16. Pertussis (whooping cough)

Pertussis mortality and morbidity rates continue to be highest in the first year of life.[13] In the US during the 1940s pertussis resulted in more infant deaths than measles, diphtheria, poliomyelitis and scarlet fever combined.[16] Beyond age 3 years mortality rates have always been relatively low. In immunised populations virtually all deaths occur in the first two months of life, and deaths in toddlers and preschool-aged children have largely disappeared. Among infants, younger age, lack of immunisation, low socioeconomic status, premature gestation, low birthweight and female gender are associated with an increased risk of fatal pertussis.[17]

Pertussis mortality and morbidity is under-reported.[18, 19] It is estimated that there are three times more deaths due to pertussis than are reported in high-income countries.[18, 20, 21] The burden of pertussis in older adults is underestimated, particularly for those with chronic respiratory conditions, and increases with age.[22, 23] Infants continue to die from pertussis despite advances in intensive care.[11, 24, 25, 26]

Following the introduction of mass immunisation, countries with consistently high immunisation coverage rates have achieved consistently low pertussis incidence rates.[27] The most pronounced decrease in incidence was seen in those aged under 10 years. Although primarily associated with low immunisation coverage, in some instances higher pertussis incidence rates are due to lower or waning vaccine efficacy or less-than-optimal immunisation schedules.[28, 29, 30] The burden of severe disease, particularly since the introduction of acellular vaccines, is highest in infants and unvaccinated young children.[31] However, less severe pertussis cases are also seen in vaccinated children who are further away from the last DTaP and, in some countries, adolescents.[32, 33, 34] Infants too young to have received more than one dose of pertussis vaccine (age 3 months or less) have the highest rate of notification, hospitalisation and death.[35, 36]

Epidemic peaks of pertussis occur every 2–5 years without the consistent seasonal pattern that is typical of most respiratory infections, although evidence from Australia suggests increased incidence (by 15 percent compared with annual average) during spring to summer months.[15] Epidemics are frequently sustained over 18 months or more, during which there are dramatic increases in hospital admission rates. Lack of change in the pertussis epidemic cycle with mass immunisation suggests minimal impact on the circulation of B. pertussis in the population, unlike other epidemic vaccine-preventable diseases, such as measles.[12, 19, 37]

Pertussis mortality in New Zealand

On average, zero to one deaths are associated with pertussis each year in New Zealand. During the 2011–2013 pertussis epidemic there were three deaths in children: two in infants aged under 6 weeks and one in an unimmunised pre-schooler.[38] No deaths from pertussis (as recorded in EpiSurv) occurred during the latest epidemic from October 2017 to May 2019.[38, 39]

Pertussis morbidity in New Zealand

Pertussis morbidity in New Zealand has usually been described using hospital discharge data. National passive surveillance data has been available since 1996, when pertussis became a notifiable disease.

Outbreaks continue to occur throughout New Zealand. For further details refer to the ESR surveillance reports for notifiable diseases and pertussis dashboard. 

Pertussis morbidity in New Zealand as described by notification data

Four epidemics have occurred since pertussis became a notifiable disease, with an epidemic peak annual number of notified cases of 4,140 in 2000, 3,485 in 2004, 5,897 in 2012 and 2956 in 2018 (see Figure 16.1).

The most recent outbreak commenced in October 2017; by the end of May 2019, there were 4,697 cases notified (2,939 laboratory-confirmed).[39] During 2019, 1206 cases were notified, an overall notification rate of 24.5 cases per 100,000 population. Of these cases, 88 (7.3 percent, incidence 148 cases per 100,000) were aged under 1 year and half of these were hospitalised. The youngest infants were at highest risk of hospitalisation with 85 percent of cases age under 2 months, 80 percent age under 3 months and 66 percent aged under 6 months hospitalised (ESR, 8 June 2020). The next highest incidence rate occurred in children aged 1–4 years (68 per 100,000). Pacific and Māori infants had the highest notification rates (300 and 177 per 100,000 respectively), and in children aged 1–4 years, MELAA ethnic group had the highest notification rate (175 per 100,000) followed by European/Other (77 per 100,000).

Figure 16.1: Pertussis notifications and hospitalisations, 1997–2019

Figure 16.2: Age distribution of notified and hospitalised pertussis cases, 2019

Funded pertussis vaccines

Other vaccines

Other acellular pertussis-containing vaccines registered (approved for use) and available (marketed) in New Zealand include:

• Tdap: Adacel (Sanofi)
• Tdap-IPV: Adacel Polio (Sanofi).

Immunogenicity

A review of published data on DTaP-IPV-HepB/Hib found it to be highly immunogenic in infants aged under 2 years for primary and booster vaccination.[45] In clinical studies there was a strong immune response against the vaccine antigens, which persisted for up to approximately six years after vaccination. A review of published clinical trial and post-marketing surveillance data supported the immunogenicity of DTaP‑IPV-HepB/Hib across a range of schedules and when administered concurrently with other vaccines.[46]

Efficacy and effectiveness

Vaccination in pregnancy

Maternal vaccination, given more than seven days before delivery, was estimated to be 91 percent (95% CI: 88–94) effective against laboratory-confirmed pertussis in infants younger than 3 months of age[47] Protection of infants is achieved both by passive antibody transfer and reduced exposure to maternal disease.[48] Tdap given in pregnancy was shown to be 85 percent more effective than post-partum vaccination in preventing pertussis in infants younger than 8 weeks of age.[49]

Timing is important because protection is not as good if the mother is vaccinated less than two weeks prior to birth.[50] Vaccinating from 16 weeks’ gestation allows time for passive transfer and accumulation of antibody in the fetus, such that by 40 weeks’ gestation, infant antibody levels at birth are higher than those in the mother.[51] Giving maternal vaccination during the second trimester rather than later provides more preterm infants with pertussis protection.[52, 53]

See section 16.5.2 for information about maternal pertussis vaccine safety.

Direct protection

The acellular pertussis vaccines approved for use in New Zealand have been shown to provide around 81–85 percent efficacy (95% CI: 51–100) against confirmed pertussis after three infant doses, with follow-up studies suggesting sustained efficacy to age 6 years.[13, 54, 55] In a Swiss study, effectiveness against pertussis hospitalisation increased with each consecutive primary dose in infants from age 2.5 months to 2 years from 42.1 percent (95% CI: 11.3–62.6) after the first dose, 83.9 percent (70.2–92.1) after the second then 98.2 percent (96.1–99.3) to 100 percent (97.9–100) after the third and fourth doses.[56]

While effective, observational data from Australia found that acellular pertussis vaccines may be less effective than the best-performing whole-cell vaccines in preventing whooping cough.[57, 58] However, the quality of the whole cell vaccine varied between countries and a Canadian study found it to be less effective than the acellular vaccine.[59]

Age-appropriate pertussis vaccination in the US was shown to reduce the severity of symptoms and complications of the disease, including 60 percent reduction in the odds of severe disease (seizure, encephalopathy, pneumonia and/or hospitalisation) in children aged 7 months to 6 years, and 30 percent reduction in post-tussive vomiting in those aged 19 months to 64 years.[60]

Duration of protection

Protection against pertussis begins to wane within several years of completion of a three-dose primary and two-dose booster immunisation series. The US has a pertussis immunisation schedule that includes three doses of acellular vaccine during infancy and booster doses at 15 to 18 months and 4 to 6 years.[61] The risk of pertussis increases in the six years after receipt of the fifth dose of this series, indicating a waning in vaccine-induced immunity over this time interval.

A decline in effectiveness was seen in children more distant from the last DTaP dose, by 27 percent per year on average.[62] Waning effectiveness is more rapid following the adolescent booster at around 35 percent per year.[63] In children, vaccine was 80 percent (95% CI: 71–86) effective against pertussis from two weeks to a year following vaccination, 84 percent (77–89) after 1–3 years, declining to 62 percent (42–75) after 4–7 years and to 41 percent (0–66) at eight or more years after vaccination.[64] A meta-analysis estimated that only 10 percent of those vaccinated with five doses of DTaP would be immune to pertussis 8.5 years after their last DTaP dose.[65]

Antibodies to pertussis toxoid, filamentous hemagglutinin and pertactin have been shown to persist five years after receipt of Tdap (Boostrix) in a study of Australian adults aged 18 years and older.[66] However, the duration of protection is unknown.

Transport according to the National Standards for Vaccine Storage and Transportation for Immunisation Providers 2017 (2nd edition).

Store at +2°C to +8°C. Do not freeze. DTaP-IPV-HepB/Hib should be stored in the dark.

The dose of DTaP-IPV-HepB/Hib, DTaP-IPV and Tdap is 0.5 mL, administered by intramuscular injection (see section 2.2.3).

Co-administration with other vaccines

DTaP-IPV-HepB/Hib, DTaP-IPV and Tdap can be administered simultaneously (at separate sites) with other vaccines or IGs.

A primary course of pertussis vaccine is given as DTaP-IPV-HepB/Hib (Infanrix-hexa) at ages 6 weeks, 3 months and 5 months, followed by a dose of DTaP-IPV (Infanrix-IPV) at age 4 years (Table 16.1). A further booster is given at age 11 years (school year 7) as Tdap (Boostrix).

It is important to administer all vaccinations on time. Delays in receipt of infant immunisations significantly increase the risk of infants being hospitalised for severe pertussis.[67]

If a course of immunisation is late or interrupted for any reason, it may be resumed without repeating prior doses (see Appendix 2). The minimum interval between doses is four weeks. A booster dose should be given no earlier than six months after the primary series.

Catch-up immunisation

See Appendix 2 for detailed catch-up immunisation information.

• DTaP-IPV-HepB/Hib or DTaP-IPV may be used for primary immunisation and boosting of children aged under 10 years.
• Tdap may be used for primary immunisation and boosting of children aged 7 to under 18 years.

Tdap is also funded:

• as a single dose for vaccination of patients from aged 65 years old (if not previously received 65-year-old Td dose, within the last 10 years)
• as single dose for vaccination of patients aged 45 years old who have not had 4 previous tetanus doses
• for vaccination of previously unimmunised or partially immunised patients
• for vaccination prior to planned or revaccination following immunosuppression (see section 16.5.3)
• for boosting of patients with tetanus-prone wounds (see section 22.5.5).

Pregnant women should receive a dose of Tdap in every pregnancy so that antibodies can pass to the fetus to provide protection from birth (funded when given any time in second or third trimester). It is recommended to be given from 16 weeks’ gestation of every pregnancy, preferably in the second trimester to protect both the mother and her infant from pertussis.[47, 51] Post-partum maternal vaccination may reduce the risk of a mother infecting her baby but does not have the added benefit of providing the baby with passive antibodies (see section 16.4.2 for details of effectiveness).

Maternal Tdap vaccination has been shown to prevent pertussis disease or reduce severity of the disease and risk of pertussis-related death in very young infants.[68] There is no evidence that Tdap vaccination affects pregnancy outcomes[68, 69, 70] or causes harm to the fetus or neonate.[68, 71]

Tdap vaccines can be given to breastfeeding women, if not given during pregnancy.[72]

Pertussis-containing vaccines are funded for vaccination or re-vaccination of eligible patients who have become immunocompromised, as follows. See also sections 4.2 and 4.2.5.

DTaP-IPV-HepB/Hib (Infanrix-hexa) and DTaP-IPV (Infanrix-IPV)

An additional four doses (as appropriate) of DTaP-IPV-HepB/Hib (for children aged under 10 years) or DTaP-IPV are funded for (re)vaccination of patients:

• post-HSCT or chemotherapy
• pre- or post-splenectomy
• pre- or post-solid organ transplant
• undergoing renal dialysis
• prior to planned or following other severely immunosuppressive regimens.

Up to an additional four doses (as appropriate) of DTaP-IPV-HepB/Hib are funded for children aged 10 years to under 18 years for (re)vaccination of patients post HSCT. This is an off-label use of this vaccine which requires a prescription from an authorised prescriber or the patient’s specialist. In this group, all prior immunity will have been lost and revaccination is equivalent to a primary immunisation schedule. DTaP-IPV-HepB/Hib not recommended for other severely immunocompromised individuals aged 10-18 years that require revaccination as they may have residual immune memory.

Tdap (Boostrix)

An additional four doses (as appropriate) of Tdap (Boostrix) are funded for patients:

• post-HSCT or chemotherapy
• pre- or post-splenectomy
• pre- or post-solid organ transplant
• undergoing renal dialysis
• prior to planned or following other severely immunosuppressive regimens.

A single dose of Tdap is funded for parents or primary caregivers of infants admitted to a neonatal intensive care unit or special care baby unit for more than three days and whose mothers had not received Tdap at least 14 days prior to baby’s birth.

Tdap is recommended but not funded, unless given as prophylaxis for a tetanus-prone wound, for protection against pertussis for:

• professions and students of professions in contact with infants, a booster dose given 5- to 10‑year intervals (depending on employer requirements), for example, lead maternity carers and other health care personnel who work in neonatal units, other clinical settings (such as GPs and practice nurses) and early childhood education services staff (see Table ‎4.9). Infants with respiratory, cardiac, neurological or other co-morbid conditions are particularly at risk from pertussis.
• household members and others who have regular close contact with a newborn, is recommended to have a booster dose of Tdap if they have not had a dose in the previous 10 years. Household members aged under 18 years who are unimmunised or incompletely immunised for their age can receive funded pertussis vaccine; see Appendix 2 for catch-up schedules.
• regardless of maternal vaccination history, all caregivers of infants born at less than 32 weeks’ gestation are recommended to receive a single dose of Tdap (see section 4.2.2)
• early childhood workers and students are recommended a Tdap booster dose at 10-year intervals, although the priority is to ensure all children attending childcare have received age-appropriate vaccination
• adults with a medical condition, not eligible for funded vaccine, who are at increased risk of severe consequences of pertussis (eg, those with chronic respiratory disease).

The only contraindication is an immediate severe anaphylactic reaction to the vaccine, or any component of the vaccine, following a previous dose.

A history of well-controlled seizures in the vaccine recipient or a family history of seizures (febrile or afebrile) or other neurologic disorder is not a contraindication to vaccination against pertussis.[50]

Although previously been considered a precaution, vaccination is recommended for infants with an unstable neurological disorder (eg, poorly controlled epilepsy or deteriorating neurological state) as they may be at high risk of severe pertussis complications.[50]

DTaP-containing vaccines (eg, DTaP-IPV-HepB/Hib and DTaP-IPV) are generally well tolerated in children,[73] including preterm (24 to 36 weeks’ gestation) and/or low birthweight (820–2,020 g) infants.[74, 75]

Local reactions commonly include pain, redness, swelling and induration at the injection site. Less common reactions include fretfulness, anorexia, vomiting, crying and slight to moderate fever. These local and systemic reactions usually occur within several hours of pertussis immunisation and spontaneously resolve within 48 hours without sequelae.[73]

Local reactions increase with age and additional doses of vaccine. The reaction may be due to some of the other vaccine components, such as aluminium. These reactions are usually minor and only last a day or so.

The adult reduced-concentration Tdap (Boostrix) vaccines have been found to have no safety concerns in those aged 10–64 years and those aged over 65 years.[76, 77, 78, 79] Studies of Tdap in pregnant women have not identified any increased risk of adverse maternal, infant or fetal outcomes.[12, 71, 80, 81, 82]

Local reactions following immunisation of adolescents with Tdap are common but usually mild. They include pain (in 75 percent of recipients), swelling (21 percent) and redness (23 percent) at the injection site.[83] Potential systemic reactions following immunisation of adolescents with Tdap include fever >38°C (5 percent), headache (16 percent), fatigue (14 percent) and gastrointestinal symptoms (10 percent).[83]

The incidence of major adverse events following primary pertussis immunisation is summarised in Table 16.2.

The local medical officer of health will advise on the management of contacts. For more details on control measures, see the Communicable Disease Control Manual pertussis chapter. 

The goal of the pertussis immunisation programme is to protect those most at risk of developing severe disease; that is, infants in the first year of life. Two key strategies for reducing the burden of disease in infants are the administration of Tdap vaccination during pregnancy and on-time infant immunisation. Vaccination during pregnancy is recommended and funded for women from the second trimester, preferably from 16 weeks’ gestation (see section 16.5.2). This is the most effective way to protect young infants. More complete and timely delivery of the current infant immunisation schedule would reduce the infant pertussis disease burden in older infants.[67] It is important that all children attending early childhood services are fully vaccinated for their age.

Data on the protective effects of indirect strategies is currently incomplete. ‘Cocoon strategy’ is the term used to describe the protection of infants by immunising those who are potential sources of B. pertussis.[91] Three identified target groups who have the most contact with young and vulnerable infants are (1) new mothers who have not had recent immunisation, family and close contacts of newborns; (2) health care workers; and (3) early childhood workers. Some protection may be provided to infants by cocoon immunisation of parents and other potential household members post-partum, may be pertinent in some circumstances where maternal vaccination did not occur, such as preterm birth, and infants in neonatal intensive care.[92]

Health care workers in particular are at increased risk of pertussis and can transmit pertussis to other health care workers and to patients.[93] Outbreaks in maternity wards, neonatal units and outpatient settings have been described.[94] Fatalities occur as a result of such nosocomial spread.[95]

Mass immunisation cannot be used to control an established community outbreak, although action to update age-appropriate vaccination in institutional settings (schools and early childhood services for staff and students) is appropriate. When an outbreak occurs, individual immunisation status should be checked, and any missing doses given. Vaccination in pregnancy is particularly important to protect the most vulnerable, young infants.

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