Viral aetiology of bronchiolitis in hospitalised children in Qatar

Bronchiolitis is considered one of the earliest and most common causes of hospitalisation among young children during their first 2 years of life [1]. Although the causative agents include bacteria, fungi and viruses, this acute infection is mainly attributed to respiratory syncytial virus, accounting for 50–90% of the cases [2, 3]. With the current utilisation of reverse transcriptase real-time polymerase chain reaction (PCR), the detection of specific viral nucleic acids facilitated a better understanding of the viral aetiology of the infection. The 2014 American Academy of Paediatrics bronchiolitis guideline recommends against the routine use of radiographic or laboratory studies on the basis that knowing the infecting pathogen would rarely alter the clinical management [4]. However, a growing body of literature has identified an association between specific infecting pathogens with short and long-term outcomes [5]. Association between viral co-infection and disease severity have been assessed in several studies but with conflicting findings [5‐7]. Although bronchiolitis is a self-limiting condition, hospitalisation rate has increased during the last two decades [3]. Assessment of bronchiolitis severity, through a combination of clinical symptoms and physical signs, remains a standard measure in daily practice though its impact on clinical outcomes, such as length of hospital stay, has yet to be confirmed. Data has been reported on seasonal variation of viral activity with conflicting evidence on its significance on disease severity and clinical outcomes [8, 9]. In Qatar, viral aetiology of bronchiolitis in children has been limited. Therefore the aims of this retrospective, descriptive study were: to determine the frequency and seasonal trends of viral pathogens causing acute bronchiolitis, and to explore the association between specific viral pathogens, disease severity and length of stay (LOS).

To our knowledge this is the first comprehensive report on viral aetiology in hospitalised children with bronchiolitis in the State of Qatar. Our study revealed that RSV and RV were the most commonly detected causative agents. This finding is in contrast to a previous report with a small sample size of 56 children with respiratory tract infection (RTI) in Qatar in which hMPV was the most frequently isolated virus [10]. Our findings are, however, in line with a number of large studies conducted in the Middle East and elsewhere [11‐14]. In Jordanian children of less than 2 years of age, RSV was a major cause of hospitalisation [11]. Other studies conducted in Saudi Arabia and Turkey reported the same [15, 16].

Geographic variations in seasonal activity of the most commonly detected respiratory viruses have been reported in the literature. In temperate countries, RSV peaks during the winter season, but with variation in the tropics. This diversity is mainly attributed to the region’s climate characteristics, i.e. relative humidity, average monthly temperature and rainfall [17‐19]. In their study, Haynes et al. assessed RSV seasonality in seven countries with diverse climate characteristics and found that RSV onset and peak timings were inconsistent with climate characteristics in all assessed countries apart from Thailand. RSV offset was found to be consistent in Guatemala [20]. Rhinovirus A was detected all year around with high proportion by the onset of summer in Japan but during the fall and spring in Cyprus while Rhinovirus C was mainly detected in the winter but during the fall and spring in Japan and Cyprus, respectively [18, 21].

In this study, RSV exhibited a strong seasonal pattern with peak activity during the fall and summer months, in contrast to RV, which showed minimal circulation during the fall.

In comparison to children with RSV only infections, children infected with RSV in combination with non-RV or RV alone were more likely to have longer LOS. However, we found no significant association between single or multiple infections and disease severity or LOS. The findings are consistent with two large studies conducted in North America and Europe [13, 14], but in contrast with previous reports where RV was associated with shorter LOS [12, 22]. These discrepancies might be related to sample size, study design and variation in host risk factors.

In this study, we noted an association between individual components of the clinical severity score and bronchiolitis outcome after adjusting for clinical and demographic factors. Similar to Ricart et al., McCallum et al. and Weisgerber et al., the data indicate that, in the Qatari community, children’s clinical characteristics are more relevant than the specific infecting viruses in determining the duration of LOS and disease severity [23‐25].

Detection of the presence of multiple infections has become common in practice although its clinical impact on disease management and predicting outcomes remains unclear [26]. By using RT-PCR to quantify viral load, a number of studies have concluded that RSV genomic load is correlated with disease severity [13, 14]. Similarly, two investigational anti-RSV drugs showed promising results in reducing viral load and clinical disease severity [27, 28].

Some studies have determined severity based on a modified Wood-Downes score or the need for paediatric intensive care unit (PICU) admission [7, 23]. In this study we analysed severity based on a clinical score that allows children’s classification according to respiratory rate, oxygen saturation and physical examination, mirroring the severity of the respiratory burden.

Previous studies have reported males to be more susceptible than females to lower RTIs across different age groups [29]. In this study the percent of males with severe bronchiolitis was as twice as that to females, 70.8 vs. 29.2%. An explanation was suggested two decades ago by Gupta et al. in which the disproportionally narrower peripheral airways in the younger males could be a possible mechanism of the observed difference [30].

Childhood respiratory infection may influence the development of chronic respiratory diseases. In a cohort of 47 Swedish hospitalised infants with RSV-bronchiolitis, asthma was prevalent in 30% of the group when aged 7 years increasing to 37% at the age of 13 [31]. While Jackson et al. noted an increase in asthma risk in children with RSV associated wheezing; RV was associated with a 10-fold increase of asthma [32]. An earlier retrospective study from Qatar noted an increase in recurrent wheezing by 44% in hospitalised infants due to RSV bronchiolitis 2 years after admission compared to 12% in the control group [33]. In the current study, 63% of the admitted children had wheezing of which 51.2% had RSV associated bronchiolitis. Compared to RSV, RV associated bronchiolitis is suggested to occur in older infants, 13 versus 5 months, who present more often with atopic dermatitis and blood eosinophilia [34].

This study has potential limitations. First, it is a retrospective study at a single hospital. Another limitation is that data on concomitant bacterial infection, viral genomic load and palivizumab prophylaxis were not collected.

In summary, RSV was the most common virus identified, followed by RV with peaks during the fall and spring seasons respectively. Our data show that the clinical presentation is more related to the duration of hospital stay and disease severity than the detected viruses.

Conducting a prospective, multi site surveillance of viral bronchiolitis in the warm, desert climate of the Gulf Cooperation Council (GCC) countries will allow for proper timing of preventable measures. Future studies within the GCC countries should investigate the interplay between climate characteristics, population’s factors and the most detectable circulating viruses.