Shuting Yue1,2, Na Li1,a, Can Jian1, Xiaoxia Dai1*
1School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an,710061, China.
2World Publishing Xi'an Corporation Ltd, Xi'an, 710003, China
Corresponding Author Details: Xiaoxia Dai, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an,710061, No.76 Yanta West Road, China. E-mail: xxiadai@xjtu.edu.cn
aCo-first Author: Na Li, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, China.
Received date: 21st April, 2018
Accepted date: 06th December, 2018
Published date: 29th January, 2019
Citation: Yue, S., Li, N., Jian, C., & Dai, X. (2019). Adenovirus infection rate of Chinese children with respiratory diseases: A Meta- analysis. J Pub Health Issue Pract 3: 133.
Copyright: ©2019, This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Objectives: To analysis the epidemiological characteristics of adenovirus infection rate of Chinese children with respiratory diseases.
Methods: Database such as PubMed, EMbase, CNKI, VIP and Wan Fang Data were searched for studies investigating adenovirus infection rate of Chinese children with respiratory diseases up to August 1st, 2018. Screened literature, exacted data, and methodological quality assessment of included studies according to the inclusion and exclusion criteria, then used the Stata11.0 for Meta-analysis.
Results: The analysis of 54 studies showed that the rate of adenovirus infection in children with respiratory diseases in China was 4.5%, and the confidence interval was 3.7% to 5.6%. Subgroup analysis indicated that the adenovirus infection rates of children with respiratory diseases in northern and southern China were 8.3% and 3.5%, respectively. The detection rate of polymerase chain reaction (PCR) was 7.8%, and the immune fluorescence and ELISA methods were 2.6% and 8.8%, respectively. The adenovirus infection rates of sample size in 1000 cases, 1000-5000 cases and more than 5000 cases were 5.8%, 4.7% and 3.1%, respectively. Adenovirus infection rates published in the 2000-2005, 2006-2010, and 2011-2018 groups were 3.5%, 1.4%, and 4.8%, respectively. The adenovirus infection rates in the 1 year, 1-3 years and 3 years were 5.3%, 4.8%, and 3.6%, respectively.
Conclusions: The adenovirus infection rate of Chinese children with respiratory diseases is different in different areas, test methods, sample size, the published time and study span.
Key words: children; adenovirus infection; respiratory diseases; meta-analysis
Adenovirus (AdV) is a kind of double-stranded DNA virus without capsular, and as far as we know that it is one of the largest and most complex DNA virus without capsular. Adenovirus consists of seven species (A-G) and more than 67 types within these species have been identified. Adenovirus could be in tonsil, lymph and intestinal tissue of the body in a long-term latent situation, it is a common pediatric pathogen responsible for a wide variety of infection. Adenovirus often cause multiple organ damage and cause acute febrile respiratory diseases, pharyngo-conjunctival fever, pneumonia, epidemic keratitis and gastroenteritis. Adenovirus has been considered an important respiratory pathogen and may cause death. Respiratory infection caused by adenovirus in non-immuno compromised patients is usually mild and self-limited. In contrast, in immune compromised patients, adenovirus infection can be disseminated and result in a considerable mortality rate [1-3]. The studies found that adenovirus pneumonia infection were mostly children, it was more serious than ordinary pneumonia and would have sequelae such as bronchiectasis, obliterative bronchiolitis and hyperlucenct lung et al [4]. Adenovirus infections could occur as outbreaks, especially where there was a concentration of military personnel or in cities. Adenovirus type 4 infection was most common in the US military [5], type 14 outbreaks were found in Chinese schools [6]. adenovirus type 3 (AdV3) was the most common genotype of respiratory adenovirus infection in many regions. There are differences in virus types in different populations and regions.
This study analyzed adenovirus infection rate of Chinese children with respiratory diseases by Meta-analysis method, and our results can be used for preventive measures, diagnosis and treatment work.
Literature: The studies which were related to adenovirus infection rate of Chinese children with respiratory diseases were included. The studies must be written in either Chinese or English.
Study subjects: The study subjects are patients aged 0-18 years with adenovirus infection respiratory diseases. The diagnosis of respiratory disease according to WHO diagnostic criterion.
Outcome: Adenovirus infection rate.
Exclusion criteria: 1. Epidemic or pandemic outbreak; 2. Immuno compromised population; 3. The studies only involved in upper or lower respiratory tract infection.
Search strategy for study identification: Database such as PubMed, EMbase, CNKI, VIP and Wan Fang Data were searched for studies investigating adenovirus infection rate of Chinese children with respiratory diseases up to March 1st, 2018. Search terms are children, adenovirus infection, respiratory disease. The search strategy for PubMed is#1 children AND #2 adenovirus infection AND #3 respiratory diseases
Study selection, data extraction and Quality assessment: Study selection was performed following the removal of duplicates in Endnote X7 software. Titles and abstracts shall then be screened following inclusion criteria, following which the full texts of potentially eligible articles will be obtained. These full texts will be screened using a standard and pre-tested form to include eligible studies. Data will include the geographic region where study was conducted, the year study was carried out and the year of publication, study design, sample size, age, season, adenovirus infection rate and detection method. The study quality evaluated by the evaluation criteria for observational study from Agency for Healthcare Research and Quality (AHRQ). The poor quality of studies will not be included to further analysis.
Statistical analysis: All identified data will be entered into Stata11.0 software for statistical analysis. Heterogeneity across studies was determined for choosing different analysis model and heterogeneity was assessed using the I2 values, assuming that I2 values of 25%, 50% and 75% represent low, medium and high heterogeneity, respectively. The subgroup analysis is used to analysis the different types of adenovirus infection rate of Chinese children with respiratory diseases and explore the source of heterogeneity. Sensitivity analysis is done to the results and the publication bias is evaluated by Egger, s Test.
]This analysis was carried out using the PRISMA. Fifty-four studies meeting the inclusion criteria were included in this study, including 309149 patients. Details of the study selection process (Figure 1).
Results of the 54 literatures enrolled, half were published in Chinese, the others were English literatures. The year of publication concentrated in between 2011 and 2018 (n=50, 93%). Most of studies used PCR (Polymerase Chain Reaction) methods (n=23, 43%), 27 studies used immunofluorescence method and 4 studies chose ELISA method. A total of 15 studies were from northern (28%), and 38 studies were from southern (70%). Summer is the season with high rate of adenovirus infection in the southern and it mostly occurred in spring and winter in the north. Among these studies, most of the patients were infants less than 5 years old. However, only nine studies had pointed out the classification of adenovirus, in which adenovirus typing was mainly type 3, followed by type 7 and type 4. In the results of quality evaluation, the scores of most studies are more than or equal to 6 points (n=29, 54%), only one study (Wang, M. 2001) scored 5 points. Table 1 presents their basic characteristics and the score of quality evaluation.
After deleted with one-way research in turn, then observed the influence. of the combined effect variable for sensitivity analysis. Figure 2 shows the result of sensitivity analysis.
Because of obvious heterogeneity among different studies, the random effect model is used for meta-analysis. 54 studies are included to further analysis.
Table 2 shows the adenovirus infection rate of Chinese children with respiratory diseases is 4.5% [95%CI (3.7%, 5.6%)], heterogeneity is high (I2=99.2%, P<0.0001). The heterogeneity will be analyzed later. Figure 3 is the forest plots.
Table: 2 Summary of Meta-analysis of adenovirus infection rate of Chinese children with respiratory diseases.
Table 3 shows the adenovirus infection rate of Chinese children with respiratory diseases in the north is 8.3%, and it is 3.5% in the south. The former is higher than the latter (P<0.05). This difference may be related to climate and living habits.
Table 4 shows the adenovirus infection rate of Chinese children with respiratory diseases by PCR methods is 7.8%, 2.6% by immunofluorescence method and 8.8% by ELISA method. The PCR and ELISA method may be more sensitive than immunofluorescence method in adenovirus detection.
Table: 3 The adenovirus infection rates of Chinese children with respiratory diseases in different regions.
The adenovirus infection rate of Chinese children with respiratory diseases in the group within 1000 cases (including 1000 cases) is 5.8%, 1000-5000 cases is 4.7%, and the group more than 5000 cases (including 5000 cases) is 3.1%. It suggests both large sample size and small sample size may affect results of studies. The analysis of sample size described in Table 5.
Table: 5 The adenovirus infection rates of Chinese children with respiratory diseases in different sample size group.
The adenovirus infection rate of Chinese children with respiratory diseases in the group within 2000-2005 is 3.5%, 2006-2010 is 1.4%, and the group within 2011-2018 is 4.8% (Table 6). The year of publication concentrated in between 2011 and 2018 (n=50, 93%). With the fluctuation of adenovirus infection, the attention paid to adenovirus is increasing.
Table: 6 The adenovirus infection rates of Chinese children with respiratory diseases in different published time group.
The adenovirus infection rate of Chinese children with respiratory diseases in the group within one year (including one year) is 5.3%, 1-3 year (including three years) is 4.8%, and the group more than three years is 3.6% (Table 7). It suggests the time span may also be an affecting factor.
Table: 7 The adenovirus infection rates of Chinese children with respiratory diseases in different time span.
There are publication bias in different groups. The subgroup of southern, and group of sample size have publication bias and these factors will be analyzed in meta regression. Table 8 shows the publication bias of subgroups in our study.
Meta regression has been done to explore the reason of heterogeneity. The random effect model is used for meta regression. The result of regression analysis expressed that the test methods and published time were the influencing factors, and 35.7% of heterogeneity can be explained by their difference. Table 9 shows the result of univariate analysis. effective and accurate.
Adenovirus is one of the more common pathogens for children and adolescents respiratory diseases, and it would cause serious pneumonia or bronchitis even death in infants. Our study analyzed the adenovirus infection rates of Chinese children with respiratory diseases by meta-analysis method. The results show the adenovirus infection rate of Chinese children with respiratory diseases is 4.5% [95%CI (3.7%, 5.6%)].
The adenovirus infection rate of Chinese children with respiratory diseases in the north is 8.3%, which higher than 3.5% in the south, and the difference is statistically significant (P<0.05). The north of China is colder than the south, and the unbalance among our regional economy are obviously. These factors may lead to huge difference in medical environment between the north and the south. The result with PCR and ELISA method (7.8%, 8.8%) are higher than the result of immunofluorescence method (2.6%), and the difference is statistically significant (P<0.05). It suggests that PCR and ELISA method may be more effective than immunofluorescence method in adenovirus detection. In the clinical work, PCR method may be more effective and accurate. The analysis of sample size showed that the result in 1000 cases, 1000-5000 cases and more than 5000 cases were 5.8%, 4.7% and 3.1%, and the result of the sample size in 1000-5000 is the most close to combined rate (4.5%), It suggests that the sample size has certain influence to research. In cross-sectional survey, large sample size may lead to heavy workload and difficult standardization and affect the survey quality, and thus it is very important to select the appropriate sample size. The adenovirus infection rate of Chinese children with respiratory diseases in the group within 1-3 year (including three years) (4.8%) are closed to combined rate (4.5%). According to the published time group, the adenovirus infection rates in 2000-2005, 2006-2010 and 2011-2018 were 3.5%, 1.4% and 4.8%, respectively. According to the data characteristics, the adenovirus has an upward trend in recent years.
The results of the meta-regression analysis showed that the test method and release time had an effect on the infection rate of adenovirus. This suggests that we should try to choose a method with high sensitivity and specificity when doing the analysis, and the early research may not be as important to the adenovirus as it is now, thus affecting the infection rate of adenovirus.
The limitation of our study is the representation of the sample size. Because the difference of medical resource in regions with uneven economic level, the bias from investigation may also affect the result of analysis.
Adenovirus is not the most common pathogen in respiratory diseases, but it will cause fatal pneumonia in younger children and often coinfect with other respiratory viruses and bacteria. Our study offered the epidemiological characteristics of adenovirus infection rate of Chinese children with respiratory diseases to provide a theoretical basis for further research on prevention and treatment in the world.
All authors declared that there are no conflicts of interest.
This work was supported by National Natural Science Foundation of China Grants 81673117 and 81573140.
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