Whooping Cough (Pertussis)

Introduction

Whooping cough is an acute respiratory infection caused by Bordetella pertussis. The name describes only one of its features, and not the one that matters most: the sound is dramatic but the danger lies in apnoea, hypoxia and secondary pneumonia in infants too young to have been immunised.

Pertussis is a notifiable disease in the UK, and suspicion alone is enough to trigger notification - you do not wait for laboratory confirmation.⁷ It follows a cyclical pattern with peaks every 3-4 years, and the UK has seen substantial resurgences, including a large outbreak in 2012 that prompted the introduction of the maternal vaccination programme, and a further resurgence in 2023-24 with infant deaths.²

For exam purposes there are three things to have straight: the phased natural history, which explains why the diagnosis is so often missed early and confirmed late; the choice of test, which depends entirely on how long the cough has lasted; and the fact that antibiotics are given to protect other people rather than to make the patient better.

Pathophysiology

B. pertussis is spread in respiratory droplets and adheres to ciliated respiratory epithelium using surface adhesins including filamentous haemagglutinin and pertactin. It does not invade the bloodstream. Almost all of the disease is caused by locally released toxins.

• Tracheal cytotoxin paralyses and then destroys the cilia, abolishing mucociliary clearance. Secretions accumulate and can only be cleared by violent coughing - which is precisely what the paroxysms are.
• Pertussis toxin causes the characteristic lymphocytosis by blocking lymphocyte migration out of the circulation, impairs neutrophil chemotaxis and macrophage killing, and contributes to the hypoglycaemia and hyperinsulinaemia sometimes seen in infants
• Adenylate cyclase toxin raises intracellular cyclic AMP in phagocytes, further impairing the immune response
• Dermonecrotic toxin and lipopolysaccharide contribute to local epithelial damage and inflammation

Two consequences follow. First, because the damage is toxin-mediated and largely done by the time the paroxysms begin, killing the organism with antibiotics late in the illness does not shorten it. Second, the extreme leucocytosis in severe infant disease is not merely a marker: white cell aggregates in the pulmonary microvasculature cause pulmonary hypertension and are the mechanism of so-called malignant pertussis.

Neither natural infection nor vaccination confers lifelong immunity. Protection wanes over roughly 4-12 years, which is why adolescents and adults act as the reservoir and are usually the source of infection for a young infant. In practice the index case is very often a coughing parent, sibling or grandparent whose own illness was dismissed as a lingering viral cough.

Clinical features

The incubation period is 7-10 days, occasionally up to 21. The illness then passes through three recognisable phases.

The paroxysm

A paroxysm is a run of coughs within one expiration, without an opportunity to breathe in, followed by a forced inspiration against a partially closed glottis - the whoop. Bouts are typically worse at night, are triggered by feeding, crying, cold air or excitement, and may end in vomiting or in brief syncope. Between bouts the child looks and behaves normally, which is a strong clue and is often the point at which the history becomes diagnostic.

• Post-tussive vomiting is one of the most specific features in an older child or adult
• Subconjunctival haemorrhages, facial petechiae and epistaxis from the raised venous pressure during paroxysms
• Tongue protrusion and cyanosis during a bout, with a red face and bulging veins
• A normal chest examination and no fever in an uncomplicated case - a high fever should make you look for secondary pneumonia
• Sleep disruption, weight loss and exhaustion, in both the child and the family

Differential diagnosis

• Viral upper or lower respiratory tract infection - the usual explanation, and the reason pertussis is missed in the catarrhal phase
• Bordetella parapertussis - a clinically identical but milder and shorter illness
• Bronchiolitis - overlaps in infants, but gives tachypnoea, wheeze and crackles rather than well periods between violent bouts
• Mycoplasma or chlamydial infection - Chlamydia trachomatis pneumonitis in the young infant gives a staccato cough, conjunctivitis and eosinophilia rather than lymphocytosis
• Inhaled foreign body - sudden onset, unilateral signs, no coryzal prodrome
• Asthma or post-viral cough - responds to bronchodilators and lacks the paroxysmal well-between-bouts pattern
• Tuberculosis - consider with weight loss, night sweats and relevant contact or travel history
• Cystic fibrosis - chronic productive cough with faltering growth and steatorrhoea

Investigations

The single most important principle is that the appropriate test depends on the duration of cough and the age of the patient, because bacterial load falls rapidly while antibody rises slowly.^1,4

Supporting investigations

• FBC - a marked lymphocytosis is characteristic. A white cell count above 30 x10^9/L in an infant, especially with a predominant lymphocytosis, predicts severe disease and possible pulmonary hypertension.
• Chest radiograph - not routine, but indicated where secondary pneumonia, pneumothorax or a foreign body is suspected. The classic but non-specific finding is perihilar infiltrates producing a shaggy right heart border.
• U&Es - hyponatraemia may complicate severe disease
• Blood glucose - hypoglycaemia can occur in infants
• Blood gas and echocardiography in a severely affected infant, to assess for respiratory failure and pulmonary hypertension

Management

Notification and admission

• Notify the local health protection team on clinical suspicion, without waiting for confirmation - this is a statutory duty⁷
• Admit any infant under 6 months who is acutely unwell, anyone with apnoea, cyanosis or significant feeding difficulty, and anyone with a complication such as pneumonia or seizures
• Have a low threshold in infants under 12 months, in whom deterioration is unpredictable and often abrupt
• Admitted patients need respiratory isolation until 48 hours of antibiotics have been given, or 21 days from the onset of symptoms if untreated

Antibiotics

Antibiotics are given if the onset of cough was within the last 21 days. Beyond that the patient is no longer infectious and treatment has no benefit at all. Even within the window, the purpose is to reduce transmission - the clinical course is largely unchanged once paroxysms are established.¹

• Infants under 1 month: clarithromycin
• Children aged 1 month and over, and adults: clarithromycin or azithromycin
• In pregnancy: erythromycin
• If a macrolide is contraindicated or not tolerated: co-trimoxazole, which is avoided in infants under 6 weeks and in pregnancy
• Treat the paroxysms symptomatically with small frequent feeds, gentle handling and a calm environment. Cough suppressants, antihistamines, corticosteroids and bronchodilators are all ineffective and should not be used.¹

Severe infant disease

Infants with apnoea, respiratory failure or an extreme leucocytosis are managed on paediatric intensive care. Supportive measures include oxygen, careful fluid and nutritional support, and mechanical ventilation where needed. Exchange transfusion or leucodepletion is used in some centres for malignant pertussis with a very high white cell count and pulmonary hypertension, on the basis that reducing the leucocyte load reduces microvascular obstruction, although the evidence is observational.

Advice for the family

Most children with pertussis are managed at home, and what the family is told largely determines whether the illness is survived comfortably or ends in a re-attendance.

• Explain the expected course honestly: paroxysms typically worsen over the first 1-2 weeks, plateau, then improve slowly over 6-12 weeks
• Feed little and often, and re-offer a feed after a bout of vomiting rather than waiting for the next scheduled one
• Keep the child upright during a paroxysm and stay with them - most bouts are frightening rather than dangerous
• Avoid known triggers where practical: cold air, cigarette smoke, vigorous exercise and excitement before sleep
• Seek urgent help for pauses in breathing, colour change, floppiness, seizures, a fever developing after the first week, or a bout the child does not recover from within a minute or so
• Keep the child away from any newborn, unimmunised infant or pregnant woman until they are no longer infectious

Public health measures

• Exclusion from school, nursery or work for 48 hours after starting appropriate antibiotics, or for 21 days from the onset of symptoms if untreated
• Chemoprophylaxis for close contacts is targeted rather than universal. It is offered where a contact is in, or is in close contact with, a priority group - unimmunised or partially immunised infants under 1 year, women from 32 weeks of pregnancy, and healthcare or childcare workers who work with infants and pregnant women - and only if the index case's cough began within the last 21 days.⁴
• Review and update immunisation in all close contacts at the same time as offering prophylaxis
• Advise the family that other household members with a persistent cough should also be assessed

Prevention

Pertussis-containing vaccines are acellular in the UK schedule and are given as combination products.³

Immunisation reduces but does not eliminate the risk of infection, and vaccinated children who do get pertussis have a milder and shorter illness. Acellular vaccines are known to give shorter-lived protection than the older whole-cell preparations, which contributes to the periodic resurgences and to the importance of boosting in pregnancy rather than relying on childhood immunity alone.

Complications

In infants

• Secondary bacterial pneumonia - the commonest cause of death
• Apnoea and hypoxia, with resulting hypoxic-ischaemic brain injury
• Pulmonary hypertension from leucocyte aggregates, the mechanism of malignant pertussis
• Seizures and encephalopathy
• Weight loss and dehydration from repeated post-tussive vomiting
• Hyponatraemia and hypoglycaemia

In older children and adults

• Subconjunctival haemorrhage, epistaxis and facial petechiae
• Rib fracture and abdominal or inguinal hernia from the force of coughing
• Pneumothorax, pneumomediastinum and surgical emphysema
• Cough syncope
• Urinary incontinence, and considerable sleep deprivation
• Bronchiectasis after severe or repeated infection, though this is uncommon

Prognosis

In an immunised older child or adult, pertussis is a miserable but self-limiting illness. The cough resolves over 6-12 weeks, giving the disease its Chinese name of the hundred-day cough, and paroxysms may briefly return with subsequent viral infections for up to a year. There is no long-term lung damage in the great majority.

For unimmunised infants the picture is very different. Almost all UK deaths occur in babies under 3 months, in whom the illness can progress from apnoea to refractory pulmonary hypertension within days. Around half of infants under 12 months with confirmed pertussis are admitted to hospital, and a significant minority require intensive care.²

That gap between the two groups is what makes the public health response the substance of this topic rather than an afterthought. Notifying promptly, treating within the 21-day window, excluding for 48 hours, targeting prophylaxis at the people who are near a newborn, and checking that every pregnant woman you meet has been offered the vaccine will do more for outcomes than anything you prescribe for the patient in front of you.