European Journal of Pediatrics (2025) 184:138

https://doi.org/10.1007/s00431-025-05978-0

RESEARCH

Severe pertussis infections in pediatric intensive care units:

a multicenter study
Nihal Akçay1 · Demet Tosun1 · İlyas Bingöl1 · İbrahim Bingöl2 · Agop Çıtak2 · Süleyman Bayraktar3 ·
Mehmet Emin Menentoğlu4 · Esra Şevketoğlu4 · Mey Talip5 · Nazlı Umman Serin5 · Ceren Bilgül6 ·
Ülkem Koçoğlu Barlas7 · Leyla Telhan8 · Ebru Şahin9 · Feyza İnceköy Girgin10 · Mehmet Arda Kılınç11 ·
Burcu Bursal12 · Canan Baydemir13

Received: 14 September 2024 / Revised: 3 January 2025 / Accepted: 7 January 2025

© The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2025

Abstract
This study aims to evaluate the clinical course of critical pertussis illness to the pediatric intensive care unit in Istanbul. The
study was conducted as a multicenter, retrospective study between January 1, 2023, and December 31, 2023. Cases with
positive polymerase chain reaction testing for Bordetella pertussis of nasopharyngeal swab samples within the first 24 h of
pediatric intensive care unit admission were recorded. We divided the patients into exchange blood transfusion group and
non-exchange blood transfusion group, comparing related factors and clinical characteristics among each group. A total of 50
children with severe pertussis were enrolled in the study, including 29 males (58%), with a median age of 9.14 weeks (range,
7.29–15.3 weeks). The mortality rate for severe pertussis was 8%. Exchange blood transfusion was performed in eight patients
(16%). There were no significant differences between patients who received exchange blood transfusion and those who did
not in terms of age, male gender, gestational age, birth weight, comorbidities, presenting symptoms, duration of cough,
prior antibiotic use, vaccination status, coinfections, PICU length of stay, or mortality (p > 0.05). Children who underwent
exchange blood transfusion had significantly higher white blood cell (WBC) counts, lymphocyte counts, neutrophil counts,
and C-reactive protein (CRP) levels compared to those who did not receive the procedure (p < 0.05). Pulmonary hypertension
was observed in 50% of the children who received exchange blood transfusion, while it was present in only 11.8% of those
who did not undergo the procedure (p < 0.05). Additionally, patients who received exchange blood transfusion had higher
incidences of respiratory failure, cardiac failure or arrest, inotrope requirement, and mechanical ventilation compared to
those who did not receive the transfusion (p < 0.05). Conclusions: Pertussis can lead to severe complications and mortality
in critically ill infants. Most severe pertussis occurred in young, unimmunized infants. Children admitted with pertussis
with high CRP level, high WBC and lymphocyte, and cardiac and respiratory failure can need exchange blood transfusion.

What is Known:
• Pertussis is a highly contagious respiratory infection caused by Bordetella pertussis, which primarily affects infants. Despite vaccination
efforts, pertussis remains a significant cause of morbidity and mortality in infants, particularly those too young to be fully vaccinated.
What is New:
• In pertussis, exchange blood transfusion may be considered in cases of severe pulmonary hypertension or cardiogenic shock, as indicated by
echocardiographic findings, in conjunction with leukocytosis observed on laboratory tests.

Keywords Children · Critical care · Exchange blood transfusion · Severe pertussis

Introduction

Pertussis, commonly referred to as whooping cough, remains

a significant public health challenge, despite being a vac-
Communicated by Tobias Tenenbaum cine-preventable disease [1]. This highly contagious respira-
Extended author information available on the last page of the article
tory illness, caused by Bordetella pertussis, predominantly

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138 Page 2 of 10 European Journal of Pediatrics (2025) 184:138

affects infants and young children, often leading to severe The management of severe pertussis is primarily support-
morbidity and mortality [2]. Other Bordetella species such ive and may involve mechanical ventilation, inhalation of
as Bordetella parapertussis, Bordetella holmesii, and Bor- nitric oxide (NO), exchange blood transfusion, and, in severe
detella bronchiseptica, which can also cause pertussis-like cases, extracorporeal membrane oxygenation (ECMO).
syndromes. However, these species generally lead to milder Exchange blood transfusion has been reported to enhance
clinical manifestations. While the introduction of effective outcomes in patients with severe pertussis who experience
vaccines in the mid-twentieth century dramatically reduced life-threatening complications that persist despite aggressive
the global incidence of pertussis, outbreaks continue to therapeutic interventions [9].
occur, even in high-income countries. Pertussis is a disease Given these developments, this study aimed to assess
observed worldwide without being restricted to a specific the clinical course of pertussis in pediatric intensive care
geographic location. Although it does not show a clear sea- units (PICUs). The primary objective was to determine the
sonal pattern, it peaks during autumn months, particularly incidence of Bordetella pertussis positive cases admitted to
in regions with low vaccination coverage, and exhibits peri- PICUs over the past year. The secondary objectives were to
odic epidemics every 3 to 5 years [3]. These resurgences are evaluate the clinical and laboratory presentations, treatment
attributed to factors such as waning immunity from acellular strategies, and disease progression in these patients.
vaccines, antigenic shifts in circulating strains, and improved
diagnostic capabilities that enhance detection [4].
The coronavirus disease 2019 (COVID-19) pandemic has
Materials and methods
disrupted routine vaccination schedules, leading to a decline
in immunization rates. However, as COVID-19 restrictions
Study population
have eased, vaccination rates have rebounded, and modeling
studies predict an increase in morbidity and mortality from
This multicenter retrospective study was conducted across
vaccine-preventable diseases. In addition, restrictions during
11 pediatric intensive care units (PICUs) in İstanbul, Tür-
the COVID-19 pandemic had a temporary reduction in the
kiye. The study included all children diagnosed with pertus-
incidence of many infectious diseases [5].
sis and admitted to these PICUs between January 1, 2023,
Pertussis, an endemic disease globally, experiences cycli-
and December 31, 2023. Pertussis diagnosis was confirmed
cal outbreaks every 3 to 5 years, even in areas with high vac-
via polymerase chain reaction (PCR) testing. Only labora-
cination coverage. Following a period of reduced incidence
tory-confirmed cases were included in the analysis. Children
during the COVID-19 pandemic, more than 25,000 pertussis
under 18 years of age who required PICU care and had a
cases were reported in Europe in 2023. The European Centre
confirmed pertussis diagnosis were eligible for inclusion.
for Disease Prevention and Control (ECDC) has reported an
Suspected cases with negative PCR results, despite clinical
increase in pertussis cases compared to pre-pandemic levels,
evidence, were not included. Because of PCR, sensitivity is
potentially linked to diminished circulation of the pathogen
highest within the first 3 weeks of symptom onset.
during the pandemic and suboptimal vaccine uptake in cer-
tain populations [6]. Similarly, data from the Centers for
Disease Control and Prevention (CDC) in 2023 indicate that Data collection
the number of pertussis cases in the USA has approximately
doubled compared to the previous year [7]. Data were collected retrospectively from medical records
The management of pertussis is primarily supportive at each participating center using standardized case report
and includes oxygen therapy, suctioning, adequate hydra- forms. For each case, demographic information, gestational
tion, and avoidance of respiratory irritants. In cases where age, comorbidities, immunization status, clinical presenta-
the disease persists, parenteral nutrition may be required. tion, date of symptom onset, admission diagnosis, illness
First-line antibiotics for pertussis include erythromycin, duration, vital signs, laboratory test results, concurrent infec-
azithromycin, and clarithromycin. Corticosteroids have not tions, complications, need for oxygen supplementation (non-
shown consistent benefits in mitigating the severity or dura- invasive and invasive methods), therapy, length of hospital
tion of the illness but may be considered for critically ill stay (LOS), and mortality were recorded.
infants. Beta-2 agonists, pertussis immune globulin, cough The severity of pediatric acute respiratory distress syn-
suppressants, and antihistamines have not proven effective. drome (pARDS) was categorized as mild, moderate, or
In cases of leukocytosis with lymphocytosis, exchange blood severe, based on the Second Pediatric Acute Lung Injury
transfusion (EBT) therapy may be considered [8]. Death Consensus Conference criteria [10]. All patients underwent
in young infants with severe pertussis is typically linked echocardiographic evaluation by a pediatric cardiologist.
to profound leukocytosis with lymphocytosis, refractory Pulmonary hypertension was diagnosed in accordance with
pulmonary hypertension (PH), and cardiogenic shock [9]. pediatric pulmonary arterial hypertension guidelines [11].
European Journal of Pediatrics (2025) 184:138 Page 3 of 10 138

There is no global consensus on the definitive criteria Results

that determine when EBT should be indicated in cases of
severe pertussis [9]. Participating centers decided on EBT During the study period, 6601 children admitted to 11
based on their own experience. We categorized the patients PICUs in Istanbul were identified in the hospital regis-
into two groups based on whether they received EBT group try. Of these, 50 (0.76%) were diagnosed with pertussis.
or non-EBT group and subsequently compared relevant fac- The median age of the patients was 9 weeks (7–16.5).
tors and clinical characteristics between these groups. The Most were young infants 1–4 months of age (n = 39; 78%)
rationale for this grouping was to evaluate disease severity (Fig. 1A). The majority of patients (58%) were male, and
and examine the effect of EBT. 78% were term. Most patients (84%) had a birth weight
greater than 2500 g. As shown in Fig. 1B, most were
unvaccinated (70%) for pertussis. Thirty percent of the
Respiratory pathogen panel patients had been vaccinated against pertussis at least
once. The number of pertussis cases admitted to PICUs in
The samples were processed using the Bio-Speedy kit Istanbul by month is shown in Fig. 1C.
(Bioeksen, Turkey) and analyzed using the multiplex real- Passive exposure to cigarette smoke in the household
time PCR method on the CFX96 Touch device (Bio-Rad was reported in 28% of patients. Overall, 10 (20%) chil-
Laboratories, Mannheim, Germany). This test is capable dren had known comorbidity. The underlying diseases
of detecting and differentiating Legionella pneumophila, were wheezy infant in 2 (4%) and type 1 diabetes mellitus
human bocavirus, human adenovirus, Bordetella pertussis, in 1 (2%), west syndrome in 1 (2%), ventricular septal
Chlamydia pneumoniae, human coronavirus OC43, human defect in 1 (2%), spinal muscular atrophy type 1 in 1 (2%),
coronavirus NL63, human coronavirus HKU1, human bronchopulmonary dysplasia in 1 (2%), severe laryngoma-
coronavirus 229E, human metapneumovirus, human rhino/ lacia in 1 (2%), and congenital human cytomegalovirus
enteroviruses, influenza A, influenza B, Mycoplasma pneu- infection in 1 (2%) case. Household contacts with pertus-
moniae, parainfluenza 1, 2, 3, and 4, respiratory syncytial sis were reported in 4% of cases, and 62% of patients had
virus A/B, severe acute respiratory syndrome coronavirus 2, visited a healthcare setting prior to the onset of pertussis
human parechovirus, Haemophilus influenzae, and Strepto- symptoms. Among the cases, 12 (24%) received antibiot-
coccus pneumoniae. The results were provided qualitatively. ics before admission to the PICUs. In our study, we used
the respiratory pathogen panel to detect viral and bacterial
coinfections. Co-infections were present in 28% of cases,
Statistical analysis with viral infections being the most common (Table 1).
The most common clinical feature among the patients
Statistical analysis was performed with IBM SPSS for Win- included respiratory distress (90%), paroxysmal cough
dows version 29.0 (IBM Corp., Armonk, NY, USA) sta- (82%), and decrease in feeding ability (58%). Seizure
tistical software package. Continuous variables were sum- and fever were less common, occurring in 8% and 22% of
marized as median (25–75 p). Categorical variables were cases. The median duration of cough was 6.5 days (3–9.5).
expressed as frequencies and percentages. Comparisons Vital signs and laboratory results of the patients are shown
between two groups were made using Fisher’s exact Chi- in Table 2. Chest X-rays were abnormal in 84% of patients,
square test, Yates’ Chi-square test and Monte Carlo Chi- with interstitial findings being the most common. Echo-
square test for categorical variables, and the Mann–Whitney cardiographic findings revealed pulmonary hypertension
U test for continuous variables. A p-value of < 0.05 was con- of varying degrees in 18% of cases. Specifically, mild
sidered statistically significant. PH was observed in 4 patients (8%), moderate PH in 2
patients (4%), and severe PH in 3 patients (6%), while the
remaining 37 patients (74%) had no evidence of PH. Other
Ethical considerations complications included pneumonia (82%), respiratory fail-
ure (68%), cardiac failure and cardiac arrest (10%), septic
This study was approved by the Ethics Committee of Health shock (4%), pleural effusion (4%), macrophage activation
Science University, Kanuni Sultan Süleyman Research and syndrome (4%), acute renal failure (2%), and rhabdomy-
training hospital (KAEK/2024.01.18). Institutional review olysis (2%). Pediatric acute respiratory distress syndrome
board approval was obtained from each participating hos- (PARDS) was diagnosed in 12 patients (24%). Of these
pital in accordance with local ethical regulations. Due to ARDS patients, 7 patients had mild ARDS, 1 patient had
the retrospective nature of the study, informed consent was moderate ARDS, and 4 patients had severe ARDS.
waived. The study was performed according to the ethical
guidelines of the Declaration of Helsinki.
138 Page 4 of 10 European Journal of Pediatrics (2025) 184:138

Fig. 1  Characteristics of pertussis cases, 1 January2023–31 December 2023 (n = 50)

Table 1  Pathogen coinfections associated with B. pertussis infection The most commonly used antibiotic therapy was azithro-
(n = 14) mycin (62%), followed by clarithromycin (36%). Methyl-
Pathogens n prednisolone at a dose of 2 mg/kg was administered to 21
patients (42%), while intravenous immunoglobulin (IVIG)
One-coinfection 7 was given to 4 patients (8%). Inotropic support was required
H. influenzae 2 for 8 patients (16%), and renal replacement therapy (RRT)
HRV 1
was provided to 2 patients (4%). Exchange blood transfu-
HMPV 1
sion was performed in a single session for 5 patients (10%)
ADV 1
and in two sessions for 3 patients (6%). High-flow nasal
SARS-CoV-2 1
cannula (HFNC) was the most frequently used respiratory
CMV 1
support (54%), followed by invasive mechanical ventilation
Two-coinfections 4
(18%), non-invasive mechanical ventilation (8%), and high-
HRV, EV 4
frequency oscillatory ventilation (2%) (Fig. 1D). No patients
Three-coinfections 2
required extracorporeal membrane oxygenation (ECMO).
PIV III, RSV, H. influenzae 1
The median duration of ventilatory support was 10.5 days,
HRV, EV, H. influenzae 1
and the median pediatric intensive care unit (PICU) stay
Four-coinfections 1
was 5.5 days. Of the 50 patients, 92% (46) improved or were
HRV, EV, ADV, S. pneumoniae 1
cured, while 8% (4) succumbed to the illness.
ADV adenovirus, CMV human cytomegalovirus, EV enterovirus, The epidemiological data, clinical manifestations, labora-
HMPV human metapneumovirus, HRV human rhinovirus, PIV tory findings, radiological findings, treatment, and outcomes
parainfluenza, H. influenzae Haemophilus influenzae, RSV respiratory were compared between EBT and non-EBT and are shown
syncytial virus, S. pneumoniae Streptococcus pneumoniae, SARS-
CoV-2 severe acute respiratory syndrome coronavirus 2
in Table 2. There was no statistically significant difference
between the two groups in terms of age, gender, gestational
age, birth weight, comorbidity, vaccination status, antibi-
otic use before admission, coinfection, and manifestations
(all p > 0.05). Respiratory rate was statistically higher in the
European Journal of Pediatrics (2025) 184:138 Page 5 of 10 138

Table 2  Epidemiological data, clinical manifestations, laboratory findings, radiological findings, treatment, and outcomes of pertussis patients
Characteristics Non-EBT n = 42 EBT n = 8 Total n = 50 p value

Age, week, median (IQR) 9 (7−15) 8 (6.5−15) 9 (7−16.5) 0.543

Male gender, n (%) 25 (59.5) 4 (50) 29 (58) 0.625
Gestational age, week, n (%) 0.121
> 37 31 (73.8) 8 (100) 39 (78)
32–36 + 6 10 (23.8) 0 10 (20)
28–31 + 6 1 (2.3) 0 1 (2)
Birth weight, g, median (IQR) 0.207
> 2500 34 (80.9) 8 (100) 42 (84)
1500–2499 7 (16.6) 0 7 (14)
1000–1499 1 (2.3) 0 1 (2)
Comorbidities, n (%) 9 (21.4) 1 (12.5) 10 (20) 0.572
Cough duration before admission(days) median (IQR) 5.5 (3−9.5) 7 (2.75−8.75) 6.5 (3−9.5) 0.862
Received antibiotics before admission, n (%) 10 (23.8) 2 (25) 12 (24) 0.944
Household contacts history, n (%) 2 (4.7) 0 2 (4) 0.538
Pertussis vaccination status, n (%) 0.381
Non-vaccinated (0 dose) 31 (73.8) 4 (50) 35 (70)
Incompletely vaccinated (1 dose or 2 doses) 9 (21.4) 4 (50) 13 (23)
Completely vaccinated (3 doses) 2 (4.7) 0 2 (4)
Coinfections, n (%) 11 (26.1) 3 (37.5) 14 (28) 0.524
Manifestations, n (%)
Paroxysmal cough 41 (97.6) 8 (100) 49 (98) 0.667
Post-tussive vomiting 14 (33.3) 5 (62.5) 19 (38) 0.124
Apnea 11 (26.1) 4 (50) 15 (30) 0.185
Cyanosis 15 (35.7) 4 (50) 19 (38) 0.456
Fever 10 (23.8) 1 (12.5) 11 (22) 0.489
Decrease in feeding ability 24 (57.1) 5 (62.5) 29 (58) 0.784
Nasal congestion, rhinorrhea 21 (50) 5 (62.5) 26 (52) 0.526
Facial flushing and/or cyanosis during coughing 20 (47.6) 5 (62.5) 25 (50) 0.451
Respiratory distress 38 (90.4) 7 (87.5) 45 (90) 0.802
Seizure 2 (4.76) 2 (25) 4 (8) 0.055
Enteritis 12 (28.5) 1 (12.5) 13 (26) 0.352
Vital and clinical signs
Heart rate (beats/min), median (IQR) 140 (123–150) 142 (132–154) 140 (125–150) 0.559
Respiratory rate (breaths/min), median (IQR) 42 (36–50) 68 (58–72) 44 (38–56) 0.001
SBP (mm Hg), median (IQR) 84 (74–90) 88 (76.5–92) 85 (75–90) 0.350
DBP (mm Hg), median (IQR) 49 (42–56) 48 (45.8–60.5) 49 (43–59) 0.588
­sPO2 (%), median (IQR) 96 (93–98) 93.5 (92.8–99.3) 95 (93–99) 0.775
Crackles, n (%) 23 (54.7) 7 (87.5) 30 (60) 0.086
Wheezing, n (%) 17 (40.4) 6 (75) 23 (46) 0.075
Laboratory values, median (IQR)
White blood cell count (­ 103/µL) 18.8 (13.5–38.7) 37.7 (28.1–58.8) 22.8 (14.4–42.1) 0.013
Lymphocyte count, ­(103/µL) 11.8 (7.0–20.2) 23.9 (14.4–35) 12.5 (8.5–24.8) 0.034
Neutrophil count, ­(103/µL) 6.30 (4.0–9.35) 16.5 (12.0–20.7) 7.88 (4.3–10.5) 0.003
Platelet count, ­(103/µL) 499 (392–623) 505 (389–625) 499 (392–625) 0.979
Hemoglobin, (g/dL) 10.1 (9.7–10.8) 10.5 (9.6–10.9) 10.2 (9.7–10.8) 0.652
Hematocrit (%) 30.8 (28.8–33.8) 32.7 (30–34.9) 30.9 (29–34.1) 0.321
ALT (U/L) 23 (14.9–31) 14.5 (9.75–19) 23 (14–30.3) 0.085
AST (U/L) 32.5 (24.9–40.8) 28.5 (23–32) 32 (24.2–39.8) 0.334
Urea (mg/dL) 10 (7–21) 12.5 (9.7–20.6) 10.5 (7.48–21) 0.289
Creatinine (mg/dL) 0.25 (0.20–0.30) 0.25 (0.18–0.30) 0.25 (0.19–0.3) 0.874
138 Page 6 of 10 European Journal of Pediatrics (2025) 184:138

Table 2  (continued)
Characteristics Non-EBT n = 42 EBT n = 8 Total n = 50 p value

Sodium (mEq/L) 138 (135–140) 138 (136–142) 138 (135–140) 0.549

Potassium (mEq/L) 4.85 (4.1–5.21) 4.9 (4.69–5.35) 4.85 (4.18–5.27) 0.368
Calcium (mg/dL) 9.61 (9–9.98) 9.6 (8.97–10.2) 9.61 (9–10) 0.874
Creatine kinase (U/L) 96 (66.8–119) 110 (88.8–156) 98.5 (70–127) 0.254
Lactate dehydrogenase (U/L) 327 (280–410) 374 (313–436) 336 (280–430) 0.398
C-reactive protein (mg/L) 1 (0.46–6.9) 4.69 (3.2–14) 1.04 (0.6–7.54) 0.032
Procalcitonin (ng/mL) 0.2 (0.09–0.53) 0.22 (0.09–0.34) 0.2 (0.09–0.5) 0.932
Troponin (ng/mL) 5.3 (0.02–24) 12.3 (7.1–16.5) 9.71 (0.06–23.6) 0.508
Ferritin (ng/mL) 299 (205–544) 513 (464–3715) 358 (218–552) 0.158
Fibrinogen (mg/dL) 247 (215–392) 269 (227–331) 247 (217–348) 0.725
Prothrombin time (s) 14.4 (13.2–15.9) 13.9 (13.2–15.3) 14.3 (13.2–15.9) 0.743
APTT (s) 30.9 (28–34.3) 30.1 (27.8–32.3) 30.6 (28–34.3) 0.851
Pro-BNP (pg/mL) 729 (325–14,339) 253 (180–1313) 625 (234–1313) 0.476

ET exchange blood transfusion, IQR interquartile range, SBP systolic blood pressure, DBP diastolic blood pressure, SpO2 peripheral capillary
oxygen saturation, WBC white blood cell, ALT alanine aminotransferase, AST aspartate aminotransferase, APTT activated partial thromboplastin
time, pro-BNP B-type natriuretic peptide, BE base excess, ARDS acute respiratory distress syndrome, AKI acute kidney injury, ECMO extracor-
poreal membrane oxygenation, IVIG intravenous immunoglobulin, HFOV high-frequency oscillatory ventilation, PICU pediatric intensive care
unit, CRP C-reactive protein, pCO2 partial pressure of carbon dioxide

EBT group (p < 0.05). There was no significant difference Germany [13]. Summer peak of the pertussis seen in our
in other vital signs, crackles, and wheezing (all p > 0.05). study was similar to the EU (Fig. 1C). The European Centre
The white blood cell count, lymphocyte count, neutrophil for Disease Prevention and Control has reported that the low
count, and the C-reactive protein were statistically higher level of pertussis activity during COVID-19 pandemic in
in the EBT group (all p < 0.05). There was no significant the EU may have increased the proportion of the population
difference in other laboratory findings (all p > 0.05). Respira- susceptible to pertussis and may be partly responsible for the
tory failure, cardiac failure and cardiac arrest, pulmonary increase observed in 2023 [12].
hypertension, inotrope requirement, IVIG used, pARDS, Pertussis can affect individuals of all ages, but it is most
and mechanical ventilation requirement were statistically common among infants and young children. Infants tend to
higher in the EBT group. There was no statistical difference experience more severe disease [14]. The children included
between the two groups in terms of lengths of hospital stay, in this study were admitted with severe pertussis patients in
lengths of intensive care unit stay, and mortality. A detailed PICU, with a median average age of 9 weeks. In this study,
summary of EBT (+) cases is presented in Table 3. 70% of the children were not vaccinated against pertussis,
and 78% were infants younger than 4 months. In Turkey,
the pertussis vaccine is administered as a pentavalent com-
Discussion bination vaccine of diphtheria, tetanus, pertussis, polio, and
Haemophilus influenzae type b (DTaP-IPV/Hib) at 2, 4, 6,
Here, we present data on an ongoing pertussis outbreak and 18 months of age. Also, the national vaccination sched-
in Istanbul, from January up to December 2023, affecting ule includes a booster dose at 48 months, delivered as a
children. This study offers critical insights into the clinical tetravalent combination vaccine (DTaP -IPA) [15]. Our study
characteristics and outcomes of pertussis patients admitted shows that nearly half of the patients experienced onset of
to pediatric intensive care units (PICUs) in Istanbul, Turkey. pertussis under 2 months, and the proportion of unvacci-
The extensive adoption of pertussis vaccination has nated infants was quite high.
resulted in a notable reduction in both the incidence and Although laboratory testing is not always necessary to
mortality of the disease. Nevertheless, recent years have wit- diagnose pertussis, it is often performed to confirm the diag-
nessed a gradual increase in the global incidence of pertus- nosis, particularly when contact prophylaxis is needed or
sis. Pertussis is common worldwide, with an increase every for public health considerations (e.g., in outbreak settings).
3–5 years. Also, pertussis increases in the European Union Laboratory testing is beneficial, especially in patients with-
(EU) during the summer months [12]. Hitz et al. observed out an exposure history. However, we emphasize that labo-
a B. pertussis seasonality with the highest number of posi- ratory confirmation should not delay the initiation of treat-
tive samples in the months from June until September in ment. PCR is an important tool for the diagnosis of pertussis.
Table 3  Clinical characteristics and outcomes of pertussis patients in undergoing exchange blood transfusion therapy
Characteristics Case 1 Case 2 Case 3 Case 4 Case 5 Case 6 Case 7 Case 8

Gender Female Male Male Male Female Male Female Female

European Journal of Pediatrics

Age (weeks) 11 4.3 28.4 200.6 8 5.4 8.7 6.9

Birth status Full term Full term Full term Full term Full term Full term Full term Full term
Birth weight (g) 2800 3500 3300 4500 3200 2500 2900 3600
Presenting symp- Fever. Cough. Cough. Dysp- Cough. Dyspnea. Cough. Dyspnea. Cough. Dysp- Cough. Dysp- Cough. Dysp- Cough. Post-tussive
toms Dyspnea. Apnea. nea. Apnea. Apnea Apnea. Decreased nea. Apnea. nea. Apnea. nea. Apnea. vomiting. Enteritis
(2025) 184:138

Decreased oral Decreased oral oral intake Decreased oral Decreased oral Decreased oral
intake intake intake intake intake
Peak WBC (× ­103/ 103.01 72.3 58.45 78.87 24.59 36.40 60.50 75.10
ml)
Peak lymphocyte 48.8 48.0 31.13 63.00 15.90 10.15 23.90 36.50
Pulmonary hyper- Severe Mild None - Severe Severe None None
tension
Chest X-ray Bilateral consolida- Bilateral consolida- Bilateral consolida- Consolidation on Consolidation on Bilateral consolida- Bilateral consoli- Bilateral consolida-
tion tion tion upper right lung upper right lung tion dation tion
Combined patho- None None None Human rhino / Human rhino / Severe acute None None
gen enterovirus. enterovirus respiratory syn-
Adenovirus. S. drome coronavi-
pneumonia rus 2
Maximum parame- 20/8 36/12 High flow nasal High flow nasal 20/5 23/8,5 31/10 NIV (EPAP: 7
ters of mechanical canula canula IPAP:14)
ventilation (PIP/
PEEP) (cmH₂O)
CRRT​ Yes None None None None None None None
Time of hospital 50 2 25 19 18 1 23 42
stay (day]
Exchange sessions Single Double Single Single Single Single Double Double
Outcome Recovered Died Recovered Recovered Recovered Died Recovered Recovered

AST aspartate aminotransferase, ALT alanine aminotransferase, WBC white blood cell count, CRRT​ continuous renal replacement therapy, PIP peak inspiratory pressure, PEEP positive end-
expiratory pressure, NIV non-invasive mechanical ventilation
*
Tests not performed on the patient
Page 7 of 10
138
138 Page 8 of 10 European Journal of Pediatrics (2025) 184:138

PCR provides faster and more sensitive results compared to reported similar mortality rates among critically ill pertus-
culture. However, careful specimen collection and transport sis patients across multiple centers [19]. This alignment
are critical to ensure that healthcare providers obtain reli- underscores the grave impact of pertussis, especially in
able diagnostic results that accurately inform patient diag- infants who may lack adequate immune protection. Our
nosis [16]. In our study, PCR testing was utilized; however, results echo Straney et al. [20], who documented signifi-
the sensitivity of this method decreases during or after the cant resource utilization in critically ill pertussis patients,
paroxysmal stage and after antibiotic therapy has been initi- reinforcing the necessity for effective prevention strategies
ated. Serologic tests could not be performed due to resource to reduce healthcare strain.
limitations. Nasopharyngeal samples were sent to the Min- Identified risk factors such as abnormal echocardio-
istry of Health Laboratory, where bacterial culture was also graphic findings and cardiac dysfunction emphasize the
conducted. Despite these efforts, our study was limited to critical importance of monitoring for cardiac compli-
the diagnosis of B. pertussis via PCR, and other Bordetella cations in pertussis patients, as supported by previous
species, such as B. parapertussis, were not systematically research. Our findings are also consistent with recent work
investigated. Other Bordetella species, including Bordetella by Poeta et al. [21], which described a pertussis outbreak
parapertussis, Bordetella bronchiseptica, and Bordetella in neonates and young infants in Italy, highlighting the
holmesii, may cause clinical syndromes similar to pertus- vulnerability of this age group and the potential for severe
sis, but they are generally less severe. These species were not outcomes.
targeted in our diagnostic approach, representing a limitation The use of multiplex PCR, which only detects B. per-
of our study. tussis, has been acknowledged as a major limitation of
Infants critically ill with pertussis encompass those pre- our study. Bordetella parapertussis and other Bordetella
senting with apnea, seizures, or pneumonia that is compli- species could not be detected. The other limitations of our
cated by respiratory failure, pulmonary hypertension, and/ study include its retrospective design and potential sam-
or cardiac failure. Complicated pneumonia is typically ple size constraints, which may affect the generalizabil-
associated with a white blood cell count of ≥ 30,000 cells/ ity of the findings. Future research should include larger,
µL [17]. Pneumonia complicated by refractory hypoxemia, prospective studies to validate these findings and explore
pulmonary hypertension, and/or cardiac failure is frequently independent mortality risk factors in critically ill pertus-
associated with severe leukocytosis and carries a mortality sis patients.
rate of up to 80%. In young infants with pertussis, a white In conclusion, this study enhances the understanding of
blood cell count (WBC) of ≥ 30,000 cells/µL correlates with pertussis in critically ill children by identifying key risk
increased disease severity and mortality [15]. Based on factors and highlighting the disease’s severity. Early diag-
experiences from the California outbreak, some infectious nosis, aggressive management, and improved vaccination
disease experts recommend ET for infants under 4 months coverage are crucial for reducing the burden of pertussis
of age who exhibit any of the following criteria: WBC and its associated mortality, especially in young infants and
count ≥ 25,000 cells/µL with a lymphocyte count ≥ 12,000 children. Our results contribute to the existing body of evi-
cells/µL, and one or more of the following conditions: car- dence on severe pertussis. We recommend that WBC and
diogenic shock, pulmonary hypertension, organ failure lymphocyte counts be closely monitored in patients with
(e.g., renal failure). Alternatively, ET may be considered in severe pertussis. If the patient is diagnosed with concomitant
cases where the total WBC count is ≥ 48,000 cells/µL with tachypnea, hypoxia, respiratory failure, heart failure, and/
a lymphocyte count ≥ 15,000 cells/µL, or if the total WBC or pulmonary hypertension, exchange transfusion should be
count is ≥ 30,000 cells/µL with a lymphocyte count ≥ 15,000 promptly initiated.
cells/µL and the rate of rise is ≥ 50% over 24 h. Additional
Acknowledgements The authors would like to thank the staff of the
indications for ET include a consistently elevated pulse rate participating institutions for their contributions.
(> 170 beats/minute), a consistently high respiratory rate
(> 70 breaths/minute), and oxygen saturation levels below Authors’ contributions N.A, D.T, İ.B, B.B and C.B. wrote the main
80% [18]. In our study, we performed ET on 8 patients diag- manuscript text. D.T. and İ.B prepared figure and tables. İ.B, A.Ç, S.B,
M.E.M, E.Ş, M.T, N.U, C.B, U.K.B, L.T, E.Ş, M.A.K and F.İ.G col-
nosed with severe pertussis. WBC median value was 37.700 lected the data in their own centers. All authors reviewed and approved
cells/µL, and lymphocyte median value was 23.900 cells/µL the final manuscript.
in our patients. All patients had pneumonia and respiratory
failure, while 4 patients had heart failure and pulmonary Data availability No datasets were generated or analysed during the
current study.
hypertension. Two of our patients died despite ET.
The mortality rate observed in our study is consistent Declarations
with recent data from the Collaborative Pediatric Critical
Care Research Network Critical Pertussis Study, which Conflict of interest The authors declare no competing interests.
European Journal of Pediatrics (2025) 184:138 Page 9 of 10 138

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Authors and Affiliations

Nihal Akçay1 · Demet Tosun1 · İlyas Bingöl1 · İbrahim Bingöl2 · Agop Çıtak2 · Süleyman Bayraktar3 ·
Mehmet Emin Menentoğlu4 · Esra Şevketoğlu4 · Mey Talip5 · Nazlı Umman Serin5 · Ceren Bilgül6 ·
Ülkem Koçoğlu Barlas7 · Leyla Telhan8 · Ebru Şahin9 · Feyza İnceköy Girgin10 · Mehmet Arda Kılınç11 ·
Burcu Bursal12 · Canan Baydemir13

* Nihal Akçay Agop Çıtak

[email protected] [email protected]
Demet Tosun Süleyman Bayraktar
[email protected] [email protected]
İlyas Bingöl Mehmet Emin Menentoğlu
[email protected] [email protected]
İbrahim Bingöl Esra Şevketoğlu
[email protected] [email protected]
 138 Page 10 of 10 European Journal of Pediatrics (2025) 184:138

4
Mey Talip Department of Pediatric Intensive Care Unit, Bakırköy
[email protected] Dr. Sadi Konuk Training and Research Hospital, University
of Health Sciences, Istanbul, Turkey
Nazlı Umman Serin
5
[email protected] Department of Pediatric Intensive Care Unit, Okmeydanı
Cemil Taşçıoğlu Training and Research Hospital, University
Ceren Bilgül
of Health Sciences, Istanbul, Turkey
[email protected]
6
Department of Pediatric Intensive Care Unit, Faculty
Ülkem Koçoğlu Barlas
of Medicine, İstanbul University, Istanbul, Turkey
[email protected]
7
Department of Pediatric Intensive Care Unit, Göztepe
Leyla Telhan
Prof. Dr. Süleyman Yalçın City Hospital, İstanbul Medeniyet
[email protected]
University, Istanbul, Turkey
Ebru Şahin 8
Department of Pediatric Intensive Care Unit, İstanbul
[email protected]
Medipol University, Istanbul, Turkey
Feyza İnceköy Girgin 9
Department of Pediatric Intensive Care Unit, Sancaktepe
[email protected]
Training and Research Hospital, University of Health
Mehmet Arda Kılınç Sciences, Istanbul, Turkey
[email protected] 10
Department of Pediatric Intensive Care Unit, Pendik Training
Burcu Bursal and Research Hospital, Marmara University, Istanbul, Turkey
[email protected] 11
Department of Pediatric Intensive Care Unit, Başakşehir
Canan Baydemir Çam Ve Sakura City Hospital, University of Health Sciences,
[email protected] Istanbul, Turkey
12
1 Pediatric Infectious Diseases Clinic, Kanuni Sultan Suleyman
Department of Pediatric Intensive Care Unit, Kanuni Sultan
Training and Research Hospital, University of Health
Süleyman Training and Research Hospital, University
Sciences, Istanbul, Turkey
of Health Sciences, Istanbul 34093, Turkey
13
2 Department of Biostatistics and Medical Informatics, Faculty
Department of Pediatric Intensive Care Unit, Acıbadem
of Medicine, Kocaeli University, Kocaeli, Turkey
Atakent Hospital, Acıbadem University, Istanbul, Turkey
3
Department of Pediatric Intensive Care Unit, Haseki Training
and Research Hospital, University of Health Sciences,
Istanbul, Turkey