Pertussis

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Pertussis is the medical name for whooping cough.

Contents

Introduction

Pertussis (whooping cough) is a highly contagious acute bacterial infection producing a characteristic respiratory illness, caused by Bordetella pertussis. Symptoms can persist for some months. It is transmitted by respiratory droplets, with an incubation period of 5-21 days (commonly 7, rarely more than 10).

LogoKeyPointsBox.pngPertussis is quite common

B pertussis probably causes more disease than recognized, in both adults and children, especially where symptoms are chronic but mild, or in the third of cases where symptoms last less than 3 weeks. Nearly 40% of children with a cough lasting ≥14 days, and 20% of adults with a prolonged cough, have evidence of recent pertussis infection.[1] Hence reported incidence depends on quality of surveillance rather than actual prevalence! Probably the same everywhere, with peaks every 2-5 yrs.

For England and Wales, vaccination rates increased from 78% for children with their 2nd birthday in 1989/90 to 94% for children with their 2nd birthday in 1998/99, with a corresponding decrease in notifications. A pre-school booster with acellular pertussis vaccine has been offered since November 2001. In some countries another booster is given after the age of ten.

In countries with high vaccine coverage, most cases of serious disease, and the majority of fatalities, occur in unimmunized young infants. Adolescents and adults and those partially protected by vaccine may become infected, but usually have milder disease. However, they can transmit the disease to susceptible individuals.

One adult patient has written very cogently of the illness.[2]

An English family doctor Douglas Jenkinson has followed up over 700 cases. [3] [4] [5] His work is summarised on a website. [6] Of considerable importance are the sound files of a whoop. Many articles on pertussis show a child about to be sick. A picture may be worth a thousand words but in this case a sound file is better.

LogoKeyPointsBox.pngSound files whoopingcough.net

Aetiology

Bordetella pertussis produces a range of toxins including tracheal cytotoxin and lipopolysaccharide. Fimbriae are also important in pathogenesis. Pertussis toxin itself (as used in the vaccine) is probably not that important. B parapertussis can produce a similar illness but it is usually milder.

Clinical features

1. Catarrhal stage lasting 1-2 weeks, with insidious onset of coryza, low-grade fever and mild occasional cough. This is when affected individuals are most infectious. There is no pharyngitis (cf viral URTI).
2. Paroxysmal stage lasting 1-6 weeks, when the diagnosis of pertussis is usually suspected. There are bursts or paroxysms of numerous, rapid coughs during which effective ventilation does not occur and the child may become hypoxic. At the end of this paroxysm children usually have a long inspiratory whoop (adults with their larger airways tend not to whoop). Vomiting commonly follows. Infants under 6 months may not have a whoop; indeed, some present with spells of apnoea rather than coughing. Between paroxysms, there may be remarkably little in the way of respiratory signs or symptoms.
3. Convalescent stage, with gradual recovery over a variable period. The reason for the prolonged symptoms is still not clear: many infections cause similar ciliary disruption but don't cause such chronic symptoms.

Complications:

  • secondary bacterial pneumonia
  • encephalopathy +/- seizures. Presumably a direct toxin effect, although hypoxia during paroxysms may contribute.
  • pressure effects due to paroxysms - pneumothorax, epistaxis, subconjunctival haemorrhages, subdural haematomas, rectal prolapse and hernias

Adults with pertussis tend not to whoop, but instead present with disturbed sleep, sweating, sinusitis or otitis, protracted cough. Cough associated with choking is characteristic, whereas sweating is not very sensitive or specific. The cough is non-productive, although there may be a sensation of retained secretions - question carefully!

The main risk of adult pertussis is to vulnerable infants. The illness is very easily spread (by droplet infection) and the cough is forceful. The aim of treatment of the adult patient with antibiotic is less to affect the severity or duration of the cough but to prevent spread.

Infection provides immunity but, as with vaccination, the immunity is not necessarily long-lasting.

Diagnosis

Clinically suspected case

Remember that pertussis is a notifiable disease, and that cases should be notified on suspicion.

An acute cough lasting 14 days or more with at least one of the following symptoms:

  • post-tussive vomiting;
  • apnoea or whoop.

In addition, someone who is coughing for any duration and is also linked epidemiologically to a confirmed case of pertussis can be considered a suspect case.

Lymphocytosis can be spectacular but is not sensitive. Due to Pertussis toxin which is specific to B pertussis and used in the vaccine - hence lymphocytosis is not seen post immunization (ie adults), in parapertussis, or in neonates (as they have transplacental antibodies).

Confirmed case

QuotationMarkLeft.png The Respiratory and Systemic Infection Laboratory and Immunisation Department of the Centre for Infections (CfI) is providing this new oral fluid service, free of charge, through HPA Health Protection Units (HPUs) specifically to seek laboratory confirmation of formally notified pertussis cases who have been coughing for more than two weeks, but whose diagnoses have not been confirmed by other methods (culture, PCR or serology). This service is also available to HPUs to support their investigations of suspected pertussis outbreaks and incidents. The newly offered oral fluid assay was developed as a surrogate for the standard serum antibody assay, both being used to estimate IgG antibody directed against Bordetella pertussis pertussis toxin (PT). Although the oral fluid assay is not as sensitive as the serum assay, samples are very easy to collect and so it is an ideal assay to use where it is difficult or inappropriate to collect a blood sample. The oral fluid assay is not a replacement for the existing serology service which remains available to NHS colleagues as a free of charge service provided in support of national surveillance for all patients with a history of coughing for more than two weeks. QuotationMarkRight.pngHealth Protection Agency[7]

Typical symptoms and isolation of Bordetella pertussis.

  • Culture from pernasal swab is not very sensitive, but is useful for genetic studies. False negative cultures mostly due to sampling late in course of disease.
  • PCR more sensitive than culture but false positives common (as usual with PCR).
  • Serology: Numerous different ELISA tests are available. Elevated IgG, or rise in IgG is diagnostic. Qualitative (pos/neg) tests probably less good than quantitative. Note that IgG will be present if vaccinated or in young infants (placental transfer). You can always test the parents (Mum may have stored serum from pregnancy to compare against).

HPA Respiratory and Systemic Infection Laboratory offers a range of tests for pertussis, including, since June 2007, oral fluid immunoglobulin testing, for notified cases of pertussis.[8][9]

Management of cases

Flowchart - management of cases of pertussis

Information required

If pertussis is suspected from history and examination in a patient presenting to a GP or hospital doctor, they should request the following information:

  • Contact details e.g. parents or next of kin, address, telephone no.
  • GP details if presenting to hospital
  • Date of Birth
  • Date of onset of symptoms
  • Vaccination history
  • Occupation if appropriate
  • Whether pregnant or just had a baby (see Pregnancy and Neonatal period.)
  • Details of household contacts i.e. persons living in the same household or institutional setting. It should be established whether a contact is at high-risk both by taking a history from the patient or close family and by checking with the GP. See below for information on what constitutes a vulnerable contact.

Laboratory confirmation

Laboratory confirmation is recommended for most sporadic cases and a sufficient number of cases to establish the diagnosis in an outbreak. See Diagnosis; the method used should be discussed with a microbiologist.

Notification

Whooping cough is notifiable by law. The GP or hospital doctor should notify the CCDC or "Proper Officer"when a case is suspected or confirmed.

Health Protection Agency Centre for Infections runs an enhanced surveillance system for B pertussis, and follow up all laboratory-positive cases. They do not need to be informed specifically of cases of vaccine failure, as long as there is a positive laboratory result.

Treatment of cases

If the date of onset of pertussis was within the previous three weeks, a course of antibiotics should be commenced. There is some evidence that this reduces the duration and severity of illness, and decreases transmission rate if started early enough (ideally in the catarrhal stage). See section "Antibiotic treatment and prophylaxis" on choice, timing, and dose of antibiotics. Otherwise, management is supportive. Hospital admission is appropriate if profound cyanosis occurs during paroxysms, or if there is apnoea. Parental concern is often the predominant factor.

Exclusion from school, work, or nursery

Children with a diagnosis of pertussis who are being treated with erythromycin should be isolated if inpatients, and excluded from schools and nurseries, for five days. Similarly, adults with a diagnosis of pertussis for which erythromycin has been commenced should be excluded for the same period if they work with children under five, or with individuals who are immunocompromised or have chronic disease.

Pregnancy

If a woman has suspected or confirmed pertussis with onset within 3 weeks prior to delivery of a baby, then she should be treated in the normal way.

IN ADDITION, the new born infant should also receive chemoprophylaxis (see "Neonatal period").

Management of contacts

Flowchart - management of contacts of cases of pertussis

When a probable or confirmed case of pertussis is diagnosed, details of household contacts should be taken as above. If any doubt exists regarding which contacts require treatment, this should be discussed with a member of the Health Protection Unit before any treatment is commenced.

There is only modest evidence of benefit from treatment, and therefore contacts should only be offered erythromycin prophylaxis if the following conditions apply:

i. The onset of pertussis in the case was within the preceding three weeks.

ii. Where a household (or equivalent setting) contains vulnerable contacts. In this case all close contacts in the following categories should be offered prophylaxis:

  • Adults and children aged ≥ 5 years if they have not received a full primary course (three doses) of pertussis vaccine, and a pre-school booster (born before 1996).
  • Children aged < 5 years if they have not received a full primary course (three doses) of pertussis vaccine.

For more information on the choice, dose, and duration of antibiotics see section "Antibiotic treatment and prophylaxis" .

Where there are no high-risk contacts in a household, no prophylaxis should be given to anyone.

Contacts to be given prophylaxis should receive treatment within 24 hours of diagnosis of pertussis in the case.

Close contacts

  • Family members or people living within a single house
  • Household-type contacts e.g. children who share a bedroom, kissing contacts ONLY IF they will continue to have household-type contact with the vulnerable individual.
  • Contacts in institutions with overnight stay in the same room (e.g. facilities for the learning disabled, hospital wards)

Vulnerable contacts

  • Unimmunised or partially immunised infants or children under five years
  • New-born infants born to symptomatic mothers
  • Individuals of any age with chronic disease e.g. asthma, congenital heart disease, regardless of immunisation status
  • Individuals of any age who are immunocompromised, regardless of immunisation status

Neonatal period

For women with probable or confirmed pertussis, where the woman is still infectious at delivery (i.e. within three weeks of onset), the new-born infant should be commenced on prophylaxis.

Antibiotic treatment and prophylaxis

Antibiotic chemotherapy should be given to cases with onset less than 21 days previously, to prevent onward transmission. There is no evidence of benefit in cases with onset ≥21 days previously. Treatment has only limited effectiveness in preventing transmission even if given before 21 days of exposure.

Antibiotic chemoprophylaxis should be offered, where vulnerable contacts are present, and onset is less than 21 days previously, to close contacts of cases as discussed above.

The dose and duration of treatment is the same for chemoprophylaxis as for chemotherapy.

Choice of antibiotics

Erythromycin

Erythromycin is usually recommended for chemotherapy and chemoprophylaxis of pertussis.

Side-effects of erythromycin tend to be gastrointestinal e.g. nausea, vomiting, diarrhoea.

Erythromycin and neonates

If erythromycin is prescribed to neonates, parents should be informed of possible increased risk of Infantile Hypertrophic Pyloric Stenosis. They should be advised to seek medical advice if symptoms develop. Symptoms include progressive non-bilious vomiting or regurgitation which may become projectile, occurring intermittently or after each feed. Lethargy, dehydration and failure to gain weight or weight loss may occur.

This needs to be balanced against the fact that infants under the age of three months have the highest rates of death and hospital admission due to pertussis.

Dose of erythromycin
  • Children up to 2 years of age: 125mg 6-hourly for 7 days.
  • Children aged 2-8 years: 250mg 6-hourly for 7 days.
  • Children over 8 years, and adults: 250-500mg 6-hourly for 7 days.

Alternative antibiotics

Clarithromycin or azithromycin may be used as an alternative to erythromycin. These have fewer gastrointestinal side-effects but are unlicensed. Azithromycin (10 mg/kg on day 1, and 5 mg/kg on days 2 through 5) is as effective as erythromycin, gastrointestinal adverse events are much less, and compliance in general was markedly better.[10]

Dose of clarithromycin
  • Child: body-weight under 8 kg, 7.5mg/kg twice daily; 8-11 kg (1-2 years), 62.5mg twice daily; 12-19 kg (3-6 years), 125mg twice daily; 20-29 kg (7-9 years), 187.5mg twice daily; 30-40 kg (10-12 years), 250mg twice daily for seven days
  • Adult: 250mg every 12 hours for seven days
Dose of azithromycin
  • Child: over 6 months 10mg/kg once daily for three days; or body-weight 15-25 kg, 200mg once daily for three days; body-weight 26-35 kg, 300mg once daily for three days; body-weight 36-45 kg, 400mg once daily for three days
  • Adult: 500mg once daily for three days

Prevention

2012 UK antenatal pertussis vaccination campaign

See 2012 UK antenatal pertussis vaccination campaign

Vaccination

Pertussis can be safely[11] and effectively prevented by vaccination. The current pertussis vaccination programme comprises a course of primary vaccinations at 2, 3, and 4 months with a five-component acellular pertussis vaccine - for more details see Childhood immunisation. Close contacts aged 3.5 – 6 years should be offered a booster dose if they have not already had one. Adults and children born before November 1996 and some children born 1996 to May 1998 will not have had the pre-school acellular booster.

Unlike many other vaccines, the protection provided by vaccination is relatively short-term, lasting for only about 5-7 years in most cases. Five-component acellular vaccines provide protection that is at least as good as whole-cell vaccine. Whether the additional protection provided by three-component vaccines is clinically important is somewhat controversial: UK experts, on the whole, believe that it is necessary;[12] experts in continental European countries, where an adolescent booster dose is usually given, tend not to agree.

Eradication would need universal program of 10 yearly boosters with a good vaccine.

An adolescent booster as used in France and Germany is not a bad idea if aiming to prevent neonatal disease by ensuring immunity among young parents. Apparent rise in adolescent cases over last 20yrs probably down to increased awareness and different diagnostic methods rather than change in organism or vaccine. Other strategies for preventing neonatal disease are targeting of parents/teachers/health care workers; immunizing pregnant women (ethically difficult); Cocoon strategy of immunizing a new baby's parents/siblings. But these targeted strategies fail to prevent a lot of primary cases in older adults. The JCVI may, in the future, recommend that an adolescent booster dose be added to the UK schedule.

Immunizing neonates would not protect them but would prime them for the second dose.

Immunisation does not have a role in the acute management of cases and contacts of pertussis.

Pertussis vaccine and vaccine scares

A study of children reported to the National Childhood Encephalopathy Study (NCES) in the 1970s erroneously concluded that whole cell pertussis vaccine may very rarely be associated with neurological illness. this caused a widespread loss of confidence in vaccination, and probably the most significant vaccine scare in the UK in the second half of the 20th century. A move to respond to fears by making separate vaccines available, so that other vaccines could be given without giving pertussis vaccine, probably reinforced people's fears. Vaccine coverage fell from about 80% in 1972, to about 30% in 1975, and there were major epidemics resulting in 68,000 notifications and 14 deaths.[13]

The Vaccine Damage Payment Act 1979 introduced the "vaccine damage payment scheme" (since amended[14]), at least partly as a result of this scare, to compensate those allegedly damaged by the vaccine. The effect was to further reinforce the perception that the vaccine was dangerous.

Subsequent studies failed to confirm the original NCES study's findings, and it is now generally accepted that there was no causal link between whole cell pertussis vaccine and "brain damage" - lasting neurological damage. Some patients may have had Dravet's syndrome.[15] The vaccine was, however, fairly strongly reactogenic, containing (as its name suggests) from whole, killed Bordetella pertussis organisms, and consequently many proteins and other immunogenic compounds. It was the most reactogenic component of the vaccines used, responsible for causing a significant number of cases of fever, and, in some cases, febrile convulsions.

In November 2001 the use of whole-cell pertussis vaccine (wP) was discontinued in favour of acellular vaccine (wP).[16] The vaccine currently used in the UK for infant immunisation against Pertussis is Pediacel(TM). In trials, Pediacel was compared with a vaccine that did not contain the acellular Pertussis component, but was otherwise identical. There was no difference in the rate of severity of adverse reactions in the two groups, showing that the acellular pertussis component is not reactogenic compared to the other components in the vaccine.

Investigative journalist Brian Deer sought out individuals who had received vaccine damage payments, and found that in most, possibly all cases, it had since become apparent that the "damage" had existed prior to vaccination, or could be firmly attributed to a cause other than the vaccine.[17]

Nevertheless, some parents remain very suspicious of Pertussis vaccine. As there is no need for an alternative vaccine - other than misplaced fears - no such vaccine is available, and parents must choose to have their child immunised with Pediacel, or not at all.

Chemoprophylaxis

Chemoprophylaxis is recommended for anyone who:

  • is in close contact with [a] vulnerable contact[s], is 5 years old or above and has not already received a pre-school booster OR
  • is in close contact with [a] vulnerable contact[s] and has not completed a primary course of vaccination.

External links

References

  1. Harnden A, Grant C, Harrison T, Perera R, Brueggemann AB, Mayon-White R, Mant D. Whooping cough in school age children with persistent cough: prospective cohort study in primary care. BMJ 2006;333:174-177. Also available here for BMJ subscribers.
  2. A patient’s journey Whooping cough Ros Levenson BMJ 2007;334:532-533 (10March), doi:10.1136/bmj.39120.556296.AE (pmid number not yet available) Full text (subscription may be required) here
  3. Whooping cough after stopping pertussis immunisation Jenkinson D 1979 BMJ 2 (6183) 207-208 subscription may be required
  4. Natural course of 500 consecutive cases of whooping cough: a general practice population study Jenkinson D BMJ. 1995 Feb 4;310(6975):299-302 subscription may be required
  5. Jenkinson D Duration of effectiveness of pertussis vaccine: evidence from a 10 year community study BMJ 1988; 296:612-614 subscription may be required
  6. whoopingcough.net
  7. New Enhanced Surveillance Test (Oral Fluid Antibody) For Pertussis: Clarification of Services Offered. Health Protection Report. 2007:1(26);3. (June 29).
  8. New enhanced surveillance test for pertussis. Health Protection Report. 2007:1(24);3. (June 15).
  9. New Enhanced Surveillance Test (Oral Fluid Antibody) For Pertussis: Clarification of Services Offered. Health Protection Report. 2007:1(26);3. (June 29).
  10. Langley JM, Halperin SA, Boucher FD, Smith B. Azithromycin is as effective as and better tolerated than erythromycin estolate for the treatment of pertussis. Pediatrics. 2004 Jul; 114(1):e96-101.
  11. Ray P et al. Encephalopathy after whole-cell pertussis or measles vaccination: lack of evidence for a causal association in a retrospective case-control study. Pediatr Infect Dis J 2006 Sep 25:768-73
  12. Miller E. Overview of recent clinical trials of acellular pertussis vaccines. Biologicals 1999;27(2):79-86.
  13. Salisbury D, Ramsay M, Noakes K. Chapter 24: Pertussis. Immunisation against infectious disease. 3rd Edition ed. London: HMSO, 2006:277-93 (See also Immunisation "Green Book".)
  14. Statutory Instrument 2002 No. 1592: The Regulatory Reform (Vaccine Damage Payments Act 1979) Order 2002. England, 2001
  15. McIntosh AM, McMahon J, Dibbens LM, Iona X, Mulley JC, Scheffer IE, Berkovic SF. Effects of vaccination on onset and outcome of Dravet syndrome: a retrospective study. The Lancet Neurology, Early Online Publication 2010(5 May) doi:10.1016/S1474-4422(10)70107-1
  16. Donaldson L, Mullally S, Smith J. Current vaccine and immunisation issues. London: Department of Health, 2001 (15 October); 1-8
  17. Deer, B. The vanishing victims: Can whooping cough jabs cause brain damage in children? The Sunday Times Magazine1998 (1 November).
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