Impact of the introduction of pneumococcal conjugate vaccination on invasive pneumococcal disease and pneumonia in The Gambia: 10 years of population-based surveillance.

BACKGROUND: The Gambia introduced seven-valent pneumococcal conjugate vaccine (PCV7) in August 2009, followed by PCV13 in May, 2011, using a schedule of three primary doses without a booster dose or catch-up immunisation. We aimed to assess the long-term impact of PCV on disease incidence. METHODS: We did 10 years of population-based surveillance for invasive pneumococcal disease (IPD) and WHO defined radiological pneumonia with consolidation in rural Gambia. The surveillance population included all Basse Health and Demographic Surveillance System residents aged 2 months or older. Nurses screened all outpatients and inpatients at all health facilities using standardised criteria for referral. Clinicians then applied criteria for patient investigation. We defined IPD as a compatible illness with isolation of Streptococcus pneumoniae from a normally sterile site (cerebrospinal fluid, blood, or pleural fluid). We compared disease incidence between baseline (May 12, 2008-May 11, 2010) and post-vaccine years (2016-2017), in children aged 2 months to 14 years, adjusting for changes in case ascertainment over time. FINDINGS: We identified 22 728 patients for investigation and detected 342 cases of IPD and 2623 cases of radiological pneumonia. Among children aged 2-59 months, IPD incidence declined from 184 cases per 100 000 person-years to 38 cases per 100 000 person-years, an 80% reduction (95% CI 69-87). Non-pneumococcal bacteraemia incidence did not change significantly over time (incidence rate ratio 0·88; 95% CI, 0·64-1·21). We detected zero cases of vaccine-type IPD in the 2-11 month age group in 2016-17. Incidence of radiological pneumonia decreased by 33% (95% CI 24-40), from 10·5 to 7·0 per 1000 person-years in the 2-59 month age group, while pneumonia hospitalisations declined by 27% (95% CI 22-31). In the 5-14 year age group, IPD incidence declined by 69% (95% CI -28 to 91) and radiological pneumonia by 27% (95% CI -5 to 49). INTERPRETATION: Routine introduction of PCV13 substantially reduced the incidence of childhood IPD and pneumonia in rural Gambia, including elimination of vaccine-type IPD in infants. Other low-income countries can expect substantial impact from the introduction of PCV13 using a schedule of three primary doses. FUNDING: Gavi, The Vaccine Alliance; Bill & Melinda Gates Foundation; UK Medical Research Council; Pfizer Ltd.

National trends in emergency department use of urinalysis, complete blood count, and blood culture for fever without a source among children aged 2 to 24 months in the pneumococcal conjugate vaccine 7 era.

OBJECTIVES: The epidemiology of serious bacterial infections in children has changed since the introduction of the pneumococcal conjugate vaccine (PCV-7) in 2000. Whether emergency department (ED) physicians have changed diagnostic approaches to fever without a source (FWS) in response is unknown. We examine trends in rates of complete blood count (CBC), urinalysis (UA), and blood cultures among 2- to 24-month-old children with FWS since the introduction of PCV-7. METHODS: The National Hospital Ambulatory Medical Care Survey-Emergency Department, 2001-2009, was used to identify visits to the ED by 2- to 24-month-old children with FWS. Rates of CBC, UA, neither CBC nor UA, and blood culture were tracked across time. Trends were identified using Joinpoint regression and bivariate and multivariate logistic regressions with year as the independent variables and ordering of each test as the dependent variables. RESULTS: In bivariate and multivariate analyses, CBC orders declined between 2004 and 2009 for visits by all children 2 to 24 months, children 2 to 11 months, and boys 2 to 24 months (adjusted odds ratio [aOR], 0.88 per year [P < 0.01]; aOR, 0.88 [P < 0.05]; and aOR, 0.83 [P < 0.01], respectively). Between 2004 and 2009, ordering neither CBC nor UA increased among all children 2 to 24 months (aOR, 1.10; P < 0.05) and among boys (aOR, 1.16; P < 0.05). Orders for blood cultures declined across the time period in bivariate analysis, but not in multivariate analysis. CONCLUSIONS: The rate of ordering a CBC for children in the 2- to 24-month age group presenting to the ED with FWS declined, a change coincident with the changing epidemiology of serious bacterial infection since the PCV-7 vaccine was introduced.

Estimation and comparison of EQ-5D health states' utility weights for pneumococcal and human papillomavirus diseases in Argentina, Chile, and the United Kingdom.

OBJECTIVES: To estimate and compare EuroQol instrument (EQ-5D) health states' values for pneumococcal and human papillomavirus (HPV) diseases in Argentina, Chile, and the United Kingdom. METHODS: Twelve vignettes were designed, pilot-tested, and administered to a convenience sample in a cross-sectional design to elicit descriptive EQ-5D state data. Country-specific EQ-5D time-trade-off-based weights were used to map these descriptive health states into local country preference weights. Descriptive analysis is reported and intercountry differences for each condition were compared using repeated measures analysis of variance. RESULTS: Seventy-three subjects completed the survey. Pneumococcal disease-related health states mean values ranged from -0.331 (sepsis, Chile) to 0.727 (auditive sequelae, Argentina). HPV-related conditions ranged from 0.152 (cervical cancer, United Kingdom) to 0.848 (cervical intraepithelial neoplasia 1, Argentina). Chile had consistently the lowest mean values in pneumococcal states and in one HPV state, whereas those of the United Kingdom were the lowest in most HPV states. Argentina had the highest mean values in both diseases. Differences in country-specific values for each health state were statistically (P < 0.001) significant except for six health states in which differences between Chilean and United Kingdom weights were nonsignificant. CONCLUSIONS: Utility values for most conditions differed statistically relevantly among analyzed countries, even though the same health states' descriptive set was valued for each. These results reflect the difference in social weights among different countries, which could be attributed to either different population values or valuation study methodologies. They stress the importance of using local preference weights for context-specific decision making.

Corticotropin-releasing hormone receptor-1 and 2 activity produces divergent resistance against stress-induced pulmonary Streptococcus pneumoniae infection.

Utilizing a murine model of S. pneumoniae infection and restraint stress, we determined how corticotropin releasing hormone (CRH-R) receptors impacts disease. CRH-R1 (antalarmin) and CRH-R2 (astressin2B) antagonists were administered intraperitoneally prior to restraint stress followed by pulmonary S. pneumoniae infection. CRH-R1 inhibition is not protective against pneumococcal disease induced by stress. Conversely, CRH-R2 inhibition attenuates stress-induced bacterial growth and significantly prevented severe sepsis. Neutrophillic responses were associated with CRH receptor-specific disease outcome providing a potential cellular target for stress-induced susceptibility to the development of severe pneumococcal disease. CRH receptor-mediated effects on immune responses could prove valuable for novel therapeutics.

[Encephalopathy associated with severe bacterial infections: "presuppurative encephalitis" or "toxi-infectious disorder"?]. / Encéphalopathie associée aux infections bactériennes sévères de l'enfant: "encéphalite présuppurative" ou "syndrome toxi-infectieux"?

Three children are reported, exhibiting encephalopathic symptoms in the course of a severe bacterial infection, though they had no sign of intracranial purulent collection nor metabolic disturbances: the first was associated with a appendicular peritonitis, the second with a purulent knee arthritis, the third with a pneumoccus septicemia. The elements are reviewed that favor either a true septic encephalitis, i.e. microscopic presuppurative foci, versus a toxiinfectious process, either by direct action of toxins or through intracerebral activation of pre-inflammatory cytokines. Whatever the mechanism involved in individual cases, the treatment is mainly based on prompt administration of the convenient antibiotics.