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Sample records for bacteremic pneumococcal pneumonia

  1. Serotype Distribution in Non-Bacteremic Pneumococcal Pneumonia

    DEFF Research Database (Denmark)

    Benfield, Thomas; Skovgaard, Marlene; Schønheyder, Henrik Carl;

    2013-01-01

    There is limited knowledge of serotypes that cause non-bacteremic pneumococcal pneumonia (NBP). Here we report serotypes, their associated disease potential and coverage of pneumococcal conjugate vaccines (PCV) in adults with NBP and compare these to bacteremic pneumonia (BP).......There is limited knowledge of serotypes that cause non-bacteremic pneumococcal pneumonia (NBP). Here we report serotypes, their associated disease potential and coverage of pneumococcal conjugate vaccines (PCV) in adults with NBP and compare these to bacteremic pneumonia (BP)....

  2. Serotype 19A bacteremic pneumococcal pneumonia after 4 doses of 13-valent conjugate vaccine: a review of pneumococcal conjugate vaccine effectiveness

    OpenAIRE

    IrohTam, Pui-Ying; Hanisch, Benjamin R.; Forward, Brennan

    2014-01-01

    We report a case of bacteremic pneumococcal pneumonia due to serotype 19A in a child who had received four doses of the 13-valent pneumococcal conjugate vaccine, and review the literature on effectiveness of this vaccine. Pediatricians should be alert to the fact that up-to-date immunization status with pneumococcal vaccine does not preclude illness from invasive disease caused by a vaccine serotype.

  3. ADULT RESPIRATORY-DISTRESS SYNDROME (ARDS) DUE TO BACTEREMIC PNEUMOCOCCAL PNEUMONIA

    NARCIS (Netherlands)

    MANNES, GPM; BOERSMA, WG; BAUR, CHJM; POSTMUS, PE

    1991-01-01

    We describe a patient, who had no pre-existing disease, with bacteraemic pneumococcal pneumonia and adult respiratory distress syndrome (ARDS), a rare complication. In spite of the use of antibiotics and intensive treatment the mortality rate of this kind of infection remains high. Streptococcus pne

  4. Adult bacteremic pneumococcal pneumonia acquired in the community: A prospective study on 101 patients Neumonía neumocóccica bacteriémica de la comunidad: Un estudio prospectivo en 101 pacientes

    OpenAIRE

    J. H. Gentile; M. D. Sparo; M. E. Mercapide; C. M. Luna

    2003-01-01

    Our objective was to describe incidence, clinical, radiographic and microbiological features of bacteremic pneumococcal pneumonia (BPP) in our environment. A total of 101 patients (7 were treated as outpatients), older than 18 years of age suffering BPP were prospectively evaluated. The incidence was 2.8 cases per 1000 admissions, 50 were males, mean age was 59.9 years (19-97), mortality was 11.8%. Eighty three percent of fatalities occurred within 3 days of admission. Mortality rate increase...

  5. A cohort study of bacteremic pneumonia

    Science.gov (United States)

    Guillamet, Cristina Vazquez; Vazquez, Rodrigo; Noe, Jonas; Micek, Scott T.; Kollef, Marin H.

    2016-01-01

    Abstract Bacteremic pneumonia is usually associated with greater mortality. However, risk factors associated with hospital mortality in bacteremic pneumonia are inadequately described. The study was a retrospective cohort study, conducted in Barnes-Jewish Hospital (2008–2015). For purposes of this investigation, antibiotic susceptibility was determined according to ceftriaxone susceptibility, as ceftriaxone represents the antimicrobial agent most frequently recommended for hospitalized patients with community-acquired pneumonia as opposed to nosocomial pneumonia. Two multivariable analyses were planned: the first model included resistance to ceftriaxone as a variable, whereas the second model included the various antibiotic-resistant species (methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, and Enterobacteriaceae). In all, 1031 consecutive patients with bacteremic pneumonia (mortality 37.1%) were included. The most common pathogens associated with infection were S aureus (34.1%; methicillin resistance 54.0%), Enterobacteriaceae (28.0%), P aeruginosa (10.6%), anaerobic bacteria (7.3%), and Streptococcus pneumoniae (5.6%). Compared with ceftriaxone-susceptible pathogens (46.8%), ceftriaxone-resistant pathogens (53.2%) were significantly more likely to receive inappropriate initial antibiotic treatment (IIAT) (27.9% vs 7.1%; P mechanical ventilation, immune suppression, prior hospitalization, prior antibiotic administration, septic shock, comorbid conditions, and severity of illness. In the second multivariable analysis that included the antibiotic-resistant species, IIAT was still associated with excess mortality, and P aeruginosa infection was identified as an independent predictor of mortality (OR 1.6, 95% CI 1.1–2.2, P = 0.047), whereas infection with ceftriaxone-resistant Enterobacteriaceae (OR 0.6, 95% CI 0.4–1.0, P = 0.050) was associated with lower mortality. More than one-third of our patients hospitalized with bacteremic

  6. Adult bacteremic pneumococcal pneumonia acquired in the community: A prospective study on 101 patients Neumonía neumocóccica bacteriémica de la comunidad: Un estudio prospectivo en 101 pacientes

    Directory of Open Access Journals (Sweden)

    J. H. Gentile

    2003-01-01

    Full Text Available Our objective was to describe incidence, clinical, radiographic and microbiological features of bacteremic pneumococcal pneumonia (BPP in our environment. A total of 101 patients (7 were treated as outpatients, older than 18 years of age suffering BPP were prospectively evaluated. The incidence was 2.8 cases per 1000 admissions, 50 were males, mean age was 59.9 years (19-97, mortality was 11.8%. Eighty three percent of fatalities occurred within 3 days of admission. Mortality rate increased with advancing age. Fever, cough and chest pain were the commonest presenting symptoms and 44% of patients had extrapulmonary manifestations. Cigarette smoking, chronic obstructive lung disease, alcoholism and congestive heart failure (CHF were the commonest underlying conditions. CHF was more frequent in non-survivors (p = 0.002. A lobar pattern at chest radiograph predominated in survivors and a diffuse pattern in non-survivors (p = 0.007. Pleural effusion (20.7%, empyema (7.9% and respiratory failure (7.9% were the main complications. Underlying diseases were present in 100% of non-survivors (p = 0.03. Ninety four percent of patients were treated with beta-lactam antibiotics. Streptococcus pneumoniae was isolated from sputum in 6 cases. Three out of 101 S. pneumoniae isolates recovered from blood samples (one from each patient presented organisms resistant to penicillin. We observed an incidence of BPP that is similar to the observed in other countries. There are clinical and radiographic differences between survivors and non-survivors. Penicillin-resistant S. pneumoniae is still an unusual problem in our area.Se evaluaron en forma prospectiva 101 pacientes > 18 años admitidos al hospital con diagnóstico de NNB. El objetivo fue conocer la incidencia y describir las características de la enfermedad, así como la susceptibilidad antibiótica de cepas invasivas de Streptococcus pneumoniae. Se halló una incidencia de 2.8 casos/1000 admisiones; 50 fueron

  7. Impact of pneumococcal vaccination in children on serotype distribution in adult community-acquired pneumonia using the serotype-specific multiplex urinary antigen detection assay.

    Science.gov (United States)

    Pletz, Mathias W; Ewig, Santiago; Rohde, Gernot; Schuette, Hartwig; Rupp, Jan; Welte, Tobias; Suttorp, Norbert; Forstner, Christina

    2016-04-29

    The aim of the study was to compare the distribution of the vaccine-serotypes covered by pneumococcal conjugate vaccines (PCV7 and PCV13) in adult patients with pneumococcal community-acquired pneumonia in Germany between the periods 2002-2006 and 2007-2011 using a novel serotype-specific multiplex urinary antigen detection assay (SSUA). Vaccination of children started with PCV7 in 2007, which was replaced by PCV13 in 2010. Following confirmation of the accuracy of SSUA in long-term stored urine samples from 112 patients with confirmed pneumonia and known pneumococcal serotype, urine samples of 391 CAPNETZ patients with documented pneumococcal pneumonia (i.e. positive BinaxNOW(®) Streptococcus pneumoniae urine antigen test) but unknown serotype were tested for the 13 vaccine-serotypes using SSUA. The proportion of PCV7-serotypes significantly decreased in adult patients with pneumonia from 30.6% (2002-6) to 13.3% (2007-11, ppneumococcal serotypes included by PCV13 remained stable during study period with a coverage of 61.5% (2002-06) and 59.7% (2007-11) in non-bacteremic pneumonia and 79% (for both periods) in bacteremic pneumonia, mainly due to an increase in pneumococcal serotypes 1, 3 and 7F during the second period. Thus, implementation of PCV7 in children in Germany in 2007 was associated with a significant decrease in vaccine-serotypes covered by PCV7 in adult patients with non-bacteremic pneumococcal pneumonia and with an elimination of PCV7 vaccine-serotypes in bacteremic pneumococcal pneumonia. PCV13 coverage remained high up to 2011, mainly due to an increase in serotypes 1, 3 and 7F. German Clinical Trials Register: DRKS00005274. PMID:27016653

  8. Case Report of Low Virulence Francisella tularensis Presented as Severe Bacteremic Pneumonia

    Science.gov (United States)

    Su, Ting-Yi; Shie, Shian-Sen; Chia, Ju-Hsin; Huang, Ching-Tai

    2016-01-01

    Abstract Tularemia is a zoonotic infection seen primarily in the Northern Hemisphere. It is caused by the bacteria Francisella tularensis. Although the ulceroglandular form of the disease is the more common manifestation of infection, F tularensis is known to cause pneumonia. F tularensis has two predominant subspecies, namely subsp. tularensis (type A) and subsp. holarctica (type B). Type B tularemia is considered to be much less virulent than type A and barely caused lethal disease and pneumonia. We reported a case with a 68-year-old man immune-compromised patient diagnosed with bacteremic pneumonia engendered by type B tularemia with initial presentation of high fever, pneumonia with pleural effusion; the diagnosis was performed using 16S rRNA gene sequence analysis. The patient's fever, pneumonia, and pleural effusion were resolved with appropriate antibiotics for tularemia. This case involving severe bacteremic pneumonia in an immune-compromised patient is rare. This case suggests that low virulence F tularensis should be included in the differential diagnoses of bacteremic pneumonia for endemic tularemia. PMID:27175638

  9. A cohort study of bacteremic pneumonia: The importance of antibiotic resistance and appropriate initial therapy?

    Science.gov (United States)

    Guillamet, Cristina Vazquez; Vazquez, Rodrigo; Noe, Jonas; Micek, Scott T; Kollef, Marin H

    2016-08-01

    Bacteremic pneumonia is usually associated with greater mortality. However, risk factors associated with hospital mortality in bacteremic pneumonia are inadequately described.The study was a retrospective cohort study, conducted in Barnes-Jewish Hospital (2008-2015). For purposes of this investigation, antibiotic susceptibility was determined according to ceftriaxone susceptibility, as ceftriaxone represents the antimicrobial agent most frequently recommended for hospitalized patients with community-acquired pneumonia as opposed to nosocomial pneumonia. Two multivariable analyses were planned: the first model included resistance to ceftriaxone as a variable, whereas the second model included the various antibiotic-resistant species (methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, and Enterobacteriaceae).In all, 1031 consecutive patients with bacteremic pneumonia (mortality 37.1%) were included. The most common pathogens associated with infection were S aureus (34.1%; methicillin resistance 54.0%), Enterobacteriaceae (28.0%), P aeruginosa (10.6%), anaerobic bacteria (7.3%), and Streptococcus pneumoniae (5.6%). Compared with ceftriaxone-susceptible pathogens (46.8%), ceftriaxone-resistant pathogens (53.2%) were significantly more likely to receive inappropriate initial antibiotic treatment (IIAT) (27.9% vs 7.1%; P mechanical ventilation, immune suppression, prior hospitalization, prior antibiotic administration, septic shock, comorbid conditions, and severity of illness. In the second multivariable analysis that included the antibiotic-resistant species, IIAT was still associated with excess mortality, and P aeruginosa infection was identified as an independent predictor of mortality (OR 1.6, 95% CI 1.1-2.2, P = 0.047), whereas infection with ceftriaxone-resistant Enterobacteriaceae (OR 0.6, 95% CI 0.4-1.0, P = 0.050) was associated with lower mortality.More than one-third of our patients hospitalized with bacteremic pneumonia died

  10. Many radiologic facies of pneumococcal pneumonia

    Energy Technology Data Exchange (ETDEWEB)

    Kantor, H.G.

    1981-12-01

    In 1978, 89 patients were treated for (S. pneumoniae) pneumonia at New York Hospital-Cornell Medical Center. Only 40 cases met rather strict diagnostic criteria. Of these, 12 demonstrated the classical consolidative (air space) pattern usually ascribed to this disease. A bronchopneumonic (patch) pattern was demonstrated in an equal number of patients; interstitial (irregular linear) infiltrates were manifest in nine cases and a mixed interstitial and patchy presentation shown in seven cases. Absence of the consolidative pattern does not exclude pneumococcal pneumonia. Bacteriologic investigation is required to determine the proper diagnosis and course of therapy.

  11. PcpA Promotes Higher Levels of Infection and Modulates Recruitment of Myeloid-Derived Suppressor Cells during Pneumococcal Pneumonia.

    Science.gov (United States)

    Walker, Melissa M; Novak, Lea; Widener, Rebecca; Grubbs, James Aaron; King, Janice; Hale, Joanetha Y; Ochs, Martina M; Myers, Lisa E; Briles, David E; Deshane, Jessy

    2016-03-01

    We used two different infection models to investigate the kinetics of the PcpA-dependent pneumococcal disease in mice. In a bacteremic pneumonia model, we observed a PcpA-dependent increase in bacterial burden in the lungs, blood, liver, bronchoalveolar lavage, and spleens of mice at 24 h postinfection. This PcpA-dependent effect on bacterial burden appeared earlier (within 12 h) in the focal pneumonia model, which lacks bacteremia or sepsis. Histological changes show that the ability of pneumococci to make PcpA was associated with unresolved inflammation in both models of infection. Using our bacteremic pneumonia model we further investigated the effects of PcpA on recruitment of innate immune regulatory cells. The presence of PcpA was associated with increased IL-6 levels, suppressed production of TRAIL, and reduced infiltration of polymorphonuclear cells. The ability of pneumococci to make PcpA negatively modulated both the infiltration and apoptosis of macrophages and the recruitment of myeloid-derived suppressor-like cells. The latter have been shown to facilitate the clearance and control of bacterial pneumonia. Taken together, the ability to make PcpA was strongly associated with increased bacterial burden, inflammation, and negative regulation of innate immune cell recruitment to the lung tissue during bacteremic pneumonia. PMID:26829988

  12. Comparative radiographic features of community acquired Legionnaires' disease, pneumococcal pneumonia, mycoplasma pneumonia, and psittacosis.

    OpenAIRE

    Macfarlane, J T; Miller, A. C.; Roderick Smith, W H; Morris, A. H.; Rose, D. H.

    1984-01-01

    The features of the chest radiographs of 49 adults with legionnaires' disease were compared with those of 91 adults with pneumococcal pneumonia (31 of whom had bacteraemia or antigenaemia), 46 with mycoplasma pneumonia, and 10 with psittacosis pneumonia. No distinctive pattern was seen for any group. Homogeneous shadowing was more frequent in legionnaires' disease (40/49 cases) (p less than 0.005), bacteraemic pneumococcal pneumonia (25/31) (p less than 0.01) and non-bacteraemic pneumococcal ...

  13. Safety and feasibility of antibiotic de-escalation in bacteremic pneumonia

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    Khasawneh FA

    2014-06-01

    Full Text Available Faisal A Khasawneh,1 Adnanul Karim,2 Tashfeen Mahmood,3 Subhan Ahmed,4 Sayyed F Jaffri,3 Mansoor Mehmood2 1Section of Infectious Diseases, 2Department of Internal Medicine, Texas Tech University Health Sciences Center, Amarillo, TX, 3Department of Internal Medicine, Deaconess Hospital, Evansville, IN, 4Section of Nephrology, Department of Internal Medicine, University of Oklahoma, Tulsa, OK, USA Background: Antibiotic de-escalation is a potential strategy advocated to conserve the effectiveness of broad-spectrum antibiotics. The aim of this study was to examine the safety and feasibility of antibiotic de-escalation in patients admitted with bacteremic pneumonia. Methods: A retrospective chart review was done for patients with bacteremic pneumonia admitted to Northwest Texas Hospital in Amarillo, TX, USA, during 2008. Antibiotic de-escalation was defined as changing the empiric antibiotic regimen to a culture-directed single agent with a narrower spectrum than the original regimen. Results: Sixty-eight patients were admitted with bacteremic pneumonia. Eight patients were not eligible for de-escalation. Among the 60 patients who were eligible for de-escalation, the treating physicians failed to de-escalate antibiotics in 27 cases (45.0%. Discharge to a long-term care facility predicted failure to de-escalate antibiotics, while an infectious diseases consultation was significantly associated with antibiotic de-escalation. The average daily cost of antibacterial therapy in the de-escalation group was $25.7 compared with $61.6 in the group where de-escalation was not implemented. The difference in mean length of hospital stay and mortality between the two groups was not statistically significant. Conclusion: Antibiotic de-escalation is a safe management strategy but unfortunately is not widely adopted. Although bacterial resistance poses a significant threat and is rising, antimicrobial de-escalation has emerged as a potential intervention that can

  14. [Prophylaxis of Community-Acquired Pneumonia Outbreaks with Pneumococcal Polysaccharide Vaccine. Prospects Analysis for Russian Military Community].

    Science.gov (United States)

    Guchev, I A; Klochkov, O I; Sinopalnikov, A I

    2016-01-01

    Pneumococcal pneumonia and other diseases caused by pneumococci still remain the main factors of high morbidity and mortality rates throughout the world. Pneumococci as the leading pathogens of community-acquired pneumonia (CAP), acute otitis media and sinusitis also cause a number of other serious systemic disorders including invasive infections with high mortality in spite of the antimicrobial resistance status and adequate antimicrobials choice. Pneumococcal infections are responsible for 5-35% or more of community-acquired pneumonias. The burden of pneumonia (up to 100-200 per thousand) is recorded among military recruits in training centers. Since the specific environment of the soldiers could be carrected, their health protection requires medical surveillance. For these reasons, polysaccharide and more immunogenic conjugated pneumococcal vaccines were developed. There is now an urgent need to understand whether such vaccines are effective in military conscripts. Controversy about the effectiveness and value of the polysaccharide (PPV-23) vaccine as a CAP morbidity restriction measure still persists. There were implemented plenty of metaanalyses of pneumococcal vaccines in adults. Some of them showed that the vaccine was effective against bacteremic pneumococcal pneumonia in 'low risk' healthy adults and elders. There have been a number of poor quality observational studies in Russia where 'all pneumonia cases' were considered as an endpoint. It remains controversial whether these observational studies provide adequate evidence to justify the use of the polysaccharide vaccine in the groups of healthy young men for whom it is being advocated. In our analysis we found weak evidence supporting pneumococcal vaccination with PPV-23 for this group. Nevertheless, favorable tendency was found to immunize. It is the reason for a trail to find pharmacoepidemiological support for vaccination by novel conjugated vaccines with better immunogenicity. PMID:27337866

  15. Burden of Severe Pneumonia, Pneumococcal Pneumonia and Pneumonia Deaths in Indian States: Modelling Based Estimates

    OpenAIRE

    Farooqui, H; Jit, M.; Heymann, DL; Zodpey, S.

    2015-01-01

    The burden of severe pneumonia in terms of morbidity and mortality is unknown in India especially at sub-national level. In this context, we aimed to estimate the number of severe pneumonia episodes, pneumococcal pneumonia episodes and pneumonia deaths in children younger than 5 years in 2010. We adapted and parameterized a mathematical model based on the epidemiological concept of potential impact fraction developed CHERG for this analysis. The key parameters that determine the distribution ...

  16. Burden of Severe Pneumonia, Pneumococcal Pneumonia and Pneumonia Deaths in Indian States: Modelling Based Estimates.

    Science.gov (United States)

    Farooqui, Habib; Jit, Mark; Heymann, David L; Zodpey, Sanjay

    2015-01-01

    The burden of severe pneumonia in terms of morbidity and mortality is unknown in India especially at sub-national level. In this context, we aimed to estimate the number of severe pneumonia episodes, pneumococcal pneumonia episodes and pneumonia deaths in children younger than 5 years in 2010. We adapted and parameterized a mathematical model based on the epidemiological concept of potential impact fraction developed CHERG for this analysis. The key parameters that determine the distribution of severe pneumonia episode across Indian states were state-specific under-5 population, state-specific prevalence of selected definite pneumonia risk factors and meta-estimates of relative risks for each of these risk factors. We applied the incidence estimates and attributable fraction of risk factors to population estimates for 2010 of each Indian state. We then estimated the number of pneumococcal pneumonia cases by applying the vaccine probe methodology to an existing trial. We estimated mortality due to severe pneumonia and pneumococcal pneumonia by combining incidence estimates with case fatality ratios from multi-centric hospital-based studies. Our results suggest that in 2010, 3.6 million (3.3-3.9 million) episodes of severe pneumonia and 0.35 million (0.31-0.40 million) all cause pneumonia deaths occurred in children younger than 5 years in India. The states that merit special mention include Uttar Pradesh where 18.1% children reside but contribute 24% of pneumonia cases and 26% pneumonia deaths, Bihar (11.3% children, 16% cases, 22% deaths) Madhya Pradesh (6.6% children, 9% cases, 12% deaths), and Rajasthan (6.6% children, 8% cases, 11% deaths). Further, we estimated that 0.56 million (0.49-0.64 million) severe episodes of pneumococcal pneumonia and 105 thousand (92-119 thousand) pneumococcal deaths occurred in India. The top contributors to India's pneumococcal pneumonia burden were Uttar Pradesh, Bihar, Madhya Pradesh and Rajasthan in that order. Our results

  17. Pneumococcal Pneumonia and Pandemic H1N1

    Centers for Disease Control (CDC) Podcasts

    2012-06-06

    Dr. George Nelson, a CDC medical officer, discusses the relationship between pneumococcal pneumonia and Pandemic H1N1.  Created: 6/6/2012 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 6/6/2012.

  18. Polyamine transporter in Streptococcus pneumoniae is essential for evading early innate immune responses in pneumococcal pneumonia.

    Science.gov (United States)

    Rai, Aswathy N; Thornton, Justin A; Stokes, John; Sunesara, Imran; Swiatlo, Edwin; Nanduri, Bindu

    2016-01-01

    Streptococcus pneumoniae is the most common bacterial etiology of pneumococcal pneumonia in adults worldwide. Genomic plasticity, antibiotic resistance and extreme capsular antigenic variation complicates the design of effective therapeutic strategies. Polyamines are ubiquitous small cationic molecules necessary for full expression of pneumococcal virulence. Polyamine transport system is an attractive therapeutic target as it is highly conserved across pneumococcal serotypes. In this study, we compared an isogenic deletion strain of S. pneumoniae TIGR4 in polyamine transport operon (ΔpotABCD) with the wild type in a mouse model of pneumococcal pneumonia. Our results show that the wild type persists in mouse lung 24 h post infection while the mutant strain is cleared by host defense mechanisms. We show that intact potABCD is required for survival in the host by providing resistance to neutrophil killing. Comparative proteomics analysis of murine lungs infected with wild type and ΔpotABCD pneumococci identified expression of proteins that could confer protection to wild type strain and help establish infection. We identified ERM complex, PGLYRP1, PTPRC/CD45 and POSTN as new players in the pathogenesis of pneumococcal pneumonia. Additionally, we found that deficiency of polyamine transport leads to up regulation of the polyamine synthesis genes speE and cad in vitro. PMID:27247105

  19. Impact of Preceding Flu-Like Illness on the Serotype Distribution of Pneumococcal Pneumonia

    Science.gov (United States)

    Song, Joon Young; Nahm, Moon H.; Cheong, Hee Jin; Kim, Woo Joo

    2014-01-01

    Background Even though the pathogenicity and invasiveness of pneumococcus largely depend on capsular types, the impact of serotypes on post-viral pneumococcal pneumonia is unknown. Methods and Findings This study was performed to evaluate the impact of capsular serotypes on the development of pneumococcal pneumonia after preceding respiratory viral infections. Patients with a diagnosis of pneumococcal pneumonia were identified. Pneumonia patients were divided into two groups (post-viral pneumococcal pneumonia versus primary pneumococcal pneumonia), and then their pneumococcal serotypes were compared. Nine hundred and nineteen patients with pneumococcal pneumonia were identified during the study period, including 327 (35.6%) cases with post-viral pneumococcal pneumonia and 592 (64.4%) cases with primary pneumococcal pneumonia. Overall, serotypes 3 and 19A were the most prevalent, followed by serotypes 19F, 6A, and 11A/11E. Although relatively uncommon (33 cases, 3.6%), infrequently colonizing invasive serotypes (4, 5, 7F/7A, 8, 9V/9A, 12F, and 18C) were significantly associated with preceding respiratory viral infections (69.7%, P<0.01). Multivariate analysis revealed several statistically significant risk factors for post-viral pneumococcal pneumonia: immunodeficiency (OR 1.66; 95% CI, 1.10–2.53), chronic lung diseases (OR 1.43; 95% CI, 1.09–1.93) and ICI serotypes (OR 4.66; 95% CI, 2.07–10.47). Conclusions Infrequently colonizing invasive serotypes would be more likely to cause pneumococcal pneumonia after preceding respiratory viral illness, particularly in patients with immunodeficiency or chronic lung diseases. PMID:24691515

  20. Streptococcus pneumoniae arginine synthesis genes promote growth and virulence in pneumococcal meningitis

    NARCIS (Netherlands)

    J.R. Piet; M. Geldhoff; B.D.C. van Schaik; M.C. Brouwer; M. Valls Seron; M.E. Jakobs; K. Schipper; Y. Pannekoek; A.H. Zwinderman; T. van der Poll; A.H.C. van Kampen; F. Baas; A van der Ende; D. van de Beek

    2014-01-01

    Streptococcus pneumoniae (pneumococcus) is a major human pathogen causing pneumonia, sepsis and bacterial meningitis. Using a clinical phenotype based approach with bacterial whole-genome sequencing we identified pneumococcal arginine biosynthesis genes to be associated with outcome in patients with

  1. Exposure of Thomsen-Friedenreich Antigen in Streptococcus pneumoniae Infection is Dependent on Pneumococcal Neuraminidase A**

    OpenAIRE

    Coats, Mamie T.; Murphy, Trudy; James C Paton; Gray, Barry; Briles, David E.

    2011-01-01

    Pneumococcal hemolytic uremic syndrome is recognized in a small portion of otherwise healthy children who have or have recently had Streptococcus pneumoniae infections, including severe pneumonia, meningitis, and bacteremia. As in other types of hemolytic uremic syndrome (HUS), pneumococcal HUS is characterized by microangiopathic hemolytic anemia, and thrombocytopenia, usually with extensive kidney damage. Although not demonstrated in vivo, the pathogenesis of pneumococcal HUS has been attri...

  2. Systemic Steroid Treatment for Severe Expanding Pneumococcal Pneumonia

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    Eran Lavi

    2015-01-01

    Full Text Available The treatment of bacterial community-acquired pneumonia (CAP is based on appropriate antibiotic therapy and supportive care such as intravenous fluids and supplemental oxygen. There is no available data regarding the use of steroids in CAP in children. We present an unusual case of a child with severe respiratory distress, on the brink of mechanical ventilation, due to a rapidly expanding pneumococcal pneumonia. The administration of systemic steroids resulted in a dramatic response with rapid improvement of clinical and radiological abnormalities followed by improvement of laboratory abnormalities. This case report should raise the awareness of the potential benefits of steroids in the treatment of severe pneumonia in children. Prospective randomized trials are needed to confirm the efficacy of steroids in this setting and to determine which patients would benefit most from this.

  3. Systemic steroid treatment for severe expanding pneumococcal pneumonia.

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    Lavi, Eran; Shoseyov, David; Simanovsky, Natalia; Brooks, Rebecca

    2015-01-01

    The treatment of bacterial community-acquired pneumonia (CAP) is based on appropriate antibiotic therapy and supportive care such as intravenous fluids and supplemental oxygen. There is no available data regarding the use of steroids in CAP in children. We present an unusual case of a child with severe respiratory distress, on the brink of mechanical ventilation, due to a rapidly expanding pneumococcal pneumonia. The administration of systemic steroids resulted in a dramatic response with rapid improvement of clinical and radiological abnormalities followed by improvement of laboratory abnormalities. This case report should raise the awareness of the potential benefits of steroids in the treatment of severe pneumonia in children. Prospective randomized trials are needed to confirm the efficacy of steroids in this setting and to determine which patients would benefit most from this. PMID:25815231

  4. Lung Dendritic Cells Facilitate Extrapulmonary Bacterial Dissemination during Pneumococcal Pneumonia

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    Alva eRosendahl

    2013-06-01

    Full Text Available Streptococcus pneumoniae is a leading cause of bacterial pneumonia worldwide. Given the critical role of dendritic cells (DCs in regulating and modulating the immune response to pathogens, we investigated here the role of DCs in S. pneumoniae lung infections. Using a well-established transgenic mouse line which allows the conditional transient depletion of DCs, we showed that ablation of DCs resulted in enhanced resistance to intranasal challenge with S. pneumoniae. DC-depleted mice exhibited delayed bacterial systemic dissemination, significantly reduced bacterial loads in the infected organs and lower levels of serum inflammatory mediators than non-depleted animals. The increased resistance of DC-depleted mice to S. pneumoniae was associated with a better capacity to restrict pneumococci extrapulmonary dissemination. Furthermore, we demonstrated that S. pneumoniae disseminated from the lungs into the regional lymph nodes in a cell-independent manner and that this direct way of dissemination was much more efficient in the presence of DCs. We also provide evidence that S. pneumoniae induces expression and activation of matrix metalloproteinase-9 (MMP-9 in cultured bone marrow-derived DCs. MMP-9 is a protease involved in the breakdown of extracellular matrix proteins and is critical for DC trafficking across extracellular matrix and basement membranes during the migration from the periphery to the lymph nodes. MMP-9 was also significantly up-regulated in the lungs of mice after intranasal infection with S. pneumoniae. Notably, the expression levels of MMP-9 in the infected lungs were significantly decreased after depletion of DCs suggesting the involvement of DCs in MMP-9 production during pneumococcal pneumonia. Thus, we propose that S. pneumoniae can exploit the DC-derived proteolysis to open tissue barriers thereby facilitating its own dissemination from the local site of infection.

  5. Pathogenesis of Pneumococcal Pneumonia in Cyclophosphamide-Induced Leukopenia in Mice

    OpenAIRE

    Wang, Erjian; Simard, Marie; Ouellet, Nathalie; Bergeron, Yves; Beauchamp, Denis; Bergeron, Michel G.

    2002-01-01

    Streptococcus pneumoniae pneumonia frequently occurs in leukopenic hosts, and most patients subsequently develop lung injury and septicemia. However, few correlations have been made so far between microbial growth, inflammation, and histopathology of pneumonia in specific leukopenic states. In the present study, the pathogenesis of pneumococcal pneumonia was investigated in mice rendered leukopenic by the immunosuppressor antineoplastic drug cyclophosphamide. Compared to the immunocompetent s...

  6. The economic burden of childhood invasive pneumococcal diseases and pneumonia in Taiwan: Implications for a pneumococcal vaccination program.

    Science.gov (United States)

    Ho, Yi-Chien; Lee, Pei-Lun; Wang, Yu-Chiao; Chen, Shiou-Chien; Chen, Kow-Tong

    2015-01-01

    Invasive pneumococcal disease (IPD) and pneumonia are the major causes of morbidity and deaths in children in the world. The management of IPD and pneumonia is an important economic burden on healthcare systems and families. The aim of this study was to assess the economic burden of IPD and pneumonia among younger children in Taiwan. We used a cost-illness approach to identify the cost categories for analysis in this study according to various perspectives. We obtained data of admission, outpatient, and emergency department visit data from the National Health Insurance Research (NHIR) database for children US dollars and were estimated by extrapolating 2008 cost data to 2013 price levels. We estimated the number of pneumococcal disease cases that were averted if the PCV-13 vaccine had been available in 2008. The total annual social and hospital costs for IPD were US $4.3 million and US $926,000, respectively. The total annual social and hospital costs for pneumonia were US $150 million and US $17 million, respectively. On average, families spent US $653 or US $218 when their child was diagnosed with IPD or pneumonia, respectively. This cost is approximately 27%-81% of the monthly salary of an unskilled worker. In conclusion, a safe and effective pediatric pneumococcal vaccine is needed to reduce the economic burden caused by pneumococcal infection. PMID:25874476

  7. Meningitis - pneumococcal

    Science.gov (United States)

    ... and older People at high risk for pneumococcus infection Alternative Names Pneumococcal meningitis Images Pneumococci organism Pneumococcal pneumonia References Swartz MN. Meningitis: bacterial, ...

  8. Severe pneumococcal pneumonia: impact of new quinolones on prognosis

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    Meybeck Agnes

    2011-03-01

    Full Text Available Abstract Background Most guidelines have been proposing, for more than 15 years, a β-lactam combined with either a quinolone or a macrolide as empirical, first-line therapy of severe community acquired pneumonia (CAP requiring ICU admission. Our goal was to evaluate the outcome of patients with severe CAP, focusing on the impact of new rather than old fluoroquinolones combined with β-lactam in the empirical antimicrobial treatments. Methods Retrospective study of consecutive patients admitted in a 16-bed general intensive care unit (ICU, between January 1996 and January 2009, for severe (Pneumonia Severity Index > or = 4 community-acquired pneumonia due to non penicillin-resistant Streptococcus pneumoniae and treated with a β-lactam combined with a fluoroquinolone. Results We included 70 patients of whom 38 received a β-lactam combined with ofloxacin or ciprofloxacin and 32 combined with levofloxacin. Twenty six patients (37.1% died in the ICU. Three independent factors associated with decreased survival in ICU were identified: septic shock on ICU admission (AOR = 10.6; 95% CI 2.87-39.3; p = 0.0004, age > 70 yrs. (AOR = 4.88; 95% CI 1.41-16.9; p = 0.01 and initial treatment with a β-lactam combined with ofloxacin or ciprofloxacin (AOR = 4.1; 95% CI 1.13-15.13; p = 0.03. Conclusion Our results suggest that, when combined to a β-lactam, levofloxacin is associated with lower mortality than ofloxacin or ciprofloxacin in severe pneumococcal community-acquired pneumonia.

  9. Influenza and pneumococcal pneumonia immunization. Protecting our high risk population.

    Science.gov (United States)

    Siegel, B R; Mahan, C S; Witte, J J; Janowski, H T

    1990-06-01

    Pneumonia and influenza (P & I) constitute Florida's sixth leading cause of death. The P & I death rate in 1987, 10.5 per 100,000, was the highest since 1978. Major target groups for one or both vaccines used in prevention, as recommended by the Immunization Practices Advisory Committee (ACIP), include persons with chronic diseases of the heart or lungs, residents of nursing homes and other chronic care facilities, and persons aged 65 and older. Despite well-defined recommendations, vaccine coverage rates in Florida are as low as 30% in persons greater than or equal to 65 years of age. Knowledge and attitude surveys demonstrate that low coverage among various population groups may be due largely to insufficient awareness and/or negative attitudes regarding pneumococcal and influenza vaccines. Conversely, recommendations by physicians and other health care providers are strongly associated with receiving either vaccine. If the incidence of P & I is to decrease substantively in Florida, much wider use of the vaccines must occur. Because so many high-risk patients depend on private physicians for health care, their role is critical to the success of Florida public health strategies to reverse P & I trends.

  10. Inhibition of Phosphodiesterase-4 during Pneumococcal Pneumonia Reduces Inflammation and Lung Injury in Mice.

    Science.gov (United States)

    Tavares, Luciana P; Garcia, Cristiana C; Vago, Juliana P; Queiroz-Junior, Celso M; Galvão, Izabela; David, Bruna A; Rachid, Milene A; Silva, Patrícia M R; Russo, Remo C; Teixeira, Mauro M; Sousa, Lirlândia P

    2016-07-01

    Pneumococcal pneumonia is a leading cause of mortality worldwide. The inflammatory response to bacteria is necessary to control infection, but it may also contribute to tissue damage. Phosphodiesterase-4 inhibitors, such as rolipram (ROL), effectively reduce inflammation. Here, we examined the impact of ROL in a pneumococcal pneumonia murine model. Mice were infected intranasally with 10(5)-10(6) CFU of Streptococcus pneumoniae, treated with ROL in a prophylactic or therapeutic schedule in combination, or not, with the antibiotic ceftriaxone. Inflammation and bacteria counts were assessed, and ex vivo phagocytosis assays were performed. ROL treatment during S. pneumoniae infection decreased neutrophil recruitment into lungs and airways and reduced lung injury. Prophylactic ROL treatment also decreased cytokine levels in the airways. Although modulation of inflammation by ROL ameliorated pneumonia, bacteria burden was not reduced. On the other hand, antibiotic therapy reduced bacteria without reducing neutrophil infiltration, cytokine level, or lung injury. Combined ROL and ceftriaxone treatment decreased lethality rates and was more efficient in reducing inflammation, by increasing proresolving protein annexin A1 (AnxA1) expression, and bacterial burden by enhancing phagocytosis. Lack of AnxA1 increased inflammation and lethality induced by pneumococcal infection. These data show that immunomodulatory effects of phosphodiesterase-4 inhibitors are useful during severe pneumococcal pneumonia and suggest their potential benefit as adjunctive therapy during infectious diseases. PMID:26677751

  11. 220D-F2 from Rubus ulmifolius kills Streptococcus pneumoniae planktonic cells and pneumococcal biofilms.

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    Sharmila J Talekar

    Full Text Available Streptococcus pneumoniae (pneumococcus forms organized biofilms to persist in the human nasopharynx. This persistence allows the pneumococcus to produce severe diseases such as pneumonia, otitis media, bacteremia and meningitis that kill nearly a million children every year. While bacteremia and meningitis are mediated by planktonic pneumococci, biofilm structures are present during pneumonia and otitis media. The global emergence of S. pneumoniae strains resistant to most commonly prescribed antibiotics warrants further discovery of alternative therapeutics. The present study assessed the antimicrobial potential of a plant extract, 220D-F2, rich in ellagic acid, and ellagic acid derivatives, against S. pneumoniae planktonic cells and biofilm structures. Our studies first demonstrate that, when inoculated together with planktonic cultures, 220D-F2 inhibited the formation of pneumococcal biofilms in a dose-dependent manner. As measured by bacterial counts and a LIVE/DEAD bacterial viability assay, 100 and 200 µg/ml of 220D-F2 had significant bactericidal activity against pneumococcal planktonic cultures as early as 3 h post-inoculation. Quantitative MIC's, whether quantified by qPCR or dilution and plating, showed that 80 µg/ml of 220D-F2 completely eradicated overnight cultures of planktonic pneumococci, including antibiotic resistant strains. When preformed pneumococcal biofilms were challenged with 220D-F2, it significantly reduced the population of biofilms 3 h post-inoculation. Minimum biofilm inhibitory concentration (MBIC50 was obtained incubating biofilms with 100 µg/ml of 220D-F2 for 3 h and 6 h of incubation. 220D-F2 also significantly reduced the population of pneumococcal biofilms formed on human pharyngeal cells. Our results demonstrate potential therapeutic applications of 220D-F2 to both kill planktonic pneumococcal cells and disrupt pneumococcal biofilms.

  12. 220D-F2 from Rubus ulmifolius kills Streptococcus pneumoniae planktonic cells and pneumococcal biofilms.

    Science.gov (United States)

    Talekar, Sharmila J; Chochua, Sopio; Nelson, Katie; Klugman, Keith P; Quave, Cassandra L; Vidal, Jorge E

    2014-01-01

    Streptococcus pneumoniae (pneumococcus) forms organized biofilms to persist in the human nasopharynx. This persistence allows the pneumococcus to produce severe diseases such as pneumonia, otitis media, bacteremia and meningitis that kill nearly a million children every year. While bacteremia and meningitis are mediated by planktonic pneumococci, biofilm structures are present during pneumonia and otitis media. The global emergence of S. pneumoniae strains resistant to most commonly prescribed antibiotics warrants further discovery of alternative therapeutics. The present study assessed the antimicrobial potential of a plant extract, 220D-F2, rich in ellagic acid, and ellagic acid derivatives, against S. pneumoniae planktonic cells and biofilm structures. Our studies first demonstrate that, when inoculated together with planktonic cultures, 220D-F2 inhibited the formation of pneumococcal biofilms in a dose-dependent manner. As measured by bacterial counts and a LIVE/DEAD bacterial viability assay, 100 and 200 µg/ml of 220D-F2 had significant bactericidal activity against pneumococcal planktonic cultures as early as 3 h post-inoculation. Quantitative MIC's, whether quantified by qPCR or dilution and plating, showed that 80 µg/ml of 220D-F2 completely eradicated overnight cultures of planktonic pneumococci, including antibiotic resistant strains. When preformed pneumococcal biofilms were challenged with 220D-F2, it significantly reduced the population of biofilms 3 h post-inoculation. Minimum biofilm inhibitory concentration (MBIC)50 was obtained incubating biofilms with 100 µg/ml of 220D-F2 for 3 h and 6 h of incubation. 220D-F2 also significantly reduced the population of pneumococcal biofilms formed on human pharyngeal cells. Our results demonstrate potential therapeutic applications of 220D-F2 to both kill planktonic pneumococcal cells and disrupt pneumococcal biofilms. PMID:24823499

  13. Vaccination for the control of childhood bacterial pneumonia - Haemophilus influenzae type b and pneumococcal vaccines

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    Diana C Otczyk

    2013-01-01

    Full Text Available Pneumonia in childhood is endemic in large parts of the world and in particular, in developing countries, as well as in many indigenous communities within developed nations. Haemophilus influenzae type b and Streptococcus pneumoniae conjugate vaccines are currently available against the leading bacterial causes of pneumonia.  The use of the vaccines in both industrialised and developing countries have shown a dramatic reduction in the burden of pneumonia and invasive disease in children.  However, the greatest threat facing pneumococcal conjugate vaccine effectiveness is serotype replacement.  The current vaccines provide serotype-specific, antibody–mediated protection against only a few of the 90+ capsule serotypes.  Therefore, there has been a focus in recent years to rapidly advance technologies that will result in broader disease coverage and more affordable vaccines that can be used in developing countries.  The next generation of pneumococcal vaccines have advanced to clinical trials.

  14. [Impact of vaccination on the epidemiology of childhood pneumonia].

    Science.gov (United States)

    Crisinel, Pierre-Alex

    2016-02-17

    The impact of vaccination on non-bacteremic Haemophilus influenza pneumonia is difficult to appreciate, in the absence of proper microbiological documentation. It has certainly been largely underestimated. Vaccination has reduced the incidence of pneumococcal pneumonia. However, the increase of incidence of empyema due to nonvaccine serotypes was observed in several countries. The replacement of Prevenar 7 by Prevenar 13 portends a decrease in the occurrence of these infections, but, unfortunately, without eliminating them completely.

  15. Changes in Childhood Pneumonia Hospitalizations by Race and Sex Associated with Pneumococcal Conjugate Vaccines.

    Science.gov (United States)

    Wiese, Andrew D; Grijalva, Carlos G; Zhu, Yuwei; Mitchel, Edward F; Griffin, Marie R

    2016-06-01

    Introduction of pneumococcal conjugate vaccines in the childhood immunization schedule was associated with decreases in all-cause pneumonia hospitalizations among black and white children in Tennessee, USA. Although racial disparities that existed before introduction of these vaccines have been substantially reduced, rates remain higher in boys than in girls among young children. PMID:27197048

  16. Recombinant activated protein C attenuates coagulopathy and inflammation when administered early in murine pneumococcal pneumonia

    NARCIS (Netherlands)

    M. Schouten; C. van 't Veer; J.J.T.H. Roelofs; B. Gerlitz; B.W. Grinnell; M. Levi; T. van der Poll

    2011-01-01

    Recombinant human activated protein C (APC), which has both anticoagulant and anti-inflammatory properties, improves survival of patients with severe sepsis. This beneficial effect is especially apparent in patients with pneumococcal pneumonia. Earlier treatment with APC in sepsis has been associate

  17. A Retrospective Study of the Clinical Burden of Hospitalized All-Cause and Pneumococcal Pneumonia in Canada

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    Shelly A. McNeil

    2016-01-01

    Full Text Available Background. Routine vaccination against Streptococcus pneumoniae is recommended in Canada for infants, the elderly, and individuals with chronic comorbidity. National incidence and burden of all-cause and pneumococcal pneumonia in Canada (excluding Quebec were assessed. Methods. Incidence, length of stay, and case-fatality rates of hospitalized all-cause and pneumococcal pneumonia were determined for 2004–2010 using ICD-10 discharge data from the Canadian Institutes for Health Information Discharge Abstract Database. Population-at-risk data were obtained from the Statistics Canada census. Temporal changes in pneumococcal and all-cause pneumonia rates in adults ≥65 years were analyzed by logistic regression. Results. Hospitalization for all-cause pneumonia was highest in children 70 years and declined significantly from 1766/100,000 to 1537/100,000 per year in individuals aged ≥65 years (P<0.001. Overall hospitalization for pneumococcal pneumonia also declined from 6.40/100,000 to 5.08/100,000 per year. Case-fatality rates were stable (11.6% to 12.3%. Elderly individuals had longer length of stay and higher case-fatality rates than younger groups. Conclusions. All-cause and pneumococcal pneumonia hospitalization rates declined between 2004 and 2010 in Canada (excluding Quebec. Direct and indirect effects from pediatric pneumococcal immunization may partly explain some of this decline. Nevertheless, the burden of disease from pneumonia remains high.

  18. The impact of heptavalent pneumococcal conjugate vaccine on the incidence of childhood community-acquired pneumonia and bacteriologically confirmed pneumococcal pneumonia in Japan.

    Science.gov (United States)

    Naito, S; Tanaka, J; Nagashima, K; Chang, B; Hishiki, H; Takahashi, Y; Oikawa, J; Nagasawa, K; Shimojo, N; Ishiwada, N

    2016-02-01

    Heptavalent pneumococcal conjugate vaccine (PCV7) was introduced to Japan in 2010. We investigated the impact of PCV7 on childhood community-acquired pneumonia (CAP) and pneumococcal pneumonia (PP). Children aged Japan, who were admitted to hospitals were enrolled to estimate the incidence of CAP based on the mid-year population. PP was determined by the presence of Streptococcus pneumoniae in cultured blood and/or sputum samples of CAP patients. The incidence of CAP and S. pneumoniae isolated from PP patients was compared before (April 2008-March 2009) and after (April 2012-March 2013) the introduction of PCV7 immunization. The annual incidence of CAP was reduced [incidence rate ratio 0·81, 95% confidence interval (CI) 0·73-0·90]. When comparing post-vaccine with pre-vaccine periods, the odds ratio for PP incidence was 0·60 (95% CI 0·39-0·93, P = 0·024). PCV7-covered serotypes markedly decreased (66·6% in pre-vaccine vs. 15·6% in post-vaccine, P culture-confirmed PP of vaccine serotypes was observed at 2 years after PCV7 vaccination. PMID:26122538

  19. Streptococcus pneumoniae colonisation in children and adolescents with asthma: impact of the heptavalent pneumococcal conjugate vaccine and evaluation of potential effect of thirteen-valent pneumococcal conjugate vaccine

    OpenAIRE

    Esposito, S.; L. Terranova; M.F. Patria; Marseglia, G L; Miraglia del Giudice, M; Bodini, A; Martelli, A.; Baraldi, E; O. Mazzina; Tagliabue, C.; A. Licari; V. Ierardi; M. Lelii; Principi, N

    2016-01-01

    Background The main aim of this study was to evaluate Streptococcus pneumoniae carriage in a group of school-aged children and adolescents with asthma because these results might indicate the theoretical risk of invasive pneumococcal disease (IPD) of such patients and the potential protective efficacy of the 13-valent pneumococcal conjugate vaccine (PCV13). Methods Oropharyngeal samples were obtained from 423 children with documented asthma (300 males, 70.9 %), and tested for the autolysin-A-...

  20. Pneumococcal pneumonia prevention among adults: is the herd effect of pneumococcal conjugate vaccination in children as good a way as the active immunization of the elderly?

    Science.gov (United States)

    Prato, Rosa; Fortunato, Francesca; Martinelli, Domenico

    2016-01-01

    The indirect protection of adults as a result of pneumococcal conjugate vaccination of infants has been discussed from different epidemiological points of view. In some countries, including Italy, even after pediatric vaccination, vaccine serotypes are still responsible for most pneumonia and invasive diseases in the elderly. Although the Community-Acquired Pneumonia Immunization Trial in Adults (CAPITA) produced encouraging results, it has not showed the efficacy of the 13-valent conjugate vaccine in preventing pneumococcal community-acquired pneumonia regardless of the number of episodes and serotype. Addressing these points by monitoring the direct impact of adult vaccination in real life distinguished from the effects of herd immunity will assist public health decision-making on the most effective adult pneumococcal vaccination strategies.

  1. Role of Nucleotide-Binding Oligomerization Domain-Containing (NOD 2 in Host Defense during Pneumococcal Pneumonia.

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    Tijmen J Hommes

    Full Text Available Streptococcus (S. pneumoniae is the most common causative pathogen in community-acquired pneumonia. Nucleotide-binding oligomerization domain-containing (NOD 2 is a pattern recognition receptor located in the cytosol of myeloid cells that is able to detect peptidoglycan fragments of S. pneumoniae. We here aimed to investigate the role of NOD2 in the host response during pneumococcal pneumonia. Phagocytosis of S. pneumoniae was studied in NOD2 deficient (Nod2-/- and wild-type (Wt alveolar macrophages and neutrophils in vitro. In subsequent in vivo experiments Nod2-/- and Wt mice were inoculated with serotype 2 S. pneumoniae (D39, an isogenic capsule locus deletion mutant (D39Δcps or serotype 3 S. pneumoniae (6303 via the airways, and bacterial growth and dissemination and the lung inflammatory response were evaluated. Nod2-/- alveolar macrophages and blood neutrophils displayed a reduced capacity to internalize pneumococci in vitro. During pneumonia caused by S. pneumoniae D39 Nod2-/- mice were indistinguishable from Wt mice with regard to bacterial loads in lungs and distant organs, lung pathology and neutrophil recruitment. While Nod2-/- and Wt mice also had similar bacterial loads after infection with the more virulent S. pneumoniae 6303 strain, Nod2-/- mice displayed a reduced bacterial clearance of the normally avirulent unencapsulated D39Δcps strain. These results suggest that NOD2 does not contribute to host defense during pneumococcal pneumonia and that the pneumococcal capsule impairs recognition of S. pneumoniae by NOD2.

  2. Pneumolysin in urine: A rapid antigen detection method to diagnose pneumococcal pneumonia in children

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    Rajalakshmi B

    2002-01-01

    Full Text Available PURPOSE: Etiological diagnosis of pneumococcal pneumonia is difficult in small children in whom blood culture cannot be done or who have already been started on antibiotics. A simple technique which can be applied at the bedside or in the outpatient department may help in obviating this problem. Detection of pneumolysin, a product of invasive pneumococci is being exploited as a diagnostic tool. METHODS: An attempt was made to detect this protein in urine of seventy children, clinically suspected and radiologically diagnosed cases of pneumonia. Seventy age and sex matched controls were included in the study. Purified pneumolysin was prepared from clinical isolates of invasive pneumococcal infections. This was used to raise polyclonal antisera in rabbits. The antisera was used to sensitise Cowan 1 Staphylococcus aureus (CoA. A slide agglutination was performed with 25 µL urine and equal quantity of the reagent. RESULTS: Results were compared with CoA reagent sensitised with antisera raised against a genetically derived pneumolysoid and capsular polysaccharide for antigen detection in the urine. Pneumolysin could be detected in 42.9% (30/70 urine samples from cases with pneumonia by the genetically derived antigen and in 37.1% samples by the in house prepared antigen, in contrast to 2.1% in healthy controls and 4.2% in children with infections other than pneumonia. The result was statistically significant. Detection of pneumolysin was slightly better than detection of capsular polysaccharide antigen in urine although the result was not statistically significant. Blood culture proved to be positive in only 29.5% cases. CONCLUSIONS: Pneumolysin detection in urine showed promising results and was found to be simple and rapid. It will help in quickening the diagnosis of pneumococcal pneumonia.

  3. Pneumococcal vaccine.

    OpenAIRE

    1999-01-01

    Streptococcus pneumoniae is a frequent cause of pneumonia and meningitis. This article looks at the pneumococcal vaccine, its uses, efficacy, and adverse effects and how vaccination may be improved. We also look at the role of the new conjugate vaccines.

  4. The Community-Acquired Pneumonia immunization Trial in Adults (CAPiTA) : What is the future of pneumococcal conjugate vaccination in elderly?

    NARCIS (Netherlands)

    Van Werkhoven, Cornelis H.; Bonten, Marc Jm

    2015-01-01

    Pneumococcal community-acquired pneumonia (PCAP) and invasive pneumococcal disease (IPD) are important causes of morbidity and mortality in elderly. In the Community-Acquired Pneumonia immunization Trial in Adults (CAPiTA), a randomized double-blind placebo-controlled trial of 84,496 community-dwell

  5. Pneumonia

    Science.gov (United States)

    ... better than treating it. Vaccines are available to prevent pneumococcal pneumonia and the flu. Other preventive measures include washing your hands frequently and not smoking. NIH: National Heart, Lung, and Blood Institute

  6. Failure of levofloxacin treatment in community-acquired pneumococcal pneumonia

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    Grossi Paolo

    2005-11-01

    Full Text Available Abstract Background Streptococcus pneumoniae is the leading cause of community-acquired pneumonia (CAP. High global incidence of macrolide and penicillin resistance has been reported, whereas fluoroquinolone resistance is uncommon. Current guidelines for suspected CAP in patients with co-morbidity factors and recent antibiotic therapy recommend initial empiric therapy using one fluoroquinolone or one macrolide associated to other drugs (amoxicillin, amoxicillin/clavulanate, broad-spectrum cephalosporins. Resistance to fluoroquinolones is determined by efflux mechanisms and/or mutations in the parC and parE genes coding for topoisomerase IV and/or gyrA and gyrB genes coding for DNA gyrase. No clinical cases due to fluoroquinolone-resistant S. pneumoniae strains have been yet reported from Italy. Case presentation A 72-year-old patient with long history of chronic obstructive pulmonary disease and multiple fluoroquinolone treatments for recurrent lower respiratory tract infections developed fever, increased sputum production, and dyspnea. He was treated with oral levofloxacin (500 mg bid. Three days later, because of acute respiratory insufficiency, the patient was hospitalized. Levofloxacin treatment was supplemented with piperacillin/tazobactam. Microbiological tests detected a S. pneumoniae strain intermediate to penicillin (MIC, 1 mg/L and resistant to macrolides (MIC >256 mg/L and fluoroquinolones (MIC >32 mg/L. Point mutations were detected in gyrA (Ser81-Phe, parE (Ile460-Val, and parC gene (Ser79-Phe; Lys137-Asn. Complete clinical response followed treatment with piperacillin/tazobactam. Conclusion This is the first Italian case of community-acquired pneumonia due to a fluoroquinolone-resistant S. pneumoniae isolate where treatment failure of levofloxacin was documented. Molecular analysis showed a group of mutations that have not yet been reported from Italy and has been detected only twice in Europe. Treatment with piperacillin

  7. Acute exposure of mice to high-dose ultrafine carbon black decreases susceptibility to pneumococcal pneumonia

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    Gordon Stephen

    2010-10-01

    Full Text Available Abstract Background Epidemiological studies suggest that inhalation of carbonaceous particulate matter from biomass combustion increases susceptibility to bacterial pneumonia. In vitro studies report that phagocytosis of carbon black by alveolar macrophages (AM impairs killing of Streptococcus pneumoniae. We have previously reported high levels of black carbon in AM from biomass smoke-exposed children and adults. We therefore aimed to use a mouse model to test the hypothesis that high levels of carbon loading of AM in vivo increases susceptibility to pneumococcal pneumonia. Methods Female outbred mice were treated with either intranasal phosphate buffered saline (PBS or ultrafine carbon black (UF-CB in PBS; 500 μg on day 1 and day 4, and then infected with S. pneumoniae strain D39 on day 5. Survival was assessed over 72 h. The effect of UF-CB on AM carbon loading, airway inflammation, and a urinary marker of pulmonary oxidative stress was assessed in uninfected animals. Results Instillation of UF-CB in mice resulted a pattern of AM carbon loading similar to that of biomass-smoke exposed humans. In uninfected animals, UF-CB treated animals had increased urinary 8-oxodG (P = 0.055, and an increased airway neutrophil differential count (P . pneumoniae, whereas morbidity and mortality after infection was reduced in UF-CB treated animals (median survival 48 h vs. 30 h, P . pneumoniae colony forming unit counts, and lower airway levels of keratinocyte-derived chemokine/growth-related oncogene (KC/GRO, and interferon gamma. Conclusion Acute high level loading of AM with ultrafine carbon black particles per se does not increase the susceptibility of mice to pneumococcal infection in vivo.

  8. Pneumococcal Vaccines

    OpenAIRE

    Chen-Fang Ho; Tzou-Yien Lin

    2005-01-01

    Streptococcus pneumoniae is the leading bacterial pathogen of infectious diseases inchildren and adolescents. The 23-valent pneumococcal polysaccharide vaccine could preventinvasive pneumococcal infection with broader serotype coverage but still has some limitations.On the other hand, 7-valent pneumococcal conjugate vaccine has been shown todecrease cases of nasopharyngeal acquired S. pneumoniae vaccine serotypes and provedherd immunity. The safety and efficacy against vaccine serotype pneumo...

  9. TNF-related apoptosis-inducing ligand (TRAIL) exerts therapeutic efficacy for the treatment of pneumococcal pneumonia in mice.

    Science.gov (United States)

    Steinwede, Kathrin; Henken, Stefanie; Bohling, Jennifer; Maus, Regina; Ueberberg, Bianca; Brumshagen, Christina; Brincks, Erik L; Griffith, Thomas S; Welte, Tobias; Maus, Ulrich A

    2012-10-22

    Apoptotic death of alveolar macrophages observed during lung infection with Streptococcus pneumoniae is thought to limit overwhelming lung inflammation in response to bacterial challenge. However, the underlying apoptotic death mechanism has not been defined. Here, we examined the role of the TNF superfamily member TNF-related apoptosis-inducing ligand (TRAIL) in S. pneumoniae-induced macrophage apoptosis, and investigated the potential benefit of TRAIL-based therapy during pneumococcal pneumonia in mice. Compared with WT mice, Trail(-/-) mice demonstrated significantly decreased lung bacterial clearance and survival in response to S. pneumoniae, which was accompanied by significantly reduced apoptosis and caspase 3 cleavage but rather increased necrosis in alveolar macrophages. In WT mice, neutrophils were identified as a major source of intraalveolar released TRAIL, and their depletion led to a shift from apoptosis toward necrosis as the dominant mechanism of alveolar macrophage cell death in pneumococcal pneumonia. Therapeutic application of TRAIL or agonistic anti-DR5 mAb (MD5-1) dramatically improved survival of S. pneumoniae-infected WT mice. Most importantly, neutropenic mice lacking neutrophil-derived TRAIL were protected from lethal pneumonia by MD5-1 therapy. We have identified a previously unrecognized mechanism by which neutrophil-derived TRAIL induces apoptosis of DR5-expressing macrophages, thus promoting early bacterial killing in pneumococcal pneumonia. TRAIL-based therapy in neutropenic hosts may represent a novel antibacterial treatment option.

  10. Serotype Distribution and Antimicrobial Resistance of Streptococcus pneumoniae prior to Introduction of the 10-Valent Pneumococcal Conjugate Vaccine in Brazil, 2000-2007: Pneumococcal Serotypes Prior to Conjugate Vaccine Introduction

    OpenAIRE

    Menezes, Ana Paula de O.; Campos, Leila C.; dos Santos, Milena S.; Azevedo, Jailton; dos Santos, Renan Cardoso Nery; Carvalho, Maria da Gloria S.; Beall, Bernard W.; Martin, Stacey W.; Salgado, Katia; Reis, Mitermayer G.; Ko, Albert I.; Reis, Joice N

    2010-01-01

    This study describes the serotype distribution and antibiotic resistance patterns among 397 S. pneumoniae meningitis case isolates recovered in Salvador, Brazil, during the period of 2000-2007, before introduction of the 10-valent pneumococcal conjugate vaccine.

  11. Impact of the factor V Leiden mutation on the outcome of pneumococcal pneumonia: a controlled laboratory study

    Science.gov (United States)

    2010-01-01

    Introduction Streptococcus (S.) pneumoniae is the most common cause of community-acquired pneumonia. The factor V Leiden (FVL) mutation results in resistance of activated FV to inactivation by activated protein C and thereby in a prothrombotic phenotype. Human heterozygous FVL carriers have been reported to be relatively protected against sepsis-related mortality. We here determined the effect of the FVL mutation on coagulation, inflammation, bacterial outgrowth and outcome in murine pneumococcal pneumonia. Methods Wild-type mice and mice heterozygous or homozygous for the FVL mutation were infected intranasally with 2*106 colony forming units of viable S. pneumoniae. Mice were euthanized after 24 or 48 hours or observed in a survival study. In separate experiments mice were treated with ceftriaxone intraperitoneally 24 hours after infection and euthanized after 48 hours or observed in a survival study. Results The FVL mutation had no consistent effect on activation of coagulation in either the presence or absence of ceftriaxone therapy, as reflected by comparable lung and plasma levels of thrombin-antithrombin complexes and fibrin degradation products. Moreover, the FVL mutation had no effect on lung histopathology, neutrophil influx, cytokine and chemokine levels or bacterial outgrowth. Remarkably, homozygous FVL mice were strongly protected against death due to pneumococcal pneumonia when treated with ceftriaxone, which was associated with more pronounced FXIII depletion; this protective effect was not observed in the absence of antibiotic therapy. Conclusions Homozygosity for the FVL mutation protects against lethality due to pneumococcal pneumonia in mice treated with antibiotics. PMID:20682036

  12. Effect of Ethanol on Fluoroquinolone Efficacy in a Rat Model of Pneumococcal Pneumonia

    Science.gov (United States)

    Olsen, Keith M.; Gentry-Nielsen, Martha; Yue, Mei; Snitily, Mary U.; Preheim, Laurel C.

    2006-01-01

    This investigation compared the effect of ethanol on fluoroquinolone antibiotic efficacy and pharmacodynamics in an ethanol-fed rat model of pneumococcal pneumonia. Male Sprague-Dawley rats received a liquid diet containing 36% of total calories as ethanol. Paired controls (pair-fed controls) were fed a liquid diet without ethanol or received rat chow. Diets began 7 days before and continued for 10 days after transtracheal infections with 10 times the 50% lethal dose of type 3 Streptococcus pneumoniae. Beginning 18 h after infection, the rats received once daily subcutaneous phosphate-buffered saline, levofloxacin, moxifloxacin, or trovafloxacin at 50 or 100 mg/kg of body weight. White blood cell counts were determined, blood samples were collected for culture, and mortality was recorded. Additional rats were killed on day 5 for pharmacodynamic studies and quantitative cultures of bronchoalveolar lavage fluid. Bacteremia occurred by day 3 in 20 of 22 untreated rats. All 22 untreated rats died by day 9. Moxifloxacin treatment was effective in all diet groups at both the 50- and 100-mg/kg doses. In contrast, 50-mg/kg doses of levofloxacin and trovafloxacin improved survival in ethanol-fed rats but were ineffective in chow-fed rats. High-dose trovafloxacin at 100 mg/kg was associated with increased mortality in pair-fed rats. The free-fraction area under the concentration-time curve/MIC ratio exceeded 50 with all antibiotics in the ethanol group but dropped below 30 with levofloxacin and trovafloxacin in the pair- and chow-fed rats, with higher mortality. Achievement of adequate antibiotic-free fraction area under the concentration-time curve/MIC ratios helps overcome ethanol-induced immune defects induced in experimental pneumococcal pneumonia. PMID:16377688

  13. Expression of activation-induced cytidine deaminase enhances the clearance of pneumococcal pneumonia: evidence of a subpopulation of protective anti-pneumococcal B1a cells.

    Science.gov (United States)

    Yamamoto, Natsuo; Kerfoot, Steven M; Hutchinson, Andrew T; Dela Cruz, Charles S; Nakazawa, Naomi; Szczepanik, Marian; Majewska-Szczepanik, Monika; Nazimek, Katarzyna; Ohana, Noboru; Bryniarski, Krzysztof; Mori, Tsutomu; Muramatsu, Masamichi; Kanemitsu, Keiji; Askenase, Philip W

    2016-01-01

    We describe a protective early acquired immune response to pneumococcal pneumonia that is mediated by a subset of B1a cells. Mice deficient in B1 cells (xid), or activation-induced cytidine deaminase (AID(-/-) ), or invariant natural killer T (iNKT) cells (Jα18(-/-) ), or interleukin-13 (IL-13(-/-) ) had impaired early clearance of pneumococci in the lung, compared with wild-type mice. In contrast, AID(-/-) mice adoptively transferred with AID(+/+) B1a cells, significantly cleared bacteria from the lungs as early as 3 days post infection. We show that this early bacterial clearance corresponds to an allergic contact sensitivity-like cutaneous response, probably due to a subpopulation of initiating B1a cells. In the pneumonia model, these B1a cells were found to secrete higher affinity antigen-specific IgM. In addition, as in contact sensitivity, iNKT cells were required for the anti-pneumococcal B1a cell initiating response, probably through early production of IL-13, given that IL-13(-/-) mice also failed to clear infection. Our study is the first to demonstrate the importance of AID in generating an appropriate B1a cell response to pathogenic bacteria. Given the antibody affinity and pneumonia resistance data, natural IgM produced by conventional B1a cells are not responsible for pneumonia clearance compared with the AID-dependent subset. PMID:26456931

  14. Long-Term Effects of Pneumococcal Conjugate Vaccine on Nasopharyngeal Carriage of S. pneumoniae, S. aureus, H. influenzae and M. catarrhalis

    NARCIS (Netherlands)

    Spijkerman, Judith; Prevaes, Sabine M. P. J.; van Gils, Elske J. M.; Veenhoven, Reinier H.; Bruin, Jacob P.; Bogaert, Debby; Wijmenga-Monsuur, Alienke J.; van den Dobbelsteen, Germie P. J. M.; Sanders, Elisabeth A. M.

    2012-01-01

    Background: Shifts in pneumococcal serotypes following introduction of 7-valent pneumococcal conjugate vaccine (PCV-7) may alter the presence of other bacterial pathogens co-inhabiting the same nasopharyngeal niche. Methodology/Principal Findings: Nasopharyngeal prevalence rates of S. pneumoniae, S.

  15. Gestational Hypothyroidism Improves the Ability of the Female Offspring to Clear Streptococcus pneumoniae Infection and to Recover From Pneumococcal Pneumonia.

    Science.gov (United States)

    Nieto, Pamela A; Peñaloza, Hernán F; Salazar-Echegarai, Francisco J; Castellanos, Raquel M; Opazo, Maria Cecilia; Venegas, Luis; Padilla, Oslando; Kalergis, Alexis M; Riedel, Claudia A; Bueno, Susan M

    2016-06-01

    Maternal thyroid hormones are essential for proper fetal development. A deficit of these hormones during gestation has enduring consequences in the central nervous system of the offspring, including detrimental learning and impaired memory. Few studies have shown that thyroid hormone deficiency has a transient effect in the number of T and B cells in the offspring gestated under hypothyroidism; however, there are no studies showing whether maternal hypothyroidism during gestation impacts the response of the offspring to infections. In this study, we have evaluated whether adult mice gestated in hypothyroid mothers have an altered response to pneumococcal pneumonia. We observed that female mice gestated in hypothyroidism have increased survival rate and less bacterial dissemination to blood and brain after an intranasal challenge with Streptococcus pneumoniae. Further, these mice had higher amounts of inflammatory cells in the lungs and reduced production of cytokines characteristic of sepsis in spleen, blood, and brain at 48 hours after infection. Interestingly, mice gestated in hypothyroid mothers had basally increased vascular permeability in the lungs. These observations suggest that gestational hypothyroidism alters the immune response and the physiology of lungs in the offspring, increasing the resistance to respiratory bacterial infections. PMID:27035652

  16. Increased Risk of Acute Kidney Injury following Pneumococcal Pneumonia: A Nationwide Cohort Study

    Science.gov (United States)

    Lin, Te-Yu; Chen, Yu-Guang; Lin, Cheng-Li; Kao, Chia-Hung

    2016-01-01

    Purpose Pneumococcal disease leads to renal complications ranging from persistent proteinuria to end-stage renal disease. Studies on the association between pneumococcal pneumonia (PP) and acute kidney injury (AKI) are scant. This study assessed the relationship between PP and risk of AKI. Methods This nationwide population-based cohort study examined data from the Taiwan National Health Insurance Research Database for the period 2000–2011. We identified inpatients with newly diagnosed PP according to the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes. In addition, we selected a comparison cohort from inpatient claims without the diagnosis of PP that was randomly frequency-matched with the PP cohort according to age, sex, index year and comorbidities. We analyzed the risks of AKI by using Cox proportional hazards regression models, adjusted for sex, age, and comorbidities. Results A total of 10,069 patients with PP and 10,069 controls were enrolled in this study. After adjustments for age, sex, and comorbidities, patients with PP had a 1.11-fold risk of developing AKI compared with the comparison cohort. Conclusion This study indicates that AKI risks are higher in patients with PP compared with the comparison cohort. Careful follow-up observation and aggressive treatment are necessary for patients with PP to reduce the risk of AKI. PMID:27362355

  17. Serological diagnosis of pneumococcal infection in children with pneumonia using protein antigens: A study of cut-offs with positive and negative controls.

    Science.gov (United States)

    Andrade, Dafne Carvalho; Borges, Igor Carmo; Ivaska, Lauri; Peltola, Ville; Meinke, Andreas; Barral, Aldina; Käyhty, Helena; Ruuskanen, Olli; Nascimento-Carvalho, Cristiana Maria

    2016-06-01

    The etiological diagnosis of infection by Streptococcus pneumoniae in children is difficult, and the use of indirect techniques is frequently warranted. We aimed to study the use of pneumococcal proteins for the serological diagnosis of pneumococcal infection in children with pneumonia. We analyzed paired serum samples from 13 Brazilian children with invasive pneumococcal pneumonia (positive control group) and 23 Finnish children with viral pharyngitis (negative control group), all aged pharyngitis were evaluated for oropharyngeal colonization, and none of them carried S. pneumoniae. We used a multiplex bead-based assay with eight proteins: Ply, CbpA, PspA1 and 2, PcpA, PhtD, StkP and PcsB. The optimal cut-off for increase in antibody level for the diagnosis of pneumococcal infection was determined for each antigen by ROC curve analysis. The positive control group had a significantly higher rate of ≥2-fold rise in antibody levels against all pneumococcal proteins, except Ply, compared to the negative controls. The cut-off of ≥2-fold increase in antibody levels was accurate for pneumococcal infection diagnosis for all investigated antigens. However, there was a substantial increase in the accuracy of the test with a cut-off of ≥1.52-fold rise in antibody levels for PcpA. When using the investigated protein antigens for the diagnosis of pneumococcal infection, the detection of response against at least one antigen was highly sensitive (92.31%) and specific (91.30%). The use of serology with pneumococcal proteins is a promising method for the diagnosis of pneumococcal infection in children with pneumonia. The use of a ≥2-fold increase cut-off is adequate for most pneumococcal proteins. PMID:26928648

  18. Impacto da vacina conjugada contra Streptococcus pneumoniae em doenças invasivas Impact of pneumococcal conjugate vaccine on the prevention of invasive pneumococcal diseases

    Directory of Open Access Journals (Sweden)

    Lucia Ferro Bricks

    2006-07-01

    Full Text Available OBJETIVOS: Rever os estudos que avaliam o impacto da vacina conjugada 7-valente na incidência de doenças invasivas por pneumococo e analisar o possível impacto dessa vacina no Brasil. FONTE DE DADOS:Foram pesquisadas as bases de dados MEDLINE, LILACS, Cochrane Database Reviews (janeiro de 2000 a janeiro de 2006, selecionando-se para análise os artigos contendo as seguintes palavras-chave: Streptococcus pneumoniae, pneumococo, vacina conjugada, resistência, antibióticos e meningite. Também foi realizada busca de informações sobre o tema nos sites do Centers for Disease Control, Ministério da Saúde e Centro de Vigilância Epidemiológica do Estado de São Paulo. SÍNTESE DOS DADOS: A vacina conjugada 7-valente reduziu a incidência de doenças invasivas por pneumococo, número de consultas por doenças respiratórias de vias aéreas superiores e inferiores, consumo de antibióticos e incidência de doenças invasivas por pneumococo por cepas resistentes a antibióticos não apenas nas crianças vacinadas, como em adultos e idosos. No Brasil, os coeficientes de incidência de doenças invasivas por pneumococo em crianças menores de 5 anos são elevados, a taxa de letalidade de meningites pneumocócicas é alta e as taxas de resistência parcial e plena à penicilina aumentaram substancialmente nos últimos 5 anos. CONCLUSÕES:Devido aos benefícios diretos e indiretos do uso em larga escala da vacina conjugada 7-valente, essa vacina deve ser incluída no calendário básico de imunização do Brasil.OBJECTIVES: To evaluate the impact of heptavalent pneumococcal conjugate vaccine in invasive pneumococcal diseases in the United States, and to analyze the potential impact of this vaccine in Brazil. SOURCES OF DATA: MEDLINE, LILACS, Cochrane Database Reviews, as well as the websites of the Centers for Disease Control and Prevention (CDC, Brazilian Ministry of Health and Centro de Vigilância Epidemiológica do Estado de São Paulo from

  19. Austrian's syndrome: The first described case of pneumococcal meningitis pneumonia and endocarditis in an injecting drug user.

    Science.gov (United States)

    Beadsworth, Mike B J; Wooton, Dan; Chenzbraun, Adrian; Beeching, Nick J

    2007-12-01

    We describe the first reported case of Austrian's syndrome in an injecting drug user (IDU). The triad of endocarditis, meningitis and pneumonia caused by invasive pneumococcal disease (IPD) is most commonly associated with excess alcohol. Injecting drug use is a recognised risk factor for IPD, whose prevalence and resistance continue to rise. We propose that injecting drug use is associated with Austrian's syndrome and that it should at least be considered in 'at risk' groups presenting with IPD. Furthermore, IDU presenting with IPD, meningitis and pneumonia should be considered for echocardiography.

  20. Economic aspects of hospital treated pneumococcal pneumonia and the results of Pneumo 23 vaccine use in Serbia

    Directory of Open Access Journals (Sweden)

    Adžić Tatjana

    2008-01-01

    Full Text Available INTRODUCTION In Serbia, there is a significant number of persons suffering of pneumococcal pneumonia. Persons aged 65 years or older, immunocompromised patients, patients with co-morbidities, such as chronic obstructive lung disease and congestive heart failure, are at the highest risk for developing pneumococcal pneumonia. Most of the patients are treated empirically, although it is often overlooked that Streptococcus pneumoniae can be resistant to the used antibiotics. The treatment costs of such inpatients and outpatients are very high. In Serbia, immunization of persons at risk to develop the diseases caused by Streptococcus pneumoniae is carried out using pneumococcus polysaccharide vaccine according to clinical indications. The exact number of immunized persons and the total number of registered patients are still unknown, but it is certain of being unjustifiably low. OBJECTIVE The goal of the study was to investigate, during a one-year period, the number and basic characteristics of persons hospitably treated for pneumonia, the type of cause of the infection, applied antibiotic medications, duration and costs of hospital treatment at the Institute for Lung Diseases and Tuberculosis of the Clinical Centre of Serbia in Belgrade. METHOD We retrospectively analyzed the medical records of patients with pneumonia treated at the Institute for Lung Diseases and Tuberculosis of the Clinical Centre of Serbia in Belgrade during 2006. RESULTS During the observed one-year period, 290 patients underwent hospital treatment, of whom the cause of the infection was confirmed in 116 (40%. The average duration of hospitalization was 12 days, with treatment cost of 32,031.74 RSD (402.42 EUR per patient. The treatment cost per patient including general and intensive care was 18,290.01 RSD (229.78 EUR. The distribution cost of Pneumo 23 vaccine in Serbia, without purchase tax, was 746.90 RSD (9.38 EUR. CONCLUSION Pneumococcal pneumonia is a significant medical

  1. Impacto de la bacteriemia en una cohorte de pacientes con neumonía neumocócica Impact of bacteremia in a cohort of patients with pneumococcal pneumonia

    Directory of Open Access Journals (Sweden)

    Ileana Palma

    2012-08-01

    vaccination (PV. METHODS: Secondary analysis of a cohort of patients with pneumococcal CAP confirmed by blood culture, sputum culture, or urinary antigen testing. Demographic, clinical, radiographic, and biochemical data were collected, as were Acute Physiology and Chronic Health Evaluation II (APACHE II and pneumonia severity index (PSI scores, comorbidities, and PV history. We drew comparisons between patients with bacteremic pneumococcal CAP (BPP and those with non-bacteremic pneumococcal CAP (NBPP. RESULTS: Forty-seven patients had BPP, and 71 had NBPP (confirmed by sputum culture in 45 and by urinary antigen testing in 26; 107 had some indication for PV. None of the BPP patients had received PV, compared with 9 of the NBPP patients (p = 0.043. Among the BPP patients, the mean age was higher (76.4 ± 11.5 vs. 67.5 ± 20.9 years, as were APACHE II and PSI scores (16.4 ± 4.6 vs. 14.1 ± 6.5 and 129.5 ± 36 vs. 105.2 ± 45, respectively, as well as the rate of ICU admission for cardiopathy or chronic renal failure (42.5% vs. 22.5%, whereas hematocrit and plasma sodium levels were lower (35.7 ± 5.8 vs. 38.6 ± 6.7% and 133.9 ± 6.0 vs. 137.1 ± 5.5 mEq/L, respectively, although mortality was similar (29.8% vs. 28.2%. CONCLUSIONS: In this population at high risk for CAP due to S. pneumoniae, the PV rate was extremely low (8.4%. Although BPP patients were more severely ill, mortality was similar between the two groups. Because PV reduces the incidence of BPP, the vaccination rate in at-risk populations should be increased.

  2. Immunization with Pneumococcal Polysaccharide Serotype 3 and Lipopolysaccharide Modulates Lung and Liver Inflammation during a Virulent Streptococcus pneumoniae Infection in Mice

    OpenAIRE

    Restori, Katherine H.; Kennett, Mary J.; Ross, A. Catharine

    2013-01-01

    Vaccination reduces morbidity and mortality from pneumonia, but its effect on the tissue-level response to infection is still poorly understood. We evaluated pneumonia disease progression, acute-phase response, and lung gene expression profiles in mice inoculated intranasally with virulent Gram-positive Streptococcus pneumoniae serotype 3 (ST 3) with and without prior immunization with pneumococcal polysaccharide ST 3 (PPS3) or after coimmunization with PPS3 and a low dose of lipopolysacchari...

  3. Multiple colonization with S. pneumoniae before and after introduction of the seven-valent conjugated pneumococcal polysaccharide vaccine.

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    Silvio D Brugger

    Full Text Available BACKGROUND: Simultaneous carriage of more than one strain of Streptococcus pneumoniae promotes horizontal gene transfer events and may lead to capsule switch and acquisition of antibiotic resistance. We studied the epidemiology of cocolonization with S. pneumoniae before and after introduction of the seven-valent conjugated pneumococcal vaccine (PCV7. METHODOLOGY: Nasopharyngeal swabs (n 1120 were collected from outpatients between 2004 and 2009 within an ongoing nationwide surveillance program. Cocolonization was detected directly from swabs by restriction fragment length polymorphism (RFLP analysis. Serotypes were identified by agglutination, multiplex PCR and microarray. PRINCIPAL FINDINGS: Rate of multiple colonization remained stable up to three years after PCV7 introduction. Cocolonization was associated with serotypes of low carriage prevalence in the prevaccine era. Pneumococcal colonization density was higher in cocolonized samples and cocolonizing strains were present in a balanced ratio (median 1.38. Other characteristics of cocolonization were a higher frequency at young age, but no association with recurrent acute otitis media, recent antibiotic exposure, day care usage and PCV7 vaccination status. CONCLUSIONS: Pneumococcal cocolonization is dominated by serotypes of low carriage prevalence in the prevaccine era, which coexist in the nasopharynx. Emergence of such previously rare serotypes under vaccine selection pressure may promote cocolonization in the future.

  4. Evolution of antimicrobial resistance and serotype distribution of Streptococcus pneumoniae isolated from children with invasive and noninvasive pneumococcal diseases in Algeria from 2005 to 2012.

    Science.gov (United States)

    Ramdani-Bouguessa, N; Ziane, H; Bekhoucha, S; Guechi, Z; Azzam, A; Touati, D; Naim, M; Azrou, S; Hamidi, M; Mertani, A; Laraba, A; Annane, T; Kermani, S; Tazir, M

    2015-07-01

    Pneumococcal infections are a major cause of morbidity and mortality in developing countries. The introduction of pneumococcal conjugate vaccines (PCVs) has dramatically reduced the incidence of pneumococcal diseases. PCVs are not currently being used in Algeria. We conducted a prospective study from 2005 to 2012 in Algeria to determine antimicrobial drug resistance and serotype distribution of Streptococcus pneumoniae from children with pneumococcal disease. Among 270 isolated strains from children, 97 (36%) were invasive disease; of these, 48% were not susceptible to penicillin and 53% not susceptible to erythromycin. A high rate of antimicrobial nonsusceptibility was observed in strains isolated from children with meningitis. The serotype distribution from pneumococci isolated from children with invasive infections was (by order of prevalence): 14, 1, 19F, 19A, 6B, 5, 3, 6A and 23F. Multidrug resistance was observed in serotypes 14, 19F, 19A and 6B. The vaccine coverage of serotypes isolated from children aged <5 years was 55.3% for PCV7, 71.1% for PCV10 and 86.8% for PCV13. Our results highlight the burden of pneumococcal disease in Algeria and the increasing S. pneumoniae antibiotic resistance. The current pneumococcal vaccines cover a high percentage of the circulating strains. Therefore, vaccination would reduce the incidence of pneumococcal disease in Algeria. PMID:26106481

  5. Evolution of antimicrobial resistance and serotype distribution of Streptococcus pneumoniae isolated from children with invasive and noninvasive pneumococcal diseases in Algeria from 2005 to 2012

    Directory of Open Access Journals (Sweden)

    N. Ramdani-Bouguessa

    2015-07-01

    Full Text Available Pneumococcal infections are a major cause of morbidity and mortality in developing countries. The introduction of pneumococcal conjugate vaccines (PCVs has dramatically reduced the incidence of pneumococcal diseases. PCVs are not currently being used in Algeria. We conducted a prospective study from 2005 to 2012 in Algeria to determine antimicrobial drug resistance and serotype distribution of Streptococcus pneumoniae from children with pneumococcal disease. Among 270 isolated strains from children, 97 (36% were invasive disease; of these, 48% were not susceptible to penicillin and 53% not susceptible to erythromycin. A high rate of antimicrobial nonsusceptibility was observed in strains isolated from children with meningitis. The serotype distribution from pneumococci isolated from children with invasive infections was (by order of prevalence: 14, 1, 19F, 19A, 6B, 5, 3, 6A and 23F. Multidrug resistance was observed in serotypes 14, 19F, 19A and 6B. The vaccine coverage of serotypes isolated from children aged <5 years was 55.3% for PCV7, 71.1% for PCV10 and 86.8% for PCV13. Our results highlight the burden of pneumococcal disease in Algeria and the increasing S. pneumoniae antibiotic resistance. The current pneumococcal vaccines cover a high percentage of the circulating strains. Therefore, vaccination would reduce the incidence of pneumococcal disease in Algeria.

  6. CCAAT/enhancer-binding protein δ facilitates bacterial dissemination during pneumococcal pneumonia in a platelet-activating factor receptor-dependent manner

    OpenAIRE

    Duitman, JanWillem; Schouten, Marcel; Groot, Angelique P.; Borensztajn, Keren S.; Daalhuisen, Joost B.; Florquin, Sandrine; van der Poll, Tom; Spek, C Arnold

    2012-01-01

    CCAAT/enhancer-binding protein δ (C/EBPδ) recently emerged as an essential player in the inflammatory response to bacterial infections. C/EBPδ levels increase rapidly after a proinflammatory stimulus, and increasing C/EBPδ levels seem to be indispensable for amplification of the inflammatory response. Here we aimed to elucidate the role of C/EBPδ in host defense in community-acquired pneumococcal pneumonia. We show that C/EBPδ−/− mice are relatively resistant to pneumococcal pneumonia, as ind...

  7. Is 13-Valent Pneumococcal Conjugate Vaccine (PCV13) Combined With 23-Valent Pneumococcal Polysaccharide Vaccine (PPSV23) Superior to PPSV23 Alone for Reducing Incidence or Severity of Pneumonia in Older Adults? A Clin-IQ

    Science.gov (United States)

    Hayward, Starla; Thompson, Lou Ann; McEachern, Andrea

    2016-01-01

    Pneumonia infection is a significant cause of morbidity and mortality worldwide. In addition to the public health concerns, pneumonia also accounts for a significant cost to the health care system. Currently there are two leading vaccines targeted against S. pneumoniae: 23-valent pneumococcal polysaccharide vaccine (PPSV23) and 13-valent pneumococcal conjugate vaccine (PCV13). Until recently the recommendation for adult pneumonia vaccination has been a single dose of PPSV23 for all adults 65 years and older. However, concerns were raised regarding the vaccine’s efficacy due to the persistent burden of pneumococcal disease in the elderly population. This paper focuses on two trials which evaluate the safety and efficacy of PCV13 in the adult population. The first study reveals improved immune response with the addition of PCV13 to PPSV23, while the second shows PCV13 was effective in the prevention of vaccine-type community-acquired pneumonia. The two studies observed adequate safety profiles for PCV13 in series with PPSV23 and with PCV13 compared to placebo. PMID:27376105

  8. Is 13-Valent Pneumococcal Conjugate Vaccine (PCV13 Combined With 23-Valent Pneumococcal Polysaccharide Vaccine (PPSV23 Superior to PPSV23 Alone for Reducing Incidence or Severity of Pneumonia in Older Adults? A Clin-IQ

    Directory of Open Access Journals (Sweden)

    Starla Hayward

    2016-04-01

    Full Text Available Pneumonia infection is a significant cause of morbidity and mortality worldwide. In addition to the public health concerns, pneumonia also accounts for a significant cost to the health care system. Currently there are two leading vaccines targeted against Streptococcus pneumoniae: 23-valent pneumococcal polysaccharide vaccine (PPSV23 and 13-valent pneumococcal conjugate vaccine (PCV13. Until recently, the recommendation for adult pneumonia vaccination has been a single dose of PPSV23 for all adults aged 65 years or older. However, concerns were raised regarding the vaccine’s efficacy due to the persistent burden of pneumococcal disease in the elderly population. This paper focuses on two trials that evaluated the safety and efficacy of PCV13 in the adult population. The first study reveals improved immune response with the addition of PCV13 to PPSV23, while the second shows PCV13 was effective in the prevention of vaccine-type community-acquired pneumonia. Both studies observed adequate safety profiles for PCV13 in series with PPSV23 and with PCV13 compared to placebo.

  9. Towards Better Evaluation of Pneumococcal Vaccines

    OpenAIRE

    Madhi, Shabir A; Heera, Jayvant R.; Locadiah Kuwanda; Klugman, Keith P.

    2005-01-01

    BACKGROUND: Pneumonia remains the leading cause of death in young children. The poor specificity of chest radiographs (CXRs) to diagnose pneumococcal pneumonia may underestimate the efficacy of pneumococcal conjugate vaccine in preventing pneumococcal pneumonia. METHODS AND FINDINGS: The efficacy of nine-valent pneumococcal conjugate vaccine among children not infected with HIV (21%; 95% confidence interval, 1%-37%) increased when CXR-confirmed pneumonia was associated with serum C-reactive p...

  10. Clinical and epidemiological characteristics of severe community-acquired pneumonia in children after introduction of the 10-valent pneumococcal vaccine

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    Lima EJF

    2015-08-01

    Full Text Available Eduardo JF Lima,1,2 Maria JG Mello,1,2 Maria FPM Albuquerque,3 Maria IL Lopes,4 George HC Serra,2 Maria AZ Abreu-Lima,2 Jailson B Correia1 1Instituto de Medicina Integral Prof. Fernando Figueira - IMIP Recife; 2Faculdade, Pernambucana de Saúde - FPS Recife; 3Centro de Pesquisas Aggeu Magalhães, FIOCRUZ; 4Hospital das Clínicas, Universidade Federal de Pernambuco - UFPE, Recife, Pernambuco, Brazil Background: Pneumonia is an important cause of morbimortality in Brazil, despite the extensive vaccination coverage and the socioeconomic improvement in the past years. Objective: To describe the epidemiological and clinical characteristics of severe community-acquired pneumonia in children after the introduction of the 10-valent pneumococcal conjugate vaccine (PCV10. Methods: A prospective study included children <5 years old hospitalized for pneumonia between October 2010 and September 2013 in a tertiary hospital. Newborns and children with comorbidities were excluded. Pneumonia classification followed the clinical and radiological criteria established by World Health Organization (WHO. Clinical history, nutritional status, immunizations, diagnosis, disease course, and prognosis were analyzed. Results: Among 452 children, almost 70% were <2 years, with no sex differences, and 10% had weight-for-age z score below than -2.0. Family income was up to one minimum wage in half the households, and 40% of mothers had completed high school. The suitability of both influenza and PCV10 vaccine schedules was ~50%. The first medical care happened later than 72 hours after the onset of symptoms in 42% of cases. Pneumonia was classified as severe or very severe in 83.9% of patients and for 23% as complicated. Global mortality was 1.5%. Hypoxia, diagnosed in 51.5% of children, looked like a better prognosis predictor than the WHO classification. Conclusion: New strategies for health care are necessary, such as the incorporation of peripheral saturometry as the

  11. How Can Pneumonia Be Prevented?

    Science.gov (United States)

    ... page from the NHLBI on Twitter. How Can Pneumonia Be Prevented? Pneumonia can be very serious and ... t last as long Fewer serious complications Pneumococcal Pneumonia Vaccine A vaccine is available to prevent pneumococcal ...

  12. 220D-F2 from Rubus ulmifolius Kills Streptococcus pneumoniae Planktonic Cells and Pneumococcal Biofilms

    OpenAIRE

    Sharmila J Talekar; Sopio Chochua; Katie Nelson; Klugman, Keith P.; Quave, Cassandra L; Vidal, Jorge E.

    2014-01-01

    Streptococcus pneumoniae (pneumococcus) forms organized biofilms to persist in the human nasopharynx. This persistence allows the pneumococcus to produce severe diseases such as pneumonia, otitis media, bacteremia and meningitis that kill nearly a million children every year. While bacteremia and meningitis are mediated by planktonic pneumococci, biofilm structures are present during pneumonia and otitis media. The global emergence of S. pneumoniae strains resistant to most commonly prescribe...

  13. Streptococcus pneumoniae meningitis in Alberta pre- and postintroduction of the 7-valent pneumococcal conjugate vaccine

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    Jennie Johnstone

    2011-01-01

    Full Text Available The objective of this study was to describe the epidemiology, clinical characteristics, microbiology and outcomes of patients of all ages with Streptococcus pneumoniae meningitis between 2000 and 2004; two years pre- and postintroduction of an S pneumoniae 7-valent conjugate vaccine program in Alberta in children younger than two years of age. The high mortality rate associated with S pneumoniae meningitis, despite appropriate therapy, suggests that prevention of S pneumoniae meningitis is critical. Despite implementation of a PCV-7 program in Alberta, rates of S pneumoniae meningitis in children younger than two years of age is still high. Thus, continued research into safe and efficacious vaccines covering a broader range of S pneumoniae serotypes is necessary.

  14. The gut microbiota plays a protective role in the host defence against pneumococcal pneumonia

    OpenAIRE

    Schuijt, T. J.; Lankelma, J.M.; Scicluna, B.P.; Melo, E; Roelofs, J.J.; Boer, de, J.W.; Hoogendijk, A.J.; Beer, de, VHJ Vincent; De Vos; Belzer, C.; Poll, van der, T.; Wiersinga, W.J.

    2015-01-01

    OBJECTIVE: Pneumonia accounts for more deaths than any other infectious disease worldwide. The intestinal microbiota supports local mucosal immunity and is increasingly recognised as an important modulator of the systemic immune system. The precise role of the gut microbiota in bacterial pneumonia, however, is unknown. Here, we investigate the function of the gut microbiota in the host defence against Streptococcus pneumoniae infections. DESIGN: We depleted the gut microbiota in C57BL/6 mice ...

  15. The Experience of 28 Cases of Clinical Treatment of Pneumococcal Pneumonia%28例肺炎球菌肺炎的临床治疗体会

    Institute of Scientific and Technical Information of China (English)

    徐翠华

    2015-01-01

    Objective To investigate the treatment of pneumococcal pneumonia.Methods28 cases of pneumococcal pneumonia patients in May 2012 to September admitted to data analysis. Results28 patients were cured and discharged without complications.Conclusion The diagnosis should be used immediately after symptomatic patients for drugs to stop the disease continues to spread.%目的:探讨肺炎球菌肺炎的治疗体会。方法对2012年5~9月收治的28例肺炎球菌肺炎患者资料进行分析。结果28例患者均治愈出院,无并发症发生。结论确诊后应立即使用对症、适合的药品制止患者病情的发展。

  16. Impact of 13-Valent Pneumococcal Conjugate Vaccination on Streptococcus pneumoniae Carriage in Young Children in Massachusetts

    Science.gov (United States)

    Lee, Grace M.; Kleinman, Ken; Pelton, Stephen I.; Hanage, William; Huang, Susan S.; Lakoma, Matthew; Dutta-Linn, Maya; Croucher, Nicholas J.; Stevenson, Abbie; Finkelstein, Jonathan A.

    2014-01-01

    Background In April 2010, a 13-valent pneumococcal conjugate vaccine (PCV13) replaced PCV7 for use in the United States. We evaluated rates of pneumococcal colonization, by serotype and antibiotic resistance, in Massachusetts communities where serial cross-sectional surveillance has been conducted for the past decade. Methods Nasopharyngeal swabs were obtained from children 0 to <7 years of age and seen by primary care providers for well child or acute illness visits in 2001, 2004, 2007, 2009, and 2011. Pneumococcal isolates were serotyped by Quellung reaction and classified as PCV7 serotypes (4, 6B, 9V, 14, 18C, 19F, 23F), additional PCV13 serotypes (1, 3, 5, 6A, 7F, 19A), or non-PCV13 serotypes. Changes in colonization and impact of PCV13 were assessed using generalized linear mixed models, adjusting for known risk factors and accounting for clustering by community. Results Introduction of PCV13 did not affect the rate of overall pneumococcal colonization (31% in 2011). Colonization with non-PCV13 serotypes increased between 2001 and 2011 for all children (odds ratio [OR] per year, 1.12; 95% confidence interval [CI], 1.10, 1.15; P < .0001). 19A remained the second most common serotype in 2011, although a decline from 2009 was observed. Penicillin (7%), erythromycin (28%), ceftriaxone (10%), and clindamycin (10%) nonsusceptibility were commonly identified, concentrated among a small number of serotypes (including 19A, 35B, 15B/C, and 15A). Among healthy children 6–23 months old, colonization with PCV13 serotypes was lower among recipients of PCV13 vaccine (adjusted OR, 0.30; 95% CI, 0.11, 0.78). This effect was not observed in 6- to 23-month-old children with a concomitant respiratory tract infection (adjusted OR 1.36; 95% CI, 0.66, 2.77) or children 2 to <7 years old (adjusted OR, 1.17; 95% CI, 0.58, 2.34). Conclusions 13-Valent pneumococcal conjugate vaccine reduced the prevalence of colonization with PCV13 serotypes among children 6–23 months old, but its

  17. Increase in Invasive Streptococcus pneumoniae Infections in Children with Sickle Cell Disease since Pneumococcal Conjugate Vaccine Licensure

    OpenAIRE

    McCavit, Timothy L.; Quinn, Charles T.; Techasaensiri, Chonnamet; Rogers, Zora R.

    2010-01-01

    Invasive pneumococcal disease (IPD) in children with sickle cell disease (SCD) has decreased with prophylactic penicillin, pneumococcal polysaccharide vaccine, and pneumococcal protein-conjugate vaccine (PCV7) usage. We report 10 IPD cases since PCV7 licensure, including a recent surge of non-vaccine serotypes. IPD continues to be a serious risk in SCD.

  18. No Resistance to Penicillin, Cefuroxime, Cefotaxime, or Vancomycin in Pneumococcal Pneumonia

    OpenAIRE

    Yayan, Josef; Ghebremedhin, Beniam; Rasche, Kurt

    2015-01-01

    Objectives: Group B Streptococcus is a primary source of pneumonia, which is a leading cause of death worldwide. During the last few decades, there has been news of growing antibiotic resistance in group B streptococci to penicillin and different antibiotic agents. This clinical study retrospectively analyzes antimicrobial resistance in inpatients who were diagnosed with group B streptococcal pneumonia. Methods: All of the required information from inpatients who were identified to have group...

  19. Functions and Regulation of NF-κB RelA during Pneumococcal Pneumonia1

    OpenAIRE

    Quinton, Lee J.; Jones, Matthew R.; Simms, Benjamin T.; Kogan, Mariya S.; Robson, Bryanne E.; Skerrett, Shawn J.; Mizgerd, Joseph P.

    2007-01-01

    Eradication of bacteria in the lower respiratory tract depends on the coordinated expression of proinflammatory cytokines and consequent neutrophilic inflammation. To determine the roles of the NF-κB subunit RelA in facilitating these events, we infected RelA-deficient mice (generated on a TNFR1-deficient background) with Streptococcus pneumoniae. RelA deficiency decreased cytokine expression, alveolar neutrophil emigration, and lung bacterial killing. S. pneumoniae killing was also diminishe...

  20. Type I Alveolar Epithelial Cells Mount Innate Immune Responses during Pneumococcal Pneumonia

    OpenAIRE

    Yamamoto, Kazuko; Ferrari, Joseph D.; Cao, Yuxia; Ramirez, Maria I.; Jones, Matthew R.; Quinton, Lee J.; Mizgerd, Joseph P.

    2012-01-01

    Pneumonia results from bacteria in the alveoli. The alveolar epithelium consists of type II cells, which secrete surfactant and associated proteins, and type I cells, which constitute 95% of the surface area and met anatomic and structural needs. Other than constitutively expressed surfactant proteins, it is unknown whether alveolar epithelial cells have distinct roles in innate immunity. Since innate immunity gene induction depends on NF-κB RelA (also known as p65) during pneumonia, we gener...

  1. EFFECTIVENESS OF THE 13-VALENT PNEUMOCOCCAL CONJUGATE VACCINE: EMERGING DATA FROM INVASIVE PNEUMOCOCCAL DISEASE, PNEUMONIA, ACUTE OTITIS MEDIA AND NASOPHARYNGEAL CARRIAGE

    OpenAIRE

    Reinert, Ralf; Taysi, Bulent

    2012-01-01

    A new WHO position paper has been published recently stressing the high priority of the inclusion of PCVs in childhood immunization programs worldwide. Planning for national use of pneumococcal vaccines should take besides other factors the distribution of pneumococcal serotypes in different age groups into consideration. In addition to the serotypes included in PCV7, PCV13 contains serotypes 1, 3, 5, 6A, 7F and 19A and this vaccine provides the broadest serotype coverage of PCVs globally. In...

  2. Decrease in Hospitalizations for Pneumonia in Children under Five Years of Age in an Indian Reservation in Panama after the Introduction of the Heptavalent Pneumococcal Conjugate Vaccine (PCV7)

    OpenAIRE

    Javier Nieto Guevara; Carlos Daza; Rebecca Smith

    2013-01-01

    This study quantifies the impact of Heptavalent-Pneumococcal Conjugate Vaccine (PCV7) in Panama on indigenous children younger than 5 years old, based on clinical pneumonia cases. This study demonstrates a significant 41.2% reduction in hospitalizations and 38.6% reduction in referrals for pneumonia following the introduction of PCV7. Burden of disease from pneumonia appears reduced in the ≤12-month- and 13-to-24-month-old groups.

  3. NK and NKT Cell Depletion Alters the Outcome of Experimental Pneumococcal Pneumonia: Relationship with Regulation of Interferon-γ Production

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    Eirini Christaki

    2015-01-01

    Full Text Available Background. Natural killer (NK and natural killer T (NKT cells contribute to the innate host defense but their role in bacterial sepsis remains controversial. Methods. C57BL/6 mice were infected intratracheally with 5 × 105 cfu of Streptococcus pneumoniae. Animals were divided into sham group (Sham; pretreated with isotype control antibody (CON group; pretreated with anti-asialo GM1 antibody (NKd group; and pretreated with anti-CD1d monoclonal antibody (NKTd group before bacterial challenge. Serum and tissue samples were analyzed for bacterial load, cytokine levels, splenocyte apoptosis rates, and cell characteristics by flow cytometry. Splenocyte miRNA expression was also analyzed and survival was assessed. Results. NK cell depletion prolonged survival. Upon inhibition of NKT cell activation, spleen NK (CD3−/NK1.1+ cells increased compared to all other groups. Inhibition of NKT cell activation led to higher bacterial loads and increased levels of serum and splenocyte IFN-γ. Splenocyte miRNA analysis showed that miR-200c and miR-29a were downregulated, while miR-125a-5p was upregulated, in anti-CD1d treated animals. These changes were moderate after NK cell depletion. Conclusions. NK cells appear to contribute to mortality in pneumococcal pneumonia. Inhibition of NKT cell activation resulted in an increase in spleen NK (CD3−/NK1.1+ cells and a higher IFN-γ production, while altering splenocyte miRNA expression.

  4. One-step multiplex PCR assay for detecting Streptococcus pneumoniae serogroups/types covered by 13-valent pneumococcal conjugate vaccine (PCV13.

    Directory of Open Access Journals (Sweden)

    Fatma Filiz Coskun-Ari

    Full Text Available The life-threatening illnesses caused by Streptococcus pneumoniae have been declined significantly after the use of pneumococcal conjugate vaccines. Continuous monitoring of the vaccine serogroups/types is necessary to follow the changing epidemiology of invasive pneumococcal diseases. Recently, the sequential multiplex PCR approach, which uses several different sets of reactions, has been commonly adopted for determining capsular serogroups/types of S. pneumoniae isolates. In our study, we focused on development of a one-step multiplex PCR assay detecting all 1, 3, 4, 5, 6A/B, 7F, 9V, 14, 18C, 19A, 19F and 23F serogroups/types targeted by PCV13. The content of multiplex PCR mix and the cycling conditions were optimized in a manner that allowed rapid and accurate serotyping of a pneumococcal isolate by performing only a single amplification reaction. In our study of 182 clinical isolates, the one-step multiplex PCR assay exhibited 100% sensitivity and specificity, suggesting that its utilization can significantly reduce the use of traditional antiserum method requiring expensive reagents.

  5. The in vivo behavior of granulocytes labeled with indium-111 in a canine model of pneumococcal pneumonia

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    Lichter, J.P.; Konopka, R.G.; Hartman, M.T.; Moser, K.M.; Spragg, R.G.

    1984-04-01

    Use of (/sup 111/In)granulocytes in the study of pulmonary inflammation requires study of their in vivo behavior. To study the pulmonary deposition of these cells and their ability to migrate from the capillary to the alveolus, we injected (/sup 111/In)granulocytes into dogs 24 h after the induction of a right lower lobe pneumococcal pneumonia. Using external imaging, we found rapid clearance of (/sup 111/In)granulocytes from the uninvolved lung (with a residual radioactivity of 24.5 +/- 4.2% at 4 h). In contrast, 83 +/- 12.4% of the initial radioactivity was present in inflamed lung at 4 h. Bronchoalveolar lavage fluid from the inflamed lung was more cellular than that from control lung, contained a greater fraction of polymorphonuclear leukocytes (82 +/- 4.1% versus 20 +/- 6.2%), and much greater cell-associated radioactivity (ratio of 423:1, inflamed to control). Autoradiography disclosed that this radioactivity was localized to consolidated alveoli and was not prominently distributed in arterioles or venules or in airways larger than 0.6 mm. We conclude that (/sup 111/In)granulocytes are biologically active in the setting of acute lung inflammation.

  6. Streptococcus pneumoniae oropharyngeal colonization in school-age children and adolescents with type 1 diabetes mellitus: Impact of the heptavalent pneumococcal conjugate vaccine.

    Science.gov (United States)

    Principi, Nicola; Iughetti, Lorenzo; Cappa, Marco; Maffeis, Claudio; Chiarelli, Franco; Bona, Gianni; Gambino, Monia; Ruggiero, Luca; Patianna, Viviana; Matteoli, Maria Cristina; Marigliano, Marco; Cipriano, Paola; Parlamento, Silvia; Esposito, Susanna

    2016-01-01

    This study evaluated Streptococcus pneumoniae colonization in children and adolescents with type 1 diabetes mellitus (DM1) to investigate the theoretical risk of invasive pneumococcal disease (IPD) in these patients and the potential protective efficacy of pneumococcal conjugate vaccines (PCVs). An oropharyngeal swab was obtained from 299 patients aged 6-17 y with DM1 who were enrolled during routine clinical visits. DNA from swabs was analyzed for S. pneumoniae using real-time polymerase chain reaction. S. pneumoniae was identified in the swabs of 148 subjects (49.8%). Colonization was strictly age-related and declined significantly in the group aged ≥15 years (odds ratio [OR] 0.28; 95% confidence interval [CI], 0.14-0.57). Carriage was also significantly influenced by sex (lower in females: OR 0.56; 95% CI, 0.35-0.91), ethnicity (less common among non-Caucasians: OR 0.34; 95% CI, 0.13-0.89), parental smoking habit (more frequent among children with at least one smoker between parents: OR 1.76; 95% CI, 0.90-2.07), and the administration of antibiotic therapy in the previous 3 months (less frequent among patients who received antibiotics: OR 0.21; 95% CI, 0.07-0.62). Multivariate analyses of the entire study population showed no association between carriage and PCV7 vaccination status. Serotypes 19F, 9V, and 4 were the most frequently identified serotypes. In conclusion, school-age children and adolescents with DM1 are frequently colonized by S. pneumoniae, and protection against pneumococcal carriage following infant and toddler vaccination was not effective after several years. Together with the need to increase vaccine uptake in all the children aged <2 years, these results suggest that PCV booster doses are needed in DM1 patients to maintain the protection offered by these vaccinations.

  7. Fluoroquinolone and Macrolide Treatment Failure in Pneumococcal Pneumonia and Selection of Multidrug-Resistant Isolates

    OpenAIRE

    Pérez-Trallero, Emilio; Marimon, José M.; Iglesias, Luis; Larruskain, Julián

    2003-01-01

    Streptococcus pneumoniae serotype 3, isolated from a penicillin-allergic patient and initially susceptible to fluoroquinolones, macrolides, lincosamides, quinupristin-dalfopristin, and telithromycin, became resistant to all these drugs during treatment. Mutations in the parC and gyrA and in the 23S rRNA and the ribosomal protein L22 genes were detected in the resistant isolates.

  8. Clinical outcome of pneumococcal meningitis during the emergence of pencillin-resistant Streptococcus pneumoniae: an observational study

    Directory of Open Access Journals (Sweden)

    Gouveia Edilane L

    2011-11-01

    Full Text Available Abstract Background Prior to the availability of generic third-generation cephalosporins, penicillins were widely used for treatment of pneumococcal meningitis in developing countries despite concerns about rising levels of penicillin resistance among pneumococcal isolates. We examined the impact of penicillin resistance on outcomes of pneumococcal meningitis over a ten year period in an infectious diseases hospital in Brazil. Methods Clinical presentation, antimicrobial therapy and outcomes were reviewed for 548 patients with culture-confirmed pneumococcal meningitis from December, 1995, to November, 2005. Pneumococcal isolates from meningitis patients were defined as penicillin-resistant if Minimum Inhibitory Concentrations for penicillin were greater than 0.06 μg/ml. Proportional hazards regression was used to identify risk factors for fatal outcomes. Results During the ten-year period, ceftriaxone replaced ampicillin as first-line therapy for suspected bacterial meningitis. In hospital case-fatality for pneumococcal meningitis was 37%. Of 548 pneumococcal isolates from meningitis cases, 92 (17% were resistant to penicillin. After controlling for age and severity of disease at admission, penicillin resistance was associated with higher case-fatality (Hazard Ratio [HR], 1.62; 95% Confidence Interval [CI], 1.08-2.43. Penicillin-resistance remained associated with higher case-fatality when initial therapy included ceftriaxone (HR, 1.68; 95% CI 1.02-2.76. Conclusions Findings support the use of third generation cephalosporin antibiotics for treatment of suspected pneumococcal meningitis even at low prevalence of pneumococcal resistance to penicillins.

  9. Identification of Pneumococcal Surface Protein A as a Lactoferrin-Binding Protein of Streptococcus pneumoniae

    OpenAIRE

    Hammerschmidt, Sven; Bethe, Gesina; H. Remane, Petra; Chhatwal, Gursharan S.

    1999-01-01

    Lactoferrin (Lf), an iron-sequestering glycoprotein, predominates in mucosal secretions, where the level of free extracellular iron (10−18 M) is not sufficient for bacterial growth. This represents a mechanism of resistance to bacterial infections by prevention of colonization of the host by pathogens. In this study we were able to show that Streptococcus pneumoniae specifically recognizes and binds the iron carrier protein human Lf (hLf). Pretreatment of pneumococci with proteases reduced hL...

  10. Proteasome β5i Subunit Deficiency Affects Opsonin Synthesis and Aggravates Pneumococcal Pneumonia.

    Science.gov (United States)

    Kirschner, Felicia; Reppe, Katrin; Andresen, Nadine; Witzenrath, Martin; Ebstein, Frédéric; Kloetzel, Peter-Michael

    2016-01-01

    Immunoproteasomes, harboring the active site subunits β5i/LMP7, β1i/LMP2, and β2i/MECL1 exert protective, regulatory or modulating functions during infection-induced immune responses. Immunoproteasomes are constitutively expressed in hematopoietic derived cells, constituting the first line of defense against invading pathogens. To clarify the impact of immunoproteasomes on the innate immune response against Streptococcus pneumoniae, we characterized the progression of disease and analyzed the systemic immune response in β5i/LMP7-/- mice. Our data show that β5i/LMP7 deficiency, which affected the subunit composition of proteasomes in murine macrophages and liver, was accompanied by reduced transcription of genes encoding immune modulating molecules such as pentraxins, ficolins, and collectins. The diminished opsonin expression suggested an impaired humoral immune response against invading pneumococci resulting in an aggravated systemic dissemination of S. pneumoniae in β5i/LMP7-/- mice. The impaired bacterial elimination in β5i/LMP7-/- mice was accompanied by an aggravated course of pneumonia with early mortality as a consequence of critical illness during the late phase of disease. In summary our results highlight an unsuspected role for immuno-subunits in modulating the innate immune response to extracellular bacterial infections. PMID:27100179

  11. Streptococcus pneumoniae Serotype Distribution and Pneumococcal Conjugate Vaccine Serotype Coverage among Pediatric Patients in East and Southeast Asia, 2000–2014: a Pooled Data Analysis

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    Stanley S. Tai

    2016-02-01

    Full Text Available Pneumococcal infection is one of the leading causes of death worldwide, especially in children of developing and underdeveloped countries. Capsular polysaccharide-based vaccines are available for the prevention of this disease. A 7-valent pneumococcal conjugate vaccine (PCV7 was licensed in 2000 for use in children less than two years of age. Subsequently, to broaden the protection, 10-valent (PCV10 and 13-valent (PCV13 vaccines were licensed in 2009 and 2010, respectively. All of these conjugate vaccines elicit an immune response that only provides protection against the infection of S. pneumoniae serotypes included in the formulation. Profiles of S. pneumoniae serotype distribution and serotype coverage for both PCV7 and PCV13 have been reported in some Asian countries/territories. But the published results cannot provide conclusive information due to the difference in studied population and geographic areas. The goals of this review are to obtain an accurate estimate of serotype coverage for PCV7, PCV10, and PCV13 and examine the change in the S. pneumoniae serotype distribution after PCV7 use among pediatric patients in East and Southeast Asia through the analysis of pooled data that were published in the English literature between 2000 and 2014.

  12. Pneumococcal Serotype 19F Conjugate Vaccine Induces Cross-Protective Immunity to Serotype 19A in a Murine Pneumococcal Pneumonia Model

    OpenAIRE

    Jakobsen, Håvard; Sigurdsson, Viktor D.; Sigurdardottir, Sigurveig; Schulz, Dominique; Jonsdottir, Ingileif

    2003-01-01

    Immunization with a pneumococcal conjugate vaccine (PNC) containing serotype 19F induces cross-reactive antibodies to 19A in mice and human infants. Active immunization with PNC and passive immunization with serum samples from infants vaccinated with PNC containing serotype 19F, but not serotype 19A, protected against lung infection caused by both serotypes in a murine model.

  13. Effectiveness of the 10-Valent Pneumococcal Conjugate Vaccine (PCV-10) in Children in Chile: A Nested Case-Control Study Using Nationwide Pneumonia Morbidity and Mortality Surveillance Data

    Science.gov (United States)

    Toscano, Cristiana M.; Alencar, Gizelton P.; Alvarez, Andrés; Valenzuela, Maria T.; Andrus, Jon; del Aguila, Roberto; Hormazábal, Juan C.; Araya, Pamela; Pidal, Paola; Matus, Cuauhtemoc R.; de Oliveira, Lucia H.

    2016-01-01

    Background The ten-valent pneumococcal conjugate vaccine (PCV10) was introduced into the Chilean National Immunization Program (NIP) in January 2011 with a 3+1 schedule (2, 4, 6 and 12 months) without catch-up vaccination. We evaluated the effectiveness of PCV10 on pneumonia morbidity and mortality among infants during the first two years after vaccine introduction. Methods This is a population-based nested case-control study using four merged nationwide case-based electronic health data registries: live birth, vaccination, hospitalization and mortality. Children born in 2010 and 2011 were followed from two moths of age for a period of two years. Using four different case definitions of pneumonia hospitalization and/or mortality (all-cause and pneumonia related deaths), all cases and four randomly selected matched controls per case were selected. Controls were matched to cases on analysis time. Vaccination status was then assessed. Vaccine effectiveness (VE) was estimated using conditional logistic regression. Results There were a total of 497,996 children in the 2010 and 2011 Chilean live-birth cohorts. PCV10 VE was 11.2% (95%CI 8.5–13.6) when all pneumonia hospitalizations and deaths were used to define cases. VE increased to 20.7 (95%CI 17.3–23.8) when ICD10 codes used to denote viral pneumonia were excluded from the case definition. VE estimates on pneumonia deaths and all-cause deaths were 71.5 (95%CI 9.0–91.8) and 34.8 (95% CI 23.7–44.4), respectively. Conclusion PCV10 vaccination substantially reduced the number of hospitalizations due to pneumonia and deaths due to pneumonia and to all-causes over this study period. Our findings also reinforce the importance of having quality health information systems for measuring VE. PMID:27058873

  14. Pneumococcal Vaccination Strategies. An Update and Perspective.

    Science.gov (United States)

    Berical, Andrew C; Harris, Drew; Dela Cruz, Charles S; Possick, Jennifer D

    2016-06-01

    Streptococcus pneumoniae is an important global pathogen that causes a wide range of clinical disease in children and adults. Pneumococcal pneumonia is by far the common presentation of noninvasive and invasive pneumococcal disease and affects the young, the elderly, and the immunocompromised disproportionately. Patients with chronic pulmonary diseases are also at higher risk for pneumococcal infections. Substantial progress over the century has been made in the understanding of pneumococcal immunobiology and the prevention of invasive pneumococcal disease through vaccination. Currently, two pneumococcal vaccines are available for individuals at risk of pneumococcal disease: the 23-valent pneumococcal polysaccharide vaccine (PPV23) and the 13-valent pneumococcal protein-conjugate vaccine (PCV13). The goal of pneumococcal vaccination is to stimulate effective antipneumococcal antibody and mucosal immunity response and immunological memory. Vaccination of infants and young children with pneumococcal conjugate vaccine has led to significant decrease in nasal carriage rates and pneumococcal disease in all age groups. Recent pneumococcal vaccine indication and schedule recommendations on the basis of age and risk factors are outlined in this Focused Review. As new pneumococcal vaccine recommendations are being followed, continued efforts are needed to address the vaccine efficacy in the waning immunity of the ever-aging population, the implementation of vaccines using two different vaccines under very specific schedules and their real world clinical and cost effectiveness, and the development of next generation pneumococcal vaccines. PMID:27088424

  15. Invasive Streptococcus pneumoniae in Canada, 2011-2014: Characterization of new candidate 15-valent pneumococcal conjugate vaccine serotypes 22F and 33F.

    Science.gov (United States)

    Golden, Alyssa R; Adam, Heather J; Zhanel, George G

    2016-05-17

    Emerging non-PCV-13 Streptococcus pneumoniae serotypes 22F and 33F are included in a new 15-valent pneumococcal conjugate vaccine currently undergoing clinical trials in the United States. This study assessed the antimicrobial resistance and genetic relatedness of these two emerging pneumococcal serotypes. Of the 5075 invasive pneumococcal isolates collected in Canada from 2011 to 2014, 9.8% (497/5075) were serotype 22F and 3.2% (160/5075) were serotype 33F. Despite being among the top 4 most common serotypes collected each study year, serotype 22F demonstrated ≥98% susceptibility to all antimicrobials tested except clarithromycin and few were multi-drug resistant (MDR) (0.8%, 4/497). Serotype 22F isolates were highly clonal (ST433), with two isolates showing high relatedness to MDR international clone Sweden(15A)-25 (ST63). Conversely, serotype 33F showed greater antimicrobial resistance, greater genetic diversity and a higher proportion of MDR isolates (8.8%, 14/160). The prevalence of serotype 33F increased significantly during 2011-2014 (p=0.005). PMID:27085174

  16. Distribution of capsular types and antimicrobial susceptibility of invasive isolates of Streptococcus pneumoniae in Colombian children. Pneumococcal Study Group in Colombia.

    Science.gov (United States)

    Castañeda, E; Leal, A L; Castillo, O; De La Hoz, F; Vela, M C; Arango, M; Trujillo, H; Levy, A; Gama, M E; Calle, M; Valencia, M L; Parra, W; Agudelo, N; Mejía, G I; Jaramillo, S; Montoya, F; Porras, H; Sánchez, A; Saa, D; Di Fabio, J L; Homma, A

    1997-01-01

    Streptococcus pneumoniae is the leading bacterial cause of childhood pneumonia in the developing world. This study describes the type distribution and antimicrobial susceptibility of invasive pneumococcal isolates from Colombian children and is part of the Sistema Regional de Vacunas (SIREVA), a PAHO regional initiative designed to determine the ideal serotype composition of a protein polysaccharide pneumococcal conjugate vaccine for use in children less than 5 years old in Latin America. In Colombia, during the study period, centres in Bogota, Medellin, and Cali collected 324 S. pneumoniae isolates from invasive diseases, 238 (73.5%) from children under the age of 2. Pneumonia was the clinical diagnosis in 41.3% cases, meningitis in 41%, and sepsis in 11.2%. The seven most frequent types included 14(21.9%), 5(10.5%), 23F(9.6%), 1(9%), 6B(9%), 19F(7.1%), and 6A(6.2%). The frequency of diminished susceptibility to penicillin (DSP) was 12%, with 8.9% of isolates showing intermediate level resistance and 3.1% showing high level resistance. Among DSP isolates, 23% were also resistant to cefotaxime, 33.3% to erythromycin, 48.7% to chloramphenicol, and 74.3% to trimethoprim/sulfamethoxazole. Multiple resistance was detected in 59% of the isolates that have DSP. Penicillin resistance was associated with types 23F (53.8%) and 14 (25.6%). These data provides information on capsular types prevalent in Colombia that will not only allow the formulation of an ideal vaccine for the region but also reinforce the need for ongoing regional surveillance.

  17. Pneumococcal infections and pneumococcal vaccine: an update.

    Science.gov (United States)

    Rytel, M W

    1982-01-01

    Pneumococcal pneumonia continues to be an important disease in terms of prevalence, morbidity and mortality. With the discovery of penicillin and its wide clinical use, the overall mortality of pneumococcal pneumonia has been significantly reduced, but problems remain. These include: 1) death rate is uninfluenced by the antibiotic in the first five days of illness; 2) death rate in certain high risk groups and in patients infected with type 3 pneumococcus exceeds 25%; and 3) penicillin resistant strains of pneumococci have emerged. Because of these and other considerations, a modern 14-valent pneumococcal vaccine has been developed by Robert Austrian and his co-workers. The vaccine has been found to be immunogenic and effective in a number of populations studied. Additional efficacy studies are needed, however, particularly in certain high risk groups, such as the elderly and immunocompromised patients.

  18. Nasopharyngeal carriage and transmission of Streptococcus pneumoniae in American Indian households after a decade of pneumococcal conjugate vaccine use.

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    Jonathan F Mosser

    Full Text Available BACKGROUND: Young children played a major role in pneumococcal nasopharyngeal carriage, acquisition, and transmission in the era before pneumococcal conjugate vaccine (PCV use. Few studies document pneumococcal household dynamics in the routine-PCV7 era. METHODS: We investigated age-specific acquisition, household introduction, carriage clearance, and intra-household transmission in a prospective, longitudinal, observational cohort study of pneumococcal nasopharyngeal carriage in 300 American Indian households comprising 1,072 participants between March 2006 and March 2008. RESULTS: Pneumococcal acquisition rates were 2-6 times higher in children than adults. More household introductions of new pneumococcal strains were attributable to children <9 years than adults ≥17 years (p<0.001, and older children (2-8 years than younger children (<2 years (p<0.008. Compared to children <2 years, carriage clearance was more rapid in older children (2-4 years, HRclearance 1.53 [95% CI: 1.22, 1.91]; 5-8 years, HRclearance 1.71 [1.36, 2.15] and adults (HRclearance 1.75 [1.16, 2.64]. Exposure to serotype-specific carriage in older children (2-8 years most consistently increased the odds of subsequently acquiring that serotype for other household members. CONCLUSIONS: In this community with a high burden of pneumococcal colonization and disease and routine PCV7 use, children (particularly older children 2-8 years drive intra-household pneumococcal transmission: first, by acquiring, introducing, and harboring pneumococcus within the household, and then by transmitting acquired serotypes more efficiently than household members of other ages.

  19. Should Pneumococcal Vaccines Eliminate Nasopharyngeal Colonization?

    OpenAIRE

    McDaniel, Larry S.; Swiatlo, Edwin

    2016-01-01

    ABSTRACT  Streptococcus pneumoniae remains an important human pathogen. For more than 100 years, there have been vaccine efforts to prevent pneumococcal infection. The pneumococcal conjugate vaccines have significantly reduced invasive disease. However, these vaccines have changed pneumococcal ecology within the human nasopharynx. We suggest that elimination of the pneumococcus from the human nasopharynx can have consequences that should be considered as the next generation of pneumococcal va...

  20. Should Pneumococcal Vaccines Eliminate Nasopharyngeal Colonization?

    Science.gov (United States)

    McDaniel, Larry S; Swiatlo, Edwin

    2016-01-01

    Streptococcus pneumoniae remains an important human pathogen. For more than 100 years, there have been vaccine efforts to prevent pneumococcal infection. The pneumococcal conjugate vaccines have significantly reduced invasive disease. However, these vaccines have changed pneumococcal ecology within the human nasopharynx. We suggest that elimination of the pneumococcus from the human nasopharynx can have consequences that should be considered as the next generation of pneumococcal vaccines is developed. PMID:27222469

  1. Serotypes and Antibiotic Susceptibility of Streptococcus pneumoniae Isolates from Invasive Pneumococcal Disease and Asymptomatic Carriage in a Pre-vaccination Period, in Algeria

    Science.gov (United States)

    Ziane, Hanifa; Manageiro, Vera; Ferreira, Eugénia; Moura, Inês B.; Bektache, Soumia; Tazir, Mohamed; Caniça, Manuela

    2016-01-01

    In Algeria, few data is available concerning the distribution of pneumococcal serotypes and respective antibiotic resistance for the current pre-vaccination period, which is a public health concern. We identified the most frequent Streptococcus pneumoniae serogroup/types implicated in invasive pneumococcal disease (IPD; n = 80) and carriage (n = 138) in Algerian children younger than 5 years old. Serogroup/types of 78 IPD isolates were identified by capsular typing using a sequential multiplex PCR. Overall, serotypes 14, 19F, 6B, 23F, 18C, 1, 5, 7F, 19A, and 3 (55% of PCV7 serotypes, 71.3% of PCV10, and 90% of PCV13) were identified. Additionally, 7.5% of the non-vaccine serotypes 6C, 9N/L, 20, 24F, 35B, and 35F, were observed. In the case of S. pneumoniae asymptomatic children carriers, the most common serogroup/types were 6B, 14, 19F, 23F, 4, 9V/A, 1, 19A, 6A, and 3 (42.7% of PCV7 serotypes, 44.2% of PCV10, and 58% of PCV13). For 6.1% of the cases co-colonization was detected. Serotypes 14, 1, 5, and 19A were more implicated in IPD (p vaccine serotypes, the rates of penicillin non-susceptible isolates were higher in no meningitis cases (80%) than in meningitis (66.7%), with serotypes 14, 19A, 19F, and 23F presenting the highest MIC levels (>2μg/ml). Resistance to cefotaxime was higher in isolates from meningitis (40.5%); however, resistance to erythromycin and co-trimoxazole (>40%) was more pronounced in no-meningeal forms. Overall, our results showed that PCV13 conjugate vaccine would cover up to 90% of the circulating isolates associated with IPD in Algeria, highlighting the importance of monitoring the frequency of S. pneumoniae serogroups/types during pre- and post-vaccination periods. PMID:27379023

  2. Invasive Pneumococcal Disease 3 Years after Introduction of 10-Valent Pneumococcal Conjugate Vaccine, the Netherlands

    OpenAIRE

    Knol, Mirjam J.; Wagenvoort, Gertjan H.J.; Sanders, Elisabeth A. M.; Elberse, Karin; Vlaminckx, Bart J.; Hester E. de Melker; van der Ende, Arie

    2015-01-01

    Three years after a 7-valent pneumococcal conjugate vaccine was replaced by a 10-valent pneumococcal conjugate vaccine in the Netherlands, we observed a decrease in incidence of invasive pneumococcal disease caused by Streptococcus pneumoniae serotypes 1, 5, and 7F. Our data do not support or exclude cross-protection against serotype 19A.

  3. Invasive pneumococcal disease leads to activation and hyperreactivity of platelets

    NARCIS (Netherlands)

    Tunjungputri, Rahajeng N.; De Jonge, Marien I.; De Greeff, Astrid; Van Selm, Saskia; Buys, Herma; Harders-Westerveen, Jose F.; Stockhofe-Zurwieden, Norbert; Urbanus, Rolf T.; de Groot, Phillip G.; Smith, Hilde E.; Van Der Ven, Andre J.; De Mast, Quirijn

    2016-01-01

    Using a novel porcine model of intravenous Streptococcus pneumoniae infection, we showed that invasive pneumococcal infections induce marked platelet activation and hyperreactivity. This may contribute to the vascular complications seen in pneumococcal infection.

  4. Invasive pneumococcal disease leads to activation and hyperreactivity of platelets

    NARCIS (Netherlands)

    Tunjungputri, Rahajeng N.; Jonge, de Marien I.; Greeff, de Astrid; Selm, van Saskia; Buys-Bergen, Herma; Harders-Westerveen, Jose F.; Stockhofe-Zurwieden, Norbert; Urbanus, Rolf T.; Groot, De Phillip G.; Smith, Hilde E.; Ven, van der Andre J.; Mast, de Quirijn

    2016-01-01

    Using a novel porcine model of intravenous Streptococcus pneumoniae infection, we showed that invasive pneumococcal infections induce marked platelet activation and hyperreactivity. This may contribute to the vascular complications seen in pneumococcal infection.

  5. The adult nasopharyngeal microbiome as a determinant of pneumococcal acquisition

    NARCIS (Netherlands)

    Cremers, Amelieke Jh; Zomer, Aldert L; Gritzfeld, Jenna F; Ferwerda, Gerben; van Hijum, Sacha Aft; Ferreira, Daniela M; Shak, Joshua R; Klugman, Keith P; Boekhorst, Jos; Timmerman, Harro M; de Jonge, Marien I; Gordon, Stephen B; Hermans, Peter Wm

    2014-01-01

    BACKGROUND: Several cohort studies have indicated associations between S. pneumoniae and other microbes in the nasopharynx. To study causal relationships between the nasopharyngeal microbiome and pneumococcal carriage, we employed an experimental human pneumococcal carriage model. Healthy adult volu

  6. The impact of pneumococcal conjugate vaccines on carriage of and disease caused by Streptococcus pneumoniae serotypes 6C and 6D in southern Israel.

    Science.gov (United States)

    Porat, Nurith; Benisty, Rachel; Givon-Lavi, Noga; Trefler, Ronit; Dagan, Ron

    2016-05-27

    The introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) followed by PCV13 resulted in a dramatic reduction in carriage and disease rates of Streptococcus pneumoniae (Sp) serotype 6B (Sp6B) and Sp6A. The structural modifications of the capsule of Sp6A and Sp6B to become Sp6C and Sp6D, respectively, raised a concern that eradication of Sp6A/Sp6B by PCV could be accompanied by an increase in Sp6C/Sp6D. This study examines the dynamics and clonal distribution of Sp6C/Sp6D relative to Sp6A/Sp6B during 1999-2014, pre- and post-PCV implementation. Sp were cultured from Blood/CSF and MEF of children pneumococcal disease, complete elimination of serogroup 6 was found in the PCV era. Similar clonal composition was found for Sp6C and Sp6D pre- and post-PCV. We conclude that Sp6C and Sp6D do not act as replacement serotypes for Sp6A and Sp6B following vaccination with PCV13. The major Sp6C and Sp6D clones present pre-PCV persisted also post-PCV implementation, suggesting that these clones possess an advantage retained post-vaccination. PMID:27113163

  7. Higher levels of mucosal antibody to pneumococcal vaccine candidate proteins are associated with reduced acute otitis media caused by Streptococcus pneumoniae in young children.

    Science.gov (United States)

    Xu, Q; Casey, J R; Pichichero, M E

    2015-09-01

    Mucosal immunity has a crucial role in controlling human respiratory tract infections. This study characterizes the naturally acquired mucosal antibody levels to three Streptococcus pneumoniae (Spn) protein antigens, pneumococcal histidine triad protein D (PhtD), pneumococcal choline binding protein A (PcpA), and pneumolysin (Ply), and assesses the association of the mucosal antibody levels with occurrence of acute otitis media (AOM) caused by Spn. Both nasopharyngeal (NP) immunoglobulin G (IgG) and IgA levels to all three proteins slightly decreased in children from 6 to 9 months of age and then gradually increased through 24 months of age. Spn NP colonization was associated with higher mucosal antibody levels to all three proteins. However, children with Spn AOM had 5-8-fold lower IgG and 3-6-fold lower IgA levels to the three proteins than children without AOM but asymptomatically colonized with Spn. Antigen-specific antibody levels in the middle ear fluid (MEF) were correlated with antibody levels in the NP. Children with AOM caused by Spn had lower antibody levels in both the MEF and NP than children with AOM caused by other pathogens. These results indicate that higher naturally acquired mucosal antibody levels to PhtD, PcpA and Ply are associated with reduced AOM caused by Spn.

  8. Preparation and testing of a Vi conjugate vaccine using pneumococcal surface protein A (PspA) from Streptococcus pneumoniae as the carrier protein.

    Science.gov (United States)

    Kothari, Neha; Genschmer, Kristopher R; Kothari, Sudeep; Kim, Jeong Ah; Briles, David E; Rhee, Dong Kwon; Carbis, Rodney

    2014-09-29

    In the current study pneumococcal surface protein A (PspA) was conjugated to Vi capsular polysaccharide from Salmonella Typhi to make available a vaccine against typhoid fever that has the potential to also provide broad protection from Streptococcus pneumoniae. High yielding production processes were developed for the purification of PspAs from families 1 and 2. The purified PspAs were conjugated to Vi with high recovery of both Vi and PspA. The processes developed especially for PspA family 2 could readily be adapted for large scale production under cGMP conditions. Previously we have shown that conjugation of diphtheria toxoid (DT) to Vi polysaccharide improves the immune response to Vi but can also enhance the response to DT. In this study it was shown that conjugation of PspA to Vi enhanced the anti-PspA response and that PspA was a suitable carrier protein as demonstrated by the characteristics of a T-cell dependent response to the Vi. We propose that a bivalent vaccine consisting of PspA from families 1 and 2 bound to Vi polysaccharide would protect against typhoid fever and has the potential to also protect against pneumococcal disease and should be considered for use in developing countries.

  9. Nanogel-based pneumococcal surface protein A nasal vaccine induces microRNA-associated Th17 cell responses with neutralizing antibodies against Streptococcus pneumoniae in macaques.

    Science.gov (United States)

    Fukuyama, Y; Yuki, Y; Katakai, Y; Harada, N; Takahashi, H; Takeda, S; Mejima, M; Joo, S; Kurokawa, S; Sawada, S; Shibata, H; Park, E J; Fujihashi, K; Briles, D E; Yasutomi, Y; Tsukada, H; Akiyoshi, K; Kiyono, H

    2015-09-01

    We previously established a nanosized nasal vaccine delivery system by using a cationic cholesteryl group-bearing pullulan nanogel (cCHP nanogel), which is a universal protein-based antigen-delivery vehicle for adjuvant-free nasal vaccination. In the present study, we examined the central nervous system safety and efficacy of nasal vaccination with our developed cCHP nanogel containing pneumococcal surface protein A (PspA-nanogel) against pneumococcal infection in nonhuman primates. When [(18)F]-labeled PspA-nanogel was nasally administered to a rhesus macaque (Macaca mulatta), longer-term retention of PspA was noted in the nasal cavity when compared with administration of PspA alone. Of importance, no deposition of [(18)F]-PspA was seen in the olfactory bulbs or brain. Nasal PspA-nanogel vaccination effectively induced PspA-specific serum IgG with protective activity and mucosal secretory IgA (SIgA) Ab responses in cynomolgus macaques (Macaca fascicularis). Nasal PspA-nanogel-induced immune responses were mediated through T-helper (Th) 2 and Th17 cytokine responses concomitantly with marked increases in the levels of miR-181a and miR-326 in the serum and respiratory tract tissues, respectively, of the macaques. These results demonstrate that nasal PspA-nanogel vaccination is a safe and effective strategy for the development of a nasal vaccine for the prevention of pneumonia in humans. PMID:25669148

  10. Population genetic structure of Streptococcus pneumoniae in Kilifi, Kenya, prior to the introduction of pneumococcal conjugate vaccine.

    Directory of Open Access Journals (Sweden)

    Angela B Brueggemann

    Full Text Available The 10-valent pneumococcal conjugate vaccine (PCV10 was introduced in Kenya in 2011. Introduction of any PCV will perturb the existing pneumococcal population structure, thus the aim was to genotype pneumococci collected in Kilifi before PCV10.Using multilocus sequence typing (MLST, we genotyped >1100 invasive and carriage pneumococci from children, the largest collection genotyped from a single resource-poor country and reported to date. Serotype 1 was the most common serotype causing invasive disease and was rarely detected in carriage; all serotype 1 isolates were members of clonal complex (CC 217. There were temporal fluctuations in the major circulating sequence types (STs; and although 1-3 major serotype 1, 14 or 23F STs co-circulated annually, the two major serotype 5 STs mainly circulated independently. Major STs/CCs also included isolates of serotypes 3, 12F, 18C and 19A and each shared ≤ 2 MLST alleles with STs that circulate widely elsewhere. Major CCs associated with non-PCV10 serotypes were predominantly represented by carriage isolates, although serotype 19A and 12F CCs were largely invasive and a serotype 10A CC was equally represented by invasive and carriage isolates.Understanding the pre-PCV10 population genetic structure in Kilifi will allow for the detection of changes in prevalence of the circulating genotypes and evidence for capsular switching post-vaccine implementation.

  11. Pneumococcal Disease

    Science.gov (United States)

    ... 000 adults age 65 years and older. Pneumococcal disease can cause serious illness and lifelong complications. Pneumococcal meningitis can cause hearing loss, seizures, blindness, and paralysis. Serious heart problems are ... its worst forms, pneumococcal disease kills one in every four to five people ...

  12. A Review of Pneumococcal Vaccines: Current Polysaccharide Vaccine Recommendations and Future Protein Antigens

    OpenAIRE

    Daniels, Calvin C.; Rogers, P. David; Shelton, Chasity M.

    2016-01-01

    This review describes development of currently available pneumococcal vaccines, provides summary tables of current pneumococcal vaccine recommendations in children and adults, and describes new potential vaccine antigens in the pipeline. Streptococcus pneumoniae, the bacteria responsible for pneumonia, otitis media, meningitis and bacteremia, remains a cause of morbidity and mortality in both children and adults. Introductions of unconjugated and conjugated pneumococcal polysaccharide vaccine...

  13. Síndrome hemolítico-urêmica relacionada à infecção invasiva pelo Streptococcus pneumoniae Hemolytic-uremic syndrome complicating invasive pneumococcal disease

    Directory of Open Access Journals (Sweden)

    Anna Leticia de O. Cestari

    2008-03-01

    Full Text Available OBJETIVO: A doença pneumocócica é importante problema de saúde pública e raramente há associação desta infecção com a síndrome hemolítico-urêmica (SHU grave. O objetivo deste artigo é relatar o caso de um paciente com esta associação. DESCRIÇÃO DO CASO: Criança do sexo masculino, com 17 meses de idade, admitida no hospital com insuficiência respiratória aguda e necessitando de suporte ventilatório. O exame radiológico mostrava extensa opacidade homogênea em hemitórax direito. A hemocultura foi positiva para Streptococcus pneumoniae. Nos exames de admissão, notaram-se: hemoglobina de 6,5g/dL, 38.000 plaquetas/mm³, uréia de 79mg/dL e creatinina de 1,64mg/dL. No primeiro dia, apresentou oligoanúria e hipervolemia, necessitando de hemodiafiltração. Evoluiu com disfunção de múltiplos órgãos e óbito no sétimo dia. A necrópsia mostrou áreas extensas de necrose cortical e tubular renal, com depósito de fibrina nas arteríolas. COMENTÁRIOS: A SHU associada ao pneumococo apresenta morbidade e mortalidade elevadas. Em crianças com doença pneumocócica invasiva e acometimento hematológico ou renal grave, deve-se estar atento a esta rara complicação. Merecem investigação os seguintes aspectos relacionados à doença: a função da detecção precoce de antígenos T ativados no diagnóstico e terapêutica, o papel do fator H na patogênese, o método ideal de substituição renal e a definição do prognóstico em longo prazo.OBJECTIVE: Pneumococcal diseases are a major public health problem. Severe hemolytic-uremic syndrome is an uncommon complication. The aim of this study is to report a child with this complication. CASE DESCRIPTION: A male child with 17 months old was admitted to the hospital, due to acute respiratory failure, needing ventilatory support. Roentgenogram demonstrated massive condensation of right lung and Streptococcus pneumonia was isolated from blood cultures. Laboratory tests showed

  14. Efficacy and effectiveness of extended-valency pneumococcal conjugate vaccines

    OpenAIRE

    Lee, Hyunju; Choi, Eun Hwa; Lee, Hoan Jong

    2014-01-01

    The 7-valent pneumococcal protein conjugate vaccine (PCV7) has been shown to be highly efficacious against invasive pneumococcal diseases and effective against pneumonia and in reducing otitis media. The introduction of PCV7 has resulted in major changes in the epidemiology of pneumococcal diseases. However, pneumococcal vaccines induce serotype-specific immunity, and a relative increase in non-vaccine serotypes has been reported following the widespread use of PCV7, leading to a need for ext...

  15. New vaccines for the prevention of pneumococcal infections.

    OpenAIRE

    Käyhty, H; Eskola, J.

    1996-01-01

    Streptococcus pneumoniae is a major cause of acute otitis media, pneumonia, bacteremia, and meningitis. Because in recent years antibiotic-resistant pneumococcal strains have been emerging throughout the world, vaccination against pneumococcal infections has become more urgent. The capsular polysaccharide vaccine that has been available is neither immunogenic nor protective in young children and other immunocompromised patients. Several pneumococcal proteins have been proposed as candidate va...

  16. The enhanced pneumococcal LAMP assay: a clinical tool for the diagnosis of meningitis due to Streptococcus pneumoniae.

    Directory of Open Access Journals (Sweden)

    Dong Wook Kim

    Full Text Available BACKGROUND: Streptococcus pneumoniae is a leading cause of invasive bacterial disease in developed and developing countries. We studied the loop-mediated isothermal amplification (LAMP technique to assess its suitability for detecting S. pneumoniae nucleic acid in cerebrospinal fluid (CSF. METHODOLOGY/PRINCIPAL FINDINGS: We established an improved LAMP assay targeting the lytA gene (Streptococcus pneumoniae [Sp] LAMP. The analytical specificity of the primers was validated by using 32 reference strains (10 Streptococcus and seven non-Streptococcus species plus 25 clinical alpha-hemolytic streptococcal strains, including four S. pneumoniae strains and 21 other strains (3 S. oralis, 17 S. mitis, and one Streptococcus species harboring virulence factor-encoding genes (lytA or ply. Within 30 minutes, the assay could detect as few as 10 copies of both purified DNA and spiked CSF specimens with greater sensitivity than conventional polymerase chain reaction (PCR. The linear determination range for this assay is 10 to 1,000,000 microorganisms per reaction mixture using real-time turbidimetry. We evaluated the clinical sensitivity and specificity of the Sp LAMP assay using 106 randomly selected CSF specimens from children with suspected meningitis in Korea, China and Vietnam. For comparison, CSF specimens were also tested against conventional PCR and culture tests. The detection rate of the LAMP method was substantially higher than the rates of PCR and culture tests. In this small sample, relative to the LAMP assay, the clinical sensitivity of PCR and culture tests was 54.5% and 33.3%, respectively, while clinical specificity of the two tests was 100%. CONCLUSIONS/SIGNIFICANCE: Compared to PCR, Sp LAMP detected S. pneumoniae with higher analytical and clinical sensitivity. This specific and sensitive LAMP method offers significant advantages for screening patients on a population basis and for diagnosis in clinical settings.

  17. Conjugation of Polysaccharide 6B from Streptococcus pneumoniae with Pneumococcal Surface Protein A: PspA Conformation and Its Effect on the Immune Response

    OpenAIRE

    Perciani, Catia T.; Barazzone, Giovana C.; Goulart, Cibelly; Carvalho, Eneas; Cabrera-Crespo, Joaquin; Gonçalves, Viviane M.; Luciana C. C. Leite; Tanizaki, Martha M.

    2013-01-01

    Despite the substantial beneficial effects of incorporating the 7-valent pneumococcal conjugate vaccine (PCV7) into immunization programs, serotype replacement has been observed after its widespread use. As there are many serotypes currently documented, the use of a conjugate vaccine relying on protective pneumococcal proteins as active carriers is a promising alternative to expand PCV coverage. In this study, capsular polysaccharide serotype 6B (PS6B) and recombinant pneumococcal surface pro...

  18. Time and dose-dependent risk of pneumococcal pneumonia following influenza: a model for within-host interaction between influenza and Streptococcus pneumoniae

    OpenAIRE

    Shrestha, Sourya; Foxman, Betsy; Dawid, Suzanne; Aiello, Allison E.; Davis, Brian M.; Berus, Joshua; Rohani, Pejman

    2013-01-01

    A significant fraction of seasonal and in particular pandemic influenza deaths are attributed to secondary bacterial infections. In animal models, influenza virus predisposes hosts to severe infection with both Streptococcus pneumoniae and Staphylococcus aureus. Despite its importance, the mechanistic nature of the interaction between influenza and pneumococci, its dependence on the timing and sequence of infections as well as the clinical and epidemiological consequences remain unclear. We e...

  19. The role of ZmpC in the clinical manifestation of invasive pneumococcal disease

    NARCIS (Netherlands)

    Cremers, A.J.H.; Kokmeijer, I.; Groh, L.; Jonge, M.I. de; Ferwerda, G.

    2014-01-01

    INTRODUCTION: The clinical severity and course of invasive pneumococcal disease (IPD) differs substantially between patients. Streptococcus pneumoniae harbors large genetic variability. Zinc metalloproteinase C (ZmpC), a secreted pneumococcal protein involved in neutrophil extravasation, inflammatio

  20. A Review of the Impact of Pneumococcal Polysaccharide Conjugate Vaccine (7-valent) on Pneumococcal Meningitis

    OpenAIRE

    Tin Tin Htar, Myint; Madhava, Harish; Balmer, Paul; Christopoulou, Dina; Menegas, Damianos; Bonnet, Eric

    2013-01-01

    Introduction Streptococcus pneumoniae is the leading cause of bacterial meningitis. Young children, the elderly and those who are immunocompromised or who suffer from chronic diseases have the highest risk of developing pneumococcal meningitis. A 7-valent pneumococcal conjugate vaccine (PCV7) was licensed in 2000 in the US and in 2001 in Europe. Methods A literature search was performed in PubMed to identify studies assessing the impact of routine childhood PCV7 vaccination on pneumococcal di...

  1. Maternal Immunization with Pneumococcal Surface Protein A Protects against Pneumococcal Infections among Derived Offspring

    OpenAIRE

    Masamitsu Kono; Muneki Hotomi; Hollingshead, Susan K.; Briles, David E.; Noboru Yamanaka

    2011-01-01

    Pathogen-specific antibody plays an important role in protection against pneumococcal carriage and infections. However, neonates and infants exhibit impaired innate and adaptive immune responses, which result in their high susceptibility to pneumococci. To protect neonates and infants against pneumococcal infection it is important to elicit specific protective immune responses at very young ages. In this study, we investigated the protective immunity against pneumococcal carriage, pneumonia, ...

  2. Evaluation of anti-pneumococcal capsular antibodies as adjunctive therapy in experimental pneumococcal meningitis

    DEFF Research Database (Denmark)

    Brandt, Christian; Frimodt-Moller, N; Lundgren, Jens Dilling;

    2006-01-01

    OBJECTIVE: Bacteraemia concomitant with meningitis has been shown to greatly affect outcome. Consequently, the efficacy of serotype-specific anti-pneumococcal antiserum (APAS) was investigated in a rat model of pneumococcal meningitis. METHODS: Rats were infected with Streptococcus pneumoniae...... at the time of infection whereas no effect was found when administered 26 h after infection. This work indicates that the clinical value of using APAS in pneumococcal meningitis may be limited...

  3. Pneumonia

    Science.gov (United States)

    ... restroom and before eating. Use lukewarm water and soap for at least 20 seconds. If soap and water are not available, using an alcohol- ... at higher risk for pneumonia? Do I have bacterial, viral or fungal pneumonia? What’s the best treatment? ...

  4. Contribution of vaccines to our understanding of pneumococcal disease

    OpenAIRE

    Klugman, Keith P.

    2011-01-01

    Pneumonia is the leading cause of mortality in children in developing countries and is also the leading infectious cause of death in adults. The most important cause of pneumonia is the Gram-positive bacterial pathogen, Streptococcus pneumoniae, also known as the pneumococcus. It has thus become the leading vaccine-preventable cause of death and is a successful and diverse human pathogen. The development of conjugate pneumococcal vaccines has made possible the prevention of pneumococcal disea...

  5. HIV Infection and the Epidemiology of Invasive Pneumococcal Disease (IPD in South African Adults and Older Children Prior to the Introduction of a Pneumococcal Conjugate Vaccine (PCV.

    Directory of Open Access Journals (Sweden)

    Susan Meiring

    Full Text Available Streptococcus pneumoniae is the commonest cause of bacteremic pneumonia among HIV-infected persons. As more countries with high HIV prevalence are implementing infant pneumococcal conjugate vaccine (PCV programs, we aimed to describe the baseline clinical characteristics of adult invasive pneumococcal disease (IPD in the pre-PCV era in South Africa in order to interpret potential indirect effects following vaccine use.National, active, laboratory-based surveillance for IPD was conducted in South Africa from 1 January 2003 through 31 December 2008. At 25 enhanced surveillance (ES hospital sites, clinical data, including HIV serostatus, were collected from IPD patients ≥ 5 years of age. We compared the clinical characteristics of individuals with IPD in those HIV-infected and -uninfected using multivariable analysis. PCV was introduced into the routine South African Expanded Program on Immunization (EPI in 2009.In South Africa, from 2003-2008, 17 604 cases of IPD occurred amongst persons ≥ 5 years of age, with an average incidence of 7 cases per 100 000 person-years. Against a national HIV-prevalence of 18%, 89% (4190/4734 of IPD patients from ES sites were HIV-infected. IPD incidence in HIV-infected individuals is 43 times higher than in HIV-uninfected persons (52 per 100 000 vs. 1.2 per 100 000, with a peak in the HIV-infected elderly population of 237 per 100 000 persons. Most HIV-infected individuals presented with bacteremia (74%, 3 091/4 190. HIV-uninfected individuals were older; and had more chronic conditions (excluding HIV than HIV-infected persons (39% (210/544 vs. 19% (790/4190, p<0.001. During the pre-PCV immunization era in South Africa, 71% of serotypes amongst HIV-infected persons were covered by PCV13 vs. 73% amongst HIV-uninfected persons, p = 0.4, OR 0.9 (CI 0.7-1.1.Seventy to eighty-five percent of adult IPD in the pre-PCV era were vaccine serotypes and 93% of cases had recognized risk factors (including HIV-infection for

  6. Streptococcus pneumoniae Serotypes and Mortality in Adults and Adolescents in South Africa: Analysis of National Surveillance Data, 2003 - 2008.

    Directory of Open Access Journals (Sweden)

    Cheryl Cohen

    Full Text Available An association between pneumococcal serotypes and mortality has been suggested. We aimed to investigate this among individuals aged ≥15 years with invasive pneumococcal disease (IPD in South Africa.IPD cases were identified through national laboratory-based surveillance at 25 sites, pre-pneumococcal conjugate vaccine (PCV introduction, from 2003-2008. We assessed the association between the 20 commonest serotypes and in-hospital mortality using logistic regression with serotype 4 (the third commonest serotype with intermediate case-fatality ratio (CFR as referent.Among 3953 IPD cases, CFR was 55% (641/1166 for meningitis and 23% (576/2484 for bacteremia (p<0.001. Serotype 19F had the highest CFR (48%, 100/207, followed by serotype 23F (39%, 99/252 and serotype 1 (38%, 246/651. On multivariable analysis, factors independently associated with mortality included serotype 1 (OR 1.9, 95%CI 1.1-3.5 and 19F (OR 2.9, 95%CI 1.4-6.1 vs. serotype 4; increasing age (25-44 years, OR 1.8, 95%CI 1.0-3.0; 45-64 years, OR 3.6, 95%CI 2.0-6.4; ≥65 years, OR 5.2, 95%CI 1.9-14.1; vs. 15-24 years; meningitis (OR 4.1, 95%CI 3.0-5.6 vs. bacteremic pneumonia; and HIV infection (OR1.7, 95%CI 1.0-2.8. On stratified multivariate analysis, serotype 19F was associated with increased mortality amongst bacteremic pneumococcal pneumonia cases, while no serotype was associated with increased mortality in meningitis cases.Mortality was increased in HIV-infected individuals, which may be reduced by increased antiretroviral therapy availability. Serotypes associated with increased mortality are included in the 10-and-13-valent PCV and may become less common in adults due to indirect effects following routine infant immunization.

  7. [Pneumococcal vaccination for children and adults].

    Science.gov (United States)

    Albrich, Werner

    2016-01-01

    Pneumococci are the leading bacterial causes of respiratory tract infections, bacteremia and meningitis. Pneumococcal conjugate vaccines (PCV) are effective and safe in young children. Their introduction led to significant reductions of invasive pneumococcal disease (IPD), pneumonia, otitis media and antibiotic-resistant pneumococcal infections. Beyond these effects in the vaccinated age groups, there is a reduction in nasopharyngeal pneumococcal carriage and therefore in transmission. This in turn led to marked reductions in IPD and pneumonia in non-vaccinated age groups, particularly elderly adults as evidence of herd protection. Recently it was shown that the 13-valent PCV13 is effective and safe in adults leading to the age-independent recommendation of PCV13 in all persons with risk factors. PMID:27268445

  8. Association of Streptococcus pneumoniae common protein antigen (CPA) antibodies and pneumococcal nasopharyngeal colonization in HIV-infected and HIV-uninfected African children.

    Science.gov (United States)

    Ditse, Z; Adrian, P V; Kuwanda, L; Madhi, S A

    2013-09-13

    Due to the high cost and limited serotype coverage of pneumococcal conjugate vaccines (PCV), pneumococcal common protein antigens (CPAs) are being investigated as potential vaccine candidates. CPAs are likely to be immunogenic in infants and could confer serotype-independent protection. There are limited data on natural antibody kinetics against CPAs in African populations. We aimed to determine the prevalence of naturally acquired antibody titres to 15 CPAs and explore their association to concurrent pneumococcal nasopharyngeal colonization in children aged 4-7 years with and without underlying HIV-infection and/or previous PCV-vaccination. A 15-plex Luminex assay was established to measure serum IgG titres against "cell-wall associated or surface-exposed" proteins (PspA, PspC, LytB, IgA1-proteinase, SP0082, PdB and PcsB), "membrane-associated" proteins (PsaA, SP0609, SP0749, PpmA, SlrA, StkP and SP2194) as well as the hypothetical protein, SP2027. Archived serum samples from HIV-uninfected (n=212) and HIV-infected (n=74) children were analyzed. Concurrent pneumococcal nasopharyngeal colonization was determined with standard microbiological methods. HIV-uninfected children had significantly higher antibody titres against PspA, PspC, PdB, SP0082, LytB, IgA1 proteinase and PcsB compared to HIV-infected children. In contrast, antibody titres against membrane associated proteins (PsaA, SP2027, PpmA and SlrA) were significantly lower in HIV-uninfected compared to HIV-infected children. Higher antibody titres against PdB, and PcsB were associated with the absence of pneumococcal colonization. There was no association between anti-CPA titres and PCV vaccination. In conclusion PdB and PcsB antigens are potential vaccine-candidates which may protect against pneumococcal colonization and consequently pneumococcal disease. PMID:23845819

  9. Antibiotic Resistance in Childhood with Pneumococcal Infection

    OpenAIRE

    Ali Gunes

    2013-01-01

    Aim: Resistance to antibiotics is better. Between should not be in capitals. Antibiotics resistant has been increasing in pneumococci that cause serious diseases such as pneumonia, meningitis in recent years. The resistance rates vary between geographic regions. In this study, we aimed to determine antibiotic resistance rates in pneumococcal infections in our region. Material and Method: This study included 31 pneumococcal strains isolated from blood, CSF and urine samples of patients with me...

  10. Meeting the Challenge: Prevention of Pneumococcal Disease with Conjugate Vaccines

    OpenAIRE

    Irma Gabriela Echániz Avilés; Fortino Solórzano Santos

    2001-01-01

    Streptococcus pneumoniae is one of the leading causes of both invasive and noninvasive diseases in the pediatric population and continues to represent a significant public health burden worldwide. The increasing incidence of antibioticresistant strains of the pathogen has complicated treatment and management of the various pneumococcal disease manifestations. Thus, the best management strategy may be the prevention of pneumococcal diseases through vaccination. Although several pneumococcal co...

  11. Update on the success of the pneumococcal conjugate vaccine

    OpenAIRE

    Kellner, JD

    2011-01-01

    Several years after the seven-valent pneumococcal conjugate vaccine (PCV7) was introduced in Canada and elsewhere, routine infant vaccination has led to near eradication of invasive pneumococcal disease caused by vaccine serotype strains in both children and adults. There have also been significant declines in pneumococcal-related disease including lobar pneumonia and otitis media. These declines have been offset, to some extent, by increases in nonvaccine serotype disease. Serotype 19A, whic...

  12. Hospitalization rates for pneumococcal disease in Brazil, 2004 - 2006

    Directory of Open Access Journals (Sweden)

    Hillegonda Maria Dutilh Novaes

    2011-06-01

    Full Text Available OBJECTIVE: To estimate hospitalization rates for pneumococcal disease based on the Brazilian Hospital Information System (SIH. METHODS: Descriptive study based on the Hospital Information System of Brazilian National Health System data from January 2004 to December 2006: number of hospitalizations and deaths for pneumococcal meningitis, pneumococcal sepsis, pneumococcal pneumonia and Streptococcus pneumoniae as the cause of diseases reported in Brazil. Data from the 2003 Brazilian National Household Survey were used to estimate events in the private sector. Pneumococcal meningitis cases and deaths reported to the Notifiable Diseases Information System during the study period were also analyzed. RESULTS: Pneumococcal disease accounted for 34,217 hospitalizations in the Brazilian National Health System (0.1% of all hospitalizations in the public sector. Pneumococcal pneumonia accounted for 64.8% of these hospitalizations. The age distribution of the estimated hospitalization rates for pneumococcal disease showed a "U"-shape curve with the highest rates seen in children under one (110 to 136.9 per 100,000 children annually. The highest hospital case-fatality rates were seen among the elderly, and for sepsis and meningitis. CONCLUSIONS: PD is a major public health problem in Brazil. The analysis based on the SIH can provide an important input to pneumococcal disease surveillance and the impact assessment of immunization programs.

  13. Identification of Streptococcus pneumoniae

    OpenAIRE

    Kaijalainen, Tarja

    2006-01-01

    Objectives: Streptococcus pneumoniae, pneumococcus, is an importanthuman pathogen that causes both serious invasive infections, suchas septicaemia, meningitis and pneumonia, as well as mild upper respiratoryinfections. It also belongs to the normal nasopharyngeal microbialflora. The purpose of this study was to compare bacteriologicalphenotypic methods with genetechnological methods in the identificationof pneumococci, especially among suspect pneumococcal isolateslacking one or more typical ...

  14. Decline in antibiotic resistance and changes in the serotype distribution of Streptococcus pneumoniae isolates from children with acute otitis media; a 2001-2011 survey by the French Pneumococcal Network.

    Science.gov (United States)

    Kempf, M; Varon, E; Lepoutre, A; Gravet, A; Baraduc, R; Brun, M; Chardon, H; Cremniter, J; Croizé, J; Dalmay, F; Demachy, M-C; Fosse, T; Grelaud, C; Hadou, T; Hamdad, F; Koeck, J-L; Luce, S; Mermond, S; Patry, I; Péchinot, A; Raymond, J; Ros, A; Segonds, C; Soullié, B; Tandé, D; Vergnaud, M; Vernet-Garnier, V; Wallet, F; Gutmann, L; Ploy, M-C; Lanotte, P

    2015-01-01

    Streptococcus pneumoniae is an important cause of acute otitis media (AOM). The aim of this study was to evaluate trends in antibiotic resistance and circulating serotypes of pneumococci isolated from middle ear fluid of French children with AOM during the period 2001-2011, before and after the introduction of the PCV-7 (2003) and PCV-13 (2010) vaccines. Between 2001 and 2011 the French pneumococcal surveillance network analysed the antibiotic susceptibility of 6683 S. pneumoniae isolated from children with AOM, of which 1569 were serotyped. We observed a significant overall increase in antibiotic susceptibility. Respective resistance (I+R) rates in 2001 and 2011 were 76.9% and 57.3% for penicillin, 43.0% and 29.8% for amoxicillin, and 28.6% and 13.0% for cefotaxime. We also found a marked reduction in vaccine serotypes after PCV-7 implementation, from 63.0% in 2001 to 13.2% in 2011, while the incidence of the additional six serotypes included in PCV-13 increased during the same period, with a particularly high proportion of 19A isolates. The proportion of some non-PCV-13 serotypes also increased between 2001 and 2011, especially 15A and 23A. Before PCV-7 implementation, most (70.8%) penicillin non-susceptible pneumococci belonged to PCV-7 serotypes, whereas in 2011, 56.8% of penicillin non-susceptible pneumococci belonged to serotype 19A. Between 2001 and 2011, antibiotic resistance among pneumococci responsible for AOM in France fell markedly, and PCV-7 serotypes were replaced by non-PCV-7 serotypes, especially 19A. We are continuing to assess the impact of PCV-13, introduced in France in 2010, on pneumococcal serotype circulation and antibiotic resistance.

  15. Pneumococcal Conjugate Vaccines Overcome Splenic Dependency of Antibody Response to Pneumococcal Polysaccharides

    OpenAIRE

    Breukels, Mijke A.; Zandvoort, Andre; van den Dobbelsteen, Germie P. J. M.; van den Muijsenberg, Adrie; Lodewijk, Monique E.; Beurret, Michel; Pieter A Klok; Timens, Wim; Rijkers, Ger T.

    2001-01-01

    Protection against infections with Streptococcus pneumoniae depends on the presence of antibodies against capsular polysaccharides that facilitate phagocytosis. Asplenic patients are at increased risk for pneumococcal infections, since both phagocytosis and the initiation of the antibody response to polysaccharides take place in the spleen. Therefore, vaccination with pneumococcal polysaccharide vaccines is recommended prior to splenectomy, which, as in the case of trauma, is not always feasi...

  16. Pneumococcal Infections

    Science.gov (United States)

    Pneumococci are a type of streptococcus bacteria. The bacteria spread through contact with people who are ill or by healthy people who carry the bacteria in the back of their nose. Pneumococcal infections can be mild or severe. The most common types of infections are Ear infections Sinus infections ...

  17. Use of procalcitonin and C-reactive protein to evaluate vaccine efficacy against pneumonia.

    Directory of Open Access Journals (Sweden)

    Shabir A Madhi

    2005-02-01

    Full Text Available BACKGROUND: Pneumonia remains the leading cause of death in young children. The poor specificity of chest radiographs (CXRs to diagnose pneumococcal pneumonia may underestimate the efficacy of pneumococcal conjugate vaccine in preventing pneumococcal pneumonia. METHODS AND FINDINGS: The efficacy of nine-valent pneumococcal conjugate vaccine among children not infected with HIV (21%; 95% confidence interval, 1%-37% increased when CXR-confirmed pneumonia was associated with serum C-reactive protein of 120 mg/l (12 mg/dl or more and procalcitonin of 5.0 ng/ml or more (64%; 95% confidence interval, 23%-83%. Similar results were observed in children infected with HIV. CONCLUSION: C-reactive protein and procalcitonin improve the specificity of CXR to diagnose pneumococcal pneumonia and may be useful for the future evaluation of the effectiveness of pneumococcal conjugate vaccine in preventing pneumococcal pneumonia.

  18. Clonal distribution of pneumococcal serotype 19F isolates from Ghana

    DEFF Research Database (Denmark)

    Sparding, Nadja; Dayie, Nicholas Tete Kwaku Dzifa; Mills, Richael O.;

    2015-01-01

    Streptococcus pneumoniae is a major cause of morbidity and mortality worldwide. Pneumococcal strains are classified according to their capsular polysaccharide and more than 90 different serotypes are currently known. In this project, three distinct groups of pneumococcal carriage isolates from Gh...... in Ghana in that many new clones were identified. This supports the importance of continued monitoring of pneumococcal carriage in Ghana and elsewhere when vaccines, e.g., PCV-13, have been introduced to monitor the possible future spread of antimicrobial resistant clones.......Streptococcus pneumoniae is a major cause of morbidity and mortality worldwide. Pneumococcal strains are classified according to their capsular polysaccharide and more than 90 different serotypes are currently known. In this project, three distinct groups of pneumococcal carriage isolates from...

  19. [Pneumococcal vaccination in obstructive lung diseases -- what can we expect?].

    Science.gov (United States)

    Rose, M; Lode, H; de Roux, A; Zielen, S

    2005-03-01

    Many countries' guidelines recommend pneumococcal vaccination for patients suffering from obstructive airway disease. This paper reviews the literature as to immunogenicity and safety of this immunization. There is no evidence for a negative effect of pneumococcal vaccination on these patients. Only a few data exist on the preventive impact of pneumococcal vaccination as to exacerbations of obstructive airway diseases. Existing studies mostly took up this question as a side aspect. The effect in children and adults appears limited. On the other hand, the pneumococcal conjugate vaccine prevents life-threatening invasive infections in children younger than 5 years, and pneumococcal polysaccharide vaccine protects healthy adults against bacteriaemic pneumonia. Thus, pneumococcal vaccination of patients suffering from obstructive airway disease is recommendable.

  20. Pneumonia due to pandemic (H1N1) 2009 influenza virus and Klebsiella pneumoniae capsular serotype K16 in a patient with nasopharyngeal cancer.

    Science.gov (United States)

    Lai, Chih-Cheng; Lee, Pei-Lin; Tan, Che-Kim; Huang, Yu-Tsung; Kao, Chiang-Lian; Wang, Jin-Town; Hsueh, Po-Ren

    2012-10-01

    Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus and group A Streptoccocus, but no Klebsiella pneumoniae were responsible for bacterial coinfections during the 2009 and previous influenza pandemics. We hereby report a case with concurrent bacteremic pneumonia due to an unusual capsular serotype K16 K. pneumoniae and pandemic (H1N1) 2009 influenza in a patient with nasopharyngeal cancer. Such a coinfection has not previously been described. PMID:22153762

  1. Adult zebrafish model for pneumococcal pathogenesis.

    Science.gov (United States)

    Saralahti, Anni; Piippo, Hannaleena; Parikka, Mataleena; Henriques-Normark, Birgitta; Rämet, Mika; Rounioja, Samuli

    2014-02-01

    Streptococcus pneumoniae (pneumococcus) is a leading cause of community acquired pneumonia, septicemia, and meningitis. Due to incomplete understanding of the host and bacterial factors contributing to these diseases optimal treatment and prevention methods are lacking. In the present study we examined whether the adult zebrafish (Danio rerio) can be used to investigate the pathophysiology of pneumococcal diseases. Here we show that both intraperitoneal and intramuscular injections of the pneumococcal strain TIGR4 cause a fulminant, dose-dependent infection in adult zebrafish, while isogenic mutant bacteria lacking the polysaccharide capsule, autolysin, or pneumolysin are attenuated in the model. Infection through the intraperitoneal route is characterized by rapid expansion of pneumococci in the bloodstream, followed by penetration of the blood-brain barrier and progression to meningitis. Using Rag1 mutant zebrafish, which are devoid of somatic recombination and thus lack adaptive immune responses, we show that clearance of pneumococci in adult zebrafish depends mainly on innate immune responses. In conclusion, this study provides evidence that the adult zebrafish can be used as a model for a pneumococcal infection, and that it can be used to study both host and bacterial factors involved in the pathogenesis. However, our results do not support the use of the zebrafish in studies on the role of adaptive immunity in pneumococcal disease or in the development of new pneumococcal vaccines.

  2. Food-borne bacteremic illnesses in febrile neutropenic children

    OpenAIRE

    Anselm Chi-wai Lee; Nellie Dawn Siao-ping Ong

    2011-01-01

    Bacteremia following febrile neutropenia is a serious complication in children with malignancies. Preventive measures are currently targeted at antimicrobial prophylaxis, amelioration of drug-induced neutropenia, and nosocomial spread of pathogens, with little attention to community-acquired infections. A retrospective study was conducted at a pediatric oncology center during a 3-year period to identify probable cases of food-borne infections with bacteremia. Twenty-one bacteremic illnesses a...

  3. Continued control of pneumococcal disease in the UK - the impact of vaccination

    OpenAIRE

    Gladstone, R.A.; Jefferies, J. M.; Faust, S. N.; Clarke, S. C.

    2011-01-01

    Streptococcus pneumoniae, also known as the pneumococcus, is an important cause of morbidity and mortality in the developed and developing world. Pneumococcal conjugate vaccines were first introduced for routine use in the USA in 2000, although the seven-valent pneumococcal conjugate vaccine (PCV7) was not introduced into the UK's routine childhood immunization programme until September 2006. After its introduction, a marked decrease in the incidence of pneumococcal disease was observed, both...

  4. Clinical and bacteriological characteristics of invasive pneumococcal disease after pneumococcal 10-valent conjugate vaccine implementation in Salvador, Brazil.

    Science.gov (United States)

    Leite, Carolina Regis; Azevedo, Jailton; Galvão, Vivian Santos; Moreno-Carvalho, Otávio; Reis, Joice Neves; Nascimento-Carvalho, Cristiana

    2016-01-01

    Invasive pneumococcal disease is a relevant public health problem in Brazil, especially among children and the elderly. In July/2010 a 10-valent pneumococcal conjugate vaccine was introduced to the immunization schedule of Brazilian children under two years of age. Between July/2010 and December/2013 we conducted a case-series study on invasive pneumococcal disease in Salvador, Brazil to describe the clinical and bacteriological profile of invasive pneumococcal disease cases during the post-implementation period. Eighty-two cases were eligible. Mean age was 31 years (interquartile range, 3-42); 17.1% and 30.5% were under 2 years and 5 years, respectively. Pneumococcal meningitis (n=64, 78.1%), bacteraemic pneumococcal pneumonia (n=12, 14.6%) and bacteraemia (n=6, 7.3%) were the clinical syndromes identified. Thirty-three different serotypes were found. Of these, serotype 14 (n=12, 14.6%) was the most common, followed by 23F (n=10, 12.2%), 12F (n=8, 9.8%), 18C (n=5, 6.1%) and 6B (n=5, 6.1%). Investigations conducted in Salvador in the pre-vaccine period did not identify serotype 12F as one of the most prevalent serotypes. Increase of serotype 12F was observed in different regions of Brazil, in the post-vaccine period. Among children under two years of age, the target group for 10-valent pneumococcal conjugate vaccine, 11 (78.6%) of the 14 isolated strains of Streptococcus pneumoniae belonged to vaccine serotypes; at least 50% of these children were not vaccinated. The relatively recent implementation of 10-valent pneumococcal conjugate vaccine in Brazil reinforces the need to maintain an active surveillance of invasive pneumococcal disease cases, considering the possible increase of invasive pneumococcal disease cases related to non-vaccine serotypes and the changes on the clinical presentation of the disease.

  5. Nasopharyngeal microbial interactions in the era of pneumococcal conjugate vaccination.

    Science.gov (United States)

    Dunne, Eileen M; Smith-Vaughan, Heidi C; Robins-Browne, Roy M; Mulholland, E Kim; Satzke, Catherine

    2013-05-01

    The nasopharynx of children is often colonised by microorganisms such as Streptococcus pneumoniae (the pneumococcus) that can cause infections including pneumonia and otitis media. In this complex environment, bacteria and viruses may impact each other through antagonistic as well as synergistic interactions. Vaccination may alter colonisation dynamics, evidenced by the rise in non-vaccine serotypes following pneumococcal conjugate vaccination. Discovery of an inverse relationship between S. pneumoniae and Staphylococcus aureus carriage generated concern that pneumococcal vaccination could increase S. aureus carriage and disease. Here we review data on co-colonisation of pathogens in the nasopharynx, focusing on S. pneumoniae and the impact of pneumococcal vaccination. Thus far, pneumococcal vaccination has not had a sustained impact on S. aureus carriage but it is associated with an increase in non-typeable Haemophilus influenzae in acute otitis media aetiology. Advances in bacterial and viral detection methodologies have facilitated research in nasopharyngeal microbiology and will aid investigation of potential vaccine-induced changes, particularly when baseline studies can be conducted prior to pneumococcal vaccine introduction.

  6. Maternal immunization with pneumococcal surface protein A protects against pneumococcal infections among derived offspring.

    Directory of Open Access Journals (Sweden)

    Masamitsu Kono

    Full Text Available Pathogen-specific antibody plays an important role in protection against pneumococcal carriage and infections. However, neonates and infants exhibit impaired innate and adaptive immune responses, which result in their high susceptibility to pneumococci. To protect neonates and infants against pneumococcal infection it is important to elicit specific protective immune responses at very young ages. In this study, we investigated the protective immunity against pneumococcal carriage, pneumonia, and sepsis induced by maternal immunization with pneumococcal surface protein A (PspA. Mother mice were intranasally immunized with recombinant PspA (rPspA and cholera toxin B subunit (CTB prior to being mated. Anti-PspA specific IgG, predominantly IgG1, was present at a high level in the serum and milk of immunized mothers and in the sera of their pups. The pneumococcal densities in washed nasal tissues and in lung homogenate were significantly reduced in pups delivered from and/or breast-fed by PspA-immunized mothers. Survival after fatal systemic infections with various types of pneumococci was significantly extended in the pups, which had received anti-PspA antibody via the placenta or through their milk. The current findings strongly suggest that maternal immunization with PspA is an attractive strategy against pneumococcal infections during early childhood.

  7. Impact of Pneumococcal Conjugate Universal Routine Vaccination on Pneumococcal Disease in Italian Children

    Directory of Open Access Journals (Sweden)

    Francesca Fortunato

    2015-01-01

    Full Text Available In Italy, the effectiveness of pneumococcal universal vaccination in preventing vaccine-type invasive pneumococcal disease (IPD in the PCV7/PCV13 shifting period was estimated to be 84.3% (95% CI: 84.0–84.6% in children <5 years. This study aims at corroborating the estimation of both the effectiveness (VE of PCVs and its impact in reducing pneumococcal diseases. A 1 : 3 matched-case-control study was conducted among children <5 years old hospitalized for IPD or pneumococcal pneumonia (PP between 2006 and 2012 in the Puglia region. Moreover, hospitalizations for pneumococcal outcomes in the pre- and postvaccination period and the hospitalization risk ratios (HRRs with 95% CIs were computed in Italy and in the first eight regions that introduced PCVs in 2006. The overall effectiveness of PCVs was 75% (95% CI: 61%–84%; it was 69% (95% CI: 30%–88% against IPD and 77% (95% CI: 61%–87% against PP. PCVs showed a significant impact on IPD and acute otitis media either at a national level or in those regions with a longer vaccination history, with a nearly 40% reduction of hospitalizations for both outcomes. Our findings provide further evidence of the effectiveness of PCVs against pneumococcal diseases and its impact on nasopharyngeal carriage in children <5 years, indicating the importance of maintaining high immunization coverage.

  8. Investigating the Effects of Probiotics on Pneumococcal Colonization Using an In Vitro Adherence Assay

    OpenAIRE

    Dunne, Eileen M.; Toh, Zheng Q.; John, Mary; Manning, Jayne; Satzke, Catherine; Licciardi, Paul

    2014-01-01

    Adherence of Streptococcus pneumoniae (the pneumococcus) to the epithelial lining of the nasopharynx can result in colonization and is considered a prerequisite for pneumococcal infections such as pneumonia and otitis media. In vitro adherence assays can be used to study the attachment of pneumococci to epithelial cell monolayers and to investigate potential interventions, such as the use of probiotics, to inhibit pneumococcal colonization. The protocol described here is used to investigate t...

  9. Recommendation for use of the newly introduced pneumococcal protein conjugate vaccines in Korea

    OpenAIRE

    Eun Hwa Choi; Kyung Hyo Kim; Yae Jean Kim; Jong Hyun Kim; Su Eun Park; Hoan Jong Lee; Byung Wook Eun; Dae Sun Jo; Kyong Min Choi; Young Jin Hong

    2011-01-01

    Streptococcus pneumoniae remains a leading cause of invasive infections including bacteremia and meningitis, as well as mucosal infections such as otitis media and pneumonia among children and adults. The 7-valent pneumococcal conjugate vaccine (PCV7) was licensed for use among infants and young children in many countries including Korea. The routine use of PCV7 has resulted in a decreased incidence of invasive pneumococcal disease (IPD) by the vaccine serotypes among the vaccinees and substa...

  10. [Invasive pneumococcal disease in two non-vaccinated pediatric cases: pleural empyema and bacteremia].

    Science.gov (United States)

    Kanık Yüksek, Saliha; Gülhan, Belgin; Tezer, Hasan; Özkaya Parlakay, Aslınur; Uzun Kenan, Bahriye; Sayed Oskovi, Hülya; Nar Ötgün, Selin

    2015-07-01

    Streptococcus pneumoniae, a gram-positive diplococcus, is the causative agent of invasive pneumococcal diseases (IPDs) characterized by severe infections such as bacteraemia, sepsis and meningitis. S.pneumoniae and IPDs are situated in the focus of the vaccine studies because of being encompassed of a significant burden of disease in the world, severe mortality and morbidities, and location in vaccine-preventable diseases group. Although S.pneumoniae has more than 90 defined serotypes, certain serotypes are often identified as the cause of IPDs. Individuals with comorbid and chronic diseases, primary or secondary immune deficiencies, and 65 years of age are at increased risk for IPDs. Currently, a 23-valent polysaccharide vaccine and also 7, 10 and 13 valent pneumococcal conjugated vaccines (PCV) have been produced for pneumococci. Phase studies of protein based vaccines, which will provide protection independent of serotypes, and 15-valent pneumococcal conjugated vaccine are still ongoing. In Turkey, in November 2008 PCV7 and in April 2011 PCV13 have been implemented in the national immunization program. First case of the pneumococcal unvaccinated cases presented in this report was a 6-year-old girl patient with pneumonia and pleural empyema due to S.pneumoniae serotype 1, without any underlying risk factors. The other case is a 52-days-old male patient, who had a history of pneumococcal septicemia in the newborn period and was followed for bacteremia associated S.pneumoniae serotype 12B and diagnosed as complement deficiency on follow-up. S.pneumoniae serotype 1 is within serotypes covered by 10 and 13 valent pneumococcal conjugate vaccines and pneumococcal polysaccharide vaccine that are in use today, and is a highly invasive strain often isolated in pneumococcal lobar pneumonia and empyema. S.pneumoniae serotype 12B is a non-vaccine serotype not included in any of conjugate and polysaccharide vaccines, and usually obtained in respiratory infections and

  11. Evaluation of anti-pneumococcal capsular antibodies as adjunctive therapy in experimental pneumococcal meningitis

    DEFF Research Database (Denmark)

    Brandt, Christian; Frimodt-Moller, N; Lundgren, Jens Dilling;

    2006-01-01

    OBJECTIVE: Bacteraemia concomitant with meningitis has been shown to greatly affect outcome. Consequently, the efficacy of serotype-specific anti-pneumococcal antiserum (APAS) was investigated in a rat model of pneumococcal meningitis. METHODS: Rats were infected with Streptococcus pneumoniae...... serotype 3. All rats received ceftriaxone starting 26 h post-infection. APAS was administered either at the time of infection or 26 h post-infection and effects were compared with rats treated with antibiotics only. RESULTS AND CONCLUSION: A significant clinical benefit was found when APAS was given...... at the time of infection whereas no effect was found when administered 26 h after infection. This work indicates that the clinical value of using APAS in pneumococcal meningitis may be limited...

  12. [Clinical burden of multi-cause and pneumococcal pneumonia, meningitis, and septicemia in Hungary. Results of a retrospective study (2006-2011)].

    Science.gov (United States)

    Ludwig, Endre; Jorgensen, Lindsay; Gray, Sharon; Munson, Samantha; Chou, Kathy; Gutterman, Elane M

    2014-09-01

    Bevezetés: Kevés adat áll rendelkezésre a konjugált pneumococcusvakcináknak a pneumonia, meningitis és septikaemia előfordulására gyakorolt hatásáról Magyarországon. Célkitűzés: A szerzők retrospektív vizsgálattal kívánták felmérni a 2006–2011 között Magyarországon minden korosztályban előforduló, kórházi kezelést igénylő, bármely kórokú és pneumococcus okozta pneumonia-, meningitis- és septikaemiaeseteket. Módszer: Összesített adatokat gyűjtöttek az Országos Egészségbiztosítási Pénztár adatbázisából előre meghatározott BNO-10-kódok segítségével. Az összehasonlítás χ2-próba segítségével készült a következők alapján: átlagos arány a védőoltás bevezetését megelőzően (2006–2007) versus átlagos arány a védőoltás bevezetését követően (2010–2011). Eredmények: A 0–4 éves korú gyermekeknél a kórházi kezelést igénylő esetek aránya jelentősen csökkent a bármely kórokú tüdőgyulladás és agyhártyagyulladás esetében, de nőtt a septikaemia esetében. A többi korcsoportnál jelentősen növekedett a bármely kórokú pneumonia- és septikaemiaesetek száma. A kórházi halálozás aránya az életkorral emelkedett. A pneumococcusspecifikus kódok korlátozott alkalmazása miatt nem állapítottak meg egyértelmű eredményeket a pneumococcus okozta betegségeket illetően. Következtetések: A bármely kórokú tüdőgyulladás és agyhártyagyulladás csökkenése a 0–4 éves korosztálynál a konjugált pneumococcusvakcinációnak a kórházi kezelés arányára gyakorolt közvetlen hatására utal. Orv. Hetil., 2014, 155(36), 1426–1436.

  13. Meeting the challenge: prevention of pneumococcal disease with conjugate vaccines

    Directory of Open Access Journals (Sweden)

    Echániz-Avilés Irma Gabriela

    2001-01-01

    Full Text Available Streptococcus pneumoniae is one of the leading causes of both invasive and noninvasive diseases in the pediatric population and continues to represent a significant public health burden worldwide. The increasing incidence of antibioticresistant strains of the pathogen has complicated treatment and management of the various pneumococcal disease manifestations. Thus, the best management strategy may be the prevention of pneumococcal diseases through vaccination. Although several pneumococcal conjugate vaccines have been clinically studied in infants and children, only a 7-valent conjugate vaccine (PNCRM7; Prevnar®/Prevenar® is currently approved for the prevention of invasive disease. Vaccination with PNCRM7 is safe and effective in infants and young children. Routine vaccination with the conjugate vaccine could improve outcomes by safeguarding against the development of antibiotic-resistant strains of S. pneumoniae, thus simplifying the management of pneumococcal disease. Additionally, the overall costs associated with the treatment of pneumococcal diseases could be substantially reduced, particularly in developing countries. The time has come for fully applying this new advancement against S. pneumoniae, to benefit the children of the world. The Spanish version of this paper is available at: http://www.insp.mx/salud/index.html

  14. Present-day concepts in radiodiagnosis of acute pneumonias in children

    International Nuclear Information System (INIS)

    An X-ray study of 300 children with pneumonias of various etiology has shown that Pneumococcus is the most frequent cause of pneumonia whereas Hemophilus and Mycoplasma pneumonia are observed less frequently. The most common types are segmental (41%), lobular (30%), focal-confluent (20%) and focal (9%). Pleuritis complicated a course of pneumonia in more than half of the patients. Pulmonary destructive changes were most frequent in pneumococcal pneumonia (20%), less frequent in Hemophilus pneumonia and undetectable in Mycoplasma pneumonia

  15. Impact of bacteremia on the pathogenesis of experimental pneumococcal meningitis

    DEFF Research Database (Denmark)

    Brandt, C.T.; Holm, D.; Liptrot, Matthew George;

    2008-01-01

    Background. Bacteremia plays a major role in the outcome of pneumococcal meningitis. This experimental study investigated how bacteremia influences the pathophysiologic profile of the brain. Methods. Rats with Streptococcus pneumoniae meningitis were randomized to 1 of 3 groups of infected study ...

  16. Novel Clones of Streptococcus pneumoniae Causing Invasive Disease in Malaysia

    OpenAIRE

    Johanna M Jefferies; Mohd Yasim Mohd Yusof; Shamala Devi Sekaran; Clarke, Stuart C.

    2014-01-01

    Although Streptococcus pneumoniae is a leading cause of childhood disease in South East Asia, little has previously been reported regarding the epidemiology of invasive pneumococcal disease in Malaysia and very few studies have explored pneumococcal epidemiology using multilocus sequence typing (MLST). Here we describe serotype, multilocus sequence type (ST), and penicillin susceptibility of thirty pneumococcal invasive disease isolates received by the University of Malaya Medical Centre betw...

  17. Efficacy of conjugate vaccines in pneumococcal infection prevention

    Directory of Open Access Journals (Sweden)

    A. L. Perova

    2014-01-01

    Full Text Available The problem of pneumococcal infection is actual for many countries of the world in connection with high incidence and mortality. Vaccination by the 7-valent conjugated pneumococcal vaccine of children till 2 years is available in Russia since 2009, 13-valent – since 2012. Objectives – an assessment of clinical and epidemiological efficacy in pneumococcal infection prevention infection by catamnesis after 7-valent conjugated pneumococcal vaccine application. Observation over incidence of pneumonia and otitis of 50 children imparted against a pneumococcal infection is made. The indicator of density of incidence of pneumonia in group of the imparted made 9,7 on 1000 (95% of CI; 9,1–10,3 in group of comparison – 92,6 on 1000 (95% of CI; 91,3–93,9. Index of efficacy of vaccination concerning pneumonia of any etiology – 9,5, effectiveness ratio – 89,5%. The indicator of density of incidence of otitis at the imparted was 1,8 times less – 155,3 on 1000 (95% of CI; 150,9–155,7 in group of comparison – 263,9 on 1000 (95% of CI; 261,7–266,1. The index and vaccination effectiveness ratio concerning acute otitis media made 1,8 and 44,3%. Thus, vaccination against pneumococcal infection is effective as concerning community acquired pneumonia, and acute otitis media of any etiology.

  18. Antibiotic Resistance in Childhood with Pneumococcal Infection

    Directory of Open Access Journals (Sweden)

    Ali Gunes

    2013-10-01

    Full Text Available Aim: Resistance to antibiotics is better. Between should not be in capitals. Antibiotics resistant has been increasing in pneumococci that cause serious diseases such as pneumonia, meningitis in recent years. The resistance rates vary between geographic regions. In this study, we aimed to determine antibiotic resistance rates in pneumococcal infections in our region. Material and Method: This study included 31 pneumococcal strains isolated from blood, CSF and urine samples of patients with meningitis, sepsis and urinary tract infections who admitted Dicle University Medicine School Children Clinic and Diyarbakir Pediatric Hospital Between December 2004-April 2007. Reproducing clinical specimens with alpha-hemolysis, optochin-sensitive, bile soluble and gram-positive diplococci morphology was defined as S. pneumoniae. The antimicrobial susceptibilities of strains were measured by the E-test method. MIC values of penicillin against pneumococci was accepted as <0.06 mg / ml value of the sensitive, 0.12-1μg/ml mid-level resistance, ≥ 2 mg / ml value of the high-level resistance. Results: It was found 16% mid-level penicillin resistance and 3.2% high-level penicillin resistance by E-test method. 80.7% of Strains were percent of the penicillin-sensitive. Seftiriakson resistance was found as 3.2%. there was not Vancomycin resistance. Discussion: We think penicillin therapy is enough effective for pneumococcal infections except serious conditions such as meningitis and sepsis. Also we think it should be supported by multicenter studies.

  19. Directed vaccination against pneumococcal disease.

    Science.gov (United States)

    Li, Yi; Hill, Andrew; Beitelshees, Marie; Shao, Shuai; Lovell, Jonathan F; Davidson, Bruce A; Knight, Paul R; Hakansson, Anders P; Pfeifer, Blaine A; Jones, Charles H

    2016-06-21

    Immunization strategies against commensal bacterial pathogens have long focused on eradicating asymptomatic carriage as well as disease, resulting in changes in the colonizing microflora with unknown future consequences. Additionally, current vaccines are not easily adaptable to sequence diversity and immune evasion. Here, we present a "smart" vaccine that leverages our current understanding of disease transition from bacterial carriage to infection with the pneumococcus serving as a model organism. Using conserved surface proteins highly expressed during virulent transition, the vaccine mounts an immune response specifically against disease-causing bacterial populations without affecting carriage. Aided by a delivery technology capable of multivalent surface display, which can be adapted easily to a changing clinical picture, results include complete protection against the development of pneumonia and sepsis during animal challenge experiments with multiple, highly variable, and clinically relevant pneumococcal isolates. The approach thus offers a unique and dynamic treatment option readily adaptable to other commensal pathogens. PMID:27274071

  20. Circulating Pneumolysin Is a Potent Inducer of Cardiac Injury during Pneumococcal Infection.

    OpenAIRE

    Yasir Alhamdi; Neill, Daniel R.; Abrams, Simon T.; Malak, Hesham A.; Reham Yahya; Richard Barrett-Jolley; Guozheng Wang; Aras Kadioglu; Cheng-Hock Toh

    2015-01-01

    Streptococcus pneumoniae accounts for more deaths worldwide than any other single pathogen through diverse disease manifestations including pneumonia, sepsis and meningitis. Life-threatening acute cardiac complications are more common in pneumococcal infection compared to other bacterial infections. Distinctively, these arise despite effective antibiotic therapy. Here, we describe a novel mechanism of myocardial injury, which is triggered and sustained by circulating pneumolysin (PLY). Using ...

  1. [Endocarditis, meningitis, pneumopathy and pneumococcal cerebral abscess in an alcoholic smoker].

    Science.gov (United States)

    Vandenbos, F; Roth, S; Montagne, N

    2001-10-01

    We report a case of mitral endocarditis caused by Streptococcus pneumoniae in a 43 year old man with history of alcohol abuse and cigarette smoking. The pneumococcal endocarditis was associated with pneumonia, meningitis and brain abscess. Only transesophageal echocardiography could confirm the presence of vegetation. The patient was treated medically with good results. PMID:11887774

  2. The persisting burden of invasive pneumococcal disease in HIV patients: an observational cohort study

    Directory of Open Access Journals (Sweden)

    Siemieniuk Reed AC

    2011-11-01

    Full Text Available Abstract Background The increasing use of highly active antiretroviral therapy (HAART and pneumococcal immunization along with shifting community exposures may have altered the burden of Streptococcus pneumoniae disease in HIV-infected persons. We describe the burden and risk factors for pneumococcal disease in the modern era of HIV care and evaluate the use of a 23-valent pneumococcal polysaccharide vaccine (PPV-23. Methods The incidence of invasive pneumococcal disease (IPD between January 1st, 2000 and January 1st, 2010 in a regional HIV population in Southern Alberta, Canada was determined by linking comprehensive laboratory and hospital surveillance data. Clinical and epidemiologic data including risk factors for S. pneumoniae, history of pneumococcal immunization, serotypes of infections, and length of any hospitalizations for pneumococcal disease were evaluated with multivariate analysis. CD4 count and viral load at immunization were evaluated with a nested case-control analysis. Results In 1946 HIV-patients with 11,099 person-years of follow up, there were 68 distinct episodes of pneumococcal disease occurring in 50 patients. Increased risk was seen if female, age >60, Aboriginal ethnicity, lower education, injection drug use, smoking, nadir CD4 Conclusions Despite universal access to intensive measures to prevent pneumococcal disease including the widespread use of HAART and PPV-23 immunization, the incidence of IPD remains high in HIV patients with its associated morbidity and mortality.

  3. PspA Family Distribution, Antimicrobial Resistance and Serotype of Streptococcus pneumoniae Isolated from Upper Respiratory Tract Infections in Japan

    OpenAIRE

    Muneki Hotomi; Akihisa Togawa; Masamitsu Kono; Yorihiko Ikeda; Shin Takei; Hollingshead, Susan K.; Briles, David E.; Kenji Suzuki; Noboru Yamanaka

    2013-01-01

    BACKGROUND: The protection against pneumococcal infections provided by currently available pneumococcal polysaccharide conjugate vaccines are restricted to the limited number of the serotypes included in the vaccine. In the present study, we evaluated the distribution of the pneumococcal capsular type and surface protein A (PspA) family of pneumococcal isolates from upper respiratory tract infections in Japan. METHODS: A total of 251 S. pneumoniae isolates from patients seeking treatment for ...

  4. Method for inducing experimental pneumococcal meningitis in outbred mice

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    Cintorino Marcella

    2004-09-01

    Full Text Available Abstract Background Streptococcus pneumoniae is the leading cause of bacterial meningitis. Pneumococcal meningitis is associated with the highest mortality among bacterial meningitis and it may also lead to neurological sequelae despite the use of antibiotic therapy. Experimental animal models of pneumococcal meningitis are important to study the pathogenesis of meningitis, the host immune response induced after infection, and the efficacy of novel drugs and vaccines. Results In the present work, we describe in detail a simple, reproducible and efficient method to induce pneumococcal meningitis in outbred mice by using the intracranial subarachnoidal route of infection. Bacteria were injected into the subarachnoid space through a soft point located 3.5 mm rostral from the bregma. The model was tested with several doses of pneumococci of three capsular serotypes (2, 3 and 4, and mice survival was recorded. Lethal doses killing 50 % of animals infected with type 2, 3 and 4 S. pneumoniae were 3.2 × 10, 2.9 × 10 and 1.9 × 102 colony forming units, respectively. Characterisation of the disease caused by the type 4 strain showed that in moribund mice systemic dissemination of pneumococci to blood and spleen occurred. Histological analysis of the brain of animals infected with type 4 S. pneumoniae proved the induction of meningitis closely resembling the disease in humans. Conclusions The proposed method for inducing pneumococcal meningitis in outbred mice is easy-to-perform, fast, cost-effective, and reproducible, irrespective of the serotype of pneumococci used.

  5. Interleukin-35 is upregulated in response to influenza virus infection and secondary bacterial pneumonia.

    Science.gov (United States)

    Chen, Yi; Wang, Chuan-jiang; Lin, Shi-hui; Zhang, Mu; Li, Sheng-yuan; Xu, Fang

    2016-05-01

    Postinfluenza pneumococcal pneumonia is an important cause of global morbidity and mortality. What causes this increased susceptibility is not well elucidated. IL-35 is a newly described cytokine in infectious tolerance. A murine model was established to study postinfluenza pneumococcal pneumonia and evaluate the role of IL-35 in host defense against postinfluenza pneumococcal pneumonia. Pulmonary IL-35 was rapidly up-regulated during murine influenza infection, which was partially mediated by type I IFN-α/β receptor signaling pathway. Secondary pneumococcal infection led to a synergistic IL-35 response in influenza-infected mice. Clinical analysis showed that IL-35 levels were significantly elevated in the patients with influenza infection compared with healthy individuals and influenza infection could induce IL-35 production from human peripheral blood mononuclear cells. These data suggest that IL-35 contributes to the increased susceptibility to secondary pneumococcal pneumonia at least in part by inhibiting the early immune response.

  6. The epidemiology of pneumococcal infection in children in the developing world.

    OpenAIRE

    Greenwood, B.

    1999-01-01

    Pneumonia causes about three million deaths a year in young children, nearly all of which are in developing countries. Streptococcus pneumoniae (the pneumococcus) is the most important bacterial cause of pneumonia in young children and so is likely to be responsible for a high proportion of these deaths. The pneumococcus is also responsible for a substantial proportion of the 100,000-500,000 deaths that occur from meningitis in children each year. The incidence of invasive pneumococcal diseas...

  7. Food-borne bacteremic illnesses in febrile neutropenic children

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    Anselm Chi-wai Lee

    2011-08-01

    Full Text Available Bacteremia following febrile neutropenia is a serious complication in children with malignancies. Preventive measures are currently targeted at antimicrobial prophylaxis, amelioration of drug-induced neutropenia, and nosocomial spread of pathogens, with little attention to community-acquired infections. A retrospective study was conducted at a pediatric oncology center during a 3-year period to identify probable cases of food-borne infections with bacteremia. Twenty-one bacteremic illnesses affecting 15 children receiving chemotherapy or hematopoietic stem cell transplantation were reviewed. Three (14% episodes were highly suspected of a food-borne origin: a 17-year-old boy with osteosarcoma contracted Sphingomonas paucimobilis septicemia after consuming nasi lemak bought from a street hawker; a 2-year-old boy with acute lymphoblastic leukemia developed Chryseobacterium meningosepticum septicemia after a sushi dinner; a 2-year-old girl was diagnosed with acute lymphoblastic leukemia and Lactobacillus bacteremia suspected to be of probiotic origin. All of them were neutropenic at the time of the infections and the bacteremias were cleared with antibiotic treatment. Food-borne sepsis may be an important, but readily preventable, cause of bloodstream infections in pediatric oncology patients, especially in tropical countries with an abundance of culinary outlets.

  8. Food-borne bacteremic illnesses in febrile neutropenic children.

    Science.gov (United States)

    Lee, Anselm Chi-Wai; Siao-Ping Ong, Nellie Dawn

    2011-08-31

    Bacteremia following febrile neutropenia is a serious complication in children with malignancies. Preventive measures are currently targeted at antimicrobial prophylaxis, amelioration of drug-induced neutropenia, and nosocomial spread of pathogens, with little attention to community-acquired infections. A retrospective study was conducted at a pediatric oncology center during a 3-year period to identify probable cases of food-borne infections with bacteremia. Twenty-one bacteremic illnesses affecting 15 children receiving chemotherapy or hematopoietic stem cell transplantation were reviewed. Three (14%) episodes were highly suspected of a food-borne origin: a 17-year-old boy with osteosarcoma contracted Sphingomonas paucimobilis septicemia after consuming nasi lemak bought from a street hawker; a 2-year-old boy with acute lymphoblastic leukemia developed Chryseobacterium meningosepticum septicemia after a sushi dinner; a 2-year-old girl was diagnosed with acute lymphoblastic leukemia and Lactobacillus bacteremia suspected to be of probiotic origin. All of them were neutropenic at the time of the infections and the bacteremias were cleared with antibiotic treatment. Food-borne sepsis may be an important, but readily preventable, cause of bloodstream infections in pediatric oncology patients, especially in tropical countries with an abundance of culinary outlets. PMID:22184532

  9. Food-borne bacteremic illnesses in febrile neutropenic children.

    Science.gov (United States)

    Lee, Anselm Chi-Wai; Siao-Ping Ong, Nellie Dawn

    2011-08-31

    Bacteremia following febrile neutropenia is a serious complication in children with malignancies. Preventive measures are currently targeted at antimicrobial prophylaxis, amelioration of drug-induced neutropenia, and nosocomial spread of pathogens, with little attention to community-acquired infections. A retrospective study was conducted at a pediatric oncology center during a 3-year period to identify probable cases of food-borne infections with bacteremia. Twenty-one bacteremic illnesses affecting 15 children receiving chemotherapy or hematopoietic stem cell transplantation were reviewed. Three (14%) episodes were highly suspected of a food-borne origin: a 17-year-old boy with osteosarcoma contracted Sphingomonas paucimobilis septicemia after consuming nasi lemak bought from a street hawker; a 2-year-old boy with acute lymphoblastic leukemia developed Chryseobacterium meningosepticum septicemia after a sushi dinner; a 2-year-old girl was diagnosed with acute lymphoblastic leukemia and Lactobacillus bacteremia suspected to be of probiotic origin. All of them were neutropenic at the time of the infections and the bacteremias were cleared with antibiotic treatment. Food-borne sepsis may be an important, but readily preventable, cause of bloodstream infections in pediatric oncology patients, especially in tropical countries with an abundance of culinary outlets.

  10. Recurrent severe invasive pneumococcal disease in an adult with previously unknown hyposplenia

    DEFF Research Database (Denmark)

    Ballegaard, Vibe C; Schejbel, Lone; Hoffmann, Steen;

    2015-01-01

    condition was found. Despite immunization against S. pneumoniae and measurement of what was interpreted as protective levels of serotype-specific IgG antibodies after vaccination, the patient suffered from a third episode of IPD. CONCLUSIONS: Individuals with predisposing medical conditions or a history of......BACKGROUND: The risk of life-threatening and invasive infections with encapsulated bacteria is increased in patients with hyposplenia or asplenia. We report a case of recurrent invasive pneumococcal meningitis in a woman with previous unknown hyposplenia. She was vaccinated after the first episode...... of meningitis and developed sufficient levels of pneumococcal antibodies. The pneumococcal strains isolated were serotype 7 F and 17 F. To our knowledge, there has been no previously reported case of recurrent invasive pneumococcal disease in a pneumococcal vaccinated adult with hyposplenia and...

  11. Next Generation Pneumococcal Vaccines

    OpenAIRE

    Kristin L Moffitt; Malley, Richard

    2011-01-01

    Currently licensed pneumococcal vaccines are based on the generation of antibodies to the pneumococcal polysaccharide, of which there are more than 90 different types. While these vaccines are highly effective against the serotypes included, their high cost and limited serotype coverage limits their usefulness worldwide, particularly in low resources areas. Thus alternative or adjunctive options are being actively pursued. This review will present these various approaches, including variation...

  12. Pneumococcal Conjugate Vaccines and Otitis Media: An Appraisal of the Clinical Trials

    OpenAIRE

    Fletcher, Mark A.; Bernard Fritzell

    2012-01-01

    Streptococcus pneumoniae is the predominant otitis media pathogen and its prevention through effective vaccination could diminish childhood illness and antibiotic use. This paper reviews 5 pneumococcal conjugate vaccine (PCV) trials that used otitis media as an endpoint: Northern California Kaiser Permanente (NCKP; vaccine, 7-valent PCV [PCV7]-CRM); Finnish Otitis Media (FinOM; vaccines, PCV7-CRM or PCV7-OMPC); Native American Trial (vaccine, PCV7-CRM); Pneumococcal Otitis Efficacy Trial (POE...

  13. Granzyme A impairs host defense during Streptococcus pneumoniae pneumonia.

    Science.gov (United States)

    van den Boogaard, Florry E; van Gisbergen, Klaas P J M; Vernooy, Juanita H; Medema, Jan P; Roelofs, Joris J T H; van Zoelen, Marieke A D; Endeman, Henrik; Biesma, Douwe H; Boon, Louis; Van't Veer, Cornelis; de Vos, Alex F; van der Poll, Tom

    2016-08-01

    Streptococcus pneumoniae is the most common causative pathogen in community-acquired pneumonia (CAP). Granzyme A (GzmA) is a serine protease produced by a variety of cell types involved in the immune response. We sought to determine the role of GzmA on the host response during pneumococcal pneumonia. GzmA was measured in bronchoalveolar lavage fluid (BALF) harvested from CAP patients from the infected and contralateral uninfected side and in lung tissue slides from CAP patients and controls. In CAP patients, GzmA levels were increased in BALF obtained from the infected lung. Human lungs showed constitutive GzmA expression by both parenchymal and nonparenchymal cells. In an experimental setting, pneumonia was induced in wild-type (WT) and GzmA-deficient (GzmA(-/-)) mice by intranasal inoculation of S. pneumoniae In separate experiments, WT and GzmA(-/-) mice were treated with natural killer (NK) cell depleting antibodies. Upon infection with S. pneumoniae, GzmA(-/-) mice showed a better survival and lower bacterial counts in BALF and distant body sites compared with WT mice. Although NK cells showed strong GzmA expression, NK cell depletion did not influence bacterial loads in either WT or GzmA(-/-) mice. These results implicate that GzmA plays an unfavorable role in host defense during pneumococcal pneumonia by a mechanism that does not depend on NK cells. PMID:27343190

  14. Understanding Pneumonia

    Science.gov (United States)

    ... and Diseases > Lung Disease Lookup > Pneumonia Learn About Pneumonia 5 Facts You Should Know about Pneumonia Pneumonia ... vaccinated and practicing good health habits What Is Pneumonia? Pneumonia is an infection in one or both ...

  15. The Impact of Order Set Use on Pneumococcal Vaccination at the Time of Admission and at the Time of Discharge for Adult Patients in an Acute Inpatient Setting

    Science.gov (United States)

    Mathew, Rekha

    2012-01-01

    Background: Pneumococcal vaccination (PV) is important as Streptococcus pneumoniae accounts for one third of all hospitalizations for community-acquired pneumonia. In 2009, 1.1 million people in the U.S. were hospitalized with pneumonia and more than 50,000 people died from the disease. The Centers for Disease Control and Prevention recommend that…

  16. Recurrent pneumococcal meningitis in a splenectomised HIV-infected patient

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    Quesne Gilles

    2003-11-01

    Full Text Available Abstract Background Streptococcus pneumoniae is a major cause of human disease, especially in pre-school children and elderly people, as well as in special risk groups such as asplenic, antibody deficient patients, or presenting disruption of natural barriers. The occurrence of pneumococcal disease has increased with the onset of the HIV epidemic and the emergence of drug-resistance. Case presentation We report the case of an HIV-1-infected patient who experienced three episodes of recurrent pneumococcal meningitis over a 4-year period, despite chemoprophylaxis and capsular vaccination. Conclusions Efficacy of anti-pneumococcal chemoprophylaxis and vaccination in HIV-infected patients are discussed in the light of this particular case.

  17. Recommendation for use of the newly introduced pneumococcal protein conjugate vaccines in Korea

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    Eun Hwa Choi

    2011-04-01

    Full Text Available Streptococcus pneumoniae remains a leading cause of invasive infections including bacteremia and meningitis, as well as mucosal infections such as otitis media and pneumonia among children and adults. The 7-valent pneumococcal conjugate vaccine (PCV7 was licensed for use among infants and young children in many countries including Korea. The routine use of PCV7 has resulted in a decreased incidence of invasive pneumococcal disease (IPD by the vaccine serotypes among the vaccinees and substantial declines in IPD among unvaccinated populations such as older children and adults as well. In addition, there are increasing evidences to suggest that routine immunization with PCV7 is changing the epidemiology of pneumococcal diseases such as serotype distribution of IPD, nasopharyngeal colonization, and antibiotic resistance patterns. In contrast, there is an increase in the number of IPDs caused by nonvaccine serotypes, though it is much smaller than overall declines of vaccine serotype diseases. Several vaccines containing additional serotypes have been developed and tested clinically in order to expand the range of serotypes of Streptococcus pneumoniae. Recently two new pneumococcal protein conjugate vaccines, 10-valent pneumococcal conjugate vaccine (PCV10 and 13-valent pneumococcal conjugate vaccine (PCV13, have been approved for use in several countries including Korea. This report summarizes the recommendations approved by the Committee on Infectious Diseases, the Korean Pediatric Society.

  18. Pneumococcal Sepsis Complicated by Splenic Abscesses and Purpura Fulminans in a 15-Month-Old Child

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    Scott Pangonis MD

    2016-02-01

    Full Text Available Streptococcus pneumoniae is an invasive organism that causes a wide range of common diseases, including sinusitis, acute otitis media, and pneumonia. Splenic abscesses and purpura fulminans (PF are rare complications of pneumococcal disease. Splenic abscesses caused by S pneumoniae have only been reported in the adult literature. PF has been described in the pediatric population as a rare complication in patients with invasive pneumococcal disease (IPD with and without underlying immunological disorders such as asplenia. Here, we report a patient with IPD complicated by splenic abscesses and PF. Our patient initially presented with bacteremia, septic shock, and disseminated intravascular coagulation. She subsequently developed PF and splenic abscesses. She survived her illness after receiving a total of 8 weeks of antibiotic therapy. This case highlights 2 rare complications of IPD and demonstrates the need to keep pneumococcal disease in the differential diagnosis even in children whose vaccination status is up to date.

  19. A compendium for Mycoplasma pneumoniae

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    Gretchen Lynn Parrott

    2016-04-01

    Full Text Available Historically, atypical pneumonia was a term used to describe an unusual presentation of pneumonia. Currently, it is used to describe the multitude of symptoms juxtaposing the classic symptoms found in cases of pneumococcal pneumonia. Specifically, atypical pneumonia is a syndrome resulting from a relatively common group of pathogens including Chlamydophila sp., and Mycoplasma pneumoniae. The incidence of M. pneumoniae pneumonia in adults is less than the burden experienced by children. Transmission rates among families indicate children may act as a reservoir and maintain contagiousness over a long period of time ranging from months to years. In adults, M. pneumoniae typically produces a mild, walking pneumonia and is considered to be one of the causes of persistent cough in patients. M. pneumoniae has also been shown to trigger the exacerbation of other lung diseases. It has been repeatedly detected in patients with bronchitis, asthma, chronic obstructive pulmonary disorder and cystic fibrosis. Recent advances in technology allow for the rapid diagnosis of M. pneumoniae through the use of polymerase chain reaction (PCR or rapid antigen tests. With this, more effort has been afforded to identify the causative etiologic agent in all cases of pneumonia. However, previous practices, including the overprescribing of macrolide treatment in China and Japan, have created increased incidence of macrolide-resistant M. pneumoniae. Reports from these countries indicate that >85% of M. pneumoniae pneumonia pediatric cases are macrolide-resistant. Despite its extensively studied past, the smallest bacterial species still inspires some of the largest questions. The developments in microbiology, diagnostic features and techniques, epidemiology, treatment and vaccines, and upper respiratory conditions associated with M. pneumoniae in adult populations are included within this review.

  20. A Compendium for Mycoplasma pneumoniae.

    Science.gov (United States)

    Parrott, Gretchen L; Kinjo, Takeshi; Fujita, Jiro

    2016-01-01

    Historically, atypical pneumonia was a term used to describe an unusual presentation of pneumonia. Currently, it is used to describe the multitude of symptoms juxtaposing the classic symptoms found in cases of pneumococcal pneumonia. Specifically, atypical pneumonia is a syndrome resulting from a relatively common group of pathogens including Chlamydophila sp., and Mycoplasma pneumoniae. The incidence of M. pneumoniae pneumonia in adults is less than the burden experienced by children. Transmission rates among families indicate children may act as a reservoir and maintain contagiousness over a long period of time ranging from months to years. In adults, M. pneumoniae typically produces a mild, "walking" pneumonia and is considered to be one of the causes of persistent cough in patients. M. pneumoniae has also been shown to trigger the exacerbation of other lung diseases. It has been repeatedly detected in patients with bronchitis, asthma, chronic obstructive pulmonary disorder, and cystic fibrosis. Recent advances in technology allow for the rapid diagnosis of M. pneumoniae through the use of polymerase chain reaction or rapid antigen tests. With this, more effort has been afforded to identify the causative etiologic agent in all cases of pneumonia. However, previous practices, including the overprescribing of macrolide treatment in China and Japan, have created increased incidence of macrolide-resistant M. pneumoniae. Reports from these countries indicate that >85% of M. pneumoniae pneumonia pediatric cases are macrolide-resistant. Despite its extensively studied past, the smallest bacterial species still inspires some of the largest questions. The developments in microbiology, diagnostic features and techniques, epidemiology, treatment and vaccines, and upper respiratory conditions associated with M. pneumoniae in adult populations are included within this review. PMID:27148202

  1. Impact of pneumococcal vaccines use on invasive pneumococcal disease in Nunavik (Quebec from 1997 to 2010

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    Jean-Baptiste Le Meur

    2014-01-01

    Full Text Available Background: In 2000, an outbreak of severe pneumonia caused by a virulent clone of serotype 1 Streptococcus pneumoniae was detected in the Nunavik region of Quebec. A mass immunization campaign was implemented in the spring of 2002, targeting persons ≥5 years of age and using the 23-valent pneumococcal polysaccharide vaccine (PPSV23. At the same time, the 7-valent pneumococcal conjugate vaccine (PCV7 was introduced into the routine immunization programme of infants, with catch-up for children up to 4 years of age. Objectives: To describe the epidemiology of invasive pneumococcal disease (IPD in relation to PPSV23 and PCV7 use. Study design and methods: Retrospective analysis of IPD cases identified by the Quebec public health laboratory during the period 1997–2010. Results: A total of 82 IPD cases were identified during the study period. In adults, serotype 1 incidence decreased following the 2002 PPSV23 mass campaign but breakthrough cases continued to occur. Following PCV7 use in children, there was a decrease in the incidence of vaccine-type IPD and replacement by other serotypes in adults. In children, a marked decrease in the annual incidence of serotypes included in PCV7 was observed following PCV7 introduction: 162/100,000 in 1997–2001 vs. 10/100,000 in 2004–2010 (p<0.01. Concomitantly, the incidence of IPD caused by serotypes not included in PCV7 increased from 29/100,000 to 109/100,000 (p=0.11. Conclusion: The mass immunization campaign using the PPSV23 in 2002 and the introduction of PCV7 for the routine immunization of infants induced important modifications in the epidemiology of IPD. IPD rates in Nunavik remain much higher than in the southern part of the province both in children and adults. More effective pneumococcal vaccines are needed to eliminate geographic disparities in IPD risk.

  2. Characterization of a pneumococcal meningitis mouse model

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    Mook-Kanamori Barry

    2012-03-01

    Full Text Available Abstract Background S. pneumoniae is the most common causative agent of meningitis, and is associated with high morbidity and mortality. We aimed to develop an integrated and representative pneumococcal meningitis mouse model resembling the human situation. Methods Adult mice (C57BL/6 were inoculated in the cisterna magna with increasing doses of S. pneumoniae serotype 3 colony forming units (CFU; n = 24, 104, 105, 106 and 107 CFU and survival studies were performed. Cerebrospinal fluid (CSF, brain, blood, spleen, and lungs were collected. Subsequently, mice were inoculated with 104 CFU S. pneumoniae serotype 3 and sacrificed at 6 (n = 6 and 30 hours (n = 6. Outcome parameters were bacterial outgrowth, clinical score, and cytokine and chemokine levels (using Luminex® in CSF, blood and brain. Meningeal inflammation, neutrophil infiltration, parenchymal and subarachnoidal hemorrhages, microglial activation and hippocampal apoptosis were assessed in histopathological studies. Results Lower doses of bacteria delayed onset of illness and time of death (median survival CFU 104, 56 hrs; 105, 38 hrs, 106, 28 hrs. 107, 24 hrs. Bacterial titers in brain and CSF were similar in all mice at the end-stage of disease independent of inoculation dose, though bacterial outgrowth in the systemic compartment was less at lower inoculation doses. At 30 hours after inoculation with 104 CFU of S. pneumoniae, blood levels of KC, IL6, MIP-2 and IFN- γ were elevated, as were brain homogenate levels of KC, MIP-2, IL-6, IL-1β and RANTES. Brain histology uniformly showed meningeal inflammation at 6 hours, and, neutrophil infiltration, microglial activation, and hippocampal apoptosis at 30 hours. Parenchymal and subarachnoidal and cortical hemorrhages were seen in 5 of 6 and 3 of 6 mice at 6 and 30 hours, respectively. Conclusion We have developed and validated a murine model of pneumococcal meningitis.

  3. Environmental and Nutritional Factors That Affect Growth and Metabolism of the Pneumococcal Serotype 2 Strain D39 and Its Nonencapsulated Derivative Strain R6

    NARCIS (Netherlands)

    Carvalho, Sandra M.; Kuipers, Oscar P.; Neves, Ana Rute; Horsburgh, Malcolm James

    2013-01-01

    Links between carbohydrate metabolism and virulence in Streptococcus pneumoniae have been recurrently established. To investigate these links further we developed a chemically defined medium (CDM) and standardized growth conditions that allowed for high growth yields of the related pneumococcal stra

  4. Impact of the introduction of the pneumococcal conjugate vaccine in the Brazilian routine childhood national immunization program.

    Science.gov (United States)

    Moreira, Marta; Cintra, Otavio; Harriague, Julie; Hausdorff, William P; Hoet, Bernard

    2016-05-27

    Brazil introduced the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV, Synflorix™, GSK Vaccines) in the routine childhood immunization program in 2010 with a 3+1 schedule (with catch-up for children pneumococcal conjugate vaccine on nasopharyngeal carriage and all the major pneumococcal disease manifestations in a single, pneumococcal conjugate vaccine-naïve, developing country. A total of 15 published articles and 13 congress abstracts were included in the analysis. In children vaccine-type and any-type invasive pneumococcal disease (including decreases in pneumococcal meningitis morbidity and mortality), on pneumonia incidence and mortality, and on otitis media. Nasopharyngeal carriage of vaccine-type and any-type pneumococci decreased after the primary doses, with no early signs of replacement with other pathogens. Finally, herd protection against vaccine-type invasive pneumococcal disease and pneumonia in unvaccinated subjects was shown in some studies for some age groups. In conclusion, pneumococcal disease decreased after the introduction of PHiD-CV into the Brazilian national immunization program. Further follow-up is needed to evaluate the long-term overall impact of PHiD-CV in the Brazilian population. PMID:27113162

  5. Diagnostic detection of Streptococcus pneumoniae PpmA in urine.

    NARCIS (Netherlands)

    Garcia-Suarez, M.M.; Cron, L.E.; Suarez-Alvarez, B.; Villaverde, R.; Gonzalez-Rodriguez, I.; Vazquez, F.; Hermans, P.W.M.; Mendez, F.J.

    2009-01-01

    Streptococcus pneumoniae infections are often difficult to diagnose accurately, as it is not uncommon for clinical samples to be culture-negative, particularly after antibiotic administration. The rapid Binax NOW S. pneumoniae urinary antigen test lacks specificity in children, owing to pneumococcal

  6. Regulation of Naturally Acquired Mucosal Immunity to Streptococcus pneumoniae in Healthy Malawian Adults and Children

    OpenAIRE

    Sarah J Glennie; Banda, Dominic; Mulwafu, Wakisa; Nkhata, Rose; Neil A Williams; Heyderman, Robert S.

    2012-01-01

    Worldwide, invasive pneumococcal disease caused by Streptococcus pneumoniae is most common in young children. In adults, disease rates decline following intermittent colonization and the acquisition of naturally acquired immunity. We characterized mucosal and systemic pneumococcal-specific T-cell responses in African children and adults who contend with intense rates of colonization, up to 100% and 60% respectively. We find most Malawian children have high pneumococcal-specific T-cell respons...

  7. Status of research and development of pediatric vaccines for Streptococcus pneumoniae.

    Science.gov (United States)

    Alderson, Mark R

    2016-06-01

    Pneumococcal disease is a major cause of morbidity and mortality in young children, particularly in the developing world. Vaccines are a critical strategy for protecting children from pneumococcal disease and licensed pneumococcal conjugate vaccines (PCVs) are having a significant impact on invasive pneumococcal disease and pneumococcal pneumonia throughout the world. Currently available PCVs do not, however, cover all pneumococcal serotypes and are complicated and relatively expensive to manufacture. While new PCV development is focused on either higher valency or more inherent affordability for developing countries, new vaccines are needed that offer serotype-independent protection. Vaccines containing proteins that are common to all pneumococcal serotypes could provide broad protection to children worldwide. Protein subunit and whole cell vaccines have advanced into Phase 1 and 2 clinical trials but face considerable challenges before they can become licensed and widely distributed. PMID:27083428

  8. Influenza and pneumococcal vaccination of the elderly in Taiwan.

    Science.gov (United States)

    Chen, Yeong-Hwang; Liou, Saou-Hsing; Chou, Chih-Chieh; Su, Wen-Lin; Loh, Ching-Hui; Lin, Shih-Ha

    2004-07-29

    In 1998, Taiwan became the first country in Asia to provide free influenza vaccination to high-risk groups, mainly the elderly. The purpose of this study is to determine: (1) the annual mortality rate from influenza and pneumococcal-related illnesses such as pneumonia, chronic bronchitis, pulmonary emphysema and asthma and (2) the effectiveness of and adverse events associated with the influenza vaccination. In the elderly, influenza vaccination caused the annual death rate due chronic bronchitis, pulmonary emphysema, and asthma to decline steadily but had no effect on the annual pneumonia death rate. The only adverse effect of concern was vertigo (in approximately 2-3%).

  9. Paroxysmal Autonomic Instability with Dystonia after Pneumococcal Meningoencephalitis

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    Layal Safadieh

    2012-01-01

    Full Text Available Streptococcus pneumoniae is a common cause of bacterial meningitis, frequently resulting in severe neurological impairment. A seven-month-old child presenting with Streptococcus pneumoniae meningoencephalitis developed right basal ganglia and hypothalamic infarctions. Daily episodes of agitation, hypertension, tachycardia, diaphoresis, hyperthermia, and decerebrate posturing were observed. The diagnosis of paroxysmal autonomic instability with dystonia was established. The patient responded to clonidine, baclofen, and benzodiazepines. Although this entity has been reported in association with traumatic brain injury, and as a sequel to some nervous system infections, this is the first case, to our knowledge, associated with pneumococcal meningoencephalitis.

  10. Pneumococcal Tricuspid Valve Endocarditis in a Young African American: A Case for Inclusion of African Americans in Pneumococcal Vaccine Criteria

    OpenAIRE

    John J. Murray; Joseph Akamah; Oghenerukevwe Odiete; Olagoke Akinwande

    2010-01-01

    Following the development of penicillin, complications from streptococcus pneumonia such as endocarditis have become rare. However, certain independent risk factors such as cigarette smoking and being of African-American (AA) decent have been associated with a higher incidence of invasive pneumococcal disease, but only cigarette smoking has been targeted by current recommendations from the Advisory Committee on Immunological Practices (ACIPs). We report a case of a young AA smoker, who develo...

  11. Metabolites in Blood for Prediction of Bacteremic Sepsis in the Emergency Room.

    Directory of Open Access Journals (Sweden)

    Anna M Kauppi

    Full Text Available A metabolomics approach for prediction of bacteremic sepsis in patients in the emergency room (ER was investigated. In a prospective study, whole blood samples from 65 patients with bacteremic sepsis and 49 ER controls were compared. The blood samples were analyzed using gas chromatography coupled to time-of-flight mass spectrometry. Multivariate and logistic regression modeling using metabolites identified by chromatography or using conventional laboratory parameters and clinical scores of infection were employed. A predictive model of bacteremic sepsis with 107 metabolites was developed and validated. The number of metabolites was reduced stepwise until identifying a set of 6 predictive metabolites. A 6-metabolite predictive logistic regression model showed a sensitivity of 0.91(95% CI 0.69-0.99 and a specificity 0.84 (95% CI 0.58-0.94 with an AUC of 0.93 (95% CI 0.89-1.01. Myristic acid was the single most predictive metabolite, with a sensitivity of 1.00 (95% CI 0.85-1.00 and specificity of 0.95 (95% CI 0.74-0.99, and performed better than various combinations of conventional laboratory and clinical parameters. We found that a metabolomics approach for analysis of acute blood samples was useful for identification of patients with bacteremic sepsis. Metabolomics should be further evaluated as a new tool for infection diagnostics.

  12. Tsukamurella tyrosinosolvens - An unusual case report of bacteremic pneumonia after lung transplantation

    Directory of Open Access Journals (Sweden)

    Dromer Claire

    2009-11-01

    Full Text Available Abstract Background Lung transplant recipients have an increased risk for actinomycetales infection secondary to immunosuppressive regimen. Case presentation A case of pulmonary infection with bacteremia due to Tsukamurella tyrosinosolvens in a 54-year old man who underwent a double lung transplantation four years previously is presented. Conclusion The identification by conventional biochemical assays was unsuccessful and hsp gene sequencing was used to identify Tsukamurella tyrosinosolvens.

  13. Carriage of streptococcus pneumoniae 3 years after start of vaccination program, the Netherlands

    NARCIS (Netherlands)

    Spijkerman, J.; van Gils, E.J.M.; Veenhoven, R.H.; Hak, E.; Yzerman, E.P.F.; van der Ende, A.; Wijmenga-Monsuur, A.J.; van den Dobbelsteen, G.P.J.M.; Sanders, E.A.M.

    2011-01-01

    To evaluate the effectiveness of the 7-valent pneumococcal conjugate vaccine (PCV7) program, we conducted a cross-sectional observational study on nasopharyngeal carriage of Streptococcus pneumoniae 3 years after implementation of the program in the Netherlands. We compared pneumococcal serotypes in

  14. Cloning of Minor Autolysin of Streptococcus Pneumoniae

    OpenAIRE

    Mahboobi, R. (MSc); Fallah Mehrabadi, J. (PhD); MR Pourmand; R Mashhadi; Haddadi, A. (MD

    2015-01-01

    Background and Objective: Increased antibiotic resistant strains and inadequacy of current vaccines against pneumococcal infections necessitate the study of novel protein antigens. It seems that minor autolysin of Streptococcus pneumoniae may have antigenicity. Thus, we aimed at cloning its gene for the first time. Material and Methods: After DNA extraction of Streptococcus pneumoniae (ATCC 49619), Specific primers were designed for amplifying minor autolysin gene fragment, using PCR. The pur...

  15. Fatal Streptococcus pneumoniae Sepsis in a Patient With Celiac Disease-Associated Hyposplenism

    Science.gov (United States)

    Ouseph, Madhu M.; Simons, Malorie; Treaba, Diana O.; Yakirevich, Evgeny; Green, Peter H.; Bhagat, Govind; Moss, Steven F.

    2016-01-01

    We present a 59-year-old male with poorly controlled celiac disease (CD) and fatal Streptococcus pneumoniae sepsis, describe the morphologic findings, and stress the need for monitoring splenic function and pneumococcal vaccination in these patients. PMID:27761478

  16. [Thousand faces of Streptococcus pneumonia (pneumococcus) infections].

    Science.gov (United States)

    Szabó, Bálint Gergely; Lénárt, Katalin Szidónia; Kádár, Béla; Gombos, Andrea; Dezsényi, Balázs; Szanka, Judit; Bobek, Ilona; Prinz, Gyula

    2015-11-01

    Incidence and mortality rates of infections caused by Streptococcus pneumoniae (pneumococcus) are high worldwide and in Hungary among paediatric as well as adult populations. Pneumococci account for 35-40% of community acquired adult pneumonias requiring hospitalization, while 25-30% of Streptococcus pneumoniae pneumonias are accompanied by bacteraemia. 5-7% of all infections are fatal but this rate is exponentially higher in high risk patients and elderly people. Mortality could reach 20% among patients with severe invasive pneumococcal infections. Complications may develop despite administration of adequate antibiotics. The authors summarize the epidemiology of pneumococcal infections, pathogenesis of non-invasive and invasive disease and present basic clinical aspects through demonstration of four cases. Early risk stratification, sampling of hemocultures, administration of antibiotics and wider application of active immunization could reduce the mortality of invasive disease. Anti-pneumococcal vaccination is advisable for adults of ≥50 years and high risk patients of ≥18 years who are susceptible to pneumococcal disease. PMID:26498896

  17. Prevention of pneumococcal diseases in the post-seven valent vaccine era: A European perspective

    Directory of Open Access Journals (Sweden)

    Weil-Olivier Catherine

    2012-09-01

    Full Text Available Abstract Background The burden of invasive pneumococcal disease in young children decreased dramatically following introduction of the 7-valent pneumococcal conjugate vaccine (PCV7. The epidemiology of S. pneumoniae now reflects infections caused by serotypes not included in PCV7. Recently introduced higher valency pneumococcal vaccines target the residual burden of invasive and non-invasive infections, including those caused by serotypes not included in PCV7. This review is based on presentations made at the European Society of Pediatric Infectious Diseases in June 2011. Discussion Surveillance data show increased circulation of the non-PCV7 vaccine serotypes 1, 3, 6A, 6C, 7 F and 19A in countries with routine vaccination. Preliminary evidence suggests that broadened serotype coverage offered by higher valency vaccines may be having an effect on invasive disease caused by some of those serotypes, including 19A, 7 F and 6C. Aetiology of community acquired pneumonia remains a difficult clinical diagnosis. However, recent reports indicate that pneumococcal vaccination has reduced hospitalisations of children for vaccine serotype pneumonia. Variations in serotype circulation and occurrence of complicated and non-complicated pneumonia caused by non-PCV7 serotypes highlight the potential of higher valency vaccines to decrease the remaining burden. PCVs reduce nasopharyngeal carriage and acute otitis media (AOM caused by vaccine serotypes. Recent investigations of the interaction between S. pneumoniae and non-typeable H. influenzae suggest that considerable reduction in severe, complicated AOM infections may be achieved by prevention of early pneumococcal carriage and AOM infections. Extension of the vaccine serotype spectrum beyond PCV7 may provide additional benefit in preventing the evolution of AOM. The direct and indirect costs associated with pneumococcal disease are high, thus herd protection and infections caused by non-vaccine serotypes

  18. New adhesin functions of surface-exposed pneumococcal proteins

    Directory of Open Access Journals (Sweden)

    Vernet Thierry

    2010-07-01

    Full Text Available Abstract Background Streptococcus pneumoniae is a widely distributed commensal Gram-positive bacteria of the upper respiratory tract. Pneumococcal colonization can progress to invasive disease, and thus become lethal, reason why antibiotics and vaccines are designed to limit the dramatic effects of the bacteria in such cases. As a consequence, pneumococcus has developed efficient antibiotic resistance, and the use of vaccines covering a limited number of serotypes such as Pneumovax® and Prevnar® results in the expansion of non-covered serotypes. Pneumococcal surface proteins represent challenging candidates for the development of new therapeutic targets against the bacteria. Despite the number of described virulence factors, we believe that the majority of them remain to be characterized. This is the reason why pneumococcus invasion processes are still largely unknown. Results Availability of genome sequences facilitated the identification of pneumococcal surface proteins bearing characteristic motifs such as choline-binding proteins (Cbp and peptidoglycan binding (LPXTG proteins. We designed a medium throughput approach to systematically test for interactions between these pneumococcal surface proteins and host proteins (extracellular matrix proteins, circulating proteins or immunity related proteins. We cloned, expressed and purified 28 pneumococcal surface proteins. Interactions were tested in a solid phase assay, which led to the identification of 23 protein-protein interactions among which 20 are new. Conclusions We conclude that whether peptidoglycan binding proteins do not appear to be major adhesins, most of the choline-binding proteins interact with host proteins (elastin and C reactive proteins are the major Cbp partners. These newly identified interactions open the way to a better understanding of host-pneumococcal interactions.

  19. PSGL-1 on Leukocytes is a Critical Component of the Host Immune Response against Invasive Pneumococcal Disease

    Science.gov (United States)

    Ramos-Sevillano, Elisa; Urzainqui, Ana; de Andrés, Belén; González-Tajuelo, Rafael; Domenech, Mirian; González-Camacho, Fernando; Sánchez-Madrid, Francisco; Brown, Jeremy S.; García, Ernesto; Yuste, Jose

    2016-01-01

    Bacterial uptake by phagocytic cells is a vital event in the clearance of invading pathogens such as Streptococcus pneumoniae. A major role of the P-selectin glycoprotein ligand-1 (PSGL-1) on leukocytes against invasive pneumococcal disease is described in this study. Phagocytosis experiments using different serotypes demonstrated that PSGL-1 is involved in the recognition, uptake and killing of S. pneumoniae. Co-localization of several clinical isolates of S. pneumoniae with PSGL-1 was demonstrated, observing a rapid and active phagocytosis in the presence of PSGL-1. Furthermore, the pneumococcal capsular polysaccharide and the main autolysin of the bacterium ―the amidase LytA― were identified as bacterial ligands for PSGL-1. Experimental models of pneumococcal disease including invasive pneumonia and systemic infection showed that bacterial levels were markedly increased in the blood of PSGL-1−/− mice. During pneumonia, PSGL-1 controls the severity of pneumococcal dissemination from the lung to the bloodstream. In systemic infection, a major role of PSGL-1 in host defense is to clear the bacteria in the systemic circulation controlling bacterial replication. These results confirmed the importance of this receptor in the recognition and clearance of S. pneumoniae during invasive pneumococcal disease. Histological and cellular analysis demonstrated that PSGL-1−/− mice have increased levels of T cells migrating to the lung than the corresponding wild-type mice. In contrast, during systemic infection, PSGL-1−/− mice had increased numbers of neutrophils and macrophages in blood, but were less effective controlling the infection process due to the lack of this functional receptor. Overall, this study demonstrates that PSGL-1 is a novel receptor for S. pneumoniae that contributes to protection against invasive pneumococcal disease. PMID:26975045

  20. The History of Mycoplasma pneumoniae Pneumonia.

    Science.gov (United States)

    Saraya, Takeshi

    2016-01-01

    In the United States in the 1930s, although the pathogen was not known, atypical pneumonia was clinically distinguished from pneumococcal pneumonia by its resistance to sulfonamides. Reimann (1938) reported seven patients with an unusual form of tracheo bronchopneumonia and severe constitutional symptoms. He believed the clinical picture of this disease differed from that of the disease caused by influenza viruses or known bacteria and instead suspected "primary atypical pneumonia." For many years, the responsible infectious agent was tentatively classified as a filterable virus that could pass through a Seitz filter to remove bacteria and was reported to be a psittacosis-like or new virus. After that, Eaton et al. (1942, 1944, 1945) identified an agent that was the principal cause of primary atypical pneumonia using cotton rats, hamsters, and chick embryos. Eaton et al. (1942, 1944, 1945) did not perform an inoculation study in human volunteers. During the 1940s, there were three groups engaged in discovering the etiology of the primary atypical pneumonia. (1) Commission on Acute Respiratory Diseases Diseases directed by John Dingle, (2) Dr. Monroe Eaton's group, the Virus Research Laboratory of the California State Public Health Department, (3) The Hospital of the Rockefeller Institute for Medical Research directed by Horsfall. During 1940s, the members of the Commission on Acute Respiratory Diseases concluded that the bacteria-free filtrates obtained from the patients, presumably containing a virus, could induce primary atypical pneumonia in human volunteers via Pinehurst trials. During 1950s, serological approaches for identification of the Eaton agent developed such as Fluorescent-Stainable Antibody, and at the beginning of the1960s, the Eaton agent successfully grew in media, and finally accepted as a cause of primary atypical pneumonia. Thus, technical difficulties with visualizing the agent and failure to recognize the full significance of the Pinehurst

  1. Prospective Study To Determine Clinical Relevance of Detection of Pneumococcal DNA in Sera of Children by PCR

    OpenAIRE

    Dagan, Ron; Shriker, Ofra; Hazan, Inbal; Leibovitz, Eugene; Greenberg, David; Schlaeffer, Francis; Levy, Rachel

    1998-01-01

    We undertook a prospective study to evaluate the accuracy of PCR of serum (aimed at the pneumococcal pneumolysin gene) at detecting pneumococcal infections in infants and children. The assay was positive for all blood and cerebrospinal fluid culture-positive samples and for 38 and 44% of patients with lobar pneumonia and acute otitis media, respectively. It was positive for 17% of healthy controls. There was a marked effect of age on the rate of positivity among healthy controls, with the hig...

  2. Activator Role of the Pneumococcal Mga-Like Virulence Transcriptional Regulator

    OpenAIRE

    Solano-Collado, Virtu; Espinosa, Manuel; Bravo, Alicia

    2012-01-01

    Global transcriptional regulators that respond to specific environmental signals are crucial in bacterial pathogenesis. In the case of the Gram-positive pathogen Streptococcus pneumoniae (the pneumococcus), the sp1800 gene of the clinical isolate TIGR4 encodes a protein that exhibits homology to the Mga “stand-alone” response regulator of the group A Streptococcus. Such a pneumococcal protein was shown to play a significant role in both nasopharyngeal colonization and development of pneumonia...

  3. Innovative Strategies Designed to Improve Adult Pneumococcal Immunizations in Safety Net Patient-Centered Medical Homes.

    Science.gov (United States)

    Park, Nina J; Sklaroff, Laura Myerchin; Gross-Schulman, Sandra; Hoang, Khathy; Tran, Helen; Campa, David; Scheib, Geoffrey; Guterman, Jeffrey J

    2016-08-01

    Streptococcus pneumoniae is a principal cause of serious illness, including bacteremia, meningitis, and pneumonia, worldwide. Pneumococcal immunization is proven to reduce morbidity and mortality in high-risk adult and elderly populations. Current pneumococcal vaccination practices are suboptimal in part because of recommendation complexity, the high cost of provider-driven immunization interventions, and outreach methods that are not patient-centric. These barriers are amplified within the safety net. This paper identifies efforts by the Los Angeles County Department of Health Services to increase pneumococcal immunization rates for adult indigent patient populations. A 4-part approach will be used to increase vaccination rates: (1) protocol driven care, (2) staff education, (3) electronic identification of eligible patients, and (4) automated patient outreach and scheduling. The proposed analytics plan and potential for scalability are described. (Population Health Management 2016;19:240-247). PMID:26824148

  4. Aspiration pneumonia

    Science.gov (United States)

    Anaerobic pneumonia; Aspiration of vomitus; Necrotizing pneumonia; Aspiration pneumonitis ... The type of bacteria that caused the pneumonia depends on: Your ... facility, for example) Whether you were recently hospitalized ...

  5. Familias de la proteína de superficie PspA de Streptococcus pneumoniae: Relación con serotipos y localización Pneumococcal surface protein A (PspA families: Relation with serotypes and clinical site of infection

    Directory of Open Access Journals (Sweden)

    Clara Mayoral

    2010-10-01

    Full Text Available PspA, proteína de superficie de Streptococcus pneumoniae es un factor de virulencia, fuertemente inmunogénica y común a todos los serotipos. Aunque el gen que codifica para esta proteína presenta una marcada heterogeneidad en la región correspondiente al N-terminal, la PspA contiene epitopes conservados de manera tal que la inmunización genera protección contra neumococos pertenecientes a diversos tipos capsulares y con distintas PspA. A pesar del marcado polimorfismo del gen pspA es posible agrupar las distintas variantes en 3 familias mayoritarias. Estas propiedades las convierten en candidatas ideales para elaborar vacunas. Debido a que la mayoría de los trabajos sobre identificación de familias fueron realizados sobre serotipos frecuentes en otros países, el objetivo fue identificar las familias de PspA de aislamientos de pacientes de nuestra región y relacionarlas con los serotipos prevalentes y patologías. Se estudiaron 70 aislamientos, provenientes de niños con infecciones invasoras. Se aplicó una PCR utilizando cebadores específicos de cada familia. El 60% fueron familia 1 y 34% familia 2. En un 6% no se identificó ninguna de las familias de PspA. Los serotipos 1 y 5 presentaron familia 1 únicamente; los serotipos 14, 6B, 19F y 18C mostraron genes de ambas familias. La familia 1 se observó en 60% de las neumonías y 50% de las meningitis. La familia 2 en 33% de neumonías y 50% de meningitis. Esta información podría ser un valioso aporte para la formulación de una vacuna regional efectiva utilizando PspA recombinante como inmunógeno.PspA, a pneumococcal surface protein, is highly immunogenic and common to all serotypes. Although pspA gene shows a great heterogeneity at the N-terminal region, PspA protein has conserved epytopes which are able to elicit protective cross-reaction against various serotypes presenting different PspA. In spite of the high polimorfism of the PspA, three majority families can be identified

  6. Pharmacokinetics of levofloxacin in the lungs of rats with pneumococcal pneumonia following intravenous administration studied by microdialysis%微透析法研究左氧氟沙星静脉注射在肺炎链球菌肺炎大鼠肺部的药动学

    Institute of Scientific and Technical Information of China (English)

    李奕; 华翔; 肖和平; 王卓; 周佳; 黄怡

    2013-01-01

    目的 观察左氧氟沙星静脉注射在肺炎链球菌肺炎大鼠肺组织中的药动学特点.方法 建立肺炎链球菌肺炎大鼠模型,模拟左氧氟沙星人体400 mg/d静脉给药,采用微透析技术对肺炎大鼠的血液及肺组织同步取样,测定其中游离左氧氟沙星浓度.结果 第20分钟,肺组织内达到高峰浓度(Cmax) (28.08±9.88) mg/L,并接近于血液药物浓度,之后两者同步下降.左氧氟沙星在肺组织内的穿透率为1.01±0.21.消除半衰期(t1/2)在血液内为(229.9±55.6) min,肺组织内为(232.8±74.2) min.血液及肺组织的药-时曲线下面积(AUC0-∞)分别为(69.46±28.69)mg·h/L和(56.21±18.11)mg·h/L(P>0.05).分布系数(AUC肺/AUC血液)为1.04±0.85.结论 左氧氟沙星静脉给药在肺炎大鼠的血液及肺组织内的游离药物浓度较高,超过了最低抑菌浓度和防耐药突变浓度,但仍处于突变选择窗相关药动学参数范围内,可能导致耐药突变菌株富集.%Objective To observe the pharmacokinetic profile of levofloxacin in the lung tissue of a rat model with pneumococcal pneumonia following intravenous administration. Methods A rat model of pneumococcal pneumonia was established. Following intravenous administration of levofloxacin (42 mg · kg-1 · d-1 ) similar to the human dose of 400 mg/d, blood and lung tissue were sampled in vivo by microdialysis at the given time points simultaneously. The concentrations of free levofloxacin were measured. Results The maximum concentration (Cmax) of free levofloxacin in lung tissue was (28. 08 ± 9. 88) mg/L at 20 min, close to the concentrations in blood. Then levofloxacin concentration in blood and lung tissue declined synchronously. The penetration rate (Clung/Cblood) was 1. 01 ± 0. 21 in lung tissue. The elimination half-life (t1/2) is (229. 9 ± 55. 6) min in blood, and (232. 8 ± 74. 2) min in lung. The area under the concentration-time curve (AUC0-∞ ) in blood and lung was (69. 46 ± 28. 69) mg

  7. Immunogenicity of a 23-valent pneumococcal polysaccharide vaccine in elderly residents of a long-term care facility

    Directory of Open Access Journals (Sweden)

    M. Teresa Valenzuela B.

    2007-06-01

    Full Text Available S. pneumoniae is a significant cause of community-acquired pneumonia in the elderly, and accounts for the majority of the pneumonia deaths among the elderly. We conducted this randomized double-blind study to evaluate the immune response to a 23-valent pneumococcal polysaccharide vaccine and the persistence of antibodies two years after the vaccination in an elderly population in Santiago, Chile. A total of 118 elderly nursing home residents received either the pneumococcal or a tetanus control vaccine. Serum samples were taken at enrolment, at two months, and at two years post-vaccination. Pre-vaccination anti-pneumococcal antibody geometric mean concentrations (GMC were similar in both study groups, with increased levels of antibodies found only against serotype 14. The pneumococcal vaccine was highly immunogenic at 2 months, and titers remained high two years after the vaccination for the 10 serotypes studied in this elderly population. The results thus support the benefits of this pneumococcal vaccine in this elderly population who are at increased risk of invasive pneumococcal disease.

  8. Interleukin-18 gene-deficient mice show enhanced defense and reduced inflammation during pneumococcal meningitis.

    NARCIS (Netherlands)

    Zwijnenburg, P.J.G.; Poll, van der T.; Florquin, S; Akira, S; Takeda, K; Roord, J.J.; Furth, van A.M.

    2003-01-01

    To determine the role of endogenous interleukin-18 (IL-18) in pneumococcal meningitis, meningitis was induced in IL-18 gene-deficient (IL-18(-/-)) and wild-type (WT) mice by intranasal inoculation of Streptococcus pneumoniae with hyaluronidase. Induction of meningitis resulted in an upregulation of

  9. Characteristics and outcomes of acute otitis media in children carrying streptococcus pneumoniae or haemophilus influenzae in their nasopharynx as a single otopathogen after introduction of the heptavalent pneumococcal conjugate vaccine.

    Science.gov (United States)

    Caeymaex, Laurence; Varon, Emmanuelle; Levy, Corinne; Béchet, Stéphane; Derkx, Véronique; Desvignes, Véronique; Doit, Catherine; Cohen, Robert

    2014-05-01

    After PCV7 implementation, clinical characteristics were investigated in 832 young children with acute otitis media, carrying a single S. pneumoniae or H. influenzae in their nasopharynx. As compared with H. influenzae, S. pneumoniae-associated acute otitis media was less frequently associated with treatment failure (odds ratio = 0.5; 95% confidence interval: 0.36-0.83) and recurrence (odds ratio = 0.4; 95% confidence interval: 0.22-0.75). Post-PCV7 serotype replacement seemed not to affect the acute otitis media characteristics in these children.

  10. Multidrug-resistant Streptococcus pneumoniae isolates from healthy Ghanaian preschool children

    DEFF Research Database (Denmark)

    Dayie, Nicholas Tete Kwaku Dzifa; Arhin, Reuben E.; Newman, Mercy J.;

    2015-01-01

    Streptococcus pneumoniae is the cause of high mortality among children worldwide. Antimicrobial treatment and vaccination are used to control pneumococcal infections. In Ghana, data on antimicrobial resistance and the prevalence of multidrug-resistant pneumococcal clones are scarce; hence, the aim...... of this study was to determine the antibiogram of S. pneumoniae recovered from Ghanaian children younger than six years of age and to what extent resistances were due to the spread of certain sero- and multilocus sequence typing (MLST) types. The susceptibility of 115 pneumococcal isolates, recovered...

  11. Recurrent invasive pneumococcal disease in children

    DEFF Research Database (Denmark)

    Ingels, Helene; Lambertsen, Lotte; Harboe, Zitta B;

    2014-01-01

    %, and 78% of the cases would have been covered by the 7-, 10-, and 13-valent pneumococcal conjugate vaccines, respectively. Conclusions: Of children with an IPD episode, 2.4% experienced rIPD, and an underlying disease was documented in 66% of these children. Investigation of underlying conditions...... laboratory-confirmed cases of IPD in children aged 0-15 y were identified from the Neisseria and Streptococcus Reference Laboratory, Statens Serum Institut, Denmark for the period 1980-2013. rIPD was defined as isolation of Streptococcus pneumoniae from any normally sterile site ≥ 30 days after an initial...... positive culture. Clinical data were obtained for all children with rIPD. Results: Of all children with IPD, 2.4% (59/2418) experienced at least 1 episode of rIPD, and an underlying condition was documented in 39 (66%). Immune deficiency due to transplantation (n = 9) was the most common disease; however...

  12. Maternal antibodies to pneumolysin but not to pneumococcal surface protein A delay early pneumococcal carriage in high-risk Papua New Guinean infants.

    Science.gov (United States)

    Francis, Jacinta P; Richmond, Peter C; Pomat, William S; Michael, Audrey; Keno, Helen; Phuanukoonnon, Suparat; Nelson, Jan B; Whinnen, Melissa; Heinrich, Tatjana; Smith, Wendy-Anne; Prescott, Susan L; Holt, Patrick G; Siba, Peter M; Lehmann, Deborah; van den Biggelaar, Anita H J

    2009-11-01

    Immunization of pregnant women can be an efficient strategy to induce early protection in infants in developing countries. Pneumococcal protein-based vaccines may have the capacity to induce pneumococcal serotype-independent protection. To understand the potential of maternal pneumococcal protein-specific antibodies in infants in high-risk areas, we studied the placental transfer of naturally acquired antibodies to pneumolysin (Ply) and pneumococcal surface protein A family 1 and 2 (PspA1 and PspA2) in relation to onset of pneumococcal nasopharyngeal carriage in infants in Papua New Guinea (PNG). In this study, 76% of the infants carried Streptococcus pneumoniae in the upper respiratory tract within the first month of life, at a median age of 19 days. Maternal and cord blood antibody titers to Ply (rho = 0.824, P < 0.001), PspA1 (rho = 0.746, P < 0.001), and PspA2 (rho = 0.631, P < 0.001) were strongly correlated. Maternal pneumococcal carriage (hazard ratio [HR], 2.60; 95% confidence interval [CI], 1.25 to 5.39) and younger maternal age (HR, 0.74; 95% CI, 0.54 to 1.00) were independent risk factors for early carriage, while higher cord Ply-specific antibody titers predicted a significantly delayed onset (HR, 0.71; 95% CI, 0.52 to 1.00) and cord PspA1-specific antibodies a significantly younger onset of carriage in PNG infants (HR, 1.57; 95% CI, 1.03 to 2.40). Maternal vaccination with a pneumococcal protein-based vaccine should be considered as a strategy to protect high-risk infants against pneumococcal disease by reducing carriage risks in both mothers and infants. PMID:19776196

  13. Maternal Antibodies to Pneumolysin but Not to Pneumococcal Surface Protein A Delay Early Pneumococcal Carriage in High-Risk Papua New Guinean Infants▿

    Science.gov (United States)

    Francis, Jacinta P.; Richmond, Peter C.; Pomat, William S.; Michael, Audrey; Keno, Helen; Phuanukoonnon, Suparat; Nelson, Jan B.; Whinnen, Melissa; Heinrich, Tatjana; Smith, Wendy-Anne; Prescott, Susan L.; Holt, Patrick G.; Siba, Peter M.; Lehmann, Deborah; van den Biggelaar, Anita H. J.

    2009-01-01

    Immunization of pregnant women can be an efficient strategy to induce early protection in infants in developing countries. Pneumococcal protein-based vaccines may have the capacity to induce pneumococcal serotype-independent protection. To understand the potential of maternal pneumococcal protein-specific antibodies in infants in high-risk areas, we studied the placental transfer of naturally acquired antibodies to pneumolysin (Ply) and pneumococcal surface protein A family 1 and 2 (PspA1 and PspA2) in relation to onset of pneumococcal nasopharyngeal carriage in infants in Papua New Guinea (PNG). In this study, 76% of the infants carried Streptococcus pneumoniae in the upper respiratory tract within the first month of life, at a median age of 19 days. Maternal and cord blood antibody titers to Ply (ρ = 0.824, P < 0.001), PspA1 (ρ = 0.746, P < 0.001), and PspA2 (ρ = 0.631, P < 0.001) were strongly correlated. Maternal pneumococcal carriage (hazard ratio [HR], 2.60; 95% confidence interval [CI], 1.25 to 5.39) and younger maternal age (HR, 0.74; 95% CI, 0.54 to 1.00) were independent risk factors for early carriage, while higher cord Ply-specific antibody titers predicted a significantly delayed onset (HR, 0.71; 95% CI, 0.52 to 1.00) and cord PspA1-specific antibodies a significantly younger onset of carriage in PNG infants (HR, 1.57; 95% CI, 1.03 to 2.40). Maternal vaccination with a pneumococcal protein-based vaccine should be considered as a strategy to protect high-risk infants against pneumococcal disease by reducing carriage risks in both mothers and infants. PMID:19776196

  14. Pneumococcal hydrogen peroxide-induced stress signaling regulates inflammatory genes.

    Science.gov (United States)

    Loose, Maria; Hudel, Martina; Zimmer, Klaus-Peter; Garcia, Ernesto; Hammerschmidt, Sven; Lucas, Rudolf; Chakraborty, Trinad; Pillich, Helena

    2015-01-15

    Microbial infections can induce aberrant responses in cellular stress pathways, leading to translational attenuation, metabolic restriction, and activation of oxidative stress, with detrimental effects on cell survival. Here we show that infection of human airway epithelial cells with Streptococcus pneumoniae leads to induction of endoplasmic reticulum (ER) and oxidative stress, activation of mitogen-associated protein kinase (MAPK) signaling pathways, and regulation of their respective target genes. We identify pneumococcal H2O2 as the causative agent for these responses, as both catalase-treated and pyruvate oxidase-deficient bacteria lacked these activities. Pneumococcal H2O2 induced nuclear NF-κB translocation and transcription of proinflammatory cytokines. Inhibition of translational arrest and ER stress by salubrinal or of MAPK signaling pathways attenuate cytokine transcription. These results provide strong evidence for the notion that inhibition of translation is an important host pathway in monitoring harmful pathogen-associated activities, thereby enabling differentiation between pathogenic and nonpathogenic bacteria. PMID:25183769

  15. Association of the pneumococcal pilus with certain capsular serotypes but not with increased virulence.

    Science.gov (United States)

    Basset, Alan; Trzcinski, Krzysztof; Hermos, Christina; O'Brien, Katherine L; Reid, Raymond; Santosham, Mathuram; McAdam, Alexander J; Lipsitch, Marc; Malley, Richard

    2007-06-01

    The recent discovery of a mobile genetic element encoding a pilus-like structure in Streptococcus pneumoniae and the demonstration of a role for the pilus in virulence in mice have led to the proposal of the use of the pilus as a candidate pneumococcal vaccine. We examined the frequency of occurrence of the pneumococcal pilus, as determined by the presence of the rrgC gene, and analyzed its association with virulence, capsular serotypes, and multilocus sequence types in the American Indian pneumococcal collection and isolates of S. pneumoniae from blood cultures collected at Children's Hospital Boston. Overall, 21.4% of strains in the American Indian collection had the rrgC gene, but there was no difference between isolates obtained from the nasopharynx and those obtained from sterile sites (blood or cerebrospinal fluid). Vaccine-type strains were significantly more likely than non-vaccine-type strains to have this pilus gene (P types, there was a high concordance (95%) between the multilocus sequence type and the presence or the absence of rrgC. Finally, in the era of the pneumococcal conjugate vaccine, the frequency of rrgC in isolates from Children's Hospital Boston has decreased significantly (42.8% before 2000 versus 21.3% after 2000; P = 0.019). Therefore, our data show that the pilus is present in a minority of strains and is associated with certain serotypes and that its frequency has been reduced by the conjugate pneumococcal vaccine. PMID:17392439

  16. August 2013 pulmonary journal club: pneumococcal vaccine déjà vu

    Directory of Open Access Journals (Sweden)

    Robbins RA

    2013-08-01

    Full Text Available No abstract available. Article truncated at 150 words. Griffin MR, Zhu Y, Moore MR, Whitney CG, Grijalva CG. U.S. hospitalizations for pneumonia after a decade of pneumococcal vaccination. N Engl J Med. 2013;369(2:155-63. [CrossRef] [PubMed] The introduction of the 7-valent pneumococcal conjugate vaccine (PCV7 into the U.S. childhood immunization schedule in 2000 has substantially reduced the incidence of vaccine-serotype invasive pneumococcal disease in young children and in unvaccinated older children and adults. By preventing the acquisition and carriage of pneumococcus in the nasopharynx of vaccinated children, PCV7 reduced the transmission of vaccine serotypes to the unvaccinated. The authors estimated the annual rates of hospitalization for pneumonia from any cause using the Nationwide Inpatient Sample database. Average annual rates of pneumonia-related hospitalizations from 1997 through 1999 (before the introduction of PCV7 and from 2007 through 2009 (well after its introduction were used to estimate annual declines in hospitalizations due to pneumonia. The annual rate of hospitalization for pneumonia among …

  17. [Pneumococcal vaccination: conjugated vaccine induces herd immunity and reduces antibiotic resistance].

    Science.gov (United States)

    Pletz, M W; Maus, U; Hohlfeld, J M; Lode, H; Welte, T

    2008-02-01

    Pneumococcal infections (pneumonia, otitis media, sinusitis, meningitis) are common and usually involve toddlers and the elderly. Currently, two pneumococcal vaccines are in clinical use. The older vaccine consists of pure capsular polysaccharides from 23 pneumococcal serotypes and induces only a limited B-cell response because polysaccharides are poor antigens that stimulate mainly B-cells. In 2000, a vaccination program with a novel 7-valent pneumococcal conjugate vaccine was launched in the U.S. The conjugation of capsular polysaccharides with a highly immunogenic diphtheria toxoid protein induces both a T cell and B cell response that results in specific humoral and mucosal immunity. Since children are the main reservoir of pneumococci, the 7-valent conjugate vaccine seems to eradicate the respective pneumococcal serotypes within the population, as demonstrated by recent US data. Pronounced herd immunity resulted in a decrease in invasive pneumococcal diseases in vaccinees and non-vaccinees as well as in a reduction of antibiotic resistance rates. However, recent data suggest a replacement of vaccine-serotypes by non-vaccine serotypes, which conquer the ecological niche created by the vaccine. In order to encounter this problem a 13-valent conjugated vaccine is currently under development.

  18. Surface Proteins and Pneumolysin of Encapsulated and Nonencapsulated Streptococcus pneumoniae Mediate Virulence in a Chinchilla Model of Otitis Media

    OpenAIRE

    Keller, Lance E.; Bradshaw, Jessica L.; Pipkins, Haley; McDaniel, Larry S.

    2016-01-01

    Streptococcus pneumoniae infections result in a range of human diseases and are responsible for almost one million deaths annually. Pneumococcal disease is mediated in part through surface structures and an anti-phagocytic capsule. Recent studies have shown that nonencapsulated S. pneumoniae (NESp) make up a significant portion of the pneumococcal population and are able to cause disease. NESp lack some common surface proteins expressed by encapsulated pneumococci, but express surface protein...

  19. SURFACE PROTEINS AND PNEUMOLYSIN OF ENCAPSULATED AND NONENCAPSULATED STREPTOCOCCUS PNEUMONIAE MEDIATE VIRULENCE IN A CHINCHILLA MODEL OF OTITIS MEDIA

    OpenAIRE

    Keller, Lance E.; Bradshaw, Jessica L.; Haley ePipkins; McDaniel, Larry S.

    2016-01-01

    Streptococcus pneumoniae infections result in a range of human diseases and are responsible for almost one million deaths annually. Pneumococcal disease is mediated in part through surface structures and an anti-phagocytic capsule. Recent studies have shown that nonencapsulated Streptococcus pneumoniae (NESp) make up a significant portion of the pneumococcal population and are able to cause disease. NESp lack some common surface proteins expressed by encapsulated pneumococci, but express surf...

  20. Cost of pneumococcal infections and cost-effectiveness analysis of pneumococcal vaccination at risk adults and elderly in Turkey.

    Science.gov (United States)

    Akin, Levent; Kaya, Mehmet; Altinel, Serdar; Durand, Laure

    2011-04-01

    Pneumococcal infections have a substantial burden in Turkey, particularly in the elderly (> 60 years) and at-risk adults (18-59 years). VCR are low at approximately 2%. The first aim of this study was the evaluation of the burden of pneumococcal infections (pneumonia and bacteremia) from a public payer perspective in elderly and at-risk adults. The second aim was the evaluation of cost effectiveness of implementing a large PPV program in these populations. A decision tree model was employed using demographic and epidemiological input obtained from Turkish official sources and international literature. Vaccination was assumed to protect for 5 years with 60% and 50% effectiveness against BPP in elderly and at-risk adults respectively. Vaccination effectiveness of 21% against NBPP was assumed for both populations. Costs input were obtained from a previous study conducted between 2002 and 2008 in a public university hospital in Ankara, Turkey. Univariate sensitivity analyses and Monte-Carlo simulations were performed. The vaccination program was cost effective and cost saving compared to no vaccination, pneumococcal vaccination with 60% coverage led to a mean of 4,695 LYG in the elderly and 2,134 LYG in at-risk adults with 40% coverage. Mean incremental savings reached 45.4 million YTL in the elderly and 21.8 million YTL in at-risk adults. This analysis suggests that pneumococcal vaccination of elderly and at-risk adults is associated with a positive return on investment from a public payer perspective and supports the continued recommendation of pneumococcal vaccines, as well as their full funding in Turkey.

  1. Association of the Pneumococcal Pilus with Certain Capsular Serotypes but Not with Increased Virulence▿

    OpenAIRE

    Basset, Alan; Trzcinski, Krzysztof; Hermos, Christina; O'Brien, Katherine L.; Reid, Raymond; Santosham, Mathuram; McAdam, Alexander J.; Lipsitch, Marc; Malley, Richard

    2007-01-01

    The recent discovery of a mobile genetic element encoding a pilus-like structure in Streptococcus pneumoniae and the demonstration of a role for the pilus in virulence in mice have led to the proposal of the use of the pilus as a candidate pneumococcal vaccine. We examined the frequency of occurrence of the pneumococcal pilus, as determined by the presence of the rrgC gene, and analyzed its association with virulence, capsular serotypes, and multilocus sequence types in the American Indian pn...

  2. Molecular epidemiology of nonencapsulated Streptococcus pneumoniae among Japanese children with acute otitis media.

    Science.gov (United States)

    Hotomi, Muneki; Nakajima, Kouji; Hiraoka, Masanobu; Nahm, Moon H; Yamanaka, Noboru

    2016-02-01

    The introduction of pneumococcal conjugate vaccine may change the epidemiology of Streptococcus pneumoniae. The increased prevalence of non-vaccine serotypes as the cause of pneumococcal diseases has already reported in the United States and Europe. However, little attention has been focused on the S. pneumoniae. In this study, nonencapsulated S. pneumoniae were identified in 15 isolates (6.4%) out of 236 pneumococcal strains obtained from the nasopharynges of children with acute otitis media (AOM), in 3 isolates (14.3%) out of 21 strains from acute rhinosinusitis, and in 2 isolates (12.5%) out of 16 nasopharyngeal carriage strains obtained from normal healthy children. Among the 20 nonencapsulated S. pneumoniae isolates, 15 (75.0%) isolates had the pspK gene. Seven sequence types (STs) were identified: ST7502 (5 strains), ST1106 (2 strains), ST7803 (2 strains), ST7786 (1 strain), ST6741 (1 strain), ST7496 (1 strain), and ST8642 (1 strain). Because nonencapsulated S. pneumoniae strains are not targeted by the current available pneumococcal vaccines, these strains will gradually become more common in nasopharyngeal carriage. The increase in colonization and dissemination of these strains would increase the risk of AOM and other systemic pneumococcal diseases against which current vaccines cannot provide protection. Nonencapsulated S. pneumoniae may thus become more prevalent as human pathogen.

  3. Distribution and Genetic Diversity of the ABC Transporter Lipoproteins PiuA and PiaA within Streptococcus pneumoniae and Related Streptococci

    OpenAIRE

    Whalan, Rachael H.; Funnell, Simon G.P.; Bowler, Lucas D.; Hudson, Michael J.; Robinson, Andrew; Dowson, Christopher G.

    2006-01-01

    Streptococcus pneumoniae is a major cause of morbidity and mortality worldwide. The existence of approximately 90 antigenically distinct capsular serotypes has greatly complicated the development of an effective pneumococcal vaccine. Virulence-associated proteins common and conserved among all capsular types now represent the best strategy to combat pneumococcal infections. PiuA and PiaA are the lipoprotein components of two pneumococcal iron ABC transporters and are required for full virulen...

  4. Population structure and drug resistance patterns of emerging non-PCV-13 Streptococcus pneumoniae serotypes 22F, 15A, and 8 isolated from adults in Ontario, Canada.

    Science.gov (United States)

    Duvvuri, Venkata R; Deng, Xianding; Teatero, Sarah; Memari, Nader; Athey, Taryn; Fittipaldi, Nahuel; Gubbay, Jonathan B

    2016-08-01

    The introduction of pneumococcal conjugate vaccines has led to the emergence of non-vaccine serotypes, which contributed to invasive pneumococcal disease in Canada and worldwide. A significant increase in the prevalence of non-13-valent pneumococcal conjugate vaccine (PCV-13)-included serotypes 22F, 15A, and 8 was observed from 2009 to 2013 in Ontario (all p valuesStreptococcus pneumoniae population structures and dynamics, and its utility in molecular surveillance. PMID:27071529

  5. Pneumococcal Vaccination: Who Needs It?

    Science.gov (United States)

    ... Resources News Newsletters Events Pneumococcal Vaccination: Who Needs It? Recommend on Facebook Tweet Share Compartir There are ... healthy, do not need to get PPSV23 because it is not effective against those conditions. For additional ...

  6. Cross-sectional study on attitudes among general practitioners towards pneumococcal vaccination for middle-aged and elderly population in Hong Kong.

    Directory of Open Access Journals (Sweden)

    Lancelot W H Mui

    Full Text Available OBJECTIVE: To study the attitudes among general practitioners towards pneumococcal vaccination for middle-aged (50-64 and elderly population (over 65 in Hong Kong and the factors affecting their decision to advise pneumococcal vaccination for those age groups. DESIGN: Cross-sectional study of general practitioners in private practice in Hong Kong. PARTICIPANTS: Members of Hong Kong Medical Association delivering general practice services in private sector. MEASURING TOOL: Self-administered questionnaire. MAIN OUTCOME MEASURES: Intention to recommend pneumococcal vaccination, barriers against pneumococcal vaccination. RESULTS: 53.4% of the respondents would actively recommend pneumococcal vaccination to elderly patients but only 18.8% would recommend for middle-aged patients. Consultation not related to pneumococcal vaccine was the main reason for not recommending pneumococcal vaccine (43.6%. Rarity of pneumonia in their daily practice was another reason with 68.4% of respondents attending five or less patients with pneumonia each year. In multivariate analysis, factors such as respondents would get vaccination when reaching age 50 (ORm 10.1, and attending 6 pneumonia cases or more per year (ORm 2.28 were found to be associated with increasing likelihood for recommending vaccination to the middle-aged. While concerns of marketing a product (ORm 0.41, consultation not related to vaccination (ORm 0.45 and limited time (ORm 0.38 were factors that reduced the likelihood. CONCLUSION: Public policy is needed to increase the awareness of impact of pneumococcal pneumonia and the availability of preventive measures.

  7. Novel clones of Streptococcus pneumoniae causing invasive disease in Malaysia.

    Directory of Open Access Journals (Sweden)

    Johanna M Jefferies

    Full Text Available Although Streptococcus pneumoniae is a leading cause of childhood disease in South East Asia, little has previously been reported regarding the epidemiology of invasive pneumococcal disease in Malaysia and very few studies have explored pneumococcal epidemiology using multilocus sequence typing (MLST. Here we describe serotype, multilocus sequence type (ST, and penicillin susceptibility of thirty pneumococcal invasive disease isolates received by the University of Malaya Medical Centre between February 2000 and January 2007 and relate this to the serotypes included in current pneumococcal conjugate vaccines. A high level of diversity was observed; fourteen serotypes and 26 sequence types (ST, (11 of which were not previously described were detected from 30 isolates. Penicillin non-susceptible pneumococci accounted for 33% of isolates. The extent of molecular heterogeneity within carried and disease-causing Malaysian pneumococci remains unknown. Larger surveillance and epidemiological studies are now required in this region to provide robust evidence on which to base future vaccine policy.

  8. Pneumococcal Surface Protein A Is Expressed In Vivo, and Antibodies to PspA Are Effective for Therapy in a Murine Model of Pneumococcal Sepsis

    OpenAIRE

    Swiatlo, E.; J. King; Nabors, G S; Mathews, B; Briles, D. E.

    2003-01-01

    Pneumococcal surface protein A (PspA) is an immunogenic protein expressed on the surface of all strains of Streptococcus pneumoniae (pneumococcus) and induces antibodies which protect against invasive infection in mice. Pneumococci used for infectious challenge in protection studies are typically collected from cultures grown in semisynthetic medium in vitro. The purpose of these studies is to confirm that PspA is expressed by pneumococci during growth in vivo at ...

  9. Dynamics of nasopharyngeal pneumococcal carriage during the course of viral bronchiolitis.

    Science.gov (United States)

    Faber, Tina E; Schuurs, Theo A; Veeger, Nic J G M; Hennus, Marije P; Bont, Louis J

    2016-08-01

    The effect of viral infection on nasopharyngeal carriage of Streptococcus pneumoniae during childhood is not well known. We studied dynamics of pneumococcal colonization by quantitative PCR during the natural course of viral bronchiolitis. At time of admission, 47 (47%) of 100 patients with bronchiolitis carried pneumococci. In patients with viral bronchiolitis who did not receive antibiotics, pneumococcal load decreased from time of admission to discharge (n = 35, cycle threshold 23 vs. 25, P = 0.0017) and from discharge to follow-up (n = 22, cycle threshold 25 vs. 40, P = 0.003). We conclude that viral respiratory infection is negatively associated with pneumococcal colonization of the upper airways. Pediatr Pulmonol. 2016;51:863-867. © 2016 Wiley Periodicals, Inc. PMID:26859410

  10. Dynamics of nasopharyngeal pneumococcal carriage during the course of viral bronchiolitis.

    Science.gov (United States)

    Faber, Tina E; Schuurs, Theo A; Veeger, Nic J G M; Hennus, Marije P; Bont, Louis J

    2016-08-01

    The effect of viral infection on nasopharyngeal carriage of Streptococcus pneumoniae during childhood is not well known. We studied dynamics of pneumococcal colonization by quantitative PCR during the natural course of viral bronchiolitis. At time of admission, 47 (47%) of 100 patients with bronchiolitis carried pneumococci. In patients with viral bronchiolitis who did not receive antibiotics, pneumococcal load decreased from time of admission to discharge (n = 35, cycle threshold 23 vs. 25, P = 0.0017) and from discharge to follow-up (n = 22, cycle threshold 25 vs. 40, P = 0.003). We conclude that viral respiratory infection is negatively associated with pneumococcal colonization of the upper airways. Pediatr Pulmonol. 2016;51:863-867. © 2016 Wiley Periodicals, Inc.

  11. Decrease in pneumococcal co-colonization following vaccination with the seven-valent pneumococcal conjugate vaccine.

    OpenAIRE

    Carina Valente; Jason Hinds; Francisco Pinto; Brugger, Silvio D.; Katherine Gould; Kathrin Mühlemann; Hermínia de Lencastre; Raquel Sá-Leão

    2012-01-01

    Understanding the epidemiology of pneumococcal co-colonization is important for monitoring vaccine effectiveness and the occurrence of horizontal gene transfer between pneumococcal strains. In this study we aimed to evaluate the impact of the seven-valent pneumococcal conjugate vaccine (PCV7) on pneumococcal co-colonization among Portuguese children. Nasopharyngeal samples from children up to 6 years old yielding a pneumococcal culture were clustered into three groups: pre-vaccine era (n = 17...

  12. Antibodies mediate formation of neutrophil extracellular traps in the middle ear and facilitate secondary pneumococcal otitis media

    NARCIS (Netherlands)

    Short, K.R.; Kockritz-Blickwede, M. von; Langereis, J.D.; Chew, K.Y.; Job, E.R.; Armitage, C.W.; Hatcher, B.; Fujihashi, K.; Reading, P.C.; Hermans, P.W.M.; Wijburg, O.L.; Diavatopoulos, D.A.

    2014-01-01

    Otitis media (OM) (a middle ear infection) is a common childhood illness that can leave some children with permanent hearing loss. OM can arise following infection with a variety of different pathogens, including a coinfection with influenza A virus (IAV) and Streptococcus pneumoniae (the pneumococc

  13. Mannose-binding lectin gene, MBL2, polymorphisms are not associated with susceptibility to invasive pneumococcal disease in children

    DEFF Research Database (Denmark)

    Lundbo, Lene Fogt; Harboe, Zitta Barrella; Clausen, Louise Nygaard;

    2014-01-01

    BACKGROUND: Most children are transiently colonized with Streptococcus pneumoniae, but very few develop invasive pneumococcal disease (IPD). Host genetic variation of innate immunity may predispose to IPD. We investigated the effect of genetic variation in the mannose-binding lectin gene, MBL2, on...

  14. Dosing Schedules for Pneumococcal Conjugate Vaccine

    Science.gov (United States)

    2014-01-01

    Since second generation pneumococcal conjugate vaccines (PCVs) targeting 10 and 13 serotypes became available in 2010, the number of national policy makers considering these vaccines has steadily increased. An important consideration for a national immunization program is the timing and number of doses—the schedule—that will best prevent disease in the population. Data on disease epidemiology and the efficacy or effectiveness of PCV schedules are typically considered when choosing a schedule. Practical concerns, such as the existing vaccine schedule, and vaccine program performance are also important. In low-income countries, pneumococcal disease and deaths typically peak well before the end of the first year of life, making a schedule that provides PCV doses early in life (eg, a 6-, 10- and 14-week schedule) potentially the best option. In other settings, a schedule including a booster dose may address disease that peaks in the second year of life or may be seen to enhance a schedule already in place. A large and growing body of evidence from immunogenicity studies, as well as clinical trials and observational studies of carriage, pneumonia and invasive disease, has been systematically reviewed; these data indicate that schedules of 3 or 4 doses all work well, and that the differences between these regimens are subtle, especially in a mature program in which coverage is high and indirect (herd) effects help enhance protection provided directly by a vaccine schedule. The recent World Health Organization policy statement on PCVs endorsed a schedule of 3 primary doses without a booster or, as a new alternative, 2 primary doses with a booster dose. While 1 schedule may be preferred in a particular setting based on local epidemiology or practical considerations, achieving high coverage with 3 doses is likely more important than the specific timing of doses. PMID:24336059

  15. A single amino acid substitution in the MurF UDP-MurNAc-pentapeptide synthetase renders Streptococcus pneumoniae dependent on CO2 and temperature

    NARCIS (Netherlands)

    Burghout, Peter; Quintero, Beatriz; Bos, Linda; Beilharz, Katrin; Veening, Jan-Willem; de Jonge, Marien I.; van der Linden, Mark; van der Ende, Arie; Hermans, Peter W. M.

    2013-01-01

    The respiratory tract pathogen Streptococcus pneumoniae encounters different levels of environmental CO2 during transmission, host colonization and disease. About 8% of all pneumococcal isolates are capnophiles that require CO2-enriched growth conditions. The underlying molecular mechanism for caphn

  16. Pediatricians′ perspectives on pneumococcal conjugate vaccines: An exploratory study in the private sector

    Directory of Open Access Journals (Sweden)

    Sanjay Zodpey

    2015-01-01

    Full Text Available There is a lack of information on supply-side determinants, their utilization, and the access to pneumococcal vaccination in India. The objective of this exploratory study was to document the perceptions and perspectives of practicing pediatricians with regard to pneumococcal conjugate vaccines (PCVs in selected metropolitan areas of India. A qualitative study was conducted to generate evidence on the perspective of pediatricians practicing in the private sector regarding pneumococcal vaccination. The pediatricians were identified from 11 metropolitan areas on the basis of PCV vaccine sales in India through multilevel stratified sampling method. Relevant information was collected through in-depth personal interviews. Finally, qualitative data analysis was carried out through standard techniques such as the identification of key domains, words, phrases, and concepts from the respondents. We observed that the majority (67.7% of the pediatricians recommended pneumococcal vaccination to their clients, whereas 32.2% recommended it to only those who could afford it. More than half (62.9% of the pediatricians had no preference for any brand and recommended both a 10-valent pneumococcal conjugate vaccine (PCV10 and a 13-valent PCV (PCV13, whereas 8.0% recommended none. An overwhelming majority (97.3% of the pediatricians reported that the main reason for a patient not following the pediatrician′s advice for pneumococcal vaccination was the price of PCV. To reduce childhood pneumonia-related burden and mortality, pediatricians should use every opportunity to increase awareness about vaccine-preventable diseases, especially vaccine-preventable childhood pneumonia among their patients.

  17. Pediatricians' perspectives on pneumococcal conjugate vaccines: An exploratory study in the private sector.

    Science.gov (United States)

    Zodpey, Sanjay; Farooqui, Habib Hasan; Chokshi, Maulik; Kumar, Balu Ravi; Thacker, Naveen

    2015-01-01

    There is a lack of information on supply-side determinants, their utilization, and the access to pneumococcal vaccination in India. The objective of this exploratory study was to document the perceptions and perspectives of practicing pediatricians with regard to pneumococcal conjugate vaccines (PCVs) in selected metropolitan areas of India. A qualitative study was conducted to generate evidence on the perspective of pediatricians practicing in the private sector regarding pneumococcal vaccination. The pediatricians were identified from 11 metropolitan areas on the basis of PCV vaccine sales in India through multilevel stratified sampling method. Relevant information was collected through in-depth personal interviews. Finally, qualitative data analysis was carried out through standard techniques such as the identification of key domains, words, phrases, and concepts from the respondents. We observed that the majority (67.7%) of the pediatricians recommended pneumococcal vaccination to their clients, whereas 32.2% recommended it to only those who could afford it. More than half (62.9%) of the pediatricians had no preference for any brand and recommended both a 10-valent pneumococcal conjugate vaccine (PCV10) and a 13-valent PCV (PCV13), whereas 8.0% recommended none. An overwhelming majority (97.3%) of the pediatricians reported that the main reason for a patient not following the pediatrician's advice for pneumococcal vaccination was the price of PCV. To reduce childhood pneumonia-related burden and mortality, pediatricians should use every opportunity to increase awareness about vaccine-preventable diseases, especially vaccine-preventable childhood pneumonia among their patients. PMID:26354401

  18. Anti Pneumococcal Activity of Azithromycin-Eudragit RS100 Nano-Formulations

    Science.gov (United States)

    Adibkia, Khosro; Khorasani, Golrokh; Payab, Shahriar; Lotfipour, Farzaneh

    2016-01-01

    Purpose: Bacterial pneumonia is a common lung infection caused by different types of bacteria. Azithromycin (AZI), an azalide antibiotic, is widely used to manage pneumococcal infections. Studies have shown that antibiotics in nanocarriers may lead to increased antibacterial activity and reduced toxicity. The aim of this work was to valuate in vitro antibacterial performance azithromycin-Eudragit RS100 nano-formulations against Streptococcus pneumoniae and Staphylococcus aureus. Methods: AZI-Eudragit RS100 nanoparticles were prepared via electrospinning technique and the in vitro antibacterial performance against S. pneumoniae and S. aureus were assessed using agar dilution method. Results: Nanofibers in the sizes about 100-300 nm in diameter and micro scale in length and nanobeads in the range of 100-500 nm were achieved. The Minimum Inhibitory Concentrations (MIC) showed an enhancement in the antimicrobial effect of AZI-Eudragit RS100 nanofibers (40 µg/ml) compare to untreated AZI solution (>160 µg/ml) against S. pneumonia. The MIC value for AZI-Eudragit RS100 nanofibers against S. aureus was >128 µg/ml, same as that of the untreated AZI solution. Conclusion: The enhanced efficiency of AZI in nanofibers could be related to the more adsorption opportunity of nanofibers to S. pneumonia capsulated cell wall which provides an antibiotic depot on the bacterial surface compared to S. aureus. AZI-Eudragit RS100 nanofibers with enhanced antimicrobial effect against S. pneumonia can be considered as a candidate for in vivo evaluations in antibiotic therapy of Pneumococcal infections.

  19. Impact of 10-valent pneumococcal conjugate vaccine on pneumococcal meningitis in children up to two years of age in Brazil

    Directory of Open Access Journals (Sweden)

    Indianara Maria Grando

    2015-02-01

    Full Text Available The objective of this study was to analyze the impact of vaccination against Streptococcus pneumoniae on the morbidity and mortality from pneumococcal meningitis in children ≤ 2 years in Brazil, from 2007 to 2012. This is a descriptive study and ecological analysis using data from the Information System on Notifiable Diseases. Pre-vaccination (2007-2009 and post-vaccination (2011-2012 periods were defined to compare incidence rates and mortality. A total of 1,311 cases and 430 deaths were reported during the study period. Incidence decreased from 3.70/100,000 in 2007 to 1.84/100,000 in 2012, and mortality decreased from 1.30/100,000 to 0.40/100,000, or 50% and 69% respectively, with the greatest impact in the 6-11 month age group. This decrease in Pneumococcal meningitis morbidity and mortality rates two years after introduction of the 10-valent pneumococcal conjugate vaccine suggests its effectiveness.

  20. Streptococcus pneumoniae-associated pneumonia complicated by purulent pericarditis: case series *

    Science.gov (United States)

    Cillóniz, Catia; Rangel, Ernesto; Barlascini, Cornelius; Piroddi, Ines Maria Grazia; Torres, Antoni; Nicolini, Antonello

    2015-01-01

    Abstract Objective: In the antibiotic era, purulent pericarditis is a rare entity. However, there are still reports of cases of the disease, which is associated with high mortality, and most such cases are attributed to delayed diagnosis. Approximately 40-50% of all cases of purulent pericarditis are caused by Gram-positive bacteria, Streptococcus pneumoniae in particular. Methods: We report four cases of pneumococcal pneumonia complicated by pericarditis, with different clinical features and levels of severity. Results: In three of the four cases, the main complication was cardiac tamponade. Microbiological screening (urinary antigen testing and pleural fluid culture) confirmed the diagnosis of severe pneumococcal pneumonia complicated by purulent pericarditis. Conclusions: In cases of pneumococcal pneumonia complicated by pericarditis, early diagnosis is of paramount importance to avoid severe hemodynamic compromise. The complications of acute pericarditis appear early in the clinical course of the infection. The most serious complications are cardiac tamponade and its consequences. Antibiotic therapy combined with pericardiocentesis drastically reduces the mortality associated with purulent pericarditis. PMID:26398760

  1. Streptococcus pneumoniae-associated pneumonia complicated by purulent pericarditis: case series

    International Nuclear Information System (INIS)

    Objective: In the antibiotic era, purulent pericarditis is a rare entity. However, there are still reports of cases of the disease, which is associated with high mortality, and most such cases are attributed to delayed diagnosis. Approximately 40-50% of all cases of purulent pericarditis are caused by Gram-positive bacteria, Streptococcus pneumoniae in particular. Methods: We report four cases of pneumococcal pneumonia complicated by pericarditis, with different clinical features and levels of severity. Results: In three of the four cases, the main complication was cardiac tamponade. Microbiological screening (urinary antigen testing and pleural fluid culture) confirmed the diagnosis of severe pneumococcal pneumonia complicated by purulent pericarditis. Conclusions: In cases of pneumococcal pneumonia complicated by pericarditis, early diagnosis is of paramount importance to avoid severe hemodynamic compromise. The complications of acute pericarditis appear early in the clinical course of the infection. The most serious complications are cardiac tamponade and its consequences. Antibiotic therapy combined with pericardiocentesis drastically reduces the mortality associated with purulent pericarditis. (author)

  2. Streptococcus pneumoniae-associated pneumonia complicated by purulent pericarditis: case series

    Energy Technology Data Exchange (ETDEWEB)

    Cilloniz, Catia; Torres, Antoni [Servicio de Neumologia, Hospital Clinic de Barcelona, Ciber de Enfermedades Respiratorias (CIBERES), Instituto de Investigacion Biomedica Agusti Pi i Sunyer, Universidad de Barcelona (Spain); Rangel, Ernesto [Facultad de Medicina, Universidad Autonoma de Nayarit, Tepic (Mexico); Barlascini, Cornelius [Servizio di Igiene e Sanita Pubblica, Ospedale Generale di Sestri Levante, Sestri Levante (Italy); Piroddi, Ines Maria Grazia; Nicolini, Antonello, E-mail: antonellonicolini@gmail.com [Servizio di Pneumologia, Ospedale Generale di Sestri Levante, Sestri Levante (Italy)

    2015-07-15

    Objective: In the antibiotic era, purulent pericarditis is a rare entity. However, there are still reports of cases of the disease, which is associated with high mortality, and most such cases are attributed to delayed diagnosis. Approximately 40-50% of all cases of purulent pericarditis are caused by Gram-positive bacteria, Streptococcus pneumoniae in particular. Methods: We report four cases of pneumococcal pneumonia complicated by pericarditis, with different clinical features and levels of severity. Results: In three of the four cases, the main complication was cardiac tamponade. Microbiological screening (urinary antigen testing and pleural fluid culture) confirmed the diagnosis of severe pneumococcal pneumonia complicated by purulent pericarditis. Conclusions: In cases of pneumococcal pneumonia complicated by pericarditis, early diagnosis is of paramount importance to avoid severe hemodynamic compromise. The complications of acute pericarditis appear early in the clinical course of the infection. The most serious complications are cardiac tamponade and its consequences. Antibiotic therapy combined with pericardiocentesis drastically reduces the mortality associated with purulent pericarditis. (author)

  3. Influenza Virus Infection Decreases Tracheal Mucociliary Velocity and Clearance of Streptococcus pneumoniae

    OpenAIRE

    Pittet, Lynnelle A.; Hall-Stoodley, Luanne; Rutkowski, Melanie R.; Harmsen, Allen G.

    2009-01-01

    Influenza virus infections increase susceptibility to secondary bacterial infections, such as pneumococcal pneumonia, resulting in increased morbidity and mortality. Influenza-induced tissue damage is hypothesized to increase susceptibility to Streptococcus pneumoniae infection by increasing adherence to the respiratory epithelium. Using a mouse model of influenza infection followed by S. pneumoniae infection, we found that an influenza infection does not increase the number of pneumococci in...

  4. Alcohol abuse and Streptococcus pneumoniae infections: Consideration of Virulence Factors and Impaired Immune Responses

    OpenAIRE

    Bhatty, Minny; Pruett, Stephen B.; Swiatlo, Edwin; Nanduri, Bindu

    2011-01-01

    Alcohol is the most frequently abused substance in the world. Both acute and chronic alcohol consumption have diverse and well documented effects on the human immune system, leading to increased susceptibility to infections like bacterial pneumonia. S. pneumoniae is the most common bacterial etiology of community acquired pneumonia world-wide. The frequency and severity of pneumococcal infections in individuals with a history of alcohol abuse is much higher than the general population. Despit...

  5. Antibiotic treatment and the diagnosis of Streptococcus pneumoniae in lower respiratory tract infections in adults

    DEFF Research Database (Denmark)

    Korsgaard, Jens; Møller, Jens Kjølseth; Kilian, Mogens

    2005-01-01

    patient was positive in both systems, making a total of 22 patients with documented pneumococcal infection. As a positive culture test was dependent on the absence of antibiotic treatment, whereas a positive urine antigen test depended on antibiotic treatment within 48 hours, the two tests were...... complementary in the diagnosis of infection with S. pneumoniae. The third group of patients with probable pneumococcal infection were identified as 26% and 20% of the remaining 137 patients with unknown or known non-pneumococcal etiology, respectively, who received recent antibiotic treatment within 2-4 weeks...... of diagnostic sampling. By comparison, 0% (p < 0.01) with documented pneumococcal infection received antibiotic treatment in weeks 2-4 prior to microbiological sampling. As such a further eight patients should be expected to have infection with S. pneumoniae but would test negative in both culture...

  6. Assessing pneumococcal meningitis association with viral respiratory infections and antibiotics: insights from statistical and mathematical models.

    Science.gov (United States)

    Opatowski, Lulla; Varon, Emmanuelle; Dupont, Claire; Temime, Laura; van der Werf, Sylvie; Gutmann, Laurent; Boëlle, Pierre-Yves; Watier, Laurence; Guillemot, Didier

    2013-08-01

    Pneumococcus is an important human pathogen, highly antibiotic resistant and a major cause of bacterial meningitis worldwide. Better prevention requires understanding the drivers of pneumococcal infection incidence and antibiotic susceptibility. Although respiratory viruses (including influenza) have been suggested to influence pneumococcal infections, the underlying mechanisms are still unknown, and viruses are rarely considered when studying pneumococcus epidemiology. Here, we propose a novel mathematical model to examine hypothetical relationships between Streptococcus pneumoniae meningitis incidence (SPMI), acute viral respiratory infections (AVRIs) and antibiotic exposure. French time series of SPMI, AVRI and penicillin consumption over 2001-2004 are analysed and used to assess four distinct virus-bacteria interaction submodels, ascribing the interaction on pneumococcus transmissibility and/or pathogenicity. The statistical analysis reveals strong associations between time series: SPMI increases shortly after AVRI incidence and decreases overall as the antibiotic-prescription rate rises. Model simulations require a combined impact of AVRI on both pneumococcal transmissibility (up to 1.3-fold increase at the population level) and pathogenicity (up to threefold increase) to reproduce the data accurately, along with diminished epidemic fitness of resistant pneumococcal strains causing meningitis (0.97 (0.96-0.97)). Overall, our findings suggest that AVRI and antibiotics strongly influence SPMI trends. Consequently, vaccination protecting against respiratory virus could have unexpected benefits to limit invasive pneumococcal infections.

  7. Characteristics and prognosis of pneumococcal endocarditis: a case-control study.

    Science.gov (United States)

    Daudin, M; Tattevin, P; Lelong, B; Flecher, E; Lavoué, S; Piau, C; Ingels, A; Chapron, A; Daubert, J-C; Revest, M

    2016-06-01

    Case series have suggested that pneumococcal endocarditis is a rare disease, mostly reported in patients with co-morbidities but no underlying valve disease, with a rapid progression to heart failure, and high mortality. We performed a case-control study of 28 patients with pneumococcal endocarditis (cases), and 56 patients with non-pneumococcal endocarditis (controls), not matched for sex and age, during the years 1991-2013, in one referral centre. Alcoholism (39.3% versus 10.7%; p endocarditis. Cardiac surgery was required in 64.3% of patients with pneumococcal endocarditis, much earlier than in patients with non-pneumococcal endocarditis (mean time from symptom onset, 14.1 ± 18.2 versus 69.0 ± 61.1 days). In-hospital mortality rates were similar (7.1% versus 12.5%). Streptococcus pneumoniae causes rapidly progressive endocarditis requiring life-saving early cardiac surgery in most cases. PMID:27021424

  8. Regulation of naturally acquired mucosal immunity to Streptococcus pneumoniae in healthy Malawian adults and children.

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    Sarah J Glennie

    Full Text Available Worldwide, invasive pneumococcal disease caused by Streptococcus pneumoniae is most common in young children. In adults, disease rates decline following intermittent colonization and the acquisition of naturally acquired immunity. We characterized mucosal and systemic pneumococcal-specific T-cell responses in African children and adults who contend with intense rates of colonization, up to 100% and 60% respectively. We find most Malawian children have high pneumococcal-specific T-cell responses in tonsil tissue and peripheral blood. In addition, frequent commensalism generates CD25(hi (Tregs which modulate mucosal pneumococcal-specific T-cell responses in some children and ≥50% of adults. We propose that immune regulation may prolong pneumococcal colonization and predispose vulnerable individuals to disease.

  9. Exposure to welding fumes and lower airway infection with Streptococcus pneumoniae

    Science.gov (United States)

    Suri, Reetika; Periselneris, Jimstan; Lanone, Sophie; Zeidler-Erdely, Patti C.; Melton, Geoffrey; Palmer, Keith T.; Andujar, Pascal; Antonini, James M.; Cohignac, Vanessa; Erdely, Aaron; Jose, Ricardo J.; Mudway, Ian; Brown, Jeremy; Grigg, Jonathan

    2015-01-01

    Background Welders are at increased risk of pneumococcal pneumonia. The mechanism for this association is not known. The capacity of pneumococci to adhere to and infect lower airway cells is mediated by host-expressed platelet-activating factor receptor (PAFR). Objective We sought to assess the effect of mild steel welding fumes (MS-WF) on PAFR-dependent pneumococcal adhesion and infection to human airway cells in vitro and on pneumococcal airway infection in a mouse model. Methods The oxidative potential of MS-WF was assessed by their capacity to reduce antioxidants in vitro. Pneumococcal adhesion and infection of A549, BEAS-2B, and primary human bronchial airway cells were assessed by means of quantitative bacterial culture and expressed as colony-forming units (CFU). After intranasal instillation of MS-WF, mice were infected with Streptococcus pneumoniae, and bronchoalveolar lavage fluid (BALF) and lung CFU values were determined. PAFR protein levels were assessed by using immunofluorescence and immunohistochemistry, and PAFR mRNA expression was assessed by using quantitative PCR. PAFR was blocked by CV-3988, and oxidative stress was attenuated by N-acetylcysteine. Results: MS-WF exhibited high oxidative potential. In A549 and BEAS-2B cells MS-WF increased pneumococcal adhesion and infection and PAFR protein expression. Both CV-3988 and N-acetylcysteine reduced MS-WF–stimulated pneumococcal adhesion and infection of airway cells. MS-WF increased mouse lung PAFR mRNA expression and increased BALF and lung pneumococcal CFU values. In MS-WF–exposed mice CV-3988 reduced BALF CFU values. Conclusions Hypersusceptibility of welders to pneumococcal pneumonia is in part mediated by the capacity of welding fumes to increase PAFR-dependent pneumococcal adhesion and infection of lower airway cells. PMID:26277596

  10. Effect of influenza and pneumococcal vaccines in elderly persons in years of low influenza activity

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    Sylvan Staffan PE

    2008-04-01

    Full Text Available Abstract Background The present prospective study was conducted from 2003–2005, among all individuals 65 years and older in Uppsala County, a region with 300 000 inhabitants situated close to the Stockholm urban area. The objective of this study was to assess the preventive effect of influenza and pneumococcal vaccination in reducing hospitalisation and length of hospital stay (LOHS even during periods of low influenza activity. The specificity of the apparent vaccine associations were evaluated in relation to the influenza seasons. Results In 2003, the total study population was 41,059, of which 12,907 (31% received influenza vaccine of these, 4,447 (11% were administered the pneumococcal vaccine. In 2004, 14,799 (34% individuals received the influenza vaccine and 8,843 (21% the pneumococcal vaccine and in 2005 16,926 (39% individuals were given the influenza vaccine and 12,340 (28% the pneumococcal vaccine. Our findings indicated that 35% of the vaccinated cohort belonged to a medical risk category (mainly those persons that received the pneumococcal vaccine. Data on hospitalisation and mortality during the 3-year period were obtained from the administrative database of the Uppsala county council. During the influenza seasons, reduction of hospital admissions and significantly shorter in-hospital stay for influenza was observed in the vaccinated cohort (below 80 years of age. For individuals who also had received the pneumococcal vaccine, a significant reduction of hospital admissions and of in-hospital stay was observed for invasive pneumococcal disease and for pneumococcal pneumonia. Effectiveness was observed for cardiac failure even in persons that also had received the pneumococcal vaccine, despite that the pneumococcal vaccinated mainly belonged to a medical risk category. Reduction of death from all causes was observed during the influenza season of 2004, in the 75–84-year old age group and in all age-groups during the influenza

  11. Clustering of serotypes in a longitudinal study of Streptococcus pneumoniae carriage in three day care centres

    OpenAIRE

    Tanskanen Antti; Syrjänen Ritva; Hoti Fabian; Leino Tuija; Auranen Kari

    2008-01-01

    Abstract Background Streptococcus pneumoniae (pneumococcus) causes a wide range of clinical manifestations that together constitute a major burden of disease worldwide. The main route of pneumococcal transmission is through asymptomatic colonisation of the nasopharynx. Studies of transmission are currently of general interest because of the impact of the new conjugate-polysaccharide vaccines on nasopharyngeal colonisation (carriage). Here we report the first longitudinal study of pneumococcal...

  12. Comparative analysis of Streptococcus pneumoniae transmission in Portuguese and Finnish day-care centres

    OpenAIRE

    Pessoa, Delphine; Hoti, Fabian; Syrjänen, Ritva; Sá-Leão, Raquel; Kaijalainen, Tarja; Gomes, M. Gabriela M.; Auranen, Kari

    2013-01-01

    Background Day-care centre (DCC) attendees play a central role in maintaining the circulation of Streptococcus pneumoniae (pneumococcus) in the population. The prevalence of pneumococcal carriage is highest in DCC attendees but varies across countries and is found to be consistently lower in Finland than in Portugal. We compared key parameters underlying pneumococcal transmission in DCCs to understand which of these contributed to the observed differences in carriage prevalence. Methods Longi...

  13. Serotype Distribution, Antibiotic Resistance and Clonality of Streptococcus pneumoniae Isolated from Immunocompromised Patients in Tunisia

    OpenAIRE

    Raddaoui, Anis; Simões, Alexandra S.; Baaboura, Rekaya; Félix, Sofia; Achour, Wafa; Ben Othman, Tarek; Béjaoui, Mohamed; Sá-Leão, Raquel; Ben Hassen, Assia

    2015-01-01

    Background Pneumococcal disease, a major cause of morbidity and mortality globally, has higher incidence among young children, the elderly and the immunocompromised of all ages. In Tunisia, pneumococcal conjugate vaccines (PCVs) are not included in the national immunization program. Also, few studies have described the epidemiology of S. pneumoniae in this country and, in particular, no molecular typing studies have been performed. The aim of this study was to evaluate serotype distribution, ...

  14. Comparative analysis of Streptococcus pneumoniae transmission in Portuguese and Finnish day-care centres

    OpenAIRE

    Pessoa, Delphine; Hoti, Fabian; Syrjänen, Ritva; Sá-Leão, Raquel; Kaijalainen, Tarja; Gomes, M. Gabriela M.; Auranen, Kari

    2013-01-01

    Day-care centre (DCC) attendees play a central role in maintaining the circulation of Streptococcus pneumoniae (pneumococcus) in the population. The prevalence of pneumococcal carriage is highest in DCC attendees but varies across countries and is found to be consistently lower in Finland than in Portugal. We compared key parameters underlying pneumococcal transmission in DCCs to understand which of these contributed to the observed differences in carriage prevalence. PneumoCarr Consortium...

  15. Increased Protection against Pneumococcal Disease by Mucosal Administration of Conjugate Vaccine plus Interleukin-12

    OpenAIRE

    Lynch, Joyce M.; Briles, David E.; Metzger, Dennis W.

    2003-01-01

    Streptococcus pneumoniae is a common cause of respiratory tract infections, its main entry route being the nasal mucosa. The recent development of pneumococcal polysaccharide conjugate vaccines has led to a dramatic improvement in protection against invasive disease in infants and children, but these vaccines have been found to be only 50 to 60% protective against bacterial carriage. In this study, we investigated the efficacy of intranasal (i.n.) conjugate vaccine delivery using interleukin-...

  16. Serotype Specific Invasive Capacity and Persistent Reduction in Invasive Pneumococcal Disease

    OpenAIRE

    Yildirim, Inci; William P Hanage; Lipsitch, Marc; Shea, Kimberly M.; STEVENSON, ABBIE; Finkelstein, Jonathan; Huang, Susan S.; Grace M Lee; Kleinman, Ken; Pelton, SI

    2010-01-01

    Defining the propensity of Streptoccocus pneumoniae (SP) serotypes to invade sterile body sites following nasopharyngeal (NP) acquisition has the potential to inform about how much invasive pneumococcal disease (IPD) may occur in a typical population with a given distribution of carriage serotypes. Data from enhanced surveillance for IPD in Massachusetts children ≤7 years in 2003/04, 2006/07 and 2008/09 seasons and surveillance of SP NP carriage during the corresponding respiratory seasons in...

  17. Nasopharyngeal Pneumococcal Serotypes Before and After Mass Azithromycin Distributions for Trachoma.

    Science.gov (United States)

    Keenan, Jeremy D; Sahlu, Ida; McGee, Lesley; Cevallos, Vicky; Vidal, Jorge E; Chochua, Sopio; Hawkins, Paulina; Gebre, Teshome; Tadesse, Zerihun; Emerson, Paul M; Gaynor, Bruce D; Lietman, Thomas M; Klugman, Keith P

    2016-06-01

    Twenty-four Ethiopian communities were randomized to receive either (1) quarterly mass azithromycin distributions for trachoma for 1 year or (2) delayed treatment. Nasopharyngeal swabs collected from separate cross-sectional population-based samples of children were processed for Streptococcus pneumoniae Mass azithromycin did not significantly alter the pneumococcal serotype distribution, and hence it would not be expected to alter vaccine coverage. PMID:27199475

  18. Selective IgM deficiency in an adult presenting with Streptococcus pneumoniae septic arthritis.

    Science.gov (United States)

    Phuphuakrat, Angsana; Ngamjanyaporn, Pintip; Nantiruj, Kanokrat; Luangwedchakarn, Voravich; Malathum, Kumthorn

    2016-02-01

    Septic arthritis caused by Streptococcus pneumoniae is uncommon. Most of the patients who have invasive pneumococcal infection have underlying diseases associated with impaired immune function. We report a case of polyarticular pneumococcal septic arthritis in a previously healthy adult as the first manifestation of selective immunoglobulin (Ig)M deficiency. The patient had no evidence of autoimmune disease or malignancy. Serum IgG, IgA, and complement levels were normal. Numbers of lymphocyte subsets were in normal range except that of CD4+ cells, which was slightly low. Invasive pneumococcal disease in a healthy adult should lead to further investigation for underlying diseases including primary immunodeficiencies.

  19. Cefditoren and ceftriaxone enhance complement-mediated immunity in the presence of specific antibodies against antibiotic-resistant pneumococcal strains.

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    Elisa Ramos-Sevillano

    Full Text Available BACKGROUND: Specific antibodies mediate humoral and cellular protection against invading pathogens such as Streptococcus pneumoniae by activating complement mediated immunity, promoting phagocytosis and stimulating bacterial clearance. The emergence of pneumococcal strains with high levels of antibiotic resistance is of great concern worldwide and a serious threat for public health. METHODOLOGY/PRINCIPAL FINDINGS: Flow cytometry was used to determine whether complement-mediated immunity against three antibiotic-resistant S. pneumoniae clinical isolates is enhanced in the presence of sub-inhibitory concentrations of cefditoren and ceftriaxone. The binding of acute phase proteins such as C-reactive protein and serum amyloid P component, and of complement component C1q, to pneumococci was enhanced in the presence of serum plus either of these antibiotics. Both antibiotics therefore trigger the activation of the classical complement pathway against S. pneumoniae. C3b deposition was also increased in the presence of specific anti-pneumococcal antibodies and sub-inhibitory concentrations of cefditoren and ceftriaxone confirming that the presence of these antibiotics enhances complement-mediated immunity to S. pneumoniae. CONCLUSIONS/SIGNIFICANCE: Using cefditoren and ceftriaxone to promote the binding of acute phase proteins and C1q to pneumococci, and to increase C3b deposition, when anti-pneumococcal antibodies are present, might help reduce the impact of antibiotic resistance in S. pneumoniae infections.

  20. [Pneumococcal carriage in mothers and children of the Panare Amerindians from the State of Bolivar, Venezuela].

    Science.gov (United States)

    Bello González, T; Rivera-Olivero, I A; Pocaterra, L; Spadola, E; Araque, M; Hermans, P W M; De Waard, J H

    2010-01-01

    In North America, the indigenous groups have been identified as a population with increased risk of pneumococcal colonization and pneumococcal invasive disease. However, little information is available from South American natives. In the present study we evaluated the nasopharyngeal carriage and serotype distribution of Streptococcus pneumoniae in mothers and children of the Panare people from Venezuela. In May 2008, in 8 distinct geographically isolated communities, 148 nasopharyngeal samples were obtained from 64 healthy mothers and 84 healthy Panare children under 5 years of age. S. pneumoniae was isolated and identified by standard techniques. Strains were typified by multiplex PCR and resistance patterns were determined by the disk diffusion method. A total of 65 strains were isolated; 11% of the mothers and 69% of the children carried S. pneumoniae. Serotypes 6B (48%), 33F (21,5%), 6A (6%), 19A (3,1%) and 23F (1,5%) were the most predominant. Of the 6 colonized mother-child pairs, 3 pairs (2 with 6B), were colonized with the same serotype. All strains were sensitive to penicillin and 13,7% were resistant to macrolides. The high colonization rates in the Panare people suggest that the children are at increased risk of pneumococcal invasive disease and could benefit from vaccination. Four conjugate vaccine serotypes (6B, 6A, 19A and 23F) representing 58 % of all strains were present in the population at the moment of sampling. Resistance to antibiotics is (still) not a problem. PMID:20461291

  1. Pneumolysin plays a key role at the initial step of establishing pneumococcal nasal colonization.

    Science.gov (United States)

    Hotomi, Muneki; Yuasa, Jun; Briles, David E; Yamanaka, Noboru

    2016-09-01

    Nasopharyngeal colonization by Streptococcus pneumoniae is an important initial step for the subsequent development of pneumococcal infections. Pneumococci have many virulence factors that play a role in colonization. Pneumolysin (PLY), a pivotal pneumococcal virulence factor for invasive disease, causes severe tissue damage and inflammation with disruption of epithelial tight junctions. In this study, we evaluated the role of PLY in nasal colonization of S. pneumoniae using a mouse colonization model. A reduction of numbers of PLY-deficient pneumococci recovered from nasal tissue, as well as nasal wash, was observed at days 1 and 2 post-intranasal challenges, but not later. The findings strongly support an important role for PLY in the initial establishment nasal colonization. PLY-dependent invasion of local nasal mucosa may be required to establish nasal colonization with S. pneumoniae. The data help provide a rationale to explain why an organism that exists as an asymptomatic colonizer has evolved virulence factors that enable it to occasionally invade and kill its hosts. Thus, the same pneumococcal virulence factor, PLY that can contribute to killing the host, may also play a role early in the establishment of nasopharynx carriage. PMID:26803756

  2. Clinical Features and Outcomes of Serotype 19A Invasive Pneumococcal Disease in Calgary, Alberta

    OpenAIRE

    Ricketson, Leah J; Otto G Vanderkooi; Wood, Melissa L; Jenine Leal; Kellner, James D

    2014-01-01

    BACKGROUND: Streptoccocus pneumoniae serotype 19A (ST19A) became an important cause of invasive pneumococcal disease (IPD) after the introduction of the conjugate vaccine.OBJECTIVE: To examine the severity and outcome of ST19A IPD compared with non-ST19A IPD.METHODS: The Calgary Area Streptococcus pneumoniae Epidemiology Research (CASPER) study collects clinical and laboratory data on all IPD cases in Calgary, Alberta. Analysis was performed on data from 2000 to 2010 comparing ST19A and non-S...

  3. Combination of pneumococcal surface protein A (PspA with whole cell pertussis vaccine increases protection against pneumococcal challenge in mice.

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    Maria Leonor S Oliveira

    Full Text Available Streptococcus pneumoniae is the leading cause of respiratory acute infections around the world. In Latin America, approximately 20,000 children under 5 years of age die of pneumococcal diseases annually. Pneumococcal surface protein A (PspA is among the best-characterized pneumococcal antigens that confer protection in animal models of pneumococcal infections and, as such, is a good alternative for the currently available conjugated vaccines. Efficient immune responses directed to PspA in animal models have already been described. Nevertheless, few low cost adjuvants for a subunit pneumococcal vaccine have been proposed to date. Here, we have tested the adjuvant properties of the whole cell Bordetella pertussis vaccine (wP that is currently part of the DTP (diphtheria-tetanus-pertussis vaccine administrated to children in several countries, as an adjuvant to PspA. Nasal immunization of BALB/c mice with a combination of PspA5 and wP or wP(low--a new generation vaccine that contains low levels of B. pertussis LPS--conferred protection against a respiratory lethal challenge with S. pneumoniae. Both PspA5-wP and PspA5-wP(low vaccines induced high levels of systemic and mucosal antibodies against PspA5, with similar profile, indicating no essential requirement for B. pertussis LPS in the adjuvant properties of wP. Accordingly, nasal immunization of C3H/HeJ mice with PspA5-wP conferred protection against the pneumococcal challenge, thus ruling out a role for TLR4 responses in the adjuvant activity and the protection mechanisms triggered by the vaccines. The high levels of anti-PspA5 antibodies correlated with increased cross-reactivity against PspAs from different clades and also reflected in cross-protection. In addition, passive immunization experiments indicated that antibodies played an important role in protection in this model. Finally, subcutaneous immunization with a combination of PspA5 with DTP(low protected mice against challenge with two

  4. Recombinant expression of Streptococcus pneumoniae capsular polysaccharides in Escherichia coli

    Science.gov (United States)

    Kay, Emily J.; Yates, Laura E.; Terra, Vanessa S.; Cuccui, Jon; Wren, Brendan W.

    2016-01-01

    Currently, Streptococcus pneumoniae is responsible for over 14 million cases of pneumonia worldwide annually, and over 1 million deaths, the majority of them children. The major determinant for pathogenesis is a polysaccharide capsule that is variable and is used to distinguish strains based on their serotype. The capsule forms the basis of the pneumococcal polysaccharide vaccine (PPV23) that contains purified capsular polysaccharide from 23 serotypes, and the pneumococcal conjugate vaccine (PCV13), containing 13 common serotypes conjugated to CRM197 (mutant diphtheria toxin). Purified capsule from S. pneumoniae is required for pneumococcal conjugate vaccine production, and costs can be prohibitively high, limiting accessibility of the vaccine in low-income countries. In this study, we demonstrate the recombinant expression of the capsule-encoding locus from four different serotypes of S. pneumoniae within Escherichia coli. Furthermore, we attempt to identify the minimum set of genes necessary to reliably and efficiently express these capsules heterologously. These E. coli strains could be used to produce a supply of S. pneumoniae serotype-specific capsules without the need to culture pathogenic bacteria. Additionally, these strains could be applied to synthetic glycobiological applications: recombinant vaccine production using E. coli outer membrane vesicles or coupling to proteins using protein glycan coupling technology. PMID:27110302

  5. Intranasal immunization with chitosan-DNA nanoparticles expressing pneumococcal polyamine transport protein D(PotD) protects mice against Streptococcus pneumoniae nasopharyngeal colonization%黏膜免疫壳聚糖-多胺转运蛋白D(PotD)DNA纳米微粒对小鼠鼻咽部肺炎链球菌定植的保护作用研究

    Institute of Scientific and Technical Information of China (English)

    徐江红; 戴文佳; 王正敏; 陈兵; 范小勇

    2010-01-01

    Objective To prepare the chitosan-potD nanoparticles and to evaluate its protective efficacy against pneumococcal nasopharyngeal colonization. Methods potD gene was amplificated from pneumococcal genome and was inserted into pVAX1 expression vectors to construct pVAX1-potD recombinant plasmid which was then transfected into 293T cell using LipofectAMINE 2000 to analyze transient potD gene expression in vitro by RT-PCR and Western blot. Chitosan-potD nanoparticles were freshly prepared by coacervation methods at each time and the characterizations of the nanoparticles were then evaluated. BALB/c mice were immunized with chitosan-potD, naked potD DNA or pVAX1 for 4 times at two-week intervals. Anti-PotD IgG, IgG1 and IgG2a levels in serum and IgA levels in nasal washes, bronchoalveolar lavage fluids (BALF) and middle ear lavages(MEL) were detected by indirect enzyme-linked immunosorbent assay (ELISA). IL-17A, IL-4 and IFN-γ levels in splenocytes were determined by double sandwich ELISA. Mice were intrannsally challenged with Streptococcus pneumoniae ATCC6303, and Pneumococci were recovered from the nasopharyngeal niche at the fifth day after challenge. Results potD gene was successfully amplificated by PCR and the sequence was confimed to be consistent with that in the Genbank. The pVAX1-potD recombinant plasmid was successfully constructed and was expressed in eukaryocytes in vitro. The mean size and zeta potential of chitosan-potD nanoparticles was 430 nm and + 20.5 mv, respectively. Chitosan-potD nanoparticles were not digested by DNase Ⅰ , while naked potD DNA was completely digested. The levels of antibodies inculding IgG, IgG1, IgG2a, IgA and cytokines including IL-17A, IL-4 and IFN-γ were significantly higher in mice immunized with chitosan-potD nanoparticles than mice with naked potD or pVAX1 ( P <0.05) only. More importantly, much less Pneumococci were recovered from mice immunized with chitosan-potD nanoparticles than the other groups(P <0

  6. A Case of Necrotizing Fasciitis due to Streptococcus pneumoniae Serotype 5 in Saskatchewan

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    Meenakshi Dawar

    2008-01-01

    Full Text Available Necrotizing fasciitis due to Streptococcus pneumoniae is a rare and grave condition, and only a few cases have been reported. Suggested risk factors include minor trauma, systemic lupus erythematosus, immunosuppression secondary to medication, use of intramuscular anti-inflammatories and alcoholism. A fatal case of pneumococcal necrotizing fasciitis that occurred in a 51-year-old woman with a history of alcohol abuse and oral anti-inflammatory use is presented. Her condition was caused by a multi-etiology outbreak of community-acquired pneumonia, from which S pneumoniae serotype 5 was also isolated. The case description outlines the subtle presentation and rapid clinical progression of this condition. Because serotype 5 antigen is included in the polysaccharide 23-valent pneumococcal vaccine, the present case highlights the importance of pneumococcal immunization programs in Canada.

  7. Use of Pneumococcal Disease Epidemiology to Set Policy and Prevent Disease during 20 Years of the Emerging Infections Program

    Science.gov (United States)

    Whitney, Cynthia G.

    2015-01-01

    Two decades ago, the Emerging Infections Program of the US Centers for Disease Control and Prevention implemented what seemed like a simple yet novel idea: a population- and laboratory-based surveillance system designed to identify and characterize invasive bacterial infections, including those caused by Streptococcus pneumoniae. This system, known as Active Bacterial Core surveillance, has since served as a flexible platform for following trends in invasive pneumococcal disease and studying vaccination as the most effective method for prevention. We report the contributions of Active Bacterial Core surveillance to every pneumococcal vaccine policy decision in the United States during the past 20 years. PMID:26291238

  8. The Use of Microarray Technology for the Analysis of Streptococcus Pneumoniae

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    Timothy J. Mitchell

    2006-04-01

    Full Text Available Streptococcus pneumoniae is an important human pathogen associated with pneumonia, septicaemia, meningitis and otitis media. It is estimated to result in over 3 million child deaths worldwide every year and an even greater number of deaths among the elderly. Prior to the complete sequencing of the genomes of S. pneumoniae TIGR4 (serotype 4 and S. pneumoniae R6 (serotype 2, we designed a custom miniarray consisting of 497 pneumococcal genes. The overall objectives of our microarray investigations were, first, to assess the genetic diversity between different S. pneumoniae serotypes, clinical isolates and also different Streptococcus species; second, we aimed to use microarray technology to examine the mechanisms by which environmental factors influence pneumococcal gene expression, and ultimately to further the understanding of how these changes in gene expression are achieved and how they may alter the virulence of the organism.

  9. Pneumonia (image)

    Science.gov (United States)

    Pneumonia is an inflammation of the lungs caused by an infection. Many different organisms can cause it, including bacteria, viruses, and fungi. Pneumonia is a common illness that affects millions of ...

  10. Mycoplasma pneumonia

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000082.htm Mycoplasma pneumonia To use the sharing features on this page, please enable JavaScript. Mycoplasma pneumonia is an infection of the lungs by ...

  11. Nasopharyngeal carriage rate of Streptococcus pneumoniae in Ugandan children with sickle cell disease

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    Kateete David P

    2012-01-01

    Full Text Available Abstract Background Nasopharyngeal carriage of Streptococcus pneumoniae is a determinant for invasive pneumococcal disease, which often complicates homozygous sickle cell disease. Here, we determined the nasopharyngeal carriage rate of S. pneumoniae in Ugandan children with homozygous sickle cell disease, who attended the outpatient Sickle Cell Clinic at Mulago National Referral hospital in Kampala, Uganda. Results S. pneumoniae occurred in 27 of the 81 children with homozygous sickle cell disease (giving a carriage rate of 33%, 27/81. Twenty three children were previously hospitalized of whom S. pneumoniae occurred in only two (9%, 2/23, while among the 58 who were not previously hospitalized it occurred in 25 (43%, 25/58, χ2 = 8.8, p = 0.003, meaning there is an association between high carriage rate and no hospitalization. Two children previously immunized with the pneumococcal conjugate vaccine did not carry the organism. Prior antimicrobial usage was reported in 53 children (65%, 53/81. There was high resistance of pneumococci to penicillin (100%, 27/27 and trimethoprime-sulfamethoxazole (97%, 26/27, but low resistance to other antimicrobials. Of the 70 children without sickle cell disease, S. pneumoniae occurred in 38 (54%, 38/70 of whom 43 were males and 27 females (53% males, 23/43, and 56% females, 15/27. Conclusion Nasopharyngeal carriage of penicillin resistant pneumococci in Ugandan children with homozygous sickle cell disease is high. While nasopharyngeal carriage of S. pneumoniae is a determinant for invasive pneumococcal disease, pneumococcal bacteremia is reportedly low in Ugandan children with sickle cell disease. Studies on the contribution of high carriage rates to invasive pneumococcal disease in these children will be helpful. This is the first report on pneumococcal carriage rate in Ugandan children with sickle cell disease.

  12. Functional polymorphisms of macrophage migration inhibitory factor as predictors of morbidity and mortality of pneumococcal meningitis

    Science.gov (United States)

    Savva, Athina; Brouwer, Matthijs C.; Valls Serón, Mercedes; Le Roy, Didier; Ferwerda, Bart; van der Ende, Arie; Bochud, Pierre-Yves; van de Beek, Diederik; Calandra, Thierry

    2016-01-01

    Pneumococcal meningitis is the most frequent and critical type of bacterial meningitis. Because cytokines play an important role in the pathogenesis of bacterial meningitis, we examined whether functional polymorphisms of the proinflammatory cytokine macrophage migration inhibitory factor (MIF) were associated with morbidity and mortality of pneumococcal meningitis. Two functional MIF promoter polymorphisms, a microsatellite (−794 CATT5–8; rs5844572) and a single-nucleotide polymorphism (−173 G/C; rs755622) were genotyped in a prospective, nationwide cohort of 405 patients with pneumococcal meningitis and in 329 controls matched for age, gender, and ethnicity. Carriages of the CATT7 and −173 C high-expression MIF alleles were associated with unfavorable outcome (P = 0.005 and 0.003) and death (P = 0.03 and 0.01). In a multivariate logistic regression model, shock [odds ratio (OR) 26.0, P = 0.02] and carriage of the CATT7 allele (OR 5.12, P = 0.04) were the main predictors of mortality. MIF levels in the cerebrospinal fluid were associated with systemic complications and death (P = 0.0002). Streptococcus pneumoniae strongly up-regulated MIF production in whole blood and transcription activity of high-expression MIF promoter Luciferase reporter constructs in THP-1 monocytes. Consistent with these findings, treatment with anti-MIF immunoglogulin G (IgG) antibodies reduced bacterial loads and improved survival in a mouse model of pneumococcal pneumonia and sepsis. The present study provides strong evidence that carriage of high-expression MIF alleles is a genetic marker of morbidity and mortality of pneumococcal meningitis and also suggests a potential role for MIF as a target of immune-modulating adjunctive therapy. PMID:26976591

  13. Pneumococcal Carriage and Antibiotic Resistance in Young Children before 13-Valent Conjugate Vaccine

    Science.gov (United States)

    WROE, PETER C.; LEE, GRACE M.; FINKELSTEIN, JONATHAN A.; PELTON, STEPHEN I.; HANAGE, WILLIAM P.; LIPSITCH, MARC; STEVENSON, ABBIE E.; RIFAS-SHIMAN, SHERYL L.; KLEINMAN, KEN; DUTTA-LINN, M. MAYA; HINRICHSEN, VIRGINIA L.; LAKOMA, MATTHEW; HUANG, SUSAN S.

    2012-01-01

    Background We sought to measure trends in Streptococcus pneumoniae (SP) carriage and antibiotic resistance in young children in Massachusetts communities after widespread adoption of heptavalent pneumococcal conjugate vaccine (PCV7) and before the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13). Methods We conducted a cross-sectional study including collection of questionnaire data and nasopharyngeal specimens among children <7 years in primary care practices from 8 Massachusetts communities during the winter season of 2008–9 and compared with to similar studies performed in 2001, 2003–4, and 2006–7. Antimicrobial susceptibility testing and serotyping were performed on pneumococcal isolates, and risk factors for colonization in recent seasons (2006–07 and 2008–09) were evaluated. Results We collected nasopharyngeal specimens from 1,011 children, 290 (29%) of whom were colonized with pneumococcus. Non-PCV7 serotypes accounted for 98% of pneumococcal isolates, most commonly 19A (14%), 6C (11%), and 15B/C (11%). In 2008–09, newly-targeted PCV13 serotypes accounted for 20% of carriage isolates and 41% of penicillin non-susceptible S. pneumoniae (PNSP). In multivariate models, younger age, child care, young siblings, and upper respiratory illness remained predictors of pneumococcal carriage, despite near-complete serotype replacement. Only young age and child care were significantly associated with PNSP carriage. Conclusions Serotype replacement post-PCV7 is essentially complete and has been sustained in young children, with the relatively virulent 19A being the most common serotype. Predictors of carriage remained similar despite serotype replacement. PCV13 may reduce 19A and decrease antibiotic-resistant strains, but monitoring for new serotype replacement is warranted. PMID:22173142

  14. Risk factors for pneumococcal nasopharyngeal colonization before and after pneumococcal conjugate vaccination in persons with HIV

    DEFF Research Database (Denmark)

    Öbrink-Hansen, Kristina; Søgaard, Ole S; Harboe, Zitta B;

    HIV-infected individuals have excess rates of invasive pneumococcal disease. We investigated risk factors for nasopharyngeal pneumococcal colonization at baseline and after 9 months in 96 HIV patients immunized twice with 7- valent pneumococcal conjugate vaccine ±1mg CPG 7909. In total, 22 patien...

  15. Variant mannose-binding lectin alleles are not associated with susceptibility to or outcome of invasive pneumococcal infection in randomly included patients

    DEFF Research Database (Denmark)

    Kronborg, Gitte; Madsen, Hans O; Pedersen, Svend S;

    2002-01-01

    Invasive pneumococcal disease is a serious infection that primarily affects very young children and elderly or immunocompromised individuals but also affects previously healthy people. Variant mannose-binding lectin (MBL) alleles are associated with recurrent infections and may be a risk factor for...... pneumococcal infections. To assess the influence of MBL genotypes on the course and outcome of invasive pneumococcal disease, clinical data for 141 adult patients were collected prospectively and their genotypes were determined. All patients included had positive blood cultures for Streptococcus pneumoniae....... The distribution of variant MBL alleles related to low MBL serum concentrations was similar among the patients and healthy individuals, and MBL genotype was not associated with infection outcome. Thus, in a random adult population with invasive pneumococcal infection, MBL does not seem to play a role...

  16. Novel Strategy To Protect against Influenza Virus-Induced Pneumococcal Disease without Interfering with Commensal Colonization.

    Science.gov (United States)

    Greene, Christopher J; Marks, Laura R; Hu, John C; Reddinger, Ryan; Mandell, Lorrie; Roche-Hakansson, Hazeline; King-Lyons, Natalie D; Connell, Terry D; Hakansson, Anders P

    2016-06-01

    Streptococcus pneumoniae commonly inhabits the nasopharynx as a member of the commensal biofilm. Infection with respiratory viruses, such as influenza A virus, induces commensal S. pneumoniae to disseminate beyond the nasopharynx and to elicit severe infections of the middle ears, lungs, and blood that are associated with high rates of morbidity and mortality. Current preventive strategies, including the polysaccharide conjugate vaccines, aim to eliminate asymptomatic carriage with vaccine-type pneumococci. However, this has resulted in serotype replacement with, so far, less fit pneumococcal strains, which has changed the nasopharyngeal flora, opening the niche for entry of other virulent pathogens (e.g., Streptococcus pyogenes, Staphylococcus aureus, and potentially Haemophilus influenzae). The long-term effects of these changes are unknown. Here, we present an attractive, alternative preventive approach where we subvert virus-induced pneumococcal disease without interfering with commensal colonization, thus specifically targeting disease-causing organisms. In that regard, pneumococcal surface protein A (PspA), a major surface protein of pneumococci, is a promising vaccine target. Intradermal (i.d.) immunization of mice with recombinant PspA in combination with LT-IIb(T13I), a novel i.d. adjuvant of the type II heat-labile enterotoxin family, elicited strong systemic PspA-specific IgG responses without inducing mucosal anti-PspA IgA responses. This response protected mice from otitis media, pneumonia, and septicemia and averted the cytokine storm associated with septic infection but had no effect on asymptomatic colonization. Our results firmly demonstrated that this immunization strategy against virally induced pneumococcal disease can be conferred without disturbing the desirable preexisting commensal colonization of the nasopharynx. PMID:27001538

  17. Pneumococcal disease in HIV-infected Malawian adults: acute mortality and long-term survival

    Science.gov (United States)

    Gordon, Stephen B.; Chaponda, Mas; Walsh, Amanda L.; Whitty, Christopher J.M.; Gordon, Melita A.; Machili, C. Edward; Gilks, Charles F.; Boeree, Martin J.; Kampondeni, Sam; Read, Robert C.; Molyneux, Malcolm E.

    2016-01-01

    Objective HIV-infected patients in Africa are vulnerable to severe recurrent infection with Streptococcus pneumoniae, but no effective preventive strategy has been developed. We set out to determine which factors influence in-hospital mortality and long-term survival of Malawians with invasive pneumococcal disease. Design, setting and patients Acute clinical features, inpatient mortality and long-term survival were described among consecutively admitted hospital patients with S. pneumoniae in the blood or cerebrospinal fluid. Factors associated with inpatient mortality were determined, and patients surviving to discharge were followed to determine their long-term outcome. Results A total of 217 patients with pneumococcal disease were studied over an 18-month period. Among these, 158 out of 167 consenting to testing (95%) were HIV positive. Inpatient mortality was 65% for pneumococcal meningitis (n = 64), 20% for pneumococcaemic pneumonia (n = 92), 26% for patients with pneumococcaemia without localizing signs (n = 43), and 76% in patients with probable meningitis (n = 17). Lowered consciousness level, hypotension, and age exceeding 55 years at presentation were associated with inpatient death, but not long-term outcome in survivors. Hospital survivors were followed for a median of 414 days; 39% died in the community during the study period. Outpatient death was associated with multilobar chest signs, oral candidiasis, and severe anaemia as an inpatient. Conclusion Most patients with pneumococcal disease in Malawi have HIV co-infection. They have severe disease with a high mortality rate. At discharge, all HIV-infected adults have a poor prognosis but patients with multilobar chest signs or anaemia are at particular risk. PMID:12131218

  18. Streptococcus pneumoniae as an agent of nosocomial infection: treatment in the era of penicillin-resistant strains

    OpenAIRE

    F. Paradisi; Corti, G.; R. Cinelli

    2001-01-01

    Abstract. Streptococcus pneumoniae is a well-known agent of community-acquired infections such as sinusitis, otitis media, pneumonia, bacterial meningitis, bacteremia, and acute exacerbations of chronic bronchitis. However, the role of S.pneumoniae as a cause of nosocomial infections of respiratory tract, bloodstream, and central nervous system is more and more recognised, primarily in high-risk patients with depression of their immune function. Therapy of pneumococcal infections is made diff...

  19. Economic evaluation of pneumococcal conjugate vaccination in The Gambia

    Directory of Open Access Journals (Sweden)

    Kim Sun-Young

    2010-09-01

    Full Text Available Abstract Background Gambia is the second GAVI support-eligible country to introduce the 7-valent pneumococcal conjugate vaccine (PCV7, but a country-specific cost-effectiveness analysis of the vaccine is not available. Our objective was to assess the potential impact of PCVs of different valences in The Gambia. Methods We synthesized the best available epidemiological and cost data using a state-transition model to simulate the natural histories of various pneumococcal diseases. For the base-case, we estimated incremental cost (in 2005 US dollars per disability-adjusted life year (DALY averted under routine vaccination using PCV9 compared to no vaccination. We extended the base-case results for PCV9 to estimate the cost-effectiveness of PCV7, PCV10, and PCV13, each compared to no vaccination. To explore parameter uncertainty, we performed both deterministic and probabilistic sensitivity analyses. We also explored the impact of vaccine efficacy waning, herd immunity, and serotype replacement, as a part of the uncertainty analyses, by assuming alternative scenarios and extrapolating empirical results from different settings. Results Assuming 90% coverage, a program using a 9-valent PCV (PCV9 would prevent approximately 630 hospitalizations, 40 deaths, and 1000 DALYs, over the first 5 years of life of a birth cohort. Under base-case assumptions ($3.5 per vaccine, compared to no intervention, a PCV9 vaccination program would cost $670 per DALY averted in The Gambia. The corresponding values for PCV7, PCV10, and PCV13 were $910, $670, and $570 per DALY averted, respectively. Sensitivity analyses that explored the implications of the uncertain key parameters showed that model outcomes were most sensitive to vaccine price per dose, discount rate, case-fatality rate of primary endpoint pneumonia, and vaccine efficacy against primary endpoint pneumonia. Conclusions Based on the information available now, infant PCV vaccination would be expected to reduce

  20. Advances in pneumococcal vaccines: what are the advantages for the elderly?

    Science.gov (United States)

    Vila-Córcoles, Angel

    2007-01-01

    Streptococcus pneumoniae causes considerable morbidity and mortality in the elderly. There are three established approaches to pneumococcal vaccination: polysaccharide vaccines, protein-polysaccharide conjugate vaccines and protein-based vaccines. This article reviews advances in anti-pneumococcal vaccines, with reference to advantages and shortcomings for the elderly in particular. The 23-valent polysaccharide pneumococcal vaccine (PPV) is currently recommended for high-risk patients and the general elderly population. Although the effectiveness of PPV against pneumonia is unclear, recent studies point to significant protective effects in preventing pneumococcal pneumonia and reducing the severity of disease in vaccinated elderly patients. PPV offers high serotype coverage and, although it is poorly immunogenic in some individuals, provides approximately 60% protection against invasive disease in the general elderly population. PPV vaccination appears cost effective for elderly patients although the vaccine might only be effective in preventing invasive disease. Additional benefits could mean a greater level of vaccine cost effectiveness. However, it is important to understand that PPV provides incomplete protection, especially in those with underlying high-risk conditions, and development of more effective pneumococcal vaccination strategies for elderly patients is still needed. In recent years, the most important advance in the prevention of pneumococcal infections in the elderly has been the introduction of a 7-valent conjugate pneumococcal vaccine (CPV) as a routine vaccination for infants. In addition to dramatically reducing invasive infection in children, CPV has been observed to have a considerable indirect protective effect in parents and grandparents. While the possibility of using CPV in elderly patients has been suggested, currently there are only limited immunogenicity data and no efficacy data in adults. The low serotype coverage is an important

  1. Inflammasomes in Pneumococcal Infection: Innate Immune Sensing and Bacterial Evasion Strategies.

    Science.gov (United States)

    Rabes, Anne; Suttorp, Norbert; Opitz, Bastian

    2016-01-01

    Streptococcus pneumoniae frequently colonizes the upper respiratory tract of healthy individuals, but also commonly causes severe invasive infections such as community-acquired pneumonia and meningitis. One of the key virulence factors of pneumococci is the pore-forming toxin pneumolysin which stimulates cell death and is involved in the evasion of some defense mechanisms. The immune system, however, employs different inflammasomes to sense pneumolysin-induced pore formation, cellular membrane damage, and/or subsequent leakage of bacterial nucleic acid into the host cell cytosol. Canonical inflammasomes are cytosolic multiprotein complexes consisting of a receptor molecule such as NLRP3 or AIM2, the adapter ASC, and caspase-1. NLRP3 and AIM2 inflammasomes mediate cell death and production of important IL-1 family cytokines to recruit leukocytes and defend against S. pneumoniae. Here, we review recent evidence that highlights inflammasomes as critical sensors of S. pneumoniae-induced cellular perturbations, summarize their role in pneumococcal infections, and discuss potential evasion strategies of some emerging pneumococcal strains. PMID:27460812

  2. Pneumococcal Vaccination in High-Risk Individuals: Are We Doing It Right?

    Science.gov (United States)

    Papadatou, Ioanna; Spoulou, Vana

    2016-05-01

    Controversy exists regarding the optimal use of the 23-valent pneumococcal conjugate vaccine for the protection of high-risk individuals, such as children and adults with immunocompromising conditions and the elderly. The effectiveness and immunogenicity of 23-valent pneumococcal polysaccharide vaccine (PPV23) are limited in such high-risk populations compared to the healthy, with meta-analyses failing to provide robust evidence on vaccine efficacy against invasive pneumococcal disease (IPD) or pneumonia. Moreover, several studies have demonstrated a PPV23-induced state of immune tolerance or hyporesponsiveness to subsequent vaccination, where the response to revaccination does not reach the levels achieved with primary vaccination. The clinical significance of hyporesponsiveness is not yet clarified, but attenuated humoral and cellular response could lead to reduced levels of protection and increased susceptibility to pneumococcal disease. As disease epidemiology among high-risk groups shows that we are still in need of maximum serotype coverage, the optimal use of PPV23 in the context of combined conjugate/polysaccharide vaccine schedules is an important priority. In this minireview, we discuss PPV23-induced hyporesponsiveness and its implications in designing highly effective vaccination schedules for the optimal protection for high-risk individuals. PMID:27009210

  3. Treated Follicular Lymphoma, Recurrent Invasive Pneumococcal Disease, Nonresponsiveness to Vaccination, and a Unique Pneumococcus

    Directory of Open Access Journals (Sweden)

    Clare Murphy

    2012-01-01

    Full Text Available A nonneutropenic patient with treated low-grade non-Hodgkin’s (Follicular lymphoma and secondary hypogammaglobulinemia recovered from pneumococcal pneumonia and septicemia (serotype 7F; ST191 subsequent to influenza A H1N1 (2009. Both infections were potentially vaccine preventable. The patient then developed pneumococcal meningitis due to a serotype 35F pneumococcus with a unique Multilocus Sequence Type (ST7004 which was not vaccine preventable. Patient management was influenced by host predisposition to pneumococcal infection, antibiotic intolerance, and poor response to polysaccharide pneumococcal vaccine. Indirect immunofluorescence with anti-human immunoglobulin confirmed a poor or intermediate response to Pneumovax II. Prophylactic erythromycin was initiated, and immunoglobulin transfusions were also commenced as a preventive strategy. ST7004 is a single locus variant of ST1635 which has been associated with the serotype 35F capsule in England. The spi gene in ST7004, which differentiates it from ST1635, is the same as the spi gene present in ST191 which could have arisen from the first disease episode suggesting that horizontal gene transfer may have occurred between different populations of pneumococci present within the patient in an attempt to evade vaccination selection pressure.

  4. Cost-effectiveness of new pneumococcal conjugate vaccines in Turkey: a decision analytical model

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    Bakır Mustafa

    2012-11-01

    Full Text Available Abstract Background Streptococcus pneumoniae infections, which place a considerable burden on healthcare resources, can be reduced in a cost-effective manner using a 7-valent pneumococcal conjugate vaccine (PCV-7. We compare the cost effectiveness of a 13-valent PCV (PCV-13 and a 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV with that of PCV-7 in Turkey. Methods A cost-utility analysis was conducted and a decision analytical model was used to estimate the proportion of the Turkish population Results PCV-13 and PHiD-CV are projected to have a substantial impact on pneumococcal disease in Turkey versus PCV-7, with 2,223 and 3,156 quality-adjusted life years (QALYs and 2,146 and 2,081 life years, respectively, being saved under a 3+1 schedule. Projections of direct medical costs showed that a PHiD-CV vaccination programme would provide the greatest cost savings, offering additional savings of US$11,718,813 versus PCV-7 and US$8,235,010 versus PCV-13. Probabilistic sensitivity analysis showed that PHiD-CV dominated PCV-13 in terms of QALYs gained and cost savings in 58.3% of simulations. Conclusion Under the modeled conditions, PHiD-CV would provide the most cost-effective intervention for reducing pneumococcal disease in Turkish children.

  5. [Anti-pneumococcal vaccine coverage for hospitalized risk patients: Assessment and suggestions for improvements].

    Science.gov (United States)

    Richard, C; Le Garlantezec, P; Lamand, V; Rasamijao, V; Rapp, C

    2016-05-01

    Streptococcus pneumoniae can cause invasive infections. Incidence and severity are linked to patients' risk factors. Due to the resistance to leading antibiotics, the anti-pneumococcal vaccination has become a major public health issue. The purpose of this survey was to evaluate the anti-pneumococcal vaccine coverage in a population of adults with risk factors. This was a prospective study that included patients with at least one recommendation for pneumococcal vaccination as indicated by the Weekly Epidemiological Bulletin (BEH), to which three further US recommendations were added (diabetes, obesity and age>65years). One hundred and thirty-four patients with an average age of 70 years were included. The physician could only confirm 68 % of the patients' vaccination status. Vaccination coverage as recommended by the BEH board was 30 % (n=54). All HIV patients were vaccinated (n=2) and the vaccination coverage was 75 % (n=8) for patients treated for autoimmune diseases and only 10 % (n=20) for patients treated with chemotherapy. Patients with no vaccination didn't know the existence of the vaccine or didn't know that vaccination was recommended to them. This study has highlighted a deficit in pneumococcal vaccination coverage and a high level of ignorance of the existence of recommended vaccination. In addition to awareness campaign for patients and caregiver training, the expansion of the vaccine e-book utilization could improve the vaccination status. PMID:26619926

  6. Characterization of some pneumococcal bacteriophages

    Energy Technology Data Exchange (ETDEWEB)

    Porter, R.D.; Guild, W.R.

    1976-08-01

    The growth of pneumococcal phages at high cell and phage densities is enhanced strongly by the substitution of potassium for sodium in the medium. Initial titers of 2 x 10/sup 10/ to 4 x 10/sup 10/ PFU/ml are readily obtained, and concentrated stocks are stable in a storage buffer described here. The mechanism of the cation effect is obscure. Phages ..omega..3 and ..omega..8 each have linear double-stranded DNA of 33 x 10/sup 6/ daltons per particle, with an apparent guanine plus cytosine content of 47 to 49 mol%, as determined by buoyancy and melting temperature, but with an unusual absorbance spectrum. Efficiency of plating is high if sufficient time is allowed for a relatively slow adsorption, which differs severalfold in rate between the two phages. Morphologically, these and other pneumococcal phages are similar to coliphage lambda but with a longer tail and tail fiber. Upon UV inactivation, ..omega..3 and ..omega..8 have D/sub 37/ values of 33 and 55 J/m/sup 2/, respectively, and each shows multiplicity reactivation. A total of 13 ts mutants have been isolated from the two phages, representing only two complementation groups; complementation and recombination occur between ..omega..3 and ..omega..8 mutants. Both phages provoke high-titer antisera with extensive cross-reactivity against a number of newly isolated pneumococcal phages.

  7. Immunization of immunosuppressed patients with pneumococcal polysaccharide vaccine

    Energy Technology Data Exchange (ETDEWEB)

    Ammann, A.J.; Schiffman, G.; Addiego, J.E.; Wara, W.M.; Wara, D.W.

    The antibody response after immunization with capsular polysaccharides of Streptococcus pneumoniae of patients with Hodgkin's disease or with carcinoma of the head and neck was studied. Patients with Hodgkin's disease who were immunized prior to the institution of immunosuppressive therapy were capable of responding to each of the pneumococcal polysaccharides evaluated. The level of antibody achieved by the patients is lower than that of normal control subjects. Nevertheless, absolute values were in the range that would be expected to result in protection. The duration of antibody response was not evaluated. Patients with carcinoma of the head and neck did not demonstrate a significant increase in antibody levels after vaccination, which was done at the time of radiation therapy. Two years after immunization antibody levels were lower with recovery at three years. However, these changes were not statistically significant. Decreased levels of antibody to pneumococcal polysaccharide types not present in the vaccine were observed. Studies of patients with carcinoma of the heat and neck demonstrated that radiation therapy has a profound immunosuppressive effect on antibody levels. More selective immunosuppressive therapy and/or an increase in the immunogenicity of the polysaccharides in the vaccine are required for protection of patients with malignancy.

  8. Heterogeneity of pneumococcal phase variants in invasive human infections

    Directory of Open Access Journals (Sweden)

    Ramirez M

    2006-07-01

    Full Text Available Abstract Background Streptococcus pneumoniae can be carried asymptomatically in the nasopharynx of its human host but can also cause a wide range of infections. A role for pneumococcal phase variants in the different lifestyles of this bacterium has been suggested but no systematic survey of the colony phenotypes of isolates associated with human infections has been undertaken. Results We report the colony opacity phenotypes of a genetically diverse set of 304 invasive isolates representing 10 serotypes. Over half of the isolates (52% presented the opaque phenotype whereas transparent variants accounted for only 26% of the total. However, the frequency of recovery of each phase variant was not uniform, while serotypes 1, 4, 12B and 23F presented the opaque phenotype more frequently than expected by chance, serotypes 3 and 14 where less frequently associated with this phenotype. Conclusion The opaque phenotype was the most frequent phenotype found among invasive isolates. An unexpected and equally important finding is the variability of the dominant opacity phenotype found among serotypes. This observation highlights the heterogeneity of opacity phenotypes in invasive isolates and lends further support to the proposal that other factors, in addition to the site of isolation, determine the opacity phenotype of a given isolate. The association between serotype and colonial opacity could help explain epidemiological differences observed among pneumococcal serotypes such as a higher invasive disease potential.

  9. Dynamic models of pneumococcal carriage and the impact of the Heptavalent Pneumococcal Conjugate Vaccine on invasive pneumococcal disease

    Directory of Open Access Journals (Sweden)

    Edmunds W John

    2010-04-01

    Full Text Available Abstract Background The 7-valent pneumococcal conjugate vaccine has been introduced in national immunisation programmes of most industrialised countries and recently in two African GAVI eligible countries (Rwanda and The Gambia. However the long term effects of PCV are still unclear, as beneficial direct and herd immunity effects might be countered by serotype replacement. Method A dynamic, age-structured, compartmental model of Streptococcus pneumoniae transmission was developed to predict the potential impact of PCV7 on the incidence of invasive disease accounting for both herd immunity and serotype replacement effects. The model was parameterised using epidemiological data from England and Wales and pre and post-vaccination surveillance data from the US. Results Model projections showed that serotype replacement plays a crucial role in determining the overall effect of a PCV7 vaccination programme and could reduce, negate or outweigh its beneficial impact. However, using the estimate of the competition parameter derived from the US post-vaccination experience, an infant vaccination programme would prevent 39,000 IPD cases in the 20 years after PCV7 introduction in the UK. Adding a catch-up campaign for under 2 or under 5 year olds would provide a further reduction of 1,200 or 3,300 IPD cases respectively, mostly in the first few years of the programme. Conclusions This analysis suggests that a PCV vaccination programme would eradicate vaccine serotypes from circulation. However, the increase in carriage of non-vaccine serotypes, and the consequent increase in invasive disease, could reduce, negate or outweigh the benefit. These results are sensitive to changes in the protective effect of the vaccine, and, most importantly, to the level of competition between vaccine and non-vaccine types. The techniques developed here can be used to assess the introduction of vaccination programmes in developing countries and provide the basis for cost

  10. Impact of pneumococcal conjugate vaccine in children morbidity and mortality in Peru: Time series analyses.

    Science.gov (United States)

    Suarez, Victor; Michel, Fabiana; Toscano, Cristiana M; Bierrenbach, Ana Luiza; Gonzales, Marco; Alencar, Airlane Pereira; Ruiz Matus, Cuauhtemoc; Andrus, Jon K; de Oliveira, Lucia H

    2016-09-01

    Streptococcus pneumoniae is the leading cause of bacterial pneumonia, meningitis and sepsis in children worldwide. Despite available evidence on pneumococcal conjugate vaccine (PCV) impact on pneumonia hospitalizations in children, studies demonstrating PCV impact in morbidity and mortality in middle-income countries are still scarce. Given the disease burden, PCV7 was introduced in Peru in 2009, and then switched to PCV10 in late 2011. National public healthcare system provides care for 60% of the population, and national hospitalization, outpatient and mortality data are available. We thus aimed to assess the effects of routine PCV vaccination on pneumonia hospitalization and mortality, and acute otitis media (AOM) and all cause pneumonia outpatient visits in children under one year of age in Peru. We conducted a segmented time-series analysis using outcome-specific regression models. Study period was from January 2006 to December 2012. Data sources included the National information systems for hospitalization, mortality, outpatient visits, and RENACE, the national database of aggregated weekly notifications of pneumonia and other acute respiratory diseases (both hospitalized and non-hospitalized). Study outcomes included community acquired pneumonia outpatient visits, hospitalizations and deaths (ICD10 codes J12-J18); and AOM outpatient visits (H65-H67). Monthly age- and sex-specific admission, outpatient visit, and mortality rates per 100,000 children aged Peru. PMID:27521230

  11. Hyposplenism as a cause of pneumococcal meningoencephalitis in an adult patient with coeliac disease

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    Paolo Caraceni

    2013-03-01

    Full Text Available Introduction: Coeliac disease can be associated with hyposplenism and splenic atrophy, which may increase the patient’s risk for fatal infections caused by Streptococcus pneumoniae or Pneumococcus. It is general opinion that many more patients with coeliac disease have died from hyposplenism-related infections than those reported in literature. Case report: A 62-year-old woman with recently diagnosed coeliac disease was hospitalized with high fever, disorientation, and nuchal rigidity. Cerebral computed tomography was negative. Laboratory tests showed an elevated leukocyte count and very high levels of C reactive protein. The cerebrospinal fluid (CSF contained an increased number of mononuclear cells associated with a low glucose level and high protein concentrations. The CSF culture was positive for Streptococcus pneumoniae. Neurological conditions rapidly deteriorated with the onset of coma, and magnetic resonance imaging of the brain revealed initial signs of encephalitis extending above and below the tentorium. Abdominal ultrasonography disclosed splenic hypotrophy that raised the suspicion of hyposplenism. The diagnosis of hyposplenism was confirmed by demonstration of Howell-Jolly bodies in a peripheral blood smear. Discussion: This is the first reported case of pneumococcal meningoencephalitis caused by splenic hypofunction in a patient with coeliac disease. When coeliac disease is diagnosed with a marked delay in an elderly patient, spleen function should always be assessed. If impaired, the patient should undergo vaccination with pneumococcal conjugate vaccine to prevent pneumococcal infections.

  12. Poor Long-Term Efficacy of Prevnar-13 in Sickle Cell Disease Mice Is Associated with an Inability to Sustain Pneumococcal-Specific Antibody Titers.

    Directory of Open Access Journals (Sweden)

    Steven M Szczepanek

    Full Text Available One of the most common causes of morbidity and mortality in children with sickle cell disease (SCD is infection with the pneumococcal bacterium (Streptococcus pneumoniae. Unfortunately, the polysaccharide-conjugate vaccine appears to be less effective in individuals with SCD when compared to the general population. We sought to better understand the relative efficacy of pneumococcal vaccination in a SCD mouse challenge model.Transgenic control and SCD mice were monitored for mortality after intranasal pneumococcal infection or pneumococcal vaccination with Prevnar-13 and type-matched challenge. Anti-pneumococcal antibody titers were measured by ELISA and opsonophagocytosis was measured in vitro.Mortality after pneumococcal infection was similar between control and SCD mice. However, after three intramuscular polysaccharide-conjugate vaccinations, all control mice were protected following high-dose intranasal infection, whereas 60% of SCD mice died. Anti-pneumococcal antibody titers showed initial IgG and IgM responses in both groups, but waning titers were observed in the SCD group, even after boosting. When functionally assayed in vitro, serum from SCD mice 13 weeks after a second booster shot maintained little to no ability to opsonize pneumococci, while serum from control mice sustained a significantly higher capacity opsonization. Thus, it appears that SCD mice do not maintain antibody responses to pneumococcal polysaccharides after Prevnar-13 vaccination, thereby leaving them susceptible to mortality after type-matched infection.Our results emphasize the need to better understand the correlates of immune protection in SCD so that pneumococcal vaccines can be improved and mortality reduced in this susceptible population.

  13. [Pneumococcal vaccines: different types and their use in practice].

    Science.gov (United States)

    Van Steenkiste, M

    2013-03-01

    Streptococcus pneumoniae is responsible for a large number of invasive infections and upper respiratory tract infections in infants, elderly and patients with high complication risk. Currently, two types of vaccine are available on the Belgian market. In the context of pharmaceutical care, it is important for pharmacists to know their specific characteristics and differences. In this article we try to explain these and to motivate their use in different patient populations. The 23-valent vaccine is different from the 13-valent vaccine, not only in number of serotypes, but also in its presentation as respectively polysaccharide- and conjugated vaccine which affects the immunogenicity. Moreover, their indication and use are also different. Finally we take a closer look at the specific use in infants and children at risk at one hand, and vaccination of eldery and adults with increased risk for severe pneumococcal infection on the other hand. PMID:23638606

  14. Viral pneumonia

    Science.gov (United States)

    ... off infection. Vaccines may help prevent pneumonia in children, the elderly, and people with diabetes, asthma, emphysema , HIV, cancer, or other chronic conditions. A drug called palivizumab ( ...

  15. Development of a multiplexed bead-based immunoassay for the simultaneous detection of antibodies to 17 pneumococcal proteins.

    Science.gov (United States)

    Shoma, S; Verkaik, N J; de Vogel, C P; Hermans, P W M; van Selm, S; Mitchell, T J; van Roosmalen, M; Hossain, S; Rahman, M; Endtz, H Ph; van Wamel, W J B; van Belkum, A

    2011-04-01

    Presently, several pneumococcal proteins are being evaluated as potential vaccine candidates. Here, we gather novel insights in the immunogenicity of PLY, PsaA, PspA, PspC, NanA, Hyl, PpmA, SlrA, Eno, IgA1-protease, PdBD, BVH-3, SP1003, SP1633, SP1651, SP0189 and SP0376. We developed a multiplex bead-based immunoassay (xMAP(®) Technology, Luminex Corporation) to simultaneously quantify antibodies against these 17 pneumococcal proteins in serum. The median fluorescence intensity (MFI) values obtained for human pooled serum with the multiplex assay were between 82% and 111% (median 94%) of those obtained with the singleplex assays. For IgG, the coefficient of variation (CV) in serum ranged from 2% to 9%, for IgA, the CV ranged from 3% to 14% and for IgM, the CV ranged from 11% to 15%. Using this immunoassay, we showed that anti-pneumococcal antibody levels exhibited extensive inter-individual variability in young children suffering from invasive pneumococcal disease. All proteins, including the proteins with, as yet, unknown function, were immunogenic. In conclusion, the multiplex Streptococcus pneumoniae immunoassay based on proteins is reproducible. This assay can be used to monitor anti-S. pneumoniae antibody responses in a material- and time-saving manner. PMID:21086008

  16. Stimulation of acetylcholine receptors impairs host defence during pneumococcal pneumonia

    NARCIS (Netherlands)

    I.A.J. Giebelen; M. Leendertse; S. Florquin; T. van der Poll

    2009-01-01

    The cholinergic nervous system can inhibit the systemic inflammation accompanying sepsis by virtue of a specific action of acetylcholine on alpha7 cholinergic receptors. The current authors sought to determine the effect of nicotine, an alpha7 cholinergic receptor agonist, on the host response to pn

  17. Long-term impact of pneumococcal polysaccharide vaccination on nasopharyngeal carriage in children previously vaccinated with various pneumococcal conjugate vaccine regimes.

    Science.gov (United States)

    Boelsen, Laura K; Dunne, Eileen M; Lamb, Karen E; Bright, Kathryn; Cheung, Yin Bun; Tikoduadua, Lisi; Russell, Fiona M; Mulholland, E Kim; Licciardi, Paul V; Satzke, Catherine

    2015-10-13

    Previously, the Fiji Pneumococcal Project (FiPP) evaluated reduced dose immunization schedules that incorporated pneumococcal protein conjugate and/or polysaccharide vaccine (PCV7 and 23vPPV, respectively). Immune hyporesponsiveness was observed in children vaccinated with 23vPPV at 12 months of age compared with children who did not receive 23vPPV. Here we assess the long-term impact of 23vPPV vaccination on nasopharyngeal carriage rates and densities of Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus and Moraxella catarrhalis. Nasopharyngeal swabs (n=194) were obtained from healthy children who participated in FiPP (now aged 5-7 years). S. pneumoniae were isolated and identified by standard culture-based methods, and serotyped using latex agglutination and the Quellung reaction. Carriage rates and densities of S. pneumoniae, H. influenzae, S. aureus and M. catarrhalis were determined using real-time quantitative PCR. There were no differences in the rate or density of S. pneumoniae, H. influenzae or M. catarrhalis carriage by PCV7 dose or 23vPPV vaccination in the vaccinated participants overall. However, differences were observed between the two main ethnic groups: Fijian children of Indian descent (Indo-Fijian) were less likely to carry S. pneumoniae, H. influenzae and M. catarrhalis, and there was evidence of a higher carriage rate of S. aureus compared with indigenous Fijian (iTaukei) children. Polysaccharide vaccination appeared to have effects that varied between ethnic groups, with 23vPPV vaccination associated with a higher carriage rate of S. aureus in iTaukei children, while there was a lower carriage rate of S. pneumoniae associated with 23vPPV vaccination in Indo-Fijian children. Overall, polysaccharide vaccination had no long-term impact on pneumococcal carriage, but may have impacted on S. aureus carriage and have varying effects in ethnic groups, suggesting current WHO vaccine schedule recommendations against the use of 23v

  18. Human Monocytes Promote Th1 and Th17 Responses to Streptococcus pneumoniae

    OpenAIRE

    Olliver, Marie; Hiew, Jeffni; Mellroth, Peter; Henriques-Normark, Birgitta; Bergman, Peter

    2011-01-01

    Streptococcus pneumoniae is a leading cause of bacterial pneumonia, meningitis, and sepsis in children. Human immunity to pneumococcal infections has been assumed to depend on anticapsular antibodies. However, recent findings from murine models suggest that alternative mechanisms, dependent on T helper cells, are also involved. Although the immunological events in which T helper cells contribute to acquired immunity have been studied in mice, little is known about how these responses are gene...

  19. Multidrug-Resistant Streptococcus pneumoniae in Poland: Identification of Emerging Clones

    OpenAIRE

    Overweg, Karin; Hermans, Peter W. M.; Trzcinski, Krzysztof; Sluijter, Marcel; De Groot, Ronald; Hryniewicz, Waleria

    1999-01-01

    Penicillin resistance among Streptococcus pneumoniae isolates has rapidly emerged in Poland during the last decade and has reached prevalence levels of up to 14.4% in 1997. In order to investigate the nature of this increase, a molecular epidemiological analysis of non-penicillin-susceptible multidrug-resistant pneumococci isolated in 1995 and 1996 was conducted. Thirty-seven patients who suffered mainly from upper respiratory tract infections and pneumococcal pneumonia were enrolled in this ...

  20. Multidrug-resistant Streptococcus pneumoniae in Poland: identification of emerging clones

    OpenAIRE

    Overweg, Karin; Hermans, Peter; Trzcinski, K.; Sluijter, Marcel; Hryniewicz, W.

    1999-01-01

    textabstractPenicillin resistance among Streptococcus pneumoniae isolates has rapidly emerged in Poland during the last decade and has reached prevalence levels of up to 14.4% in 1997. In order to investigate the nature of this increase, a molecular epidemiological analysis of non-penicillin-susceptible multidrug-resistant pneumococci isolated in 1995 and 1996 was conducted. Thirty-seven patients who suffered mainly from upper respiratory tract infections and pneumococcal pneumonia were enrol...

  1. Plasma gelsolin improves lung host defense against pneumonia by enhancing macrophage NOS3 function

    OpenAIRE

    Yang, Zhiping; Chiou, Terry Ting-Yu; Stossel, Thomas P.; Kobzik, Lester

    2015-01-01

    Plasma gelsolin (pGSN) functions as part of the “extracellular actin-scavenging system,” but its potential to improve host defense against infection has not been studied. In a mouse model of primary pneumococcal pneumonia, recombinant human pGSN (rhu-pGSN) caused enhanced bacterial clearance, reduced acute inflammation, and improved survival. In vitro, rhu-pGSN rapidly improved lung macrophage uptake and killing of bacteria (Streptococcus pneumoniae, Escherichia coli, and Francisella tularens...

  2. Complement Factor H Serum Levels Determine Resistance to Pneumococcal Invasive Disease.

    Science.gov (United States)

    van der Maten, Erika; Westra, Dineke; van Selm, Saskia; Langereis, Jeroen D; Bootsma, Hester J; van Opzeeland, Fred J H; de Groot, Ronald; Ruseva, Marieta M; Pickering, Matthew C; van den Heuvel, Lambert P W J; van de Kar, Nicole C A J; de Jonge, Marien I; van der Flier, Michiel

    2016-06-01

    Streptococcus pneumoniae is a major cause of life-threatening infections. Complement activation plays a vital role in opsonophagocytic killing of pneumococci in blood. Initial complement activation via the classical and lectin pathways is amplified through the alternative pathway amplification loop. Alternative pathway activity is inhibited by complement factor H (FH). Our study demonstrates the functional consequences of the variability in human serum FH levels on host defense. Using an in vivo mouse model combined with human in vitro assays, we show that the level of serum FH correlates with the efficacy of opsonophagocytic killing of pneumococci. In summary, we found that FH levels determine a delicate balance of alternative pathway activity, thus affecting the resistance to invasive pneumococcal disease. Our results suggest that variation in FH expression levels, naturally occurring in the human population, plays a thus far unrecognized role in the resistance to invasive pneumococcal disease. PMID:26802141

  3. Effects of Infant Pneumococcal Conjugate Vaccination on Serotype Distribution in Invasive Pneumococcal Disease among Children and Adults in Germany.

    Science.gov (United States)

    van der Linden, Mark; Falkenhorst, Gerhard; Perniciaro, Stephanie; Imöhl, Matthias

    2015-01-01

    This study describes the effects of the introduction of universal infant pneumococcal conjugate vaccination in 2006 on invasive pneumococcal disease (IPD) among children and adults in Germany with a focus on the dynamics of serotype distribution in vaccinated and non-vaccinated age groups. Over a period of 22 years (1992-2014), microbiological diagnostic laboratories from all over Germany have been sending isolates of IPD cases to the German National Reference Center for Streptococci on a voluntary basis. Streptococcus pneumoniae isolates were serotyped using Neufeld's Quellung method. Among children vaccination (1997-2006) to 23.5% in the early vaccination period (2007-2010; p = 1.30E-72) and sank further to 5.2% in the late vaccination period (2010-2014; p = 4.59E-25). Similar reductions were seen for the separate age groups vaccination period (1992-2006) to 24.7% (p = 3.78E-88) in the early vaccination period and 8.2% (p = 5.97E-161) in the late vaccination period. Both among children and among adults, the non-PCV7 serotypes 1, 3, 7F and 19A significantly increased in the early vaccination period. After the switch from PCV7 to PVC10/PCV13 for infant vaccination in 2010, serotypes 1, 6A and 7F significantly decreased. A decrease in serotype 19A was only observed in 2013-2014, as compared to 2010-2011 (children p = 4.16E-04, adults p = 6.98E-06). Among adults, serotype 3, which strongly increased in the early vaccination period (p = 4.44E-15), remained at a constant proportion in the late vaccination period. The proportion of non-PCV13 vaccine serotypes increased over the whole vaccination period, with serotypes 10A, 12F, 23B, 24F and 38 most significantly increasing among children and serotypes 6C, 12F, 15A, 22F and 23B increasing among adults. Eight years of childhood pneumococcal conjugate vaccination have had a strong effect on the pneumococcal population in Germany, both among the target group for vaccination as well as among older children and adults.

  4. Pulmonary immunostimulation with MALP-2 in influenza virus-infected mice increases survival after pneumococcal superinfection.

    Science.gov (United States)

    Reppe, Katrin; Radünzel, Peter; Dietert, Kristina; Tschernig, Thomas; Wolff, Thorsten; Hammerschmidt, Sven; Gruber, Achim D; Suttorp, Norbert; Witzenrath, Martin

    2015-12-01

    Pulmonary infection with influenza virus is frequently complicated by bacterial superinfection, with Streptococcus pneumoniae being the most prevalent causal pathogen and hence often associated with high morbidity and mortality rates. Local immunosuppression due to pulmonary influenza virus infection has been identified as a major cause of the pathogenesis of secondary bacterial lung infection. Thus, specific local stimulation of the pulmonary innate immune system in subjects with influenza virus infection might improve the host defense against secondary bacterial pathogens. In the present study, we examined the effect of pulmonary immunostimulation with Toll-like receptor 2 (TLR-2)-stimulating macrophage-activating lipopeptide 2 (MALP-2) in influenza A virus (IAV)-infected mice on the course of subsequent pneumococcal superinfection. Female C57BL/6N mice infected with IAV were treated with MALP-2 on day 5 and challenged with S. pneumoniae on day 6. Intratracheal MALP-2 application increased proinflammatory cytokine and chemokine release and enhanced the recruitment of leukocytes, mainly neutrophils, into the alveolar space of IAV-infected mice, without detectable systemic side effects. Local pulmonary instillation of MALP-2 in IAV-infected mice 24 h before transnasal pneumococcal infection considerably reduced the bacterial number in the lung tissue without inducing exaggerated inflammation. The pulmonary viral load was not altered by MALP-2. Clinically, MALP-2 treatment of IAV-infected mice increased survival rates and reduced hypothermia and body weight loss after pneumococcal superinfection compared to those of untreated coinfected mice. In conclusion, local immunostimulation with MALP-2 in influenza virus-infected mice improved pulmonary bacterial elimination and increased survival after subsequent pneumococcal superinfection. PMID:26371127

  5. EFFICACY AND SAFETY OF 23-VALENT PNEUMOCOCCAL POLYSACCHARIDE VACCINE IN PATIENTS WITH RHEUMATOID ARTHRITIS

    Directory of Open Access Journals (Sweden)

    M. S. Naumtseva

    2015-01-01

    Full Text Available Objective: to study the clinical efficacy, immunogenicity, and safety of a 23-valent pneumococcal vaccine in patients with rheumatoid arthritis (RA. Subjects and methods. The investigation enrolled 70 patients (55 women and 15 men aged 23–70 years, including 40 patients with RA and 30 people without systemic inflammatory rheumatic diseases (a control group who had a recent history of 2 and more cases of lower respiratory tract infections (bronchitis, pneumonia. When included, all the patients received anti-inflammatory therapy with methotrexate (MT (n = 24, leflunomide (LEF (n = 6, or MT + tumor necrosis factor-α (TNF-α inhibitors (n = 10. A single 0.5-ml dose of the 23-valent pneumococcal vaccine Pneumo-23 (Sanofi Pasteur was administered subcutaneously or intramuscularly during continuous MT or LEF therapy for the underlying disease or 3–4 weeks before the use of a TNF-α inhibitor. During control visits (1 and 3 months and 1 year after administration of the vaccine, the patients underwent physical examination and routine clinical and laboratory studies. Results. No clinical and radiological symptoms of pneumonia were recorded in any case during a 12-month follow-up. The RA and control groups showed a more than 2-fold increase in anti-pneumococcal antibody levels 1 year after vaccination. The vaccine was well tolerated by 50 patients. Sixteen patients were observed to have pain, cutaneous swelling and hyperemia and 4 had subfebrility. There were neither episodes of RA exacerbation nor new autoimmune disorders during the follow-up. Conclusion. The findings suggest that 23-valent pneumococcal vaccine shows a good clinical efficacy, adequate immunogenicity, and good tolerability in the patients with RA. 

  6. Cost-effectiveness of adult pneumococcal conjugate vaccination in the Netherlands.

    Science.gov (United States)

    Mangen, Marie-Josée J; Rozenbaum, Mark H; Huijts, Susanne M; van Werkhoven, Cornelis H; Postma, Douwe F; Atwood, Mark; van Deursen, Anna M M; van der Ende, Arie; Grobbee, Diederick E; Sanders, Elisabeth A M; Sato, Reiko; Verheij, Theo J M; Vissink, Conrad E; Bonten, Marc J M; de Wit, G Ardine

    2015-11-01

    The Community-Acquired Pneumonia Immunization Trial in Adults (CAPiTA) demonstrated the efficacy of 13-valent pneumococcal conjugate vaccine (PCV13) in preventing vaccine-type community-acquired pneumonia and vaccine-type invasive pneumococcal disease in elderly subjects. We examined the cost-effectiveness of PCV13 vaccination in the Netherlands. Using a Markov-type model, incremental cost-effectiveness ratios (ICER) of PCV13 vaccination in different age- and risk-groups for pneumococcal disease were evaluated using a societal perspective. Estimates of quality-adjusted life-years (QALYs), costs, vaccine efficacy and epidemiological data were based on the CAPiTA study and other prospective studies. The base-case was PCV13 vaccination of adults aged 65-74 years compared to no vaccination, assuming no net indirect effects in base-case due to paediatric 10-valent pneumococcal conjugate vaccine use. Analyses for age- and risk-group specific vaccination strategies and for different levels of hypothetical herd effects from a paediatric PCV programme were also conducted. The ICER for base-case was €8650 per QALY (95% CI 5750-17,100). Vaccination of high-risk individuals aged 65-74 years was cost-saving and extension to medium-risk individuals aged 65-74 years yielded an ICER of €2900. Further extension to include medium- and high-risk individuals aged ≥18 years yielded an ICER of €3100.PCV13 vaccination is highly cost-effective in the Netherlands. The transferability of our results to other countries depends upon vaccination strategies already implemented in those countries.

  7. Accuracy of Phenotypic Methods for Identification of Streptococcus pneumoniae Isolates Included in Surveillance Programs▿

    OpenAIRE

    Richter, Sandra S.; Heilmann, Kristopher P.; Dohrn, Cassie L.; Riahi, Fathollah; Beekmann, Susan E.; Doern, Gary V.

    2008-01-01

    Similarities between Streptococcus pneumoniae and viridans group streptococci may result in misidentification of these organisms. In surveillance programs which assess antimicrobial resistance rates among respiratory tract pathogens, such identification errors could lead to overestimates of pneumococcal resistance rates. DNA probe analysis (Gen-Probe, San Diego, CA), the bile solubility test, optochin susceptibility, colony morphology, and the capsular swelling reaction with Omni serum (State...

  8. Enhanced adherence of Strontococcus pneumoniae to human epithelial cells infected with respiratory syncytial virus

    NARCIS (Netherlands)

    Hament, JM; Aerts, PC; Fleer, A; Van Dijk, H; Kimpen, JLL; Wolfs, TFW

    2004-01-01

    In the present study, we analyzed the effect of a preceding respiratory syncytial virus (RSV) infection of human respiratory epithelial cells on the adherence of Streptococcus pneumoniae tested by means of a cytometric fluorescence assay. Adherence of clinically relevant pneumococcal serotypes 3, 9,

  9. Draft Genome Sequence of the Streptococcus pneumoniae Avery Strain A66

    OpenAIRE

    Hahn, Christoph; Harrison, Ewan M.; Parkhill, Julian; Holmes, Mark A.; Paterson, Gavin K.

    2015-01-01

    We have used HiSeq 2000 technology to generate a draft genome sequence of Streptococcus pneumoniae strain A66. This is a common study strain used in investigations of pneumococcal bacterium-host interactions and was used in the seminal genetic studies of Avery et al.

  10. Identification and characterization of novel virulence factors in Streptococcus pneumoniae

    OpenAIRE

    Wartha, Florian

    2008-01-01

    Streptococcus pneumoniae (the pneumococcus) is a major human pathogen with high morbidity and mortality worldwide. Increased antibiotic resistance and insufficient vaccination contribute to the re-emerging of this pathogen. Identifying novel virulence factors could lead to a better understanding of the pathology of pneumococcal disease and result in novel therapeutic approaches. We were able to show the presence of a surface-exposed pilus structure in pneumococci, made u...

  11. Temporal trends in invasive pneumococcal disease and pneumococcal serotypes over 7 decades

    DEFF Research Database (Denmark)

    Harboe, Zitta B; Benfield, Thomas L; Valentiner-Branth, Palle;

    2010-01-01

    BACKGROUND: Pneumococcal infections have historically played a major role in terms of morbidity and mortality. We explored historical trends of invasive pneumococcal disease (IPD) and pneumococcal serotypes in a population exposed to limited antibiotic selective pressure and conjugate pneumococcal...... vaccination (PCV). METHODS: Retrospective cohort study based on nationwide laboratory surveillance data on IPD collected uninterruptedly in Denmark during 1938-2007. Changes in the reported incidence and trends of pneumococcal serotypes were explored using nonlinear regression analysis. RESULTS: There were 25...... serotype 19A increased before introduction of PCV. Between 1993 and 2007, the level of resistance to macrolides and beta-lactams was 6%. CONCLUSIONS: The epidemiology of IPD and single serotypes has constantly changed over the past 7 decades. PCV serotypes appeared to dominate the pneumococcal population....

  12. Lack of SOS repair in Streptococcus pneumoniae

    International Nuclear Information System (INIS)

    Wild-type strains of Streptococcus pneumoniae were non-mutable by UV radiation and thymidine starvation. Moreover, UV-irradiated pneumococcal ω2 phages were not reactivated in an irradiated host. This suggests that, in pneumococcus, there is no efficient inducible repair process similar to the SOS repair described in detail for E. coli. We also report that mutations cannot be induced by a process thought to be linked to competence during transformation with isogenic wild-type DNA either on wild-type strains or in strains in which the hex function of excision and repair of mismatched bases is inactive. (orig.)

  13. Pneumococcal Acquisition Among Infants Exposed to HIV in Rural Malawi: A Longitudinal Household Study.

    Science.gov (United States)

    Heinsbroek, Ellen; Tafatatha, Terence; Chisambo, Christina; Phiri, Amos; Mwiba, Oddie; Ngwira, Bagrey; Crampin, Amelia C; Read, Jonathan M; French, Neil

    2016-01-01

    The prevalence of Streptococcus pneumoniae (pneumococcus) carriage is higher in adults who are infected with human immunodeficiency virus (HIV) than in adults who are not. We hypothesized that infants exposed to HIV become carriers of nasopharyngeal pneumococcus earlier and more frequently than infants who are not exposed to HIV. We compared infant pneumococcal acquisition by maternal HIV status and household exposure in Karonga District, Malawi, in 2009-2011, before the introduction of pneumococcal conjugate vaccine. Nasopharyngeal swabs were collected every 4-6 weeks in the first year of life from infants with known HIV-exposure status, their mothers, and other household members. We studied infant pneumococcal acquisition by maternal HIV status, serotype-specific household exposure, and other risk factors, including seasonality. We recruited 54 infants who were exposed to HIV and 131 infants who were not. There was no significant difference in pneumococcal acquisition by maternal HIV status (adjusted rate ratio (aRR) = 1.00, 95% confidence interval (CI): 0.87, 1.15). Carriage by the mother was associated with greater acquisition of the same serotype (aRR = 3.09, 95% CI: 1.47, 6.50), but the adjusted population attributable fraction was negligible (1.9%, 95% CI: 0.0, 4.3). Serotype-specific exposure to children under 5 years of age was associated with higher acquisition (aRR = 4.30, 95% CI: 2.80, 6.60; adjusted population attributable fraction = 8.8%, 95% CI: 4.0, 13.4). We found no evidence to suggest that maternal HIV infection would affect the impact of pneumococcal vaccination on colonization in this population. PMID:26628514

  14. Indirect effect of 7-valent pneumococcal conjugate vaccine on pneumococcal carriage in newborns in rural Gambia: a randomised controlled trial.

    Directory of Open Access Journals (Sweden)

    Uzochukwu Egere

    Full Text Available BACKGROUND: Gambian infants frequently acquire Streptococcus pneumoniae soon after birth. We investigated the indirect effect of 7-valent pneumococcal conjugate vaccine (PCV-7 on pneumococcal acquisition in newborn Gambian babies. METHODS: Twenty-one villages were randomised to receive PCV-7 to all subjects (11 vaccinated villages or to infants aged 2-30 months (10 control villages. Other control villagers received Meningococcal C conjugate vaccine. From 328 babies born during the trial, nasopharyngeal swabs were collected after birth, then weekly until 8 weeks of age when they received their first dose of PCV-7. Pneumococcal carriage and acquisition rates were compared between the study arms and with a baseline study. RESULTS: 57.4% of 2245 swabs were positive for S. pneumoniae. Overall carriage was similar in both arms. In vaccinated villages fewer infants carried pneumococci of vaccine serotypes (VT (16.9% [31/184] vs. 37.5% [54/144], p<0.001 and more carried pneumococci of non-vaccine serotypes (NVT (80.9% [149/184] vs. 75.7% [109/144], p = 0.246. Infants from vaccinated villages had a significantly lower acquisition rate of VT (HR 0.39 [0.26-0.58], p<0.001 and increased acquisition of NVT (HR 1.16 [0.87-1.56], p = 0.312. VT carriage (51.6% vs. 37.5%, p = 031 in control and 46.1% vs. 16.8%, p<0.001 in vaccinated villages and acquisition rates (HR 0.68 [0.50-0.92], p = 0.013 in control villages and HR 0.31 [0.19-0.50], p<.001 in vaccinated villages were significantly lower in both study arms than in the baseline study. NVT carriage (63.2% vs. 75.7%, p = 0.037 in control and 67.2% vs. 75.3%, p = 0.005 in vaccinated villages and acquisition rates (HR 1.48 [1.06-2.06], p = 0.022 and (HR 1.52 [1.11-2.10], p = 0.010 respectively were significantly higher. CONCLUSION: PCV-7 significantly reduced carriage of VT pneumococci in unvaccinated infants. This indirect effect likely originated from both the child and adult vaccinated populations. Increased

  15. Impact of pneumococcal conjugate vaccine in children morbidity and mortality in Peru: Time series analyses.

    Science.gov (United States)

    Suarez, Victor; Michel, Fabiana; Toscano, Cristiana M; Bierrenbach, Ana Luiza; Gonzales, Marco; Alencar, Airlane Pereira; Ruiz Matus, Cuauhtemoc; Andrus, Jon K; de Oliveira, Lucia H

    2016-09-01

    Streptococcus pneumoniae is the leading cause of bacterial pneumonia, meningitis and sepsis in children worldwide. Despite available evidence on pneumococcal conjugate vaccine (PCV) impact on pneumonia hospitalizations in children, studies demonstrating PCV impact in morbidity and mortality in middle-income countries are still scarce. Given the disease burden, PCV7 was introduced in Peru in 2009, and then switched to PCV10 in late 2011. National public healthcare system provides care for 60% of the population, and national hospitalization, outpatient and mortality data are available. We thus aimed to assess the effects of routine PCV vaccination on pneumonia hospitalization and mortality, and acute otitis media (AOM) and all cause pneumonia outpatient visits in children under one year of age in Peru. We conducted a segmented time-series analysis using outcome-specific regression models. Study period was from January 2006 to December 2012. Data sources included the National information systems for hospitalization, mortality, outpatient visits, and RENACE, the national database of aggregated weekly notifications of pneumonia and other acute respiratory diseases (both hospitalized and non-hospitalized). Study outcomes included community acquired pneumonia outpatient visits, hospitalizations and deaths (ICD10 codes J12-J18); and AOM outpatient visits (H65-H67). Monthly age- and sex-specific admission, outpatient visit, and mortality rates per 100,000 children aged impact in morbidity and mortality in children aged <1year. Vaccine effectiveness was 26.2% (95% CI 16.9-34.4) for AOM visits, 35% (95% CI 8.6-53.8) for mortality due to pneumonia, and 20.6% (95% CI 10.6-29.5) for weekly cases of pneumonia hospitalization and outpatient visits notified to RENACE. We used secondary data sources which are usually developed for other non-epidemiologic purposes. Despite some data limitations, our results clearly demonstrate the overall benefit of PCV vaccination in Peru.

  16. Viral pneumonia

    Science.gov (United States)

    More serious infections can result in respiratory failure, liver failure, and heart failure. Sometimes, bacterial infections occur during or just after viral pneumonia, which may lead to more serious forms ...

  17. PCR-Based Serotyping of Streptococcus pneumoniae from Culture-Negative Specimens: Novel Primers for Detection of Serotypes within Serogroup 18.

    Science.gov (United States)

    Tanmoy, Arif M; Saha, Senjuti; Darmstadt, Gary L; Whitney, Cynthia G; Saha, Samir K

    2016-08-01

    Six multiplex-compatible PCR primers were designed to distinguish Streptococcus pneumoniae serotypes within serogroup 18 from culturable/nonculturable pneumococcal specimens, with no cross-reactivity with other serotypes and respiratory organisms. These primers will aid in the generation of better data on vaccine/nonvaccine serotypes in invasive and carriage pneumococcal surveillance and contribute to future vaccine formulation and impact studies. PMID:27252464

  18. Cirrhosis-induced defects in innate pulmonary defenses against Streptococcus pneumoniae

    Directory of Open Access Journals (Sweden)

    Vander Top Elizabeth A

    2007-10-01

    Full Text Available Abstract Background The risk of mortality from pneumonia caused by Streptococcus pneumoniae is increased in patients with cirrhosis. However, the specific pneumococcal virulence factors and host immune defects responsible for this finding have not been clearly established. This study used a cirrhotic rat model of pneumococcal pneumonia to identify defect(s in innate pulmonary defenses in the cirrhotic host and to determine the impact of the pneumococcal toxin pneumolysin on these defenses in the setting of severe cirrhosis. Results No cirrhosis-associated defects in mucociliary clearance of pneumococci were found in these studies, but early intrapulmonary killing of the organisms before the arrival of neutrophils was significantly impaired. This defect was exacerbated by pneumolysin production in cirrhotic but not in control rats. Neutrophil-mediated killing of a particularly virulent type 3 pneumococcal strain also was significantly diminished within the lungs of cirrhotic rats with ascites. Levels of lysozyme and complement component C3 were both significantly reduced in bronchoalveolar lavage fluid from cirrhotic rats. Finally, complement deposition was reduced on the surface of pneumococci recovered from the lungs of cirrhotic rats in comparison to organisms recovered from the lungs of control animals. Conclusion Increased mortality from pneumococcal pneumonia in this cirrhotic host is related to defects in both early pre-neutrophil- and later neutrophil-mediated pulmonary killing of the organisms. The fact that pneumolysin production impaired pre-neutrophil-mediated pneumococcal killing in cirrhotic but not control rats suggests that pneumolysin may be particularly detrimental to this defense mechanism in the severely cirrhotic host. The decrease in neutrophil-mediated killing of pneumococci within the lungs of the cirrhotic host is related to insufficient deposition of host proteins such as complement C3 on their surfaces. Pneumolysin

  19. Molecular characterization of pneumococcal isolates from pets and laboratory animals.

    Directory of Open Access Journals (Sweden)

    Mark van der Linden

    Full Text Available BACKGROUND: Between 1986 and 2008 Streptococcus pneumoniae was isolated from 41 pets/zoo animals (guinea pigs (n = 17, cats (n = 12, horses (n = 4, dogs (n = 3, dolphins (n = 2, rat (n = 2, gorilla (n = 1 treated in medical veterinary laboratories and zoos, and 44 laboratory animals (mastomys (multimammate mice; n = 32, mice (n = 6, rats (n = 4, guinea pigs (n = 2 during routine health monitoring in an animal facility. S. pneumoniae was isolated from nose, lung and respiratory tract, eye, ear and other sites. METHODOLOGY/PRINCIPAL FINDINGS: Carriage of the same isolate of S. pneumoniae over a period of up to 22 weeks was shown for four mastomys. Forty-one animals showed disease symptoms. Pneumococcal isolates were characterized by optochin sensitivity, bile solubility, DNA hybridization, pneumolysin PCR, serotyping and multilocus sequence typing. Eighteen of the 32 mastomys isolates (56% were optochin resistant, all other isolates were optochin susceptible. All mastomys isolates were serotype 14, all guinea pig isolates serotype 19F, all horse isolates serotype 3. Rats had serotypes 14 or 19A, mice 33A or 33F. Dolphins had serotype 23F, the gorilla serotype 14. Cats and dogs had many different serotypes. Four isolates were resistant to macrolides, three isolates also to clindamycin and tetracycline. Mastomys isolates were sequence type (ST 15 (serotype 14, an ST/serotype combination commonly found in human isolates. Cats, dogs, pet rats, gorilla and dolphins showed various human ST/serotype combinations. Lab rats and lab mice showed single locus variants (SLV of human STs, in human ST/serotype combinations. All guinea pig isolates showed the same completely new combination of known alleles. The horse isolates showed an unknown allele combination and three new alleles. CONCLUSIONS/SIGNIFICANCE: The isolates found in mastomys, mice, rats, cats, dogs, gorilla and dolphins are most likely identical to human pneumococcal isolates. Isolates from

  20. Cost-effectiveness of 2 + 1 dosing of 13-valent and 10-valent pneumococcal conjugate vaccines in Canada

    Directory of Open Access Journals (Sweden)

    Earnshaw Stephanie R

    2012-04-01

    Full Text Available Abstract Background Thirteen-valent pneumococcal conjugate vaccine (PCV13 and 10-valent pneumococcal conjugate vaccine (PCV10 are two recently approved vaccines for the active immunization against Streptococcus pneumoniae causing invasive pneumococcal disease in infants and children. PCV13 offers broader protection against Streptococcus pneumoniae; however, PCV10 offers potential protection against non-typeable Haemophilus influenza (NTHi. We examined public health and economic impacts of a PCV10 and PCV13 pediatric national immunization programs (NIPs in Canada. Methods A decision-analytic model was developed to examine the costs and outcomes associated with PCV10 and PCV13 pediatric NIPs. The model followed individuals over the remainder of their lifetime. Recent disease incidence, serotype coverage, population data, percent vaccinated, costs, and utilities were obtained from the published literature. Direct and indirect effects were derived from 7-valent pneumococcal vaccine. Additional direct effect of 4% was attributed to PCV10 for moderate to severe acute otitis media to account for potential NTHi benefit. Annual number of disease cases and costs (2010 Canadian dollars were presented. Results In Canada, PCV13 was estimated to prevent more cases of disease (49,340 when considering both direct and indirect effects and 7,466 when considering direct effects only than PCV10. This translated to population gains of 258 to 13,828 more quality-adjusted life-years when vaccinating with PCV13 versus PCV10. Annual direct medical costs (including the cost of vaccination were estimated to be reduced by $5.7 million to $132.8 million when vaccinating with PCV13. Thus, PCV13 dominated PCV10, and sensitivity analyses showed PCV13 to always be dominant or cost-effective versus PCV10. Conclusions Considering the epidemiology of pneumococcal disease in Canada, PCV13 is shown to be a cost-saving immunization program because it provides substantial public

  1. NNDSS - Table II. Invasive Pneumococcal to Legionellosis

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Invasive Pneumococcal to Legionellosis - 2015.In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the...

  2. NNDSS - Table II. Invasive Pneumococcal to Legionellosis

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Invasive Pneumococcal to Legionellosis - 2014.In this Table, all conditions with a 5-year average annual national total of more than or equals...

  3. NNDSS - Table II. Invasive Pneumococcal to Legionellosis

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Invasive Pneumococcal to Legionellosis - 2016. In this Table, provisional* cases of selected†notifiable diseases (≥1,000 cases reported during...

  4. Dexamethasone Treatment Reverses Cognitive Impairment but Increases Brain Oxidative Stress in Rats Submitted to Pneumococcal Meningitis

    OpenAIRE

    Tatiana Barichello; Santos, Ana Lucia B.; Cintia Silvestre; Generoso, Jaqueline S.; Cipriano, Andreza L.; Fabricia Petronilho; Felipe Dal-Pizzol; Comim, Clarissa M.; João Quevedo

    2011-01-01

    Pneumococcal meningitis is associated with a significant mortality rate and neurologic sequelae. The animals received either 10  μ L of saline or a S. pneumoniae suspension and were randomized into different groups: sham: placebo with dexamethasone 0.7 mg/kg/1 day; placebo with dexamethasone 0.2 mg/kg/7 days; meningitis groups: dexamethasone 0.7 mg/kg/1 day and dexamethasone 0.2 mg/kg/7 days. Ten days after induction we evaluated memory and oxidative stress parameters in hippocampus and corte...

  5. Macrophage serum markers in pneumococcal bacteremia: Prediction of survival by soluble CD163

    DEFF Research Database (Denmark)

    Møller, Holger Jon; K. Moestrup, Søren; Wejse, Christian;

    2006-01-01

    with pneumococcal bacteremia. DESIGN: Observational cohort study. SETTING: Five university hospitals in Denmark. PATIENTS: A total of 133 patients with Streptococcus pneumoniae bacteremia (positive blood culture) and 133 age- and gender-matched controls. INTERVENTIONS: Samples were collected for biochemical...... were observed in patients who needed intensive care (hemodialysis, p = .0011; hypotension, p = .0014; mechanical ventilation, p = .0019). Significantly lower levels of sCD163, ferritin, transcobalamin, and suPAR (but not C-reactive protein) were measured in patients > or =75 yrs. In patients

  6. How Is Pneumonia Treated?

    Science.gov (United States)

    ... page from the NHLBI on Twitter. How Is Pneumonia Treated? Treatment for pneumonia depends on the type ... can go back to their normal routines. Bacterial Pneumonia Bacterial pneumonia is treated with medicines called antibiotics. ...

  7. Impact of Pneumococcal Conjugate Universal Routine Vaccination on Pneumococcal Disease in Italian Children

    OpenAIRE

    Francesca Fortunato; Domenico Martinelli; Maria Giovanna Cappelli; Vanessa Cozza; Rosa Prato

    2015-01-01

    In Italy, the effectiveness of pneumococcal universal vaccination in preventing vaccine-type invasive pneumococcal disease (IPD) in the PCV7/PCV13 shifting period was estimated to be 84.3% (95% CI: 84.0–84.6%) in children

  8. Streptococcus pneumoniae Enhances Human Respiratory Syncytial Virus Infection In Vitro and In Vivo.

    Directory of Open Access Journals (Sweden)

    D Tien Nguyen

    Full Text Available Human respiratory syncytial virus (HRSV and Streptococcus pneumoniae are important causative agents of respiratory tract infections. Both pathogens are associated with seasonal disease outbreaks in the pediatric population, and can often be detected simultaneously in infants hospitalized with bronchiolitis or pneumonia. It has been described that respiratory virus infections may predispose for bacterial superinfections, resulting in severe disease. However, studies on the influence of bacterial colonization of the upper respiratory tract on the pathogenesis of subsequent respiratory virus infections are scarce. Here, we have investigated whether pneumococcal colonization enhances subsequent HRSV infection. We used a newly generated recombinant subgroup B HRSV strain that expresses enhanced green fluorescent protein and pneumococcal isolates obtained from healthy children in disease-relevant in vitro and in vivo model systems. Three pneumococcal strains specifically enhanced in vitro HRSV infection of primary well-differentiated normal human bronchial epithelial cells grown at air-liquid interface, whereas two other strains did not. Since previous studies reported that bacterial neuraminidase enhanced HRSV infection in vitro, we measured pneumococcal neuraminidase activity in these cultures but found no correlation with the observed infection enhancement in our model. Subsequently, a selection of pneumococcal strains was used to induce nasal colonization of cotton rats, the best available small animal model for HRSV. Intranasal HRSV infection three days later resulted in strain-specific enhancement of HRSV replication in vivo. One S. pneumoniae strain enhanced HRSV both in vitro and in vivo, and was also associated with enhanced syncytium formation in vivo. However, neither pneumococci nor HRSV were found to spread from the upper to the lower respiratory tract, and neither pathogen was transmitted to naive cage mates by direct contact. These

  9. Influenza A virus alters pneumococcal nasal colonization and middle ear infection independently of phase variation.

    Science.gov (United States)

    Wren, John T; Blevins, Lance K; Pang, Bing; King, Lauren B; Perez, Antonia C; Murrah, Kyle A; Reimche, Jennifer L; Alexander-Miller, Martha A; Swords, W Edward

    2014-11-01

    Streptococcus pneumoniae (pneumococcus) is both a widespread nasal colonizer and a leading cause of otitis media, one of the most common diseases of childhood. Pneumococcal phase variation influences both colonization and disease and thus has been linked to the bacteria's transition from colonizer to otopathogen. Further contributing to this transition, coinfection with influenza A virus has been strongly associated epidemiologically with the dissemination of pneumococci from the nasopharynx to the middle ear. Using a mouse infection model, we demonstrated that coinfection with influenza virus and pneumococci enhanced both colonization and inflammatory responses within the nasopharynx and middle ear chamber. Coinfection studies were also performed using pneumococcal populations enriched for opaque or transparent phase variants. As shown previously, opaque variants were less able to colonize the nasopharynx. In vitro, this phase also demonstrated diminished biofilm viability and epithelial adherence. However, coinfection with influenza virus ameliorated this colonization defect in vivo. Further, viral coinfection ultimately induced a similar magnitude of middle ear infection by both phase variants. These data indicate that despite inherent differences in colonization, the influenza A virus exacerbation of experimental middle ear infection is independent of the pneumococcal phase. These findings provide new insights into the synergistic link between pneumococcus and influenza virus in the context of otitis media.

  10. Epidemiology of invasive pneumococcal disease in Saudi Arabian children younger than 5years of age.

    Science.gov (United States)

    Almazrou, Yagob; Shibl, Atef M; Alkhlaif, Riyadh; Pirçon, Jean-Yves; Anis, Sameh; Kandeil, Walid; Hausdorff, William P

    2016-06-01

    This study evaluated the incidence, serotype distribution, and antimicrobial susceptibility of invasive pneumococcal disease (IPD) in Saudi Arabian children. This multicenter, prospective, clinical surveillance study included children under 5years of age, residents of one of the seven study health areas, who were brought to a study hospital with suspicion of IPD. Bacterial isolates from sterile site samples, collected less than 24h after hospital visit/admission, were identified, serotyped, and tested for antibiotic susceptibility. Between June 2007 and January 2009, 631 episodes of suspected IPD were recorded, and 623 were included in the analysis. One child (0.2%) had previously received one dose of a pneumococcal vaccine. Forty-seven episodes were positive for Streptococcus pneumoniae and three for Haemophilus influenzae. The incidence of confirmed IPD cases was estimated to be 2.5-21.6 per 100,000 children (Vaccination of Saudi Arabian children with expanded-coverage conjugate pneumococcal vaccines containing serotypes 1 and 5 could have a substantial impact to prevent IPD in this population. PMID:26368823

  11. Dried Saliva Spots: A Robust Method for Detecting Streptococcus pneumoniae Carriage by PCR

    Directory of Open Access Journals (Sweden)

    Cassandra L. Krone

    2016-03-01

    Full Text Available The earliest studies in the late 19th century on Streptococcus pneumoniae (S. pneumoniae carriage used saliva as the primary specimen. However, interest in saliva declined after the sensitive mouse inoculation method was replaced by conventional culture, which made isolation of pneumococci from the highly polymicrobial oral cavity virtually impossible. Here, we tested the feasibility of using dried saliva spots (DSS for studies on pneumococcal carriage. Saliva samples from children and pneumococcus-spiked saliva samples from healthy adults were applied to paper, dried, and stored, with and without desiccant, at temperatures ranging from −20 to 37 °C for up to 35 days. DNA extracted from DSS was tested with quantitative-PCR (qPCR specifically for S. pneumoniae. When processed immediately after drying, the quantity of pneumococcal DNA detected in spiked DSS from adults matched the levels in freshly spiked raw saliva. Furthermore, pneumococcal DNA was stable in DSS stored with desiccant for up to one month over a broad range of temperatures. There were no differences in the results when spiking saliva with varied pneumococcal strains. The collection of saliva can be a particularly useful in surveillance studies conducted in remote settings, as it does not require trained personnel, and DSS are resilient to various transportation conditions.

  12. Circulating Pneumolysin Is a Potent Inducer of Cardiac Injury during Pneumococcal Infection.

    Science.gov (United States)

    Alhamdi, Yasir; Neill, Daniel R; Abrams, Simon T; Malak, Hesham A; Yahya, Reham; Barrett-Jolley, Richard; Wang, Guozheng; Kadioglu, Aras; Toh, Cheng-Hock

    2015-05-01

    Streptococcus pneumoniae accounts for more deaths worldwide than any other single pathogen through diverse disease manifestations including pneumonia, sepsis and meningitis. Life-threatening acute cardiac complications are more common in pneumococcal infection compared to other bacterial infections. Distinctively, these arise despite effective antibiotic therapy. Here, we describe a novel mechanism of myocardial injury, which is triggered and sustained by circulating pneumolysin (PLY). Using a mouse model of invasive pneumococcal disease (IPD), we demonstrate that wild type PLY-expressing pneumococci but not PLY-deficient mutants induced elevation of circulating cardiac troponins (cTns), well-recognized biomarkers of cardiac injury. Furthermore, elevated cTn levels linearly correlated with pneumococcal blood counts (r=0.688, p=0.001) and levels were significantly higher in non-surviving than in surviving mice. These cTn levels were significantly reduced by administration of PLY-sequestering liposomes. Intravenous injection of purified PLY, but not a non-pore forming mutant (PdB), induced substantial increase in cardiac troponins to suggest that the pore-forming activity of circulating PLY is essential for myocardial injury in vivo. Purified PLY and PLY-expressing pneumococci also caused myocardial inflammatory changes but apoptosis was not detected. Exposure of cultured cardiomyocytes to PLY-expressing pneumococci caused dose-dependent cardiomyocyte contractile dysfunction and death, which was exacerbated by further PLY release following antibiotic treatment. We found that high PLY doses induced extensive cardiomyocyte lysis, but more interestingly, sub-lytic PLY concentrations triggered profound calcium influx and overload with subsequent membrane depolarization and progressive reduction in intracellular calcium transient amplitude, a key determinant of contractile force. This was coupled to activation of signalling pathways commonly associated with cardiac

  13. Circulating Pneumolysin Is a Potent Inducer of Cardiac Injury during Pneumococcal Infection.

    Directory of Open Access Journals (Sweden)

    Yasir Alhamdi

    2015-05-01

    Full Text Available Streptococcus pneumoniae accounts for more deaths worldwide than any other single pathogen through diverse disease manifestations including pneumonia, sepsis and meningitis. Life-threatening acute cardiac complications are more common in pneumococcal infection compared to other bacterial infections. Distinctively, these arise despite effective antibiotic therapy. Here, we describe a novel mechanism of myocardial injury, which is triggered and sustained by circulating pneumolysin (PLY. Using a mouse model of invasive pneumococcal disease (IPD, we demonstrate that wild type PLY-expressing pneumococci but not PLY-deficient mutants induced elevation of circulating cardiac troponins (cTns, well-recognized biomarkers of cardiac injury. Furthermore, elevated cTn levels linearly correlated with pneumococcal blood counts (r=0.688, p=0.001 and levels were significantly higher in non-surviving than in surviving mice. These cTn levels were significantly reduced by administration of PLY-sequestering liposomes. Intravenous injection of purified PLY, but not a non-pore forming mutant (PdB, induced substantial increase in cardiac troponins to suggest that the pore-forming activity of circulating PLY is essential for myocardial injury in vivo. Purified PLY and PLY-expressing pneumococci also caused myocardial inflammatory changes but apoptosis was not detected. Exposure of cultured cardiomyocytes to PLY-expressing pneumococci caused dose-dependent cardiomyocyte contractile dysfunction and death, which was exacerbated by further PLY release following antibiotic treatment. We found that high PLY doses induced extensive cardiomyocyte lysis, but more interestingly, sub-lytic PLY concentrations triggered profound calcium influx and overload with subsequent membrane depolarization and progressive reduction in intracellular calcium transient amplitude, a key determinant of contractile force. This was coupled to activation of signalling pathways commonly associated with

  14. Bacterial Invasion of the Inner Ear in Association With Pneumococcal Meningitis

    DEFF Research Database (Denmark)

    Møller, Martin Nue; Brandt, Christian; Østergaard, Christian;

    2014-01-01

    OBJECTIVE: To examine the pathways of bacterial invasion and subsequent spreading in the inner ear during pneumococcal meningitis. STUDY DESIGN: A well-established adult rat model of Streptococcus pneumoniae meningitis was used. METHODS: Thirty rats were inoculated intrathecally with S. pneumoniae...... spreading were found within the inner ear. Bacterial elimination was evidenced by engulfment by macrophages within the inner ear. CONCLUSION: From the meninges, pneumococci invade the inner ear through the cochlear aqueduct during the first days of infection, whereas hematogenous invasion via the spiral...... scala vestibuli of the basal turn of the cochlea, hematogenous spreading occurred to the spiral ligament and into the cochlear endolymph, subsequently to the vestibular endolymph. We found no evidence of alternative routes for bacterial invasion in the inner ear. Several internal barriers to bacterial...

  15. Molecular Epidemiology of Pneumococcal Colonization in Response to Pneumococcal Conjugate Vaccination in Children with Recurrent Acute Otitis Media

    OpenAIRE

    Bogaert, D.; Veenhoven, R.H.; Sluijter, M.; Wannet, W. J. W.; Rijkers, G.T.; Mitchell, T J; Clarke, S. C.; Goessens, W.H.F.; Schilder, A. G.; Sanders, E. A. M.; de Groot, R.; Hermans, P. W. M.

    2005-01-01

    A randomized double-blind trial with a 7-valent pneumococcal conjugate vaccine was conducted in The Netherlands among 383 children, aged 1 to 7 years, with a history of recurrent acute otitis media. No effect of vaccination on the pneumococcal colonization rate was found. However, a shift in serotype distribution was clearly observed (R. Veenhoven et al., Lancet 361:2189-2195, 2003). We investigated the molecular epidemiology of 921 pneumococcal isolates retrieved from both the pneumococcal v...

  16. Clinical and bacteriological characteristics of invasive pneumococcal disease after pneumococcal 10-valent conjugate vaccine implementation in Salvador, Brazil

    OpenAIRE

    Carolina Regis Leite; Jailton Azevedo; Vivian Santos Galvão; Otávio Moreno-Carvalho; Joice Neves Reis; Cristiana Nascimento-Carvalho

    2016-01-01

    Abstract Invasive pneumococcal disease is a relevant public health problem in Brazil, especially among children and the elderly. In July/2010 a 10-valent pneumococcal conjugate vaccine was introduced to the immunization schedule of Brazilian children under two years of age. Between July/2010 and December/2013 we conducted a case-series study on invasive pneumococcal disease in Salvador, Brazil to describe the clinical and bacteriological profile of invasive pneumococcal disease cases during t...

  17. SMC is recruited to oriC by ParB and promotes chromosome segregation in Streptococcus pneumoniae

    NARCIS (Netherlands)

    Minnen, Anita; Attaiech, Laetitia; Thon, Maria; Gruber, Stephan; Veening, Jan-Willem

    2011-01-01

    Segregation of replicated chromosomes is an essential process in all organisms. How bacteria, such as the oval-shaped human pathogen Streptococcus pneumoniae, efficiently segregate their chromosomes is poorly understood. Here we show that the pneumococcal homologue of the DNA-binding protein ParB re

  18. A Biomathematical Model of Pneumococcal Lung Infection and Antibiotic Treatment in Mice.

    Directory of Open Access Journals (Sweden)

    Sibylle Schirm

    Full Text Available Pneumonia is considered to be one of the leading causes of death worldwide. The outcome depends on both, proper antibiotic treatment and the effectivity of the immune response of the host. However, due to the complexity of the immunologic cascade initiated during infection, the latter cannot be predicted easily. We construct a biomathematical model of the murine immune response during infection with pneumococcus aiming at predicting the outcome of antibiotic treatment. The model consists of a number of non-linear ordinary differential equations describing dynamics of pneumococcal population, the inflammatory cytokine IL-6, neutrophils and macrophages fighting the infection and destruction of alveolar tissue due to pneumococcus. Equations were derived by translating known biological mechanisms and assuming certain response kinetics. Antibiotic therapy is modelled by a transient depletion of bacteria. Unknown model parameters were determined by fitting the predictions of the model to data sets derived from mice experiments of pneumococcal lung infection with and without antibiotic treatment. Time series of pneumococcal population, debris, neutrophils, activated epithelial cells, macrophages, monocytes and IL-6 serum concentrations were available for this purpose. The antibiotics Ampicillin and Moxifloxacin were considered. Parameter fittings resulted in a good agreement of model and data for all experimental scenarios. Identifiability of parameters is also estimated. The model can be used to predict the performance of alternative schedules of antibiotic treatment. We conclude that we established a biomathematical model of pneumococcal lung infection in mice allowing predictions regarding the outcome of different schedules of antibiotic treatment. We aim at translating the model to the human situation in the near future.

  19. Prevent Pneumonia

    Centers for Disease Control (CDC) Podcasts

    2015-08-06

    CDC’s Matthew Westercamp explains what pneumonia is, its symptoms, and how to prevent it.  Created: 8/6/2015 by National Center for Immunization and Respiratory Diseases (NCIRD), Division of Bacterial Diseases (DBD), Respiratory Diseases Branch (RDB).   Date Released: 8/6/2015.

  20. Atypical pneumonia

    Science.gov (United States)

    ... America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis . 2007;44:S27-S72. PMID: 17278083 ... by: Denis Hadjiliadis, MD, Associate Professor of Medicine, Pulmonary, Allergy and Critical Care, Perelman ...

  1. A Serine-Threonine Kinase (StkP Regulates Expression of the Pneumococcal Pilus and Modulates Bacterial Adherence to Human Epithelial and Endothelial Cells In Vitro.

    Directory of Open Access Journals (Sweden)

    Jenny A Herbert

    Full Text Available The pneumococcal serine threonine protein kinase (StkP acts as a global regulator in the pneumococcus. Bacterial mutants deficient in StkP are less virulent in animal models of infection. The gene for this regulator is located adjacent to the gene for its cognate phosphatase in the pneumococcal genome. The phosphatase dephosphorylates proteins phosphorylated by StkP and has been shown to regulate a number of key pneumococcal virulence factors and to modulate adherence to eukaryotic cells. The role of StkP in adherence of pneumococci to human cells has not previously been reported. In this study we show StkP represses the pneumococcal pilus, a virulence factor known to be important for bacterial adhesion. In a serotype 4 strain regulation of the pilus by StkP modulates adherence to human brain microvascular endothelial cells (HBMEC and human lung epithelial cells. This suggests that the pneumococcal pilus may play a role in adherence during infections such as meningitis and pneumonia. We show that regulation of the pilus occurs at the population level as StkP alters the number of pili-positive cells within a single culture. As far as we are aware this is the first gene identified outside of the pilus islet that regulates the biphasic expression of the pilus. These findings suggest StkPs role in cell division may be linked to regulation of expression of a cell surface adhesin.

  2. Xylitol-supplemented nutrition enhances bacterial killing and prolongs survival of rats in experimental pneumococcal sepsis

    Directory of Open Access Journals (Sweden)

    Svanberg Martti

    2008-03-01

    Full Text Available Abstract Background Xylitol has antiadhesive effects on Streptococcus pneumoniae and inhibits its growth, and has also been found to be effective in preventing acute otitis media and has been used in intensive care as a valuable source of energy. Results We evaluated the oxidative burst of neutrophils in rats fed with and without xylitol. The mean increase in the percentage of activated neutrophils from the baseline was higher in the xylitol-exposed group than in the control group (58.1% vs 51.4%, P = 0.03 for the difference and the mean induced increase in the median strength of the burst per neutrophil was similarly higher in the xylitol group (159.6 vs 140.3, P = 0.04. In two pneumococcal sepsis experiments rats were fed either a basal powder diet (control group or the same diet supplemented with 10% or 20% xylitol and infected with an intraperitoneal inoculation of S. pneumoniae after two weeks. The mean survival time was 48 hours in the xylitol groups and 34 hours in the control groups (P Conclusion Xylitol has beneficial effects on both the oxidative killing of bacteria in neutrophilic leucocytes and on the survival of rats with experimental pneumococcal sepsis.

  3. Xylitol-supplemented nutrition enhances bacterial killing and prolongs survival of rats in experimental pneumococcal sepsis

    Science.gov (United States)

    Renko, Marjo; Valkonen, Päivi; Tapiainen, Terhi; Kontiokari, Tero; Mattila, Pauli; Knuuttila, Matti; Svanberg, Martti; Leinonen, Maija; Karttunen, Riitta; Uhari, Matti

    2008-01-01

    Background Xylitol has antiadhesive effects on Streptococcus pneumoniae and inhibits its growth, and has also been found to be effective in preventing acute otitis media and has been used in intensive care as a valuable source of energy. Results We evaluated the oxidative burst of neutrophils in rats fed with and without xylitol. The mean increase in the percentage of activated neutrophils from the baseline was higher in the xylitol-exposed group than in the control group (58.1% vs 51.4%, P = 0.03 for the difference) and the mean induced increase in the median strength of the burst per neutrophil was similarly higher in the xylitol group (159.6 vs 140.3, P = 0.04). In two pneumococcal sepsis experiments rats were fed either a basal powder diet (control group) or the same diet supplemented with 10% or 20% xylitol and infected with an intraperitoneal inoculation of S. pneumoniae after two weeks. The mean survival time was 48 hours in the xylitol groups and 34 hours in the control groups (P < 0.001 in log rank test). Conclusion Xylitol has beneficial effects on both the oxidative killing of bacteria in neutrophilic leucocytes and on the survival of rats with experimental pneumococcal sepsis. PMID:18334022

  4. TNF Drives Monocyte Dysfunction with Age and Results in Impaired Anti-pneumococcal Immunity.

    Directory of Open Access Journals (Sweden)

    Alicja Puchta

    2016-01-01

    Full Text Available Monocyte phenotype and output changes with age, but why this occurs and how it impacts anti-bacterial immunity are not clear. We found that, in both humans and mice, circulating monocyte phenotype and function was altered with age due to increasing levels of TNF in the circulation that occur as part of the aging process. Ly6C+ monocytes from old (18-22 mo mice and CD14+CD16+ intermediate/inflammatory monocytes from older adults also contributed to this "age-associated inflammation" as they produced more of the inflammatory cytokines IL6 and TNF in the steady state and when stimulated with bacterial products. Using an aged mouse model of pneumococcal colonization we found that chronic exposure to TNF with age altered the maturity of circulating monocytes, as measured by F4/80 expression, and this decrease in monocyte maturation was directly linked to susceptibility to infection. Ly6C+ monocytes from old mice had higher levels of CCR2 expression, which promoted premature egress from the bone marrow when challenged with Streptococcus pneumoniae. Although Ly6C+ monocyte recruitment and TNF levels in the blood and nasopharnyx were higher in old mice during S. pneumoniae colonization, bacterial clearance was impaired. Counterintuitively, elevated TNF and excessive monocyte recruitment in old mice contributed to impaired anti-pneumococcal immunity since bacterial clearance was improved upon pharmacological reduction of TNF or Ly6C+ monocytes, which were the major producers of TNF. Thus, with age TNF impairs inflammatory monocyte development, function and promotes premature egress, which contribute to systemic inflammation and is ultimately detrimental to anti-pneumococcal immunity.

  5. Impact of Pneumococcal Conjugate Universal Routine Vaccination on Pneumococcal Disease in Italian Children.

    Science.gov (United States)

    Fortunato, Francesca; Martinelli, Domenico; Cappelli, Maria Giovanna; Cozza, Vanessa; Prato, Rosa

    2015-01-01

    In Italy, the effectiveness of pneumococcal universal vaccination in preventing vaccine-type invasive pneumococcal disease (IPD) in the PCV7/PCV13 shifting period was estimated to be 84.3% (95% CI: 84.0-84.6%) in children children vaccination history, with a nearly 40% reduction of hospitalizations for both outcomes. Our findings provide further evidence of the effectiveness of PCVs against pneumococcal diseases and its impact on nasopharyngeal carriage in children <5 years, indicating the importance of maintaining high immunization coverage.

  6. Streptococcus pneumoniae carriage in the Gaza strip.

    Directory of Open Access Journals (Sweden)

    Gili Regev-Yochay

    Full Text Available BACKGROUND: Pneumococcal infections cause major morbidity and mortality in developing countries. We report the epidemiology of S. pneumoniae carriage in a developing region, the Gaza strip, and evaluate the theoretical coverage of carriage strains by pneumococcal conjugate vaccines (PCVs. METHODOLOGY: In 2009 we conducted a cross-sectional survey of S. pneumoniae carriage in healthy children and their parents, living throughout the Gaza strip. Data were collected and nasopharyngeal swabs were obtained. Antibiotic susceptibilities were determined by Vitek-2 and serotypes by the Quellung reaction. PRINCIPAL FINDINGS: S. pneumoniae carriage was detected in 189/379 (50% of children and 30/376 (8% of parents. Carriage prevalence was highest in children <6 months of age (63%. Significant predictors for child carriage were number of household members and DCC attendance. The proportion of pediatric and adults isolates with serotypes included in PCV7 were 32% and 20% respectively, and 46% and 33% in PCV13 respectively. The most prominent non-vaccine serotypes (NVT were 35B, 15B/C and 23B. Penicillin-nonsusceptible strains were carried by 70% of carriers, penicillin-resistant strains (PRSP by 13% and Multi-drug-resistant (MDR by 30%. Of all PRSP isolates 54% belonged to serotypes included in PCV7 and 71% in the PCV13. Similarly, 59% and 73% of MDR-SP isolates, would theoretically be covered by PCV7 and PCV13, respectively. CONCLUSIONS: This study demonstrates that, PCV13-included strains were carried by 46% and 33% of pediatric and adult subjects respectively. In the absence of definitive data regarding the virulence of the NVT strains, it is difficult to predict the effect of PCVs on IPD in this region.

  7. Comparison of a Classical Phagocytosis Assay and a Flow Cytometry Assay for Assessment of the Phagocytic Capacity of Sera from Adults Vaccinated with a Pneumococcal Conjugate Vaccine

    OpenAIRE

    Jansen, Wouter T. M.; Väkeväinen-Anttila, Merja; Käyhty, Helena; Nahm, Moon; Bakker, N.; Verhoef, Jan; Snippe, Harm; Verheul, André F. M.

    2001-01-01

    Antibody- and complement-mediated phagocytosis is the main defense mechanism against Streptococcus pneumoniae. A standardized, easy to perform phagocytosis assay for pneumococci would be a great asset for the evaluation of the potential efficacy of (experimental) pneumococcal vaccines. Such an assay could replace the laborious phagocytosis assay of viable pneumococci (classical killing assay). Therefore, a newly developed phagocytosis assay based on flow cytometry (flow assay) was compared wi...

  8. Effects of recombinant IL-17F intranasal inoculation against Streptococcus pneumoniae infection in a murine model.

    Science.gov (United States)

    Chen, Ling; Guo, Sheng; Wu, Liangxia; Hao, Chunli; Xu, Wanting; Zhang, Jianhua

    2015-01-01

    Interleukin-17F (IL-17F) is an important member of IL-17 cytokine family, which plays important roles in host defense against microbial infections. Streptococcus pneumoniae is a common pathogen associated with several invasive and noninvasive pneumococcal diseases, and mucosal immune response plays crucial roles in defenses against pneumococcal infection. Thus, intranasal inoculation may be an alternative approach against pneumococci. In this study, BALB/c mice were intranasally inoculated with recombinant IL-17F (rIL-17F) prior to S. pneumoniae (American Type Culture Collection 6303, serotype 3) infection. As compared with the control group, numbers of total leukocyte, neutrophil, and macrophage in lungs were significantly increased in mice inoculated with rIL-17F. The levels of macrophage inflammatory protein 1α (MIP-1α), MIP-2β, and interferon γ were significantly increased in bronchoalveolar lavage fluid and culture supernatant of splenocytes from mice inoculated with rIL-17F. rIL-17F inoculation also significantly elevated β-defensin-2 expression in lung tissues. Furthermore, compared with S. pneumoniae infection group, rIL-17F inoculation prior to infection significantly reduced S. pneumoniae colonization in lungs. These findings demonstrated that rIL-17F intranasal inoculation strengthened host defense against pneumococci, which may be developed to prevent pneumococcal infection. PMID:25196250

  9. Use of 23-valent pneumococcal polysaccharide vaccine and 13-valent pneumococcal conjugate vaccine among adults%23价肺炎链球菌多糖疫苗和13价肺炎链球菌结合疫苗在成年人中的应用

    Institute of Scientific and Technical Information of China (English)

    朱朗; 陈磊; 林纪胜; 高强; 王见冬; 王新立; 蔡芳

    2015-01-01

    Streptococcus pneumoniae is an important pathogen causing serious diseases such as pneumonia, septicemia and meningitis in people of all ages, especially in young children and the eldly worldwide.These diseases can be prevented by pneumococcal vaccines.In countries where pneumococcal vaccines have been introduced in national immunization program, the incidence of pneumococcal diseases and the carriage of pneumococcal vaccine serotypes decreased dramatically in children, and indirect herd protection was developed among unvaccinated people.The utilization of 23-valent pneumococcal polysaccharide vaccine and 13-valent pneumococcal conjugate vaccine are discussed in this article.%肺炎链球菌是引起全球不同年龄人群,尤其是幼儿和老年人肺炎、败血症和脑膜炎等严重疾病的重要病原菌,由肺炎链球菌导致的这些疾病可以通过疫苗进行预防.在将肺炎链球菌疫苗纳入国家免疫计划的国家,儿童肺炎链球菌病的发病率以及疫苗型肺炎链球菌的携带率大大降低,且可在未免疫人群中产生间接保护作用.此文对23价肺炎链球菌多糖疫苗和1 3价肺炎链球菌结合疫苗在成年人中的应用进行探讨.

  10. Female resistance to pneumonia identifies lung macrophage nitric oxide synthase-3 as a therapeutic target

    DEFF Research Database (Denmark)

    Yang, Zhiping; Huang, Yuh-Chin T; Koziel, Henry;

    2014-01-01

    To identify new approaches to enhance innate immunity to bacterial pneumonia, we investigated the natural experiment of gender differences in resistance to infections. Female and estrogen-treated male mice show greater resistance to pneumococcal pneumonia, seen as greater bacterial clearance......). Epidemiologic data show decreased hospitalization for pneumonia in women receiving estrogen or statins (known to activate NOS3). Pharmacologic targeting of NOS3 with statins or another small-molecule compound (AVE3085) enhanced macrophage bacterial killing, improved bacterial clearance, and increased host...... survival in both primary and secondary (post-influenza) pneumonia. The data identify a novel mechanism for host defense via NOS3 and suggest a potential therapeutic strategy to reduce secondary bacterial pneumonia after influenza....

  11. Aromatic Esters of Bicyclic Amines as Antimicrobials against Streptococcus pneumoniae.

    Science.gov (United States)

    de Gracia Retamosa, María; Díez-Martínez, Roberto; Maestro, Beatriz; García-Fernández, Esther; de Waal, Bas; Meijer, E W; García, Pedro; Sanz, Jesús M

    2015-11-01

    A double approach was followed in the search of novel inhibitors of the surface choline-binding proteins (CBPs) of Streptococcus pneumoniae (pneumococcus) with antimicrobial properties. First, a library of 49 rationally-designed esters of alkyl amines was screened for their specific binding to CBPs. The best binders, being esters of bicyclic amines (EBAs), were then tested for their in vitro effect on pneumococcal growth and morphology. Second, the efficiency of EBA-induced CBP inhibition was enhanced about 45,000-fold by multivalency effects upon synthesizing a poly(propylene imine) dendrimer containing eight copies of an atropine derivative. Both approaches led to compounds that arrest bacterial growth, dramatically decrease cell viability, and exhibit a protection effect in animal disease models, demonstrating that the pneumococcal CBPs are adequate targets for the discovery of novel antimicrobials that overcome the currently increasing antimicrobial resistance issues. PMID:26377931

  12. Biological and Epidemiological Features of Antibiotic-Resistant Streptococcus pneumoniae in Pre- and Post-Conjugate Vaccine Eras: a United States Perspective.

    Science.gov (United States)

    Kim, Lindsay; McGee, Lesley; Tomczyk, Sara; Beall, Bernard

    2016-07-01

    Streptococcus pneumoniae inflicts a huge disease burden as the leading cause of community-acquired pneumonia and meningitis. Soon after mainstream antibiotic usage, multiresistant pneumococcal clones emerged and disseminated worldwide. Resistant clones are generated through adaptation to antibiotic pressures imposed while naturally residing within the human upper respiratory tract. Here, a huge array of related commensal streptococcal strains transfers core genomic and accessory resistance determinants to the highly transformable pneumococcus. β-Lactam resistance is the hallmark of pneumococcal adaptability, requiring multiple independent recombination events that are traceable to nonpneumococcal origins and stably perpetuated in multiresistant clonal complexes. Pneumococcal strains with elevated MICs of β-lactams are most often resistant to additional antibiotics. Basic underlying mechanisms of most pneumococcal resistances have been identified, although new insights that increase our understanding are continually provided. Although all pneumococcal infections can be successfully treated with antibiotics, the available choices are limited for some strains. Invasive pneumococcal disease data compiled during 1998 to 2013 through the population-based Active Bacterial Core surveillance program (U.S. population base of 30,600,000) demonstrate that targeting prevalent capsular serotypes with conjugate vaccines (7-valent and 13-valent vaccines implemented in 2000 and 2010, respectively) is extremely effective in reducing resistant infections. Nonetheless, resistant non-vaccine-serotype clones continue to emerge and expand. PMID:27076637

  13. Drug-resistance in Streptococcus pneumoniae isolates among Spanish middle aged and older adults with community-acquired pneumonia

    Directory of Open Access Journals (Sweden)

    Raga-Luria Xavier

    2009-03-01

    Full Text Available Abstract Background Pneumococcal diseases remain a major cause of morbidity and mortality worldwide. Updated data on drug-resistance from different populations may be important to recognize changes in disease patterns. This study assessed current levels of penicilin resistance among Streptococcus Pneumoniae causing pneumonia in Spanish middle age and older adults. Methods Antimicrobial susceptibility was tested for 104 consecutive isolates of Streptococcus pneumoniae recovered from patients 50 years or older with radiographically confirmed pneumonia in the region of Tarragona (Spain between 2002 and 2007. According to the minimum inhibitory concentration of tested antimicrobials (penicillin, erythromycin, cefotaxime and levofloxacin strains were classified as susceptible or resistant. Antimicrobial resistance was determined for early cases (2002–2004 and contemporary cases (2005–2007. Results Twenty-seven (25.9% were penicillin-resistant strains (19 strains with intermediate resistance and 8 strains with high resistance. Penicillin-resistance was higher in 2002–2004 than in 2005–2007 (39.5% vs 18.2%, p = 0.017. Of 27 penicillin-resistant strains, 10 (37% were resistant to erythromycin, 8 (29.6% to cefotaxime, 2 (7.4% to levofloxacin, and 4 (14.8% were identified as multidrug resistant. Case-fatality rate was higher among those patients who had an infection caused by any penicillin susceptible strain (16.9% than in those with infections due to penicillin-resistant strains. Conclusion Resistance to penicillin among Streptococcus pneumoniae remains high, but such resistance does not result in increased mortality in patients with pneumococcal pneumonia.

  14. Streptococcus pneumoniae biofilm formation and dispersion during colonization and disease

    Directory of Open Access Journals (Sweden)

    Yashuan eChao

    2015-01-01

    Full Text Available Streptococcus pneumoniae (the pneumococcus is a common colonizer of the human nasopharynx. Despite a low rate of invasive disease, the high prevalence of colonization results in millions of infections and over 1 million deaths per year, mostly in individuals under the age of 5 and the elderly. Colonizing pneumococci form well-organized biofilm communities in the nasopharyngeal environment, but the specific role of biofilms and their interaction with the host during colonization and disease is not yet clear. Pneumococci in biofilms are highly resistant to antimicrobial agents and this phenotype can be recapitulated when pneumococci are grown on respiratory epithelial cells under conditions found in the nasopharyngeal environment. Pneumococcal biofilms display lower levels of virulence in vivo and provide an optimal environment for increased genetic exchange both in vitro and in vivo, with increased natural transformation seen during co-colonization with multiple strains. Biofilms have also been detected on mucosal surfaces during pneumonia and middle ear infection, although the role of these biofilms in the disease process is debated. Recent studies have shown that changes in the nasopharyngeal environment caused by concomitant virus infection, changes in the microflora, inflammation, or other host assaults trigger active release of pneumococci from biofilms. These dispersed bacteria have distinct phenotypic properties and transcriptional profiles different from both biofilm and broth-grown, planktonic bacteria, resulting in a significantly increased virulence in vivo.In this review we discuss the properties of pneumococcal biofilms, the role of biofilm formation during pneumococcal colonization, including their propensity for increased ability to exchange genetic material, as well as mechanisms involved in transition from asymptomatic biofilm colonization to dissemination and disease of otherwise sterile sites. Greater understanding of

  15. FastStats: Pneumonia

    Science.gov (United States)

    ... this? Submit What's this? Submit Button NCHS Home Pneumonia Recommend on Facebook Tweet Share Compartir Data are ... Mortality data Centers for Disease Control and Prevention: Pneumonia American Lung Association : Pneumonia Get Email Updates To ...

  16. What Is Pneumonia?

    Science.gov (United States)

    ... page from the NHLBI on Twitter. What Is Pneumonia? Pneumonia (nu-MO-ne-ah) is an infection in ... such as bacteria, viruses, and fungi—can cause pneumonia. The infection inflames your lungs' air sacs, which ...

  17. Mycoplasma pneumoniae Infections

    Science.gov (United States)

    ... Issues Listen Español Text Size Email Print Share Mycoplasma pneumoniae Infections Page Content Article Body Some lung ... walking pneumonia), are caused by an organism called Mycoplasma pneumoniae. It is spread from person to person ...

  18. [Pathogenicity and pneumococcal capsular genes].

    Science.gov (United States)

    García, E; García, P; López, R

    1994-01-01

    Pneumococci remain to be one of the most prominent human pathogens. Increasing efforts are being dedicated to the development of improved vaccines with wider specificity. Since a clear understanding of the genetics of capsular types in Streptococcus pneumoniae is missing, our efforts are oriented to characterize, at the molecular level, the genes involved in capsular polysaccharide biosynthesis. We have cloned and sequenced a chromosomal DNA fragment of a clinical isolate of type 3 pneumococcus and showed that it contains a type 3 specific gene as well as genes common to other serotypes.

  19. Contribution of IL-1 to resistance to Streptococcus pneumoniae infection.

    Science.gov (United States)

    Kafka, Daniel; Ling, Eduard; Feldman, Galia; Benharroch, Daniel; Voronov, Elena; Givon-Lavi, Noga; Iwakura, Yoichiro; Dagan, Ron; Apte, Ron N; Mizrachi-Nebenzahl, Yaffa

    2008-09-01

    The role of IL-1 in susceptibility to Streptococcus pneumoniae infection was studied in mice deficient in genes of the IL-1 family [i.e. IL-1alpha-/-, IL-1beta-/-, IL-1alpha/beta-/- and IL-1R antagonist (IL-1Ra)-/- mice] following intra-nasal inoculation. Intra-nasal inoculation of S. pneumoniae of IL-1beta-/- and IL-1alpha/beta-/- mice displayed significantly lower survival rates and higher nasopharyngeal and lung bacterial load as compared with control, IL-1alpha-/- and IL-1Ra-/- mice. Treatment of IL-1beta-/- mice with rIL-1beta significantly improved their survival. A significant increase in blood neutrophils was found in control, IL-1alpha-/- and IL-1Ra-/- but not in IL-1beta-/- and IL-1alpha/beta-/- mice. Local infiltrates of neutrophils and relatively preserved organ architecture were observed in the lungs of IL-1alpha-/- and control mice. However, S. pneumoniae-infected IL-1beta-/-, IL-1alpha/beta-/- and IL-1Ra-/- mice demonstrated diffuse pneumonia and tissue damage. Altogether, all three isoforms contribute to protection against S. pneumoniae; our results point to differential role of IL-1alpha and IL-1beta in the pathogenesis and control of S. pneumoniae infection and suggest that IL-1beta has a major role in resistance to primary pneumococcal infection while the role of IL-1alpha is less important.

  20. Acute Disseminated Encephalomyelitis Following Pneumococcal Meningitis Infection

    OpenAIRE

    Majzoobi; Mamani; Ghiasian; Abdoli

    2014-01-01

    Introduction Acute disseminated encephalomyelitis (ADEM) is an acute inflammatory and demyelinating disease of the central nervous system, resulting in various neurological symptoms. Usually, the disease appears following vaccination or systemic viral infections. In rare cases, the disease appears following pneumococcal infections. Case Presentation The patient was a 27 year-old man who was referred to the clinic following a few d...

  1. Continued Impact of Pneumococcal Conjugate Vaccine on Carriage in Young Children

    Science.gov (United States)

    Huang, Susan S.; Hinrichsen, Virginia L.; Stevenson, Abbie E.; Rifas-Shiman, Sheryl L.; Kleinman, Ken; Pelton, Stephen I.; Lipsitch, Marc; Hanage, William P.; Lee, Grace M.; Finkelstein, Jonathan A.

    2009-01-01

    OBJECTIVES The goals were to assess serial changes in Streptococcus pneumoniae serotypes and antibiotic resistance in young children and to evaluate whether risk factors for carriage have been altered by heptavalent pneumococcal conjugate vaccine (PCV7). METHODS Nasopharyngeal specimens and questionnaire/medical record data were obtained from children 3 months to <7 years of age in primary care practices in 16 Massachusetts communities during the winter seasons of 2000–2001 and 2003–2004 and in 8 communities in 2006–2007. Antimicrobial susceptibility testing and serotyping were performed with S pneumoniae isolates. RESULTS We collected 678, 988, and 972 specimens during the sampling periods in 2000–2001, 2003–2004, and 2006–2007, respectively. Carriage of non-PCV7 serotypes increased from 15% to 19% and 29% (P < .001), with vaccine serotypes decreasing to 3% of carried serotypes in 2006–2007. The relative contribution of several non-PCV7 serotypes, including 19A, 35B, and 23A, increased across sampling periods. By 2007, commonly carried serotypes included 19A (16%), 6A (12%), 15B/C (11%), 35B (9%), and 11A (8%), and high-prevalence serotypes seemed to have greater proportions of penicillin nonsusceptibility. In multivariate models, common predictors of pneumococcal carriage, such as child care attendance, upper respiratory tract infection, and the presence of young siblings, persisted. CONCLUSIONS The virtual disappearance of vaccine serotypes in S pneumoniae carriage has occurred in young children, with rapid replacement with penicillin-nonsusceptible nonvaccine serotypes, particularly 19A and 35B. Except for the age group at highest risk, previous predictors of carriage, such as child care attendance and the presence of young siblings, have not been changed by the vaccine. PMID:19564254

  2. Nanogel-based PspA intranasal vaccine prevents invasive disease and nasal colonization by Streptococcus pneumoniae.

    Science.gov (United States)

    Kong, Il Gyu; Sato, Ayuko; Yuki, Yoshikazu; Nochi, Tomonori; Takahashi, Haruko; Sawada, Shinichi; Mejima, Mio; Kurokawa, Shiho; Okada, Kazunari; Sato, Shintaro; Briles, David E; Kunisawa, Jun; Inoue, Yusuke; Yamamoto, Masafumi; Akiyoshi, Kazunari; Kiyono, Hiroshi

    2013-05-01

    To establish a safer and more effective vaccine against pneumococcal respiratory infections, current knowledge regarding the antigens common among pneumococcal strains and improvements to the system for delivering these antigens across the mucosal barrier must be integrated. We developed a pneumococcal vaccine that combines the advantages of pneumococcal surface protein A (PspA) with a nontoxic intranasal vaccine delivery system based on a nanometer-sized hydrogel (nanogel) consisting of a cationic cholesteryl group-bearing pullulan (cCHP). The efficacy of the nanogel-based PspA nasal vaccine (cCHP-PspA) was tested in murine pneumococcal airway infection models. Intranasal vaccination with cCHP-PspA provided protective immunity against lethal challenge with Streptococcus pneumoniae Xen10, reduced colonization and invasion by bacteria in the upper and lower respiratory tracts, and induced systemic and nasal mucosal Th17 responses, high levels of PspA-specific serum immunoglobulin G (IgG), and nasal and bronchial IgA antibody responses. Moreover, there was no sign of PspA delivery by nanogel to either the olfactory bulbs or the central nervous system after intranasal administration. These results demonstrate the effectiveness and safety of the nanogel-based PspA nasal vaccine system as a universal mucosal vaccine against pneumococcal respiratory infection. PMID:23460513

  3. Discovery of prenylated flavonoids with dual activity against influenza virus and Streptococcus pneumoniae

    Science.gov (United States)

    Grienke, Ulrike; Richter, Martina; Walther, Elisabeth; Hoffmann, Anja; Kirchmair, Johannes; Makarov, Vadim; Nietzsche, Sandor; Schmidtke, Michaela; Rollinger, Judith M.

    2016-01-01

    Influenza virus neuraminidase (NA) is the primary target for influenza therapeutics. Severe complications are often related to secondary pneumonia caused by Streptococcus pneumoniae (pneumococci), which also express NAs. Recently, a NA-mediated lethal synergism between influenza A viruses and pneumococci was described. Therefore, dual inhibitors of both viral and bacterial NAs are expected to be advantageous for the treatment of influenza. We investigated the traditional Chinese herbal drug sāng bái pí (mulberry root bark) as source for anti-infectives. Two prenylated flavonoid derivatives, sanggenon G (4) and sanggenol A (5) inhibited influenza A viral and pneumococcal NAs and, in contrast to the approved NA inhibitor oseltamivir, also planktonic growth and biofilm formation of pneumococci. Evaluation of 27 congeners of 5 revealed a correlation between the degree of prenylation and bioactivity. Abyssinone-V 4′-methyl ether (27) inhibited pneumococcal NA with IC50 = 2.18 μM, pneumococcal growth with MIC = 5.63 μM, and biofilm formation with MBIC = 4.21 μM, without harming lung epithelial cells. Compounds 5 and 27 also disrupt the synergism between influenza A virus and pneumococcal NA in vitro, hence functioning as dual-acting anti-infectives. The results warrant further studies on whether the observed disruption of this synergism is transferable to in vivo systems. PMID:27257160

  4. Host immunity in the protective response to nasal immunization with a pneumococcal antigen associated to live and heat-killed Lactobacillus casei

    Directory of Open Access Journals (Sweden)

    Vintiñi Elisa O

    2011-08-01

    Full Text Available Abstract Background At present, available pneumococcal vaccines have failed to eradicate infections caused by S. pneumoniae. Search for effective vaccine continues and some serotype independent pneumococcal proteins are considered as candidates for the design of new vaccines, especially a mucosal vaccine, since pneumococci enter the body through mucosal surfaces. Selection of the appropriate adjuvant is important for mucosal vaccines, and lactic acid bacteria (LAB with immunostimulant properties are promissory candidates. In this work, we assessed the adjuvant effect of a probiotic strain, Lactobacillus casei (L. casei, when nasally administered with a pneumococcal antigen (pneumococcal protective protein A: PppA for the prevention of pneumococcal infection. Adjuvanticity of both live (LcV and heat-killed (LcM was evaluated and humoral and cellular antigen-specific immune response was assessed in mucosal and systemic compartments. The potential mechanisms induced by nasal immunization were discussed. Results Nasal immunization of young mice with PppA+LcV and PppA+LcM induced anti-PppA IgA and IgG antibodies in mucosal and systemic compartments and levels of these specific antibodies remained high even at day 45 after the 3rd Immunization (3rd I. These results were correlated with IL-4 induction by the mixture of antigen plus LcV and LcM. Also, PppA+Lc (V and M induced stimulation of Th1 and Th17 cells involved in the defence against pneumococci. The protection against pneumococcal respiratory challenge at day 30 after the 3rd I showed that PppA+LcV and PppA+LcM immunizations significantly reduced pathogen counts in nasal lavages while prventing their passage into lung and blood. Survival of mice immunized with the co-application of PppA plus LcV and LcM was significantly higher than in mice immunized with PppA alone and control mice when intraperitoneal challenge was performed. No significant differences between the treatments involving LcV and

  5. Effectiveness and cost-effectiveness of general immunisation of infants and young children with the heptavalent conjugated pneumococcal vaccine

    Directory of Open Access Journals (Sweden)

    Stürzlinger, Heidi

    2005-11-01

    Full Text Available Background: The European Agency for the Evaluation of Medicinal Products (EMEA granted market authorisation to the heptavalent pneumococcal vaccine Prevenar (Wyeth in the year 2001. The indication of Prevenar is the active immunisation of infants and young children under the age of two against invasive disease caused by Streptococcus pneumonia serotypes 4, 6B, 9V, 14, 18C, 19F and 23F. At the time of this study the German vaccination scheme advises the immunisation with Prevenar only for children at high risk. Objectives: The objective of the study is first to determine the efficacy and effectiveness of the immunisation of all children with the heptavalent conjugated pneumococcal vaccine in Germany and second, whether a general recommendation for vaccination of all children would be cost-effective. Methods: A systematic literature search was performed in 29 relevant databases for the period of January 1999 to June 2004. Thus 1,884 articles were identified which were then assessed according to predefined selection criteria. Results: There is evidence for the medical effectiveness of Prevenar against invasive pneumococcal disease caused by the covered serotypes from a major double-blinded RCT undertaken in California. The vaccine shows lower values of effectiveness against otitis media and pneumonia. The values for effectiveness of the vaccine in Germany are below the data for California because of the different incidence of Serotypes. The cost-effectiveness rates for an immunisation of all children with Prevenar vary across different countries. One reason - besides different Health Systems - can be seen in the uncertainty about the duration of protection, another in the assumption on regional serotype coverage of the vaccine. From the healthcare payers' perspective a general vaccination of all children in Germany is not cost-effective, from a societal perspective the benefits from vaccination could prevail the cost. The actual price of the

  6. Molecular characterization of Streptococcus pneumoniae isolated from children in Suzhou before the introduction of pneumococcal vaccine%疫苗引入前苏州地区儿童肺炎链球菌的分子流行病学特征研究

    Institute of Scientific and Technical Information of China (English)

    耿倩; 张涛; 陈蓉; 丁云芳; 郝创利; 林玉尊; Steven Black; 赵根明

    2014-01-01

    目的 了解苏州地区在7价肺炎链球菌结合疫苗(7 heptavalent pneumococcal conjugate vaccine,PCV7)引入前,不同临床治疗压力下肺炎链球菌分离株的耐药特征、血清分型及国际流行耐药克隆株(pneumococcal molecular epidemiology network,PMEN)的流行情况.方法 收集2006年3月~2007年3月期间苏州大学附属儿童医院住院治疗的呼吸道感染儿童(病例组)和非呼吸道感染儿童(对照组)中分离的肺炎链球菌134株,进行抗生素敏感性分析和血清型分型,并对其中86株大环内酯类药物菌株进行基因分型.结果 病例组抗生素的使用率高于对照组(x2=111.19,P<0.001).病例组分离的菌株血清型以19F、19A和14为主,对照组菌株常见的血清型为6B、19F和23F,两组PCV7血清型覆盖率分别为58.3%和68.1%.对照组菌株对常用抗生素的敏感性均高于病例组(均有P <0.05).菌株基因分型共检测出10种PMEN克隆株,最常见的为Taiwan19F-14克隆株.PMEN克隆株对常用抗菌药物的不敏感率高于非PMEN克隆株.结论 在我国引入PCV7前,在抗生素等治疗压力下,苏州地区肺炎链球菌的耐药情况严重,以Taiwan19F-14克隆株流行为主,多种PMEN克隆株并存.

  7. Genome-wide identification of Streptococcus pneumoniae genes essential for bacterial replication during experimental meningitis

    DEFF Research Database (Denmark)

    Molzen, T E; Burghout, P; Bootsma, H J;

    2010-01-01

    Meningitis is the most serious of invasive infections caused by the Gram-positive bacterium Streptococcus pneumoniae. Vaccines protect only against a limited number of serotypes, and evolving bacterial resistance to antimicrobials impedes treatment. Further insight into the molecular pathogenesis...... genes mutants of which had become attenuated or enriched, respectively, during infection. The results point to essential roles for capsular polysaccharides, nutrient uptake, and amino acid biosynthesis in bacterial replication during experimental meningitis. The GAF phenotype of a subset of identified...... of invasive pneumococcal disease is required in order to enable the development of new or adjunctive treatments and/or pneumococcal vaccines that are efficient across serotypes. We applied genomic array footprinting (GAF) in the search for S. pneumoniae genes that are essential during experimental meningitis...

  8. Impacts of the 13-valent pneumococcal conjugate vaccine in children

    OpenAIRE

    Susanna Esposito; Nicola Principi

    2015-01-01

    Applications of the heptavalent pneumococcal conjugate vaccine (PCV7) in the pediatric immunization schedule have dramatically reduced the incidence of pneumococcal diseases in both vaccinated children and unvaccinated individuals of all ages. However, increased infections caused by non-PCV7 serotypes have been reported by several groups. To overcome this problem, new vaccines covering more serotypes including the emerging serotypes have been developed. The 13-valent pneumococcal conjugate va...

  9. Pneumococcal Conjugate Vaccine for Adults: A New Paradigm

    OpenAIRE

    Paradiso, Peter R

    2012-01-01

    A 13-valent pneumococcal conjugate vaccine has been studied in adults aged ≥50 years to compare the immune response to that induced by the 23-valent pneumococcal polysaccharide vaccine, which has been the standard of care over the past 30 years. The results demonstrate that adults, regardless of whether they are naive or previously vaccinated with the polysaccharide vaccine, have an overall superior antibody response when vaccinated with the conjugate vaccine compared with the pneumococcal po...

  10. Pneumococcal vaccination of older adults: Conjugate or polysaccharide?

    OpenAIRE

    Fedson, David S; Guppy, Martin J.

    2013-01-01

    Invasive pneumococcal disease continues to be important problem for older adults. Pneumococcal polysaccharide vaccine (PPV23) has a clinical effectiveness of 43–81%, and following primary vaccination and revaccination, antibody responses last 5–10 y. Hyporesponsiveness to a second dose of vaccine has not been shown to be a significant problem. The use of pneumococcal conjugate vaccines (initially PCV7; more recently PCV13) has led to a dramatic fall in the incidence of conjugate vaccine-type ...

  11. Meteorological effects on the incidence of pneumococcal bacteremia in Denmark

    DEFF Research Database (Denmark)

    Tvedebrink, Torben; Lundbye-Christensen, Søren; Thomsen, Reimar W.;

    The seasonal nature of invasive pneumococcal disease with peak incidences during winter months is well recognized (Dowell 2003, Talbot 2005, Watson 2006). However few detailed studies of the temporal relationship between actual climatic changes and subsequent pneumococcal disease are available. We...... perform an 8-year longitudinal population-based ecological study in a Danish county to examine whether foregoing changes in meteorological parameters, including temperature, relative humidity, precipitation, and wind velocity, predicted variations in pneumococcal bacteremia (PB) incidence....

  12. Multiplex PCR to determine Streptococcus pneumoniae serotypes causing otitis media in the Republic of Ireland with further characterisation of antimicrobial susceptibilities and genotypes.

    LENUS (Irish Health Repository)

    Vickers, I

    2011-03-01

    The purpose of this study was to determine the serotypes, genotypes and antimicrobial susceptibilities of Streptococcus pneumoniae causing otitis media (OM) in children in Dublin, Ireland. S. pneumoniae isolates (n = 28) from spontaneously discharging OM were studied. Serotyping was performed using a previously undescribed multiplex polymerase chain reaction (PCR) scheme in combination with serological methods. Multilocus sequence typing (MLST) was performed using standard procedures. Antimicrobial susceptibility testing was performed using the Etest method. Fourteen different S. pneumoniae serotypes were identified. The five most common serotypes were 3, 19F, 19A, 14 and 6A, which accounted for 68% of all infections. The 7-valent pneumococcal conjugate vaccine (PCV7), 10-valent pneumococcal conjugate vaccine (PHiD-CV) and 13-valent pneumococcal conjugate vaccine (PCV13) provided potential coverages of 43%, 46% and 86%, respectively. Reduced susceptibility to penicillin was evident for 25% of isolates and was associated with serotypes 14, 19A, 19F and 9V. A total of 21 different sequence types (STs) were identified. Pneumococcal Molecular Epidemiology Network (PMEN) clones or their variants represented 54% (15\\/28) of all isolates. Continued monitoring and characterisation of S. pneumoniae causing OM in Ireland is warranted in order to guide future vaccine and treatment policies.

  13. Treatment of Streptococcus pneumoniae disease in children%儿童肺炎链球菌性疾病的治疗

    Institute of Scientific and Technical Information of China (English)

    陆权

    2011-01-01

    肺炎链球菌性疾病(尤其侵袭性肺炎链球菌性疾病)是5岁以下儿童较常见的感染性疾病,肺炎链球菌对抗菌药物的耐药性给临床治疗带来新的挑战.本文综述儿科肺炎链球菌性疾病、肺炎链球菌的耐药现状,并重点评论肺炎链球菌性疾病的治疗策略,包括肺炎链球菌性肺炎、中耳炎、鼻窦炎、脑膜炎和其他侵袭性肺炎链球菌性疾病,积极防治肺炎链球菌性疾病将加速联合国千年发展目标的实现.%Streptococcus pneumoniae disease(PD) especially as invasive pneumococcal disease (IPD)is more common in children younger than 5. The resistance of Streptococcus pneumoniae against antibacterial agents brings new challenges for clinical treatment. This paper reviews PD and Streptococcus pneumoniae resistance, especially focuses on the strategies of treatment for PD including pneumococcal pneumonia, otitis media, sinusitis, meningitis and other invasive pneumococcal diseases. Active prevention and control of pneumococcal disease will speed up the implementation of the United Nations Millennium Development Goals.

  14. On the analysis of the virulence nature of TIGR4 and R6 strains of Streptococcus pneumoniae using genome comparison tools

    Indian Academy of Sciences (India)

    R Jothi; K Manikandakumar; K Ganesan; S Parthasarathy

    2007-09-01

    Comparative genome sequence analysis is a powerful technique for gaining insights into any genome of interest. Streptococcus pneumoniae is a human pathogen, which causes life-threatening diseases, such as pneumoniae, bacteremia, meningitis, etc. After the whole genome of two strains of S. pneumoniae, the virulent TIGR4 and non-pathogenic R6 were sequenced; there is a hope that comparing the genomes will allow an identification of the genes responsible for its virulence and thus the development of treatment and control. Many antimicrobial drugs have diminished the risk from pneumococcal disease because of its multi-drug resistance nature. Several pneumococcal proteins are also being investigated, as virulence factors as potential vaccine or drug targets. Structural and biochemical studies of these pneumococcal virulence factors have facilitated the development of novel antibiotics or protein antigen-based vaccines for the treatment of pneumococcal disease. Here we describe the comparison between the genomes of two strains of S. pneumoniae with few existing genomics databases and tools available in the public domain websites. By comparing nucleotide and protein sequences of the two strains, we investigate the existing differences and similarities. Mainly we focus on the virulence factors and its encoding genes in TIGR4 and how do they differ from R6 strain.

  15. KLF4-dependent IL-10 expression in lung epithelial cells by Streptococcus pneumoniae

    OpenAIRE

    Steinicke, Robert

    2011-01-01

    Although the release of potent pro-inflammatory mediators is central for mounting an efficient host response in infections, excessive inflammation may lead to deleterious tissue damage. This is highlighted in severe pneumococcal pneumonia, in which the delicate balance among a robust inflammatory response to kill pneumococci and loss of organ function determines outcome of disease. Therefore we assessed the regulation of the potent anti-inflammatory cytokine IL-10 in pneumococci infection. S....

  16. Nasopharyngeal carriage of community-acquired, antibiotic-resistant Streptococcus pneumoniae in a Zambian paediatric population.

    OpenAIRE

    Woolfson, A; Huebner, R.; Wasas, A; Chola, S.; Godfrey-Faussett, P.; Klugman, K.

    1997-01-01

    The emergence of antibiotic-resistant Streptococcus pneumoniae is an international health problem. Apart from South Africa few data on pneumococcal resistance are available for sub-Saharan Africa. This study examines the nasopharyngeal carriage and prevalence of antibiotic resistance in pneumococci isolated from 260 Zambian children aged < 6 years. Pneumococci were isolated from 71.9% of the children; the odds of carrying organisms were twice as high among children < 2 years of age compared w...

  17. Antagonism between penicillin and erythromycin against Streptococcus pneumoniae in vitro and in vivo

    DEFF Research Database (Denmark)

    Johansen, H K; Jensen, T G; Dessau, R B;

    2000-01-01

    The combination of beta-lactam antibiotics and macrolides is often recommended for the initial empirical treatment of acute pneumonia in order to obtain activity against the most important pathogens. Theoretically, this combination may be inexpedient, as the bacteriostatic agent may antagonize th...... and in vivo between penicillin and erythromycin suggests that ss-lactam antibiotics and macrolides should not be administered together unless pneumococcal infection is ruled out....

  18. Programmed protection of foreign DNA from restriction allows pathogenicity island exchange during pneumococcal transformation.

    Directory of Open Access Journals (Sweden)

    Calum Johnston

    2013-02-01

    Full Text Available In bacteria, transformation and restriction-modification (R-M systems play potentially antagonistic roles. While the former, proposed as a form of sexuality, relies on internalized foreign DNA to create genetic diversity, the latter degrade foreign DNA to protect from bacteriophage attack. The human pathogen Streptococcus pneumoniae is transformable and possesses either of two R-M systems, DpnI and DpnII, which respectively restrict methylated or unmethylated double-stranded (ds DNA. S. pneumoniae DpnII strains possess DpnM, which methylates dsDNA to protect it from DpnII restriction, and a second methylase, DpnA, which is induced during competence for genetic transformation and is unusual in that it methylates single-stranded (ss DNA. DpnA was tentatively ascribed the role of protecting internalized plasmids from DpnII restriction, but this seems unlikely in light of recent results establishing that pneumococcal transformation was not evolved to favor plasmid exchange. Here we validate an alternative hypothesis, showing that DpnA plays a crucial role in the protection of internalized foreign DNA, enabling exchange of pathogenicity islands and more generally of variable regions between pneumococcal isolates. We show that transformation of a 21.7 kb heterologous region is reduced by more than 4 logs in dpnA mutant cells and provide evidence that the specific induction of dpnA during competence is critical for full protection. We suggest that the integration of a restrictase/ssDNA-methylase couplet into the competence regulon maintains protection from bacteriophage attack whilst simultaneously enabling exchange of pathogenicicy islands. This protective role of DpnA is likely to be of particular importance for pneumococcal virulence by allowing free variation of capsule serotype in DpnII strains via integration of DpnI capsule loci, contributing to the documented escape of pneumococci from capsule-based vaccines. Generally, this finding is the

  19. Disease Isolates of Streptococcus pseudopneumoniae and Non-Typeable S. pneumoniae Presumptively Identified as Atypical S. pneumoniae in Spain

    OpenAIRE

    Dora Rolo; Simões, Alexandra S.; Arnau Domenech; Asunción Fenoll; Josefina Liñares; Hermínia de Lencastre; Carmen Ardanuy; Raquel Sá-Leão

    2013-01-01

    We aimed to obtain insights on the nature of a collection of isolates presumptively identified as atypical Streptococcus pneumoniae recovered from invasive and non-invasive infections in Spain. One-hundred and thirty-two isolates were characterized by: optochin susceptibility in ambient and CO(2)-enriched atmosphere; bile solubility; PCR-based assays targeting pneumococcal genes lytA, ply, pspA, cpsA, Spn9802, aliB-like ORF2, and a specific 16S rRNA region; multilocus sequence analysis; and a...

  20. The burden of pneumococcal disease in the Canadian population before routine use of the seven-valent pneumococcal conjugate vaccine

    OpenAIRE

    Adrienne Morrow; Philippe De Wals; Geneviève Petit; Maryse Guay; Lonny James Erickson

    2007-01-01

    BACKGROUND: In the United States, implementation of the seven-valent conjugate vaccine into childhood immunization schedules has had an effect on the burden of pneumococcal disease in all ages of the population. To evaluate the impact in Canada, it is essential to have an estimate of the burden of pneumococcal disease before routine use of the vaccine.METHODS: The incidence and costs of pneumococcal disease in the Canadian population in 2001 were estimated from various sources, including publ...

  1. Immunogenicity and Tolerance of a 7-Valent Pneumococcal Conjugate Vaccine in Nonresponders to the 23-Valent Pneumococcal Vaccine

    OpenAIRE

    Zielen, S; Bühring, I.; Strnad, N.; Reichenbach, J; Hofmann, D.

    2000-01-01

    There is still a lack of effective vaccination strategies for patients with a deficient antibody response to bacterial polysaccharide antigens. In an open trial, we evaluated the immunogenicity and tolerance of a new 7-valent pneumococcal conjugate vaccine in 22 infection-prone nonresponders to pneumococcal polysaccharide vaccine and 21 controls. In the patient group, nonresponsiveness was confirmed by repeated vaccination with a 23-valent pneumococcal polysaccharide vaccine. The study protoc...

  2. PD-1 suppresses protective immunity to Streptococcus pneumoniae through a B cell-intrinsic mechanism

    Science.gov (United States)

    McKay, Jerome T.; Egan, Ryan P.; Yammani, Rama D.; Chen, Lieping; Shin, Tahiro; Yagita, Hideo; Haas, Karen M.

    2015-01-01

    Despite the emergence of the PD-1:PD-1 ligand (PD-L) regulatory axis as a promising target for treating multiple human diseases, remarkably little is known about how this pathway regulates responses to extracellular bacterial infections. We found that PD-1−/− mice, as well as wild type mice treated with a PD-1 blocking antibody, exhibited significantly increased survival against lethal Streptococcus pneumoniae infection following either priming with low-dose pneumococcal respiratory infection or S. pneumoniae-capsular polysaccharide immunization. Enhanced survival in mice with disrupted PD-1:PD-L interactions was explained by significantly increased proliferation, isotype switching, and IgG production by pneumococcal capsule-specific B cells. Both PD-1 ligands, B7-H1 and B7-DC, contributed to PD-1-mediated suppression of protective capsule-specific IgG. Importantly, PD-1 was induced on capsule-specific B cells and suppressed IgG production and protection against pneumococcal infection in a B cell-intrinsic manner. These results provide the first demonstration of a physiologic role for B cell-intrinsic PD-1 expression in vivo. In summary, our study reveals that B cell-expressed PD-1 plays a central role in regulating protection against S. pneumoniae, and thereby represents a promising target for bolstering immunity to encapsulated bacteria. PMID:25624454

  3. Tratamento cirúrgico de pneumonia necrosante: análise de quatro casos Surgical treatment of necrotizing pneumonia: analysis of four cases

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    FERNANDO LUIZ WESTPHAL

    2000-02-01

    Full Text Available A pneumonia necrosante é uma patologia grave que surge como complicação rara de pneumonia lobar. Quatro crianças na faixa etária entre dez e 28 meses foram hospitalizadas com pneumonia bacteriana aguda, evoluindo com toxemia, derrame pleural e insuficiência respiratória, respondendo insatisfatoriamente a antibioticoterapia e drenagem pleural. Todos os pacientes foram submetidos a tratamento cirúrgico para descorticação pulmonar e ressecção de tecido pulmonar necrosado. Complicações como fístulas broncopleurais ocorreram em dois pacientes, havendo óbito em um dos casos. Os autores concluem que a ressecção pulmonar de emergência é indicada quando a necrose pulmonar é diagnosticada em pacientes septicêmicos ou com fístula broncopleural de alto débito, visando a melhora do prognóstico dessas crianças, mesmo cientes de que o índice de morbimortalidade nesses casos é alto.Necrotizing pneumonia is a serious complication of lobar pneumonia. Four children aged between ten months and three years were admitted with acute bacteremic pneumonia and developed sepsis, pleural effusion, and respiratory distress despite adequate antibiotic treatment and chest tube drainage. Decortication and pulmonary resection were performed in all of them. The observed complications were bronchopleural fistula and one death. The emergency pulmonary resection is indicated when pulmonary necrosis is associated to sepsis and massive bronchopleural fistula. In such circumstances, morbidity and mortality are higher than in other conditions.

  4. CT manifestations of adult mycoplasma pneumoniae pneumonia

    International Nuclear Information System (INIS)

    Objective: To study the conventional CT and HRCT manifestations of adult mycoplasma pneumoniae pneumonia. Methods: Conventional CT and HRCT were performed in 16 adult patients with mycoplasma pneumoniae pneumonia proven by serology. The CT images were retrospectively analyzed. Results: Areas of ground-glass opacity (GGO) were found in 12 cases. GGO showed lobular or patchy distribution in 9 cases. Air-space consolidation was observed in 8 cases, 'tree in bud' sign in 9, thickening of the interlobular septa in 3, and thickening of bronchovascular bundle in 1. 15 cases had two or more findings simultaneously. Conclusion: Mycoplasma pneumoniae pneumonia has some characteristic CT findings, which can help to distinguish it from bacterial pneumonia

  5. Compared effectiveness of the 7-valent pneumococcal conjugate vaccine in children with the 13-valent vaccine in adults.

    Science.gov (United States)

    Gaillat, J

    2013-06-01

    13-valent-pneumococcal conjugated vaccine was recently approved in the USA and Europe for adults 50 years of age or more. But this approval was followed by recommendations limiting its use to immunocompromised and asplenic patients. The extension of indications to adults was based on the well-demonstrated clinical effectiveness in infants less than 2 years of age, and on a better immune response either quantitatively or qualitatively with conjugated vaccines compared to the immunogenicity of plain polysaccharide vaccines. Nevertheless, the issue was to know whether results observed with the 7-valent pneumococcal conjugate vaccine in children are reproducible in adults with the 13-valent. The answer was given by comparing the epidemiological and physiopathological data, and the immunological response of the two populations. Very few clinical effectiveness studies in adults are available. We had for aim to assess these various issues in infants and adults. A lot of questions remain, such as the unknown impact of serotype replacement with the 13-valent pneumococcal conjugated vaccine on the clinical epidemiology and emergent Streptococcus pneumoniae pathogenicity, while waiting for the CAPITA study results expected in 2014.

  6. Antimicrobial susceptibility pattern of invasive pneumococcal isolates in North West Nigeria

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    Garba Iliyasu

    2015-01-01

    Full Text Available Background: An alarming increase in infections due to penicillin non-susceptible pneumococci (PNSP has been documented in nearly all countries. Increasingly, PNSP are also resistant to other antibiotics, and a growing number of clinical failures following the use of these agents have been reported. Aims: To determine the resistance pattern of pneumococcal isolates from patients with invasive pneumococcal infection in North West Nigeria. Materials and Methods: In a cross-sectional study clinical specimens were obtained from patients with community acquired pneumonia (CAP, meningitis and bacteraemia over a 2 year period. Pneumococcus strains were identified. Isolates were tested against a panel of antibiotics using E-test strips, and interpreted according to the CLSI criteria. 0.06 ΅g/ml was used as break point for penicillin. Analysis was carried out using descriptive statistics; relationships determined using chi-squared or Fisher′s exact tests, with P < 0.05 regarded as significant. Results: Total number of isolates was 132. Twenty-two (16.7% of the isolates were fully sensitive to penicillin while 73 (55.3% and 37 (28.0% were intermediately and fully resistant, respectively. One hundred and twenty-seven (96.2% of the isolates were fully resistant to trimethoprim-sulphamethoxazole. Eleven (8.5% were fully resistant to amoxicillin and 104 (78.8% and 17 (12.9% were intermediately resistant and fully susceptible. One hundred and six (80.3% of the isolates were fully susceptible to chloramphenicol. Resistance to penicillin was shown to infer resistance to other antibiotics. Conclusions: Pneumococcal resistance is common in North West Nigeria. Ceftriaxone retains excellent activity against most of the invasive isolate, while trimethoprim-sulphamethoxazole is almost uniformly resistant.

  7. Development of a TaqMan Array Card for Pneumococcal Serotyping on Isolates and Nasopharyngeal Samples.

    Science.gov (United States)

    Pholwat, Suporn; Sakai, Fuminori; Turner, Paul; Vidal, Jorge E; Houpt, Eric R

    2016-07-01

    Streptococcus pneumoniae is both a commensal and a major pathogen that causes invasive disease in people of all ages. The introduction of serotype-specific pneumococcal vaccines has reduced the burden of disease but has also led to replacement with new strains; thus, serotyping remains important for vaccine-related disease surveillance. Conventional serotyping methods are laborious and expensive. We developed an easy-to-perform genotypic TaqMan array card (TAC) to identify S. pneumoniae strains, including lytA-based sequences, and 53 sequence-specific PCRs to identify 74 serotypes/serogroups covering all current vaccine types as well as prevalent nonvaccine types. The TAC method was evaluated on 146 clinical S. pneumoniae isolates and 13 nonpneumococcal species that naturally inhabit the upper respiratory tract and yielded 97% (142/146) sensitivity and 100% (13/13) specificity versus results of standard Quellung serotyping. The calculated limit of detection was 20 to 200 fg (∼8 to 84 genome equivalents) per reaction. On 23 blinded nasopharyngeal specimens that were pneumococcus culture positive, the TAC pan-pneumococcus lytA assay was positive in 21 (91% sensitivity versus culture). On TAC lytA-positive specimens, a serotype result was obtained on 86%, and the result was 95% accurate versus the subsequent culture's Quellung result. TAC also detected mixed serotypes in two specimens where Quellung detected only the predominant serotype. This TAC method yields fast and comprehensive serotyping compared to the standard method and may be useful on direct specimens. PMID:27170020

  8. Vigilancia epidemiológica prospectiva de la enfermedad neumocócica invasora y de la neumonía en niños de San José, Costa Rica Prospective epidemiologic surveillance of invasive pneumococcal disease and pneumonia in children in San José, Costa Rica

    OpenAIRE

    Adriano Arguedas; Arturo Abdelnour; Carolina Soley; Elias Jimenez; Ana Laura Jimenez; Darmendra Ramcharran; Nurith Porat; Ron Dagan; Sharon Gray; Gail L Rodgers

    2012-01-01

    Justificación y objetivo: Streptococcus pneumoniae es globalmente la primera causa de muertes inmunoprevenibles en niños menores de 5 años. Métodos: entre 2007 y 2009 se realizó una vigilancia prospectiva con base poblacional en niños de 28 días a 36 meses en San José, Costa Rica. Se determinaron la incidencia de la enfermedad neumocócica invasora y de neumonía confirmada clínicamente y por radiografía, la distribución de serotipos y la sensibilidad a los antibióticos. Resultados: participaro...

  9. Assessment of health benefits and cost-effectiveness of 10-valent and 13-valent pneumococcal conjugate vaccination in Kenyan children.

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    Philip Ayieko

    Full Text Available BACKGROUND: The GAVI Alliance supported 10-valent pneumococcal conjugate vaccine (PCV10 introduction in Kenya. We estimated the cost-effectiveness of introducing either PCV10 or the 13-valent vaccine (PCV13 from a societal perspective and explored the incremental impact of including indirect vaccine effects. METHODS: The costs and effects of pneumococcal vaccination among infants born in Kenya in 2010 were assessed using a decision analytic model comparing PCV10 or PCV13, in turn, with no vaccination. Direct vaccine effects were estimated as a reduction in the incidence of pneumococcal meningitis, sepsis, bacteraemic pneumonia and non-bacteraemic pneumonia. Pneumococcal disease incidence was extrapolated from a population-based hospital surveillance system in Kilifi and adjustments were made for variable access to care across Kenya. We used vaccine efficacy estimates from a trial in The Gambia and accounted for serotype distribution in Kilifi. We estimated indirect vaccine protection and serotype replacement by extrapolating from the USA. Multivariable sensitivity analysis was conducted using Monte Carlo simulation. We assumed a vaccine price of US$ 3.50 per dose. FINDINGS: The annual cost of delivering PCV10 was approximately US$14 million. We projected a 42.7% reduction in pneumococcal disease episodes leading to a US$1.97 million reduction in treatment costs and a 6.1% reduction in childhood mortality annually. In the base case analysis, costs per discounted DALY and per death averted by PCV10, amounted to US$ 59 (95% CI 26-103 and US$ 1,958 (95% CI 866-3,425, respectively. PCV13 introduction improved the cost-effectiveness ratios by approximately 20% and inclusion of indirect effects improved cost-effectiveness ratios by 43-56%. The break-even prices for introduction of PCV10 and PCV13 are US$ 0.41 and 0.51, respectively. CONCLUSIONS: Introducing either PCV10 or PCV13 in Kenya is highly cost-effective from a societal perspective. Indirect

  10. Pneumococcal Infections - Multiple Languages: MedlinePlus

    Science.gov (United States)

    ... this page, please enable JavaScript. Chinese - Traditional (繁體中文) Farsi (فارسی) Russian (Русский) Spanish (español) Tagalog (Tagalog) Thai ( ... Action Coalition; Centers for Disease Control and Prevention Farsi (فارسی) Pneumococcal Conjugate Vaccine English (Farsi) واکسن توأمان ...

  11. Influenza and pneumococcal vaccination: patient perceptions

    OpenAIRE

    Findlay, P.; Gibbons, Y; Primrose, W; Ellis, G.; Downie, G

    2000-01-01

    The efficacy of the influenza vaccine in reducing mortality and hospital admissions is established, particularly in the elderly. However, up to 50% of those at risk do not receive the vaccine. These patients are also at risk from pneumococcal infection and there is considerable overlap between the target group for each vaccine.
This study sought to identify at risk individuals from consecutive admissions to an acute geriatric unit and to gain an insight into their perceptions with regard to v...

  12. Characterization of some pneumococcal bacteriophages. [Ultraviolet radiation

    Energy Technology Data Exchange (ETDEWEB)

    Porter, R.D.; Guild, W.R.

    1976-08-01

    The growth of pneumococcal phages at high cell and phage densities is enhanced strongly by the substitution of potassium for sodium in the medium. Initial titers of 2 x 10/sup 10/ to 4 x 10/sup 10/ PFU/ml are readily obtained, and concentrated stocks are stable in a storage buffer described here. The mechanism of the cation effect is obscure. Phages ..omega..3 and ..omega..8 each have linear double-stranded DNA of 33 x 10/sup 6/ daltons per particle, with an apparent guanine plus cytosine content of 47 to 49 mol percent, as determined by buoyancy and melting temperature, but with an unusual absorbance spectrum. Efficiency of plating is high if sufficient time is allowed for a relatively slow adsorption, which differs several-fold in rate between the two phages. Morphologically, these and other pneumococcal phages are similar to coliphage lambda but with a longer tail and tail fiber. Upon UV inactivation, ..omega..3 and ..omega..8 have D/sub 37/ values of 33 and 55 J/m/sup 2/, respectively, and each shows multiplicity reactivation. A total of 13 ts mutants have been isolated from the two phages, representing only two complementation groups; complementation and recombination occur between ..omega..3 and ..omega..8 mutants. Both phages provoke high-titer antisera with extensive cross-reactivity against a number of newly isolated pneumococcal phages.

  13. Acute Disseminated Encephalomyelitis Following Pneumococcal Meningitis Infection

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    Majzoobi

    2014-10-01

    Full Text Available Introduction Acute disseminated encephalomyelitis (ADEM is an acute inflammatory and demyelinating disease of the central nervous system, resulting in various neurological symptoms. Usually, the disease appears following vaccination or systemic viral infections. In rare cases, the disease appears following pneumococcal infections. Case Presentation The patient was a 27 year-old man who was referred to the clinic following a few days of fever and cold with consciousness deficit and right hemiplegia. Based on the analysis of cerebrospinal fluid (CSF and diagnosis of pneumococcal meningitis, he received suitable antibiotic treatment. Despite complete return of consciousness, good general condition, and negative smear and culture of CSF, fever continued and no considerable improvement was observed in the hemiplegia. Therefore, brain magnetic resonance imaging (MRI was performed and according to the findings, treatment was started with the diagnosis of acute disseminated encephalomyelitis. Treatment with prednisolone at first obviated the fever and after a month brought about a complete hemiplegia cure. Following the status of the patient after three months, his MRI clearly showed considerable reduction in lesions. Discussion There is possible occurrence of ADEM following pneumococcal meningitis. Regarding the occurrence of neurological symptoms such as visual disturbance, hemiparesis or hemiplegia following bacterial meningitis, ADEM can be considered as one of the differential diagnoses to be accompanied by MRI. Acute disseminated encephalomyelitis should be treated using suitable dose of corticosteroids.

  14. Capsular switching as a strategy to increase pneumococcal virulence in experimental otitis media model.

    Science.gov (United States)

    Sabharwal, Vishakha; Stevenson, Abbie; Figueira, Marisol; Orthopoulos, George; Trzciński, Krzysztof; Pelton, Stephen I

    2014-04-01

    We hypothesized that capsular switch event, in which pneumococcus acquires a new capsule operon by horizontal gene transfer, may result in emergence of strains with increased virulence in acute otitis media. Using serotype 6A strain from a patient with invasive pneumococcal disease and clonally distant serotype 6C strain isolated from asymptomatic carrier we created 6A:6C (6A background with 6C capsule) capsular transformants and applied whole genome macro-restriction analysis to assess conservation of the 6A chassis. Next, we assessed complement (C3) and antibodies deposition on surface of pneumococcal cells and tested capsule recipient, capsule donor and two 6A:6C transformants for virulence in chinchilla experimental otitis media model. Both 6A:6C(1 or 2) transformants bound less C3 compared to 6C capsule-donor strain but more compared to serotype 6A capsule-recipient strain. Pneumococci were present in significantly higher proportion of ears among animals challenged with either of two 6A:6C(1 or 2) transformants compared to chinchillas infected with 6C capsule-donor strain [p < 0.001] whereas a significantly decreased proportion of ears were infected with 6A:6C(1 or 2) transformants as compared to 6A capsule-recipient strain. Our observations though limited to two serotypes demonstrate that capsular switch events can result in Streptococcus pneumoniae strains of enhanced virulence for respiratory tract infection.

  15. Renal infarction as a presentation of Austrian syndrome: thromboembolic phenomenon of pneumococcal endocarditis.

    Science.gov (United States)

    Mankongpaisarnrung, Charoen; Soontrapa, Suthipong; Nantsupawat, Teerapat; Desai, Vipul; Nugent, Kenneth

    2012-09-01

    A 52-year-old unvaccinated and splenectomized man presented with fever, altered sensorium, bilateral flank pain and chest discomfort accompanied with paroxysmal atrial fibrillation with a rapid ventricular response. An abdominal computed tomography scan was performed, which revealed a right renal infarct and splenosis. Transthoracic echocardiography was performed, which demonstrated an echodense structure on the mitral valve with mitral regurgitation and a vegetation on the aortic valve with aortic regurgitation. Subsequently, he was found to have pneumococcal infective endocarditis, pneumococcal pneumonia and bacterial meningitis, namely Austrian syndrome. He underwent an early aortic valve and mitral valve repair but still had a poor clinical outcome. Renal infarction has a mortality of approximately 13.2%, which is strongly influenced by the underlying diseases and infectious complications. Medical and surgical treatment initiated in a timely manner is often inadequate. The authors report the first case of Austrian syndrome presenting with renal infarction as a clue to an embolic event associated with infective endocarditis in this study.

  16. Cost-effectiveness of heptavalent conjugate pneumococcal vaccine (Prevenar) in Germany: considering a high-risk population and herd immunity effects.

    Science.gov (United States)

    Lloyd, Adam; Patel, Nishma; Scott, David A; Runge, Claus; Claes, Christa; Rose, Markus

    2008-02-01

    In Germany, the seven-valent conjugate vaccine Prevenar is recommended for use in children at high risk of pneumococcal disease. Recent data suggest that giving conjugate vaccine to all children may lead to a decline in pneumococcal disease in unvaccinated adults, a phenomenon known as herd immunity. This analysis evaluated the cost and economic consequences in Germany of vaccinating (1) children at high risk, (2) all children when considering only benefits for vaccinated individuals and (3) all children when also considering herd immunity benefits. Costs in the model included vaccination, management of meningitis, bacteraemia, pneumonia and acute otitis media, insurance payments to parents and the costs of care for long-term disabilities. The model estimated that the cost-effectiveness of vaccination would be 38,222 euros per life year gained in children at high risk and 100,636 euros per life year gained in all children when not considering herd immunity. When considering herd immunity effects, the model estimated that offering vaccination for all children would reduce adult deaths by 3,027 per year, and vaccination would be broadly cost neutral. The findings are sensitive to the effect of conjugate vaccine on the rates of pneumonia and invasive disease in the elderly. If the herd immunity effect of conjugate vaccination in Germany is similar to that observed elsewhere, offering vaccine to all children will be more attractive than the current policy of restricting vaccination to children at high risk of pneumococcal disease.

  17. Prevalence of nasopharyngeal pneumococcal colonization in children and antimicrobial susceptibility profiles of carriage isolates

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    Julie Y. Zhou

    2015-10-01

    Full Text Available Nasopharyngeal (NP pneumococcal carriage predisposes children to pneumococcal infections. Defining the proportion of pneumococcal isolates that are antibiotic-resistant enables the appropriate choice of empiric therapies. The antibiogram of NP carriage isolates derived from a pediatric population following the introduction of the 13-valent pneumococcal conjugate vaccine was defined in this study.

  18. The status of invasive pneumococcal disease among children younger than 5 years of age in north-west Lombardy, Italy

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    Riva Enrica

    2012-05-01

    Full Text Available Abstract Background Streptococcus pneumoniae is a leading cause of invasive infection in young children causing morbidity and mortality. Active surveillance systems of invasive pneumococcal disease (IPD are recommended worldwide. The aim of this study was to estimate the current incidence of IPD and to describe the serotype distribution and the antimocrobial susceptibility of S. pneumoniae isolates in children aged less than 5 years residing in North-West Lombardy, Italy. Methods A twelve-month prospective active surveillance system recruited all children aged less than 5 years admitted for suspicion of IPD at emergency room of ten hospitals located in the monitored area. Blood samples were taken in all participants for confirmation of IPD based on isolation of S. pneumoniae from blood. Pneumococcal meningitis and sepsis were additionally confirmed by cerebrospinal fluid analysis. Serotyping and antimicrobial susceptibility testing were performed on isolates from blood. Results A total of 15 confirmed cases of IPD were detected among 135 recruited children, including pneumonia (n = 8, bacteremia (n = 4, sepsis (n = 2 and meningitis (n = 1. The annual IPD incidence rate was 50.0/100,000 (95%CI, 30.5-82.5/100,000. Incidence was 58.3/100,000 (28.8-120.1/100,000 among children aged less than 2 years and 44.4/100,000 (22.9-87.5/100,000 among children aged 2–4 years. Thirteen isolates were typified. The most common serotype was 19A (23.1% that together with serotypes 1, 7F and 19F accounted for 69.2% of typified isolates. Serotypes 14, 23F, 12B and 15C were also identified. The 7- and 13-valent pneumococcal conjugate vaccines covered respectively 30.8% and 84.6% of typified IPD cases. One isolate (serotype 15C was penicillin-resistant and caused meningitis. Conclusions The inclusion of the 13-valent pneumococcal conjugate vaccine in immunization programs of young children might be considered to reduce incidence and morbidity

  19. High nasopharyngeal carriage of non-vaccine serotypes in Western Australian aboriginal people following 10 years of pneumococcal conjugate vaccination.

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    Deirdre A Collins

    Full Text Available BACKGROUND: Invasive pneumococcal disease (IPD continues to occur at high rates among Australian Aboriginal people. The seven-valent pneumococcal conjugate vaccine (7vPCV was given in a 2-4-6-month schedule from 2001, with a 23-valent pneumococcal polysaccharide vaccine (23vPPV booster at 18 months, and replaced with 13vPCV in July 2011. Since carriage surveillance can supplement IPD surveillance, we have monitored pneumococcal carriage in western Australia (WA since 2008 to assess the impact of the 10-year 7vPCV program. METHODS: We collected 1,500 nasopharyngeal specimens from Aboriginal people living in varied regions of WA from August 2008 until June 2011. Specimens were cultured on selective media. Pneumococcal isolates were serotyped by the quellung reaction. RESULTS: Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis were carried by 71.9%, 63.2% and 63.3% respectively of children <5 years of age, and 34.6%, 22.4% and 27.2% of people ≥5 years. Of 43 pneumococcal serotypes identified, the most common were 19A, 16F and 6C in children <5 years, and 15B, 34 and 22F in older people. 7vPCV serotypes accounted for 14.5% of all serotypeable isolates, 13vPCV for 32.4% and 23vPPV for 49.9%, with little variation across all age groups. Serotypes 1 and 12F were rarely identified, despite causing recent IPD outbreaks in WA. Complete penicillin resistance (MIC ≥2µg/ml was found in 1.6% of serotype 19A (5.2%, 19F (4.9% and 16F (3.2% isolates and reduced penicillin susceptibility (MIC ≥0.125µg/ml in 24.9% of isolates, particularly 19F (92.7%, 19A (41.3%, 16F (29.0%. Multi-resistance to cotrimoxazole, tetracycline and erythromycin was found in 83.0% of 23F isolates. Among non-serotypeable isolates 76.0% had reduced susceptibility and 4.0% showed complete resistance to penicillin. CONCLUSIONS: Ten years after introduction of 7vPCV for Aboriginal Australian children, 7vPCV serotypes account for a small proportion of carried

  20. Epidemiological and Economic Burden of Pneumococcal Disease in Canadian Children

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    Geneviève Petit

    2003-01-01

    Full Text Available BACKGROUND: With the arrival of a new conjugate pneumococcal vaccine, it is important to estimate the burden of pneumococcal diseases in Canadian children. The epidemiological data and the economic cost of these diseases are crucial elements in evaluating the relevance of a vaccination program.

  1. 42 CFR 410.57 - Pneumococcal vaccine and flu vaccine.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 2 2010-10-01 2010-10-01 false Pneumococcal vaccine and flu vaccine. 410.57 Section 410.57 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES MEDICARE PROGRAM SUPPLEMENTARY MEDICAL INSURANCE (SMI) BENEFITS Medical and Other Health Services § 410.57 Pneumococcal vaccine and flu...

  2. Evaluation of Streptococcus pneumoniae in bile samples: A case series review.

    Science.gov (United States)

    Itoh, Naoya; Kawamura, Ichiro; Tsukahara, Mika; Mori, Keita; Kurai, Hanako

    2016-06-01

    Although Streptococcus pneumoniae is an important pathogen of humans, pneumococcal cholangitis is rare because of the rapid autolysis of S. pneumoniae. The aim of this case series was to review patients with bile cultures positive for S. pneumoniae. This study was a single center retrospective case series review of patients with S. pneumoniae in their bile at a tertiary-care cancer center between September 2002 and August 2015. Subjects consisted of all patients in whom S. pneumoniae was isolated in their bile during the study period. Bile specimens for culture were obtained from biliary drainage procedures such as endoscopic retrograde biliary drainage, endoscopic nasobiliary drainage, and percutaneous transhepatic biliary drainage. There were 20 patients with bile cultures positive for S. pneumoniae during the study period. All patients presented with extrahepatic obstructive jaundice due to hepatopancreatobiliary tumors. Nineteen of 20 patients underwent the placement of plastic intrabiliary tubes. The mean time between the first-time drainage and the positive culture was 26 days (range 0-313 days). Although 12 of 20 patients met our definition of cholangitis, 5 were clinically treated with antibiotics based on a physician's assessment of whether there was a true infection. The present study is the largest case series of patients with S. pneumoniae in their bile. Based on our findings, the isolation of S. pneumoniae from bile may be attributed to the placement of biliary drainage devices. PMID:27025902

  3. DC-SIGN specifically recognizes Streptococcus pneumoniae serotypes 3 and 14.

    Science.gov (United States)

    Koppel, Estella A; Saeland, Eirikur; de Cooker, Désirée J M; van Kooyk, Yvette; Geijtenbeek, Teunis B H

    2005-01-01

    The Gram-positive bacterium Streptococcus pneumoniae is the leading causative pathogen in community-acquired pneumonia. The ever-increasing frequency of antibiotic-resistant S. pneumoniae strains severely hampers effective treatments. Thus, a better understanding of the mechanisms involved in the pathogenesis of pneumococcal disease is needed; in particular, of the initial interactions that take place between the host and the bacterium. Recognition of pathogens by dendritic cells is one of the most crucial steps in the induction of an immune response. For efficient pathogen recognition, dendritic cells express various kinds of receptors, including the DC-specific C-type lectin DC-SIGN. Pathogens such as Mycobacterium tuberculosis and HIV target DC-SIGN to escape immunity. Here the in vitro binding of DC-SIGN with S. pneumoniae was investigated. DC-SIGN specifically interacts with S. pneumoniae serotype 3 and 14 in contrast to other serotypes such as 19F. While the data described here suggest that DC-SIGN interacts with S. pneumoniae serotype 14 through a ligand expressed by the capsular polysaccharide, the binding to S. pneumoniae serotype 3 appears to depend on an as yet unidentified ligand. Despite the binding capacity of the capsular polysaccharide of S. pneumoniae 14 to DC-SIGN, no immunomodulatory effects on the dendritic cells were observed. The immunological consequences of the serotype-specific capacity to interact with DC-SIGN should be further explored and might result in new insights in the development of new and more potent vaccines.

  4. Nitric oxide synthase 2A (NOS2A polymorphisms are not associated with invasive pneumococcal disease

    Directory of Open Access Journals (Sweden)

    Ollier William ER

    2009-03-01

    Full Text Available Abstract Background Streptococcus pneumoniae (pneumococcus is responsible for over one million deaths per year, with young children, the elderly and immunocompromised individuals being most at risk. Approximately half of East African children have been reported to be asymptomatic carriers of pneumococcus with invasive infection occurring after the disruption of the respiratory membrane which is believed to be caused by the host immune response. Racial incidence of invasive pneumococcal disease (IPD is higher in certain populations even after adjusting for environmental factors suggesting a genetic component to disease susceptibility. The nitric oxide synthase 2A (NOS2A gene is responsible for the production of nitric oxide under pathological conditions including host defence against bacterial infection. Nitric oxide is a modulator of apoptotic and inflammatory cascades and endothelial permeability. We hypothesised that genetic variants within this gene may predispose to disease risk and survival. Methods A cohort of 299 children with IPD (221 meningitis, 41 pneumonia and 37 with bacteraemia and 931 age matched controls from Malawi were used in this study. We investigated nine haplotype tagging single nucleotide polymorphisms within the NOS2A gene and compared the presence or absence of the minor alleles in cases and controls and survivors and non-survivors within the cases. Results We observed no significant associations between cases and controls or with survival in either all IPD cases or in the separate analysis of meningitis cases. A near significant association was obtained for the comparison of rs8078340 in cases and controls (p-value, 0.078. However, results were unadjusted for multiple testing. Conclusion Our results suggest that polymorphic variation within the NOS2A gene does not influence invasive pneumococcal disease susceptibility or survival.

  5. Alternative Pathway Inhibition by Exogenous Factor H Fails to Attenuate Inflammation and Vascular Leakage in Experimental Pneumococcal Sepsis in Mice.

    Science.gov (United States)

    van der Maten, Erika; van Selm, Saskia; Langereis, Jeroen D; Bootsma, Hester J; van Opzeeland, Fred J H; de Groot, Ronald; de Jonge, Marien I; van der Flier, Michiel

    2016-01-01

    Streptococcus pneumoniae is a common cause of sepsis. Effective complement activation is an important component of host defence against invading pathogens, whilst excessive complement activation has been associated with endothelial dysfunction and organ damage. The alternative pathway amplification loop is important for the enhancement of complement activation. Factor H is a key negative regulator of the alternative pathway amplification loop and contributes to tight control of complement activation. We assessed the effect of inhibition of the alternative pathway on sepsis associated inflammation and disease severity using human factor H treatment in a clinically relevant mice model of pneumococcal sepsis. Mice were infected intravenously with live Streptococcus pneumoniae. At the first clinical signs of infection, 17 hours post-infection, mice were treated with ceftriaxone antibiotic. At the same time purified human factor H or in controls PBS was administered. Treatment with human factor H did not attenuate disease scores, serum pro-inflammatory cytokines, or vascular permeability and did not significantly affect C3 and C3a production at 26 h post-infection. Therefore, we conclude that inhibition of the alternative complement pathway by exogenous human factor H fails to attenuate inflammation and vascular leakage at a clinically relevant intervention time point in pneumococcal sepsis in mice. PMID:26872035

  6. Prevalence of Pharyngeal Pneumococcal Carriers and Succeptibility Patterns among Children of Day Care Centers in Yazd District,Iran

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    M Mohammad - Zadeh

    2004-04-01

    Full Text Available Introduction: Streptococcus pneumoniae is one of the most important causes of pneumonia, meningitis and septicemia. Decades after successful treatment of this infection with penicillin, frequency of penicillin resistance is reportedly on the rise throughout the world. This cross sectional study was designed in Yazd to determine the prevalence of pneumococcal pharyngeal carriers and its succeptibility pattern in children of day care centers. Method & materials : Two hundred children were selected randomly from 10 day care centers and pharyngeal swabs were collected and cultured in February, 2002. Results :51% of our study sample were boys and 49% were girls. Their age range was between 7 and 65 months. Prevalence of pharyngeal carriers was 37.5%. The rate of resistance detected was as follows: 50% to penicillin, 62.5% to erythromycin and TMP,SMX, 30.6% to tetracycline, 15.3 % to cephalothin, 5.6% to ceftizoxime and 4.2% to ciprofloxacin. Conclusion: We conclude that penicillin is not the drug of choice in invasive pneumococcal infections in Yazd and a third gereration cephalosporin should be used instead as the first line of treatment while awaiting the culture and sensitivity results.

  7. The lectin pathway of complement activation is a critical component of the innate immune response to pneumococcal infection.

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    Youssif M Ali

    Full Text Available The complement system plays a key role in host defense against pneumococcal infection. Three different pathways, the classical, alternative and lectin pathways, mediate complement activation. While there is limited information available on the roles of the classical and the alternative activation pathways of complement in fighting streptococcal infection, little is known about the role of the lectin pathway, mainly due to the lack of appropriate experimental models of lectin pathway deficiency. We have recently established a mouse strain deficient of the lectin pathway effector enzyme mannan-binding lectin associated serine protease-2 (MASP-2 and shown that this mouse strain is unable to form the lectin pathway specific C3 and C5 convertases. Here we report that MASP-2 deficient mice (which can still activate complement via the classical pathway and the alternative pathway are highly susceptible to pneumococcal infection and fail to opsonize Streptococcus pneumoniae in the none-immune host. This defect in complement opsonisation severely compromises pathogen clearance in the lectin pathway deficient host. Using sera from mice and humans with defined complement deficiencies, we demonstrate that mouse ficolin A, human L-ficolin, and collectin 11 in both species, but not mannan-binding lectin (MBL, are the pattern recognition molecules that drive lectin pathway activation on the surface of S. pneumoniae. We further show that pneumococcal opsonisation via the lectin pathway can proceed in the absence of C4. This study corroborates the essential function of MASP-2 in the lectin pathway and highlights the importance of MBL-independent lectin pathway activation in the host defense against pneumococci.

  8. Invasive pneumococcal disease in Danish children, 1996-2007, prior to the introduction of heptavalent pneumococcal conjugate vaccine

    DEFF Research Database (Denmark)

    Winther, Thilde N; Kristensen, Tim D; Kaltoft, Margit S;

    2008-01-01

    Aim: The aim of this study was to document the epidemiology, microbiology and outcome of invasive pneumococcal disease (IPD) among children quality surveillance data, just prior to the introduction of the heptavalent pneumococcal conjugate vaccine (PCV7) into the Danish routine...... children vaccination....

  9. Molecular epidemiology of pneumococcal colonization in response to pneumococcal conjugate vaccination in children with recurrent acute otitis media.

    NARCIS (Netherlands)

    Bogaert, D.; Veenhoven, R.H.; Sluijter, M.; Wannet, W.J.B.; Rijkers, G.T.; Mitchell, T.J.; Clarke, S.C.; Goessens, W.H.F.; Schilder, A.G.M.; Sanders, E.A.M.; Groot, R. de; Hermans, P.W.M.

    2005-01-01

    A randomized double-blind trial with a 7-valent pneumococcal conjugate vaccine was conducted in The Netherlands among 383 children, aged 1 to 7 years, with a history of recurrent acute otitis media. No effect of vaccination on the pneumococcal colonization rate was found. However, a shift in serotyp

  10. Pneumococcal Infection among Children before Introduction of 13-Valent Pneumococcal Conjugate Vaccine, Cambodia

    OpenAIRE

    Turner, Paul; Turner, Claudia; Suy, Kuong; Soeng, Sona; Ly, Sokeng; Miliya, Thyl; Goldblatt, David; Day, Nicholas P. J.

    2015-01-01

    Vaccination of children with pneumococcal conjugate vaccine (PCV13) was initiated in Cambodia in 2015. To determine baseline data, we collected samples from children in 2013 and 2014. PCV13 serotypes accounted for 62.7% of colonizing organisms in outpatients and 88.4% of invasive pneumococci overall; multidrug resistance was common. Thus, effectiveness of vaccination should be high.

  11. Pneumococcal Infection among Children before Introduction of 13-Valent Pneumococcal Conjugate Vaccine, Cambodia.

    Science.gov (United States)

    Turner, Paul; Turner, Claudia; Suy, Kuong; Soeng, Sona; Ly, Sokeng; Miliya, Thyl; Goldblatt, David; Day, Nicholas P J

    2015-11-01

    Vaccination of children with pneumococcal conjugate vaccine (PCV13) was initiated in Cambodia in 2015. To determine baseline data, we collected samples from children in 2013 and 2014. PCV13 serotypes accounted for 62.7% of colonizing organisms in outpatients and 88.4% of invasive pneumococci overall; multidrug resistance was common. Thus, effectiveness of vaccination should be high. PMID:26488597

  12. The epidemiology of invasive pneumococcal disease in the Canadian North from 1999 to 2010

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    Melissa Helferty

    2013-08-01

    Full Text Available Introduction . The International Circumpolar Surveillance network is a population-based surveillance system that collects data on invasive pneumococcal disease (IPD in Northern Canada. A 7-valent pneumococcal conjugate vaccine was first introduced in some regions of Northern Canada in 2002, followed by 10-valent (2009 and 13-valent (PCV-13 vaccines (2010. A 23-valent polysaccharide (PPV-23 vaccine was first introduced in 1988 for special populations and adults aged 65 years and older. To describe the epidemiology in the context of pneumococcal vaccination programs, we analysed surveillance data from Northern Canada from 1999 to 2010. Methods . A standardized case report form capturing demographic and clinical information was completed for all IPD cases in Northern Canada meeting the national case definition. Isolates were sent to a reference laboratory for confirmation, serotyping and antimicrobial resistance testing. Both laboratory and epidemiological data were sent to the Public Health Agency of Canada for analysis. Population denominators were obtained from Statistics Canada. Results . From 1999 to 2010, 433 IPD cases were reported (average 36 cases per year. Incidence was greatest among infants aged <2 years and among those aged 65 years and older, with an average annual incidence of 133 and 67 cases per 100,000 population, respectively. After a peak in incidence in 2008, rates among infants have declined. Incidence rates varied from 2 to 16 times greater, depending on the year, among Aboriginals compared to non-Aboriginals. Hospitalization was reported in 89% of all cases and the case fatality ratio was 6.0%. Clinical manifestations varied, with some patients reporting >1 manifestation. Pneumonia was the most common (70%, followed by bacteremia/septicaemia (30% and meningitis (8%. Approximately, 42% of cases aged <2 years in 2009 and 2010 had serotypes covered by the PCV-13. In addition, the majority (89% of serotypes isolated in cases

  13. Streptococcus pneumoniae from Palestinian nasopharyngeal carriers: serotype distribution and antimicrobial resistance.

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    Abedelmajeed Nasereddin

    Full Text Available Infections of Streptococcus pneumoniae in children can be prevented by vaccination; left untreated, they cause high morbidity and fatalities. This study aimed at determining the nasopharyngeal carrier rates, serotype distribution and antimicrobial resistance patterns of S. pneumoniae in healthy Palestinian children under age two prior to the full introduction of the pneumococcal 7-valent conjugate vaccine (PCV7, which was originally introduced into Palestine in a pilot trial in September, 2010. In a cross sectional study, nasopharyngeal specimens were collected from 397 healthy children from different Palestinian districts between the beginning of November 2012 to the end of January 2013. Samples were inoculated into blood agar and suspected colonies were examined by amplifying the pneumococcal-specific autolysin gene using a real-time PCR. Serotypes were identified by a PCR that incorporated different sets of specific primers. Antimicrobial susceptibility was measured by disk diffusion and MIC methods. The resulting carrier rate of Streptococcus pneumoniae was 55.7% (221/397. The main serotypes were PCV7 serotypes 19F (12.2%, 23F (9.0%, 6B (8.6% and 14 (4% and PCV13 serotypes 6A (13.6% and 19A (4.1%. Notably, serotype 6A, not included in the pilot trial (PCV7 vaccine, was the most prevalent. Resistance to more than two drugs was observed for bacteria from 34.1% of the children (72/211 while 22.3% (47/211 carried bacteria were susceptible to all tested antibiotics. All the isolates were sensitive to cefotaxime and vancomycin. Any or all of these might impinge on the type and efficacy of the pneumococcal conjugate vaccines and antibiotics to be used for prevention and treatment of pneumococcal disease in the country.

  14. Role of an iron-dependent transcriptional regulator in the pathogenesis and host response to infection with Streptococcus pneumoniae.

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    Radha Gupta

    Full Text Available Iron is a critical cofactor for many enzymes and is known to regulate gene expression in many bacterial pathogens. Streptococcus pneumoniae normally inhabits the upper respiratory mucosa but can also invade and replicate in lungs and blood. These anatomic sites vary considerably in both the quantity and form of available iron. The genome of serotype 4 pneumococcal strain TIGR4 encodes a putative iron-dependent transcriptional regulator (IDTR. A mutant deleted at idtr (Δidtr exhibited growth kinetics similar to parent strain TIGR4 in vitro and in mouse blood for up to 48 hours following infection. However, Δidtr was significantly attenuated in a murine model of sepsis. IDTR down-regulates the expression of ten characterized and putative virulence genes in nasopharyngeal colonization and pneumonia. The host cytokine response was significantly suppressed in sepsis with Δidtr. Since an exaggerated inflammatory response is associated with a poor prognosis in sepsis, the decreased inflammatory response could explain the increased survival with Δidtr. Our results suggest that IDTR, which is dispensable for pneumococcal growth in vitro, is associated with regulation of pneumococcal virulence in specific host environments. Additionally, IDTR ultimately modulates the host cytokine response and systemic inflammation that contributes to morbidity and mortality of invasive pneumococcal disease.

  15. Adjuvant TACE inhibitor treatment improves the outcome of TLR2-/- mice with experimental pneumococcal meningitis

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    Neumann Ulf

    2007-04-01

    Full Text Available Abstract Background Streptococcus (S. pneumoniae meningitis has a high lethality despite antibiotic treatment. Inflammation is a major pathogenetic factor, which is unresponsive to antibiotics. Therefore adjunctive therapies with antiinflammatory compounds have been developed. TNF484 is a TNF-alpha converting enzyme (TACE inhibitor and has been found efficacious in experimental meningitis. Toll-like receptor 2 (TLR2 contributes to host response in pneumococcal meningitis by enhancing bacterial clearing and downmodulating inflammation. In this study, TNF484 was applied in mice, which lacked TLR2 and exhibited a strong meningeal inflammation. Methods 103 CFU S. pneumoniae serotype 3 was inoculated subarachnoidally into C57BL/6 wild type (wt mice or TLR2-/-, CD14-/- and CD14-/-/TLR2-/- mice. Severity of disease and survival was followed over 9 days. Response to antibiotics (80 mg/kg ceftriaxone i.p. for 5 days and/or TACE inhibitor treatment (1 mg/kg s.c. twice daily for 4 days was evaluated. Animals were sacrificed after 12, 24, and 48 h for analysis of bacterial load in cerebrospinal fluid (CSF and brain and for TNF and leukocyte measurements in CSF. Results TLR2-/- mice were significantly sicker than the other mouse strains 24 h after infection. All knockout mice showed higher disease severity after 48 h and died earlier than wt mice. TNF release into CSF was significantly more elevated in TLR2-/- than in the other strains after 24 h. Brain bacterial numbers were significantly higher in all knockout than wt mice after 24 h. Modulation of outcome by antibiotic and TACE inhibitor treatment was evaluated. With antibiotic therapy all wt, CD14-/- and TLR2-/-/CD14-/- mice, but only 79% of TLR2-/- mice, were rescued. TACE inhibitor treatment alone did not rescue, but prolonged survival in wt mice, and in TLR2-/- and CD14-/- mice to the values observed in untreated wt mice. By combined antibiotic and TACE inhibitor treatment 95% of TLR2-/- mice were

  16. Prevalence and clonal distribution of pcpA, psrP and Pilus-1 among pediatric isolates of Streptococcus pneumoniae.

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    Laura Selva

    Full Text Available Streptococcus pneumoniae is the leading cause of vaccine-preventable deaths globally. The objective of this study was to determine the distribution and clonal type variability of three potential vaccine antigens: Pneumococcal serine-rich repeat protein (PsrP, Pilus-1, and Pneumococcal choline binding protein A (PcpA among pneumococcal isolates from children with invasive pneumococcal disease and healthy nasopharyngeal carriers. We studied by Real-Time PCR a total of 458 invasive pneumococcal isolates and 89 nasopharyngeal pneumococcal isolates among children (total = 547 strains collected in Barcelona, Spain, from January 2004 to July 2010. pcpA, psrP and pilus-1 were detected in 92.8%, 51.7% and 14.4% of invasive isolates and in 92.1%, 48.3% and 18% of carrier isolates, respectively. Within individual serotypes the prevalence of psrP and pilus-1 was highly dependent on the clonal type. pcpA was highly prevalent in all strains with the exception of those belonging to serotype 3 (33.3% in serotype 3 isolates vs. 95.1% in other serotypes; P<.001. psrP was significantly more frequent in those serotypes that are less apt to be detected in carriage than in disease; 58.7% vs. 39.1% P<.001. Antibiotic resistance was associated with the presence of pilus-1 and showed a negative correlation with psrP. These results indicate that PcpA, and subsequently Psrp and Pilus-1 together might be good candidates to be used in a next-generation of multivalent pneumococcal protein vaccine.

  17. Pneumonia - adults - discharge

    Science.gov (United States)

    You have pneumonia, which is an infection in your lungs. In the hospital, your doctors and nurses helped you breathe better. ... body get rid of the germs that cause pneumonia. They also made sure you got enough liquids ...

  18. Pneumocystis Pneumonia (PCP)

    Science.gov (United States)

    ... 2014 Select a Language: Fact Sheet 515 Pneumocystis Pneumonia (PCP) WHAT IS PCP? HOW IS PCP TREATED? ... BEST? THE BOTTOM LINE WHAT IS PCP? Pneumocystis pneumonia (PCP or pneumocystis) is the most common opportunistic ...

  19. Pneumococcal meningitis: epidemiological profile pre- and post-introduction of the pneumococcal 10-valent conjugate vaccine

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    Tatiane E. Hirose

    2015-04-01

    Full Text Available OBJECTIVES: To evaluate the possible effects of the introduction of the pneumococcal conjugate 10-valent vaccine schedule in the state of Parana on pneumococcal meningitis cases and to assess the distribution of serotypes among cases. METHOD: Cross-sectional study with retrospective data collection of cases of pneumococcal meningitis in the state of Paraná reported to Sistema de Informação de Agravos de Notificação (SINAN, from 1998 to 2011. A total of 1,339 cases of pneumococcal meningitis were analyzed; 1,205 cases from the pre-vaccine period (1998-2009 were compared to 134 cases from the post-vaccine period (2010-2011. Descriptive and comparative statistical analyses (chi-squared test and prevalence ratio were performed using JMP 5.1.2 statistical software (JMP Statistical Discovery, North Carolina, USA and EPI INFO 6 (Centers for Disease Control and Prevention, Georgia, EUA. RESULTS: There was a significant reduction in the mean rates of incidence and mortality in the general population. The analysis of cases in the pre- and post-vaccination periods in the age groups covered by vaccination (younger than 2 years showed significant reductions in incidence rates (6.01 cases/100,000 to 2.49 cases/100,000 individuals and mortality (1.85 cases/100,000 population to 0.47 cases/100,000 population, while the mean lethality rate did not change significantly. There was a significant reduction in cases whose serotypes are included in the vaccine (80.7% to 53.3%. CONCLUSION: Even after a short time of use, the 10-valent pneumococcal conjugate vaccine has already had a significant impact in reducing the incidence and mortality of meningitis cases among infants, as well as the reduction of cases whose serotypes are included in the vaccine.

  20. Progress in Pneumococcal Adherence and Virulence Factor A%肺炎链球菌粘附和毒力因子A研究进展

    Institute of Scientific and Technical Information of China (English)

    郭旭光; 冀天星; 夏勇

    2013-01-01

    肺炎链球菌(Streptococcus pneumoniae,SP)普遍定植于呼吸道,是人类重要的侵袭性病原菌之一,是社区获得性肺炎、中耳炎、脑膜炎、菌血症、鼻窦炎的主要病原菌.肺炎链球菌粘附和毒力因子A (pneumococcal adherence and virulence factor A,PavA)是肺炎链球菌早期感染和侵袭过程中关键的毒力因子.体外试验表明,缺失PavA的肺炎链球菌的突变株其粘附和侵入上皮细胞和内皮细胞的能力明显下降.作为一种保护性抗原,其诱导的细胞和体液免疫可以有效的抵抗肺炎链球菌的感染,是肺炎链球菌新一代疫苗的候选蛋白.但是,PavA在肺炎链球菌与人肺上皮细胞交互对话中作用机制的研究尚属空白,本文就肺炎链球菌粘附和毒力因子A得最新研究进展作一综述.%Streptococcus pneumoniae is a natural resident of the upper and lower respiratory tracts of humans, as well as the major cause of community acquired pneumonia and bacterial meningitis, has been shown to transiently invade epithelial and endothelial cells. Pneumococcal adherence and virulence factor A (PavA) is displayed to the cell outer surface of Streptococcus pneumoniae and mediates pneumococcal binding to epithelial cell lines.PavA, which lacks a typical gram-positive signal sequence and cell surface anchorage motif, is essential for pneumococcal virulence. However, the mechanism of PavA in the interactive dialogue in the Streptococcus pneumoniae with human lung epithelial cells is still unknown.

  1. Disease isolates of Streptococcus pseudopneumoniae and non-typeable S. pneumoniae presumptively identified as atypical S. pneumoniae in Spain.

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    Dora Rolo

    Full Text Available We aimed to obtain insights on the nature of a collection of isolates presumptively identified as atypical Streptococcus pneumoniae recovered from invasive and non-invasive infections in Spain. One-hundred and thirty-two isolates were characterized by: optochin susceptibility in ambient and CO(2-enriched atmosphere; bile solubility; PCR-based assays targeting pneumococcal genes lytA, ply, pspA, cpsA, Spn9802, aliB-like ORF2, and a specific 16S rRNA region; multilocus sequence analysis; and antimicrobial susceptibility. By multilocus sequence analysis, 61 isolates were S. pseudopneumoniae, 34 were pneumococci, 13 were S. mitis, and 24 remained unclassified as non-pneumococci. Among S. pseudopneumoniae isolates, 51 (83.6% were collected from respiratory tract samples; eight isolates were obtained from sterile sources. High frequency of non-susceptibility to penicillin (60.7% and erythromycin (42.6% was found. Only 50.8% of the S. pseudopneumoniae isolates displayed the typical optochin phenotype originally described for this species. None harbored the cpsA gene or the pneumococcal typical lytA restriction fragment length polymorphism. The Spn9802 and the specific 16S rRNA regions were detected among the majority of the S. pseudopneumoniae isolates (n = 59 and n = 49, respectively. The ply and pspA genes were rarely found. A high genetic diversity was found and 59 profiles were identified. Among the S. pneumoniae, 23 were capsulated and 11 were non-typeable. Three non-typeable isolates, associated to international non-capsulated lineages, were recovered from invasive disease sources. In conclusion, half of the atypical pneumococcal clinical isolates were, in fact, S. pseudopneumoniae and one-fourth were other streptococci. We identified S. pseudopneumoniae and non-typeable pneumococci as cause of disease in Spain including invasive disease.

  2. Emerging resistant serotypes of invasive Streptococcus pneumoniae

    Science.gov (United States)

    Elshafie, Sittana; Taj-Aldeen, Saad J

    2016-01-01

    Background Streptococcus pneumoniae is the leading cause of meningitis and sepsis. The aim of the study was to analyze the distribution, vaccine serotype coverage, and antibiotic resistance of S. pneumoniae serotypes isolated from patients with invasive diseases, after the introduction of pneumococcal 7-valent conjugated vaccine (PCV-7). Methods A total of 134 isolates were collected from blood and cerebrospinal fluid specimens at Hamad Hospital during the period from 2005 to 2009. Isolate serotyping was done using the Quellung reaction. The prevaccination period was considered before 2005. Results The most common serotypes for all age groups were 3 (12.70%), 14 (11.90%), 1 (11.90%), 19A (9.00%), 9V (5.20%), 23F (5.20%), and 19F (4.50%). Coverage rates for infant conjugated vaccine (PCV-10), and the 13-valent conjugated vaccine (PCV-13) were 34.78%, 52.17%, and 78.26%, respectively. Coverage rates of these vaccines were 50%, 67.86%, and 75% for the 2–5 years age group; 27.12%, 40.68%, and 64.41% for the age group 6–64 years; and 25%, 33.33%, and 66.67% for the ≥65 years age group, respectively. The percentage of nonsusceptible isolates to penicillin, cefotaxime, and erythromycin were 43.86%, 16.66%, and 22.81%, respectively. Thirty-seven isolates (32.46%) were multidrug resistant (MDR) and belonged to serotypes 14, 19A, 19F, 23F, 1, 9V, 12F, 4, 6B, 3, and 15A. Compared to previous results before the introduction of PCV-7, there was a significant reduction in penicillin-nonsusceptable S. pneumoniae from 66.67% to 43.86%, and a slight insignificant reduction in erythromycin nonsusceptible strains from 27.60% to 22.8%, while there was a significant increase in cefotaxime nonsusceptible strains from 3.55% to 16.66%. Conclusion Invasive pneumococcal strains and the emergence of MDR serotypes is a global burden that must be addressed through multiple strategies, including vaccination, antibiotic stewardship, and continuous surveillance. PMID:27418844

  3. Pneumococcal Bacteremia Requiring Hospitalization in Rural Thailand: An Update on Incidence, Clinical Characteristics, Serotype Distribution, and Antimicrobial Susceptibility, 2005-2010.

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    Julia Rhodes

    Full Text Available Streptococcus pneumoniae is an important cause of morbidity and mortality in Southeast Asia, but regional data is limited. Updated burden estimates are critical as pneumococcal conjugate vaccine (PCV is highly effective, but not yet included in the Expanded Program on Immunization of Thailand or neighboring countries.We implemented automated blood culture systems in two rural Thailand provinces as part of population-based surveillance for bacteremia. Blood cultures were collected from hospitalized patients as clinically indicated.From May 2005- March 2010, 196 cases of pneumococcal bacteremia were confirmed in hospitalized patients. Of these, 57% had clinical pneumonia, 20% required mechanical ventilation, and 23% (n = 46 died. Antibiotic use before blood culture was confirmed in 25% of those with blood culture. Annual incidence of hospitalized pneumococcal bacteremia was 3.6 per 100,000 person-years; rates were higher among children aged <5 years at 11.7 and adults ≥65 years at 14.2, and highest among infants <1 year at 33.8. The median monthly case count was higher during December-March compared to the rest of the year 6.0 vs. 1.0 (p<0.001. The most common serotypes were 23F (16% and 14 (14%; 61% (74% in patients <5 years were serotypes in the 10-valent PCV (PCV 10 and 82% (92% in <5 years in PCV 13. All isolates were sensitive to penicillin, but non-susceptibility was high for co-trimoxazole (57%, erythromycin (30%, and clindamycin (20%.We demonstrated a high pneumococcal bacteremia burden, yet underestimated incidence because we captured only hospitalized cases, and because pre-culture antibiotics were frequently used. Our findings together with prior research indicate that PCV would likely have high serotype coverage in Thailand. These findings will complement ongoing cost effectiveness analyses and support vaccine policy evaluation in Thailand and the region.

  4. Outbreaks of Streptococcus pneumoniae carriage in day care cohorts in Finland – implications for elimination of transmission

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    Auranen Kari

    2009-06-01

    Full Text Available Abstract Background Day care centre (DCC attendees play a central role in maintaining the circulation of Streptococcus pneumoniae (pneumococcus in the population. Exposure within families and within DCCs are the main risk factors for colonisation with pneumococcal serotypes in DCC attendees. Methods Transmission of serotype specific carriage was analysed with a continuous time event history model, based on longitudinal data from day care attendees and their family members. Rates of acquisition, conditional on exposure, were estimated in a Bayesian framework utilising latent processes of carriage. To ensure a correct level of exposure, non-participating day care attendees and their family members were included in the analysis. Posterior predictive simulations were used to quantify transmission patterns within day care cohorts, to estimate the basic reproduction number for pneumococcal carriage in a population of day care cohorts, and to assess the critical vaccine efficacy against carriage to eliminate pneumococcal transmission. Results The model, validated by posterior predictive sampling, was successful in capturing the strong temporal clustering of pneumococcal serotypes in the day care cohorts. In average 2.7 new outbreaks of pneumococcal carriage initiate in a day care cohort each month. While 39% of outbreaks were of size one, the mean outbreak size was 7.6 individuals and the mean length of an outbreak was 2.8 months. The role of families in creating and maintaining transmission was minimal, as only 10% of acquisitions in day care attendees were from family members. Considering a population of day care cohorts, a child-to-child basic reproduction number was estimated as 1.4 and the critical vaccine efficacy against acquisition of carriage as 0.3. Conclusion Pneumococcal transmission occurs in serotype specific outbreaks of carriage, driven by within-day-care transmission and between-serotype competition. An amplifying effect of the day

  5. Antimicrobial activities of Eugenia caryophyllata extract and its major chemical constituent eugenol against Streptococcus pneumoniae.

    Science.gov (United States)

    Yadav, Mukesh Kumar; Park, Seok-Won; Chae, Sung-Won; Song, Jae-Jun; Kim, Ho Chul

    2013-12-01

    In this study, we investigate the antimicrobial activities of both Eugenia caryophyllata (Ec) extract and its major component eugenol (4-allyl-2-methoxyphenol) against Streptococcus pneumoniae. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined by microdilution method. Pneumococcal biofilms were detected by crystal-violet microtiter plate assay, followed by colony-forming unit counts and visualized by scanning electron microscope (SEM). The synergistic effect of eugenol and penicillin was determined by checker-board method. Both the eugenol and the Ec extract inhibited pneumococcal growth in a concentration-dependent manner. The MIC and MBC of eugenol were 0.06% and 0.12%, respectively. Eugenol at a concentration of 0.12% completely killed S. pneumoniae within 60 min of exposure. The kill rate of planktonic cells was most rapid during the first 15 min of contact with eugenol. The addition of eugenol or Ec extract inhibited in vitro biofilm formation. In already established biofilms, the inhibitory effect of eugenol or Ec extract was more significant in terms of cell viability than in terms of disruption of the biofilm matrix. SEM analysis revealed non-viable and disruptive action of eugenol on the cell membrane of bacteria of biofilms. It was found that eugenol and penicillin produced a synergistic effect against S. pneumoniae. In conclusion, eugenol and Ec extract efficiently inhibited S. pneumoniae in planktonic growth and within biofilms.

  6. Serotype and genotype distribution among invasive Streptococcus pneumoniae isolates in Colombia, 2005-2010.

    Science.gov (United States)

    Parra, Eliana L; Ramos, Viviana; Sanabria, Olga; Moreno, Jaime

    2014-01-01

    In Colombia, a laboratory-based surveillance of invasive Streptococcus pneumoniae isolates as part of SIREVA II PAHO has been conducted since 1994. This study describes the serotype distribution, antimicrobial resistance, and genetic relationships of pneumococcal isolates recovered in Colombia from 2005 to 2010. In this study, demographic data of invasive S. pneumoniae isolates were analyzed, and antimicrobial susceptibility patterns were determined. Pulse field gel electrophoresis (n = 629) and multilocus sequence typing (n = 10) were used to determine genetic relationship of isolates with minimal inhibitory concentration to penicillin ≥0.125 µg/mL. A total of 1775 isolates of S. pneumoniae were obtained. Fifteen serotypes accounted for 80.7% of isolates. Serotype 14 (23.1%) was the most frequent in the general population. Penicillin resistance was 30.7% in meningitis and 9.0% in non-meningitis. Clones Spain(6B)ST90, Spain(9V)ST156, Spain(23F)ST81, and Colombia(23F)ST338 were associated to isolates. Additionally, serotype 6A isolates were associated with ST460 and ST473, and 19A isolates with ST276, ST320, and ST1118. In conclusion, the surveillance program provided updated information of trends in serotype distribution, antimicrobial resistance and the circulation of clones in invasive pneumococcal diseases. These results could be helpful to understand the epidemiology of S. pneumoniae in Colombia, and provide a baseline to measure the impact of vaccine introduction.

  7. Recombination rates of Streptococcus pneumoniae isolates with both erm(B) and mef(A) genes.

    Science.gov (United States)

    Lee, Ji-Young; Song, Jae-Hoon; Ko, Kwan Soo

    2010-08-01

    Erythromycin-resistant Streptococcus pneumoniae isolates containing both erm(B) and mef(A) genes have a higher rate of multidrug resistance (MDR). We investigated the relationships between the presence of erythromycin resistance determinants and the recombination rate. We determined the mutation and recombination frequencies of 46 S. pneumoniae isolates, which included 19 with both erm(B) and mef(A), nine with only erm(B), six with only mef(A), and 11 erythromycin-susceptible isolates. Mutation frequency values were estimated as the number of rifampin-resistant colonies as a proportion of total viable count. Genotypes and serotypes of isolates with the hyper-recombination phenotype were determined. Twelve S. pneumoniae isolates were hypermutable and four isolates were determined to have hyper-recombination frequency. Streptococcus pneumoniae isolates with both erm(B) and mef(A) genes did not show a high mutation frequency. In contrast, all isolates with a hyper-recombination phenotype contained both erm(B) and mef(A) genes. In addition, the recombination rate of isolates with both erm(B) and mef(A) genes was statistically higher than the rate of other isolates. The dual presence of erm(B) and mef(A) genes in some pneumococcal isolates may be associated with high recombination frequency. This may be one of the reasons for the frequent emergence of MDR in certain pneumococcal isolates.

  8. Etiology of childhood community acquired pneumonia and its implications for vaccination

    Directory of Open Access Journals (Sweden)

    Nascimento-Carvalho Cristiana M.C.

    2001-01-01

    Full Text Available Pneumonia is an important cause of morbidity and mortality among children throughout the world. Vaccines are available for some organisms, but they are underutilized and/or still in development. To evaluate the potential impact of vaccines, we review studies in which the etiology of childhood community-acquired pneumonia was recorded. In North America and Europe (9 studies, the etiology of pneumonia was established in 62% of studied children (range 43%-88% by use of noninvasive specific methods for microbiologic diagnosis. The most often identified agents were S. pneumoniae (22%, respiratory syncytial virus (RSV (20%, Haemophilus influenzae (7%, and Mycoplasma pneumoniae (15%. In Africa and South America (8 studies, bacteria were recovered from 56% (range 32%-68% of severely ill children studied by lung aspirate. The most often isolated bacteria were Streptococcus pneumoniae (33% and Haemophilus influenzae (21%. A high percentage of H. influenzae strains were not serotype b. Throughout the world, children requiring hospitalization were most likely to have infection caused by pneumococcus H. influenzae or RSV. Out patients also had Mycoplasma pneumoniae. Countries in Africa and Asia recorded 2 to 10 times more children with pneumonia (7 to 40/100 annually than in the USA. Widespread use of pneumococcal and H. influenzae type b conjugate vaccines could reduce the frequency of childhood pneumonia by one-third. Further reduction will require development of non-type b H. influenzae, RSV and M. pneumoniae vaccines. This could result in a > 50% reduction of pneumonia in children. This goal should be sought and achieved as soon as possible.

  9. Impacts of the 13-Valent Pneumococcal Conjugate Vaccine in Children.

    Science.gov (United States)

    Esposito, Susanna; Principi, Nicola

    2015-01-01

    Applications of the heptavalent pneumococcal conjugate vaccine (PCV7) in the pediatric immunization schedule have dramatically reduced the incidence of pneumococcal diseases in both vaccinated children and unvaccinated individuals of all ages. However, increased infections caused by non-PCV7 serotypes have been reported by several groups. To overcome this problem, new vaccines covering more serotypes including the emerging serotypes have been developed. The 13-valent pneumococcal conjugate vaccine (PCV13) currently covers the 7 PCV7 serotypes (4, 6B, 9V, 14, 18C, 19F, and 23F) and 6 additional serotypes 1, 3, 5, 6A, 7F, and 19A. After the first year of PCV13 applications in the immunization schedule in young children, global evaluation studies demonstrated that PCV13 provided a wider coverage and more effective prevention than PCV7 against invasive pneumococcal diseases (IPDs), mucosal pneumococcal diseases, and pneumococcal carriage. We reviewed the effects of PCV13 in the control of pneumococcal diseases in children based on previous studies.

  10. Severe pneumococcal disease and temporary splenic dysfunction.

    OpenAIRE

    Pelly, M. D.; Huo, Z.; Henderson, D. C.; Soni, N.

    1997-01-01

    We report a patient presenting with pneumonia in whom temporary splenic dysfunction was diagnosed by counting pitted red blood cells. This under-recognised condition caused a transient immunosuppression which may have had serious implications for our patient's recovery.

  11. Association of Serotype-Specific Antibody Concentrations and Functional Antibody Titers with Subsequent Pneumococcal Carriage in Toddlers Immunized with a 9-Valent Pneumococcal Conjugate Vaccine

    OpenAIRE

    Simell, Birgit; Nurkka, Anu; Lahdenkari, Mika; Givon-Lavi, Noga; Käyhty, Helena; Dagan, Ron; Jokinen, Jukka

    2012-01-01

    Association of pneumococcal nasopharyngeal carriage with the concentration and opsonophagocytic activity (OPA) of serum serotype-specific antibodies was determined for toddlers 1 month after immunization with a 9-valent pneumococcal conjugate vaccine. Higher anti-serotype 14 and anti-serotype 19F IgG and anti-serotype 14 IgM correlated with a lowered probability of pneumococcal acquisition. Postvaccination OPA did not correlate with pneumococcal carriage.

  12. Maternal Antibodies to Pneumolysin but Not to Pneumococcal Surface Protein A Delay Early Pneumococcal Carriage in High-Risk Papua New Guinean Infants▿

    OpenAIRE

    Francis, Jacinta P.; Peter C Richmond; Pomat, William S.; Michael, Audrey; Keno, Helen; Phuanukoonnon, Suparat; Nelson, Jan B.; Whinnen, Melissa; Heinrich, Tatjana; Smith, Wendy-Anne; Prescott, Susan L.; Holt, Patrick G; Siba, Peter M.; Lehmann, Deborah; Anita H J van den Biggelaar

    2009-01-01

    Immunization of pregnant women can be an efficient strategy to induce early protection in infants in developing countries. Pneumococcal protein-based vaccines may have the capacity to induce pneumococcal serotype-independent protection. To understand the potential of maternal pneumococcal protein-specific antibodies in infants in high-risk areas, we studied the placental transfer of naturally acquired antibodies to pneumolysin (Ply) and pneumococcal surface protein A family 1 and 2 (PspA1 and...

  13. Allergic lung inflammation alters neither susceptibility to Streptococcus pneumoniae infection nor inducibility of innate resistance in mice

    Directory of Open Access Journals (Sweden)

    Evans Christopher M

    2009-07-01

    Full Text Available Abstract Background Protective host responses to respiratory pathogens are typically characterized by inflammation. However, lung inflammation is not always protective and it may even become deleterious to the host. We have recently reported substantial protection against Streptococcus pneumoniae (pneumococcal pneumonia by induction of a robust inflammatory innate immune response to an inhaled bacterial lysate. Conversely, the allergic inflammation associated with asthma has been proposed to promote susceptibility to pneumococcal disease. This study sought to determine whether preexisting allergic lung inflammation influences the progression of pneumococcal pneumonia or reduces the inducibilty of protective innate immunity against bacteria. Methods To compare the effect of different inflammatory and secretory stimuli on defense against pneumonia, intraperitoneally ovalbumin-sensitized mice were challenged with inhaled pneumococci following exposure to various inhaled combinations of ovalbumin, ATP, and/or a bacterial lysate. Thus, allergic inflammation, mucin degranulation and/or stimulated innate resistance were induced prior to the infectious challenge. Pathogen killing was evaluated by assessing bacterial CFUs of lung homogenates immediately after infection, the inflammatory response to the different conditions was evaluated by measurement of cell counts of bronchoalveolar lavage fluid 18 hours after challenge, and mouse survival was assessed after seven days. Results We found no differences in survival of mice with and without allergic inflammation, nor did the induction of mucin degranulation alter survival. As we have found previously, mice treated with the bacterial lysate demonstrated substantially increased survival at seven days, and this was not altered by the presence of allergic inflammation or mucin degranulation. Allergic inflammation was associated with predominantly eosinophilic infiltration, whereas the lysate-induced response

  14. Cloning and nucleotide sequence of the Streptococcus pneumoniae hyaluronidase gene and purification of the enzyme from recombinant Escherichia coli.

    OpenAIRE

    Berry, A M; Lock, R A; Thomas, S M; Rajan, D P; Hansman, D.; Paton, J C

    1994-01-01

    A gene bank of Sau3A1-generated Streptococcus pneumoniae type 23 DNA fragments was constructed in Escherichia coli K-12 with the low-copy-number cosmid vector pOU61cos. Clone lysates were screened by immunoblotting using a mouse antiserum raised against a crude pneumococcal hyaluronidase preparation. One immunoreactive clone was isolated, and it produced high level of hyaluronidase activity. This clone contained a recombinant cosmid (designated pJCP800) with an approximately 35-kb DNA insert,...

  15. Detection and serotyping of pneumococci in community acquired pneumonia patients without culture using blood and urine samples

    OpenAIRE

    Elberse, K. (Karin); Mens, S.; Cremers, A.J.; Meijvis, S.C.A.; Vlaminckx, B.; de Jonge, M. I.; Meis, J. F. G. M.; Blauwendraat, C.; Pol, I. van de; Schouls, L. M.

    2015-01-01

    Background Treatment of community acquired pneumonia (CAP) patients with antibiotics before laboratory-confirmed diagnosis leads to loss of knowledge on the causative bacterial pathogen. Therefore, an increasing number of pneumococcal infections is identified using non-culture based techniques. However, methods for serotyping directly on the clinical specimen remain scarce. Here we present three approaches for detection and serotyping of pneumococci using samples from patients with CAP. Metho...

  16. Streptococcus pneumoniae Infection of Host Epithelial Cells via Polymeric Immunoglobulin Receptor Transiently Induces Calcium Release from Intracellular Stores*

    OpenAIRE

    Asmat, T. M.; Agarwal, V; Rath, S.; Hildebrandt, J.-P.; Hammerschmidt, S.

    2011-01-01

    The pneumococcal surface protein C (PspC) is a major adhesin of Streptococcus pneumoniae (pneumococci) that interacts in a human-specific manner with the ectodomain of the human polymeric immunoglobulin receptor (pIgR) produced by respiratory epithelial cells. This interaction promotes bacterial colonization and bacterial internalization by initiating host signal transduction cascades. Here, we examined alterations of intracellular calcium ([Ca2+]i) levels in epithelial cells during host cell...

  17. 儿童肺炎链球菌感染的防治进展%Prevention and Therapy of Pneumococcal Disease in Children

    Institute of Scientific and Technical Information of China (English)

    黎全华; 杨永弘

    2013-01-01

    Streptococcus pneumoniae is one of the major pathogens of pneumonia, as wel as otitis media, sinusitis, septicemia and meningitis in children. The pneumococcal vaccination is an important measure to prevent pneumococcal disease, providing good protection to vaccinees and creating herd immunity ef ect, reducing the use of antibiotic. This article briefly describes the prevalence, drug resistance to Streptococcus pneumoniae, vaccination and other preventive strategies of pneumococca l disease.%  肺炎链球菌是引起儿童肺炎、脑膜炎、菌血症等疾病的主要致病菌之一。近年来,世界各地多重耐药肺炎链球菌的出现,导致很多抗菌药物治疗无效。接种肺炎链球菌疫苗是预防儿童肺炎链球菌感染的重要措施之一,不仅可以很好的保护接种者避免感染肺炎链球菌相关疾病,而且还能产生群体免疫效果,减少抗生素的使用。

  18. Exome Array Analysis of Susceptibility to Pneumococcal Meningitis

    Science.gov (United States)

    Kloek, Anne T.; van Setten, Jessica; van der Ende, Arie; Bots, Michiel L.; Asselbergs, Folkert W.; Serón, Mercedes Valls; Brouwer, Matthijs C.; van de Beek, Diederik; Ferwerda, Bart

    2016-01-01

    Host genetic variability may contribute to susceptibility of bacterial meningitis, but which genes contribute to the susceptibility to this complex disease remains undefined. We performed a genetic association study in 469 community-acquired pneumococcal meningitis cases and 2072 population-based controls from the Utrecht Health Project in order to find genetic variants associated with pneumococcal meningitis susceptibility. A HumanExome BeadChip was used to genotype 102,097 SNPs in the collected DNA samples. Associations were tested with the Fisher exact test. None of the genetic variants tested reached Bonferroni corrected significance (p-value pathophysiology of pneumococcal meningitis. PMID:27389768

  19. Bacteremia causes hippocampal apoptosis in experimental pneumococcal meningitis

    DEFF Research Database (Denmark)

    Andersen, Christian Østergaard; Leib, S.L.; Rowland, Ian J;

    2010-01-01

    -specific pneumococcal antibodies (n=14), and III. uninfected controls (n=6). RESULTS: Pneumococcal meningitis resulted in a significantly higher apoptosis score 0.22 (0.18-0.35) compared to uninfected controls (0.02 (0.00-0.02), Mann Whitney test, P=0.0003). Also, meningitis with an attenuation of bacteremia...... by antibody treatment resulted in significantly reduced apoptosis (0.08 (0.02-0.20), P=0.01) as compared to meningitis. CONCLUSIONS: Our results demonstrate that bacteremia accompanying meningitis plays an important role in the development of hippocampal injury in pneumococcal meningitis....

  20. Immunogenicity of a 7-valent pneumococcal conjugate vaccine (PCV7) and impact on carriage in Venezuelan children at risk of invasive pneumococcal diseases

    NARCIS (Netherlands)

    Rivera-Olivero, I.A.; Nogal, B. del; Fuentes, M.; Cortez, R.; Bogaert, D.; Hermans, P.W.M.; Waard, J.H. de

    2014-01-01

    BACKGROUND AND AIMS: We evaluated the immunogenicity of the 7-valent pneumococcal conjugate vaccine (PCV7), and its impact on pneumococcal carriage in Venezuelan children at high risk for invasive pneumococcal disease (IPD). METHODS: 82 children (age 2-59 months) with sickle cell anemia (n=22), chro

  1. Antimicrobial Activity of Novel Synthetic Peptides Derived from Indolicidin and Ranalexin against Streptococcus pneumoniae.

    Directory of Open Access Journals (Sweden)

    Hassan Mahmood Jindal

    Full Text Available Antimicrobial peptides (AMPs represent promising alternatives to conventional antibiotics in order to defeat multidrug-resistant bacteria such as Streptococcus pneumoniae. In this study, thirteen antimicrobial peptides were designed based on two natural peptides indolicidin and ranalexin. Our results revealed that four hybrid peptides RN7-IN10, RN7-IN9, RN7-IN8, and RN7-IN6 possess potent antibacterial activity against 30 pneumococcal clinical isolates (MIC 7.81-15.62µg/ml. These four hybrid peptides also showed broad spectrum antibacterial activity (7.81µg/ml against S. aureus, methicillin resistant S. aureus (MRSA, and E. coli. Furthermore, the time killing assay results showed that the hybrid peptides were able to eliminate S. pneumoniae within less than one hour which is faster than the standard drugs erythromycin and ceftriaxone. The cytotoxic effects of peptides were tested against human erythrocytes, WRL-68 normal liver cell line, and NL-20 normal lung cell line. The results revealed that none of the thirteen peptides have cytotoxic or hemolytic effects at their MIC values. The in silico molecular docking study was carried out to investigate the binding properties of peptides with three pneumococcal virulent targets by Autodock Vina. RN7IN6 showed a strong affinity to target proteins; autolysin, pneumolysin, and pneumococcal surface protein A (PspA based on rigid docking studies. Our results suggest that the hybrid peptides could be suitable candidates for antibacterial drug development.

  2. High-Level Genetic Diversity among Invasive Streptococcus pneumoniae Isolates in Turkey.

    Science.gov (United States)

    Guldemir, Dilek; Acar, Sumeyra; Otgun, Selin Nar; Unaldi, Ozlem; Gozalan, Aysegul; Ertek, Mustafa; Durmaz, Riza

    2016-05-20

    This study obtained information on the serotypes and molecular typing characteristics of Streptococcus pneumoniae strains causing invasive diseases in Turkey. Sixty-eight S. pneumoniae isolates causing invasive pneumococcal diseases were collected from different regions of Turkey from 2009 to 2011. The isolates were characterized by performing multilocus sequence typing (MLST), pulsed-field gel electrophoresis (PFGE), and capsular serotyping, and 25 different serotypes were identified. Serotypes 19F, 23F, 1, 14, and 7F were common and accounted for 52.9% of all the serotypes. In addition, 54 different PFGE profiles (pulsotypes) were observed. Twenty-three of the 68 (33.8%) isolates were clustered into 9 pulsotypes. MLST analysis yielded 36 sequence types, of which 12 (33.3%) were novel. A comparison of results with the global pneumococcal MLST database by performing eBURST analysis showed that our strains belonged to 20 different clonal complexes and 5 singletons. In addition, we identified 4 new alleles: 2 gdh, 1 xpt, and 1 ddl. Thus, the results of this study highlighted a high level of diversity among pneumococcal isolates. In addition, the study identified a case of possible capsular switching. PMID:26255730

  3. Prophage spontaneous activation promotes DNA release enhancing biofilm formation in Streptococcus pneumoniae.

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    Margarida Carrolo

    Full Text Available Streptococcus pneumoniae (pneumococcus is able to form biofilms in vivo and previous studies propose that pneumococcal biofilms play a relevant role both in colonization and infection. Additionally, pneumococci recovered from human infections are characterized by a high prevalence of lysogenic bacteriophages (phages residing quiescently in their host chromosome. We investigated a possible link between lysogeny and biofilm formation. Considering that extracellular DNA (eDNA is a key factor in the biofilm matrix, we reasoned that prophage spontaneous activation with the consequent bacterial host lysis could provide a source of eDNA, enhancing pneumococcal biofilm development. Monitoring biofilm growth of lysogenic and non-lysogenic pneumococcal strains indicated that phage-infected bacteria are more proficient at forming biofilms, that is their biofilms are characterized by a higher biomass and cell viability. The presence of phage particles throughout the lysogenic strains biofilm development implicated prophage spontaneous induction in this effect. Analysis of lysogens deficient for phage lysin and the bacterial major autolysin revealed that the absence of either lytic activity impaired biofilm development and the addition of DNA restored the ability of mutant strains to form robust biofilms. These findings establish that limited phage-mediated host lysis of a fraction of the bacterial population, due to spontaneous phage induction, constitutes an important source of eDNA for the S. pneumoniae biofilm matrix and that this localized release of eDNA favors biofilm formation by the remaining bacterial population.

  4. Respiratory Review of 2012: Pneumonia

    OpenAIRE

    Yoon, Young-Soon

    2012-01-01

    Pneumonia is the cause of significant morbidity and mortality, despite advances in diagnosis and antibacterial treatment. Pneumonia is often misdiagnosed and mistreated up until recently. Recent classification of pneumonia consists of community-acquired pneumonia, health care-associated pneumonia, hospital-acquired pneumonia, and ventilator-associated pneumonia. The etiology, risk factors, and treatment are different among them. This article briefly introduces new concepts and ideas in biomar...

  5. High rate of pneumococcal bacteremia in a prospective cohort of older children and adults in an area of high HIV prevalence in rural western Kenya

    Directory of Open Access Journals (Sweden)

    Oundo Joseph

    2010-06-01

    Full Text Available Abstract Background Although causing substantial morbidity, the burden of pneumococcal disease among older children and adults in Africa, particularly in rural settings, is not well-characterized. We evaluated pneumococcal bacteremia among 21,000 persons ≥5 years old in a prospective cohort as part of population-based infectious disease surveillance in rural western Kenya from October 2006-September 2008. Methods Blood cultures were done on patients meeting pre-defined criteria - severe acute respiratory illness (SARI, fever, and admission for any reason at a referral health facility within 5 kilometers of all 33 villages where surveillance took place. Serotyping of Streptococcus pneumoniae was done by latex agglutination and quellung reaction and antibiotic susceptibility testing was done using broth microdilution. We extrapolated incidence rates based on persons with compatible illnesses in the surveillance population who were not cultured. We estimated rates among HIV-infected persons based on community HIV prevalence. We projected the national burden of pneumococcal bacteremia cases based on these rates. Results Among 1,301 blood cultures among persons ≥5 years, 52 (4% yielded pneumococcus, which was the most common bacteria isolated. The yield was higher among those ≥18 years than 5-17 years (6.9% versus 1.6%, p 95%. The crude rate of pneumococcal bacteremia was 129/100,000 person-years, and the adjusted rate was 419/100,000 person-years. Nineteen (61% of 31 patients with HIV results were HIV-positive. The adjusted rate among HIV-infected persons was 2,399/100,000 person-years (Rate ratio versus HIV-negative adults, 19.7, 95% CI 12.4-31.1. We project 58,483 cases of pneumococcal bacteremia will occur in Kenyan adults in 2010. Conclusions Pneumococcal bacteremia rates were high among persons ≥5 years old, particularly among HIV-infected persons. Ongoing surveillance will document if expanded use of highly-active antiretroviral

  6. Cost-Effectiveness Analysis of Universal Vaccination of Adults Aged 60 Years with 23-Valent Pneumococcal Polysaccharide Vaccine versus Current Practice in Brazil.

    Directory of Open Access Journals (Sweden)

    Patrícia Coelho de Soárez

    Full Text Available To evaluate the cost-effectiveness of introducing universal vaccination of adults aged 60 years with the 23-valent pneumococcal polysaccharide vaccine (PPV23 into the National Immunization Program (NIP in Brazil.Economic evaluation using a Markov model to compare two strategies: (1 universal vaccination of adults aged 60 years with one dose of PPV23 and 2 current practice (vaccination of institutionalized elderly and elderly with underlying diseases. The perspective was from the health system and society. Temporal horizon was 10 years. Discount rate of 5% was applied to costs and benefits. Clinical syndromes of interest were invasive pneumococcal disease (IPD including meningitis, sepsis and others and pneumonia. Vaccine efficacy against IPD was obtained from a meta-analysis of randomized control trials and randomized studies, whereas vaccine effectiveness against pneumonia was obtained from cohort studies. Resource utilization and costs were obtained from the Brazilian Health Information Systems. The primary outcome was cost per life year saved (LYS. Univariate and multivariate sensitivity analysis were performed.The universal vaccination strategy avoided 7,810 hospitalizations and 514 deaths, saving 3,787 years of life and costing a total of USD$31,507,012 and USD$44,548,180, respectively, from the health system and societal perspective. The universal immunization would result in ICERs of USD$1,297 per LYS, from the perspective of the health system, and USD$904 per LYS, from the societal perspective.The results suggest that universal vaccination of adults aged 60 years with the 23-valent pneumococcal polysaccharide vaccine (PPV23 is a very cost-effective intervention for preventing hospitalization and deaths for IPD and pneumonia is this age group in Brazil.

  7. Characterization of Pneumococcal Genes Involved in Bloodstream Invasion in a Mouse Model.

    Directory of Open Access Journals (Sweden)

    Layla K Mahdi

    Full Text Available Streptococcus pneumoniae (the pneumococcus continues to account for significant morbidity and mortality worldwide, causing life-threatening diseases such as pneumonia, bacteremia and meningitis, as well as less serious infections such as sinusitis, conjunctivitis and otitis media. Current polysaccharide vaccines are strictly serotype-specific and also drive the emergence of non-vaccine serotype strains. In this study, we used microarray analysis to compare gene expression patterns of either serotype 4 or serotype 6A pneumococci in the nasopharynx and blood of mice, as a model to identify genes involved in invasion of blood in the context of occult bacteremia in humans. In this manner, we identified 26 genes that were significantly up-regulated in the nasopharynx and 36 genes that were significantly up-regulated in the blood that were common to both strains. Gene Ontology classification revealed that transporter and DNA binding (transcription factor activities constitute the significantly different molecular functional categories for genes up-regulated in the nasopharynx and blood. Targeted mutagenesis of selected genes from both niches and subsequent virulence and pathogenesis studies identified the manganese-dependent superoxide dismutase (SodA as most likely to be essential for colonization, and the cell wall-associated serine protease (PrtA as important for invasion of blood. This work extends our previous analyses and suggests that both PrtA and SodA warrant examination in future studies aimed at prevention and/or control of pneumococcal disease.

  8. Addiction of Hypertransformable Pneumococcal Isolates to Natural Transformation for In Vivo Fitness and Virulence.

    Science.gov (United States)

    Li, Guiling; Liang, Zhuowen; Wang, Xiatai; Yang, Yonghong; Shao, Zhujun; Li, Machao; Ma, Yueyun; Qu, Fen; Morrison, Donald A; Zhang, Jing-Ren

    2016-06-01

    Natural genetic transformation of Streptococcus pneumoniae, an important human pathogen, mediates horizontal gene transfer for the development of drug resistance, modulation of carriage and virulence traits, and evasion of host immunity. Transformation frequency differs greatly among pneumococcal clinical isolates, but the molecular basis and biological importance of this interstrain variability remain unclear. In this study, we characterized the transformation frequency and other associated phenotypes of 208 S. pneumoniae clinical isolates representing at least 30 serotypes. While the vast majority of these isolates (94.7%) were transformable, the transformation frequency differed by up to 5 orders of magnitude between the least and most transformable isolates. The strain-to-strain differences in transformation frequency were observed among many isolates producing the same capsule types, indicating no general association between transformation frequency and serotype. However, a statistically significant association was observed between the levels of transformation and colonization fitness/virulence in the hypertransformable isolates. Although nontransformable mutants of all the selected hypertransformable isolates were significantly attenuated in colonization fitness and virulence in mouse infection models, such mutants of the strains with relatively low transformability had no or marginal fitness phenotypes under the same experimental settings. This finding strongly suggests that the pneumococci with high transformation capability are "addicted" to a "hypertransformable" state for optimal fitness in the human host. This work has thus provided an intriguing hint for further investigation into how the competence system impacts the fitness, virulence, and other transformation-associated traits of this important human pathogen. PMID:27068094

  9. Clonal expansion within pneumococcal serotype 6C after use of seven-valent vaccine.

    Directory of Open Access Journals (Sweden)

    Nicholas J Loman

    Full Text Available Streptococcus pneumoniae causes invasive infections, primarily at the extremes of life. A seven-valent conjugate vaccine (PCV7 is used to protect against invasive pneumococcal disease in children. Within three years of PCV7 introduction, we observed a fourfold increase in serotype 6C carriage, predominantly due to a single clone. We determined the whole-genome sequences of nineteen S. pneumoniae serotype 6C isolates, from both carriage (n = 15 and disease (n = 4 states, to investigate the emergence of serotype 6C in our population, focusing on a single multi-locus sequence type (MLST clonal complex 395 (CC395. A phylogenetic network was constructed to identify different lineages, followed by analysis of variability in gene sets and sequences. Serotype 6C isolates from this single geographical site fell into four broad phylogenetically distinct lineages. Variation was seen in the 6C capsular locus and in sequences of genes encoding surface proteins. The largest clonal complex was characterised by the presence of lantibiotic synthesis locus. In our population, the 6C capsular locus has been introduced into multiple lineages by independent capsular switching events. However, rapid clonal expansion has occurred within a single MLST clonal complex. Worryingly, plasticity exists within current and potential vaccine-associated loci, a consideration for future vaccine use, target selection and design.

  10. NASOPHARYNGEAL CARRIAGE OF STREPTOCOCCUS PNEUMONIAE IN HEALTHY CHILDREN UNDER FIVE YEARS OLD IN CENTRAL LOMBOK REGENCY, INDONESIA.

    Science.gov (United States)

    Hadinegoro, Sri Rezeki; Prayitno, Ari; Khoeri, Miftahuddin Majid; Djelantik, I Gusti Gede; Dewi, Nurhandini Eka; Indriyani, Sang Ayu Kompiang; Muttaqin, Zainul; Mudaliana, Siti; Safari, Dodi

    2016-05-01

    Colonization with Streptococcus pneumoniae is mostly symptomless, but can progress to respiratory or even systemic disease. We investigated nasopharyngeal carriage of Streptococcus pneumoniae in healthy children under five years of age in Central Lombok Regency, Indonesia. This cross sectional study was carried out in 2012 among 1,200 healthy children aged 2 to 60 months. A multiplex sequential PCR was employed to determine serotype of cultured S. pneumoniae and a disk diffusion method to assess susceptibility to antimicrobial drugs. S. pneumoniae was cultured from 554 children and the most frequent serotypes found were 6A/B (22% of pneumococcal strains), 19F (11%), 23F (10%), 15B/C (8%), and 19A and 14 (4% each). The majority of strains were still susceptible to clindamycin (97%), erythromycin (87%), chloramphenicol (81%), and penicillin (72%), with only 41% and 38% susceptible to tetracycline and sulfamethoxazole/trimethoprim, respectively. Continuous surveillance of S. pneumoniae carriage is important for future pneumococcal vaccination programs in Indonesia.

  11. NASOPHARYNGEAL CARRIAGE OF STREPTOCOCCUS PNEUMONIAE IN HEALTHY CHILDREN UNDER FIVE YEARS OLD IN CENTRAL LOMBOK REGENCY, INDONESIA.

    Science.gov (United States)

    Hadinegoro, Sri Rezeki; Prayitno, Ari; Khoeri, Miftahuddin Majid; Djelantik, I Gusti Gede; Dewi, Nurhandini Eka; Indriyani, Sang Ayu Kompiang; Muttaqin, Zainul; Mudaliana, Siti; Safari, Dodi

    2016-05-01

    Colonization with Streptococcus pneumoniae is mostly symptomless, but can progress to respiratory or even systemic disease. We investigated nasopharyngeal carriage of Streptococcus pneumoniae in healthy children under five years of age in Central Lombok Regency, Indonesia. This cross sectional study was carried out in 2012 among 1,200 healthy children aged 2 to 60 months. A multiplex sequential PCR was employed to determine serotype of cultured S. pneumoniae and a disk diffusion method to assess susceptibility to antimicrobial drugs. S. pneumoniae was cultured from 554 children and the most frequent serotypes found were 6A/B (22% of pneumococcal strains), 19F (11%), 23F (10%), 15B/C (8%), and 19A and 14 (4% each). The majority of strains were still susceptible to clindamycin (97%), erythromycin (87%), chloramphenicol (81%), and penicillin (72%), with only 41% and 38% susceptible to tetracycline and sulfamethoxazole/trimethoprim, respectively. Continuous surveillance of S. pneumoniae carriage is important for future pneumococcal vaccination programs in Indonesia. PMID:27405132

  12. Clinical experience of the 23-valent capsular polysaccharide pneumococcal vaccination in HIV-1-infected patients receiving highly active antiretroviral therapy: a prospective observational study.

    Science.gov (United States)

    Hung, Chien-Ching; Chen, Mao-Yuan; Hsieh, Szu-Min; Hsiao, Chin-Fu; Sheng, Wang-Hwei; Chang, Shan-Chwen

    2004-05-01

    To assess the impact of vaccination with 23-valent pneumococcal polysaccharide vaccine on the risks for development of pneumococcal disease, all-cause community-acquired pneumonia, HIV progression, and mortality and immunologic and virologic responses among HIV-1-infected patients treated with highly active antiretroviral therapy (HAART), we conducted a 2-year prospective observational cohort study at a university hospital in Taiwan. A total of 305 HIV-1-infected patients who received 23-valent pneumococcal vaccine (vaccinees) and 203 patients who did not (non-vaccinees) were prospectively observed between 1 June 2000 and 31 October 2002. Changes of CD4+ and plasma viral load (PVL) from baseline to week 4 of vaccination were assessed in 31 randomly selected vaccinees. The incidence of pneumococcal disease and bacteremia of vaccinees was 2.1 per 1000 patient-years (PY) (95% confidence interval (95% CI), 1.7-2.5 per 1000 PY) over the median observation of 641 days (range, 37-832 days) following vaccination while that of non-vaccinee was 21.8 per 1000 PY (95% CI, 20.1-23.7 per 1000 PY) and 7.3 per 1000 PY (95% CI, 7.0-7.6 per 1000 PY), respectively, over the observation of 500 days (range, 32-851 days), with an adjusted odds ratio (AOR) for developing pneumococcal disease of 0.085 (95% CI, 0.010-0.735) and for bacteremia of 0.22 (95% CI, 0.018-2.561). The median CD4+ count increased by 45 x 10(6) l(-1) (P = 0.01) and median PVL change was 0 log(10) copies/ml (range of decrease, -0.74 to 2.47 log(10) copies/ml) after 1 month of pneumococcal vaccination among the subgroup of 31 vaccinees receiving HAART. The median CD4+ count increase from baseline to the end of study was 149 x 10(6) l(-1) for vaccinees and 107 x 10(6) l(-1) for non-vaccinees (P = 0.21). The AOR of developing all-cause community-acquired pneumonia and new AIDS-defining opportunistic illnesses (OI) of vaccinees as compared to non-vaccinees was 1.876 (95% CI, 0.785-4.485) and 0.567 (95% CI, 0

  13. Induction of Central Host Signaling Kinases during Pneumococcal Infection of Human THP-1 Cells.

    Science.gov (United States)

    Kohler, Thomas P; Scholz, Annemarie; Kiachludis, Delia; Hammerschmidt, Sven

    2016-01-01

    Streptococcus pneumoniae is a widespread colonizer of the mucosal epithelia of the upper respiratory tract of human. However, pneumococci are also responsible for numerous local as well as severe systemic infections, especially in children under the age of five and the elderly. Under certain conditions, pneumococci are able to conquer the epithelial barrier, which can lead to a dissemination of the bacteria into underlying tissues and the bloodstream. Here, specialized macrophages represent an essential part of the innate immune system against bacterial intruders. Recognition of the bacteria through different receptors on the surface of macrophages leads thereby to an uptake and elimination of bacteria. Accompanied cytokine release triggers the migration of leukocytes from peripheral blood to the site of infection, where monocytes differentiate into mature macrophages. The rearrangement of the actin cytoskeleton during phagocytosis, resulting in the engulfment of bacteria, is thereby tightly regulated by receptor-mediated phosphorylation cascades of different protein kinases. The molecular cellular processes including the modulation of central protein kinases are only partially solved. In this study, the human monocytic THP-1 cell line was used as a model system to examine the activation of Fcγ and complement receptor-independent signal cascades during infection with S. pneumoniae. Pneumococci cultured either in chemically defined or complex medium showed no significant differences in pneumococcal phagocytosis by phorbol 12-myristate 13-acetate (PMA) differentiated THP-1 cells. Double immuno-fluorescence microscopy and antibiotic protection assays demonstrated a time-dependent uptake and killing of S. pneumoniae 35A inside of macrophages. Infections of THP-1 cells in the presence of specific pharmacological inhibitors revealed a crucial role of actin polymerization and importance of the phosphoinositide 3-kinase (PI3K) and Protein kinase B (Akt) as well during

  14. Induction of central host signalling kinases during pneumococcal infection of human THP-1 cells

    Directory of Open Access Journals (Sweden)

    Thomas Peter Kohler

    2016-04-01

    Full Text Available Streptococcus pneumoniae is a widespread colonizer of the mucosal epithelia of the upper respiratory tract of human. However, pneumococci are also responsible for numerous local as well as severe systemic infections, especially in children under the age of five and the elderly. Under certain conditions, pneumococci are able to conquer the epithelial barrier, which can lead to a dissemination of the bacteria into underlying tissues and the bloodstream. Here, specialized macrophages represent an essential part of the innate immune system against bacterial intruders. Recognition of the bacteria through different receptors on the surface of macrophages leads thereby to an uptake and elimination of bacteria. Accompanied cytokine release triggers the migration of leukocytes from peripheral blood to the site of infection, where monocytes differentiate into mature macrophages. The rearrangement of the actin cytoskeleton during phagocytosis, resulting in the engulfment of bacteria, is thereby tightly regulated by receptor-mediated phosphorylation cascades of different protein kinases. The molecular cellular processes including the modulation of central protein kinases are only partially solved. In this study, the human monocytic THP-1 cell line was used as a model system to examine the activation of Fcγ and complement receptor-independent signal cascades during infection with S. pneumoniae. Pneumococci cultured either in chemically defined or complex medium showed no significant differences in pneumococcal phagocytosis by phorbol 12-myristate 13-acetate (PMA differentiated THP-1 cells. Double immuno-fluorescence microscopy and antibiotic protection assays demonstrated a time-dependent uptake and killing of S. pneumoniae 35A inside of macrophages. Infections of THP-1 cells in the presence of specific pharmacological inhibitors revealed a crucial role of actin polymerization and importance of the phosphoinositide 3-kinase (PI3K and Protein kinase B (Akt

  15. Serotype-specific changes in invasive pneumococcal disease after pneumococcal conjugate vaccine introduction

    DEFF Research Database (Denmark)

    Feikin, Daniel R; Kagucia, Eunice W; Loo, Jennifer D;

    2013-01-01

    BACKGROUND: Vaccine-serotype (VT) invasive pneumococcal disease (IPD) rates declined substantially following introduction of 7-valent pneumococcal conjugate vaccine (PCV7) into national immunization programs. Increases in non-vaccine-serotype (NVT) IPD rates occurred in some sites, presumably...... representing serotype replacement. We used a standardized approach to describe serotype-specific IPD changes among multiple sites after PCV7 introduction. METHODS AND FINDINGS: Of 32 IPD surveillance datasets received, we identified 21 eligible databases with rate data ≥ 2 years before and ≥ 1 year after PCV7...... introduction. Expected annual rates of IPD absent PCV7 introduction were estimated by extrapolation using either Poisson regression modeling of pre-PCV7 rates or averaging pre-PCV7 rates. To estimate whether changes in rates had occurred following PCV7 introduction, we calculated site specific rate ratios...

  16. Impact of 13-Valent Pneumococcal Conjugate Vaccination in Invasive Pneumococcal Disease Incidence and Mortality

    DEFF Research Database (Denmark)

    Harboe, Zitta Barrella; Dalby, Tine; Weinberger, Daniel M;

    2014-01-01

    conjugate vaccine (PCV7) (2008-2010), and PCV13 (2011-2013) periods were estimated. Predicted incidences of serotypes were estimated controlling for cyclical trends from historical patterns observed during the past 20 years. RESULTS: We observed a 21% reduction (95% confidence interval [CI], 17%-25%) in IPD......BACKGROUND: The impact of the 13-valent pneumococcal conjugate vaccine (PCV13) at the population level is unclear. We explored PCV13's effect in reducing invasive pneumococcal disease (IPD)-related morbidity and mortality, and whether serotype-specific changes were attributable to vaccination...... incidence in the total population after PCV13's introduction, and a 71% reduction (95% CI, 62%-79%) in children aged vaccine effectiveness. We estimated a 28% reduction (95% CI, 18%-37%) in IPD-related 30-day mortality, from 3.4 deaths (95% CI, 3.2-3.6) per 100 000 population...

  17. Pneumococcal serotypes and mortality following invasive pneumococcal disease: a population-based cohort study

    DEFF Research Database (Denmark)

    Harboe, Zitta B; Thomsen, Reimar W; Riis, Anders;

    2009-01-01

    younger than age 5 y. Age, male sex, meningitis, high comorbidity level, alcoholism, and early decade of diagnosis were significantly associated with mortality. Among individuals aged 5 y and older, serotypes 31, 11A, 35F, 17F, 3, 16F, 19F, 15B, and 10A were associated with highly increased mortality...... as compared with serotype 1 (all: adjusted odds ratio >or=3, pchildhood-related mortality. CONCLUSIONS: Specific pneumococcal serotypes...

  18. Recurrent invasive pneumococcal disease in children--host factors and vaccination response.

    Science.gov (United States)

    Ingels, Helene Andrea Sinclair

    2015-07-01

    Streptococcus pneumoniae is still a leading cause of septicaemia, pneumonia and meningitis in young children world-wide with over half a million children dying annually from pneumococcal disease.  Some children are prone to repeated episodes of invasive pneumococcal disease (IPD) because of an underlying predisposing disease. Recurrent IPD (rIPD) is a rarity and published reports on rIPD are limited by having few children included, selected groups of patients or short follow-up periods. Deficiencies in the innate or adaptive immune system have been described in children with rIPD, but the frequency of immunodeficiency among such patients is unknown. The aim of this PhD thesis was to examine paediatric cases of laboratory-confirmed rIPD, over a 33-year period in Denmark, to determine risk factors and study aspects of the immunological background for this problem in children. In October 2007, a seven-valent pneumococcal conjugate vaccine (PCV7) was implemented in the Danish infant immunization programme. An additional aim of the thesis was to examine the impact of vaccination on a population level, following the first three years of general PCV7 vaccination in Denmark. The thesis consists of three papers, which are all directly or indirectly based on data retrieved from the National Streptococcus Pneumoniae Registry. This registry is nationwide and dates back to 1938. The registry contains data from all laboratory-confirmed cases of IPD in Denmark and is continually updated for national surveillance. In Paper 1, we conducted a 33-year retrospective nationwide study of paediatric rIPD. By using data from the National Streptococcus Pneumoniae Registry combined with clinical data from hospital records, we could describe one of the largest known cohorts of children (n:59) with rIPD . We covered epidemiological, microbiological, and clinical features of this clinical entity. Of all children experiencing rIPD, 47% had a known predisposing underlying disease at the time of

  19. Evaluation and improvement of real-time PCR assays targeting lytA, ply, and psaA genes for detection of pneumococcal DNA.

    Science.gov (United States)

    Carvalho, Maria da Gloria S; Tondella, Maria Lucia; McCaustland, Karen; Weidlich, Luciana; McGee, Lesley; Mayer, Leonard W; Steigerwalt, Arnold; Whaley, Melissa; Facklam, Richard R; Fields, Barry; Carlone, George; Ades, Edwin W; Dagan, Ron; Sampson, Jacquelyn S

    2007-08-01

    The accurate diagnosis of pneumococcal disease has frequently been hampered not only by the difficulties in obtaining isolates of the organism from patient specimens but also by the misidentification of pneumococcus-like viridans group streptococci (P-LVS) as Streptococcus pneumoniae. This is especially critical when the specimen comes from the respiratory tract. In this study, three novel real-time PCR assays designed for the detection of specific sequence regions of the lytA, ply, and psaA genes were developed (lytA-CDC, ply-CDC, and psaA, respectively). These assays showed high sensitivity (<10 copies for lytA-CDC and ply-CDC and an approximately twofold less sensitivity for psaA). Two additional real-time PCR assays for lytA and ply described previously for pneumococcal DNA detection were also evaluated. A panel of isolates consisting of 67 S. pneumoniae isolates (44 different serotypes and 3 nonencapsulated S. pneumoniae isolates from conjunctivitis outbreaks) and 104 nonpneumococcal isolates was used. The 67 S. pneumoniae isolates were reactive in all five assays. The new real-time detection assays targeting the lytA and psaA genes were the most specific for the detection of isolates confirmed to be S. pneumoniae, with lytA-CDC showing the greatest specificity. Both ply PCRs were positive for all isolates of S. pseudopneumoniae, along with 13 other isolates of other P-LVS isolates confirmed to be non-S. pneumoniae by DNA-DNA reassociation. Thus, the use of the ply gene for the detection of pneumococci can lead to false-positive reactions in the presence of P-LVS. The five assays were applied to 15 culture-positive cerebrospinal fluid specimens with 100% sensitivity; and serum and ear fluid specimens were also evaluated. Both the lytA-CDC and psaA assays, particularly the lytA-CDC assay, have improved specificities compared with those of currently available assays and should therefore be considered the assays of choice for the detection of pneumococcal DNA

  20. Evaluation and Improvement of Real-Time PCR Assays Targeting lytA, ply, and psaA Genes for Detection of Pneumococcal DNA▿

    Science.gov (United States)

    Carvalho, Maria da Gloria S.; Tondella, Maria Lucia; McCaustland, Karen; Weidlich, Luciana; McGee, Lesley; Mayer, Leonard W.; Steigerwalt, Arnold; Whaley, Melissa; Facklam, Richard R.; Fields, Barry; Carlone, George; Ades, Edwin W.; Dagan, Ron; Sampson, Jacquelyn S.

    2007-01-01

    The accurate diagnosis of pneumococcal disease has frequently been hampered not only by the difficulties in obtaining isolates of the organism from patient specimens but also by the misidentification of pneumococcus-like viridans group streptococci (P-LVS) as Streptococcus pneumoniae. This is especially critical when the specimen comes from the respiratory tract. In this study, three novel real-time PCR assays designed for the detection of specific sequence regions of the lytA, ply, and psaA genes were developed (lytA-CDC, ply-CDC, and psaA, respectively). These assays showed high sensitivity (<10 copies for lytA-CDC and ply-CDC and an approximately twofold less sensitivity for psaA). Two additional real-time PCR assays for lytA and ply described previously for pneumococcal DNA detection were also evaluated. A panel of isolates consisting of 67 S. pneumoniae isolates (44 different serotypes and 3 nonencapsulated S. pneumoniae isolates from conjunctivitis outbreaks) and 104 nonpneumococcal isolates was used. The 67 S. pneumoniae isolates were reactive in all five assays. The new real-time detection assays targeting the lytA and psaA genes were the most specific for the detection of isolates confirmed to be S. pneumoniae, with lytA-CDC showing the greatest specificity. Both ply PCRs were positive for all isolates of S. pseudopneumoniae, along with 13 other isolates of other P-LVS isolates confirmed to be non-S. pneumoniae by DNA-DNA reassociation. Thus, the use of the ply gene for the detection of pneumococci can lead to false-positive reactions in the presence of P-LVS. The five assays were applied to 15 culture-positive cerebrospinal fluid specimens with 100% sensitivity; and serum and ear fluid specimens were also evaluated. Both the lytA-CDC and psaA assays, particularly the lytA-CDC assay, have improved specificities compared with those of currently available assays and should therefore be considered the assays of choice for the detection of pneumococcal DNA

  1. Invasive pneumococcal infection despite 7-valent conjugated vaccine

    Directory of Open Access Journals (Sweden)

    Sebastien Joye

    2013-03-01

    Full Text Available Despite good cover with 7-valent vaccination, invasive pneumococcal infections may still be misdiagnosed and may lead to lifethreatening situations or death in young children. New serotypes are emerging and, therefore, clinicians must keep a high level of suspicion in young children regardless of their vaccination status. We report three cases of invasive pneumococcal infection due to new serotypes not covered by the 7-valent conjugated vaccine, two of which led children to death.

  2. A Systematic Review of the Serotype Distribution of Streptococcus Pneumoniae (pneumococcus) among all Cases under 18 Years Old of Pneumococcal Infection in China%中国≤18岁人群肺炎球菌相关病例中肺炎球菌血清型分布的系统评价

    Institute of Scientific and Technical Information of China (English)

    韦宁; 安志杰; 王华庆

    2014-01-01

    目的 了解中国≤18岁人群肺炎球菌相关病例中肺炎球菌血清型分布,及7价肺炎球菌多糖结合疫苗(7-valent Pneumococcal Polysaccharide Conjugate Vaccine,PPCV7)、13价(13-valent)PPCV(PPCV13)血清型覆盖情况,为制定疫苗免疫策略提供参考.方法 采用系统评价方法,在中国医院知识数据库、万方数据库和美国国立图书馆(Pubmed)中检索相关文献,对符合条件文献的信息进行提取,采用中位数(Median,M)和四分位数区间(QuartileRange,Q)对血清型分布和疫苗的血清型覆盖情况进行分析.结果 系统评价共收集符合条件的文献28篇,结果显示,中国1996 ~2004年≤18岁人群肺炎球菌相关病例中,肺炎球菌主要血清型分布是:23F占16.7%(Q:11.6%~20.4%)、19F占13.8% (Q:11.9% ~34.1%)、6A占9.9%(Q:7.1% ~ 13.2%).在南方,19F占30.2% (Q:16.3% ~35.3%)、23F占16.9% (Q:14.0%~19.6%)、6A占9.4%(Q:7.6%~11.0%);在北方,6A占13.2%(Q:6.6% ~ 16.5%)、23F占11.6% (Q:10.8% ~20.9%)、19F占10.0% (Q:8.7% ~11.9%).2005 ~ 2013年,19F占28.7%(Q:20.8% ~42.2%)、19A占15.2%(Q:10.2% ~ 19.7%)、23F占9.7%(Q:5.9% ~ 12.3%).在南方,19F占42.3% (Q:28.6% ~62.2%)、19A占16.9%占(Q:3.3%~19.6%)、23F占11.5%(Q:4.3%~15.2%);在北方,19A占20.6%(Q:6.4% ~ 33.9%)、19F占18.6%(Q:11.5% ~28.6%)、23F占9.8%(Q:9.3%~13.6%).≤5岁人群侵袭性肺炎球菌血清型分布是:19A占33.3% (Q:31.2% ~33.3%)、19F占16.7% (Q:14.1% ~19.6%)、14占12.9% (Q:9.2% ~16.3%).≤18岁人群疫苗血清型覆盖情况为:1996 ~ 2004年,PPCV7为59.5%(Q:40.0% ~64.2%),南方为63.6%(Q:60.4% ~65.4%),北方为40.0% (Q:36.8% ~46.7%);PPCV13为75.7% (Q:66.7% ~83.3%),南方为79.5% (Q:68.9% ~83.8%),北方为70.0% (Q:58.4% ~75.1%).2005 ~ 2013年,PPCV7为60.2%(Q:52.0% ~67.1

  3. Effective management in clusters of pneumococcal disease: a systematic review.

    Science.gov (United States)

    Basarab, Marina; Ihekweazu, Chikwe; George, Robert; Pebody, Richard

    2011-02-01

    Outbreaks of serious pneumococcal disease can occur with high attack rates in certain settings. We systematically reviewed studies of interventions implemented in pneumococcal clusters and those reporting the effect of antibiotics on carriage reduction to assess the effectiveness of interventions. Evidence was graded according to the Scottish Intercollegiate Guidelines Network system. Of 28 identified cluster reports, one showed that administration of antibiotics to close contacts reduced risk of pneumococcal disease. In three of four clusters where rifampicin chemoprophylaxis was used and in four of five clusters where penicillin was used no further cases were seen after intervention. In clusters where pneumococcal polysaccharide vaccine was used, subsequent cases occurred, all within around 2 weeks of vaccination, which suggests delayed benefit with this approach (evidence grade D). Use of infection control measures alone was reported in eight clusters, with no further cases being reported in seven (grade D). From 21 selected carriage studies, large carriage reductions were observed consistently with use of penicillin and azithromycin, with median values being 90% and 73%, respectively (grade C). The findings were presented to a working group for pneumococcal cluster guidelines and used to develop key recommendations on the management of clusters that supported prompt use of amoxicillin or azithromycin chemoprophylaxis, pneumococcal vaccination for close contacts, and implementation of infection control measures. PMID:21272792

  4. Microbial factors and host responses affecting severity of pneumococcal disease and pneumococcal carriage

    OpenAIRE

    Sandgren, Andreas

    2005-01-01

    Streptococcus pneumoniae, also known as the pneumococcus, is a human specific bacterium and causes infections like otitis media, sinusitis, pneumonia, sepsis and meningitis. However, these bacteria are also frequent colonizers of the nasopharynx of healthy individuals, especially children. The major virulence factor in pneumococci is the polysaccharide capsule, which protects against phagocytosis. The death of pneumococci releases high amounts of potent mediators of inflamma...

  5. Pneumococcal antibody concentrations of subjects in communities fully or partially vaccinated with a seven-valent pneumococcal conjugate vaccine.

    OpenAIRE

    Ota, Martin O. C.; Anna Roca; Christian Bottomley; Philip C. Hill; Uzochukwu Egere; Brian Greenwood; Adegbola, Richard A.

    2012-01-01

    BACKGROUND A recent trial with PCV-7 in a rural Gambian community showed reduced vaccine-type pneumococcal carriage in fully vaccinated compared with control communities. We measured pneumococcal polysaccharide antibody concentrations in this trial to understand further the mechanisms underlying the observed changes. METHODS A single-blind, cluster-randomized (by village) trial was conducted in 21 Gambian villages. In 11 villages, all residents received PCV-7 (Vaccine group); in 10 contr...

  6. Serotype distribution of Streptococcus pneumoniae in children with invasive diseases in Turkey: 2008-2014.

    Science.gov (United States)

    Ceyhan, Mehmet; Ozsurekci, Yasemin; Gürler, Nezahat; Öksüz, Lütfiye; Aydemir, Sohret; Ozkan, Sengul; Yuksekkaya, Serife; Keser Emiroglu, Melike; Gültekin, Meral; Yaman, Akgün; Kiremitci, Abdurrahman; Yanık, Keramettin; Karli, Arzu; Ozcinar, Hatice; Aydin, Faruk; Bayramoglu, Gulcin; Zer, Yasemin; Gulay, Zeynep; Gayyurhan, Efgan Dogan; Gül, Mustafa; Özakın, Cüneyt; Güdücüoğlu, Hüseyin; Perçin, Duygu; Akpolat, Nezahat; Ozturk, Candan; Camcıoğlu, Yıldız; Karadağ Öncel, Eda; Çelik, Melda; Şanal, Laser; Uslu, Hakan

    2016-01-01

    Successful vaccination policies for protection from invasive pneumococcal diseases (IPD) dependent on determination of the exact serotype distribution in each country. We aimed to identify serotypes of pneumococcal strains causing IPD in children in Turkey and emphasize the change in the serotypes before and after vaccination with 7-valent pneumococcal conjugate vaccine (PCV-7) was included and PCV-13 was newly changed in Turkish National Immunization Program. Streptococcus pneumoniae strains were isolated at 22 different hospitals of Turkey, which provide healthcare services to approximately 65% of the Turkish population. Of the 335 diagnosed cases with S. pneumoniae over the whole period of 2008-2014, the most common vaccine serotypes were 19F (15.8%), 6B (5.9%), 14 (5.9%), and 3 (5.9%). During the first 5 y of age, which is the target population for vaccination, the potential serotype coverage ranged from 57.5 % to 36.8%, from 65.0% to 44.7%, and from 77.4% to 60.5% for PCV-7, PCV-10, and PCV-13 in 2008-2014, respectively. The ratio of non-vaccine serotypes was 27.2% in 2008-2010 whereas was 37.6% in 2011-2014 (p=0.045). S. penumoniae serotypes was less non-susceptible to penicillin as compared to our previous results (33.7 vs 16.5 %, p=0.001). The reduction of those serotype coverage in years may be attributed to increasing vaccinated children in Turkey and the increasing non-vaccine serotype may be explained by serotype replacement. Our ongoing IPD surveillance is a significant source of information for the decision-making processes on pneumococcal vaccination. PMID:26325175

  7. Serotype distribution of Streptococcus pneumoniae in children with invasive diseases in Turkey: 2008–2014

    Science.gov (United States)

    Ceyhan, Mehmet; Ozsurekci, Yasemin; Gürler, Nezahat; Öksüz, Lütfiye; Aydemir, Sohret; Ozkan, Sengul; Yuksekkaya, Serife; Keser Emiroglu, Melike; Gültekin, Meral; Yaman, Akgün; Kiremitci, Abdurrahman; Yanık, Keramettin; Karli, Arzu; Ozcinar, Hatice; Aydin, Faruk; Bayramoglu, Gulcin; Zer, Yasemin; Gulay, Zeynep; Gayyurhan, Efgan Dogan; Gül, Mustafa; Özakın, Cüneyt; Güdücüoğlu, Hüseyin; Perçin, Duygu; Akpolat, Nezahat; Ozturk, Candan; Camcıoğlu, Yıldız; Karadağ Öncel, Eda; Çelik, Melda; Şanal, Laser; Uslu, Hakan

    2016-01-01

    Successful vaccination policies for protection from invasive pneumococcal diseases (IPD) dependent on determination of the exact serotype distribution in each country. We aimed to identify serotypes of pneumococcal strains causing IPD in children in Turkey and emphasize the change in the serotypes before and after vaccination with 7-valent pneumococcal conjugate vaccine (PCV-7) was included and PCV-13 was newly changed in Turkish National Immunization Program. Streptococcus pneumoniae strains were isolated at 22 different hospitals of Turkey, which provide healthcare services to approximately 65% of the Turkish population. Of the 335 diagnosed cases with S. pneumoniae over the whole period of 2008–2014, the most common vaccine serotypes were 19F (15.8%), 6B (5.9%), 14 (5.9%), and 3 (5.9%). During the first 5 y of age, which is the target population for vaccination, the potential serotype coverage ranged from 57.5 % to 36.8%, from 65.0% to 44.7%, and from 77.4% to 60.5% for PCV-7, PCV-10, and PCV-13 in 2008–2014, respectively. The ratio of non-vaccine serotypes was 27.2% in 2008–2010 whereas was 37.6% in 2011–2014 (p=0.045). S. penumoniae serotypes was less non-susceptible to penicillin as compared to our previous results (33.7 vs 16.5 %, p=0.001). The reduction of those serotype coverage in years may be attributed to increasing vaccinated children in Turkey and the increasing non-vaccine serotype may be explained by serotype replacement. Our ongoing IPD surveillance is a significant source of information for the decision-making processes on pneumococcal vaccination. PMID:26325175

  8. Glucocorticoid-Augmented Efferocytosis Inhibits Pulmonary Pneumococcal Clearance in Mice by Reducing Alveolar Macrophage Bactericidal Function.

    Science.gov (United States)

    Stolberg, Valerie R; McCubbrey, Alexandra L; Freeman, Christine M; Brown, Jeanette P; Crudgington, Sean W; Taitano, Sophina H; Saxton, Bridget L; Mancuso, Peter; Curtis, Jeffrey L

    2015-07-01

    Inhaled corticosteroids (ICS) increase community-acquired pneumonia (CAP) incidence in patients with chronic obstructive pulmonary disease (COPD) by unknown mechanisms. Apoptosis is increased in the lungs of COPD patients. Uptake of apoptotic cells (ACs) ("efferocytosis") by alveolar macrophages (AMøs) reduces their ability to combat microbes, including Streptococcus pneumoniae, the most common cause of CAP in COPD patients. Having shown that ICS significantly increase AMø efferocytosis, we hypothesized that this process, termed glucocorticoid-augmented efferocytosis, might explain the association of CAP with ICS therapy in COPD. To test this hypothesis, we studied the effects of fluticasone, AC, or both on AMøs of C57BL/6 mice in vitro and in an established model of pneumococcal pneumonia. Fluticasone plus AC significantly reduced TLR4-stimulated AMø IL-12 production, relative to either treatment alone, and decreased TNF-α, CCL3, CCL5, and keratinocyte-derived chemoattractant/CXCL1, relative to AC. Mice treated with fluticasone plus AC before infection with viable pneumococci developed significantly more lung CFUs at 48 h. However, none of the pretreatments altered inflammatory cell recruitment to the lungs at 48 h postinfection, and fluticasone plus AC less markedly reduced in vitro mediator production to heat-killed pneumococci. Fluticasone plus AC significantly reduced in vitro AMø killing of pneumococci, relative to other conditions, in part by delaying phagolysosome acidification without affecting production of reactive oxygen or nitrogen species. These results support glucocorticoid-augmented efferocytosis as a potential explanation for the epidemiological association of ICS therapy of COPD patients with increased risk for CAP, and establish murine experimental models to dissect underlying molecular mechanisms. PMID:25987742

  9. Differential activation of inflammatory pathways in A549 type II pneumocytes by Streptococcus pneumoniae strains with different adherence properties

    Directory of Open Access Journals (Sweden)

    Horvat Rebecca T

    2006-04-01

    Full Text Available Abstract Background Adherence of Streptococcus pneumoniae bacteria to lung cells is a first step in the progression from asymptomatic carriage to pneumonia. Adherence abilities vary widely among S. pneumoniae patient isolates. In this study, the binding properties of S. pneumoniae isolates and the effects of binding on activation of the Nuclear Factor-Kappa-B (NFκB pathway and cytokine secretion by type II pneumocytes were measured. Methods Mechanisms of high- and low-binding S. pneumoniae adherence to A549 cells were investigated by blocking putative receptors on bacteria and host cells with antibody and by eluting choline-binding proteins off of bacterial surfaces. NFκB activation was measured by western blot and immunocytochemistry and cytokine secretion was detected by a protein array. Results This study shows that S. pneumoniae isolates from pneumonia patients (n = 298 can vary by as much as 1000-fold in their ability to bind to human lung epithelial cells. This difference resulted in differential activation of the NFκB pathway. High-, but not low-binding S. pneumoniae used Choline-binding protein A (CbpA to bind to complement component C3 on epithelial cell surfaces. Interleukin-8 (IL-8 was the only cytokine secreted by cells treated with either low- or high-binding S. pneumoniae. Conclusion These results indicate that S. pneumoniae clinical isolates are not homogeneous in their interaction with host epithelial cells. The differential activation of host cells by high- and low-binding S. pneumoniae strains could have implications for the treatment of pneumococcal pneumonia and for vaccine development.

  10. 肺炎球菌疫苗的研究进展%Research progress of pneumococcal vaccine

    Institute of Scientific and Technical Information of China (English)

    唐静; 叶强

    2010-01-01

    肺炎链球菌(即肺炎球菌)导致的疾病在世界各地都是严重的公共健康问题,包括肺炎、脑膜炎、发热性菌血症、中耳炎、鼻窦炎、气管炎等感染.体内外研究显示,肺炎球菌多糖疫苗对成年人肺炎球菌引发的疾病能起到积极的预防作用,但由于多糖疫苗无法刺激产生持续的抗体应答,所以不适用于2岁以下的婴幼儿;而将荚膜多糖与载体蛋白耦联的结合型肺炎球菌疫苗对2岁以下的婴幼儿或免疫缺陷的人群起到积极的保护作用,扩大了使用范围,提高了保护力.本文阐述了预防肺炎球菌疾病疫苗的研究进展,从全菌体疫苗、以菌体荚膜多糖为成分的多糖疫苗直到多糖结合疫苗的发展过程.同时总结了目前国内外结合疫苗的研究现状,认为应将开发安全、有效、价格合理、对肺炎球菌性疾病保护范围广的肺炎球菌疫苗作为高度优先的研究项目.%The diseases caused by Streptococcus pneumoniae (pneumococcus) are serious public health problems around the world, including pneumonia, meningitis, febrile bacteraemia, otitis media,sinusitis and bronchitis. In vivo studies have shown that pneumococcal polysaccharide vaccine can play an active role in prevention of pneumococcal diseases in adults. Because polysaccharide vaccine can not stimulate to produce sustained antibody response,it dose not refer to infants under two years old. And the conjugated pneumococcal vaccine of capsular polysaccharides and carrier protein plays an actively protective role for infants under two years old or immunocompromised people,expands the scope of use,and improves the protection force. This article reports the research progress of pneumococcal vaccine,the development from the whole bacterial vaccine, polysaccharide vaccine composed by bacterial capsular polysaccharide to polysaccharide conjugate vaccine. This review also summarizes the current research status of vaccine at home and

  11. Clustering of serotypes in a longitudinal study of Streptococcus pneumoniae carriage in three day care centres

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    Tanskanen Antti

    2008-12-01

    Full Text Available Abstract Background Streptococcus pneumoniae (pneumococcus causes a wide range of clinical manifestations that together constitute a major burden of disease worldwide. The main route of pneumococcal transmission is through asymptomatic colonisation of the nasopharynx. Studies of transmission are currently of general interest because of the impact of the new conjugate-polysaccharide vaccines on nasopharyngeal colonisation (carriage. Here we report the first longitudinal study of pneumococcal carriage that records serotype specific exposure to pneumococci simultaneously within the two most important mixing groups, families and day care facilities. Methods We followed attendees (N = 59 with their family members (N = 117 and the employees (N = 37 in three Finnish day care centres for 9 months with monthly sampling of nasopharyngeal carriage. Pneumococci were cultured, identified and serotyped by standard methods. Results Children in day care constitute a core group of pneumococcal carriage: of the 36 acquisitions of carriage with documented exposure to homologous pneumococci, the attendee had been exposed in her/his day care centre in 35 cases and in the family in 9 cases. Day care children introduce pneumococci to the family: 66% of acquisitions of a new serotype in a family were associated with simultaneous or previous carriage of the same type in the child attending day care. Consequently, pneumococcal transmission was found to take place as micro-epidemics driven by the day care centres. Each of the three day care centres was dominated by a serotype of its own, accounting for 100% of the isolates of that serotype among all samples from the day care attendees. Conclusion The transmission of pneumococci is more intense within than across clusters defined by day care facilities. The ensuing micro-epidemic behaviour enhances pneumococcal transmission.

  12. Clustering of serotypes in a longitudinal study of Streptococcus pneumoniae carriage in three day care centres

    Science.gov (United States)

    Leino, Tuija; Hoti, Fabian; Syrjänen, Ritva; Tanskanen, Antti; Auranen, Kari

    2008-01-01

    Background Streptococcus pneumoniae (pneumococcus) causes a wide range of clinical manifestations that together constitute a major burden of disease worldwide. The main route of pneumococcal transmission is through asymptomatic colonisation of the nasopharynx. Studies of transmission are currently of general interest because of the impact of the new conjugate-polysaccharide vaccines on nasopharyngeal colonisation (carriage). Here we report the first longitudinal study of pneumococcal carriage that records serotype specific exposure to pneumococci simultaneously within the two most important mixing groups, families and day care facilities. Methods We followed attendees (N = 59) with their family members (N = 117) and the employees (N = 37) in three Finnish day care centres for 9 months with monthly sampling of nasopharyngeal carriage. Pneumococci were cultured, identified and serotyped by standard methods. Results Children in day care constitute a core group of pneumococcal carriage: of the 36 acquisitions of carriage with documented exposure to homologous pneumococci, the attendee had been exposed in her/his day care centre in 35 cases and in the family in 9 cases. Day care children introduce pneumococci to the family: 66% of acquisitions of a new serotype in a family were associated with simultaneous or previous carriage of the same type in the child attending day care. Consequently, pneumococcal transmission was found to take place as micro-epidemics driven by the day care centres. Each of the three day care centres was dominated by a serotype of its own, accounting for 100% of the isolates of that serotype among all samples from the day care attendees. Conclusion The transmission of pneumococci is more intense within than across clusters defined by day care facilities. The ensuing micro-epidemic behaviour enhances pneumococcal transmission. PMID:19116005

  13. Non-typeable Haemophilus influenzae and Streptococcus pneumoniae as primary causes of acute otitis media in colombian children: a prospective study

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    Castrejon Maria M

    2011-01-01

    Full Text Available Abstract Background Acute otitis media (AOM is one of the most frequently encountered bacterial infections in children aged Streptococcus pneumoniae (S. pneumoniae and non-typeable Haemophilus influenzae (NTHi are historically identified as primary AOM causes. Nevertheless, recent data on bacterial pathogens causing AOM in Latin America are limited. This prospective study aimed to identify and characterize bacterial etiology and serotypes of AOM cases including antimicrobial susceptibility in Methods From February 2008 to January 2009, children ≥3 months and Results Of the 106 enrolled children, 99 were included in the analysis. Bacteria were cultured from 62/99 (63% of samples with S. pneumoniae, H. influenzae, or S. pyogenes. The most commonly isolated bacteria were H. influenzae in 31/99 (31% and S. pneumoniae in 30/99 (30% of samples. The majority of H. influenzae episodes were NTHi (27/31; 87%. 19F was the most frequently isolated pneumococcal serotype (10/30; 33%. Of the 30 S. pneumoniae positive samples, 8/30 (27% were resistant to tetracycline, 5/30 (17% to erythromycin and 8/30 (27% had intermediate resistance to penicillin. All H. influenzae isolates tested were negative to beta-lactamase. Conclusions NTHi and S. pneumoniae are the leading causes of AOM in Colombian children. A pneumococcal conjugate vaccine that prevents both pathogens could be useful in maximizing protection against AOM.

  14. Vaccination of risk groups in England using the 13 valent pneumococcal conjugate vaccine : economic analysis

    NARCIS (Netherlands)

    Rozenbaum, Mark H.; van Hoek, Albert Jan; Fleming, Douglas; Trotter, Caroline L.; Miller, Elizabeth; Edmunds, W. John

    2012-01-01

    Objective To estimate the cost effectiveness of vaccinating people with high risk conditions against invasive pneumococcal disease using the 13 valent pneumococcal conjugate vaccine. Design Economic evaluation using a cohort model from the perspective of healthcare providers. Setting England. Partic

  15. Using the overlay assay to qualitatively measure bacterial production of and sensitivity to pneumococcal bacteriocins.

    Science.gov (United States)

    Maricic, Natalie; Dawid, Suzanne

    2014-09-30

    Streptococcus pneumoniae colonizes the highly diverse polymicrobial community of the nasopharynx where it must compete with resident organisms. We have shown that bacterially produced antimicrobial peptides (bacteriocins) dictate the outcome of these competitive interactions. All fully-sequenced pneumococcal strains harbor a bacteriocin-like peptide (blp) locus. The blp locus encodes for a range of diverse bacteriocins and all of the highly conserved components needed for their regulation, processing, and secretion. The diversity of the bacteriocins found in the bacteriocin immunity region (BIR) of the locus is a major contributor of pneumococcal competition. Along with the bacteriocins, immunity genes are found in the BIR and are needed to protect the producer cell from the effects of its own bacteriocin. The overlay assay is a quick method for examining a large number of strains for competitive interactions mediated by bacteriocins. The overlay assay also allows for the characterization of bacteriocin-specific immunity, and detection of secreted quorum sensing peptides. The assay is performed by pre-inoculating an agar plate with a strain to be tested for bacteriocin production followed by application of a soft agar overlay containing a strain to be tested for bacteriocin sensitivity. A zone of clearance surrounding the stab indicates that the overlay strain is sensitive to the bacteriocins produced by the pre-inoculated strain. If no zone of clearance is observed, either the overlay strain is immune to the bacteriocins being produced or the pre-inoculated strain does not produce bacteriocins. To determine if the blp locus is functional in a given strain, the overlay assay can be adapted to evaluate for peptide pheromone secretion by the pre-inoculated strain. In this case, a series of four lacZ-reporter strains with different pheromone specificity are used in the overlay.

  16. Serotype Specific Invasive Capacity and Persistent Reduction in Invasive Pneumococcal Disease

    Science.gov (United States)

    Yildirim, Inci; Hanage, William P.; Lipsitch, Marc; Shea, Kimberly M.; Stevenson, Abbie; Finkelstein, Jonathan; Huang, Susan S.; Lee, Grace M.; Kleinman, Ken; Pelton, SI

    2011-01-01

    Defining the propensity of Streptoccocus pneumoniae (SP) serotypes to invade sterile body sites following nasopharyngeal (NP) acquisition has the potential to inform about how much invasive pneumococcal disease (IPD) may occur in a typical population with a given distribution of carriage serotypes. Data from enhanced surveillance for IPD in Massachusetts children ≤7 years in 2003/04, 2006/07 and 2008/09 seasons and surveillance of SP NP carriage during the corresponding respiratory seasons in 16 Massachusetts communities in 2003/04 and 8 of the 16 communities in both 2006/07 and 2008/09 were used to compute a serotype specific “invasive capacity (IC)” by dividing the incidence of IPD due to serotype x by the carriage prevalence of that same serotype in children of the same age. A total of 206 IPD and 806 NP isolates of SP were collected during the study period. An approximate 50-fold variation in the point estimates between the serotypes having the highest (18C, 33F, 7F, 19A, 3 and 22F) and lowest (6C, 23A, 35F, 11A, 35B, 19F, 15A, and 15BC) IC was observed. Point estimates of IC for most of the common serotypes currently colonizing children in Massachusetts were low and likely explain the continued reduction in IPD from the pre-PCV era in the absence of specific protection against these serotypes. Invasive capacity differs among serotypes and as new pneumococcal conjugate vaccines are introduced, ongoing surveillance will be essential to monitor whether serotypes with high invasive capacity emerge (e.g. 33F, 22F) as successful colonizers resulting in increased IPD incidence due to replacement serotypes. PMID:21029807

  17. The BR domain of PsrP interacts with extracellular DNA to promote bacterial aggregation; structural insights into pneumococcal biofilm formation

    Science.gov (United States)

    Schulte, Tim; Mikaelsson, Cecilia; Beaussart, Audrey; Kikhney, Alexey; Deshmukh, Maya; Wolniak, Sebastian; Pathak, Anuj; Ebel, Christine; Löfling, Jonas; Fogolari, Federico; Henriques-Normark, Birgitta; Dufrêne, Yves F.; Svergun, Dmitri; Nygren, Per-Åke; Achour, Adnane

    2016-01-01

    The major human pathogen Streptococcus pneumoniae is a leading cause of disease and death worldwide. Pneumococcal biofilm formation within the nasopharynx leads to long-term colonization and persistence within the host. We have previously demonstrated that the capsular surface-associated pneumococcal serine rich repeat protein (PsrP), key factor for biofilm formation, binds to keratin-10 (KRT10) through its microbial surface component recognizing adhesive matrix molecule (MSCRAMM)-related globular binding region domain (BR187–385). Here, we show that BR187–385 also binds to DNA, as demonstrated by electrophoretic mobility shift assays and size exclusion chromatography. Further, heterologous expression of BR187–378 or the longer BR120–378 construct on the surface of a Gram-positive model host bacterium resulted in the formation of cellular aggregates that was significantly enhanced in the presence of DNA. Crystal structure analyses revealed the formation of BR187–385 homo-dimers via an intermolecular β-sheet, resulting in a positively charged concave surface, shaped to accommodate the acidic helical DNA structure. Furthermore, small angle X-ray scattering and circular dichroism studies indicate that the aggregate-enhancing N-terminal region of BR120–166 adopts an extended, non-globular structure. Altogether, our results suggest that PsrP adheres to extracellular DNA in the biofilm matrix and thus promotes pneumococcal biofilm formation. PMID:27582320

  18. Serotypes and patterns of antibiotic resistance in strains causing invasive pneumococcal disease in children less than 5 years of age.

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    Chunfeng Liu

    Full Text Available OBJECTIVE: The serotypes and patterns of antibiotic resistance of Streptococcus pneumoniae (S. pneumoniae strains that cause invasive pneumococcal disease (IPD in infants were analyzed to provide guidance for clinical disease prevention and treatment. METHODS: The clinical features of confirmed IPD were evaluated in 61 patients, less than 5 years of age, who were admitted to our hospital between January 2009 and December 2011. The serotypes and antibiotic resistance of strains of S.pneumoniae were determined using the capsular swelling method and the E-test. RESULTS: A total of 61 invasive strains were isolated. The serotype distribution of those isolates were 19A (41.0%, 14 (19.7%, 19F (11.5%, 23F (9.8%, 8 (4.9%, 9V (4.9%, 1 (3.3%, and 4, 6B, and 20 (each 1.6%. The percentage of S. pneumoniae strains resistant to erythromycin, clindamycin, and cotrimoxazole were 100%, 86.9%, and 100%, respectively. The percentage of S. pneumoniae strains resistant to penicillin, amoxicillin/clavulanic acid, cefuroxime, ceftriaxone, cefotaxime, cefepime, and meropenem were 42.6%, 18.0%, 82.0%, 18.0%, 13.1%, 13.1%, and 36.1%, respectively. The percentage of multidrug-resistant strains was 95.6%. Strains of all serotypes isolated in this study were highly resistant to erythromycin, cotrimoxazole, and clindamycin. Strains with serotype 19A had the highest rates of resistance. CONCLUSIONS: Serotype 19A strains were most frequently isolated from children with IPD treated in our hospital. The strains causing IPD are highly resistant to antibiotics.

  19. Distance to health services affects local-level vaccine efficacy for pneumococcal conjugate vaccine (PCV) among rural Filipino children.

    Science.gov (United States)

    Root, Elisabeth Dowling; Lucero, Marilla; Nohynek, Hanna; Anthamatten, Peter; Thomas, Deborah S K; Tallo, Veronica; Tanskanen, Antti; Quiambao, Beatriz P; Puumalainen, Taneli; Lupisan, Socorro P; Ruutu, Petri; Ladesma, Erma; Williams, Gail M; Riley, Ian; Simões, Eric A F

    2014-03-01

    Pneumococcal conjugate vaccines (PCVs) have demonstrated efficacy against childhood pneumococcal disease in several regions globally. We demonstrate how spatial epidemiological analysis of a PCV trial can assist in developing vaccination strategies that target specific geographic subpopulations at greater risk for pneumococcal pneumonia. We conducted a secondary analysis of a randomized, placebo-controlled, double-blind vaccine trial that examined the efficacy of an 11-valent PCV among children less than 2 y of age in Bohol, Philippines. Trial data were linked to the residential location of each participant using a geographic information system. We use spatial interpolation methods to create smoothed surface maps of vaccination rates and local-level vaccine efficacy across the study area. We then measure the relationship between distance to the main study hospital and local-level vaccine efficacy, controlling for ecological factors, using spatial autoregressive models with spatial autoregressive disturbances. We find a significant amount of spatial variation in vaccination rates across the study area. For the primary study endpoint vaccine efficacy increased with distance from the main study hospital from -14% for children living less than 1.5 km from Bohol Regional Hospital (BRH) to 55% for children living greater than 8.5 km from BRH. Spatial regression models indicated that after adjustment for ecological factors, distance to the main study hospital was positively related to vaccine efficacy, increasing at a rate of 4.5% per kilometer distance. Because areas with poor access to care have significantly higher VE, targeted vaccination of children in these areas might allow for a more effective implementation of global programs. PMID:24550454

  20. Anti‐pneumococcal antibody titre measurement: what useful information does it yield?

    OpenAIRE

    Balmer, Paul; Cant, Andrew J.; Borrow, Ray

    2006-01-01

    Measuring and interpretation of the immune response to pneumococcal polysaccharides is a complex field, owing to the diversity of the pneumococcal polysaccharide capsular types, different vaccine formulations including both polysaccharide and conjugate vaccines, diverse pneumococcal serological assays, lack of immunogenicity data for the conjugate in a number of at‐risk groups and complex vaccine schedules. Even the reasons for performing pneumococcal serology can be complex, as assays may be...

  1. Genetic stability of pneumococcal isolates during 35 days of human experimental carriage

    OpenAIRE

    Gladstone, R.A.; Gritzfeld, J.F.; Coupland, P.; S. B. Gordon; Bentley, S.D.

    2015-01-01

    Background Pneumococcal carriage is a reservoir for transmission and a precursor to pneumococcal disease. The experimental human pneumococcal carriage model provides a useful tool to aid vaccine licensure through the measurement of vaccine efficacy against carriage (VEcol). Documentation of the genetic stability of the experimental human pneumococcal carriage model is important to further strengthen confidence in its safety and conclusions, enabling it to further facilitate vaccine licensure ...

  2. Symptoms, Diagnosis and Treatment of Pneumonia

    Science.gov (United States)

    ... Lung Health and Diseases > Lung Disease Lookup > Pneumonia Pneumonia Symptoms, Causes, and Risk Factors Anyone can get ... risk for pneumonia. What Are the Symptoms of Pneumonia? Pneumonia symptoms can vary from mild to severe, ...

  3. Serotype Distribution, Antimicrobial Susceptibility, and Molecular Epidemiology of Streptococcus pneumoniae Isolated from Children in Shanghai, China.

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    Fen Pan

    Full Text Available Streptococcus pneumoniae is a common pathogenic cause of pediatric infections. This study investigated the serotype distribution, antimicrobial susceptibility, and molecular epidemiology of pneumococci before the introduction of conjugate vaccines in Shanghai, China.A total of 284 clinical pneumococcal isolates (270, 5, 4,3, and 2 of which were isolated from sputum, bronchoalveolar lavage fluid, blood, cerebral spinal fluid, and ear secretions, respectively from children less than 14 years of age who had not been vaccinated with a conjugate vaccine, were collected between January and December in 2013. All isolates were serotyped by multiplex polymerase chain reaction or quellung reactions and antimicrobial susceptibility testing was performed using the broth microdilution method. The molecular epidemiology of S.pneumoniae was analyzed by multilocus sequence typing (MLST.Among the 284 pneumococcal isolates, 19F (33.5%, 19A (14.1%, 23F (12.0%, and 6A (8.8% were the most common serotypes and the coverage rates of the 7-, 10-, and 13-valent pneumococcal conjugate vaccines (PCV7, PCV10, and PCV13 were 58.6%, 59.4% and 85.1%, respectively. Antimicrobial susceptibility showed that the prevalence rates of S.pneumoniae resistance to penicillin were 11.3% (32/284. Approximately 88.0% (250/284 of the isolates exhibited multi-drug resistance. MLST analysis revealed a high level of diversity, with 65 sequence types (STs among 267 isolates. Specifically, the four predominant STs were ST271 (24.3%, 65/267, ST320 (11.2%, 30/267, ST81 (9.7%, 26/267, and ST3173 (5.2%, 14/267, which were mainly associated with serotypes 19F, 19A, 23F, and 6A, respectively.The prevalent serotypes among clinical isolates from children were 19F, 19A, 23F, and 6A and these isolates showed high resistance rates to β-lactams and macrolides. The Taiwan19F-14 clone played a predominant role in the dissemination of pneumococcal isolates in Shanghai, China. Therefore, continued and

  4. Pneumococcal Vaccine and Patients with Pulmonary Diseases

    OpenAIRE

    Mirsaeidi, Mehdi; Ebrahimi, Golnaz; Allen, Mary Beth; Aliberti, Stefano

    2014-01-01

    Chronic pulmonary diseases describe chronic diseases that affect the airways and lung parenchyma. Examples of common chronic pulmonary diseases include asthma, bronchiectasis, chronic obstructive lung disease, lung fibrosis, sarcoidosis, pulmonary hypertension and cor pulmonale. Pulmonary infection is considered a significant cause of mortality in patients with chronic pulmonary diseases. Streptococcus pneumoniae is the leading isolated bacteria from adult patients with community-acquired pne...

  5. Clinical case review: A method to improve identification of true clinical and radiographic pneumonia in children meeting the World Health Organization definition for pneumonia

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    Ruutu Petri

    2008-07-01

    Full Text Available Abstract Background The World Health Organization's (WHO case definition for childhood pneumonia, composed of simple clinical signs of cough, difficult breathing and fast breathing, is widely used in resource poor settings to guide management of acute respiratory infections. The definition is also commonly used as an entry criteria or endpoint in different intervention and disease burden studies. Methods A group of paediatricians conducted a retrospective review of clinical and laboratory data including C-reactive protein concentration and chest radiograph findings among Filipino children hospitalised in the Bohol Regional Hospital who were enrolled in a pneumococcal vaccine efficacy study and had an episode of respiratory disease fulfilling the WHO case definition for clinical pneumonia. Our aim was to evaluate which disease entities the WHO definition actually captures and what is the probable aetiology of respiratory infections among these episodes diagnosed in this population. Results Among the 12,194 children enrolled to the vaccine study we recorded 1,195 disease episodes leading to hospitalisation which fulfilled the WHO criteria for pneumonia. In total, 34% of these episodes showed radiographic evidence of pneumonia and 11% were classified as definitive or probable bacterial pneumonia. Over 95% of episodes of WHO-defined severe pneumonia (with chest indrawing had an acute lower respiratory infection as final diagnosis whereas 34% of those with non-severe clinical pneumonia had gastroenteritis or other non-respiratory infection as main cause of hospitalisation. Conclusion The WHO definition for severe pneumonia shows high specificity for acute lower respiratory infection and provides a tool to compare the total burden of lower respiratory infections in different settings. Trial registration ISRCTN62323832

  6. Meeting the challenge: prevention of pneumococcal disease with conjugate vaccines Al encuentro del reto: prevención de la enfermedad neumocócica con vacunas conjugadas

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    Irma Gabriela Echániz-Avilés

    2001-08-01

    Full Text Available Streptococcus pneumoniae is one of the leading causes of both invasive and noninvasive diseases in the pediatric population and continues to represent a significant public health burden worldwide. The increasing incidence of antibioticresistant strains of the pathogen has complicated treatment and management of the various pneumococcal disease manifestations. Thus, the best management strategy may be the prevention of pneumococcal diseases through vaccination. Although several pneumococcal conjugate vaccines have been clinically studied in infants and children, only a 7-valent conjugate vaccine (PNCRM7; Prevnar®/Prevenar® is currently approved for the prevention of invasive disease. Vaccination with PNCRM7 is safe and effective in infants and young children. Routine vaccination with the conjugate vaccine could improve outcomes by safeguarding against the development of antibiotic-resistant strains of S. pneumoniae, thus simplifying the management of pneumococcal disease. Additionally, the overall costs associated with the treatment of pneumococcal diseases could be substantially reduced, particularly in developing countries. The time has come for fully applying this new advancement against S. pneumoniae, to benefit the children of the world. The Spanish version of this paper is available at: http://www.insp.mx/salud/index.htmlStreptococcus pneumoniae es uno de los principales agentes causantes de enfermedades invasoras y no invasoras en la población pediátrica y sigue representando uno de los principales problemas de salud pública a nivel mundial. La incidencia creciente de cepas resistentes a diversos antimicrobianos ha complicado el tratamiento y manejo de varias de las manifestaciones de la enfermedad neumocócica. Con éstas consideraciones, la mejor estrategia de manejo es la prevención de éstas enfermedades a través de la vacunación. A pesar de que se han estudiado diversas vacunas neumocócicas conjugadas en niños, solo una

  7. Polymorphism in a lincRNA Associates with a Doubled Risk of Pneumococcal Bacteremia in Kenyan Children.

    Science.gov (United States)

    Rautanen, Anna; Pirinen, Matti; Mills, Tara C; Rockett, Kirk A; Strange, Amy; Ndungu, Anne W; Naranbhai, Vivek; Gilchrist, James J; Bellenguez, Céline; Freeman, Colin; Band, Gavin; Bumpstead, Suzannah J; Edkins, Sarah; Giannoulatou, Eleni; Gray, Emma; Dronov, Serge; Hunt, Sarah E; Langford, Cordelia; Pearson, Richard D; Su, Zhan; Vukcevic, Damjan; Macharia, Alex W; Uyoga, Sophie; Ndila, Carolyne; Mturi, Neema; Njuguna, Patricia; Mohammed, Shebe; Berkley, James A; Mwangi, Isaiah; Mwarumba, Salim; Kitsao, Barnes S; Lowe, Brett S; Morpeth, Susan C; Khandwalla, Iqbal; Blackwell, Jenefer M; Bramon, Elvira; Brown, Matthew A; Casas, Juan P; Corvin, Aiden; Duncanson, Audrey; Jankowski, Janusz; Markus, Hugh S; Mathew, Christopher G; Palmer, Colin N A; Plomin, Robert; Sawcer, Stephen J; Trembath, Richard C; Viswanathan, Ananth C; Wood, Nicholas W; Deloukas, Panos; Peltonen, Leena; Williams, Thomas N; Scott, J Anthony G; Chapman, Stephen J; Donnelly, Peter; Hill, Adrian V S; Spencer, Chris C A

    2016-06-01

    Bacteremia (bacterial bloodstream infection) is a major cause of illness and death in sub-Saharan Africa but little is known about the role of human genetics in susceptibility. We conducted a genome-wide association study of bacteremia susceptibility in more than 5,000 Kenyan children as part of the Wellcome Trust Case Control Consortium 2 (WTCCC2). Both the blood-culture-proven bacteremia case subjects and healthy infants as controls were recruited from Kilifi, on the east coast of Kenya. Streptococcus pneumoniae is the most common cause of bacteremia in Kilifi and was thus the focus of this study. We identified an association between polymorphisms in a long intergenic non-coding RNA (lincRNA) gene (AC011288.2) and pneumococcal bacteremia and replicated the results in the same population (p combined = 1.69 × 10(-9); OR = 2.47, 95% CI = 1.84-3.31). The susceptibility allele is African specific, derived rather than ancestral, and occurs at low frequency (2.7% in control subjects and 6.4% in case subjects). Our further studies showed AC011288.2 expression only in neutrophils, a cell type that is known to play a major role in pneumococcal clearance. Identification of this novel association will further focus research on the role of lincRNAs in human infectious disease. PMID:27236921

  8. A Case of Waterhouse-Friderichsen Syndrome Resulting from an Invasive Pneumococcal Infection in a Patient with a Hypoplastic Spleen

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    Kazumasa Emori

    2016-01-01

    Full Text Available A 50-year-old male was brought to our emergency department by ambulance with complaints of pain and numbness in both legs. At arrival, purple spots were evident on his neck and face. Examination of the vital sign indicated septic shock. Laboratory data and blood gas analysis revealed disseminated intravascular coagulation, multiple organ failure, and metabolic acidosis. Peripheral blood smears revealed Howell-Jolly bodies, indicating decreased splenic function. A rapid urinary pneumococcal antigen test was also found to be positive. After admission to the intensive care unit, extensive treatment, including polymyxin-B direct hemoperfusion and administration of methylprednisolone and broad spectrum antibiotics was immediately initiated. Despite of our efforts to save his life, the patient died six hours after the arrival. The following day, blood cultures revealed the presence of Streptococcus pneumoniae. An autopsy revealed a hypoplastic spleen and a bilateral adrenal hemorrhage, indicating acute adrenal insufficiency caused by sepsis. Finally, the patient was diagnosed with Waterhouse-Friderichsen syndrome. Although severe infection may be seen in the splenectomized patients, it should be noted that patients with a hypoplastic spleen may have acute severe infections. We, therefore, report a case of Waterhouse-Friderichsen syndrome resulting from an invasive pneumococcal infection in a patient with a hypoplastic spleen.

  9. Bacterial pneumonias--evaluation of various sputum culture methods.

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    Verenkar M

    1993-04-01

    Full Text Available With an objective of improving diagnostic value of sputum in bacterial pneumonias, 50 uncomplicated ′community′ acquired cases were studied using Gram staining of sputum along with bedside inoculation with/without dilution of the specimen. Gram staining of sputum samples collected before treatment revealed pneumococcal infection in 46% cases. The results were however inconclusive on samples sent by routine procedure involving logistic delay. Cultural analysis of sputum processed by three different techniques showed that bedside inoculation of sputum after dilution to be the most efficient technique yielding Streptococcus pneumoniae in 34% cases, Gram positive cocci in lesser number (20%, Gram negative rods (GNR in 18% cases. Sputum samples processed bedside without dilution yielded a lower number of pneumococci and other Gram positive cocci (24% & 16% cases respectively. Routine processing of sputum, involving logistic delay yielded a high number of Gram negative rods (62%, indicating their overgrowth. Thus bedside inoculation of sputum after dilution coupled with direct Gram staining serves as a simple and yet valuable laboratory aid in the diagnosis of uncomplicated ′community′ acquired bacterial pneumonias.

  10. Bronchitis and Pneumonia

    Science.gov (United States)

    ... What is the difference between bronchitis and pneumonia? Bronchitis is most often a bacte- rial or viral infection that causes swelling of the tubes (bronchioles) leading to the lungs. Pneumonia is an acute or chronic disease marked by inflammation of the ...

  11. Reduction of Streptococcus pneumoniae Colonization and Dissemination by a Nonopsonic Capsular Polysaccharide Antibody

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    Christopher R. Doyle

    2016-02-01

    Full Text Available Streptococcus pneumoniae colonization of the nasopharynx (NP is a prerequisite for invasive pneumococcal disease (IPD. The marked reduction in IPD that followed the routine use of pneumococcal polysaccharide conjugate vaccines (PCVs has been linked to reduced NP colonization with vaccine-included serotypes (STs, with the caveat that PCVs are less effective against pneumonia than against IPD. Although PCV-elicited opsonic antibodies that enhance phagocytic killing of the homologous ST are considered a key correlate of PCV-mediated protection, recent studies question this relationship for some STs, including ST3. Studies with monoclonal antibodies (MAbs to the pneumococcal capsular polysaccharide (PPS of ST3 (PPS3 have shown that nonopsonic, as well as opsonic, antibodies can each protect mice against pneumonia and sepsis, but the effect of these types of MAbs on NP colonization is unknown. In this study, we determined the effects of protective opsonic and nonopsonic PPS3 MAbs on ST3 NP colonization in mice. Our results show that a nonopsonic MAb reduced early NP colonization and prevented ST3 dissemination to the lungs and blood, but an opsonic MAb did not. Moreover, the opsonic MAb induced a proinflammatory NP cytokine response, but the nonopsonic MAb had an antiinflammatory effect. The effect of the nonopsonic MAb on colonization did not require its Fc region, but its antiinflammatory effect did. Our findings challenge the paradigm that opsonic MAbs are required to prevent NP colonization and suggest that further studies of the activity of nonopsonic antibodies could advance our understanding of mechanisms of PCV efficacy and provide novel correlates of protection.

  12. Characterisation of Invasive Streptococcus pneumoniae Isolated from Cambodian Children between 2007 - 2012.

    Directory of Open Access Journals (Sweden)

    Catrin E Moore

    Full Text Available The 13-valent pneumococcal vaccine (PCV13 was introduced in Cambodia in January 2015. There are limited data concerning the common serotypes causing invasive pneumococcal disease (IPD. Knowledge of the circulating pneumococcal serotypes is important to monitor epidemiological changes before and after vaccine implementation.All episodes of IPD defined by the isolation of Streptococcus pneumoniae from blood, cerebrospinal fluid or other sterile site in Cambodian children admitted to the Angkor Hospital for Children in Siem Reap, Northwestern Cambodia, between 1st January 2007 and 1st July 2012 were retrospectively studied. Streptococcus pneumoniae isolates that could be retrieved underwent phenotypic typing and whole genome sequencing.There were 90 Cambodian children hospitalized with IPD with a median (IQR age of 2.3 years (0.9-6.2. The case fatality was 15.6% (95% CI 8-23. Of 50 Streptococcus pneumoniae isolates available for further testing, 46% were penicillin non-susceptible and 8% were ceftriaxone non-susceptible, 78% were cotrimoxazole resistant, 30% were erythromycin resistant and 30% chloramphenicol resistant. There were no significant changes in resistance levels over the five-year period. The most common serotypes were 1 (11/50; 22%, 23F (8/50; 16%, 14 (6/50; 12%, 5 (5/50; 10% and 19A (3/50; 6%. Coverage by PCV7, PCV10 and PCV13 was 44%, 76% and 92% respectively. We identified novel multilocus sequence types and resistotypes using whole genome sequencing.This study suggests IPD is an important disease in Cambodian children and can have a significant mortality. PCV13 coverage of the serotypes determined in studied strains was high and consistent with another recent study. The phenotypic resistance patterns observed were similar to other regional studies. The use of whole genome sequencing in the present study provides additional typing and resistance information together with the description of novel sequence types and resistotypes.

  13. Characterisation of Invasive Streptococcus pneumoniae Isolated from Cambodian Children between 2007 – 2012

    Science.gov (United States)

    Giess, Adam; Soeng, Sona; Sar, Poda; Kumar, Varun; Nhoung, Pheakdey; Bousfield, Rachel; Turner, Paul; Stoesser, Nicole; Day, Nicholas P. J.; Parry, Christopher M.

    2016-01-01

    Background The 13-valent pneumococcal vaccine (PCV13) was introduced in Cambodia in January 2015. There are limited data concerning the common serotypes causing invasive pneumococcal disease (IPD). Knowledge of the circulating pneumococcal serotypes is important to monitor epidemiological changes before and after vaccine implementation. Methods All episodes of IPD defined by the isolation of Streptococcus pneumoniae from blood, cerebrospinal fluid or other sterile site in Cambodian children admitted to the Angkor Hospital for Children in Siem Reap, Northwestern Cambodia, between 1st January 2007 and 1st July 2012 were retrospectively studied. Streptococcus pneumoniae isolates that could be retrieved underwent phenotypic typing and whole genome sequencing. Results There were 90 Cambodian children hospitalized with IPD with a median (IQR) age of 2.3 years (0.9–6.2). The case fatality was 15.6% (95% CI 8–23). Of 50 Streptococcus pneumoniae isolates available for further testing, 46% were penicillin non-susceptible and 8% were ceftriaxone non-susceptible, 78% were cotrimoxazole resistant, 30% were erythromycin resistant and 30% chloramphenicol resistant. There were no significant changes in resistance levels over the five-year period. The most common serotypes were 1 (11/50; 22%), 23F (8/50; 16%), 14 (6/50; 12%), 5 (5/50; 10%) and 19A (3/50; 6%). Coverage by PCV7, PCV10 and PCV13 was 44%, 76% and 92% respectively. We identified novel multilocus sequence types and resistotypes using whole genome sequencing. Conclusions This study suggests IPD is an important disease in Cambodian children and can have a significant mortality. PCV13 coverage of the serotypes determined in studied strains was high and consistent with another recent study. The phenotypic resistance patterns observed were similar to other regional studies. The use of whole genome sequencing in the present study provides additional typing and resistance information together with the description of novel

  14. Enhanced detection and serotyping of Streptococcus pneumoniae using multiplex polymerase chain reaction

    Directory of Open Access Journals (Sweden)

    Jong Gyun Ahn

    2012-11-01

    Full Text Available &lt;B&gt;Purpose:&lt;/B&gt; Methods for quick and reliable detection of &lt;I&gt;Streptococcus pneumoniae&lt;/I&gt; are needed for the diagnosis of pneumococcal disease and vaccine studies. This study aimed to show that sequential multiplex polymerase chain reaction (PCR is more efficient than conventional culture in achieving &lt;I&gt;S. pneumoniae -positive&lt;/i&gt; results. &lt;B&gt;Methods:&lt;/B&gt; Nasopharyngeal (NP secretions were obtained from 842 pediatric patients admitted with lower respiratory infections at Severance Children’s Hospital in Korea between March 2009 and June 2010. For identification and serotype determination of pneumococci from the NP secretions, the secretions were evaluated via multiplex PCR technique with 35 serotype-specific primers arranged in 8 multiplex PCR sets and conventional bacteriological culture technique. &lt;B&gt;Results:&lt;/B&gt; Among the results for 793 samples that underwent both bacterial culture and PCR analysis for pneumococcal detection, 153 (19.3% results obtained by PCR and 81 (10.2% results obtained by conventional culture technique were positive for S. pneumoniae. The predominant serotypes observed, in order of decreasing frequency, were 19A (23%, 6A/B (16%, 19F (11%, 15B/C (5%, 15A (5%, and 11A (4%; further, 26% of the isolates were non-typeable. &lt;B&gt;Conclusion:&lt;/B&gt; As opposed to conventional bacteriological tests, PCR analysis can accurately and rapidly identify pneumococcal serotypes.

  15. Age-Stratified Prevalences of Pneumococcal-Serotype-Specific Immunoglobulin G in England and Their Relationship to the Serotype-Specific Incidence of Invasive Pneumococcal Disease Prior to the Introduction of the Pneumococcal 7-Valent Conjugate Vaccine▿

    OpenAIRE

    Balmer, Paul; Borrow, Ray; Findlow, Jamie; Warrington, Rosalind; Frankland, Sarah; Waight, Pauline; George, Robert; Andrews, Nick; Miller, Elizabeth

    2007-01-01

    Recent changes to the childhood immunization schedule in the United Kingdom have resulted in the inclusion of the 7-valent pneumococcal conjugate vaccine. However, the seroprevalence of pneumococcal antibodies in the population was unknown. To address this, we measured pneumococcal, age-specific immunoglobulin G (IgG) concentrations specific for nine serotypes by an assay run on the Bioplex platform, using 2,664 serum samples collected in England from 2000 to 2004. The lowest concentrations o...

  16. Osteopontin promotes host defense during Klebsiella pneumoniae-induced pneumonia

    NARCIS (Netherlands)

    G.J.W. van der Windt; J.J. Hoogerwerf; A.F. de Vos; S. Florquin; T. van der Poll

    2010-01-01

    Klebsiella pneumoniae is a common cause of nosocomial pneumonia. Osteopontin (OPN) is a phosphorylated glycoprotein involved in inflammatory processes, some of which is mediated by CD44. The aim of this study was to determine the role of OPN during K. pneumoniae-induced pneumonia. Wild-type (WT) and

  17. Pneumococcal serotype distribution in adults with invasive disease and in carrier children in Italy: Should we expect herd protection of adults through infants' vaccination?

    Science.gov (United States)

    Azzari, Chiara; Cortimiglia, Martina; Nieddu, Francesco; Moriondo, Maria; Indolfi, Giuseppe; Mattei, Romano; Zuliani, Massimo; Adriani, Beatrice; Degl'Innocenti, Roberto; Consales, Guglielmo; Aquilini, Donatella; Bini, Giancarlo; Di Natale, Massimo Edoardo; Canessa, Clementina; Ricci, Silvia; de Vitis, Elisa; Mangone, Giusi; Bechini, Angela; Bonanni, Paolo; Pasinato, Angela; Resti, Massimo

    2016-01-01

    The 7-valent pneumococcal conjugate vaccine (PCV7) produced a significant herd protection in unvaccinated adult population mostly because of pneumococcus carriage decrease in vaccinated children. It is not known if the 13-valent pneumococcal vaccine can give similar effect on adults. Aims of the work were to evaluate whether the 6 additional serotypes are present in nasopharynx of children and serotype distribution in invasive pneumococcal infections (IPD) in adults. Realtime-PCR was used to evaluate pneumococcal serotypes in adults with confirmed IPD and in nasopharyngeal swabs (NP) from 629 children not vaccinated or vaccinated with PCV7 and resident in the same geographical areas. Two hundred twenty-one patients (116 males, median 67.9 years) with IPD were studied (pneumonia n = 103, meningitis n = 61 sepsis n = 50, other n = 7). Two hundred twelve were serotyped. The most frequent serotypes were 3, (31/212; 14.6%), 19A, (19/212; 9.0%), 12 (17/212; 8.0%), 7F, (14/212; 6.6%). In NP of children, the frequency of those serotypes causing over 50% of IPD in adults was very low, ranging from 0.48% for serotype 7F to 7.9% for serotype 19A. On the other side serotype 5, very frequent in NP (18.7%) caused children NP. We suggest that herd protection obtainable with the additional 6 serotypes included in PCV13 may be more limited than that demonstrated with PCV7 in the past. In order to reduce the burden of disease in adults, adults should be offered a specific vaccination program with highly immunogenic PCV.

  18. 新型肺炎链球菌疫苗研究进展%Advances in the research of new pneumococcal vaccines

    Institute of Scientific and Technical Information of China (English)

    徐江红; 陈兵

    2009-01-01

    肺炎链球菌是肺炎、脑膜炎、败血症、中耳炎和鼻窦炎的主要致病菌.目前针对肺炎链球菌疾病的预防主要是以多糖为基础的23价多糖疫苗和7价多糖蛋白结合疫苗,但因其有血清型的限制,应用有很大的局限性.因此以肺炎链球菌表面毒力因子或蛋白为基础的、无血清型限制的肺炎链球菌蛋白疫苗将成为新型肺炎链球菌疫苗发展的方向,此文综述了肺炎链球菌蛋白疫苗的研究进展.%Streptococcus prteumoniae is a major pathogen for community-acquired pneumonia,meningitis,septicemia,otitis media,and sinusitis.The licensed polysaceharide-based 23-valent pneumococcal polysaccharide vaccine and 7-valent pneumococcal polysaccharide-protein conjugate vaccine (PCV7) only elicit protective antibodies against the infection caused by serotypes that are included in the vaccines.To broaden the protection,the use of pneumococcal serotype-indepondent protein vaccines based on surface protein components will be a feasible and preferable alternative.In this review,advances in the research of pneumococcal protein vaccines are discussed.

  19. Outbreaks of Streptococcus pneumoniae carriage in day care cohorts in Finland – implications for elimination of transmission

    OpenAIRE

    Auranen Kari; Leino Tuija; Erästö Panu; Hoti Fabian

    2009-01-01

    Abstract Background Day care centre (DCC) attendees play a central role in maintaining the circulation of Streptococcus pneumoniae (pneumococcus) in the population. Exposure within families and within DCCs are the main risk factors for colonisation with pneumococcal serotypes in DCC attendees. Methods Transmission of serotype specific carriage was analysed with a continuous time event history model, based on longitudinal data from day care attendees and their family members. Rates of acquisit...

  20. In Vitro Activities of Cethromycin (ABT-773), a New Ketolide, against Streptococcus pneumoniae Strains That Are Not Susceptible to Penicillin or Macrolides

    OpenAIRE

    Mason, Edward O.; Lamberth, Linda B.; Wald, Ellen R.; Bradley, John S.; Barson, William J.; Kaplan, Sheldon L.

    2003-01-01

    Pneumococcal resistance to antimicrobials presents problems to physicians for empirical treatment of acute otitis media (AOM). Three hundred thirty-three isolates of Streptococcus pneumoniae selected for nonsusceptibility to penicillin (MIC >0.1 μg/ml) from the middle ear (n = 325) or mastoid (n = 8) of children seen between 1994 and 2000 at four children's hospitals in the United States were tested by broth microdilution for susceptibility to nine antibiotics. Using NCCLS 2002 breakpoints, r...