The Nasopharyngeal Microbiota of Children With Respiratory Infections in Botswana

Abstract

Background Nearly half of child pneumonia deaths occur in sub-Saharan Africa. Microbial communities in the nasopharynx are a reservoir for pneumonia pathogens and remain poorly described in African children. Methods Nasopharyngeal swabs were collected from children with pneumonia (N=204), children with upper respiratory infection symptoms (N=55), and healthy children (N=60) in Botswana between April 2012 and April 2014. We sequenced the V3 region of the bacterial 16S ribosomal RNA gene and used partitioning around medoids to cluster samples into microbiota biotypes. We then used multivariable logistic regression to examine whether microbiota biotypes were associated with pneumonia and upper respiratory infection symptoms. Results Mean ages of children with pneumonia, children with upper respiratory infection symptoms, and healthy children were 8.2, 11.4, and 8.0 months, respectively. Clustering of nasopharyngeal microbiota identified five distinct biotypes: Corynebacterium/Dolosigranulum-dominant (23%), Haemophilus-dominant (11%), Moraxella-dominant (24%), Staphylococcus-dominant (13%), and Streptococcus-dominant (28%). The Haemophilus-dominant [odds ratio (OR): 13.55, 95% confidence interval (CI): 2.10–87.26], the Staphylococcus-dominant (OR: 8.27, 95% CI: 2.13–32.14), and the Streptococcus-dominant (OR: 39.97, 95% CI: 6.63–241.00) biotypes were associated with pneumonia. The Moraxella-dominant (OR: 3.71, 95% CI: 1.09–12.64) and Streptococcus-dominant (OR: 12.26, 95% CI: 1.81–83.06) biotypes were associated with upper respiratory infection symptoms. In children with pneumonia, HIV infection was associated with a lower relative abundance of Dolosigranulum (P=0.03). Conclusions Pneumonia and upper respiratory infection symptoms are associated with distinct nasopharyngeal microbiota biotypes in African children. A lower abundance of the commensal genus Dolosigranulum may contribute to the higher pneumonia risk of HIV-infected children.

Microbiome characteristics of induced sputum compared to bronchial fluid and upper airway samples

“…Recent work has given insight into the relationship between airway microbiota in the upper airways of children with acute infection, with results which differ from the present study. For example, there is evidence that in the context of acute upper and lower respiratory tract infection, different bacterial species predominate in the nasopharynx (eg, Proteobacteria and Firmicutes which contrast with Actinobacteria and Fusobacteria in our study) . The characteristics of the nasopharyngeal microbiota also change during the course of acute otitis media infection …”

“…We compared community structures and diversity across patient cohorts to determine if inter‐cohort differences in structure were seen. To achieve this a rarefaction sampling analysis was carried out using a standard methodology . In order to minimize the risk for contamination, we sought to identify a high (ie, conservative) number of sequences required to characterize bacteria from the samples.…”

Early nasal microbiota and acute respiratory infections during the first years of life

“…The Australian study found that Moraxella enrichment at the time of ARI was significantly associated with higher risks of LRTI 11. In contrast, in case-control studies, Moraxella -dominant airway microbiota has been found to be associated with lower risks of severe bronchiolitis8 and RSV hospitalisation,12 and not to be associated with pneumonia in children 13. However, in these studies, the nasal microbiota was investigated at the time of severe infection (with possible dysbiosis), which may explain the difference in results.…”

Interaction between the nasal microbiota and S. pneumoniae in the context of live-attenuated influenza vaccine

“…Previous studies have focussed on the interactions between different respiratory pathogens only, largely disregarding the ecological background these bacteria are embedded in 17 . More recently, next-generation sequencing-based studies have emerged, describing associations between pneumococcal presence and density and the local microbiota [18][19][20] . For example, it has repeatedly been demonstrated that Corynebacterium and Dolosigranulum spp.…”