Clinical review: Paediatric pertussis

Section 1: Epidemiology and aetiology
Section 2: Making the diagnosis
Section 3: Managing the condition
Section 4: Prognosis
Section 5: Case study
Section 6: Evidence base

Section 1: Epidemiology and aetiology

Whooping cough (pertussis) is a URTI caused by the Gram-negative bacterium Bordetella pertussis.^1,2 It is notifiable in England. Humans are the only host for B pertussis.

Transmission is by respiratory droplets. Up to 90% of household contacts will develop the disease.² Patients are infectious from about one week after exposure to up to three weeks after they develop a cough.^1,2

Before the introduction of the pertussis vaccine, up to 170,000 cases occurred in England and Wales per year, with a peak of more than 2,000 deaths notified in 1941.

Whole cell pertussis vaccine was introduced in the 1950s and by 1972, rates of pertussis had fallen to about 2,000 cases per year.² Public scares regarding a link between pertussis vaccination and brain damage reduced coverage from 80% to 30% between 1977 and 1983, resulting in an increase in notifications and deaths.

Since then, vaccine uptake has increased, the whole cell vaccine was replaced with the acellular vaccine in 2004 and rates of pertussis fell steadily until 2011 and 2012, which saw a significant rise in cases, especially in babies aged less than three months, with 13 deaths in this group (figures up to November 2012).³

Protective antibodies from vaccination only persist for approximately 10 years, therefore adults are at risk of developing the disease even if they are fully vaccinated, and in some situations now are the major reservoir of infection in a community.

The youngest infants, most at risk of pneumonia and death from pertussis, are often unvaccinated or have only received one dose, so a high level of vaccination needs to be maintained in siblings, young adults and relatives, as well as the community, to prevent neonatal cases. 

In April 2012 a national outbreak was declared and because of a significant increase in infant deaths the DH announced a temporary immunisation programme for pregnant women at around 20 weeks gestation.

The primary purpose of this maternal programme is to boost passively transferred pertussis antibodies from mother to baby. Maternal vaccine coverage peaked at 62.3% in December 2014. There have been no safety concerns and a >90% effectiveness. In 2016 the programme was extended for a further five years.

Section 2: Making the diagnosis

Difficulty occurs when diagnosing vaccinated individuals, small infants, older children or adults without classical symptoms.

The incubation period is from seven to 10 days. In classical whooping cough, the patient often develops a cold and catarrh, progressing to an irritant cough that worsens, becomes chronic and may have the typical whoop, a protracted coughing spasm ending in a sharp drawing of breath.

Whoop is often not present in older children and adults, but the cough may continue for months. In infants, especially those less than three months old, whoop is often absent.

Apnoea is frequently seen in the youngest patients following coughing, or instead of the cough. Mortality is highest in the youngest infants, often following pneumonic consolidation. Other complications include vomiting during coughing, subconjunctival haemorrhages, pneumonia and reduced oxygen saturations that if severe, can lead to hypoxic brain damage, encephalitis, seizure and death.^1,2

Investigations
Nasal swab with culture on Bordet-Gengou agar is the preferred isolation method, but can take seven to 10 days. Cotton throat swabs should not be used; they have a reduced likelihood of isolating B pertussis.

 The organism is very sensitive and is affected by processing delays. The likelihood of a positive culture decreases with time after symptom onset, from approximately 60% within in the catarrhal phase to 10% or less after four weeks.⁵

Since 2014, regional PHE laboratories now offer a pertussis PCR service for all ages, both for hospital and primary care settings. PCR is more sensitive than culture as the organisms does not need to be viable, however, PCR is less likely to be positive if symptoms have been present for more than three weeks. Nasopharyngeal swabs are best for PCR testing, but throat swabs may be used, for example in community settings.

Serology/anti-pertussis toxin IgG measurement, at least 14 days after the onset of cough, is a reliable method of confirming cases. It is unreliable in infants and can only be interpreted reliably if no vaccine has been given in the past 12 months. It is only useful where culture and PCR are unlikely to yield positive results. PCR coupled with serology may partly account for the recent increase in numbers of confirmed cases.⁵

Differential diagnosis

A differential diagnosis in infants with apnoea and respiratory distress includes bronchiolitis, especially respiratory syncytial virus, and pneumonia.

Other infections to consider include sepsis, meningitis or a seizure disorder. In older children or adults with chronic cough,asthma, pneumonia and TB need to be excluded, and in adults, carcinoma.

Section 3: Managing the condition

In most patients, symptomatic treatment is all that is required. There is limited evidence that treating symptomatic patients has any effect on the clinical course of the disease.⁶

However, treatment does reduce nasal carriage and infectivity. Azithromycin (three to five days) or clarithromycin (seven days) have fewer side-effects and are as effective as longer courses of erythromycin (erythromycin is first choice for pregnant women, if they have macrolide allergy use Septrin; see Evidence Base).^7,8 

Intensive care
Infants aged less than three months who are hospitalised with pertussis often require high dependence/intensive care support.

Compared with historical controls, patients who required intensive care ventilation had a better outcome if they had received exchange transfusions to reduce their marked lymphocytosis; however, there are no RCTs of this and therefore the practice is not widespread.

Infants who fail conventional ventilation are sometimes offered extracorporeal membrane oxygenation, but even then the prognosis is poor.

When a case of pertussis is suspected or confirmed, the vaccine history of other children in the family and close contacts up to 10 years of age needs to be taken. If they have not been vaccinated or have an incomplete pertussis history, vaccination should be completed.

Pertussis is generally not a major problem for children with illnesses that predispose to complications with other respiratory viruses (for example, immune deficiency, HIV, congenital cardiac disease). They should be managed as any other child who might contract pertussis and treated if they develop symptoms.

Chemoprophylaxis has limited benefit,⁷ so should only be given when symptoms in the index case occurred less than 21 days before and the contact is in either of these groups:⁵

• They are under one year of age and have received fewer than three doses of pertussis
• They are at risk of transmitting to a vulnerable individual and have not had vaccine more than one week and less than five years ago
• Pregnant women (>32 weeks' gestation, or vaccinate them)
• Healthcare workers working with infants and pregnant women
• People whose work involves regular close contact with infants too young to be fully vaccinated (<4 months="" li="">
• People who share a household with an infant too young to be fully vaccinated

Immunisation is offered to all children under 10 years old (three to four doses), DTaP/IPV/Hib vaccine (pre-school).³Vaccination is generally not recommended for those older than 10 years, even if unvaccinated, unless pregnant. More detail is available from the DH Green Book, chapter 24 and in Guidelines for the Public Health Management of Pertussis in England.^3,8

Section 4: Prognosis

Older children and adults often have mild or atypical illness, but up to 50% will cough for 10 weeks or more.

Minor complications include epistaxis, nausea, vomiting and subconjunctival haemorrhages.

Unvaccinated infants aged less than six months, especially those less than three months, are more likely to have severe disease, develop complications, and require hospitalisation.

Pneumonia is common, occurring in up to 20% of infants (13% of adults) but bronchiectasis is rare. Seizures (1-2% of infants; 0.3-0.6% of adults) or encephalitis are more common in infants.

Those with underlying diseases are at higher risk of complications. Pertussis mortality is rare but 83% of deaths occur in infants and in 1.6% of hospitalised infants.

Section 5: Case study

A five-week-old baby was seen with culture-confirmed pertussis. The chest X-ray confirmed right upper lobe consolidation and right and left lower zone changes.

The infant first presented with a cough, which was diagnosed as bronchiolitis. On day two of admission, the infant was noted to whoop and the clinical diagnosis of pertussis was made. The patient deteriorated but avoided intubation.

The stay in hospital was for more than two weeks and the cough persisted for more than three months and was associated with marked failure to thrive, which slowly resolved. By five months of age, the infant had returned to normal, with a normal chest X-ray.

We elected to start erythromycin, despite the lack of evidence that it has any effect on outcome. This was because mortality is highest in those aged under three months, especially those aged under six weeks, and at that stage, we were unsure whether this child would significantly worsen. Reducing infectivity was a bonus.

Vaccinating contacts
This child had two siblings aged two and four years and the mother's partner worked in a nursery with infants and children. In such a case, the vaccination history of the siblings needs to be confirmed.

Both children had received two doses of their primary immunisations, and the four-year-old had received the preschool booster.

The two-year-old should receive a further dose of DTaP/IPV/Hib and a booster at least one year later. The four-year-old should receive a further DTaP/IPV/Hib booster at least one year after the preschool booster.

The mother's partner needs to be offered chemoprophylaxis to prevent transmission to infants who will not be fully vaccinated.

However, if all infants in their care have received three doses of DTaP/IPV/Hib, prophylaxis will not be warranted.

This case should be notified.

Section 6: Evidence base

There have been several Cochrane Database meta-analyses on pertussis.

• The first review demonstrated that the multicomponent (>3) acellular vaccine had approximately 85% efficacy at preventing typical whooping cough and 71-78% efficacy at preventing mild disease. This was significantly better than the one or two component vaccines. Cochrane Database Syst Rev 2012 Mar 14; 3: CD001478.
• The second review found no evidence that symptomatic treatment in pertussis had any significant effect. Cochrane Database Syst Rev 2012 May 16; 5: CD003257.
• The third found that a short course of macrolide antibiotics was as effective as a longer course in eradicating B pertussis but had fewer side-effects. Antibiotic treatment did not affect the clinical course of the disease. There was no evidence that prophylactic antibiotics prevented disease. Cochrane Database Syst Rev 2007 Jul 18; (3): CD004404.

Guidelines

• Chapter 24 of the DH Green Book covers the basics of pertussis infections, with information on which patients should be given which vaccines, when and what to do if doses have been missed. 
• There is an update on pregnant women at: www.nhs.uk/Conditions/pregnancy-and-baby/Pages/ whooping-cough-vaccination-pregnant.aspx
• The Health Protection Agency has information on epidemiology in England and Wales at:www.hpa.org.uk/Topics/InfectiousDiseases/InfectionsAZ/WhoopingCough/ EpidemiologicalData/

• Dr Scott Hackett, consultant in paediatric allergy, immunology and infectious diseases at Birmingham Heartlands Hospital.

This is an updated version of an article that was first published in Februay 2013.

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References

1. Wood N, McIntyre P. Pertussis: review of epidemiology, diagnosis, management and prevention. Paediatr Respir Rev 2008; 9(3): 201-11.
2. HPA. Whooping Cough (Pertussis) 
3. DH. Immunisation, the safest way to protect individuals and communities from infectious diseases. Green Book, Chapter 24, Pertussis; updated April 2016. 
4. Zhang L Prietsch SO, Axelsson I et al. Acellular vaccines for preventing whooping cough in children. Cochrane Database Syst Rev 2012; 3: CD001478.
5. HPA. Guidelines for the Public Health Management of Pertussis; updated October 2012.
6. Bettiol S, Wnag K, Thompson SJ et al. Symptomatic treatment of the cough in whooping cough. Cochrane Database Syst Rev 2012; 5: CD003257.
7. Altunaiji S, Kukuruzovic R, Curtis N et al. Antibiotics for whooping cough (pertussis). Cochrane Database Syst Rev 2007; 3: CD004404.
8. The Pertussis Guidelines Group, Public Health England. Guidelines for the Public Health Management of Pertussis in England. July 2016.