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.

Upper airways colonisation of Streptococcus pneumoniae in adults aged 60 years and older: A systematic review of prevalence and individual participant data meta-analysis of risk factors.

BACKGROUND: Colonisation with Streptococcus pneumoniae can lead to invasive pneumococcal disease and pneumonia. Pneumococcal acquisition and prevalence of colonisation are high in children. In older adults, a population susceptible to pneumococcal disease, colonisation prevalence is reported to be lower, but studies are heterogeneous. METHODS: This is a systematic review and meta-analysis of prevalence of, and risk factors for, pneumococcal colonisation in adults ≥ 60 years of age (PROSPERO #42016036891). We identified peer-reviewed studies reporting the prevalence of S. pneumoniae colonisation using MEDLINE and EMBASE (until April 2016), excluding studies of acute disease. Participant-level data on risk factors were sought from each study. FINDINGS: Of 2202 studies screened, 29 were analysable: 18 provided participant-level data (representing 6290 participants). Prevalence of detected pneumococcal colonisation was 0-39% by conventional culture methods and 3-23% by molecular methods. In a multivariate analysis, colonisation was higher in persons from nursing facilities compared with the community (odds ratio (OR) 2•30, 95% CI 1•26-4•21 and OR 7•72, 95% CI 1•15-51•85, respectively), in those who were currently smoking (OR 1•69, 95% CI 1•12-2•53) or those who had regular contact with children (OR 1•93, 95%CI 1•27-2•93). Persons living in urban areas had significantly lower carriage prevalence (OR 0•43, 95%CI 0•27-0•70). INTERPRETATION: Overall prevalence of pneumococcal colonisation in older adults was higher than expected but varied by risk factors. Future studies should further explore risk factors for colonisation, to highlight targets for focussed intervention such as pneumococcal vaccination of high-risk groups. FUNDING: No funding was required.

Derivation and validation of a universal vital assessment (UVA) score: a tool for predicting mortality in adult hospitalised patients in sub-Saharan Africa.

BACKGROUND: Critical illness is a leading cause of morbidity and mortality in sub-Saharan Africa (SSA). Identifying patients with the highest risk of death could help with resource allocation and clinical decision making. Accordingly, we derived and validated a universal vital assessment (UVA) score for use in SSA. METHODS: We pooled data from hospital-based cohort studies conducted in six countries in SSA spanning the years 2009-2015. We derived and internally validated a UVA score using decision trees and linear regression and compared its performance with the modified early warning score (MEWS) and the quick sepsis-related organ failure assessment (qSOFA) score. RESULTS: Of 5573 patients included in the analysis, 2829 (50.8%) were female, the median (IQR) age was 36 (27-49) years, 2122 (38.1%) were HIV-infected and 996 (17.3%) died in-hospital. The UVA score included points for temperature, heart and respiratory rates, systolic blood pressure, oxygen saturation, Glasgow Coma Scale score and HIV serostatus, and had an area under the receiver operating characteristic curve (AUC) of 0.77 (95% CI 0.75 to 0.79), which outperformed MEWS (AUC 0.70 (95% CI 0.67 to 0.71)) and qSOFA (AUC 0.69 (95% CI 0.67 to 0.72)). CONCLUSION: We identified predictors of in-hospital mortality irrespective of the underlying condition(s) in a large population of hospitalised patients in SSA and derived and internally validated a UVA score to assist clinicians in risk-stratifying patients for in-hospital mortality. The UVA score could help improve patient triage in resource-limited environments and serve as a standard for mortality risk in future studies.

Early warning scores generated in developed healthcare settings are not sufficient at predicting early mortality in Blantyre, Malawi: a prospective cohort study.

AIM: Early warning scores (EWS) are widely used in well-resourced healthcare settings to identify patients at risk of mortality. The Modified Early Warning Score (MEWS) is a well-known EWS used comprehensively in the United Kingdom. The HOTEL score (Hypotension, Oxygen saturation, Temperature, ECG abnormality, Loss of independence) was developed and tested in a European cohort; however, its validity is unknown in resource limited settings. This study compared the performance of both scores and suggested modifications to enhance accuracy. METHODS: A prospective cohort study of adults (≥18 yrs) admitted to medical wards at a Malawian hospital. Primary outcome was mortality within three days. Performance of MEWS and HOTEL were assessed using ROC analysis. Logistic regression analysis identified important predictors of mortality and from this a new score was defined. RESULTS: Three-hundred-and-two patients were included. Fifty-one (16.9%) died within three days of admission. With a cut-point ≥2, the HOTEL score had sensitivity 70.6% (95% CI: 56.2 to 82.5) and specificity 59.4% (95% CI: 53.0 to 65.5), and was superior to MEWS (cut-point ≥5); sensitivity: 58.8% (95% CI: 44.2 to 72.4), specificity: 56.2% (95% CI: 49.8 to 62.4). The new score, dubbed TOTAL (Tachypnoea, Oxygen saturation, Temperature, Alert, Loss of independence), showed slight improvement with a cut-point ≥2; sensitivity 76.5% (95% CI: 62.5 to 87.2) and specificity 67.3% (95% CI: 61.1 to 73.1). CONCLUSION: Using an EWS generated in developed healthcare systems in resource limited settings results in loss of sensitivity and specificity. A score based on predictors of mortality specific to the Malawian population showed enhanced accuracy but not enough to warrant clinical use. Despite an assumption of common physiological responses, disease and population differences seem to strongly determine the performance of EWS. Local validation and impact assessment of these scores should precede their adoption in resource limited settings.