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Introduction: Pneumococcal colonisation is regarded as a pre-requisite for developing pneumococcal disease. In children previous studies have reported pneumococcal colonisation to be a symptomatic event and described a relationship between symptom severity/frequency and colonisation density. The evidence for this in adults is lacking in the literature. This study uses the experimental human pneumococcal challenge (EHPC) model to explore whether pneumococcal colonisation is a symptomatic event in healthy adults., Methods: Healthy participants aged 18-50 were recruited and inoculated intra-nasally with either Streptococcus pneumoniae (serotypes 6B, 23F) or saline as a control. Respiratory viral swabs were obtained prior to inoculation. Nasal and non-nasal symptoms were then assessed using a modified Likert score between 1 (no symptoms) to 7 (cannot function). The rate of symptoms reported between the two groups was compared and a correlation analysis performed., Results: Data from 54 participants were analysed. 46 were inoculated with S. pneumoniae (29 with serotype 6B, 17 with serotype 23F) and 8 received saline (control). In total, 14 became experimentally colonised (30.4%), all of which were inoculated with serotype 6B. There was no statistically significant difference in nasal (p = 0.45) or non-nasal symptoms (p = 0.28) between the inoculation group and the control group. In those who were colonised there was no direct correlation between colonisation density and symptom severity. In the 22% (12/52) who were co-colonised, with pneumococcus and respiratory viruses, there was no statistical difference in either nasal or non-nasal symptoms (virus positive p = 0.74 and virus negative p = 1.0)., Conclusion: Pneumococcal colonisation using the EHPC model is asymptomatic in healthy adults, regardless of pneumococcal density or viral co-colonisation., Competing Interests: The authors have declared that no competing interests exist.

Current diagnostic tests are ineffective for identifying the etiological pathogen in hospitalized adults with lower respiratory tract infections (LRTIs). The association of pneumococcal colonization with disease has been suggested as a means to increase the diagnostic precision. We compared the pneumococcal colonization rates and the densities of nasal pneumococcal colonization by (i) classical culture and (ii) quantitative real-time PCR (qPCR) targetinglytAin patients with LRTIs admitted to a hospital in the United Kingdom and control patients. A total of 826 patients were screened for inclusion in this prospective case-control study. Of these, 38 patients were recruited, 19 with confirmed LRTIs and 19 controls with other diagnoses. Nasal wash (NW) samples were collected at the time of recruitment. Pneumococcal colonization was detected in 1 patient with LRTI and 3 controls (P= 0.6) by classical culture. By qPCR, pneumococcal colonization was detected in 10 LRTI patients and 8 controls (P= 0.5). Antibiotic usage prior to sampling was significantly higher in the LRTI group than in the control group (19 versus 3;P< 0.001). With a clinically relevant cutoff of >8,000 copies/ml on qPCR, pneumococcal colonization was found in 3 LRTI patients and 4 controls (P> 0.05). We conclude that neither the prevalence nor the density of nasal pneumococcal colonization (by culture and qPCR) can be used as a method of microbiological diagnosis in hospitalized adults with LRTI in the United Kingdom. A community-based study recruiting patients prior to antibiotic therapy may be a useful future step., (Copyright © 2016 Collins et al.)

Rationale: New vaccines are urgently needed to protect the vulnerable from bacterial pneumonia. Clinical trials of pneumonia vaccines are slow and costly, requiring tens of thousands of patients. Studies of pneumococcal vaccine efficacy against colonization have been proposed as a novel method to down-select between vaccine candidates., Objectives: Using our safe and reproducible experimental human pneumococcal colonization model, we aimed to determine the effect of 13-valent pneumococcal conjugate vaccine (PCV) on colonization., Methods: A total of 100 healthy participants aged 18-50 years were recruited into this double-blind randomized placebo-controlled trial. They were randomly assigned to PCV (n = 49) or hepatitis A (control, n = 50) vaccination and inoculated with 80,000 CFU/100 μl of Streptococcus pneumoniae (6B) per naris., Measurements and Main Results: Participants were followed up for 21 days to determine pneumococcal colonization by culture of nasal wash. The PCV group had a significantly reduced rate of 6B colonization (10% [5 of 48]) compared with control subjects (48% [23 of 48]) (risk ratio, 0.22; confidence interval, 0.09-0.52; P < 0.001). Density of colonization was reduced in the PCV group compared with the control group following inoculation. The area under the curve (density vs. day) was significantly reduced in the PCV compared with control group (geometric mean, 259 vs. 11,183; P = 0.017)., Conclusions: PCV reduced pneumococcal colonization rate, density, and duration in healthy adults. The experimental human pneumococcal colonization model is a safe, cost-effective, and efficient method to determine the protective efficacy of new vaccines on pneumococcal colonization; PCV provides a gold standard against which to test these novel vaccines. Clinical trial registered with, Isrctn: 45340436.

Background: Many patients with pneumonia and lower respiratory tract infection that could be treated as outpatients according to their clinical severity score, are in fact admitted to hospital. We investigated whether, with medical and social input, these patients could be discharged early and treated at home., Objectives: (1) To assess the feasibility of providing an early supported discharge scheme for patients with pneumonia and lower respiratory tract infection (2) To assess the patient acceptability of a study comprising of randomisation to standard hospital care or early supported discharge scheme., Design: Randomised controlled trial., Setting: Liverpool, UK. Two University Teaching hospitals; one city-centre, 1 suburban in Liverpool, a city with high deprivation scores and unemployment rates., Participants: 200 patients screened: 14 community-dwelling patients requiring an acute hospital stay for pneumonia or lower respiratory tract infection were recruited., Intervention: Early supported discharge scheme to provide specialist respiratory care in a patient's own home as a substitute to acute hospital care., Main Outcome Measures: Primary - patient acceptability. Secondary - safety/mortality, length of hospital stay, readmission, patient/carer (or next of kin) satisfaction, functional status and symptom improvement., Results: 42 of the 200 patients screened were eligible for early supported discharge; 10 were only identified at the point of discharge, 18 declined participation and 14 were randomised to either early supported discharge or standard hospital care. The total hospital length of hospital stay was 8.33 (1-31) days in standard hospital care and 3.4 (1-7) days in the early supported discharge scheme arm. In the early supported discharge scheme arm patient carers reported higher satisfaction with care and there were less readmissions and hospital-acquired infections., Limitations: A small study in a single city. This was a feasibility study and therefore not intended to compare outcome data., Conclusions: An early supported discharge scheme for patients with pneumonia and lower respiratory tract infection was feasible. Larger numbers of patients would be eligible if future work included patients with dementia and those residing in care homes., Trial Registration: ISRCTN25542492.