Nasopharyngeal Codetection of Haemophilus influenzae and Streptococcus pneumoniae Shapes Respiratory Syncytial Virus Disease Outcomes in Children

Abstract

Background The role of nasopharyngeal bacteria on RSV disease has been underestimated. We measured the frequency and quantitative detection of potentially pathogenic bacteria in the upper respiratory tract of infants with RSV infection over seven respiratory seasons, and their impact on clinical outcomes. Methods Children <2 years old with mild (outpatients; n=115) or severe (inpatients; n=566) RSV infection, and matched healthy controls (n=161) were prospectively enrolled. Nasopharyngeal samples were obtained for RSV, S. pneumoniae, S. aureus, M. catarrhalis, and H. influenzae detection and quantitation by PCR. Multivariable models were constructed to identify variables predictive of severe disease. Results S. pneumoniae, H. influenzae, and M. catarrhalis, but not S. aureus, were detected more frequently in RSV-infected children (84%) than healthy controls (46%; p<0.001). Detection of S. pneumoniae and/or H. influenzae was associated with fever, more frequent antibiotic treatment, worse radiologic findings, and higher neutrophil counts (p<0.01). In adjusted analyses S. pneumoniae/H. influenzae co-detection was associated with greater odds (OR; 95% CI) of hospitalization (2.25 [1.07-4.74), higher disease severity scores (1.93 [1.14-3.26]), prolonged oxygen administration (2.23 [1.01-4.91]), and longer hospitalization (2.53 [1.33-4.79]). Conclusions Nasopharyngeal co-detection of S. pneumoniae and H. influenzae in infants with RSV infection is associated with increased disease severity.

Overnutrition, Nasopharyngeal Pathogenic Bacteria and Proinflammatory Cytokines in Infants with Viral Lower Respiratory Tract Infections

“…We found that the simultaneous detection of S. pneumoniae and H. influenzae was the most frequent combination, which is in agreement with previous studies [24,25]. On the other hand, only two patients showed the simultaneous co-detection of S. pneumoniae and S. aureus, which has also been previously reported in young children with RSV infections [4]. The negative association between S. pneumoniae and S. aureus appears to be associated with immune-mediated inter-species inferences [24,26,27] and possibly by the nutritional status.…”

“…Aliquots of NPA aspirates stored at −80 °C were used to identify and quantitate four pathogenic bacteria ( Streptococcus pneumoniae , Staphylococcus aureus , Moraxella catarrhalis , and Hemophilus influenzae ) by real time (RT)-PCR with published primers [ 4 ]. Bacterial loads were measured in copies/mL and log 10 transformed for analyses.…”

“…The upper respiratory tract is colonized with different microorganisms that can potentially become pathogenic and cause secondary infections. The most frequent bacterial pathogens in children’s upper respiratory tract are Streptococcus pneumoniae , Staphylococcus aureus , Hemophilus influenzae , and Moraxella catarrhalis [ 3 , 4 , 5 ]. In addition, respiratory viral infections have proven to favor the colonization and replication of opportunistic bacteria that can lead to secondary infections, such as otitis media or pneumonia [ 6 , 7 ].…”

“…Respiratory syncytial virus (RSV) is the foremost cause of LRTI, leading to hospitalization in infants and young children worldwide [ 8 , 9 ]. The interactions between RSV and the nasopharyngeal microbiota could modulate the host immune response, potentially affecting clinical disease severity [ 3 , 4 ]. Whether overnutrition modulates the presence of potential pathogenic bacteria and of cytokine concentrations during viral LRTI in infants and young children is not fully known.…”

The importance of viral testing in infants and young children with bronchiolitis

“… 9 Furthermore, emerging evidence indicates that bacterial superinfections involving the lower respiratory tract are not as infrequent as traditionally reported in infants with RSV infection. 10 Another point of controversy is the potential benefit of systemic corticosteroids. While multiple studies have demonstrated the lack of benefit of steroids in infants with RSV LRTI, 11 their role in bronchiolitis caused by other respiratory viruses is being recognized.…”