Background

Acute respiratory infections (ARIs) remain one of the most common major public health threats [1]. There were approximate 11.9 million episodes of severe acute lower respiratory infections (ALRI) resulted in hospital admissions in young children worldwide [2], and ARIs-related pneumonia was one of the leading cause of death that due to infectious disease in China (> 30,000 deaths annually) as well as globally (935,000 in 2013) [3, 4]. There were, as have been suggested, associations of several viral agents with ARIs, such as: respiratory syncytial virus (RSV), human rhinovirus (HRV), human metapneumovirus (HMPV), influenza virus (IFV), parainfluenza virus (PIV), adenovirus (ADV) and human bocavirus (BoV), accounting for about 35–87% of children with ARI [5]. Viral co-infections occurred in 4–33% of children hospitalized with ARIs, and may indicate an increasing risk for clinical outcome [6, 7]. Further, bacterial infections such as: Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus, Pseudomonas aeruginosa and Klebsiella pneumoniae, et al., were commonly observed in the later stage of diseases due to immune-compromised viral infections [8].

Similarities among ARI symptoms hampers the diagnostic and therapeutic efficacy among infected children, and inappropriate medication options may lead to the potential of viral escape mutants or bacterial resistance [8]. The composition of ARIs is geographically diverse and is largely associated with the epidemic status of each ARIs and climate conditions [9, 10]. The prevalence of ARIs varies from 14.6 to 94.3% among hospitalized children with respiratory infections in some metropolitan cities such as Bei**g, Shanghai and Shenzhen in China [11,12,13,8]. Immune status of infants is different from adults, and the amount of maternal antibodies attenuate distinctly, which would make infants susceptible to respiratory viral infections. The onset of disease is an interplay of immune pathology and viral pathology and prevention measures need to be taken into account [28].

It has been suggested that multiplex PCR techniques demonstrate a high detection rate of viral co-infections [29]. In this target population, mixed respiratory virus had a proportion of 14.9%, with RSV/PIV the most frequent combination. Previous research showed proportions of viral co-infection ranged from 4.0 to 24.7%, with RSV, IFV, HPMV the common viruses present in co-infections. Different incidence of co-infection may be due to high single infection rates of certain viruses, overlap** epidemic seasons, target pathogens as well as methodology. Evidence for increased clinical severity of viral single infections versus co-infections is controversial [30,31,32,33]. The impact of co-infection on clinical presentations may rely on the specific agent involved, as well as viral load [32, 33]. Experimental studies of simultaneous respiratory infections are scarce. However, one study showed by mathematical modeling, found that one virus can block replication of another due to competition for resources, which may have implications for the treatment regimens of simultaneous viral infections [34].

Despite vaccination, pneumonia still remains a serious public health issue in the world [35]. In this study, children > 1 year seemed to suffer more from bacterial infections than younger children. The WHO reports that pneumonia is the forgotten killer of children and one of the main disease burdens worldwide [36]. Pneumonia is the most serious result of ARIs and is often due to bacterial infection [37]. S. pneumoniae, H. influenzae type b are the leading causes of bacterial pneumonia in children worldwide [38, 39]. Under-nutrition, lack of breast-feeding, crowding, exposure to indoor air pollution, low birth weight and diarrhea have been identified as risk factors for pneumonia [40, 41]. Etiologic studies could provide information on the prevalence of bacterial infections, which may help achieve a reduction in child mortality.

The incidence of respiratory viral/bacterial co-infection in young children ranged from 1 to 44% [42]. In the current study, we observed a respiratory viral/bacterial co-infection proportion of 13.9% (240/1728). S.pneumoniae, S. aureus, H. influenzae and Pseudomonas species were common bacterial co-pathogens. Influenza pandemics over the last 100 years have strengthened the association of bacterial super-infection and influenza infection [42, 43]. There are mounting data indicating that virus infection can predispose to bacterial colonization and overgrowth, which adversely affect the pathogenesis of respiratory infections [44, 45]. Disruption of the epithelial barrier, up regulation of adhesion proteins, production of viral factors and alterations in immune responses are several known mechanisms [44, 45]. Increased morbidity with bacterial co-infections was found in children, leading to increased duration of mechanical ventilation, longer hospital stays and admission to pediatric intensive care units [42, 46]. However, the statistical association was weak and sporadic in some studies, and additional longitudinal cohort studies may be needed to reveal the contribution of bacterial to viral ARIs.

There was a paucity of study that was conducted for etiologies of ARIs among hospitalized children in this area. Including 14 different respiratory pathogens (both viruses and bacteria), recruiting almost 2000 hospitalized children, over 5-year period, this current study revealed pathogens profiles, co-infection pattern, clinical features, and seasonality among hospitalized children with ARIs in Chengdu, west China. There are however some limitations in this study. Outpatients were not recruited and the study lacked an asymptomatic control group. Positive rates may be somewhat lower as other potential viral pathogens were not included (e.g. enteroviruses, HCoV NL63 and HKU1). In addition, virus genoty** and strain identification (such as HRV A/B/C) would be helpful for understanding viral epidemics and associated disease severity.

Conclusions

In conclusion, this 5-year consecutive surveillance research confirmed that respiratory viruses, especially RSV and HRV, were the leading potential cause of ARIs in hospitalized children in Chengdu, west China. Co-infections were associated with severity of illness in infants, who tended to have increased risks of ARIs. This study gives us better information on the pathogen profiles, clinical association, co-infection combinations, and seasonal features of ARIs in hospitalized children in this area. Moreover, future efforts in reducing the impact of ARIs will depend on a commitment to fund and implement programs to utilize available vaccines, especially vaccines on RSV, HRV and S. pneumoniae in in this region, and to develop new vaccines against common pathogens.