Pertussis is mainly caused by the bacterium Bordetella pertussis (B. pertussis). Although 86% of the global target child population had received the recommended 3 doses of DTP-containing vaccine during infancy in 2018, according to the World Health Organization, its control remains a challenge.1,2 Pertussis is especially severe in infants and young children.3–5 Surveillance of incidence and severity of pertussis is key to monitor the impact of vaccination programs, requiring adaptations of recommendations if necessary.6,7 We have previously reported findings from the Swiss Sentinel Surveillance Network on burden of disease in the general population and hospitalizations due to pertussis in children under the age of 16 years from the Swiss Pediatric Surveillance Unit (SPSU).8,9 In 2013, new recommendations in the Swiss national immunization schedule were implemented: a booster dose for adolescents and young adults with close contact to infants <6 months of age, and 1 dose for pregnant women regardless of their previous pertussis vaccination status.10 SPSU based reporting of pertussis resumed in 2013 to evaluate the effects of the new recommendations. Here, we report the findings of the surveillance period from 2013 to 2019.
METHODS
Data Collection
The SPSU is a nationwide surveillance system where all pediatric clinics in Switzerland report defined rare childhood diseases leading to hospitalizations in children under 16 years of age on a monthly basis.9
Case Definition
Reported cases were included in this study if laboratory confirmed by polymerase chain reaction, culture, or serology and fulfilled the clinical case definition. A clinical case of pertussis was defined as (i) signs and symptoms of disease compatible with pertussis (physician diagnosis); (ii) a cough lasting ≥14 days accompanied by at least 1 of the following symptoms: paroxysmal cough, whooping or posttussive vomiting; or (iii) the occurrence of apnea in infants (defined as age <12 months) regardless of duration of cough.
Data Analyses
For each new case notification to the SPSU central office at the Federal Office of Public Health, a standardized questionnaire was sent to the reporting clinic to collect prespecified demographic and clinical characteristics.9 Questionnaires were evaluated for completeness, and, in case of missing data, the reporting institution was contacted for clarification. Data were entered into an Excel datasheet for analysis.
Descriptive analyses were performed for the epidemiology and frequencies of patients’ characteristics. Age-specific proportionate changes in hospitalized cases of pertussis comparing the first with the second half of the current surveillance period were conducted. The respective 95% confidence intervals were calculated with GraphPad Prism Software (version 8.4.3., San Diego, CA) for selected percentages as appropriate using the method of Wilson with modifications by Brown et al.11
RESULTS
During the study period from January 2013 to December 2019, there were 33 pediatric units or hospitals in Switzerland, all of which participate in the SPSU projects; compliance was 100% during the whole study period.
Epidemiology
Two hundred ninety-four cases of pertussis were reported to the SPSU; 81 were excluded for various reasons, mainly erroneous reporting of nonhospitalized patients. Of the remaining 213 cases, including 3 pairs of twins, 91 (43%) were females and 208 (98%) had laboratory confirmed B. pertussis infections (203 by polymerase chain reaction and 5 by culture); 187 (88%) also fulfilled the clinical case definition. The 5 cases without laboratory confirmation fulfilled the clinical case definition (Table, Supplemental Digital Content 1, https://links.lww.com/INF/E112).
Reported case numbers were continuously declining during the surveillance period from 51 (24%) cases in 2013 to 14 (7%) in 2019, except for a slight, intermittent increase in 2016 and 2017. Similarly, during the same years, an intermittent increase was also noted in reported out-patient cases via the Swiss Sentinel Surveillance Network (Table, Supplemental Digital Content 2, https://links.lww.com/INF/E113). Mean annual hospitalization rate was 2.3 (range: 1.0 in 2019 to 3.9 in 2013) per 100,000 children <16 years of age and 31.3 (range: 13.9 in 2018 to 55.3 in 2013) in infants.
In Table 1, a decrease in case numbers from the first to the second half of the surveillance period is demonstrated, which was most pronounced in young infants.
TABLE 1. -
Case Counts by Age Categories and Surveillance Periods
| Age Category |
January 1, 2013, to June 30, 2016 |
July 1, 2016, to December 31, 2019 |
In- or Decrease |
Total (January 01, 2013, to December 31, 2019) |
| N (%)* |
N (%)* |
% (95% CI) |
N (%) |
| <1 mo |
15 (12) |
8 (9) |
–47 (–25 to –70) |
23 (11) |
| 1 mo |
37 (30) |
23 (26) |
–38 (–24 to –54) |
60 (28) |
| <2 mo (cumulative) |
52 (42) |
31 (35) |
–40 (–28 to –54) |
83 (39) |
| 2 mo |
21 (17) |
16 (18) |
–24 (–11 to –45) |
37 (17) |
| 3–5 mo |
26 (21) |
22 (25) |
–15 (–6 to –34) |
48 (23) |
| <6 mo (cumulative) |
99 (80) |
69 (78) |
–30 (–22 to –40) |
168 (79) |
| 6–11 mo |
11 (9) |
6 (7) |
–45 (–21 to –72) |
17 (8) |
| 12–23 mo |
4 (3) |
5 (6) |
+25 (1 to 70) |
9 (4) |
| ≥2 yr |
10 (8) |
9 (10) |
–10 (–1 to –40) |
19 (9) |
| Total |
124 (58)†
|
89 (42)†
|
–28 (–21 to –37) |
213 (100) |
| Extrapolated cases by Swiss Sentinel System§
|
30’117 (58) |
21,970 (42) |
–27 (–27 to –28) |
52,087 (100) |
*Percentage of all reported cases in that period.
†Percentage of total surveillance period 2013–2019.
§Personal Communication Damir Perisa (Federal Office of Public Health, Switzerland, May 26, 2020).
CI indicates confidence interval.
General Patient Characteristics
The majority (N = 168; 79%) of hospitalized children were infants <6 months of age, including 83 (39%) <2 months old (range 16 days–15 years; median 11.6 weeks). Six patients were preterm infants (all <2 months of age when admitted to hospital), but none of them were <33 gestational weeks.
Disease Characteristics
The mean time interval between onset of clinical signs or symptoms of pertussis and hospitalization was 10.7 days (median: 9; range: 0–48) across all ages with a minimum of 5.4 days in neonates (median: 4.5; range: 1–16) and >10 days from 2 months of age onwards. Throughout all age categories, the main reason for hospitalization was severe cough or coughing spells (Table 2). Mean duration of hospitalization was 8 days (median 5, range 2–47) and highest in neonates (Table, Supplemental Digital Content 3, https://links.lww.com/INF/E114).
TABLE 2. -
Reasons for Hospitalization by Age Categories*
| Age Category |
Patients |
Cough/Coughing Spells |
Cyanosis |
Monitoring and Observation |
Feeding Difficulties and Vomiting |
Apnea |
Dyspnea |
Others |
| N known/N total (%) |
N (%) |
N (%) |
N (%) |
N (%) |
N (%) |
N (%) |
N (%) |
| <1 mo |
22/23 (96) |
15 (68) |
4 (18) |
1 (5) |
3 (14) |
4† (18) |
2 (9) |
6 (27) |
| 1 mo |
58/60 (97) |
35 (60) |
13 (22) |
15 (26) |
12 (21) |
7 (12) |
3 (5) |
6 (10) |
| 2 mo |
34/37 (92) |
21 (62) |
8 (24) |
8 (24) |
4 (12) |
8 (24) |
0 (0) |
3 (9) |
| 3–5 mo |
46/48 (96) |
33 (72) |
14 (30) |
11 (24) |
4 (9) |
8† (17) |
2 (4) |
0 (0) |
| 6–11 mo |
17 /17 (100) |
13 (76) |
2 (12) |
4 (24) |
3 (18) |
1 (6) |
1 (6) |
2 (12) |
| 12–23 mo |
9/9 (100) |
4 (44) |
1 (11) |
0 (0) |
0 (0) |
1 (11) |
2 (22) |
2 (22) |
| ≥2 yr |
18/19 (95) |
13 (72) |
4 (22) |
1 (6) |
5 (28) |
1 (6) |
1 (6) |
5 (28) |
| Total |
204/ 213 (96) |
134 (66) |
46 (23) |
40 (20) |
31 (15) |
30 (15) |
11 (5) |
24 (12) |
*In some patients, more than 1 reason for hospitalization was reported.
†Including1patient with an ALTE.
ALTE indicates apparent life-threatening event.
Eighty-five percent of all patients had at least 1 complication due to pertussis, most commonly cyanosis and dyspnea (>50%), especially in infants, whereas pneumonia, cerebral convulsions, and encephalopathy were rare (<5%). Accordingly, requirement for intensive care treatment was highest in neonates (52%) and sharply decreased with increasing age; 17% of patients needed some sort of respiratory support (Table, Supplemental Digital Content 4, https://links.lww.com/INF/E115). Three children died: 2 previously healthy neonates (whose mothers were not vaccinated against pertussis during pregnancy) and one 18-month-old unvaccinated patient. They suffered from severe complications, including pneumonia, encephalopathy, cerebral convulsions and hyperleukocytosis, respectively, leading to death 8 to 11 days after admission. The resulting case fatality rate was 1.4% overall and 8.7% in neonates.
Most patients (133/211; 63%) had received clarithromycin for a mean duration of 7.7 days (median: 7) or azithromycin (N = 61; 29%) for a mean and median of 5 days each. Five (2%) patients did not receive antibiotic treatment for unspecified reasons.
Immunization Status
The majority of patients (122 of 213; 57%) were old enough at onset of disease to have received at least 1 dose of pertussis vaccine, and, in 112 cases, information regarding number of doses, date of immunization and age was complete. Forty-seven (42%) patients were unimmunized, 3 (3%) were incompletely immunized according to age. Although in the remaining 62 (55%) children pertussis immunization status was up-to-date, including 10 children in whom the next dose was already due, most of them were too young to have completed their primary series. Of the 65 children with a history of ≥1 dose of pertussis vaccine, 14 had onset of disease <2 weeks after the first dose, 31 patients ≥2 weeks after the first dose (and <2 weeks after the second dose), 6 had it ≥2 weeks after the second dose, and in 9, 4 and 1 children onset was ≥2 weeks after their third, fourth and sixth dose, respectively. Only in 4 of 168 (2%) infants who acquired pertussis before 6 months of age had the mother been vaccinated during pregnancy at 17 and 31 weeks of gestation, respectively. In 2 of these patients, timing of immunization during pregnancy was not reported. In 1 instance, the unvaccinated mother was even the source of pertussis in her child.
DISCUSSION
When comparing the current study period (2013 to 2019) with the preceding one (2006 to 2010), the mean annual hospitalization rates (per 100,000) were similar in children <16 years of age (2.6 versus 2.3) but decreased slightly from 38.8 to 31.3 in infants. Specifically, when comparing the first 3.5 with the following 3.5 years of the current observation period, case numbers in infants decreased by 32% from 110 to 75 (Table 1). When we compared hospitalizations in children from this study with all reported pertussis cases in Switzerland from the sentinel system,8 total cases in the population declined by 57% from 10,140 (2013) to 4374 (2019), while hospitalizations in infants <2 months declined by 68% from 22 to 7 (Table, Supplemental Digital Content 2, https://links.lww.com/INF/E113). This indicates an impact of pertussis immunization in pregnancy, the extent of which appears to be very similar to reports from other countries such as England, United States, Spain, Argentina, Australia, and Brazil.12–18
As expected, the great majority (79%) of the 213 hospitalized cases were <6 months of age and not or incompletely immunized. Pertussis severe enough to lead to hospitalization is not surprising in partially immunized individuals because vaccine efficacy increases only stepwise from dose to dose.19
Immunization against pertussis during the second or third trimester of pregnancy was recommended in Switzerland in 2013,10 but, unfortunately, its initial uptake was slow with 4% of pregnant women having received pertussis immunization in 2013 and 2014, 10% in 2015 and 13% in 2016.20 Acceptance has since increased and our most recent systematic assessment revealed that the proportion of immunized pregnant women had increased to 61% in late 2019 (Cremer et al, manuscript in preparation). This probably explains the gradual decline of pertussis hospitalizations in infants <2 months of age throughout the surveillance period, disproportionately stronger compared with older age groups. Although our study design did not allow formal assessment of vaccine effectiveness, the low number of breakthrough cases of pertussis in young infants whose mothers had been immunized during pregnancy is reassuring.
Indirect protection of young infants by immunizing their mothers with Tdap against pertussis in every pregnancy is currently the most promising measure, and it is safe and effective.21 Immunization with a stand-alone pertussis vaccine has also been proposed22 but has not been evaluated.
Our study has strengths and limitations. A major strength is the nationwide and standardized reporting of pertussis cases through SPSU and the high proportion of laboratory confirmed cases. Still, we may have underestimated the true number of cases as underreporting occurs in surveillance systems such as the SPSU.23 Further, underrecognition and underdiagnosis of pertussis are likely factors which may also have contributed to falsely low case numbers,24 but there is no reason to believe that this is any different from previous years; therefore, the observed trend of decreasing cases is promising. Finally, it is a shortcoming of our study that White Blood Cell counts were not systematically recorded. Given that extreme leukocytosis is a risk factor for severe pertussis and even death in young infants,25 such information should be recorded consistently in future pertussis surveillance projects.
In conclusion, control of the disease remains challenging, mainly due to failure to vaccinate rather than vaccine failure.
Acknowledgments
We thank the representatives of the paediatric units in Switzerland: M. Albisetti; W. Bär; M. Bianchetti; H. U. Bucher; L. Buetti; F. Cachat; A. Castiglione; C. Däster; P. Diebold; Z. Dovhunovà; G. Duvoisin; S. Ferroni; S. Fluri; M. Gebauer; M. Gehri; E. Giannoni; L. Hegi; K. Held-Egli; M. Horn; P. Imahorn; T. Karen; C. Kind; L. Kottanattu; B. Laubscher; U. Lips; H. Madlon; V. Maghaouri-Slim; A. Malzacher; J. Mc Dougall; J.-C. Minet; M. Mönkhoff; A. Moser; A. Niederer; V. Pezzoli; N. Piol; K. Posfay Barbe; G. Ramos y Munoz; L. Reinhard; T. Riedel; H. Roten; C. Rudin; K. P. Rühs; M. Russo; V. Schlumbom; N. Schöbi; G. Simonetti; S. Stirnemann; C. Stüssi; E. Süess; R. Tabin; M. Tomaske; R. Villiger; S. Wellmann; J. Wildhaber; M. Wopmann; G. Zeilinger; A. Zemmouri; S.-A. Zoubir and all the dedicated physicians for taking care of the patients and helping to complete the questionnaires.
We acknowledge administrative support by Daniela Beeli and codesigning of the study questionnaire with UH as well as database management by Damir Perisa, Swiss Public Health Office, Berne. Thomas Erb, University of Basel Children’s Hospital, kindly calculated 95% confidence intervals for Table 1.
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