The primary pathogens causing CAP among children encompass a diverse range of typical bacteria, atypical bacteria, and viruses, as supported by previous studies [15–17]. Understanding the aetiology of CAP is crucial for effective diagnosis, treatment, and prevention strategies. In our particular study, we aimed to shed light on the prevalence and patterns of pathogen involvement in paediatric CAP cases. Remarkably, our findings revealed a high prevalence rate of pathogen detection by PCR in 97% of patients. This emphasises the potential impact of these pathogens on the occurrence of CAP in the community.
What makes our study particularly intriguing is the discovery that a substantial proportion of patients, approximately 87%, exhibited co-infections with multiple pathogens. This suggests a complex interplay between different agents, potentially contributing to the severity and complexity of the disease. In some cases, we observed up to eight different pathogens coexisting within a single patient, suggesting the multifactorial nature of CAP. These co-infections involving multiple pathogens raise important questions about the mechanisms underlying their simultaneous presence and the potential synergistic effects they may have on disease progression [16, 18]. Similarly, in a prospective descriptive study conducted among 141 Chinese children with severe CAP [19], the authors showed that 92.2% of patients were positive for at least one pathogen by RT-PCR. In addition, 47.7% of patients were co-infected. The five most frequent bacteria species detected by PCR among children with pneumonia were H. influenzae, S. pneumoniae, Methicillin-resistant S. aureus, M. catarrhalis and M. pneumoniae [19, 20]. Further research is needed to unravel the intricate interactions between these pathogens and their role in shaping the clinical presentation and outcomes of paediatric CAP. Notably, studies involving healthy control patients might help to assess the role of pathogens in CAP symptoms. Moreover, identifying specific pathogens which are responsible for CAP in children is vital for appropriate and targeted treatment. Our study contributes to the growing body of evidence supporting the need for comprehensive diagnostic approaches that can detect multiple pathogens simultaneously. This is particularly important in cases of co-infections, where the use of broad-spectrum antibiotics alone may not be sufficient to effectively combat the diverse array of pathogens involved [2].
Among the viral pathogens detected, human rhinovirus accounted for the highest incidence at 46%. This finding highlights the substantial role played by rhinovirus in paediatric CAP cases. Additionally, respiratory syncytial virus (RSV) was responsible for 24% of the cases, making it another prominent viral pathogen associated with CAP in children. The study also identified human enterovirus (17%) and human parainfluenza viruses (17%) as significant contributors to the burden of disease. Understanding the viral aetiology of CAP in children is crucial for accurate diagnosis, appropriate management, and the development of effective preventive measures [2]. Indeed, these are viral agents for which there is no pharmaceutical prevention or specific treatment. Therefore, community infection prevention and monitoring of CAP patients caused by viruses is very important when it comes to reducing the burden of disease as well as the rate of inappropriate antibiotic use. The overuse of antibiotics in children with pneumonia has been reported not only in Thai Binh, Vietnam, but also in many other places around the world, especially in low-income countries.
In terms of bacterial pathogens, H. influenzae, S. pneumoniae and M. catarrhalis were the most frequently isolated. This finding aligns perfectly with previous research, which has consistently emphasised the significant role of these bacteria as causative agents of paediatric CAP [19, 20]. The presence of these three bacterial pathogens underscores the complex microbial landscape involved in paediatric CAP. It is worth noting that while these bacteria accounted for a substantial proportion of cases, other pathogens, including viruses and atypical bacteria, may also contribute to the development of CAP in children [7]. Continued research efforts are essential to further comprehend the epidemiology, pathogenesis, and antibiotic susceptibility patterns of these bacterial pathogens in paediatric CAP. Understanding the prevalence and distribution of these bacteria, as well as the associated risk factors for the severity of disease and clinical outcomes will aid in the development of targeted prevention strategies, appropriate diagnostic approaches, and effective treatment regimens [21].
Regarding risk factors for severe pneumonia among children, our study found that the presence of smokers in the family, CRP level ≥ 50 mg/dL, respiratory syncytial virus, and H. influenzae were associated with a risk of severe disease.
Previous studies have consistently shown that children exposed to household smoke are more vulnerable to respiratory infections, including pneumonia, compared to those living in smoke-free environments [3, 22]. The link between household smoking and severe pneumonia in children has been quantified through various epidemiological studies. One such study, conducted on a large scale, revealed that the odds of severe pneumonia occurring in children exposed to household smoke were doubled compared to those from smoke-free homes [22]. Indeed, children admitted to the hospital for CAP from households where there were two or more smokers experienced an extended duration of hospitalisation and demonstrated a higher likelihood of needing intensive care, as compared to children from smoke-free households [22]. This finding underscores the detrimental impact of passive smoke on the respiratory health of children, highlighting the urgent need for effective tobacco control measures to protect vulnerable individuals.
Several studies have demonstrated a strong association between an increase in CRP levels and the risk of severe pneumonia in children, as shown in one meta-analysis [23]. Elevated CRP levels in pneumonia patients often indicate a more aggressive inflammatory response and a higher burden of infection. These children are more likely to experience severe respiratory distress, hypoxia, and other life-threatening complications. In previous studies, patients with high CRP levels were at a significantly higher risk of developing severe pneumonia, requiring admission to the intensive care unit (ICU), and experiencing longer hospital stays [24, 25]. Another study by Masarweh et al. reported that elevated CRP levels were associated with a higher likelihood of developing pleural effusion, empyema, or necrotising pneumonia, all of which are indicators of severe disease [26].
RSV is known as a leading cause of lower respiratory tract infections in infants and young children [27]. RSV infection can range from mild respiratory symptoms to severe pneumonia, especially in vulnerable populations. Several studies have established a strong correlation between RSV infection and the increased severity of pneumonia in children. RSV-associated pneumonia often presents with rapid progression, increased respiratory distress, and a higher risk of complications, including the need for hospitalisation and intensive care [27].
H. influenzae is a bacterial pathogen that commonly colonises children’s respiratory tracts. However, certain strains can cause invasive diseases such as pneumonia [28]. H. influenzae type B pneumonia is characterised by rapid onset, high fever, respiratory distress, and an increased likelihood of complications [28]. Timely diagnosis and treatment is essential to minimise the morbidity and mortality associated with H. influenzae-induced pneumonia. Several factors contribute towards the increased risk of severe pneumonia associated with H. influenzae infection [29]. Firstly, H. influenzae possesses various virulence factors that facilitate its colonisation and invasion of the respiratory tract. Secondly, children, especially those with underlying conditions or weakened immune systems, are particularly susceptible to H. influenzae pneumonia. Children attending day-care centres, living in crowded environments, or exposed to passive smoking are at higher risk of acquiring H. influenzae infections due to their increased exposure to respiratory secretions and compromised respiratory defences [30].
Despite our efforts, this study has some limitations. Although RTIs cover a broad spectrum of diseases and severities, outpatients were not enrolled in this study. Consequently, the results are only representative of hospitalised patients. The study was conducted in a single hospital over a short period of time. The results only present a snapshot of aetiologies of hospital CAP in Vietnamese children. The highly sensitive nature of RT-PCR makes it possible to detect the remaining material of dead pathogens together with active pathogens. Some patients may have infections with viruses or bacteria which were not included in our study (including measles) or with pathogens yet to be discovered. The pathogens found in the nasopharyngeal provide only indirect proof of the aetiologies of pneumonia and the detection of some pathogens by PCR might indicate respiratory carriage that does not necessarily account for the symptoms. However, a recent study showed a concordance in pathogen identification in the upper and lower respiratory tracts of children with pneumonia [19]. Another limitation of our study is the lack of a control group to assess the magnitude of healthy carriage of viruses and bacteria. Finally, due to responses to the second, third, and fourth waves of the COVID-19 pandemic in Vietnam, lockdowns and restriction measures were executed, which made it complicated to include patients and potentially affected the epidemiology of RTIs in Vietnam.