Pertussis



Whooping cough or pertussis is a highly contagious drip infection, widespread worldwide, but more than 90% of cases are reported from developing countries. The causative agent is the gram-negative bacterium Bordetella pertussis. Most patients are reported between the ages of 15 and 19 years. In adolescents and adults, pertussis tends to be mild or atypical, so it escapes attention and is not reported. These underdiagnosed patients are a source of infection for under-immunized infants and toddlers, for whom whooping cough is a serious, life-threatening disease. In recent years, there have been 4 deaths in the Czech Republic of small, unvaccinated children who have become infected by family members.

Regular pertussis vaccination was started in the Czech Republic as early as 1958. In 2003, an acellular vaccine was introduced, and on 1 January 2007, basic vaccination with a six-component vaccine with an acellular pertussis component was introduced. Vaccination cannot be started until the 9th week of life. Immunity gradually decreases with age (as well as after the disease), so since 2009 it has been revaccinated between the ages of 10 and 11. Vaccination of children in the Czech Republic is high, but after vaccination, the so-called post-vaccination immunity gradually develops, so it is possible to get sick within 3-5 years after vaccination. Nevertheless, vaccination is very important because it reduces the likelihood of a severe course of the disease and reduces the circulation of the agent in the population.

Pathogenesis

 * Infectious agent - Bordetella pertussis, a strictly aerobic gram-negative cocobacillus.
 * It produces a number of biologically active substances, some of which play a key role in adhesion and colonization (pertussis toxin, filamentous hemagglutinin, pertactin) or affect the typical clinical picture (pertussis toxin, dermonecrotic toxin, adenylate cyclase, tracheal cytotoxin). Pertussis toxin - improves the binding of microbes to the cilia of the airway epithelium, promotes mucus production and systemic manifestations, such as the histamine effect, causes lymphocytosis.
 * It causes inflammation to necrosis of the ciliated epithelium of the respiratory tract.
 * Bordetellae multiply and colonize the ciliated epithelium of the airways after entering the susceptible organism. During the catarrhal stage, they occur most in the larynx and nasopharynx, where they cause catarrhal inflammation to necrosis of the mucosal epithelium, but do not break into the bloodstream. A typical picture of the disease is peribronchitis. Paralysis of mucociliary transport, including action on cough receptors, produces an irritating cough, typical of the paroxysmal stage. Viscous secretion stagnates in the bronchioles, there may be small atelectasis and emphysema. Bordetell toxins enter the bloodstream and cause long-term systemic symptoms, regardless of antibiotic treatment. Pertussis complications can also be caused by the mechanical effects of persistent cough.
 * Parapertussis - a similar disease with a shorter duration of symptoms and mostly with a milder course. The causative agent is Bordetella parapertussis.

Epidemiology
Pertussis occurs worldwide, including in developed European countries. In the Czech Republic, infectious diseases are among the mandatory and long-term monitored. In the period before the introduction of vaccination, the morbidity reached tens of thousands of cases per year (with a maximum in 1956). After the introduction of nationwide compulsory vaccination in 1958, the number of cases of whooping cough declined rapidly, but never reached zero. An increasing trend in the disease has been registered since 1993. Previously, most patients aged 10–14 were reported, but since 2012, most patients are aged 15–19. In the adult population, the disease is often underestimated, unknown and little reported.


 * Incubation period: 6-21 days. The incidence of the disease fluctuates in 3-7 year cycles and this trend also persists in the immunized population. For susceptible individuals, the infectivity is up to 90%.
 * Transmission: close contact, droplets, aerosol.
 * The most infectious is a person in the catarrhal stage of the disease and in the first 2 weeks after the onset of cough. (A non-immune infant can excrete Bordetella for up to 6 weeks, whereas a vaccinated adolescent usually shorter for about 2 weeks.)
 * Bordetella from a nasopharyngeal swab can be captured even until the fifth day of macrolide treatment. During this time, it is advisable to isolate the patient. After a illness, there is a solid long-term, but not lifelong immunity.
 * There is no cross-immunity between B. pertussis and B. parapertussis.
 * Transplacental transmission of IgG antibodies is insufficient, therefore children < 3 months who have not yet been vaccinated may become ill!

Clinical manifestation
Clinical definition of pertussis - a cough lasting at least 2 weeks with one of the following symptoms:


 * coughing fits,
 * whooping cough,
 * vomiting after a cough attack without other obvious causes,
 * apnea pause in infants.

The incubation period is 7 to 21 days.

The disease usually lasts 6 to 8 weeks and has 3 stages:


 * 1) catarrhal (1 to 2 weeks);
 * 2) paroxysmal (2 to 6 weeks);
 * 3) convalescent (1 to 3 weeks).

The period of infectivity begins at the end of the incubation period, is highest in the early period of the catarrhal stage, then gradually decreases and usually ends 3 weeks after the onset of the paroxysmal stage or 5 days after antibiotic treatment.

The clinical manifestation depends, among other factors, on age and the state of immunity. The classic course is observed in children under 10 years of age and can be divided into 3 stages:


 * 1) Catarrhal stage:
 * 2) * Colds, coughing, usually lasting 10-15 days. It is usually clinically indistinguishable from other upper respiratory catarrhs, which prevents early diagnosis and effective antibiotic treatment.
 * 3) * General symptoms such as anorexia, fever, fatigue are insignificant and may not be expressed
 * 4) Paroxysmal stage:
 * 5) * Numerous typical bouts of irritating cough.
 * 6) ** At the apex of the attack, there may be apnea pauses followed by a loud wheezing ("crowing" inspiration), the exhalation is usually stakatous. (Children of the youngest age groups are particularly prone to apnea.)
 * 7) ** Paroxysms of cough recur daily for 6-10 weeks, but even longer in older children and more than half of adolescents. Seizures are more common at night and are quite exhausting. They can be caused by any external stimulus, food, emotions, temperature change.
 * 8) * At the same time, cyanosis may be characterized by hypoxia, nausea and vomiting.
 * 9) * With long-term exhaustion, younger children may again experience hypoventilation due to respiratory muscle fatigue and develop dangerous hypercapnia.
 * 10) * The condition between coughing fits is completely asymptomatic, which distinguishes pertussis from other respiratory infections.
 * 11) Convalescence stage:
 * 12) * There is an increased readiness to cough for minimal stimuli, but the severity of seizures and their frequency decreases.

Complications
The frequency of complications depends inversely on the patient's age.


 * Related to the mechanical effect of persistent cough - subconjunctival hemorrhage, epistaxis, subarachnoid and intraventricular hemorrhage, rupture of the tongue.
 * Bacterial superinfection Streptococcus pneumoniae → otitis and pneumonia.
 * Frequent vomiting → dehydration and development of MAL with tetanus convulsions.
 * Toxoinfectious encephalopathies are accompanied by convulsions or disorders of consciousness.
 * Elevated intrathoracic and intra-abdominal pressure result in atelectasis, pneumothorax, pneumomediastinum and hernias.
 * Pertussis in non-immunized infants has the most severe course. Cyanosis apnea attacks may not be accompanied by a typical cough. Mortality in this group reaches 1 %.

Diagnosis

 * Clinical diagnosis of pertussis on the basis of symptoms alone is difficult in the current epidemiological situation, especially in adults, where there are atypical symptoms. The classic symptoms of pertussis occur in very young children who have not been completely vaccinated.
 * Unvaccinated children typically have leukocytosis in their blood counts. Leukocytosis is not a typical finding after vaccination with at least one dose of vaccine.
 * In many cases, the X-ray finding is normal.
 * The gold standard is a cultivation that has high specificity but low sensitivity, i.e. low capture of B. pertussis. The sensitivity of cultivation decreases with time from the onset of disease symptoms. Another disadvantage is getting the result in a few days.
 * Detection of the causative agent in nasopharyngeal swabs by PCR - PCR sensitivity decreases with time from the onset of symptoms of the disease.
 * Serological examination of specific anti-PT antibodies of IgG class by ELISA method. In patients up to 5 years after the last pertussis vaccination, it is difficult to distinguish between post-vaccination and post-infection antibodies, so examination of so-called paired sera with a 4-6 week interval is recommended, when a minimum 4-fold increase is a sufficiently confirmatory result. When testing only one serum sample, the recommended diagnostic limit is the amount of anti-PT IgG antibodies > 94-110 EU / ml, which indicates a recent or active infection.

Recommended procedure in case of clinical suspicion:


 * neonates and young children - nasopharyngeal swab and / or PCR and / or culture aspirate (high specificity but low sensitivity) as soon as possible after the onset of symptoms;
 * vaccinated children and adults with cough lasting less than 2 weeks - nasopharyngeal collection for PCR and culture;
 * older children and adults - determination of IgG class anti PT (against pertussis toxin);
 * adolescents and adults with cough lasting longer than 3 weeks - PCR and anti PT IgG determination.

Bordetell cultivation takes longer (3-7 days). Preparation of a special Bordet-Gengou soil that has a short expiration. Collection of material - swab from the back wall of the nasopharynx or larynx, is usually performed in the morning on an empty stomach. The tampon on the wire bends at a slightly obtuse angle before collection. The tongue is held with a wooden spatula or a clean cloth. Capture from standard tonsil sampling is minimal. Inoculation must be prompt, so the collection of material is best done at the patient's bedside. Negative cultivation does not rule out the disease.

Differential diagnostics

 * Infections that are presented with "pertussis" cough - pertussis cough syndrome is caused by adenoviruses, RSV, influenza, parainfluenza, H. influenzae, M. pneumoniae, Ch. pneumoniae.
 * In children, cough attacks should be also taken into account the possibility of foreign body aspiration or cystic fibrosis.

Treatment
The drugs of choice are macrolides - azithromycin, clarithromycin, erythromycin. Tetracyclines and cotrimoxazole are also effective. It is important to start antibiotic therapy early, which will alleviate the course of the disease and reduce the risk of transmission to other perceived individuals. It is ideal to start treatment at the catarrhal stage before the destruction of the ciliated epithelium. In the case of late treatment, antibiotics no longer affect the paroxysmal course of the disease due to the presence of toxins in the airways, but at least minimize transmission to other individuals.

Post-exposure antibiotic prophylaxis is suitable for susceptible individuals in a family occurrence who are expected to be at high risk of severe course - ie children under 1 year of age (especially under 4 months of age) and pregnant women in the third trimester of pregnancy.

Hospitalization is recommended for infants, for older children in case of a complicated course. For infants < 3 months or for children with hypoxia, desaturation, cyanosis, apnea, placement in the ICU with continuous monitoring of vital functions is necessary.

Prevention
Pertussis vaccination is a part of compulsory vaccination in the Czech Republic. In the Czech Republic, an acellular vaccine is used, which is part of combined vaccines together with diphtheria and tetanus toxoid:


 * DTaP (Infanrix, also part of Pediacel, Hexacima vaccines) - for children from 2 months of age,
 * Tdap (Adacel, Boostrix) - for children from 7 years and adults under 65 years; a vaccine with a reduced dose of diphtheria toxoid (or tetanus toxoid) and acellular pertussis subunits.

The acellular pertussis vaccine contains: pertussis toxin, filamentous hemagglutinin, pertactin and fimbriae.

The American Center for Disease Control and Prevention (CDC) recommends vaccinating all women in the third trimester of pregnancy to prevent pertussis in early infancy.

Related articles

 * Cough
 * Vaccination calendar
 * Bordetella parapertussis
 * Bordetella pertussis