Poltekita: Jurnal Ilmu Kesehatan Vol.17 No.1 May 2023: Hal.

203-210
http://jurnal.poltekkespalu.ac.id/index.php/JIK p-ISSN: 1907-459X e-ISSN: 2527-7170

Case Study

Leukocytosis as a Predictor of Clinical Worsening and Complications in Children with

Pertussis: A Systematic Review of Case Study
Bakhtiar 1*, Inayah Zhiaul Muttaqin 1, Ghazi Maulana2, Ghina Tsurayya3, Garsia
Safana3
1
Department of Pediatrics, Faculty of Medicine, Universitas Syiah Kuala, Zainoel Abidin
General Hospital, Banda Aceh, Indonesia
2
Study Program of Medical Profession, Faculty of Medicine, Universitas Syiah Kuala,
Zainoel Abidin General Hospital, Banda Aceh, Indonesia
3
Study Program of Medical Education, Faculty of Medicine, Universitas Syiah Kuala,
Banda Aceh, Indonesia

(Correspondence author's e-mail, [email protected] / +628116831966)

ABSTRACT
Pertussis is a highly contagious disease with clinical features ranging from mild to severe and
various complications. Hematological examination, especially the leukocyte count, can predict the
possibility of clinical deterioration with several complications, such as pneumonia. This case study aimed
to assess whether leukocytosis could indicate the clinical worsening of pertussis in children. This
research method is a systematic review on a case study. The subject of this case study is a child with
pertussis experiencing clinical deterioration. Prominent laboratory data in this case study includes
leukocytosis. This systematic review aims to analyze the association between leukocytosis and the clinical
deterioration of this case study. Literature search procedure using PubMed, Cochrane, and Google
Scholar search instruments. The keywords used are "pertussis," "risk factor," and "and children." Using
the limitations of randomized controlled clinical trials, systematic reviews, meta-analyses, cohorts, and
cross-sectional or case series, the language of instruction is English, and publications within the last 20
years. Overall, 16,666 articles were obtained, consisting of 43 pieces from PubMed; only two papers
were valid. Of the 3,123 articles on the Cochrane, only two are valid. Likewise, out of 13,500 articles on
Google Scholar, only two are valid. Furthermore, it was traced based on the aspect of duplication, then
three papers were found, which were cohort studies. It was concluded that leukocytosis predicts clinical
deterioration and complications in children with pertussis.
Keywords: Pertussis, Clinical Deterioration, Pneumonia, Leukocytosis.
https://doi.org/10.33860/jik.v17i1.2211
© 2023 by the authors. Submitted for possible open access publication under the terms and conditions of the Creative
Commons Attribution (CC BY SA) license (https://creativecommons.org/licenses/by-sa/4.0/).

INTRODUCTION
Pertussis is a highly contagious disease 4%. In one study in infants, mortality was 70%
with clinical features ranging from mild to and higher in infants under 6 weeks (84%) 3.
severe and various complications 1,2. From The infant mortality rate in the United States is
various reports, pertussis is also a disease with 2.4 per 1 million, and 90% of all deaths from
a high mortality rate. World Health pertussis occur in infants under six months of
Organization (WHO) estimates that pertussis age 4,5.
affects nearly 240 million children under five Pertussis is a highly contagious
years of age each year and causes 160,000 respiratory tract infection most commonly
deaths in this age group, with a mortality rate of affecting young, unimmunized, or incompletely

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immunized infants 6–8. The typical clinical instruments. The keywords used are "pertussis,"
features of pertussis include recurrent "risk factor," and "and children." Using the
paroxysmal coughing, inspiratory whoops, and limitations of randomized controlled clinical
vomiting after coughing. The classic disease trials, systematic reviews, meta-analyses,
characterized by three phases (catarrhal, cohorts, and cross-sectional or case series, the
paroxysmal and convalescent) has been seen language of instruction is English, and
less frequently since the start of immunization publications within the last 20 years.
6,9,10
. This clinical picture varies in each child,
depending on the phase of the disease. In severe RESULTS
infections, pertussis causes several
complications that begin with clinical Pertussis is a highly contagious disease
worsening. One of these clinical worsening with clinical features ranging from mild to
occurs when pertussis causes difficulties in the severe and various complications. The disese
form of pneumonia (lung infection) 6,11,12. caused by infection with Bordetella pertussis
Clinical worsening of pneumonia must can be divided into three phases: catarrhal,
be anticipated as an effort to prevent paroxysmal, and convalescent. A definite
complications so that death does not occur. diagnosis is made based on laboratory tests,
Because of this, clinical data must be sought namely the finding of Bordetella pertussis,
which can be used as indicators for predicting either by culture, Polymerase Chain Reaction
clinical worsening of pertussis in children 1,12. (PCR), or serological examination. 6–8.
In several cases of pneumonia that occur as a A 12-year-old girl was brought to the
complication of pertussis, an increase in Emergency Room (IGD) at Zainoel Abidin
leukocyte levels (leukocytosis) is always found. General Hospital, Banda Aceh. This patient was
The clinical question here is whether the a referral from the Teungku Chik Ditiro
laboratory picture of leukocytosis can be used Hospital, Sigli, Pidie District, with a diagnosis
as an early indicator in predicting clinical of pneumonia, with a clinical picture of
worsening in children with pertussis. 1,10. shortness of breath, who had previously been
Therefore, this case study aimed to see whether treated for four days. On examination at the
clinical worsening or severe complications in Emergency room of Zainoel Abidin General
pertussis were caused by leukocytosis. This Hospital, information was obtained that the
pertussis case study was conducted using a child had before shortness of breath. Every
systematic review approach. cough experience feels continuous for a long
time, followed by vomiting after every cough.
METHOD The cough had been experienced for about two
weeks before being treated at the Teungku Chik
We conducted this case study with a Ditiro Hospital. On physical examination at
focus on investigating the relationship between Zainoel Abidin General Hospital, it was found:
increased leukocytosis as a predictor of the blood pressure 110/70 mmHg, pulse 110 beats
likelihood of clinical deterioration in a child per minute, rapid respiration of 50 times per
with pertussis. The research methodology minute. The chest appeared retracted, and lung
employed in this study is a systematic review of crackles were found on auscultation. The
a case study. The subject of this case study is a laboratory examination results showed Hb:
child with pertussis who experienced clinical 12.5gr/dL. Hematocrit: 37%, leukocytes:
deterioration. Prominent laboratory data 20,400/mm3. Lung x-rays showed infiltrates in
includes leukocytosis. The association between both lung fields.
leukocytosis and clinical deterioration in this Due to a history of severe, persistent
case study is analyzed using systematic review cough and shortness of breath, this patient was
procedures. diagnosed with pertussis and pneumonia. Other
A systematic review of case study was data that supporting pneumonia are of crackles
carried out to answer whether leukocytosis on auscultation and an infiltrate is found on a
indicates clinical deterioration in children with chest X-ray. Concerning a loud cough, it must
pertussis. Literature search procedure by be proven whether it is caused by pertussis.
searching literature online, using PubMed, Therefore, the Polymerase Chain Reaction
Cochrane, and Google Scholar search (PCR) was examined against the Bordetella

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Pertussis bacteria to determine the cause of and was advised to seek outpatient treatment.
pertussis. From the laboratory examination, the Five days later, the patient returned to the
results were found: a positive PCR was found children's polyclinic, Zainoel Abidin General
for Bordetella pertussis. With the discovery of Hospital. At the last examination, the patient
these laboratory results, the definite diagnosis is was very healthy.
pertussis. Pneumonia that occurs, in this case, is In this case, pneumonia was found in a
a clinical worsening and complications of child with pertussis as a form of clinical
pertussis. Because the diagnosis is pertussis and deterioration complication. Laboratory
pneumonia, the therapy is antibiotics following examination revealed the presence of
causative germ, namely Bordetella pertussis. leukocytosis. A systematic review was
The selected antibiotics are conducted to investigate whether leukocytosis
Azithromycin and Cefotaxime. These two can be used as a predictor of clinical
antibiotics were chosen to anticipate the deterioration.
possibility of other bacteria causing pneumonia. Through the search method with the
Lang’s selection of antibiotics is intended to above criteria, a total of 16,666 articles were
prevent further deterioration, which can result obtained in the early stages. Of the 43 articles
in respiratory failure. Uncontrolled clinical searched with PubMed, two were valid. Of the
worsening with the occurrence of respiratory 3,123 articles on the Cochrane, only two are
failure can cause death. Other procedures for valid. Likewise, out of 13,500 articles on
this patient during treatment include Google Scholar, only two are valid. So only six
administering oxygen, traditional healers, and papers are useful in the initial stage.
multivitamins. This patient was treated at Furthermore, screening of titles and
Zainoel Abidin General Hospital for one week. abstracts was carried out to determine articles
Because it showed an excellent improvement, that were relevant to the previous problem.
the infusion was stopped. Antibiotics was stop. However, when traced based on the duplication
Other medicines are only in the form of aspect, three papers were found: cohort studies
multivitamins. The patient was discharged from (see Figure 1). The articles obtained are then
the hospital summarized in Table 1.

b ed oc ane

bst act sea c and title

ncl sion c ite ia case se ies c oss

sectional st d co o t ando i ed
cont olled clinical t ial o
s ste atic e ie eta anal ses
li ited to t e last ea s
licate a ticles

Figure 1. Literature selection flow

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Table 1. Summary of Characteristic and Outcome of Included Studies.
Article Kang, et al.,2 Shi, et al.,3 Palvo, et al.,13
Title Clinical characteristics Mortality risk factors among Severe pertussis
of 967 children with hospitalized infection A clinic
e t ssis a single‑cente children with severe pathological study
anal sis o e an 8‑ ea pertussis
period in Beijing,
China
Design Retrospective Cohort Study Retrospective Cohort Study Retrospective Cohort
Study
Publication 2021 2021 2017
Location Beijing, China Guangzhou, China Brazil
Aims Knowing the clinical Assessing risk factors for Assessing the
symptoms of severe mortality in patients epidemiology and
pertussis, describing admitted with severe clinical symptoms of
pertussis in infants pertussis children with severe
under three months, assessing pertussis who were
risk factors for severe hospitalized in Brazil,
pertussis. investigating the risk
factors for PICU
admission and death, and
evaluating the autopsy
findings of children who
died with pertussis.
Participant 967 children 144 children 55 children
Outcome • Vomiting after coughing, • The mortality for severe • Leukocytosis on
paroxysmal cyanosis, pertussis was 34.2%, admission is
decreased post-tussive heart with associated with
rate, hypoxemia, severe • patients younger than six morbidity and
pneumonia, and mechanical • weeks making up most mortality in children
ventilation were significantly deaths. treated with pertussis.
ig e t an in t e ≥ t ee • WBC > 70.0 × 109/L and • Implementation of
months group (p <0.05). PH are independent prevention strategies
• Paroxysmal cough, post-tussive prognostic variables is crucial to reduce
vomiting, paroxysmal cyanosis, associated with death. the incidence of
flushing/cyanosis/fever during disease, especially in
coughing, increased leukocytes young infants who
(leukocytosis), and chest X-ray are not immunized.
showing
pneumonia/consolidation/
• atelectasis are essential
indications of severe pertussis.

DISCUSSION were age <18 years, symptoms with pertussis

diagnostic criteria, and positive PCR results for
The first study was a retrospective pertussis. While the exclusion criteria were the
cohort study conducted by Kang et al. 2 on 227 emergence of cough due to congenital
children with pertussis who were treated abnormalities of the airways, the appearance of
between March 2011 and December 2018. The cough due to airway compression due to various
researchers divided them into two groups, causes, personal or family history of allergic
namely the severe and non-severe pertussis reactions and non-specific inflammatory
group. Patients with severe pertussis were reactions such as allergic cough or asthma,
defined as having any symptoms: recurrent postnasal drip syndrome, eosinophilic
apnea, hypoxemia (PaO2 <80 mm Hg), bronchitis, and cough due to gastroesophageal
pertussis encephalopathy, or cardiac reflux, cytomegalovirus pneumonia, and
compromise. Inclusion criteria in this study pulmonary tuberculosis.
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 The second study was a Randomized infections. Upper infections caused by viruses
Controlled Trial study conducted by Shi et al. 3 and sometimes appear atypical 15–17 15–17.
On 144 pertussis patients treated at Guangzhou In this case study, the patient was
Women and Children's Medical Center China referred from the district hospital with
from January 2016 to December 2019. The complaints of shortness of breath. The definite
recerchers divided them to into two outcame diagnosis of shortness of breath is pneumonia.
groups, namely group of patients who survived The sound of crackles on lung examination
and who died during treatment. Criteria for reinforced this. An X-ray examination also
severe pertussis include children aged 0-18 found infiltrates in both lung fields. However,
years with laboratory results confirming the diagnosis of pertussis in this patient was
pertussis. They are included if there is treatment suspected due to the presence of persistent and
in the Pediatrics Intensive Care Unit (PICU) for persistent cough. A definite diagnosis of
at least 24 hours or death, hyperleukocytosis in pertussis was obtained from the results of
t e fo of le koc te al es ≥ x 3/mm3, laboratory tests, namely a PCR examination
pulmonary hypertension based on criteria from with a positive outcome for Bordatella pertussis
1,12
the European Society of Cardiology (ESC) and .
European Respiratory Society. The inclusion Clinical manifestations of pertussis are
criteria in this study were that patients had to influenced by age, disease stage, previous
undergo all the following examinations: All immunization or infection history, passive
patients must be positive for Bordetella immunity, and previous antibiotic treatment 18.
pertussis based on the PCR test. All patients Studies show that the most common clinical
should undergo an immunofluorescence virus symptoms of pertussis infection in children are
test for nasopharyngeal secretions in the acute paroxysmal cough, inspiratory whoop, and
phase. All patients should have a chest X-ray post-cough vomiting, with less common signs
done. Patients with incomplete data were such as cyanosis and apnea. Cases of B.
excluded from this study. pertussis are often reported in spring and
The third study was conducted by summer, according to those reported in several
Palvo, et al. 13 , a randomized controlled trial on studies 1,14,19.
55 patients treated at a tertiary-care university Infection caused by B. pertussis can be
hospital in Brazil from 1 January 2008 to 31 divided into three phases: catarrhal,
December 2014. The researchers divided them paroxysmal, and convalescent 20. The first
into two groups, namely, the group of patients phase is the catarrhal phase which begins 1-2
who died and recovered. The inclusion criteria weeks after exposure and lasts 7-14 days. This
were all children aged 0-18 years who were condition is indistinguishable from an upper
treated with laboratory confirmation of respiratory tract infection, and the symptoms
pertussis. Laboratory confirmation includes include rhinorrhea, mild cough, malaise, and
isolation of B. pertussis from nasopharyngeal low-grade fever. The second phase is the
aspiration with positive pertussis culture and/or paroxysmal phase. This phase lasts 1-4 weeks
PCR. Patients with clinical symptoms and is dominated by a heavy cough. This phase
suspicious of pertussis but without laboratory is characterized by paroxysmal coughing or a
confirmation were excluded from the study. series of coughing during a single expiration,
The World Health Organization which causes a decrease in lung volume.
(WHO) and the Centers for Disease Control and Paroxysmal cough followed by forceful
Prevention (CDC) provide case definitions of inspiration, which, in infants and children with
pertussis. A clinical case can be defined as a the smaller trachea, is associated with the
person with a cough for at least two weeks and whooping sound characteristic of "whooping
any of the following symptoms: paroxysmal cough." Paroxysmal cough is often associated
cough, inspiratory whoop, or post-cough with vomiting and post-cough fatigue. The third
vomiting. Confirmed cases are described as phase is the recovery phase. This phase occurs
suspected by one of the following laboratory after 2-3 months, and severity of the cough
tests: (1) positive culture from the gradually decreases 10,15,21.
nasopharyngeal sample, (2) positive PCR test, The incubation period for pertussis is
and (3) positive serology result 14. Diagnosis is usually 7-10 days, ranging from 4-21 days.
often delayed or missed because pertussis However, in households, one-fifth of cases
mimics symptoms of respiratory tract occur more than four weeks after the onset of
207
symptoms in the primary case. B. pertussis children. A non-paroxysmal cough may persist
adheres to the mucosa of the nasopharynx, for weeks 1,12,24 when the disease is cured.
1,12,24
trachea, bronchi, and bronchioles, increasing .
the secretion of mucus, which is initially thin Clinical worsening of pertussis can be
and thick. The classic disease is most often seen prevented by providing adequate therapy,
in non-immunized children, lasts 6-12 weeks, especially by choosing the right antibiotics,
and is clinically divided into three stages: which can be: erythromycin, azithromycin, or
catarrhal, paroxysmal, and convalescent 10,16,20. lincomycin. If leukocytosis is found (the
A meta-analysis study from Moore 22 number of leukocytes above average), it is
states that "Posttussive vomiting" is a clinical anticipated immediately by looking at
symptom that can establish a clinical diagnosis additional clinical possibilities or the possibility
in a sample of children with a sensitivity of 60% of early complications 16. Antibiotics combine
and a specificity of 66% with a CI of 95%, one of the standard antibiotics (erythromycin,
"Positive Likelihood Ratio" 1.76 and "Negative azithromycin, or lincomycin) with other
Likelihood Ratio" 0.6 . Other previous meta- antibiotics, such as cefotaxime. This effort is
analyses studies also showed similar results, more to minimize the risk of complications or
namely the study of Cornia et al., providing clinical worsening 10,11,17,25.
results of clinical symptoms that can be used as
a reference for establishing the diagnosis of CONCLUSION
pertussis. Paroxysmal cough with a sensitivity
of 86% and a specificity of 24%, "Positive Leukocytosis in children with pertussis
Likelihood Ratio" 1.1. “ ostt ssi e o iting” can serve as a predictor for the likelihood of
with 70% sensitivity and 61% specificity, clinical deterioration and complications.
“ ositi e Likeli ood Ratio” 1,8. While Therefore, laboratory examinations
Inspiratory whoop with 50% sensitivity and (hematology) should be consistently performed
73% specificity, "Positive Likelihood Ratio" 4. in every child diagnosed with pertussis to
Pertussis is a disease caused by facilitate adequate therapeutic planning,
Bordetella pertussis. Therefore, the focus of thereby preventing clinical deterioration and
laboratory tests to establish the diagnosis of this complications. Clinically, pertussis caused by
disease is to find evidence of infection with B. pertussis infection is a highly contagious
Bordetella pertussis. Another examination is to disease with clinical features ranging from mild
look at the hematological picture of the patient. to severe and various complications.
The leukocyte count, for example, usually Due to the proven risk factor for the
increases between 15,000 and 20,000/mm3 but clinical worsening of pertussis, namely,
can be normal or as high as 60,000/mm3. From increased levels of leukocytosis, managing
the leukocyte count, usually, 60-80% are pertussis patients requires hematological
lymphocytes. Leukocytosis with a white blood examination, especially the number of
cell count of more than 25,000/mm3 was seen leukocytes. If leukocytosis is found, the
in 40% of children 20. selection of antibiotics must be adequate by
Several complications may occur in combining standard drugs (Azithromycin,
pertussis with severe infection due to clinical Erythromycin, or Lincomycin) with other
deterioration. A series of rapid coughing antibiotics, such as a combination with
characterize paroxysms without taking a breath, cefotaxime.
followed by a characteristic whoop, an attempt
to inhale through a swollen glottis. During the ACKNOWLEDGEMENT
paroxysmal phase, the patient may experience In general, we would like to thank all those who
cyanosis and vomiting. Several paroxysmal have helped care for the patient used in this case
steps may occur successively within minutes study. In particular, thank you to the doctors and
and can leave the patient exhausted. Paroxysms nurses in the pediatric ward, Laboratory, and
can be caused by stimuli such as eating, Radiology Section of Zainoel Abidin General
laughing, or crying, and are usually worse at Hospital.
night. During the paroxysmal phase, the patient
may appear to average 23. Pertussis is usually
not associated with fever but with CONFLICTS OF INTEREST
lymphocytosis, especially in infants and young The authors declare no conflict of interest.
208
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