To describe clinical characteristics and hs-CRP, procalcitonin, interleukinee-6 of severe viral pneumonia and co-infection with other viruses or/and bacteria among children under 5 years old at National Hospital of Pediatrics from January, 2015 to March, 2017.
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RESEARCH ON CLINICAL CHARACTERISTICS AND hs-CRP,
PROCALCITONIN, INTERLEUKINE-6 IN CHILDREN UNDER
5 YEARS OLD WITH SEVERE VIRAL PNEUMONIA
AND CO-INFECTION
Nguyen Thi Ngoc Tran 1 ; Do Quyet 2 ; Dao Minh Tuan 1
SUMMARY
Objectives: To describe clinical characteristics and hs-CRP, procalcitonin, interleukinee-6 of
severe viral pneumonia and co-infection with other viruses or/and bacteria among children
under 5 years old at National Hospital of Pediatrics from January, 2015 to March, 2017
Subjects and methods: Descriptive, cross-sectional study on 53 children under 5 years old were
diagnosed with severe viral pneumonia co-infection with other viruses or/and bacteria Results:
Pneumonia caused by syncytial respiratory virus in 14 patients (26.4%), influenza A in 13
patients (24.5%), Adenovirus in 12 patients (22.6%), Rhinovirus in 10 patients (18.9%) and
influenza B in 4 patients (7.6%) Children could be co-infected with other viruses or/and
bacteria Haemophilus influenza co-infection rate was the highest (19 patients = 45.2%),
followed by Klebsiella pneumoniae and Pseudomonas aeruginosa (19.1%) The lowest rate of
bacterial co-infection was Burkholderia cepacia and Staphylococcus aureus (1 case = 2.4%) In
the bacterial co-infection group, rate of cyanosis was the lowest (20.6%); the highest rate of
cyanosis was in the group of viral-bacterial co-infections (100.0%) The difference between
three groups was significant (p < 0.05) There was no difference in other clinical characteristics
and hs-CRP, procalcitonin, interleukine-6 among three groups (p > 0.05) Conclusion: The
incidence of children with pneumonia had co-infection in syncytial respiratory virus group was
the highest Children could be co-infected with other viruses or/and bacteria Haemophilus
influenza co-infection rate was the highest The difference of cyanosis between three groups
was significant There was no difference in other clinical characteristics and hs-CPR,
procalcitonin, interleukine-6 among three groups
* Keywords: Pneumonia; Co-infection; Children.
INTRODUCTION
In Vietnam, on average, children get
acute respiratory infections from 3 - 5 times
every year, including 1 - 2 times of
pneumonia [1] The number of children
with pneumonia accounts for 30 - 40% of cases of examination and treatment in hospitals Death rate of pneumonia accounts for 75% of death cases from respiratory diseases and 30 - 35% of death cases
1 National Hospital of Pediatrics
2 Vietnam Military Medical University
Corresponding author: Nguyen Thi Ngoc Tran (dr.ngoctran259@yahoo.com.vn)
Date received: 04/09/2019
Date accepted: 11/10/2019
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among children [1] The incidence of viral
pneumonia is quite high, accounting for
60 - 70% [1] Common viruses that cause
pneumonia are syncytial respiratory virus
(RSV), influenza, Rhinovirus, Adenovirus
[5] More than one-third of cases of viral
and bacterial co-infection aggravate the
disease [6, 7]
Currently, the viral diagnostic method
has many advantages to help identify the
cause quickly and accurately such as fast
antigen detection test, real-time PCR and
multi-primed PCR with high sensitivity and
specificity
The study of factors evaluating severe
conditions such as CRP (as well as
hs-CRP), procalcitonin (PCT) and
cytokines (such as interleukine-1 (IL-1),
IL-6, IL-8, IL-10 and HMGB-1) will facilitate
diagnosis, differential diagnosis (viral and
bacterial infections), prognosis and
appropriate treatment, avoiding misuse
of antibiotic use Especially, IL-6 exhibits
very specify for acute inflammation
Up to now, no much studies about
viral pneumonia co-infection and other
inflammation factors in pneumonia due
to co-infection with bacteria and other
viruses in Vietnamese children have been
carried out
Therefore, we have conducted the
project with aims: To describe the clinical
characteristics and hs-CRP, PCT, IL-6 of
severe viral pneumonia and co-infection
with bacteria and/or other viruses in under
5 years old children at National Hospital
of Pediatrics from January, 2015 to March,
2017
SUBJECTS AND METHODS
1 Subjects
53 patients under 5 years old, who were diagnosed with severe viral pneumonia due to co-infection with bacteria and/or other viruses, were treated at National Hospital of Pediatrics from January, 2015
to March, 2017
* Exclusion criteria:
- Patients were under 1 month of age and older than 5 years old
- Patients had non-viral pneumonia (pneumonia after drowning, chemical pneumonia, aspiration pneumonia)
- Patients had chronic, associated congenital diseases (airway malformation, congenital lung disease, liver failure, kidney failure )
- Patients were eligible to participate in the study but the parents or guardian did not agree to participate
2 Methods
- Study design: Descriptive, cross-sectional study
- Sample size: 53 patients
* Diagnosis of severe viral pneumonia with co-infection:
- Diagnosis of pneumonia: Patients were diagnosed with pneumonia according to WHO (2013) criteria: Cough or having difficulty in breathing, rapid breathing, intercostal muscle external retraction, cracker, crepitation, X-ray image of infiltrated parenchyma [4]
- Diagnosis of severe pneumonia: A child with cough or having difficulty in breathing, plus at least one of the following main symptoms: Cyanosis or
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SpO2 < 90%, severe respiratory failure
(wheezing and severe chest retraction)
Signs of pneumonia with severe general
signs such as not drinking or giving up
or vomitting everything, coma or
unconsciousness, seizures
- Diagnosis of viral pneumonia with
co-infection: Patients with two or more of
the following tests are positive: Rapid
test of influenza A, B, RSV, RT-PCR
of influenza A, B, RSV, Adenovirus,
Rhinovirus and bacterial culture are
positive in nasopharyngeal fluid test
* Study techniques:
- Clinical symptoms:
+ Systemic symptoms: Temperature,
breathing rate, heart rate, weight, SpO2
+ Functional symptoms: Cough, wheezing,
runny nose, vomiting, convulsions
+ Examination of respiratory entity
symptoms: Difficulty in breathing, chest
retraction, nasal flaring, head-bobbing with each breath, intercostal muscle contraction, rales in the lungs
+.Other symptoms: Skin rash, conjunctivitis, hepatomegaly, vomiting, diarrhea
- Subclinical:
+ Index: hs-CRP, PCT, IL-6, PaO2 + Rapid test for influenza A, B, RSV; RT-PCR for Adenovirus, Rhinovirus + Bacterial culture
* Criteria of evaluation applied in the study:
- hs-CRP: Normal: ≤ 0.5 mg/dL
- PCT: Increase: > 0.05 ng/mL; normal:
≤ 0.05 ng/mL
- IL-6: Unit pg/mL (study)
- PaO2: Normal 70 - 99 mmHg
- Microbiological test: Negative or positive
* Data analysis: By STATA 14.0 software.
RESULTS
During the study period from January, 2015 to March, 2017, there were 53 patients with viral pneumonia co-infected with bacteria and/or viruses
Table 1: Characteristics of microbiology (n = 53)
1 baterium
2 bacteria
3 bacteria
1 virus
1 baterium + 1 virus
1 bacterium +
2 viruses Virus
Among 14 children with RSV co-infection, 8 cases infected only 1 bacterium In 13 children with influenza A infection, 6 children infected with 1 virus In the groups of children with Adenovirus, Rhinovirus and influenza B, the majority number of children were infected with only 1 bacterium
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Table 2: Charateristics of bacterial co-infection (n*
= 42)
Bacterial co-infection
Patients with each type of bacteria (n = 48)
Percentage of co-infected patients
(%)
Percentage of all patients (%)
( * n: Number of patients with severe viral pneumonia co-infection)
The highest incidence was Haemophilus influenza co-infection (45.2%), followed by Klebsiella pneumoniae and Pseudomonas aeruginosa (19.1%) The lowest incidences were Burkholderia cepacia and Staphylococcus aureus (1 case = 2.4%)
Table 3: Clinical characteristics of patients with co-infected pneumonia (n = 53)
Co-infection
Bacteria (n = 34)
Virus (n = 11)
Bacteria + virus (n = 8)
Symptoms
p
Systemic
Respiratory
Others
(*: Fisher’s exact test)
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Among the co-infection groups, the cyanosis rate was the lowest with 20.6% The highest incidence was found in the co-infection with bacteria and viruses (100.0%) The difference between three groups was significant (p < 0.05) There was no difference in other characteristics among three groups (p > 0.05)
Table 4: Characteristics of respiratory failure in co-infected pneumonia patients (n = 53)
Co-infection
Bacteria (n = 34)
Virus (n = 11)
Bacteria + virus (n = 8)
Characteristics
p
SpO 2
0.23*
Moderate respiratory failure 6 17.6 2 18.2 0 0.0
PaO 2
0.61*
(*: Fisher’s exact test)
There was no difference in respiratory failure groups among three groups (p > 0.05)
Table 5: Subclinical characteristics in co-infected pneumonia patients (n = 53)
Co-infection
Bacteria (n = 34) Virus (n = 11) Bacteria + virus (n = 8)
Index
Median 25th - 75th Median 25th - 75th Median 25th - 75th
p
(*: Kruska-Wallis test)
hs-CRP had the fastest increase in the co-infection group (median = 12.7), followed
by the co-infection with virus group (median = 4.1), co-infection with viruses and bacteria (median = 4.0) Similarly, PCT had the highest increase in the co-infection group only (median = 2.3), followed by the co-infection with viruses and bacteria (median = 1.0), the lowest one was in the co-infection group with virus only (median = 0.4) IL-6 had the highest one in the co-infection group with both virus and bacteria (median = 24.8), followed by the co-infection group with virus only (median = 10.6), the lowest increase was in the co-infection group with bacteria (median = 5.4) However, all differences were not significant (p > 0.05)
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DISCUSSION
1 Characteristics of co-infected
viral-bacterial infection
Childhood viral pneumonia is a
common illness, with an incidence of
36 - 40 episodes/1,000 children/year in
those < 5 years old The concomitant
viral-bacterial infection can cause the
severe pneumonia in children O'Brien K.L
(2000) determined that preceding
influenza infection (H1N1) was directly
associated with pneumococcal illness in
children [8] Juven had shown that more
than one-half of all community-acquired
pneumonia were infected with bacteria
and viruses [9]
In this study, in 14 patients with RSV
infection, 8 patients had co-infection with
1 bacterium In 13 children with influenza
A infection, 6 children were infected with
1 virus In the groups infected with
Adenovirus, Rhinovirus and influenza B,
the majority number of children had only 1
bacterial co-infection The results also
showed that the incidence of Haemophilus
influenza was the highest (45.2%),
Klebsiella pneumoniae and Pseudomonas
aeruginosa 19.1% The lowest incidences
were in Burkholderia cepacia and
Staphylococcus aureus (1 case) In
addition, in the RSV infective group, there
were 3 cases of co-infection with two or
more bacteria and 1 case of co-infection
with one type of virus and one type of
bacteria Meanwhile, in Adenovirus
infective group, the number of infected
children were 1 and 2 cases, respectively
Comparing with the Andrew’s study
(2001), it was found that, in 58 patients
who identified the cause of pneumonia, 65% of patients infected with 1 virus, 35% were co-infected [10]
In a recent study by Nascimento et al (2013) on 25 children with pneumonia having pleural effusion showed that 22%
of cases of co-infection with bacteria and virus, of which co-infection with parainfluenza 1/3 and influenza A, RSV and influenza A were common [11] Juven (2000) found evidence of viral-bacterial infection in 30% of the children with pneumonia, a result which was in agreement with previous studies [9]
According to study by Olli Ruuskanen, 49% of pneumonia cases in the study group were viral infected, of which the number of children infected with Rhinovirus was the highest at 18%, RSV was 16%,
influenza A was 9 %, influenza B and
Adenovirus were 8% [6]
Li Li et al (2016) studied 1,702 children with lower respiratory tract infection, the co-infection rate among Rhinovirus-type C group was 61% [12]
Research by Dao Minh Tuan and Nguyen Thi Ngoc Tran on 56 children with Adenovirus pneumonia showed that patients could be co-infected with 1 virus and other bacteria (16/56 children with Rhinovirus, 14 with CMV, 2 with RSV), 2 infected with influenza A, influenza B, 10 infected with bacteria, 3 infected with
Mycoplasma) [2]
Children with broncho-pneumonia infected with Adenovirus had a high rate
of co-infection Rhinovirus was the highest co-infection, the second was CMV co-infection, the third was bacterial co-infection This showed the importance
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of isolating children, not only avoiding the
spread of Adenovirus to other children but
also helping them to avoid new infections
[2]
Tran Thi Thuy's study showed that
Adenovirus pneumonia patients had 9.0%
of bacterial co-infection: 3 cases of
pneumococcal infection, 2 cases of
Haemophilus influenza infection, 1 case
of Moracela catarhalis infection There
were 28.0% of cases with virus co-infection:
mainly Rhinovirus (25.0%), RSV (4.0%)
and influenza A/B (2.0%) [3]
In general, the incidence of co-infection
with bacteria and/or virus was the highest
in the RSV group, the lowest in the
influenza B group and the Rhinovirus
group
2 Clinical and subclinical
characteristics
This study showed that the majority of
clinical and subclinical symptoms appeared
to be non-specificed among co-infection
groups (including bacterial co-infection,
viral co-infection and co-infection with
bacteria and viruses)
While symptoms such as fever,
tachycardia and runny nose were different
between groups of infants infected with
the virus alone, these symptoms did not
differ between co-infected groups except
cyanosis Among the co-infection groups,
the lowest cyanosis rate was 20.6%; the
highest rate was found in the group of
bacteria and virus infections (100.0%)
The difference between the two groups
was statistically significant (p < 0.05)
The results of the subclinical analysis
also showed that there were no significant
differences between the three groups in
terms of pulmonary X-ray, subclinical indicators such as Hb, hs-CRP, PCT or IL-6 The co-infected group only had a higher number of white blood cells than the co-infected group
According to Toikka, it was shown that the increase of serum PCT, CRP and IL-6 had little value in the differences of bacterial and viral pneumonia in children
However, in some patients with very high serum PCT, CRP or IL-6, bacterial pneumonia was possible [13]
CONCLUSION
Children with pneumonia with co-infection
in RSV group had the highest incidence
The child may be co-infected with other viruses or bacteria Haemophilus influenza co-infection had the highest rate The differences between the three groups for cyanotic symptoms were statistically significant There were no differences in other clinical features and hs-CPR, PCT, IL-6 between the three groups
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