key: cord-0982606-gclrtie7
authors: Li, Xuechao; Li, Juansheng; Meng, Lei; Zhu, Wanqi; Liu, Xinfeng; Yang, Mei; Yu, Deshan; Niu, Lixia; Shen, Xiping
title: Viral etiologies and epidemiology of patients with acute respiratory infections based on sentinel hospitals in Gansu Province, Northwest China, 2011‐2015
date: 2018-02-22
journal: J Med Virol
DOI: 10.1002/jmv.25040
sha: db8420a511f2532d80387c4945adbbcf88b10307
doc_id: 982606
cord_uid: gclrtie7

Understanding etiological role and epidemiological profile is needed to improve clinical management and prevention of acute respiratory infections (ARIs). A 5‐year prospective study about active surveillance for outpatients and inpatients with ARIs was conducted in Gansu province, China, from January 2011 to November 2015. Respiratory specimens were collected from patients and tested for eight respiratory viruses using polymerase chain reaction (PCR) or reverse transcription polymerase chain reaction (RT‐PCR). In this study, 2768 eligible patients with median age of 43 years were enrolled including pneumonia (1368, 49.2%), bronchitis (435, 15.7%), upper respiratory tract infection or URTI (250, 9.0%), and unclassified ARI (715, 25.8%). Overall, 29.2% (808/2768) were positive for any one of eight viruses, of whom 130 cases were identified with two or more viruses. Human rhinovirus (HRV) showed the highest detection rate (8.6%), followed by influenza virus (Flu, 7.3%), respiratory syncytial virus (RSV, 6.1%), human coronavirus (hCoV, 4.3%), human parainfluenza (PIV, 4.0%), adenovirus (ADV, 2.1%), human metapneumovirus (hMPV, 1.6%), and human bocavirus (hBoV, 0.7%). Compared with URTI, RSV was more likely identified in pneumonia (χ(2) = 12.720, P < 0.001) and hCoV was more commonly associated with bronchitis than pneumonia (χ(2) = 15.019, P < 0.001). In patients aged less than 5 years, RSV showed the highest detection rate and hCoV was the most frequent virus detected in adults and elderly. The clear epidemical seasons were observed in HRV, Flu, and hCoV infections. These findings could serve as a reference for local health authorities in drawing up further plans to prevent and control ARIs associated with viral etiologies.

distribution, 70% of children who died from ARIs were in Southeast Asia and Africa. 2 In China, despite the mortality of live births reduced significantly in past decades, ARIs were still the main cause of children mortality. 3 Several studies have reported the prevalence of respiratory viruses causing ARIs in China [4] [5] [6] [7] [8] ; however most of these studies were conducted in developed regions of eastern coastal China. Thus, this paper presents data on the epidemiology of viral etiologies associated with ARIs in Gansu Province, which located in a relatively undeveloped area of China and aims to provide basic data of viral etiologies of ARIs to direct local disease prevention and control.

This study was approved by the Ethics Review Committee of Chinese Center for Disease Control and Prevention (CDC) and all participants were informed of the study objectives, and written consent was obtained from patients or guardians. Inpatients and outpatients were first screened by physicians of sentinel hospitals for ARIs and if they met inclusion criteria as follows, these patients would be enrolled into our study. A patient was considered to be having ARIs if they had: (1) at least one of listed manifestation of acute infection: measured fever (≥38°C), abnormal white blood cell (WBC) differential, leukocytosis (a WBC count more than 10 000/µL) or leucopenia (a WBC count less than 4000/µL), and chill; (2) at least one of listed signs/symptoms: cough, sputum, shortness of breath, lung auscultation abnormality (rale or wheeze), tachypnoea, and chest pain. Among ARIs patients, those with a chest radiograph demonstrating punctuate, patchy or uniform density opacity were defined as having radiographic evidence of pneumonia. 5 The diagnosis for each patient admitted in this study was made by attending physicians and based on standard clinical criteria. Thus, pneumonia was diagnosed with fever, tachypnoea, chest pain, and respiratory distress where focal or diffuse crackles or decreased vesicular sounds were present on auscultation. Chest radiograph was used to distinguish pneumonia and other ARIs, but some diagnosis of pneumonia were based on clinical criteria alone. Bronchitis was diagnosed in whom upper respiratory symptoms preceded lower respiratory symptoms of wheeze, dyspnea, and signs of respiratory distress. Upper respiratory tract infections were diagnosed based on symptoms such as cough, runny nose, sore throat, and coryza. ARIs other than pneumonia, bronchitis, and upper respiratory tract infections were defined as unclassified ARIs.

Respiratory specimens (nasopharyngeal swab or aspirate, sputum, bronchoalveolar lavage, or lung puncture aspirate) were collected in ARIs patients and placed immediately in viral transport media (VTM).

Collected specimens were stored at 4-8°C at the local hospital and were transferred to the sentinel laboratories for diagnostic testing. Viral molecular tests were completed within 24 h after collection; otherwise specimens in VTM should be stored at −70°C.

Every specimen from patients was detected for eight viruses.

The viral nucleic acid was directly extracted from specimens by commercial kits (QIAmpMiniElute Virus Spin kit, QIAamp Viral RNA Mini kit or RNeasy Mini kit, Qiagen, Valencia, CA) recommended by surveillance protocol. ADV and hBoV were determined by Polymerase chain reaction (PCR). 9,10 Reverse transcription-Polymerase chain reaction (RT-PCR) was performed to detect the other six viruses. [11] [12] [13] [14] The primer sequences of PCR or RT-PCR were shown in Table 1 . If any one of the targeted viruses was detected in the specimens, the patient was considered to be positive for that viral etiology. The cases where only one virus identified were labelled as single infection, two etiologies were co-infection, and three or more were multiple-infection.

Demographic characteristics, clinical symptoms were collected by staff of sentinel hospitals through a standardized questionnaire of protocol.

Data were analyzed using SPSS (v20.0, SPSS, Chicago, IL). Two tailed Mann-Whitney test was used to compare median of two groups and comparison of median in more than two groups used Kruskal-Wallis test. Categorical data was performed using Chi-square test or Fisher exact test. P-value < 0.05 was considered to be statistically significant. 

Of all 2768 ARIs patients tested for eight viruses, 808 (29.2%) were positive for at least one virus. The median age of these patients was lower than patients who were negative for any respiratory viruses (P < 0.05, Mann-Whitney test). HRV showed the highest detection rate (Table 3) .

Of 2336 inpatients, 29.8% tested positive for at least one virus.

This rate was similar to that of outpatients (χ 2 = 3.027, P > 0.05). The most common virus was HRV, with 8.3% (195/2336) detected in inpatients and 9.7% (42/432) in outpatients, whereas the detection rate of HRV had no difference between two groups (χ 2 = 0.880, P > 0.05). Compared with outpatients, only RSV and PIV were more likely detected in inpatients (RSV: χ 2 = 4.206, P < 0.05; PIV: χ 2 = 4.849, 

All of ARIs patients were divided into six age groups. The overall detection rate between age groups had significant difference Apart from hMPV and hBoV, each of else respiratory viruses incidence differed among age groups (Table 5 ).

Over the 59 months study period, there were clear seasonal peaks for HRV, Flu, and hCoV infections. HRV infections were occurred each month throughout the year during 5 years with an annual a peak in September-October (Figure 1, panel A) . Flu and hCoV infections showed a similarly circulation of one peak annually, with the peak of Flu infections was observed during December-January and hCoV during July to August (Figure 1, panels B and D) . RSV and PIV did not show the clear epidemic season (Figure 1 , panels C and E). Due to the infections of ADV, hMPV, and hBoV appeared sporadically among our study period, we did not present seasonal distributions of these viruses in Figure 1 .

Before this study there was a similar report about prevalence of children infected with respiratory viruses in Gansu province. 15 However, that study was only based on children aged less than 

of patients but also in each of diagnosis groups. Highest detection rate (45.3%) in patients aged 1-5 years indicated that ARIs still was a risk factor for younger children's health, although the mortality due to respiratory tract infections decreased more than 35% in this age population. 17 Pneumonia, a leading cause of mortality of children less than 5 years especially in developing country, 18 was commercially available, such as inactivated vaccine, which was administered intramuscularly or intranasally. [29] [30] [31] However, it had an extremely low coverage rate in China. 32 We considered Influenza vaccine should be used in widespread areas to reduce the incidence of influenza disease in Gansu. It should be noted that PIV was a another major virus for children aged 1-5 years besides RSV, which was in agreement with studies conducted before. [33] [34] [35] This finding indicated that local pediatricians not only took priority over RSV infections but 

Global mortality, disability, and the contribution of risk factors: global burden of disease study

Estimates of world-wide distribution of child deaths from acute respiratory infections

Causes of deaths in children younger than 5 years in China

Study on the viral etiology of acute respiratory tract infections in Shanghai area during 2009-2010

Prevalence of human respiratory viruses in adults with acute respiratory tract infections in Beijing

Identification of viral and atypical bacterial pathogens in children hospitalized with acute respiratory infections in Hong Kong by multiplex PCR assays

Viral Etiology of acute respiratory tract infections in hospitalized children and adults in Shandong Province

Prevalence of respiratory viruses among children hospitalized from respiratory infections in Shenzhen, China

Polymerase chain reaction for detection of adenoviruses in stool samples

Bocavirus infection in hospitalized children

Simultaneous detection of influenza A, B, and C viruses, respiratory syncytial virus, and adenoviruses in clinical samples by multiplex reverse transcription nested-PCR assay

Simultaneous detection of fourteen respiratory viruses in clinical specimens by two multiplex reverse transcription nested-PCR assays

Children with respiratory disease associated with metapneumovirus in Hong Kong

Characterization and complete genome sequence of a novel coronavirus, coronavirus HKU1, from patients with pneumonia

Viral etiology of acute respiratory infection in Gansu Province, China

Viral etiologies of hospitalized acute lower respiratory infection patients in China

Estimates of the global, regional, and national morbidity, mortality, and aetiologies of lower respiratory tract infections in 195 countries: a systematic analysis for the Global Burden of Disease Study

Acute lower respiratory infections in developing countries

Respiratory syncytial virus and other respiratory viral infections in older adults with moderate to severe influenza-like illness

Viral infection in adults hospitalized with community-acquired pneumonia: prevalence, pathogens, and presentation

Human coronaviruses: clinical features and phylogenetic analysis

Molecular characterization of human respiratory syncytial virus in the Philippines

Impact of respiratory syncytial virus infection as a cause of lower respiratory tract infection in children younger than 3 years of age in Japan

Global burden of acute lower respiratory infections due to respiratory syncytial virus in young children: a systematic review and meta-analysis

Respiratory syncytial virus hospitalization and mortality: systematic review and meta-analysis

Detection and typing by molecular techniques of respiratory viruses in children hospitalized for acute respiratory infection in Rome, Italy

Respiratory consequences of rhinovirus infection

The common cold: a review of the literature

The common cold

Review of intranasal influenza vaccine

Pre-clinical and clinical investigation of the safety of a novel adjuvant for intranasal immunization

Seasonal influenza vaccine supply and target vaccinated population in China

Viral and atypical bacterial detection in acute respiratory infection in children under five years

Viral etiology of severe pneumonia among Kenyan young infants and children

Acute viral lower respiratory tract infections in Cambodian children: clinical and epidemiologic characteristics

Frequency and natural history of rhinovirus infections in adults during autumn

Prevalence of human coronaviruses in adults with acute respiratory tract infections in Beijing

Epidemiology and clinical presentations of the four human coronaviruses 229E, HKU1, NL63, and OC43 detected over 3 years using a novel multiplex real-time PCR method

Viral etiologies and epidemiology of patients with acute respiratory infections based on sentinel hospitals in Gansu Province

The authors have declared that no competing interests exist.

http://orcid.org/0000-0002-6485-6970