Clinical Topic A-Z Clinical Speciality

Whooping cough

Whooping cough
D014917Whooping cough
D010567Pertussis Vaccine
Child healthInfections and infestationsRespiratory
2010-12-17Last revised in December 2010

Whooping cough - Summary

Whooping cough, also known as pertussis, is a highly infectious disease caused by the bacterium Bordetella pertussis. It is spread by aerosol droplets released during coughing.

The name of the infection is derived from the characteristic 'whoops' that occur in younger children, and is caused by sharp inhalation of breath during bouts of paroxysmal cough. It disproportionately affects young children and infants.

Whooping cough is now relatively rare compared with the prevaccination era.

The incubation period of whooping cough usually lasts for about 7 days and it is considered to be infectious for 3 weeks after the onset of initial symptoms.

Whooping cough has three phases of symptoms.

The catarrhal phase lasts about a week and is characterized by the development of a dry, unproductive cough.

The paroxysmal phase may last for a month or more and is characterized by whooping, post-tussive vomiting, and generalized symptoms.

The convalescent phase may last an additional 2 months or more, and is characterized by gradual improvement in the frequency and severity of symptoms.

A clinical diagnosis of whooping cough can be made if the person has:

Clinical features consistent with whooping cough, particularly if they are not fully immunized, or have been in contact with a person who is confirmed or suspected as having whooping cough.

Had an acute cough for 14 days or more without another apparent cause and has one or more of following: inspiratory whoop, post-tussive vomiting, or paroxysmal cough.

Other conditions which can present in a similar way to whooping cough include other infections and non-infectious conditions, such as asthma, chronic obstructive pulmonary disease, post-infectious cough, post-nasal drip, gastro-oesophageal reflux, and malignancy.

Whooping cough is a notifiable disease. If there is any suspicion of infection because of clinical features, the local Health Protection Unit (HPU) should be notified by telephone as soon as is practicable, and in writing within 3 days.

In the management of whooping cough:

People who are seriously unwell should be admitted to hospital (a low threshold is required if aged 6 months of age or less).

An antibiotic (usually a macrolide, such as erythromycin or clarithromycin) should be prescribed to all people with confirmed whooping cough who have had an onset of cough within the previous 21 days.

Advice should be given on rest, adequate fluid intake, the use of paracetamol or ibuprofen for symptomatic relief, and being in contact with other people.

Close contacts may require antibiotic prophylaxis.

Have I got the right topic?

0months3060monthsBoth

This CKS topic covers the management of whooping cough (pertussis), and post-exposure to whooping cough.

This CKS topic does not cover prevention of whooping cough through vaccination. This is covered in a separate CKS topic on Immunizations - childhood.

There are separate CKS topics on Cough - acute with chest signs in children and Feverish children - risk assessment.

The target audience for this CKS topic is healthcare professionals working within the NHS in the UK, and providing first contact or primary healthcare.

How up-to-date is this topic?

How up-to-date is this topic?

Changes

Last revised in December 2010

February 2013 — minor update. The 2013 QIPP options for local implementation have been added to this topic [NICE, 2013].

November 2012 — minor update. Text and prescriptions have been revised to include updated guidance from the Health Protection Agency [HPA, 2012a]. Key changes include:

Updated prevalence data.

New definitions of priority groups requiring prophylaxis.

Revised recommendations regarding choice of antibiotic.

Revised recommendations for the use of pertussis-containing vaccine in contacts aged 10 years and older.

October 2012 — minor update. The 2012 QIPP options for local implementation have been added to this topic [NPC, 2012].

July 2011 — minor update. More recent prevalence data from the Health Protection Agency added [HPA, 2011]. Issued in September 2011.

July 2011 — minor update. More exact paracetamol dosing for children has been introduced by the Medicines and Healthcare products Regulatory Agency [MHRA, 2011]. Prescriptions have been updated to reflect the revised dosing. Issued in July 2011.

May 2011 — minor update. The 2010/2011 QIPP options for local implementation have been added to this topic [NPC, 2011]. Issued in June 2011.

March 2011 — minor update to make the topic consistent with guidance produced by the Health Protection Agency. Issued in March 2011.

September to December 2010 — this is a new CKS topic. The evidence-base has been reviewed in detail, and recommendations are clearly justified and transparently linked to the supporting evidence.

Update

New evidence

Evidence-based guidelines

No new evidence-based guidelines since 1 November 2010

HTAs (Health Technology Assessments)

No new HTAs since 1 November 2010.

Economic appraisals

No new economic appraisals relevant to England since 1 November 2010.

Systematic reviews and meta-analyses

No new systematic review or meta-analysis since 1 November 2010.

Primary evidence

No new randomized controlled trials published in the major journals since 1 November 2010.

New policies

No new national policies or guidelines since 1 November 2010.

New safety alerts

No new safety alerts since 1 November 2010.

Changes in product availability

No changes in product availability since 1 November 2010.

Goals and outcome measures

Goals

To support primary healthcare professionals:

To recognize and make a clinical diagnosis of whooping cough

To notify whooping cough, and confirm infection through laboratory investigation when required

To appropriately treat people with whooping cough with antibiotics

To appropriately use antibiotic prophylaxis for close household contacts (and advise on return to schools and work to reduce infectivity)

To admit children with life-threatening infection or complications

QIPP — Options for local implementation

QIPP — Options for local implementation

Non-steroidal anti-inflammatory drugs (NSAIDs)

Review the appropriateness of NSAID prescribing widely and on a routine basis, especially in people who are at higher risk of both gastrointestinal (GI) and cardiovascular (CV) morbidity and mortality (e.g. older patients).

If initiating an NSAID is obligatory, use ibuprofen (1200 mg per day or less) or naproxen (1000 mg per day or less).

Review patients currently prescribed NSAIDs. If continued use is necessary, consider changing to ibuprofen (1200 mg per day or less) or naproxen (1000 mg per day or less).

Review and, where appropriate, revise prescribing of etoricoxib to ensure it is in line with MHRA advice and the NICE clinical guideline on osteoarthritis [CSM, 2005; NICE, 2008].

Co-prescribe a proton pump inhibitor (PPI) with NSAIDs for people with osteoarthritis, rheumatoid arthritis, or low back pain (for people over 45 years) in accordance with NICE guidance [NICE, 2008; NICE, 2009a; NICE, 2009b].

Take account of drug interactions when co-prescribing NSAIDs with other medicines (see Summaries of Product Characteristics). For example, co-prescribing NSAIDs with ACE inhibitors or angiotensin receptor blockers (ARBs) may pose particular risks to renal function; this combination should be especially carefully considered and regularly monitored if continued.

Antibiotic prescribing — especially quinolones and cephalosporins

Review and, where appropriate, revise current prescribing practice and use implementation techniques to ensure prescribing is in line with Health Protection Agency (HPA) guidance.

Review the total volume of antibiotic prescribing against local and national data.

Review the use of quinolones and cephalosporin prescribing against local and national data.

[NICE, 2013]

Background information

Definition

What is it?

Whooping cough, also known as pertussis, is a highly infectious disease caused by the bacterium Bordetella pertussis, which produces pertussis toxin and other substances which are believed to have an important pathogenic role in the disease. The name of the infection is derived from the characteristic 'whoops' that occur in younger children, and is caused by sharp inhalation of breath during bouts of paroxysmal cough.

The incubation period of whooping cough usually lasts for about 7 days (range 5–21 days).

Three phases of symptoms develop:

The catarrhal phase causes a dry, unproductive cough, and may be preceded by prodromal symptoms typical of upper respiratory tract infection. This phase lasts up to a week.

The paroxysmal phase, characterized by whooping, post-tussive vomiting, and generalized symptoms, may last a month or more.

The convalescent phase, characterized by gradual improvement in symptoms, may last an additional 2 months or more.

Whooping cough is considered to be infectious for 3 weeks after the onset of initial symptoms.

It is spread by aerosol droplets released during coughing.

Once contracted, a person can still become infected with pertussis (that is they lack full immunity), but subsequent infections are usually less severe. Similarly, vaccination does not always prevent infection, but it usually attenuates the disease.

[Crowcroft and Pebody, 2006; DH, 2010; Waters and Halperin, 2010; HPA, 2012b]

Prevalence

How common is it?

Before the introduction of the pertussis vaccine in the 1950s, pertussis was endemic in the UK, with an average of 120,000 notifications per year.

Vaccination had an immediate impact on the incidence of pertussis, but public and professional concerns about the safety of pertussis vaccination led to a decrease in uptake, and subsequent major epidemics in 1977–1979 and 1981–1983 [DH, 2010]. At present in the UK, primary immunization against pertussis is provided by the combined diphtheria, tetanus, pertussis, polio, and Haemophilus influenzae type B (DTaP/IPV/Hib) vaccine and DTaP/IPV booster vaccine, which have an uptake of more than 90% [HPA, 2012a].

Whooping cough is now relatively rare compared with the prevaccination era, with 103 people per 100,000 population confirmed cases in 2011 [HPA, 2012a]. Typically, there is a 3–4 year cyclical pattern, with 2007–2008 and 2011–2012 reported as peak years [HPA, 2012a].

Since mid-2011, there has been a considerable increase in pertussis activity in the UK. The greatest numbers of cases are in adolescents and young adults but the highest rates are in infants less than three months of age [HPA, 2012a]. A national outbreak was declared in April 2012.

Whooping cough is underdiagnosed in the UK [Crowcroft and Pebody, 2006].

A prospective cohort study (set in UK general practice) of 172 children presenting with 14 days or more of cough performed serological testing to ascertain if they were infected with Bordetella pertussis. More than a third of children had serological evidence of pertussis (37.2%, 95% CI 30.0% to 44.4%) [Harnden et al, 2006].

A study set in UK general practice estimated that there was an incidence of pertussis of 330 per 100,000 population. This compared with a statutory notification rate of less than 4 per 100,000 [Miller et al, 2000].

Another study found that 23% of infants and children admitted to hospital with severe of life-threatening respiratory symptoms tested positive for pertussis [Crowcroft et al, 2003].

Whooping cough disproportionately affects young children and infants [Crowcroft and Pebody, 2006].

Maternal antibodies offer some passive immunity during the first few months of life. However, adequate protection against pertussis usually requires several doses of vaccine, which leaves infants particularly susceptible to infection.

Prognosis

What is the prognosis?

For people who have not previously contracted whooping cough and are not vaccinated, whooping cough causes a protracted cough which may last for 3 months or more (pertussis has been referred to as 'the one hundred day cough').

For people who have some immunity (that is they have been previously vaccinated or have previously contracted the infection), whooping cough tends to be more short lived, with milder or atypical symptoms.

[Crowcroft and Pebody, 2006; Munoz, 2006; Waters and Halperin, 2010]

Complications

What are the complications?

The mortality rate caused by pertussis in children 6 months of age or less is estimated to be 3.5%, compared with 0.03% in the general population. Rarely, very young children may die suddenly with no obvious symptoms of pertussis.

Serious complications of pertussis include:

Apnoea.

Pneumonia (usually caused by secondary bacterial infection).

Seizures.

Encephalopathy (rare in adults).

Otitis media (caused by secondary bacterial infection) is a less serious but common complication in children. Unilateral hearing loss has also rarely been reported.

Increased intrathoracic and intra-abdominal pressure caused by violent and/or prolonged coughing can cause:

Pneumothorax.

Umbilical and inguinal hernias, and rectal prolapse.

Rib fracture and herniation of lumbar discs.

Urinary incontinence.

Less severe complications such as subconjunctival or scleral haemorrhage, and facial and truncal petechiae (bleeding under the skin).

Frequent post-tussive vomiting can lead to severe dehydration and/or malnutrition.

[Frydenberg and Starr, 2004; Crowcroft and Pebody, 2006; Gregory, 2006; Waters and Halperin, 2010]

Diagnosis

Diagnosis of whooping cough

Clinical features

What are the clinical features of whooping cough?

Early prodromal symptoms are often indistinguishable from those of other upper respiratory infections, and include nasal discharge, conjunctivitis, malaise, sore throat, and low-grade fever.

The catarrhal phase, which lasts about a week, is characterized by the development of a dry, unproductive cough. Pertussis is rarely diagnosed during this stage unless there has been contact with a person who is known to be infected.

The paroxysmal phase typically occurs about 1 week after the catarrhal phase. Between coughing fits (paroxysms), the person is usually relatively well, and can often sleep. Paroxysmal episodes:

Are more common at night, may be triggered by external stimuli (for example cold, noise), and may number more than 30 paroxysms in 24 hours. Typically, the cough paroxysm consists of a short expiratory burst followed by an inspiratory gasp, causing the 'whoop' sound. However, this is less common in older people (who may have simple cough), and in children younger than 3 months of age (who may present with apnoea alone).

May yield thick mucous plugs or watery secretions. However, there are usually no other chest signs (such as wheeze or crackle) unless pneumonia has developed.

May be severe enough to cause cyanosis in children, and are frequently associated with vomiting (known as post-tussive vomiting). Adults may experience sweating attacks with facial flushing, and rarely, cough syncope.

During the convalescent phase, there is a gradual improvement in the frequency and severity of symptoms, over the course of weeks or months.

Basis for recommendation

Basis for recommendation

The clinical features of whooping cough are described in the textbook Principles and practice of infectious diseases [Waters and Halperin, 2010], and in narrative reviews [Braman, 2006; Gregory, 2006; Harnden, 2009].

A prospective cohort study (set in UK general practice) in 172 children presenting with 14 days or more of cough performed serological testing to ascertain if they were infected with Bordetella pertussis [Harnden et al, 2006].

More than one third of children had serological evidence of pertussis (37.2%, 95% CI 30.0% to 44.4%). However, there was evidence that vaccination protected against whooping cough (odds ratio [OR] 0.18, 95% CI 0.05 to 0.68).

Children with pertussis were more likely to present with whoop (OR 2.85, 95% CI 1.39 to 5.82), vomiting (OR 4.35, 95% CI 2.04 to 9.25), or sputum production (OR 2.39, 95% CI 1.14 to 5.02).

Children diagnosed with pertussis were also significantly more likely to continue coughing after 2 months, have more than five episodes of coughing a day, and have sleep disturbance.

Making a clinical diagnosis

When should I make a clinical diagnosis of whooping cough?

Make a clinical diagnosis of whooping cough if the person:

Has clinical features consistent with whooping cough, particularly if the person is not fully immunized, or has been in contact with a person who is confirmed or suspected as having whooping cough.

Has had an acute cough for 14 days or more without another apparent cause, and has one or more of the following:

Inspiratory whoop.

Post-tussive vomiting.

Paroxysmal cough (coughing fits).

Contact the local Health Protection Unit regarding notification and confirmation of the infection.

Consider a different cause of infection if these criteria are not met, or symptoms are atypical (but bear in mind that very young children, adults, and people who have some immunity due to prior infection or vaccination may have atypical symptoms).

Basis for recommendation

Basis for recommendation

The criteria for the clinical diagnosis of whooping cough are based on expert opinion from the guideline HPA guidelines for the public health management of pertussis, published by the Health Protection Agency [HPA, 2012a].

Whooping cough should always be considered as a cause of protracted cough as it tends to be underdiagnosed in primary care [Harnden, 2009].

It is important to identify pertussis because [Dodhia et al, 2002]:

An unexplained persistent cough can cause anxiety, and may result in inappropriate investigations, treatment, and referral.

Spread of whooping cough to household contacts can be prevented if the index case is treated with antibiotics. It is particularly important to prevent transmission to young infants, who may have no immunity to the disease and are most at risk from serious complications, including death.

Surveillance of whooping cough is necessary to assess the efficacy of the vaccine, and to estimate the burden of the disease on the wider community.

Differential diagnosis

What else may cause similar features to whooping cough?

Consider pertussis-like syndrome. Other pathogens can cause similar symptoms to those caused by Bordetella pertussis, but symptoms are usually less severe because pertussin toxin is not produced. Possible causative pathogens (none of which are prevented by vaccination) include:

Bordetella parapertussis.

Mycoplasma pneumoniae.

Chlamydia trachomatis.

Chlamydia pneumoniae.

Adenoviruses.

Consider other non-infectious causes of cough, including:

Asthma.

Chronic obstructive pulmonary disease (in adults).

Post-infectious cough.

Post-nasal drip.

Gastro-oesophageal reflux.

Underlying malignancy.

Basis for recommendation

Basis for recommendation

Information on the differential diagnosis of whooping cough is based on expert opinion from narrative reviews [Frydenberg and Starr, 2004; Tiwari et al, 2005; Braman, 2006; Crowcroft and Pebody, 2006; Shields et al, 2008].

Notification and confirmation

How should I notify and confirm whooping cough?

Whooping cough is a notifiable disease. If there is any suspicion of infection because of clinical features, notify the local Health Protection Unit (HPU) by telephone as soon as is practicable, and in writing within 3 days.

Enquire with the HPU about testing for confirmation and surveillance purposes. Depending on the age of the person and the duration of symptoms, a nasopharyngeal aspirate or nasopharyngeal/pernasal swab (for culture or PCR [polymerase chain reaction] testing) or blood sample (for serology) may be required.

Ask for advice on the use nasopharyngeal aspirates or blood sampling if the expertise is not available in primary care (for example, there is difficulty because the person is a young child or infant).

Whooping cough is confirmed when a person with clinical features consistent with pertussis:

Has Bordetella pertussis isolated from a nasopharyngeal aspirate or swab, or

Has anti-pertussis toxin IgG (immunoglobulin G) concentration of more than 70 IU/mL (in the absence of vaccination within the past year), or

Is B. pertussis PCR-positive on any clinical specimen.

Basis for recommendation

Basis for recommendation

This recommendation is based on expert opinion from the guideline HPA guidelines for the public health management of pertussis, published by the Health Protection Agency (HPA) [HPA, 2012a].

Culture

The HPA recommends that culture should be used to diagnose whooping cough in its early stage (for instance in a person who has had symptoms for less than 2 weeks) [HPA, 2012a].

However, culture may not always be suitable in primary care because [Crowcroft and Pebody, 2006; Harnden, 2009]:

The sensitivity of culture is variable, falling from 15–45% in the first 3 weeks, to zero in later stages of the illness, and results take 3–5 days to obtain.

It is not necessary to perform sensitivity testing of pertussis to antibiotics, as Bordetella pertussis is known to be almost invariably sensitive to macrolide antibiotics [Kerr and Preston, 2001].

Culture requires collection using a pernasal swab or nasopharyngeal aspirate, which are unpleasant and difficult to collect in primary care. In addition, incorrect sampling technique may further reduce the sensitivity of culture [Crowcroft and Pebody, 2006].

Genome detection using polymerase chain reaction

Polymerase chain reaction (PCR) has improved sensitivity when compared with culture and is invaluable in confirming whooping cough in young infants [HPA, 2012a]. However, this test is not always readily available.

Serology (for anti-pertussis toxin IgG antibody levels)

The HPA recommend serology should be used to diagnose whooping cough when symptoms have been present for 2 weeks or more [HPA, 2012a].

Infants less than 3 months of age may not develop measurable antibodies, and results may be confounded by recent pertussis vaccination.

Test results may be confounded by recent pertussis vaccination.

Diagnosis of whooping cough in primary care is usually made using serology, through the detection of anti-pertussis toxin immunoglobulin G (anti-PT IgG). This has an estimated sensitivity of 76% and a specificity of 99% across all age ranges during the later stages of the infection [Crowcroft and Pebody, 2006].

In practice, serology may be the preferred diagnostic option in primary care if there are practical difficulties in obtaining and transporting pernasal swabs or nasopharyngeal aspirates [Harnden, 2009].

Management

Management

Scenario: Management : covers the management of people with suspected or confirmed whooping cough and their close contacts.

Scenario: Management

Scenario: Management of whooping cough

0months3060monthsBoth

Management of whooping cough

How should I manage a person with whooping cough?

Admit people who are seriously unwell (for example they are cyanotic or have periods of apnoea).

Have a low threshold for admitting infants of 6 months of age or younger.

Prescribe an antibiotic to all people with suspected or confirmed whooping cough who have had onset of cough within the previous 21 days.

For most people, a macrolide antibiotic is indicated.

For pregnant women:

In the last month of pregnancy, prescribe an antibiotic to prevent ongoing transmission to the infant.

Earlier in pregnancy, consider antibiotic treatment based on the likely clinical benefit for the woman.

Advise the person to:

Rest.

Drink adequate fluids.

Take paracetamol or ibuprofen for symptomatic relief (aspirin should be avoided in children younger than 16 years of age).

Provide information about whooping cough (a whooping cough fact sheet (pdf) is available from the Health Protection Agency).

Offer advice on exclusion from school or work:

Children with suspected or confirmed whooping cough should stay away from school or nursery for 5 days after starting antibiotics, or 21 days after the onset of cough (whichever is sooner). Asymptomatic contacts do not need to be excluded.

Healthcare workers should seek further advice regarding exclusion from work. For people who work in other settings, contact with vulnerable individuals should be avoided for 5 days after starting antibiotics, or 21 days after the onset of cough.

Contact with young children (especially infants of 6 months of age or younger) should be specifically avoided.

Inform that, even with antibiotics, whooping cough is likely to cause a protracted (non-infectious) cough that may take several weeks to completely resolve. However, symptoms are likely to be less severe and resolve quicker if the person has been immunized or has had the infection before.

Consider whether close contacts require antibiotic prophylaxis.

When the person has sufficiently recovered from the acute symptoms, encourage them to undergo any outstanding vaccinations if applicable (see the CKS topic on Immunizations - childhood).

Pregnant women should be vaccinated with a pertussis-containing vaccine between 28 and 38 weeks (see the CKS topic on Antenatal care - uncomplicated pregnancy).

The following acute interventions are not recommended:

Pertussis immunoglobulin.

Oral, inhaled, or intramuscular corticosteroids.

Beta-agonists (for example salbutamol).

Diphenhydramine (an antihistamine).

Basis for recommendation

Basis for recommendation

These recommendations are in line with the guideline HPA guidelines for the public health management of pertussis, published by the Health Protection Agency (HPA) [HPA, 2012a].

Treatment with antibiotics

This recommendation is based on evidence from randomized controlled trials (RCTs) that antibiotics are effective at eradicating infection (and therefore preventing transmission of whooping cough) [Altunaiji et al, 2007]. However, antibiotics probably have little clinical benefit, especially if they are started later than 7 days from the onset of cough [Crowcroft and Pebody, 2006].

Antibiotics should be started as soon as possible after the onset of symptoms to eradicate infection and limit transmission. The effect of antibiotics on reducing symptoms is limited, especially when given late during whooping cough, and the HPA therefore recommends that treatment is only commenced if the person presents within 3 weeks of symptom onset [HPA, 2012a].

Erythromycin the preferred antibiotic for treating women in the last month of pregnancy to prevent ongoing transmission to the infant [HPA, 2012a].

Although it is generally considered safe to us erythromycin earlier in pregnancy, antibiotics are unlikely to have any clinical benefit, unless given in the early stages of the illness and any decision to use erythromycin earlier in pregnancy should be base on the likely benefit for the woman and the presence of any vulnerable close contacts [HPA, 2012a].

Self-care advice

The natural history of whooping cough is described in the textbook Principles and practice of infectious diseases (see Prognosis) [Waters and Halperin, 2010].

Adequate fluid intake should be maintained when symptoms of upper respiratory tract infection are present, to replace fluid lost by fever, sweating, and nasal discharge. However, there have been no controlled trials confirming the benefit of this [Guppy et al, 2005]. Whooping cough may also cause severe post-tussive vomiting which can lead to significant dehydration [Waters and Halperin, 2010].

Paracetamol and ibuprofen are recommended for the symptomatic relief of pertussis on the basis that they reduce fever and pain (including headache and myalgia).

The antipyretic and analgesic efficacy of paracetamol and ibuprofen have been confirmed by RCTs in several conditions, including other upper respiratory tract infections (influenza and the common cold) [Eccles, 2006].

The National Institute for Health and Care Excellence (NICE) recommends that antipyretic drugs 'should be considered in children with fever who appear distressed or unwell'. However, the routine use of antipyretic drugs to reduce temperature in children with no other symptoms or discomfort is not recommended [NICE, 2007].

Aspirin is not usually recommended as it has a less favourable adverse effect profile. It is contraindicated in children younger than 16 years of age, because of the risk of Reye's syndrome [BNF for Children, 2010].

Information about whooping cough

Guidance from the HPA states that children with suspected whooping cough should be kept away from school or nursery for 5 days after the initiation of antibiotic treatment, or 21 days after the onset of cough if not treated [HPA, 2012a].

This is primarily to prevent spread infection, as pertussis is most infectious at this stage.

Young infants (6 months of age and younger) have a mortality rate which is 100-fold greater than for adults [Frydenberg and Starr, 2004], and special care should be taken to ensure they are not exposed to pertussis before their primary vaccinations.

Treatments not recommended

Other interventions (pertussis immunoglobulin, corticosteroids, beta-agonists, and diphenhydramine) are not recommended as there is no evidence to support their effectiveness [Munoz, 2006; Waters and Halperin, 2010].

Management of contacts

How should I manage a person who has been in contact with whooping cough?

Offer a course of antibiotic prophylaxis to all close contacts when the following conditions apply:

The onset of disease in the person who has been clinically or microbiologically diagnosed with pertussis (the 'index case') occurred within the previous 21 days, and

They are in a priority group.

Advise that exclusion from work or school for asymptomatic contacts is not required.

Offer immunization to all people who have been offered antibiotic prophylaxis.

Un-immunized and partly-immunized contacts up to 10 years of age should complete the schedule of the Childhood Immunisation Programme with the appropriate vaccination. See the CKS topic on Immunizations - childhood.

A booster dose of pertussis containing vaccine is recommended for people aged 10 years or older who have not received a dose of Td-IPV in the preceding month and have not received a pertussis booster in the past 5 years.

Close contacts

Close contacts

A close contact is considered to be:

A family member or a person living in the same household as the person with whooping cough, or

A person in an institutional setting with overnight stays in the same room as the person with whooping cough.

Other types of contacts, for example contacts at work or school, are not generally considered as close contacts, although each person should be assessed on an individual basis when vulnerable contacts are involved.

[HPA, 2012a]

Priority groups for public health action

Priority groups for public health action

These include individuals who are either themselves at increased risk of complications following whooping cough (group 1) and individuals at risk of transmitting the infection to those at increased risk (group 2).

Group 1 (individuals at increased risk of severe complications):

Infants less than 1 year old who have received less than three doses of pertussis-containing vaccine.

Group 2 (individuals at increased risk of transmitting to individuals in Group 1, and who have not received a pertussis-containing vaccine more than 1 week and less than 5 years ago):

Pregnant women at 32 weeks or more of gestation.

Healthcare workers working with infants and pregnant women.

People whose work involves regular close or prolonged contact with infants too young to be fully vaccinated (less than 4 months).

People who share a household with an infant too young to be fully vaccinated (less than 4 months).

[HPA, 2012a]

Basis for recommendation

Basis for recommendation

These recommendations are in line with the guideline HPA guidelines for the public health management of pertussis, published by the Health Protection Agency (HPA) [HPA, 2012a].

Assessment of risk

The description of 'contacts' is based on expert opinion, gained from knowledge of the infectiousness of pertussis. However, this is not an exact definition, and clinical judgement should always be applied to individual cases, particularly where vulnerable contacts are concerned [Dodhia et al, 2002].

It is important to identify 'vulnerable contacts' as this group are both more susceptible to infection and the consequences of infection are likely to be more severe. However, it is also important to identify non-vulnerable contacts as they can still incubate and transmit infection [Crowcroft and Pebody, 2006].

Antibiotic prophylaxis

There is only limited evidence from randomized controlled trials (RCTs) of the clinical benefit of antibiotic prophylaxis [Altunaiji et al, 2007]. One larger RCT found that prophylaxis with erythromycin reduced the incidence of microbiological infection (but not clinical infection) of household contacts compared with placebo [Halperin et al, 1999].

There is some observational evidence that antibiotic prophylaxis is effective at reducing clinical symptoms in vulnerable people (these groups tend to be excluded from RCTs), and it is on this basis that chemoprophylaxis is recommended [Dodhia et al, 2002].

Advise on exclusion

The HPA states 'exclusion for asymptomatic contacts is not required' [HPA, 2012a].

Pertussis immunization

Immunization is recommended for all children according to guidelines in 'the Green Book', published by the Department of Health [DH, 2010]. This will provide future protection against pertussis as well as other infectious diseases, such as diphtheria, tetanus, poliomyelitis, and Haemophilus influenzae type B.

The HPA recommends that a booster of dTaP-IPV (tetanus, diphtheria, pertussis, and polio vaccine) is given to people 10 years or older who have not received a dose of Td-IPV (tetanus, diphtheria, and polio vaccine) in the preceding month or a pertussis booster in the past 5 years [HPA, 2012a].

Although duration of immunity has not been clearly established, limited evidence suggests a duration of protection of 5–6 years.

Antibiotic regimen

What antibiotic treatment should I prescribe?

A macrolide antibiotic is recommended first line for treatment and post-exposure prophylaxis.

Clarithromycin is preferred in infants less than 1 month of age.

Azithromycin and clarithromycin are preferred in children aged 1 month or older, and in adults.

Erythromycin is the macrolide of choice for pregnant women.

Cotrimoxazole is recommended if macrolides are contraindicated or cannot be tolerated (off-label indication).

For full information on dosing regimens of antibiotics, including in children and infants, see Prescriptions.

Basis for recommendation

Basis for recommendation

These recommendations are in line with the guideline HPA guidelines for the public health management of pertussis, published by the Health Protection Agency (HPA) [HPA, 2012a].

There is evidence from comparative randomized controlled trials (RCTs) that macrolides (erythromycin, clarithromycin, and azithromycin) are at least as effective as other antibiotics at eradicating Bordetella pertussis, although they do not usually alter the clinical course of the disease [Altunaiji et al, 2007].

In practice, macrolides are preferred over other antibiotics for both treatment and prophylaxis because of their pharmacodynamic and pharmacokinetic properties, and because so far resistance of B. pertussis to macrolides is minimal [Kerr and Preston, 2001].

The HPA recommends azithromycin and clarithromycin as the preferred macrolide in children over 1 year and adults because of the adverse effects associated with erythromycin [HPA, 2012a]. CKS has extrapolated this to include children aged 1 month and older.

The HPA recommends clarithromycin as the preferred macrolide for use in neonates, noting that there is limited data on the use of azithromycin in this age group [HPA, 2012a].

Cotrimoxazole has been found to be as effective as erythromycin in one RCT [Altunaiji et al, 2007], and is recommended as an alternative choice if macrolides are contraindicated [Munoz, 2006]. It is not licensed for the treatment or chemoprophylaxis of whooping cough [BNF 60, 2010].

Admission and referral

When should I admit or refer a person with whooping cough?

Inform the hospital of the need for appropriate isolation before admission or referral.

Admit people (usually children) who:

Are 6 months of age or younger and acutely unwell.

Have significant breathing difficulties caused by whooping cough (for example periods of apnoea or severe paroxysms, or who has cyanosis).

Have developed other significant complications (for example seizures or pneumonia).

Basis for recommendation

Basis for recommendation

Inform the hospital of the requirement for isolation before admission

National guidelines recommend that people with whooping cough who require management in hospital should be treated in isolation [Dodhia et al, 2002].

Referral recommendations

Referral recommendations are based on expert opinion and reflect the serious nature of whooping cough in young children.

The mortality rate for pertussis in children of 6 months of age or less is estimated to be 3.5%, compared with 0.03% in the general population [Frydenberg and Starr, 2004].

Treatment in secondary care

Treatment of pertussis in secondary care is largely supportive, and may include: intensive monitoring (for example of vital signs, paroxysms, and apnoea); parenteral rehydration following post-tussive vomiting; provision of oxygen; treatment of secondary infections; and mechanical ventilation [Munoz, 2006; Waters and Halperin, 2010].

Evidence

Evidence

Supporting evidence

For information on the effectiveness of the pertussis vaccine, see the Supporting evidence section on Vaccines for pertussis in the CKS topic on Immunizations - childhood.

Antibiotics for treatment

Evidence on antibiotics for treatment of whooping cough

There is a lack of evidence from placebo controlled trials that antibiotics are of clinical benefit in the treatment of whooping cough, although there is evidence that they are effective at eradicating the infection and preventing transmission. There is little evidence from randomized controlled trials (RCTs) that any antibiotic regimen is more effective than another. Macrolides are recommended as first-line treatment because they have been proven to be effective and the incidence of resistance to them is very low.

A Cochrane systematic review (search date: March 2007) identified 11 trials (10 randomized and one quasi-randomized; 1954 participants) that investigated the effectiveness of antibiotics in the treatment of whooping cough [Altunaiji et al, 2007]. The trials were performed between 1953 and 2004, and were of variable quality. Various outcomes were reported, meaning only limited meta-analyses could be conducted on the data.

Nine trials compared different regimens of antibiotics.

Only one RCT included a placebo arm (with 10 participants). Oxytetracycline and erythromycin were found to be superior to placebo in terms of microbiological eradication (relative risk [RR] 17, 95% CI 1.11 to 259.89; RR 19, 95% CI 1.25 to 287.93, respectively).

In general, antibiotics were found to be equally effective in terms of clinical cure and improvement, although one RCT found erythromycin estolate was superior to erythromycin ethylsuccinate (RR 3.43, 95% CI 1.16 to 10.13).

No antibiotic was found to be superior to another in terms of mortality (although deaths in any groups were rare), microbiological eradication, or complications.

Azithromycin and clarithromycin were both found to cause fewer adverse effects than erythromycin (RR 0.38, 95% CI 0.19 to 0.75; RR 0.72, 95% CI 0.53 to 0.97 respectively).

Four trials compared different durations of antibiotics.

Shorter courses of antibiotics (3–7 days) were found to be as effective as longer courses (10–14 days) in terms of clinical improvement, microbiological eradication, and microbiological relapse.

A meta-analysis of three RCTs found shorter courses of erythromycin caused fewer adverse effects than longer courses (RR 0.66, 95% CI 0.52 to 0.83).

The authors concluded that although antibiotics were effective at eradicating Bordetella pertussis, they probably do not significantly alter the clinical course of the disease. For the purpose of eradication, azithromycin or clarithromycin were recommended, with co-trimoxazole as an option if macrolides are contraindicated.

In practice, antibiotic choice is guided by the pharmacokinetics and pharmacodynamics of the drug and bacterial sensitivity, rather than controlled trials [Kerr and Preston, 2001]. Macrolides are recommended as first-line treatment because they:

Exhibit good pharmacokinetics, being rapidly absorbed and distributed in soft tissue.

Have good in vitro activity against B. pertussis.

Are generally considered to have a well-established safety profile, although erythromycin in particular can cause gastrointestinal upset.

Are rarely associated with bacterial resistance (for instance there have only been two documented cases of B. pertussis resistance to erythromycin).

Antibiotics for prophylaxis

Evidence on antibiotics for prophylaxis of whooping cough

CKS found no evidence from randomized controlled trials (RCTs) or other types of study that antibiotic prophylaxis of whooping cough is effective at reducing the rate of clinical infection. There is some evidence that antibiotic prophylaxis reduces the rate of microbiological infection.

A Cochrane systematic review (search date: March 2007) identified two RCTs that investigated the effectiveness of antibiotics for the chemoprophylaxis of whooping cough [Altunaiji et al, 2007].

One RCT in 91 children (60 vaccinated) found prophylaxis with erythromycin did not significantly reduce the rate of infection or clinical symptoms of household contacts compared with placebo.

The authors of the Cochrane systematic review found that, after sensitivity analysis, one RCT in 310 children showed no significant benefit in terms of preventing clinical or microbiological infection. However, the authors of the original study stated that four households in the erythromycin group developed microbiological infection, compared with 15 households in the placebo group (protective efficacy 67.5%, 95% CI 7.6 to 88.7%) [Halperin et al, 1999].

The authors of the review concluded that there was 'insufficient evidence to determine the benefit of prophylactic treatment of pertussis contacts'.

A systematic review (search date: circa 1996) with a broader inclusion criteria than the Cochrane systematic review identified an additional four 'analytical studies' (cohort and case series studies) and seven 'descriptive studies' (uncontrolled observational studies). Broadly speaking, studies described in the review concurred with the RCTs described in the Cochrane systematic review [Dodhia and Miller, 1998].

Search strategy

Scope of search

A literature search was conducted for guidelines, systematic reviews and randomized controlled trials on the primary care management of Whooping cough, with additional searches in the following area:

Post exposure prophylaxis

Search dates

Medline and Embase

January 1970 – November 2010

Key search terms

Various combinations of searches were carried out. The terms listed below are the core search terms that were used for Medline.

exp Whooping Cough/, whooping cough.tw, pertussis.tw, Bordetella pertussis.tw, exp Bordetella pertussis/

exp Chemoprevention/, exp Antibiotic Prophylaxis/

Table 1 . Key to search terms.
Search commands Explanation
/ indicates a MeSH subject heading with all subheadings selected
.tw indicates a search for a term in the title or abstract
exp indicates that the MeSH subject heading was exploded to include the narrower, more specific terms beneath it in the MeSH tree
$ indicates that the search term was truncated (e.g. wart$ searches for wart and warts)
Topic specific literature search sources

British Thoracic Society

Health Protection Agency

Sources of guidelines

National Institute for Health and Care Excellence (NICE)

Scottish Intercollegiate Guidelines Network (SIGN)

Royal College of Physicians

Royal College of General Practitioners

National Guidelines Clearinghouse

New Zealand Guidelines Group

Canadian Medical Association

Institute for Clinical Systems Improvement

Guidelines International Network

NICE Evidence - National Library of Guidelines

National Health and Medical Research Council (Australia)

Royal Australian College of General Practitioners

Royal College of Nursing

Health Protection Agency

National Resource for Infection Control

CREST

World Health Organization

NHS Scotland National Patient Pathways

Agency for Healthcare Research and Quality

TRIP database

Patient UK Guideline links

UK Ambulance Service Clinical Practice Guidelines

RefHELP NHS Lothian Referral Guidelines

Medline (with guideline filter)

Alberta Medical Association

British Columbia Medical Association

University of Michigan Medical School

Michigan Quality Improvement Consortium

Singapore Ministry of Health

Sources of systematic reviews and meta-analyses

The Cochrane Library :

Systematic reviews

Protocols

Database of Abstracts of Reviews of Effects

Medline (with systematic review filter)

EMBASE (with systematic review filter)

Sources of health technology assessments and economic appraisals

NIHR Health Technology Assessment programme

The Cochrane Library :

NHS Economic Evaluations

Health Technology Assessments

Canadian Agency for Drugs and Technologies in Health

International Network of Agencies for Health Technology Assessment

Sources of randomized controlled trials

The Cochrane Library :

Central Register of Controlled Trials

Medline (with randomized controlled trial filter)

EMBASE (with randomized controlled trial filter)

Sources of evidence based reviews and evidence summaries

Bandolier

Drug & Therapeutics Bulletin

MeReC

NPCi

DynaMed

TRIP database

Central Services Agency COMPASS Therapeutic Notes

Sources of national policy

Department of Health

Health Management Information Consortium (HMIC)

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