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Citation: Principi, N.; Bianchini, S.;
Esposito, S. Pertussis Epidemiology in
Children: The Role of Maternal
Immunization. Vaccines 2024,12, 1030.
https://doi.org/10.3390/
vaccines12091030
Academic Editor: Gianluca Straface
Received: 14 July 2024
Revised: 30 August 2024
Accepted: 4 September 2024
Published: 9 September 2024
Copyright: © 2024 by the authors.
Licensee MDPI, Basel, Switzerland.
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Attribution (CC BY) license (https://
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4.0/).
Review
Pertussis Epidemiology in Children: The Role of
Maternal Immunization
Nicola Principi 1, Sonia Bianchini 2and Susanna Esposito 3, *
1Universitàdegli Studi di Milano, 20122 Milan, Italy; nicola.principi@unimi.it
2Pediatric Unit, ASST Santi Carlo e Paolo, 20153 Milan, Italy; bianchini.sonia@outlook.it
3Pediatric Clinic, Department of Medicine and Surgery, University of Parma, 43121 Parma, Italy
*Correspondence: susannamariaroberta.esposito@unipr.it
Abstract: In the last twelve months, a significant global increase in pertussis cases has been observed,
particularly among infants under three months of age. This age group is at the highest risk for severe
disease, hospitalization, and death. Maternal immunization with the Tdap vaccine during pregnancy
has been recommended to protect newborns by transferring maternal antibodies transplacentally.
This review examines the current epidemiology of pertussis, the importance of preventing it in young
children, and the effectiveness of maternal immunization. Despite the proven benefits of maternal
vaccination, which has been found effective in pertussis prevention in up to 90% of cases, coverage
remains suboptimal in many countries. Factors contributing to low vaccination rates include vaccine
hesitancy due to low trust in health authority assessments, safety concerns, practical barriers to
vaccine access, and the impact of the COVID-19 pandemic, which disrupted routine vaccination
services. The recent increase in pertussis cases may also be influenced by the natural cyclic nature of
the disease, increased Bordetella pertussis (Bp) activity in older children and adults, and the genetic
divergence of circulating Bp strains from vaccine antigens. Given the high efficacy of maternal
vaccination in preventing pertussis in infants, increasing coverage rates is crucial. Efforts to improve
vaccine uptake should address barriers to access and vaccine hesitancy, ensuring consistent immune
protection for the youngest and most vulnerable populations. Enhanced maternal vaccination could
significantly reduce the incidence of whooping cough in infants, decreasing related hospitalizations
and deaths.
Keywords: Bordetella pertussis; maternal immunization; pertussis; pertussis vaccine; whooping cough
1. Introduction
Over the past twelve months, there has been a notable and concerning increase in
pertussis (whooping cough) cases across multiple countries, including regions in India and
Africa. This rise in reported cases, while alarming, must be interpreted with caution due
to several factors, such as incomplete case detection and variations in diagnostic methods
across regions [
1
]. Nonetheless, the recent surge in diagnosed cases is difficult to dismiss,
particularly given the scale of the increase and its widespread nature. For instance, in
the United States, the number of pertussis cases reported in the early months of 2024
was significantly higher than during the same period in 2023. While these numbers are
comparable to those observed in 2019, prior to the COVID-19 pandemic, they suggest that
the current increase may not necessarily indicate a new pertussis epidemic. Instead, it
might reflect a return to pre-pandemic pertussis patterns following the lifting of COVID-19
mitigation measures [
2
]. However, in many other countries, the epidemiological data
suggest a different scenario, supporting the hypothesis of an actual pertussis epidemic.
In the European Union and European Economic Area (EU/EEA) countries, for exam-
ple, there has been a sharp rise in pertussis cases since mid-2023, with 32,037 cases reported
in just the first three months of 2024. This figure is comparable to the totals reported for the
Vaccines 2024,12, 1030. https://doi.org/10.3390/vaccines12091030 https://www.mdpi.com/journal/vaccines
Vaccines 2024,12, 1030 2 of 12
entire year in 2019 and in earlier years, indicating the possibility of an ongoing epidemic [
3
].
Similarly, in England, the situation has escalated dramatically. Between January and June
2024, the UK Health Security Agency (UKHSA) reported 10,493 laboratory-confirmed cases
of pertussis, resulting in nine deaths. This represents a significant increase compared to
the mere 856 cases reported throughout the entire year of 2023. Notably, the number of
confirmed cases during the second quarter of 2024 surpassed those recorded in any quarter
during the 2012 outbreak year, which was one of the most severe in recent history [4].
The rise in pertussis cases is not confined to high-income countries. In India, the
situation has also shown troubling signs. According to recent data from the National
Centre for Disease Control (NCDC) in India, there has been a 30% increase in pertussis
cases in 2024 compared to the previous year, with approximately 7500 cases reported by
mid-year [
5
]. This rise is particularly concerning in rural regions, where access to healthcare
and vaccination is limited. The state of Uttar Pradesh alone reported over 1200 cases in
the first half of 2024, nearly double the number reported in the same period of 2023 [
5
].
These figures highlight the urgent need for enhanced surveillance and vaccination efforts
in India.
In Africa, the situation is equally alarming. Several countries have reported significant
increases in pertussis cases. For instance, in Nigeria, the Ministry of Health recorded over
8000 pertussis cases between January and June 2024, marking a 40% increase compared to
the same period in 2023 [
6
]. This rise is particularly notable in areas with low vaccination
coverage, such as the northern regions of the country, where healthcare infrastructure is
underdeveloped. Similarly, in South Africa, there has been a marked increase in pertussis
incidence, with over 5000 cases reported in the first half of 2024, compared to 3200 cases in
the same period of 2023 [
6
]. These increases have raised concerns about the effectiveness of
existing vaccination programs and the need for more robust public health interventions.
Figure 1summarizes the global trends in pertussis cases among infants under 3 months
across different regions between 2023 and 2024.
Vaccines 2024, 12, x FOR PEER REVIEW 2 of 12
reported in just the first three months of 2024. This figure is comparable to the totals re-
ported for the entire year in 2019 and in earlier years, indicating the possibility of an on-
going epidemic [3]. Similarly, in England, the situation has escalated dramatically. Be-
tween January and June 2024, the UK Health Security Agency (UKHSA) reported 10,493
laboratory-confirmed cases of pertussis, resulting in nine deaths. This represents a signif-
icant increase compared to the mere 856 cases reported throughout the entire year of 2023.
Notably, the number of confirmed cases during the second quarter of 2024 surpassed
those recorded in any quarter during the 2012 outbreak year, which was one of the most
severe in recent history [4].
The rise in pertussis cases is not confined to high-income countries. In India, the sit-
uation has also shown troubling signs. According to recent data from the National Centre
for Disease Control (NCDC) in India, there has been a 30% increase in pertussis cases in
2024 compared to the previous year, with approximately 7500 cases reported by mid-year
[5]. This rise is particularly concerning in rural regions, where access to healthcare and
vaccination is limited. The state of Uar Pradesh alone reported over 1200 cases in the first
half of 2024, nearly double the number reported in the same period of 2023 [5]. These
figures highlight the urgent need for enhanced surveillance and vaccination efforts in In-
dia.
In Africa, the situation is equally alarming. Several countries have reported signifi-
cant increases in pertussis cases. For instance, in Nigeria, the Ministry of Health recorded
over 8000 pertussis cases between January and June 2024, marking a 40% increase com-
pared to the same period in 2023 [6]. This rise is particularly notable in areas with low
vaccination coverage, such as the northern regions of the country, where healthcare infra-
structure is underdeveloped. Similarly, in South Africa, there has been a marked increase
in pertussis incidence, with over 5000 cases reported in the first half of 2024, compared to
3200 cases in the same period of 2023 [6]. These increases have raised concerns about the
effectiveness of existing vaccination programs and the need for more robust public health
interventions.
Figure 1 summarizes the global trends in pertussis cases among infants under 3
months across different regions between 2023 and 2024.
Figure 1.
The surge in pertussis cases has impacted all age groups, with the highest incidence
observed among younger infants. In England, approximately 4% of these cases occurred
in children under 3 months old, a rate that is double that of 2012, which was the last year
Figure 1. Global trends in pertussis cases among infants under three months of age (2023–2024).
The surge in pertussis cases has impacted all age groups, with the highest incidence
observed among younger infants. In England, approximately 4% of these cases occurred
in children under 3 months old, a rate that is double that of 2012, which was the last year
before the introduction of preventive measures specifically targeting this vulnerable age
group [
4
]. This age group is also at the greatest risk of mortality; alarmingly, 9 out of the
Vaccines 2024,12, 1030 3 of 12
29 pertussis-related deaths between 2013 and 2024 occurred within the first six months of
2024 alone [4].
Maternal vaccination has been widely regarded as the most effective strategy for
protecting neonates and young infants from pertussis before they are old enough to receive
the primary immunization series themselves [
7
]. However, the global rise in cases among
infants under 3 months old has raised important questions about the true effectiveness of
this preventive measure and the potential influence of other external factors that might be
contributing to the observed trends.
In this review, we delve into the current epidemiology of pertussis, emphasizing the
critical importance of preventing this disease in young children. We also evaluate the effec-
tiveness of maternal immunization with the Tdap vaccine, explore maternal immunization
coverage rates, and examine the potential reasons behind the increased incidence of pertus-
sis in younger children. To ensure a comprehensive and systematic review of the available
literature on pertussis, we conducted an extensive search of the MEDLINE/PubMed
database, covering the period from January 2000 to 15 May 2024. This time frame was
chosen to capture the most relevant studies, particularly those reflecting changes in per-
tussis epidemiology, advances in vaccine development, and shifts in public health policies
following the COVID-19 pandemic. The search strategy employed a combination of Medi-
cal Subject Headings (MeSH) terms and free-text keywords to maximize the retrieval of
pertinent articles. The search terms included disease and pathogen-specific terms such
as “pertussis”, “Bordetella pertussis”, and “whooping cough”. To address prevention and
vaccination, we included terms like “pertussis prevention”, “pertussis vaccine”, and “Tdap
vaccine”. Finally, to ensure relevance to the target populations, we used terms such as
“children”, “infants”, and “maternal immunization”. Boolean operators were used to
effectively combine these terms, ensuring that the search captured studies relevant to the
key aspects of pertussis epidemiology, prevention, and vaccination. Articles were included
in the review based on several criteria. We considered only peer-reviewed studies with
rigorous study designs, including randomized placebo-controlled trials, controlled clinical
trials, double-blind randomized controlled studies, systematic reviews, and meta-analyses.
The review focused on studies involving children, infants, and pregnant women, as these
populations are most relevant to the objectives of the review. Articles needed to report
on outcomes related to pertussis incidence, the effectiveness of maternal immunization
with the Tdap vaccine, vaccination coverage rates, or factors contributing to the increased
incidence of pertussis in young children. Only articles published in English were included
to maintain consistency, and the time frame was limited to studies published between
January 2000 and 15 May 2024 to capture recent developments and long-term trends. We
excluded articles that did not meet these criteria. Non-peer-reviewed articles, such as
abstracts, case reports, commentaries, and editorials, were excluded due to their lower
level of evidence. Studies focusing exclusively on adults or elderly populations, without
addressing pertussis in children, infants, or pregnant women, were also excluded. Articles
that did not report on relevant outcomes, such as those focused on unrelated respiratory
illnesses or general public health interventions not specific to pertussis, were removed
from consideration. Additionally, if multiple publications reported on the same study
population or dataset, only the most comprehensive or recent publication was included
to avoid duplication of data. The initial search identified a total of 1243 articles. After
removing duplicates, 987 articles remained. We then screened the titles and abstracts of
these articles for relevance, which led to the exclusion of 742 articles that did not meet the
inclusion criteria. A detailed review of the full texts of the remaining 245 articles resulted
in the exclusion of an additional 150 articles based on the aforementioned criteria. In the
end, 70 articles were included in this review. These studies provided comprehensive data
on the epidemiology of pertussis, the effectiveness of maternal immunization, vaccination
coverage rates, and potential reasons behind the increased incidence of pertussis in young
children. The included studies were critically appraised for quality and relevance, with
a particular focus on those that provided robust data and clear conclusions. The findings
Vaccines 2024,12, 1030 4 of 12
from these studies form the basis of our discussion on the current state of pertussis pre-
vention and the challenges that remain in protecting young children from this potentially
deadly disease.
2. Why Pertussis Should Be Prevented in Younger Children
In infants, particularly those under 3 months of age, pertussis is an underdiagnosed,
severe, and risky disease [
8
,
9
]. Underdiagnosis is due to the low sensitivity of clinical
suspicion in these subjects. Unlike older children, younger infants do not exhibit the classic
three stages of disease progression (catarrhal, paroxysmal, and convalescent), making
diagnosis more challenging. Initial symptoms often resemble a mild, viral upper respiratory
tract infection, including nasal congestion, runny nose, sneezing, mild or no fever, and
watery eyes. As the disease progresses, cough frequency and severity increase, but rarely
to paroxysmal levels. Respiratory symptoms can mimic bronchiolitis.
A study in Italy involving 195 children hospitalized for respiratory infection who
were later found positive for Bordetella pertussis (Bp) infection revealed that pertussis was
clinically suspected in only 68 cases (34.87%). The suspicion rate was significantly lower
(27.9%) in children under 3 months, who were often misdiagnosed with bronchiolitis [10].
The most severe cases occur in children under 3 months. In the same study, it was noted
that patients admitted to pediatric intensive care units (PICU) were younger than ward
patients (42.8 vs. 240 days; p< 0.0007) and had longer hospital stays (24.7 vs. 7.52 days;
p< 0.003).
Severe manifestations can include apnea, pulmonary hypertension, acute res-
piratory distress syndrome, encephalopathy, respiratory failure, cardiovascular collapse,
and septic shock [
11
]. Moreover, compared to mild cases, severe cases have a higher leuko-
cyte count
(35,800 ±20,530/mm3
vs. 19,410
±
8590/mm
3
) and severe hyperleukocytosis
(18.18% vs. 0%, p< 0.05) [12].
Despite intensive care, death can occur. A study of 144 hospi-
talized children with severe pertussis, 56.9% of whom were under 3 months old, found that
38 patients were admitted to the PICU, and 13 died. Most deaths (77%) occurred in chil-
dren under 6 weeks, with pulmonary hypertension (PHT) being the most common cause
(odds ratio [OR] 323.29; 95% confidence interval [CI] 16.01–6529.42;
p< 0.001) [13].
Similar
findings were evidenced in a study carried out in eight French PICU enrolling 23 younger
infants with severe pertussis. A total of 9 out of 23 (40%) died; they presented more fre-
quently with cardiovascular failure (100% vs. 36%, p= 0.003) and PHT
(100% vs. 29%,
p= 0.002) than the survivors [14].
3. Maternal Vaccination for the Prevention of Pertussis in Younger Infants
Evidence indicating that younger infants are at the highest risk of severe pertussis,
hospitalization, and death has led experts to recommend maternal immunization during
the latter part of pregnancy. This strategy aims to reduce the clinical burden of pertussis
in infants infected by Bp [
15
]. The transplacental transfer of maternal antibodies to the
fetus is thought to protect the child after birth, especially during the first few months of
life. On the other hand, administration of the pertussis vaccine to neonates and younger
infants is not feasible due to their immature immune systems. Moreover, interventions
such as the administration of tetanus toxoid, reduced diphtheria toxoid, and acellular
pertussis vaccine (Tdap) to unvaccinated postpartum mothers and other family members of
newborn infants to protect infants from pertussis (cocooning strategy) have proven difficult
to implement and are generally ineffective [
16
]. Despite parents being considered putative
transmitters of Bp to their infants, only few studies have shown a significant reduction
of pertussis incidence in younger children whose parents had been immunized before or
immediately after birth [
17
]. In contrast, several other studies have clearly shown that rates
and severity of pertussis infection in younger infants did not differ after the implementation
of postpartum cocooning [18–22].
Studies evaluating the impact of Tdap administration to pregnant women have con-
sistently demonstrated its positive effects. Significant amounts of antibodies against
vaccine antigens—pertussis toxin (PT), pertactin (PRN), and filamentous hemagglutinin
Vaccines 2024,12, 1030 5 of 12
(FHA)—have been detected in cord blood and young infant serum samples. Comparing
pertussis antibody levels in cord blood of pertussis-vaccinated mothers to cord blood of
control (placebo or unvaccinated) mothers, it was shown that geometric mean concentration
(GMC) ratios (Tdap/control) for pertussis antibodies ranged from 2.7 to 22.2 for PT, 3.4 to
21.2 for FHA and 5.5 to 44.0 for PRN [
23
]. Unfortunately, a direct correlation of protection
for pertussis is lacking. Moreover, comparisons between studies are difficult due to different
laboratories and assays used, the timing of the vaccination during pregnancy, study design,
and the epidemiological background of the study population. However, these antibody
levels are considered indicative of substantial protection against the disease [
16
]. Clinical
studies have confirmed this assumption [
24
,
25
]. For example, Amirthalingam et al. [
25
]
compared pertussis epidemiology in England before and after the implementation of mater-
nal immunization programs. With a coverage rate of 64%, maternal immunization resulted
in a 78% (95% CI 72–83%) reduction in pertussis cases and a 68% (95% CI 61–74%) reduction
in hospital admissions for children under 3 months. This age group was the only one where
pertussis cases decreased compared to the pre-immunization period [
25
]. The evidence
that Tdap can be administered to pregnant women without significant risk to the mother,
fetus, or infant has further supported the introduction of maternal immunization in several
countries [26].
Later studies have definitively confirmed the efficacy and clinical relevance of maternal
immunization, addressing issues such as the optimal timing for Tdap administration and
potential reactogenicity. An epidemiological evaluation conducted in England concluded
that maternal immunization is effective even during periods of sustained Bp circulation and
is independent of the acellular vaccine antigen composition [
27
]. The protection afforded by
maternal immunization is extended by the administration of the infant’s first immunization
dose. This study evaluated pertussis incidence across all ages during the three years
following the introduction of maternal immunization, a period marked by a significant
increase in pertussis cases among those over one year old. Compared to the three years
before the maternal program’s introduction, cases in infants under three months dropped
from 60.4 to 12.7 per 100,000, with vaccine efficacy over 90%. Pertussis-related deaths also
decreased, with efficacy calculated at 95% (95% CI 79–100%) [
27
]. Additionally, maternal
vaccination was found effective even after infants received their first primary dose (VE,
82%; 95% CI 65–91%).
In the USA, a retrospective cohort study enrolling 148,981 neonates born in California
from 2010 to 2015 has shown [
28
] that the efficacy of maternal Tdap administration was
91.4% (95% CI; 19.5–99.1%) during the first 2 months of life and 69.0% (95% CI
43.6–82.9%)
during the entire first year of life. Similar findings at least for children in the first two months
of life were reported in a time-trend analysis of infant pertussis from 1 January 2000 to 31
December 2019 [
29
]. Comparing the pre-maternal Tdap vaccination period (2000–2010) with
the post-maternal Tdap vaccination period (2012–2019) and focusing on infants younger
than 2 months and those aged 6–11 months, the impact of maternal vaccination on pertussis
incidence was measured by evaluating slope differences between the two periods. During
the study period, 57,460 pertussis cases in children under 12 months were reported, with
19,322 (33.6%) in infants under 2 months. Before Tdap vaccine administration to pregnant
women, annual pertussis incidence did not change in children under 2 months and slightly
increased in older infants. However, after introducing maternal vaccination, a significant
reduction in pertussis incidence in infants under 2 months was observed (slope,
−
14.53 per
100,000 infants per year; p= 0.001), whereas incidence in the older group did not change
significantly (slope, 1.42 per 100,000 infants per year; p= 0.29) [30].
Initially, maternal immunization was recommended at 28–32 weeks of gestation to
balance antibody transplacental passage and pertussis IgG level decay in fetal blood, en-
suring elevated antibody levels in cord blood. However, the optimal timing for Tdap
administration during pregnancy remains debated, with studies suggesting different rec-
ommendations. Abu Raya et al. reported that both PT and FHA concentrations were
significantly higher in newborns’ cord sera when immunization occurred during gesta-
Vaccines 2024,12, 1030 6 of 12
tional weeks (GW) 27–30 (+6) compared to GW 31–36 and GW > 36 [
30
]. Eberhart et al.
found higher geometric mean concentrations (GMCs) of cord blood antibodies to PT and
FHA in children born full-term to mothers who received Tdap in the second trimester (GW
13–25) compared to those immunized in the third trimester (GW ≥GW) [31].
In the UK, it was found that the efficacy of maternal vaccination was equivalent in
infants with mothers vaccinated in the second or in the third trimester of pregnancy [
32
].
On the contrary, data collected in the USA seemed to suggest that vaccination during the
third trimester could be more effective (77.7%; 95% CI, 48.3–90.4) than first- or second-
trimester vaccination (64.3%; 95% CI
−
13.8% to 88.8%), although CIs overlapped [
33
].
This explains why scientific societies have revised their recommendations, expanding the
gestational window for maternal immunization, despite the slight differences regarding the
best time for vaccine administration. In the EU/EEA, Tdap vaccination is recommended
between GA 16 and 36 weeks [
34
], in the UK from GA 16 to 32 weeks, with a preference
for around GA 20 weeks, and in the USA, vaccination is recommended between GA 27
and 36 weeks, preferably early in this period [
35
]. However, the flexibility supports earlier
maternal immunization, which may protect preterm neonates and increase vaccination
opportunities.
Table 1shows the key findings related to the effectiveness of maternal Tdap immu-
nization based on various studies selected in the manuscript.
Table 1. Effectiveness of maternal immunization against pertussis.
Study/Author Country Year Key-Findings
Amirthalingam et al. [25] England 2012–2013 Effectiveness of 78%
Baxter et al. [28] USA 2010–2015 Effectiveness of 91.4%
Skoff et al. [33] USA 2000–2019 Effectiveness of 77.7% (3rd trimester)
Eberhardt et al. [31] Switzerland 2022
Higher antibody levels when administered in 2nd trimester
Perrett et al. [23] Multiple countries 2020 High antibody transfer
Concerns that maternal immunization might erode the effectiveness of primary vacci-
nation at later ages appear minimal. Studies have shown that children born to vaccinated
mothers have a lower immune response to primary pertussis immunization than those
without maternal immunization, with reduced antibody concentrations against several
pertussis antigens [
36
,
37
] and lower antibody avidity [
38
]. Moreover, it was found that
the blunting response following maternal pertussis immunization is heterologous, also
causing decreased immune response to the polio vaccine and to other vaccines that contain
modified diphtheria or tetanus toxins as carrier proteins, such as pneumococcal conjugate
vaccines [
39
]. Despite these findings, pertussis incidence evaluations in children with
and without maternal immunization who received recommended pertussis vaccine doses
during infancy suggest that any risk is minimal and can be masked by natural variations
in pertussis incidence over time. Briga et al. concluded that no reason exists to debate
maternal immunization as a mandatory measure to reduce pertussis risks in younger
infants [40].
4. Maternal Immunization Coverage
The evidence that maternal Tdap immunization reduces infant pertussis risk quickly
led to official national recommendations in the USA [
41
] and the UK [
42
] in 2011 and 2012,
respectively. In subsequent years, maternal immunization was recommended in several
other countries, including 24 of the 30 EU/EEA countries, Canada, Australia, and most
Central and South American countries [
7
,
43
]. However, many populous and developed
countries, such as China and Japan [
44
,
45
], and EU/EEA countries like Bulgaria, Estonia,
Finland, Malta, and Slovakia, have not yet implemented national Tdap administration
initiatives for pregnant women [46].
Even in countries with strong maternal immunization support, coverage remains
suboptimal. In the USA, six years after the Advisory Committee on Immunization Practices
Vaccines 2024,12, 1030 7 of 12
(ACIP) recommended maternal immunization, coverage was only 56.3% and 31.4% in 2017,
based on data from the MarketScan Commercial and Multi-State Medicaid Databases [
47
].
These levels remained unchanged before the COVID-19 pandemic [
48
] and when the
pandemic was nearing its end. During the 2022–2023 influenza season, coverage was only
55.4% [49].
In England, between 1 October 2012 and 3 September 2013, the average vaccine
coverage was 64% [
25
]. The highest coverage was 76% in December 2016, but it gradually
declined to 58% in June 2023 [
50
]. In the EU/EEA, only nine countries reported maternal
immunization coverage in 2023, with significant variation from 1.6% in Czechia to 88.5%
in Spain. Coverage in Slovenia, Romania, and Germany was 6.5%, 8.8%, and 39.7%,
respectively [
46
]. Some countries also reported lower coverage in 2023 than in previous
years, indicating a decline in adherence to official recommendations.
Figure 2illustrates the relationship between maternal immunization coverage and
pertussis incidence among infants under 3 months old. Each point represents a differ-
ent country, showing how higher vaccination coverage generally correlates with lower
incidence rates.
Vaccines 2024, 12, x FOR PEER REVIEW 7 of 12
Finland, Malta, and Slovakia, have not yet implemented national Tdap administration in-
itiatives for pregnant women [46].
Even in countries with strong maternal immunization support, coverage remains
suboptimal. In the USA, six years after the Advisory Commiee on Immunization Prac-
tices (ACIP) recommended maternal immunization, coverage was only 56.3% and 31.4%
in 2017, based on data from the MarketScan Commercial and Multi-State Medicaid Data-
bases [47]. These levels remained unchanged before the COVID-19 pandemic [48] and
when the pandemic was nearing its end. During the 2022–2023 influenza season, coverage
was only 55.4% [49].
In England, between 1 October 2012 and 3 September 2013, the average vaccine cov-
erage was 64% [25]. The highest coverage was 76% in December 2016, but it gradually
declined to 58% in June 2023 [50]. In the EU/EEA, only nine countries reported maternal
immunization coverage in 2023, with significant variation from 1.6% in Czechia to 88.5%
in Spain. Coverage in Slovenia, Romania, and Germany was 6.5%, 8.8%, and 39.7%, re-
spectively [46]. Some countries also reported lower coverage in 2023 than in previous
years, indicating a decline in adherence to official recommendations.
Figure 2 illustrates the relationship between maternal immunization coverage and
pertussis incidence among infants under 3 months old. Each point represents a different
country, showing how higher vaccination coverage generally correlates with lower inci-
dence rates.
Figure 2.
Several factors may explain the lower-than-expected maternal Tdap vaccination cov-
erage. A systematic review and meta-analysis of studies published by 22 November 2018,
on maternal vaccine acceptance found that healthcare professional (HCP) recommenda-
tion is the most important factor influencing uptake. When a specialist in obstetrics and
gynecology or a midwife recommends the vaccine, the odds of accepting pertussis im-
munization increase tenfold (OR 10.33, 95% CI 5.49–19.43) [51]. However, other factors
may lead pregnant women to disregard HCP recommendations. Over 30% of pregnant
women refuse the Tdap vaccine despite HCP suggestions [52]. Low trust in health author-
ity assessments has been linked to vaccine hesitancy and refusal [53]. A 2019 study in Nor-
way involving 1148 pregnant women at GA 20–40 weeks confirmed that this applies to
Tdap maternal vaccinations [54].
Figure 2. Maternal immunization coverage and pertussis incidence in infants under 3 months.
Several factors may explain the lower-than-expected maternal Tdap vaccination cover-
age. A systematic review and meta-analysis of studies published by 22 November 2018, on
maternal vaccine acceptance found that healthcare professional (HCP) recommendation is
the most important factor influencing uptake. When a specialist in obstetrics and gynecol-
ogy or a midwife recommends the vaccine, the odds of accepting pertussis immunization
increase tenfold (OR 10.33, 95% CI 5.49–19.43) [
51
]. However, other factors may lead preg-
nant women to disregard HCP recommendations. Over 30% of pregnant women refuse
the Tdap vaccine despite HCP suggestions [
52
]. Low trust in health authority assessments
has been linked to vaccine hesitancy and refusal [
53
]. A 2019 study in Norway involving
1148 pregnant women at GA 20–40 weeks confirmed that this applies to Tdap maternal
vaccinations [54].
Safety concerns or fear of side effects are significant factors, overshadowing the risk
of severe disease in the child. Infertility, autism spectrum disorders, and pregnancy-
related problems like miscarriage, preterm birth, and birth defects are common reasons for
vaccine hesitancy [
55
–
57
]. Practical barriers, including physical accessibility, also impact
immunization coverage, even among mothers initially positive about vaccination [
58
]. The
COVID-19 pandemic further exacerbated these issues. A review of studies from 29 countries
Vaccines 2024,12, 1030 8 of 12
showed a general decline in vaccination coverage (up to
−
79%) during the pandemic, with
significant disruptions in vaccination service accessibility and delivery [
59
]. This decline
affected all vaccines, including those containing pertussis antigens [60].
5. Potential Reasons for the Increase in Pertussis Incidence in Younger Infants
Several factors could explain the recent significant increase in pertussis cases among in-
fants under three months of age. Epidemiological studies have shown that larger epidemics
of pertussis tend to occur every three to five years, even without significant variations
in vaccination coverage [
61
]. This suggests that the current epidemic, which also affects
younger infants, may be a manifestation of the natural cyclic nature of the disease, as
suggested by US health authorities. It is well known that a pertussis vaccine administered
in the first year of life provides immunity that declines over time and that most of adults do
not have pertussis-specific antibodies and are vulnerable to infection of Bp [
62
,
63
]. More-
over, the acellular pertussis vaccine, currently used in most countries for immunization,
prevents people from getting sick, but it does not prevent them from becoming infected
and spreading the disease. Both factors create the basis for the development of periodic
epidemics that can have the highest occurrence in children during the first months of life,
especially those without any immune protection. The current pertussis epidemic has been
observed across all age groups, indicating a greater exposure risk for younger infants.
Studies have shown that parents (20–48%) and siblings (19–53%) are common sources of Bp
infection for infants [
64
,
65
]. Thus, a sudden increase in Bp activity in the general population
may have significantly contributed to the rise in pertussis cases in younger infants.
The increased circulation of Bp may be partly attributed to the restrictions implemented
to contain the COVID-19 pandemic. During 2020–2022, pertussis prevalence was very low,
which may have decreased natural boosting and increased the proportion of the population
susceptible to pertussis. In the EU/EEA, the notification rate in 2022 was 0.4 cases per
100,000 population, which was the lowest rate in over a decade. [
66
,
67
]. In the USA, in
2021 only 2116 pertussis cases were reported, compared to 18,917 in 2019. When Bp began
to circulate again, the number of pertussis cases increased. Additionally, the reduction
in vaccine administration during the COVID-19 pandemic contributed to the increase in
unprotected individuals. A study in 10 US jurisdictions during March–May 2020 showed
that DTaP vaccine doses administered to children under 24 months and children aged
2–6 years
declined by a median of 15.7% and 60.3%, respectively, compared with the same
period in 2018 and 2019 [68].
Another potential factor in the recent pertussis epidemic could be the genetic diver-
gence of circulating Bp strains away from vaccine antigens. Evidence suggests that the use
of acellular pertussis vaccines has led to the emergence of Bp strains with increased PT
production, PRN deficiency, and mutations in other vaccine antigens, potentially enabling
vaccine escape. Currently, over 90% of Bp strains circulating in the EU possess one or more
of these genotypes, which may contribute to the reduced efficacy of maternal vaccination
in pregnant women and the increase in pertussis cases among younger infants [69].
Regarding maternal immunization, coverage has remained relatively unchanged in
many countries and has slightly declined in others, with declining trends starting before the
recent pandemic. This suggests that recent variations in maternal immunization coverage
have played a minor role in the development of the epidemic in younger infants. More
significant, however, is the generally low maternal coverage, which leaves many younger
infants without consistent immune protection during the first weeks of life worldwide.
This, combined with increased Bp activity, appears to explain most of the recent pertussis
cases in younger infants [
69
]. Given the high effectiveness of maternal vaccination, higher
coverage levels than those currently present in various countries could significantly reduce
the number of whooping cough cases in younger infants, thereby reducing hospitalizations
and deaths from this serious infectious disease [70].
Vaccines 2024,12, 1030 9 of 12
6. Conclusions
In recent months, a pertussis epidemic has emerged globally, with a particularly alarm-
ing rise in cases among infants under three months old—the age group most vulnerable
to hospitalization and death from the disease. The review highlights that maternal immu-
nization is a critical strategy for protecting these young infants, significantly reducing their
risk of contracting pertussis. Despite the well-documented benefits of maternal immuniza-
tion, the current pertussis control strategies appear insufficient, as evidenced by the surge
in cases.
Available data consistently show that maternal immunization provides significant
protective effects against pertussis in newborns. However, the recent increase in whooping
cough cases among infants under three months old suggests that the broader circulation of
Bp in the general population has led to higher exposure risks for these vulnerable infants.
This trend underscores a critical gap in current pertussis control strategies, namely low
maternal vaccination coverage.
To effectively combat this epidemic, it is imperative to adopt a multifaceted approach
to enhance pertussis prevention. First and foremost, increasing maternal vaccination
coverage must be a priority. This requires concerted efforts at both policy and community
levels. Health authorities should implement targeted campaigns to raise awareness about
the importance of maternal immunization, particularly focusing on pregnant women and
healthcare providers. These campaigns should address common barriers to vaccination,
such as misinformation, vaccine hesitancy, and limited access to healthcare services.
In addition to boosting maternal immunization rates, broader public health strategies
should be reinforced. These include strengthening routine childhood vaccination programs,
ensuring timely administration of booster doses, and enhancing surveillance systems to
monitor pertussis incidence more effectively. Furthermore, public health policies should
consider the integration of pertussis vaccination into prenatal care routines, making it a
standard practice during pregnancy. This could be supported by providing vaccines at
no cost in prenatal clinics and offering incentives for healthcare providers to promote and
administer the vaccine.
Another key recommendation is the expansion of research initiatives to better un-
derstand the epidemiology of pertussis and the factors contributing to the recent increase
in cases. This includes investigating potential changes in the pathogen itself, such as
mutations that may affect vaccine efficacy, and exploring the impact of population immu-
nity levels following the COVID-19 pandemic. Research should also focus on optimizing
vaccine formulations and schedules to enhance their effectiveness in different populations.
Finally, international collaboration is crucial in addressing this global health challenge.
Countries should share data, strategies, and resources to create a coordinated response to
the pertussis epidemic. Global health organizations can play a pivotal role in facilitating
these collaborations and providing guidance on best practices for pertussis control.
Author Contributions: N.P. wrote the first draft of the manuscript; S.B. performed the literature
analysis; S.E. revised the manuscript and gave a substantial scientific contribution. All authors have
read and agreed to the published version of the manuscript.
Funding: This research received no external funding.
Institutional Review Board Statement: Not applicable.
Informed Consent Statement: Not applicable.
Data Availability Statement: Not applicable.
Conflicts of Interest: The authors declare no conflicts of interest.
Vaccines 2024,12, 1030 10 of 12
References
1.
Domenech de Cellès, M.; Rohani, P. Pertussis vaccines, epidemiology and evolution. Nat. Rev. Microbiol. 2024, 1–14. [CrossRef]
[PubMed]
2.
Centers for Disease Control and Prevention. Pertussis Surveillance and Trends. Available online: https://www.cdc.gov/
pertussis/php/surveillance/index.html#:~:text=Preliminary%20data%20show%20that%20more,2019,%20prior%20to%20the%
20pandemic (accessed on 28 June 2024).
3.
Wang, H.; Fu, M.; Chen, W.; Ma, Y. Post-COVID-19 pandemic changes in pertussis incidence among patients with acute respiratory
tract infections in Zhejiang. China Front Microbiol. 2024,15, 1448997.
4.
Gov. UK. Confirmed Cases of Pertussis in England by Month. Available online: https://www.gov.uk/government/publications/
pertussis-epidemiology-in-england-2024/confirmed-cases-of-pertussis-in-england-by-month (accessed on 28 June 2024).
5.
National Centre for Disease Control (NCDC), India. Pertussis Surveillance Data. 2024. Available online: https://ncdc.mohfw.gov.
in/ (accessed on 30 August 2024).
6.
Ministry of Health, Nigeria and South Africa. Pertussis Incidence Reports. 2024. Available online: https://africacdc.org/
download/africa-cdc-weekly-event-based-surveillance-report-march-2024/ (accessed on 30 August 2024).
7.
Esposito, S.; Stefanelli, P.; Fry, N.K.; Fedele, G.; He, Q.; Paterson, P.; Tan, T.; Knuf, M.; Rodrigo, C.; Weil Olivier, C.; et al. Pertussis
Prevention: Reasons for Resurgence, and Differences in the Current Acellular Pertussis Vaccines. Front. Immunol. 2019,10, 1344.
[CrossRef]
8. Polinori, I.; Esposito, S. Clinical Findings and Management of Pertussis. Adv. Exp. Med. Biol. 2019,1183, 151–160. [PubMed]
9.
Principi, N.; Litt, D.; Terranova, L.; Picca, M.; Malvaso, C.; Vitale, C.; Fry, N.K.; Esposito, S. The Italian Pertussis Group For
Persistent Cough In Children. Pertussis-associated persistent cough in previously vaccinated children. J. Med. Microbiol. 2017,66,
1699–1702. [CrossRef]
10.
Di Camillo, C.; Vittucci, A.C.; Antilici, L.; Ciarlitto, C.; Linardos, G.; Concato, C.; Linardos, G.; Concato, C.; Lancella, L.; Villani, A.
Pertussis in early life: Underdiagnosed, severe, and risky disease. A seven-year experience in a pediatric tertiary-care hospital.
Hum. Vaccin. Immunother. 2021,17, 705–713. [CrossRef] [PubMed]
11. Guo, S.; Zhu, Y.; Guo, Q.; Wan, C. Severe pertussis in infants: A scoping review. Ann. Med. 2024,56, 2352606. [PubMed]
12.
Wang, C.; Zhang, H.; Zhang, Y.; Xu, L.; Miao, M.; Yang, H.; Liu, Y.; He, S.; Pang, L. Analysis of clinical characteristics of severe
pertussis in infants and children: A retrospective study. BMC Pediatr. 2021,21, 65. [CrossRef] [PubMed]
13.
Shi, T.; Wang, L.; Du, S.; Fan, H.; Yu, M.; Ding, T.; Xu, X.; Zhang, D.; Huang, L.; Lu, G. Mortality risk factors among hospitalized
children with severe pertussis. BMC Infect. Dis. 2021,21, 1057. [CrossRef]
14.
Coquaz-Garoudet, M.; Ploin, D.; Pouyau, R.; Hoffmann, Y.; Baleine, J.F.; Boeuf, B.; Patural, H.; Millet, A.; Labenne, M.; Vialet, R.;
et al. Malignant pertussis in infants: Factors associated with mortality in a multicenter cohort study. Ann. Intensive Care. 2021,11,
70. [CrossRef]
15.
Abu-Raya, B.; Maertens, K.; Edwards, K.M.; Omer, S.B.; Englund, J.A.; Flanagan, K.L.; Snape, M.D.; Amirthalingam, G.;
Leuridan, E.; Damme, P.V.; et al. Global Perspectives on Immunization During Pregnancy and Priorities for Future Research and
Development: An International Consensus Statement. Front. Immunol. 2020,11, 1282. [CrossRef]
16. Amirthalingam, G. Strategies to control pertussis in infants. Arch. Dis. Child. 2013,98, 552–555. [CrossRef]
17.
Quinn, H.E.; Snelling, T.L.; Habig, A.; Chiu, C.; Spokes, P.J.; McIntyre, P.B. Parental Tdap boosters and infant pertussis: A
case-control study. Pediatrics 2014,134, 713–720. [CrossRef] [PubMed]
18.
Blain, A.E.; Lewis, M.; Banerjee, E.; Kudish, K.; Liko, J.; McGuire, S.; Selvage, D.; Watt, J.; Martin, S.W.; Skoff, T.H. An assessment
of the cocooning strategy for preventing infant pertussis-united states, 2011. Clin. Infect Dis 2016,63, S221–S226. [CrossRef]
[PubMed]
19.
Skowronski, D.M.; Janjua, N.Z.; Tsafack, E.P.; Ouakki, M.; Hoang, L.; De Serres, G. The number needed to vaccinate to prevent
infant pertussis hospitalization and death through parent cocoon immunization. Clin Infect. Dis. 2012,54, 318–327. [CrossRef]
[PubMed]
20.
Castagnini, L.A.; Healy, C.M.; Rench, M.A.; Wootton, S.H.; Munoz, F.M.; Baker, C.J. Impact of maternal postpartum tetanus and
diphtheria toxoids and acellular pertussis immunization on infant pertussis infection. Clin. Infect. Dis. 2012,54, 78–84. [CrossRef]
[PubMed]
21.
Healy, C.M.; Rench, M.A.; Wootton, S.H.; Castagnini, L.A. Evaluation of the impact of a pertussis cocooning program on infant
pertussis infection. Pediatr. Infect. Dis. J. 2015,34, 22–26. [CrossRef]
22.
Carcione, D.; Regan, A.K.; Tracey, L.; Mak, D.B.; Gibbs, R.; Dowse, G.K.; Bulsara, M.; Effler, P.V. The impact of parental postpartum
pertussis vaccination on infection in infants: A population-based study of cocooning in Western Australia. Vaccine 2015,33,
5654–5661. [CrossRef]
23.
Perrett, K.P.; Halperin, S.A.; Nolan, T.; Martínez Pancorbo, C.; Tapiero, B.; Martinón-Torres, F.; Stranak, Z.; Virta, M.; Vanderkooi,
O.G.; Kosina, P.; et al. Immunogenicity, transplacental transfer of pertussis antibodies and safety following pertussis immunization
during pregnancy: Evidence from a randomized, placebo-controlled trial. Vaccine 2020,38, 2095–2104. [CrossRef]
24. Dabrera, G.; Amirthalingam, G.; Andrews, N.; Campbell, H.; Ribeiro, S.; Kara, E.; Fry, N.K.; Ramsay, M. A case-control study to
estimate the effectiveness of maternal pertussis vaccination in protecting newborn infants in England and Wales, 2012–2013. Clin.
Infect. Dis. 2015,60, 333–337. [CrossRef]
Vaccines 2024,12, 1030 11 of 12
25.
Amirthalingam, G.; Andrews, N.; Campbell, H.; Ribeiro, S.; Kara, E.; Donegan, K.; Fry, N.K.; Miller, E.; Ramsay, M. Effectiveness
of maternal pertussis vaccination in England: An observational study. Lancet 2014,384, 1521–1528. [CrossRef]
26.
Donegan, K.; King, B.; Bryan, P. Safety of pertussis vaccination in pregnant women in UK: Observational study. BMJ 2014,
349, g4219. [CrossRef]
27.
Amirthalingam, G.; Campbell, H.; Ribeiro, S.; Fry, N.K.; Ramsay, M.; Miller, E.; Andrews, N. Sustained Effectiveness of the
Maternal Pertussis Immunization Program in England 3 Years Following Introduction. Clin. Infect. Dis. 2016,63 (Suppl. 4),
S236–S243. [CrossRef] [PubMed]
28.
Baxter, R.; Bartlett, J.; Fireman, B.; Lewis, E.; Klein, N.P. Effectiveness of Vaccination during Pregnancy to Prevent Infant Pertussis.
Pediatrics 2017,139, e20164091. [CrossRef] [PubMed]
29.
Skoff, T.H.; Deng, L.; Bozio, C.H.; Hariri, S. US Infant Pertussis Incidence Trends Before and After Implementation of the Maternal
Tetanus, Diphtheria, and Pertussis Vaccine. JAMA Pediatr. 2023,177, 395–400. [CrossRef]
30.
Abu Raya, B.; Srugo, I.; Kessel, A.; Peterman, M.; Bader, D.; Gonen, R.; Bamberger, E. The effect of timing of maternal tetanus,
diphtheria, and acellular pertussis (Tdap) immunization during pregnancy on newborn pertussis antibody levels—A prospective
study. Vaccine 2014,32, 5787–5793. [CrossRef]
31.
Eberhardt, C.S.; Blanchard-Rohner, G.; Lemaître, B.; Boukrid, M.; Combescure, C.; Othenin-Girard, V.; Chilin, A.; Petre, J.; de
Tejada, B.M.; Siegrist, C.A. Maternal Immunization Earlier in Pregnancy Maximizes Antibody Transfer and Expected Infant
Seropositivity Against Pertussis. Clin. Infect. Dis. 2016,62, 829–836. [CrossRef]
32.
Amirthalingam, G.; Campbell, H.; Ribeiro, S.; Stowe, J.; Tessier, E.; Litt, D.; Fry, N.K.; Andrews, N. Optimization of Timing of
Maternal Pertussis Immunization from 6 Years of Postimplementation Surveillance Data in England. Clin. Infect. Dis. 2023,76,
e1129–e1139. [CrossRef] [PubMed]
33.
Skoff, T.H.; Blain, A.E.; Watt, J.; Scherzinger, K.; McMahon, M.; Zansky, S.M.; Kudish, K.; Cieslak, P.R.; Lewis, M.; Shang, N.;
et al. Impact of the US maternal tetanus, diphtheria, and acellular pertussis vaccination program on preventing pertussis in
infants <2 months of age: A case-control evaluation. Clin. Infect. Dis. 2017,65, 1977–1983. [PubMed]
34.
European Centre for Diseases Prevention and Control. Vaccine Schedule. Available online: https://vaccine-schedule.ecdc.
europa.eu/Scheduler/ByDisease?SelectedDiseaseId=2&SelectedCountryIdByDisease=-1#:~:text=The%20use%20of%20a%20
dTap,third%20trimester%20(ideally%2028%20weeks (accessed on 28 June 2024).
35.
Centers for Disease Control and Prevention. Tdap (Pertussis) Vaccine and Pregnancy. Available online: https://www.cdc.gov/
vaccines/pregnancy/hcp-toolkit/tdap-vaccine-pregnancy.html#:~:text=Recommend%20and%20administer%20or%20refer,
antibody%20transfer%20to%20the%20infant. (accessed on 28 June 2024).
36.
Barug, D.; Pronk, I.; van Houten, M.A.; Versteegh, F.G.A.; Knol, M.J.; van de Kassteele, J.; Berbers, G.A.; Sanders, E.A.; Rots, N.Y.
Maternal pertussis vaccination and its effects on the immune response of infants aged up to 12 months in the Netherlands: An
open-label, parallel, randomised controlled trial. Lancet Infect. Dis. 2019,19, 392–401. [CrossRef]
37.
Abu-Raya, B.; Maertens, K.; Munoz, F.M.; Zimmermann, P.; Curtis, N.; Halperin, S.A.; Rots, N.; Barug, D.; Holder, B.; Kampmann,
B.; et al. The Effect of Tetanus-Diphtheria-Acellular-Pertussis Immunization During Pregnancy on Infant Antibody Responses:
Individual-Participant Data Meta-Analysis. Front. Immunol. 2021,12, 689394. [CrossRef]
38.
Caboré, R.N.; Maertens, K.; Dobly, A.; Leuridan, E.; Van Damme, P.; Huygen, K. Influence of maternal vaccination against
diphtheria, tetanus, and pertussis on the avidity of infant antibody responses to a pertussis containing vaccine in Belgium.
Virulence 2017,8, 1245–1254. [CrossRef]
39.
Zimmermann, P.; Perrett, K.P.; Messina, N.L.; Donath, S.; Ritz, N.; van der Klis, F.R.M.; Curtis, N. The Effect of Maternal
Immunisation During Pregnancy on Infant Vaccine Responses. EClinicalMedicine 2019,13, 21–30. [CrossRef]
40.
Briga, M.; Goult, E.; Brett, T.S.; Rohani, P.; Domenech de Cellès, M. Maternal pertussis immunization and the blunting of routine
vaccine effectiveness: A meta-analysis and modeling study. Nat. Commun. 2024,15, 921. [CrossRef]
41.
Sawyer, M.; Liang, J.L.; Messonnier, N.; Clark, T.A. Updated recommendations for use of tetanus toxoid, reduced diphtheria
toxoid, and acellular pertussis vaccine (Tdap) in pregnant women—Advisory Committee on Immunization Practices (ACIP),
2012. Morb. Mortal. Wkly. Rep. 2013,62, 131–135.
42.
GOV. UK Pregnant Women to be Offered Whooping Cough Vaccination. Available online: https://www.gov.uk/government/
news/pregnant-women-to-be-offered-whooping-cough-vaccination (accessed on 28 June 2024).
43.
Esposito, S.; Principi, N. Prevention of pertussis: An unresolved problem. Hum. Vaccin. Immunother. 2018,14, 2452–2459.
[CrossRef]
44.
Zhang, J.; Deng, J.; Yang, Y. Pertussis vaccination in Chinese children with increasing reported pertussis cases. Lancet Infect. Dis.
2022,22, 21–22. [CrossRef]
45.
Hiiragi, K.; Obata, S.; Miyagi, E.; Aoki, S. The current status, attitudes, and practices concerning maternal pertussis vaccination in
obstetric delivery facilities in Kanagawa Prefecture, Japan: A questionnaire survey. Hum. Vaccin. Immunother. 2021,17, 4235–4238.
[CrossRef] [PubMed]
46.
European Centre for Disease Prevention and Control. Increase of Pertussis Cases in the EU/EEA. Technical Annex 1. Available
online: https://www.ecdc.europa.eu/sites/default/files/documents/Increase%20in%20pertussis%20cases%20in%20the%20
EU-EEA%20-%20May%202024%20FINAL.pdf (accessed on 28 June 2004).
47.
Ghaswalla, P.; Poirrier, J.E.; Packnett, E.R.; Irwin, D.E.; Gray, S.R.; Buck, P.O. Maternal Immunization in the U.S.: A Nationwide
Retrospective Cohort Study. Am. J. Prev. Med. 2019,57, e87–e93. [CrossRef] [PubMed]
Vaccines 2024,12, 1030 12 of 12
48.
Isenhour, C.J.; Skoff, T.H.; Lindley, M.C.; Zhou, F.; Hariri, S. Tetanus, Diphtheria, and Acellular Pertussis Vaccination Coverage
among Publicly Insured Pregnant Women, U.S., 2016–2019. AJPM Focus 2022,2, 100060. [CrossRef]
49.
Razzaghi, H.; Kahn, K.E.; Calhoun, K.; Garacci, E.; Skoff, T.H.; Ellington, S.R.; Jatlaoui, T.C.; Black, C.L. Influenza, Tdap, and
COVID-19 Vaccination Coverage and Hesitancy Among Pregnant Women—United States, April 2023. Morb. Mortal. Wkly. Rep.
2023,72, 1065–1071. [CrossRef]
50.
Nuffieldtrust. Vaccination Coverage for Children and Mothers. Available online: https://www.nuffieldtrust.org.uk/resource/
vaccination-coverage-for-children-and- mothers-1 (accessed on 28 June 2024).
51.
Kilich, E.; Dada, S.; Francis, M.R.; Tazare, J.; Chico, R.M.; Paterson, P.; Larson, H.J. Factors that influence vaccination decision-
making among pregnant women: A systematic review and meta-analysis. PLoS ONE 2020,15, e0234827. [CrossRef] [PubMed]
52.
Kahn, K.E.; Black, C.L.; Ding, H.; Williams, W.W.; Lu, P.-J.; Fiebelkorn, A.P.; Havers, F.P.; D’Angelo, D.V.; Cheung, A.; Ruther, N.A.
Influenza and Tdap Vaccination Coverage among Pregnant Women—United States, April 2018. Morb. Mortal. Wkly. Rep. 2018,67,
1055–1059. [CrossRef] [PubMed]
53.
Krastev, S.; Krajden, O.; Vang, Z.M.; Juárez, F.P.; Solomonova, E.; Goldenberg, M.J.; Weinstock, D.; Smith, M.J.; Dervis, E.; Pilat, D.;
et al. Institutional trust is a distinct construct related to vaccine hesitancy and refusal. BMC Public Health 2023,23, 2481. [CrossRef]
54.
Hansen, B.T.; Winje, B.A.; Stålcrantz, J.; Greve-Isdahl, M. Predictors of maternal pertussis vaccination acceptance among pregnant
women in Norway. Hum. Vaccin. Immunother. 2024,20, 2361499. [CrossRef]
55.
Vilca, L.M.; Cesari, E.; Tura, A.M.; Di Stefano, A.; Vidiri, A.; Cavaliere, A.F.; Cetin, I. Barriers and facilitators regarding influenza
and pertussis maternal vaccination uptake: A multi-center survey of pregnant women in Italy. Eur. J. Obstet. Gynecol. Reprod. Biol.
2020,247, 10–15. [CrossRef] [PubMed]
56.
Bödeker, B.; Walter, D.; Reiter, S.; Wichmann, O. Cross-sectional study on factors associated with influenza vaccine uptake and
pertussis vaccination status among pregnant women in Germany. Vaccine 2014,32, 4131–4139. [CrossRef]
57.
Wilcox, C.R.; Calvert, A.; Metz, J.; Kilich, E.; MacLeod, R.; Beadon, K.; Heath, P.T.; Khalil, A.; Finn, A.; Snape, M.D.; et al.
Determinants of Influenza and Pertussis Vaccination Uptake in Pregnancy: A Multicenter Questionnaire Study of Pregnant
Women and Healthcare Professionals. Pediatr. Infect. Dis. J. 2019,38, 625–630. [CrossRef]
58.
Filip, G.; Sala, A.; Modolo, V.; Arnoldo, L.; Brunelli, L.; Driul, L. Vaccination: Adherence and Hesitancy among Pregnant Women
for COVID-19, Pertussis, and Influenza Vaccines. Vaccines 2024,12, 427. [CrossRef]
59.
Yunusa, A.; Cabral, C.; Anderson, E. The impact of the COVID-19 pandemic on the uptake of routine maternal and infant vaccines
globally: A systematic review. PLoS Glob Public Health 2022,2, e0000628. [CrossRef]
60.
Dalton, M.; Sanderson, B.; Robinson, L.J.; Homer, C.S.E.; Pomat, W.; Danchin, M.; Vaccher, S. Impact of COVID-19 on routine
childhood immunisations in low- and middle-income countries: A scoping review. PLoS Glob Public Health 2023,3, e0002268.
[CrossRef]
61. Decker, M.D.; Edwards, K.M. Pertussis (Whooping Cough). J. Infect. Dis. 2021,224 (12 Suppl. 2), S310–S320. [CrossRef]
62.
Berbers, G.; van Gageldonk, P.; Kassteele, J.V.; Wiedermann, U.; Desombere, I.; Dalby, T.; Toubiana, J.; Tsiodras, S.; Ferencz, I.P.;
Mullan, K. Circulation of pertussis and poor protection against diphtheria among middle-aged adults in 18 European countries.
Nat. Commun. 2021,12, 2871. [CrossRef]
63.
Papagiannis, D.; Thireos, E.; Mariolis, A.; Katsioulis, A.; Gartzonika, K.; Malliaraki, N.; Agnantis, C.; Tsaras, K.; Malli, F.; Rouka,
E.C.; et al. Pertussis Prevalence in Adult Pop-ulation in Greece: A Seroprevalence Nationwide Study. Vaccines 2022,10, 1511.
[CrossRef] [PubMed]
64.
Wendelboe, A.M.; Njamkepo, E.; Bourillon, A.; Floret, D.D.; Gaudelus, J.; Gerber, M.; Grimprel, E.; Greenberg, D.; Halperin, S.;
Liese, J.; et al. Transmission of Bordetella pertussis to young infants. Pediatr. Infect. Dis. J. 2007,26, 293–299. [CrossRef] [PubMed]
65.
Bianchini, S.; Argentiero, A.; Camilloni, B.; Silvestri, E.; Alunno, A.; Esposito, S. Vaccination against Paediatric Respiratory
Pathogens. Vaccines 2019,7, 16. [CrossRef]
66.
European Centre for Disease Prevention and Control (ECDC). Pertussis—Annual Epidemiological Report for 2022. Stock-Holm:
ECDC. 2024. Available online: https://www.ecdc.europa.eu/sites/default/files/documents/PERT_AER_2022_Report.pdf
(accessed on 28 June 2024).
67.
Centers for Disease Control and Prevention. Pertussis Cases by Year (1922–2022). Available online: https://www.cdc.gov/
pertussis/php/surveillance/pertussis-cases-by-year.html (accessed on 15 August 2024).
68.
Patel Murthy, B.; Zell, E.; Kirtland, K.; Jones-Jack, N.; Harris, L.; Sprague, C.; Schultz, J.; Le, Q.; Bramer, C.A.; Kuramoto, S.; et al.
Impact of the COVID-19 Pandemic on Admin-istration of Selected Routine Childhood and Adolescent Vaccinations—10 U.S.
Jurisdictions, March–September 2020. Morb. Mortal. Wkly. Rep. 2021,70, 840–845. [CrossRef]
69.
Brandal, L.T.; Vestrheim, D.F.; Bruvik, T.; Roness, R.B.; Bjørnstad, M.L.; Greve-Isdahl, M.; Steens, A.; Brynildsrud, O.B. Evolution
of Bordetella pertussis in the acellular vaccine era in Norway, 1996 to 2019. Eur. J. Clin. Microbiol. Infect. Dis. 2022,41, 913–924.
[CrossRef]
70.
Esposito, S. Prevention of pertussis: From clinical trials to Real World Evidence. J. Prev. Med. Hyg. 2018,59, E177–E186. [PubMed]
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