Epidemiological Markers for Interactions AmongStreptococcus pneumoniae,Haemophilus influenzae, andStaphylococcus aureusin Upper Respiratory Tract Carriage

Lewnard, Joseph A; Givon-Lavi, Noga; Huppert, Amit; Pettigrew, Melinda M.; Regev‐Yochay, Gili; Dagan, Ron; Weinberger, Daniel M.

doi:10.1093/infdis/jiv761

Cited by 51 publications

(68 citation statements)

References 49 publications

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“…Several observational studies have shown that S. aureus prevalence is negatively associated with the presence of S. pneumoniae (3). Successful clearance of the S. pneumoniae from the nasopharyngeal niche by vaccination using the pneumococcal conjugate vaccine-7 (PCV-7) has been correlated with increased colonization of S. aureus (29,58) and, depending on the level of serotype replacement, in some studies also increased colonization with H. influenzae (26,27).…”

Section: Discussionmentioning

confidence: 99%

“…There is a growing literature that supports the model that, in the nasopharynx, S. pneumoniae is a harmless commensal bacterium which by "competitive exclusion" inhibits colonization by other harmful potential pathogens, such as Streptococcus pyogenes and Staphylococcus aureus (26,27), that are more prevalent in children immunized with the conjugate vaccines. Although cocolonization of S. pneumoniae and Haemophilus influenzae is common, it is unclear whether the observed pneumococcal serotype replacement in the nasopharynx results in an increased bacterial burden of H. influenzae (27,28) or not (26,29).…”

mentioning

confidence: 99%

“…Although cocolonization of S. pneumoniae and Haemophilus influenzae is common, it is unclear whether the observed pneumococcal serotype replacement in the nasopharynx results in an increased bacterial burden of H. influenzae (27,28) or not (26,29). Niche exclusion has been described in other systems.…”

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confidence: 99%

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Novel Strategy To Protect against Influenza Virus-Induced Pneumococcal Disease without Interfering with Commensal Colonization

Greene

Marks

et al. 2016

Infect Immun

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dStreptococcus pneumoniae commonly inhabits the nasopharynx as a member of the commensal biofilm. Infection with respiratory viruses, such as influenza A virus, induces commensal S. pneumoniae to disseminate beyond the nasopharynx and to elicit severe infections of the middle ears, lungs, and blood that are associated with high rates of morbidity and mortality. Current preventive strategies, including the polysaccharide conjugate vaccines, aim to eliminate asymptomatic carriage with vaccinetype pneumococci. However, this has resulted in serotype replacement with, so far, less fit pneumococcal strains, which has changed the nasopharyngeal flora, opening the niche for entry of other virulent pathogens (e.g., Streptococcus pyogenes, Staphylococcus aureus, and potentially Haemophilus influenzae). The long-term effects of these changes are unknown. Here, we present an attractive, alternative preventive approach where we subvert virus-induced pneumococcal disease without interfering with commensal colonization, thus specifically targeting disease-causing organisms. In that regard, pneumococcal surface protein A (PspA), a major surface protein of pneumococci, is a promising vaccine target. Intradermal (i.d.) immunization of mice with recombinant PspA in combination with LT-IIb(T13I), a novel i.d. adjuvant of the type II heat-labile enterotoxin family, elicited strong systemic PspA-specific IgG responses without inducing mucosal anti-PspA IgA responses. This response protected mice from otitis media, pneumonia, and septicemia and averted the cytokine storm associated with septic infection but had no effect on asymptomatic colonization. Our results firmly demonstrated that this immunization strategy against virally induced pneumococcal disease can be conferred without disturbing the desirable preexisting commensal colonization of the nasopharynx.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Novel Strategy To Protect against Influenza Virus-Induced Pneumococcal Disease without Interfering with Commensal Colonization

Greene

Marks

et al. 2016

Infect Immun

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“…The study enrolled healthy children aged 2-30 months from the local Jewish (n = 400) and Bedouin (n = 369) populations. The Bedouin population is transitioning from nomadic lifestyles to permanent settlements and has a lower socioeconomic status, larger family sizes, and higher pneumococcal and NTHi carriage and disease rates than the Jewish population despite access to the same medical care [5,8,19,20].…”

Section: Carriage Datamentioning

confidence: 99%

“…Among healthy children, the 2 species appear together in carriage more often than would be expected by chance [6], and cocolonization is associated with higher-density bacterial carriage for both species [7]. These associations cannot be explained by conventional risk factors for carriage, such as age, season, antibiotic receipt, and daycare attendance [8], suggesting that bacterial characteristics or host-immune factors mediate interspecies interaction [9]. Facilitative interactions between species occur in biofilms during OM [10] and may also explain the tendency of different species to occur together in upper respiratory tract carriage.…”

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confidence: 98%

Density, Serotype Diversity, and Fitness ofStreptococcus pneumoniaein Upper Respiratory Tract Cocolonization With NontypeableHaemophilus influenzae

et al. 2016

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Background. Coinfections by Streptococcus pneumoniae and nontypeable Haemophilus influenzae (NTHi) are frequently implicated in complex otitis media. Whereas upper respiratory tract carriage precedes disease for both pathogens, interactions between species in cocolonized hosts are poorly understood. We compared colonization densities and the diversity and fitness of pneumococcal serotypes in single-species and mixed-species colonization.Methods. We analyzed nasopharyngeal pneumococcal carriage and nasopharyngeal and oropharyngeal NTHi carriage in 13 541 samples collected over 6909 study visits from 769 children 2-30 months old in a 7-valent pneumococcal conjugate vaccine dosing trial. We measured density associations between the species and compared pneumococcal serotype diversity during and in the absence of NTHi colonization. We used logistic regression to quantify associations between NTHi colonization and previously published pneumococcal serotype factors related to fitness.Results. Densities of the 2 species were positively associated when they co-occur in the nasopharynx. NTHi colonization was associated with reduced pneumococcal serotype diversity among children 2-18 months old and was more prevalent among children carrying pneumococcal serotypes with greater capsular thickness, neutrophil resistance, and metabolic efficiency.Conclusions. Pneumococcal-NTHi cocolonization is associated with an elevated density of both species and with reduced diversity and increased fitness of pneumococcal serotypes. NTHi colonization may create a selective environment favoring pneumococci with immune-evasive phenotypes.

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Nasal swab bacteriology by PCR during the first 24‐months of life: A prospective birth cohort study

Palmu

Ware

Lambert

et al. 2019

Pediatric Pulmonology

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Background Most respiratory bacterial carriage studies in children are based on cross‐sectional samples or longitudinal studies with infrequent sampling points. The prospective Observational Research in Childhood Infectious Diseases birth cohort study intensively evaluated the community‐based epidemiology of respiratory viruses and bacteria during the first 2‐years of life. Here we report the bacteriologic findings. Methods Pregnant women in Brisbane, Australia were recruited between September 2010 and October 2012, and their healthy newborn children were followed for the first 2‐years of life. Parents kept a daily symptom diary for the study child, collected a weekly anterior nose swab and completed an illness burden diary when their child met pre‐defined illness criteria. Specimens were tested for respiratory bacteria by real‐time polymerase chain reaction (PCR) assays and those containing human genomic DNA, deemed as high‐quality, were analyzed. Results Altogether 8100 high‐quality nasal swab specimens from 158 enrolled children were analyzed. Streptococcus pneumoniae, Moraxella catarrhalis, and Haemophilus influenzae were detected in 42.4%, 38.9%, and 14.8% of these samples, respectively. Concomitant detection of bacteria was common. In contrast, Bordetella pertussis, B. parapertussis, Mycoplasma pneumoniae, Chlamydia pneumoniae, and Simkania negevensis were rarely identified. The prevalence of the three major bacteria was higher with increasing age and in the winter and spring months. Siblings and childcare attendance were the other risk factors identified. Conclusions We confirmed the feasibility of frequent nasal swabbing by parents for studying bacterial colonization. PCR detected the major respiratory tract bacteria with expected high frequencies, but atypical bacteria were found rarely in this cohort.

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Epidemiological Markers for Interactions AmongStreptococcus pneumoniae,Haemophilus influenzae, andStaphylococcus aureusin Upper Respiratory Tract Carriage

Cited by 51 publications

References 49 publications

Novel Strategy To Protect against Influenza Virus-Induced Pneumococcal Disease without Interfering with Commensal Colonization

Novel Strategy To Protect against Influenza Virus-Induced Pneumococcal Disease without Interfering with Commensal Colonization

Density, Serotype Diversity, and Fitness ofStreptococcus pneumoniaein Upper Respiratory Tract Cocolonization With NontypeableHaemophilus influenzae

Nasal swab bacteriology by PCR during the first 24‐months of life: A prospective birth cohort study

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