgA antibodies (>12 IU/ml) against PT)

From today's perspective, eradication of pertussis is not possible. Due to the limited duration of immunity both after natural disease and after complete vaccination, each person can become reinfected and ill several times in their lifetime. The goals of the current vaccination strategy in Germany are therefore the earliest possible and complete vaccination protection for infants and young children who are particularly at risk from B. pertussis (basic immunization). In addition, booster immunization is necessary in preschool and adolescent age as well as in adults to maintain the clinical efficacy of the vaccine protection and to minimize transmission to unvaccinated and non-immune individuals.

For vaccination strategies, see below. Pertussis

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2. De Serres G et al.(2000) Morbidity of pertussis in adolescents and adults. J Infect Dis 182:174-179
3. European Centre for Disease Prevention and Control. Guidance and Protocol for the serological diagnosis of human infection with Bordetella pertussis. Stockholm2012
4. Guiso N et al. (2011) What to do and what not to do in serological diagnosis of pertussis: recommendations from EU reference laboratories. Eur J Clin Microbiol Infect Dis 30:307-312.
5. Heymann DL (2015) . Control of communicable diseases manual. 20 ed. Washington, D.C.: American Public Health Association.
6. Heininger U et al.(1997) Clinical findings in Bordetella pertussis infections: results of a prospective multicenter surveillance study. Pediatrics 100:e10
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8. Kadlec K et al.(2018) Antimicrobial resistance in Bordetella bronchiseptica. Microbiol Spectr 6(4).
9. Lebel MH et al. (2001) Efficacy and safety of clarithromycin versus erythromycin for the treatment of pertussis: a prospective, randomized, single blind trial. Pediatr Infect Dis J 20:1149-1154
10. Liese JG et al (2013) Pertussis. In: DGPI, ed. DGPI Handbook of infections in children and adolescents. Stuttgart-New York: Georg Thieme Verlag pp 434-439.
11. Radcliffe C et al (2020) Bordetella bronchiseptica: a rare cause of meningitis. BMC Infect Dis 20:922.
12. RKI(2021) Guide to pertussis. https://www.rki.de/DE/Content/Infekt/EpidBull/Merkblaetter/Ratgeber_Pertussis.html
13. Srinivasan R et al.(2005) Are newer macrolides effective in eradicating carriage of pertussis? Arch Dis Child 90:322-324
14. Woods P et al (2020) Bordetella bronchiseptica Pneumonia in an Adolescent: Case Report and Review of the Pediatric Literature. Clin Pediatr (Phila) 59:322-328