Abstract
Colonization of the nasopharynx by Streptococcus pneumoniae is a necessary precursor to pneumococcal diseases that result in morbidity and mortality worldwide. The nasopharynx is also host to other bacterial species, including the common pathogens Staphylococcus aureus, Haemophilus influenzae, and Moraxella catarrhalis. To better understand how these bacteria change in relation to pneumococcal colonization, we used species-specific quantitative PCR to examine bacterial densities in 52 subjects 7 days before, and 2, 7, and 14 days after controlled inoculation of healthy human adults with S. pneumoniae serotype 6B. Overall, 33 (63%) of subjects carried S. pneumoniae post-inoculation. The baseline presence and density of S. aureus, H. influenzae, and M. catarrhalis were not statistically associated with likelihood of successful pneumococcal colonization at this study’s sample size, although a lower rate of pneumococcal colonization in the presence of S. aureus (7/14) was seen compared to that in the presence of H. influenzae (12/16). Among subjects colonized with pneumococci, the number also carrying either H. influenzae or S. aureus fell during the study and at 14 days post-inoculation, the proportion carrying S. aureus was significantly lower among those who were colonized with S. pneumoniae (p = 0.008) compared to non-colonized subjects. These data on bacterial associations are the first to be reported surrounding experimental human pneumococcal colonization and show that co-colonizing effects are likely subtle rather than absolute.
Highlights
Streptococcus pneumoniae is a resident of the human nasopharynx as well as an important pathogen responsible for 1.3 million deaths in children under 5 annually [1]
To assess whether carriage of Haemophilus influenzae (Hi), Staphylococcus aureus (Sa), or Moraxella catarrhalis (Mc) was associated with likelihood of S. pneumoniae (Sp) colonization post-inoculation, we examined carriage as both a binary variable and a continuous variable
Serotype 6B is a clinically important serotype of S. pneumoniae; a recent metaanalysis found that pneumonia patients infected with 6B were at an increased risk of death [24]
Summary
Streptococcus pneumoniae (commonly called the pneumococcus) is a resident of the human nasopharynx as well as an important pathogen responsible for 1.3 million deaths in children under 5 annually [1]. S. pneumoniae (Sp) shares the nasopharyngeal niche with other bacterial species including the pathogens Staphylococcus aureus (Sa), Haemophilus influenzae (Hi) and Moraxella catarrhalis (Mc). With the introduction of pneumococcal conjugate vaccines (PCV) worldwide, the relationship between nasopharyngeal carriage of Sp and other bacterial pathogens is of special interest. Cross-sectional studies have demonstrated an inverse association between carriage of S. aureus and vaccine-type S. pneumoniae [3,4,5] and studies of PCV introduction have found increased prevalence of S. aureus carriage following PCV roll-out [6,7,8]. Other cross-sectional studies have found positive correlations between Sp and Hi [5,9,10], and between Sp and Mc [11,12,13], while a longitudinal study by Spijkerman et al found that the prevalence of Hi increased 3 and 4.5 years after PCV-7 administration but the prevalence of Mc remained unchanged [8]. No study to date has examined the ecological effect of controlled inoculation with Sp on other bacterial residents of the nasopharynx
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