[Vaccination status and factors associated with pneumococcal vaccination in geriatric short-stay care]. / Statut vaccinal et facteurs associés à la vaccination antipneumococcique en court séjour gériatrique.

Nearly two-thirds of geriatric short-stay patients were eligible for pneumococcal vaccination. Among patients eligible for vaccination, less than 5 % had received at least one injection of pneumococcal vaccine on admission. We found no modifiable factors associated with vaccination status, but several avenues for improving vaccination coverage.

Impact of the addition of azithromycin to antimalarials used for seasonal malaria chemoprevention on antimicrobial resistance of Streptococcus pneumoniae.

OBJECTIVE: A trial was conducted in Burkina Faso and Mali to investigate whether addition of azithromycin to the antimalarials used for seasonal malaria chemoprevention reduces mortality and hospital admissions of children. We tested the sensitivity of nasal isolates of Streptococcus pneumoniae obtained during this trial to azithromycin and other antibiotics. METHODS: Azithromycin or placebo was administered monthly, in combination with the antimalarials used for seasonal malaria chemoprevention, for four months, over the annual malaria transmission seasons of 2014, 2015, and 2016. Nasopharyngeal swabs were collected from 2773 Burkinabe and 2709 Malian children on seven occasions: in July and December each year prior to and after drug administration, and at a final survey in early 2018. Pneumococci were isolated from nasopharyngeal swabs and tested for sensitivity to azithromycin and other antibiotics. RESULTS: A total of 5482 samples were collected. In Burkina Faso, the percentage of pneumococcal isolates resistant to azithromycin among children who had received it increased from 4.9% (95% CI: 2.4%, 9.9%) before the intervention to 25.6% (95% CI: 17.6%, 35.7%) afterward. In Mali, the increase was from 7.6% (95% CI: 3.8%, 14.4%) to 68.5% (95% CI: 55.1%, 79.4%). The percentage of resistant isolates remained elevated (17.7% (95% CI: 11.1%, 27.1%) in Burkina Faso and 19.1% (95% CI: 13.5%, 26.3%) in Mali) among children who had received azithromycin 1 year after stopping the intervention. An increase in resistance to azithromycin was also observed in children who had received a placebo but it was less marked. CONCLUSION: Addition of azithromycin to the antimalarial combination used for seasonal malaria chemoprevention was associated with an increase in resistance of pneumococci to azithromycin and erythromycin, which persisted 1 year after the last administration of azithromycin.

OBJECTIF: Un essai a été mené au Burkina Faso et au Mali pour investiguer si l'addition d'azithromycine aux antipaludéens utilisés dans le cadre de la chimioprévention du paludisme saisonnier réduisait la mortalité et les hospitalisations d'enfants. Nous avons testé la sensibilité à l'azithromycine et à d'autres antibiotiques pour les isolats nasaux de Streptococcus pneumoniae obtenus lors de cet essai. MÉTHODES: L'azithromycine ou un placebo a été administré mensuellement, en association avec les antipaludéens utilisés pour la chimioprévention du paludisme saisonnier, pendant 4 mois, durant les saisons de transmission annuelle du paludisme de 2014, 2015 et 2016. Des échantillons nasopharyngés ont été prélevés sur écouvillons chez 2.773 enfants burkinabés et 2.709 enfants maliens lors de 7 occasions: en juillet et en décembre chaque année avant et après l'administration du médicament, ainsi que lors d'une surveillance finale au début de 2018. Les pneumocoques ont été isolés à partir d'écouvillons nasopharyngés et soumis à des tests de sensibilité à l'azithromycine et à d'autres antibiotiques. RÉSULTATS: 5.482 échantillons ont été collectés. Au Burkina Faso, le pourcentage d'isolats de pneumocoque résistants à l'azithromycine chez les enfants qui l'avaient reçu était passé de 4,9% (IC95%: 2,4%, 9,9%) avant l'intervention à 25,6% (IC95%: 17,6-35,7%) après. Au Mali, l'augmentation est passée de 7,6% (IC95%: 3,8-14,4%) à 68,5% (IC95%: 55,1-79,4%). Le pourcentage d'isolats résistants est resté élevé (17,7% (IC95%: 11,1-27,1%) au Burkina Faso et 19,1% (IC95%: 13,5-26,3%) au Mali) chez les enfants ayant reçu l'azithromycine un an après arrêter l'intervention. Une augmentation de la résistance à l'azithromycine a également été observée chez les enfants ayant reçu un placebo, mais elle était moins marquée. CONCLUSION: L'ajout d'azithromycine à la combinaison antipaludique utilisée pour la chimioprévention du paludisme saisonnier était associé à une augmentation de la résistance du pneumocoque à l'azithromycine et à l'érythromycine, qui persistait un an après la dernière administration d'azithromycine.

Health policy for sickle cell disease in Africa: experience from Tanzania on interventions to reduce under-five mortality.

Tanzania has made considerable progress towards reducing childhood mortality, achieving a 57% decrease between 1980 and 2011. This epidemiological transition will cause a reduction in the contribution of infectious diseases to childhood mortality and increase in contribution from non-communicable diseases (NCDs). Haemoglobinopathies are amongst the most common childhood NCDs, with sickle cell disease (SCD) being the commonest haemoglobinopathy in Africa. In Tanzania, 10,313 children with SCD under 5 years of age (U5) are estimated to die every year, contributing an estimated 7% of overall deaths in U5 children. Key policies that governments in Africa are able to implement would reduce mortality in SCD, focusing on newborn screening and comprehensive SCD care programmes. Such programmes would ensure that interventions such as prevention of infections using penicillin plus prompt diagnosis and treatment of complications are provided to all individuals with SCD.

Evaluation of pneumococcal urinary antigen testing for respiratory tract infection investigations.

OBJECTIVE: The pneumococcal urinary antigen test enables rapid bacteriological diagnosis in respiratory tract infections. The objective was to identify factors associated with a positive pneumococcal urinary antigen test result. PATIENTS AND METHODS: This seven-year retrospective monocentric study was performed on consecutive patients presenting with respiratory tract infections reported as pneumococcal-positive. Epidemiological, biological, and radiological factors were analyzed, and severity scores were calculated. RESULTS: A total of 223 patients were included. Significant associations were observed between positive test results and age over 65years (P=0.01), positive test results and immunosuppression factors (blood disease [25% Ag+ group vs. 4% Ag- group, P=0.001], immunosuppressive therapy [10% Ag+ group vs. 0% Ag- group, P=0.02]). Clinically, fever (64% Ag+ group vs. 42% Ag- group, P=0.01) and cough (46% Ag+ group vs. 19% Ag- group, P<0.01) were associated with a positive result, as were radiological alveolar opacities (67% Ag+ group vs. 44% Ag- group, P=0.01). High PSI score was associated with the Ag+ group (79% vs. 56% Ag- group, P=0.001). CONCLUSION: Age, immunosuppressive factors, typical pneumococcal symptoms, and PSI scores were associated with a positive pneumococcal urinary antigen result.

Hospital cost of invasive pneumococcal disease in children aged under 15 years old in Tunisia.

BACKGROUND: Pneumococcal infections are an important cause of morbidity and mortality in the world and in Tunisia. Data on the economic burden of these infections are needed to inform decision-making to include pneumococcal vaccinations in routine childhood immunization. AIMS: This study aimed to estimate the medical cost of hospitalizations due to invasive pneumococcal disease (pneumonia and meningitis) among children aged under 15 years old in Tunisia. METHODS: A prospective multicentre study was conducted in 15 paediatric departments, across different socio-economic areas of Tunisia, from June 2014 to May 2015. All children aged under 15 years old who were hospitalized for pneumococcal pneumonia or confirmed bacterial meningitis were enrolled. A case report form was completed for every eligible case. Activity Based Costing method was used to estimate the hospital cost. Data entry and statistical analysis were conducted using SPSS, version 20.0. RESULTS: During the study period, 727 children were hospitalized for pneumococcal pneumonia and 60 children were hospitalized for bacterial meningitis, among them 21(35%) had confirmed pneumococcal meningitis. The median hospital cost for pneumococcal pneumonia was 353.910 Tunisian Dinars (TND) and TND 1680.632 for pneumococcal meningitis. Using overall data extrapolation, it was estimated that nearly 1091 hospitalizations for pneumococcal pneumonia and 69 hospitalizations for pneumococcal meningitis occurred each year in Tunisian children aged under 15 years of age, incurring total costs of TND 502 079.408. CONCLUSION: The economic burden of pneumococcal infections seems to be substantial in Tunisia. The estimated costs does not reflect the real costs of this infection. Cost-effectiveness studies would be helpful to inform policy-makers to take appropriate decisions.

[Alterations in responses to vaccines in older people]. / Altération des réponses vaccinales avec l'âge.

The aging population raises a number of public health issues including a need to address the severity and frequency of infections observed in older people. Vaccines play an important role in prevention. However, immunosenescence alters the intensity and quality of vaccine responses, thus limiting the impact of recommendations directed after 65 years for vaccination against flu, pneumococci, pertussis, tetanus and zoster. Immunosenescence, aggravated by co-morbidities, varies with age, becoming apparent after 60-65 years and more profound after 85 years. All stages of vaccine responses are affected by immunosenescence, from the innate immunity required to activate these responses to the induction of protective antibody responses and immune memory. Nevertheless, the capacity to develop new responses to primary vaccination is more affected than the ability to respond to recalls, although this is also impaired. Responses to vaccines are differentially altered depending on vaccine and age. Influenza vaccines are modestly immunogenic and several meta-analyses agree an estimate for efficacy of about 50% against virologically-proven flu and 40% against flu-related deaths. The anti-pneumococcal 23-valent non-conjugated vaccine does not induce memory while the 13-valent conjugated one does, but their efficacy are likely to be similar between 70 to 52% before 75 years. A sequential vaccination program with the 13-valent primo-vaccination followed by the 23-valent, recommended in immune-suppressed patients, is currently being studied in France. The waning of immunity to pertussis makes recalls necessary in the elderly who develop good antibody responses. Several research avenues are currently being pursued to try improve the degree of protection conferred by these vaccines in elderly.

[Influenzae and pneumococcal vaccination rate in an internal medicine ward]. / Couverture vaccinale antigrippale et antipneumococcique dans un service de médecine interne.

INTRODUCTION: Vaccination against influenza virus and Streptococcus pneumoniae is a global health priority and authorities, on the basis of recent publications, have recently updated French recommendations. The aim of this study was to describe the influenzae and pneumococcal vaccination's rate in an internal medicine ward. MATERIAL AND METHODS: All patients consecutively hospitalized during a 10 week-period in an internal medicine ward were included. The reasons for non-vaccination and the impact of an educational program for corrective measures were reported. RESULTS: Overall, 198 consecutive patients were included; 93 (47%) were immunocompromised; 142 (71.2%) had an indication for pneumococcal vaccination and 171 (86.4%) for influenza vaccination but only 16.2% and 55% of them were vaccinated against these microorganisms, respectively. Prior pneumococcal vaccination was more frequently observed in immunocompromised patients than in non-immunocompromised patients (21.1 versus 6.4%; P=0.029), but no significant difference was observed for influenza vaccine. Corrective measures were initiated in 46 patients (39%), non-immunized against S. pneumoniae. CONCLUSION: These results underline the very low prevalence of pneumococcal vaccination rate in at-risk hospitalized patients, as compared with influenza, despite recent recommendations.

Biphasic lung injury during Streptococcus pneumoniae infection in a murine model.

OBJECTIVES: Streptococcus pneumoniae is the leading cause of community-acquired pneumonia. We aimed to analyze the epithelial response to S. pneumoniae-induced lung injury. METHODS: Using an in vitro model with 16HBE cells and experimental in vivo murine model of acute lung injury, we analyzed the epithelial response to S. pneumoniae. Lung epithelial cell monolayers were exposed to S. pneumoniae and permeability was assessed by transepithelial resistance (TER) measurement and organization and expression of junction proteins. Functional consequences were studied with an in vivo murine model measuring alveolar permeability, distal alveolar fluid clearance (DAFC), and the alveolar inflammatory response. RESULTS: In vitro, S. pneumoniae induced a dose-dependent decrease in transepithelial resistance, which was associated with significant modifications in the organization of junction proteins assessed by immunofluorescence staining and expression after 6hours of exposure. In vivo, S. pneumoniae induced a transient increase in alveolar permeability with an adequate increase in DAFC 6hours post infection. In a second phase, a permanent increased permeability was associated with a major decrease in DAFC. CONCLUSION: Overall, the epithelial response to S. pneumoniae followed a biphasic pattern with an initial reversible increase in permeability related to the alteration of tight and adherens junctions and a second phase associated with an epithelial injury with a major increase in permeability with a decreased DAFC reflecting an injured alveolar capillary barrier.

Community-acquired pneumonia and positive urinary antigen tests: Factors associated with targeted antibiotic therapy.

BACKGROUND: The use of rapid microbiological tests is supported by antimicrobial stewardship policies. Targeted antibiotic therapy (TAT) for community-acquired pneumonia (CAP) with positive urinary antigen test (UAT) has been associated with a favorable impact on outcome. We aimed to determine the factors associated with TAT prescription. PATIENTS AND METHODS: We conducted a retrospective multicenter study including all patients presenting with CAP and positive UAT for Streptococcus pneumoniae or Legionella pneumophila from January 2010 to December 2013. Patients presenting with aspiration pneumonia, coinfection, and neutropenia were excluded. CAP severity was assessed using the Pneumonia Severity Index (PSI). TAT was defined as the administration of amoxicillin for pneumococcal infection and either macrolides or fluoroquinolones (inactive against S. pneumoniae) for Legionella infection. RESULTS: A total of 861 patients were included, including 687 pneumococcal infections and 174 legionellosis from eight facilities and 37 medical departments. TAT was prescribed to 273 patients (32%). Four factors were found independently associated with a lower rate of TAT: a PSI score≥4 (OR 0.37), Hospital A (OR 0.41), hospitalization in the intensive care unit (OR 0.44), and cardiac comorbidities (OR 0.60). Four other factors were associated with a high rate of TAT: positive blood culture for S. pneumoniae (OR 2.32), Hospitals B (OR 2.34), E (OR 2.68), and H (OR 9.32). CONCLUSION: TAT in CAP with positive UAT was related to the hospitals as well as to patient characteristics.

[Improvement of pneumococcal immunization coverage in older patients]. / Amélioration de la couverture vaccinale anti-pneumococcique chez le sujet âgé.

PURPOSE: To study pneumococcal immunization coverage in older patients in hospital, and the impact of two actions aiming at improving this coverage. METHODS: We reported a prospective and descriptive study conducted from November 2009 to August 2010, including all new patients ≥75 years old received in a geriatric short-stay department and residing in Val-de-Marne, France. This study was performed in three successive three-month periods, to assess the vaccination coverage in the months following hospital release. Period I was the reference; Period II included an awareness campaign of general practitioners relying on the hospitalization discharge report, containing an indication for the vaccination; Period III consisted in a systematic proposal of vaccination by the geriatric hospital department. RESULTS: Indication for pneumococcal vaccination has been given to 139 patients (61.2%) in 227 processed questionnaires. The main indication was heart failure for 105 patients (75.5%). Twenty-four patients were already vaccinated (17.2%). No vaccination was reported in the three months following period I in 33 included patients. The awareness campaign targeting regular doctors resulted in only one vaccination out of 37 patients. Immunization coverage in the department had reached 84.5% of inoculation (38 of 45 patients). CONCLUSION: Pneumococcal vaccination is often prescribed in elderly patients but generally not executed. The awareness campaign did not result in a big enough immunization coverage improvement, compared to a codified proposal of vaccination during hospital stay.

Longitudinal DRG-based survey of all-cause and pneumococcal pneumonia and meningitis for inpatients in France (2005-2010).

OBJECTIVE: This population-based retrospective study quantified the burden of all-cause and pneumococcal pneumonia and meningitis in the Rhône-Alpes region of France from 2005 to 2010, when the 7-valent pneumococcal conjugate vaccine uptake increased from 50 to>90% in children. PATIENTS AND METHODS: Hospital admission data was obtained from the French Diagnosis Related Groups program database (French acronym PMSI). Patients were residents of the Rhône-Alpes region hospitalized for the diseases of interest during 2005-2010. Hospitalization and in-hospital mortality rates were calculated by age, sex, and year on the basis of the Rhône-Alpes region population. Hospitalization and in-hospital mortality rates were compared using Chi(2) tests with statistical significance adjusted for multiple comparisons. RESULTS: The highest hospitalization rates by age group were: all-cause pneumonia, oldest group (>65 years); all-cause and pneumococcal meningitis, youngest group (0-4 years), and pneumococcal pneumonia, youngest and oldest groups. Hospitalization rates significantly decreased for all-cause pneumonia (5-19 years: -12.71%) and all-cause meningitis (20-49 years: -29.22%). Pneumococcal disease rates did not significantly change in any age group. Mortality rates from all-cause pneumonia and meningitis were highest in the oldest age groups. CONCLUSIONS: The burden of all-cause and pneumococcal pneumonia and meningitis remains substantial. Significant changes (decreases) between 2005 and 2010 in hospitalization rates were limited and varied among age groups, most likely because this study began 2 years after PCV7 was first introduced in France for children at broadly-defined high risk. Further research is needed on the relationship between serotype epidemiology and clinical patterns of disease.

Pediatric invasive pneumococcal disease in Senegal.

OBJECTIVES: We aimed to describe the clinical, epidemiological, and outcome characteristics of IPD case patients hospitalized at the Albert-Royer National Children's Hospital (French acronym CHNEAR) to evaluate the disease burden of IPDs in a pediatric hospital of Dakar (Senegal). PATIENTS AND METHODS: All children aged 0-15 years hospitalized at the CHNEAR between January 1st, 2008 and December 31st, 2013 for a documented IPD were included in the study. Medical history, risk factors, clinical, bacteriological, and outcome data was collected. Data was then analyzed using the SPSS software, version 16 (Pearson's Chi(2) test: a P-value<0.05 was considered statistically significant). RESULTS: A total of 218 IPD patients were hospitalized at the CHNEAR during the study period (hospital prevalence: 0.79%). The mean age was 36.1 months. The male to female ratio was 1.27 (122 boys and 96 girls). Infants<2 years of age represented 61.46% of patients. Prior antibiotic therapy was found in 54% of patients but details were lacking. Infection sites were mostly meningeal (61%) and pleuropulmonary (28.9%). The main isolated serotypes were 1, 6A, 14, 5, and 23F. Case fatality was 17.4% and it was five times higher for pneumococcal meningitis. CONCLUSION: IPDs are very common in children in Senegal. Infants<2 years of age are particularly affected. The very high case fatality (17%) was significantly associated with meningeal infection sites hence the need for better access to pneumococcal vaccines.

Usefulness of pneumococcal antigen urinary testing in the intensive care unit?

OBJECTIVES: The use of pneumococcal antigen urinary tests is substantially increasing and is associated with a significant cost. The relevant use of this test in the intensive care unit (ICU) should be better defined. Our aim was to define the role of this test in relation to other microbiological tests. We described a series of patients admitted to the ICU for an invasive pneumococcal disease (IPD). PATIENTS AND METHODS: We conducted a retrospective and descriptive study of the microbiological tests used to diagnose IPD in patients admitted to the ICU of the University Hospital in Bordeaux. Our aim was to measure the sensitivity of these bacteriological tests and of the BinaxNOWS. pneumoniae test. RESULTS: Between 2009 and 2013, 148 patients were admitted for an IPD. A lower respiratory tract infection was diagnosed in 96.6% of them (143 patients). The overall ICU case fatality rate was 17.6%. The sensitivity of the pneumococcal antigen urinary test, sputum bacteriological examination, and blood cultures was respectively 83%, 37.6%, and 29.7%. S. pneumoniae was isolated from at least one bacteriological sample in 48.6% of patients, but in 51.4%, the diagnosis was only based on the results of the pneumococcal antigen urinary test. CONCLUSION: We suggest performing a pneumococcal antigen urinary test when an IPD is suspected, only if the bacteriological tests are still negative after 48hours. This strategy would result in a substantial cost saving. Patients would not face any additional risks as the result of the pneumococcal antigen urinary test does not have any impact on the initially prescribed antibiotic therapy.

Ten years of experience with the pneumococcal conjugate 7-valent vaccine in children.

In children, pneumococcus became the predominant infectious agent, after the routine use of the Hib conjugate vaccine dramatically decreased Haemophilus Influenzae type b prevalence. The incidence of invasive pneumococcal infections (IPI) and of non-invasive infections due to vaccine serotypes (VS) decreased by 80% in Europe along with a 30-40% decrease in the global incidence of IPI in this age group, after the implementation of Prevenar 7(®) routine immunization in children below 2 years of age. The decrease of IPI due to VS in other age groups was an indirect benefit. The moderate increase of non-vaccinal serotype IPI incidence did not impede the benefit of the overall program. Serotype 19A was the most frequent and carried resistance to antibiotics. Prevenar 13(®), a second-generation vaccine with six new serotypes, replaced Prevenar 7(®) in most countries after 2010, with available evidence of its effectiveness (United Kingdom, US, France).