key: cord-325613-oamw57gx
authors: Zhong, Peipei; Zhang, Hailin; Chen, Xiaofang; Lv, Fangfang
title: Clinical characteristics of the lower respiratory tract infection caused by a single infection or coinfection of the human parainfluenza virus in children
date: 2019-05-29
journal: J Med Virol
DOI: 10.1002/jmv.25499
sha: 
doc_id: 325613
cord_uid: oamw57gx

BACKGROUND: Human parainfluenza virus (HPIV), usually combined with other pathogens, causes lower respiratory tract infection (LRTI) in children. However, clinical characteristics of HPIV coinfection with other pathogens were unclear. This study aimed to investigate the viral and atypical bacterial etiology of LRTI in children and compare the clinical characteristics of HPIV single infection with those of coinfection. METHODS: This study included 1335 patients, aged between 1 to 71 months, diagnosed with LRTI in Yuying Children's Hospital, Zhejiang, China, from December 2013 to June 2015. Nasopharyngeal secretions were collected, and respiratory pathogens were detected using Multiplex polymerase chain reaction. The clinical data of patients were collected and analyzed. RESULTS: At least 1 pathogen was detected in 1181/1335 (88.5%) patients. The pathogens identified most frequently were respiratory syncytial virus, human rhinovirus, HPIV, adenovirus, and human metapneumovirus. The coinfection rate was 24.8%. HPIV coinfection with other viruses was more associated with running nose, shortness of breath, and oxygen support compared with HPIV single infection. Moreover, HPIV coinfection with atypical bacteria was more related to running nose, moist rales, and longer hospital duration compared with HPIV single infection, and also to longer hospital duration compared with coinfection with other viruses. CONCLUSIONS: This study demonstrated that viral infections were highly associated with LRTI and the rate of coinfection was high. HPIV single infection was milder than coinfection with other viruses. Moreover, HPIV coinfection with atypical bacteria was more serious than HPIV single infection and coinfection with other viruses.

commercialized multiplex PCR kits have been developed, allowing the simultaneous detection of a large panel of viruses and atypical bacteria in clinical practice. 3 Several studies used this molecular diagnostic tool to show that viral infections accounted for a large proportion of LRTIs. In addition, mixed infections were identified frequently. [4] [5] [6] Several studies discussed the clinical characteristics of coinfection compared with single virus infection, but most of them analyzed on a general basis or focused solely on respiratory syncytial virus (RSV). [5] [6] [7] As one of the most common pathogens of LRTI, human parainfluenza virus (HPIV) is found worldwide, especially in children aged less than 5 years. 8 HPIV can cause severe respiratory infection and accounts for 9 to 30% inpatient children admitted due to acute respiratory infection. 9 An increasing number of recent studies focused on HPIV, especially the epidemiology and presentation of four types of HPIV. 10 However, a few studies discussed coinfections with HPIV. Therefore, this study aimed to investigate the viral and HPIV-positive patients were divided into three groups based on the test results: HPIV single infection, coinfection with other viruses, and coinfection with atypical bacteria. The diagnosis of LRTI for each patient was performed by at least two attending physicians based on Zhu Futang Practice of Pediatrics, 8th edition. 11 It was defined according to the clinical symptoms, including severe cough, fever, tachypnea, wheezing, and respiratory distress signs such as nasal flaring, retraction, cyanosis, and abnormal auscultatory findings (wheezing and crackles), or radiologic evidence indicative of an LRTI.

Clinical syndromes of bronchitis, bronchiolitis, and pneumonia were included in the LRTI category. Bronchitis was diagnosed based on the clinical manifestations including severe cough with or without fever, symmetrical breath sounds without permanent rales on auscultation, and increased bronchovascular shadows in chest X-ray examination.

Bronchiolitis was recognized in patients aged <24 months with lower respiratory symptoms of wheezing, tachypnea, and signs of respiratory distress such as nasal flaring, intercostal/subcostal retractions, and central cyanosis. The diagnosis of pneumonia was established based on clinical findings, including fever, tachypnea, and respiratory distress, with the presence of focal or diffuse crackles, decreased vesicular sounds, and radiographic findings such as patchy and macular shadows and/or atelectasis, and/or air bronchograms. The pertussis-like cough was defined based on clinical signs including spasmodic cough, inspiratory whoop, and posttussive vomiting. Data included demographic information, subjective symptoms, physical examination findings, hospital course and management, radiographic findings, and laboratory results. 

The data were analyzed using SPSS (version 17.0; SPSS, Inc., IL). They were expressed as mean, standard deviation, median, quartile, frequency, and percentage. Continuous variables with a normal distribution were compared using analysis of variance, whereas other variables were compared using the Mann-Whitney U test. The categorical data were evaluated using the χ 2 and Fisherʼs exact tests. A P value less than .05 was considered statistically significant (two-tailed).

The study was submitted to the local ethics committee for approval.

Oral information was given together with a paper explaining the content of the study. A consent form was signed by a parent or legal guardian before the inclusion of each patient in the study.

The flow of the study is depicted in Figure 1 Table 1 ). The total coinfection rate was 24.8%. HCoV showed the highest coinfection rate of 65.0%, followed by InfB (63.9%), HBoV (59.3%), ADV (56.5%), and HRV (51.7%). Table 3 ).

The clinical characteristics of HPIV-positive patients were compared (Table 4 ). The most common diagnosis was pneumonia, followed by bronchiolitis and bronchitis. A few patients (5.4-12.5%) in each group had a pertussis-like cough. HPIV coinfection with other viruses was more associated with running nose and shortness of breath (χ 2 = 5.235; P = 0.022; χ 2 = 7.87; P = 0.005), and more patients needed oxygen support (χ 2 = 6.539; P = 0.011) compared with HPIV single infection.

Neutrophil percentage was higher in coinfection with viruses than in HPIV single infection (χ 2 = 5.744; P = 0.017). Moreover, HPIV coinfection with atypical bacteria was more related to running nose (χ 2 = 6.511; P = 0.011), moist rales (χ 2 = 5.167; P = 0.023), and longer hospital duration (χ 2 = 5.904; P = 0.015) compared with HPIV single infection, and also to longer hospital duration compared with coinfection with other viruses (χ 2 = 4.847; P = 0.028). This study revealed a high coinfection detection rate of 24.8%.

The previously reported rate was 18 to 65% in patients with ARI. 4, 5, 17, 19 It appears that coinfections are related to the prolonged period of viral persistence in the mucosa of the respiratory tract. 20 The large difference in the coinfection rate is probably due to the age and severity of patients enrolled. Infants and toddlers have an extremely high rate of virus coinfection compared with older children and adults. 19 Singleton et al 21 Coinfection with virus took the major part, of which HRV, RSV, and ADV were the most frequently detected agents. The fastest growing virus HRV was most commonly found in combination with HPIV, possibly due to the same age and seasonal distribution and the specific characteristics of the two viruses. 18, 22 Children aged less than 3 years had a higher positive rate of HPIV compared with children older than 3 years, indicating that young children are vulnerable to respiratory infection. [15] [16] [17] Only eight patients were coinfected with HPIV and atypical bacteria in the present study.

One hypothesis to explain the relative paucity of the codetections is that infections with these pathogens exhibit different age and seasonal distributions.

Several studies focused on the association between the severity of illness and coinfection, but no consensus has been reached. Some studies showed that viral coinfection did not increase severity, 17, 23 some studies indicated that virus single infection increased the risk of severe situations, 24 Laboratory examination PCT＞0.5 ng/mL 6 (9.7) 3 (6.7) 0 (0) The unit for peak and bottom of WBC was 10 9 /L; the normal value was 4-12 × 10 9 /L. d The unit for CRP was mg/L; the normal value was 0-8 mg/L. e Leukocytosis was defined as WBC more than 12 × 10 9 /L. f CRP increase was defined as CRP more than 8 mg/L. g Leukopenia was defined as WBC less than 4 × 10 9 /L. The quantitative data were expressed as median(quartile). The count data were expressed as numbers (%) of each group. 

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Clinical characteristics of the lower respiratory tract infection caused by a single infection or coinfection of the human parainfluenza virus in children

The authors thank the colleagues at the Department of Childrenʼs

Hospital, for their support during the study.

Zhejiang Province (2015C37026).

The authors declare that there are no conflict of interest.

http://orcid.org/0000-0003-0531-4917