Introduction
Respiratory syncytial virus (RSV), parainfluenza virus (PIV), and human metapneumovirus
(HMPV) are enveloped, nonsegmented, negative-sense, single-stranded RNA viruses belonging to the
Paramyxoviridae family
. These viruses are a significant cause of morbidity and mortality globally, especially among children in developing countries [
1‐
7]. RSV is the most important pathogenic infection of childhood worldwide, causing a variety of manifestations from mild upper respiratory tract illnesses or otitis media to severe and potentially life-threatening lower respiratory tract illnesses [
6,
8‐
11]. Four PIV types (PIV1–4) have been identified [
12,
13]. PIV1 and PIV2 are best known as the cause of croup whereas PIV3 is a common cause of bronchiolitis and pneumonia [
7]. PIV4 infection has low prevalence [
13]. HMPV was first discovered in patients with acute respiratory illness (ARI) in 2001 [
14]. Since then, HMPV has been associated with ARI in children as well as elderly and immunocompromised adults [
15‐
17]. RSV, PIV, and HMPV are also important causes of nosocomial infection, which might be life-threatening in certain individuals, such as transplant or immunocompromised patients [
18‐
25]. Until now, no effective vaccine for RSV has been available. The RSV-specific monoclonal antibody palivizumab has been advocated for use as prophylaxis in high-risk patients against RSV infection [
26‐
28]. However, there is no available vaccine or specific antiviral treatment for PIV and HMPV infection. Consequently, it is imperative to conduct further research, especially in low- and middle-income countries, to understand the epidemiological features of these pathogens in different areas and populations.
In general, the prevalence of viruses can vary because of factors such as geographical location, climatic conditions, population, and social activity [
29]. Guangzhou, which is located on the subtropical coast of China, has a maritime subtropical monsoon climate. Guangzhou is China’s first gateway hub to Southeast Asia and Oceania. The city is densely populated and frequent exchanges of domestic and international personnel and materials take place in the area. Guangzhou has been a hotbed of activity for various respiratory pathogens. Investigation of respiratory pathogen epidemics in the region is critical.
In this study, we analyzed paramyxovirus infection among children hospitalized with ARI over a 7-year period in Guangzhou, and we collected local meteorological data for climate correlation analysis. These data will be helpful for the prevention and control of these viruses.
Discussion
ARI is one of the most common human diseases resulting in high mortality and mobility, and it is predominantly caused by respiratory viruses [
31,
32]. Paramyxoviruses, including RSV, PIV, and HMPV, are the most important respiratory viruses in patients with ARI all over the world, especially among children under 5 years old [
33,
34]. These viruses are also an important cause of nosocomial infection [
18‐
25]. Currently, no effective vaccines or drugs have been developed against these viruses, except palivizumab for RSV prophylaxis [
18]. Thus, additional research must be carried out. In the present study, we sought to analyze the features of paramyxovirus infection and correlation with meteorological conditions in a subtropical region of southern China, by collecting respiratory samples from pediatric patients (≤ 14 years old) hospitalized with ARI in Guangzhou and testing for RSV, PIV, HMPV, and other common respiratory pathogens. Meteorological data were also collected between July 2009 and June 2016, for further correlation analysis. The goal of the study was to reveal information that could be useful in the prevention and control of these viruses.
The median age of the 11,398 enrolled pediatric patients was 1.8 years (IQR, 0.8–3.8), indicating the high public health burden among infants and young children, as previously reported [
33,
34]. Nearly half of all patients had positive test results for one or more of the pathogens of interest; moreover, all pathogens in the panel were detected, indicating the complexity and diversity of ARI etiology (Table
1). Higher pathogen prevalence was found among male patients than female ones (
p = 0.002), similar to previous reports [
35]. RSV, infA, MP, ADV, HRV, and PIV were the six most frequently detected pathogens in this study (Fig.
1); these results are consistent with previous reports from China as well as international studies [
1,
2,
35,
36].
RSV, PIV, and HMPV are the most important respiratory viruses, causing lower respiratory illnesses among children worldwide [
4‐
6,
33]. In this study, RSV, PIV, and HMPV were the first (14.8%), sixth (4.4%), and ninth (2.8%) most frequently detected pathogens (Table
1, Fig.
1). In children with positive results for these three paramyxoviruses, the median age was highest in children who were HMPV positive and lowest for those positive for RSV. RSV mostly affected children under 2 years old, and the prevalence decreased with age (
p < 0.001). PIV showed peak prevalence among patients aged 4–6 months (
p < 0.001), and there was high HMPV prevalence among patients aged 4 months to 5 years (
p < 0.001) (Fig.
2). The different age distributions of these three viruses may be helpful in determining appropriate pediatric care and disease diagnosis; however, laboratory testing is still necessary because of the complex diversity and similarities in clinical manifestations of respiratory pathogens [
1,
2,
4].
In general, the epidemiology of the main respiratory viruses in patients with ARI has been closely monitored in developed countries; however, these data are less available in developing countries, mostly because of the high cost of these studies. RSV is known to occur in well-defined, recurrent epidemics during the cold season in temperate climates [
6], with peaks occurring more often during the rainy season in tropical and subtropical areas; locations close to the equator have less consistent patterns, with some showing nearly continuous RSV activity and varying seasonal peaks [
37]. In this study, we found that RSV occurred during the change of seasons from winter to spring and from summer to autumn. This pattern is similar to those in previous reports [
38]. HMPV had a similar epidemic pattern to RSV, consistent with previous reports from other subtropical areas [
39,
40], and differed from the pattern in temperate climates, which peaks at the end of winter or in early spring [
41,
42]. In previous reports from the USA, PIV is second only to RSV as a cause of hospitalization for ARI (2–17%) among children aged younger than 5 years [
12,
43,
44]. Seasonal peaks of PIV are mostly driven by PIV-3 and PIV-1, whereas there are a small number of PIV2 and especially PIV4 infections [
45,
46]. In this study, PIV was isolated throughout the year and appeared to alternate with peaks in RSV and HMPV infection, increasing as autumn turned to winter and summer turned to autumn (Fig.
3). These results differ from previous reports of biennial PIV epidemics [
45,
47]. The different geographic location might lead to the different seasonal distribution of PIV observed in the present study.
In addition to pathogenic characteristics, pathogenic epidemics are closely related to geographic environment, local climate, social development level, population structure, ethnic characteristics, social interaction, and so forth. Guangzhou has a maritime subtropical monsoon climate, with high temperatures (mean temperature 21.8 ± 5.8 °C) and high relative humidity (77.2 ± 7.3%). Investigation of respiratory pathogen epidemics in the region is of great importance. In this study, we analyzed the correlation between the prevalence of paramyxoviruses among pediatric hospitalized patients and meteorological conditions in Guangzhou. Multiple linear regression analysis was performed with monthly RSV, PIV, and HMPV prevalence as the dependent variable and current mean temperature (or mean temperature in the preceding month), mean relative humidity, mean wind speed, and sunshine duration as the independent variables. Regression models were established for RSV, PIV, and HMPV using the current monthly temperature model (
p < 0.05) (Table
2). However, regression models using mean temperature in the preceding month model were not established. In general, the trend of associations between climate factors and respiratory pathogen activity varies with geographic location [
35,
48‐
53]. In this study, RSV and HMPV had similar seasonal distribution patterns, and both were negatively correlated with sunshine duration (Table
2, Fig.
4); this might be owing to the sensitivity of RSV and HMPV to ultraviolet light. In subtropical and temperate regions, RSV prevalence is more consistently positively correlated with lower temperatures and higher relative humidity [
48]. However, we found a negative correlation between RSV prevalence and relative humidity (
p < 0.05) (Table
2, Fig.
4), which might be owing to the high relative humidity in the Guangzhou region (monthly mean relative humidity 77.2 ± 7.3%). PIV had an alternating seasonal distribution pattern with RSV and HMPV in this study. PIV incidence was negatively correlated with relative humidity, similar to RSV; however, PIV incidence was positively correlated with mean temperature, and the absolute value of the correlation coefficient of relative humidity (|− 0.194|) was smaller than the absolute value of the correlation coefficient of temperature (|0.328|) (Table
2), which means that the effect of temperature on the distribution of PIV was greater than the relative humidity. This might explain the different distribution patterns between RSV and PIV. Overall, the established models were found to be of value for understanding the epidemic patterns of RSV, PIV, and HMPV (Fig.
4).
Some limitations of this study should be noted. First, because our study was mainly focused on the circulation of paramyxoviruses among hospitalized patients with ARI, paramyxoviruses in outpatients and the asymptomatic population were not included. Second, many factors can affect virus epidemics; meteorological data analysis alone may be insufficient to reach a final conclusive interpretation. Third, the current study was only conducted in three hospitals and may not be representative of the overall population.
In conclusion, this study provided a better understanding of paramyxoviruses infection and highlighted the correlation with climate factors, revealing the potential for modeling and risk assessment. The findings of this work will help public health authorities and clinicians to improve strategies for controlling paramyxoviruses infection.
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