Experimental Human Pneumococcal Colonization in Older Adults Is Feasible and Safe, Not Immunogenic.

Rationale: Pneumococcal colonization is key to the pathogenesis of invasive disease but is also immunogenic in young adults, protecting against recolonization. Colonization is rarely detected in older adults, despite high rates of pneumococcal disease.Objectives: To establish experimental human pneumococcal colonization in healthy adults aged 50-84 years, to measure the immune response to pneumococcal challenge, and to assess the protective effect of prior colonization against autologous strain rechallenge.Methods: Sixty-four participants were inoculated with Streptococcus pneumoniae (serotype 6B; 80,000 cfu in each nostril). Colonization was determined by bacterial culture of nasal wash, and humoral immune responses were assessed by anticapsular and antiprotein IgG concentrations.Measurements and Main Results: Experimental colonization was established in 39% of participants (25/64) with no adverse events. Colonization occurred in 47% (9/19) of participants aged 50-59 compared with 21% (3/14) in those aged ≥70 years. Previous pneumococcal polysaccharide vaccination did not protect against colonization. Colonization did not confer serotype-specific immune boosting, with a geometric mean titer (95% confidence interval) of 2.7 µg/ml (1.9-3.8) before the challenge versus 3.0 (1.9-4.7) 4 weeks after colonization (P = 0.53). Furthermore, pneumococcal challenge without colonization led to a drop in specific antibody concentrations from 2.8 µg/ml (2.0-3.9) to 2.2 µg/ml (1.6-3.0) after the challenge (P = 0.006). Antiprotein antibody concentrations increased after successful colonization. Rechallenge with the same strain after a median of 8.5 months (interquartile range, 6.7-10.1) led to recolonization in 5/16 (31%).Conclusions: In older adults, experimental pneumococcal colonization is feasible and safe but demonstrates different immunological outcomes compared with younger adults in previous studies.

Innate and adaptive nasal mucosal immune responses following experimental human pneumococcal colonization.

Streptococcus pneumoniae (Spn) is a common cause of respiratory infection, but also frequently colonizes the nasopharynx in the absence of disease. We used mass cytometry to study immune cells from nasal biopsy samples collected following experimental human pneumococcal challenge in order to identify immunological mechanisms of control of Spn colonization. Using 37 markers, we characterized 293 nasal immune cell clusters, of which 7 were associated with Spn colonization. B cell and CD8+CD161+ T cell clusters were significantly lower in colonized than in non-colonized subjects. By following a second cohort before and after pneumococcal challenge we observed that B cells were depleted from the nasal mucosa upon Spn colonization. This associated with an expansion of Spn polysaccharide-specific and total plasmablasts in blood. Moreover, increased responses of blood mucosal associated invariant T (MAIT) cells against in vitro stimulation with pneumococcus prior to challenge associated with protection against establishment of Spn colonization and with increased mucosal MAIT cell populations. These results implicate MAIT cells in the protection against pneumococcal colonization and demonstrate that colonization affects mucosal and circulating B cell populations.

Innate and adaptive nasal mucosal immune responses following experimental human pneumococcal colonization

Streptococcus pneumoniae (Spn) is a common cause of respiratory infection, but also frequently colonizes the nasopharynx in the absence of disease. We used mass cytometry to study immune cells from nasal biopsy samples collected following experimental human pneumococcal challenge in order to identify immunological mechanisms of control of Spn colonization. Using 37 markers, we characterized 293 nasal immune cell clusters, of which 7 were associated with Spn colonization. B cell and CD161+CD8+ T cell clusters were significantly lower in colonized than in noncolonized subjects. By following a second cohort before and after pneumococcal challenge we observed that B cells were depleted from the nasal mucosa upon Spn colonization. This associated with an expansion of Spn polysaccharide–specific and total plasmablasts in blood. Moreover, increased responses of blood mucosa-associated invariant T (MAIT) cells against in vitro stimulation with pneumococcus prior to challenge associated with protection against establishment of Spn colonization and with increased mucosal MAIT cell populations. These results implicate MAIT cells in the protection against pneumococcal colonization and demonstrate that colonization affects mucosal and circulating B cell populations.

Innate and adaptive nasal mucosal immune responses following experimental human pneumococcal colonization

Streptococcus pneumoniae (Spn) is a common cause of respiratory infection, but also frequently colonizes the nasopharynx in the absence of disease. We used mass cytometry to study immune cells from nasal biopsy samples collected following experimental human pneumococcal challenge in order to identify immunological mechanisms of control of Spn colonization. Using 37 markers, we characterized 293 nasal immune cell clusters, of which 7 were associated with Spn colonization. B cell and CD161+CD8+ T cell clusters were significantly lower in colonized than in noncolonized subjects. By following a second cohort before and after pneumococcal challenge we observed that B cells were depleted from the nasal mucosa upon Spn colonization. This associated with an expansion of Spn polysaccharide–specific and total plasmablasts in blood. Moreover, increased responses of blood mucosa-associated invariant T (MAIT) cells against in vitro stimulation with pneumococcus prior to challenge associated with protection against establishment of Spn colonization and with increased mucosal MAIT cell populations. These results implicate MAIT cells in the protection against pneumococcal colonization and demonstrate that colonization affects mucosal and circulating B cell populations.

Evaluating the use of Floseal haemostatic matrix in the treatment of epistaxis: a prospective, control-matched longitudinal study.

Epistaxis is a common cause of emergency admissions in ENT. The use of Floseal haemostatic matrix in the treatment of epistaxis has been investigated in a number of studies in North America. We aimed to report a UK-based experience in the context of the current UK management paradigm. The study was designed as a prospective, unrandomised, control-matched longitudinal study. Cases were matched to controls in order to reduce the risk of bias. The overall treatment success rate for Floseal was 75 %, similar to the rates reported by studies based in North America. Nasal packing carried a success rate of 85 % and there was no statistically significant difference between the success rates of both treatments. Anecdotally Floseal can also be used successfully in thrombocyctopenic patients. There was a trend towards a shorter length of stay in the Floseal group, but this was not statistically significant. The 7-day readmission rate was 10 % for both the groups. This controlled study demonstrates that Floseal has a similar treatment success rate to nasal packing and that there may be a trend towards a shorter length of stay.

Treatment outcomes of midfacial segment pain: experience from the Liverpool multi-disciplinary team facial pain clinic.

OBJECTIVES: Midfacial segment pain (MSP) has the characteristics of tension-type headache which is confined to the midface cor- responding to the second division of the trigeminal nerve. This review presents treatment outcomes of MSP patients managed at the Multi-disciplinary Team (MDT) Facial Pain Clinic in Liverpool. METHODOLOGY: Prospective clinical outcome performed in a tertiary referral centre for complex facial pain syndromes. MAIN OUTCOME MEASURES: Sino-Nasal Outcome Test (SNOT). Clinical "success" was defined as an improvement in total SNOT score of >9 points and a reduction of the ear-facial symptoms sub-domain score by ≥50% from baseline. RESULTS: The average age of the cohort was 49 years, with an average follow-up of 12 months. The overall pre-treatment total SNOT-22 score was 59.5 which improved significantly to 42 at latest follow-up. Although the average scores of all sub-domains improved, only the ear-facial symptoms and psychological issues sub-domains achieved statistical significance. When the criterion for success was applied, nine patients fulfilled this definition at an average of 12 months follow-up. The baseline total SNOT score in this cohort improved from 60.6 to 19.7. Half of these patients achieved success within 18 months of commencing treatment and the probability of attaining success at long-term follow-up was high. CONCLUSIONS: Treatment of midfacial segment facial pain is complex and requires follow-up to achieve any meaningful clinical outcome.