Journal of Medical Virology
Epidemiological Characteristics and Immune Status of Children With Respiratory Syncytial Virus Qing Ye,1,2 Wen-Xia Shao,3 Shi-Qiang Shang,1* Yan-Xiang Pan,1 Hong-Qiang Shen,1 and Xue-Jun Chen1 1
Clinical Laboratory, The Children’s Hospital of Zhejiang University School of Medicine, Hangzhou, China Zhejiang Key Laboratory for Diagnosis and Treatment of Neonatal Diseases, Hangzhou, China 3 Clinical Laboratory, Hangzhou First People’s Hospital, Hangzhou, China 2
Respiratory Syncytial Virus (RSV) infections are the dominant cause of pneumonia in children. In order to determine the epidemiological characteristics and immune status of children with Respiratory Syncytial Virus, a prospective study was performed among patients with RSV infection. Comparisons between RSV pneumonia group and normal control group, RSV pneumonia group had lower IL-2 (median levels, pg/ml: 3.8 vs. 5.1, P < 0.01), and higher IL-4 (median levels, pg/ ml: 3.2 vs. 2.4, P < 0.01), IL-10 (median levels, pg/ml: 12.2 vs. 2.3, P < 0.01), and IFN-g (median levels, pg/ml: 13.4 vs. 4.6, P < 0.01). The level of IgE among pneumonia patients caused by RSV increased sharply (median levels, mg/L: 48.1 vs. 8.8, P < 0.01). Another amazing finding is that after birth, the degree of IgE of the children infected by RSV increases gradually with age. This effect is at its peak in 0.6 years old. The IgE and eosinophil levels were higher when patients suffered from RSV pneumonia with wheeze (IgE median levels, IU/ml: with wheeze: 72.74 vs. without wheeze: 11.5, P < 0.05; eosinophil median levels, 109/l: with wheeze: 0.21 vs. without wheeze: 0.05, P < 0.05). The main morbidity crowd is the children under the age of 1 year old. The downregulation of IL2 and the upregulation of IL-4, IL-10, IFN-g, and IgE happen after RSV infection. J. Med. Virol. # 2014 Wiley Periodicals, Inc.
KEY WORDS:
respiratory syncytial virus; allergy; immune regulation; immunoglobulin E
INTRODUCTION Asthma is among the most prevalent chronic diseases; in children, it now leads the chronic disease C 2014 WILEY PERIODICALS, INC.
statistics. There are an estimated 300 million asthmatics worldwide [Masoli et al., 2004]. This condition represents a significant financial burden, as it is estimated that asthma causes a loss in disabilityadjusted life years that amounts to 15 million per year worldwide [Masoli et al., 2004]. A number of observations and studies have demonstrated repeatedly that virus-induced inflammation might act to disrupt normal lung function at a point in life when the lung is growing and experiencing significant anatomic changes. In order to determine the epidemiological characteristics and immune status of children with Respiratory Syncytial Virus (RSV), a prospective study was performed among patients with RSV infection. MATERIALS AND METHODS Patients This study was performed prospectively from January 2012 to December 2013 and was approved by the Institutional Review Board of Zhejiang University. Informed written consent was obtained from guardians on the behalf of the minor/child participants involved in the study. Patients who met the following criteria were enrolled: (1) children under the age of 18 years old; (2) who was diagnosed to have pneumonia [Harris et al., 2011] or capillary bronchitis [Diagnosis and Bronchiolitis, 2006] caused by Respiratory Syncytial Virus. Pneumonia and capillary bronchitis were diagnosed on the basis of radiological findings and clinical features, including paroxysmal cough, expiratory dyspnea, fever, and rale. Respiratory Syncytial Virus was detected by immunofluorescence in nasopharyngeal swabs. Patients with a history of previous Correspondence to: Shi-Qiang Shang, Clinical Laboratory, The Children’s Hospital of Zhejiang University School of Medicine, Hangzhou, China. E-mail: [email protected] Accepted 15 July 2014
DOI 10.1002/jmv.24047 Published online in Wiley Online Library (wileyonlinelibrary.com).
2
Ye et al.
respiratory infection or any other underlying disease were excluded from the study. The presence of other pathogens was tested in parallel using specific laboratory tests, including immunofluorescence to detect respiratory virus such as Adenovirus, Parainfluenza Virus, and Influenza Virus; sputum and blood cultures for bacteria; and PCR to detect EB Virus, Mycoplasma Pneumoniae, Chlamydia Pneumoniae, Human Metapneumovirus, and Chlamydia Trachomatis. At the onset of pneumonia, blood samples and nasopharyngeal swabs specimens were taken for microbiological analyses and serum Th1/Th2 cytokine determination immediately. Chest radiography, CT scan, and abdominal ultrasound were performed to check the sites of infection if necessary. Measurement of Serum Cytokines, IgE and Eosinophil The blood samples were centrifuged at 1,000 g at 20˚C for 20 min after clotting. The serum was carefully harvested and underwent the Th1/Th2 cytokine measurement by 320 flow cytometry immediately. Concentrations of IL-2, IL-4, IL-6, IL-10, tumor necrosis factor (TNF)-a, and interferon (IFN)-g were determined quantitatively by the CBA kit–BDTM CBA Human Th1/Th2 Cytokine Kit II (BD Biosciences, San Jose, CA). The minimal and maximum limits of detection for all six cytokines were 1.0 and 5,000 pg/ml, respectively. Serum total IgE levels were determined using UniCAP total IgE kits (Pharmacia). Eosinophil was counted by automatic Blood Cell Counter (Sysmex XS-800i, Japan). Statistical Analysis The comparisons between the two groups were performed using the x2 or Fisher’s exact test for categorical variables and Mann–Whitney U test (for two groups) for continuous variables. All statistical analyses were performed using SPSS Statistics18.0 software. P < 0.05 was considered to be statistically significant. RESULTS Patients’ Characteristics As shown in Figure 1, the research involved 12,132 children, including 10,852 patients with negative RSV test and 1,280 patients with positive RSV test. Among the 1,280 patients with positive RSV test included RSV pneumonia (n ¼ 204), RSV capillary bronchitis (n ¼ 60), and mixed infection (n ¼ 1016). Patients with RSV pneumonia (n ¼ 204) were characterized by allergic history, including 64 patients with previous allergic history (34 cases with eczema, 12 cases with urticaria, 10 cases with penicillin anaphylaxis, and 8 cases with Henoch-Schonlein purpura); and by the occurrence of parental allergy history, J. Med. Virol. DOI 10.1002/jmv
including 36 patients whose parents had allergy history (14 cases with allergic rhinitis, 7 cases with penicillin anaphylaxis, 6 cases with drug rash, 6 cases with food allergy and 3 cases with asthma). Among the 204 patients with RSV pneumonia, there were 122 cases with wheeze. The 204 episodes of RSV pneumonia occurred in 204 patients, with a median age of 0.6 years old (range, 0.1–7.7 years old) and a male to female ratio of 3.25. One hundred healthy children without fever and any other signs of infection were enrolled as the control cohort. The median age of the control group was 0.8 years old (range, 0.1–8.5 years old) with a male to female ratio of 3.23. The gender and age between RSV pneumonia group and control group were comparable (P > 0.05). Boys exceeded girls in RSV infected children, but there were no difference between IgE and eosinophil levels (median levels, IU/ml: IgE: 21.35 vs. 21.25, P ¼ 0.529; median levels, 109/l: eosinophil: 0.12 vs. 0.14, P ¼ 0.412). The Epidemiological Characteristics of RSV Infection Total 1,280 patients tested positive for RSV, as shown in Figure 2, about half of the RSV infection occurred within six months, and 90% of infections occur within one year old. RSV infection rate was higher in January, February, March, and December, respectively, 23%, 26%, 24%, and 12%. May, June, July, August, September, October, and November were low period of RSV infection; infection rates were less than 9%. (As shown in Fig. 3).
Serum Cytokine Levels, IgE and Eosinophil in Control Group and RSV Pneumonia Group The research detected the cytokine levels, IgE and eosinophil of 204 Children with RSV pneumonia. One hundred healthy children were enrolled as the control cohort. The levels of six cytokines, IgE and eosinophil in the normal control group and RSV pneumonia group are shown in Table I. Comparisons between RSV pneumonia group and normal control group: RSV pneumonia group had lower IL-2 (median levels, pg/ml: 3.8 vs. 5.1, P < 0.01), and higher IL-4 (median levels, pg/ml: 3.2 vs. 2.4, P < 0.01), IL-10 (median levels, pg/ml: 12.2 vs. 2.3, P < 0.01), and IFN-g (median levels, pg/ml: 13.4 vs. 4.6, P < 0.01). The level of IgE among pneumonia patients caused by RSV increased sharply (median levels, mg/l: 48.1 vs. 8.8, P < 0.01). Among the 204 Children with RSV pneumonia, the degree of IgE of the children increased gradually with age. This effect was at its peak in 0.6 years old. After 0.68 years old, this effect decreased gradually with the growth of the age. The IgE level was highest when children infected by RSV during 0.3 to 1.0 years old (IgE median levels, IU/ml: 1.0
RSV Infection in Children
3
Fig. 1. The flow chart of the study. Sixty four patients with previous allergic history: 34 cases with eczema, 12 cases with urticaria, 10 cases with penicillin anaphylaxis, and 8 cases with Henoch-Schonlein purpura; 36 patients whose parents had allergy history: 14 cases with allergic rhinitis, 7 cases with penicillin anaphylaxis, 6 cases with drug rash, 6 cases with food allergy, and 3 cases with asthma.
years old: 27.35, P < 0.01). (Fig. 4) However, the IgE levels in the normal controls do not show above pattern. The Analysis of the Affecting Factors of IgE and Eosinophil Levels After RSV Infection
Fig. 2. Age distribution of patients with RSV infection. Total 1,280 patients with test positive for RSV included RSV pneumonia (n ¼ 204), RSV capillary bronchitis (n ¼ 60), and mixed infection (n ¼ 1,016). This chart showed their age distribution.
Median levels of IgE were 48.1 IU/ml and 28.2 IU/ ml and median levels of eosinophil were 0.15 109/l and 0.05 109/l, respectively (RSV pneumonia: n ¼ 204 vs RSV capillary bronchitis: n ¼ 60). Median levels of IgE were 54.97 IU/ml and 44.97 IU/ml and median levels of eosinophil were 0.17 109/l, and 0.07 109/l, respectively (patients had previous allergic history: n ¼ 64 vs patients had no previous allergic history: n ¼ 140). Median levels of IgE were 50.07 IU/ml and 47.67 IU/ml and median levels of eosinophils in patients were 0.21 109/l and 0.13 109/l, respectively (patients whose parents had allergy history: n ¼ 36 vs patients whose parents had no allergy history: n ¼ 168). IgE and eosinophil levels had nothing to do with children’ allergic history, their parental allergy history, and disease J. Med. Virol. DOI 10.1002/jmv
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Fig. 3. Detection rate of RSV in each month. The research involved 12,132 children, including 10,852 patients with test negative for RSV and 1,280 patients with test positive for RSV. This chart showed their detection rate of RSV in each month. The positive specimen bars are displayed on the top of total specimen bars.
types after RSV infection, but there were higher IgE and eosinophil levels when patients suffered from RSV pneumonia with wheeze (IgE median levels, IU/ ml: with wheeze: 72.74 vs. without wheeze: 11.5, P < 0.05; eosinophil median levels, 109/l: with wheeze: 0.21 vs. without wheeze: 0.05, P < 0.05), as shown in Figure 5. DISCUSSION The rapid spread of respiratory viruses has attracted considerable attention, especially with the frequent outbreaks of H5N1 and H1N1 in the past time. How respiratory viruses are sustained is not yet known clearly. Among these factors [Dowell, 2001; Lowen et al., 2007; Rafiefard et al., 2008; Fabbiani et al., 2009; Khamis et al., 2012; Hirsh et al., 2014; Karadag-Oncel et al., 2014], such as host susceptibility, viral mutation, seasonal behavior and effects of meteorological factors, play key roles in epidemics and the seasonal prevalence of RSV. RSV infection rates were higher in January, February,
March, and December, respectively, 23%, 26%, 24%, and 12%, as the weather of these months is the coldest in the south of China. May, June, July, August, September, October, and November were low period of RSV infection, and the infection rates were less than 9%, when the weather has warmed up. There were significant differences of RSV infection rates among populations with different age and gender. A total of 1,280 patients with positive RSV test, as shown in Figure 2, about half of the RSV infection occurred in patients within six months old, and 90% of infections occurred in patients within one year old. The main morbidity was in children under the age of one year old. Additionally, it seemed that boys were more likely to suffer from RSV pneumonia with a male to female ratio of 3.25. Comparisons between RSV pneumonia group and normal control group: RSV pneumonia group had lower IL-2 (median levels, pg/ml: 3.8 vs. 5.1, P < 0.01), and higher IL-4 (median levels, pg/ml: 3.2 vs. 2.4, P < 0.01), IL-10 (median levels, pg/ml: 12.2 vs.
TABLE I. Serum Cytokine Levels, IgE and Eosinophil in the Control Group and Patients With RSV Pneumonia Parameters IL-2 (pg/ml) IL-4 (pg/ml) IL-6 (pg/ml) IL-10 (pg/ml) TNF-a (pg/ml) INF-g (pg/ml) IgE (mg/l) Eosnophils (109)
Respiratory syncytial virus (n ¼ 204) 3.8 3.2 18.3 12.2 3.4 13.4 48.1 0.15
(1.5 ! 7.0) (1.4 ! 7.4) (1.4 ! 244.4) (1.7 ! 78.6) (1.0 ! 24.4) (2.4 ! 74.8) (4.3 ! 5790.0) (0.01 ! 0.64)
Normal control (n ¼ 100) 5.1 2.4 4.3 2.3 2.1 4.6 8.8 0.11
(2.7 ! 7.2) (1.1 ! 2.9) (1.2 ! 8.5) (1.3 ! 3.4) (1.3 ! 2.7) (3.3 ! 7.8) (4.3 ! 26.4) (0.05 ! 0.25)
P value
Epidemiological Characteristics and Immune Status of Children With Respiratory Syncytial Virus Qing Ye,1,2 Wen-Xia Shao,3 Shi-Qiang Shang,1* Yan-Xiang Pan,1 Hong-Qiang Shen,1 and Xue-Jun Chen1 1
Clinical Laboratory, The Children’s Hospital of Zhejiang University School of Medicine, Hangzhou, China Zhejiang Key Laboratory for Diagnosis and Treatment of Neonatal Diseases, Hangzhou, China 3 Clinical Laboratory, Hangzhou First People’s Hospital, Hangzhou, China 2
Respiratory Syncytial Virus (RSV) infections are the dominant cause of pneumonia in children. In order to determine the epidemiological characteristics and immune status of children with Respiratory Syncytial Virus, a prospective study was performed among patients with RSV infection. Comparisons between RSV pneumonia group and normal control group, RSV pneumonia group had lower IL-2 (median levels, pg/ml: 3.8 vs. 5.1, P < 0.01), and higher IL-4 (median levels, pg/ ml: 3.2 vs. 2.4, P < 0.01), IL-10 (median levels, pg/ml: 12.2 vs. 2.3, P < 0.01), and IFN-g (median levels, pg/ml: 13.4 vs. 4.6, P < 0.01). The level of IgE among pneumonia patients caused by RSV increased sharply (median levels, mg/L: 48.1 vs. 8.8, P < 0.01). Another amazing finding is that after birth, the degree of IgE of the children infected by RSV increases gradually with age. This effect is at its peak in 0.6 years old. The IgE and eosinophil levels were higher when patients suffered from RSV pneumonia with wheeze (IgE median levels, IU/ml: with wheeze: 72.74 vs. without wheeze: 11.5, P < 0.05; eosinophil median levels, 109/l: with wheeze: 0.21 vs. without wheeze: 0.05, P < 0.05). The main morbidity crowd is the children under the age of 1 year old. The downregulation of IL2 and the upregulation of IL-4, IL-10, IFN-g, and IgE happen after RSV infection. J. Med. Virol. # 2014 Wiley Periodicals, Inc.
KEY WORDS:
respiratory syncytial virus; allergy; immune regulation; immunoglobulin E
INTRODUCTION Asthma is among the most prevalent chronic diseases; in children, it now leads the chronic disease C 2014 WILEY PERIODICALS, INC.
statistics. There are an estimated 300 million asthmatics worldwide [Masoli et al., 2004]. This condition represents a significant financial burden, as it is estimated that asthma causes a loss in disabilityadjusted life years that amounts to 15 million per year worldwide [Masoli et al., 2004]. A number of observations and studies have demonstrated repeatedly that virus-induced inflammation might act to disrupt normal lung function at a point in life when the lung is growing and experiencing significant anatomic changes. In order to determine the epidemiological characteristics and immune status of children with Respiratory Syncytial Virus (RSV), a prospective study was performed among patients with RSV infection. MATERIALS AND METHODS Patients This study was performed prospectively from January 2012 to December 2013 and was approved by the Institutional Review Board of Zhejiang University. Informed written consent was obtained from guardians on the behalf of the minor/child participants involved in the study. Patients who met the following criteria were enrolled: (1) children under the age of 18 years old; (2) who was diagnosed to have pneumonia [Harris et al., 2011] or capillary bronchitis [Diagnosis and Bronchiolitis, 2006] caused by Respiratory Syncytial Virus. Pneumonia and capillary bronchitis were diagnosed on the basis of radiological findings and clinical features, including paroxysmal cough, expiratory dyspnea, fever, and rale. Respiratory Syncytial Virus was detected by immunofluorescence in nasopharyngeal swabs. Patients with a history of previous Correspondence to: Shi-Qiang Shang, Clinical Laboratory, The Children’s Hospital of Zhejiang University School of Medicine, Hangzhou, China. E-mail: [email protected] Accepted 15 July 2014
DOI 10.1002/jmv.24047 Published online in Wiley Online Library (wileyonlinelibrary.com).
2
Ye et al.
respiratory infection or any other underlying disease were excluded from the study. The presence of other pathogens was tested in parallel using specific laboratory tests, including immunofluorescence to detect respiratory virus such as Adenovirus, Parainfluenza Virus, and Influenza Virus; sputum and blood cultures for bacteria; and PCR to detect EB Virus, Mycoplasma Pneumoniae, Chlamydia Pneumoniae, Human Metapneumovirus, and Chlamydia Trachomatis. At the onset of pneumonia, blood samples and nasopharyngeal swabs specimens were taken for microbiological analyses and serum Th1/Th2 cytokine determination immediately. Chest radiography, CT scan, and abdominal ultrasound were performed to check the sites of infection if necessary. Measurement of Serum Cytokines, IgE and Eosinophil The blood samples were centrifuged at 1,000 g at 20˚C for 20 min after clotting. The serum was carefully harvested and underwent the Th1/Th2 cytokine measurement by 320 flow cytometry immediately. Concentrations of IL-2, IL-4, IL-6, IL-10, tumor necrosis factor (TNF)-a, and interferon (IFN)-g were determined quantitatively by the CBA kit–BDTM CBA Human Th1/Th2 Cytokine Kit II (BD Biosciences, San Jose, CA). The minimal and maximum limits of detection for all six cytokines were 1.0 and 5,000 pg/ml, respectively. Serum total IgE levels were determined using UniCAP total IgE kits (Pharmacia). Eosinophil was counted by automatic Blood Cell Counter (Sysmex XS-800i, Japan). Statistical Analysis The comparisons between the two groups were performed using the x2 or Fisher’s exact test for categorical variables and Mann–Whitney U test (for two groups) for continuous variables. All statistical analyses were performed using SPSS Statistics18.0 software. P < 0.05 was considered to be statistically significant. RESULTS Patients’ Characteristics As shown in Figure 1, the research involved 12,132 children, including 10,852 patients with negative RSV test and 1,280 patients with positive RSV test. Among the 1,280 patients with positive RSV test included RSV pneumonia (n ¼ 204), RSV capillary bronchitis (n ¼ 60), and mixed infection (n ¼ 1016). Patients with RSV pneumonia (n ¼ 204) were characterized by allergic history, including 64 patients with previous allergic history (34 cases with eczema, 12 cases with urticaria, 10 cases with penicillin anaphylaxis, and 8 cases with Henoch-Schonlein purpura); and by the occurrence of parental allergy history, J. Med. Virol. DOI 10.1002/jmv
including 36 patients whose parents had allergy history (14 cases with allergic rhinitis, 7 cases with penicillin anaphylaxis, 6 cases with drug rash, 6 cases with food allergy and 3 cases with asthma). Among the 204 patients with RSV pneumonia, there were 122 cases with wheeze. The 204 episodes of RSV pneumonia occurred in 204 patients, with a median age of 0.6 years old (range, 0.1–7.7 years old) and a male to female ratio of 3.25. One hundred healthy children without fever and any other signs of infection were enrolled as the control cohort. The median age of the control group was 0.8 years old (range, 0.1–8.5 years old) with a male to female ratio of 3.23. The gender and age between RSV pneumonia group and control group were comparable (P > 0.05). Boys exceeded girls in RSV infected children, but there were no difference between IgE and eosinophil levels (median levels, IU/ml: IgE: 21.35 vs. 21.25, P ¼ 0.529; median levels, 109/l: eosinophil: 0.12 vs. 0.14, P ¼ 0.412). The Epidemiological Characteristics of RSV Infection Total 1,280 patients tested positive for RSV, as shown in Figure 2, about half of the RSV infection occurred within six months, and 90% of infections occur within one year old. RSV infection rate was higher in January, February, March, and December, respectively, 23%, 26%, 24%, and 12%. May, June, July, August, September, October, and November were low period of RSV infection; infection rates were less than 9%. (As shown in Fig. 3).
Serum Cytokine Levels, IgE and Eosinophil in Control Group and RSV Pneumonia Group The research detected the cytokine levels, IgE and eosinophil of 204 Children with RSV pneumonia. One hundred healthy children were enrolled as the control cohort. The levels of six cytokines, IgE and eosinophil in the normal control group and RSV pneumonia group are shown in Table I. Comparisons between RSV pneumonia group and normal control group: RSV pneumonia group had lower IL-2 (median levels, pg/ml: 3.8 vs. 5.1, P < 0.01), and higher IL-4 (median levels, pg/ml: 3.2 vs. 2.4, P < 0.01), IL-10 (median levels, pg/ml: 12.2 vs. 2.3, P < 0.01), and IFN-g (median levels, pg/ml: 13.4 vs. 4.6, P < 0.01). The level of IgE among pneumonia patients caused by RSV increased sharply (median levels, mg/l: 48.1 vs. 8.8, P < 0.01). Among the 204 Children with RSV pneumonia, the degree of IgE of the children increased gradually with age. This effect was at its peak in 0.6 years old. After 0.68 years old, this effect decreased gradually with the growth of the age. The IgE level was highest when children infected by RSV during 0.3 to 1.0 years old (IgE median levels, IU/ml: 1.0
RSV Infection in Children
3
Fig. 1. The flow chart of the study. Sixty four patients with previous allergic history: 34 cases with eczema, 12 cases with urticaria, 10 cases with penicillin anaphylaxis, and 8 cases with Henoch-Schonlein purpura; 36 patients whose parents had allergy history: 14 cases with allergic rhinitis, 7 cases with penicillin anaphylaxis, 6 cases with drug rash, 6 cases with food allergy, and 3 cases with asthma.
years old: 27.35, P < 0.01). (Fig. 4) However, the IgE levels in the normal controls do not show above pattern. The Analysis of the Affecting Factors of IgE and Eosinophil Levels After RSV Infection
Fig. 2. Age distribution of patients with RSV infection. Total 1,280 patients with test positive for RSV included RSV pneumonia (n ¼ 204), RSV capillary bronchitis (n ¼ 60), and mixed infection (n ¼ 1,016). This chart showed their age distribution.
Median levels of IgE were 48.1 IU/ml and 28.2 IU/ ml and median levels of eosinophil were 0.15 109/l and 0.05 109/l, respectively (RSV pneumonia: n ¼ 204 vs RSV capillary bronchitis: n ¼ 60). Median levels of IgE were 54.97 IU/ml and 44.97 IU/ml and median levels of eosinophil were 0.17 109/l, and 0.07 109/l, respectively (patients had previous allergic history: n ¼ 64 vs patients had no previous allergic history: n ¼ 140). Median levels of IgE were 50.07 IU/ml and 47.67 IU/ml and median levels of eosinophils in patients were 0.21 109/l and 0.13 109/l, respectively (patients whose parents had allergy history: n ¼ 36 vs patients whose parents had no allergy history: n ¼ 168). IgE and eosinophil levels had nothing to do with children’ allergic history, their parental allergy history, and disease J. Med. Virol. DOI 10.1002/jmv
4
Ye et al.
Fig. 3. Detection rate of RSV in each month. The research involved 12,132 children, including 10,852 patients with test negative for RSV and 1,280 patients with test positive for RSV. This chart showed their detection rate of RSV in each month. The positive specimen bars are displayed on the top of total specimen bars.
types after RSV infection, but there were higher IgE and eosinophil levels when patients suffered from RSV pneumonia with wheeze (IgE median levels, IU/ ml: with wheeze: 72.74 vs. without wheeze: 11.5, P < 0.05; eosinophil median levels, 109/l: with wheeze: 0.21 vs. without wheeze: 0.05, P < 0.05), as shown in Figure 5. DISCUSSION The rapid spread of respiratory viruses has attracted considerable attention, especially with the frequent outbreaks of H5N1 and H1N1 in the past time. How respiratory viruses are sustained is not yet known clearly. Among these factors [Dowell, 2001; Lowen et al., 2007; Rafiefard et al., 2008; Fabbiani et al., 2009; Khamis et al., 2012; Hirsh et al., 2014; Karadag-Oncel et al., 2014], such as host susceptibility, viral mutation, seasonal behavior and effects of meteorological factors, play key roles in epidemics and the seasonal prevalence of RSV. RSV infection rates were higher in January, February,
March, and December, respectively, 23%, 26%, 24%, and 12%, as the weather of these months is the coldest in the south of China. May, June, July, August, September, October, and November were low period of RSV infection, and the infection rates were less than 9%, when the weather has warmed up. There were significant differences of RSV infection rates among populations with different age and gender. A total of 1,280 patients with positive RSV test, as shown in Figure 2, about half of the RSV infection occurred in patients within six months old, and 90% of infections occurred in patients within one year old. The main morbidity was in children under the age of one year old. Additionally, it seemed that boys were more likely to suffer from RSV pneumonia with a male to female ratio of 3.25. Comparisons between RSV pneumonia group and normal control group: RSV pneumonia group had lower IL-2 (median levels, pg/ml: 3.8 vs. 5.1, P < 0.01), and higher IL-4 (median levels, pg/ml: 3.2 vs. 2.4, P < 0.01), IL-10 (median levels, pg/ml: 12.2 vs.
TABLE I. Serum Cytokine Levels, IgE and Eosinophil in the Control Group and Patients With RSV Pneumonia Parameters IL-2 (pg/ml) IL-4 (pg/ml) IL-6 (pg/ml) IL-10 (pg/ml) TNF-a (pg/ml) INF-g (pg/ml) IgE (mg/l) Eosnophils (109)
Respiratory syncytial virus (n ¼ 204) 3.8 3.2 18.3 12.2 3.4 13.4 48.1 0.15
(1.5 ! 7.0) (1.4 ! 7.4) (1.4 ! 244.4) (1.7 ! 78.6) (1.0 ! 24.4) (2.4 ! 74.8) (4.3 ! 5790.0) (0.01 ! 0.64)
Normal control (n ¼ 100) 5.1 2.4 4.3 2.3 2.1 4.6 8.8 0.11
(2.7 ! 7.2) (1.1 ! 2.9) (1.2 ! 8.5) (1.3 ! 3.4) (1.3 ! 2.7) (3.3 ! 7.8) (4.3 ! 26.4) (0.05 ! 0.25)
P value
