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Indian Pediatr 2021;58:1056-1058 |
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Clinical Patterns and Risk Factors for
Pneumonia Caused by Atypical Bacteria in Vietnamese Children
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Phan Le Thanh Huong, 1
Pham Thu Hien,2 Nguyen Thi
Phong Lan,1 Dao Minh Tuan,2
Dang Duc Anh,1 Tran Quang
Binh1,3
From 1National Institute of Hygiene and Epidemiology, 2Vietnam
National Children’s Hospital, and 3Dinh Tien Hoang Institute of
Medicine; Hanoi, Vietnam.
Correspondence to: Assoc. Prof. Tran Quang Binh, Head,
Laboratory of Molecular Genetics, National Institute of Hygiene and
Epidemiology, 1 Yersin Street, Hanoi 100000 Vietnam.
Email: [email protected]
Received: January 18, 2020;
Initial review: February 22, 2020;
Accepted: August 24, 2020.
Published online: August 13, 2021;
PII: S097475591600361
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Objectives: To investigate clinical
characteristics and risk factors for atypical community-acquired
pneumonia (CAP) in children. Methods: Multiplex polymerase chain
reaction and specific IgM determination were used to detect atypical
bacteria in 661 hospitalized children aged 1-15 years with CAP. Clinical
and epidemiological patterns were compared between typical and atypical
CAP. Results: Children in atypical CAP group manifested
significantly lower rates of wheezing, bronchial rales, and interstitial
pneumonia and showed higher rates of asthma history, headache, chest
pain, and lobar pneumonia . Age group, season of disease onset, asthma
history, duration of symptom onset to hospital admission, and
radiological findings were the significant risk factors for atypical CAP
on multivariate logistic regression analysis. Conclusions: The
clinical characteristics and risk factors can be used to identify a
child at high risk of atypical CAP.
Keywords: Asthma, Evaluation, Identification, Lower
respiratory tract infection.
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C
hildhood pneumonia is
a considerable public
health problem worldwide [1]. Atypical
pathogens are increasingly being recognized
as important causes of community acquired pneumonia (CAP) [2-4].
Since these atypical bacteria cannot be cultured using standard
methods [5] and microbiological diagnosis of atypical CAP has
been limited due to inadequate laboratory diagnostic facilities
in developing countries, the clinical practice guidelines
highlight the importance of signs suspicious for atypical CAP in
children to help guide antibiotic selection [6,7]. However, such
signs have not been well defined yet. The aforementioned
problems prompted us to conduct the study to identify clinical
characteristics of atypical CAP and the important risk factors
which help pediatricians predict children with atypical CAP.
METHODS
The study was conducted at the National
Hospital of Pediatrics from July, 2010 through March, 2012. The
study proposal was approved by the Research Ethics Committee of
the hospital. The detailed methodology has been previously
reported [4]. In summary, the socio-demographic characteristics
and potential risk factors were collected on standardized
questionnaires by interviewing the patient’s parents. After
evaluating clinical manifestation and chest X-ray,
bronchoalveolar lavage and two blood samples were taken from all
the recruited patients for laboratory diagnosis. Multiplex
polymerase chain reaction [8-10] and IgM/IgG antibody-based
enzyme-linked immunosorbent assay were used to detect
Mycoplasma pneumoniae, Chlamydophila pneumoniae and
Legionella pneumophila [4]. Of the total 722 children aged
1-15 years with CAP, 661 children without mixed typical and
atypical pneumonia were the study subjects.
Statistical analysis: Multivariate
logistic regression analyses with backward stepwise method were
performed to test several models for identifying risk factors
of atypical CAP. The final model presented the most significant
risk factors for atypical CAP. The area under a receiver
operating characteristic curve (AUC) was calculated [11]. The
selection of an optimal threshold was based on the Youden index
[12], and the sensitivity and the specificity of the model were
calculated. The nomogram for identifying an individual with high
risk of atypical CAP was constructed based on the variable
estimates from the final model. A P value of less than
0.05 was considered statistically significant. The statistical
procedures were performed using SPSS version 16.0 (SPSS,
Chicago, USA) and R statistics version 3.5.3 [13].
RESULTS
There was no statistical difference between
atypical and typical CAP in socioeconomic status except for age
group and season of disease onset (Web Table I).
Table I shows the clinical and laboratory
characteristics among children with atypical and typical CAP.
Fever (or high fever), cough, sore throat, and tachypnea were
the most common signs and not different between atypical and
typical CAP. Children showed significantly lower rates of
wheezing, bronchial breathing, leukocyte counts, and
interstitial pneumonia and higher rates of asthma history,
headache, chest pain, and lobar pneumonia in atypical CAP
compared to typical CAP.
Table I Clinical Pattern and Laboratory Values in Vietnamese Children With Pneumonia (N=661)
| Characteristics |
Community-acquired
pneumonia |
|
Typical |
Atypical |
|
(n=507) |
(n=154) |
| Clinical |
|
|
| Fever |
476 (93.9) |
145 (94.2) |
|
High fever (≥38.5oC) |
345 (68.0) |
113 (73.4) |
| Cough |
498 (98.2) |
151 (98.1) |
| Sore throat |
404 (79.7) |
123 (79.9) |
| Tachypnea |
406 (80.1) |
128 (83.1) |
| Wheezingc |
392 (77.3) |
97 (63.0) |
|
Moist rales |
364 (71.8) |
98 (63.6) |
|
Bronchial breathingd |
334 (65.9) |
86 (55.8) |
| Headachec |
79 (15.6) |
48 (31.2) |
|
Chest paind |
69 (13.6) |
32 (20.8) |
|
Chest indrawingb
|
177 (38.7) |
38 (35.5) |
| Diarrhea |
178 (35.1) |
49 (31.8) |
| Skin rash |
51 (10.1) |
24 (15.6) |
| Radiological findings |
|
|
|
Interstitial pneumoniab,e |
95 (18.7) |
14 (9.1) |
|
Lobar pneumoniad |
128 (25.2) |
54 (35.1) |
| Asthmac |
24 (4.7) |
24 (15.6) |
| C-reactive protein (mg/L) a |
18 (6-36) |
24 (10-36) |
| Anemia |
229 (45.2) |
82 (53.2) |
| Count |
|
|
| Leukocytes (X109/L) a |
14 (10-19) |
12 (8.5-18.5) |
| Neutrophils (%)a |
58 (43-69) |
56 (43-67) |
| Lymphocytes (%)a |
30 (20-43) |
31 (21-43) |
| Eosinophils (%)a |
0 (0-1) |
1 (0-2) |
| Platelets (X109/L) a |
328 (259-399) |
334 (259-422) |
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Data shown as no. (%) or amedian (IQR); bIn children
aged<5 y; cP<0.001; dP<0.05; eP=0.005. |
The potential risk factors for atypical CAP
were analyzed using multivariate logistic regression including
factors found significant on univariate analysis. The final
model involved the most significant risk factors for atypical
CAP including age group, season of disease onset, asthma
history, duration of symptom onset to hospital admission, and
radiological findings (Table II). Based on parameter
estimates of the final model, the prediction nomogram was
constructed for individualizing the probability of atypical CAP
(Web Fig. 1). The final model had AUC of 0.736
(95% CI 0.691-0.781), the optimal cut-off value of 17.8%,
sensitivity of 79.9% and specificity of 57.0%.
Table II Risk Factors on Multivariate Logistic Regression for Atypical Pneumonia in Vietnamese Children (N=661)
| Independent risk factor |
OR (95% CI) |
P value |
| Age group |
|
|
| 1 - <2 y |
1.0 |
- |
| 2 - <5 y |
1.50 (0.96-2.36) |
0.07 |
| 5 - <10 y |
5.63 (3.14-10.1) |
<0.001 |
| ≥10 y |
2.65 (0.94-7.48) |
0.06 |
| Season |
|
|
| Spring |
1.0 |
- |
| Summer |
0.59 (0.34-1.03) |
0.06 |
| Fall |
0.46 (0.27-0.77) |
0.004 |
| Winter |
0.40 (0.22-0.72) |
0.002 |
| Asthma |
4.63 (2.39-8.99) |
< 0.001 |
| Radiological findings |
|
|
| Interstitial pneumonia |
1.0 |
- |
| Broncho-alveolitis |
2.00 (1.03-3.87) |
0.04 |
| Lobar pneumonia |
2.48 (1.23-5.01) |
0.01 |
| Pleuropneumonia and others |
2.80 (0.86-9.15) |
0.09 |
| Duration between symptom onset and
hospital admission |
|
|
| <1 wk |
1.0 |
- |
| 1-2 wk |
1.84 (1.21-2.78) |
0.004 |
| >2 wk |
0.51 (0.25-1.03) |
0.06 |
DISCUSSION
The present study depicted the clinical
patterns of atypical CAP compared with typical CAP. The risk
factors and nomogram for identifying a child with high risk of
atypical CAP were also reported.
To date, there have not been many reports on
clinical signs suggestive of atypical CAP. In adults, the
guidelines set up parameters and criteria for the differential
diagnosis of atypical pneumonia and bacterial pneumonia based on
clinical symptoms, physical signs and laboratory data [14]. In
children, such parameters and criteria have not been well
defined yet. We previously reported the clinical patterns of 52
children with atypical pneumonia caused by M. pneumoniae
[15]. In agreement with our finding, a study in Thailand [16]
reported that lobar pneumonia was associated with atypical CAP
in children. Age has also been found as an important risk
factor for atypical pneumonia in several studies [16,17].
The strength of the study was prospective
recruitment of a large sample of children with CAP through four
seasons of the year. Moreover, the investigations combining
serologic and molecular tests were performed to maximize the
diagnostic yield of atypical CAP. The study limitations
were no urine test for detection of L. pneumophila
antigen, and low sensitivity and specificity of the prediction
model. Further independent studies should be conducted to
validate and evaluate the performance of the prediction model.
In conclusion, the study indicated the
clinical characteristics of atypical CAP in comparison
with typical CAP. Age group, season of disease onset, asthma
history, duration of symptom onset to hospital admission, and
radiological findings were the independent risk factors for
atypical CAP in children. The nomogram constructed from the risk
factors may be used to identify a child at high risk of atypical
CAP; although, confirmation of the findings from studies in
various regions are required.
Acknowledgements: Prof. Nguyen Thanh Liem
– Former Director of the Vietnam National Children’s Hospital
for helpfully supporting the study, Ms. Do Thi Bich Ngoc and to
our colleagues at National Institute of Hygiene & Epidemiology
and Vietnam National Children’s Hospital for technical help.
Ethics clearance: Research Ethics
Committee Vietnam National Children’s Hospital; No. 1124/HDDD,
dated 2 June, 2010.
Contributors: PLTH: conceptualized and
designed the study, designed and performed laboratory analyses,
drafted the initial manuscript, reviewed and revised the
manuscript; PTH: recruited patients, collected and entered data,
follow-up patients; NTPL: participated in laboratory analyses,
reviewed the manuscript; DMT: designed the study, recruited
patients, follow –up patients, participated in discussion and
interpretation of the findings; DDA: had a substantial
contribution in experimental design and interpretation of ELISA
and multiplex PCR, critically reviewed the manuscript; TQB:
cleaned data, supervised data collection, performed statistical
analyses and interpretation of findings, critically reviewed and
revised the manuscript. All authors read and approved the final
manuscript.
Funding: National Foundation for Science
and Technology Development (NAFOSTED), grant no. 106.03-2010.36
from The Ministry of Science and Technology, Vietnam.
Competing interest: None stated.
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What this Study Adds?
• Age group, season of disease
onset, asthma history, duration of symptom onset to
hospital admission, and radiological findings identify a
child at high risk of atypical community-acquired
pneumonia.
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