Whooping Cough

Epidemiology

Before a vaccine was introduced in the 1950’s around 120,000 cases occurred annually in England and Wales (1), compared to 929 laboratory-confirmed cases of pertussis reported throughout 2023 (2,3). Classically, pertussis was a highly infectious disease of infants, particularly those under 3 months of age who were yet to be vaccinated.

Pertussis is a cyclical disease that peaks every 3 to 5 years, with the last cyclical increase occurring in 2016 and the last major outbreak occurring in 2012, in which 9710 laboratory-confirmed cases occurred in England and Wales (2,3). Intervention measures implemented to help control the spread of COVID-19 between March 2020 and July 2021 also had an impact on other infectious diseases, including pertussis, resulting in pertussis activity being exceptionally low across England from April 2020 until Summer 2023, after which case numbers began to increase (2).

However, since 2006 incidence has risen rapidly in older children and adults, with the overwhelming majority of cases now occurring in those aged 15 and over (2,3). This increase in cases diagnosed in older children and adults is likely due to the introduction of improved diagnostic tests rather than a true rise in incidence (4).

Despite this increase, cases in older children and adults tend to be much milder, whilst infants remain most at risk of hospitalisation and death due to pertussis (5).

Vaccination

The whooping cough vaccine is given as part of the 6-in-1 vaccine offered to children at 2, 3 and 4 months of age, with a booster at 3 years and 4 months, as part of the 4-in-1 pre-school vaccines (1). Immunity granted by the vaccination wanes after 5 to 10 years, but infection is much milder in adolescents and adults (7).

In 2012, a temporary program of vaccination of pregnant women was introduced in the UK, with the aim of conferring passive immunity in the first few months of life (to offer protection before vaccination) through the transfer of maternal antibodies in utero (5). This program was extended in 2014 for at least another 5 years after it was found to be safe and effective (5).

Pathophysiology

Bordetella Pertussis is a gram-negative bacillus which spreads through aerosolised droplets produced by the cough or sneeze of an infected individual. The bacteria attach to the respiratory epithelium and produce toxins which paralyse the cilia and promote inflammation, impairing the clearance of respiratory secretions, which leads to a cough (8).

Bordetella Pertussis is highly contagious, with up to 90% of household contacts developing the disease (9).

Risk factors

The primary risk factors for pertussis are non-vaccination and exposure to an infected individual (especially during the catarrhal phase) (8).

Clinical features

Whooping cough has three phases of symptoms: catarrhal, paroxysmal and convalescent (1).

The first phase, the catarrhal phase, lasts 1 to 2 weeks and produces symptoms including:

• Rhinitis
• Conjunctivitis
• Irritability
• Sore throat
• Low-grade fever
• Dry cough

As these symptoms mimic other upper respiratory tract infections, pertussis is rarely diagnosed at this stage unless there has been contact with an individual known to be infected. People are most infectious during this stage (1).

The second phase is the paroxysmal phase, which typically lasts for 1-6 weeks but can last up to 10 weeks. This is the time when complications frequently occur. This phase is characterised by episodes of severe paroxysms of coughing consisting of a short expiratory burst followed by an inspiratory gasp, producing the classic “whoop” sound. A paroxysm is a rapid, violent and uncontrolled coughing fit, which occurs as a result of difficulty when expelling thick mucus from the tracheobronchial tree (1).

In infants below 3 months of age, the “whoop” is less common and apnoea is more often a feature. These paroxysms of coughing are more common at night, are often followed by vomiting (post-tussive vomiting) and may be severe enough to cause cyanosis in children.

Adults may experience sweating attacks with facial flushing, and rarely, cough syncope. Fever is absent or minimal.

Finally, the third phase is the convalescent phase, during which the cough gradually decreases in frequency and severity. This phase may last up to 3 months (1).

In uncomplicated pertussis, there is often little to find on examination. There is sometimes a low-grade fever. Conjunctival haemorrhages and facial petechiae may be present due to vigorous coughing; however, chest auscultation is usually normal (11).

Differential diagnoses

The main differential diagnoses to consider in a child presenting with a paroxysmal cough are listed below, with key features that increase the likelihood of each diagnosis in bullet points beneath (12).

Bronchiolitis/viral respiratory infection

• Wheeze and / or crackles (absent in pertussis)
• Age under 1 year
• Acute history

Mycoplasma pneumonia

• Chest signs: Wheeze and/or crackles (absent in pertussis)
• No lymphocytosis and usually a normal white cell count
• Nasopharyngeal PCR confirmation

Bacterial pneumonia

• Chest signs: Focal crackles
• High temperature

Asthma

• Chronic night-time cough, or exercise-induced cough

• Recurrent episodes of breathlessness or wheeze relieved by bronchodilators (absent in pertussis)

• Personal or family history of atopy, eg. eczema, hayfever or asthma

Tuberculosis

• Chronic cough
• Growth failure/weight loss (absent in pertussis)
• History of contact with an individual with TB, or travel to a TB endemic country
• Tuberculin skin test findings
  

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Investigations

Investigations used to diagnose pertussis differ depending on the patient’s age, duration of symptoms, and local laboratory facilities.

If the cough is less than 2 weeks in duration, a culture isolating B. pertussis from a nasopharyngeal aspirate or nasopharyngeal swab is recommended. PCR testing of a nasopharyngeal swab may also be done in severe illness as results are available sooner than with cultures.

If the cough is greater than 2 weeks in duration, anti-pertussis toxin IgG serology is recommended in children under 5 and adults, whereas anti-pertussis toxin IgG detection in oral fluid (OFT) is recommended in children aged 2-17. A limitation of both serology and oral fluid testing is that a pertussis vaccine within the last year can produce a false positive (1).

FBC usually reveals a lymphocytosis (+/- elevated white cell count).

Whooping cough is a notifiable disease; therefore, if suspected, notify the local UK Health Security Agency (UKHSA) health protection team within 3 days.

Management

Hospital admission (with appropriate isolation) is indicated for those:

• Who are under 6 months of age and acutely unwell
• With significant breathing difficulties, e.g. apnoeic episodes, cyanosis, respiratory distress or severe paroxysms of coughing
• Feeding difficulties
• With significant complications, e.g. pneumonia or seizures

Antibiotics do not alter the clinical course once the disease is established; however, they may reduce the period of infectivity when given early on in the course of the illness. A macrolide antibiotic should be prescribed when the duration of the cough is less than 21 days:

• For those under 1 month, clarithromycin is preferred. 
• Azithromycin or Clarithromycin are preferred for children over 1 month
• Co-trimoxazole is the 2^nd line antibiotic where macrolides are contra-indicated or poorly tolerated (however this should not be prescribed to pregnant women or infants under 6 weeks) (1)
• For pregnant women, prescribe erythromycin. The 2^nd line option is azithromycin and 3^rd line clarithromycin. (1)

Further management is supportive, including rest, paracetamol and/or ibuprofen for symptomatic relief and adequate fluid intake to prevent dehydration.

Parents should be notified that despite antibiotic treatment the cough may take up to 3 months to resolve. In addition, parents should be made aware of the symptoms of possible complications and to seek medical help if these develop. The child should avoid nursery or school for 14 days from the onset of coughing, or have had antibiotics for 48 hours (1).

Antibiotic prophylaxis should be offered to close contacts when coughing has started within the previous 14 days, and the close contact is considered to be a ‘vulnerable’ individual. (1).

Complications

More serious complications include:

• Secondary bacterial pneumonia (up to 20% of infants)
• Seizures
• Encephalopathy (rare)

Less serious complications include:

• Otitis media

Complications and a poor prognosis are most likely in unvaccinated young infants, with a mortality rate of 3.5% in children under 6 months of age compared to 0.03% in those over 6 months. In those with some immunity (vaccination or previous pertussis infection) the disease is usually mild and serious complications are very rare (1).

References

Authors:

1st Author: Trainee doctor Sam Romaine

Senior review: Dr Razi Paracha, Paediatric ST5

Updated by: Dr Amina Shabbir and Dr Sara Kussad