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Sample records for pneumococcal invasive disease

  1. Invasive pneumococcal disease in Australia, 2006.

    PubMed

    Roche, Paul W; Krause, Vicki; Cook, Heather; Barralet, Jenny; Coleman, David; Sweeny, Amy; Fielding, James; Giele, Carolien; Gilmour, Robin; Holland, Ros; Kampen, Riemke; Brown, Mitchell; Gilbert, Lyn; Hogg, Geoff; Murphy, Denise

    2008-03-01

    Enhanced surveillance for invasive pneumococcal disease (IPD) was carried out in all Australian states and territories in 2006 with comprehensive comparative data available since 2002. There were 1,445 cases of IPD notified to the National Notifiable Diseases Surveillance System in Australia in 2006; a notification rate of 7 cases per 100,000 population. The rates varied between states and territories and by geographical region with the highest rates in the Northern Territory, the jurisdiction with the largest proportion of Indigenous people. Invasive pneumococcal disease was reported most frequently in those aged 85 years or over (30.8 cases per 100,000 population) and in children aged one year (26.5 cases per 100,000 population). There were 130 deaths attributed to IPD resulting in an overall case fatality rate of 9%. The overall rate of IPD in Indigenous Australians was 4.3 times the rate in non-indigenous Australians. The rate of IPD in the under two years population continued to fall in 2006, but the rate in Indigenous children (73 cases per 100,000 population) was significantly greater than in non-Indigenous children (21 cases per 100,000 population). The rates of disease caused by serotypes in the 7-valent pneumococcal conjugate vaccine (7vPCV) decreased between 2002 and 2006 by 78% in children aged under two years as a result of the introduction of a universal childhood 7vPCV immunisation program. Significant decreases in IPD caused by 7vPCV serotypes also occurred in the 2-14 years and 65 years or over age groups. Rates of disease caused by non-7vPCV in the same periods were little changed. Serotypes were identified in 94% of all notified cases, with 43% of disease caused by serotypes in the 7vPCV and 85% caused by serotypes in the 23-valent polysaccharide pneumococcal vaccine (23vPPV). The number of invasive pneumococcal isolates with reduced penicillin susceptibility remains low and reduced susceptibility to third generation cephalosporins is rare.

  2. Invasive pneumococcal disease in Australia, 2005.

    PubMed

    Roche, Paul; Krause, Vicki; Cook, Heather; Bartlett, Mark; Coleman, David; Davis, Craig; Fielding, James; Giele, Carolien; Gilmour, Robin; Holland, Ros; Kampen, Riemke

    2007-03-01

    Enhanced surveillance for invasive pneumococcal disease (IPD) was carried out in all Australian states and territories in 2005 with comparative data available since 2001. There were 1,680 cases of IPD notified to the National Notifiable Diseases Surveillance System in Australia in 2005; a notification rate of 8.3 cases per 100,000 population. The rates varied between states and territories and by geographical region with the highest rates in the Northern Territory, the jurisdiction with the largest proportion of Indigenous people. Invasive pneumococcal disease was reported most frequently in those aged 85 years or over (41 cases per 100,000 population) and in 1-year-old children (36.5 cases per 100,000 population). Enhanced data provided additional information on 1,015 (60%) of all notified cases. The overall rate of IPD in Indigenous Australians was 8.6 times the rate in non-Indigenous Australians. There were 126 deaths attributed to IPD resulting in an overall case fatality rate of 7.5%. While the rate of IPD in the Indigenous under 2-year-old population decreased from 219 cases per 100,000 population since targeted introduction of the 7-valent conjugate pneumococcal vaccine (7vPCV) in 2001, the rate in 2005 (94 cases per 100,000 population) was significantly greater than in non-Indigenous children (20.4 cases per 100,000 population). Rates of disease in all children aged less than 2 years, caused by serotypes in the 7vPCV decreased by 75% between 2004 and 2005 as a result of the introduction of a universal childhood 7vPCV immunisation program. Significant decreases in IPD caused by 7vPCV serotypes also occurred in the 2-14 years and 65 years or over age groups. There is no evidence of replacement disease with non-vaccine serotypes. Serotypes were identified in 90% of all notified cases, with 61% of disease caused by serotypes in the 7vPCV and 88% caused by serotypes in the 23-valent polysaccharide pneumococcal vaccine (23vPPV). Reduced penicillin susceptibility

  3. Seasonal variation in penicillin susceptibility and invasive pneumococcal disease.

    PubMed

    Iroh Tam, Pui-Ying; Madoff, Lawrence C; O'Connell, Michael; Pelton, Stephen I

    2015-04-01

    We evaluated prospectively laboratory surveillance data from Massachusetts to investigate whether seasonal variation in invasive pneumococcal disease is associated with the proportion of penicillin-susceptible isolates. The proportion of penicillin-susceptible isolates associated with invasive pneumococcal disease varied by season, with proportions highest in the winter and lowest in the summer, and rates of invasive disease were highest in the autumn and winter seasons and lowest in the summer.

  4. Seasonal Variation in Penicillin Susceptibility and Invasive Pneumococcal Disease

    PubMed Central

    Tam, Pui-Ying Iroh; Madoff, Lawrence C.; O'Connell, Michael; Pelton, Stephen I.

    2014-01-01

    We evaluated prospectively laboratory surveillance data from Massachusetts to investigate whether seasonal variation in invasive pneumococcal disease is associated with the proportion of penicillin susceptible isolates. The proportion of penicillin susceptible isolates associated with invasive pneumococcal disease varied by season, with proportions highest in the winter and lowest in the summer, and rates of invasive disease were highest in the autumn and winter seasons and lowest in the summer. PMID:25379834

  5. Increased Invasive Pneumococcal Disease, North East England, UK

    PubMed Central

    Houseman, Catherine; Hughes, Gareth J.; Chapman, Kaye E.; Wilson, Deborah

    2017-01-01

    Since April 2014, invasive pneumococcal disease incidence has increased substantially across North East England, United Kingdom, reversing the decline that followed the 2006 introduction of pneumococcal conjugate vaccines. Significant increases occurred in 23-valent polysaccharide vaccine serotypes and nonvaccine serotypes. Trends in other regions and long-term effects of multivalent vaccines require further investigation. PMID:27983490

  6. Pediatric Invasive Pneumococcal Disease in the United States in the Era of Pneumococcal Conjugate Vaccines

    PubMed Central

    2012-01-01

    Summary: Invasive infections caused by Streptococcus pneumoniae continue to be a major cause of morbidity and mortality worldwide, especially in children under 5 years of age. In the United States, 90% of invasive pneumococcal infections in children are caused by 13 serotypes of S. pneumoniae. The licensure (in 2000) and subsequent widespread use of a heptavalent pneumococcal conjugate vaccine (PCV7) have had a significant impact on decreasing the incidence of serious invasive pneumococcal disease (IPD) in all age groups, especially in children under 2 years of age. However, the emergence of replacement non-PCV7 serotypes, especially serotype 19A, has resulted in an increase in the incidence of serious and invasive infections. In 2010, a 13-valent PCV was licensed in the United States. However, the impact that this vaccine will have on IPD remains to be seen. The objectives of this review are to discuss the epidemiology of serious and invasive pneumococcal infections in the United States in the PCV era and to review some of the pneumococcal vaccines that are in development. PMID:22763632

  7. Medical microbiology: laboratory diagnosis of invasive pneumococcal disease.

    PubMed

    Werno, Anja M; Murdoch, David R

    2008-03-15

    The laboratory diagnosis of invasive pneumococcal disease (IPD) continues to rely on culture-based methods that have been used for many decades. The most significant recent developments have occurred with antigen detection assays, whereas the role of nucleic acid amplification tests has yet to be fully clarified. Despite developments in laboratory diagnostics, a microbiological diagnosis is still not made in most cases of IPD, particularly for pneumococcal pneumonia. The limitations of existing diagnostic tests impact the ability to obtain accurate IPD burden data and to assess the effectiveness of control measures, such as vaccination, in addition to the ability to diagnose IPD in individual patients. There is an urgent need for improved diagnostic tests for pneumococcal disease--especially tests that are suitable for use in underresourced countries.

  8. Rapid diagnosis of invasive pneumococcal disease in pediatric population.

    PubMed

    Picazo, Juan Jose; Contreras, Jesús Ruiz; Ríos, Esther; Culebras, Esther; Rodríguez-Avial, Iciar; Méndez, Cristina; Betriu, Carmen

    2013-05-01

    The aim of this study was to evaluate the Binax NOW immunochromatographic pneumococcal antigen test for the identification of Streptococcus pneumoniae in pleural and cerebrospinal fluids from children with suspected invasive pneumococcal disease. The results were compared with those obtained by PCR. Binax NOW was applied to these samples as recommended by the manufacturer for urine and cerebrospinal samples. Detection of pneumococcal DNA was performed by real-time PCR assay targeting the autolysin gene (lytA). Of the 199 samples analyzed, 131 were positive by both Binax NOW and lytA PCR, and 36 samples were negative by both techniques. Using the real-time PCR as a comparative method to the Binax for the detection of S. pneumoniae, the sensitivity and specificity of Binax NOW was 88% and 72.5%, respectively. Of the 145 positive samples analyzed by Binax NOW, 119 showed intense coloring of the sample line and 26 showed weak intensity. Conventional culture is the most common method in clinical settings, but Binax NOW is an easier and faster test for identifying S. pneumoniae in pleural and cerebrospinal fluids from children with suspected invasive pneumococcal disease.

  9. Immunodeficiency Among Children with Recurrent Invasive Pneumococcal Disease

    PubMed Central

    Schejbel, Lone; Lundstedt, A.C.; Jensen, Lise; Laursen, Inga A.; Ryder, Lars P.; Heegaard, Niels H.H.; Konradsen, Helle; Christensen, Jens Jørgen; Heilmann, Carsten; Marquart, Hanne V.

    2015-01-01

    Background: Recurrent invasive pneumococcal disease (rIPD) occurs mostly in children with an underlying disease, but some cases remain unexplained. Immunodeficiency has been described in children with rIPD, but the prevalence is unknown. We used a nationwide registry of all laboratory-confirmed cases of rIPD to identify cases of unexplained rIPD and examine them for immunodeficiency. Methods: Cases of rIPD in children 0–15 years of age from 1980 to 2008 were identified. Children without an obvious underlying disease were screened for complement function, T-cell, B-cell, natural killer--cell counts and concentration of immunoglobulins. B-cell function was evaluated by measuring antibody response to polysaccharide-based pneumococcal vaccination and the extent of fraction of somatic hypermutation. Toll-Like receptor (TLR) signaling function and mutations in key TLR-signaling molecules were examined. Results: In total, rIPD were observed in 54 children (68 cases of rIPD of 2192 IPD cases). Children with classical risk factors for IPD were excluded, and among the remaining 22 children, 15 were eligible for analysis. Of these 6 (40%) were complement C2-deficient. Impaired vaccination response was found in 6 children of whom 3 were C2 deficient. One patient had a severe TLR signaling dysfunction. No mutations in IRAK4, IKBKG or MYD88 were found. Conclusion: Of an unselected cohort of children with rIPD at least 11% were C2 deficient. Data suggest that screening for complement deficiencies and deficient antibody response to pneumococcal vaccines in patients with more than 1 episode of IPD is warranted. PMID:25831419

  10. Retrospective study of prognostic factors in pediatric invasive pneumococcal disease

    PubMed Central

    Peng, Chun-Chih; Chang, Hung-Yang; Huang, Daniel Tsung-Ning; Chang, Lung; Lei, Wei-Te

    2017-01-01

    Streptococcus pneumoniae remains the leading causative pathogen in pediatric pneumonia and bacteremia throughout the world. The invasive pneumococcal disease (IPD) is known as isolation of S. pneumoniae from a normally sterile site (e.g., blood, cerebrospinal fluid, synovial fluid, pericardial fluid, pleural fluid, or peritoneal fluid). The aim of this study is to survey the clinical manifestations and laboratory results of IPD and identify the prognostic factors of mortality. From January 2001 to December 2006, a retrospective review of chart was performed in a teaching hospital in Taipei. The hospitalized pediatric patients with the diagnosis of pneumonia, arthritis, infectious endocarditis, meningitis or sepsis were recruited. Among them, 50 patients were pneumococcal infections proved by positive culture results or antigen tests. Clinical manifestations, laboratory data and hospitalization courses were analyzed. The median age was 3.5-year-old and there were 30 male patients (60%). Eight patients (16%) had underlying disease such as leukemia or congenital heart disease. Hemolytic uremic syndrome (HUS) was observed in ten patients and extracorporeal membrane oxygenation (ECMO) was performed in three patients. Leukocytosis, elevated C-reactive protein and AST level were noted in most of the patients. The overall mortality rate was 10%. We found that leukopenia, thrombocytopenia and high CRP level were significant predictors for mortality. In conclusion, S. pneumoniae remains an important health threat worldwide and IPD is life-threatening with high mortality rate. We found leukopenia, thrombocytopenia, and high CRP levels to be associated with mortality in pediatric IPD, and these factors are worthy of special attention at admission. Although we failed to identify a statistically significant prognostic factor in multivariate analysis due to relatively small sample size, we suggest an aggressive antibiotic treatment in patients with these factors at admission

  11. Invasive Pneumococcal Disease After Implementation of 13-Valent Conjugate Vaccine

    PubMed Central

    Madoff, Lawrence C.; Coombes, Brandon; Pelton, Stephen I.

    2014-01-01

    OBJECTIVE: To examine whether there is a different clinical profile and severity of invasive pneumococcal disease (IPD) in children caused by nonvaccine types in the era of 13-valent pneumococcal conjugate vaccine (PCV13). METHODS: Observational study of childhood IPD in Massachusetts based on state public health surveillance data comparing pre-PCV13 (2007–2009) and post-PCV13 (2010–2012) eras. RESULTS: There were 168 pre-PCV13 cases of IPD and 85 post-PCV13 cases of IPD in Massachusetts children ≤5 years of age. PCV13 serotypes declined by 18% in the first 2 years after PCV13 use (P = .011). In the post-PCV13 phase, a higher proportion of children were hospitalized (57.6% vs 50.6%), and a higher proportion of children had comorbidity (23.5% vs 19.6%). Neither difference was statistically significant, nor were comparisons of IPD caused by vaccine and nonvaccine types. Children with comorbidities had higher rates of IPD caused by a nonvaccine type (27.6% vs 17.2%; P = .085), were more likely to be hospitalized (80.4% vs 50%; P < .0001), and were more likely to have a longer hospital stay (median of 3 days vs 0.5 days; P = .0001). CONCLUSIONS: Initial data suggest that nonvaccine serotypes are more common in children with underlying conditions, who have greater morbidity from disease. In the post-PCV13 era, a larger proportion of patients are hospitalized, but mortality rates are unchanged. Routine vaccination with PCV13 may not be enough to reduce the risk in patients with comorbidity. PMID:25002663

  12. Late onset invasive pneumococcal disease in a liver transplanted patient: beyond the Austrian syndrome.

    PubMed

    Belvisi, V; Del Borgo, C; Morelli, F; Marocco, R; Tieghi, T; Fabietti, P; Vetica, A; Lichtner, M; Mastroianni, C M

    2013-06-01

    Invasive disease caused by Streptococcus pneumoniae is a major cause of morbidity and mortality in high-risk individuals with severe comorbidities, including asplenia, chronic alcoholism, and altered immune status. The risk of invasive pneumococcal disease has been significantly higher in transplant patients compared with the general population. Here, we report an unusual case of a disseminated pneumococcal infection with meningitis, endocarditis, spondylodiscitis, and muscle abscess in an asplenic patient on chronic immunosuppressive therapy for liver transplantation performed 17 years before.

  13. Pneumococcal Disease

    MedlinePlus

    ... Newsroom Blogs Image Library News Conferences Press Releases Radio Public Service Announcements Real Stories, Real People Share ... National Foundation for Infectious Diseases (NFID) Pneumococcal Disease Radio Public Service Announcement National Foundation for Infectious Diseases ( ...

  14. Cigarette Smoke Attenuates the Nasal Host Response to Streptococcus pneumoniae and Predisposes to Invasive Pneumococcal Disease in Mice

    PubMed Central

    Shen, Pamela; Morissette, Mathieu C.; Vanderstocken, Gilles; Gao, Yang; Hassan, Muhammad; Roos, Abraham; Thayaparan, Danya; Merlano, Maria; Dorrington, Michael G.; Nikota, Jake K.; Bauer, Carla M. T.; Kwiecien, Jacek M.; Labiris, Renee; Bowdish, Dawn M. E.; Stevenson, Christopher S.

    2016-01-01

    Streptococcus pneumoniae is a leading cause of invasive bacterial infections, with nasal colonization an important first step in disease. While cigarette smoking is a strong risk factor for invasive pneumococcal disease, the underlying mechanisms remain unknown. This is partly due to a lack of clinically relevant animal models investigating nasal pneumococcal colonization in the context of cigarette smoke exposure. We present a model of nasal pneumococcal colonization in cigarette smoke-exposed mice and document, for the first time, that cigarette smoke predisposes to invasive pneumococcal infection and mortality in an animal model. Cigarette smoke increased the risk of bacteremia and meningitis without prior lung infection. Mechanistically, deficiency in interleukin 1α (IL-1α) or platelet-activating factor receptor (PAFR), an important host receptor thought to bind and facilitate pneumococcal invasiveness, did not rescue cigarette smoke-exposed mice from invasive pneumococcal disease. Importantly, we observed cigarette smoke to attenuate nasal inflammatory mediator expression, particularly that of neutrophil-recruiting chemokines, normally elicited by pneumococcal colonization. Smoking cessation during nasal pneumococcal colonization rescued nasal neutrophil recruitment and prevented invasive disease in mice. We propose that cigarette smoke predisposes to invasive pneumococcal disease by suppressing inflammatory processes of the upper respiratory tract. Given that smoking prevalence remains high worldwide, these findings are relevant to the continued efforts to reduce the invasive pneumococcal disease burden. PMID:26930709

  15. Changes in the features of invasive pneumococcal disease after introduction of the seven-valent pneumococcal conjugate vaccine in a regional core hospital of Kochi, Japan.

    PubMed

    Miyahara, Hiroyuki; Maruyama, Hidehiko; Kanazawa, Akane; Iwasaki, Yuka; Shigemitsu, Yusuke; Watanabe, Hirokazu; Tokorodani, Chiho; Miyazawa, Mari; Nakata, Yusei; Nishiuchi, Ritsuo; Kikkawa, Kiyoshi

    2015-01-01

    Since the introduction of the seven-valent pneumococcal conjugate vaccine (PCV7) in 2007, invasive pneumococcal disease has declined, but the incidence of Streptococcus pneumoniae serotype 19A has risen worldwide. The present study examined changes in the features of invasive pneumococcal disease since the introduction of the PCV7 in Kochi, Japan. Pediatric cases of invasive pneumococcal disease were investigated before and after vaccine introduction (January 2008 to December 2013). Cases of invasive pneumococcal disease tended to decrease after PCV7 introduction. In addition, before introduction of the vaccine, most serotypes causing invasive pneumococcal disease were those included in the vaccine. However, after the introduction, we found cases infected by serotypes not covered by vaccine. Penicillin-resistant S. pneumoniae was the predominant serotype causing invasive pneumococcal disease before introduction of the PCV7, and the susceptibility of this serotype to antibiotics improved after vaccine introduction. Serotype isolates identified after vaccine introduction were also relatively susceptible to antibiotic therapy, but decreased susceptibility is expected.

  16. Population-Based Surveillance for Invasive Pneumococcal Disease in Homeless Adults in Toronto

    PubMed Central

    Plevneshi, Agron; Svoboda, Tomislav; Armstrong, Irene; Tyrrell, Gregory J.; Miranda, Anna; Green, Karen; Low, Donald; McGeer, Allison

    2009-01-01

    Background Identification of high-risk populations for serious infection due to S. pneumoniae will permit appropriately targeted prevention programs. Methods We conducted prospective, population-based surveillance for invasive pneumococcal disease and laboratory confirmed pneumococcal pneumonia in homeless adults in Toronto, a Canadian city with a total population of 2.5 M, from January 1, 2002 to December 31, 2006. Results We identified 69 cases of invasive pneumococcal disease and 27 cases of laboratory confirmed pneumococcal pneumonia in an estimated population of 5050 homeless adults. The incidence of invasive pneumococcal disease in homeless adults was 273 infections per 100,000 persons per year, compared to 9 per 100,000 persons per year in the general adult population. Homeless persons with invasive pneumococcal disease were younger than other adults (median age 46 years vs 67 years, P<.001), and more likely than other adults to be smokers (95% vs. 31%, P<.001), to abuse alcohol (62% vs 15%, P<.001), and to use intravenous drugs (42% vs 4%, P<.001). Relative to age matched controls, they were more likely to have underlying lung disease (12/69, 17% vs 17/272, 6%, P = .006), but not more likely to be HIV infected (17/69, 25% vs 58/282, 21%, P = .73). The proportion of patients with recurrent disease was five fold higher for homeless than other adults (7/58, 12% vs. 24/943, 2.5%, P<.001). In homeless adults, 28 (32%) of pneumococcal isolates were of serotypes included in the 7-valent conjugate vaccine, 42 (48%) of serotypes included in the 13-valent conjugate vaccine, and 72 (83%) of serotypes included in the 23-valent polysaccharide vaccine. Although no outbreaks of disease were identified in shelters, there was evidence of clustering of serotypes suggestive of transmission of pathogenic strains within the homeless population. Conclusions Homeless persons are at high risk of serious pneumococcal infection. Vaccination, physical structure changes or

  17. Systematic Evaluation of Serotypes Causing Invasive Pneumococcal Disease among Children Under Five: The Pneumococcal Global Serotype Project

    PubMed Central

    Johnson, Hope L.; Deloria-Knoll, Maria; Levine, Orin S.; Stoszek, Sonia K.; Freimanis Hance, Laura; Reithinger, Richard; Muenz, Larry R.; O'Brien, Katherine L.

    2010-01-01

    Background Approximately 800,000 children die each year due to pneumococcal disease and >90% of these deaths occur in developing countries where few children have access to life-saving serotype-based vaccines. Understanding the serotype epidemiology of invasive pneumococcal disease (IPD) among children is necessary for vaccine development and introduction policies. The aim of this study was to systematically estimate the global and regional distributions of serotypes causing IPD in children <5 years of age. Methods and Findings We systematically reviewed studies with IPD serotype data among children <5 years of age from the published literature and unpublished data provided by researchers. Studies conducted prior to pneumococcal conjugate vaccine (PCV) introduction, from 1980 to 2007, with ≥12 months of surveillance, and reporting ≥20 serotyped isolates were included. Serotype-specific proportions were pooled in a random effects meta-analysis and combined with PD incidence and mortality estimates to infer global and regional serotype-specific PD burden. Of 1,292, studies reviewed, 169 were included comprising 60,090 isolates from 70 countries. Globally and regionally, six to 11 serotypes accounted for ≥70% of IPD. Seven serotypes (1, 5, 6A, 6B, 14, 19F, 23F) were the most common globally; and based on year 2000 incidence and mortality estimates these seven serotypes accounted for >300,000 deaths in Africa and 200,000 deaths in Asia. Serotypes included in both the 10- and 13-valent PCVs accounted for 10 million cases and 600,000 deaths worldwide. Conclusions A limited number of serotypes cause most IPD worldwide. The serotypes included in existing PCV formulations account for 49%–88% of deaths in Africa and Asia where PD morbidity and mortality are the highest, but few children have access to these life-saving vaccines. Please see later in the article for the Editors' Summary PMID:20957191

  18. Invasive pneumococcal disease complicated by cerebral vasculitis, transient diabetes insipidus and spondylodiscitis.

    PubMed

    Ribeiro, Sofia; Domingues, Vital; Faria, Raquel M; Mendonça, Teresa

    2013-08-19

    Invasive pneumococcal disease (IPD) is a potential life-threatening situation that requires immediate recognition and treatment. Cerebrovascular complications are uncommon and have been reported less frequently in adults than in children. We report a case of 59-year-old man with IPD complicated by cerebral vasculitis, transient central diabetes insipidus and spondylodiscitis. Each of these complications is rare and needs specific approach. Their association is even rarer and to the best of our knowledge this is the first case reported.

  19. Sex differences in invasive pneumococcal disease and the impact of pneumococcal conjugate vaccination in the Netherlands, 2004 to 2015

    PubMed Central

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

    2017-01-01

    Implementation of pneumococcal conjugate vaccines in the Netherlands (PCV7 in 2006 and PCV10 in 2011) for infants caused a shift in serotypes in invasive pneumococcal disease (IPD). We explored sex differences in serotype-specific IPD incidence before and after vaccine introduction. Incidences in the pre-PCV7 (June 2004–May 2006), post-PCV7 (June 2008–May 2011) and post-PCV10 period (June 2013–May 2015), stratified by age, were compared. Incidence was higher in men for all age groups (overall in men: 16.7, 15.5 and 14.4/100,000 and women: 15.4, 13.6 and 13.9/100,000 pre-PCV7, post-PCV7 and post-PCV10, respectively), except for 20–39 year-olds after PCV7 and 40–64 year-olds after PCV10 introduction. After PCV7 and PCV10 introduction, the overall IPD incidence decreased in men aged 20–39 years (from 5.3 pre-PCV7 to 4.7 and 2.6/100,000 post-PCV7 and post-PCV10, respectively), whereas it showed a temporary increase in women (from 3.9/100,000 pre-PCV7 to 5.0/100,000 post-PCV7 and back to 4.0/100,000 post-PCV10) due to replacement disease. PCV10 herd effects were observed throughout, but in women older than 40 years, a significant increase in non-PCV10 serotype offset a decrease in overall IPD incidence. Ongoing surveillance of IPD incidence by sex is important to evaluate the long-term effects of PCV implementation. PMID:28300529

  20. Invasive pneumococcal disease and pandemic (H1N1) 2009, Denver, Colorado, USA.

    PubMed

    Nelson, George E; Gershman, Kenneth A; Swerdlow, David L; Beall, Bernard W; Moore, Matthew R

    2012-02-01

    Pneumococcal pneumonia was a complication during previous influenza pandemics but was not evident initially during pandemic (H1N1) 2009. During October 2009 in Denver, Colorado, USA, invasive pneumococcal disease (IPD) and pandemic (H1N1) 2009 peaked simultaneously, which suggests a link. We compared cases of IPD in October 2009 with cases in February 2009, the most recent peak month of seasonal influenza. During October 2009, we observed 58 IPD cases, which was 3× the average number of IPD cases that usually occur in October in Denver. Patients with IPD in October 2009 were younger and more likely to have chronic lung disease than patients who had IPD in February 2009; a total of 10/47 patients had influenza, and 33/53 patients had influenza-like illness. Thus, ≈17%-62% cases of IPD may have been associated with pandemic (H1N1) 2009. Pneumococcal disease prevention strategies should be emphasized during future influenza pandemics.

  1. Pneumococcal Disease in the Era of Pneumococcal Conjugate Vaccine.

    PubMed

    Yildirim, Inci; Shea, Kimberly M; Pelton, Stephen I

    2015-12-01

    Universal immunization of infants and toddlers with pneumococcal conjugate vaccines over the last 15 years has dramatically altered the landscape of pneumococcal disease. Decreases in invasive pneumococcal disease, all-cause pneumonia, empyema, mastoiditis, acute otitis media, and complicated otitis media have been reported from multiple countries in which universal immunization has been implemented. Children with comorbid conditions have higher rates of pneumococcal disease and increased case fatality rates compared with otherwise healthy children, and protection for the most vulnerable pediatric patients will require new strategies to address the underlying host susceptibility and the expanded spectrum of serotypes observed.

  2. Recurrent Invasive Pneumococcal Disease in Children: Underlying Clinical Conditions, and Immunological and Microbiological Characteristics

    PubMed Central

    Alsina, Laia; Basteiro, Maria G.; de Paz, Hector D.; Iñigo, Melania; de Sevilla, Mariona F.; Triviño, Miriam; Juan, Manel; Muñoz-Almagro, Carmen

    2015-01-01

    Purpose Clinical, immunological and microbiological characteristics of recurrent invasive pneumococcal disease (IPD) in children were evaluated, differentiating relapse from reinfection, in order to identify specific risk factors for both conditions. Methods All patients <18 years-old with recurrent IPD admitted to a tertiary-care pediatric center from January 2004 to December 2011 were evaluated. An episode of IPD was defined as the presence of clinical findings of infection together with isolation and/or pneumococcal DNA detection by Real-Time PCR in any sterile body fluid. Recurrent IPD was defined as 2 or more episodes in the same individual at least 1 month apart. Among recurrent IPD, we differentiated relapse (same pneumococcal isolate) from reinfection. Results 593 patients were diagnosed with IPD and 10 patients died. Among survivors, 23 episodes of recurrent IPD were identified in 10 patients (1.7%). Meningitis was the most frequent form of recurrent IPD (10 episodes/4 children) followed by recurrent empyema (8 episodes/4 children). Three patients with recurrent empyema caused by the same pneumococcal clone ST306 were considered relapses and showed high bacterial load in their first episode. In contrast, all other episodes of recurrent IPD were considered reinfections. Overall, the rate of relapse of IPD was 0.5% and the rate of reinfection 1.2%. Five out of 7 patients with reinfection had an underlying risk factor: cerebrospinal fluid leak (n = 3), chemotherapy treatment (n = 1) and a homozygous mutation in MyD88 gene (n = 1). No predisposing risk factors were found in the remainder. Conclusions recurrent IPD in children is a rare condition associated with an identifiable risk factor in case of reinfection in almost 80% of cases. In contrast, recurrent IPD with pleuropneumonia is usually a relapse of infection. PMID:25738983

  3. Serotype-Specific Changes in Invasive Pneumococcal Disease after Pneumococcal Conjugate Vaccine Introduction: A Pooled Analysis of Multiple Surveillance Sites

    PubMed Central

    Feikin, Daniel R.; Kagucia, Eunice W.; Loo, Jennifer D.; Link-Gelles, Ruth; Puhan, Milo A.; Cherian, Thomas; Levine, Orin S.; Whitney, Cynthia G.; O’Brien, Katherine L.; Moore, Matthew R.

    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 by dividing observed by expected IPD rates for each post-PCV7 year. We calculated summary rate ratios (RRs) using random effects meta-analysis. For children <5 years old, overall IPD decreased by year 1 post-PCV7 (RR 0·55, 95% CI 0·46–0·65) and remained relatively stable through year 7 (RR 0·49, 95% CI 0·35–0·68). Point estimates for VT IPD decreased annually through year 7 (RR 0·03, 95% CI 0·01–0·10), while NVT IPD increased (year 7 RR 2·81, 95% CI 2·12–3·71). Among adults, decreases in overall IPD also occurred but were smaller and more variable by site than among children. At year 7 after introduction, significant reductions were observed (18–49 year-olds [RR 0·52, 95% CI 0·29–0·91], 50–64 year-olds [RR 0·84, 95% CI 0·77–0·93], and ≥65 year-olds [RR 0·74, 95% CI 0·58–0·95]). Conclusions Consistent and significant decreases in both overall and VT IPD in children occurred quickly and were sustained for 7 years after PCV7 introduction, supporting use of PCVs. Increases in NVT IPD occurred in most sites, with variable magnitude

  4. Epidemiology of Serotype 1 Invasive Pneumococcal Disease, South Africa, 2003-2013.

    PubMed

    von Mollendorf, Claire; Cohen, Cheryl; Tempia, Stefano; Meiring, Susan; de Gouveia, Linda; Quan, Vanessa; Lengana, Sarona; Karstaedt, Alan; Dawood, Halima; Seetharam, Sharona; Lekalakala, Ruth; Madhi, Shabir A; Klugman, Keith P; von Gottberg, Anne

    2016-02-01

    In South Africa, 7-valent pneumococcal conjugate vaccine (PCV) was introduced in April 2009 and replaced with 13-valent PCV in April 2011. We describe the epidemiology of serotype 1 Streptococcus pneumoniae disease during the pre- and post-PCV eras (2003-2013). Using laboratory-based invasive pneumococcal disease (IPD) surveillance, we calculated annual incidences, identified IPD clusters, and determined serotype 1-associated factors. Of 46,483 IPD cases, 4,544 (10%) were caused by serotype 1. Two clusters of serotype 1 infection were detected during 2003-2004 and 2008-2012, but incidence decreased after 2011. Among children <5 years of age, those who had non-serotype 1 IPD had shorter hospital stays, fewer cases of penicillin-nonsusceptible disease, and lower HIV prevalence and in-hospital death rates than did those with serotype 1 IPD; similar factors were noted for older patients. Serotype 1 IPD had distinctive clinical features in South Africa, and annual incidences fluctuated, with decreases noted after the introduction of PCV13.

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

    PubMed Central

    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

  6. Recurrent invasive pneumococcal disease in children--host factors and vaccination response.

    PubMed

    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

  7. Invasive pneumococcal diseases in children in Hokkaido, Japan from April 2000, to March 2015.

    PubMed

    Sakata, Hiroshi

    2016-01-01

    In Japan, the 7-valent pneumococcal conjugate vaccine (PCV-7) became commercially available as a voluntary vaccine in March 2010. It was included in the routine immunization schedule in April 2013 and was replaced by PCV-13 in November 2013. We evaluated 146 cases of invasive pneumococcal disease (IPD) in 142 children (2 developed the disease twice, and 1 developed it three times) treated in the northern district of Hokkaido, Japan from April 2000 to March 2015, before and after the introduction of PCV-7. The incidence rate per 100,000 people aged <5 years showed an increasing trend between April 2000 and March 2010, and reached 87.5 per 100,000 people per year between April 2009 and March 2010, which was immediately before the introduction of PCV-7. Subsequently, the incidence rate started to show a decreasing trend and reached as low as 9.5 per 100,000 people per year between April 2013 and March 2014. However, the incidence rate showed an increasing trend again between April 2014 and March 2015, reaching 33.4 per 100,000 people per year. Serotyping was performed for the 77 strains collected between April 2000 and March 2010. The most frequently isolated serotype was 6B (31.2%), followed by 23F (14.3%) and 19F (13.0%). Among them, 55 strains were covered by PCV-7 (71.4%), and 64 strains were covered by PCV-13 (83.1%). Of the 33 strains collected between April 2010 and March 2015, 14 were covered by PCV-7 (42.4%) and 16 were covered by PCV-13 (48.4%), showing a significant decrease (p < 0.01).

  8. Laboratory surveillance of invasive pneumococcal disease in Australia, 2003 predicting the future impact of the universal childhood conjugate vaccine program.

    PubMed

    Watson, Michael; Roche, Paul; Bayley, Kathy; Bell, Jan M; Collignon, Peter; Gilbert, Gwendolyn L; Hogg, Geoff; Keil, Anthony D; Krause, Vicki; Murphy, Denise; Smith, Helen V; Brown, Mitchell; Stylianopoulos, Joanne; Turnidge, John

    2004-01-01

    A comprehensive invasive pneumococcal disease (IPD) laboratory surveillance program was carried out in Australia in 2003. This program provided data on the prevalence of pneumococcal serotypes and antimicrobial resistance. There were 1,995 isolates tested with 34 per cent (683) from children aged less than five years and 27 per cent (535) from the elderly aged more than 65 years. One thousand eight hundred and sixty were isolates from blood, 79 from CSF and 56 from other sterile sites. In young children, 84 per cent of isolates were a serotype and 92 per cent a serogroup in the 7-valent pneumococcal conjugate vaccine (7vPCV). Of penicillin resistant isolates in children less than five years of age 85 per cent and 98 per cent were a serotype and serogroup in the 7vPCV respectively. When the universal 7vPCV vaccine program in young children is introduced in 2005, a proportion of cases of IPD should also be prevented in young adults (estimated reduction of 54 cases annually) and elderly Australians (an estimated reduction of 110 cases annually) as a result of improved herd immunity. Pneumococcal serotypes with higher rates of penicillin resistance (19F, 14 and 6B) were more prevalent in the elderly than in young children. In contrast, erythromycin resistance was more common in children less than five years of age (24%) compared to the elderly (15%). The predominant serotype with erythromycin resistance in Australia was serotype 14 and thus there is likely to be a major reduction in erythromycin resistance as a result of 7vPCV vaccination. Continued surveillance of pneumococcal serotype distribution and antibiotic susceptibility will be essential in order to identify serotype replacement by non-vaccine serotypes and to monitor the overall impact of current and future vaccine programs on invasive pneumococcal disease in Australia, not only in young children but also in other age groups.

  9. Prediction of Pneumococcal Conjugate Vaccine Effectiveness against Invasive Pneumococcal Disease Using Opsonophagocytic Activity and Antibody Concentrations Determined by Enzyme-Linked Immunosorbent Assay with 22F Adsorption ▿

    PubMed Central

    Schuerman, L.; Wysocki, J.; Tejedor, J. C.; Knuf, M.; Kim, K.-H.; Poolman, J.

    2011-01-01

    We compared the abilities of two serological readouts, antipolysaccharide IgG antibody concentrations and opsonophagocytic activity (OPA) titers, to predict the clinical effectiveness of the 7-valent pneumococcal conjugate vaccine (7vCRM) against invasive pneumococcal disease (IPD). We also assessed the accuracy of the previously established thresholds for GlaxoSmithKline's enzyme-linked immunosorbent assay with 22F adsorption (22F-ELISA) (≥0.2 μg/ml) and OPA assay (titer, ≥8) in predicting effectiveness. We showed that following a 3-dose 7vCRM primary vaccination, the serological response rates as determined using thresholds of ≥0.2 μg/ml IgG and an OPA titer of ≥8 corresponded well with overall effectiveness against IPD. In addition, the OPA assay seemed to better predict serotype-specific effectiveness than enzyme-linked immunoassay. Finally, when applied to post-dose-2 immune responses, both thresholds also corresponded well with the overall IPD effectiveness following a 2-dose 7vCRM primary vaccination. These results support the importance of the OPA assay in evaluating immune responses to pneumococcal conjugate vaccines. PMID:21994351

  10. Forecasting Trends in Invasive Pneumococcal Disease among Elderly Adults in Quebec

    PubMed Central

    Zhou, Z.; Deceuninck, G.; Lefebvre, B.

    2017-01-01

    Background. In Canada, the current recommendation is to offer PPV23 to adults ≥ 65 years. PCV13 is now licensed for adults. Methods. Invasive pneumococcal disease (IPD) cases in adults 65–74 years of age in the Quebec notifiable diseases registry were classified into five serotype categories. Poisson regression models were fitted to monthly rates observed in 2000–2014 and predictions were made for 2015–2024, using theoretical assumptions regarding indirect effects of childhood vaccination and serotype replacement. Results. IPD rates caused by PCV7 serotypes decreased markedly since PCV7 introduction for children in December 2004. This trend is also underway for additional PCV13 serotypes except serotype 3. Additional PPV23 serotypes and nonvaccine serotypes have been on rise since 2004 and this is expected to continue. A small decrease in overall IPD incidence in the next decade is predicted. The proportion of PCV13 serotypes represented 33% of IPD cases in 2014 and would be 20% (95% CI: 15% to 28%) in 2024. PPV23 coverage was 53% in 2014 and is expected to be 47% (95% CI: 26% to 85%) in 2024. Conclusion. The potential usefulness of a combined PCV13 + PPV23 program for elderly adults would decrease over time but PCV13 would be the only option to prevent serotype 3 IPD. PMID:28246534

  11. 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

    PubMed Central

    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.

    2015-01-01

    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

  12. Clonal and serotype dynamics of serogroup 6 isolates causing invasive pneumococcal disease in Portugal: 1999-2012

    PubMed Central

    Diamantino-Miranda, Jorge; Aguiar, Sandra Isabel; Carriço, João André; Melo-Cristino, José

    2017-01-01

    Although serogroup 6 was among the first to be recognized among Streptococcus pneumoniae, several new serotypes were identified since the introduction of pneumococcal conjugate vaccines (PCVs). A decrease of the 6B-2 variant among invasive pneumococcal disease (IPD), but not 6B-1, was noted post conjugate vaccine introduction, underpinned by a decrease of CC273 isolates. Serotype 6C was associated with adult IPD and increased in this age group representing two lineages (CC315 and CC395), while the same lineages expressed other serogroup 6 serotypes in children. Taken together, these findings suggest a potential cross-protection of PCVs against serotype 6C IPD among vaccinated children but not among adults. Serotype 6A became the most important serogroup 6 serotype in children but it decreased in adult IPD. No other serogroup 6 serotypes were detected, so available phenotypic or simple genotypic assays remain adequate for distinguishing serotypes within serogroup 6 isolates. PMID:28152029

  13. Capture-Recapture Estimators in Epidemiology with Applications to Pertussis and Pneumococcal Invasive Disease Surveillance

    PubMed Central

    Braeye, Toon; Verheagen, Jan; Mignon, Annick; Flipse, Wim; Pierard, Denis; Huygen, Kris; Schirvel, Carole; Hens, Niel

    2016-01-01

    Introduction Surveillance networks are often not exhaustive nor completely complementary. In such situations, capture-recapture methods can be used for incidence estimation. The choice of estimator and their robustness with respect to the homogeneity and independence assumptions are however not well documented. Methods We investigated the performance of five different capture-recapture estimators in a simulation study. Eight different scenarios were used to detect and combine case-information. The scenarios increasingly violated assumptions of independence of samples and homogeneity of detection probabilities. Belgian datasets on invasive pneumococcal disease (IPD) and pertussis provided motivating examples. Results No estimator was unbiased in all scenarios. Performance of the parametric estimators depended on how much of the dependency and heterogeneity were correctly modelled. Model building was limited by parameter estimability, availability of additional information (e.g. covariates) and the possibilities inherent to the method. In the most complex scenario, methods that allowed for detection probabilities conditional on previous detections estimated the total population size within a 20–30% error-range. Parametric estimators remained stable if individual data sources lost up to 50% of their data. The investigated non-parametric methods were more susceptible to data loss and their performance was linked to the dependence between samples; overestimating in scenarios with little dependence, underestimating in others. Issues with parameter estimability made it impossible to model all suggested relations between samples for the IPD and pertussis datasets. For IPD, the estimates for the Belgian incidence for cases aged 50 years and older ranged from 44 to58/100,000 in 2010. The estimates for pertussis (all ages, Belgium, 2014) ranged from 24.2 to30.8/100,000. Conclusion We encourage the use of capture-recapture methods, but epidemiologists should preferably

  14. Pneumococcal Disease: Diagnosis and Treatment

    MedlinePlus

    ... of antibiotics may also slow or reverse drug-resistant pneumococcal infections. Related Pages Global Pneumococcal Vaccination World Health Organization National Foundation for Infectious Diseases Sepsis File Formats Help: How do I view ...

  15. Phage-Derived Protein Induces Increased Platelet Activation and Is Associated with Mortality in Patients with Invasive Pneumococcal Disease

    PubMed Central

    Cremers, Amelieke J.; van der Gaast-de Jongh, Christa E.; Ferwerda, Gerben; Meis, Jacques F.; Roeleveld, Nel; Bentley, Stephen D.; Pastura, Alexander S.; van Hijum, Sacha A. F. T.; van der Ven, Andre J.; de Mast, Quirijn; Zomer, Aldert

    2017-01-01

    ABSTRACT To improve our understanding about the severity of invasive pneumococcal disease (IPD), we investigated the association between the genotype of Streptococcus pneumoniae and disease outcomes for 349 bacteremic patients. A pneumococcal genome-wide association study (GWAS) demonstrated a strong correlation between 30-day mortality and the presence of the phage-derived gene pblB, encoding a platelet-binding protein whose effects on platelet activation were previously unknown. Platelets are increasingly recognized as key players of the innate immune system, and in sepsis, excessive platelet activation contributes to microvascular obstruction, tissue hypoperfusion, and finally multiorgan failure, leading to mortality. Our in vitro studies revealed that pblB expression was induced by fluoroquinolones but not by the beta-lactam antibiotic penicillin G. Subsequently, we determined pblB induction and platelet activation by incubating whole blood with the wild type or a pblB knockout mutant in the presence or absence of antibiotics commonly administered to our patient cohort. pblB-dependent enhancement of platelet activation, as measured by increased expression of the α-granule protein P-selectin, the binding of fibrinogen to the activated αIIbβ3 receptor, and the formation of platelet-monocyte complex occurred irrespective of antibiotic exposure. In conclusion, the presence of pblB on the pneumococcal chromosome potentially leads to increased mortality in patients with an invasive S. pneumoniae infection, which may be explained by enhanced platelet activation. This study highlights the clinical utility of a bacterial GWAS, followed by functional characterization, to identify bacterial factors involved in disease severity. PMID:28096486

  16. [Pneumococcal disease and its prevention. The heptavalent pneumococcal conjugate vaccine].

    PubMed

    de Arístegui Fernández, J; Corretger Rauet, J M; García Martín, F; Hernández-Sampelayo, T; Moraga Llop, F A; Rodrigo Gonzalo De Liria, C; Ruiz Contreras, J

    2002-01-01

    Pneumococcal disease is a major cause of morbidity, hospitalization and mortality. Two age groups show a greater incidence and severity of the disease: children under the age of 5 years (mainly during the first 2 years of life) and adults aged more than 65 years. The heptavalent pneumococcal conjugate vaccine, which was commercialized in Spain in June 2001, is efficacious in children aged less than 2 years and, unlike the non-conjugate 23-valent vaccine, it induces immunological memory. In Spain the heptavalent vaccine covers 80 % of serotypes causing pneumococcal invasive disease and acute otitis media in children aged 2-59 months. The heptavalent vaccine has been shown to be immunogenic, efficacious and safe. It has proven efficacy in the prevention of invasive disease caused by the seven vaccine serotypes. In addition, it significantly decreases pneumonia and also prevent acute otitis media. The vaccine is preferably indicated in children aged less than 2 years; children aged 2-5 years may also benefit from the vaccine but those in risk groups should be prioritized. Greater knowledge of the epidemiology of pneumococcal disease and the efficiency of this vaccine in Spain will determine whether it should be included in the immunization schedule.

  17. Antibiotic resistance and serotype distribution of invasive pneumococcal diseases before and after introduction of pneumococcal conjugate vaccine in the Kingdom of Saudi Arabia (KSA).

    PubMed

    Shibl, Atef M; Memish, Ziad A; Al-Kattan, Khaled M

    2012-12-31

    Streptococcus pneumoniae is one of the most common bacterial causes of morbidity and mortality worldwide, causing life threatening infections such as meningitis, pneumonia and febrile bacteremia, particular among young children. The severity and frequency of S. pneumoniae infection and emergence of drug-resistant isolates have highlighted the need for prevention of invasive pneumococcal disease (IPD) as the best method for controlling disease; to better achieve this, more information is needed about serotype distribution and patterns of antibiotic resistance in children in the Kingdom of Saudi Arabia (KSA). Cases of pneumococcal infections in children aged <5 years, recorded in hospitals throughout KSA from 2005 to 2010 were reviewed for serotyping and for antibiotic susceptibility. This covers the time period just before limited introduction of 7-valent pneumococcal conjugate vaccine (PCV7) in 2006, to its introduction into the national immunization program in 2008, until right after a switch to PCV13 in 2010. Case definition required isolation of S. pneumoniae from blood, cerebrospinal fluid, or any sterile biological fluid. Isolates from 311 eligible cases were collected from different regions across KSA, 250 from blood and 61 from cerebrospinal fluid. The most frequently isolated IPD serotypes were 23F, 19F, 6B, 5 and 1. Over the course of the study, there was significant rise of serotype 19A (covered by PCV13 but not PCV7), which accounted for 20% of isolates of IPD in Western and 5% in Central regions in the last 2 years in KSA. There was a notable decrease in serotype 18C over this period, one of the PCV7 serotypes. Serotype coverage for PCV7, PCV10, PCV13 in children <5 years was 53%, 80%, and 91%, respectively across the Kingdom from 2005 to 2010. A total of 66% of IPD isolates were penicillin-resistant, and 62% were erythromycin-resistant. Continued surveillance is critical to measure the emerging of new serotypes and antibiotic resistance strain, and the

  18. Comparison of secular trends in pneumococcal serotypes causing invasive disease in Denver, Colorado (1971-2004) and serotype coverage by marketed pneumococcal vaccines.

    PubMed

    Akduman, D; Ehret, J M; Judson, F N

    2006-11-01

    Invasive pneumococcal isolates from three hospitals in Denver, CO, USA were serotyped between 1971 and 2004. Serotype 14 was most common (13.2%), and other prevalent serotypes (3, 4, 6, 9 and 19) together accounted for 44.1% of the isolates. All prevalent serotypes and 91.3% of the total isolates were covered by pneumococcal polysaccharide vaccine, while 79.1% of prevalent serotypes and 56.7% of total isolates were covered by pneumococcal conjugate vaccine. Serotypes 6, 9 and 14 were more common in the final decade than in the first decade studied (37.3% vs. 20.2%), whereas serotypes 3 and 23 were more common in the first decade (18.5% vs. 11.0%).

  19. Insight Into Resistance Phenotypes of Emergent Non 13-valent Pneumococcal Conjugate Vaccine Type Pneumococci Isolated From Invasive Disease After 13-valent Pneumococcal Conjugate Vaccine Implementation in France

    PubMed Central

    Janoir, Claire; Lepoutre, Agnès; Gutmann, Laurent; Varon, Emmanuelle

    2016-01-01

    Background. In 2010, the pneumococcal 13-valent conjugate vaccine (PCV13), containing 6 additional serotypes including the multidrug-resistant 19A, replaced the PCV7 in France. This study aimed at analyzing trends in antibiotic resistance in invasive pneumococcal disease (IPD) isolates in France after PCV13 introduction. Methods. A total of 5243 pneumococci isolated from IPD in 2008–2009 (late PCV7 era) and 2011–2012 (PCV13 era) were studied according to their serotype and antibiotic resistance profile. Multilocus sequence typing analysis was performed on strains of the predominant serotypes (12F and 24F) isolated from young children. Results. Overall, the prevalence of antibiotic resistance decreased in France (−21.5% for penicillin from 2008–2009 to 2011–2012), mainly driven by the decline of the 19A serotype. Among non-PCV13 serotypes that concomitantly emerged, serotypes 12F, 24F, 15A, and 35B were consistently associated with resistance to 1 or more antibiotics. In children under 2 years, serotypes 15A, 35B, and 24F accounted together for 37.8% and 31.9% of penicillin-nonsusceptible and erythromycin-resistant isolates, respectively. Chloramphenicol and cotrimoxazole resistance were mainly associated with serotypes 12F and 24F, respectively. Genetic analysis showed that although emergence of serotype 12F pneumococci resulted from the expansion of various pre-existing lineages, increase in serotype 24F was related to the clonal expansion of the ST162 penicillin-susceptible cotrimoxazole-resistant lineage. Conclusions. We showed that decline of PCV13-related IPD was associated with a decline in antibiotic resistance in France, but that it likely favored the spread of several resistant nonvaccine serotypes. However, antibiotic resistance does not seem to be the only element that may drive this phenomenon. PMID:26955644

  20. The epidemiology of invasive pneumococcal disease in older adults from 2007 to 2014 in Ontario, Canada: a population-based study

    PubMed Central

    Desai, Shalini; Policarpio, Michelle E.; Wong, Kenney; Gubbay, Jonathan; Fediurek, Jill; Deeks, Shelley

    2016-01-01

    Background: In Ontario, pneumococcal conjugate vaccines (PCVs) have been sequentially introduced into the publicly funded childhood vaccination program since 2005. A 23-valent polysaccharide pneumococcal vaccine (PPV23) has been routinely recommended for adults aged 65 years and older since 1996. To determine the effect of herd immunity, we examined the epidemiology of invasive pneumococcal disease in adults aged 65 years and older. Methods: Invasive pneumococcal disease is a provincially reportable disease. We were therefore able to conduct a descriptive epidemiologic analysis that included assessing time trends for patients aged 65 years and older using surveillance data from 2007 to 2014. Using serotype information within the surveillance data, cases were grouped into categories according to vaccine type and periods and then compared using Poisson regression. Results: A total of 3825 cases of invasive pneumococcal disease were reported among adults aged 65 years and older, for an overall annualized incidence of 25.4 cases per 100 000 population. There was a decrease in incidence due to serotypes included in 7-valent PCV (3.0 to 0.7 cases per 100 000 population) (p < 0.001). For 13-valent PCV serotypes, there was a decrease in incidence between 2011 and 2014 (9.8 to 5.3 cases per 100 000 population (p < 0.001)). Serotypes unique to PPV23 and those not included in a vaccine increased from 2.3 to 5.8 and from 2.4 to 7.2 cases per 100 000 population, respectively (p < 0.001). Interpretation: In older adults, among serotypes contained in PCVs, we have shown a decrease in incidence of invasive pneumococcal disease. This is likely due to herd immunity from the childhood program. A burden of illness due to unique PPV23 serotypes and those that are not covered by a vaccine exists and has increased over time. PMID:27730119

  1. Reduced incidence of invasive pneumococcal disease after introduction of the 13-valent conjugate vaccine in Navarre, Spain, 2001-2013.

    PubMed

    Guevara, Marcela; Ezpeleta, Carmen; Gil-Setas, Alberto; Torroba, Luis; Beristain, Xabier; Aguinaga, Aitziber; García-Irure, José Javier; Navascués, Ana; García-Cenoz, Manuel; Castilla, Jesús

    2014-05-07

    Pneumococcal conjugate vaccines (PCVs) were licensed for use in children and became available for private purchase in Spain in 2001 (PCV7), 2009 (PCV10) and 2010 (PCV13). This study evaluates changes in the incidence of invasive pneumococcal disease (IPD) and the pattern of serotypes isolated in Navarre, Spain, between the period of use of PCV7 (2004-2009) and that of PCV13 (2010-2013). The percentage of children <2 years who received at least one dose of PCV in these periods ranged from 25 to 61% and 61 to 78%, respectively. Between the periods 2004-2009 and 2010-2013 IPD incidence declined by 37%, from 14.9 to 9.4 cases/100,000 inhabitants (p<0.001). In children <5 years it fell by 69% (p<0.001), in persons aged 5-64 years, by 34% (p<0.001), and in those ≥ 65, by 23% (p=0.024). The incidence of cases due to PCV13 serotypes declined by 81% (p<0.001) in children <5 years and by 52% (p<0.001) in the whole population. No significant changes were seen in the distribution of clinical presentations or in disease severity. The incidence of IPD has declined and the pattern of serotypes causing IPD has changed notably in children and moderately in adults following the replacement of PCV7 by PCV13.

  2. An eHealth Project on Invasive Pneumococcal Disease: Comprehensive Evaluation of a Promotional Campaign

    PubMed Central

    Gasparini, Roberto; Bonanni, Paolo; Icardi, Giancarlo; Amicizia, Daniela; Arata, Lucia; Carozzo, Stefano; Signori, Alessio; Bechini, Angela; Boccalini, Sara

    2016-01-01

    Background The recently launched Pneumo Rischio eHealth project, which consists of an app, a website, and social networking activity, is aimed at increasing public awareness of invasive pneumococcal disease (IPD). The launch of this project was prompted by the inadequate awareness of IPD among both laypeople and health care workers, the heavy socioeconomic burden of IPD, and the far from optimal vaccination coverage in Italy, despite the availability of safe and effective vaccines. Objective The objectives of our study were to analyze trends in Pneumo Rischio usage before and after a promotional campaign, to characterize its end users, and to assess its user-rated quality. Methods At 7 months after launching Pneumo Rischio, we established a 4-month marketing campaign to promote the project. This intervention used various approaches and channels, including both traditional and digital marketing strategies. To highlight usage trends, we used different techniques of time series analysis and modeling, including a modified Mann-Kendall test, change-point detection, and segmented negative binomial regression of interrupted time series. Users were characterized in terms of demographics and IPD risk categories. Customer-rated quality was evaluated by means of a standardized tool in a sample of app users. Results Over 1 year, the app was accessed by 9295 users and the website was accessed by 143,993 users, while the project’s Facebook page had 1216 fans. The promotional intervention was highly effective in increasing the daily number of users. In particular, the Mann-Kendall trend test revealed a significant (P ≤.01) increasing trend in both app and website users, while change-point detection analysis showed that the first significant change corresponded to the start of the promotional campaign. Regression analysis showed a significant immediate effect of the intervention, with a mean increase in daily numbers of users of 1562% (95% CI 456%-4870%) for the app and 620

  3. Pneumococcal Disease: Types of Infection

    MedlinePlus

    ... Programs Related Pages Global Pneumococcal Vaccination World Health Organization National Foundation for Infectious Diseases Sepsis Types of Infection Recommend on Facebook Tweet Share Compartir ...

  4. Invasive Pneumococcal Disease Among HIV-Infected and HIV-Uninfected Adults in a Large Integrated Healthcare System.

    PubMed

    Marcus, Julia L; Baxter, Roger; Leyden, Wendy A; Muthulingam, Dharushana; Yee, Arnold; Horberg, Michael A; Klein, Daniel B; Towner, William J; Chao, Chun R; Quesenberry, Charles P; Silverberg, Michael J

    2016-10-01

    It is unclear whether HIV-infected individuals remain at higher risk of invasive pneumococcal disease (IPD) compared with HIV-uninfected individuals. We conducted a cohort study of HIV-infected and demographically matched HIV-uninfected adults within Kaiser Permanente Northern California during the period 1996-2011. We used Poisson models to obtain rate ratios (RRs) for incident IPD associated with HIV infection and other risk factors. Among 13,079 HIV-infected and 137,643 HIV-uninfected adults, the IPD rate per 100,000 person-years was 160 (n = 109 events) for HIV-infected and 8 (n = 75 events) for HIV-uninfected subjects, with an adjusted RR of 13.0 [95% confidence interval (CI): 9.1-18.7]. For HIV-infected individuals, IPD incidence per 100,000 person-years decreased by 71% during study follow-up, from 305 in 1996-1999 to 88 in 2010-2011 (p < 0.001), with an adjusted RR of 6.6 (95% CI: 2.7-16.1) compared with HIV-uninfected subjects in 2010-2011. Risk factors for IPD among HIV-infected individuals included black compared with white race/ethnicity, smoking, cancer, and higher HIV RNA levels. The 23-valent pneumococcal polysaccharide vaccination was not associated with a reduced risk of IPD in HIV-infected or HIV-uninfected individuals. Among HIV-infected IPD cases, the most common serotype was 19A (33%), and 59% of serotypes were covered by the 13-valent pneumococcal conjugate vaccine (PCV13). Despite a dramatic decline in IPD incidence for HIV-infected adults since 1996, IPD rates were nearly sevenfold higher compared with HIV-uninfected adults in recent years, even after adjustment for risk factors. Timely antiretroviral therapy initiation, risk reduction strategies, and recent guidelines recommending PCV13 use may further reduce IPD incidence among HIV patients.

  5. A nationwide surveillance of invasive pneumococcal disease in adults in Israel before an expected effect of PCV7.

    PubMed

    Regev-Yochay, Gili; Rahav, Galia; Strahilevitz, Jacob; Bishara, Jihad; Katzir, Michal; Chowers, Michal; Finkelstein, Renato; Chazan, Bibiana; Zimhony, Oren; Dagan, Ron

    2013-05-01

    Pneumococcal infections in adults vary in severity and incidence is affected by childhood vaccination policy. Here, we try to define the host determinants and the interaction with specific serotypes that result in invasive pneumococcal disease (IPD) before an expected effect of pneumococcal conjugate vaccines. A nationwide active surveillance was initiated on July 2009, at the time of national implementation of PCV7 in Israel. The surveillance included all 27 laboratories and medical centers performing blood cultures in Israel, providing all blood and CSF pneumococcal isolates from persons ≥18y. Capture-recapture method assured that >95% of all cases were reported. IPD outcome and medical history were recorded and isolates were serotyped. Four hundred and sixty IPD cases were reported (annual incidence [/100,000] of 9.25). Incidence increased with age, from 2.6 among 18-34y to 66.8 among ≥85y. The most common diagnosis was pneumonia (72.4%), followed by bacteremia with no apparent focus (20.2%). Case fatality rate increased with age and number of comorbidities (34.5% for ≥75y or those with ≥3 comorbidities vs. 9.2-11.2% among <65y or those with no comorbidities; p=0.015). Variables independently associated with mortality were: age ≥75, chronic renal failure, malignancy, neurosurgery, alcohol abuse, multi-lobar pneumonia and sepsis with no apparent focus. The predominant serotypes in patients 18-49y were 1, 5, 8, 7F and 9V (constituting 56.3% in this age-group vs. 11.9% in ≥75y; p<0.01). The predominant serotypes among patients ≥75y were 3, 19A, 23F and 14 (40.3% of this age-group vs. 12.9% of 18-49y; p<0.01). Overall, PCV7 and PCV13 covered 25.6% and 63.7% of isolates, respectively, and 30.9% and 67.9% of isolates in mortality cases respectively. This nationwide active surveillance provides the baseline incidence, mortality rates and risk group distributions of IPD in adults before expected PCV effect.

  6. Pneumococcal Disease Fast Facts

    MedlinePlus

    ... Home About Pneumococcal Types of Infection Risk Factors & Transmission Symptoms & Complications Diagnosis & Treatment Prevention Photos Fast Facts Pneumococcal Vaccination For Clinicians Streptococcus pneumoniae Transmission Clinical Features Risk Factors Diagnosis & Management Prevention For ...

  7. [Pneumococcal vaccine recommendations in chronic respiratory diseases].

    PubMed

    Casas Maldonado, F; Alfageme Michavila, I; Barchilón Cohen, V S; Peis Redondo, J I; Vargas Ortega, D A

    2014-09-01

    Community-acquired pneumonia is an acute respiratory infectious disease which has an incidence of 3-8 cases/1,000 inhabitants, and increases with age and comorbidities. The pneumococcus is the organism most frequently involved in community-acquired pneumonia in the adult (30-35%). Around 40% of patients with community-acquired pneumonia require hospital admission, and around 10% need to be admitted to an intensive care unit. The most serious forms of pneumococcal infection include invasive pneumococcal disease (IPD), which covers cases of bacteremia (associated or not to pneumonia), meningitis, pleuritis, arthritis, primary peritonitis and pericarditis. Currently, the biggest problem with the pneumococcus is the emergence of resistance to antimicrobial agents, and its high morbimortality, despite the use of appropriate antibiotics and proper medical treatment. Certain underlying medical conditions increase the risk of IPD and its complications, especially, from the respiratory diseases point of view, smoking and chronic respiratory diseases. Pneumococcal disease, according to the WHO, is the first preventable cause of death worldwide in children and adults. Among the strategies to prevent IPD is vaccination. WHO considers that its universal introduction and implementation against pneumococcus is essential and a priority in all countries. There are currently 2 pneumococcal vaccines for adults: the 23 serotypes polysaccharide and conjugate 13 serotypes. The scientific societies represented here have worked to develop some recommendations, based on the current scientific evidence, regarding the pneumococcal vaccination in the immunocompetent adult with chronic respiratory disease and smokers at risk of suffering from IPD.

  8. Invasive pneumococcal infection in South and West England.

    PubMed Central

    Smith, M. D.; Stuart, J.; Andrews, N. J.; Telfer Brunton, W. A.; Cartwright, K. A.

    1998-01-01

    Variation in the incidence of invasive pneumococcal disease across South and West England, in 1995, was measured through a survey of microbiology laboratories. A 100% response rate was achieved. The incidence by laboratory varied between 5.2 and 20.4 per 100,000 catchment population (P < 0.001). Adjusting for pneumococcal vaccine uptake rate in over 65 year olds, hospital admission rates, blood culture system used and for the age and sex structure of the population, did not account for this variation. When blood culture sampling rates were included in a logistic regression model, the variation between laboratories was much less and of lower statistical significance (P = 0.019). Higher rates of blood culture sampling were associated with a higher incidence of invasive pneumococcal disease. Consistently high sampling should be encouraged because a higher diagnostic rate should result in more selective prescribing of antibiotics, and secondly because improved ascertainment of severe pneumococcal infections is a prerequisite for the evaluation of new pneumococcal conjugate vaccines. PMID:9593479

  9. Evaluating the impact of PCV-10 on invasive pneumococcal disease in Brazil: A time-series analysis

    PubMed Central

    Andrade, Ana Lucia; Minamisava, Ruth; Policena, Gabriela; Cristo, Elier B; Domingues, Carla Magda S; de Cunto Brandileone, Maria Cristina; Almeida, Samanta Cristine Grassi; Toscano, Cristiana Maria; Bierrenbach, Ana Luiza

    2016-01-01

    Routine infant immunization with 10-valent pneumococcal conjugate vaccine (PCV-10) began in Brazil in 2010. The impact of the PCV-10 on rates of invasive pneumococcal disease (IPD) at the population level was not yet evaluated. Serotype-specific IPD changes after PCV-10 introduction is still to be determined. Data from national surveillance system for notifiable diseases (SINAN) and national reference laboratory for S. pneumoniae in Brazil (IAL) were linked to enhance case ascertainment of IPD. An interrupted time-series analysis was conducted to predict trends in the postvaccination IPD rates in the absence of PCV-10 vaccination, taking into consideration seasonality and secular trends. PCVs serotype-specific distribution were assessed before (2008–2009) and after (2011–2013) the introduction of PCV-10 in the immunization program. A total of 9,827 IPD cases were identified from 2008–2013 when combining SINAN and IAL databases. Overall, PCV-10 types decreased by 41.3% after PCV-10 vaccination period, mostly in children aged 2–23 months, while additional PCV-13 serotypes increased by 62.8% mainly in children under 5-year of age. For children aged 2–23 months, targeted by the immunization program, we observed a 44.2% (95%CI, 15.8–72.5%) reduction in IPD rates. In contrast, significant increase in IPD rates were observed for adults aged 18–39 y (18.9%, 95%CI 1.1–36.7%), 40–64 y (52.5%, 95%CI 24.8–80.3%), and elderly ≥ 65 y (79.3%, 95%CI 62.1–96.5%). This is the first report of a time-series analysis for PCV impact in IPD conducted at national level data in a developing country. We were able to show significant impact of PCV-10 on IPD for age groups targeted by vaccination in Brazil, 3 y after its introduction. No impact on other age groups was demonstrated. PMID:26905679

  10. Evaluating the impact of PCV-10 on invasive pneumococcal disease in Brazil: A time-series analysis.

    PubMed

    Andrade, Ana Lucia; Minamisava, Ruth; Policena, Gabriela; Cristo, Elier B; Domingues, Carla Magda S; de Cunto Brandileone, Maria Cristina; Almeida, Samanta Cristine Grassi; Toscano, Cristiana Maria; Bierrenbach, Ana Luiza

    2016-01-01

    Routine infant immunization with 10-valent pneumococcal conjugate vaccine (PCV-10) began in Brazil in 2010. The impact of the PCV-10 on rates of invasive pneumococcal disease (IPD) at the population level was not yet evaluated. Serotype-specific IPD changes after PCV-10 introduction is still to be determined. Data from national surveillance system for notifiable diseases (SINAN) and national reference laboratory for S. pneumoniae in Brazil (IAL) were linked to enhance case ascertainment of IPD. An interrupted time-series analysis was conducted to predict trends in the postvaccination IPD rates in the absence of PCV-10 vaccination, taking into consideration seasonality and secular trends. PCVs serotype-specific distribution were assessed before (2008-2009) and after (2011-2013) the introduction of PCV-10 in the immunization program. A total of 9,827 IPD cases were identified from 2008-2013 when combining SINAN and IAL databases. Overall, PCV-10 types decreased by 41.3% after PCV-10 vaccination period, mostly in children aged 2-23 months, while additional PCV-13 serotypes increased by 62.8% mainly in children under 5-year of age. For children aged 2-23 months, targeted by the immunization program, we observed a 44.2% (95%CI, 15.8-72.5%) reduction in IPD rates. In contrast, significant increase in IPD rates were observed for adults aged 18-39 y (18.9%, 95%CI 1.1-36.7%), 40-64 y (52.5%, 95%CI 24.8-80.3%), and elderly ≥ 65 y (79.3%, 95%CI 62.1-96.5%). This is the first report of a time-series analysis for PCV impact in IPD conducted at national level data in a developing country. We were able to show significant impact of PCV-10 on IPD for age groups targeted by vaccination in Brazil, 3 y after its introduction. No impact on other age groups was demonstrated.

  11. Hospitalization for Invasive Pneumococcal Disease in a National Sample of Children with Sickle Cell Disease Before and After PCV7 Licensure

    PubMed Central

    McCavit, Timothy L.; Xuan, Lei; Zhang, Song; Flores, Glenn; Quinn, Charles T.

    2012-01-01

    Objective To estimate national hospitalization rates for invasive pneumococcal disease (IPD) in children with sickle cell disease (SCD) before and after the 2000 licensure of the heptavalent pneumococcal conjugate vaccine (PCV7). Procedure We performed a retrospective trend analysis of the 1994-2007 Nationwide Inpatient Sample databases. Hospitalizations involving children with SCD and IPD were identified by ICD-9CM code. The primary outcomes, the annual hospitalization rate for IPD in children with SCD and the proportion of hospitalizations for IPD per 100 total SCD hospitalizations, were analyzed using multivariable linear regression and contingency analysis, respectively. Results A total of 1,242 hospitalizations for IPD in SCD patients were identified from 1994-2007, with a mortality rate of 2.4%. The national mean annual rate of IPD hospitalization decreased by 65%, from 131.8 cases/year from 1994-2000 to 45.5 cases/year from 2001-2007 (p=0.001). The national proportion of hospitalizations for IPD per 100 total SCD hospitalizations decreased from 0.4 to 0.15 (p<0.0001) over the same interval. Following PCV7 licensure, the mean annual cumulative hospital days and cumulative hospital charges decreased nationally by 53% and 36%, respectively. Conclusion In a national sample, PCV7 licensure is temporally associated with a nearly three fold reduction in IPD hospitalizations in children with SCD. PMID:21793185

  12. Indirect Effects of Pneumococcal Conjugate Vaccines in National Immunization Programs for Children on Adult Pneumococcal Disease

    PubMed Central

    2016-01-01

    The pneumococcal conjugate vaccine (PCV) was developed to overcome the limitations of the pneumococcal polysaccharide vaccine, which produces poor immunogenicity in infants younger than 2 years. As many countries have included PCVs in national immunization programs for children, the incidence of invasive pneumococcal disease caused by vaccine type Streptococcus pneumoniae has declined markedly, not only among the vaccinated pediatric population, but also among unvaccinated adults. In this review, we present a concise overview of the indirect effects of mass pediatric PCV immunization on unvaccinated adults. PMID:28032483

  13. Effect of the different 13-valent pneumococcal conjugate vaccination uptakes on the invasive pneumococcal disease in children: Analysis of a hospital-based and population-based surveillance study in Madrid, Spain, 2007-2015

    PubMed Central

    Picazo, Juan; Ruiz-Contreras, Jesús; Casado-Flores, Juan; Negreira, Sagrario; Baquero, Fernando; Hernández-Sampelayo, Teresa; Otheo, Enrique; Méndez, Cristina

    2017-01-01

    In the Community of Madrid, the 13-valent pneumococcal conjugate vaccine (PCV13) replaced the 7-valent (PCV7) in the fully government-funded Regional Immunization Program (RIP) in May, 2010, but was later excluded in May, 2012, and included again in January, 2015. These unique changes allowed us to assess the impact of the different pneumococcal vaccination policies on PCV13 uptake in infants and on the incidence rate (IR) of invasive pneumococcal disease (IPD) in children <15 years old. In this prospective, active, surveillance study, we estimated PCV13 uptakes, IR and incidence rate ratios (IRR) for total IPD and for IPD caused by PCV13- and non-PCV13 serotypes in children <15 years, stratified by age, in four periods with different vaccination policies: fully government-funded PCV7 vaccination, fully government-funded PCV13, mixed public/private funding and only private funding. Vaccine uptakes reached 95% in periods with public-funded pneumococcal vaccination, but fell to 67% in the private funding period. Overall, IR of IPD decreased by 68% (p<0.001) in 2014–15, due to 93% reduction in the IR of PCV13-type IPD (p<0.001) without significant changes in non-PCV13-type IPD. A fully government-funded PCV13 vaccination program lead to high vaccine uptake and dramatic reductions in both overall and PCV13-type IPD IR. When this program was switched to private PCV13 vaccination, there was a fall in vaccine coverage and stagnation in the decline of PCV13-type IPD with data suggesting a weakening of herd immunity. PMID:28207888

  14. Serotype 10A in case patients with invasive pneumococcal disease: a pilot study of PCR-based serotyping in New Jersey.

    PubMed

    Pitts, Samantha I; Apostolou, Andria; DasGupta, Sarmila; Delgado, Nelson; Kirn, Thomas J; Montana, Barbara; Tan, Christina; McHugh, Lisa A

    2015-01-01

    In 2008, the New Jersey Department of Health (NJDOH) identified a 21.1% increase in reported invasive pneumococcal disease (IPD). In 2009, NJDOH piloted nucleic acid-based serotyping to characterize serotypes causing IPD. From April through September, NJDOH received specimens from 149 of 302 (49%) case patients meeting our case definition. An uncommon serotype, 10A, accounted for 25.2% of IPD overall and was identified in 12 counties, but it was associated with one county (rate ratio = 5.4, 95% confidence interval [CI] 2.1, 11.8). NJDOH subsequently conducted a case-control study to assess the presentation of and clinical risk factors for 10A IPD. Case patients with 10A IPD were more likely to have had immunosuppression, asthma, and multiple chronic medical conditions than control subjects had (odds ratio [OR] = 2.6, 95% CI 1.1, 6.3; OR=4.7, 95% CI 1.7, 13.2; and OR=2.3, 95% CI 1.0, 5.2, respectively). State-based pneumococcal serotype testing identified an uncommon serotype in New Jersey. Continued pneumococcal serotype surveillance might help the NJDOH identify and respond to future serotype-specific increases.

  15. Pneumococcal Disease in the Era of Pneumococcal Conjugate Vaccine

    PubMed Central

    Yildirim, Inci; Shea, Kimberly M.

    2015-01-01

    SYNOPSIS Universal immunization of infants and toddlers with PCVs over the past 15 years has dramatically altered the landscape of pneumococcal disease. Decreases in IPD, all cause pneumonia, empyema, mastoiditis, acute otitis media and complicated otitis media have been reported from multiple countries where universal immunization has been implemented. The introduction of the vaccine has also led to expanded understanding of pneumococcal disease; observations have confirmed that most pneumococci are transmitted from children to adults, not all pneumococcal serotypes are equal in terms of common clinical syndromes, likelihood of antibiotic resistance, or likelihood of progression to disease once colonization occurs. Children with comorbid conditions have higher rates of pneumococcal disease and increased case fatality rates compared to otherwise healthy children, and protection for the most vulnerable pediatric patients will require new strategies to address the underlying host susceptibility and the expanded spectrum of serotypes observed. PMID:26610421

  16. Pneumococcal serotype distribution in adults with invasive disease and in carrier children in Italy: Should we expect herd protection of adults through infants' vaccination?

    PubMed

    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 <1% IPD. In conclusion serotypes causing IPD in adults are very rarely found in 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.

  17. Effect of Serotype on Focus and Mortality of Invasive Pneumococcal Disease: Coverage of Different Vaccines and Insight into Non-Vaccine Serotypes

    PubMed Central

    van Hoek, Albert Jan; Andrews, Nick; Waight, Pauline A.; George, Robert; Miller, Elizabeth

    2012-01-01

    Background Differences in pathogenicity between pneumococcal serotypes are important when assessing the potential benefit of different valency vaccines. We investigated the effect of serotype on clinical presentation, outcome, and quality of life lost from invasive pneumococcal disease (IPD) in the context of the 7, 10, and 13 valent pneumococcal conjugate vaccines (PCV7, PCV10, PCV13). Method Serotyped IPD cases in England were linked to the national dataset of hospital admissions for April 2002 to March 2011. Based on patients’ diagnostic codes and vital status at the end of the admission, disease focus (meningitis, empyema, sepsis, or respiratory disease) and case fatality rates by serotype and age group (5, 5–64, and 65 years and over) were obtained. Using these data the quality adjusted life years (QALY) lost from the IPD remaining when use of PCV7 stopped in 2010 was estimated for the serotypes covered by higher valency vaccines. Results The linked dataset contained 23,688 cases with information on diagnosis, mortality, and serotype. There were significant differences between serotypes in the propensity to cause meningitis, death, and QALY loss in each of the investigated age groups. As a result, vaccines’ coverage of disease burden differed by endpoint. For example, in children under 5 years in 2009/10, PCV10 covered 39% of meningitis, 19% of deaths and 28% of the QALY loss of attributable to IPD, whereas the respective percentages for PCV13 were 65%, 67%, and 66%. The highest QALY loss per serotype in this age group was for 6A. Non-PCV serotypes causing the highest QALY loss were 22F and 33F in <5 year olds and 31 in older individuals. Conclusion Marked differences exist between serotypes in clinical presentation and outcome, and these should be considered when evaluating the potential impact of higher valency vaccines on overall disease burden and associated QALY loss. PMID:22815698

  18. Impact of 13-Valent Pneumococcal Conjugate Vaccine Used in Children on Invasive Pneumococcal Disease in Children and Adults in the United States: Analysis of Multisite, Population-based Surveillance

    PubMed Central

    Moore, Matthew R.; Link-Gelles, Ruth; Schaffner, William; Lynfield, Ruth; Lexau, Catherine; Bennett, Nancy M.; Petit, Susan; Zansky, Shelley M.; Harrison, Lee H.; Reingold, Arthur; Miller, Lisa; Scherzinger, Karen; Thomas, Ann; Farley, Monica M.; Zell, Elizabeth R.; Taylor, Thomas H.; Pondo, Tracy; Rodgers, Loren; McGee, Lesley; Beall, Bernard; Jorgensen, James H.; Whitney, Cynthia G.

    2016-01-01

    SUMMARY Background In 2000, 7-valent pneumococcal conjugate vaccine (PCV7) was introduced in the U.S. and resulted in dramatic reductions in invasive pneumococcal disease (IPD) and modest increases in non-PCV7-type IPD. In 2010, a 13-valent pneumococcal conjugate vaccine (PCV13) replaced PCV7 in the U.S. immunization schedule. We evaluated the effect of PCV13 use in children on IPD in children and adults in the U.S. Methods We used laboratory- and population-based data on incidence of IPD from CDC’s Emerging Infections Program / Active Bacterial Core surveillance in a time-series model to estimate the impact of vaccination. Cases of IPD during July 2004–June 2013 were classified as being caused by the PCV13 serotypes against which PCV7 has no effect (PCV13/nonPCV7). Findings Compared with incidence expected among children <5 years old if PCV7 alone had been continued, incidence of IPD overall and IPD caused by PCV13/nonPCV7 serotypes declined by 64% (95% interval estimate [IE] 59–68 %) and 93% (95%IE 91–94), respectively, by July 2012–June 2013. Among adults, incidence of IPD overall and PCV13/nonPCV7-type IPD also declined by 12–32% and 58–72%, respectively, depending on age. In all age groups, reductions were driven principally by changes in incidence of serotypes 19A and 7F. We estimate that over 30,000 cases of IPD and 3,000 deaths were averted in the first 3 years following PCV13 introduction. Interpretation PCV13 has reduced IPD among all ages when used routinely in children in the U.S. Serotypes 19A and 7F, which emerged after PCV7 introduction, have been effectively controlled. PMID:25656600

  19. Direct, indirect and total effects of 13-valent pneumococcal conjugate vaccination on invasive pneumococcal disease in children in Navarra, Spain, 2001 to 2014: cohort and case-control study.

    PubMed

    Guevara, Marcela; Barricarte, Aurelio; Torroba, Luis; Herranz, Mercedes; Gil-Setas, Alberto; Gil, Francisco; Bernaola, Enrique; Ezpeleta, Carmen; Castilla, Jesús

    2016-01-01

    We estimated the direct, indirect and total effects of the 13-valent pneumococcal conjugate vaccine (PCV13) on invasive pneumococcal disease (IPD) in children. A population-based cohort study followed children aged between 2.5 and 59 months between 2001 and 2014 in Navarra, Spain. IPD incidence was compared by PCV status and period. All cases diagnosed from July 2010 to December 2014 and eight matched controls per case were analysed to estimate the adjusted direct effect of PCV13. A total of 120,980 children were followed and 206 IPD cases were detected. Compared with unvaccinated children in the baseline period (2001-2004), overall IPD incidence in 2011-2014 (76% average PCV coverage) declined equally in vaccinated (total effect: 76%; hazard ratio (HR): 0.24; 95% confidence interval (CI): 0.14-0.40) and unvaccinated children (indirect effect: 78%; HR: 0.22; 95% CI: 0.09-0.55). IPD incidence from non-PCV13 serotypes increased among vaccinated children (HR: 2.84; 95% CI: 1.02-7.88). The direct effect of one or more doses of PCV13 against vaccine serotypes was 95% (odds ratio: 0.05; 95% CI: 0.01-0.55). PCV13 was highly effective in preventing vaccine-serotype IPD. The results suggest substantial and similar population-level vaccine benefits in vaccinated and unvaccinated children through strong total and indirect effects.

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

    PubMed Central

    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 <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. PMID:26351644

  1. Serotype 3 Remains the Leading Cause of Invasive Pneumococcal Disease in Adults in Portugal (2012-2014) Despite Continued Reductions in Other 13-Valent Conjugate Vaccine Serotypes.

    PubMed

    Horácio, Andreia N; Silva-Costa, Catarina; Lopes, Joana P; Ramirez, Mário; Melo-Cristino, José

    2016-01-01

    Since 2010 the 13-valent pneumococcal conjugate vaccine (PCV13) replaced the 7-valent vaccine (PCV7) as the leading pneumococcal vaccine used in children through the private sector. Although, neither of the PCVs were used significantly in adults, changes in adult invasive pneumococcal disease (IPD) were expected due to herd protection. We characterized n = 1163 isolates recovered from IPD in adults in 2012-2014 with the goal of documenting possible changes in serotype prevalence and antimicrobial resistance. Among the 54 different serotypes detected, the most frequent, accounting for half of all IPD, were serotypes: 3 (14%), 8 (11%), 19A (7%), 22F (7%), 14 (6%), and 7F (5%). The proportion of IPD caused by PCV7 serotypes remained stable during the study period (14%), but was smaller than in the previous period (19% in 2009-2011, p = 0.003). The proportion of IPD caused by PCV13 serotypes decreased from 51% in 2012 to 38% in 2014 (p < 0.001), mainly due to decreases in serotypes 7F and 19A. However, PCV13 serotype 3 remained relatively stable and the most frequent cause of adult IPD. Non-PCV13 serotypes continued the increase initiated in the late post-PCV7 period, with serotypes 8 and 22F being the most important emerging serotypes. Serotype 15A increased in 2012-2014 (0.7% to 3.5%, p = 0.011) and was strongly associated with antimicrobial resistance. However, the decreases in resistant isolates among serotypes 14 and 19A led to an overall decrease in penicillin non-susceptibility (from 17 to 13%, p = 0.174) and erythromycin resistance (from 19 to 13%, p = 0.034). Introduction of PCV13 in the NIP for children, as well as its availability for adults may further alter the serotypes causing IPD in adults in Portugal and lead to changes in the proportion of resistant isolates.

  2. Serotype 3 Remains the Leading Cause of Invasive Pneumococcal Disease in Adults in Portugal (2012–2014) Despite Continued Reductions in Other 13-Valent Conjugate Vaccine Serotypes

    PubMed Central

    Horácio, Andreia N.; Silva-Costa, Catarina; Lopes, Joana P.; Ramirez, Mário; Melo-Cristino, José; Vaz, Teresa

    2016-01-01

    Since 2010 the 13-valent pneumococcal conjugate vaccine (PCV13) replaced the 7-valent vaccine (PCV7) as the leading pneumococcal vaccine used in children through the private sector. Although, neither of the PCVs were used significantly in adults, changes in adult invasive pneumococcal disease (IPD) were expected due to herd protection. We characterized n = 1163 isolates recovered from IPD in adults in 2012–2014 with the goal of documenting possible changes in serotype prevalence and antimicrobial resistance. Among the 54 different serotypes detected, the most frequent, accounting for half of all IPD, were serotypes: 3 (14%), 8 (11%), 19A (7%), 22F (7%), 14 (6%), and 7F (5%). The proportion of IPD caused by PCV7 serotypes remained stable during the study period (14%), but was smaller than in the previous period (19% in 2009–2011, p = 0.003). The proportion of IPD caused by PCV13 serotypes decreased from 51% in 2012 to 38% in 2014 (p < 0.001), mainly due to decreases in serotypes 7F and 19A. However, PCV13 serotype 3 remained relatively stable and the most frequent cause of adult IPD. Non-PCV13 serotypes continued the increase initiated in the late post-PCV7 period, with serotypes 8 and 22F being the most important emerging serotypes. Serotype 15A increased in 2012–2014 (0.7% to 3.5%, p = 0.011) and was strongly associated with antimicrobial resistance. However, the decreases in resistant isolates among serotypes 14 and 19A led to an overall decrease in penicillin non-susceptibility (from 17 to 13%, p = 0.174) and erythromycin resistance (from 19 to 13%, p = 0.034). Introduction of PCV13 in the NIP for children, as well as its availability for adults may further alter the serotypes causing IPD in adults in Portugal and lead to changes in the proportion of resistant isolates. PMID:27790208

  3. Invasive pneumococcal infection despite 7-valent conjugated vaccine

    PubMed Central

    Joye, Sebastien; Gao, Anja; Kayemba-Kay’s, Simon; Cotting, Jacques; Perez, Marie-Hélène

    2013-01-01

    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. PMID:24765491

  4. Invasive pneumococcal infection despite 7-valent conjugated vaccine.

    PubMed

    Joye, Sebastien; Gao, Anja; Kayemba-Kay's, Simon; Cotting, Jacques; Perez, Marie-Hélène

    2013-01-25

    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.

  5. The incidence of pediatric invasive Haemophilus influenzae and pneumococcal disease in Chiba prefecture, Japan before and after the introduction of conjugate vaccines.

    PubMed

    Ishiwada, Naruhiko; Hishiki, Haruka; Nagasawa, Koo; Naito, Sachiko; Sato, Yasunori; Chang, Bin; Sasaki, Yuko; Kimura, Kouji; Ohnishi, Makoto; Shibayama, Keigo

    2014-09-22

    The Haemophilus influenzae type b (Hib) vaccine and the heptavalent pneumococcal conjugate vaccine (PCV7) were introduced in Japan in 2008 and 2010, respectively. In 2011, immunization with these two vaccines was encouraged throughout Japan through a governmental program. Children treated in Chiba prefecture for culture-proven invasive H. influenzae disease (IHiD) and invasive Streptococcus pneumoniae disease (IPD) were identified in a prefectural surveillance study from 2008 to 2013. The incidence rate ratio (IRR) and its confidence interval (CI) were calculated to compare the 3 years before and after governmental financial support for vaccination. The average number of IHiD and IPD cases among children <5 years of age in 2011-2013 decreased 84% (IRR: 0.16, 95% CI: 0.09-0.26, p<0.0001) and 51% (IRR: 0.49, 95% CI: 0.37-0.63, p<0.0001) compared with those occurring in 2008-2010. The most common non-PCV7 serotype encountered in 2011 and 2013 was 19A. After governmental subsidization of Hib and PCV7 vaccination, IHiD and IPD decreased in Chiba prefecture, Japan. Continuous surveillance is necessary to determine the effectiveness of these two vaccines and for detection of emerging invasive serotypes.

  6. Seasonal Drivers of Pneumococcal Disease Incidence: Impact of Bacterial Carriage and Viral Activity

    PubMed Central

    Weinberger, Daniel M.; Grant, Lindsay R.; Steiner, Claudia A.; Weatherholtz, Robert; Santosham, Mathuram; Viboud, Cécile; O'Brien, Katherine L.

    2014-01-01

    Background. Winter-seasonal epidemics of pneumococcal disease provide an opportunity to understand the drivers of incidence. We sought to determine whether seasonality of invasive pneumococcal disease is caused by increased nasopharyngeal transmission of the bacteria or increased susceptibility to invasive infections driven by cocirculating winter respiratory viruses. Methods. We analyzed pneumococcal carriage and invasive disease data collected from children <7 years old in the Navajo/White Mountain Apache populations between 1996 and 2012. Regression models were used to quantify seasonal variations in carriage prevalence, carriage density, and disease incidence. We also fit a multivariate model to determine the contribution of carriage prevalence and RSV activity to pneumococcal disease incidence while controlling for shared seasonal factors. Results. The seasonal patterns of invasive pneumococcal disease epidemics varied significantly by clinical presentation: bacteremic pneumococcal pneumonia incidence peaked in late winter, whereas invasive nonpneumonia pneumococcal incidence peaked in autumn. Pneumococcal carriage prevalence and density also varied seasonally, with peak prevalence occurring in late autumn. In a multivariate model, RSV activity was associated with significant increases in bacteremic pneumonia cases (attributable percentage, 15.5%; 95% confidence interval [CI], 1.8%–26.1%) but was not associated with invasive nonpneumonia infections (8.0%; 95% CI, −4.8% to 19.3%). In contrast, seasonal variations in carriage prevalence were associated with significant increases in invasive nonpneumonia infections (31.4%; 95% CI, 8.8%–51.4%) but not with bacteremic pneumonia. Conclusions.The seasonality of invasive pneumococcal pneumonia could be due to increased susceptibility to invasive infection triggered by viral pathogens, whereas seasonality of other invasive pneumococcal infections might be primarily driven by increased nasopharyngeal

  7. Immunologic studies in pneumococcal disease.

    PubMed

    Dee, T H; Schiffman, G; Sottile, M I; Rytel, M W

    1977-06-01

    Many patients die from pneumococcal disease despite the availability of effective antimicrobial agents. Immunologic studies including detection, typing, and quantitation of serum pneumococcal capsular polysaccharide (PCP) antigen by counterimmunoelectrophoresis (CIE), quantitation of PCP antibody by radioimmunoassay (RIA), and quantitation of serum complement components C3, C4, and C3PA and serum immunoglobulins IgG, IgM, and IgA by the radial immunodiffusion technique of Mancini were performed with the sera of 18 patients. Five patients died (group I), and 13 survived (group II) pneumococcal infection. Both groups were comparable in age, underlying disease, and leukopenia on admission. All patients of group I and 10 of 13 (77%) of group II patients were bacteremic. Two patients in each group had an extrapulmonary focus infection. PCP antigen was detected in the sera of all group I and nine of 13 group II patients. PCP antigen levels were larger than or equal to 15 microng/ml in four of five group I and two of 13 group II patients (p = 0.022). Levels of antibody to PCP exceeded 100 ng/ml of antibody nitrogen (AbN) in 10 of 12 group II and one of five group I patients (p = 0.027) during the course of illness. All group I patients and three of 12 group II patients had decreased levels of one or more complement components on admission (p less than 0.01). One or more complement components remained decreased until death in four group I patients but returned to normal or elevated levels in all group II patients. No difference in serum immunoglobulin concentrations were found.

  8. Directed vaccination against pneumococcal disease

    PubMed Central

    Li, Yi; Hill, Andrew; Beitelshees, Marie; Shao, Shuai; Knight, Paul R.; Hakansson, Anders P.; Pfeifer, Blaine A.; Jones, Charles H.

    2016-01-01

    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

  9. Development and preliminary data on the use of a mobile app specifically designed to increase community awareness of invasive pneumococcal disease and its prevention

    PubMed Central

    Panatto, Donatella; Domnich, Alexander; Gasparini, Roberto; Bonanni, Paolo; Icardi, Giancarlo; Amicizia, Daniela; Arata, Lucia; Bragazzi, Nicola Luigi; Signori, Alessio; Landa, Paolo; Bechini, Angela; Boccalini, Sara

    2016-01-01

    ABSTRACT Given the growing use and great potential of mobile apps, this project aimed to develop and implement a user-friendly app to increase laypeople's knowledge and awareness of invasive pneumococcal disease (IPD). Despite the heavy burden of IPD, the documented low awareness of IPD among both laypeople and healthcare professionals and far from optimal pneumococcal vaccination coverage, no app specifically targeting IPD has been developed so far. The app was designed to be maximally functional and conceived in accordance with user-centered design. Its content, layout and usability were discussed and formally tested during several workshops that involved the principal stakeholders, including experts in IPD and information technology and potential end-users. Following several workshops, it was decided that, in order to make the app more interactive, its core should be a personal “checker” of the risk of contracting IPD and a user-friendly risk-communication strategy. The checker was populated with risk factors identified through both Italian and international official guidelines. Formal evaluation of the app revealed its good readability and usability properties. A sister web site with the same content was created to achieve higher population exposure. Seven months after being launched in a price- and registration-free modality, the app, named “Pneumo Rischio,” averaged 20.9 new users/day and 1.3 sessions/user. The first in-field results suggest that “Pneumo Rischio” is a promising tool for increasing the population's awareness of IPD and its prevention through a user-friendly risk checker. PMID:26795065

  10. Effectiveness of the 7-valent pneumococcal conjugate vaccine against vaccine-type invasive disease among children in Uruguay: an evaluation using existing data.

    PubMed

    Picón, Teresa; Alonso, Lucía; García Gabarrot, Gabriela; Speranza, Noelia; Casas, Mariana; Arrieta, Fernando; Camou, Teresa; Rosa, Raquel; De Oliveira, Lucia Helena; Verani, Jennifer Rabke

    2013-07-02

    The 7-valent pneumococcal conjugate vaccine (PCV7) was introduced into the routine immunization program in Uruguay in March 2008 with a 2-dose primary series (given at 2 and 4 months) plus a booster (at 12 months) and a catch-up campaign (two doses given at 15 and 17 months). We used a case-control methodology and existing laboratory surveillance and immunization registry data from Uruguay to evaluate PCV7 effectiveness against vaccine-type invasive pneumococcal disease (VT-IPD). Cases of VT-IPD (with pneumococcus obtained from a normally sterile site) were identified through the National Reference Laboratory. Age- and neighborhood-matched controls were obtained through a national immunization registry in which all children are enrolled at birth regardless of vaccine receipt; all eligible controls were included. Immunization status of cases and controls was assessed through the immunization registry, and conditional logistic regression was used to calculate PCV7 effectiveness. Between April 2008 and February 2010, 44 cases of VT-IPD among children<5 years were identified; 43 (98%) of those children were located in the registry. Among located case patients, 7 (16.3%) were age-eligible to have received at least one dose of PCV7. A total of 637 matched controls were included. Vaccine effectiveness was 91.3% (95% CI: 46.4, 98.6) for ≥ 1 PCV7 doses and 94.8% (95% CI: 43.1, 99.5) for ≥ 2 PCV7 doses. Using existing data we demonstrated high effectiveness of PCV7 against VT-IPD in Uruguay-a middle-income country using a 2-dose primary series plus a booster dose and a limited catch-up campaign. These data also highlight the utility of surveillance and high-quality immunization registries for evaluating the effectiveness of vaccines.

  11. Development and preliminary data on the use of a mobile app specifically designed to increase community awareness of invasive pneumococcal disease and its prevention.

    PubMed

    Panatto, Donatella; Domnich, Alexander; Gasparini, Roberto; Bonanni, Paolo; Icardi, Giancarlo; Amicizia, Daniela; Arata, Lucia; Bragazzi, Nicola Luigi; Signori, Alessio; Landa, Paolo; Bechini, Angela; Boccalini, Sara

    2016-04-02

    Given the growing use and great potential of mobile apps, this project aimed to develop and implement a user-friendly app to increase laypeople's knowledge and awareness of invasive pneumococcal disease (IPD). Despite the heavy burden of IPD, the documented low awareness of IPD among both laypeople and healthcare professionals and far from optimal pneumococcal vaccination coverage, no app specifically targeting IPD has been developed so far. The app was designed to be maximally functional and conceived in accordance with user-centered design. Its content, layout and usability were discussed and formally tested during several workshops that involved the principal stakeholders, including experts in IPD and information technology and potential end-users. Following several workshops, it was decided that, in order to make the app more interactive, its core should be a personal "checker" of the risk of contracting IPD and a user-friendly risk-communication strategy. The checker was populated with risk factors identified through both Italian and international official guidelines. Formal evaluation of the app revealed its good readability and usability properties. A sister web site with the same content was created to achieve higher population exposure. Seven months after being launched in a price- and registration-free modality, the app, named "Pneumo Rischio," averaged 20.9 new users/day and 1.3 sessions/user. The first in-field results suggest that "Pneumo Rischio" is a promising tool for increasing the population's awareness of IPD and its prevention through a user-friendly risk checker.

  12. Rates of Pneumococcal Disease in Adults With Chronic Medical Conditions

    PubMed Central

    Shea, Kimberly M.; Edelsberg, John; Weycker, Derek; Farkouh, Raymond A.; Strutton, David R.; Pelton, Stephen I.

    2014-01-01

    Background.  Although it is widely accepted that adults with immunocompromising conditions are at greatly increased risk of pneumococcal infection, the extent of risk among immunocompetent adults with chronic medical conditions is less certain, particularly in the current era of universal vaccination of children with pneumococcal conjugate vaccines. Methods.  We conducted a retrospective cohort study using data from 3 healthcare claims repositories (2006–2010) to compare rates of pneumococcal disease in immunocompetent adults with chronic medical conditions (“at-risk”) and immunocompromised adults (“high-risk”), with rates in adults without these conditions (“healthy”). Risk profiles and episodes of pneumococcal disease—all-cause pneumonia, pneumococcal pneumonia, and invasive pneumococcal disease (IPD)—were ascertained from diagnosis, procedure, and drug codes. Results.  Rates of all-cause pneumonia among at-risk persons aged 18–49 years, 50–64 years, and ≥65 years were 3.2 (95% confidence interval [CI], 3.1–3.2), 3.1 (95% CI, 3.1–3.1), and 3.0 (95% CI, 3.0–3.0) times the rates in age-matched healthy counterparts, respectively. We identified rheumatoid arthritis, systemic lupus erythematosus, Crohn's disease, and neuromuscular or seizure disorders as additional at-risk conditions for pneumococcal disease. Among persons with at-risk conditions, the rate of all-cause pneumonia substantially increased with the accumulation of concurrent at-risk conditions (risk stacking): among persons 18–49 years, rate ratios increased from 2.5 (95% CI, 2.5–2.5) in those with 1 at-risk condition to 6.2 (95% CI, 6.1–6.3) in those with 2 conditions, and to 15.6 (95% CI, 15.3–16.0) in those with ≥3 conditions. Findings for pneumococcal pneumonia and IPD were similar. Conclusions.  Despite widespread use of pneumococcal conjugate vaccines, rates of pneumonia and IPD remain disproportionately high in adults with at-risk conditions

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

    PubMed

    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 < 0.01), whereas serotype 6A was exclusively isolated from carriers (p < 0.01). Deaths associated with IPD were related to serotypes 19A, 14, 18C, and one non-typeable isolate. Among IPD related to 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.

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

    PubMed Central

    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 < 0.01), whereas serotype 6A was exclusively isolated from carriers (p < 0.01). Deaths associated with IPD were related to serotypes 19A, 14, 18C, and one non-typeable isolate. Among IPD related to 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

  15. Hospitalizations for pneumonia, invasive diseases and otitis in Tuscany (Italy), 2002-2014: Which was the impact of universal pneumococcal pediatric vaccination?

    PubMed

    Boccalini, Sara; Varone, Ornella; Chellini, Martina; Pieri, Luca; Sala, Antonino; Berardi, Cesare; Bonanni, Paolo; Bechini, Angela

    2017-02-01

    Streptococcus pneumoniae is the main causative organism of acute media otitis in children and meningitis and bacterial pneumonia in the community. Since 2008 in Tuscany, central Italy, the pneumococcal conjugate vaccine (7-valent vaccine, switched to 13-valent vaccine in 2010) was actively offered free of charge to all newborns. Aim of the study is to evaluate the impact of pneumococcal pediatric vaccination in the Tuscan population on hospitalizations potentially caused by S. pneumoniae, during pre-vaccination (PVP, 2002-2007) and vaccination period (VP, 2009-2014). We analyzed hospital discharge records (HDRs) of all hospitals in Tuscany from 2002 to 2014. Hospitalizations potentially due to pneumococcal diseases were 347, 221. The general hospitalization rate was 716/100,000 inhabitants during PVP and 753/100,000 in VP, with a decrease of 29.1% in the age-group 0-9 y ("target" of the vaccination program) and an increase of 75.7% in subjects >64 y of age. During VP, admission days and hospitalization costs increased (6.2% and 24.2%, respectively), especially in patients >64 y (12.9% and 33.8%, respectively); in children <10 y decreased by 21.2% and 12.8%, respectively. The pneumococcal pediatric vaccination resulted in the decrease of hospitalizations in younger but the expected indirect effect in the elderly was not reported, justifying the Tuscan recommendation to extend the vaccination to subjects > 64 y.

  16. [Epidemiological analysis of the incidence of invasive and non-invasive pneumococcal infections in different population groups].

    PubMed

    Martynova, A V; Turkutiukov, V B

    2007-01-01

    Despite modern achievements in diagnostics and treatment, invasive and non-invasive pneumococcal infections remain a topical public health problem. To a large extent, it is connected with the absence or inconsistence of evidence-based information on this kind of infection. In this paper, retrospective analysis of the incidence of pneumococcal infections was performed on the basis of medical records available today in every health institution; the peculiarities of their nosologic structure were revealed. Among invasive forms, pneumococcal pneumonias prevailed (50.06%); apparent hypodiagnostics of pneumococcal meningitis was noted (only 4.02%). Among non-invasive forms, acute otitis with various complications prevailed (47.5%), acute sinusitis was registered in 37.5% of cases, and other ENT diseases (sphenoiditis, frontitis, ethmoiditis, etc.) were registered in 15% of cases. The study found that the main risk factors in these patients had been different ENT diseases which the patients had suffered from during the previous three months before the actual illness. Thus, the necessity for the development and perfection of techniques of microbiological diagnostics and the development of epidemiological control methods on their basis are obvious.

  17. Whole-genome Sequencing for Surveillance of Invasive Pneumococcal Diseases in Ontario, Canada: Rapid Prediction of Genotype, Antibiotic Resistance and Characterization of Emerging Serotype 22F

    PubMed Central

    Deng, Xianding; Memari, Nader; Teatero, Sarah; Athey, Taryn; Isabel, Marc; Mazzulli, Tony; Fittipaldi, Nahuel; Gubbay, Jonathan B.

    2016-01-01

    Background: Molecular typing is essential for inferring genetic relatedness between bacterial pathogens. In this study, we applied whole genome sequencing (WGS) for rapid prediction of sequence type and antibiotic resistance for invasive pneumococcal isolates. Methods: 240 isolates from adults (≥50 years old) in Ontario, Canada during 2009 to 2013 were subjected to WGS. Sequence type, antibiotic susceptibility and resistance were predicted directly from short reads. Emerging non-vaccine serotype 22F was further characterized by WGS. Results: Sequence type was successfully determined for 98.3% of isolates. The overall sensitivity and specificity for antibiotic resistance prediction were 95 and 100% respectively, compared to standard susceptibility testing methods. WGS-based phylogeny divided emerging 22F (ST433) strains into two distinct clades: clade A harboring a 23 kb-prophage and anti-phage PhD/Doc system and clade B with virulence-related proteases. Five isolates in clade A developed macrolide resistance via 5.1 kb mega element recombination (encoding mefE and msrD), while one isolate in clade B displayed quinolone resistance via a gyrA mutation. Conclusions: WGS is valuable for routine surveillance of pneumococcal clinical isolates and facilitates prediction of genotype and antibiotic resistance. The emergence of 22F in Ontario in the post-vaccine era and evidence of evolution and divergence of the 22F population warrants heightened pneumococcal molecular surveillance. PMID:28082965

  18. Whole-genome Sequencing for Surveillance of Invasive Pneumococcal Diseases in Ontario, Canada: Rapid Prediction of Genotype, Antibiotic Resistance and Characterization of Emerging Serotype 22F.

    PubMed

    Deng, Xianding; Memari, Nader; Teatero, Sarah; Athey, Taryn; Isabel, Marc; Mazzulli, Tony; Fittipaldi, Nahuel; Gubbay, Jonathan B

    2016-01-01

    Background: Molecular typing is essential for inferring genetic relatedness between bacterial pathogens. In this study, we applied whole genome sequencing (WGS) for rapid prediction of sequence type and antibiotic resistance for invasive pneumococcal isolates. Methods: 240 isolates from adults (≥50 years old) in Ontario, Canada during 2009 to 2013 were subjected to WGS. Sequence type, antibiotic susceptibility and resistance were predicted directly from short reads. Emerging non-vaccine serotype 22F was further characterized by WGS. Results: Sequence type was successfully determined for 98.3% of isolates. The overall sensitivity and specificity for antibiotic resistance prediction were 95 and 100% respectively, compared to standard susceptibility testing methods. WGS-based phylogeny divided emerging 22F (ST433) strains into two distinct clades: clade A harboring a 23 kb-prophage and anti-phage PhD/Doc system and clade B with virulence-related proteases. Five isolates in clade A developed macrolide resistance via 5.1 kb mega element recombination (encoding mefE and msrD), while one isolate in clade B displayed quinolone resistance via a gyrA mutation. Conclusions: WGS is valuable for routine surveillance of pneumococcal clinical isolates and facilitates prediction of genotype and antibiotic resistance. The emergence of 22F in Ontario in the post-vaccine era and evidence of evolution and divergence of the 22F population warrants heightened pneumococcal molecular surveillance.

  19. Active hospital-based surveillance of invasive pneumococcal disease and clinical pneumonia in infants and young children in two Polish counties

    PubMed Central

    Sluzewski, Wojciech; Gutterman, Elane; Jouve, Sylvie; Moscariello, Michele; Balter, Ivana

    2016-01-01

    Introduction Invasive pneumococcal disease (IPD) incidence, serotype distribution, and antibiotic susceptibility of Streptococcus pneumoniae were estimated in children aged 28 days to < 60 months. Material and methods One-year prospective, hospital-based surveillance was conducted starting on February 15, 2008, at two children's hospitals serving the city and surrounding county of Poznań and Poznański, Poland. Eligible children had fever ≥ 39.0°C or physician-suspected IPD. Blood cultures were obtained from all children, cerebrospinal fluid in suspected meningitis cases, and chest radiographs (CXRs) in suspected pneumonia cases. Results Seven of 1,581 eligible children had confirmed IPD. Estimated IPD incidence per 100,000 children was 11.89 (95% CI: 4.78–24.50) overall and 20.1 (95% CI: 6.52–46.84) in subjects aged 28 days to < 24 months. One S. pneumoniae isolate of each of the following serotypes was obtained: 6B, 14, 23A, 23F, and 33F. Two isolates were resistant to both trimethoprim-sulfamethoxazole and erythromycin. Clinical pneumonia incidence among children aged 28 days to < 24 months and 24 months to < 60 months was 3,151.3 (95% CI: 2934.7–3379.7) and 962.7 (95% CI: 861.2–10,072.9) per 100,000 children, respectively. CXR-confirmed pneumonia rates in the same groups were 1,035.7 (95% CI: 913.2–1,170.1) and 379.8 (95% CI: 317.1–451.3) per 100,000 children, respectively. Conclusions IPD is an important cause of morbidity in Poznań and Poznański county, Poland. Among participants aged < 5 years with fever or suspected IPD, pneumonia was the most common diagnosis and was highest in children aged < 24 months. PMID:27279858

  20. The evidence for using conjugate vaccines to protect HIV-infected children against pneumococcal disease.

    PubMed

    Bliss, Sandra J; O'Brien, Katherine L; Janoff, Edward N; Cotton, Mark F; Musoke, Philippa; Coovadia, Hoosen; Levine, Orin S

    2008-01-01

    Pneumococcal conjugate vaccines (PCVs) are a potentially useful complement to existing treatment strategies in HIV-infected children, for whom pneumococcal infections are common and serious. This Review summarises available data on the burden of pneumococcal disease and the safety and efficacy of PCVs in HIV-infected children. The data demonstrate that children with HIV have significantly increased risk of pneumococcal disease compared with uninfected children; the serotypes included in currently licensed or near-licensure conjugate vaccines include most serotypes that cause invasive pneumococcal disease (IPD) in HIV-infected children and adults; PCVs provide substantial protection against IPD and clinical pneumonia when given to HIV-infected infants; and HIV-infected adults gain an indirect benefit when children in the community are vaccinated. PCV should be considered as an important intervention for improving the lives of HIV-infected children.

  1. Towards New Broader Spectrum Pneumococcal Vaccines: The Future of Pneumococcal Disease Prevention

    PubMed Central

    Lee, Lucia H.; Gu, Xin-Xing; Nahm, Moon H.

    2014-01-01

    Seven-valent pneumococcal conjugate vaccine (PCV7) introduction and routine pediatric use has substantially reduced the burden of Streptococcus pneumoniae disease worldwide. However, a significant amount of disease burden, due to serotypes not contained in PCV7, still exists globally. A newly recognized serotype, 6C, was until recently, identified and reported as serotype 6A. This review summarizes the serotype epidemiology of pneumococcal disease pre- and post-introduction of PCV7, available post-marketing surveillance data following the introduction of higher valency pneumococcal vaccines (PCV10, PCV13) and future prospects for the development of new pneumococcal vaccines. PMID:26344470

  2. Hospitalizations for pneumonia, invasive diseases and otitis in Tuscany (Italy), 2002-2014: Which was the impact of universal pneumococcal pediatric vaccination?

    PubMed Central

    Varone, Ornella; Chellini, Martina; Pieri, Luca; Sala, Antonino; Berardi, Cesare; Bechini, Angela

    2017-01-01

    ABSTRACT Streptococcus pneumoniae is the main causative organism of acute media otitis in children and meningitis and bacterial pneumonia in the community. Since 2008 in Tuscany, central Italy, the pneumococcal conjugate vaccine (7-valent vaccine, switched to 13-valent vaccine in 2010) was actively offered free of charge to all newborns. Aim of the study is to evaluate the impact of pneumococcal pediatric vaccination in the Tuscan population on hospitalizations potentially caused by S. pneumoniae, during pre-vaccination (PVP, 2002–2007) and vaccination period (VP, 2009–2014). We analyzed hospital discharge records (HDRs) of all hospitals in Tuscany from 2002 to 2014. Hospitalizations potentially due to pneumococcal diseases were 347, 221. The general hospitalization rate was 716/100,000 inhabitants during PVP and 753/100,000 in VP, with a decrease of 29.1% in the age-group 0–9 y (“target” of the vaccination program) and an increase of 75.7% in subjects >64 y of age. During VP, admission days and hospitalization costs increased (6.2% and 24.2%, respectively), especially in patients >64 y (12.9% and 33.8%, respectively); in children <10 y decreased by 21.2% and 12.8%, respectively. The pneumococcal pediatric vaccination resulted in the decrease of hospitalizations in younger but the expected indirect effect in the elderly was not reported, justifying the Tuscan recommendation to extend the vaccination to subjects > 64 y. PMID:27925848

  3. American Academy of Pediatrics. Committee on Infectious Diseases. Technical report: prevention of pneumococcal infections, including the use of pneumococcal conjugate and polysaccharide vaccines and antibiotic prophylaxis.

    PubMed

    Overturf, G D

    2000-08-01

    Pneumococcal infections are the most common invasive bacterial infections in children in the United States. The incidence of invasive pneumococcal infections peaks in children younger than 2 years, reaching rates of 228/100,000 in children 6 to 12 months old. Children with functional or anatomic asplenia (including sickle cell disease [SCD]) and children with human immunodeficiency virus infection have pneumococcal infection rates 20- to 100-fold higher than those of healthy children during the first 5 years of life. Others at high risk of pneumococcal infections include children with congenital immunodeficiency; chronic cardiopulmonary disease; children receiving immunosuppressive chemotherapy; children with immunosuppressive neoplastic diseases; children with chronic renal insufficiency, including nephrotic syndrome; children with diabetes; and children with cerebrospinal fluid leaks. Children of Native American (American Indian and Alaska Native) or African American descent also have higher rates of invasive pneumococcal disease. Outbreaks of pneumococcal infection have occurred with increased frequency in children attending out-of-home care. Among these children, nasopharyngeal colonization rates of 60% have been observed, along with pneumococci resistant to multiple antibiotics. The administration of antibiotics to children involved in outbreaks of pneumococcal disease has had an inconsistent effect on nasopharyngeal carriage. In contrast, continuous penicillin prophylaxis in children younger than 5 years with SCD has been successful in reducing rates of pneumococcal disease by 84%. Pneumococcal polysaccharide vaccines have been recommended since 1985 for children older than 2 years who are at high risk of invasive disease, but these vaccines were not recommended for younger children and infants because of poor antibody response before 2 years of age. In contrast, pneumococcal conjugate vaccines (Prevnar) induce proposed protective antibody responses (>.15

  4. Capsular serotypes and antimicrobial susceptibilities of Streptococcus pneumoniae causing invasive pneumococcal disease from 2009-2012 with an emphasis on serotype 19A in bacteraemic pneumonia and empyema and β-lactam resistance.

    PubMed

    Lee, Meng-Rui; Chen, Chung-Ming; Chuang, Tzu-Yi; Huang, Yu-Tsung; Hsueh, Po-Ren

    2013-11-01

    Capsular serotypes and antimicrobial susceptibilities of Streptococcus pneumoniae isolates that cause invasive pneumococcal disease (IPD) were studied and the role of serotype 19A in the development of bacteraemic pneumonia and empyema was investigated. Subjects comprised 98 patients (56 adults and 42 children) who were treated for IPD at a university-affiliated tertiary referral centre in Taiwan during 2009-2012. Serotypes of the isolates were identified using the latex agglutination method. In vitro susceptibilities of the isolates to 13 antimicrobial agents were determined using the broth microdilution method and were interpreted as recommended by the Clinical and Laboratory Standards Institute. During the study period, bacteraemic pneumonia was the most common type of infection (43/98; 43.9%), followed by primary bacteraemia (30/98; 30.6%). Serotype 19A was the most common serotype (23/98; 23.5%) in all patients. Fourteen (70.0%) of 20 children (47.6% of all children) with serotype 19A infection had pneumonia with empyema, whilst eight patients had concomitant bacteraemia. 7-valent pneumococcal conjugated vaccine (PCV-7), PCV-10, PCV-13 and 23-valent pneumococcal polysaccharide vaccine (PPV-23) had coverage rates of 37.8%, 38.8%, 79.6% and 77.6%, respectively. A substantial increase in the proportion of serotype 15A (6.1%) and 6A (8.2%) was found. In addition, there was a significant reduction in rates of susceptibility of serotype 19A isolates to penicillin, cefotaxime and ceftriaxone but not to azithromycin or any quinolone tested compared with those of non-19A isolates. The prevalence of serotypes 19A, 15A and 6A in patients with IPD increased markedly during the period, especially in children with bacteraemic pneumonia and empyema.

  5. Using whole genome sequencing to identify resistance determinants and predict antimicrobial resistance phenotypes for year 2015 invasive pneumococcal disease isolates recovered in the United States.

    PubMed

    Metcalf, B J; Chochua, S; Gertz, R E; Li, Z; Walker, H; Tran, T; Hawkins, P A; Glennen, A; Lynfield, R; Li, Y; McGee, L; Beall, B

    2016-12-01

    Our whole genome sequence (WGS) pipeline was assessed for accurate prediction of antimicrobial phenotypes. For 2316 invasive pneumococcal isolates recovered during 2015 we compared WGS pipeline data to broth dilution testing (BDT) for 18 antimicrobials. For 11 antimicrobials categorical discrepancies were assigned when WGS-predicted MICs and BDT MICs predicted different categorizations for susceptibility, intermediate resistance or resistance, ranging from 0.9% (tetracycline) to 2.9% (amoxicillin). For β-lactam antibiotics, the occurrence of at least four-fold differences in MIC ranged from 0.2% (meropenem) to 1.0% (penicillin), although phenotypic retesting resolved 25%-78% of these discrepancies. Non-susceptibility to penicillin, predicted by penicillin-binding protein types, was 2.7% (non-meningitis criteria) and 23.8% (meningitis criteria). Other common resistance determinants included mef (475 isolates), ermB (191 isolates), ermB + mef (48 isolates), tetM (261 isolates) and cat (51 isolates). Additional accessory resistance genes (tetS, tet32, aphA-3, sat4) were rarely detected (one to three isolates). Rare core genome mutations conferring erythromycin-resistance included a two-codon rplD insertion (rplD69-KG-70) and the 23S rRNA A2061G substitution (six isolates). Intermediate cotrimoxazole-resistance was associated with one or two codon insertions within folP (238 isolates) or the folA I100L substitution (38 isolates), whereas full cotrimoxazole-resistance was attributed to alterations in both genes (172 isolates). The two levofloxacin-resistant isolates contained parC and/or gyrA mutations. Of 11 remaining isolates with moderately elevated MICs to both ciprofloxacin and levofloxacin, seven contained parC or gyrA mutations. The two rifampin-resistant isolates contained rpoB mutations. WGS-based antimicrobial phenotype prediction was an informative alternative to BDT for invasive pneumococci.

  6. Prevention of pneumococcal disease through vaccination.

    PubMed

    Gentile, Angela; Bazán, Virginia

    2011-09-14

    The Millennium Development Goals (MDGs), adopted by world leaders in the year 2000 with an aim to accomplish them by 2015, provide concrete benchmarks for tackling extreme poverty in its many dimensions. One aim is to reduce by two thirds the mortality rate among children <5 years of age. The deaths of nearly 3 million children under 5 each year worldwide can be attributed to diarrhea and pneumonia. Pneumonia, one form of pneumococcal disease, causes almost 1 in 5 deaths of children under 5 worldwide-more than 1.6 million children each year. Pneumococcal disease is preventable by vaccination; because antibiotic resistance is a growing problem worldwide, there is a great need to promote effective pneumococcal vaccines. Vaccines differ from other types of drugs, because they are administered to healthy individuals. Therefore, a good safety profile is required, there is a large governmental regulatory role, and low efficacy is unacceptable. Other important considerations are as follows: vaccines are often used in infants, are typically given in multiple doses, the manufacturing is a larger part of cost, requires high regulatory and quality control burden and minimization of costs. From a biological standpoint, the induction of vaccine-mediated protection is a complex procedure. Long-term protection typically requires the persistence of anti-microbial antibodies and/or the generation of immune memory cells capable of rapid and effective reactivation after microbial re-exposure. Appreciation of the predominant role of B cells in the efficacy of current vaccines should not minimize the importance of generating a T cell response, as this is essential for the induction of high affinity antibodies and immune memory. Pneumococcal capsular polysaccharides typically elicit B cell responses in a T-independent manner. Because of this, capsular polysaccharides are poorly immunogenic in children below 2 years of age and will generate an IgM isotype-based primary response with only

  7. Burden of Pneumococcal Disease in Northern Togo before the Introduction of Pneumococcal Conjugate Vaccine

    PubMed Central

    Moïsi, Jennifer C.; Makawa, Makawa-Sy; Tall, Haoua; Agbenoko, Kodjo; Njanpop-Lafourcade, Berthe-Marie; Tamekloe, Stanislas; Amidou, Moussa; Mueller, Judith E.; Gessner, Bradford D.

    2017-01-01

    Background S. pneumoniae is a leading cause of meningitis morbidity and mortality in the African meningitis belt, but little is known of its contribution to the burden of pneumonia in the region. We aimed to estimate the incidence of pneumococcal disease in children and adults in northern Togo, before the introduction of pneumococcal conjugate vaccine (PCV). Methods and findings From May 1st 2010 to April 30th 2013, we systematically enrolled all hospitalized patients meeting a case definition of suspected meningitis or clinical pneumonia, residing in Tone or Cinkasse districts, northern Togo and providing informed consent. We collected clinical data and tested biological specimens according to standardized procedures, including bacteriology and PCR testing of cerebro-spinal fluid for meningitis patients and blood cultures and whole blood lytA PCR for pneumonia patients. Chest X-rays (CXR) were interpreted using the WHO methodology. We included 404 patients with meningitis (104 <5 years of age) and 1550 with pneumonia (251 <5 years) over the study period. Of these, 78 (19%) had pneumococcal meningitis (13 <5 years), 574 (37%) had radiologically-confirmed pneumonia (83 <5 years) and 73 (5%) had culture-confirmed pneumococcal pneumonia (2 <5 years). PCV13 serotypes caused 79% (54/68) of laboratory-confirmed pneumococcal meningitis and 83% (29/35) of culture-confirmed pneumococcal pneumonia. Serotype 1 predominated in meningitis (n = 33) but not in pneumonia patients (n = 1). The incidence of pneumococcal disease was 7.5 per 100,000 among children <5 years of age and 14.8 in persons 5 years of age and above in the study area. When considering CXR-confirmed and blood PCR-positive pneumonia cases as likely pneumococcal, incidence estimates increased to 43.7 and 66.0 per 100,000 in each of these age groups, respectively. Incidence was at least 3-fold higher when we restricted the analysis to the urban area immediately around the study hospitals. Conclusions Our findings

  8. Genotypes of Invasive Pneumococcal Isolates Recently Recovered from Italian Patients

    PubMed Central

    Dicuonzo, Giordano; Gherardi, Giovanni; Gertz, Robert E.; D'Ambrosio, Fabio; Goglio, Antonio; Lorino, Giulia; Recchia, Simona; Pantosti, Annalisa; Beall, Bernard

    2002-01-01

    We examined 73 recent invasive pneumococcal isolates within selected areas of Italy for genotypic variability. Thirty-three genomic macrorestriction types were found, three of which represented multiple serotypes. Restriction fragment patterns of pbp2b, pbp2x, and pspA were conserved within the majority of isolates that shared macrorestriction types. Of the nine macrorestriction types found among the 22 penicillin-nonsusceptible Streptococus pneumoniae (PNSP) isolates, seven comprised isolates with allelic profiles showing five to seven allelic matches to profiles in the multilocus sequence typing database (www.mlst.net); however, three of the seven profiles represented serotypes not previously associated with these clonal clusters. Two PNSP macrorestriction types represented new clones with unique allelic profiles. Allelic profiles obtained from isolates of 3 of the 25 macrorestriction types found among the 51 penicillin-susceptible S. pneumoniae (PSSP) isolates were closely related to previously described profiles. One PSSP isolate was a novel type 24F isolate related to the multiresistant clone France9V-3. This work reports new PNSP strains and new serotype-clone associations. PMID:12354862

  9. Study of Invasive Pneumococcal Infection in Adults with Reference to Penicillin Resistance

    PubMed Central

    Muley, Vrishali Avinash; Ghadage, Dnyaneshwari Purushottam; Yadav, Gauri Eknath; Bhore, Arvind Vamanrao

    2017-01-01

    Background: Invasive pneumococcal infections often prove rapidly fatal, even where good medical treatment is readily available. In developed countries, up to 20% of people who contract pneumococcal meningitis die; however, in developing world, mortality is closer to 50%, even among hospitalized patients. The World Health Organization estimated 600,000–800,000 adult deaths each year from pneumococcal pneumonia, meningitis, and sepsis. Aims: This study aims to estimate isolation rate of invasive pneumococcal infection in adults, to determine the antimicrobial susceptibility profile of Streptococcus pneumoniae isolates and to study the associated risk factors. Materials and Methods: A total of 120 patients with suspected invasive infection such as meningitis, septicemia, and pleural effusion, were included in the study. Various clinical specimens such as pus, cerebrospinal fluid, and other sterile body fluids were processed for isolation and identification of S. pneumoniae. Kirby–Bauer disc diffusion method was performed to determine the antimicrobial susceptibility profile. Minimum inhibitory concentration test was performed to determine the penicillin resistance. Results: Of 120 patients, 40 (33.33%) cases were proven by culture to have an invasive pneumococcal infection. The most common clinical condition observed was meningitis followed by pneumonia with pleural effusion and sepsis. Pneumococcal isolates exhibited 40% resistance to cotrimoxazole and 12.73% to chloramphenicol. Two meningeal isolates exhibited penicillin resistance. Comorbidities observed in 21 (52.5%) cases were mainly Diabetes mellitus, smoking, and alcoholism. Conclusions: Invasive pneumococcal infection has poor prognosis and penicillin-resistant strains have become increasingly common. This study emphasizes the importance of judicious use of antibiotics, especially to refrain their use in mild self-limiting upper respiratory infections. PMID:28042214

  10. Incidence of pediatric invasive pneumococcal disease in the Island of Majorca (2008-2010), an area with non-universal vaccination, and estimations of serotype & children population coverage by available conjugate vaccines

    PubMed Central

    2013-01-01

    Background The World Health Organization reported in 2007 that inclusion of PCV7 in national immunization programs should be seen as a priority, also encouraging countries to conduct appropriate surveillances for monitoring the impact of vaccination. These analyses should be conducted in specific geographical areas and should be aimed to evolution of invasive pneumococcal disease (IPD), by age groups, clinical presentation, and vaccine serotypes (and non-vaccine serotypes to detect possible replacement). This study aimed to monitor the evolution of IPD incidence in children <15 years requiring hospitalization in the Island of Majorca. Methods A prospective clinical surveillance of all culture and/or PCR-confirmed IPD in children <15 years was performed in all hospitals in the Island of Majorca (approximately 900,000 inhabitants) from January 2008 to December 2010. Incidence rate (IR) was calculated as cases/100000 inhabitants using children population data. Results 66 IPDs were identified: 39 (59.1%) parapneumonic pneumococcal empyema (PPE), 16 (24.2%) bacteremic pneumonia (BP), 7 (10.6%) primary bacteremia, 3 (4.5%) meningitis, and 1 (1.5%) osteomyelitis. IRs in the three-year study period were: 64.22 for children 12- < 24 months, 37.21 for those 24-59 months, 22.62 for those <12 months, and 3.98 for children >59 months. By study year, IRs were 21.25 in 2008, 19.89 in 2009 and 9.80 in 2010. The reduction found in 2010 was significant and due to significant reductions in IRs of IPDs caused by serotypes included in PCV10 and PCV13. Overall, estimated serotype coverage by conjugate vaccines was 12.1% for PCV7, 37.9% for PCV10 and 65.2% for PCV13. Of the 66 hospitalized children with IPD, 20 had received at least one dose of PCV7 (13 cases with identified serotype). None of these 13 cases was caused by PCV7 serotypes, all were caused by PCV13 serotypes and only 53.8% by PCV10 serotypes. Conclusions The results of the present study evidence the importance of

  11. Pneumococcal Disease: Risk Factors and Transmission

    MedlinePlus

    ... With conditions that weaken the immune system (HIV/AIDS, cancer, or damaged/absent spleen) With cochlear implants or cerebrospinal fluid (CSF) leaks (escape of the fluid that surrounds the brain and spinal cord) Who smoke cigarettes Transmission Pneumococcal bacteria spread from person-to-person by ...

  12. Streptococcus pneumoniae capsule determines disease severity in experimental pneumococcal meningitis

    PubMed Central

    Grandgirard, Denis; Valente, Luca G.; Täuber, Martin G.; Leib, Stephen L.

    2016-01-01

    Streptococcus pneumoniae bacteria can be characterized into over 90 serotypes according to the composition of their polysaccharide capsules. Some serotypes are common in nasopharyngeal carriage whereas others are associated with invasive disease, but when carriage serotypes do invade disease is often particularly severe. It is unknown whether disease severity is due directly to the capsule type or to other virulence factors. Here, we used a clinical pneumococcal isolate and its capsule-switch mutants to determine the effect of capsule, in isolation from the genetic background, on severity of meningitis in an infant rat model. We found that possession of a capsule was essential for causing meningitis. Serotype 6B caused significantly more mortality than 7F and this correlated with increased capsule thickness in the cerebrospinal fluid (CSF), a stronger inflammatory cytokine response in the CSF and ultimately more cortical brain damage. We conclude that capsule type has a direct effect on meningitis severity. This is an important consideration in the current era of vaccination targeting a subset of capsule types that causes serotype replacement. PMID:27009189

  13. Serotype distribution and antimicrobial resistance of invasive and noninvasive pneumococcal isolates in Tunisia.

    PubMed

    Marzouk, Manel; Ferjani, Asma; Bouafia, Nabiha; Harb, Hanen; Ben Salem, Youssef; Boukadida, Jalel

    2015-02-01

    Pneumococcal conjugate vaccines have not yet been introduced into the national program for childhood vaccination in Tunisia. The aim of this 7-year study was to obtain local data about serotype distribution and antimicrobial resistance of Streptococcus pneumoniae. A total of 203 isolates of culture confirmed that S. pneumoniae was evaluated. Invasive (n=108) and noninvasive (n=95) pneumococcal isolates were obtained from patients aged from 1 month to 85 years old. Considering all age groups, vaccine coverage was 40%, 62%, and 68% for PCV7, PCV10, and PCV13 serotypes, respectively. Overall, 31% of these isolates were penicillin G nonsusceptible. The most prevalent serotypes identified were those found in currently available pneumococcal conjugate vaccines, emphasizing the importance of implementing the vaccine in the routine immunization schedule at the national level.

  14. Effectiveness of the 23-Valent Pneumococcal Polysaccharide Vaccine (PPV23) against Pneumococcal Disease in the Elderly: Systematic Review and Meta-Analysis

    PubMed Central

    Remschmidt, Cornelius; Harder, Thomas; Hummers-Pradier, Eva; Wichmann, Ole; Bogdan, Christian

    2017-01-01

    Background Routine vaccination of elderly people against pneumococcal diseases is recommended in many countries. National guidelines differ, recommending either the 23-valent polysaccharide vaccine (PPV23), the 13-valent conjugate vaccine (PCV13) or both. Considering the ongoing debate on the effectiveness of PPV23, we performed a systematic literature review and meta-analysis of the vaccine efficacy/effectiveness (VE) of PPV23 against invasive pneumococcal disease (IPD) and pneumococcal pneumonia in adults aged ≥60 years living in industrialized countries. Methods We searched for pertinent clinical trials and observational studies in databases MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews. We assessed the risk of bias of individual studies using the Cochrane Risk of Bias tool for randomized controlled trials and the Newcastle-Ottawa Scale for observational studies. We rated the overall quality of the evidence by GRADE criteria. We performed meta-analyses of studies grouped by outcome and study design using random-effects models. We applied a sensitivity analysis excluding studies with high risk of bias. Results We identified 17 eligible studies. Pooled VE against IPD (by any serotype) was 73% (95%CI: 10–92%) in four clinical trials, 45% (95%CI: 15–65%) in three cohort studies, and 59% (95%CI: 35–74%) in three case-control studies. After excluding studies with high risk of bias, pooled VE against pneumococcal pneumonia (by any serotype) was 64% (95%CI: 35–80%) in two clinical trials and 48% (95%CI: 25–63%) in two cohort studies. Higher VE estimates in trials (follow-up ~2.5 years) than in observational studies (follow-up ~5 years) may indicate waning protection. Unlike previous meta-analyses, we excluded two trials with high risk of bias regarding the outcome pneumococcal pneumonia, because diagnosis was based on serologic methods with insufficient specificity. Conclusions Our meta

  15. T Regulatory Cells Control Susceptibility to Invasive Pneumococcal Pneumonia in Mice

    PubMed Central

    Neill, Daniel R.; Fernandes, Vitor E.; Wisby, Laura; Haynes, Andrew R.; Ferreira, Daniela M.; Laher, Ameera; Strickland, Natalie; Gordon, Stephen B.; Denny, Paul; Kadioglu, Aras; Andrew, Peter W.

    2012-01-01

    Streptococcus pneumoniae is an important human pathogen responsible for a spectrum of diseases including pneumonia. Immunological and pro-inflammatory processes induced in the lung during pneumococcal infection are well documented, but little is known about the role played by immunoregulatory cells and cytokines in the control of such responses. We demonstrate considerable differences in the immunomodulatory cytokine transforming growth factor (TGF)-β between the pneumococcal pneumonia resistant BALB/c and susceptible CBA/Ca mouse strains. Immunohistochemistry and flow cytometry reveal higher levels of TGF-β protein in BALB/c lungs during pneumococcal pneumonia that correlates with a rapid rise in lung Foxp3+Helios+ T regulatory cells. These cells have protective functions during pneumococcal pneumonia, because blocking their induction with an inhibitor of TGF-β impairs BALB/c resistance to infection and aids bacterial dissemination from lungs. Conversely, adoptive transfer of T regulatory cells to CBA/Ca mice, prior to infection, prolongs survival and decreases bacterial dissemination from lungs to blood. Importantly, strong T regulatory cell responses also correlate with disease-resistance in outbred MF1 mice, confirming the importance of immunoregulatory cells in controlling protective responses to the pneumococcus. This study provides exciting new evidence for the importance of immunomodulation during pulmonary pneumococcal infection and suggests that TGF-β signalling is a potential target for immunotherapy or drug design. PMID:22563306

  16. Antibiotic susceptibility rates of invasive pneumococci before and after the introduction of pneumococcal conjugate vaccination in Germany.

    PubMed

    Imöhl, Matthias; Reinert, Ralf René; van der Linden, Mark

    2015-10-01

    Continuous nationwide surveillance of invasive pneumococcal disease (IPD) was conducted in Germany. A total of 22,208 isolates from invasive pneumococcal disease were collected between July 1, 1992 and June 30, 2013. The present study was conducted to analyze changes in antimicrobial susceptibility and pneumococcal vaccine coverage after the introduction of pneumococcal conjugate vaccination in Germany. Most of the isolates originated from adults ≥16 years (82.5%), while 17.5% were obtained from children <16 years. Penicillin resistance was observed in 7.2% of meningitis cases both among children and adults during the entire study period. In the post-PCV13 period, the resistance rate was 11.3% in children and 10.0% in adults, which is higher than in the pre-PCV7 and post-PCV7 periods. In the non-meningitis group, an overall penicillin nonsusceptibility rate (intermediate resistance and resistance) of 0.5% was detected both among children and adults. Nonsusceptibility rates among children were 6.3% (pre-PCV7), 7.6% (post-PCV7) and 9.0% (post-PCV13). The corresponding nonsusceptibility rates among adults were 4.4%, 6.0% and 7.9%, respectively. Concerning cefotaxime, in meningitis cases 0.8% of all isolates were intermediate and 0.5% resistant among children, while among adults, 0.9% were intermediate and 0.2% resistant. In non meningitis cases, cefotaxime nonsusceptibility rates were 0.5% in children and 0.3% in adults. Macrolide nonsusceptibility rates were lower in the post-PCV13 period (children 8.2%; adults 8.8%) than in the post-PCV7 period (children 17.3%; adults 13.0%) and the pre-PCV7 period (children 24.8%; adults 13.3%). In the pre-PCV7 period, macrolide resistance was mainly caused by M-phenotype clones carrying the mefA gene. In the post-PCV7/13 period, ermB (MLSb-phenotype) was the dominant resistance marker. Overall nonsusceptibility rates were 5.5% for clindamycin (intermediate 0.3%, resistant 5.2%), 0.7% for levofloxacin (intermediate 0

  17. [Pneumococcal disease in adults: Risk levels and vaccine recommendations].

    PubMed

    Vila-Córcoles, Angel; Ochoa-Gondar, Olga

    2017-02-01

    There are currently two anti-pneumococcal vaccines available for use in adults: the classical 23-valent polysaccharide pneumococcal vaccine (PPV23) and the new 13-valent pneumococcal conjugate vaccine (PCV13). The main advantage of the PCV13 is the potentially better immunogenicity, with its major disadvantages being the higher cost and the lower serotype-coverage than the PPV23. The currently available scientific evidence supports the following basic recommendations: (i)among adults with greatest risk (basically asplenia and immunocompromised), a dual vaccination (PCV13+PPV23) is recommended; (ii)among adults with increased risk (basically persons >65years-old and patients 15-64years with chronic pulmonary or heart disease, diabetes and/or alcoholism), a single vaccination with PPV23 is recommended (single dose in primo-vaccinated >65years; re-vaccination at 5-10years in those primo-vaccinated <65years-old); and (iii) in the rest of adults (risk normal/low) vaccination is not recommended.

  18. Epidemiology of pneumococcal serotype 6A and 6C among invasive and carriage isolates from Alaska, 1986–2009☆

    PubMed Central

    Rudolph, Karen; Bruce, Michael; Bruden, Dana; Zulz, Tammy; Wenger, Jay; Reasonover, Alisa; Harker-Jones, Marcella; Hurlburt, Debby; Hennessy, Thomas

    2015-01-01

    We investigated serotype 6A/6C invasive pneumococcal disease (IPD) incidence, genetic diversity, and carriage before and after 7-valent pneumococcal conjugate vaccine (PCV7) introduction in Alaska. IPD cases (1986–2009) were identified through population-based laboratory surveillance. Isolates were initially serotyped by conventional methods, and 6C isolates were differentiated from 6A by polymerase chain reaction. Among invasive and carriage isolates initially typed as 6A, 35% and 50% were identified as 6C, respectively. IPD rates caused by serotype 6A or 6C among children <5 years did not change from the pre- to post-PCV7 period (P = 0.71 and P = 0.09, respectively). Multilocus sequence typing of IPD isolates revealed 28 sequence types. The proportion of serotype 6A carriage isolates decreased from 7.4% pre-PCV7 to 1.8% (P < 0.001) during 2008–2009; the proportion of serotype 6C carriage isolates increased from 3.0% to 8.4% (P = 0.004) among children <5 years. Continued surveillance is warranted to monitor changes in serotype distribution and prevalence. PMID:23276772

  19. Pneumococcal Vaccine to Counter Emerging Infectious Disease Threat in the Military

    DTIC Science & Technology

    2001-12-01

    clinical trial of the currently In 1945, the first successful trial of a polyvalent polysaccha- available 23- valent pneumococcal vaccine . The purpose...December 2001 1088 Pneumococcal Vaccine bers are affected by pneumococcal disease; however, because of Board 35 recommended that the 23- valent ...pnoeumococcal vaccines years studied to date. The efficacy of the conjugate 7- valent Athe bi-oeti peuis cc vacspcilcone, witvaccine in children appears to also

  20. A public health and budget impact analysis of vaccinating at-risk adults and the elderly against pneumococcal diseases in Germany.

    PubMed

    Jiang, Yiling; Gauthier, Aline; Annemans, Lieven; van der Linden, Mark; Nicolas-Spony, Laurence; Bresse, Xavier

    2012-10-01

    To assess the comparative public health and budget impact over 5 years of several pneumococcal vaccination strategies (23-valent pneumococcal polysaccharide vaccine [PPV23] and/or 13-valent pneumococcal conjugate vaccine [PCV13]) in Germany, within the context of changing invasive pneumococcal disease (IPD) incidence over time. A multi-cohort, population-based Markov model was developed. Uncertainty around vaccine effectiveness, costs and IPD incidence change was handled through scenario analyses. Between 2012 and 2016, the introduction of PCV13 in adults, compared with the use of PPV23, would be associated with a net estimated budget increase of €59.7 million (+6.7%) to €151.6 million (+13.7%). Impact on IPD incidence ranged from -113 cases (-0.8%) to +298 cases (+2.8%). Introducing PCV13 in adults is expected to significantly affect healthcare budgets. Adult vaccination with PPV23 remains the optimal vaccination strategy from public health and budget perspectives.

  1. AdcAII of Streptococcus pneumoniae Affects Pneumococcal Invasiveness

    PubMed Central

    Brown, Lindsey R.; Gunnell, Steven M.; Cassella, Adam N.; Keller, Lance E.; Scherkenbach, Lisa A.; Mann, Beth; Brown, Matthew W.; Hill, Rebecca; Fitzkee, Nicholas C.; Rosch, Jason W.; Tuomanen, Elaine I.; Thornton, Justin A.

    2016-01-01

    Across bacterial species, metal binding proteins can serve functions in pathogenesis in addition to regulating metal homeostasis. We have compared and contrasted the activities of zinc (Zn2+)-binding lipoproteins AdcA and AdcAII in the Streptococcus pneumoniae TIGR4 background. Exposure to Zn2+-limiting conditions resulted in delayed growth in a strain lacking AdcAII (ΔAdcAII) when compared to wild type bacteria or a mutant lacking AdcA (ΔAdcA). AdcAII failed to interact with the extracellular matrix protein laminin despite homology to laminin-binding proteins of related streptococci. Deletion of AdcA or AdcAII led to significantly increased invasion of A549 human lung epithelial cells and a trend toward increased invasion in vivo. Loss of AdcAII, but not AdcA, was shown to negatively impact early colonization of the nasopharynx. Our findings suggest that expression of AdcAII affects invasiveness of S. pneumoniae in response to available Zn2+ concentrations. PMID:26752283

  2. [Pneumococcal vaccination for persons 65 years of age and older].

    PubMed

    van den Bosch, W J H M

    2002-05-04

    In the Netherlands, in contrast to other countries, pneumococcal vaccination for older people and people at risk is not routine, except for patients under special circumstances, such as after a splenectomy. Although pneumococcal vaccination is an effective way to prevent invasive pneumococcal disease in young healthy persons, there is no conclusive evidence that it is effective in older people and people at risk without a good immune response. Pneumococcal disease can be an important complication of an ordinary flu. Because there is a high level of vaccination against influenza in the Netherlands, the risk of pneumococcal disease is low compared to other countries in the world. Adding a pneumococcal vaccine to the influenza vaccination could decrease the degree of protection against influenza. The experimental introduction of pneumococcal vaccination does not seem to lead to an increase in the number of patients that refuse vaccination against influenza.

  3. Risk of hospitalization due to pneumococcal disease in adults in Spain. The CORIENNE study

    PubMed Central

    Gil-Prieto, Ruth; Pascual-Garcia, Raquel; Walter, Stefan; Álvaro-Meca, Alejandro; Gil-De-Miguel, Ángel

    2016-01-01

    ABSTRACT Pneumococcal disease causes a high burden of disease in adults, leading to high rates of hospitalization, especially in the elderly. All hospital discharges for pneumococcal disease and pneumococcal pneumonia among adults over 18 y of age reported in first diagnostic position in 2011 (January 1, 2011 through December 31, 2011) were obtained. A total of 10,861 hospital discharges due to pneumococcal disease were reported in adults in Spain in 2011 with an annual incidence of hospitalization of 0.285 (CI 95%: 0.280–0.291) per 1,000 population over 18 y old. Case-fatality rate was 8%. Estimated cost of these hospitalisations in 2011 was more than 57 million €. Pneumococcal pneumonia accounted for the 92% of the hospital discharges All the chronic condition studied: asplenia, chronic respiratory disease, chronic heart disease, chronic renal disease, Diabetes Mellitus and immunosuppression, increased the risk of hospitalization in patients with pneumococcal pneumonia, especially in those aged 18–64 y old. Case-fatality rate among adult patients hospitalized with at least one underlying condition was significantly higher than among patients without comorbidities. Our results identified asplenia, chronic respiratory disease, chronic heart disease, chronic renal disease, chronic liver disease, Diabetes Mellitus and immunosuppression as risk groups for hospitalization. Older adults, immunocompromised patients and immunocompetent patients with underlying conditions could benefit from vaccination. PMID:26901683

  4. Rethinking risk for pneumococcal disease in adults: the role of risk stacking.

    PubMed

    Pelton, Stephen I; Shea, Kimberly M; Weycker, Derek; Farkouh, Raymond A; Strutton, David R; Edelsberg, John

    2015-01-01

    Using data from 3 private healthcare claims repositories, we evaluated the incidence of pneumococcal disease among adults with US Advisory Committee on Immunization Practices (ACIP) defined at-risk conditions or rheumatoid arthritis, lupus, Crohn's disease, and neuromuscular disorder/seizures and those with traditional high-risk conditions. We observed that adults with ≥2 concurrent comorbid conditions had pneumococcal disease incidence rates that were as high as or higher than rates observed in those with traditional high-risk conditions.

  5. Pneumococcal vaccination--current situation and perspectives.

    PubMed

    Madar, R; Strakova, J; Baska, T; Kavcova, E; Straka, S

    2005-01-01

    The authors carried out a survey in outpatient and hospitalised patients with risk factors for invasive pneumococcal disease in a tertiary-care medical faculty affiliated hospital. Data were collected by individual interviews and verified against the medical records of all addressed patients. The authors also attempted to discover the attitude of general practitioners (GPs) from 2 Slovak districts towards the pneumococcal vaccine by means of an anonymous questionnaire. Out of the total of 154 addressed patients, 128 (83.1%) had at least one risk factor for acquiring invasive pneumococcal disease. However, only 8 (6.3%) of them had ever been administered pneumococcal vaccine. Out of 34 hospitalised patients with at least one risk factor 82.4 % had not received any pneumococcal vaccination in the past. When subdivided according to age and risk factors (chronic respiratory, cardiovascular, uropoetic, metabolic, immunne system disorders, asplenia), vaccination coverage in all groups was very low, ranging between --9.3%. In an anonymous questionnaire 74 (94.9%) out of 77 surveyed GPs referred to a lack of information on the polysaccharide pneumococcal vaccine and 22 (28.2%) expressed their general distrust towards vaccination of any kind. The main role in increasing the disturbingly low pneumococcal vaccination coverage lies in the hands of medical professionals, especially GPs who should inform their patients about the possibility of a free vaccine and who should make an effort to explain to their patients the benefit of pneumococcal vaccination. (Tab. 4, Reft 9.)

  6. Postvaccination Increase in Serotype 19A Pneumococcal Disease in Norway Is Driven by Expansion of Penicillin-Susceptible Strains of the ST199 Complex

    PubMed Central

    Steinbakk, Martin; Aaberge, Ingeborg S.; Caugant, Dominique A.

    2012-01-01

    Serotype replacement in invasive pneumococcal disease has been observed after widespread use of the 7-valent pneumococcal conjugate vaccine (PCV7). Replacement is dominated by penicillin-nonsusceptible serotype 19A in several countries. Antibiotic selection pressure has been proposed to interact with immunization, leading to rapid replacement. In Norway, where prescription of antibiotics is limited, post-PCV7 replacement by serotype 19A is dominated by penicillin-susceptible clones. Hence, serotype 19A replacement occurs, although it is not driven by antibiotic selection pressure. PMID:22237889

  7. Pneumococcal disease in the Arabian Gulf: recognizing the challenge and moving toward a solution.

    PubMed

    Feldman, Charles; Abdulkarim, Emad; Alattar, Fatma; Al Lawati, Faryal; Al Khatib, Hisham; Al Maslamani, Muna; Al Obaidani, Idris; Al Salah, Mosaab; Farghaly, Mohamed; Husain, Entesar H; Mokadas, Eiman

    2013-12-01

    Pneumococcal disease has substantial incidence, morbidity and mortality in older adults. Decreased birth rates and longer lifespans indicate that the global population is aging, although rates of aging differ between countries [1]. In 2010, the proportion of the population aged >60 years in the general Arab Region was 7%, and this proportion is expected to rise to 19% by 2050 for the region as a whole [2]; the United Nations estimates for the individual countries of the Arabian Gulf by 2050 are 25.7%, 24.9%, 20.7%, 26.7% and 10.5% in the Kuwait, Bahrain, Qatar, United Arab Emirates (UAE) and Oman, respectively, which are comparable to the 26.9% predicted for the USA and lower than that predicted in European countries, in which the 2050 estimates are 32.7%, 34.0% and 38.1% for France, the UK and Germany, respectively [1]. Globally and in the Gulf Region, pneumococcal disease is an increasingly important public health burden in the elderly. The burden of pneumococcal disease can be reduced by effective vaccination programs, but the recommendations on pneumococcal vaccination in adults vary widely. The major barriers to vaccine implementation among healthcare professionals are an incomplete awareness of pneumococcal disease and the vaccination options in adults. The Gulf Advocate Group calls for healthcare providers in the countries of the Arabian Gulf (Kuwait, Bahrain, Qatar, United Arab Emirates and Oman) to support awareness and education programs about adult pneumococcal disease, particularly in high-risk groups such as those >65 years of age, those with type 2 diabetes mellitus, hematological malignancy, organ and bone marrow transplantation or chronic kidney or lung diseases and pilgrims undertaking the Hajj to improve pneumococcal disease surveillance and optimize and disseminate recommendations for adult vaccination. The Gulf Advocate Group recommends following the U.S. Centers for Disease Control and Prevention (CDC) guidelines for pneumococcal vaccination [3,4].

  8. Advances in pneumococcal antibiotic resistance.

    PubMed

    Song, Jae-Hoon

    2013-10-01

    Antimicrobial resistance and serotypes in Streptococcus pneumoniae have been evolving with the widespread use of antibiotics and the introduction of pneumococcal conjugate vaccines (PCV). Particularly, among various types of antimicrobial resistance, macrolide resistance has most remarkably increased in many parts of the world, which has been reported to be >70% among clinical isolates from Asian countries. Penicillin resistance has dramatically decreased among nonmeningeal isolates due to the changes in resistance breakpoints, although resistance to other β-lactams such as cefuroxime has increased. Multidrug resistance became a serious concern in the treatment of invasive pneumococcal diseases, especially in Asian countries. After PCV7 vaccination, serotype 19A has emerged as an important cause of invasive pneumococcal diseases which was also associated with increasing prevalence of multidrug resistance in pneumococci. Widespread use of PCV13, which covers additional serotypes 3, 6A and 19A, may contribute to reduce the clonal spread of drug-resistant 19A pneumococci.

  9. Complement component 5 contributes to poor disease outcome in humans and mice with pneumococcal meningitis.

    PubMed

    Woehrl, Bianca; Brouwer, Matthijs C; Murr, Carmen; Heckenberg, Sebastiaan G B; Baas, Frank; Pfister, Hans W; Zwinderman, Aeilko H; Morgan, B Paul; Barnum, Scott R; van der Ende, Arie; Koedel, Uwe; van de Beek, Diederik

    2011-10-01

    Pneumococcal meningitis is the most common and severe form of bacterial meningitis. Fatality rates are substantial, and long-term sequelae develop in about half of survivors. Disease outcome has been related to the severity of the proinflammatory response in the subarachnoid space. The complement system, which mediates key inflammatory processes, has been implicated as a modulator of pneumococcal meningitis disease severity in animal studies. Additionally, SNPs in genes encoding complement pathway proteins have been linked to susceptibility to pneumococcal infection, although no associations with disease severity or outcome have been established. Here, we have performed a robust prospective nationwide genetic association study in patients with bacterial meningitis and found that a common nonsynonymous complement component 5 (C5) SNP (rs17611) is associated with unfavorable disease outcome. C5 fragment levels in cerebrospinal fluid (CSF) of patients with bacterial meningitis correlated with several clinical indicators of poor prognosis. Consistent with these human data, C5a receptor-deficient mice with pneumococcal meningitis had lower CSF wbc counts and decreased brain damage compared with WT mice. Adjuvant treatment with C5-specific monoclonal antibodies prevented death in all mice with pneumococcal meningitis. Thus, our results suggest C5-specific monoclonal antibodies could be a promising new antiinflammatory adjuvant therapy for pneumococcal meningitis.

  10. Complement component 5 contributes to poor disease outcome in humans and mice with pneumococcal meningitis

    PubMed Central

    Woehrl, Bianca; Brouwer, Matthijs C.; Murr, Carmen; Heckenberg, Sebastiaan G.B.; Baas, Frank; Pfister, Hans W.; Zwinderman, Aeilko H.; Morgan, B. Paul; Barnum, Scott R.; van der Ende, Arie; Koedel, Uwe; van de Beek, Diederik

    2011-01-01

    Pneumococcal meningitis is the most common and severe form of bacterial meningitis. Fatality rates are substantial, and long-term sequelae develop in about half of survivors. Disease outcome has been related to the severity of the proinflammatory response in the subarachnoid space. The complement system, which mediates key inflammatory processes, has been implicated as a modulator of pneumococcal meningitis disease severity in animal studies. Additionally, SNPs in genes encoding complement pathway proteins have been linked to susceptibility to pneumococcal infection, although no associations with disease severity or outcome have been established. Here, we have performed a robust prospective nationwide genetic association study in patients with bacterial meningitis and found that a common nonsynonymous complement component 5 (C5) SNP (rs17611) is associated with unfavorable disease outcome. C5 fragment levels in cerebrospinal fluid (CSF) of patients with bacterial meningitis correlated with several clinical indicators of poor prognosis. Consistent with these human data, C5a receptor–deficient mice with pneumococcal meningitis had lower CSF wbc counts and decreased brain damage compared with WT mice. Adjuvant treatment with C5-specific monoclonal antibodies prevented death in all mice with pneumococcal meningitis. Thus, our results suggest C5-specific monoclonal antibodies could be a promising new antiinflammatory adjuvant therapy for pneumococcal meningitis. PMID:21926466

  11. Serotype-specific mortality from invasive Streptococcus pneumoniae disease revisited

    PubMed Central

    Martens, Pernille; Worm, Signe Westring; Lundgren, Bettina; Konradsen, Helle Bossen; Benfield, Thomas

    2004-01-01

    Background Invasive infection with Streptococcus pneumoniae (pneumococci) causes significant morbidity and mortality. Case series and experimental data have shown that the capsular serotype is involved in the pathogenesis and a determinant of disease outcome. Methods Retrospective review of 464 cases of invasive disease among adults diagnosed between 1990 and 2001. Multivariate Cox proportional hazard analysis. Results After adjustment for other markers of disease severity, we found that infection with serotype 3 was associated with an increased relative risk (RR) of death of 2.54 (95% confidence interval (CI): 1.22–5.27), whereas infection with serotype 1 was associated with a decreased risk of death (RR 0.23 (95% CI, 0.06–0.97)). Additionally, older age, relative leucopenia and relative hypothermia were independent predictors of mortality. Conclusion Our study shows that capsular serotypes independently influenced the outcome from invasive pneumococcal disease. The limitations of the current polysaccharide pneumococcal vaccine warrant the development of alternative vaccines. We suggest that the virulence of pneumococcal serotypes should be considered in the design of novel vaccines. PMID:15228629

  12. Non-Invasive Pneumococcal Pneumonia in Portugal—Serotype Distribution and Antimicrobial Resistance

    PubMed Central

    Horácio, Andreia N.; Lopes, Joana P.; Ramirez, Mário; Melo-Cristino, José

    2014-01-01

    There is limited information on the serotypes causing non-invasive pneumococcal pneumonia (NIPP). Our aim was to characterize pneumococci causing NIPP in adults to determine recent changes in serotype prevalence, the potential coverage of pneumococcal vaccines and changes in antimicrobial resistance. Serotypes and antimicrobial susceptibility profiles of a sample of 1300 isolates recovered from adult patients (≥18 yrs) between 1999 and 2011 (13 years) were determined. Serotype 3 was the most frequent cause of NIPP accounting for 18% of the isolates. The other most common serotypes were 11A (7%), 19F (7%), 19A (5%), 14 (4%), 22F (4%), 23F (4%) and 9N (4%). Between 1999 and 2011, there were significant changes in the proportion of isolates expressing vaccine serotypes, with a steady decline of the serotypes included in the 7-valent conjugate vaccine from 31% (1999–2003) to 11% (2011) (P<0.001). Taking together the most recent study years (2009–2011), the potential coverage of the 13-valent conjugate vaccine was 44% and of the 23-valent polysaccharide vaccine was 66%. While erythromycin resistance increased from 8% in 1999–2003 to 18% in 2011 (P<0.001), no significant trend was identified for penicillin non-susceptibility, which had an average value of 18.5%. The serotype distribution found in this study for NIPP was very different from the one previously described for IPD, with only two serotypes in common to the ones responsible for half of each presentation in 2009–2011 – serotypes 3 and 19A. In spite of these differences, the overall prevalence of resistant isolates was similar in NIPP and in IPD. PMID:25075961

  13. Risk factors for pneumococcal nasopharyngeal colonization before and after pneumococcal conjugate vaccination in persons with HIV: brief report.

    PubMed

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

    2012-04-01

    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 patients (23%) were colonized, 11 at baseline only, four at both baseline and 9 months, and seven at 9 months only. Compared to non-colonized patients, more colonized patients were smokers, had lower CD4+ nadir and had an AIDS-diagnosis. Immunization, antiretroviral treatment and the CPG adjuvant had no impact on colonization. These results suggest preventive strategies in addition to pneumococcal immunization.

  14. Pneumococcal colonisation density: a new marker for disease severity in HIV-infected adults with pneumonia

    PubMed Central

    Albrich, Werner C; Madhi, Shabir A; Adrian, Peter V; van Niekerk, Nadia; Telles, Jean-Noel; Ebrahim, N; Messaoudi, Melina; Paranhos-Baccalà, Glaucia; Giersdorf, Sven; Vernet, Guy; Mueller, Beat; Klugman, Keith P

    2014-01-01

    Objective A high genomic load of Pneumococcus from blood or cerebrospinal fluid has been associated with increased mortality. We aimed to analyse whether nasopharyngeal colonisation density in HIV-infected patients with community-acquired pneumonia (CAP) is associated with markers of disease severity or poor outcome. Methods Quantitative lytA real-time PCR was performed on nasopharyngeal swabs in HIV-infected South African adults hospitalised for acute CAP at Chris Hani Baragwanath Hospital, Soweto, South Africa. Pneumonia aetiology was considered pneumococcal if any sputum culture or Gram stain, urinary pneumococcal C-polysaccharide-based antigen, blood culture or whole blood lytA real-time PCR revealed pneumococci. Results There was a moderate correlation between the mean nasopharyngeal colonisation densities and increasing CURB65 scores among all-cause patients with pneumonia (Spearman correlation coefficient r=0.15, p=0.06) or with the Pitt bacteraemia score among patients with pneumococcal bacteraemia (p=0.63). In patients with pneumococcal pneumonia, nasopharyngeal pneumococcal colonisation density was higher among non-survivors than survivors (7.7 vs 6.1 log10 copies/mL, respectively, p=0.02) and among those who had pneumococci identified from blood cultures and/or by whole blood lytA real-time PCR than those with non-bacteraemic pneumococcal pneumonia (6.6 vs 5.6 log10 copies/mL, p=0.03). Nasopharyngeal colonisation density correlated positively with the biomarkers procalcitonin (Spearman correlation coefficient r=0.37, p<0.0001), proadrenomedullin (r=0.39, p=0.008) and copeptin (r=0.30, p=0.01). Conclusions In addition to its previously reported role as a diagnostic tool for pneumococcal pneumonia, quantitative nasopharyngeal colonisation density also correlates with mortality and prognostic biomarkers. It may also be useful as a severity marker for pneumococcal pneumonia in HIV-infected adults. PMID:25113557

  15. South Asia symposium on pneumococcal disease and the promise of vaccines – Meeting report

    PubMed Central

    Kumar, Rakesh; Arora, Narendra; Santosham, Mathuram

    2016-01-01

    Despite the licensure of the pneumococcal conjugate vaccine (PCV) in the US and other Western countries for over 14 years, as of September 2014 only 4 South Asian countries were using PCV in their universal immunization program. To generate momentum toward addressing this issue a “South Asia symposium on pneumococcal disease and the promise of vaccines” was organized just prior to the 9th international symposium on pneumococci and pneumococcal diseases held in India recently. Leading scientists, program managers, and decision makers including ministry officials from the region participated in the meeting. The participants discussed available data on pneumococcal disease burden in South Asia, surveillance methods, efficacy and safety of pneumococcal conjugate vaccines (PCV), the status of PCV introduction, programmatic challenges in introducing PCV and available data on the impact of PCV in South Asia and globally. There was a strong consensus that available data on disease burden and the global experience with PCV justified the introduction PCV in all Asian countries in order to accelerate the gains in child survival in the region. PMID:27026150

  16. Rethinking Risk for Pneumococcal Disease in Adults: The Role of Risk Stacking

    PubMed Central

    Pelton, Stephen I.; Shea, Kimberly M.; Weycker, Derek; Farkouh, Raymond A.; Strutton, David R.; Edelsberg, John

    2015-01-01

    Using data from 3 private healthcare claims repositories, we evaluated the incidence of pneumococcal disease among adults with US Advisory Committee on Immunization Practices (ACIP) defined at-risk conditions or rheumatoid arthritis, lupus, Crohn's disease, and neuromuscular disorder/seizures and those with traditional high-risk conditions. We observed that adults with ≥2 concurrent comorbid conditions had pneumococcal disease incidence rates that were as high as or higher than rates observed in those with traditional high-risk conditions. PMID:26034770

  17. Invasive bacterial diseases in northern Canada.

    PubMed

    Degani, Naushaba; Navarro, Christine; Deeks, Shelley L; Lovgren, Marguerite

    2008-01-01

    International Circumpolar Surveillance (ICS) is a population-based invasive bacterial disease surveillance network. Participating Canadian regions include Yukon, Northwest Territories, Nunavut, and northern regions of Québec and Labrador (total population 132,956, 59% aboriginal). Clinical and demographic information were collected by using standardized surveillance forms. Bacterial isolates were forwarded to reference laboratories for confirmation and serotyping. After pneumococcal conjugate vaccine introduction, crude annual incidence rates of invasive Streptococcus pneumoniae decreased from 34.0/100,000 population (1999-2002) to 23.6/100,000 population (2003-2005); substantial reductions were shown among aboriginals. However, incidence rates of S. pneumoniae, Haemophilus influenzae, and group A streptococci were higher in aboriginal populations than in non-aboriginal populations. H. influenzae type b was rare; 52% of all H. influenzae cases were caused by type a. Data collected by ICS contribute to the understanding of the epidemiology of invasive bacterial diseases among northern populations, which assists in formulation of prevention and control strategies, including immunization recommendations.

  18. Prophylactic antibiotics for preventing pneumococcal infection in children with sickle cell disease.

    PubMed

    Hirst, Ceri; Owusu-Ofori, Shirley

    2014-11-06

    Background This is an update of a Cochrane Review first published in 2002, and previously updated in 2012. People with sickle cell disease are particularly susceptible to infection. Infants and very young children are especially vulnerable, and the 'Co-operative Study of Sickle Cell Disease' observed an incidence rate of 10 per 100 patient years of pneumococcal septicaemia in children under the age of three.Vaccines, including customary pneumococcal vaccines, may be of limited use in this age group. Therefore, prophylactic penicillin regimens may be advisable for this population.Objectives To assess the effects of prophylactic antibiotic regimens for preventing pneumococcal infection in children with sickle cell disease.Search methods We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register, which is comprised of references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Date of the most recent search: 26 June 2014.Selection criteria All randomised or quasi-randomised controlled trials comparing prophylactic antibiotics to prevent pneumococcal infection in children with sickle cell disease with placebo, no treatment or a comparator drug.Data collection and analysis Both authors independently extracted data and assessed trial quality.Main results Five trials were identified by the initial search, of which three trials met the inclusion criteria. All of the included trials showed a reduced incidence of infection in children with sickle cell disease (SS or Sβ0Thal) receiving prophylactic penicillin. In trials which investigated initiation of penicillin on risk of pneumococcal infection, the odds ratio was 0.37 (95% CI 0.16 to 0.86), while for withdrawal the odds ratio was 0.49 (95% CI 0.09 to 2.71). Adverse drug effects were rare and minor. Rates of pneumococcal infection were found to be relatively low in children over the age

  19. Pneumococcal vaccination in adults: recommendations, trends, and prospects.

    PubMed

    Targonski, Paul V; Poland, Gregory A

    2007-06-01

    The US Centers for Disease Control and Prevention recommends vaccination against Streptococcus pneumoniae for all people age 65 and older and also for younger people at high risk. However, experts continue to debate the efficacy of the vaccine; most observational studies found it beneficial, while clinical trials were inconclusive as a group. Although pneumococcal vaccination may or may not protect against pneumonia or death from any cause, it does significantly decrease the risk of invasive pneumococcal disease and is worthwhile for this reason.

  20. Pneumococcal Antibody Titers

    PubMed Central

    Abghari, Pamella F.; Poowuttikul, Pavadee; Secord, Elizabeth

    2017-01-01

    Purpose: Immunoglobulin replacement is the mainstay treatment in patients with humoral immunodeficiencies, yet a handful of patients continue to develop sinopulmonary infections while on therapy. The objective of our study was to compare immunoglobulin G (IgG) pneumococcal antibody levels in patients with humoral immune deficiencies who have been on intravenous immunoglobulin (IVIG) replacement for at least 1 year to those on subcutaneous immunoglobulin (SCIG) therapy for at least 1 year. Methods: A retrospective chart review was completed on 28 patients. These patients’ ages ranged between 1 and 61 years. Pneumococcal serotype titers obtained at least 1 year after initiating therapy were compared between patients on IVIG (19 patients) and SCIG (9 patients). Results: A comparison between the groups demonstrated that SCIG achieved a higher percentage of serotype titers protective for noninvasive disease (≥1.3) and 100% protection for invasive disease (≥0.2). Our data also demonstrated a similar lack of protection (less than 50% ≥1.3) in 9N, 12F, and 23F on IVIG and 4, 9N, 12F, and 23F on SCIG. Conclusions: Our data demonstrated that serotypes 1, 3, 4, 9N, 12F, and 23F exhibited the lowest random IgG means while on IVIG, which was comparable to other published studies that looked at the mean IgG levels. In addition, our retrospective chart review demonstrated a greater number of therapeutic pneumococcal titers with SCIG in comparison to IVIG. PMID:28321436

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

    PubMed Central

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

    2016-01-01

    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

  2. Intraclonal Variations Among Streptococcus pneumoniae Isolates Influence the Likelihood of Invasive Disease in Children

    PubMed Central

    Browall, Sarah; Norman, Martin; Tångrot, Jeanette; Galanis, Ilias; Sjöström, Karin; Dagerhamn, Jessica; Hellberg, Christel; Pathak, Anuj; Spadafina, Tiziana; Sandgren, Andreas; Bättig, Patrick; Franzén, Oscar; Andersson, Björn; Örtqvist, Åke; Normark, Staffan; Henriques-Normark, Birgitta

    2014-01-01

    Background. Pneumococcal serotypes are represented by a varying number of clonal lineages with different genetic contents, potentially affecting invasiveness. However, genetic variation within the same genetic lineage may be larger than anticipated. Methods. A total of 715 invasive and carriage isolates from children in the same region and during the same period were compared using pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing. Bacterial genome sequencing, functional assays, and in vivo virulence mice studies were performed. Results. Clonal types of the same serotype but also intraclonal variants within clonal complexes (CCs) showed differences in invasive-disease potential. CC138, a common CC, was divided into several PFGE patterns, partly explained by number, location, and type of temperate bacteriophages. Whole-genome sequencing of 4 CC138 isolates representing PFGE clones with different invasive-disease potentials revealed intraclonal sequence variations of the virulence-associated proteins pneumococcal surface protein A (PspA) and pneumococcal choline-binding protein C (PspC). A carrier isolate lacking PcpA exhibited decreased virulence in mice, and there was a differential binding of human factor H, depending on invasiveness. Conclusions. Pneumococcal clonal types but also intraclonal variants exhibited different invasive-disease potentials in children. Intraclonal variants, reflecting different prophage contents, showed differences in major surface antigens. This suggests ongoing immune selection, such as that due to PspC-mediated complement resistance through varied human factor H binding, that may affect invasiveness in children. PMID:24009156

  3. Pneumococcal Carriage in Children under Five Years in Uganda-Will Present Pneumococcal Conjugate Vaccines Be Appropriate?

    PubMed Central

    Kalyango, Joan; Alfvén, Tobias; Darenberg, Jessica; Kadobera, Daniel; Bwanga, Freddie; Peterson, Stefan; Henriques-Normark, Birgitta; Källander, Karin

    2016-01-01

    Background Pneumonia is the major cause of death in children globally, with more than 900,000 deaths annually in children under five years of age. Streptococcus pneumoniae causes most deaths, most often in the form of community acquired pneumonia. Pneumococcal conjugate vaccines (PCVs) are currently being implemented in many low-income countries. PCVs decrease vaccine-type pneumococcal carriage, a prerequisite for invasive pneumococcal disease, and thereby affects pneumococcal disease and transmission. In Uganda, PCV was launched in 2014, but baseline data is lacking for pneumococcal serotypes in carriage. Objectives To study pneumococcal nasopharyngeal carriage and serotype distribution in children under 5 years of age prior to PCV introduction in Uganda Methods Three cross-sectional pneumococcal carriage surveys were conducted in 2008, 2009 and 2011, comprising respectively 150, 587 and 1024 randomly selected children aged less than five years from the Iganga/Mayuge Health and Demographic Surveillance Site. The caretakers were interviewed about illness history of the child and 1723 nasopharyngeal specimens were collected. From these, 927 isolates of S. pneumoniae were serotyped. Results Overall, the carriage rate of S. pneumoniae was 56% (957/1723). Pneumococcal carriage was associated with illness on the day of the interview (OR = 1.50, p = 0.04). The most common pneumococcal serotypes were in descending order 19F (16%), 23F (9%), 6A (8%), 29 (7%) and 6B (7%). One percent of the strains were non-typeable. The potential serotype coverage rate for PCV10 was 42% and 54% for PCV13. Conclusion About half of circulating pneumococcal serotypes in carriage in the Ugandan under-five population studied was covered by available PCVs. PMID:27829063

  4. [Statement of the Advisory Immunization Committee of the Chilean Society of Infectious Diseases on the emergence of serotype 19A pneumococcal infection and the use of pneumococcal conjugated vaccine in Chilean children].

    PubMed

    Potin, Marcela; Fica, Alberto; Wilhem, Jan; Cerda, Jaime; Contreras, Lily; Escobar, Carola; Moreno, Gabriela; Muñoz, Alma; Véliz, Liliana

    2016-06-01

    Inclusion of the 10-valent pneumococcal conjugated vaccine (PCV10) in the Chilean infant vaccination Program in 2011 was followed by a reduction of hospital admissions and pneumonia-related deaths in this age group. However, a progressive increase of serotype 19A pneumococcal isolates (not included in PCV10) has been observed. According to the analysis of pneumococcal strains performed by the national reference laboratory of the Institute of Public Health as part of a national surveillance on invasive pneumococcal infections, the relative proportion of serotype 19A isolates increased from <5% before 2010 to 12-23% in years 2014-2015. Serotype 19A represented 4-8% of the isolates in the pre-vaccine era among children less than 2 years, increasing to 25% during 2014. This increase has been documented in two-thirds of the national territory. Aimong children <5 years of age, 25% of 19A serotype isolates from non-meningeal infections were penicillin resistant wheras from meningeal infections near 100% were penicillin resistant. Genetic analysis indicates that 48% of these 19A strains belong to clonal complex 320, recognized for its pandemic potential and high antimicrobial resistance. Among children, most invasive infections secondary to serotype 19A have occurred in patients fully vaccinated with PCV10. These epidemiological changes indicate an increase in invasive pneumococcal infections by serotype 19A in Chile and the need to control this problem by changing the current PCV10 for the PCV13 vaccine containing serotype 19A.

  5. Increased incidence of adult pneumococcal pneumonia during school holiday periods

    PubMed Central

    Rodrigo, Chamira; Bewick, Thomas; Sheppard, Carmen; Greenwood, Sonia; McKeever, Tricia M.; Slack, Mary; Lim, Wei Shen

    2017-01-01

    Child contact is a recognised risk factor for adult pneumococcal disease. Peaks in invasive pneumococcal disease incidence observed during winter holidays may be related to changes in social dynamics. This analysis was conducted to examine adult pneumococcal community-acquired pneumonia (CAP) incidence during school holiday periods. Between September 2008 and 2013, consecutive adults admitted to hospitals covering the Greater Nottingham area with a diagnosis of CAP were studied. Pneumococcal pneumonia was detected using culture and antigen detection methods. Of 2221 adults studied, 575 (25.9%) were admitted during school holidays and 643 (29.0%) had pneumococcal CAP. CAP of pneumococcal aetiology was significantly more likely in adults admitted during school holidays compared to term time (35.3% versus 26.7%; adjusted OR 1.38, 95% CI 1.11–1.72, p=0.004). Over the 5-year period, the age-adjusted incidence of hospitalised pneumococcal CAP was higher during school holidays compared to term time (incident rate ratio 1.35, 95% CI 1.14–1.60, p<0.001); there was no difference in rates of all-cause CAP or non-pneumococcal CAP. Reported child contact was higher in individuals with pneumococcal CAP admitted during school holidays compared to term time (42.0% versus 33.7%, OR 1.43, 95% CI 1.00–2.03, p=0.046). Further study of transmission dynamics in relation to these findings and to identify appropriate intervention strategies is warranted. PMID:28326311

  6. A multilocus sequence typing scheme for Streptococcus pneumoniae: identification of clones associated with serious invasive disease.

    PubMed

    Enright, M C; Spratt, B G

    1998-11-01

    The population biology of Streptococcus pneumoniae is poorly understood. Most of the important issues could be addressed by the molecular characterization of large, well sampled populations from carriage and from the different manifestations of pneumococcal disease. The authors have therefore developed a pneumococcal multilocus sequence typing scheme and database by sequencing approximately 450 bp fragments of seven housekeeping loci from 295 isolates. The combination of alleles at the seven loci provided an allelic profile, or sequence type (ST), and the relatedness between isolates was obtained by constructing a dendrogram from the matrix of pairwise differences between STs. The typing scheme was validated using pneumococci of known genetic relatedness and could resolve >6 billion STs. Among 274 isolates from recent cases of invasive pneumococcal disease in eight countries, 143 STs were resolved, but 12 STs contained at least five isolates (range 5-21 isolates). The repeated recovery of indistinguishable isolates from invasive disease in different countries implies that these STs define strains with an increased capacity to cause invasive disease. The relationship between STs and serotypes suggested that, in the longer term, capsular genes have been distributed horizontally within the pneumococcal population, but in the short term, expansion of clones occurs with only occasional changes of serotype. The multilocus sequence typing scheme provides a powerful new approach to the characterization of pneumococci, since it provides molecular typing data that are electronically portable between laboratories, and which can be used to probe aspects of the population and evolutionary biology of these organisms. A Web site for the molecular characterization of pneumococci by MLST is available (http ://mlst.zoo.ox.ac.uk).

  7. The Saudi Thoracic Society pneumococcal vaccination guidelines-2016

    PubMed Central

    Alharbi, N. S.; Al-Barrak, A. M.; Al-Moamary, M. S.; Zeitouni, M. O.; Idrees, M. M.; Al-Ghobain, M. O.; Al-Shimemeri, A. A.; Al-Hajjaj, Mohamed S.

    2016-01-01

    Streptococcus pneumoniae (pneumococcus) is the leading cause of morbidity and mortality worldwide. Saudi Arabia is a host to millions of pilgrims who travel annually from all over the world for Umrah and the Hajj pilgrimages and are at risk of developing pneumococcal pneumonia or invasive pneumococcal disease (IPD). There is also the risk of transmission of S. pneumoniae including antibiotic resistant strains between pilgrims and their potential global spread upon their return. The country also has unique challenges posed by susceptible population to IPD due to people with hemoglobinopathies, younger age groups with chronic conditions, and growing problem of antibiotic resistance. Since the epidemiology of pneumococcal disease is constantly changing, with an increase in nonvaccine pneumococcal serotypes, vaccination policies on the effectiveness and usefulness of vaccines require regular revision. As part of the Saudi Thoracic Society (STS) commitment to promote the best practices in the field of respiratory diseases, we conducted a review of S. pneumoniae infections and the best evidence base available in the literature. The aim of the present study is to develop the STS pneumococcal vaccination guidelines for healthcare workers in Saudi Arabia. We recommend vaccination against pneumococcal infections for all children <5 years old, adults ≥50 years old, and people ≥6 years old with certain risk factors. These recommendations are based on the presence of a large number of comorbidities in Saudi Arabia population <50 years of age, many of whom have risk factors for contracting pneumococcal infections. A section for pneumococcal vaccination before the Umrah and Hajj pilgrimages is included as well. PMID:27168856

  8. Pneumococcal Infections: MedlinePlus Health Topic

    MedlinePlus

    ... Disease Control and Prevention) - PDF Also in Spanish Topic Image MedlinePlus Email Updates Get Pneumococcal Infections updates ... ray Meningitis - pneumococcal Sputum gram stain Related Health Topics Meningitis Pneumonia Sepsis Sinusitis Streptococcal Infections National Institutes ...

  9. Education does pay off: pneumococcal vaccine screening and administration in hospitalized adult patients with pneumonia.

    PubMed

    Kruspe, Rachel; Lillis, Rebecca; Daberkow, Dayton W; Blais, Christopher M; Wilbright, Wayne; Gupta, Shaminder; Gould, Cynthia A; Sun, Tony; Martinez, Jorge A; deBoisblanc, Ben; Ladabaum, Uri; Sanders, Charles V; Lopez, Fred A

    2003-01-01

    Streptococcus pneumoniae-associated infections are an important cause of hospitalization and mortality in high-risk and elderly patients. Even in the setting of appropriate therapy, the case fatality rate of invasive pneumococcal disease in the elderly may approach 40%. Since approximately 40,000 people die annually from pneumococcal-associated disease, it represents a substantial target for vaccine-preventable, bacterial fatalities. The 23-valent pneumococcal polysaccharide vaccine has proven consistently effective in preventing invasive pneumococcal disease. Despite its endorsement by numerous specialty societies, the pneumococcal vaccine is underutilized in the inpatient setting. In a recent report of quality indicators for Medicare beneficiaries, the percentage of Medicare beneficiaries in Louisiana admitted with pneumonia who were screened or received the pneumococcal vaccination prior to discharge was only 4%, the lowest percentage in the United States. The Louisiana State University-New Orleans Internal Medicine Department and its house staff embarked upon a retrospective study to determine its baseline pneumococcal vaccination or screening rates for all patients with pneumonia on its inpatient services at the The Medical Center of Louisiana in New Orleans from July 2000 through June 2001. From July 2001 through June 2002 an intensive educational intervention concentrating on the indications and benefits of pneumococcal vaccination was directed toward the Louisiana State University Internal Medicine house staff assigned to the inpatient service. Retrospective analysis for pneumococcal vaccine screening and administration of charts of all patients with pneumonia on the LSU Medicine service from July 2001 through June 2002 was performed in order to determine the effects of the intervention. Data from the pre-educational intervention period revealed a baseline pneumococcal vaccine screening or administration rate of 11% for all patients with pneumonia on the

  10. Serotype distribution of pneumococci isolated from pediatric patients with acute otitis media and invasive infections, and potential coverage of pneumococcal conjugated vaccines.

    PubMed

    Reijtman, Vanesa; Fossati, Sofía; Hernández, Claudia; Sommerfleck, Patricia; Bernáldez, Patricia; Litterio, Mirta; Berberian, Griselda; Regueira, Mabel; Lopardo, Horacio

    2013-01-01

    A 16-month prospective, descriptive study was conducted on pneumococcal serotype distribution isolated from children with acute otitis media (AOM) and invasive infections (INV). Eighty-nine children with pneumococcal INV and 324 with a first episode of AOM were included. Bacterial pathogens (N = 326) were isolated from the middle-ear fluid of 250 patients. A total of 30 pneumococcal serotypes were identified. Prevalent serotypes were 14, 19A, 9V, 3, 19F, 6A, 23F, and 18C in AOM and 14, 1, 19A, 5, 12F, 6B, and 18C in INV. Potential coverage with PCV10 vaccine would be 46.5 % and 60.7 % for pneumococci involved in AOM and INV, respectively; it would be 71.7 % and 73 % with PCV13. PCV10, conjugated with a Haemophilus protein, would have an immunologic coverage of 39.9 % for AOM vs. 18.5 % with PCV13. However, differences in the prevention of INV were crucial for the decision to include the 13-valent vaccine in the national calendar for children less than two years old in Argentina.

  11. Pneumococcal vaccination among HIV-infected adult patients in the era of combination antiretroviral therapy

    PubMed Central

    Lee, Kuan-Yeh; Tsai, Mao-Song; Kuo, Kuang-Che; Tsai, Jen-Chih; Sun, Hsin-Yun; Cheng, Aristine C; Chang, Sui-Yuan; Lee, Chen-Hsiang; Hung, Chien-Ching

    2014-01-01

    HIV-infected patients remain at higher risk for pneumococcal disease than the general population despite immune reconstitution and suppression of HIV replication with combination antiretroviral therapy. Vaccination with 23-valent pneumococcal polysaccharide vaccine (PPV23) composed of T-cell-independent antigens has been recommended to reduce the risk of pneumococcal disease in HIV-infected adults. However, given the heterogeneity of study design, execution and subjects enrolled, studies examining serological responses to PPV23 yielded conflicting results and observational studies of clinical effectiveness only provided moderate evidence to support the routine use of PPV23 in HIV-infected adults. Pneumococcal conjugate vaccine (PCV), with conjugation of the capsular polysaccharide to a protein carrier, is more immunogenic than PPV23 and has been demonstrated to protect against pneumococcal disease in HIV-infected children and recurrent invasive pneumococcal disease in HIV-infected adolescents and adults. Guidelines have recently been revised to recommend that HIV-infected patients aged 19 y or older receive one dose of 13-valent pneumococcal conjugate vaccine (PCV13) followed by a booster vaccination with PPV23. In this paper, we review the studies using different vaccination strategies to improve immunogenicity among HIV-infected adult patients. PMID:25483681

  12. Serotype and clonal evolution of penicillin-nonsusceptible invasive Streptococcus pneumoniae in the 7-valent pneumococcal conjugate vaccine era in Italy.

    PubMed

    Gherardi, Giovanni; D'Ambrosio, Fabio; Visaggio, Daniela; Dicuonzo, Giordano; Del Grosso, Maria; Pantosti, Annalisa

    2012-09-01

    The percentage of invasive penicillin-nonsusceptible pneumococci (PNSSP) isolated in Italy in the seven-valent pneumococcal conjugate vaccine (PCV7) era moderately increased in comparison to the pre-PCV7 era. Increase of nonvaccine serotypes was observed among PNSSP. The most frequent PNSSP clones were the same as those identified in the pre-PCV7 era, although they were present in different proportions. Clonal expansion, emergence of new clones, and acquisition of penicillin resistance by established clones contributed to the maintenance of penicillin resistance.

  13. Streptococcus pneumoniae in biofilms are unable to cause invasive disease due to altered virulence determinant production.

    PubMed

    Sanchez, Carlos J; Kumar, Nikhil; Lizcano, Anel; Shivshankar, Pooja; Dunning Hotopp, Julie C; Jorgensen, James H; Tettelin, Hervé; Orihuela, Carlos J

    2011-01-01

    It is unclear whether Streptococcus pneumoniae in biofilms are virulent and contribute to development of invasive pneumococcal disease (IPD). Using electron microscopy we confirmed the development of mature pneumococcal biofilms in a continuous-flow-through line model and determined that biofilm formation occurred in discrete stages with mature biofilms composed primarily of dead pneumococci. Challenge of mice with equal colony forming units of biofilm and planktonic pneumococci determined that biofilm bacteria were highly attenuated for invasive disease but not nasopharyngeal colonization. Biofilm pneumococci of numerous serotypes were hyper-adhesive and bound to A549 type II pneumocytes and Detroit 562 pharyngeal epithelial cells at levels 2 to 11-fold greater than planktonic counterparts. Using genomic microarrays we examined the pneumococcal transcriptome and determined that during biofilm formation S. pneumoniae down-regulated genes involved in protein synthesis, energy production, metabolism, capsular polysaccharide (CPS) production, and virulence. We confirmed these changes by measuring CPS by ELISA and immunoblotting for the toxin pneumolysin and the bacterial adhesins phosphorylcholine (ChoP), choline-binding protein A (CbpA), and Pneumococcal serine-rich repeat protein (PsrP). We conclude that biofilm pneumococci were avirulent due to reduced CPS and pneumolysin production along with increased ChoP, which is known to bind C-reactive protein and is opsonizing. Likewise, biofilm pneumococci were hyper-adhesive due to selection for the transparent phase variant, reduced CPS, and enhanced production of PsrP, CbpA, and ChoP. These studies suggest that biofilms do not directly contribute to development of IPD and may instead confer a quiescent mode of growth during colonization.

  14. Allergic Lung Inflammation Reduces Tissue Invasion and Enhances Survival from Pulmonary Pneumococcal Infection in Mice, Which Correlates with Increased Expression of Transforming Growth Factor β1 and SiglecF(low) Alveolar Macrophages.

    PubMed

    Sanfilippo, Alan M; Furuya, Yoichi; Roberts, Sean; Salmon, Sharon L; Metzger, Dennis W

    2015-07-01

    Asthma is generally thought to confer an increased risk for invasive pneumococcal disease (IPD) in humans. However, recent reports suggest that mortality rates from IPD are unaffected in patients with asthma and that chronic obstructive pulmonary disease (COPD), a condition similar to asthma, protects against the development of complicated pneumonia. To clarify the effects of asthma on the subsequent susceptibility to pneumococcal infection, ovalbumin (OVA)-induced allergic lung inflammation (ALI) was induced in mice followed by intranasal infection with A66.1 serotype 3 Streptococcus pneumoniae. Surprisingly, mice with ALI were significantly more resistant to lethal infection than non-ALI mice. The heightened resistance observed following ALI correlated with enhanced early clearance of pneumococci from the lung, decreased bacterial invasion from the airway into the lung tissue, a blunted inflammatory cytokine and neutrophil response to infection, and enhanced expression of transforming growth factor β1 (TGF-β1). Neutrophil depletion prior to infection had no effect on enhanced early bacterial clearance or resistance to IPD in mice with ALI. Although eosinophils recruited into the lung during ALI appeared to be capable of phagocytizing bacteria, neutralization of interleukin-5 (IL-5) to inhibit eosinophil recruitment likewise had no effect on early clearance or survival following infection. However, enhanced resistance was associated with an increase in levels of clodronate-sensitive, phagocytic SiglecF(low) alveolar macrophages within the airways following ALI. These findings suggest that, while the risk of developing IPD may actually be decreased in patients with acute asthma, additional clinical data are needed to better understand the risk of IPD in patients with different asthma phenotypes.

  15. What do we know about the cost-effectiveness of pneumococcal conjugate vaccination in older adults?

    PubMed

    Newall, A T

    2016-10-02

    The cost-effectiveness of 13-type pneumococcal conjugate vaccine (PCV13) use in older adults, and the relative merits when compared to the 23-type polysaccharide pneumococcal vaccine (PPV23), has been a topic of much debate. Although a number of economics evaluations have been conducted many of these were completed before the availability of critical data on PCV13 efficacy in older adults. Recent studies using this data have found conflicting results. This may in part reflect differences in the level of herd protection from infant pneumococcal vaccination programs in different countries. The costs and benefits of pneumococcal vaccination in adults are likely to rest on several critical parameters: the magnitude pneumococcal disease in older adults and the serotypes responsible for it, the efficacy of each vaccine against invasive and non-invasive pneumonia, the duration of vaccine protection, and differences in vaccine price. The ongoing changes in pneumococcal disease patterns highlight the need for economic evaluations to use recent serotype-specific disease estimates from the setting under consideration. In countries that do recommend PCV13 use in adults, post-implementation economic evaluation (using data from after a program is implemented) may be useful to help inform potential future changes to vaccine recommendations as well as the maximum price that should be paid for the vaccines in future negotiations.

  16. Influenza and Pneumococcal Vaccinations for Patients With Chronic Obstructive Pulmonary Disease (COPD)

    PubMed Central

    Sehatzadeh, S

    2012-01-01

    Executive Summary In July 2010, the Medical Advisory Secretariat (MAS) began work on a Chronic Obstructive Pulmonary Disease (COPD) evidentiary framework, an evidence-based review of the literature surrounding treatment strategies for patients with COPD. This project emerged from a request by the Health System Strategy Division of the Ministry of Health and Long-Term Care that MAS provide them with an evidentiary platform on the effectiveness and cost-effectiveness of COPD interventions. After an initial review of health technology assessments and systematic reviews of COPD literature, and consultation with experts, MAS identified the following topics for analysis: vaccinations (influenza and pneumococcal), smoking cessation, multidisciplinary care, pulmonary rehabilitation, long-term oxygen therapy, noninvasive positive pressure ventilation for acute and chronic respiratory failure, hospital-at-home for acute exacerbations of COPD, and telehealth (including telemonitoring and telephone support). Evidence-based analyses were prepared for each of these topics. For each technology, an economic analysis was also completed where appropriate. In addition, a review of the qualitative literature on patient, caregiver, and provider perspectives on living and dying with COPD was conducted, as were reviews of the qualitative literature on each of the technologies included in these analyses. The Chronic Obstructive Pulmonary Disease Mega-Analysis series is made up of the following reports, which can be publicly accessed at the MAS website at: http://www.hqontario.ca/en/mas/mas_ohtas_mn.html. Chronic Obstructive Pulmonary Disease (COPD) Evidentiary Framework Influenza and Pneumococcal Vaccinations for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis Smoking Cessation for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis Community-Based Multidisciplinary Care for Patients With Stable Chronic Obstructive

  17. Macrophage migration inhibitory factor promotes clearance of pneumococcal colonization.

    PubMed

    Das, Rituparna; LaRose, Meredith I; Hergott, Christopher B; Leng, Lin; Bucala, Richard; Weiser, Jeffrey N

    2014-07-15

    Human genetic polymorphisms associated with decreased expression of macrophage migration inhibitory factor (MIF) have been linked to the risk of community-acquired pneumonia. Because Streptococcus pneumoniae is the leading cause of community-acquired pneumonia and nasal carriage is a precursor to invasive disease, we explored the role of MIF in the clearance of pneumococcal colonization in a mouse model. MIF-deficient mice (Mif(-/-)) showed prolonged colonization with both avirulent (23F) and virulent (6A) pneumococcal serotypes compared with wild-type animals. Pneumococcal carriage led to both local upregulation of MIF expression and systemic increase of the cytokine. Delayed clearance in the Mif(-/-) mice was correlated with reduced numbers of macrophages in upper respiratory tract lavages as well as impaired upregulation of MCP-1/CCL2. We found that primary human monocyte-derived macrophages as well as THP-1 macrophages produced MIF upon pneumococcal infection in a pneumolysin-dependent manner. Pneumolysin-induced MIF production required its pore-forming activity and phosphorylation of p38-MAPK in macrophages, with sustained p38-MAPK phosphorylation abrogated in the setting of MIF deficiency. Challenge with pneumolysin-deficient bacteria demonstrated reduced MIF upregulation, decreased numbers of macrophages in the nasopharynx, and less effective clearance. Mif(-/-) mice also showed reduced Ab response to pneumococcal colonization and impaired ability to clear secondary carriage. Finally, local administration of MIF was able to restore bacterial clearance and macrophage accumulation in Mif(-/-) mice. Our work suggests that MIF is important for innate and adaptive immunity to pneumococcal colonization and could be a contributing factor in genetic differences in pneumococcal disease susceptibility.

  18. Meningitis - pneumococcal

    MedlinePlus

    ... causes meningitis. Causes Pneumococcal meningitis is caused by Streptococcus pneumoniae bacteria (also called pneumococcus, or S pneumoniae ). This type ... Saunders; 2015:chap 89. Wood JB, Peters TR. Streptococcus pneumoniae (pneumococcus). In: Kliegman RM, Stanton BF, St. Geme ...

  19. Invasive disease caused by nontuberculous mycobacteria, Tanzania.

    PubMed

    Crump, John A; van Ingen, Jakko; Morrissey, Anne B; Boeree, Martin J; Mavura, Daudi R; Swai, Britta; Thielman, Nathan M; Bartlett, John A; Grossman, Henning; Maro, Venance P; van Soolingen, Dick

    2009-01-01

    Data on nontuberculous mycobacterial (NTM) disease in sub-Saharan Africa are limited. During 2006-2008, we identified 3 HIV-infected patients in northern Tanzania who had invasive NTM; 2 were infected with "Mycobacterium sherrisii" and 1 with M. avium complex sequevar MAC-D. Invasive NTM disease is present in HIV-infected patients in sub-Saharan Africa.

  20. Serotype distribution of Streptococcus pneumoniae in children with invasive diseases in Turkey: 2008–2014

    PubMed Central

    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

  1. Serotype distribution of Streptococcus pneumoniae in children with invasive diseases in Turkey: 2008-2014.

    PubMed

    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.

  2. Population-Based Analysis of Invasive Nontypeable Pneumococci Reveals That Most Have Defective Capsule Synthesis Genes

    PubMed Central

    Sherwood, Logan K.; Nahm, Moon H.; Beall, Bernard

    2014-01-01

    Since nasopharyngeal carriage of pneumococcus precedes invasive pneumococcal disease, characteristics of carriage isolates could be incorrectly assumed to reflect those of invasive isolates. While most pneumococci express a capsular polysaccharide, nontypeable pneumococci are sometimes isolated. Carriage nontypeables tend to encode novel surface proteins in place of a capsular polysaccharide synthetic locus, the cps locus. In contrast, capsular polysaccharide is believed to be indispensable for invasive pneumococcal disease, and nontypeables from population-based invasive pneumococcal disease surveillance have not been extensively characterized. We received 14,328 invasive pneumococcal isolates through the Active Bacterial Core surveillance program during 2006–2009. Isolates that were nontypeable by Quellung serotyping were characterized by PCR serotyping, sequence analyses of the cps locus, and multilocus sequence typing. Eighty-eight isolates were Quellung-nontypeable (0.61%). Of these, 79 (89.8%) contained cps loci. Twenty-two nontypeables exhibited serotype 8 cps loci with defects, primarily within wchA. Six of the remaining nine isolates contained previously-described aliB homologs in place of cps loci. Multilocus sequence typing revealed that most nontypeables that lacked capsular biosynthetic genes were related to established non-encapsulated lineages. Thus, invasive pneumococcal disease caused by nontypeable pneumococcus remains rare in the United States, and while carriage nontypeables lacking cps loci are frequently isolated, such nontypeable are extremely rare in invasive pneumococcal disease. Most invasive nontypeable pneumococci possess defective cps locus genes, with an over-representation of defective serotype 8 cps variants. PMID:24831650

  3. Expansion of Serotype Coverage in the Universal Pediatric Vaccination Calendar: Short-Term Effects on Age- and Serotype-Dependent Incidence of Invasive Pneumococcal Clinical Presentations in Madrid, Spain

    PubMed Central

    Ruiz-Contreras, Jesus; Casado-Flores, Juan; Negreira, Sagrario; García-de-Miguel, Maria-Jesus; Hernández-Sampelayo, Teresa; Otheo, Enrique; Méndez, Cristina

    2013-01-01

    In Madrid, Spain, the 13-valent pneumococcal conjugate vaccine (PCV13) replaced PCV7 in the pediatric universal vaccination calendar in June 2010. A prospective clinical surveillance that included all children hospitalized with culture- and/or PCR-confirmed invasive pneumococcal disease (IPD) was performed in all Madrid hospitals. The incidence rates (IRs) (defined as the number of cases/100,000 inhabitants aged <15 years) in the PCV7 (May 2007 to April 2010) versus PCV13 (May 2011 to April 2012) periods were compared. There were 499 cases in the PCV7 period and 79 cases in the PCV13 period. Globally, the IR significantly decreased from 17.09 (PCV7 period) to 7.70 (PCV13 period), with significant decreases (PCV7 versus PCV13 periods) in all age groups for bacteremic pneumonia (5.51 versus 1.56), parapneumonic pneumococcal empyema (PPE) (5.72 versus 3.12), and meningitis (2.16 versus 0.97). In the PCV13 period, significant reductions (the IR in the PCV7 period versus the IR in the PCV13 period) were found in IPDs caused by PCV13 serotypes (13.49 versus 4.38), and specifically by serotypes 1 (globally [4.79 versus 2.53], for bacteremic pneumonia [2.23 versus 0.97], and for PPE [2.26 versus 1.17]), serotype 5 (globally [1.88 versus 0.00], for bacteremic pneumonia [0.89 versus 0.00], and for PPE [0.55 versus 0.00]), and serotype 19A (globally [3.77 versus 0.49], for bacteremic pneumonia [0.72 versus 0.00], for PPE [0.89 versus 0.00], and for meningitis [0.62 versus 0.00]). IPDs caused by non-PCV13 serotypes did not increase (IR, 3.60 in the PCV7 period versus 3.31 in the PCV13 period), regardless of age or presentation. No IPDs caused by the PCV13 serotypes were found in children who received 3 doses of PCV13. The number of hospitalization days and sanitary costs were significantly lower in the PCV13 period. The switch from PCV7 to PCV13 in the universal pediatric vaccination calendar provided sanitary and economical benefits without a replacement by non-PCV13

  4. Expansion of serotype coverage in the universal pediatric vaccination calendar: short-term effects on age- and serotype-dependent incidence of invasive pneumococcal clinical presentations in Madrid, Spain.

    PubMed

    Picazo, Juan; Ruiz-Contreras, Jesus; Casado-Flores, Juan; Negreira, Sagrario; García-de-Miguel, Maria-Jesus; Hernández-Sampelayo, Teresa; Otheo, Enrique; Méndez, Cristina

    2013-10-01

    In Madrid, Spain, the 13-valent pneumococcal conjugate vaccine (PCV13) replaced PCV7 in the pediatric universal vaccination calendar in June 2010. A prospective clinical surveillance that included all children hospitalized with culture- and/or PCR-confirmed invasive pneumococcal disease (IPD) was performed in all Madrid hospitals. The incidence rates (IRs) (defined as the number of cases/100,000 inhabitants aged <15 years) in the PCV7 (May 2007 to April 2010) versus PCV13 (May 2011 to April 2012) periods were compared. There were 499 cases in the PCV7 period and 79 cases in the PCV13 period. Globally, the IR significantly decreased from 17.09 (PCV7 period) to 7.70 (PCV13 period), with significant decreases (PCV7 versus PCV13 periods) in all age groups for bacteremic pneumonia (5.51 versus 1.56), parapneumonic pneumococcal empyema (PPE) (5.72 versus 3.12), and meningitis (2.16 versus 0.97). In the PCV13 period, significant reductions (the IR in the PCV7 period versus the IR in the PCV13 period) were found in IPDs caused by PCV13 serotypes (13.49 versus 4.38), and specifically by serotypes 1 (globally [4.79 versus 2.53], for bacteremic pneumonia [2.23 versus 0.97], and for PPE [2.26 versus 1.17]), serotype 5 (globally [1.88 versus 0.00], for bacteremic pneumonia [0.89 versus 0.00], and for PPE [0.55 versus 0.00]), and serotype 19A (globally [3.77 versus 0.49], for bacteremic pneumonia [0.72 versus 0.00], for PPE [0.89 versus 0.00], and for meningitis [0.62 versus 0.00]). IPDs caused by non-PCV13 serotypes did not increase (IR, 3.60 in the PCV7 period versus 3.31 in the PCV13 period), regardless of age or presentation. No IPDs caused by the PCV13 serotypes were found in children who received 3 doses of PCV13. The number of hospitalization days and sanitary costs were significantly lower in the PCV13 period. The switch from PCV7 to PCV13 in the universal pediatric vaccination calendar provided sanitary and economical benefits without a replacement by non-PCV13

  5. [Recommendations for prevention of community-acquired pneumonia with bacteremia as the leading form of invasive pneumococcal infections in the population of people over 50 years of age and risk groups above 19 years of age].

    PubMed

    Albrecht, Piotr; Antczak, Adam; Hryniewicz, Waleria; Skoczyńska, Anna; Radzikowski, Andrzej; Kedziora-Kornatowska, Kornelia; Bernatowska, Ewa; Stompór, Tomasz; Grodzicki, Tomasz; Gyrczuk, Ewa; Imiela, Jacek; Jedrzejczak, Wiesław; Windak, Adam

    2014-02-01

    Invasive pneumococcal disease (IPD) is a main cause of mortality associated with pneumococcal infections. Although, IPD is regarding mainly small children and persons in the age > 65 years, the investigations showed that because of IPD exactly sick persons are burdened with the greatest mortality in the older age, rather than of children. The most frequent form of IPD is community acquired pneumonia (CAP) with the bacteremia. The presence of even a single additional risk factor is increasing the probability of the unfavorable descent of pneumococcal infection. The risk factors for IPD and/or pneumonia with bacteremia apart from the age are among others asthma (> 2 x), chronic obstructive pulmonary disease (COPD), sarcoidosis (4 x), idiopathic pulmonary fibrosis (5 x), bronchiectases (2 x), allergic alveolitis (1.9 x) and pneumoconiosis (2 x), type 1 diabetes (4.4 x), type 2 diabetes (1.2 x), autoimmune diseases (e.g. rheumatoid arthritis (4.2 to 14.9 x), kidney failure with the necessity to dialysis (12 x), immunosuppression, cardiovascular disease, alcoholism and cancers. Examinations show that the best method of IPD and CAP preventing are pneumococcal vaccinations. On the market for ages 23-valent polysaccharide vaccine (PPV23) is available covering close the 90% of IPD triggering stereotypes. Her role in preventing CAP is uncertain and the immunological answer after vaccination at older persons and after revaccination is weak. Widely discussed disadvantageous effects of growing old of the immunological system show on the benefit from applying the immunization inducing the immunological memory, i.e. of conjugated vaccines which are activating the T-dependent reply and are ensuring the readiness for the effective secondary response. Examinations so far conducted with conjugated 7-valent and 13-valent (PCV13) vaccines at persons in the age > 50 years are confirming these expectations. Also sick persons can take benefits from PCV13 applying back from so-called IPD

  6. Invasive pneumococci before the introduction of pneumococcal conjugate vaccine in Turkey: antimicrobial susceptibility, serotype distribution, and molecular identification of macrolide resistance.

    PubMed

    Altun, Hatice Uludag; Hascelik, Gülsen; Gür, Deniz; Eser, Özgen Köseoglu

    2015-02-01

    This study evaluates the antimicrobial susceptibilities and serotype distributions of invasive Streptococcus pneumoniae (SP) isolates identified in a Turkish hospital before the introduction of the 7-valent pneumococcal conjugate vaccine (PCV7). The susceptibilities of all isolates were determined by evaluating six antibiotics: penicillin (PEN), ceftriaxone (CRO), levofloxacin (LEV), erythromycin (ERY), clindamycin (CD), and vancomycin (VAN). Serotyping and amplification of macrolide resistance genes were performed. Sixteen (50%) and four (2%) isolates were resistant to PEN and LEV, respectively. No isolates demonstrated VAN resistance. Intermediate resistance to CRO was found in 4% of all invasive isolates. Twenty-three (12.6%) isolates were resistant to ERY. Four (2%) invasive SP isolates demonstrated multidrug resistance. Serogroups 3, 5, 6, 8, 9, and 23 were the most common in both age groups. The potential coverage rates of PCV7 and PCV13 were 44.1 and 66.1% in children and 39.8 and 71.5% in adults, respectively. Continuous surveillance of antimicrobial resistance is required.

  7. Pneumococcal conjugated vaccine: PHiD-CV.

    PubMed

    Dinleyici, Ener Cagri; Yargic, Zeynel Abidin

    2009-11-01

    At the beginning of a new century, we have gained significant achievements against pneumococcal infections by using conjugated pneumococcal vaccines. In January 2009, the EMEA issued a positive opinion about, and recommended the approval of, GlaxoSmithKline's pediatric pneumococcal candidate vaccine, which is indicated for active immunization against invasive pneumococcal disease (IPD) and acute otitis media caused by Streptococcus pneumoniae in infants and children from 6 weeks up to 2 years of age. The approved 10-valent pneumococcal vaccine (PHiD-CV) contains all serotypes in 7-valent pneumococcal conjugate vaccine (PCV-7) plus serotypes 1, 5 and 7F. Protein D from nontypeable Haemophilus influenzae is the carrier protein for eight serotypes, while tetanus and diphtheria toxins are in the carrier proteins for the remaining two serotypes. It has also been proved that PHiD-CV is immunogenic, safe and well-tolerated in children. This vaccine can be coadministered with routinely used pediatric vaccines. Noninferiority criteria of PHiD-CV compared with PCV-7 were established in shared serotypes, except for serotypes 6B and 23F, and PHiD-CV is immunogenic for additional serotypes as assessed by the percentage of subjects with antibody concentrations. PHiD-CV is also immunogenic for ten serotypes as assessed by post-primary and post-booster dose opsonophagocytic activity responses. Vaccine efficacy against IPD and other conditions should be monitored for shared serotypes and also additional serotypes during the postmarketing period. Optimal scheduling, safety and immunogenicity data in children with different risk factors for IPD, or whether it will provide herd immunity, are the questions waiting for answers in the postmarketing period. Further studies are needed to assess the potential advantages of protein D as a carrier and the potential efficacy of this new vaccine against H. influenzae. The potential public health efficacy of PHiD-CV in low-income countries

  8. Dynamics and Determinants of Pneumococcal Antibodies Specific against 13 Vaccine Serotypes in the Pre-Vaccination Era

    PubMed Central

    Prins-van Ginkel, Annemarijn C.; Berbers, Guy A. M.; Grundeken, Lucienne H.; Tcherniaeva, Irina; Wittenberns, Jelle I.; Elberse, Karin; Mollema, Liesbeth; de Melker, Hester E.; Knol, Mirjam J.

    2016-01-01

    Introduction Introduction of pneumococcal conjugate vaccines (PCVs) for infants decreased overall invasive pneumococcal disease (IPD), while non-vaccine serotype IPD increased. To fully understand this serotype replacement, knowledge about serotype dynamics in the pre-vaccine era is needed. In addition to IPD surveillance and carriage studies, the serotype replacement can be investigated by serosurveillance studies. The current study compared the results of two Dutch serosurveillance studies conducted in 1995–1996 (PIENTER1) and 2006–2007 (PIENTER2). Methods Participants in these studies donated a blood sample and completed a questionnaire. Pneumococcal antibodies of serotypes included in PCV13 were measured with a fluorescent-bead based multiplex immunoassay. Geometric mean antibody concentrations (GMCs) and determinants of pneumococcal antibody levels were investigated. Results GMCs were higher in PIENTER2 for serotypes 1, 6A, 6B, 9V, 18C, 19F and 23F and lower for 3 and 5. Age, day care attendance, household size, vaccination coverage, and urbanisation rate were associated with pneumococcal antibodies in children. Education level, ethnicity, age, low vaccination coverage sample, urbanisation rate, and asthma/COPD were associated with pneumococcal antibodies in elderly. The determinants significantly associated with pneumococcal IgG were slightly different for the elderly in PIENTER1 compared to the elderly in PIENTER2. Conclusion Although most of the serotype antibody levels remained stable, some of the serotype-specific antibody levels varied during the pre-vaccine era, indicating that exposure of certain serotypes changes without interference of PCVs. PMID:26796783

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

    PubMed

    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.

  10. PspA Family Distribution, unlike Capsular Serotype, Remains Unaltered following Introduction of the Heptavalent Pneumococcal Conjugate Vaccine

    PubMed Central

    Croney, Christina M.; Coats, Mamie T.; Nahm, Moon H.; Briles, David E.

    2012-01-01

    Pneumococcal conjugate vaccines (PCVs) are recommended for the prevention of invasive pneumococcal disease (IPD) in young children. Since the introduction of the heptavalent pneumococcal vaccine (PCV7) in 2000, IPD caused by serotypes in the vaccine has almost been eliminated, and previously uncommon capsular serotypes now cause most cases of pediatric IPD in the United States. One way to protect against these strains would be to add cross-reactive protein antigens to new vaccines. One such protein is pneumococcal surface protein A (PspA). Prior to 2000, PspA families 1 and 2 were expressed by 94% of isolates. Because PCV7 vaccine pressure has resulted in IPD caused by capsular serotypes that were previously uncommon and unstudied for PspA expression, it was possible that many of the new strains expressed different PspA antigens or even lacked PspA. Of 157 pediatric invasive pneumococcal isolates collected at a large pediatric hospital in Alabama between 2002 and 2010, only 60.5% had capsular serotypes included in PCV13, which came into general use in Alabama after our strains were collected. These isolates included 17 serotypes that were not covered by PCV13. Nonetheless, pneumococcal capsular serotype replacement was not associated with changes in PspA expression; 96% of strains in this collection expressed PspA family 1 or 2. Continued surveillance will be critical to vaccine strategies to further reduce IPD. PMID:22539473

  11. 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?

    PubMed

    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.

  12. Dominance of multidrug-resistant Denmark(14)-32 (ST230) clone among Streptococcus pneumoniae serotype 19A isolates causing pneumococcal disease in Bulgaria from 1992 to 2013.

    PubMed

    Setchanova, Lena Petrova; Alexandrova, Alexandra; Dacheva, Daniela; Mitov, Ivan; Kaneva, Radka; Mitev, Vanio

    2015-02-01

    A pneumococcal conjugate vaccine (PCV10) was introduced in Bulgarian national immunization program since April 2010. Clonal composition based on pulsed-field gel electrophoresis and multilocus sequence typing genotyping of 52 serotype 19A Streptococcus pneumoniae isolates was analyzed. These were invasive and respiratory isolates collected between 1992 and 2013 from both children (78.8% <5 years) and adults with pneumococcal infections. Multidrug resistance was found in 82.7% of all 19A isolates. The most prevalent genotype (63.5%) among serotype 19A pneumococcal strains was the multidrug-resistant clonal complex CC230, which is a capsular switched variant of the Denmark(14)-32 (ST230) global clone. The most frequent sequence type (ST) was ST230 (48.1%) and together with four other closely related STs (15.4%), belonging to ST1611, ST276, ST7466, and ST2013, which were single- and double-locus variants; they were included in the main CC230. The disappearance of highly drug-resistant ST663 clone and emergence of new clones as CC320 and CC199 was also observed among the rest 19A isolates. A comparison of clonal composition between invasive and noninvasive isolates did not show a great genetic diversity among both kinds of isolates. Continuous surveillance of serotype 19A population following the introduction of PCV10 is essential to evaluate the impact of the vaccine on the epidemiology of this serotype.

  13. 42 CFR 410.57 - Pneumococcal vaccine and flu vaccine.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 2 2012-10-01 2012-10-01 false Pneumococcal vaccine and flu vaccine. 410.57... § 410.57 Pneumococcal vaccine and flu vaccine. (a) Medicare Part B pays for pneumococcal vaccine and its administration when reasonable and necessary for the prevention of disease, if the vaccine is ordered by a...

  14. 42 CFR 410.57 - Pneumococcal vaccine and flu vaccine.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 2 2013-10-01 2013-10-01 false Pneumococcal vaccine and flu vaccine. 410.57... § 410.57 Pneumococcal vaccine and flu vaccine. (a) Medicare Part B pays for pneumococcal vaccine and its administration when reasonable and necessary for the prevention of disease, if the vaccine is ordered by a...

  15. 42 CFR 410.57 - Pneumococcal vaccine and flu vaccine.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 2 2014-10-01 2014-10-01 false Pneumococcal vaccine and flu vaccine. 410.57... § 410.57 Pneumococcal vaccine and flu vaccine. (a) Medicare Part B pays for pneumococcal vaccine and its administration when reasonable and necessary for the prevention of disease, if the vaccine is ordered by a...

  16. 42 CFR 410.57 - Pneumococcal vaccine and flu vaccine.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 2 2011-10-01 2011-10-01 false Pneumococcal vaccine and flu vaccine. 410.57... § 410.57 Pneumococcal vaccine and flu vaccine. (a) Medicare Part B pays for pneumococcal vaccine and its administration when reasonable and necessary for the prevention of disease, if the vaccine is ordered by a...

  17. 42 CFR 410.57 - Pneumococcal vaccine and flu vaccine.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 2 2010-10-01 2010-10-01 false Pneumococcal vaccine and flu vaccine. 410.57... § 410.57 Pneumococcal vaccine and flu vaccine. (a) Medicare Part B pays for pneumococcal vaccine and its administration when reasonable and necessary for the prevention of disease, if the vaccine is ordered by a...

  18. 13-valent pneumococcal conjugate vaccine.

    PubMed

    2011-01-01

    The 7-valent pneumococcal conjugate vaccine (4, 6B, 9V, 14, 18C, 19F, 23F) is the standard vaccine for the prevention of invasive pneumococcal infections in infants and children under 5 years of age. A 13-valent pneumococcal conjugate vaccine (with the addition of valences 1, 3, 5, 6A, 7F and 19A) has now been authorised to replace the 7-valent vaccine within the European Union. This new vaccine, adapted to recent epidemiological data on invasive pneumococcal infections, is supposed to cover at least 80% of pneumococcal infections in Europe. The protective potency of the 13-valent vaccine has not yet been tested in clinical trials. Clinical evaluation is based on two immunogenicity studies, in which the immunogenic potency of the 13-valent vaccine was similar to that of the 7-valent vaccine for their shared serotypes, but lower for serotypes 3, 6B and 9V. For these last two serotypes and for the new serotypes, the usual target antibody titre was reached after a booster injection. This was not the case for valence 3. * The vaccine used in immunogenicity studies did not contain polysorbate 80 (an excipient), and a non-inferiority study of the marketed vaccine containing polysorbate 80 was therefore conducted in 500 children. Non-inferiority was established for all 13 valences after the booster injection, but not for valences 6B and 23F after primary vaccination. According to the results of 10 studies, simultaneous administration of the 13-valent pneumococcal conjugate vaccine does not affect the immunogenicity of other vaccines generally administered before the age of 5 years. Other immunogenicity studies support the use of a variety of vaccine schedules for infants and children under 5 years of age who have not yet been vaccinated or who have started vaccination with the 7-valent vaccine. Increasing the number of valences in the vaccine from 7 to 13 led to no marked increase in local adverse effects (hypersensitivity, indurations, erythema) or systemic reactions

  19. Multi-Serotype Pneumococcal Nasopharyngeal Carriage Prevalence in Vaccine Naïve Nepalese Children, Assessed Using Molecular Serotyping

    PubMed Central

    Kandasamy, Rama; Gurung, Meeru; Thapa, Anushil; Ndimah, Susan; Adhikari, Neelam; Murdoch, David R.; Kelly, Dominic F.; Waldron, Denise E.; Gould, Katherine A.; Thorson, Stephen; Shrestha, Shrijana; Hinds, Jason; Pollard, Andrew J.

    2015-01-01

    Invasive pneumococcal disease is one of the major causes of death in young children in resource poor countries. Nasopharyngeal carriage studies provide insight into the local prevalence of circulating pneumococcal serotypes. There are very few data on the concurrent carriage of multiple pneumococcal serotypes. This study aimed to identify the prevalence and serotype distribution of pneumococci carried in the nasopharynx of young healthy Nepalese children prior to the introduction of a pneumococcal conjugate vaccine using a microarray-based molecular serotyping method capable of detecting multi-serotype carriage. We conducted a cross-sectional study of healthy children aged 6 weeks to 24 months from the Kathmandu Valley, Nepal between May and October 2012. Nasopharyngeal swabs were frozen and subsequently plated on selective culture media. DNA extracts of plate sweeps of pneumococcal colonies from these cultures were analysed using a molecular serotyping microarray capable of detecting relative abundance of multiple pneumococcal serotypes. 600 children were enrolled into the study: 199 aged 6 weeks to <6 months, 202 aged 6 months to < 12 months, and 199 aged 12 month to 24 months. Typeable pneumococci were identified in 297/600 (49·5%) of samples with more than one serotype being found in 67/297 (20·2%) of these samples. The serotypes covered by the thirteen-valent pneumococcal conjugate vaccine were identified in 44·4% of samples containing typeable pneumococci. Application of a molecular serotyping approach to identification of multiple pneumococcal carriage demonstrates a substantial prevalence of co-colonisation. Continued surveillance utilising this approach following the introduction of routine use of pneumococcal conjugate vaccinates in infants will provide a more accurate understanding of vaccine efficacy against carriage and a better understanding of the dynamics of subsequent serotype and genotype replacement. PMID:25643355

  20. A comparative public health and budget impact analysis of pneumococcal vaccines: The French case

    PubMed Central

    Jiang, Yiling; Gervais, Frédéric; Gauthier, Aline; Baptiste, Charles; Martinon, Prescilla; Bresse, Xavier

    2015-01-01

    In 2002, a pneumococcal conjugate vaccine (PCV) was introduced to French infants and toddlers. A change has been witnessed in the incidence of pneumococcal diseases in adults: the incidence of invasive pneumococcal disease (IPD) of serotypes covered by PCV decreased, and serotypes not covered by PCV increased. This study aimed to quantify the public health and budget impact of pneumococcal vaccination strategies in at-risk adults in France over 5 years. A previously published population-based Markov model was adapted to the French situation. At-risk adults received either PPV23 (pneumococcal polysaccharide vaccine; for the immunocompetent) or PCV13 (for the immunosuppressed). The strategy was compared to PCV13 alone. Uncertainty was addressed using extreme scenario analyses. Between 2014 and 2018, vaccination with PPV23/PCV13 led to a higher reduction in terms of IPD and non-bacteremic pneumococcal pneumonia cases avoided in most scenarios analyzed when compared to PCV13 alone. For budget impact, none of the scenarios was in favor of PCV13. Under conservative coverage assumptions, the total incremental budget impact ranged from € 39.8 million to € 69.3 million if PCV13 were to replace PPV23 in the immunocompetent. With the epidemiological changes of pneumococcal diseases and the broader serotype coverage of PPV23, the current program remains an optimal strategy from public health perspective. Given the additional budget required for the use of PCV13 alone and its uncertain public health benefits, vaccination with PPV23 remains the preferred strategy. PMID:26267239

  1. Changes in the composition of the pneumococcal population and in IPD incidence in The Netherlands after the implementation of the 7-valent pneumococcal conjugate vaccine.

    PubMed

    Elberse, Karin E M; van der Heide, Han G J; Witteveen, Sandra; van de Pol, Ingrid; Schot, Corrie S; van der Ende, Arie; Berbers, Guy A M; Schouls, Leo M

    2012-12-14

    The implementation of nationwide pneumococcal vaccination may lead to alterations in the pneumococcal population due to selective pressure induced by the vaccine. To monitor such changes, pneumococcal isolates causing invasive pneumococcal disease (IPD) before (2004-2005, n=1154) and after (2008-2009, n=1190) the implementation of the 7-valent pneumococcal vaccine (PCV7) in 2006 in the national immunization program (NIP) of The Netherlands were characterized by molecular typing using multiple-locus variable number tandem repeat analysis (MLVA) and capsular sequence typing (CST). The IPD incidence after the implementation of PCV7 in children <5 years of age declined, mainly due to an impressive reduction of cases caused by vaccine serotypes. In the age group of patients ≥5 years of age, the overall IPD incidence remained constant, but the IPD incidence due to vaccine serotypes declined in this age cohort as well, indicating herd immunity. IPD incidence of non-vaccine serotypes 1 and 22F isolates increased significantly and a shift in genetic background of the isolates belonging to these serotypes was observed. In general the composition of the pneumococcal population remained similar after the introduction of PCV7. Both before and after introduction of the vaccine several possible capsular switch events were noticed. We found 4 isolates from the pre-vaccination period in which the serotype 19F capsular locus had been horizontally transferred to a different genetic background. Remarkably, none of the 5 post-vaccination isolates in which we observed possible capsule switch belonged to the 19F serotype, possibly due to vaccine induced pressure. In the post-vaccine implementation period we found no evidence for capsular switch of a vaccine serotype to a non-vaccine serotype, indicating that capsular switch is not the main driving force for replacement. This study provides insights into the effects of nationwide vaccination on the pneumococcal population causing IPD.

  2. Minimally Invasive Surgery for Inflammatory Bowel Disease

    PubMed Central

    Holder-Murray, Jennifer; Marsicovetere, Priscilla

    2015-01-01

    Abstract: Surgical management of inflammatory bowel disease is a challenging endeavor given infectious and inflammatory complications, such as fistula, and abscess, complex often postoperative anatomy, including adhesive disease from previous open operations. Patients with Crohn's disease and ulcerative colitis also bring to the table the burden of their chronic illness with anemia, malnutrition, and immunosuppression, all common and contributing independently as risk factors for increased surgical morbidity in this high-risk population. However, to reduce the physical trauma of surgery, technologic advances and worldwide experience with minimally invasive surgery have allowed laparoscopic management of patients to become standard of care, with significant short- and long-term patient benefits compared with the open approach. In this review, we will describe the current state-of the-art for minimally invasive surgery for inflammatory bowel disease and the caveats inherent with this practice in this complex patient population. Also, we will review the applicability of current and future trends in minimally invasive surgical technique, such as laparoscopic “incisionless,” single-incision laparoscopic surgery (SILS), robotic-assisted, and other techniques for the patient with inflammatory bowel disease. There can be no doubt that minimally invasive surgery has been proven to decrease the short- and long-term burden of surgery of these chronic illnesses and represents high-value care for both patient and society. PMID:25989341

  3. Invasive mucormycosis in chronic granulomatous disease

    PubMed Central

    Al-Otaibi, Abdulnasir M.; Al-Shahrani, Dayel A.; Al-Idrissi, Eman M.; Al-Abdely, Hail M.

    2016-01-01

    Mucormycosis is a rare opportunistic fungal infection that occurs in certain immunocompromised patients. We present 2 cases of invasive mucormycosis due to Rhizopus spp. in patients with chronic granulomatous disease (CGD) and discuss their clinical presentation, management challenges, and outcomes. PMID:27146621

  4. Behind the data: Establishing the Network for Surveillance for Pneumococcal Diseases in the East African Region, netSPEAR

    PubMed Central

    Amos, Ben; Kisakye, Annet; Makewa, Douglas; Mudhune, Sandra; Mwamtemi, Hadija; Nansera, Dennis; Ngwiri, Thomas; Wamae, Maranga; English, Mike

    2009-01-01

    In a region with high rates of mortality among children aged <5 years, the underfunded health care systems of sub-Saharan Africa have few resources available to perform surveillance activities that can help determine the causes of morbidity and mortality in the region. At present, there are few examples of attempts to promote public health care surveillance that might inform current debates about how to expand and improve surveillance, particularly for bacterial diseases. Driven by this gap in knowledge, we attempted to explore the successes and failures of the Network for Surveillance of Pneumococcal Disease in the East African Region and to share the experiences of what are essentially non research public-sector hospitals in East Africa, with the hopes that surveillance systems for other diseases, especially those that require complex diagnostic support, may be informed by these experiences. The state of services essential for surveillance and the measures taken to overcome any shortcomings are described, as is the progress made in improving clinical diagnosis, laboratory processing, and data management. For surveillance to play a role in public health care, ministries of health and associated institutions must own and push forward the surveillance agenda, with support from global partners, and take advantage of the developments that have been achieved within the institutions. PMID:19191612

  5. Pneumococcal Carriage in Sub-Saharan Africa—A Systematic Review

    PubMed Central

    Usuf, Effua; Bottomley, Christian; Adegbola, Richard A.; Hall, Andrew

    2014-01-01

    Background Pneumococcal epidemiology varies geographically and few data are available from the African continent. We assess pneumococcal carriage from studies conducted in sub-Saharan Africa (sSA) before and after the pneumococcal conjugate vaccine (PCV) era. Methods A search for pneumococcal carriage studies published before 2012 was conducted to describe carriage in sSA. The review also describes pneumococcal serotypes and assesses the impact of vaccination on carriage in this region. Results Fifty-seven studies were included in this review with the majority (40.3%) from South Africa. There was considerable variability in the prevalence of carriage between studies (I-squared statistic = 99%). Carriage was higher in children and decreased with increasing age, 63.2% (95% CI: 55.6–70.8) in children less than 5 years, 42.6% (95% CI: 29.9–55.4) in children 5–15 years and 28.0% (95% CI: 19.0–37.0) in adults older than 15 years. There was no difference in the prevalence of carriage between males and females in 9/11 studies. Serotypes 19F, 6B, 6A, 14 and 23F were the five most common isolates. A meta-analysis of four randomized trials of PCV vaccination in children aged 9–24 months showed that carriage of vaccine type (VT) serotypes decreased with PCV vaccination; however, overall carriage remained the same because of a concomitant increase in non-vaccine type (NVT) serotypes. Conclusion Pneumococcal carriage is generally high in the African continent, particularly in young children. The five most common serotypes in sSA are among the top seven serotypes that cause invasive pneumococcal disease in children globally. These serotypes are covered by the two PCVs recommended for routine childhood immunization by the WHO. The distribution of serotypes found in the nasopharynx is altered by PCV vaccination. PMID:24465464

  6. [Minimally Invasive Treatment of Esophageal Benign Diseases].

    PubMed

    Inoue, Haruhiro

    2016-07-01

    As a minimally invasive treatment of esophageal achalasia per-oral endoscopic myotomy( POEM) was developed in 2008. More than 1,100 cases of achalasia-related diseases received POEM. Success rate of the procedure was more than 95%(Eckerdt score improvement 3 points and more). No serious( Clavian-Dindo classification III b and more) complication was experienced. These results suggest that POEM becomes a standard minimally invasive treatment for achalasia-related diseases. As an off-shoot of POEM submucosal tumor removal through submucosal tunnel (per-oral endoscopic tumor resection:POET) was developed and safely performed. Best indication of POET is less than 5 cm esophageal leiomyoma. A novel endoscopic treatment of gastroesophageal reflux disease (GERD) was developed. Anti-reflux mucosectomy( ARMS) is nearly circumferential mucosal reduction of gastric cardia mucosa. ARMS is performed in 56 consecutive cases of refractory GERD. No major complications were encountered and excellent clinical results. Best indication of ARMS is a refractory GERD without long sliding hernia. Longest follow-up case is more than 10 years. Minimally invasive treatments for esophageal benign diseases are currently performed by therapeutic endoscopy.

  7. Conjugation of PEG-hexadecane markedly increases the immunogenicity of pneumococcal polysaccharide conjugate vaccine.

    PubMed

    Chang, Xin; Yu, Weili; Ji, Shaoyang; Shen, Lijuan; Tan, Aijuan; Hu, Tao

    2017-02-24

    Streptococcus pneumoniae is a serious Gram-positive pathogen that can lead to an invasive pneumococcal disease with high mortality rate. Pneumococcal capsular polysaccharide (PS) is a key virulence determinant and its immunogenicity can be increased by conjugation with a carrier protein. However, the PS-specific cellular and humoral immunity of pneumococcal conjugate vaccine needs further improvement. Hexadecane (HD) is an element of lipid that decorates the surface of nearly all microbial classes. Polyethylene glycol (PEG)-HD conjugate (PEG-HD) is soluble and can act as an adjuvant. In the present study, a novel pneumococcal polysaccharide conjugate vaccine was prepared by conjugation of tetanus toxoid (TT) portion of PS-TT conjugate (PS-TT) with PEG-HD. As compared with PS-TT, conjugation with PEG-HD led to an 8.0-fold increase in the PS-specific IgG titers. Conjugation with PEG-HD also gave rise to 34.9-, 3.6- and 7.7-fold increase in the IFN-γ, TNF-α and IL-5 levels, respectively. Thus, the conjugated PEG-HD has a stimulatory adjuvant activity to potentiate a robust humoral and cellular immunity. Our proposed conjugate was expected to act as an effective pneumococcal conjugate vaccine for prevention of S. pneumoniae infections.

  8. Pneumococcal vaccine (image)

    MedlinePlus

    Pneumococcal vaccine is an immunization against Streptococcus pneumoniae , a bacterium that frequently causes meningitis and pneumonia in the elderly, and people with chronic illnesses. Pneumococcal pneumonia accounts for 10 to ...

  9. Towards the 13-valent pneumococcal conjugate universal vaccination

    PubMed Central

    Martinelli, Domenico; Pedalino, Biagio; Cappelli, Maria Giovanna; Caputi, Giovanni; Sallustio, Anna; Fortunato, Francesca; Tafuri, Silvio; Cozza, Vanessa; Germinario, Cinzia; Chironna, Maria; Prato, Rosa; surveillance of pediatric IPD, Apulian Group for the

    2014-01-01

    Pneumococcal disease epidemiology has changed after introduction of pneumococcal conjugate vaccines. Seven-valent vaccine (PCV7) has been effective in reducing invasive pneumococcal disease (IPD). In Europe, PCV13 effectiveness was estimated at 78% (95% CI: −18–96%) for 2-priming doses. In Italy, PCV7 was introduced in 2006 in the childhood immunization schedule and replaced with PCV13 in 2010. In Apulia, vaccination coverage has reached 95.1% (birth-cohort 2010). We estimated PCV program effectiveness and its impact on S. pneumoniae diseases. PCV Effectiveness: We used the screening method. We calculated the Proportion of Population Vaccinated from immunization registries and detected cases through a laboratory-confirmed surveillance among hospitalized children ≤60 months. A confirmed IPD case was a child with PCR positive for S. pneumoniae. Differences among children were assessed with the Chi-square or the Fisher exact test (P value < 0.05). PCV Impact: We constructed time series using outcome-specific Poisson regression models: hospitalization rate in pre-PCV era and hospitalization risk ratios (RRs) with 95% CIs for both PCV7 and PCV7/PCV13 shifting era. We calculated hospitalization RR with 95% CIs comparing pre-PCV years with vaccination period. The PCV effectiveness was 84.3% (95% CI: 84.0–84.6%). In May 2010-January 2013, we enrolled 159 suspected IPD of whom 4 were confirmed. Two (fully vaccinated) were caused by serotype 9V, 1 (not vaccinated) by serotype 3, 1 (vaccinated with 2 PCV13 doses) by 15B/C. The most important reduction was for pneumococcal pneumonia (RR: 0.43, 95% CI: 0.21–0.90). The PCV program show promising results in terms of both PCV13 effectiveness and its impact in reducing IPD in children <5 years. PMID:24096297

  10. Vaccination of adults with 23-valent pneumococcal polysaccharide vaccine induces robust antibody responses against pneumococcal serotypes associated with serious clinical outcomes

    PubMed Central

    Ciprero, Karen L.; Marchese, Rocio D.; Richard, Patrick; Baudin, Martine; Sterling, Tina M.; Manoff, Susan B.; Radley, David; Stek, Jon E.; Soubeyrand, Benoît; Grabenstein, John D.; Samson, Sandrine I.; Musey, Luwy K.

    2016-01-01

    ABSTRACT PNEUMOVAX™ 23, a 23-valent polysaccharide pneumococcal vaccine (PPV23), covers 65% to 91% of the isolates recovered from adult cases of invasive pneumococcal disease. Several studies have demonstrated that pneumococcal serotypes 31, 11A, 35F, 17F, 3, 16F, 19F, 15B, and 10A are associated with higher case-fatality or meningitis rates than other pneumococcal serotypes. This study (U05-PnPS-403; EudraCT: 2008-003648-12) evaluated the immune response followings administration of PPV23 for 4 of these serotypes (10A, 11A, 15B, and 17F), that are included in PPV23 but not in licensed pneumococcal conjugate vaccines. Serotype-specific IgG geometric mean concentrations (GMCs) and geometric mean fold-rises (GMFRs) for these 4 serotypes were measured by a validated enzyme-linked immunosorbent assay (ELISA) in 104 subjects >50 y of age who were enrolled in a study evaluating the safety and immunogenicity of a single-dose of PPV23. At 1 month post-vaccination, GMCs for serotypes10A, 11A, 15B and 17F were 6.5, 4.3, 14.7, and 5.1 µg/mL, respectively. GMFRs from baseline were 9.0, 4.5, 8.4, and 11.5, respectively. The percentages of subjects achieving >2-fold increases in IgG GMCs between pre-vaccination and 1 month post-vaccination were 90%, 85%, 88% and 89%, respectively. In conclusion, PPV23 induces a robust immune response in adults to pneumococcal serotypes 10A, 11A, 15B, and 17F, which have been associated with elevated case-fatality or meningitis rates. PMID:27002793

  11. Herd immunity and pneumococcal conjugate vaccine: a quantitative model.

    PubMed

    Haber, Michael; Barskey, Albert; Baughman, Wendy; Barker, Lawrence; Whitney, Cynthia G; Shaw, Kate M; Orenstein, Walter; Stephens, David S

    2007-07-20

    Invasive pneumococcal disease in older children and adults declined markedly after introduction in 2000 of the pneumococcal conjugate vaccine for young children. An empirical quantitative model was developed to estimate the herd (indirect) effects on the incidence of invasive disease among persons >or=5 years of age induced by vaccination of young children with 1, 2, or >or=3 doses of the pneumococcal conjugate vaccine, Prevnar (PCV7), containing serotypes 4, 6B, 9V, 14, 18C, 19F and 23F. From 1994 to 2003, cases of invasive pneumococcal disease were prospectively identified in Georgia Health District-3 (eight metropolitan Atlanta counties) by Active Bacterial Core surveillance (ABCs). From 2000 to 2003, vaccine coverage levels of PCV7 for children aged 19-35 months in Fulton and DeKalb counties (of Atlanta) were estimated from the National Immunization Survey (NIS). Based on incidence data and the estimated average number of doses received by 15 months of age, a Poisson regression model was fit, describing the trend in invasive pneumococcal disease in groups not targeted for vaccination (i.e., adults and older children) before and after the introduction of PCV7. Highly significant declines in all the serotypes contained in PCV7 in all unvaccinated populations (5-19, 20-39, 40-64, and >64 years) from 2000 to 2003 were found under the model. No significant change in incidence was seen from 1994 to 1999, indicating rates were stable prior to vaccine introduction. Among unvaccinated persons 5+ years of age, the modeled incidence of disease caused by PCV7 serotypes as a group dropped 38.4%, 62.0%, and 76.6% for 1, 2, and 3 doses, respectively, received on average by the population of children by the time they are 15 months of age. Incidence of serotypes 14 and 23F had consistent significant declines in all unvaccinated age groups. In contrast, the herd immunity effects on vaccine-related serotype 6A incidence were inconsistent. Increasing trends of non

  12. Mucosal and systemic immunization with a novel attenuated pneumococcal vaccine candidate confer serotype independent protection against Streptococcus pneumoniae in mice.

    PubMed

    Wu, Kaifeng; Yao, Run; Wang, Hong; Pang, Dan; Liu, Yusi; Xu, Hongmei; Zhang, Shuai; Zhang, Xuemei; Yin, Yibing

    2014-07-16

    Despite the availability of effective vaccines, Streptococcus pneumoniae is still one of the major infectious diseases causing substantial morbidity and mortality in children under 5 years old. In this study, we demonstrate the protective efficacy of S. pneumoniae SPY1, a novel live attenuated vaccine strain against pneumococcal infection in murine models. This strain was characterized by defects in three important pneumococcal virulence factors including capsule, teichoic acids and pneumolysin. The lactate dehydrogenase assays and in vivo animal experiments demonstrated a significantly attenuated virulence and a reduced nasopharyngeal colonization for the SPY1 strain. We also show that mucosal and systemic immunization with the live SPY1 strain induced protective immune responses against pneumococci. Mucosal immunization with SPY1 offered better protection against colonization challenge with strains TIGR4 and serotype 19F than systemic SPY1 immunization. In invasive infection models, mucosal vaccination with the SPY1 strain conferred complete protection against D39 and clinical serotype 6B and 3 strains. Notably, intranasal vaccination with the SPY1 strain conferred superior protection against pneumococcal invasive disease compared with the commercial available vaccines. SPY1 strain was shown to elicit high levels of serotype-independent antibodies and a mixed cellular immune response. Besides, the SPY1 serum was able to passively protect mice against invasive challenge with D39 strain, indicating the protective effect of the antibody-mediated responses. Together, the SPY1 strain may be a promising live vaccine strain to protect pneumococcal infection.

  13. Dynamic Changes in the Streptococcus pneumoniae Transcriptome during Transition from Biofilm Formation to Invasive Disease upon Influenza A Virus Infection

    PubMed Central

    Marks, Laura R.; Kong, Yong; Gent, Janneane F.; Roche-Hakansson, Hazeline

    2014-01-01

    Streptococcus pneumoniae is a leading cause of infectious disease globally. Nasopharyngeal colonization occurs in biofilms and precedes infection. Prior studies have indicated that biofilm-derived pneumococci are avirulent. However, influenza A virus (IAV) infection releases virulent pneumococci from biofilms in vitro and in vivo. Triggers of dispersal include IAV-induced changes in the nasopharynx, such as increased temperature (fever) and extracellular ATP (tissue damage). We used whole-transcriptome shotgun sequencing (RNA-seq) to compare the S. pneumoniae transcriptome in biofilms, bacteria dispersed from biofilms after exposure to IAV, febrile-range temperature, or ATP, and planktonic cells grown at 37°C. Compared with biofilm bacteria, actively dispersed S. pneumoniae, which were more virulent in invasive disease, upregulated genes involved in carbohydrate metabolism. Enzymatic assays for ATP and lactate production confirmed that dispersed pneumococci exhibited increased metabolism compared to those in biofilms. Dispersed pneumococci also upregulated genes associated with production of bacteriocins and downregulated colonization-associated genes related to competence, fratricide, and the transparent colony phenotype. IAV had the largest impact on the pneumococcal transcriptome. Similar transcriptional differences were also observed when actively dispersed bacteria were compared with avirulent planktonic bacteria. Our data demonstrate complex changes in the pneumococcal transcriptome in response to IAV-induced changes in the environment. Our data suggest that disease is caused by pneumococci that are primed to move to tissue sites with altered nutrient availability and to protect themselves from the nasopharyngeal microflora and host immune response. These data help explain pneumococcal virulence after IAV infection and have important implications for studies of S. pneumoniae pathogenesis. PMID:25135685

  14. Experience with pneumococcal polysaccharide conjugate vaccine (conjugated to CRM197 carrier protein) in children and adults.

    PubMed

    Durando, P; Faust, S N; Fletcher, M; Krizova, P; Torres, A; Welte, T

    2013-10-01

    Streptococcus pneumoniae-related infections are a major cause of morbidity and mortality in people of all ages worldwide. Pneumococcal vaccine development started in 1911 with a whole cell vaccine and more recently multivalent plain polysaccharide and polysaccharide conjugate vaccines have been developed. The recent vaccines rely on capsular polysaccharide antigens to induce serotype-specific immune responses. We summarize here the presentations on pneumococcal polysaccharide conjugate vaccine (conjugated to CRM197 carrier protein) given during the integrated symposium organized and funded by Pfizer International Operations during the 22nd European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) 31 March to 3 April 2012, London, UK. A dramatic reduction in the incidence of invasive pneumococcal diseases (IPD) due to vaccine serotypes (VST-IPD) has been reported since the introduction of a hepta-valent pneumococcal conjugate vaccine (PCV7). An indirect (herd) effect has been demonstrated to be associated with PCV7 infant vaccination programmes, with many studies reporting reductions in VST-IPD in populations that are not eligible for PCV7 vaccination. Since 2010, a 13-valent pneumococcal conjugate vaccine (PCV13) has been introduced into national immunization programmes and results from early surveillance suggest that this vaccine also has an impact on the serotypes unique to PCV13, as well as continuing to protect against the PCV7 serotypes. Data from a passive surveillance system in Europe in 2009, for instance, showed that the highest incidence of IPD remains in those aged >65 years and in children <5 years. PCV13 has now been licensed for vaccination of adults >50 years based on safety and immunogenicity data; an efficacy trial is being conducted. Regardless of previous pneumococcal vaccination status, if the use of 23-valent polysaccharide is considered appropriate, it is recommended to give PCV13 first. Novel immunization strategies remain

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

    PubMed

    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.

  16. Tailoring the strategies to specific shortages: pneumococcal conjugate vaccine.

    PubMed

    Peter, Georges

    2006-03-01

    Less than 1 year after recommendations for the routine vaccination of infants with the newly licensed 7-valent polysaccharide-protein conjugate pneumococcal vaccine were issued in February 2000, shortages of the 7-valent polysaccharide-protein conjugate pneumococcal vaccine supply began to occur. A national shortage developed in 2001, involving both the public and private sectors, and it resulted in temporary recommendations to conserve vaccine supply for infants and young children at the highest risk for invasive disease. Multiple factors contributed to this vaccine shortage, including demand that exceeded the expectations of the manufacturer and the need for compliance with the Good Manufacturing Practice of the US Food and Drug Administration. Of the possible strategies that might have averted this shortage, establishment of a vaccine stockpile is the most likely solution. However, establishing a stockpile for a newly licensed vaccine, such as 7-valent polysaccharide-protein conjugate pneumococcal vaccine, presents unique challenges. Improved communication with physicians and parents regarding changes in vaccine schedules also will promote better adherence to recommended changes and conservation of limited vaccine supplies during a shortage.

  17. Fluoroquinolone resistance of Streptococcus pneumoniae isolates causing invasive disease: special focus on zabofloxacin.

    PubMed

    Kim, Tark; Park, Su-Jin; Chong, Yong Pil; Park, Ki-Ho; Lee, Yu-Mi; Hong, Hyo-Lim; Kim, Hee Seung; Kim, Eun Sil; Lee, Sungkyoung; Choi, Dong Rack; Kim, Sung-Han; Jeong, Jin-Yong; Lee, Sang-Oh; Choi, Sang-Ho; Woo, Jun Hee; Kim, Yang Soo

    2016-10-01

    The present study examined the in vitro activity of various antibiotics including zabofloxacin, against isolates responsible for invasive pneumococcal diseases. Between 1997 and 2008, a total of 208 isolates were collected from sterile fluids, including blood (n=196, 94.2%), pleural fluid (n=5, 2.4%), cerebrospinal fluid (n=5, 2.4%), and ascites (n=2, 1.0%). Zabofloxacin showed the lowest MIC50 (0.015μg/mL) and MIC90 (0.025μg/mL) values of all the tested antibiotics. Rates of isolates resistant to penicillin (MIC ≥8μg/mL), ceftriaxone (MIC ≥4μg/mL) and levofloxacin (MIC ≥8μg/mL) were 3.4%, 0.4% and 2.0%, respectively. Four isolates (2.0%) were resistant to levofloxacin, and zabofloxacin showed low MICs (range, 0.025-0.125μg/mL). Zabofloxacin shows potent in vitro activity against S. pneumoniae isolates that caused invasive disease, even strains that are resistant to levofloxacin.

  18. The role of television advertising in increasing pneumococcal vaccination coverage among the elderly, North Coast, New South Wales, 2006.

    PubMed

    Wallace, Cate; Corben, Paul; Turahui, John; Gilmour, Robin

    2008-10-01

    North Coast Area Health Service (NCAHS) conducted a seven week television advertising campaign to raise community awareness of the availability of free adult pneumococcal vaccination and to increase coverage among North Coast residents in high risk groups. Effectiveness of the campaign was evaluated by examining vaccine ordering patterns of North Coast vaccination providers from 2005/2006 as a proxy for vaccination coverage. In the months during and immediately following (June-September 2006) the advertising campaign, a significantly higher proportion of vaccines were despatched to North Coast immunisation service providers. The advertising campaign was an effective strategy to promote vaccination among NCAHS residents not immunised in the first year of the National Pneumococcal Program for Older Australians. This higher immunisation coverage is expected to contribute to the statewide trend of significant reductions in invasive pneumococcal disease (IPD) notifications.

  19. Immunogenicity and safety of CRM₁₉₇ conjugated 9-valent pneumococcal and meningococcal C combination vaccine in healthy infants.

    PubMed

    Mallet, Eric; Brachet, Elisabeth; Fernsten, Philip; Laudat, France; Razmpour, Ahmad; Gruber, William C

    2011-08-05

    Streptococcus pneumoniae and Neisseria meningitidis cause invasive disease in children aged <2 years. While individual conjugate vaccines are available to protect this age group against these pathogens, availability of a vaccine combining these antigens into a single injection is desirable. This study randomized 467 healthy infants to receive 4 doses of combination 9-valent pneumococcal and meningococcal serogroup C conjugate vaccine (9vPnC-MnCC) or 9-valent pneumococcal conjugate vaccine (9vPnC). Percentages of subjects achieving immunoglobulin G (IgG) antibody concentrations ≥0.35μg/mL and geometric mean IgG concentrations for each pneumococcal serotype in the 9vPnC-MnCC group were noninferior compared to the 9vPnC group. Both vaccines were well-tolerated.

  20. [Streptococcus pneumoniae Vaccination in Children and Adolescents at High Risk of Invasive Pneumococcal Disease].

    PubMed

    Tendais-Almeida, Marta; Ferreira-Magalhães, Manuel; Alves, Inês; Tavares, Margarida; Azevedo, Inês

    2015-01-01

    Introdução: Em Portugal, a vacinação anti-pneumocócica é gratuita e recomendada pela Direção-Geral da Saúde na população pediátrica de alto risco para doença invasiva pneumocócica. O objetivo deste estudo foi analisar o cumprimento vacinal numa população pediátrica seguida em consulta hospitalar. Material e Métodos: Estudo observacional transversal, em crianças com diagnóstico de alto risco de doença invasiva pneumocócica e consulta num hospital nível três, entre julho e dezembro de 2014. Os dados foram obtidos através do processo clínico, Boletim Individual de Saúde e Plataforma de Dados da Saúde®. Resultados: Dos 122 participantes, 95,9% realizaram, pelo menos, uma dose de vacina mas, destes, só 64,8% efetuaram o esquema completo. O cumprimento do esquema vacinal foi melhor nos de idade inferior a cinco anos (p < 0,01). A proporção de crianças com esquema completo foi de: 100% nas hemoglobinopatias, 100% nas infeções por vírus da imunodeficiência humana, 66,7% nos prematuros com idade gestacional ⤠28 semanas, 62,5% nos esplenectomizados e 54,7% na síndrome de Down. As crianças têm mais esquemas completos quando são seguidas em consulta de Infeciologia (100%) e de Pneumologia pediátricas (88,2%). O grupocom idade superior a cinco anos está mais vacinado com a vacina polissacarida 23-valente do que o dos 2-5 anos (74,5% vs 40,5%; p < 0,01).Discussão: A maioria da nossa população de alto risco para doença invasiva pneumocócica efetuou vacinação anti-pneumocócica, mas apenas dois terços completaram o esquema recomendado, sendo a maior falha na administração da vacina polissacarida 23-valente. Conclusões: Embora estes resultados sejam melhores do que em países europeus com recomendações semelhantes, é necessário explorar as causas das falhas observadas para otimizar a vacinação.

  1. The pharmacoeconomics of pneumococcal conjugate vaccines in Latin America.

    PubMed

    Giglio, Norberto; Micone, Paula; Gentile, Angela

    2011-09-14

    Streptococcus pneumoniae continues to be the most important causative agent of invasive bacterial infections in children and is the most common cause of vaccine-preventable deaths in children less than 5 years of age. Due to some conditions in the Latin America region, economic assessments of pneumococcal conjugate vaccines (PCVs) have unique characteristics. First, distribution of S. pneumoniae serotypes, and thus coverage by vaccines that incorporate certain serotypes, varies within the region and compared with other parts of the world. Second, the mortality rate of pneumococcal infections in developing countries is significantly higher than in the US and Europe. Third, the economies of the Latin American region are very different from those of developed countries. For these reasons, the Pan American Health Organization (PAHO) is promoting the need for economic valuation studies of the impact of pneumococcal vaccines Latin America. Given the importance of pneumonia in the burden of pneumococcal disease in Latin America, the number of pneumonia cases prevented by the vaccine has a large impact on the economic valuation of PCVs, due to a strong correlation with numbers of deaths averted, quality-adjusted life-years (QALYs) gained or disability-adjusted life-years (DALYs) avoided. In terms of cost, analysis of impact on acute otitis media (short-term) and sequelae (long-term) show a significant and important expenditure avoided by vaccination. Cost-effectiveness is significantly modified by vaccine cost, mortality due to pneumonia, vaccine efficacy/effectiveness and herd immunity. Finally the validity of certain assumptions based on the uncertainty of the data should be considered in economic assessments of new PCVs. These include assumptions related to the impact on otitis media, estimates of efficacy/effectiveness based on measured antibody levels and the extrapolation to PCV10 and PCV13 of previous experience with PCV7.

  2. A Cross-Sectional Observational Study of Pneumococcal Carriage in Children, Their Parents, and Older Adults Following the Introduction of the 7-Valent Pneumococcal Conjugate Vaccine

    PubMed Central

    Hamaluba, Mainga; Kandasamy, Rama; Ndimah, Susan; Morton, Richard; Caccamo, Marisa; Robinson, Hannah; Kelly, Sarah; Field, Aimee; Norman, Lily; Plested, Emma; Thompson, Ben A.V.; Zafar, Azhar; Kerridge, Simon A.; Lazarus, Rajeka; John, Tessa; Holmes, Jane; Fenlon, Shannon N.; Gould, Katherine A.; Waight, Pauline; Hinds, Jason; Crook, Derrick; Snape, Matthew D.; Pollard, Andrew J.

    2015-01-01

    Abstract Using nasopharyngeal carriage as a marker of vaccine impact, pneumococcal colonization and its relation to invasive disease were examined in children, their parents, and older adults in the United Kingdom following introduction of 7-valent pneumococcal conjugate vaccine (PCV7) and prior to 13-valent pneumococcal conjugate vaccine (PCV13). A cross-sectional observational study was conducted, collecting nasopharyngeal swabs from children aged 25 to 55 months who had previously received 3 doses of PCV7, their parents, and adults aged ≥65 years. Pneumococcal serotyping was conducted according to World Health Organization guidelines with nontypeable isolates further analyzed by molecular serotyping. A national invasive disease surveillance program was conducted throughout the corresponding period. Pneumococcus was isolated from 47% of children, 9% of parents, and 2.2% of older adults. For these groups, the percentage of serotypes covered by PCV7 were 1.5%, 0.0%, and 15.4%, with a further 20.1%, 44.4%, and 7.7% coverage added by those in PCV13. In each group, the percentage of disease due to serotypes covered by PCV7 were 1.0%, 7.4% and 5.1% with a further 65.3%, 42.1%, and 61.4% attributed to those in PCV13. The prevalence of carriage is the highest in children, with direct vaccine impact exemplified by low carriage and disease prevalence of PCV7 serotypes in vaccinated children, whereas the indirect effects of herd protection are implied by similar observations in unvaccinated parents and older adults. PMID:25569650

  3. [Pneumococcal vaccine: protection of adults and reduction of antibiotic resistence by vaccination of children with a conjugated vaccine].

    PubMed

    Pletz, Mathias W

    2011-06-01

    Pneumococcal infections (pneumonia, otitis media, sinusitis, meningitis) are common and usually involve toddlers, immunocompromised and the elderly. Main reservoir of pneumococci is the nasopharyngeal zone of healthy carriers, especially of toddlers. Currently, two types of pneumococcal vaccines are in clinical use, which induce production of antibodies against capsular polysaccharides. The older vaccine consists of pure capsular polysaccharides. It induces a limited immunity, because polysaccharides are poor antigens that stimulate mainly B-cells. In children under two years of age this vaccine is not used, because it does not induce a sufficient immunologic response, presumably because of the immaturity of their immune system. In 2000, a vaccination program with a novel pneumococcal vaccine was launched in the USA. This vaccine contains capsular polysaccharides, that are conjugated with a highly immunogenic protein. It induces both a T cell and B cell response that results in specific humoral and mucosal immunity. U.S. data demonstrate, that serotypes covered by the conjugated vaccine can be reduced in the whole population by vaccination of children being the main reservoir of pneumococci. This so called ,,herd protection" results in a decrease in invasive pneumococcal diseases in vaccinees and non-vaccinees as well as in a reduction of antibiotic resistance rates by reducing resistant pneumococcal cones.

  4. Minimally invasive surgery for thyroid eye disease.

    PubMed

    Naik, Milind Neilkant; Nair, Akshay Gopinathan; Gupta, Adit; Kamal, Saurabh

    2015-11-01

    Thyroid eye disease (TED) can affect the eye in myriad ways: proptosis, strabismus, eyelid retraction, optic neuropathy, soft tissue changes around the eye and an unstable ocular surface. TED consists of two phases: active, and inactive. The active phase of TED is limited to a period of 12-18 months and is mainly managed medically with immunosuppression. The residual structural changes due to the resultant fibrosis are usually addressed with surgery, the mainstay of which is orbital decompression. These surgeries are performed during the inactive phase. The surgical rehabilitation of TED has evolved over the years: not only the surgical techniques, but also the concepts, and the surgical tools available. The indications for decompression surgery have also expanded in the recent past. This article discusses the technological and conceptual advances of minimally invasive surgery for TED that decrease complications and speed up recovery. Current surgical techniques offer predictable, consistent results with better esthetics.

  5. Minimally invasive surgery for thyroid eye disease

    PubMed Central

    Naik, Milind Neilkant; Nair, Akshay Gopinathan; Gupta, Adit; Kamal, Saurabh

    2015-01-01

    Thyroid eye disease (TED) can affect the eye in myriad ways: proptosis, strabismus, eyelid retraction, optic neuropathy, soft tissue changes around the eye and an unstable ocular surface. TED consists of two phases: active, and inactive. The active phase of TED is limited to a period of 12–18 months and is mainly managed medically with immunosuppression. The residual structural changes due to the resultant fibrosis are usually addressed with surgery, the mainstay of which is orbital decompression. These surgeries are performed during the inactive phase. The surgical rehabilitation of TED has evolved over the years: not only the surgical techniques, but also the concepts, and the surgical tools available. The indications for decompression surgery have also expanded in the recent past. This article discusses the technological and conceptual advances of minimally invasive surgery for TED that decrease complications and speed up recovery. Current surgical techniques offer predictable, consistent results with better esthetics. PMID:26669337

  6. Clearance of Pneumococcal Colonization in Infants Is Delayed through Altered Macrophage Trafficking

    PubMed Central

    Siegel, Steven J.; Tamashiro, Edwin; Weiser, Jeffrey N.

    2015-01-01

    Infections are a common cause of infant mortality worldwide, especially due to Streptococcus pneumoniae. Colonization is the prerequisite to invasive pneumococcal disease, and is particularly frequent and prolonged in children, though the mechanisms underlying this susceptibility are unknown. We find that infant mice exhibit prolonged pneumococcal carriage, and are delayed in recruiting macrophages, the effector cells of clearance, into the nasopharyngeal lumen. This lack of macrophage recruitment is paralleled by a failure to upregulate chemokine (C-C) motif ligand 2 (Ccl2 or Mcp-1), a macrophage chemoattractant that is required in adult mice to promote clearance. Baseline expression of Ccl2 and the related chemokine Ccl7 is higher in the infant compared to the adult upper respiratory tract, and this effect requires the infant microbiota. These results demonstrate that signals governing macrophage recruitment are altered at baseline in infant mice, which prevents the development of appropriate innate cell infiltration in response to pneumococcal colonization, delaying clearance of pneumococcal carriage. PMID:26107875

  7. Safety and immunogenicity of a single dose 23-valent pneumococcal polysaccharide vaccine in Russian subjects.

    PubMed

    Ciprero, Karen; Zykov, Kirill A; Briko, Nikolay I; Shekar, Tulin; Sterling, Tina M; Bitieva, Elizaveta; Stek, Jon E; Musey, Luwy

    2016-08-02

    Pneumococcal infection is a major cause of pneumonia, bacteremia, and meningitis. Incidence of pneumococcal disease (PD) varies worldwide. The 23-valent pneumococcal polysaccharide vaccine (PPV23) displays an acceptable safety profile and has been demonstrated cost-effective in reducing burden of PD.

  8. The relationship between pneumococcal serotypes and antibiotic resistance.

    PubMed

    Song, Jae-Hoon; Dagan, Ron; Klugman, Keith P; Fritzell, Bernard

    2012-04-05

    Streptococcus pneumoniae (SP) causes significant burden of disease, including invasive pneumococcal disease and noninvasive diseases such as pneumonia and acute otitis media. SP has at least 93 different capsular serotypes, with the various serotypes having different propensities for producing disease or developing antibiotic resistance. An increase in the prevalence of antibiotic-resistant SP serotypes has been observed globally. The objective of this paper was to examine the relationship between antibiotic resistance and SP serotypes, with a primary focus on studies published in the past 10 years. Changing trends in antibiotic resistance and serotype distribution during this time, including those before and after the introduction of 7-valent pneumococcal conjugate vaccine (PCV7), were analyzed. Factors that influence the prevalence of antibiotic-resistant serotypes include antibiotic selection pressure, the use of PCV7, and the emergence and spread of antibiotic-resistant clones. The emergence of multidrug resistant serotype 19A is of particular concern. Antibiotic-resistant SP is a global problem that must be addressed through multiple strategies, including national vaccination programs, antibiotic control programs, and ongoing surveillance.

  9. Clinical effectiveness of pneumococcal vaccine. Meta-analysis.

    PubMed Central

    Hutchison, B. G.; Oxman, A. D.; Shannon, H. S.; Lloyd, S.; Altmayer, C. A.; Thomas, K.

    1999-01-01

    OBJECTIVE: To determine the clinical effectiveness of pneumococcal vaccine. DATA SOURCES: Computerized searches of MEDLINE, EMBASE, and SCISEARCH databases were performed, reference lists of retrieved articles were reviewed, and first authors of published studies were contacted. STUDY SELECTION: Studies of use of pneumococcal vaccines in adults were included if the study design was a randomized or quasi-randomized controlled trial and at least one of the following clinical outcomes was reported: vaccine-type systemic pneumococcal infection, systemic pneumococcal infection, vaccine-type pneumococcal pneumonia, pneumococcal pneumonia, non-vaccine-type pneumococcal pneumonia. SYNTHESIS: Study quality was assessed and descriptive information concerning the study populations, interventions, and outcome measurements was extracted for 13 trials involving more than 65,000 patients. Estimates of vaccine efficacy, based on a meta-analysis of randomized and quasi-randomized trials, were determined for clinical outcomes. CONCLUSIONS: Vaccination with pneumococcal polysaccharide vaccine can be expected to reduce the risk of systemic infection due to pneumococcal types included in the vaccine by 83% and systemic infection due to all pneumococci by 73%. We found no evidence that the vaccine was less efficacious for the elderly, institutionalized people, or those with chronic disease. PMID:10540698

  10. Epidemiology of vaccine-preventable invasive diseases in Catalonia in the era of conjugate vaccines

    PubMed Central

    Ciruela, Pilar; Martínez, Ana; Izquierdo, Conchita; Hernández, Sergi; Broner, Sonia; Muñoz-Almagro, Carmen; Domínguez, Àngela; of Catalonia Study Group, the Microbiological Reporting System

    2013-01-01

    We investigated the incidence and distribution of cases of invasive pneumococcal disease (IPD), invasive meningococcal disease (IMD) and invasive Hemophilus influenzae disease (IHiD) notified by hospital laboratories to the Microbiological Reporting System of Catalonia between 2005 and 2009. Incidence rates were compared using the rate ratio (RR) and 95% CI were calculated. A value of p < 0.05 was considered statistically significant. Of the 6,661 cases, 6,012 were IPD, 436 IMD and 213 IHiD. The global annual incidence per 105 inhabitants was 16.62 (95% CI 16.20–17.04) for IPD, 1.21 (95% CI 1.09–1.32) for IMD and 0.59 (95% CI 0.51–0.67) for IHiD. IPD increased in 2009 compared with 2005 (RR:1.55, 95%CI: 1.43–1.70) and IMD and IHiD remained stable. Pneumonia was the most-frequent clinical manifestation of IPD (75.6%) and IHiD (44.1%) and meningoencephalitis with or without sepsis for IMD (70.6%). The male:female ratio was 1.37 for IPD, 1.0 for IMD and 1.15 for IHiD. The age groups with the highest incidence were the ≤ 2 y and 2–4 y groups for IPD (66.40 and 50.66/100,000 persons-year) and IMD (14.88 and 7.26/100,000 persons-year) and the ≤ 2 y and ≥ 65 y groups for IHiD (1.88 and 1.89/100,000 persons-year). The most-frequent serotypes were serotype 1 (19.0%) in IPD and untypeable serotypes (60.8%) in IHiD. Serogroup B (78.3%) was the most frequent in IMD. S. pneumoniae is the most-frequent agent causing invasive disease in Catalonia. The main clinical manifestations were pneumonia in IPD and IHiD and meningitis in IMD. The main causative agent of meningitis was N. meningitidis in people aged < 20 y and S. pneumoniae in people aged ≥ 20 y. Vaccination with conjugate vaccines may reduce the risk of infectious disease in our setting. PMID:23303166

  11. Trend of invasive pneumococal disease (IPD) in a South Western, Nigerian hospital.

    PubMed

    Olanrewaju, Motayo Babatunde; Olusola, Akingbade; Victor, Nwadike; Olabode, Shobayo; Joseph, Ogiogwa; Akiniyi, Akinduti; Iheanyi, Okonko

    2016-01-01

    The recent introduction of the Heptavalent-pneumococcal vaccine (PCV-7) by private pharmaceutical companies in Nigeria, has generated interest in invasive bacterial diseases particularly IPD. Our objective in this study is to investigate the trend and occurrence rate of IPD in Abeokuta, Nigeria. Suspected IPD cases were assessed from Jan 2010 to Dec 2010 for demographic and Microbiological characteristics. Bacterial isolations and antibiotics susceptibility testing followed standard bacteriological procedure. Overall 471 cases of probable IPD was assessed, with 21(4.5%) cases of suspected pneumonia, 109(23.1%) cases of suspected meningitis, and 341(72.4%) cases of suspected septicaemia. Confirmed IPD cases were 9 with 2 cases of meningitis, 3 cases of septicaemia and 4 cases of pneumonia. Age range distribution showed, high distribution of IPD cases among children >1 with 5(55.6%) there was a statistically significant difference in gender p< 0.05 (X2 test) with females recording a higher occurrence than males. We conclude by advocating for better detection methods against IPD meningitis cases, and continuous surveillance into the serotypes of streptococcus pneumonia as well inclusion of the PCV vaccine into our childhood immunization program.

  12. [Pneumococcal vaccines. New conjugate vaccines for adults].

    PubMed

    Campins Martí, Magda

    2015-11-01

    Pneumococcal infections are a significant cause of morbidity and mortality, and are one of the 10 leading causes of death worldwide. Children under 2 years have a higher incidence rate, followed by adults over 64 years. The main risk group are individuals with immunodeficiency, and those with anatomical or functional asplenia, but can also affect immunocompetent persons with certain chronic diseases. Significant progress has been made in the last 10 years in the prevention of these infections. Until a few years ago, only the 23-valent non-conjugate pneumococcal vaccine was available. Its results were controversial in terms of efficacy and effectiveness, and with serious limitations on the type of immune response induced. The current possibility of using the 13-valent conjugate vaccine in adults has led to greater expectations in improving the prevention of pneumococcal disease in these age groups.

  13. Invasive fungal disease in PICU: epidemiology and risk factors

    PubMed Central

    2012-01-01

    Candida and Aspergillus spp. are the most common agents responsible for invasive fungal infections in children. They are associated with a high mortality and morbidity rate as well as high health care costs. An important increase in their incidence has been observed during the past two decades. In infants and children, invasive candidiasis is five times more frequent than invasive aspergillosis. Candida sp. represents the third most common agent found in healthcare-associated bloodstream infections in children. Invasive aspergillosis is more often associated with hematological malignancies and solid tumors. Recommendations concerning prophylactic treatment for invasive aspergillosis have been recently published by the Infectious Diseases Society of America. Candida albicans is the main Candida sp. associated with invasive candidiasis in children, even if a strong trend toward the emergence of Candida non-albicans has been observed. The epidemiology and the risk factors for invasive fungal infections are quite different if considering previously healthy children hospitalized in the pediatric intensive care unit, or children with a malignancy or a severe hematological disease (leukemia). In children, the mortality rate for invasive aspergillosis is 2.5 to 3.5 higher than for invasive candidiasis (respectively 70% vs. 20% and 30%). PMID:22356683

  14. Pneumococcal Vaccines (PCV, PPSV)

    MedlinePlus

    ... to 2-Year-Old Your Child's Immunizations: Pneumococcal Vaccines (PCV, PPSV) KidsHealth > For Parents > Your Child's Immunizations: ... or HIV infection); or cochlear implants. Why the Vaccines Are Recommended Children younger than 2 years old, ...

  15. Pneumococcal Vaccines (PCV, PPSV)

    MedlinePlus

    ... Your 1- to 2-Year-Old Your Child's Immunizations: Pneumococcal Vaccines (PCV, PPSV) KidsHealth > For Parents > Your ... but also help stop the infections from spreading. Immunization Schedule PCV13 immunizations are given to all infants ...

  16. Pneumococcal Polysaccharide Vaccine

    MedlinePlus

    ... the United States.Treatment of pneumococcal infections with penicillin and other drugs used to be more effective. ... get another dose. Anyone who has a severe allergy to any component of PPSV should not receive ...

  17. [General epidemiology of invasive fungal disease].

    PubMed

    Pemán, Javier; Salavert, Miguel

    2012-02-01

    Invasive mycoses associated with high morbidity and mortality rates are increasing among immunocompromised or severely ill patients. Candida, Cryptococcus, Pneumocystis and Aspergillus are most prevalent agents with varying distribution as regards geography, patient condition and hospital units. The latest multicentre candidaemia survey conducted in Spain, showed C. albicans as the most frequently isolated species followed by C. parapsilosis, C. glabrata, C. tropicalis and C. krusei in contrast with other European or American studies where C. glabrata was second in rank. Aspergillus spp. is the leading agent causing invasive mycoses among filamentous fungi followed by Fusarium spp., Scedosporium spp. and zygomycetes. Aspergillus fumigatus is the most common agent in invasive aspergillosis (and azole-resistant isolates have been reported) but in the last few years Aspergillus flavus, Aspergillus nidulans and Aspergillus terreus have been isolated with increasing frequency variable with geographical factors, patients' underlying conditions or previous antifungal treatments.

  18. Invasive aspergillosis: new insights into disease, diagnostic and treatment.

    PubMed

    Karthaus, Meinolf; Buchheidt, Dieter

    2013-01-01

    Aspergillus infections are a threat to in patients with hematological malignancies. Known risk factors are profound and long lasting neutropenia, uncontrolled graft versus host disease, continuous administration of steroids and environmental factors such as hospital construction. Numerous efforts have been undertaken for prophylaxis of invasive aspergillosis in high-risk populations. Most of them failed to demonstrate survival advantages. Prophylaxis makes sense, since diagnosis and treatment of invasive aspergillosis remain difficult. The introduction of non-culture based tools for the diagnosis of invasive aspergillosis is an important step forward for early and sensitive diagnosis of invasive aspergillosis. Early treatment is the cornerstone of a successful management of invasive aspergillosis. Substantial improvement came with the introduction of lipid formulations of amphotericin B in the early 1990s. Voriconazole was the first azole that improved the overall survival for patients with invasive aspergillosis. Newer azoles and the echinocandins were introduced for the treatment of invasive aspergillosis in the late 1990s. Voriconazole and liposomal amphotericin B allow a safer and more effective treatment of invasive aspergillosis when compared with amphotericin B-desoxycholate. Combination of antifungal agents has been introduced in clinical trials. Up to now no significant benefit has been obtained with antifungal combination compared to voriconazole alone. Because mortality of invasive aspergillosis remains up to more than 50%, prophylaxis, early diagnosis and early initiation of antifungal therapy are of utmost importance for the reduction of invasive aspergillosis related mortality. Despite all advances in the management of invasive aspergillosis important questions remain unresolved. This article reviews the current state and new insights in the management of invasive aspergillosis and points out clinicians unmet needs.

  19. IL-17A and complement contribute to killing of pneumococci following immunization with a pneumococcal whole cell vaccine.

    PubMed

    Campos, Ivana B; Herd, Muriel; Moffitt, Kristin L; Lu, Ying-Jie; Darrieux, Michelle; Malley, Richard; Leite, Luciana C C; Gonçalves, Viviane M

    2017-03-01

    The pneumococcal whole cell vaccine (PWCV) has been investigated as an alternative to polysaccharide-based vaccines currently in use. It is a non-encapsulated killed vaccine preparation that induces non-capsular antibodies protecting mice against invasive pneumococcal disease (IPD) and reducing nasopharyngeal (NP) carriage via IL-17A activation of mouse phagocytes. Here, we show that PWCV induces antibody and IL-17A production to protect mice against challenge in a fatal aspiration-sepsis model after only one dose. We observed protection even with a boiled preparation, attesting to the stability and robustness of the vaccine. PWCV antibodies were shown to bind to different encapsulated strains, but complement deposition on the pneumococcal surface was observed only on serotype 3 strains; using flow cytometer methodology, variations in PWCV quality, as in the boiled vaccine, were detected. Moreover, anti-PWCV induces phagocytosis of different pneumococcal serotypes by murine peritoneal cells in the presence of complement or IL-17A. These findings suggest that complement and IL-17A may participate in the process of phagocytosis induced by PWCV antibodies. IL-17A can stimulate phagocytic cells to kill pneumococcus and this is enhanced in the presence of PWCV antibodies bound to the bacterial cell surface. Our results provide further support for the PWCV as a broad-range vaccine against all existing serotypes, potentially providing protection for humans against NP colonization and IPD. Additionally, we suggest complement deposition assay as a tool to detect subtle differences between PWCV lots.

  20. [Pneumococcal vaccines in children: an update].

    PubMed

    Potin, Marcela

    2014-08-01

    Conjugated pneumococal vaccines had a notable impact on prevention of invasive pneumococcal disease (IPD) in vacccinated and non vaccinated (herd immunity) populations. In Chile a 10 valent conjugated vaccine (PCV10) was introduced in the Nacional Immunization Program (NIP) in 2011, initially in a 3+1 schedule at 2, 4, 6 and 12 months of age, and since 2012 in a 2+1 schedule (2, 4 and 12 months). In prematures schedule 3+1 was maintained. No catch up or high risk groups vaccination strategies were used. The inclusion of PCV10 has reduced the rates of IPD; 66% in infants less than 12 months old and a 60% in 12-24 months old. After 3 years of the introduction of PCV10, no herd immunity has been seen. Serotype replacement shows an increase of ST 3 but not ST19A. Surveillance shows that another vaccine with 13 serotypes (PCV13) would cover an additional 5 to 10% of cases. The nule herd immunity and more extense coverage of PCV13, suggests that NIP should switch from PCV10 to PCV13.

  1. Promises and pitfalls of live attenuated pneumococcal vaccines.

    PubMed

    Rosch, Jason W

    2014-01-01

    The pneumococcus is a remarkably adaptable pathogen whose disease manifestations range from mucosal surface infections such as acute otitis media and pneumonia to invasive infections such as sepsis and meningitis. Currently approved vaccines target the polysaccharide capsule, of which there are over 90 distinct serotypes, leading to rapid serotype replacement in vaccinated populations. Substantial progress has been made in the development of a universal pneumococcal vaccine, with efforts focused on broadly conserved and protective protein antigens. An area attracting considerable attention is the potential application of live attenuated vaccines to confer serotype-independent protection against mucosal and systemic infection. On the basis of recent work to understand the mucosal and systemic responses to nasal administration of pneumococci and to develop novel attenuation strategies, the prospect of a practical and protective live vaccine remains promising.

  2. Invasive bacterial infections in Gambians with sickle cell anemia in an era of widespread pneumococcal and hemophilus influenzae type b vaccination.

    PubMed

    Soothill, Germander; Darboe, Saffiatou; Bah, Gibril; Bolarinde, Lawal; Cunnington, Aubrey; Anderson, Suzanne T

    2016-12-01

    There is relatively little data on the etiology of bacterial infections in patients with sickle cell anemia (SCA) in West Africa, and no data from countries that have implemented conjugate vaccines against both Streptococcus pneumoniae and Haemophilus influenzae type b (Hib).We conducted a retrospective analysis of SCA patients admitted to the Medical Research Council Unit, The Gambia, during a 5-year period when there was high coverage of Hib and Pneumococcal conjugate vaccination. We evaluated 161 admissions of 126 patients between April 2010 and April 2015.Pathogenic bacteria were identified in blood cultures from 11 of the 131 admissions that had cultures taken (8.4%, 95% CI 4.5-14.1%). The most frequent isolate was Salmonella Typhimurium (6/11; 54.5%), followed by Staphylococcus aureus (2/11; 18.2%) and other enteric Gram-negative pathogens (2/11; 18.2%) and there was 1 case of H influenzae non-type b bacteremia (1/11; 9.1%). There were no episodes of bacteremia caused by S pneumoniae or Hib.The low prevalence of S pneumoniae and Hib and the predominance of nontyphoidal Salmonella as a cause of bacteremia suggest the need to reconsider optimal antimicrobial prophylaxis and the empirical treatment regimens for patients with SCA.

  3. Invasive bacterial infections in Gambians with sickle cell anemia in an era of widespread pneumococcal and hemophilus influenzae type b vaccination

    PubMed Central

    Soothill, Germander; Darboe, Saffiatou; Bah, Gibril; Bolarinde, Lawal; Cunnington, Aubrey; Anderson, Suzanne T.

    2016-01-01

    Abstract There is relatively little data on the etiology of bacterial infections in patients with sickle cell anemia (SCA) in West Africa, and no data from countries that have implemented conjugate vaccines against both Streptococcus pneumoniae and Haemophilus influenzae type b (Hib). We conducted a retrospective analysis of SCA patients admitted to the Medical Research Council Unit, The Gambia, during a 5-year period when there was high coverage of Hib and Pneumococcal conjugate vaccination. We evaluated 161 admissions of 126 patients between April 2010 and April 2015. Pathogenic bacteria were identified in blood cultures from 11 of the 131 admissions that had cultures taken (8.4%, 95% CI 4.5–14.1%). The most frequent isolate was Salmonella Typhimurium (6/11; 54.5%), followed by Staphylococcus aureus (2/11; 18.2%) and other enteric Gram-negative pathogens (2/11; 18.2%) and there was 1 case of H influenzae non-type b bacteremia (1/11; 9.1%). There were no episodes of bacteremia caused by S pneumoniae or Hib. The low prevalence of S pneumoniae and Hib and the predominance of nontyphoidal Salmonella as a cause of bacteremia suggest the need to reconsider optimal antimicrobial prophylaxis and the empirical treatment regimens for patients with SCA. PMID:27930540

  4. Cost-effectiveness and cost utility analysis of three pneumococcal conjugate vaccines in children of Peru

    PubMed Central

    2013-01-01

    Background The clinical and economic burden associated with invasive and non-invasive pneumococcal and non-typeable Haemophilus influenzae (NTHi) diseases is substantial in the Latin America and Caribbean region, where pneumococcal vaccines have only been introduced to a few countries. This study analyzed the cost-effectiveness and cost utility of three different pneumococcal conjugate vaccines (PCVs) for Peru. Methods A Markov model that simulated the disease processes in a birth cohort over a lifetime, within 1,128 month cycles was used to evaluate the cost-effectiveness of 10-valent pneumococcal NTHi protein D conjugate vaccine (PHiD-CV) and 7- and 13-valent PCVs (PCV-7 and PCV-13). Expected quality-adjusted life years (QALYs), cost-savings and incremental cost-effectiveness ratios (ICERs) were calculated. Results Without vaccination, pneumonia was associated with the greatest health economic burden (90% of QALYs lost and 63% of lifetime direct medical costs); while acute otitis media (AOM) was responsible for 1% of QALYs lost and 25% of direct medical costs. All vaccines were predicted to be cost-effective for Peru, with PHiD-CV being most cost-effective. PHiD-CV was predicted to generate 50 more QALYs gained and required a reduced investment (−US$ 3.4 million) versus PCV-13 (discounted data), and was therefore dominant and cost saving. The probabilistic sensitivity analysis showed that PHiD-CV generated more QALYs gained at a reduced cost than PCV-13 in 84% of the simulations and less QALYs gains at a reduced cost in 16%. Additional scenarios using different assumptions on vaccine efficacies based on previous evidence were explored, but no significant change in the overall cost-effective results were observed. Conclusions The results of this modeling study predict that PCVs are likely to be a cost-effective strategy to help relieve the epidemiological and economic burden associated with pediatric pneumococcal and NTHi diseases for Peru. PHiD-CV is likely

  5. Diversity of pneumococcal surface protein A (PspA) among prevalent clones in Spain

    PubMed Central

    2009-01-01

    Background PspA is recognized as a major pneumococcal virulence factor and a possible vaccine candidate. The aim of this study was to analyze the PspA family and clade distribution among 112 Spanish pneumococci representatives of dominant clones among patients with invasive disease (n = 66) and nasopharyngeal healthy carriage in children (n = 46). Results PspA family 2 was predominant among invasive (63.6%) and carriage (54.3%) pneumococcal isolates. No PspA family 3 isolates were detected and only one strain was PspA negative. Although four clonal complexes contained strains of different clades, a clear association between clade and multi locus sequence typing results was found. Clades 1, 3 and 4 were associated with a wide variety of sequence types (ST) related to multiresistant and antibiotic-susceptible worldwide-disseminated clones. Clade 1 was associated with Spain6B-ST90, Spain14-ST18, Colombia5-ST289, Sweden1-ST306, Denmark14-ST230 and Sweden1-ST304 clones. Clade 3 was associated with Spain23F-ST81, Spain9V-ST156, Tennessee14-ST67, Netherlands3-ST180 and Netherlands7F-ST191 clones. Clade 4 was related to Sweden15A-ST63, Netherlands18C-ST113 and Greece21-ST193 clones. In contrast, PspA clade was not related to serotype, age or clinical origin of the isolates. Conclusion PspA clades were associated with genotypes. PspA family 2 and family 1 were dominant among major Spanish pneumococcal clones isolated from patients with invasive disease and nasopharyngeal carriage in children. PMID:19419534

  6. [Invasive mould disease in haematological patients].

    PubMed

    Ruiz-Camps, Isabel; Jarque, Isidro

    2014-01-01

    Invasive mould infections (IMI) are a persistent problem with high morbidity and mortality rates among patients receiving chemotherapy for hematological malignancies and hematopoietic stem cell transplant recipients. Management of IMI in this setting has become increasingly complex with the advent of new antifungal agents and diagnostic tests, which have resulted in different therapeutic strategies (prophylactic, empirical, pre-emptive, and directed). A proper assessment of the individual risk for IMI appears to be critical in order to use the best prophylactic and therapeutic approach and increase the survival rates. Among the available antifungal drugs, the most frequently used in the hematologic patient are fluconazole, mould-active azoles (itraconazole, posaconazole and voriconazole), candins (anidulafungin, caspofungin and micafungin), and lipid formulations of amphotericin B. Specific recommendations for their use, and criteria for selecting the antifungal agents are discussed in this paper.

  7. Strain features and distributions in pneumococci from children with invasive disease before and after 13-valent conjugate vaccine implementation in the USA

    PubMed Central

    Metcalf, B.J.; Gertz, R.E.; Gladstone, R.A.; Walker, H.; Sherwood, L.K.; Jackson, D.; Li, Z.; Law, C.; Hawkins, P.A.; Chochua, S.; Sheth, M.; Rayamajhi, N.; Bentley, S.D.; Kim, L.; Whitney, C.G.; McGee, L.; Beall, B.

    2016-01-01

    The effect of second-generation pneumococcal conjugate vaccines on invasive pneumococcal disease (IPD) strain distributions have not yet been well described. We analysed IPD isolates recovered from children aged <5 years through Active Bacterial Core surveillance before (2008–2009; n = 828) and after (2011–2013; n = 600) 13-valent pneumococcal conjugate vaccine (PCV13) implementation. We employed conventional testing, PCR/electrospray ionization mass spectrometry and whole genome sequence (WGS) analysis to identify serotypes, resistance features, genotypes, and pilus types. PCV13, licensed in February 2010, effectively targeted all major 19A and 7F genotypes, and decreased antimicrobial resistance, primarily owing to removal of the 19A/ST320 complex. The strain complex contributing most to the remaining β-lactam resistance during 2011–2013 was 35B/ST558. Significant emergence of non-vaccine clonal complexes was not evident. Because of the removal of vaccine serotype strains, positivity for one or both pilus types (PI-1 and PI-2) decreased in the post-PCV13 years 2011–2013 relative to 2008–2009 (decreases of 32–55% for PI-1, and >95% for PI-2 and combined PI-1 + PI-2). β-Lactam susceptibility phenotypes correlated consistently with transpeptidase region sequence combinations of the three major penicillin-binding proteins (PBPs) determined through WGS analysis. Other major resistance features were predictable by DNA signatures from WGS analysis. Multilocus sequence data combined with PBP combinations identified progeny, serotype donors and recipient strains in serotype switch events. PCV13 decreased the frequency of all PCV13 serotype clones and concurrently decreased the frequency of strain subsets with resistance and/or adherence features conducive to successful carriage. Our results serve as a reference describing key features of current paediatric IPD strains in the USA after PCV13 implementation. PMID:26363404

  8. Population Structure of Streptococcus pneumoniae Causing Invasive Disease in Adults in Portugal before PCV13 Availability for Adults: 2008-2011

    PubMed Central

    Horácio, Andreia N.; Silva-Costa, Catarina; Diamantino-Miranda, Jorge; Lopes, Joana P.; Ramirez, Mario; Melo-Cristino, José

    2016-01-01

    Among the 1660 isolates recovered from invasive pneumococcal disease (IPD) in adults (> = 18 yrs) in 2008–2011, a random sample of ≥50% of each serotype (n = 871) was chosen for MLST analysis and evaluation for the presence and type of pilus islands (PIs). The genetic diversity was high with 206 different sequence types (STs) detected, but it varied significantly between serotypes. The different STs represented 80 clonal complexes (CCs) according to goeBURST with the six more frequent accounting for more than half (50.6%) of the isolates—CC156 (serotypes 14, 9V and 23F), CC191 (serotype 7F), CC180 (serotype 3), CC306 (serotype 1), CC62 (serotypes 8 and 11A) and CC230 (serotype 19A). Most of the isolates (n = 587, 67.3%) were related to 29 Pneumococcal Molecular Epidemiology Network recognized clones. The overall proportion of isolates positive for any of the PIs was small (31.9%) and declined gradually during the study period (26.6% in 2011), mostly due to the significant decline of serotype 1 which is associated with PI-2. The changes in serotypes that occurred in adult IPD after the introduction of the seven-valent pneumococcal conjugate vaccine (PCV7) for children were mostly due to the expansion of previously circulating clones, while capsular switching was infrequent and not related to vaccine use. The reduction of IPD caused by PCV7 serotypes in the years following PCV7 implementation did not result in a decline of antimicrobial resistance in part due to the selection of resistant genotypes among serotypes 14 and 19A. PMID:27168156

  9. Safety and immunogenicity of a new 13-valent pneumococcal conjugate vaccine versus a licensed 7-valent pneumococcal conjugate vaccine: a study protocol of a randomised non-inferiority trial in China

    PubMed Central

    Chen, Jing Jing; Yuan, Lin; Huang, Zhen; Shi, Nian Min; Zhao, Yu Liang; Xia, Sheng Li; Li, Guo Hua; Li, Rong Cheng; Li, Yan Ping; Yang, Shu Yuan; Xia, Jie Lai

    2016-01-01

    Introduction The invasive pneumococcal diseases (IPDs) caused by Streptococcus pneumoniae pose an enormous threat to children under 5 years of age. However, routine use of pneumococcal conjugate vaccines could aid in reducing the incidence of IPDs. The purpose of this clinical trial is to assess the non-inferiority of the investigational 13-valent pneumococcal conjugate vaccine (PCV13) to the currently licensed 7-valent pneumococcal conjugate vaccine (PCV7). Methods and analysis 1040 infants will receive a three-dose series of either PCV13 or PCV7 at ages 3, 4 and 5 months, respectively, and a booster dose at 12–15 months. Primary end points are the percentage of participants reaching a serotype-specific IgG concentration of ≥0.35 µg/mL and the IgG antibody geometric mean concentrations (GMCs) measured 30 days after the primary immunisation. Secondary end points include the percentage of vaccine recipients reaching a serotype-specific IgG concentration threshold of 1.0 µg/mL, the percentage of participants reaching the pneumococcal opsonophagocytic assay (OPA) titre threshold of 1:8, and the geometric mean titres (GMTs) of OPA measured 30 days after primary and booster doses. The number of standard IgG responders and IgG GMCs measured 30 days after the booster immunisation will also be determined. To evaluate differences between two groups, the sequential testing of the non-inferiority of PCV13 for the seven common serotypes and its effectiveness in treating the six additional serotypes will be performed. Ethics and dissemination Ethics approvals have been granted by the Ethics Committees at the three provinces involved in this study: Shanxi, Henan and Hebei. The trial will be reported in accordance with the CONSORT guidance. Trial registration number NCT02736240. PMID:27798013

  10. Minimally invasive surgical treatment of valvular heart disease.

    PubMed

    Goldstone, Andrew B; Joseph Woo, Y

    2014-01-01

    Cardiac surgery is in the midst of a practice revolution. Traditionally, surgery for valvular heart disease consisted of valve replacement via conventional sternotomy using cardiopulmonary bypass. However, over the past 20 years, the increasing popularity of less-invasive procedures, accompanied by advancements in imaging, surgical instrumentation, and robotic technology, has motivated and enabled surgeons to develop and perform complex cardiac surgical procedures through small incisions, often eliminating the need for sternotomy or cardiopulmonary bypass. In addition to the benefits of improved cosmesis, minimally invasive mitral valve surgery was pioneered with the intent of reducing morbidity, postoperative pain, blood loss, hospital length of stay, and time to return to normal activity. This article reviews the current state-of-the-art of minimally invasive approaches to the surgical treatment of valvular heart disease.

  11. Pharyngeal colonization by Kingella kingae in children with invasive disease.

    PubMed

    Yagupsky, Pablo; Porat, Nurith; Pinco, Erica

    2009-02-01

    Kingella kingae organisms isolated from the blood of 3 children with invasive infections were identical by pulsed field gel electrophoresis and random amplified polymorphic DNA-polymerase chain reaction analysis to those recovered from the patients' pharynx, demonstrating the likely role of upper respiratory tract colonization in the pathogenesis of the disease caused by this bacterium.

  12. Invasive Type e Haemophilus influenzae Disease in Italy

    PubMed Central

    degli Atti, Marta Luisa Ciofi; Cardines, Rita; Salmaso, Stefania; Renna, Giovanna; Mastrantonio, Paola

    2003-01-01

    We describe the first reported cases of invasive type e Haemophilus influenzae disease in Italy. All five cases occurred in adults. The isolates were susceptible to ampicillin and eight other antimicrobial agents. Molecular analysis showed two distinct type e strains circulating in Italy, both containing a single copy of the capsulation locus. PMID:12604001

  13. Common invasive fungal diseases: an overview of invasive candidiasis, aspergillosis, cryptococcosis, and Pneumocystis pneumonia.

    PubMed

    Schmiedel, Yvonne; Zimmerli, Stephan

    2016-01-01

    Every year, Candida, Aspergillus, Cryptococcus and Pneumocystis infect an estimated two million individuals worldwide. Most are immunocompromised or critically ill. Candida is the most common fungal pathogen of the critically ill and of recipients of transplanted abdominal organs. In high-risk haemato-oncological patients, in contrast, the introduction of antifungal prophylaxis with fluconazole and later with mould-active posaconazole has led to a remarkable reduction of invasive candidiasis and is likely to have a similar effect on invasive aspergillosis. Invasive aspergillosis remains the dominant invasive fungal disease (IFD) of haemato-oncological patients and solid-organ transplant recipients and is increasingly found in individuals with exacerbated chronic obstructive pulmonary disease on corticosteroids. In the developed world, owing to antiretroviral therapy Pneumocystis pneumonia and cryptococcosis have become rare in patients with human immunodeficiency virus (HIV) and are mainly found in solid-organ transplant recipients or immunocompromised patients. In the developing world, cryptococcosis remains a common and highly lethal disease of HIV positive individuals. With invasive candidiasis and invasive aspergillosis, timely diagnosis is the principal challenge. The clinical presentation is nonspecific and current diagnostic tests lack sensitivity and specificity. The combination of several tests improves sensitivity, but not specificity. Standardised polymerase chain-reaction-based assays may be promising tools for more rapid and specific diagnosis of candidiasis and invasive aspergillosis. Nevertheless, initiation of treatment is often based solely on clinical suspicion. Empirical therapy, however, may lead to over-treatment of patients without IFD or it may miss its target in the case of resistance. Despite the success of antifungal prophylaxis in reducing the incidence of IFDs in haemato-oncological patients, there are a considerable number of

  14. Advances in non-invasive imaging of intracranial vascular disease.

    PubMed Central

    Jäger, H. R.; Grieve, J. P.

    2000-01-01

    Intra-arterial catheter angiography has, in the past, been the mainstay for the investigation of intracranial vascular disease. It is, however, invasive, usually requires in-patients admission, and is associated with a rate of neurological complications between 1% and 3%. In recent years, magnetic resonance angiography (MRA) and CT angiography (CTA) have emerged as non-invasive alternatives for imaging blood vessels and have made a significant impact on neuroradiological investigations. It is the purpose of this article to explain the basic technical principles of these two methods and to give an overview of their current clinical applications. PMID:10700757

  15. Vaccines against invasive Salmonella disease: current status and future directions.

    PubMed

    MacLennan, Calman A; Martin, Laura B; Micoli, Francesca

    2014-01-01

    Though primarily enteric pathogens, Salmonellae are responsible for a considerable yet under-appreciated global burden of invasive disease. In South and South-East Asia, this manifests as enteric fever caused by serovars Typhi and Paratyphi A. In sub-Saharan Africa, a similar disease burden results from invasive nontyphoidal Salmonellae, principally serovars Typhimurium and Enteritidis. The existing Ty21a live-attenuated and Vi capsular polysaccharide vaccines target S. Typhi and are not effective in young children where the burden of invasive Salmonella disease is highest. After years of lack of investment in new Salmonella vaccines, recent times have seen increased interest in the area led by emerging-market manufacturers, global health vaccine institutes and academic partners. New glycoconjugate vaccines against S. Typhi are becoming available with similar vaccines against other invasive serovars in development. With other new vaccines under investigation, including live-attenuated, protein-based and GMMA vaccines, now is an exciting time for the Salmonella vaccine field.

  16. Comparison of Serotype Prevalence of Pneumococci Isolated from Middle Ear, Lower Respiratory Tract and Invasive Disease Prior to Vaccination in Iceland

    PubMed Central

    Haraldsson, Gunnsteinn; Erlendsdóttir, Helga; Haraldsson, Ásgeir; Kristinsson, Karl G.

    2017-01-01

    Background Information on pneumococcal serotype distribution before vaccination is a prerequisite for evaluation of vaccine effect. The aim was to investigate the prevalence of pneumococcal serotypes isolated from middle ear (ME), lower respiratory tract (LRT) and from invasive disease (IPD) in Iceland prior to implementation of ten-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine (PHiD-CV-10) into the infant vaccination program (April 2011). Methods and findings All isolates cultured 2007–2011 from ME, LRT and IPD identified as pneumococci were serotyped and tested for susceptibility at the Clinical Microbiology Department, Landspitali University Hospital that serves approximately 85% of the Icelandic population. Pneumococcal isolates were 1711 and 1616 (94.4%) were available for serotyping and included. Isolates belonging to PHiD-CV10 serotypes (VTs) were 1052 (65.1%). Isolates from ME were 879 (54.4%), with 639 (72.7%) from 0–1 year old patients and 651 of VTs (74%). Isolates from LRT were 564 (34.9%), with 292 (51.8%) from ≥65 years old patients, and 300 (53.2%) of VTs. IPD isolates were 173 (10.7%), although more evenly distributed according to age than isolates from the other sites most were from adults and the youngest age group,101 (58.4%) isolates were of VTs. The most common serotype was 19F, 583 (36.1%). Its prevalence was highest in ME, 400 (45.5%), 172 (30.5%) in LRT and 11 isolates (6.4%), in IPD. Penicillin non-susceptible isolates were 651 (40.3%), mainly belonging to VTs, 611 (93.9%), including 535 (82.2%) of 19F. Conclusions Multiresistant isolates of serotype 19F were highly prevalent, especially from ME of young children but also from LRT of adults. Serotype 14 was the most common serotype in IPD. The rate of VTs was high and almost all PNSP were of VTs. There was great difference in vaccine coverage between sampling sites, also reflecting difference in vaccine coverage by age groups. PMID:28125588

  17. Serotype Distribution and Antimicrobial Susceptibilities of Invasive Streptococcus pneumoniae Isolates from Adults in Korea from 1997 to 2012.

    PubMed

    Kim, Chung Jong; Song, Jin-Su; Choi, Su-Jin; Song, Kyoung Ho; Choe, Pyeong Gyun; Park, Wan Beom; Bang, Ji Hwan; Kim, Eu Suk; Park, Sang Won; Kim, Hong Bin; Kim, Nam-Joong; Kim, Eui-Chong; Oh, Myoung-don

    2016-05-01

    In Republic of Korea, a 7-valent pneumococcal conjugated vaccine (PCV7) was licensed for use in infants in 2003, and 13-valent PCV (PCV13) replaced it since 2010. We investigated trends in serotype distribution and antibiotic susceptibility of pneumococcal isolates from adult patients with invasive pneumococcal diseases (IPD). Invasive pneumococcal isolates from adult patients of ≥ 16 years of age were collected from 1997 to 2012. Serotypes of the isolates were determined by the Quellung reaction. Distribution of serotypes was analyzed according to the vaccine types. Antibiotic susceptibility was tested by using E-test strips. A total of 272 invasive pneumococcal isolates were included. The most common serotypes were serotype 19F (8.5%, 23/272), and serotype 3 (8.1%, 22/272), and 24.6% (67/272) of the isolates were of non-vaccine serotypes. Of the 272 isolates, 2.6% (7/272) were penicillin MICs of ≥ 4 µg/mL. The proportion of the PCV13 serotypes decreased from 63.3% (50/79) in 1997-2003 to 48.6% (17/35) in 2011-2012, whereas that of non-vaccine serotypes was 26.6% (21/79) and 25.7% (9/35), respectively, for the same periods. The proportion of the PCV13 serotypes showed a decreasing trend among adult patients with IPD over the study period.

  18. Molecular resistance mechanisms of macrolide-resistant invasive Streptococcus pneumoniae isolates from Alaska, 1986 to 2010.

    PubMed

    Rudolph, Karen; Bulkow, Lisa; Bruce, Michael; Zulz, Tammy; Reasonover, Alisa; Harker-Jones, Marcella; Hurlburt, Debby; Hennessy, Thomas

    2013-11-01

    The rapid emergence of antibiotic-resistant pneumococcal strains has reduced treatment options. The aim of this study was to determine antimicrobial susceptibilities, serotype distributions, and molecular resistance mechanisms among macrolide-resistant invasive pneumococcal isolates in Alaska from 1986 to 2010. We identified cases of invasive pneumococcal disease in Alaska from 1986 to 2010 through statewide population-based laboratory surveillance. All invasive pneumococcal isolates submitted to the Arctic Investigations Program laboratory were confirmed by standard microbiological methods and serotyped by slide agglutination and the Quellung reaction. MICs were determined by the broth microdilution method, and macrolide-resistant genotypes were determined by multiplex PCR. Among 2,923 invasive pneumococcal isolates recovered from 1986 to 2010, 270 (9.2%) were nonsusceptible to erythromycin; 177 (66%) erythromycin-nonsusceptible isolates demonstrated coresistance to penicillin, and 167 (62%) were multidrug resistant. The most frequent serotypes among the macrolide-resistant isolates were serotypes 6B (23.3%), 14 (20.7%), 19A (16.7%), 9V (8.9%), 19F (6.3%), 6A (5.6%), and 23F (4.8%). mef and erm(B) genes were detected in 207 (77%) and 32 (12%) of the isolates, respectively. Nineteen (7%) of the erythromycin-nonsusceptible isolates contained both mef and erm(B) genotypes; 15 were of serotype 19A. There was significant year-to-year variation in the proportion of isolates that were nonsusceptible to erythromycin (P < 0.001). Macrolide resistance among pneumococcal isolates from Alaska is mediated predominantly by mef genes, and this has not changed significantly over time. However, there was a statistically significant increase in the proportion of isolates that possess both erm(B) and mef, primarily due to serotype 19A isolates.

  19. [Consensus document on pneumococcal vaccination in adults at risk by age and underlying clinical conditions. 2017 Update].

    PubMed

    González-Romo, F; Picazo, J J; García Rojas, A; Labrador Horrillo, M; Barrios, V; Magro, M C; Gil Gregorio, P; de la Cámara, R; Rodríguez, A; Barberán, J; Botía Martínez, F; Linares Rufo, M; Jimeno Sanz, I; Portolés, J M; Sanz Herrero, F; Espinosa Arranz, J; García-Sánchez, V; Galindo Izquierdo, M; Mascarós, E

    2017-04-01

    Invasive pneumococcal disease (IPD) and pneumococcal pneumonia (PP) represent an important health problem among aging adults and those with certain underlying pathologies and some diseases, especially immunosuppressed and some immunocompetent subjects, who are more susceptible to infections and present greater severity and worse evolution. Among the strategies to prevent IPD and PP, vaccination has its place, although vaccination coverage in this group is lower than desirable. Nowadays, there are 2 vaccines available for adults. Polysacharide vaccine (PPV23), used in patients aged 2 and older since decades ago, includes a greater number of serotypes (23), but it does not generate immune memory, antibody levels decrease with time, causes an immune tolerance phenomenon, and have no effect on nasopharyngeal colonization. PCV13 can be used from children 6 weeks of age to elderly and generates an immune response more powerful than PPV23 against most of the 13 serotypes included in it. In the year 2013 the 16 most directly related to groups of risk of presenting IPD publised a series of vaccine recommendations based on scientific evidence regarding anti-pneumococcal vaccination in adults with underlying pathologies and special conditions. A commitment was made about updating it if new scientific evidence became available. We present an exhaustive revised document focusing mainly in recommendation by age in which some more Scientific Societies have been involved.

  20. Lactate dehydrogenase is the key enzyme for pneumococcal pyruvate metabolism and pneumococcal survival in blood.

    PubMed

    Gaspar, Paula; Al-Bayati, Firas A Y; Andrew, Peter W; Neves, Ana Rute; Yesilkaya, Hasan

    2014-12-01

    Streptococcus pneumoniae is a fermentative microorganism and causes serious diseases in humans, including otitis media, bacteremia, meningitis, and pneumonia. However, the mechanisms enabling pneumococcal survival in the host and causing disease in different tissues are incompletely understood. The available evidence indicates a strong link between the central metabolism and pneumococcal virulence. To further our knowledge on pneumococcal virulence, we investigated the role of lactate dehydrogenase (LDH), which converts pyruvate to lactate and is an essential enzyme for redox balance, in the pneumococcal central metabolism and virulence using an isogenic ldh mutant. Loss of LDH led to a dramatic reduction of the growth rate, pinpointing the key role of this enzyme in fermentative metabolism. The pattern of end products was altered, and lactate production was totally blocked. The fermentation profile was confirmed by in vivo nuclear magnetic resonance (NMR) measurements of glucose metabolism in nongrowing cell suspensions of the ldh mutant. In this strain, a bottleneck in the fermentative steps is evident from the accumulation of pyruvate, revealing LDH as the most efficient enzyme in pyruvate conversion. An increase in ethanol production was also observed, indicating that in the absence of LDH the redox balance is maintained through alcohol dehydrogenase activity. We also found that the absence of LDH renders the pneumococci avirulent after intravenous infection and leads to a significant reduction in virulence in a model of pneumonia that develops after intranasal infection, likely due to a decrease in energy generation and virulence gene expression.

  1. A Perspective on Invasive Salmonella Disease in Africa.

    PubMed

    Crump, John A; Heyderman, Robert S

    2015-11-01

    Salmonella enterica is a leading cause of community-acquired bloodstream infection in Africa. The contribution of typhoidal and nontyphoidal Salmonella serovars to invasive disease varies considerably in place and time, even within the same country. Nonetheless, many African countries are now thought to experience typhoid fever incidence >100 per 100,000 per year with approximately 1% of patients dying. Invasive nontyphoidal Salmonella (iNTS) disease was estimated to cause 3.4 million illnesses and 681 316 deaths in 2010, with the most disease in Africa. Antimicrobial drug resistance is a growing problem in S. enterica that threatens to further compromise patient outcomes. Reservoirs for nontyphoidal Salmonella and the predominant routes of transmission for typhoidal and nontyphoidal Salmonella are not well understood in Africa, hampering the design of evidence-based, non-vaccine- and vaccine-based prevention measures. It is difficult to distinguish clinically invasive Salmonella disease from febrile illnesses caused by other pathogens. Blood cultures are the mainstay of laboratory diagnosis, but lack sensitivity due to the low magnitude of bacteremia, do not produce results at point of care, and are not widely available in Africa. Serologic approaches to diagnosis remain inaccurate, and nucleic acid amplification tests are also compromised by low concentrations of bacteria. High-throughput whole-genome sequencing, together with a range of novel analytic pipelines, has provided new insights into the complex pattern of epidemiology, pathogenesis, and host adaptation. Concerted efforts are therefore needed to apply these new tools in the context of high-quality field surveillance to improve diagnosis, patient management, control, and prevention of invasive Salmonella infections in Africa.

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

    PubMed

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

    2013-09-06

    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 explore an immune-mediated model of the viral-bacterial interaction that quantifies the timing and the intensity of the interaction. Taking advantage of the wealth of knowledge gained from animal models, and the quantitative understanding of the kinetics of pathogen-specific immunological dynamics, we formulate a mathematical model for immune-mediated interaction between influenza virus and S. pneumoniae in the lungs. We use the model to examine the pathogenic effect of inoculum size and timing of pneumococcal invasion relative to influenza infection, as well as the efficacy of antivirals in preventing severe pneumococcal disease. We find that our model is able to capture the key features of the interaction observed in animal experiments. The model predicts that introduction of pneumococcal bacteria during a 4-6 day window following influenza infection results in invasive pneumonia at significantly lower inoculum size than in hosts not infected with influenza. Furthermore, we find that antiviral treatment administered later than 4 days after influenza infection was not able to prevent invasive pneumococcal disease. This work provides a quantitative framework to study interactions between influenza and pneumococci and has the potential to accurately quantify the interactions. Such quantitative understanding can form a basis for effective clinical care, public health policies and pandemic preparedness.

  3. Pneumococcal Vaccination Guidance for Post-Acute and Long-Term Care Settings: Recommendations From AMDA's Infection Advisory Committee.

    PubMed

    Nace, David A; Archbald-Pannone, Laurie R; Ashraf, Muhammad S; Drinka, Paul J; Frentzel, Elizabeth; Gaur, Swati; Mahajan, Dheeraj; Mehr, David R; Mercer, William C; Sloane, Philip D; Jump, Robin L P

    2017-02-01

    Efforts at preventing pneumococcal disease are a national health priority, particularly in older adults and especially in post-acute and long-term care settings The Advisory Committee on Immunization Practices recommends that all adults ≥65 years of age, as well as adults 18-64 years of age with specific risk factors, receive both the recently introduced polysaccharide-protein conjugate vaccine against 13 pneumococcal serotypes as well as the polysaccharide vaccine against 23 pneumococcal serotypes. Nursing facility licensure regulations require facilities to assess the pneumococcal vaccination status of each resident, provide education regarding pneumococcal vaccination, and administer the appropriate pneumococcal vaccine when indicated. Sorting out the indications and timing for 13 pneumococcal serotypes and 23 pneumococcal serotypes administration is complex and presents a significant challenge to healthcare providers. Here, we discuss the importance of pneumococcal vaccination for older adults, detail AMDA-The Society for Post-Acute and Long-Term Care Medicine (The Society)'s recommendations for pneumococcal vaccination practice and procedures, and offer guidance to postacute and long-term care providers supporting the development and effective implementation of pneumococcal vaccine policies.

  4. Real-time qPCR improves meningitis pathogen detection in invasive bacterial-vaccine preventable disease surveillance in Fiji

    PubMed Central

    Dunne, Eileen M.; Mantanitobua, Silivia; Singh, Shalini P.; Reyburn, Rita; Tuivaga, Evelyn; Rafai, Eric; Tikoduadua, Lisi; Porter, Barbara; Satzke, Catherine; Strachan, Janet E.; Fox, Kimberly K.; Jenkins, Kylie M.; Jenney, Adam; Baro, Silo; Mulholland, E. Kim; Kama, Mike; Russell, Fiona M.

    2016-01-01

    As part of the World Health Organization Invasive Bacterial-Vaccine Preventable Diseases (IB-VPD) surveillance in Suva, Fiji, cerebrospinal fluid (CSF) samples from suspected meningitis patients of all ages were examined by traditional methods (culture, Gram stain, and latex agglutination for bacterial antigen) and qPCR for Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae. Of 266 samples tested, pathogens were identified in 47 (17.7%). S. pneumoniae was the most common pathogen detected (n = 17) followed by N. meningitidis (n = 13). The use of qPCR significantly increased detection of IB-VPD pathogens (P = 0.0001): of 35 samples that were qPCR positive for S. pneumoniae, N. meningitidis, and H. influenzae, only 10 were culture positive. This was particularly relevant for N. meningitidis, as only 1/13 cases was culture positive. Molecular serotyping by microarray was used to determine pneumococcal serotypes from 9 of 16 (56%) of samples using DNA directly extracted from CSF specimens. Results indicate that qPCR significantly increases detection of S. pneumoniae, N. meningitidis, and H. influenzae in CSF, and that application of molecular diagnostics is a feasible way to enhance local and global surveillance for IB-VPD. PMID:28009001

  5. Delayed recognition of fatal invasive meningococcal disease in adults

    PubMed Central

    Ezeoke, Ifeoma; Antwi, Mike; Del Rosso, Paula E.; Dorsinville, Marie; Isaac, Beth M.; Hayden, Althea; Hoffman, Robert S.; Weingart, Scott D.; Weiss, Don

    2016-01-01

    Introduction: Invasive meningococcal disease can be difficult to detect early in its course when patients may appear well and the severity of their illness is obscured by non-specific complaints. Case presentation: We report five cases of meningococcal sepsis in adult patients who presented to an emergency department early in the course of their disease, but whose severity of illness was not recognized. Conclusion: Suspicion of meningococcal sepsis should be heightened in the setting of hypotension, tachycardia, elevated shock index, leukopaenia with left shift, thrombocytopaenia and hypokalaemia, prompting early sepsis care. PMID:28348753

  6. Minimally invasive surgical treatment for kidney stone disease.

    PubMed

    Rodríguez, Dayron; Sacco, Dianne E

    2015-07-01

    Minimally invasive interventions for stone disease in the United States are mainly founded on 3 surgical procedures: extracorporeal shock wave lithotripsy, ureteroscopic lithotripsy, and percutaneous nephrolithotomy. With the advancement of technology, treatment has shifted toward less invasive strategies and away from open or laparoscopic surgery. The treatment chosen for a patient with stones is based on the stone and patient characteristics. Each of the minimally invasive techniques uses an imaging source, either fluoroscopy or ultrasound, to localize the stone and an energy source to fragment the stone. Extracorporeal shock wave lithotripsy uses a shock wave energy source generated outside the body to fragment the stone. In contrast, with ureteroscopy, laser energy is placed directly on the stone using a ureteroscope that visualizes the stone. Percutaneous nephrolithotomy requires dilation of a tract through the back into the renal pelvis so that instruments can be inserted directly onto the stone to fragment or pulverize it. The success of the surgical intervention relies on performing the least invasive technique with the highest success of stone removal.

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

    PubMed

    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.

  8. V-akt murine thymoma viral oncogene homolog 3 (AKT3) contributes to poor disease outcome in humans and mice with pneumococcal meningitis.

    PubMed

    Valls Serón, Mercedes; Ferwerda, Bart; Engelen-Lee, JooYeon; Geldhoff, Madelijn; Jaspers, Valery; Zwinderman, Aeilko H; Tanck, Michael W; Baas, Frank; van der Ende, Arie; Brouwer, Matthijs C; van de Beek, Diederik

    2016-05-18

    Pneumococcal meningitis is the most common and severe form of bacterial meningitis. Fatality rates are substantial, and long-term sequelae develop in about half of survivors. Here, we have performed a prospective nationwide genetic association study using the Human Exome BeadChip and identified gene variants in encoding dynactin 4 (DCTN4), retinoic acid early transcript 1E (RAET1E), and V-akt murine thymoma viral oncogene homolog 3 (AKT3) to be associated with unfavourable outcome in patients with pneumococcal meningitis. No clinical replication cohort is available, so we validated the role of one of these targets, AKT3, in a pneumococcal meningitis mouse model. Akt3 deficient mice had worse survival and increased histopathology scores for parenchymal damage (infiltration) and vascular infiltration (large meningeal artery inflammation) but similar bacterial loads, cytokine responses, compared to wild-type mice. We found no differences in cerebrospinal fluid cytokine levels between patients with risk or non-risk alleles. Patients with the risk genotype (rs10157763, AA) presented with low scores on the Glasgow Coma Scale and high rate of epileptic seizures. Thus, our results show that AKT3 influences outcome of pneumococcal meningitis.

  9. [Advice of the French Superior Council on Public Health (section on transmissible diseases) relative to vaccination by heptavalent pneumococcal conjugate vaccine (Prevanar). Meeting of March 8, 2002].

    PubMed

    2002-08-01

    This article is the full-length text (including arguments and recommendations) written by the Conseil Supérieur d'Hygiène Publique de France, in its session of march 8th 2002, expressing its opinion on the immunization policy with the heptavalent pneumococcal conjugate vaccine (Prevenar).

  10. Necrotizing pneumonia and acute purulent pericarditis caused by Streptococcus pneumoniae serotype 19A in a healthy 4-year-old girl after one catch-up dose of 13-valent pneumococcal conjugate vaccine.

    PubMed

    Lu, Shay; Tsai, Jeng-Dau; Tsao, Ten-Fu; Liao, Pei-Fen; Sheu, Ji-Nan

    2016-08-01

    Streptococcus pneumoniae is a common cause of infectious diseases in children that may lead to life-threatening complications. Acute purulent pericarditis is an uncommon complication of S. pneumoniae in the antibiotic era. A healthy 4-year-old girl was admitted with pneumonia and pleural effusion. She had received one catch-up dose of 13-valent pneumococcal conjugate vaccine at 2 years of age. She rapidly developed necrotizing pneumonia, complicated by bronchopleural fistula presenting as subcutaneous emphysema and pneumothorax and acute purulent pericarditis. S. pneumoniae serotype 19A was subsequently identified from blood, empyema and pericardial fluid cultures. After appropriate antibiotic therapy and a right lower lobectomy, her condition stabilized and she promptly recovered. This case highlights two rare potential clinical complications of pneumococcal disease in a child: necrotizing pneumonia and acute purulent pericarditis. This is the first report of a child who received just one catch-up dose of 13-valent pneumococcal conjugate vaccine at 2 years of age, as per the United States' Advisory Committee on Immunization Practice's recommendations, but who still developed severe invasive pneumococcal disease with life-threatening complications caused by S. pneumoniae serotype 19A.

  11. Necrotizing pneumonia and acute purulent pericarditis caused by Streptococcus pneumoniae serotype 19A in a healthy 4-year-old girl after one catch-up dose of 13-valent pneumococcal conjugate vaccine.

    PubMed

    Lu, Shay; Tsai, Jeng-Dau; Tsao, Ten-Fu; Liao, Pei-Fen; Sheu, Ji-Nan

    2016-01-29

    Streptococcus pneumoniae is a common cause of infectious diseases in children that may lead to life-threatening complications. Acute purulent pericarditis is an uncommon complication of S. pneumoniae in the antibiotic era. A healthy 4-year-old girl was admitted with pneumonia and pleural effusion. She had received one catch-up dose of 13-valent pneumococcal conjugate vaccine at 2 years of age. She rapidly developed necrotizing pneumonia, complicated by bronchopleural fistula presenting as subcutaneous emphysema and pneumothorax and acute purulent pericarditis. S. pneumoniae serotype 19A was subsequently identified from blood, empyema and pericardial fluid cultures. After appropriate antibiotic therapy and a right lower lobectomy, her condition stabilized and she promptly recovered. This case highlights two rare potential clinical complications of pneumococcal disease in a child: necrotizing pneumonia and acute purulent pericarditis. This is the first report of a child who received just one catch-up dose of 13-valent pneumococcal conjugate vaccine at 2 years of age, as per the United States' Advisory Committee on Immunization Practice's recommendations, but who still developed severe invasive pneumococcal disease with life-threatening complications caused by S. pneumoniae serotype 19A.

  12. Following in real time the impact of pneumococcal virulence factors in an acute mouse pneumonia model using bioluminescent bacteria.

    PubMed

    Saleh, Malek; Abdullah, Mohammed R; Schulz, Christian; Kohler, Thomas; Pribyl, Thomas; Jensch, Inga; Hammerschmidt, Sven

    2014-02-23

    Pneumonia is one of the major health care problems in developing and industrialized countries and is associated with considerable morbidity and mortality. Despite advances in knowledge of this illness, the availability of intensive care units (ICU), and the use of potent antimicrobial agents and effective vaccines, the mortality rates remain high(1). Streptococcus pneumoniae is the leading pathogen of community-acquired pneumonia (CAP) and one of the most common causes of bacteremia in humans. This pathogen is equipped with an armamentarium of surface-exposed adhesins and virulence factors contributing to pneumonia and invasive pneumococcal disease (IPD). The assessment of the in vivo role of bacterial fitness or virulence factors is of utmost importance to unravel S. pneumoniae pathogenicity mechanisms. Murine models of pneumonia, bacteremia, and meningitis are being used to determine the impact of pneumococcal factors at different stages of the infection. Here we describe a protocol to monitor in real-time pneumococcal dissemination in mice after intranasal or intraperitoneal infections with bioluminescent bacteria. The results show the multiplication and dissemination of pneumococci in the lower respiratory tract and blood, which can be visualized and evaluated using an imaging system and the accompanying analysis software.

  13. A Decade of Invasive Meningococcal Disease Surveillance in Poland

    PubMed Central

    Skoczyńska, Anna; Waśko, Izabela; Kuch, Alicja; Kadłubowski, Marcin; Gołębiewska, Agnieszka; Foryś, Małgorzata; Markowska, Marlena; Ronkiewicz, Patrycja; Wasiak, Katarzyna; Kozińska, Aleksandra; Matynia, Bożena; Hryniewicz, Waleria

    2013-01-01

    Background Neisseria meningitidis is a leading etiologic agent of severe invasive disease. The objective of the study was to characterise invasive meningococcal disease (IMD) epidemiology in Poland during the last decade, based on laboratory confirmed cases. Methods The study encompassed all invasive meningococci collected between 2002 and 2011 in the National Reference Centre for Bacterial Meningitis. The isolates were re-identified and characterised by susceptibility testing, MLST analysis, porA and fetA sequencing. A PCR technique was used for meningococcal identification directly from clinical materials. Results In the period studied, 1936 cases of IMD were confirmed, including 75.6% identified by culture. Seven IMD outbreaks, affecting mostly adolescents, were reported; all were caused by serogroup C meningococci of ST-11. The highest incidence was observed among children under one year of age (15.71/100,000 in 2011). The general case fatality rate in the years 2010–2011 was 10.0%. Meningococci of serogroup B, C, Y and W-135 were responsible for 48.8%, 36.6%, 1.2% and 1.2% of cases, respectively. All isolates were susceptible to third generation cephalosporins, chloramphenicol, ciprofloxacin, and 84.2% were susceptible to penicillin. MLST analysis (2009–2011) revealed that among serogroup B isolates the most represented were clonal complexes (CC) ST-32CC, ST-18CC, ST-41/44CC, ST-213CC and ST-269CC, and among serogroup C: ST-103CC, ST-41/44CC and ST-11CC. Conclusions The detection of IMD in Poland has changed over time, but observed increase in the incidence of the disease was mostly attributed to changes in the surveillance system including an expanded case definition and inclusion of data from non-culture diagnostics. PMID:23977184

  14. Epidemiology of Invasive Haemophilus influenzae Disease, Europe, 2007–2014

    PubMed Central

    Economopoulou, Assimoula; Dias, Joana Gomes; Bancroft, Elizabeth; Ramliden, Miriam; Celentano, Lucia Pastore

    2017-01-01

    We describe the epidemiology of invasive Haemophilus influenzae disease during 2007–2014 in 12 European countries and assess overall H. influenzae disease trends by serotype and patient age. Mean annual notification rate was 0.6 cases/100,000 population, with an increasing annual trend of 3.3% (95% CI 2.3% to 4.3%). The notification rate was highest for patients <1 month of age (23.4 cases/100,000 population). Nontypeable H. influenzae (NTHi) caused 78% of all cases and showed increasing trends among persons <1 month and >20 years of age. Serotype f cases showed an increasing trend among persons >60 years of age. Serotype b cases showed decreasing trends among persons 1–5 months, 1–4 years, and >40 years of age. Sustained success of routine H. influenzae serotype b vaccination is evident. Surveillance systems must adopt a broad focus for invasive H. influenzae disease. Increasing reports of NTHi, particularly among neonates, highlight the potential benefit of a vaccine against NTHi. PMID:28220749

  15. Changing trends in serotype distribution and antimicrobial susceptibility of Streptococcus pneumoniae causing invasive diseases in Central Thailand, 2009-2012.

    PubMed

    Phongsamart, Wanatpreeya; Srifeungfung, Somporn; Chatsuwan, Tanittha; Nunthapisud, Pongpun; Treerauthaweeraphong, Vipa; Rungnobhakhun, Pimpha; Sricharoenchai, Sirintip; Chokephaibulkit, Kulkanya

    2014-01-01

    To describe the trends in serotype distribution and antimicrobial susceptibility of S. pneumoniae causing invasive pneumococcal diseases (IPD) we tested 238 pneumococci isolates from normally sterile sites between 2009 and 2012 and compared these findings with previous data collected within our network. Serotyping was performed for 15 serotypes contained in the 7-,10-, 13-, and experimental 15-valent pneumococcal conjugate vaccines (PCV). The most common serotypes found were 6B (13.9%), 19A (12.6%), 14 (8.0%), 18C (5.9%), and 6A (3.8%); and 39.9% were non-PCV15 serotypes. One of 81 patients with available data had breakthrough infection with vaccine serotype (19F). There was a significant increase of serotype 19A among children ≤5 years (5.6% in 2000-2009 vs 18.3% in 2009-2012, P = 0.003). The all-age serotype coverage was 36.4%, 41.5%, 59.3%, and 59.7% for PCV7, PCV10, PCV13, and PCV 15, respectively. The corresponding coverage in children ≤5 years were 46.4%, 48.8%, 73.2%, and 73.2% respectively. High susceptibilities to penicillin (89.7%), cefotaxime (95.7%), cefditoren (90.2% by Spanish breakpoints), ofloxacin (97.9%), and levofloxacin (100%), but low to cefdinir (50.0%), cefditoren (45.1% by US-FDA breakpoints), macrolides (<50%), clindamycin (67.7%), tetracycline (41.4%), and trimethoprim-sulfamethoxazole (32.4%) were observed. Serotype 19A was less susceptible to penicillin (80.0 vs 91.2%, P = 0.046), cefditoren (66.7 vs 95.5% by Spanish breakpoints, P = 0.004), and tetracycline (9.1 vs 45.5%, P = 0.024) than non-19A isolates. These data emphasize the need for continued surveillance to monitor changes in serotypes as well as antimicrobial susceptibilities in order to guide strategies for prevention and treatment.

  16. Changing trends in serotype distribution and antimicrobial susceptibility of Streptococcus pneumoniae causing invasive diseases in Central Thailand, 2009–2012

    PubMed Central

    Phongsamart, Wanatpreeya; Srifeungfung, Somporn; Chatsuwan, Tanittha; Nunthapisud, Pongpun; Treerauthaweeraphong, Vipa; Rungnobhakhun, Pimpha; Sricharoenchai, Sirintip; Chokephaibulkit, Kulkanya

    2014-01-01

    To describe the trends in serotype distribution and antimicrobial susceptibility of S. pneumoniae causing invasive pneumococcal diseases (IPD) we tested 238 pneumococci isolates from normally sterile sites between 2009 and 2012 and compared these findings with previous data collected within our network. Serotyping was performed for 15 serotypes contained in the 7-,10-, 13-, and experimental 15-valent pneumococcal conjugate vaccines (PCV). The most common serotypes found were 6B (13.9%), 19A (12.6%), 14 (8.0%), 18C (5.9%), and 6A (3.8%); and 39.9% were non-PCV15 serotypes. One of 81 patients with available data had breakthrough infection with vaccine serotype (19F). There was a significant increase of serotype 19A among children ≤5 years (5.6% in 2000–2009 vs 18.3% in 2009–2012, P = 0.003). The all-age serotype coverage was 36.4%, 41.5%, 59.3%, and 59.7% for PCV7, PCV10, PCV13, and PCV 15, respectively. The corresponding coverage in children ≤5 years were 46.4%, 48.8%, 73.2%, and 73.2% respectively. High susceptibilities to penicillin (89.7%), cefotaxime (95.7%), cefditoren (90.2% by Spanish breakpoints), ofloxacin (97.9%), and levofloxacin (100%), but low to cefdinir (50.0%), cefditoren (45.1% by US-FDA breakpoints), macrolides (<50%), clindamycin (67.7%), tetracycline (41.4%), and trimethoprim-sulfamethoxazole (32.4%) were observed. Serotype 19A was less susceptible to penicillin (80.0 vs 91.2%, P = 0.046), cefditoren (66.7 vs 95.5% by Spanish breakpoints, P = 0.004), and tetracycline (9.1 vs 45.5%, P = 0.024) than non-19A isolates. These data emphasize the need for continued surveillance to monitor changes in serotypes as well as antimicrobial susceptibilities in order to guide strategies for prevention and treatment. PMID:25424794

  17. Cost-effectiveness of heptavalent conjugate pneumococcal vaccine (Prevenar) in Germany: considering a high-risk population and herd immunity effects.

    PubMed

    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.

  18. [Invasive yeast diseases in solid organ transplant recipients].

    PubMed

    Muñoz, Patricia; Aguado, José María

    2016-01-01

    Invasive yeast diseases are uncommon nowadays in solid organ transplant recipients. Invasive candidiasis (2%) usually presents during the first month after transplantation in patients with risk factors. Both common and transplant-specific risk factors have been identified, allowing very efficacious targeted prophylaxis strategies. The most common clinical presentations are fungaemia and local infections near the transplantation area. Cryptococcosis is usually a late infection. Its incidence remains stable and the specific risk factors have not been identified. When cryptococcosis is detected very early, transmission with the allograft should be considered. The most common clinical presentations include meningitis, pneumonia, and disseminated infection. Intracranial hypertension and immune reconstitution syndrome have to be considered. No therapeutic clinical trials have been conducted in solid organ transplant recipients, thus treatment recommendations are derived from data obtained from the general population. It is particularly important to consider the possibility of drug-drug interactions, mainly between azoles and calcineurin inhibitors. Both invasive candidiasis and cryptococcosis increase the mortality significantly in solid organ transplant recipients.

  19. Invasive non-Typhi Salmonella disease in Africa.

    PubMed

    Morpeth, Susan C; Ramadhani, Habib O; Crump, John A

    2009-08-15

    Invasive non-Typhi Salmonella is endemic to sub-Saharan Africa, where it is a leading cause of bloodstream infection. Some host risk factors have been established, but little is known about environmental reservoirs and predominant modes of transmission, so prevention strategies are underdeveloped. Although foodborne transmission from animals to humans predominates in high-income countries, it has been postulated that transmission between humans, both within and outside health care facilities, may be important in sub-Saharan Africa. Antimicrobial resistance to ampicillin, trimethoprim-sulfamethoxazole, and chloramphenicol is common among non-Typhi Salmonella strains; therefore, wider use of alternative agents may be warranted for empirical therapy. Development of vaccines targeting the leading invasive non-Typhi Salmonella serotypes Typhimurium and Enteritidis is warranted. The clinical presentation of non-Typhi Salmonella bacteremia is nonspecific and, in the absence of blood culture, may be confused with other febrile illnesses, such as malaria. Much work remains to be done to understand and control invasive non-Typhi Salmonella disease in sub-Saharan Africa.

  20. A trial of 7-valent Pneumococcal Conjugate Vaccine in HIV-infected Adults

    PubMed Central

    French, Neil; Gordon, Stephen B; Mwalukomo, Thandie; White, Sarah A; Mwafulirwa, Gershom; Longwe, Herbert; Mwaiponya, Martin; Zijlstra, Eduard E; Molyneux, Malcolm E; Gilks, Charles F

    2010-01-01

    Background: Streptococcus pneumoniae is a leading and serious co-infection of HIV-infected adults, particularly in Africa. Prevention of disease by vaccination with the current 23-valent polysaccharide vaccine is sub-optimal. Protein conjugate vaccines offer a further option for protection but no data exist on their clinical efficacy in any adult population. Methods: We conducted a double-blind randomized placebo-controlled clinical efficacy trial of the seven-valent conjugate pneumococcal vaccine in predominantly HIV-infected Malawian adults who had recovered from documented invasive pneumococcal disease (IPD). Vaccine was given as a two dose schedule four weeks apart. The primary end-point was a further episode of IPD caused by a vaccine-serotype or serotype-6A (VST/6A) pneumococcus. Results: Between February 2003 and October 2007, 496 individuals (44% male, 88% HIV seropositive) were followed for 798 person years of observation. There were 67 IPD events in 52 individuals, all in the HIV infected sub-group. There were 24 VST/6A events (19 VST, five 6A) in 24 participants, 5 in vaccine and 19 in the placebo recipients, a vaccine efficacy of 74% (95% CI 30% - 90%). There were 73 deaths in the vaccine arm and 63 in the placebo arm, Hazard Ratio 1.18 (95% confidence intervals 0.84 -1.66). Compared to placebo, serious adverse events were significantly lower (3 vs 17, p = 0.002) and minor adverse events significantly higher (41 vs 13, p = 0.003 ) in vaccine recipients. Conclusions: The seven-valent pneumococcal conjugate vaccine protects HIV infected adults from recurrent IPD of vaccine serotype or serotype 6A. PMID:20200385

  1. Pneumococcal DNA is not detectable in the blood of healthy carrier children by real-time PCR targeting the lytA gene.

    PubMed

    Azzari, Chiara; Cortimiglia, Martina; Moriondo, Maria; Canessa, Clementina; Lippi, Francesca; Ghiori, Federica; Becciolini, Laura; de Martino, Maurizio; Resti, Massimo

    2011-06-01

    The diagnosis of invasive pneumococcal disease (IPD) is currently based on culture methods, which lack sensitivity, especially after antibiotic therapy. Molecular methods have improved sensitivity and do not require viable bacteria; however, their use is complicated by reports of low specificity with some assays. The present study investigated the specificity of a real-time PCR targeting lytA for the detection of IPD. A group of 147 healthy children, aged 6 months to 16 years (mean 6.4 years, median 4.9 years, interquartile range 6.4 years), who were in hospital for routine examinations, were tested for pneumococcal carrier status and for the presence of detectable pneumococcal DNA in their blood by real-time PCR targeting the pneumococcal lytA gene. In addition, 35 culture-positive biological samples were analysed. Urine was examined for the presence of pneumococcal DNA and C-polysaccharide antigen. Carriage was detected in 77 of the 147 subjects (52.4 %); however, regardless of carrier status, none of the subjects had a positive result from blood. Analysis of the culture-positive biological samples yielded positive results in 100 % (15/15) of cerebrospinal fluid samples and 95 % (19/20) of blood samples. All urine samples from healthy carriers were negative for DNA, whilst antigenuria was detected in 44/77 carriers (57.1 %). In conclusion, real-time PCR is both sensitive and specific and can be a useful tool in the routine diagnosis of IPD. Its sensitivity, which surpasses that of other methods for this purpose, does not come at the cost of reduced specificity.

  2. Pneumococcal resistance to antibiotics.

    PubMed Central

    Klugman, K P

    1990-01-01

    The geographic distribution of pneumococci resistant to one or more of the antibiotics penicillin, erythromycin, trimethoprim-sulfamethoxazole, and tetracycline appears to be expanding, and there exist foci of resistance to chloramphenicol and rifampin. Multiply resistant pneumococci are being encountered more commonly and are more often community acquired. Factors associated with infection caused by resistant pneumococci include young age, duration of hospitalization, infection with a pneumococcus of serogroup 6, 19, or 23 or serotype 14, and exposure to antibiotics to which the strain is resistant. At present, the most useful drugs for the management of resistant pneumococcal infections are cefotaxime, ceftriaxone, vancomycin, and rifampin. If the strains are susceptible, chloramphenicol may be useful as an alternative, less expensive agent. Appropriate interventions for the control of resistant pneumococcal outbreaks include investigation of the prevalence of resistant strains, isolation of patients, possible treatment of carriers, and reduction of usage of antibiotics to which the strain is resistant. The molecular mechanisms of penicillin resistance are related to the structure and function of penicillin-binding proteins, and the mechanisms of resistance to other agents involved in multiple resistance are being elucidated. Recognition is increasing of the standard screening procedure for penicillin resistance, using a 1-microgram oxacillin disk. PMID:2187594

  3. Bone marrow invasion in multiple myeloma and metastatic disease.

    PubMed

    Vilanova, J C; Luna, A

    2016-04-01

    Magnetic resonance imaging (MRI) of the spine is the imaging study of choice for the management of bone marrow disease. MRI sequences enable us to integrate structural and functional information for detecting, staging, and monitoring the response the treatment of multiple myeloma and bone metastases in the spine. Whole-body MRI has been incorporated into different guidelines as the technique of choice for managing multiple myeloma and metastatic bone disease. Normal physiological changes in the yellow and red bone marrow represent a challenge in analyses to differentiate clinically significant findings from those that are not clinically significant. This article describes the findings for normal bone marrow, variants, and invasive processes in multiple myeloma and bone metastases.

  4. Pneumococcal Conjugate Vaccine (PCV13)

    MedlinePlus

    ... the United States.Treatment of pneumococcal infections with penicillin and other drugs is not as effective as ... should not get PCV13.Anyone with a severe allergy to any component of PCV13 should not get ...

  5. Reactogenicity, safety and immunogenicity of a protein-based pneumococcal vaccine in Gambian children aged 2-4 years: A phase II randomized study.

    PubMed

    Odutola, A; Ota, M O; Ogundare, E O; Antonio, M; Owiafe, P; Worwui, A; Greenwood, B; Alderson, M; Traskine, M; Verlant, V; Dobbelaere, K; Borys, D

    2016-01-01

    Pneumococcal conjugate vaccines (PCVs) have been successful in preventing invasive pneumococcal disease but effectiveness has been challenged by replacement of vaccine serotypes with non-vaccine serotypes. Vaccines targeting common pneumococcal protein(s) found in most/all pneumococci may overcome this limitation. This phase II study assessed safety and immunogenicity of a new protein-based pneumococcal vaccine containing polysaccharide conjugates of 10 pneumococcal serotypes combined with pneumolysin toxoid(dPly) and pneumococcal histidine triad protein D(PhtD) (PHiD-CV/dPly/PhtD-30) in African children. 120 Gambian children (2-4 years, not previously vaccinated against Streptococcus pneumoniae) randomized (1:1) received a single dose of PHiD-CV/dPly/PhtD-30 or PCV13. Adverse events occurring over 4 d post-vaccination were reported, and blood samples obtained pre- and 1-month post-vaccination. Serious adverse events were reported for 6 months post-vaccination. Solicited local and systemic adverse events were reported at similar frequency in each group. One child (PHiD-CV/dPly/PhtD-30 group) reported a grade 3 local reaction to vaccination. Haematological and biochemical parameters seemed similar pre- and 1-month post-vaccination in each group. High pre-vaccination Ply and PhtD antibody concentrations were observed in each group, but only increased in PHiD-CV/dPly/PhtD-30 vaccinees one month post-vaccination. One month post-vaccination, for each vaccine serotype ≥96.2% of PHiD-CV/dPly/PhtD-30 vaccinees had serotype-specific polysaccharide antibody concentrations ≥0.20µg/mL except serotypes 6B (80.8%) and 23F (65.4%), and ≥94.1% had OPA titres of ≥8 except serotypes 1 (51.9%), 5 (38.5%) and 6B (78.0%), within ranges seen in PCV13-vaccinated children. A single dose of PHiD-CV/dPly/PhtD-30 vaccine, administered to Gambian children aged 2-4 y not previously vaccinated with a pneumococcal vaccine, was well-tolerated and immunogenic.

  6. Impact on CDC Guideline Compliance After Incorporating Pharmacy in a Pneumococcal Vaccination Screening Process.

    PubMed

    Pickren, Elizabeth; Crane, Brad

    2016-12-01

    Background: Centers for Disease Control and Prevention (CDC) guidelines for pneumococcal vaccinations were updated in 2014. Given the complexity of the guidelines and the fact that hospitals are no longer required to keep records for pneumococcal vaccinations, many hospitals are determining whether to continue this service. Objective: The primary objective of this study was to determine the impact on compliance with the revised pneumococcal vaccination guidelines from the CDC after involving pharmacy in the screening and selection processes. Secondary objectives were to determine the impact of the new process on inappropriate vaccination duplications, the time spent by pharmacy on assessments, and financial outcomes. Methods: This institutional review board (IRB)-approved, retrospective, cohort study examined all patients who received a pneumococcal vaccination from January to February 2016 after implementing a new process whereby pharmacy performed pneumococcal vaccination screening and selection (intervention group). These patients were compared to patients who received a pneumococcal vaccination from January to February 2015 (control group). Results: Of 274 patients who received a pneumococcal vaccine, 273 were included in the study. Compliance to CDC guidelines increased from 42% to 97%. Noncompliant duplications decreased from 16% to 2%. In the intervention group, labor cost for assessments and expenditure for vaccines increased. For Medicare patients, the increased reimbursement balanced the increased expenditure in the intervention group. Conclusions: Involving pharmacy in the pneumococcal vaccine screening and selection process improves compliance to CDC guidelines, but further clinical and financial analysis is needed to determine financial sustainability of the new process.

  7. Pneumococcal Capsules and Their Types: Past, Present, and Future

    PubMed Central

    Geno, K. Aaron; Gilbert, Gwendolyn L.; Song, Joon Young; Skovsted, Ian C.; Klugman, Keith P.; Jones, Christopher; Konradsen, Helle B.

    2015-01-01

    SUMMARY Streptococcus pneumoniae (the pneumococcus) is an important human pathogen. Its virulence is largely due to its polysaccharide capsule, which shields it from the host immune system, and because of this, the capsule has been extensively studied. Studies of the capsule led to the identification of DNA as the genetic material, identification of many different capsular serotypes, and identification of the serotype-specific nature of protection by adaptive immunity. Recent studies have led to the determination of capsular polysaccharide structures for many serotypes using advanced analytical technologies, complete elucidation of genetic basis for the capsular types, and the development of highly effective pneumococcal conjugate vaccines. Conjugate vaccine use has altered the serotype distribution by either serotype replacement or switching, and this has increased the need to serotype pneumococci. Due to great advances in molecular technologies and our understanding of the pneumococcal genome, molecular approaches have become powerful tools to predict pneumococcal serotypes. In addition, more-precise and -efficient serotyping methods that directly detect polysaccharide structures are emerging. These improvements in our capabilities will greatly enhance future investigations of pneumococcal epidemiology and diseases and the biology of colonization and innate immunity to pneumococcal capsules. PMID:26085553

  8. Cost-effectiveness analysis of pneumococcal conjugate vaccine 13-valent in older adults in Colombia

    PubMed Central

    2014-01-01

    Background Nowadays, there are two vaccination strategies in Colombia to prevent pneumococcal diseases in people over 50 years. Our aim is to estimate cost-effectiveness of pneumococcal conjugate vaccine 13-valent (PCV13) versus pneumococcal polysaccharide vaccine 23-valent (PPSV23) to prevent pneumococcal diseases and their related mortality in people over 50 years old in Colombia. Methods A Markov model was developed with national data, including pneumococcal serotypes distribution in Colombia between 2005 and 2010. Vaccination of a cohort was simulated and a five year time horizon was assumed. Analysis was done from a perspective of a third party payer. Direct costs were provided by a national insurance company; sensitive univariate and probabilistic analysis were done for epidemiological and clinical effectiveness parameters and costs. Results PCV13 avoids 3 560 deaths by pneumococcal infections versus PPSV23 and 4 255 deaths versus no vaccine. PCV13 prevents 79 633 cases by all-cause pneumonia versus PPSV23 and 81 468 cases versus no vaccine. Total costs (healthcare and vaccines costs) with PCV13 would be U.S. $ 97,587,113 cheaper than PPSV23 and it would save U.S. $ 145,196,578 versus no vaccine. Conclusion PCV13 would be a cost-saving strategy in the context of a mass vaccination program in Colombia to people over 50 years old because it would reduce burden of disease and specific mortality by pneumococcal diseases, besides, it saves money versus PPSV23. PMID:24679135

  9. Phase 3 trial evaluating the immunogenicity, safety, and tolerability of manufacturing scale 13-valent pneumococcal conjugate vaccine.

    PubMed

    Gadzinowski, Janusz; Albrecht, Piotr; Hasiec, Barbara; Konior, Ryszard; Dziduch, Jerzy; Witor, Anita; Mellelieu, Tracey; Tansey, Susan P; Jones, Thomas; Sarkozy, Denise; Emini, Emilio A; Gruber, William C; Scott, Daniel A

    2011-04-05

    13-valent pneumococcal conjugate vaccine (PCV13) includes polysaccharide conjugates from six pneumococcal serotypes in addition to those in the licensed 7-valent vaccine, thereby offering expanded protection against pneumococcal disease. The phase 3 trial reported here was conducted per a regulatory requirement to evaluate the immunogenicity, safety, and tolerability of two lots of the final PCV13 formulation that differed with respect to production scale but not the manufacturing process. The anti-pneumococcal polysaccharide immunogenicity and safety/tolerability were found to be similar between the two PCV13 vaccine lots.

  10. Invasive non-typhoidal salmonella disease: an emerging and neglected tropical disease in Africa.

    PubMed

    Feasey, Nicholas A; Dougan, Gordon; Kingsley, Robert A; Heyderman, Robert S; Gordon, Melita A

    2012-06-30

    Invasive strains of non-typhoidal salmonellae have emerged as a prominent cause of bloodstream infection in African adults and children, with an associated case fatality of 20-25%. The clinical presentation of invasive non-typhoidal salmonella disease in Africa is diverse: fever, hepatosplenomegaly, and respiratory symptoms are common, and features of enterocolitis are often absent. The most important risk factors are HIV infection in adults, and malaria, HIV, and malnutrition in children. A distinct genotype of Salmonella enterica var Typhimurium, ST313, has emerged as a new pathogenic clade in sub-Saharan Africa, and might have adapted to cause invasive disease in human beings. Multidrug-resistant ST313 has caused epidemics in several African countries, and has driven the use of expensive antimicrobial drugs in the poorest health services in the world. Studies of systemic cellular and humoral immune responses in adults infected with HIV have revealed key host immune defects contributing to invasive non-typhoidal salmonella disease. This emerging pathogen might therefore have adapted to occupy an ecological and immunological niche provided by HIV, malaria, and malnutrition in Africa. A good understanding of the epidemiology of this neglected disease will open new avenues for development and implementation of vaccine and public health strategies to prevent infections and interrupt transmission.

  11. Duelling timescales of host mixing and disease spread determine invasion of disease in structured populations

    USGS Publications Warehouse

    Cross, P.C.; Lloyd-Smith, J. O.; Johnson, P.L.F.; Getz, W.M.

    2005-01-01

    The epidemic potential of a disease is traditionally assessed using the basic reproductive number, R0. However, in populations with social or spatial structure a chronic disease is more likely to invade than an acute disease with the same R0, because it persists longer within each group and allows for more host movement between groups. Acute diseases ‘perceive’ a more structured host population, and it is more important to consider host population structure in analyses of these diseases. The probability of a pandemic does not arise independently from characteristics of either the host or disease, but rather from the interaction of host movement and disease recovery timescales. The R* statistic, a group-level equivalent of R0, is a better indicator of disease invasion in structured populations than the individual-level R0.

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

    PubMed

    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 <0.01), smoking (60.7% versus 21.4%; p <0.01), the absence of previously known valve disease (82.1% versus 60.7%; p 0.047), heart failure (64.3% versus 23.2%; p <0.01) and shock (53.6% versus 23.2%; p <0.01) were more common in pneumococcal than in non-pneumococcal 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.

  13. Isavuconazole: a new extended spectrum triazole for invasive mold diseases.

    PubMed

    Ananda-Rajah, Michelle R; Kontoyiannis, Dimitrios

    2015-01-01

    Isavuconazole is the first broad spectrum prodrug triazole with efficacy against invasive fungal diseases including aspergillosis and mucormycosis. Characteristics include linear dose-proportional pharmacokinetics, intravenous and oral formulations allowing therapeutic streamlining, once daily dosing, absence of nephrotoxic solubilizing agents and excellent oral bioavailability independent of prandial status and gastric acidity. An open label noncomparator study demonstrated encouraging results for isavuconazole as primary or salvage therapy for a range of fungi including mucormycosis. Isavuconazole had fewer premature drug discontinuations and adverse events in the eye, hepatobiliary and psychiatry systems than the comparator agent, voriconazole in a randomized double-blind clinical trial. Cross-resistance of isavuconazole best correlates with voriconazole. In vitro resistance is not invariably predictive of clinical failure. Isavuconazole signals progress in pharmacokinetics, bioavailability and toxicity/tolerability supported by clinical efficacy from Phase III trials.

  14. [Non-invasive brain stimulation for Parkinson's disease].

    PubMed

    Gajo, Gianandrea; Pollak, Pierre; Lüscher, Christian; Benninger, David

    2015-04-29

    Parkinson's disease (PD) is a major socio-economic burden increasing with the aging population. In advanced PD, the emergence of symptoms refractory to conventional therapy poses a therapeutic challenge. The success of deep brain stimulation (DBS) and advances in the understanding of the pathophysiology of PD have raised interest in non-invasive brain stimulation (NIBS) as an alternative therapeutic tool. NIBS could offer an alternative approach for patients at risk who are excluded from surgery and/or to treat refractory symptoms. The treatment of the freezing of gait, a major cause of disability and falls in PD patients, could be enhanced by transcranial direct current stimulation (tDCS). A therapeutic study is currently performed at the Department of Neurology at the CHUV.

  15. Capsular switching as a strategy to increase pneumococcal virulence in experimental otitis media model.

    PubMed

    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.

  16. Global burden of invasive nontyphoidal Salmonella disease, 2010(1).

    PubMed

    Ao, Trong T; Feasey, Nicholas A; Gordon, Melita A; Keddy, Karen H; Angulo, Frederick J; Crump, John A

    2015-06-01

    Nontyphoidal Salmonella is a major cause of bloodstream infections worldwide, and HIV-infected persons and malaria-infected children are at increased risk for the disease. We conducted a systematic literature review to obtain age group-specific, population-based invasive nontyphoidal Salmonella (iNTS) incidence data. Data were categorized by HIV and malaria prevalence and then extrapolated by using 2010 population data. The case-fatality ratio (CFR) was determined by expert opinion consensus. We estimated that 3.4 (range 2.1-6.5) million cases of iNTS disease occur annually (overall incidence 49 cases [range 30-94] per 100,000 population). Africa, where infants, young children, and young adults are most affected, has the highest incidence (227 cases [range 152-341] per 100,000 population) and number of cases (1.9 [range 1.3-2.9] million cases). An iNTS CFR of 20% yielded 681,316 (range 415,164-1,301,520) deaths annually. iNTS disease is a major cause of illness and death globally, particularly in Africa. Improved understanding of the epidemiology of iNTS is needed.

  17. Many radiologic facies of pneumococcal pneumonia

    SciTech Connect

    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.

  18. Emergence of Multidrug-Resistant Pneumococcal Serotype 35B among Children in the United States.

    PubMed

    Olarte, Liset; Kaplan, Sheldon L; Barson, William J; Romero, José R; Lin, Philana Ling; Tan, Tina Q; Hoffman, Jill A; Bradley, John S; Givner, Laurence B; Mason, Edward O; Hultén, Kristina G

    2017-03-01

    Streptococcus pneumoniae serotype 35B is a nonvaccine serotype associated with high rates of penicillin nonsusceptibility. An increase in the proportion of multidrug-resistant (MDR) 35B isolates has recently been reported. The genetic events contributing to the emergence of MDR serotype 35B are unknown. The sequence type (ST) composition of 78 serotype 35B isolates obtained from pediatric patients with invasive pneumococcal disease from 1994 to 2014 and 48 isolates from pediatric patients with otitis media (noninvasive) from 2011 to 2014 was characterized by multilocus sequence typing (MLST). The most common STs were ST558 (69.2%), ST156 (10.3%), and ST452 (3.8%). Two major clonal complexes (CC), CC558 and CC156, were identified by eBURST analysis. Overall, 91% (71/78) of isolates were penicillin nonsusceptible and 16.7% (13/78) were MDR. Among all invasive serotype 35B isolates, MDR isolates increased significantly, from 2.9% (1/35) to 27.9% (12/43) (P = 0.004), after the 13-valent pneumococcal conjugate vaccine (PCV13) was introduced. All CC156 isolates were identified after the introduction of PCV13 (0/35 [0%] before versus 9/43 [20.9%] after; P = 0.003) and were MDR. All CC156 isolates had similar antimicrobial susceptibility patterns; in contrast, high variability in antimicrobial susceptibility was observed among CC558 isolates. The distributions of CC558 and CC156 among invasive and noninvasive isolates were not different. The increased prevalence of MDR serotype 35B after the introduction of PCV13 was directly associated with the emergence of ST156. Genotyping suggests that capsular switching has occurred between MDR vaccine serotypes belonging to ST156 (e.g., 9V, 14, and 19A) and serotype 35B.

  19. Molecular characteristics of penicillin-binding protein 2b, 2x and 1a sequences in Streptococcus pneumoniae isolates causing invasive diseases among children in Northeast China.

    PubMed

    Zhou, X; Liu, J; Zhang, Z; Liu, Y; Wang, Y; Liu, Y

    2016-04-01

    Streptococcus pneumoniae is one of the common pathogens causing severe invasive infections in children. This study aimed to investigate the serotype distribution and variations of penicillin-binding proteins (PBPs) 2b, 2x and 1a in S. pneumoniae isolates causing invasive diseases in Northeast China. A total of 256 strains were isolated from children with invasive pneumococcal disease (IPD) from January 2000 to October 2014. All strains were serotyped and determined for antibiotic resistance. The amplicons of penicillin-binding domains in pbp1a, pbp2b and pbp2x genes were sequenced for variation identification. The most prevalent serotypes of isolates in IPD children were 19A, 14, 19F, 23F and 6B. 19A and 19F were the most frequent serotypes of penicillin-resistant S. pneumoniae (PRSP), which present with high resistance to amoxicillin, cefotaxime, ceftriaxone and meropenem. The numbers of amino acid substitutions of penicillin-non-susceptible S. pneumoniae (PNSP) isolates were higher than those of penicillin-sensitive S. pneumoniae isolates in all the PBP genes (p < 0.01). The patterns of amino acid mutation in PBP2b, PBP2x and PBP1a were unique and different from those of other countries. All of the serotype 19A and 19F PRSP isolates carried 25 amino acid mutations, including Ala618 → Gly between positions 560 and 675 in PBP2b and Thr338 → Ala substitutions in PBP2x. The amino acid alterations in PBP2b, PBP2x and PBP1a from S. pneumoniae were closely associated with resistance to β-lactam antibiotics. This study provides new data for further monitoring of genetic changes related to the emergence and spread of resistance to β-lactam antibiotics in China.

  20. Pneumococcal Disease: Symptoms and Complications

    MedlinePlus

    ... causes up to half of middle ear infections (otitis media). Symptoms include: Ear pain A red, swollen ear ... empyema occurring at the same time. Sinus and ear infections are usually mild and are much more common ...

  1. A Computerized Pneumococcal Vaccination Reminder System in the Adult Emergency Department

    PubMed Central

    Dexheimer, Judith W; Talbot, Thomas R.; Ye, Fei; Shyr, Yu; Jones, Ian; Gregg, William M; Aronsky, Dominik

    2011-01-01

    Background Pneumococcal vaccination is an effective strategy to prevent invasive pneumococcal disease in the elderly. Emergency Department (ED) visits present an underutilized opportunity to increase vaccination rates; however, designing a sustainable vaccination program in an ED is challenging. We examined whether an information technology supported approach would provide a feasible and sustainable method to increase vaccination rates in an adult ED. Methods During a 1-year period we prospectively evaluated a team-oriented, workflow-embedded reminder system that integrated four different information systems. The computerized triage application screened all patients 65 years and older for pneumococcal vaccine eligibility with information from the electronic patient record. For eligible patients the computerized provider order entry system reminded clinicians to place a vaccination order, which was passed to the order tracking application. Documentation of vaccine administration was then added to the longitudinal electronic patient record. The primary outcome was the vaccine administration rate in the ED. Multivariate logistic regression analysis was used to estimate the odds ratios and their 95% confidence intervals, representing the overall relative risks of ED workload related variables associated with vaccination rate. Results Among 3,371 patients 65 years old and older screened at triage 1,309 (38.8%) were up-to-date with pneumococcal vaccination and 2,062 (61.2%) were eligible for vaccination. Of the eligible patients, 621 (30.1%) consented to receive the vaccination during their ED visit. Physicians received prompts for 428 (68.9%) patients. When prompted, physicians declined to order the vaccine in 192 (30.9%) patients, while 222 (10.8%) of eligible patients actually received the vaccine. The computerized reminder system increased vaccination rate from a baseline of 38.8% to 45.4%. Vaccination during the ED visit was associated younger age (OR: 0.972, CI: 0

  2. Generation and Improvement of Effector Function of a Novel Broadly Reactive and Protective Monoclonal Antibody against Pneumococcal Surface Protein A of Streptococcus pneumoniae

    PubMed Central

    Cho, Rebecca; Groff, Brian C.; Kubota, Tsuguo; Destito, Giuseppe; Laudenslager, John; Koriazova, Lilia; Tahara, Tomoyuki; Kanda, Yutaka

    2016-01-01

    A proof-of-concept study evaluating the potential of Streptococcus pneumoniae Pneumococcal Surface Protein A (PspA) as a passive immunization target was conducted. We describe the generation and isolation of several broadly reactive mouse anti-PspA monoclonal antibodies (mAbs). MAb 140H1 displayed (i) 98% strain coverage, (ii) activity in complement deposition and opsonophagocytic killing (OPK) assays, which are thought to predict the in vivo efficacy of anti-pneumococcal mAbs, (iii) efficacy in mouse sepsis models both alone and in combination with standard-of-care antibiotics, and (iv) therapeutic activity in a mouse pneumonia model. Moreover, we demonstrate that antibody engineering can significantly enhance anti-PspA mAb effector function. We believe that PspA has promising potential as a target for the therapy of invasive pneumococcal disease by mAbs, which could be used alone or in conjunction with standard-of-care antibiotics. PMID:27171010

  3. Global parasite and Rattus rodent invasions: The consequences for rodent-borne diseases.

    PubMed

    Morand, Serge; Bordes, Frédéric; Chen, Hsuan-Wien; Claude, Julien; Cosson, Jean-François; Galan, Maxime; Czirják, Gábor Á; Greenwood, Alex D; Latinne, Alice; Michaux, Johan; Ribas, Alexis

    2015-09-01

    We summarize the current knowledge on parasitism-related invasion processes of the globally invasive Rattus lineages, originating from Asia, and how these invasions have impacted the local epidemiology of rodent-borne diseases. Parasites play an important role in the invasion processes and successes of their hosts through multiple biological mechanisms such as "parasite release," "immunocompetence advantage," "biotic resistance" and "novel weapon." Parasites may also greatly increase the impact of invasions by spillover of parasites and other pathogens, introduced with invasive hosts, into new hosts, potentially leading to novel emerging diseases. Another potential impact is the ability of the invader to amplify local parasites by spillback. In both cases, local fauna and humans may be exposed to new health risks, which may decrease biodiversity and potentially cause increases in human morbidity and mortality. Here we review the current knowledge on these processes and propose some research priorities.

  4. Clonal expansion of the macrolide resistant ST386 within pneumococcal serotype 6C in France.

    PubMed

    Janoir, Claire; Cohen, Robert; Levy, Corinne; Bingen, Edouard; Lepoutre, Agnès; Gutmann, Laurent; Varon, Emmanuelle

    2014-01-01

    In France, the use of the 7-valent pneumococcal conjugate vaccine (PCV7) lead to an overall significant decrease in PCV7 invasive pneumococcal disease (IPD) incidence. However, the decrease in vaccine serotype prevalence was partially counterbalanced by the serotype replacement phenomenon. In this study, we analyzed the role of the newly described serotype 6C as one of the replacement serotypes. This work was conducted on a large time scale from the early PCV7 era (2002-2003) to the PCV13 era (2010-2011), both on IPD strains recovered from the whole population and nasopharyngeal colonizing strains isolated in infant less than two years, who are known to be the main reservoir for pneumococci. Serotype 6C took advantage over 6A and 6B serotypes, which both decreased over time. A continuous and significant increase in 6C IPD was observed in adults along the study period; in contrast, in children less than two years, only an increase in 6C nasopharyngeal carriage was found, the prevalence of serotype 6C in IPD remaining very low over time. Among 101 6C invasive and colonizing strains studied by MLST, 24 STs were found to be related to three major clonal complexes, CC395, CC176, and CC315. STs related to CC176 tend to disappear after 2009 and were essentially replaced by ST386 (CC315), which dramatically increased over time. This clonal expansion may be explained by the erythromycin and tetracycline resistances associated with this clone. Finally, the decrease observed in nasopharyngeal 6C carriage since 2010, likely related to the PCV13 introduction in the French immunization schedule, is expected to lead to a decrease in 6C IPD in adults thereafter.

  5. Clonal Expansion of the Macrolide Resistant ST386 within Pneumococcal Serotype 6C in France

    PubMed Central

    Janoir, Claire; Cohen, Robert; Levy, Corinne; Bingen, Edouard; Lepoutre, Agnès; Gutmann, Laurent; Varon, Emmanuelle

    2014-01-01

    In France, the use of the 7-valent pneumococcal conjugate vaccine (PCV7) lead to an overall significant decrease in PCV7 invasive pneumococcal disease (IPD) incidence. However, the decrease in vaccine serotype prevalence was partially counterbalanced by the serotype replacement phenomenon. In this study, we analyzed the role of the newly described serotype 6C as one of the replacement serotypes. This work was conducted on a large time scale from the early PCV7 era (2002–2003) to the PCV13 era (2010–2011), both on IPD strains recovered from the whole population and nasopharyngeal colonizing strains isolated in infant less than two years, who are known to be the main reservoir for pneumococci. Serotype 6C took advantage over 6A and 6B serotypes, which both decreased over time. A continuous and significant increase in 6C IPD was observed in adults along the study period; in contrast, in children less than two years, only an increase in 6C nasopharyngeal carriage was found, the prevalence of serotype 6C in IPD remaining very low over time. Among 101 6C invasive and colonizing strains studied by MLST, 24 STs were found to be related to three major clonal complexes, CC395, CC176, and CC315. STs related to CC176 tend to disappear after 2009 and were essentially replaced by ST386 (CC315), which dramatically increased over time. This clonal expansion may be explained by the erythromycin and tetracycline resistances associated with this clone. Finally, the decrease observed in nasopharyngeal 6C carriage since 2010, likely related to the PCV13 introduction in the French immunization schedule, is expected to lead to a decrease in 6C IPD in adults thereafter. PMID:24603763

  6. The potential impact of pneumococcal conjugate vaccine in Africa: Considerations and early lessons learned from the South African experience.

    PubMed

    Madhi, Shabir A; Nunes, Marta C

    2016-01-01

    The introduction of pneumococcal conjugate vaccine (PCV) into the South African public immunization program since 2009 adopted a novel vaccination schedule of 3 doses at 6, 14 and 40 weeks of age. Over the past 5 y it has been shown that infant PCV immunization in South Africa is effective in reducing the burden of invasive pneumococcal disease (IPD) among HIV-infected and HIV-uninfected children. Furthermore, indirect protection of unvaccinated age-groups (including high risk groups such as HIV-infected adults) against IPD was demonstrated despite the absence of any substantial catch-up campaign of older children. This indirect effect against IPD is corroborated by the temporal reduction in vaccine-serotype colonization among age-groups targeted for PCV immunization as well as unvaccinated HIV-infected and HIV-uninfected adults, which was evident within 2 y of PCV introduction into the immunization program. Vaccine effectiveness has also been demonstrated in children against presumed bacterial pneumonia. The evaluation of the impact of PCV in South Africa, however, remains incomplete. The knowledge gaps remaining include the evaluation of PCV on the incidence of all-cause pneumonia hospitalization among vaccinated and unvaccinated age-groups. Furthermore, ongoing surveillance is required to determine whether there is ongoing replacement disease by non-vaccine serotypes, which could offset the early gains associated with the immunization program in the country.

  7. Primary invasive extramammary Paget disease on penoscrotum: a clinicopathological analysis of 41 cases.

    PubMed

    Shu, Bo; Shen, Xu-Xia; Chen, Peng; Fang, Xin-Zhi; Guo, Yong-Lian; Kong, Yun-Yi

    2016-01-01

    To investigate the clinicopathological and immunohistochemical features and prognostic factors for invasive extramammary Paget disease (EMPD) on penoscrotum, we described the clinical presentations, histopathology, and follow-up courses of 41 cases. The age of the patients ranged from 42 to 84 years. All the patients were treated with wide surgical excision, and 14 were confirmed to have lymph node metastasis. During follow-up, 18 patients (43.9%) developed local or distant recurrence, and 13 patients (31.7%) died of the disease. Histologically, glandular formation with true lumina within the epidermis was found in 29 cases, and signet ring cells were seen in 11 cases. In invasive components, nodular/micronodular growth pattern, glandular formation, and strands/solid sheets existed in 95.1% (39/41), 43.9% (18/41), and 24.4% (10/41) of the cases, respectively. More than half of the cases had at least 2 different types of invasive growth pattern. CK7 was diffusely positive in all cases, whereas CK20 was focally positive in 8 cases. GCDFP-15 was expressed to a variable degree in 24 cases. Presence of strands/solid sheets, lymphovascular invasion, and perineural invasion in invasive EMPD were found to be correlated with higher lymph node metastatic rate. Univariate analysis revealed that patients with one of the following prognostic factors: delay in diagnosis more than 7.5 years, depth of invasion more than 1 mm, invasive pattern of strands/solid sheets, marked inflammation, lymphovascular invasion, and lymph node metastasis at diagnosis, had significantly shorter cancer-specific survival. We concluded that invasive EMPD is a rare malignant skin neoplasm with morphological diversity. Invasive pattern of strands/solid sheets is significantly associated with both lymph node metastasis and worse prognosis. Delay in diagnosis, depth of invasion, marked inflammation, lymphovascular invasion, and regional lymph node status are important prognostic factors.

  8. Analysis of non-typeable Haemophilus influenzae in invasive disease reveals lack of the capsule locus.

    PubMed

    Lâm, T-T; Claus, H; Frosch, M; Vogel, U

    2016-01-01

    Among invasive Haemophilus influenzae, unencapsulated strains have largely surpassed the previously predominant serotype b (Hib) because of Hib vaccination. Isolates without the genomic capsule (cap) locus are designated non-typeable H. influenzae (NTHi). They are different from capsule-deficient variants that show deletion of the capsule transport gene bexA within the cap locus. The frequency of capsule-deficient variants in invasive disease is unknown. We analysed 783 unencapsulated invasive isolates collected over 5 years in Germany and found no single capsule-deficient isolate. Invasive unencapsulated strains in Germany were exclusively NTHi. A negative serotyping result by slide agglutination was therefore highly predictive for NTHi.

  9. Exome Array Analysis of Susceptibility to Pneumococcal Meningitis

    PubMed Central

    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 <5 × 10−7). Our strongest signals associated with susceptibility to pneumococcal meningitis were rs139064549 on chromosome 1 in the COL11A1 gene (p = 1.51 × 10−6; G allele OR 3.21 [95% CI 2.05–5.02]) and rs9309464 in the EXOC6B gene on chromosome 2 (p = 6.01 × 10−5; G allele OR 0.66 [95% CI 0.54–0.81]). The sequence kernel association test (SKAT) tests for associations between multiple variants in a gene region and pneumococcal meningitis susceptibility yielded one significant associated gene namely COL11A1 (p = 1.03 × 10−7). Replication studies are needed to validate these results. If replicated, the functionality of these genetic variations should be further studied to identify by which means they influence the pathophysiology of pneumococcal meningitis. PMID:27389768

  10. Factors associated with pneumococcal polysaccharide vaccination of the elderly in Spain: A cross-sectional study.

    PubMed

    Domínguez, Angela; Soldevila, Núria; Toledo, Diana; Godoy, Pere; Torner, Núria; Force, Luis; Castilla, Jesús; Mayoral, José María; Tamames, Sonia; Martín, Vicente; Egurrola, Mikel; Sanz, Francisco; Astray, Jenaro; Project Pi12/02079 Working Group

    2016-07-02

    Vaccination of the elderly is an important factor in limiting the impact of pneumonia in the community. The aim of this study was to investigate the factors associated with pneumococcal polysaccharide vaccination in patients aged ≥ 65 years hospitalized for causes unrelated to pneumonia, acute respiratory disease, or influenza-like illness in Spain. We made a cross-sectional study during 2013-2014. A bivariate analysis was performed comparing vaccinated and unvaccinated patients, taking into account sociodemographic variables and risk medical conditions. A multivariate analysis was performed using multilevel regression models. 921 patients were included; 403 (43.8%) had received the pneumococcal vaccine (394 received the polysaccharide vaccine). Visiting the general practitioner ≥ 3 times during the last year (OR = 1.79; 95% CI 1.25-2.57); having received the influenza vaccination in the 2013-14 season (OR = 2.57; 95% CI 1.72-3.84) or in any of the 3 previous seasons (OR = 11.70; 95% CI 7.42-18.45) were associated with receiving the pneumococcal polysaccharide vaccine. Pneumococcal vaccination coverage of hospitalized elderly people is low. The elderly need to be targeted about pneumococcal vaccination and activities that encourage healthcare workers to proactively propose vaccination might be useful. Educational campaigns aimed at the elderly could also help to increase vaccination coverages and reduce the burden of pneumococcal disease in the community.

  11. Invasive Meningococcal Disease in Scotland, 1994 to 1999, with Emphasis on Group B Meningococcal Disease

    PubMed Central

    Kyaw, Moe H.; Clarke, Stuart C.; Christie, Peter; Jones, Ian G.; Campbell, Harry

    2002-01-01

    A review was carried out on 774 invasive meningococcal isolates reported to the active meningococcal surveillance system in Scotland from 1994 to 1999. This showed that serogroups B (51.7%) and C (39.2%) caused the majority of disease. The six common PorB proteins (4, 1, 15, 2B, 12, and 21) and PorA proteins (serosubtypes) (P1.4, P1.15, P1.9, P1.14, P1.7, and P1.16) accounted for 50 and 51% of all group B isolates, respectively, during the study period. PMID:11980971

  12. A Review of Diagnostic Methods for Invasive Fungal Diseases: Challenges and Perspectives.

    PubMed

    Falci, Diego R; Stadnik, Claudio M B; Pasqualotto, Alessandro C

    2017-03-29

    Invasive fungal diseases are associated with a high morbidity and mortality, particularly in the context of immunosuppression. Diagnosis of invasive fungal diseases is usually complicated by factors such as poor clinical suspicion and unspecific clinical findings. Access to modern diagnostic tools is frequently limited in developing countries. Here, we describe five real-life clinical cases from a Brazilian tertiary hospital, in order to illustrate how to best select diagnostic tests in patients with different fungal infections.

  13. Potential carrier priming effect in Australian infants after 7-valent pneumococcal conjugate vaccine introduction

    PubMed Central

    Tashani, Mohamed; Jayasinghe, Sanjay; Harboe, Zitta B; Rashid, Harunor; Booy, Robert

    2016-01-01

    AIM To investigate evidence of clinical protection in infants after one dose of 7-valent pneumococcal conjugate vaccine (7vPCV) owing to carrier priming. METHODS Using Australian National Notifiable Diseases Surveillance System data, we conducted a descriptive analysis of cases of vaccine type invasive pneumococcal disease (VT-IPD) during “catch-up” years, when 7vPCV was carrier primed by prior administration of DTPa vaccine. We compared the number of VT-IPD cases occurring 2-9 wk after a single dose of 7vPCV (carrier primed), with those < 2 wk post vaccination, when no protection from 7vPCV was expected yet. Further comparison was conducted to compare the occurrence of VT-IPD cases vs non-VT-IPD cases after a single carrier-primed dose of 7vPCV. RESULTS We found four VT-IPD cases occurring < 2 wk after one carrier primed dose of 7vPCV while only one case occurred 2-9 wk later. Upon further comparison with the non-VT-IPD cases that occurred after one carrier primed dose of 7vPCV, two cases were detected within 2 wk, whereas seven occurred within 2-9 wk later; suggesting a substantial level of protection from VT-IPD occurring from 2 wk after carrier-primed dose of 7vPCV. CONCLUSION This data suggest that infants may benefit from just one dose of 7vPCV, likely through enhanced immunity from carrier priming effect. If this is proven, an adjusted 2-dose schedule (where the first dose of PCV is not given until after DTPa) may be sufficient and more cost-effective. PMID:27610348

  14. Bias with respect to socioeconomic status: A closer look at zip code matching in a pneumococcal vaccine effectiveness study.

    PubMed

    Link-Gelles, Ruth; Westreich, Daniel; Aiello, Allison E; Shang, Nong; Weber, David J; Holtzman, Corinne; Scherzinger, Karen; Reingold, Arthur; Schaffner, William; Harrison, Lee H; Rosen, Jennifer B; Petit, Susan; Farley, Monica; Thomas, Ann; Eason, Jeffrey; Wigen, Christine; Barnes, Meghan; Thomas, Ola; Zansky, Shelley; Beall, Bernard; Whitney, Cynthia G; Moore, Matthew R

    2016-12-01

    In 2010, 13-valent pneumococcal conjugate vaccine (PCV13) was introduced in the US for prevention of invasive pneumococcal disease in children. Individual-level socioeconomic status (SES) is a potential confounder of the estimated effectiveness of PCV13 and is often controlled for in observational studies using zip code as a proxy. We assessed the utility of zip code matching for control of SES in a post-licensure evaluation of the effectiveness of PCV13 (calculated as [1-matched odds ratio]*100). We used a directed acyclic graph to identify subsets of confounders and collected SES variables from birth certificates, geo-coding, a parent interview, and follow-up with medical providers. Cases tended to be more affluent than eligible controls (for example, 48.3% of cases had private insurance vs. 44.6% of eligible controls), but less affluent than enrolled controls (52.9% of whom had private insurance). Control of confounding subsets, however, did not result in a meaningful change in estimated vaccine effectiveness (original estimate: 85.1%, 95% CI 74.8-91.9%; adjusted estimate: 82.5%, 95% CI 65.6-91.1%). In the context of a post-licensure vaccine effectiveness study, zip code appears to be an adequate, though not perfect, proxy for individual SES.

  15. Minimally Invasive Procedures - Direct and Video-Assisted Forms in the Treatment of Heart Diseases

    PubMed Central

    Castro, Josué Viana; Melo, Emanuel Carvalho; Silva, Juliana Fernandes; Rebouças, Leonardo Lemos; Corrêa, Larissa Chagas; Germano, Amanda de Queiroz; Machado, João José Aquino

    2014-01-01

    Background Minimally invasive cardiovascular procedures have been progressively used in heart surgery. Objective To describe the techniques and immediate results of minimally invasive procedures in 5 years. Methods Prospective and descriptive study in which 102 patients were submitted to minimally invasive procedures in direct and video-assisted forms. Clinical and surgical variables were evaluated as well as the in hospital follow-up of the patients. Results Fourteen patients were operated through the direct form and 88 through the video-assisted form. Between minimally invasive procedures in direct form, 13 had aortic valve disease. Between minimally invasive procedures in video-assisted forms, 43 had mitral valve disease, 41 atrial septal defect and four tumors. In relation to mitral valve disease, we replaced 26 and reconstructed 17 valves. Aortic clamp, extracorporeal and procedure times were, respectively, 91,6 ± 21,8, 112,7 ± 27,9 e 247,1 ± 20,3 minutes in minimally invasive procedures in direct form. Between minimally invasive procedures in video-assisted forms, 71,6 ± 29, 99,7 ± 32,6 e 226,1 ± 42,7 minutes. Considering intensive care and hospitalization times, these were 41,1 ± 14,7 hours and 4,6 ± 2 days in minimally invasive procedures in direct and 36,8 ± 16,3 hours and 4,3 ± 1,9 days in minimally invasive procedures in video-assisted forms procedures. Conclusion Minimally invasive procedures were used in two forms - direct and video-assisted - with safety in the surgical treatment of video-assisted, atrial septal defect and tumors of the heart. These procedures seem to result in longer surgical variables. However, hospital recuperation was faster, independent of the access or pathology. PMID:24553983

  16. Antimicrobial resistance and management of invasive Salmonella disease.

    PubMed

    Kariuki, Samuel; Gordon, Melita A; Feasey, Nicholas; Parry, Christopher M

    2015-06-19

    Invasive Salmonella infections (typhoidal and non-typhoidal) cause a huge burden of illness estimated at nearly 3.4 million cases and over 600,000 deaths annually especially in resource-limited settings. Invasive non-typhoidal Salmonella (iNTS) infections are particularly important in immunosuppressed populations especially in sub-Saharan Africa, causing a mortality of 20-30% in vulnerable children below 5 years of age. In these settings, where routine surveillance for antimicrobial resistance is rare or non-existent, reports of 50-75% multidrug resistance (MDR) in NTS are common, including strains of NTS also resistant to flouroquinolones and 3rd generation cephalosporins. Typhoid (enteric) fever caused by Salmonella Typhi and Salmonella Paratyphi A remains a major public health problem in many parts of Asia and Africa. Currently over a third of isolates in many endemic areas are MDR, and diminished susceptibility or resistance to fluoroquinolones, the drugs of choice for MDR cases over the last decade is an increasing problem. The situation is particularly worrying in resource-limited settings where the few remaining effective antimicrobials are either unavailable or altogether too expensive to be afforded by either the general public or by public health services. Although the prudent use of effective antimicrobials, improved hygiene and sanitation and the discovery of new antimicrobial agents may offer hope for the management of invasive salmonella infections, it is essential to consider other interventions including the wider use of WHO recommended typhoid vaccines and the acceleration of trials for novel iNTS vaccines. The main objective of this review is to describe existing data on the prevalence and epidemiology of antimicrobial resistant invasive Salmonella infections and how this affects the management of these infections, especially in endemic developing countries.

  17. Postoperative Recurrence of Invasive Thymoma with Cold Agglutinin Disease and Autoimmune Hemolytic Anemia.

    PubMed

    Yoneda, Taro; Koba, Hayato; Tanimura, Kota; Ogawa, Naohiko; Watanabe, Satoshi; Hara, Johsuke; Abo, Miki; Sone, Takashi; Kimura, Hideharu; Kasahara, Kazuo

    A 50-year-old man presented to our hospital in 1995. Invasive thymoma was diagnosed and extended thymectomy and left upper lobe partial resection were performed. In 2013, he complained of dyspnea. Chest computed tomography showed postoperative recurrence of invasive thymoma. Several chemotherapies were administered. Severe anemia and an increase in the total bilirubin level were observed with chemotherapies. In additional, an examination showed that the direct Coombs test was positive. Cold agglutinin was also high. We herein experienced a rare case of postoperative recurrence of invasive thymoma with cold agglutinin disease and autoimmune hemolytic anemia.

  18. Impact of Pneumococcal Conjugate Vaccines on the Incidence of Pneumonia in Hospitalized Children after Five Years of Its Introduction in Uruguay

    PubMed Central

    Hortal, María; Estevan, Miguel; Meny, Miguel; Iraola, Inés; Laurani, Hilda

    2014-01-01

    Background Data on the burden of pneumococcal disease and the most frequent serotypes demonstrated that invasive disease and pneumonia were important manifestations affecting children under 5 years of age. Therefore, pneumococcal diseases prevention became a public health priority. Uruguay was the first Latin American country to incorporate PCV7 into its National Immunization Program. The aim of this study is to compare the incidence rates for hospitalized pneumonia in children from the pre PCV introduction period and the following five years of PCVs application in Uruguay. Methods and Findings Population-based surveillance of pneumonia hospitalization rates, in children, less than 14 years of age, had been performed prior pneumococcal vaccination, and continued following PCV7 introduction and PCV13 replacement, using the same methodology. Hospitalized children with pneumonia were enrolled from January 1, 2009 through December 31st, 2012. The study was carried out in an area with a population of 238,002 inhabitants of whom 18, 055 were under five years of age. Patients with acute lower respiratory infections for whom a chest radiograph was performed on admission were eligible. Digitalized radiographs were interpreted by a reference radiologist, using WHO criteria. Pneumonia was confirmed in 2,697 patients, 1,267 with consolidated and 1,430 with non consolidated pneumonia of which incidence decrease, between 2009 and 2012, was 27.3% and 46.4% respectively. 2001–2004 and 2009–2012 comparison showed a significant difference of 20.4% for consolidated pneumonia hospitalizations. A significant incidence decline was recorded among children 6 to 35 months of age. Conclusions An overall significant reduction in pneumonia hospitalizations was observed following the introduction of PCV7 and furthermore following the change to PCV13. PMID:24905093

  19. Early diagnosis of invasive mould infections and disease.

    PubMed

    Lamoth, Frédéric; Calandra, Thierry

    2017-03-01

    Invasive mould infections (IMIs), such as invasive aspergillosis or mucormycosis, are a major cause of death in patients with haematological cancer and in patients receiving long-term immunosuppressive therapy. Early diagnosis and prompt initiation of antifungal therapy are crucial steps in the management of patients with IMI. The diagnosis of IMI remains a major challenge, with an increased spectrum of fungal pathogens and a diversity of clinical and radiological presentations within the expanding spectrum of immunocompromised hosts. Diagnosis is difficult to establish and is expressed on a scale of probability (proven, probable and possible). Imaging (CT scan), microbiological tools (direct examination, culture, PCR, fungal biomarkers) and histopathology are the pillars of the diagnostic work-up of IMI. None of the currently available diagnostic tests provides sufficient sensitivity and specificity alone, so the optimal approach relies on a combination of multiple diagnostic strategies, including imaging, fungal biomarkers (galactomannan and 1,3-β-d-glucan) and molecular tools. In recent years, the development of PCR for filamentous fungi (primarily Aspergillus or Mucorales) and the progress made in the standardization of fungal PCR technology, may lead to future advances in the field. The appropriate diagnostic approach for IMI should be individualized to each centre, taking into account the local epidemiology of IMI and the availability of diagnostic tests.

  20. [Serotype distribution of Streptococcus pneumoniae isolated from invasive infections at the Hospital de Niños of Santa Fe].

    PubMed

    Mayoral, C; Baroni, M R; Giani, R; Virgolini, S; Zurbriggen, L; Regueira, M

    2008-01-01

    The serotype distribution of Streptococcus pneumoniae varies through time. The introduction of pneumococcal conjugate vaccines showed a decreased prevalence of pneumococcal invasive isolates belonging to serotype 14 and an increase of serotypes not therein included. In 1993, the Hospital de Niños of Santa Fe began surveillance of the serotype distribution of invasive S. pneumoniae disease. In the period 2003-2005, 76 isolates were analysed by studying the correlation between serotype and pathology, age and MIC of penicillin. Serotype 14 was the most frequent followed by serotypes 1, 6B, 18C, 7F, 19 F and 5. Serotype 14 showed a statistically significant correlation with MICs of penicillin ranging from 0,5 to 2 mg/l. Although this serotype was more frequently observed in pneumonia than in meningitis, there was not a significant association with any particular pathology. Serotypes 14 and 1, were prevalent among children under and over 2 years old, respectively. Most of these isolates with MICs of penicillin = 2 mg/l, were from patients with pneumonia and not with meningitis. The serotype distribution was similar to that during the period 1993-99, with the exception of serotypes 18C, 4, 12F and 22F which had never been found before. The emergence of these serotypes makes it essential to continue surveillance to determine which conjugated vaccine formulation would be suitable to prevent the most frequent pneumococcal invasive infections.

  1. Invasive paget disease of the breast: clinicopathologic study of an underrecognized entity in the breast.

    PubMed

    Duan, Xiuzhen; Sneige, Nour; Gullett, Ashley E; Prieto, Victor G; Resetkova, Erika; Andino, Lizmarie M; Wu, Yun; Gilcrease, Micharl Z; Bedrosian, Isabelle; Dawood, Shaheenah; Arun, Banu; Albarracin, Constance T

    2012-09-01

    Mammary Paget disease (MPD) is considered an intraepidermal manifestation of an underlying mammary carcinoma. In contrast to extramammary Paget disease, invasion of mammary Paget cells into the dermis (invMPD) has not been reported, except for 2 cases described in Rosen's textbook. Our study was designed to identify the presence of dermal invasion of mammary Paget cells and characterize the associated clinicopathologic features. Slides from 146 MPD patients were retrieved. Six cases of invMPD were identified. One case of invMPD was not associated with an underlying breast cancer, 1 was associated with invasive ductal carcinoma (IDC), 1 with ductal carcinoma in situ (DCIS) with microinvasion, and 3 with DCIS only. The underlying breast carcinomas was separate from the area of invMPD. The depth of invasion, measured from the dermal-epidermal junction to the focus of deepest invasion, ranged from 0.02 to 0.9 mm. The horizontal extent ranged from 0.01 to 4.0 mm. Lymph node with isolated tumor clusters was present in case 1, which had no underlying carcinoma but had the greatest extent of invasion, and in case 3, which had DCIS with microinvasion. One patient (case 1) died of unrelated causes 2 years later, and the remaining patients were alive without disease at last follow-up. In summary, we describe 6 cases of MPD with invasion of Paget cells into the dermis and provide histopathologic criteria for the diagnosis of this rare and underrecognized entity. Further studies are required to determine whether invasion in MPD has clinical significance.

  2. Pulmonary pathophysiology of pneumococcal pneumonia.

    PubMed

    Light, R B

    1999-09-01

    Respiratory failure is one of the most important causes of death in patients with acute pneumococcal pneumonia. There are two forms that may or may not coexist: ventilatory failure and hypoxemic respiratory failure. Ventilatory failure is principally caused by mechanical changes in the lungs resulting from pneumonia. Inflammatory exudate fills alveoli at slightly less than their normal functional residual capacity (FRC), causing a volume loss at FRC roughly proportional to the extent of the pulmonary infiltrate. Because this consolidated air space does not inflate easily at higher transpulmonary pressures, at higher lung volumes the volume loss is proportionally greater. This loss of volume reduces total lung compliance and increases the work of breathing. There is also evidence that the dynamic compliance of the remaining ventilated lung is reduced in pneumococcal pneumonia, possibly by reduction in surfactant activity, further increasing the work of breathing. Arterial hypoxemia early in acute pneumococcal pneumonia is principally caused by persistence of pulmonary artery blood flow to consolidated lung resulting in an intrapulmonary shunt, but also, to a varying degree, it is caused by intrapulmonary oxygen consumption by the lung during the acute phase and by ventilation-perfusion mismatch later. The persistence of pulmonary blood flow to consolidated lung appears to be caused by a relative failure of the hypoxic pulmonary vasoconstriction (HPV) mechanism during acute pneumonia, which is at least caused by endogenous vasodilator prostaglandins associated with the inflammatory process but also by other as yet undefined mechanisms. During convalescence, arterial oxygenation improves as blood flow to consolidated lung falls. The magnitude of the intrapulmonary shunt may be influenced by a number of factors that modify the distribution of pulmonary blood flow. Factors that tend to increase flow to consolidated lung and worsen shunt include endogenous vasodilator

  3. Tumor Wide Horizontal Invasion Predicts Local Recurrence for Scrotal Extramammary Paget’s Disease

    PubMed Central

    Wang, Lujia; Feng, Chenchen; Zhou, Minwei; Zhou, Zhongwen; Ding, Guanxiong; Gao, Peng; Ding, Qiang; Wu, Zhong

    2017-01-01

    Extramammary Paget’s disease (EMPD) is a rare malignancy, and little was known about its prognostic factors and optimal treatment. In the current study, we aimed to discuss clinical and pathological features of scrotal EMPD and determine the prognostic factors for cancer-specific survival and local recurrence. A total of 206 patients with scrotal EMPD lesions surgically treated at our institute were studied. All clinical and pathological data were reviewed. Immunohistochemical staining of TP53 and Ki67 was examined as well. At the last follow-up, 175 patients (84.95%) were alive. Twelve patients (5.83%) had died of the disease due to distant metastases. Fifteen patients (7.28%) developed local recurrences of scrotal EMPD. Ki67 expression was significantly elevated in patients with wide horizontal invasion (P = 0.003). In univariate analysis, high invasion level, presence of nodule, presence of lymphovascular invasion, adnexa invasion, lymph node metastasis and high p53 expression were significant factors for poor cancer-specific survival. In multivariate analysis, high p53 expression was significantly correlated with poor cancer-specific survival. Wide horizontal invasion was independently correlated with local recurrence-free survival of scrotal EMPD. In conclusion, wide horizontal invasion is an independent risk factor for local recurrence-free survival in the patients with scrotal EMPD. PMID:28322288

  4. Cost-Effectiveness Analysis of Universal Vaccination of Adults Aged 60 Years with 23-Valent Pneumococcal Polysaccharide Vaccine versus Current Practice in Brazil

    PubMed Central

    de Soárez, Patrícia Coelho; Sartori, Ana Marli Christovam; Freitas, Angela Carvalho; Nishikawa, Álvaro Mitsunori; Novaes, Hillegonda Maria Dutilh

    2015-01-01

    Objective 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. Methods 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. Results 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. Conclusion 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. PMID:26114297

  5. Rapid non-invasive tests for diagnostics of infectious diseases

    NASA Astrophysics Data System (ADS)

    Malamud, Daniel

    2014-06-01

    A rapid test for an infectious disease that can be used at point-of-care at a physician's office, a pharmacy, or in the field is critical for the prompt and appropriate therapeutic intervention. Ultimately by treating infections early on will decrease transmission of the pathogen. In contrast to metabolic diseases or cancer where multiple biomarkers are required, infectious disease targets (e.g. antigen, antibody, nucleic acid) are simple and specific for the pathogen causing the disease. Our laboratory has focused on three major infectious disease; HIV, Tuberculosis, and Malaria. These diseases are pandemic in much of the world thus putting natives, tourists and military personnel at risk for becoming infected, and upon returning to the U.S., transmitting these diseases to their contacts. Our devices are designed to detect antigens, antibodies or nucleic acids in blood or saliva samples in less than 30 minutes. An overview describing the current status of each of the three diagnostic platforms is presented. These microfluidic point-of-care devices will be relatively inexpensive, disposable, and user friendly.

  6. A Non-Human Primate Model of Severe Pneumococcal Pneumonia

    PubMed Central

    Reyes, Luis F.; Restrepo, Marcos I.; Hinojosa, Cecilia A.; Soni, Nilam J.; Shenoy, Anukul T.; Gilley, Ryan P.; Gonzalez-Juarbe, Norberto; Noda, Julio R.; Winter, Vicki T.; de la Garza, Melissa A.; Shade, Robert E.; Coalson, Jacqueline J.; Giavedoni, Luis D.; Anzueto, Antonio; Orihuela, Carlos J.

    2016-01-01

    Rationale Streptococcus pneumoniae is the leading cause of community-acquired pneumonia and infectious death in adults worldwide. A non-human primate model is needed to study the molecular mechanisms that underlie the development of severe pneumonia, identify diagnostic tools, explore potential therapeutic targets, and test clinical interventions during pneumococcal pneumonia. Objective To develop a non-human primate model of pneumococcal pneumonia. Methods Seven adult baboons (Papio cynocephalus) were surgically tethered to a continuous monitoring system that recorded heart rate, temperature, and electrocardiography. Animals were inoculated with 109 colony-forming units of S. pneumoniae using bronchoscopy. Three baboons were rescued with intravenous ampicillin therapy. Pneumonia was diagnosed using lung ultrasonography and ex vivo confirmation by histopathology and immunodetection of pneumococcal capsule. Organ failure, using serum biomarkers and quantification of bacteremia, was assessed daily. Results Challenged animals developed signs and symptoms of pneumonia 4 days after infection. Infection was characterized by the presence of cough, tachypnea, dyspnea, tachycardia and fever. All animals developed leukocytosis and bacteremia 24 hours after infection. A severe inflammatory reaction was detected by elevation of serum cytokines, including Interleukin (IL)1Ra, IL-6, and IL-8, after infection. Lung ultrasonography precisely detected the lobes with pneumonia that were later confirmed by pathological analysis. Lung pathology positively correlated with disease severity. Antimicrobial therapy rapidly reversed symptomology and reduced serum cytokines. Conclusions We have developed a novel animal model for severe pneumococcal pneumonia that mimics the clinical presentation, inflammatory response, and infection kinetics seen in humans. This is a novel model to test vaccines and treatments, measure biomarkers to diagnose pneumonia, and predict outcomes. PMID:27855182

  7. Influenza and pneumococcal vaccine coverage among a random sample of hospitalised persons aged 65 years or more, Victoria.

    PubMed

    Andrews, Ross M; Skull, Susan A; Byrnes, Graham B; Campbell, Donald A; Turner, Joy L; McIntyre, Peter B; Kelly, Heath A

    2005-01-01

    This study was undertaken to assess the uptake of influenza and pneumococcal vaccination based on provider records of the hospitalised elderly, a group at high risk of influenza and pneumococcal disease. The study used a random sample of 3,204 admissions at two Victorian teaching hospitals for patients, aged 65 years or more who were discharged between 1 April 2000 and 31 March 2002. Information on whether the patient had received an influenza vaccination within the year prior to admission or pneumococcal vaccination within the previous five years was ascertained from the patient's nominated medical practitioner/vaccine provider. Vaccination records were obtained from providers for 82 per cent (2,804/2,934) of eligible subjects. Influenza vaccine coverage was 70.9 per cent (95% CI 68.9-72.9), pneumococcal coverage was 52.6 per cent (95% CI 50.4-54.8) and 46.6 per cent (95% CI 44.4-48.8) had received both vaccines. Coverage for each vaccine increased seven per cent over the two study years. For pneumococcal vaccination, there was a marked increase in 1998 coinciding with the introduction of Victoria's publicly funded program. Influenza and pneumococcal vaccine coverage in eligible hospitalised adults was similar to, but did not exceed, estimates in the general elderly population. Pneumococcal vaccination coverage reflected the availability of vaccine through Victoria's publicly funded program. A nationally funded pneumococcal vaccination program for the elderly, as announced recently, should improve coverage. However, these data highlight the need for greater awareness of pneumococcal vaccine among practitioners and for systematic recording of vaccination status, as many of these subjects will soon become eligible for revaccination.

  8. 75 FR 48707 - Proposed Vaccine Information Materials for Pneumococcal Conjugate Vaccine and Human...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-11

    ... HUMAN SERVICES Centers for Disease Control and Prevention Proposed Vaccine Information Materials for Pneumococcal Conjugate Vaccine and Human Papillomavirus Vaccines AGENCY: Centers for Disease Control and...: Under the National Childhood Vaccine Injury Act (NCVIA) (42 U.S.C. 300aa-26), the CDC must...

  9. Non-Invasive Molecular Imaging of Disease Activity in Atherosclerosis

    PubMed Central

    Dweck, Marc R; Aikawa, Elena; Newby, David E; Tarkin, Jason; Rudd, James; Narula, Jagat; Fayad, Zahi A.

    2016-01-01

    Major focus has been placed on the identification of vulnerable plaques as a means of improving the prediction of myocardial infarction. However, this strategy has recently been questioned on the basis that the majority of these individual coronary lesions do not in fact go on to cause clinical events. Attention is therefore shifting to alternative imaging modalities that might provide a more complete pan-coronary assessment of the atherosclerotic disease process. These include markers of disease activity with the potential to discriminate between patients with stable burnt-out disease that is no longer metabolically active and those with active atheroma, faster disease progression and increased risk of infarction. This review will examine how novel molecular imaging approaches can provide such assessments, focusing on inflammation and microcalcification activity, the importance of these processes to coronary atherosclerosis and the advantages and challenges posed by these techniques. PMID:27390335

  10. [Pneumococcal surface protein A and new approaches for pneumococcal vaccine development].

    PubMed

    Vorob'ev, D S; Semenova, I B

    2011-01-01

    The problem of pneumococcal infections is pressing for the whole world. Existing vaccines based only on pneumococci polysaccharide antigens or polysaccharide antigens and diphtherial anatoxin are not capable of protecting from all serotypes of the microorganism. Reasonability of creation of pneumococcal vaccine based on surface proteins of Streptococcus pneumoniae is discussed in the literature. One of such key pneumococcal proteins is pneumococcal surface protein A (PSPA), because it is detected in all the S. pneumoniae strains, has cross activity and switches B-cell immune response to T-cell. Currently the development of conjugated vaccine based on surface proteins and capsule polysaccharides of pneumococcus seems promising.

  11. Clinical and Molecular Epidemiology of Haemophilus influenzae Causing Invasive Disease in Adult Patients

    PubMed Central

    Puig, Carmen; Grau, Imma; Tubau, Fe; Calatayud, Laura; Pallares, Roman; Liñares, Josefina

    2014-01-01

    Objectives The epidemiology of invasive Haemophilus influenzae (Hi) has changed since the introduction of the Hi type b (Hib) vaccine. The aim of this study was to analyze the clinical and molecular epidemiology of Hi invasive disease in adults. Methods Clinical data of the 82 patients with Hi invasive infections were analyzed. Antimicrobial susceptibility, serotyping, and genotyping were studied (2008–2013). Results Men accounted for 63.4% of patients (whose mean age was 64.3 years). The most frequent comorbidities were immunosuppressive therapy (34.1%), malignancy (31.7%), diabetes, and COPD (both 22%). The 30-day mortality rate was 20.7%. The majority of the strains (84.3%) were nontypeable (NTHi) and serotype f was the most prevalent serotype in the capsulated strains. The highest antimicrobial resistance was for cotrimoxazole (27.1%) and ampicillin (14.3%). Twenty-three isolates (32.9%) had amino acid changes in the PBP3 involved in resistance. Capsulated strains were clonal and belonged to clonal complexes 6 (serotype b), 124 (serotype f), and 18 (serotype e), whereas NTHi were genetically diverse. Conclusions Invasive Hi disease occurred mainly in elderly and those with underlying conditions, and it was associated with a high mortality rate. NTHi were the most common cause of invasive disease and showed high genetic diversity. PMID:25379704

  12. Direct Ex-Vivo Evaluation of Pneumococcal Specific T-Cells in Healthy Adults

    PubMed Central

    Aslam, Aamir; Chapel, Helen; Ogg, Graham

    2011-01-01

    Streptococcus pneumoniae is an encapsulated bacterium that causes significant global morbidity and mortality. The nasopharynxes of children are believed to be the natural reservoir of pneumococcus and by adulthood nasopharyngeal carriage is infrequent; such infrequency may be due to demonstrable pneumococcal specific T and B-cell responses. HLA Class 2 tetrameric complexes have been used to characterise antigen specific T-cell responses in a variety of models of infection. We therefore sought to determine the frequency and phenotype of pneumococcal specific T-cells, using a novel HLA-DRB1*1501 tetramer complex incorporating a recently defined T-cell epitope derived from the conserved pneumococcal serine/threonine kinase (StkP). We were able to detect direct ex-vivo StkP446–60-tetramer binding in HLA-DRB1*1501 adults. These StkP446–60-tetramer binding T-cells had increased CD38 expression and were enriched in CCR7- CD45RA+ expression indicating recent and on-going activation and differentiation. Furthermore, these StkP446–60-tetramer binding T-cells demonstrated rapid effector function by secreting interferon-gamma on stimulation with recombinant StkP. This is the first study to directly enumerate and characterise pneumococcal specific T-cells using HLA class 2 tetrameric complexes. We found that ex-vivo pneumococcal-specific T cells were detectable in healthy adults and that they were enriched with cell surface markers associated with recent antigen exposure and later stages of antigen-driven differentiation. It is likely that these activated pneumococcal specific T-cells reflect recent immunostimulatory pneumococcal exposure in the nasopharynx and it is possible that they may be preventing subsequent colonisation and disease. PMID:22039412

  13. Variant histology in bladder cancer: how it should change the management in non-muscle invasive and muscle invasive disease?

    PubMed Central

    Klaile, Yvonne; Schlack, Katrin; Boegemann, Martin; Steinestel, Julie; Schrader, Andres Jan

    2016-01-01

    Bladder cancer (BC) is a frequent type of carcinoma with an estimated incidence of approximately 100,000 men and women each year in the European Union (EU) with an associated mortality of 30,000 of these patients. In more than 70% the disease is diagnosed in a non-muscle invasive stage with the chance of minimally invasive, local treatment only, which might be required repetitively due to high rate of recurrence. In contrast, muscle invasive or metastatic stages need multimodal treatment strategies including surgical treatment and chemotherapy (CTX) in neoadjuvant (NAC), adjuvant, or palliative settings. Therapy recommendations and guidelines mainly refer to the most common histological type of BC, pure urothelial carcinoma (UC). However, BC can be classified as urothelial and non-UC. Non-urothelial BC and variants of UC account for up to 25% of all BCs. Further discrimination can be made into epithelial and non-epithelial non-UC. Most of the non-UCs are of epithelial origin (approximately 90%) including squamous-cell carcinoma, adenocarcinoma and small-cell carcinoma. Non-epithelial tumors are rare and include variants as sarcoma, carcinosarcoma, paraganglioma, melanoma and lymphoma. Even though it is unclear whether the prognosis of non-urothelial cancer truly differs from that of UC, there is evidence that additional variant histology might prognosticate an impaired prognosis. Accordingly, aggressive behavior and often advanced stages at primary presentation are frequently observed in non-UC arguing for radical and sometimes different treatment strategies as compared to pure UC. This review aims to summarize the available data for the most common histological variants of non-urothelial BC. PMID:27785426

  14. Invasive Paget disease of the breast: 20 years of experience at a single institution.

    PubMed

    Lee, Hyun-Woo; Kim, Tae Eun; Cho, Soo Youn; Kim, Seok Won; Kil, Won Ho; Lee, Jeong Eon; Nam, Seok Jin; Cho, Eun Yoon

    2014-12-01

    Mammary Paget disease with dermal invasion (invMPD) is rare, and its prognosis remains largely unknown. We reviewed MPD cases diagnosed at our institution and analyzed the clinicopathological characteristics of invMPD and non-invMPD to compare their incidences and outcomes. We retrospectively reviewed 205 cases of women diagnosed as having MPD between 1994 and 2013. Sixteen of 205 MPD cases (7.8%) had dermal invasion. Twelve of 16 invMPD cases had separate, underlying invasive breast carcinoma, and 3 invMPD cases had ductal carcinoma in situ. To exclude the influence of underlying disease on prognosis, we compared prognosis of invMPD with matched non-invMPD. The mean depth and extent of Paget cell invasion in invMPD cases were 0.637 and 1.268 mm, respectively. The horizontal extent of MPD was significantly larger in invMPD versus non-invMPD (mean, 14.31 mm versus 7.35 mm; P = .002). Distant metastasis and disease-related death were observed in 12.6% (24/189) and 12.1% (23/189) of non-invMPD patients, respectively, compared with 6.3% (1/16) and 6.3% (1/16) of invMPD patients; this difference was not significant (P = .7 and P = .7). Clinical outcomes of the invMPD patients were also not significantly different from the matched non-invMPD patients. In this study, MPD extent significantly correlated with MPD invasion. However, other clinicopathological parameters were not associated with dermal MPD invasion. Dermal MPD invasion was rare and did not predict regional lymph node metastasis or poor prognosis. The prognosis is usually similar for invMPD and non-invMPD, and MPD must be distinguished from locally advanced breast cancer presenting as satellite skin nodules.

  15. Capsules of virulent pneumococcal serotypes enhance formation of neutrophil extracellular traps during in vivo pathogenesis of pneumonia

    PubMed Central

    Moorthy, Anandi Narayana; Rai, Prashant; Jiao, Huipeng; Wang, Shi; Tan, Kong Bing; Qin, Liang; Watanabe, Hiroshi; Zhang, Yongliang; Teluguakula, Narasaraju; Chow, Vincent Tak Kwong

    2016-01-01

    Neutrophil extracellular traps (NETs) are released by activated neutrophils to ensnare and kill microorganisms. NETs have been implicated in tissue injury since they carry cytotoxic components of the activated neutrophils. We have previously demonstrated the generation of NETs in infected murine lungs during both primary pneumococcal pneumonia and secondary pneumococcal pneumonia after primary influenza. In this study, we assessed the correlation of pneumococcal capsule size with pulmonary NETs formation and disease severity. We compared NETs formation in the lungs of mice infected with three pneumococcal strains of varying virulence namely serotypes 3, 4 and 19F, as well as a capsule-deficient mutant of serotype 4. In primary pneumonia, NETs generation was strongly associated with the pneumococcal capsule thickness, and was proportional to the disease severity. Interestingly, during secondary pneumonia after primary influenza infection, intense pulmonary NETs generation together with elevated myeloperoxidase activity and cytokine dysregulation determined the disease severity. These findings highlight the crucial role played by the size of pneumococcal capsule in determining the extent of innate immune responses such as NETs formation that may contribute to the severity of pneumonia. PMID:27034012

  16. Immune Response to Invasive Group B Streptococcus Disease in Adults

    PubMed Central

    Rench, Marcia A.; Rinaudo, C. Daniela; Fabbrini, Monica; Tuscano, Giovanna; Buffi, Giada; Bartolini, Erika; Bonacci, Stefano; Baker, Carol J.; Margarit, Immaculada

    2016-01-01

    Immunization of nonpregnant adults could help prevent invasive group B Streptococcus (GBS) infections, but adult immune responses have not been investigated. We defined capsular polysaccharide (CPS) and pilus island (PI) surface antigen distribution and expression and immune responses to GBS infection in nonpregnant adults. Prospective surveillance from 7 hospitals in Houston, Texas, USA, identified 102 adults with GBS bacteremia; 43% had skin/soft tissue infection, 16% bacteremia without focus, and 12% osteomyelitis. CPS-specific IgG was determined by ELISA and pilus-specific IgG by multiplex immunoassay. CPS types were Ia (24.5%), Ib (12.7%), II (9.8%), III (16.7%), IV (13.7%), and V (12.7%); 9.8% were nontypeable by serologic methods. Pili, expressed by 89%, were most often PI-2a. CPS and pilus-specific IgG increased during convalescence among patients with strains expressing CPS or PI. All GBS expressed CPS or PI; 79% expressed both. Increased antibodies to CPS and PI during recovery suggests that GBS bacteremia in adults is potentially vaccine preventable. PMID:27767008

  17. Immunization with Pneumococcal Surface Protein K of Nonencapsulated Streptococcus pneumoniae Provides Protection in a Mouse Model of Colonization.

    PubMed

    Keller, Lance E; Luo, Xiao; Thornton, Justin A; Seo, Keun-Seok; Moon, Bo Youn; Robinson, D Ashley; McDaniel, Larry S

    2015-11-01

    Current vaccinations are effective against encapsulated strains of Streptococcus pneumoniae, but they do not protect against nonencapsulated Streptococcus pneumoniae (NESp), which is increasing in colonization and incidence of pneumococcal disease. Vaccination with pneumococcal proteins has been assessed for its ability to protect against pneumococcal disease, but several of these proteins are not expressed by NESp. Pneumococcal surface protein K (PspK), an NESp virulence factor, has not been assessed for immunogenic potential or host modulatory effects. Mammalian cytokine expression was determined in an in vivo mouse model and in an in vitro cell culture system. Systemic and mucosal mouse immunization studies were performed to determine the immunogenic potential of PspK. Murine serum and saliva were collected to quantitate specific antibody isotype responses and the ability of antibody and various proteins to inhibit epithelial cell adhesion. Host cytokine response was not reduced by PspK. NESp was able to colonize the mouse nasopharynx as effectively as encapsulated pneumococci. Systemic and mucosal immunization provided protection from colonization by PspK-positive (PspK(+)) NESp. Anti-PspK antibodies were recovered from immunized mice and significantly reduced the ability of NESp to adhere to human epithelial cells. A protein-based pneumococcal vaccine is needed to provide broad protection against encapsulated and nonencapsulated pneumococci in an era of increasing antibiotic resistance and vaccine escape mutants. We demonstrate that PspK may serve as an NESp target for next-generation pneumococcal vaccines. Immunization with PspK protected against pneumococcal colonization, which is requisite for pneumococcal disease.

  18. Antiretroviral Therapy as Prevention of … Pneumococcal Infections?

    PubMed Central

    Leporrier, Jérémie; Delbos, Valérie; Unal, Guillemette; Honoré, Patricia; Etienne, Manuel; Bouchaud, Olivier; Caron, François

    2016-01-01

    Background. Despite antiretroviral therapy, it is generally believed that the risk for pneumococcal infections (PnIs) is high among patients infected with human immunodeficiency virus (HIV). However, most studies in this field have been conducted before 2010, and the proportion of virologically suppressed patients has drastically increased in these latter years thanks to larger indications and more effective antiretroviral regimens. This study aimed to re-evaluate the current risk of PnI among adult patients infected with HIV. Methods. The incidence of PnI was evaluated between 1996 and 2014 in 2 French regional hospitals. The 80 most recent cases of PnI (2000–2014) were retrospectively compared with 160 controls (HIV patients without PnI) to analyze the residual risk factors of PnI. Results. Among a mean annual follow-up cohort of 1616 patients, 116 PnIs were observed over 18 years. The risk factors of PnI among patients infected with HIV were an uncontrolled HIV infection or “classic” risk factors of PnI shared by the general population such as addiction, renal or respiratory insufficiency, or hepatitis B or C coinfection. Pneumococcal vaccination coverage was low and poorly targeted, because only 5% of the cases had been previously vaccinated. The incidence of invasive PnIs among HIV patients with a nonvirologically suppressed infection or comorbidities was 12 times higher than that reported in the general population at the country level (107 vs 9/100000 patients), whereas the incidence among virologically suppressed HIV patients without comorbidities was lower (7.6/100000 patients). Conclusions. Human immunodeficiency virus infection no longer per se seems to be a significant risk factor for PnI, suggesting a step-down from a systematic to an “at-risk patient” targeted pneumococcal vaccination strategy. PMID:28018929

  19. Invasive Potential of Nonencapsulated Disease Isolates of Neisseria meningitidis

    PubMed Central

    Johswich, Kay O.; Zhou, Jianwei; Law, Dennis K. S.; St. Michael, Frank; McCaw, Shannon E.; Jamieson, Frances B.; Cox, Andrew D.; Tsang, Raymond S. W.

    2012-01-01

    The capsule of Neisseria meningitidis is the major virulence factor that enables this bacterium to overcome host immunity elicited by complement and phagocytes, rendering it capable of surviving in blood. As such, nonencapsulated N. meningitidis isolates are generally considered nonpathogenic. Here, we consider the inherent virulence of two nonencapsulated N. meningitidis isolates obtained from our national surveillance of infected blood cultures in Canada. Capsule deficiency of both strains was confirmed by serology and PCR for the ctrA to ctrD genes and siaA to siaC genes, as well as siaD genes specific to serogroups B, C, Y, and W135. In both strains, the capsule synthesis genes were replaced by the capsule null locus, cnl-2. In accordance with a lack of capsule, both strains were fully susceptible to killing by both human and baby rabbit complement. However, in the presence of cytidine-5′ monophospho-N-acetylneuraminic acid (CMP-NANA), allowing for lipooligosaccharide (LOS) sialylation, a significant increase of resistance to complement killing was observed. Mass spectrometry of purified LOS did not reveal any uncommon modifications that would explain their invasive phenotype. Finally, in a mouse intraperitoneal challenge model, these nonencapsulated isolates displayed enhanced virulence relative to an isogenic mutant of serogroup B strain MC58 lacking capsule (MC58ΔsiaD). Virulence of all nonencapsulated isolates tested was below that of encapsulated serogroup B strains MC58 and B16B6. However, whereas no mortality was observed with MC58ΔsiaD, 5/10 mice succumbed to infection with strain 2275 and 2/11 mice succumbed to strain 2274. Our results suggest the acquisition of a new virulence phenotype by these nonencapsulated strains. PMID:22508859

  20. Serotype IV Sequence Type 468 Group B Streptococcus Neonatal Invasive Disease, Minnesota, USA

    PubMed Central

    Teatero, Sarah; Ferrieri, Patricia

    2016-01-01

    To further understand the emergence of serotype IV group B Streptococcus (GBS) invasive disease, we used whole-genome sequencing to characterize 3 sequence type 468 strains isolated from neonates in Minnesota, USA. We found that strains of tetracycline-resistant sequence type 468 GBS have acquired virulence genes from a putative clonal complex 17 GBS donor by recombination. PMID:27767922

  1. Surveillance for Invasive Meningococcal Disease in Children, US–Mexico Border, 2005–20081

    PubMed Central

    Sugerman, David E.; Ginsberg, Michele M.; Hopkins, Jackie; Hurtado-Montalvo, Jose Antonio; Lopez-Viera, Jose Luis; Lara-Muñoz, Cesar Arturo; Rivas-Landeros, Rosa M.; Volker, Maria Luisa; Leake, John A.

    2011-01-01

    We reviewed confirmed cases of pediatric invasive meningococcal disease in Tijuana, Mexico, and San Diego County, California, USA, during 2005–2008. The overall incidence and fatality rate observed in Tijuana were similar to those found in the US, and serogroup distribution suggests that most cases in Tijuana are vaccine preventable. PMID:21392455

  2. Minimally invasive surgery for inflammatory bowel disease: Review of current developments and future perspectives

    PubMed Central

    Neumann, Philipp-Alexander; Rijcken, Emile

    2016-01-01

    Patients with inflammatory bowel disease (IBD) comprise a population of patients that have a high likelihood of both surgical treatment at a young age and repetitive operative interventions. Therefore surgical procedures need to aim at minimizing operative trauma with best postoperative recovery. Minimally invasive techniques have been one of the major advancements in surgery in the last decades and are nowadays almost routinely performed in colorectal resections irrespective of underlying disease. However due to special disease related characteristics such as bowel stenosis, interenteric fistula, abscesses, malnutrition, repetitive surgeries, or immunosuppressive medications, patients with IBD represent a special cohort with specific needs for surgery. This review summarizes current evidence of minimally invasive surgery for patients with Crohn’s disease or ulcerative colitis and gives an outlook on the future perspective of technical advances in this highly moving field with its latest developments in single port surgery, robotics and trans-anal techniques. PMID:27158537

  3. Invasion speeds of Triatoma dimidiata, vector of Chagas disease: An application of orthogonal polynomials method.

    PubMed

    Mesk, Mohammed; Mahdjoub, Tewfik; Gourbière, Sébastien; Rabinovich, Jorge E; Menu, Frédéric

    2016-04-21

    Demographic processes and spatial dispersal of Triatoma dimidiata, a triatomine species vector of Chagas disease, are modeled by integrodifference equations to estimate invasion capacity of this species under different ecological conditions. The application of the theory of orthogonal polynomials and the steepest descent method applied to these equations, allow a good approximation of the abundance of the adult female population and the invasion speed. We show that: (1) under the same mean conditions of demography and dispersal, periodic spatial dispersal results in an invasion speed 2.5 times larger than the invasion speed when spatial dispersal is continuous; (2) when the invasion speed of periodic spatial dispersal is correlated to adverse demographic conditions, it is 34.7% higher as compared to a periodic dispersal that is correlated to good demographic conditions. From our results we conclude, in terms of triatomine population control, that the invasive success of T. dimidiata may be most sensitive to the probability of transition from juvenile to adult stage. We discuss our main theoretical predictions in the light of observed data in different triatomines species found in the literature.

  4. Draft Genome Sequences of Six Nontypeable Haemophilus influenzae Strains That Establish Bacteremia in the Infant Rat Model of Invasive Disease

    PubMed Central

    VanWagoner, Timothy M.; Seale, Thomas W.; Mussa, Huda J.; Cole, Brett K.; Whitby, Paul W.; Stull, Terrence L.

    2015-01-01

    Haemophilus influenzae is an important cause of invasive disease. The infant rat is the accepted model of invasive H. influenzae disease. Here, we report the genome sequences of six nontypeable H. influenzae strains that establish bacteremia in the infant rat. PMID:26404588

  5. Non-Invasive Measurements of Carboxyhemoglobin and Methemoglobin in Children with Sickle Cell Disease

    PubMed Central

    Caboot, Jason B.; Jawad, Abbas F.; McDonough, Joseph M.; Bowdre, Cheryl Y.; Arens, Raanan; Marcus, Carole L.; Mason, Thornton B.A.; Smith-Whitley, Kim; Ohene-Frempong, Kwaku; Allen, Julian L.

    2012-01-01

    SUMMARY Assessment of oxyhemoglobin saturation in patients with sickle cell disease (SCD) is vital for prompt recognition of hypoxemia. The accuracy of pulse oximeter measurements of blood oxygenation in SCD patients is variable, partially due to carboxyhemoglobin (COHb) and methemoglobin (MetHb), which decrease the oxygen content of blood. This study evaluated the accuracy and reliability of a non-invasive pulse co-oximeter in measuring COHb and MetHb percentages (SpCO and SpMet) in children with SCD. We hypothesized that measurements of COHb and MetHb by non-invasive pulse co-oximetry agree within acceptable clinical accuracy with those made by invasive whole blood co-oximetry. Fifty children with SCD-SS underwent pulse co-oximetry and blood co-oximetry while breathing room air. Non-invasive COHb and MetHb readings were compared to the corresponding blood measurements. The pulse co-oximeter bias was 0.1% for COHb and −0.22% for MetHb. The precision of the measured SpCO was ±2.1% within a COHb range of 0.4–6.1%, and the precision of the measured SpMet was ±0.33% within a MetHb range of 0.1–1.1%. Non-invasive pulse co-oximetry was useful in measuring COHb and MetHb levels in children with SCD. Although the non-invasive technique slightly overestimated the invasive COHb measurements and slightly underestimated the invasive MetHb measurements, there was close agreement between the two methods. PMID:22328189

  6. Nasopharyngeal antibodies to pneumococcal pneumolysin in children with acute otitis media.

    PubMed Central

    Virolainen, A; Jero, J; Käyhty, H; Karma, P; Eskola, J; Leinonen, M

    1995-01-01

    Pneumolysin, an intracellular protein toxin of all clinically relevant pneumococcal serotypes, is released in vivo during the autolysis of pneumococci and is believed to pave the way for intact pneumococci to invade and cause disease. Therefore, antibodies to pneumolysin should prevent its destructive function. We measured antibodies to pneumococcal pneumolysin in acute- and convalescent-phase nasopharyngeal aspirate samples of 120 children (median age, 2.5 years) with acute otitis media by enzyme immunoassay. Nasopharyngeal immunoglobulin M (IgM) and IgG class antibodies to pneumolysin were rarely detectable, whereas IgA class antibody was detected often, occurred independently of serum IgA antibody in serum, and correlated with the presence of the secretory component in pneumococcal antibody, indicating local production of IgA antibodies. Nasopharyngeal IgA antibody to pneumolysin was detected in 93% of the children already in the acute phase of otitis. Twenty percent of the children developed at least a threefold rise in the pneumolysin-specific IgA antibody concentration by the convalescent phase of otitis, with the youngest at 6 months of age, regardless of the pneumococcal findings in the nasopharynx or middle ear fluid. We suggest that nasopharyngeal IgA antibody to pneumolysin can be produced early in life by pneumococcal colonization. PMID:8574834

  7. Noninvasive and invasive pulmonary function in mouse models of obstructive and restrictive respiratory diseases.

    PubMed

    Vanoirbeek, Jeroen A J; Rinaldi, Manuela; De Vooght, Vanessa; Haenen, Steven; Bobic, Sonja; Gayan-Ramirez, Ghislaine; Hoet, Peter H M; Verbeken, Erik; Decramer, Marc; Nemery, Benoit; Janssens, Wim

    2010-01-01

    Pulmonary function analysis is an important tool in the evaluation of mouse respiratory disease models, but much controversy still exists on the validity of some tests. Most commonly used pulmonary function variables of humans are not routinely applied in mice, and the question of which pulmonary function is optimal for the monitoring of a particular disease model remains largely unanswered. Our study aimed to delineate the potential and restrictions of existing pulmonary function techniques in different respiratory disease models, and to determine some common variables between humans and mice. A noninvasive (unrestrained plethysmography) and two invasive pulmonary function devices (forced maneuvers system from Buxco Research Systems [Wilmington, NC] and forced oscillation technique from SCIREQ [Montreal, PQ, Canada]) were evaluated in well-established models of asthma (protein and chemical induced): a model of elastase-induced pulmonary emphysema, and a model of bleomycin-induced pulmonary fibrosis. In contrast to noninvasive tests, both invasive techniques were efficacious for the quantification of parenchymal disease via changes in functional residual capacity, total lung capacity, vital capacity, and compliance of the respiratory system. Airflow obstruction and airflow limitation at baseline were only present in emphysema, but could be significantly induced after methacholine challenge in mice with asthma, which correlated best with an increase of respiratory resistance. Invasive pulmonary functions allow distinction between respiratory diseases in mice by clinically relevant variables, and should become standard in the functional evaluation of pathological disease models.

  8. Utility of R0 as a predictor of disease invasion in structured populations

    USGS Publications Warehouse

    Cross, P.C.; Johnson, P.L.F.; Lloyd-Smith, J. O.; Getz, W.M.

    2007-01-01

    Early theoretical work on disease invasion typically assumed large and well-mixed host populations. Many human and wildlife systems, however, have small groups with limited movement among groups. In these situations, the basic reproductive number, R0, is likely to be a poor predictor of a disease pandemic because it typically does not account for group structure and movement of individuals among groups. We extend recent work by combining the movement of hosts, transmission within groups, recovery from infection and the recruitment of new susceptibles into a stochastic model of disease in a host metapopulation. We focus on how recruitment of susceptibles affects disease invasion and how population structure can affect the frequency of superspreading events (SSEs). We show that the frequency of SSEs may decrease with the reduced movement and the group sizes due to the limited number of susceptible individuals available. Classification tree analysis of the model results illustrates the hierarchical nature of disease invasion in host metapopulations. First, the pathogen must effectively transmit within a group (R0 > 1), and then the pathogen must persist within a group long enough to allow for movement among the groups. Therefore, the factors affecting disease persistence - such as infectious period, group size and recruitment of new susceptibles - are as important as the local transmission rates in predicting the spread of pathogens across a metapopulation. ?? 2006 The Royal Society.

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

    PubMed

    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.

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

    PubMed Central

    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. PMID:26575615

  11. [Mini-invasive operations in patients with vessels diseases].

    PubMed

    Kalinin, A A; Kutyrev, O E; Sakharov, A B; Patlachuk, M V; Aldoshina, V V; Ter-Akopian, A V; Nosenko, E M; Kriuchkova, O V

    2014-01-01

    Hybrid operations combining open and endovascular surgeries are used in cardio-vascular surgery for the last 10-15 years. It leads to decrease complications frequency and mortality in case of pronounced comorbidities and severe heart, aorta and its branches disease. Authors have experience in performing of 10 hybrid surgeries and 7 aneurysms endoprosthesis of abdominal aorta. All operated patients had severe comorbidities which significantly increase risk of open surgery. These comorbidities were contraindication for open surgery in patients with abdominal aorta aneurysm. Thanks to introduction into practice hybrid operations and aorta aneurysms endoprosthesis the authors decreased complications frequency and avoided deaths in operated patients.

  12. Streptococcus pneumoniae biofilm formation and dispersion during colonization and disease

    PubMed Central

    Chao, Yashuan; Marks, Laura R.; Pettigrew, Melinda M.; Hakansson, Anders P.

    2015-01-01

    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 one 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 pneumococcal biofilm

  13. Amebic infections in asymptomatic homosexual men, lack of evidence of invasive disease.

    PubMed Central

    Sorvillo, F J; Strassburg, M A; Seidel, J; Visvesvara, G S; Mori, K; Todd, A; Portigal, L; Finn, M; Agee, B A

    1986-01-01

    A survey for enteric infections in 140 asymptomatic homosexual men who attended a community clinic revealed a high prevalence of infection with Entamoeba histolytica (27.1 per cent) and Giardia lamblia (15.7 per cent). In contrast, the prevalence of elevated indirect hemagglutination (IHA) titers (greater than or equal to 1:128), which indicate invasive amebiasis, was low (5.7 per cent). Our findings suggest that only a limited amount of invasive amebic disease is occurring in this group of homosexual men. PMID:2874747

  14. Genomic Epidemiology of Penicillin-Nonsusceptible Pneumococci with Nonvaccine Serotypes Causing Invasive Disease in the United States.

    PubMed

    Andam, Cheryl P; Mitchell, Patrick K; Callendrello, Alanna; Chang, Qiuzhi; Corander, Jukka; Chaguza, Chrispin; McGee, Lesley; Beall, Bernard W; Hanage, William P

    2017-04-01

    Conjugate vaccination against seven pneumococcal serotypes (PCV7) reduced disease prevalence due to antibiotic-resistant strains throughout the 2000s. However, diseases caused by resistant nonvaccine type (NVT) strains increased. Some of these emerging strains were derived from vaccine types (VT) that had changed their capsule by recombination. The introduction of a vaccine targeting 13 serotypes (PCV13) in 2010 has led to concern that this scenario will repeat itself. We generated high-quality draft genomes from 265 isolates of NVT pneumococci not susceptible to penicillin (PNSP) in 2009 and compared them with the genomes of 581 isolates from 2012 to 2013 collected by the Active Bacterial Core surveillance (ABCs) of the Centers for Disease Control and Prevention (CDC). Of the seven sequence clusters (SCs) identified, three SCs fell into a single lineage associated with serogroup 23, which had an origin in 1908 as dated by coalescent analysis and included isolates with a divergent 23B capsule locus. Three other SCs represented relatively deep-branching lineages associated with serotypes 35B, 15A, and 15BC. In all cases, the resistant clones originated prior to 2010, indicating that PNSP are at present dominated by descendants of NVT clones present before vaccination. With one exception (15BC/ST3280), these SCs were related to clones identified by the Pneumococcal Molecular Epidemiology Network (PMEN). We conclude that postvaccine diversity in NVT PNSP between 2009 and 2013 was driven mainly by the persistence of preexisting strains rather than through de novo adaptation, with few cases of serotype switching. Future surveillance is essential for documenting the long-term dynamics and resistance of NVT PNSP.

  15. Symptomatic Primary Selective Immunoglobulin M Deficiency with Nonprotective Pneumococcal Titers Responsive to Subcutaneous Immunoglobulin Treatment.

    PubMed

    Patel, Shiven S; Fergeson, Jennifer E; Glaum, Mark C; Lockey, Richard F

    2016-01-01

    Selective immunoglobulin M deficiency (SIgMD) is a rare disorder with varying clinical features. The prevalence of SIgMD is 0.03-3%. Patients may be asymptomatic or else present with recurrent infection, autoimmunity, atopic disease and/or malignancy. About 50% of patients with symptomatic SIgMD also have impaired antibody responses to the pneumococcal polysaccharide vaccine. We report on an adult who presented with symptomatic SIgMD with impaired pneumococcal polysaccharide antibody responses and lymphopenia, who experienced a significant clinical improvement in the frequency of infections after subcutaneous immunoglobulin replacement therapy.

  16. Whole Genome Sequencing of 39 Invasive Streptococcus pneumoniae Sequence Type 199 Isolates Revealed Switches from Serotype 19A to 15B

    PubMed Central

    Lucas, Marie; Brandt, Christian; Herrmann, Leonie; Albersmeier, Andreas; Blom, Jochen; Goesmann, Alexander

    2017-01-01

    Streptococcus pneumoniae is a major pathogen that causes different invasive pneumococcal diseases (IPD). The pneumococcal polysaccharide capsule is a main virulence factor. More than 94 capsule types have been described, but only a limited number of capsule types accounted for the majority of IPD cases before the introduction of pneumococcal vaccines. After the introduction of the conjugated pneumococcal vaccine PCV7, which covered the seven most frequent serotypes in IPD in the USA, an increase in IPD caused by non-vaccine serotypes was observed, and serotype 19A, which belongs to sequence type (ST) 199, was among the most prevalent STs. After the introduction of the extended vaccine PCV13, which includes serotype 19A, serogroup 15B/C increased in IPD. Therefore, whole genome sequences of 39 isolates of ST199 from Germany (collected between 1998 and 2011) with serotype 19A (n = 24) and serogroup 15B/C (n = 15) were obtained using an Illumina platform and were analysed to identify capsular switches within ST199. Two 19A to 15B/C serotype switch events were identified. Both events occurred before the introduction of PCV7, which indicates that a capsular switch from 19A to 15B among ST199 isolates is not unusual and is not directly linked to the vaccination. The observed serotype replacement appears to be the result of a vacant niche due to the displacement of vaccine serotypes that is now successfully occupied by ST199 clones. PMID:28046133

  17. Whole Genome Sequencing of 39 Invasive Streptococcus pneumoniae Sequence Type 199 Isolates Revealed Switches from Serotype 19A to 15B.

    PubMed

    Makarewicz, Oliwia; Lucas, Marie; Brandt, Christian; Herrmann, Leonie; Albersmeier, Andreas; Rückert, Christian; Blom, Jochen; Goesmann, Alexander; van der Linden, Mark; Kalinowski, Jörn; Pletz, Mathias W

    2017-01-01

    Streptococcus pneumoniae is a major pathogen that causes different invasive pneumococcal diseases (IPD). The pneumococcal polysaccharide capsule is a main virulence factor. More than 94 capsule types have been described, but only a limited number of capsule types accounted for the majority of IPD cases before the introduction of pneumococcal vaccines. After the introduction of the conjugated pneumococcal vaccine PCV7, which covered the seven most frequent serotypes in IPD in the USA, an increase in IPD caused by non-vaccine serotypes was observed, and serotype 19A, which belongs to sequence type (ST) 199, was among the most prevalent STs. After the introduction of the extended vaccine PCV13, which includes serotype 19A, serogroup 15B/C increased in IPD. Therefore, whole genome sequences of 39 isolates of ST199 from Germany (collected between 1998 and 2011) with serotype 19A (n = 24) and serogroup 15B/C (n = 15) were obtained using an Illumina platform and were analysed to identify capsular switches within ST199. Two 19A to 15B/C serotype switch events were identified. Both events occurred before the introduction of PCV7, which indicates that a capsular switch from 19A to 15B among ST199 isolates is not unusual and is not directly linked to the vaccination. The observed serotype replacement appears to be the result of a vacant niche due to the displacement of vaccine serotypes that is now successfully occupied by ST199 clones.

  18. Effects of climate change, invasive species, and disease on the distribution of native European crayfishes.

    PubMed

    Capinha, César; Larson, Eric R; Tricarico, Elena; Olden, Julian D; Gherardi, Francesca

    2013-08-01

    Climate change will require species to adapt to new conditions or follow preferred climates to higher latitudes or elevations, but many dispersal-limited freshwater species may be unable to move due to barriers imposed by watershed boundaries. In addition, invasive nonnative species may expand into new regions under future climate conditions and contribute to the decline of native species. We evaluated future distributions for the threatened European crayfish fauna in response to climate change, watershed boundaries, and the spread of invasive crayfishes, which transmit the crayfish plague, a lethal disease for native European crayfishes. We used climate projections from general circulation models and statistical models based on Mahalanobis distance to predict climate-suitable regions for native and invasive crayfishes in the middle and at the end of the 21st century. We identified these suitable regions as accessible or inaccessible on the basis of major watershed boundaries and present occurrences and evaluated potential future overlap with 3 invasive North American crayfishes. Climate-suitable areas decreased for native crayfishes by 19% to 72%, and the majority of future suitable areas for most of these species were inaccessible relative to native and current distributions. Overlap with invasive crayfish plague-transmitting species was predicted to increase. Some native crayfish species (e.g., noble crayfish [Astacus astacus]) had no future refugia that were unsuitable for the modeled nonnative species. Our results emphasize the importance of preventing additional introductions and spread of invasive crayfishes in Europe to minimize interactions between the multiple stressors of climate change and invasive species, while suggesting candidate regions for the debatable management option of assisted colonization.

  19. Characterization of multivalent pneumococcal conjugate vaccines.

    PubMed

    Katkocin, D M

    2000-01-01

    A new heptavalent pneumococcal conjugate vaccine, designed to protect against disease due to serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F, was formulated with aluminium phosphate adjuvant and analysed before testing in infants. Analyses were complicated by the presence of the adjuvant, and by the low level of each antigen; for example, all serotypes were formulated at 2 microg of saccharide /dose (except 6B which was formulated at 4 microg). Type specific analyses were performed on the formulated vaccine, and included determination of immunogenicity and antigenicity; the former was measured by ELISA following immunization of rabbits, the latter was measured by rate nephelometry. Non serotype specific information was also collected, and included total and adsorbed saccharide (by Anthrone assay), and total and adsorbed protein (by Lowry assay). These preclinical data supported the use of the vaccine in infants in a large randomized double-blinded clinical trial in a multiethnic population. The results of this trial show that the vaccine is safe and efficacious. Collectively, the data will be used to support licensure of the heptavalent vaccine, and documents successful scale-up of the formulation process to manufacturing level.

  20. Single-Step Multiplex PCR Assay for Determining 92 Pneumococcal Serotypes

    PubMed Central

    Ercibengoa, María; Santacatterina, Erica; Alonso, Marta; Pérez-Trallero, Emilio

    2016-01-01

    For pneumococcal disease surveillance, simple and cost-effective methods capable of determining all serotypes are needed. Combining a single-tube multiplex PCR with fluorescently labeled primers followed by amplicon analysis using automated fluorescent capillary electrophoresis, each serotype of 92 reference isolates and 297 recently collected clinical isolates was successfully determined. PMID:27280423

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

    PubMed

    McNeil, Shelly A; Qizilbash, Nawab; Ye, Jian; Gray, Sharon; Zanotti, Giovanni; Munson, Samantha; Dartois, Nathalie; Laferriere, Craig

    2016-01-01

    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 <5 years and in adults >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.

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

    PubMed Central

    McNeil, Shelly A.; Qizilbash, Nawab; Ye, Jian; Gray, Sharon; Zanotti, Giovanni; Munson, Samantha; Dartois, Nathalie; Laferriere, Craig

    2016-01-01

    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 <5 years and in adults >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. PMID:27445530

  3. Invasive Group B Streptococcal Disease in South Africa: Importance of Surveillance Methodology

    PubMed Central

    Cohen, Cheryl; von Gottberg, Anne; Meiring, Susan; Cutland, Clare L.; Schrag, Stephanie J.; Madhi, Shabir A.

    2016-01-01

    Data on neonatal group B streptococcal (GBS) invasive disease burden are needed to refine prevention policies. Differences in surveillance methods and investigating for cases can lead to varying disease burden estimates. We compared the findings of laboratory-based passive surveillance for GBS disease across South Africa, and for one of the provinces compared this to a real-time, systematic, clinical surveillance in a population-defined region in Johannesburg, Soweto. Passive surveillance identified a total of 799 early-onset disease (EOD, <7 days age) and 818 LOD (late onset disease, 7–89 days age) cases nationwide. The passive surveillance provincial incidence varied for EOD (range 0.00 to 1.23/1000 live births), and was 0.03 to 1.04/1000 live births for LOD. The passive surveillance rates for Soweto, were not significantly different compared to those from the systematic surveillance (EOD 1.23 [95%CI 1.06–1.43] vs. 1.50 [95%CI 1.30–1.71], respectively, rate ratio 0.82 [95%CI 0.67–1.01]; LOD 1.04 [95% CI 0.90–1.23] vs. 1.22 [95%CI 1.05–1.42], rate ratio 0.85 [95% CI 0.68–1.07]). A review of the few cases missed in the passive system in Soweto, suggested that missing key identifiers, such as date of birth, resulted in their omission during the electronic data extraction process. Our analysis suggests that passive surveillance provides a modestly lower estimate of invasive GBS rates compared to real time sentinel-site systematic surveillance, however, this is unlikely to be the reason for the provincial variability in incidence of invasive GBS disease in South Africa. This, possibly reflects that invasive GBS disease goes undiagnosed due to issues related to access to healthcare, poor laboratory capacity and varying diagnostic procedures or empiric antibiotic treatment of neonates with suspected sepsis in the absence of attempting to making a microbiological diagnosis. An efficacious GBS vaccine for pregnant women, when available, could be used as a

  4. Non-invasive Diagnosis of Fibrosis in Non-alcoholic Fatty Liver Disease.

    PubMed

    Arora, Anil; Sharma, Praveen

    2012-06-01

    Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in developed as well as in developing countries. Its prevalence continues to rise currently affecting approximately 20-30% of adults and 10% of children in the United States. Non-alcoholic fatty liver disease represents a wide spectrum of conditions ranging from fatty liver, which in general follows a benign non-progressive clinical course, to non-alcoholic steatohepatitis (NASH), a more serious form of NAFLD that may progress to cirrhosis and end-stage liver disease. Liver biopsy remains the gold standard for evaluating the degree of hepatic necroinflammation and fibrosis; however, several non-invasive investigations, such as serum biomarkers, have been developed to establish the diagnosis and also to evaluate treatment response. There has been a substantial development of non-invasive risk scores, biomarker panels, and radiological modalities to identify at risk patients with NAFLD without recourse to liver biopsy on a routine basis. Examples include combination of serum markers like NAFLD fibrosis score (NFS), BARD score, fibrometer, FIB4, and non-invasive tools like fibroscan which assess fibrosis in patients with NAFLD. Other markers of fibrosis that have been evaluated include high-sensitivity C-reactive protein, plasma pentraxin 3, interleukin-6, and cytokeratin-18. This review focuses on the methods currently available in daily clinical practice in hepatology and touches briefly on the potential future markers under investigation.

  5. Non-invasive Diagnosis of Fibrosis in Non-alcoholic Fatty Liver Disease

    PubMed Central

    Arora, Anil; Sharma, Praveen

    2012-01-01

    Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in developed as well as in developing countries. Its prevalence continues to rise currently affecting approximately 20-30% of adults and 10% of children in the United States. Non-alcoholic fatty liver disease represents a wide spectrum of conditions ranging from fatty liver, which in general follows a benign non-progressive clinical course, to non-alcoholic steatohepatitis (NASH), a more serious form of NAFLD that may progress to cirrhosis and end-stage liver disease. Liver biopsy remains the gold standard for evaluating the degree of hepatic necroinflammation and fibrosis; however, several non-invasive investigations, such as serum biomarkers, have been developed to establish the diagnosis and also to evaluate treatment response. There has been a substantial development of non-invasive risk scores, biomarker panels, and radiological modalities to identify at risk patients with NAFLD without recourse to liver biopsy on a routine basis. Examples include combination of serum markers like NAFLD fibrosis score (NFS), BARD score, fibrometer, FIB4, and non-invasive tools like fibroscan which assess fibrosis in patients with NAFLD. Other markers of fibrosis that have been evaluated include high-sensitivity C-reactive protein, plasma pentraxin 3, interleukin-6, and cytokeratin-18. This review focuses on the methods currently available in daily clinical practice in hepatology and touches briefly on the potential future markers under investigation. PMID:25755423

  6. Optimizing Outcomes in Immunocompromised Hosts: Understanding the Role of Immunotherapy in Invasive Fungal Diseases

    PubMed Central

    Ravikumar, Sharada; Win, Mar Soe; Chai, Louis Yi Ann

    2015-01-01

    A major global concern is the emergence and spread of systemic life-threatening fungal infections in critically ill patients. The increase in invasive fungal infections, caused most commonly by Candida and Aspergillus species, occurs in patients with impaired defenses due to a number of reasons such as underlying disease, the use of chemotherapeutic and immunosuppressive agents, broad-spectrum antibiotics, prosthetic devices and grafts, burns, neutropenia and HIV infection. The high morbidity and mortality associated with these infections is compounded by the limited therapeutic options and the emergence of drug resistant fungi. Hence, creative approaches to bridge the significant gap in antifungal drug development needs to be explored. Here, we review the potential anti-fungal targets for patient-centered therapies and immune-enhancing strategies for the prevention and treatment of invasive fungal diseases. PMID:26635780

  7. Non-invasive assessment of bleeding pulmonary artery aneurysms due to Behçet disease.

    PubMed

    Greene, R M; Saleh, A; Taylor, A K; Callaghan, M; Addis, B J; Nzewi, O C; van Zyl, W V

    1998-01-01

    Because of its ability to depict intravascular, intramural, and extramural pathology, non-invasive imaging is well suited to assessing life-threatening hemoptysis that may complicate Behçet disease. We made exclusive use of CT angiography supplemented by MR to identify pulmonary thromboembolism, mediastinal lymphadenopathy, and bilateral pulmonary artery aneurysms with signs of previous unilateral rupture. Two-dimensional reformatted CT images provided surgeons with a road map of upstream and downstream vascular relationships prior to aneurysm resection. Imaging findings were confirmed by surgery and pathology. Non-invasive imaging proved to be a useful alternative to standard catheter arteriography in the preoperative assessment of hemoptysis in this patient with Behçet disease.

  8. Otitis-Prone Children Produce Functional Antibodies to Pneumolysin and Pneumococcal Polysaccharides

    PubMed Central

    Wiertsema, Selma P.; Corscadden, Karli J.; Mateus, Tulia; Mullaney, Gemma L.; Zhang, Guicheng; Richmond, Peter C.; Thornton, Ruth B.

    2016-01-01

    ABSTRACT The pneumococcus is a major otitis media (OM) pathogen, but data are conflicting regarding whether otitis-prone children have impaired humoral immunity to pneumococcal antigens. We and others have shown that otitis-prone and healthy children have similar antibody titers to pneumococcal proteins and polysaccharides (vaccine and nonvaccine types); however, the quality of antibodies from otitis-prone children has not been investigated. Antibody function, rather than titer, is considered to be a better correlate of protection from pneumococcal disease. Therefore, we compared the capacities of antibodies from otitis-prone (cases) and healthy (controls) children to neutralize pneumolysin, the pneumococcal toxin currently in development as a vaccine antigen, and to opsonize pneumococcal vaccine and nonvaccine serotypes. A pneumolysin neutralization assay was conducted on cholesterol-depleted complement-inactivated sera from 165 cases and 61 controls. A multiplex opsonophagocytosis assay (MOPA) was conducted on sera from 20 cases and 20 controls. Neutralizing and opsonizing titers were calculated with antigen-specific IgG titers to determine antibody potency for pneumolysin, pneumococcal conjugate vaccine (PCV) polysaccharides, and non-PCV polysaccharides. There was no significant difference in antibody potencies between cases and controls for the antigens tested. Antipneumolysin neutralizing titers increased with the number of episodes of acute OM, but antibody potency did not. Pneumolysin antibody potency was lower in children colonized with pneumococci than in noncarriers, and this was significant for the otitis-prone group (P < 0.05). The production of functional antipneumococcal antibodies in otitis-prone children demonstrates that they respond to the current PCV and are likely to respond to pneumolysin-based vaccines as effectively as healthy children. PMID:28031178

  9. Disease Progression in Plasmodium knowlesi Malaria Is Linked to Variation in Invasion Gene Family Members

    PubMed Central

    Divis, Paul C.; Siner, Angela; Zainudin, Ramlah; Wong, Ing Tien; Lu, Chan Woon; Singh-Khaira, Sarina K.; Millar, Scott B.; Lynch, Sean; Willmann, Matthias; Singh, Balbir; Krishna, Sanjeev; Cox-Singh, Janet

    2014-01-01

    Emerging pathogens undermine initiatives to control the global health impact of infectious diseases. Zoonotic malaria is no exception. Plasmodium knowlesi, a malaria parasite of Southeast Asian macaques, has entered the human population. P. knowlesi, like Plasmodium falciparum, can reach high parasitaemia in human infections, and the World Health Organization guidelines for severe malaria list hyperparasitaemia among the measures of severe malaria in both infections. Not all patients with P. knowlesi infections develop hyperparasitaemia, and it is important to determine why. Between isolate variability in erythrocyte invasion, efficiency seems key. Here we investigate the idea that particular alleles of two P. knowlesi erythrocyte invasion genes, P. knowlesi normocyte binding protein Pknbpxa and Pknbpxb, influence parasitaemia and human disease progression. Pknbpxa and Pknbpxb reference DNA sequences were generated from five geographically and temporally distinct P. knowlesi patient isolates. Polymorphic regions of each gene (approximately 800 bp) were identified by haplotyping 147 patient isolates at each locus. Parasitaemia in the study cohort was associated with markers of disease severity including liver and renal dysfunction, haemoglobin, platelets and lactate, (r = ≥0.34, p = <0.0001 for all). Seventy-five and 51 Pknbpxa and Pknbpxb haplotypes were resolved in 138 (94%) and 134 (92%) patient isolates respectively. The haplotypes formed twelve Pknbpxa and two Pknbpxb allelic groups. Patients infected with parasites with particular Pknbpxa and Pknbpxb alleles within the groups had significantly higher parasitaemia and other markers of disease severity. Our study strongly suggests that P. knowlesi invasion gene variants contribute to parasite virulence. We focused on two invasion genes, and we anticipate that additional virulent loci will be identified in pathogen genome-wide studies. The multiple sustained entries of this diverse pathogen into the

  10. Disease progression in Plasmodium knowlesi malaria is linked to variation in invasion gene family members.

    PubMed

    Ahmed, Atique M; Pinheiro, Miguel M; Divis, Paul C; Siner, Angela; Zainudin, Ramlah; Wong, Ing Tien; Lu, Chan Woon; Singh-Khaira, Sarina K; Millar, Scott B; Lynch, Sean; Willmann, Matthias; Singh, Balbir; Krishna, Sanjeev; Cox-Singh, Janet

    2014-08-01

    Emerging pathogens undermine initiatives to control the global health impact of infectious diseases. Zoonotic malaria is no exception. Plasmodium knowlesi, a malaria parasite of Southeast Asian macaques, has entered the human population. P. knowlesi, like Plasmodium falciparum, can reach high parasitaemia in human infections, and the World Health Organization guidelines for severe malaria list hyperparasitaemia among the measures of severe malaria in both infections. Not all patients with P. knowlesi infections develop hyperparasitaemia, and it is important to determine why. Between isolate variability in erythrocyte invasion, efficiency seems key. Here we investigate the idea that particular alleles of two P. knowlesi erythrocyte invasion genes, P. knowlesi normocyte binding protein Pknbpxa and Pknbpxb, influence parasitaemia and human disease progression. Pknbpxa and Pknbpxb reference DNA sequences were generated from five geographically and temporally distinct P. knowlesi patient isolates. Polymorphic regions of each gene (approximately 800 bp) were identified by haplotyping 147 patient isolates at each locus. Parasitaemia in the study cohort was associated with markers of disease severity including liver and renal dysfunction, haemoglobin, platelets and lactate, (r = ≥ 0.34, p =  <0.0001 for all). Seventy-five and 51 Pknbpxa and Pknbpxb haplotypes were resolved in 138 (94%) and 134 (92%) patient isolates respectively. The haplotypes formed twelve Pknbpxa and two Pknbpxb allelic groups. Patients infected with parasites with particular Pknbpxa and Pknbpxb alleles within the groups had significantly higher parasitaemia and other markers of disease severity. Our study strongly suggests that P. knowlesi invasion gene variants contribute to parasite virulence. We focused on two invasion genes, and we anticipate that additional virulent loci will be identified in pathogen genome-wide studies. The multiple sustained entries of this diverse pathogen into the human

  11. Is minimally invasive thoracoscopic surgery the new benchmark for treating mitral valve disease?

    PubMed Central

    Goldstone, Andrew B.

    2016-01-01

    The treatment of mitral valve disease remains dynamic; surgeons and patients must now choose between many different surgical options when addressing mitral regurgitation and mitral stenosis. Notably, advances in imaging and surgical instrumentation allow surgeons to perform less invasive mitral valve surgery that spares the sternum. With favorable long-term data now emerging, we compare the benefits and risks of thoracoscopic mitral valve surgery with that through conventional sternotomy or surgery that is robot-assisted. PMID:27942489

  12. Extramammary Paget’s Disease of Anal Canal Associated With Rectal Adenoma Without Invasive Carcinoma

    PubMed Central

    Chumbalkar, Vaibhav; Jennings, Timothy A.; Ainechi, Sanaz; Lee, Edward C.; Lee, Hwajeong

    2016-01-01

    Extramammary Paget’s disease (EMPD) is a rare disease which is found in apocrine-rich locations such as anogenital region, axilla and rarely in other sites. Perianal EMPD is often reported as the involvement of perianal skin, but involvement of anal mucosa is very rare. Based on pathogenesis and association with either synchronous or metachronous malignancy, EMPD can be divided into primary and secondary types. Treatment approach for these two types of Paget’s disease and their prognosis is different, thus it is important to make the distinction. Secondary type of Paget’s disease is almost always described in association with invasive malignancy. While secondary Paget’s disease arising in association with ductal carcinoma in situ of the breast is common, secondary EMPD associated with precursor lesion of the rectum without invasion is exceedingly rare. We report a very rare case of secondary Paget’s disease of the anal canal in association with rectal tubular adenoma (precursor lesion) without malignancy. PMID:28058078

  13. Insights into Parkinson's disease models and neurotoxicity using non-invasive imaging

    SciTech Connect

    Sanchez-Pernaute, Rosario; Jenkins, Bruce G.; Isacson, Ole

    2005-09-01

    Loss of dopamine in the nigrostriatal system causes a severe impairment in motor function in patients with Parkinson's disease and in experimental neurotoxic models of the disease. We have used non-invasive imaging techniques such as positron emission tomography (PET) and functional magnetic resonance imaging (MRI) to investigate in vivo the changes in the dopamine system in neurotoxic models of Parkinson's disease. In addition to classic neurotransmitter studies, in these models, it is also possible to characterize associated and perhaps pathogenic factors, such as the contribution of microglia activation and inflammatory responses to neuronal damage. Functional imaging techniques are instrumental to our understanding and modeling of disease mechanisms, which should in turn lead to development of new therapies for Parkinson's disease and other neurodegenerative disorders.

  14. Topoisomerase II{alpha} expression correlates with diminished disease-free survival in invasive breast cancer

    SciTech Connect

    O'Connor, John K. . E-mail: joconno@yahoo.com; Hazard, Lisa J.; Lee, R. Jeffrey; Fischbach, Jennifer; Gaffney, David K.

    2006-08-01

    Purpose: Topoisomerase II{alpha} (Topo II{alpha}) plays a role in DNA replication and is the molecular target for anthracyline-based chemotherapy. The purpose of this study was to evaluate the relationship between Topo II{alpha} expression and survival in patients with invasive breast cancer. Methods and Materials: Formalin-fixed, paraffin-embedded tumor specimens from 24 women with invasive breast cancer were stained for Topo II{alpha} expression. All women underwent mastectomy. Radiotherapy was given at University of Utah Department of Radiation Oncology. Of the patients, 23 (96%) received chemotherapy. The level of Topo II{alpha} expression within tumor cells was compared with clinical factors and overall survival. Results: The median percentage of tumor cells expressing Topo II{alpha} was 70%. Increased Topo II{alpha} tumor expression significantly correlated with diminished disease-free survival. Five-year disease-free survival was 100% for patients with <70% of breast cancer cells expressing Topo II{alpha} compared with 42% for patients with {>=}70% Topo II{alpha} expression (p 0.008). The level of Topo II{alpha} expression within tumor cells correlated with T stage (p = 0.008) but not with other pathologic factors. Conclusions: Increased Topo II{alpha} expression significantly correlated with diminished disease-free survival in patients with invasive breast cancer. These findings may indicate a role for Topo II{alpha} expression as a prognostic factor in breast cancer.

  15. [Current aspects of invasive diseases caused by Candida and other yeast fungi].

    PubMed

    Pemán, Javier; Quindós, Guillermo

    2016-01-01

    Invasive candidiasis is the most common invasive fungal disease causing an unacceptably high mortality. Candida albicans remains the predominant origin, but an epidemiological shift has been described in the last decades. Some species of Candida have emerged as an important cause of severe candidaemia and can exhibit reduced susceptibility to the current antifungal agents. Candida parapsilosis has been associated with candidaemia in neonates and young adults, whereas Candida glabrata, Candida tropicalis, and Candida krusei are most frequently isolated in blood cultures from older patients (>65 years). Other yeasts are becoming important causes of invasive mycoses, such as Cryptococcus, Trichosporon, Malassezia, Geotrichum or Saprochaete/Magnusiomyces. Cryptococcosis is more relevant as a cause of meningitis in HIV-infected people, but cryptococcal infections are also a clinical challenge in transplant recipients. Diagnosis remains an important problem, causing unacceptable delays in starting a correct and direct treatment. However, there are some new approaches that can help in the prompt and specific diagnosis of invasive yeast infections, such as in situ hybridisation using PNA-FISH probes, causal agent identification in blood cultures using MALDi-TOF MS, or new and rapid nucleic acids detection assays.

  16. Laboratory-based diagnosis of pneumococcal pneumonia: state of the art and unmet needs.

    PubMed

    Vernet, G; Saha, S; Satzke, C; Burgess, D H; Alderson, M; Maisonneuve, J-F; Beall, B W; Steinhoff, M C; Klugman, K P

    2011-05-01

    In view of the increasing use of pneumococcal vaccines, especially in the developing world, there is a need for appropriate diagnostics to understand the aetiology of pneumonia, to define the burden of pneumococcal disease, and to monitor vaccine efficacy and effectiveness. This article summarizes a meeting on the diagnosis, detection and serotyping of pneumococcal disease organized by PATH and Fondation Mérieux (18-20 October 2009, Fondation Mérieux Conference Centre, Les Pensières, France). Workers and experts met to discuss the gaps in the microbiology-based diagnosis of Streptococcus pneumoniae disease, with special emphasis on pneumonia. The meeting was designed to evaluate the state of the art of pneumococcal diagnostics and serotyping methodologies, identify research and development needs, and propose new guidelines to public health authorities to support the introduction of vaccines. Regarding detection, the main recommendations were to encourage chest X-rays and antigen detection in urine. Large-scale studies are needed to evaluate the diagnostic utility of test algorithms that associate chest X-rays, antigen detection in urine, S. pneumoniae quantitative PCR in nasopharyngeal aspirates and sputum, and C-reactive protein or procalcitonin measurement in blood. Efforts should be focused on proteomics to identify pneumococcus-specific antigens in urine or host markers in blood expressed during pneumonia. It was recommended to develop S. pneumoniae typing capacities, to understand the epidemiology of pneumococcal disease, and to evaluate vaccine effectiveness. Simple and effective approaches are encouraged, and new technologies based on beads, microarrays or deep sequencing should be developed to determine, in a single test capsular serotype, resistance profile and genotype.

  17. Gene expression in cortex and hippocampus during acute pneumococcal meningitis

    PubMed Central

    Coimbra, Roney S; Voisin, Veronique; de Saizieu, Antoine B; Lindberg, Raija LP; Wittwer, Matthias; Leppert, David; Leib, Stephen L

    2006-01-01

    Background Pneumococcal meningitis is associated with high mortality (~30%) and morbidity. Up to 50% of survivors are affected by neurological sequelae due to a wide spectrum of brain injury mainly affecting the cortex and hippocampus. Despite this significant disease burden, the genetic program that regulates the host response leading to brain damage as a consequence of bacterial meningitis is largely unknown. We used an infant rat model of pneumococcal meningitis to assess gene expression profiles in cortex and hippocampus at 22 and 44 hours after infection and in controls at 22 h after mock-infection with saline. To analyze the biological significance of the data generated by Affymetrix DNA microarrays, a bioinformatics pipeline was used combining (i) a literature-profiling algorithm to cluster genes based on the vocabulary of abstracts indexed in MEDLINE (NCBI) and (ii) the self-organizing map (SOM), a clustering technique based on covariance in gene expression kinetics. Results Among 598 genes differentially regulated (change factor ≥ 1.5; p ≤ 0.05), 77% were automatically assigned to one of 11 functional groups with 94% accuracy. SOM disclosed six patterns of expression kinetics. Genes associated with growth control/neuroplasticity, signal transduction, cell death/survival, cytoskeleton, and immunity were generally upregulated. In contrast, genes related to neurotransmission and lipid metabolism were transiently downregulated on the whole. The majority of the genes associated with ionic homeostasis, neurotransmission, signal transduction and lipid metabolism were differentially regulated specifically in the hippocampus. Of the cell death/survival genes found to be continuously upregulated only in hippocampus, the majority are pro-apoptotic, while those continuously upregulated only in cortex are anti-apoptotic. Conclusion Temporal and spatial analysis of gene expression in experimental pneumococcal meningitis identified potential targets for therapy. PMID

  18. Comparative Genome Sequencing Reveals Within-Host Genetic Changes in Neisseria meningitidis during Invasive Disease

    PubMed Central

    Klughammer, Johanna; Dittrich, Marcus; Blom, Jochen; Mitesser, Vera; Vogel, Ulrich; Frosch, Matthias; Goesmann, Alexander; Müller, Tobias

    2017-01-01

    Some members of the physiological human microbiome occasionally cause life-threatening disease even in immunocompetent individuals. A prime example of such a commensal pathogen is Neisseria meningitidis, which normally resides in the human nasopharynx but is also a leading cause of sepsis and epidemic meningitis. Using N. meningitidis as model organism, we tested the hypothesis that virulence of commensal pathogens is a consequence of within host evolution and selection of invasive variants due to mutations at contingency genes, a mechanism called phase variation. In line with the hypothesis that phase variation evolved as an adaptation to colonize diverse hosts, computational comparisons of all 27 to date completely sequenced and annotated meningococcal genomes retrieved from public databases showed that contingency genes are indeed enriched for genes involved in host interactions. To assess within-host genetic changes in meningococci, we further used ultra-deep whole-genome sequencing of throat-blood strain pairs isolated from four patients suffering from invasive meningococcal disease. We detected up to three mutations per strain pair, affecting predominantly contingency genes involved in type IV pilus biogenesis. However, there was not a single (set) of mutation(s) that could invariably be found in all four pairs of strains. Phenotypic assays further showed that these genetic changes were generally not associated with increased serum resistance, higher fitness in human blood ex vivo or differences in the interaction with human epithelial and endothelial cells in vitro. In conclusion, we hypothesize that virulence of meningococci results from accidental emergence of invasive variants during carriage and without within host evolution of invasive phenotypes during disease progression in vivo. PMID:28081260

  19. Risk of death from pneumococcal pneumonia is a stable serotype-associated property: a meta-analysis

    PubMed Central

    Weinberger, Daniel M.; Harboe, Zitta B.; Sanders, Elisabeth A.M.; Ndiritu, Moses; Klugman, Keith P.; Rückinger, Simon; Dagan, Ron; Adegbola, Richard; Cutts, Felicity; Johnson, Hope L.; O’Brien, Katherine L.; Scott, J. Anthony; Lipsitch, Marc

    2010-01-01

    Background The 92 capsular serotypes of Streptococcus pneumoniae differ greatly in nasopharyngeal carriage prevalence, invasiveness and disease incidence. There has been some debate, though, as to whether serotype independently affects the outcome of invasive pneumococcal disease (IPD). Published studies have shown variable results with regards to case-fatality ratios for specific serotypes and the role of host factors in affecting these relationships. We evaluated whether risk of death from IPD is a stable serotype-associated property across studies, and then compared the pooled effect estimates with epidemiologic and biological correlates. Methods We performed a systematic review and meta-analysis of serotype-specific disease outcome for pneumonia and meningitis cases. Study-specific estimates of risk of death (risk ratio, RR) were pooled from 9 studies that provided serotype-specific data on pneumonia and meningitis using a random-effects method with serotype 14 as the reference. Pooled RRs were compared to RRs from adult cases with low co-morbidity scores to evaluate potential confounding by host factors. Results There were significant differences in the RR estimates between serotypes among bacteremic pneumonia cases. Overall, types 1, 7F and 8 were associated with decreased RRs and types 3, 6A, 6B, 9N and 19F were associated with increased RRs. Outcomes among meningitis cases did not differ significantly between types. Serotypes with increased RRs tended to have a high carriage prevalence, low invasiveness, and were more heavily encapsulated in vitro. These results suggest that IPD outcome, like other epidemiologic measures, is a stable serotype-associated property. PMID:20715907

  20. Immunogenicity and safety of a 23-valent pneumococcal polysaccharide vaccine in Chinese healthy population aged >2 years: A randomized, double-blinded, active control, phase III trial

    PubMed Central

    Kong, Yujia; Zhang, Wei; Jiang, Zhiwei; Wang, Ling; Li, Chanjuan; Li, Yanping; Xia, Jielai

    2015-01-01

    Streptococcus pneumoniae is an important pathogen causing invasive diseases such as sepsis, meningitis, and pneumonia. Vaccines have become the most effective way to prevent pneumococcal infections. This phase III trial was designed to evaluate the immunogenicity and safety of a 23-valent pneumococcal polysaccharide vaccine in Chinese healthy population aged >2 years. We conducted a randomized, double-blinded, active-controlled, multicenter trial in which 1660 healthy population (>2 years of age) were randomly assigned in a 1 : 1 ratio to receive 2 intramuscular doses of either the treatment vaccine or the active control vaccine, PNEUMOVAX 23. The surveillance period was 30 days. The primary end point was the 2-fold increase rate of anti-pneumococcal antibody for all 23 included serotypes in each group. In the intention-to-treat cohort, the 2-fold increase rate of anti-pneumococcal antibody for 23 included serotypes varied from 62.47% to 97.01% in the treatment group, and from 51.49% to 95.77% in the control group. According to −10% non-inferiority margin and 95% confidence intervals of rate difference, almost all included serotypes of the treatment group reached non-inferiority to control group except for serotype 6B, the lower limit of rate difference of which was −10.00%, equal to the non-inferiority margin. The 2-fold increase rates of anti-pneumococcal antibody were significantly higher in the treatment group for serotype 2, 3, 4, 10A, 11A and 20. Furthermore, for all 23 serotypes, IgG geometric mean concentrations (GMCs) at day 30 were significantly higher in treatment group for serotype 2, 3, 4, 9V, 10A, 11A, 15B, 18C, 19A, 22F and 33F. Higher geometric mean fold increase (GMFI) were also observed in the treatment group correspondingly. Serious adverse events occurred in 3 of 830 participants in the treatment group (0.36%) and 2 of 830 participants in the control group (0.24%). No death occurred during the trial. The frequencies of both solicited and

  1. Breath Analysis as a Potential and Non-Invasive Frontier in Disease Diagnosis: An Overview

    PubMed Central

    Pereira, Jorge; Porto-Figueira, Priscilla; Cavaco, Carina; Taunk, Khushman; Rapole, Srikanth; Dhakne, Rahul; Nagarajaram, Hampapathalu; Câmara, José S.

    2015-01-01

    Currently, a small number of diseases, particularly cardiovascular (CVDs), oncologic (ODs), neurodegenerative (NDDs), chronic respiratory diseases, as well as diabetes, form a severe burden to most of the countries worldwide. Hence, there is an urgent need for development of efficient diagnostic tools, particularly those enabling reliable detection of diseases, at their early stages, preferably using non-invasive approaches. Breath analysis is a non-invasive approach relying only on the characterisation of volatile composition of the exhaled breath (EB) that in turn reflects the volatile composition of the bloodstream and airways and therefore the status and condition of the whole organism metabolism. Advanced sampling procedures (solid-phase and needle traps microextraction) coupled with modern analytical technologies (proton transfer reaction mass spectrometry, selected ion flow tube mass spectrometry, ion mobility spectrometry, e-noses, etc.) allow the characterisation of EB composition to an unprecedented level. However, a key challenge in EB analysis is the proper statistical analysis and interpretation of the large and heterogeneous datasets obtained from EB research. There is no standard statistical framework/protocol yet available in literature that can be used for EB data analysis towards discovery of biomarkers for use in a typical clinical setup. Nevertheless, EB analysis has immense potential towards development of biomarkers for the early disease diagnosis of diseases. PMID:25584743

  2. Recommendations for Risk Categorization and Prophylaxis of Invasive Fungal Diseases in Hematological Malignancies: A Critical Review of Evidence and Expert Opinion (TEO-4)

    PubMed Central

    Boğa, Can; Bolaman, Zahit; Çağırgan, Seçkin; Karadoğan, İhsan; Özcan, Mehmet Ali; Özkalemkaş, Fahir; Saba, Rabin; Sönmez, Mehmet; Şenol, Esin; Akan, Hamdi; Akova, Murat

    2015-01-01

    This is the last of a series of articles on invasive fungal infections prepared by opinion leaders in Turkey. The aim of these articles is to guide clinicians in managing invasive fungal diseases in hematological malignancies and stem cell transplantation based on the available best evidence in this field. The previous articles summarized the diagnosis and treatment of invasive fungal disease and this article aims to explain the risk categorization and guide the antifungal prophylaxis in invasive fungal disease. PMID:26316478

  3. Non-invasive imaging of flow and vascular function in disease of the aorta

    PubMed Central

    Whitlock, Matthew C.; Hundley, W. Gregory

    2015-01-01

    With advancements in technology and a better understanding of human cardiovascular physiology, research as well as clinical care can go beyond dimensional anatomy offered by traditional imaging and investigate aortic functional properties and the impact disease has on this function. Linking the knowledge of the histopathological changes with the alterations in aortic function observed on noninvasive imaging results in a better understanding of disease pathophysiology. Translating this to clinical medicine, these noninvasive imaging assessments of aortic function are proving to be able to diagnosis disease, better predict risk, and assess response to therapies. This review is designed to summarize the various hemodynamic measures that can characterize the aorta, the various non-invasive techniques, and applications for various disease states. PMID:26381770

  4. Fibrosis assessment: impact on current management of chronic liver disease and application of quantitative invasive tools.

    PubMed

    Wang, Yan; Hou, Jin-Lin

    2016-05-01

    Fibrosis, a common pathogenic pathway of chronic liver disease (CLD), has long been indicated to be significantly and most importantly associated with severe prognosis. Nowadays, with remarkable advances in understanding and/or treatment of major CLDs such as hepatitis C, B, and nonalcoholic fatty liver disease, there is an unprecedented requirement for the diagnosis and assessment of liver fibrosis or cirrhosis in various clinical settings. Among the available approaches, liver biopsy remains the one which possibly provides the most direct and reliable information regarding fibrosis patterns and changes in the parenchyma at different clinical stages and with different etiologies. Thus, many endeavors have been undertaken for developing methodologies based on the strategy of quantitation for the invasive assessment. Here, we analyze the impact of fibrosis assessment on the CLD patient care based on the data of recent clinical studies. We discuss and update the current invasive tools regarding their technological features and potentials for the particular clinical applications. Furthermore, we propose the potential resolutions with application of quantitative invasive tools for some major issues in fibrosis assessment, which appear to be obstacles against the nowadays rapid progress in CLD medicine.

  5. [Is bone biopsy necessary for the diagnosis of metabolic bone diseases? Non- invasive assessment of bone turn over markers could define the cause of metabolic bone diseases].

    PubMed

    Suzuki, Atsushi

    2011-09-01

    Recent advances of the measurement of bone turn over markers contribute to non-invasive assessment of bone-metabolic disorders. We can detect the cause of the metabolic disorders with bone turn over markers and hormonal profiles more easily than before. Today, we can diagnose and treat metabolic bone diseases without invasive procedure such as bone biopsy.

  6. Invasive aspergillosis. Disease spectrum, treatment practices, and outcomes. I3 Aspergillus Study Group.

    PubMed

    Patterson, T F; Kirkpatrick, W R; White, M; Hiemenz, J W; Wingard, J R; Dupont, B; Rinaldi, M G; Stevens, D A; Graybill, J R

    2000-07-01

    A review of representative cases of invasive aspergillosis was conducted to describe current treatment practices and outcomes. Eighty-nine physicians experienced with aspergillosis completed case forms on 595 patients with proven or probable invasive aspergillosis diagnosed using modifications of the Mycoses Study Group criteria. Pulmonary disease was present in 56%, with disseminated infection in 19%. The major risk factors for aspergillosis were bone marrow transplantation (32%) and hematologic malignancy (29%), but patients had a variety of underlying conditions including solid organ transplants (9%), AIDS (8%), and pulmonary diseases (9%). Overall, high antifungal failure rates occurred (36%), and complete antifungal responses were noted in only 27%. Treatment practices revealed that amphotericin B alone (187 patients) was used in most severely immunosuppressed patients while itraconazole alone (58 patients) or sequential amphotericin B followed by itraconazole (93 patients) was used in patients who were less immunosuppressed than patients receiving amphotericin B alone. Response rate for patients receiving amphotericin B alone was poor, with complete responses noted in only 25% and death due to or with aspergillosis in 65%. In contrast, patients receiving itraconazole alone or following amphotericin B had death due to or with Aspergillus in 26% and 36%, respectively. These results confirm that mortality from invasive aspergillosis in severely immunosuppressed patients remains high even with standard amphotericin B. Improved responses were seen in the less immunosuppressed patients receiving sequential amphotericin B followed by itraconazole and those receiving itraconazole alone. New approaches and new therapies are needed to improve the outcome of invasive aspergillosis in high-risk patients.

  7. Serotype and genotype distribution among invasive Streptococcus pneumoniae isolates in Colombia, 2005-2010.

    PubMed

    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.

  8. Serotype and Genotype Distribution among Invasive Streptococcus pneumoniae Isolates in Colombia, 2005–2010

    PubMed Central

    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 Spain6BST90, Spain9VST156, Spain23FST81, and Colombia23FST338 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. PMID:24416330

  9. Pneumococcal Infections - Multiple Languages: MedlinePlus

    MedlinePlus

    ... List of All Topics All Pneumococcal Infections - Multiple Languages To use the sharing features on this page, please enable JavaScript. Chinese - Traditional (繁體中文) Farsi (فارسی) Russian (Русский) Spanish (español) Vietnamese (Tiếng Việt) Chinese - Traditional ( ...

  10. Raman Spectrometric Detection Methods for Early and Non-Invasive Diagnosis of Alzheimer's Disease.

    PubMed

    Huang, Chia-Chi; Isidoro, Ciro

    2017-03-18

    The continuous increasing rate of patients suffering of Alzheimer's disease (AD) worldwide requires the adoption of novel techniques for non-invasive early diagnosis and monitoring of the disease. Here we review the various Raman spectroscopic techniques, including Fourier Transform-Raman spectroscopy, surface-enhanced Raman scattering spectroscopy, coherent anti-Stokes Raman scattering spectroscopy, and confocal Raman microspectroscopy, that could be used for the diagnosis of AD. These techniques have shown the potential to detect AD biomarkers, such as the amyloid-β peptide and the tau protein, or the neurotransmitters involved in the disease (e.g., Glutamate and γ-Aminobutyric acid), or the typical structural alterations in specific brain areas. The possibility to detect the specific biomarkers in liquid biopsies and to obtain high resolution 3D microscope images of the affected area make the Raman spectroscopy a valuable ally in the early diagnosis and monitoring of AD.

  11. New insights into invasive aspergillosis--from the pathogen to the disease.

    PubMed

    Binder, Ulrike; Lass-Flörl, Cornelia

    2013-01-01

    Disease manifestations with Aspergillus spp. are very diverse and dependent on interaction between the fungus and the host. Invasive aspergillosis (IA) is the most severe form of Aspergillus - associated disease found in immunocompromised hosts. Infections are mainly due to Aspergillus (A.) fumigatus, an air-borne opportunistic pathogen that causes 90% of IA. Mortality rate of this disease is still very high (50-95%), partly because of diagnostic difficulties, limited antifungal treatment options, weak conditions of patients at risk; but also in part because understanding of virulence factors involved in A. fumigatus pathogenicity and interactions of the pathogen with the host immune system is still poor. This review focuses on properties of A. fumigatus in terms of putative virulence factors and interactions of the pathogen with a main focus on the innate immune system.

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

    PubMed

    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.

  13. Is household antibiotic use a risk factor for antibiotic-resistant pneumococcal infection?

    PubMed Central

    Kwan-Gett, T. S.; Davis, R. L.; Shay, D. K.; Black, S.; Shinefield, H.; Koepsell, T.

    2002-01-01

    We used microbiology and pharmacy data from health-maintenance organizations to determine whether antibiotic use by a household member increases the risk of penicillin-non-susceptible pneumococcal disease. Though it has been well established that an individual's antibiotic use increases one's risk of antibiotic-resistant infection, it is unclear whether the risk is increased if a member of one's household is exposed to antibiotics. We therefore conducted a case-control study of patients enrolled in health maintenance organizations in Western Washington and Northern California. Cases were defined as individuals with penicillin-non-susceptible pneumococcal infection; controls were individuals with penicillin-susceptible pneumococcal infection. Socioeconomic variables were obtained by linking addresses with 1997 census block group data. One-hundred and thirty-four cases were compared with 798 controls. Individual antibiotic use prior to diagnosis increased the odds of penicillin non-susceptibility, with the strongest effect seen for beta-lactam use within 2 months (OR 1.8, 95% CI 1.2, 2.8). When household antibiotic use by persons other than the patient were considered, at 4 months prior to diagnosis there was a trend towards an association between penicillin non-susceptibility and beta-lactam antibiotic use, and a possible association in a small subgroup of patients with eye and ear isolates. However, no significant overall pattern of association was seen. We conclude that though antibiotic use of any kind within 2 months prior to diagnosis is associated with an increased risk of penicillin-non-susceptible pneumococcal disease, there is no significant overall pattern of association between household antibiotic use and penicillin-non-susceptible pneumococcal infection. PMID:12558332

  14. Development of a whole cell pneumococcal vaccine: BPL inactivation, cGMP production, and stability.

    PubMed

    Gonçalves, Viviane M; Dias, Waldely O; Campos, Ivana B; Liberman, Celia; Sbrogio-Almeida, Maria E; Silva, Eliane P; Cardoso, Celso P; Alderson, Mark; Robertson, George; Maisonneuve, Jean-François; Tate, Andrea; Anderson, Porter; Malley, Richard; Fratelli, Fernando; Leite, Luciana C C

    2014-02-19

    Pneumococcal infections impose a large burden of disease on the human population, mainly in developing countries, and the current pneumococcal vaccines offer serotype-specific protection, but do not cover all pathogenic strains, leaving populations vulnerable to disease caused by non-vaccine serotypes. The pneumococcal whole cell vaccine is a low-cost strategy based on non-capsular antigens common to all strains, inducing serotype-independent immunity. Therefore, we developed the process for the cGMP production of this cellular vaccine. Initially, three engineering runs and two cGMP runs were performed in 60-L bioreactors, demonstrating the consistency of the production process, as evaluated by the growth curves, glucose consumption and metabolite formation (lactate and acetate). Cell recovery by tangential filtration was 92 ± 13 %. We optimized the conditions for beta-propiolactone (BPL) inactivation of the bacterial suspensions, establishing a maximum cell density of OD600 between 27 and 30, with a BPL concentration of 1:4000 (v/v) at 150 rpm and 4 °C for 30 h. BPL was hydrolyzed by heating for 2h at 37 °C. The criteria and methods for quality control were defined using the engineering runs and the cGMP Lots passed all specifications. cGMP vaccine Lots displayed high potency, inducing between 80 and 90% survival in immunized mice when challenged with virulent pneumococci. Sera from mice immunized with the cGMP Lots recognized several pneumococcal proteins in the extract of encapsulated strains by Western blot. The cGMP whole cell antigen bulk and whole cell vaccine product lots were shown to be stable for up to 12 and 18 months, respectively, based upon survival assays following i.p. challenge. Our results show the consistency and stability of the cGMP whole cell pneumococcal vaccine lots and demonstrate the feasibility of production in a developing country setting.

  15. Pneumococcal Vaccination Recommendations for Children and Adults by Age and/or Risk Factor

    MedlinePlus

    Pneumococcal Vaccination Recommendations for Children 1 and Adults by Age and/or Risk Factor Routine Recommendations for Pneumococcal Conjugate ... X X X X X 1 For PCV13 vaccination of healthy children, see “Recommen- dations for Pneumococcal ...

  16. Non-invasive assessment of liver fibrosis in patients with alcoholic liver disease

    PubMed Central

    Lombardi, Rosa; Buzzetti, Elena; Roccarina, Davide; Tsochatzis, Emmanuel A

    2015-01-01

    Alcoholic liver disease (ALD) consists of a broad spectrum of disorders, ranging from simple steatosis to alcoholic steatohepatitis and cirrhosis. Fatty liver develops in more than 90% of heavy drinkers, however only 30%-35% of them develop more advanced forms of ALD. Therefore, even if the current “gold standard” for the assessment of the stage of alcohol-related liver injury is histology, liver biopsy is not reasonable in all patients who present with ALD. Currently, although several non-invasive fibrosis markers have been suggested as alternatives to liver biopsy in patients with ALD, none has been sufficiently validated. As described in other liver disease, the diagnostic accuracy of such tests in ALD is acceptable for the diagnosis of significant fibrosis or cirrhosis but not for lesser fibrosis stages. Existing data suggest that the use of non-invasive tests could be tailored to first tier screening of patients at risk, in order to diagnose early patients with progressive liver disease and offer targeted interventions for the prevention of decompensation. We review these tests and critically appraise the existing evidence. PMID:26494961

  17. Modelling disease introduction as biological control of invasive predators to preserve endangered prey.

    PubMed

    Oliveira, Nuno M; Hilker, Frank M

    2010-02-01

    Invasive species are a significant cause of bio-diversity loss particularly in island ecosystems. It has been suggested to release pathogenic parasites as an efficient control measure of these mostly immune-naïve populations. In order to explore the potential impacts of such bio-control approach, we construct and investigate mathematical models describing disease dynamics in a host population that acts as a predator embedded in a simple food chain. The consequences of Feline Immunodeficiency Virus (FIV) introduction into a closed ecosystem are addressed using a bi-trophic system, comprising an indigenous prey (birds) and an introduced predator (cats). Our results show that FIV is unlikely to fully eradicate cats on sub-Antarctic islands, but it can be efficient in depressing their population size, allowing for the recovery of the endangered prey. Depending on the ecological setting and disease transmission mode (we consider proportionate mixing as well as mass action), successful pathogen invasion can induce population oscillations that are not possible in the disease-free predator-prey system. These fluctuations can be seen as a mixed blessing from a management point of view. On the one hand, they may increase the extinction risk of the birds. On the other hand, they provide an opportunity to eradicate cats more easily in combination with other methods such as trapping or culling.

  18. Posaconazole prophylaxis--impact on incidence of invasive fungal disease and antifungal treatment in haematological patients.

    PubMed

    Peterson, Lisa; Ostermann, Julia; Rieger, Heidi; Ostermann, Helmut; Rieger, Christina Theresa

    2013-11-01

    Since two large-scale, randomised studies on posaconazole prophylaxis have demonstrated a clear benefit for patients at high risk for contracting invasive fungal disease (IFD), posaconazole prophylaxis has been adopted as standard of care for this patient collective. Several years on from implementation at our institution, we wanted to evaluate its impact on the incidence and use of empirical antifungal therapy in a real-life setting. We analysed retrospectively incidence and severity of IFD in high-risk patients with prophylaxis, using a historical cohort as comparator. A total of 200 patients had either received the extended spectrum triazole posaconazole in prophylactic dosage of 200 mg tid or empirical antifungal therapy. Disease events were analysed by application of the revised EORTC/MSG definitions for IFD. Before posaconazole prophylaxis, we recorded 57/100 cases of IFD which was reduced to 28/100 with prophylaxis. The empirical use of antifungal drugs was reduced to 41% from 91% in the non-prophylaxis cohort. Furthermore, we observed a shift in the categorisation of IFD according to EORTC/MSG criteria. Our data suggest that posaconazole was effective in reducing the rate and probability of invasive fungal disease in high-risk patients.

  19. Population genetics of the Asian tiger mosquito Aedes albopictus, an invasive vector of human diseases.

    PubMed

    Goubert, C; Minard, G; Vieira, C; Boulesteix, M

    2016-09-01

    The Asian tiger mosquito Aedes albopictus is currently one of the most threatening invasive species in the world. Native to Southeast Asia, the species has spread throughout the world in the past 30 years and is now present in every continent but Antarctica. Because it was the main vector of recent Dengue and Chikungunya outbreaks, and because of its competency for numerous other viruses and pathogens such as the Zika virus, A. albopictus stands out as a model species for invasive diseases vector studies. A synthesis of the current knowledge about the genetic diversity of A. albopictus is needed, knowing the interplays between the vector, the pathogens, the environment and their epidemiological consequences. Such resources are also valuable for assessing the role of genetic diversity in the invasive success. We review here the large but sometimes dispersed literature about the population genetics of A. albopictus. We first debate about the experimental design of these studies and present an up-to-date assessment of the available molecular markers. We then summarize the main genetic characteristics of natural populations and synthesize the available data regarding the worldwide structuring of the vector. Finally, we pinpoint the gaps that remain to be addressed and suggest possible research directions.

  20. Caspofungin for the treatment of invasive fungal disease in hematological patients (ProCAS Study).

    PubMed

    Jarque, I; Tormo, M; Bello, J L; Rovira, M; Batlle, M; Julià, A; Tabares, S; Rivas, C; Fernández-Sevilla, A; García-Boyero, R; Debén, G; González-Campos, J; Capote, F J; Sanz, M A

    2013-02-01

    Caspofungin is an echinocandin with proven efficacy in invasive candidiasis (IC) and invasive aspergillosis (IA). This multicenter, prospective, non-comparative, observational ProCAS study was aimed to assess the effectiveness and safety of caspofungin in adult hematological patients with IC or IA under everyday clinical conditions. Favorable outcomes included complete and partial responses on the last day of caspofungin therapy. Safety was assessed up to 14 days post-caspofungin. A total of 115 patients (69 male) with a median age of 52 years (range, 23-78 years) were analyzed. Underlying disease was acute myeloid leukemia in 45 patients (39%), and 21 (18%) were allogeneic stem cell transplant recipients. Thirty-four (29.5%) patients had a diagnosis of IA and 26 (22.6%) had IC (candidemia). The median duration of caspofungin therapy was 14 days (range, 1-100). The overall favorable response rate was 77% (20/26) for patients with IC (69% first-line) and 79% (27/34) for those with IA. Antifungal therapy with caspofungin was generally well tolerated, only two (1.7%) patients having a non-serious drug-related adverse reaction. These results suggest that caspofungin, either alone or in combination, should be considered an effective and safe option for the treatment of invasive mycoses in patients with severe hematological disorders.

  1. Population genetics of the Asian tiger mosquito Aedes albopictus, an invasive vector of human diseases

    PubMed Central

    Goubert, C; Minard, G; Vieira, C; Boulesteix, M

    2016-01-01

    The Asian tiger mosquito Aedes albopictus is currently one of the most threatening invasive species in the world. Native to Southeast Asia, the species has spread throughout the world in the past 30 years and is now present in every continent but Antarctica. Because it was the main vector of recent Dengue and Chikungunya outbreaks, and because of its competency for numerous other viruses and pathogens such as the Zika virus, A. albopictus stands out as a model species for invasive diseases vector studies. A synthesis of the current knowledge about the genetic diversity of A. albopictus is needed, knowing the interplays between the vector, the pathogens, the environment and their epidemiological consequences. Such resources are also valuable for assessing the role of genetic diversity in the invasive success. We review here the large but sometimes dispersed literature about the population genetics of A. albopictus. We first debate about the experimental design of these studies and present an up-to-date assessment of the available molecular markers. We then summarize the main genetic characteristics of natural populations and synthesize the available data regarding the worldwide structuring of the vector. Finally, we pinpoint the gaps that remain to be addressed and suggest possible research directions. PMID:27273325

  2. Geosmithia argillacea: An Emerging Cause of Invasive Mycosis in Human Chronic Granulomatous Disease

    PubMed Central

    Challipalli, Malliswari; Anderson, Victoria; Shea, Yvonne R.; Marciano, Beatriz; Hilligoss, Dianne; Marquesen, Martha; DeCastro, Rosamma; Liu, Yen-chun; Sutton, Deanna A.; Wickes, Brian L.; Kammeyer, Patricia L.; Sigler, Lynne; Sullivan, Kathleen; Kang, Elizabeth M.; Malech, Harry L.; Holland, Steven M.; Zelazny, Adrian M.

    2011-01-01

    Background. Chronic granulomatous disease (CGD) is an inherited disorder of the nicotinamide adenine dinucleotide phosphate oxidase that leads to defective production of microbicidal superoxide and other oxidative radicals, resulting in increased susceptibility to invasive infections, especially those due to fungi. Methods. Geosmithia argillacea was identified from cultured isolates by genomic sequencing of the internal transcribed spacer region. Isolates previously identified as Paecilomyces variotii, a filamentous fungus closely resembling G. argillacea, were also examined. Results. We identified G. argillacea as the cause of invasive mycosis in 7 CGD patients. In 5 cases, the fungus had been previously identified morphologically as P. variotii. All patients had pulmonary lesions; 1 had disseminated lesions following inhalational pneumonia. Infections involved the chest wall and contiguous ribs in 2 patients and disseminated to the brain in 1 patient. Four patients with pneumonia underwent surgical intervention. All patients responded poorly to medical treatment, and 3 died. Conclusions. We report the first cases of invasive mycosis caused by G. argillacea in CGD patients. G. argillacea infections in CGD are often refractory and severe with a high fatality rate. Surgical intervention has been effective in some cases. G. argillacea is a previously underappreciated and frequently misidentified pathogen in CGD that should be excluded when P. variotii is identified morphologically. PMID:21367720

  3. Invasive fungal infection following reduced-intensity cord blood transplantation for adult patients with hematologic diseases.

    PubMed

    Miyakoshi, Shigesaburo; Kusumi, Eiji; Matsumura, Tomoko; Hori, Akiko; Murashige, Naoko; Hamaki, Tamae; Yuji, Koichiro; Uchida, Naoyuki; Masuoka, Kazuhiro; Wake, Atsushi; Kanda, Yoshinobu; Kami, Masahiro; Tanaka, Yuji; Taniguchi, Shuichi

    2007-07-01

    Invasive fungal infection (IFI) is a significant complication after allogeneic hematopoietic stem cell transplantation (HSCT); however, we have little information on its clinical features after reduced intensity cord blood transplantation (RICBT) for adults. We reviewed medical records of 128 patients who underwent RICBT at Toranomon Hospital between March 2002 and November 2005. Most of the patients received purine-analogbased preparative regimens. Graft-versus-host disease (GVHD) prophylaxis was a continuous infusion of either tacrolimus 0.03 mg/kg or cyclosporine 3 mg/kg. IFI was diagnosed according to the established EORTC/NIH-MSG criteria. IFI was diagnosed in 14 patients. Thirteen of the 14 had probable invasive pulmonary aspergillosis and the other had fungemia resulting from Trichosporon spp. Median onset of IFI was day 20 (range: 1-82), and no patients developed IFI after day 100. Three-year cumulative incidence of IA was 10.2%. Four of the 13 patients with invasive aspergillosis (IA) developed grade II-IV acute GVHD, and their IA was diagnosed before the onset of acute GVHD. The mortality rate of IFI was 86%. Multivariate analysis revealed that the use of prednisolone >0.2 mg/kg (relative risk 7.97, 95% confidence interval 2.24-28.4, P = .0014) was a significant risk factor for IA. This study suggests that IFI is an important cause of deaths after RICBT, and effective strategies are warranted to prevent IFI.

  4. A community outbreak of invasive and non-invasive group A beta-haemolytic streptococcal disease in a town in South Wales.

    PubMed Central

    El-Bouri, K. W.; Lewis, A. M.; Okeahialam, C. A.; Wright, D.; Tanna, A.; Joynson, D. H.

    1998-01-01

    An increase in the incidence of invasive and non-invasive infections caused by group A beta-haemolytic streptococci (GAS) was noted in and around the town of Glynneath (population approx. 4000) in West Glamorgan, South Wales between 1 January and 30 June 1995. A total of 133 cases was ascertained with 127 (96%) occurring between 1 March and 30 June 1995. Six patients had invasive disease (one died) and all presented at the peak of the outbreak. There were 127 non-invasive cases of whom 7 were hospitalized. The outbreak was investigated to determine its extent and whether it was caused by a single M-serotype of GAS. Serotyping showed that 13 different M-serotypes were involved with the M1 serotype predominating. The overall incidence of GAS invasive disease in West Glamorgan (population 365,000) increased sevenfold from a crude incidence of 0.5/10(5) per year in 1994 to 3.5/10(5) per year in 1995, but fell back to 0.75/10(5) per year in 1996. Eighty-two (80%) out of 102 individuals affected by GAS replied to a health questionnaire; sore throat was the commonest symptom reported (97%). Thirty-nine of these index cases identified at least one other member of their household who had experienced similar symptoms. The interval between the onset of illness in members of a single household was 0-83 days with a mean of 22 days. The mean duration of illness was 13.5 days and 61% of patients were treated with penicillin V for a mean duration of 9.3 days. Twenty-one per cent of GAS isolates were erythromycin-resistant and the M4 and M6 serotypes were especially resistant to erythromycin (87.5 and 100% resistance, respectively). Penicillin V failed to eradicate GAS from the throats of 25% of assessable patients. In this community, an outbreak of non-invasive disease caused by GAS was linked in time and place with an outbreak of serious invasive disease. PMID:10030699

  5. A community outbreak of invasive and non-invasive group A beta-haemolytic streptococcal disease in a town in South Wales.

    PubMed

    El-Bouri, K W; Lewis, A M; Okeahialam, C A; Wright, D; Tanna, A; Joynson, D H

    1998-12-01

    An increase in the incidence of invasive and non-invasive infections caused by group A beta-haemolytic streptococci (GAS) was noted in and around the town of Glynneath (population approx. 4000) in West Glamorgan, South Wales between 1 January and 30 June 1995. A total of 133 cases was ascertained with 127 (96%) occurring between 1 March and 30 June 1995. Six patients had invasive disease (one died) and all presented at the peak of the outbreak. There were 127 non-invasive cases of whom 7 were hospitalized. The outbreak was investigated to determine its extent and whether it was caused by a single M-serotype of GAS. Serotyping showed that 13 different M-serotypes were involved with the M1 serotype predominating. The overall incidence of GAS invasive disease in West Glamorgan (population 365,000) increased sevenfold from a crude incidence of 0.5/10(5) per year in 1994 to 3.5/10(5) per year in 1995, but fell back to 0.75/10(5) per year in 1996. Eighty-two (80%) out of 102 individuals affected by GAS replied to a health questionnaire; sore throat was the commonest symptom reported (97%). Thirty-nine of these index cases identified at least one other member of their household who had experienced similar symptoms. The interval between the onset of illness in members of a single household was 0-83 days with a mean of 22 days. The mean duration of illness was 13.5 days and 61% of patients were treated with penicillin V for a mean duration of 9.3 days. Twenty-one per cent of GAS isolates were erythromycin-resistant and the M4 and M6 serotypes were especially resistant to erythromycin (87.5 and 100% resistance, respectively). Penicillin V failed to eradicate GAS from the throats of 25% of assessable patients. In this community, an outbreak of non-invasive disease caused by GAS was linked in time and place with an outbreak of serious invasive disease.

  6. The diagnosis and management of pre-invasive breast disease: The role of new diagnostic techniques

    PubMed Central

    Nerurkar, Ashutosh; Osin, Peter

    2003-01-01

    In recent years we have seen significantly increased use of minimally invasive diagnostic techniques in the management of breast disease. There is wide recognition of fine needle aspiration and core biopsy as the principal diagnostic methods. However, concerns exist regarding their reliability. This article provides a brief overview of the major diagnostic issues related to use of fine needle aspiration, core biopsy and ductal lavage. It summarizes areas of use for each technique, outlines the main diagnostic pitfalls and their causes, and provides a perspective on future developments in the field. PMID:14580247

  7. Non-invasive assessment of Alzheimer's disease neurofibrillary pathology using 18F-THK5105 PET.

    PubMed

    Okamura, Nobuyuki; Furumoto, Shozo; Fodero-Tavoletti, Michelle T; Mulligan, Rachel S; Harada, Ryuichi; Yates, Paul; Pejoska, Svetlana; Kudo, Yukitsuka; Masters, Colin L; Yanai, Kazuhiko; Rowe, Christopher C; Villemagne, Victor L

    2014-06-01

    Non-invasive imaging of tau pathology in the living brain would be useful for accurately diagnosing Alzheimer's disease, tracking disease progression, and evaluating the treatment efficacy of disease-specific therapeutics. In this study, we evaluated the clinical usefulness of a novel tau-imaging positron emission tomography tracer 18F-THK5105 in 16 human subjects including eight patients with Alzheimer's disease (three male and five females, 66-82 years) and eight healthy elderly controls (three male and five females, 63-76 years). All participants underwent neuropsychological examination and 3D magnetic resonance imaging, as well as both 18F-THK5105 and 11C-Pittsburgh compound B positron emission tomography scans. Standard uptake value ratios at 90-100 min and 40-70 min post-injection were calculated for 18F-THK5105 and 11C-Pittsburgh compound B, respectively, using the cerebellar cortex as the reference region. As a result, significantly higher 18F-THK5105 retention was observed in the temporal, parietal, posterior cingulate, frontal and mesial temporal cortices of patients with Alzheimer's disease compared with healthy control subjects. In patients with Alzheimer's disease, the inferior temporal cortex, which is an area known to contain high densities of neurofibrillary tangles in the Alzheimer's disease brain, showed prominent 18F-THK5105 retention. Compared with high frequency (100%) of 18F-THK5105 retention in the temporal cortex of patients with Alzheimer's disease, frontal 18F-THK5105 retention was less frequent (37.5%) and was only observed in cases with moderate-to-severe Alzheimer's disease. In contrast, 11C-Pittsburgh compound B retention was highest in the posterior cingulate cortex, followed by the ventrolateral prefrontal, anterior cingulate, and superior temporal cortices, and did not correlate with 18F-THK5105 retention in the neocortex. In healthy control subjects, 18F-THK5105 retention was ∼10% higher in the mesial temporal cortex than in the

  8. Anaphylaxis to the 23-valent pneumococcal vaccine: a second explored case by means of immediate-reading skin tests with pneumococcal vaccines.

    PubMed

    Ponvert, C; Scheinmann, P; de Blic, J

    2010-12-06

    Anaphylaxis to pneumococcal vaccines is rare. In the only one child with anaphylaxis to a first injection of the 23-valent pneumococcal vaccine that has been explored, skin tests and specific IgE determination diagnosed immediate-type hypersensitivity to pneumococcal antigens. We report the case of a child who tolerated three injections of the 7-valent pneumococcal vaccine, but experienced anaphylaxis to a fourth injection of the 23-valent vaccine. Immediate responses in skin tests diagnosed immediate-type hypersensitivity to the two vaccines. Immunizations with the 7-valent pneumococcal vaccine may induce IgE-dependent sensitization to pneumococcal antigens, responsible for anaphylaxis to subsequent injections of pneumococcal vaccines.

  9. Recent developments in the management of invasive fungal infections in patients with oncohematological diseases.

    PubMed

    Ruhnke, Markus; Schwartz, Stefan

    2016-12-01

    Patients with hematological cancer have a high risk of invasive fungal diseases (IFDs). These infections are mostly life threatening and an early diagnosis and initiation of appropriate antifungal therapy are essential for the clinical outcome. Most commonly, Aspergillus and Candida species are involved. However, other non-Aspergillus molds are increasingly be identified in cases of documented IFDs. Important risk factors are long lasting granulocytopenia with neutrophil counts below 500/μl for more than 10 days or graft-versus-host disease resulting from allogeneic stem-cell transplantation. For definite diagnosis of IFD, various diagnostic tools have to be applied, including conventional mycological culture and nonconventional microbiological tests such as antibody/antigen and molecular tests, as well as histopathology and radiology. In the last few years, various laboratory methods, like the Aspergillus GM immunoassay (Aspergillus GM EIA), 1,3-ß-D-glucan (BG) assay or polymerase chain reaction (PCR) techniques have been developed for better diagnosis. Since no single indirect test, including radiological methods, provides the definite diagnosis of an invasive fungal infection, the combination of different diagnostic procedures, which include microbiological cultures, histological, serological and molecular methods like PCR together with the pattern of clinical presentation, may currently be the best strategy for the prompt diagnosis, initiation and monitoring of IFDs. Early start of antifungal therapy is mandatory, but clinical diagnostics often do not provide clear evidence of IFD. Integrated care pathways have been proposed for management and therapy of IFDs with either the diagnostic driven strategy using the preemptive antifungal therapy as opposed to the clinical or empirical driven strategy using the 'traditional' empirical antifungal therapy. Antifungal agents preferentially used for systemic therapy of invasive fungal infections are amphotericin B

  10. Recent developments in the management of invasive fungal infections in patients with oncohematological diseases

    PubMed Central

    Ruhnke, Markus; Schwartz, Stefan

    2016-01-01

    Patients with hematological cancer have a high risk of invasive fungal diseases (IFDs). These infections are mostly life threatening and an early diagnosis and initiation of appropriate antifungal therapy are essential for the clinical outcome. Most commonly, Aspergillus and Candida species are involved. However, other non-Aspergillus molds are increasingly be identified in cases of documented IFDs. Important risk factors are long lasting granulocytopenia with neutrophil counts below 500/μl for more than 10 days or graft-versus-host disease resulting from allogeneic stem-cell transplantation. For definite diagnosis of IFD, various diagnostic tools have to be applied, including conventional mycological culture and nonconventional microbiological tests such as antibody/antigen and molecular tests, as well as histopathology and radiology. In the last few years, various laboratory methods, like the Aspergillus GM immunoassay (Aspergillus GM EIA), 1,3-ß-D-glucan (BG) assay or polymerase chain reaction (PCR) techniques have been developed for better diagnosis. Since no single indirect test, including radiological methods, provides the definite diagnosis of an invasive fungal infection, the combination of different diagnostic procedures, which include microbiological cultures, histological, serological and molecular methods like PCR together with the pattern of clinical presentation, may currently be the best strategy for the prompt diagnosis, initiation and monitoring of IFDs. Early start of antifungal therapy is mandatory, but clinical diagnostics often do not provide clear evidence of IFD. Integrated care pathways have been proposed for management and therapy of IFDs with either the diagnostic driven strategy using the preemptive antifungal therapy as opposed to the clinical or empirical driven strategy using the ‘traditional’ empirical antifungal therapy. Antifungal agents preferentially used for systemic therapy of invasive fungal infections are amphotericin B

  11. Clinical considerations in the early treatment of invasive mould infections and disease.

    PubMed

    Mercier, Toine; Maertens, Johan

    2017-03-01

    Different therapeutic strategies for invasive fungal diseases have been explored, each with particular strengths and weaknesses. Broad-spectrum antifungal prophylaxis seems logical, but selective use is important due to its substantial disadvantages, including interference with diagnostic assays, selection for resistance, drug toxicity and drug-drug interactions. Antimould prophylaxis should be restricted to high-risk groups, such as patients undergoing intensive chemotherapy for acute myeloid leukaemia or myelodysplastic syndrome, allogeneic HSCT patients with prior invasive fungal infection, graft-versus-host-disease or extended neutropenia, recipients of a solid organ transplant, or patients with a high-risk inherited immunodeficiency. An empirical approach, whereby mould-active therapy is started in neutropenic patients with fever unresponsive to broad-spectrum antibiotics, is widely applied but incurs the clinical and cost penalties associated with overtreatment. A benefit for all-cause mortality using empirical therapy has not been shown, but it is recommended for high-risk patients who remain febrile after 4-7 days of broad-spectrum antibiotics and in whom extended neutropenia is anticipated. There is growing interest in delaying antifungal treatment until an invasive fungal infection is confirmed ('pre-emptive' or 'diagnostics-driven' management), prompted by the development of more sensitive diagnostic techniques. Comparisons of empirical versus pre-emptive regimens are sparse, particularly with modern triazole agents, but treatment costs are lower with pre-emptive therapy and the available evidence has not indicated reduced efficacy. Pre-emptive treatment may be appropriate in neutropenic patients who remain febrile after administration of broad-spectrum antibiotics but who are clinically stable. Further work is required to define accurately the specific patient subgroups in which each management approach is optimal.

  12. Risk factors for levofloxacin-nonsusceptible Streptococcus pneumoniae in community-acquired pneumococcal pneumonia: a nested case-control study.

    PubMed

    Kang, C-I; Song, J-H; Kim, S H; Chung, D R; Peck, K R; So, T M; Hsueh, P-R

    2014-01-01

    This study was performed to evaluate the clinical features of community-onset levofloxacin-nonsusceptible pneumococcal pneumonia and to identify risk factors for levofloxacin resistance. Using the database of a surveillance study of community-acquired pneumococcal infections in Asian countries, we conducted a nested case-control study to identify risk factors for levofloxacin-nonsusceptible S. pneumoniae in community-acquired pneumonia in adults. Of 981 patients with pneumococcal pneumonia, 46 (4.7 %) had levofloxacin-nonsusceptible S. pneumoniae, of whom 39 evaluable cases were included in the analysis. All cases were from Korea, Taiwan, and Hong Kong. Among patients with levofloxacin-susceptible S. pneumoniae, 490 controls were selected based on patient country. Of the 39 cases of levofloxacin-nonsusceptible pneumococcal pneumonia, 23 (59.0 %) were classified as healthcare-associated, while 164 (33.5 %) of the 490 controls of levofloxacin-susceptible S. pneumoniae (P = 0.001) were classified as healthcare-associated. Multivariate analysis showed that previous treatment with fluoroquinolones, cerebrovascular disease, and healthcare-associated infection were significantly associated with levofloxacin-nonsusceptible pneumococcal pneumonia (all P < 0.05). Levofloxacin-nonsusceptible pneumococci pose an important new public health threat in our region, and more information on the emergence and spread of these resistant strains will be necessary to prevent spread throughout the population.

  13. Development and evaluation of a novel vaccine against prevalent invasive multi-drug resistant strains of Streptococcus pneumoniae

    PubMed Central

    Bahy, Rehab H.; Hamouda, Hayam M.; Shahat, Amal S.; Amin, Magdy A.

    2016-01-01

    Streptococcus pneumoniae is a pathogen that causes serious invasive infections, such as septicemia, meningitis and pneumonia in addition to mild upper respiratory tract infections. Protection from pneumococcal diseases is thought to be mediated mainly by serotype-specific antibodies to capsular antigens. Pneumococcal conjugate vaccine consists of sugars (polysaccharides) from the capsule of the bacterium S. pneumoniae that are conjugated to a carrier protein. Three pneumococcal conjugated vaccines, each directed against a group of serotypes, are registered in Egypt; however, local vaccine production is required to cover the most prevalent serotypes. In this work, capsular polysaccharide from the most current and prevalent serotypes in Egypt were extracted, purified and conjugated to bovine serum albumin (BSA). The polysaccharide protein conjugate was purified through ultrafiltration technique and molecular size distribution was compared to an available vaccine. The immunogenicity of the prepared vaccine was examined via two methods: First, by measuring the levels of the elicited antibodies in the sera of the vaccinated mice; second, by challenging the vaccinated groups of mice with approximately 107 CFU of each specific serotype and determining the degree of protection the developled vaccine offers. Our results show that the developed conjugated capsular polysaccharide vaccine is highly immunogenic and protective in mice. This finding illustrates the importance of tracking the most recent and predominant peneumococcal serotypes to generate effective vaccines, instead of using expensive imported vaccines with large number of serotypes which might not be even present in the community. PMID:27917323

  14. Stromal genes discriminate preinvasive from invasive disease, predict outcome, and highlight inflammatory pathways in digestive cancers

    PubMed Central

    Saadi, Amel; Shannon, Nicholas B.; Lao-Sirieix, Pierre; O’Donovan, Maria; Walker, Elaine; Clemons, Nicholas J.; Hardwick, James S.; Zhang, Chunsheng; Das, Madhumita; Save, Vicki; Novelli, Marco; Balkwill, Frances; Fitzgerald, Rebecca C.

    2010-01-01

    The stromal compartment is increasingly recognized to play a role in cancer. However, its role in the transition from preinvasive to invasive disease is unknown. Most gastrointestinal tumors have clearly defined premalignant stages, and Barrett’s esophagus (BE) is an ideal research model. Supervised clustering of gene expression profiles from microdissected stroma identified a gene signature that could distinguish between BE metaplasia, dysplasia, and esophageal adenocarcinoma (EAC). EAC patients overexpressing any of the five genes (TMEPAI, JMY, TSP1, FAPα, and BCL6) identified from this stromal signature had a significantly poorer outcome. Gene ontology analysis identified a strong inflammatory component in BE disease progression, and key pathways included cytokine–cytokine receptor interactions and TGF-β. Increased protein levels of inflammatory-related genes significantly up-regulated in EAC compared with preinvasive stages were confirmed in the stroma of independent samples, and in vitro assays confirmed functional relevance of these genes. Gene set enrichment analysis of external datasets demonstrated that the stromal signature was also relevant in the preinvasive to invasive transition of the stomach, colon, and pancreas. These data implicate inflammatory pathways in the genesis of gastrointestinal tract cancers, which can affect prognosis. PMID:20080664

  15. Pneumococcal Meningitis in Children: Epidemiology, Serotypes, and Outcomes From 1997–2010 in Utah

    PubMed Central

    Ampofo, Krow; Byington, Carrie L.; Filloux, Francis; Hersh, Adam L.; Blaschke, Anne J.; Cowan, Priscilla; Korgenski, Kent; Mason, Edward O.; Pavia, Andrew T.

    2013-01-01

    BACKGROUND: After licensure of the 7-valent pneumococcal conjugate vaccine (PCV7) in the United States in 2000, the incidence of pediatric pneumococcal meningitis decreased significantly. However, cases continue to occur. It is unknown whether meningitis due to PCV7 and non-PCV7 serotypes causes similar morbidity and mortality. METHODS: We performed a retrospective cohort study of laboratory-confirmed pneumococcal meningitis among Utah children from 1997 to 2010. We reviewed medical records and obtained clinical data during the acute illness and follow-up data on neurologic sequelae. RESULTS: Sixty-eight cases of meningitis were identified. PCV7 serotypes caused 64% of cases before and 25% of cases after licensure of PCV7 (P < .01). The age range was similar before and after PCV7 licensure (P = .5). The overall case fatality rate was 13% and was similar among cases caused by PCV7 and non-PCV7 serotypes (P = .7). Children with PCV7 serotypes were more likely to require mechanical ventilation (68% vs 34%; P < .01). Of all survivors, 63% had neurologic sequelae, and the proportion was similar after infection with PCV7 or non-PCV7 serotypes (P = .1). More than one-half (54%) of all children who developed pneumococcal meningitis in the PCV7 period were eligible for PCV7 and had not been immunized. CONCLUSIONS: Pneumococcal meningitis continues to be associated with high mortality and morbidity; death and neurologic sequelae are common with both PCV7 and non-PCV7 serotype meningitis. The substantial burden of this disease and continued cases among unimmunized children reinforce the need for more effective immunization strategies and continued surveillance in the era of PCV13. PMID:23979090

  16. Influenza and Pneumococcal Vaccination in Hematological Malignancies: a Systematic Review of Efficacy, Effectiveness, and Safety

    PubMed Central

    La Torre, Giuseppe; Mannocci, Alice; Colamesta, Vittoria; D’Egidio, Valeria; Sestili, Cristina; Spadea, Antonietta

    2016-01-01

    Background The risk of getting influenza and pneumococcal disease is higher in cancer patients, and serum antibody levels tend to be lower in patients with hematological malignancy. Objective To assess flu and pneumococcal vaccinations efficacy, effectiveness, and safety in onco-hematological patients. Methods Two systematic reviews and possible meta-analysis were conducted to summarize the results of all primary study in the scientific literature about the flu and pneumococcal vaccine in onco-hematological patients. Literature searches were performed using Pub-Med and Scopus databases. StatsDirect 2.8.0 was used for the analysis. Results 22 and 26 studies were collected respectively for flu and pneumococcal vaccinations. Protection rate of booster dose was 30% (95% CI=6–62%) for H1N1. Pooled prevalence protection rate of H3N2 and B was available for meta-analysis only for first dose, 42.6% (95% CI=23.2 – 63.3 %) and 39.6 % (95% CI=26%–54.1%) for H3N2 and B, respectively. Response rate of booster dose resulted 35% (95% CI=19.7–51.2%) for H1N1, 23% (95% CI=16.6–31.5%) for H3N2, 29% (95% CI=21.3–37%) for B. Conclusion Despite the low rate of response, flu, and pneumococcal vaccines are worthwhile for patients with hematological malignancies. Patients undergoing chemotherapy in particular rituximab, splenectomy, transplant recipient had lower and impaired response. No serious adverse events were reported for both vaccines. PMID:27648207

  17. Improving pneumococcal vaccination rates of medical inpatients in urban Nepal using quality improvement measures

    PubMed Central

    Bock, Allison; Chintamaneni, Kathan; Rein, Lisa; Frazer, Tifany; Kayastha, Gyan; MacKinney, Theodore

    2016-01-01

    Streptococcus pneumoniae infection is associated with high morbidity and mortality in low income countries. In Nepal, there is a high lung disease burden and incidence of pneumonia due to multiple factors including indoor air pollution, dust exposure, recurrent infections, and cigarette smoking. Despite the ready availability of effective pneumococcal vaccines (PNV), vaccine coverage rates remain suboptimal globally. Quality Improvement (QI) principles could be applied to improve compliance, but it is a virtually new technology in Nepal. This QI study for Patan Hospital sought to introduce the concept of QI there, to measure the baseline pneumococcal vaccination rate of qualifying adult patients discharged from the medical wards and to assess reasons for non-vaccination. QI interventions were instituted to improve this rate, measuring the effectiveness of QI methods to produce the desired outcomes using the Model for Improvement, Plan-Do-Study-Change (PDSA) methodology. In the three week baseline assessment, 2 out of 81 (2%) eligible patients recalled ever receiving a prior pneumococcal vaccine; 68 (84%) unvaccinated patients responded that they were not asked or were unaware of the PNV. After the QI interventions, the pneumococcal vaccination rate significantly increased to 42% (23/56, p<0.001). Post-intervention, the leading reason for non-vaccination was cost (20%, 11/56). Only 5 (9%) unvaccinated patients were not asked or were unaware of the PNV, a significant change in that process outcome from baseline (p<0.001). Quality improvement measures were effective in increasing pneumococcal vaccination rates, despite the limited familiarity with QI methods at this major teaching hospital. QI techniques may be useful in this and other efforts to improve quality in resource-limited settings, without great cost. PMID:27933153

  18. Impaired serotype-specific immune function following pneumococcal vaccination in infants with prior carriage.

    PubMed

    Licciardi, Paul V; Russell, Fiona M; Balloch, Anne; Burton, Robert L; Nahm, Moon H; Gilbert, Gwendolyn; Tang, Mimi L K; Mulholland, Edward K

    2014-04-25

    The impact of prior nasopharyngeal carriage on serotype-specific IgG responses following immunization with pneumococcal conjugate vaccines (PCV) has recently been described. This report extends these findings to describe the attenuation of functional immune responses following 23-valent pneumococcal polysaccharide vaccination (PPS). We report the attenuation of immune responses following booster with the 23-valent pneumococcal polysaccharide vaccination (PPS) in infants with prior nasopharyngeal carriage of Streptococcus pneumoniae. Fijian infants who were part of a phase II randomized, controlled trial of reduced dose PCV7 schedules were the basis of this study. Pneumococcal carriage was determined at 6, 9 and 12 months of age, prior to PPS immunization. Serum samples collected at 18 weeks (post-PCV7), 12 months (pre-PPS), 12.5 months and 17 months (post-PPS) of age were assessed for serotype-specific IgG and opsonophagocytic responses. The most frequently carried serotypes were 6B (N=11), 19F (N=14) and 23F (N=23). Significantly lower serotype-specific IgG for 19F, 23F but not 6B post-PPS were detected in infants with homologous serotype carriage prior to PPS compared with non-carriers (N=230). However, OPA levels for 6B and 23F were lower in infants that carried these serotypes. Pneumococcal carriage with 19F or 23F at any time prior to PPS immunization in infants at 12 months of age who were previously primed with PCV resulted in serotype-specific hyporesponsiveness that persisted until 17 months of age. These results may have implications for the timing of infant vaccine schedules, particularly in high disease burden settings.

  19. Climate, demographic factors and geographical variations in the incidence of invasive meningococcal disease in Italy.

    PubMed

    Vescio, F; Busani, L; Mughini Gras, L; Fazio, C; Neri, A; Avellis, L; Rezza, G; Stefanelli, P

    2015-06-01

    We investigated the effect of climatic, demographic factors and intra-country geographical variations on the incidence of invasive meningococcal disease (IMD) in Italy. For this purpose, incidence rates of IMD cases reported in Italy between 1994 and 2012 were calculated, and a cluster analysis was performed. A geographical gradient was determined, with lower incidence rates in central and southern Italy, compared to the northern parts, where most clusters were observed. IMD rates were higher in medium-sized towns than in villages. Adults were at lower risk of IMD than children aged ⩽4 years. IMD incidence tended to decrease with increasing monthly mean temperatures (incidence rate ratio 0·94, 95% confidence interval 0·90-0·99). In conclusion, geographical variations in IMD incidence were found, where age and temperature were associated with disease occurrence. Whether geographical variations should be considered in national intervention plans is still a matter for discussion.

  20. Invasive Blackberry Species in Oregon, USA: Their Identity and Susceptibility to Rust Disease, and Implications for Biological Control

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Two of five species of European blackberry (Rubus fruticosus L. Aggregate) along the West Coast of the United States are invasive, and they are also similar in appearance. Biological control by Phragmidium violaceum, causal agent of a rust disease, was under consideration when rust-diseased blackber...

  1. Signal transducer and activator of transcription 3 mutation with invasive eosinophilic disease

    PubMed Central

    Swender, David; Chernin, Leah; Hafez-Khayyata, Said; Ochs, Hans; Tcheurekdjian, Haig; Hostoffer, Robert

    2012-01-01

    Hyper-IgE syndrome (HIES), or Jobs disease, is a rare immunologic disorder characterized by the triad of staphylococcal abscesses, pneumonia with pneumatocele formation, and elevated IgE. It has been shown to have multiple modes of inheritance, autosomal dominant being more common than autosomal recessive, with sporadic cases as well. A mutation in signal transducer and activator of transcription 3 (STAT3) gene has been linked to the development of the sporadic and dominant forms of HIES. Peripheral eosinophilia, typically greater than two standard deviations from the normal population, is often seen in association with HIES. Despite these elevated levels of blood eosinophils, there have been no reported cases of invasive eosinophilic disease, such as eosonophilic esophagitic. Here we report the first description, to our knowledge, of a patient with HIES with a STAT3 mutation involving exon 12, Thr389Ile, and invasive eosinophilic disease of the esophagus. STAT3 modulates the expression of several genes that control central cell processes such as growth and death in response to external soluble stimuli. A mutation in the STAT3 molecule may affect the eosinophil's response to IL-5 and thus reduce the chemotaxic ability of those cells to migrate into tissues. This may then explain the paucity of eosinophilic infiltrative disease in patients with STAT3 mutations. The level of eosinophilic involvement may be related to the site or type of mutation within the STAT3 molecule. As more data are collected, we may be able to assess whether certain mutations dictate different clinical outcomes, which could prove helpful in directing therapy. PMID:23342295

  2. The effect of physicians' awareness on influenza and pneumococcal vaccination rates and correlates of vaccination in patients with diabetes in Turkey: an epidemiological Study "diaVAX".

    PubMed

    Satman, Ilhan; Akalin, Sema; Cakir, Bekir; Altinel, Serdar

    2013-12-01

    We aimed to examine the effect of increased physician awareness on the rate and determinants of influenza and pneumococcal vaccinations in diabetic patients. Diabetic patients (n = 5682, mean [SD] age: 57.3 [11.6] years, 57% female) were enrolled by 44 physicians between Sept 2010 and Jan 2011. The physicians were initially questioned regarding vaccination practices, and then, they attended a training program. During the last five years, the physicians recommended influenza and pneumococcal vaccinations to 87.9% and 83.4% of the patients, respectively; however; only 27% of the patients received the influenza and 9.8% received the pneumococcal vaccines. One year after the training, the vaccination rates increased to 63.3% and 40.7%, respectively. The logistic regression models revealed that variables which increased the likelihood of having been vaccinated against influenza were: longer duration of diabetes, presence of hyperlipidemia and more use of concomitant medications whereas more use of anti-hyperglycemic medications was associated with increased odds of vaccination. On the other hand, older age, longer duration of diabetes and presence of a cardiovascular disease were variables which decreased the likelihood of having been vaccinated against pneumococcal disease during the past five years. However, during the study period, variables which decreased the odds of having been vaccinated included: older age and anti-hyperglycemic medications for influenza, and presence of hyperlipidemia and a family history of hypertension for pneumococcal disease. While variables which increased the likelihood of vaccination in the same period were: increased number of co-morbidities for influenza, and family history of diabetes for pneumococcal disease. We conclude that increased awareness of physicians may help improve vaccination rates against influenza and pneumococcal disease. However, diabetic patients with more severe health conditions are less likely to having been

  3. Antimicrobial susceptibilities and serotypes of Streptococcus pneumoniae isolates from elderly patients with pneumonia and acute exacerbation of chronic obstructive pulmonary disease.

    PubMed

    Pérez-Trallero, Emilio; Marimón, José M; Larruskain, Julián; Alonso, Marta; Ercibengoa, María

    2011-06-01

    In the elderly, Streptococcus pneumoniae is the most common cause of pneumonia and one of the most frequently isolated pathogens in cases of acute exacerbation of chronic obstructive pulmonary disease (AECOPD). This study was conducted to compare the pneumococcal isolates obtained during episodes of AECOPD and pneumonia in patients of ≥65 years old and to analyze whether in patients with AECOPD and pneumonia within a short interval, the same isolate caused both episodes. This laboratory-based study was performed between 2005 and 2008. Pneumococcal isolates from episodes of pneumonia (n = 401) and AECOPD (n = 398), matched one-to-one by date of isolation, were characterized. The serotypes and genotypes of other pneumococcal isolates causing pneumonia and AECOPD in the same patient were compared. In patients with pneumonia, COPD as an underlying disease was not associated with more-drug-resistant pneumococci. In contrast, isolates causing AECOPD showed higher rates of resistance than those causing pneumonia. Serotypes 1, 3, and 7F were more frequent in pneumonia. The same pneumococcus was involved in 25.7% (9/35 patients) of patients with two consecutive AECOPD episodes but in only 6.3% (2/32 patients) of COPD patients with pneumonia and exacerbation (Fisher's exact test; P = 0.047). Less invasive serotypes were isolated more often in AECOPD and were more resistant to antimicrobials. The presence of a specific pneumococcal serotype in AECOPD does not predict the etiology of subsequent pneumonia.

  4. Incidence of Pneumococcal Pneumonia among Adults in Rural Thailand, 2006–2011: Implications for Pneumococcal Vaccine Considerations

    PubMed Central

    Piralam, Barameht; Tomczyk, Sara M.; Rhodes, Julia C.; Thamthitiwat, Somsak; Gregory, Christopher J.; Olsen, Sonja J.; Praphasiri, Prabda; Sawatwong, Pongpun; Naorat, Sathapana; Chantra, Somrak; Areerat, Peera; Hurst, Cameron P.; Moore, Matthew R.; Muangchana, Charung; Baggett, Henry C.

    2015-01-01

    The incidence of pneumococcal pneumonia among adults is a key driver for the cost-effectiveness of pneumococcal conjugate vaccine used among children. We sought to obtain more accurate incidence estimates among adults by including results of pneumococcal urine antigen testing (UAT) from population-based pneumonia surveillance in two Thai provinces. Active surveillance from 2006 to 2011 identified acute lower respiratory infection (ALRI)–related hospital admissions. Adult cases of pneumococcal pneumonia were defined as hospitalized ALRI patients aged ≥ 18 years with isolation of Streptococcus pneumoniae from blood or with positive UAT. Among 39,525 adult ALRI patients, we identified 481 pneumococcal pneumonia cases (105 by blood culture, 376 by UAT only). Estimated incidence of pneumococcal pneumonia hospitalizations was 30.5 cases per 100,000 persons per year (2.2 and 28.3 cases per 100,000 persons per year by blood culture and UAT, respectively). Incidence varied between 22.7 in 2007 and 43.5 in 2010, and increased with age to over 150 per 100,000 persons per year among persons aged ≥ 70 years. Viral coinfections including influenza A/B, respiratory syncytial virus (RSV), and adenovirus occurred in 11% (44/409) of pneumococcal pneumonia cases tested. Use of UAT to identify cases of pneumococcal pneumonia among adults in rural Thailand substantially increases estimates of pneumococcal pneumonia burden, thereby informing cost-effectiveness analyses and vaccine policy decisions. PMID:26503277

  5. PneumococcaL meningitis in french children before and after the introduction of pneumococcal conjugate vaccine.

    PubMed

    Levy, Corinne; Varon, Emmanuelle; Bingen, Edouard; Lécuyer, Aurélie; Boucherat, Michel; Cohen, Robert

    2011-02-01

    In France, despite a high rate of pneumococcal conjugate vaccine coverage, the number of cases of pneumococcal meningitis in children did not decline significantly between 2001–2002 (n = 264) and 2007–2008 (n = 244). A decline was observed among children < 2 years old (185 [70.1%] to 134 [54.9%] cases; P = 0.0004), but was counterbalanced by an increase among children ≥ 2 years old (79 [29.9%] to 110 [45.1%] cases). Mean age increased significantly, from 2.3 (median 0.8) to 3.8 (median 1.5) years. After pneumococcal conjugate vaccine 7 implementation, a wide diversity of serotypes implicated in pneumococcalmeningitis was observed; serotypes 19A and 7F were the most frequent.

  6. Outcomes in Patients With Hemophilia and von Willebrand Disease Undergoing Invasive or Surgical Procedures.

    PubMed

    Chapin, John; Bamme, Jaqueline; Hsu, Fraustina; Christos, Paul; DeSancho, Maria

    2017-03-01

    Adults with hemophilia A (HA), hemophilia B (HB), and von Willebrand disease (VWD) frequently require surgery and invasive procedures. However, there is variability in perioperative management guidelines. We describe our periprocedural outcomes in this setting. A retrospective chart review from January 2006 to December 2012 of patients with HA, HB, and VWD undergoing surgery or invasive procedures was conducted. Type of procedures, management including the use of continuous factor infusion, and administration of antifibrinolytics were reviewed. Adverse outcomes were defined as acute bleeding (<48 hours), delayed bleeding (≥48 hours), transfusion, inhibitor development, and thrombosis. We identified 59 patients with HA and HB. In all, 24 patients had severe hemophilia and 12 had mild/moderate hemophilia. Twelve patients had inhibitors. There were also 5 female carriers of HA and 6 patients with VWD. There were 34 major surgeries (26 orthopedic, 8 nonorthopedic) and 129 minor surgeries. Continuous infusion was used in 55.9% of major surgeries versus 8.5% of minor surgeries. Antifibrinolytics were administered in 14.7% of major surgeries versus 23.2% of minor surgeries. In all, 4 patients developed acute bleeding and 10 patients developed delayed bleeding. Delayed bleeding occurred in 28.6% of genitourinary procedures and in 16.1% of dental procedures. Five patients acquired an inhibitor and 2 had thrombosis. In conclusion, patients with HA, HB, or VWD had similar rates of adverse outcomes when undergoing minor surgeries or major surgeries. This finding underscores the importance of an interdisciplinary management and procedure-specific guidelines for patients with hemophilia and VWD prior to even minor invasive procedures.

  7. Extensive invasive extramammary Paget disease evaluated by F-18 FDG PET/CT: a case report.

    PubMed

    Li, Zu-Gui; Qin, Xiao-Jing

    2015-01-01

    Extramammary Paget disease (EMPD) is a rare cutaneous, intraepithelial adenocarcinoma. Because of its rarity, little is known about the value of fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in evaluating this disease. Our case report aims to increase current knowledge of FDG PET/CT in EMPD as a noninvasive imaging tool for assessing the extension of the disease and detecting distant metastases.We reported a 64-year-old Chinese man who presented with a slowly progressive, ill-margined erythematous lesion with a crusted, eroded, and scaly surface involving multiple sites of penis, scrotum, left pelvic wall, hip, groin, and thigh for >4 years, which became extensive in the past 1 year. He was referred for an FDG PET/CT examination to further evaluate the lesions. A following skin biopsy was performed to obtain a definitive histological diagnosis.FDG PET/CT imaging revealed mild FDG uptake at the extensive cutaneous lesion with subcutaneous invasion, involvement of lymph nodes, and multiple intense FDG-avid of skeletal metastases. According to the appearance of FDG PET/CT, a provisional diagnosis of advanced cutaneous malignancy was made. Histopathology findings indicated characteristic of EMPD. The patient was treated with radiation therapy and died from complications 2 months after the last dose of radiotherapy.Our case highlighted that a whole-body FDG PET/CT should be incorporated into the diagnostic algorithm of EMPD to give a comprehensive assessment of this disease.

  8. Global practices of meningococcal vaccine use and impact on invasive disease

    PubMed Central

    Ali, Asad; Jafri, Rabab Zehra; Messonnier, Nancy; Tevi-Benissan, Carol; Durrheim, David; Eskola, Juhani; Fermon, Florence; Klugman, Keith P; Ramsay, Mary; Sow, Samba; Zhujun, Shao; Bhutta, Zulfiqar; Abramson, Jon

    2014-01-01

    A number of countries now include meningococcal vaccines in their routine immunization programs. This review focuses on different approaches to including meningococcal vaccines in country programs across the world and their effect on the burden of invasive meningococcal disease (IMD) as reflected by pre and post-vaccine incidence rates in the last 20 years. Mass campaigns using conjugated meningococcal vaccines have lead to control of serogroup C meningococcal disease in the UK, Canada, Australia, Spain, Belgium, Ireland, and Iceland. Serogroup B disease, predominant in New Zealand, has been dramatically decreased, partly due to the introduction of an outer membrane vesicle (OMV) vaccine. Polysaccharide vaccines were used in high risk people in Saudi Arabia and Syria and in routine immunization in China and Egypt. The highest incidence region of the meningitis belt initiated vaccination with the serogroup A conjugate vaccine in 2010 and catch-up vaccination is ongoing. Overall results of this vaccine introduction are encouraging especially in countries with a moderate to high level of endemic disease. Continued surveillance is required to monitor effectiveness in countries that recently implemented these programs. PMID:24548156

  9. Budget impact analysis of a pneumococcal vaccination programme in the 65-year-old Spanish cohort using a dynamic model

    PubMed Central

    2013-01-01

    Background This study aimed to assess the costs and clinical benefits of the 13-valent pneumococcal conjugate vaccine (PCV13) administered annually to the 65-year-old cohort in Spain versus the alternative of not vaccinating patients and treating them only when infected. Methods Cases of pneumococcal disease avoided were calculated through a dynamic model based on the work of Anderson and May (1999). Sixty-six percent of the 65-year-old cohort was assumed to have been vaccinated with one PCV13 dose (304,492 subjects). Base-case estimated vaccine effectiveness and serotype coverage were 58% and 60%, respectively. Disease-related costs were calculated based on published data. Results Over the 5-year period, a total of 125,906 cases of pneumococcal disease would be avoided. Net savings of €102 million would be obtained. The cost-saving distribution was not homogeneous, starting in the 2nd year and increasing through the 5th. To demonstrate model robustness, an additional scenario analysis was performed using extreme values of model parameters (vaccination programme coverage, vaccine effectiveness, discount rate and disease costs). Under those scenarios, net savings were always achieved. Conclusions Based on the assumptions of the model, the 65-year-cohort pneumococcal vaccination campaign appears to be a cost-saving intervention in the Spanish population under different scenarios. PMID:23578307

  10. Cord blood Streptococcus pneumoniae-specific cellular immune responses predict early pneumococcal carriage in high-risk infants in Papua New Guinea.

    PubMed

    Francis, J P; Richmond, P C; Strickland, D; Prescott, S L; Pomat, W S; Michael, A; Nadal-Sims, M A; Edwards-Devitt, C J; Holt, P G; Lehmann, D; van den Biggelaar, A H J

    2017-03-01

    In areas where Streptococcus pneumoniae is highly endemic, infants experience very early pneumococcal colonization of the upper respiratory tract, with carriage often persisting into adulthood. We aimed to explore whether newborns in high-risk areas have pre-existing pneumococcal-specific cellular immune responses that may affect early pneumococcal acquisition. Cord blood mononuclear cells (CBMC) of 84 Papua New Guinean (PNG; high endemic) and 33 Australian (AUS; low endemic) newborns were stimulated in vitro with detoxified pneumolysin (dPly) or pneumococcal surface protein A (PspA; families 1 and 2) and compared for cytokine responses. Within the PNG cohort, associations between CBMC dPly and PspA-induced responses and pneumococcal colonization within the first month of life were studied. Significantly higher PspA-specific interferon (IFN)-γ, tumour necrosis factor (TNF)-α, interleukin (IL)-5, IL-6, IL-10 and IL-13 responses, and lower dPly-IL-6 responses were produced in CBMC cultures of PNG compared to AUS newborns. Higher CBMC PspA-IL-5 and PspA-IL-13 responses correlated with a higher proportion of cord CD4 T cells, and higher dPly-IL-6 responses with a higher frequency of cord antigen-presenting cells. In the PNG cohort, higher PspA-specific IL-5 and IL-6 CBMC responses were associated independently and significantly with increased risk of earlier pneumococcal colonization, while a significant protective effect was found for higher PspA-IL-10 CBMC responses. Pneumococcus-specific cellular immune responses differ between children born in pneumococcal high versus low endemic settings, which may contribute to the higher risk of infants in high endemic settings for early pneumococcal colonization, and hence disease.

  11. Phylogenetic Analysis of Invasive Serotype 1 Pneumococcus in South Africa, 1989 to 2013

    PubMed Central

    Allam, Mushal; Tempia, Stefano; Wolter, Nicole; de Gouveia, Linda; von Mollendorf, Claire; Jolley, Keith A.; Mbelle, Nontombi; Wadula, Jeannette; Cornick, Jennifer E.; Everett, Dean B.; McGee, Lesley; Breiman, Robert F.; Gladstone, Rebecca A.; Bentley, Stephen D.; Klugman, Keith P.; von Gottberg, Anne

    2016-01-01

    Serotype 1 is an important cause of invasive pneumococcal disease in South Africa and has declined following the introduction of the 13-valent pneumococcal conjugate vaccine in 2011. We genetically characterized 912 invasive serotype 1 isolates from 1989 to 2013. Simpson's diversity index (D) and recombination ratios were calculated. Factors associated with sequence types (STs) were assessed. Clonal complex 217 represented 96% (872/912) of the sampled isolates. Following the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13), ST diversity increased in children <5 years (D, 0.39 to 0.63, P = 0.002) and individuals >14 years (D, 0.35 to 0.54, P < 0.001): ST-217 declined proportionately in children <5 years (153/203 [75%] versus 21/37 [57%], P = 0.027) and individuals >14 years (242/305 [79%] versus 96/148 [65%], P = 0.001), whereas ST-9067 increased (4/684 [0.6%] versus 24/228 [11%], P < 0.001). Three subclades were identified within ST-217: ST-217C1 (353/382 [92%]), ST-217C2 (15/382 [4%]), and ST-217C3 (14/382 [4%]). ST-217C2, ST-217C3, and single-locus variant (SLV) ST-8314 (20/912 [2%]) were associated with nonsusceptibility to chloramphenicol, tetracycline, and co-trimoxazole. ST-8314 (20/912 [2%]) was also associated with increased nonsusceptibility to penicillin (P < 0.001). ST-217C3 and newly reported ST-9067 had higher recombination ratios than those of ST-217C1 (4.344 versus 0.091, P < 0.001; and 0.086 versus 0.013, P < 0.001, respectively). Increases in genetic diversity were noted post-PCV13, and lineages associated with antimicrobial nonsusceptibility were identified. PMID:26962082

  12. Need for Optimisation of Immunisation Strategies Targeting Invasive Meningococcal Disease in the Netherlands

    PubMed Central

    Bousema, Josefien Cornelie Minthe; Ruitenberg, Joost

    2015-01-01

    Invasive meningococcal disease (IMD) is a severe bacterial infectious disease with high mortality and morbidity rates worldwide. In recent years, industrialised countries have implemented vaccines targeting IMD in their National Immunisation Programmes (NIPs). In 2002, the Netherlands successfully implemented a single dose of meningococcal serogroup C conjugate vaccine at the age of 14 months and performed a single catch-up for children ≤18 years of age. Since then the disease disappeared in vaccinated individuals. Furthermore, herd protection was induced, leading to a significant IMD reduction in non-vaccinated individuals. However, previous studies revealed that the current programmatic immunisation strategy was insufficient to protect the population in the foreseeable future. In addition, vaccines that provide protection against additional serogroups are now available. This paper describes to what extent the current strategy to prevent IMD in the Netherlands is still sufficient, taking into account the burden of disease and the latest scientific knowledge related to IMD and its prevention. In particular, primary MenC immunisation seems not to provide long-term protection, indicating a risk for possible recurrence of the disease. This can be combatted by implementing a MenC or MenACWY adolescent booster vaccine. Additional health benefits can be achieved by replacing the primary MenC by a MenACWY vaccine. By implementation of a recently licensed MenB vaccine for infants in the NIP, the greatest burden of disease would be targeted. This paper shows that optimisation of the immunisation strategy targeting IMD in the Netherlands should be considered and contributes to create awareness concerning prevention optimisation in other countries. PMID:26673336

  13. Need for Optimisation of Immunisation Strategies Targeting Invasive Meningococcal Disease in the Netherlands.

    PubMed

    Bousema, Josefien Cornelie Minthe; Ruitenberg, Joost

    2015-09-13

    Invasive meningococcal disease (IMD) is a severe bacterial infectious disease with high mortality and morbidity rates worldwide. In recent years, industrialised countries have implemented vaccines targeting IMD in their National Immunisation Programmes (NIPs). In 2002, the Netherlands successfully implemented a single dose of meningococcal serogroup C conjugate vaccine at the age of 14 months and performed a single catch-up for children ≤18 years of age. Since then the disease disappeared in vaccinated individuals. Furthermore, herd protection was induced, leading to a significant IMD reduction in non-vaccinated individuals. However, previous studies revealed that the current programmatic immunisation strategy was insufficient to protect the population in the foreseeable future. In addition, vaccines that provide protection against additional serogroups are now available. This paper describes to what extent the current strategy to prevent IMD in the Netherlands is still sufficient, taking into account the burden of disease and the latest scientific knowledge related to IMD and its prevention. In particular, primary MenC immunisation seems not to provide long-term protection, indicating a risk for possible recurrence of the disease. This can be combatted by implementing a MenC or MenACWY adolescent booster vaccine. Additional health benefits can be achieved by replacing the primary MenC by a MenACWY vaccine. By implementation of a recently licensed MenB vaccine for infants in the NIP, the greatest burden of disease would be targeted. This paper shows that optimisation of the immunisation strategy targeting IMD in the Netherlands should be considered and contributes to create awareness concerning prevention optimisation in other countries.

  14. Safety and preliminary immunogenicity of Cuban pneumococcal conjugate vaccine candidate in healthy children: a randomized phase I clinical trial.

    PubMed

    Dotres, Carlos P; Puga, Rinaldo; Ricardo, Yariset; Broño, Carmen R; Paredes, Beatriz; Echemendía, Vladimir; Rosell, Sandra; González, Nadezhda; García-Rivera, Dagmar; Valdés, Yury; Goldblatt, David; Vérez-Bencomo, Vicente

    2014-09-15

    A new heptavalent conjugate vaccine (PCV7-TT) is under development in Cuba. PCV7-TT contains 2 μg of serotypes 1, 5, 14, 18C, 19F, 23F and 4 μg of 6B, each one conjugated to tetanus toxoid (TT). This vaccine was designed with the serotypes that cause most invasive pneumococcal diseases (IPD) worldwide. In the present study, we investigated the safety and explored the immunogenicity of PCV7-TT during a controlled, randomized and double blind clinical trial phase I in 4-5-year-old children. PCV7-TT was well tolerated and as safe as Synflorix used as control vaccine. Following a single-dose vaccination, all individual serotypes included in PCV7-TT induced statistically significant increase of IgG GMC and OPA GMT. These are the first clinical results of PCV7-TT in children and they pave the way toward next clinical trials in children and infants. This clinical trial was published in the Cuban Public Register of Clinical Trials with code RPCEC00000173.

  15. Launching Invasive, First-in-Human Trials against Parkinson’s Disease: Ethical Considerations

    PubMed Central

    London, Alex John; Ravina, Bernard; Ramsay, Tim; Bernstein, Mark; Fine, Alan; Stahnisch, Frank W.

    2009-01-01

    The decision to initiate invasive, first-in-human trials involving Parkinson’s disease presents a vexing ethical challenge. Such studies present significant surgical risks, and high degrees of uncertainty about intervention risks and biological effects. We argue that maintaining a favorable risk-benefit balance in such circumstances requires a higher than usual degree of confidence that protocols will lead to significant direct and/or social benefits. One critical way of promoting such confidence is through the application of stringent evidentiary standards for preclinical studies. We close with a series of recommendations for strengthening the internal and external validity of preclinical studies, reducing their tendency toward optimism and publication biases, and improving the knowledge base used to design and evaluate preclinical studies. PMID:19672990

  16. Non-invasive ventilation in chronic obstructive pulmonary disease: management of acute type 2 respiratory failure.

    PubMed

    Roberts, C M; Brown, J L; Reinhardt, A K; Kaul, S; Scales, K; Mikelsons, C; Reid, K; Winter, R; Young, K; Restrick, L; Plant, P K

    2008-10-01

    Non-invasive ventilation (NIV) in the management of acute type 2 respiratory failure in patients with chronic obstructive pulmonary disease (COPD) represents one of the major technical advances in respiratory care over the last decade. This document updates the 2002 British Thoracic Society guidance and provides a specific focus on the use of NIV in COPD patients with acute type 2 respiratory failure. While there are a variety of ventilator units available most centres now use bi-level positive airways pressure units and this guideline refers specifically to this form of ventilatory support although many of the principles encompassed are applicable to other forms of NIV. The guideline has been produced for the clinician caring for COPD patients in the emergency and ward areas of acute hospitals.

  17. Review of invasive meningococcal disease during the last 40 years in Turkey.

    PubMed

    Bakir, Mustafa; Altinel, Serdar

    2015-01-01

    Due to the lack of comprehensive surveillance data representing Turkey, the authors aimed to derive information by panoramically reviewing all articles related to invasive meningococcal disease (IMD) published in the last 40 years. The following databases were reviewed: Ulakbim (the national database), BIOSIS Previews (from 1995), Evidence-Based Medicine Reviews-Cochrane Database of Systematic Reviews (from 2005), Embase (from 1996), Ovid MEDLINE(R) (from 1946) and Journals@Ovid Full Text (2014). Twenty-seven articles, 10 published in international journals and 17 in national journals, were identified. Only two were multicenter sentinel meningitis surveillance studies. Also, 74% of IMD patients were aged 5 years or younger and the median overall case fatality rate during childhood was 18.44%. Turkey is a country where meningococcal vaccination on a national basis is recommended by WHO. A vaccination strategy for serogroups B and W135 targeting the first 5 years, covering especially the first 12 months, would be appropriate.

  18. The use of echocardiography for the non-invasive evaluation of coronary artery disease.

    PubMed

    Sirtori, Cesare R; Labombarda, Fabien; Castelnuovo, Samuela; Perry, Rebecca

    2017-03-01

    In the Western world, there are now millions of patients who undergo clinical procedures that evaluate coronary artery status each year. Methods span from direct imaging using angiography, computerized tomography, to nuclear magnetic imaging as well as to functional studies, such as positron emission tomography. These techniques have provided significant information to physicians, but there is still need for an improved accessibility. Angiographic methods are expensive and expose the patient to significant amounts of radiation, undesirable in younger patients. Among the novel technologies for coronary diagnostics, transthoracic echocardiography (TTE) of coronary arteries has provided an important alternative, particularly in everyday practice. Diagnostic arterial TTE can allow determination of the coronary wall lumen in at least three major coronary segments (left main [LM], left arterial descending [LAD] and right coronary artery [RCA]). Coronary wall thickness using the LAD has been preliminarily shown to be related to the risk of coronary events. Since it is well ascertained that coronary lesions found in any location indicate that at least 80% of the coronary tree is affected, this is very important clinical information. Evaluation of coronary status by TTE is a novel technology providing important information in ischemic syndromes, in cases of coronary malformations and other coronary diseases. KEY MESSAGES Coronary evaluation can be carried out by a variety of both invasive and non-invasive methods, many requiring radiation exposure or patient immobility. Transthoracic echocardiography (TTE) of the coronaries can, in particular, evaluate the coronary wall thickness, and this may be directly related to the coronary disease risk. TTE is a useful method for the monitoring of coronary flow reserve and can allow the detection of coronary malformations.

  19. Urinalysis for interleukin-8 in the non-invasive diagnosis of acute and chronic inflammatory diseases

    PubMed Central

    Taha, A; Grant, V; Kelly, R

    2003-01-01

    Background and aims: Given its role in mediating inflammation, the use of urinary interleukin-8 (IL-8) was assessed in the non-invasive diagnosis of acute and chronic inflammatory diseases. Methods: IL-8 was measured by an enzyme linked immunosorbent assay in random urine samples (1 ml each) carrying code numbers and taken from 208 patients: 177 adults and 31 children presenting with a range of active or inactive inflammatory conditions. Results: In the appropriate controls and in patients with inactive inflammation, the median urinary IL-8 levels ranged from 7–12 pg/ml, compared with 104 pg/ml in active ulcerative colitis (p = 0.002), 54 in active Crohn's disease (p = 0.025), 93 in active rheumatoid arthritis (p = 0.001), 107 in acute cholecystitis (p<0.0001), 127 in acute appendicitis (p = 0.0001), and 548 pg/ml in urinary tract infection (p<0.0001). Children with non-viral inflammation/infection also had higher IL-8 values (median, 199 pg/ml; p = 0.0001) than those with viral infection (median, 7 pg/ml) or non-specific conditions (median, 10 pg/ml). In the study group as a whole urinary IL-8 values correlated positively with peripheral blood white cell count (r = 0.32; p < 0.001), erythrocyte sedimentation rate (r = 0.41; p<0.001), and C-reactive protein (r = 0.33; p<0.001). Conclusion: Taking the appropriate clinical situation into account, urinary IL-8 measurement helps in the non-invasive assessment of active inflammation in at least a number of common acute and chronic conditions. PMID:12697917

  20. The continuing role of Haemophilus influenzae type b carriage surveillance as a mechanism for early detection of invasive disease activity.

    PubMed

    Jacups, Susan P

    2011-12-01

    Prior to the introduction of Haemophilus influenzae type b (Hib) conjugate vaccines, Hib was the leading cause of bacterial meningitis in children under five years of age worldwide. In countries that have adopted Hib vaccination schedules, invasive disease has reduced markedly. Oro-naso pharyngeal carriage is recognized as the most significant source of infection. Hib carriage is significantly associated with poverty, such as overcrowding, poor ventilation in houses, lack of running water, and high smoking rates. Additionally, many Indigenous minority groups report high rates of Hib carriage. A resurgence of Hib disease among Alaskan children in the 1990s, lead to a change in approach to eliminate Hib disease and carriage in high-risk populations. This new approach identifies strategies for eliminating Hib disease focusing on the reservoirs of colonization within families and communities. Monitoring Hib carriage continues to offer an early warning system, whereby intervention could prevent invasive disease resurgence.

  1. Non-invasive detection of periodontal disease using diffuse reflectance spectroscopy: a clinical study

    NASA Astrophysics Data System (ADS)

    Prasanth, Chandra Sekhar; Betsy, Joseph; Subhash, Narayanan; Jayanthi, Jayaraj L.; Prasanthila, Janam

    2012-03-01

    In clinical diagnostic procedures, gingival inflammation is considered as the initial stage of periodontal breakdown. This is often detected clinically by bleeding on probing as it is an objective measure of inflammation. Since conventional diagnostic procedures have several inherent drawbacks, development of novel non-invasive diagnostic techniques assumes significance. This clinical study was carried out in 15 healthy volunteers and 25 patients to demonstrate the applicability of diffuse reflectance (DR) spectroscopy for quantification and discrimination of various stages of inflammatory conditions in periodontal disease. The DR spectra of diseased lesions recorded using a point monitoring system consisting of a tungsten halogen lamp and a fiber-optic spectrometer showed oxygenated hemoglobin absorption dips at 545 and 575 nm. Mean DR spectra on normalization shows marked differences between healthy and different stages of gingival inflammation. Among the various DR intensity ratios investigated, involving oxy Hb absorption peaks, the R620/R575 ratio was found to be a good parameter of gingival inflammation. In order to screen the entire diseased area and its surroundings instantaneously, DR images were recorded with an EMCCD camera at 620 and 575 nm. We have observed that using the DR image intensity ratio R620/R575 mild inflammatory tissues could be discriminated from healthy with a sensitivity of 92% and specificity of 93%, and from moderate with a sensitivity of 83% and specificity of 96%. The sensitivity and specificity obtained between moderate and severe inflammation are 82% and 76% respectively.

  2. Aspergillus tanneri sp. nov., a New Pathogen That Causes Invasive Disease Refractory to Antifungal Therapy

    PubMed Central

    Sugui, Janyce A.; Peterson, Stephen W.; Clark, Lily P.; Nardone, Glenn; Folio, Les; Riedlinger, Gregory; Zerbe, Christa S.; Shea, Yvonne; Henderson, Christina M.; Zelazny, Adrian M.; Holland, Steven M.

    2012-01-01

    The most common cause of invasive aspergillosis (IA) in patients with chronic granulomatous disease (CGD) is Aspergillus fumigatus followed by A. nidulans; other aspergilli rarely cause the disease. Here we review two clinical cases of fatal IA in CGD patients and describe a new etiologic agent of IA refractory to antifungal therapy. Unlike typical IA caused by A. fumigatus, the disease caused by the new species was chronic and spread from the lung to multiple adjacent organs. Mycological characteristics and the phylogenetic relationship with other aspergilli based on the sequence analysis of Mcm7, RPB2, and Tsr1 indicated that the new species, which we named as A. tanneri, belongs to Aspergillus section Circumdati. The species has a higher amphotericin B, voriconazole, and itraconazole MIC and causes more chronic infection in CGD mice than A. fumigatus. This is the first report documenting IA in CGD patients caused by a species belonging to the Aspergillus section Circumdati that is inherently resistant to azoles and amphotericin B. Unlike the results seen with many members of Aspergillus section Circumdati, ochratoxin was not detected in filtrates of cultures grown in various media. Our phenotypic and genetic characterization of the new species and the case reports will assist future diagnosis of infection caused by A. tanneri and lead to more appropriate patient management. PMID:22855513

  3. Pneumococcal prophages are diverse, but not without structure or history

    PubMed Central

    Brueggemann, Angela B.; Harrold, Caroline L.; Rezaei Javan, Reza; van Tonder, Andries J.; McDonnell, Angus J.; Edwards, Ben A.

    2017-01-01

    Bacteriophages (phages) infect many bacterial species, but little is known about the diversity of phages among the pneumococcus, a leading global pathogen. The objectives of this study were to determine the prevalence, diversity and molecular epidemiology of prophages (phage DNA integrated within the bacterial genome) among pneumococci isolated over the past 90 years. Nearly 500 pneumococcal genomes were investigated and RNA sequencing was used to explore prophage gene expression. We revealed that every pneumococcal genome contained prophage DNA. 286 full-length/putatively full-length pneumococcal prophages were identified, of which 163 have not previously been reported. Full-length prophages clustered into four major groups and every group dated from the 1930–40 s onward. There was limited evidence for genes shared between prophage clusters. Prophages typically integrated in one of five different sites within the pneumococcal genome. 72% of prophages possessed the virulence genes pblA and/or pblB. Individual prophages and the host pneumococcal genetic lineage were strongly associated and some prophages persisted for many decades. RNA sequencing provided clear evidence of prophage gene expression. Overall, pneumococcal prophages were highly prevalent, demonstrated a structured population, possessed genes associated with virulence, and were expressed under experimental conditions. Pneumococcal prophages are likely to play a more important role in pneumococcal biology and evolution than previously recognised. PMID:28218261

  4. Pneumococcal prophages are diverse, but not without structure or history.

    PubMed

    Brueggemann, Angela B; Harrold, Caroline L; Rezaei Javan, Reza; van Tonder, Andries J; McDonnell, Angus J; Edwards, Ben A

    2017-02-20

    Bacteriophages (phages) infect many bacterial species, but little is known about the diversity of phages among the pneumococcus, a leading global pathogen. The objectives of this study were to determine the prevalence, diversity and molecular epidemiology of prophages (phage DNA integrated within the bacterial genome) among pneumococci isolated over the past 90 years. Nearly 500 pneumococcal genomes were investigated and RNA sequencing was used to explore prophage gene expression. We revealed that every pneumococcal genome contained prophage DNA. 286 full-length/putatively full-length pneumococcal prophages were identified, of which 163 have not previously been reported. Full-length prophages clustered into four major groups and every group dated from the 1930-40 s onward. There was limited evidence for genes shared between prophage clusters. Prophages typically integrated in one of five different sites within the pneumococcal genome. 72% of prophages possessed the virulence genes pblA and/or pblB. Individual prophages and the host pneumococcal genetic lineage were strongly associated and some prophages persisted for many decades. RNA sequencing provided clear evidence of prophage gene expression. Overall, pneumococcal prophages were highly prevalent, demonstrated a structured population, possessed genes associated with virulence, and were expressed under experimental conditions. Pneumococcal prophages are likely to play a more important role in pneumococcal biology and evolution than previously recognised.

  5. Pneumococcal Vertebral Osteomyelitis after Epidural Injection: A Rare Event

    PubMed Central

    Johnson, Tamara M; Chitturi, Chandrika; Lange, Michael; Suh, Jin S; Slim, Jihad

    2016-01-01

    Streptococcus pneumoniae vertebral infections have rarely been reported. Herein, we report a case of pneumococcal vertebral osteomyelitis with paraspinal and epidural abscesses as well as concomitant bacteremia following epidural injection. This will be the second case in the literature reporting pneumococcal vertebral osteomyelitis related to epidural manipulation. PMID:27621563

  6. Cost-effectiveness analysis of pneumococcal polysaccharide vaccination from age 60 in São Paulo State, Brazil

    PubMed Central

    Neto, Joao Tonolio; Gagliardi, Anna; Pinho, Amanda; Durand, Laure; Fonseca, Marcelo

    2011-01-01

    Vaccination of adults aged 60 years and older against Streptococcus pneumonia is not recommended in Brazil. The 23-valent polysaccharide pneumococcal vaccine (PPV23) is only available for institutionalized persons or with underlying diseases despite the substantial medical and economic burden related to pneumococcal infections in adults over than 59 years. The study aimed at evaluating the cost effectiveness of implementing a large PPV program in this population. This analysis was performed using a static decision tree model. Demographic and epidemiological data were obtained from Brazilian official sources and international literature. Economic data were obtained from a study performed in 2007 in a public and a private hospital located in Sao Paulo. Vaccination was assumed to protect for 5 years with 60% effectiveness against bacteremic pneumococcal pneumonia (BPP) and 21% effectiveness against non bacteremic pneumococcal pneumonia (NBPP). Deterministic and sensitivity analyses were performed. The pneumococcal polysaccharide vaccination saved 5,218 life year gained (LYG). The vaccination program was found to be cost effective in the social security and public health care perspectives with a mean incremental cost-effectiveness ratio of R$10,887 and R$8,281 per LYG respectively. Results were sensitive to the vaccine effectiveness against NBPP, the incidence and case-fatality rate of NBPP. From a societal perspective, PPV23 program for adults 60 and older was found to be cost-saving. Pneumococcal polysaccharide vaccination is clinically and economically favored over the present vaccination strategy, in which persons aged over 59 years in Sao Paulo have not been vaccinated. PMID:21941088

  7. Pre-clinical evaluation of a 15-valent pneumococcal conjugate vaccine (PCV15-CRM197) in an infant-rhesus monkey immunogenicity model.

    PubMed

    Skinner, Julie M; Indrawati, Lani; Cannon, Jayme; Blue, Jeffrey; Winters, Michael; Macnair, John; Pujar, Narahari; Manger, Walter; Zhang, Yuhua; Antonello, Joseph; Shiver, John; Caulfield, Michael; Heinrichs, Jon H

    2011-11-08

    The incidence of invasive pneumococcal disease (IPD), caused by the approximately 91 serotypes of Streptococcus pneumoniae (PN), varies geographically and temporally as a result of changing epidemiology and vaccination patterns as well as due to regional measurement differences. Prevnar(®) (Pfizer), the first licensed pneumococcal conjugate vaccine (PCV), comprises polysaccharides (PS) from 7 serotypes conjugated to the mutant diphtheria toxin carrier protein, CRM197. In the United States and elsewhere, this vaccine has been highly efficacious in reducing the incidence of IPD caused by vaccine serotypes, however, the incidence of non-vaccine serotypes (e.g., 19A, 22F, and 33F) has increased, resulting in the need for vaccines with higher valencies. In response, 10- and 13-valent PCVs have recently been licensed. To further increase serotype coverage, we have developed a 15-valent PCV containing PS from serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F and 33F conjugated to CRM197 and formulated on aluminum phosphate adjuvant. Vaccine immunogenicity was evaluated in infant rhesus monkeys since they, like human infants, respond poorly to unconjugated PN PS. Infant (2-3 month old) rhesus monkeys were vaccinated three times with PCV-15 or Prevnar(®) at 2 month intervals, and serotype-specific IgG antibodies were measured using a multiarray electrochemiluminescence (ECL) assay. The results indicate that antibody responses to PCV-15 and Prevnar(®) were comparable for the 7 common serotypes and that post-vaccination responses to PCV-15 were >10-fold higher than baseline for the 8 additional serotypes.

  8. Predicting the impact of new pneumococcal conjugate vaccines: serotype composition is not enough.

    PubMed

    Hausdorff, William P; Hoet, Bernard; Adegbola, Richard A

    2015-03-01

    Streptococcus pneumoniae is a major cause of childhood morbidity and mortality worldwide. A heptavalent polysaccharide-protein conjugate vaccine (PCV) has proven highly effective in preventing pneumococcal disease in industrialized countries. Two higher-valent pneumococcal conjugate vaccines are now widely available, even in the poorest countries. These differ from each other in the number of serotypes and carrier proteins used for their conjugation. Some have assumed that the only meaningful clinical difference between PCV formulations is a function of the number of serotypes each contains. A careful review of recent clinical data with these and several unlicensed PCV formulations points to important similarities but also that some key properties of each vaccine likely differ from one another.

  9. Empyema and bacteremic pneumococcal pneumonia in children under five years of age*, **

    PubMed Central

    Cardoso, Maria Regina Alves; Nascimento-Carvalho, Cristiana Maria Costa; Ferrero, Fernando; Berezin, Eitan Naaman; Ruvinsky, Raul; Sant'Anna, Clemax Couto; Brandileone, Maria Cristina de Cunto; March, Maria de Fátima Bazhuni Pombo; Maggi, Ruben; Feris-Iglesias, Jesus; Benguigui, Yehuda; Camargos, Paulo Augusto Moreira

    2014-01-01

    We compared bacteremic pneumococcal pneumonia (BPP) and pneumococcal empyema (PE), in terms of clinical, radiological, and laboratory findings, in under-fives. A cross-sectional nested cohort study, involving under-fives (102 with PE and 128 with BPP), was conducted at 12 centers in Argentina, Brazil, and the Dominican Republic. Among those with PE, mean age was higher; disease duration was longer; and tachypnea, dyspnea, and high leukocyte counts were more common. Among those with BPP, fever and lethargy were more common. It seems that children with PE can be distinguished from those with BPP on the basis of clinical and laboratory findings. Because both conditions are associated with high rates of morbidity and mortality, prompt diagnosis is crucial. PMID:24626272

  10. Antigen-Independent Restriction of Pneumococcal Density by Mucosal Adjuvant Cholera Toxin Subunit B.

    PubMed

    Kuipers, Kirsten; Diavatopoulos, Dimitri A; van Opzeeland, Fred; Simonetti, Elles; van den Kieboom, Corné H; Kerstholt, Mariska; Borczyk, Malgorzata; van IngenSchenau, D; Brandsma, Eelke T; Netea, Mihai G; de Jonge, Marien I

    2016-11-15

    For many bacterial respiratory infections, development of (severe) disease is preceded by asymptomatic colonization of the upper airways. For Streptococcus pneumoniae, the transition to severe lower respiratory tract infection is associated with an increase in nasopharyngeal colonization density. Insight into how the mucosal immune system restricts colonization may provide new strategies to prevent clinical symptoms. Several studies have provided indirect evidence that the mucosal adjuvant cholera toxin subunit B (CTB) may confer nonspecific protection against respiratory infections. Here, we show that CTB reduces the pneumococcal load in the nasopharynx, which required activation of the caspase-1/11 inflammasome, mucosal T cells, and macrophages. Our findings suggest that CTB-dependent activation of the local innate response synergizes with noncognate T cells to restrict bacterial load. Our study not only provides insight into the immunological components required for containment and clearance of pneumococcal carriage, but also highlights an important yet often understudied aspect of adjuvants.

  11. Antibody response to 7-valent conjugated pneumococcal vaccine in patients with chronic lymphocytic leukaemia.

    PubMed

    Sinisalo, Marjatta; Vilpo, Juhani; Itälä, Maija; Väkeväinen, Merja; Taurio, Jyrki; Aittoniemi, Janne

    2007-12-21

    Chronic lymphocytic leukaemia (CLL) is a common adulthood mature B-cell neoplasm. Infections are the most important cause of mortality in this condition, and Streptococcus pneumoniae has been considered the most important single pathogen. We investigated the immunogenicity of 7-valent pneumococcal conjugate vaccine in patients with CLL. The study material comprised 52 patients with CLL and 25 age- and sex-matched controls. The subjects were vaccinated with Prevenar pneumococcal conjugate vaccine. Serum samples were taken for antibody determinations before and four weeks after vaccination. Antibody response rates to vaccine antigens were lower in patients with CLL compared to controls. However, if the vaccine had been administered at an early stage of the disease, i.e. before commencement of chemotherapy and the development of hypogammaglobulinaemia, a significant vaccination response to at least six antigens was obtained in almost 40% of the CLL patients. Our results indicate that early administration of conjugate vaccine may be beneficial in CLL.

  12. Treatment Costs of Pneumonia, Meningitis, Sepsis, and Other Diseases among Hospitalized Children in Viet Nam

    PubMed Central

    Anh, Dang Duc; Tho, Le Huu; Kim, Soon Ae; Nyambat, Batmunkh; Kilgore, Paul

    2010-01-01

    The aim of this study was to estimate the costs of treatment of children who present with the signs and symptoms of invasive bacterial diseases in Khanh Hoa province, Viet Nam. The study was an incidence-based cost-of-illness analysis from the health system perspective. The hospital costs included labour, materials and capital costs, both direct and indirect. Costs were determined for 980 children, with an average age of 12.67 months (standard deviation±11.38), who were enrolled in a prospective surveillance at the Khanh Hoa General Hospital during 2005-2006. Of them, 57% were male. By disease-category, 80% were suspected of having pneumonia, 8% meningitis, 3% very severe disease consistent with pneumococcal sepsis, and 9% other diseases. Treatment costs for suspected pneumonia, meningitis, very severe disease, and other diseases were US$ 31, US$ 57, US$ 73, and US$ 24 respectively. Costs ranged from US$ 24 to US$ 164 across different case-categories. Both type of disease and age of patient had statistically significant effects on treatment costs. The results showed that treatment costs for bacterial diseases in children were considerable and might differ by as much as seven times among invasive pneumococcal diseases. Changes in costs were sensitive to both age of patient and case-category. These cost-of-illness data will be an important component in the overall evidence base to guide the development of vaccine policy in Viet Nam. PMID:20941894

  13. The pneumococcal alpha-glycerophosphate oxidase enhances nasopharyngeal colonization through binding to host glycoconjugates.

    PubMed

    Mahdi, Layla K; Higgins, Melanie A; Day, Christopher J; Tiralongo, Joe; Hartley-Tassell, Lauren E; Jennings, Michael P; Gordon, David L; Paton, Adrienne W; Paton, James C; Ogunniyi, Abiodun D

    2017-03-03

    Streptococcus pneumoniae (the pneumococcus) is a major human pathogen, causing a broad spectrum of diseases including otitis media, pneumonia, bacteraemia and meningitis. Here we examined the role of a potential pneumococcal meningitis vaccine antigen, alpha-glycerophosphate oxidase (SpGlpO), in nasopharyngeal colonization. We found that serotype 4 and serotype 6A strains deficient in SpGlpO have significantly reduced capacity to colonize the nasopharynx of mice, and were significantly defective in adherence to human nasopharyngeal carcinoma cells in vitro. We also demonstrate that intranasal immunization with recombinant SpGlpO significantly protects mice against subsequent nasal colonization by wild type serotype 4 and serotype 6A strains. Furthermore, we show that SpGlpO binds strongly to lacto/neolacto/ganglio host glycan structures containing the GlcNAcβ1-3Galβ disaccharide, suggesting that SpGlpO enhances colonization of the nasopharynx through its binding to host glycoconjugates. We propose that SpGlpO is a promising vaccine candidate against pneumococcal carriage, and warrants inclusion in a multi-component protein vaccine formulation that can provide robust, serotype-independent protection against all forms of pneumococcal disease.

  14. Report of Two Cases of Aseptic Meningitis with Persistence of Pneumococcal Cell Wall Components in Cerebrospinal Fluid after Pneumococcal Meningitis▿

    PubMed Central

    Angoulvant, François; Lachenaud, Julie; Mariani-Kurkdjian, Patricia; Aubertin, Guillaume; Houdouin, Véronique; Lorrot, Mathie; de Los Angeles, Laure; Bingen, Edouard; Bourrillon, Antoine; Faye, Albert

    2006-01-01

    We describe two cases of aseptic meningitis occurring some time after pneumococcal meningitis. Both cases may have resulted from an inflammatory response to persistent pneumococcal cell membrane components, as the cerebrospinal fluid samples were positive by the Binax NOW Streptococcus pneumoniae antigen test. Potential mechanisms and diagnostic impact are discussed. PMID:17005744

  15. Pneumococcal septicemia despite pneumococcal vaccine and prescription of penicillin prophylaxis in children with sickle cell anemia.

    PubMed

    Buchanan, G R; Smith, S J

    1986-05-01

    Although polyvalent pneumococcal vaccine and prophylactic penicillin are used to prevent overwhelming Streptococcus pneumoniae septicemia in infants and young children with sickle cell anemia, infection rates remain high. We have reviewed our seven-year experience with a regimen of twice daily oral penicillin V potassium prophylaxis in 88 affected children. The median age at the start of prophylaxis was 10 months, and the median duration of prophylaxis was 29 months (range, three months to seven years). The total period of observation of patients who were prescribed penicillin was 248 person-years. Most patients also received one or two doses of polyvalent pneumococcal vaccine. Despite penicillin prophylaxis and pneumococcal vaccine, eight episodes of S pneumoniae septicemia have occurred and three have been fatal. Four episodes were in children older than 3 years. Suboptimal compliance with the prescribed oral penicillin regimen was usually apparent. With one possible exception, the infections occurred when penicillin had not been taken during the previous 24 hours. The S pneumoniae septicemia rate in this patient population, 3.2 per 100 person-years, is somewhat less than that described in previous reports of children not receiving penicillin but is still unacceptably high. Vigorous advocacy of a penicillin prophylaxis regimen does not eliminate the risk of pneumococcal septicema in this patient population.

  16. Revised Definitions of Invasive Fungal Disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group

    PubMed Central

    De Pauw, Ben; Walsh, Thomas J.; Donnelly, J. Peter; Stevens, David A.; Edwards, John E.; Calandra, Thierry; Pappas, Peter G.; Maertens, Johan; Lortholary, Olivier; Kauffman, Carol A.; Denning, David W.; Patterson, Thomas F.; Maschmeyer, Georg; Bille, Jacques; Dismukes, William E.; Herbrecht, Raoul; Hope, William W.; Kibbler, Christopher C.; Kullberg, Bart Jan; Marr, Kieren A.; Muñoz, Patricia; Odds, Frank C.; Perfect, John R.; Restrepo, Angela; Ruhnke, Markus; Segal, Brahm H.; Sobel, Jack D.; Sorrell, Tania C.; Viscoli, Claudio; Wingard, John R.; Zaoutis, Theoklis; Bennett, John E.

    2009-01-01

    Background Invasive fungal diseases are important causes of morbidity and mortality. Clarity and uniformity in defining these infections are important factors in improving the quality of clinical studies. A standard set of definitions strengthens the consistency and reproducibility of such studies. Methods After the introduction of the original European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group definitions, advances in diagnostic technology and the recognition of areas in need of improvement led to a revision of this document. The revision process started with a meeting of participants in 2003, to decide on the process and to draft the proposal. This was followed by several rounds of consultation until a final draft was approved in 2005. This was made available for 6 months to allow public comment, and then the manuscript was prepared and approved. Results The revised definitions retain the original classifications of “proven,” “probable,” and “possible” invasive fungal disease, but the definition of “probable” has been expanded, whereas the scope of the category “possible” has been diminished. The category of proven invasive fungal disease can apply to any patient, regardless of whether the patient is immunocompromised, whereas the probable and possible categories are proposed for immunocompromised patients only. Conclusions These revised definitions of invasive fungal disease are intended to advance clinical and epidemiological research and may serve as a useful model for defining other infections in high-risk patients. PMID:18462102

  17. First report of Puccinia psidii caused rust-disease epiphytotic on the invasive shrub Rhodomyrtus tomentosa in Florida

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Rhodomyrtus tomentosa (Aiton) Hassk. (downy-rose myrtle, Family: Myrtaceae) of south Asian origin is an invasive shrub that has formed monotypic stands in Florida. During the winter and spring of 2010-2012, a rust disease of epiphytotic proportion was observed on young foliage, stem terminals and i...

  18. Clonal Complex 17 Group B Streptococcus strains causing invasive disease in neonates and adults originate from the same genetic pool

    PubMed Central

    Teatero, Sarah; Ramoutar, Erin; McGeer, Allison; Li, Aimin; Melano, Roberto G.; Wasserscheid, Jessica; Dewar, Ken; Fittipaldi, Nahuel

    2016-01-01

    A significant proportion of group B Streptococcus (GBS) neonatal disease, particularly late-onset disease, is associated with strains of serotype III, clonal complex (CC) 17. CC17 strains also cause invasive infections in adults. Little is known about the phylogenetic relationships of isolates recovered from neonatal and adult CC17 invasive infections. We performed whole-genome-based phylogenetic analysis of 93 temporally and geographically matched CC17 strains isolated from both neonatal and adult invasive infections in the metropolitan region of Toronto/Peel, Canada. We also mined the whole-genome data to reveal mobile genetic elements carrying antimicrobial resistance genes. We discovered that CC17 GBS strains causing neonatal and adult invasive disease are interspersed and cluster tightly in a phylogenetic tree, signifying that they are derived from the same genetic pool. We identified limited variation due to recombination in the core CC17 genome. We describe that loss of Pilus Island 1 and acquisition of different mobile genetic elements carrying determinants of antimicrobial resistance contribute to CC17 genetic diversity. Acquisition of some of these mobile genetic elements appears to correlate with clonal expansion of the strains that possess them. Our results provide a genome-wide portrait of the population structure and evolution of a major disease-causing clone of an opportunistic pathogen. PMID:26843175

  19. Client views and attitudes to non-invasive prenatal diagnosis for sickle cell disease, thalassaemia and cystic fibrosis.

    PubMed

    Hill, Melissa; Compton, Cecilia; Karunaratna, Madhavi; Lewis, Celine; Chitty, Lyn

    2014-12-01

    In the near future the availability of non-invasive prenatal diagnosis (NIPD) for single gene disorders will change the prenatal diagnosis options available to couples who are carriers of conditions such as cystic fibrosis, sickle cell disorder and thalassaemia. Client opinions about NIPD are needed to inform the implementation of NIPD for single gene disorders. This qualitative study used two focus groups (n = 12) and one-to-one interviews (n = 16) with carriers and support group representatives of sickle cell disease, thalassaemia and cystic fibrosis. Discussions were digitally recorded, transcribed verbatim and analysed using thematic analysis. Opinions about NIPD were very positive and participants valued the opportunity to have safe and early testing. Uptake of prenatal testing is likely to increase as women who had previously declined invasive testing expressed interest in having NIPD. Participant concerns about NIPD centred on the need for accuracy to be high to be used for subsequent decision making about termination of pregnancy. Participants also raised concerns that less thought may be given to having a blood test compared to an invasive test and that the perceived ease of a blood test may bring increased pressure to have testing. Participants thought NIPD should be offered through existing specialist services to ensure appropriate genetic counseling and support. Maintaining all testing options is important as some people may prefer invasive testing over NIPD if invasive testing was more accurate or if invasive testing could give information about other conditions such as Down syndrome.

  20. Immunity status of invasive pulmonary aspergillosis patients with structural lung diseases in Chinese adults

    PubMed Central

    Liang, Shuo; Jiang, Rong; Lu, Hai-Wen; Mao, Bei; Li, Man-Hui; Li, Cheng-Wei; Gu, Shu-Yi; Bai, Jiu-Wu

    2017-01-01

    Background Invasive pulmonary aspergillosis (IPA) is a fungal infection frequently observed in patients with immune dysfunction, such as those suffering from structural lung diseases. Nevertheless, studies assessing IPA combined with other common respiratory diseases remain scarce, particularly those regarding the immune status of its patients. Different structural lung diseases are known to differently affect patient immune status; however, the mechanisms by which this is conferred have yet to be determined. Thus, our study aims to compare the immune status of IPA patients with the structural lung diseases chronic obstructive pulmonary diseases (COPD), interstitial lung disease (ILD) and non-cystic fibrosis bronchiectasis (NCFB). Methods This study was performed retrospectively with data collected over the years 2004 to 2013 at Shanghai Pulmonary Hospital, Tongji University, and included 77 patients whose lower respiratory tract (LRT) samples tested positive for. Our analysis considered blood examinations of CD3+, CD4+, CD8+, CD4+/CD8+, IgG, IgA and IgM levels. Results CD4+/CD8+ double positive cells, representing cell-mediated immunity, were less abundant in IPA patients with COPD than those with ILD and NCFB (0.81±0.09 vs. 1.39±0.25 and 0.81±0.09 vs. 1.57±0.06, respectively, P<0.001). In agreement with this result, corticosteroid and broad-spectrum antibiotic use were most common in individuals with COPD (57%). IgA levels, which indicate humoral immunity, were lower in IPA patients with NCFB than those with COPD or ILD (0.95±0.28 vs. 1.64±0.40 g/L and 0.95±0.28 vs. 3.16±0.83 g/L, respectively, P<0.001). Conclusions Immunity status differs between IPA patients with different structural lung diseases. Among IPA patients with COPD, ILD and NCFB, those with COPD have the lowest cell-mediated immunity, while those with NCFB have the lowest humoral immunity. PMID:28275471

  1. [Biological factors influencing infectious diseases transmitted by invasive species of mosquitoes].

    PubMed

    Boštíková, Vanda; Pasdiorová, Markéta; Marek, Jan; Prášil, Petr; Salavec, Miloslav; Sleha, Radek; Střtítecká, Hana; Blažek, Pavel; Hanovcová, Irena; Šošovičková, Renáta; Špliňo, Milan; Smetana, Jan; Chlíbek, Roman; Hytych, Václav; Kuča, Kamil; Boštík, Pavel

    2016-06-01

    Studies focused on arbovirus diseases transmitted by invasive species of mosquitoes have become increasingly significant in recent years, due to the fact that these vectors have successfully migrated to Europe and become established in the region. Mosquitoes, represented by more than 3 200 species, occur naturally worldwide, except in Antarctica. They feed on the blood of warm-blooded animals and by this route, they are capable of transmitting dangerous diseases. Some species can travel a distance of 10 km per night and can fly continuously for up to 4 hours at a speed of 1-2 km/h. Most species are active at night, in the evening or morning. It usually takes a mosquito female about 50 seconds to penetrate the skin of mammals and the subsequent blood meal usually takes about 2.5 minutes. Mosquitoes live for several weeks or months, depending on the environmental conditions. The VectorNet project is a European network of information exchange and sharing of data relating to the geographical distribution of arthropod vectors and transmission of infectious agents between human populations and animals. It aims at the development of strategic plans and vaccination policies which are the main tasks of this time, as well as the development and application of new disinfectants to control vector populations.

  2. Non-invasive brain stimulation to assess and modulate neuroplasticity in Alzheimer's disease.

    PubMed

    Boggio, Paulo Sérgio; Valasek, Claudia Aparecida; Campanhã, Camila; Giglio, Ana Carolina Alem; Baptista, Nathalia Ishikawa; Lapenta, Olivia Morgan; Fregni, Felipe

    2011-10-01

    Alzheimer's disease (AD) is a neurodegenerative and progressive disease related to a gradual decline in cognitive functions such as memory, attention, perceptual-spatial abilities, language, and executive functions. Recent evidence has suggested that interventions promoting neural plasticity can induce significant cognitive gains especially in subjects at risk of or with mild AD. Transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) are non-invasive techniques that can induce significant and long-lasting changes in focal and non-focal neuroplasticity. In this review, we present initial preliminary evidence that TMS and tDCS can enhance performance in cognitive functions typically impaired in AD. Also, we reviewed the initial six studies on AD that presented early findings showing cognitive gains such as in recognition memory and language associated with TMS and tDCS treatment. In addition, we showed that TMS has also been used to assess neuroplasticity changes in AD supporting the notion that cortical excitability is changed in AD due to the neurodegenerative process. Due to the safe profile, cost of these tools, and initial clinical trials results, further studies are warranted in order to replicate and extend the initial findings of rTMS and tDCS as cognitive enhancers in AD. Further trials should explore different targets of stimulation along with different paradigms of stimulation including combination with behavioural interventions.

  3. Lipopolysaccharide subtypes of Haemophilus influenzae type b from an outbreak of invasive disease.

    PubMed Central

    Inzana, T J; Pichichero, M E

    1984-01-01

    Thirty isolates of Haemophilus influenzae type b were obtained during an outbreak of invasive H. influenzae type b disease and were classified by the electrophoretic profile of their lipopolysaccharide (LPS). The LPS was extracted by a rapid micromethod and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and silver staining. The isolates could be divided into 1 of 14 subtypes based on the profile of two to four bands. No subtype was predominant. However, all isolates obtained from duplicate sites of the same individual were of the same subtype. Isolates obtained from two patients (6 weeks apart) who attended the same day-care center differed in LPS subtype but were identical in their major outer membrane protein electrophoretic profile. Nasopharyngeal cultures were obtained from healthy children, their immediate families, and employees of the day-care center. Of 13 H. influenzae isolates examined from these contacts, only 1 was type b, which was obtained from a day-care worker and had the same LPS subtype and major outer membrane protein electrophoretic profile as one of the disease isolates. The remaining nasopharyngeal isolates were untypable, and most, but not all, were different in LPS pattern. Thus, LPS subtyping of H. influenzae type b may be useful in examining the predominance or transmission of a strain during an outbreak and may distinguish some strains not differentiated by outer membrane protein pattern. Images PMID:6333433

  4. Kingella kingae Expresses Four Structurally Distinct Polysaccharide Capsules That Differ in Their Correlation with Invasive Disease

    PubMed Central

    Porsch, Eric A.; Seed, Patrick C.; Heiss, Christian; Naran, Radnaa; Amit, Uri; Yagupsky, Pablo; Azadi, Parastoo; St. Geme, Joseph W.

    2016-01-01

    Kingella kingae is an encapsulated gram-negative organism that is a common cause of osteoarticular infections in young children. In earlier work, we identified a glycosyltransferase gene called csaA that is necessary for synthesis of the [3)-β-GalpNAc-(1→5)-β-Kdop-(2→] polysaccharide capsule (type a) in K. kingae strain 269–492. In the current study, we analyzed a large collection of invasive and carrier isolates from Israel and found that csaA was present in only 47% of the isolates. Further examination of this collection using primers based on the sequence that flanks csaA revealed three additional gene clusters (designated the csb, csc, and csd loci), all encoding predicted glycosyltransferases. The csb locus contains the csbA, csbB, and csbC genes and is associated with a capsule that is a polymer of [6)-α-GlcpNAc-(1→5)-β-(8-OAc)Kdop-(2→] (type b). The csc locus contains the cscA, cscB, and cscC genes and is associated with a capsule that is a polymer of [3)-β-Ribf-(1→2)-β-Ribf-(1→2)-β-Ribf-(1→4)-β-Kdop-(2→] (type c). The csd locus contains the csdA, csdB, and csdC genes and is associated with a capsule that is a polymer of [P-(O→3)[β-Galp-(1→4)]-β-GlcpNAc-(1→3)-α-GlcpNAc-1-] (type d). Introduction of the csa, csb, csc, and csd loci into strain KK01Δcsa, a strain 269–492 derivative that lacks the native csaA gene, was sufficient to produce the type a capsule, type b capsule, type c capsule, and type d capsule, respectively, indicating that these loci are solely responsible for determining capsule type in K. kingae. Further analysis demonstrated that 96% of the invasive isolates express either the type a or type b capsule and that a disproportionate percentage of carrier isolates express the type c or type d capsule. These results establish that there are at least four structurally distinct K. kingae capsule types and suggest that capsule type plays an important role in promoting K. kingae invasive disease. PMID:27760194

  5. Effectiveness of the 10-Valent Pneumococcal Nontypeable Haemophilus influenzae Protein D–Conjugated Vaccine (PHiD-CV) Against Carriage and Acute Otitis Media—A Double-Blind Randomized Clinical Trial in Finland

    PubMed Central

    Vesikari, Timo; Forsten, Aino; Seppä, Ilkka; Kaijalainen, Tarja; Puumalainen, Taneli; Soininen, Anu; Traskine, Magali; Lommel, Patricia; Schoonbroodt, Sonia; Hezareh, Marjan; Moreira, Marta; Borys, Dorota; Schuerman, Lode

    2016-01-01

    After administering the 10-valent pneumococcal polysaccharide nontypeable Haemophilus influenzae protein D–conjugated vaccine (PHiD-CV) to children aged 2–18 months, we observed a reduction in vaccine-type nasopharyngeal carriage, resulting in a reduction of overall pneumococcal nasopharyngeal carriage, which may be important for indirect vaccine effects. We noted a trend toward reduction of acute otitis media. Background This trial (ClinicalTrials.gov identifier NCT00839254), nested within a cluster-randomized double-blind invasive pneumococcal disease effectiveness study in Finland (ClinicalTrials.gov identifier NCT00861380), assessed the effectiveness of the 10-valent pneumococcal polysaccharide nontypeable Haemophilus influenzae protein D–conjugated vaccine (PHiD-CV or PCV10) against bacterial nasopharyngeal carriage and acute otitis media (AOM). Methods Infants (aged 6 weeks to 6 months) received the PHiD-CV or a control vaccine (hepatitis B) (schedule 3+1 or 2+1). Nasopharyngeal swabs were collected at 4 time points post-vaccination from all of the infants and at pre-vaccination from a subset. Parent-reported physician-diagnosed AOM was assessed from first vaccination until last contact (mean follow-up, 18 months). Vaccine effectiveness (VE) was derived as (1 – relative risk)*100, accounting for cluster design in AOM analysis. Significant VE was assessed descriptively (positive lower limit of the non-adjusted 95% confidence interval [CI]). Results The vaccinated cohort included 5093 infants for carriage assessment and 4117 infants for AOM assessment. Both schedules decreased vaccine-serotype carriage, with a trend toward a lesser effect from the 2+1 schedule ( VE across timpoints 19%–56% [3+1] and 1%–38% [2+1]). Trends toward reduced pneumococcal carriage (predominantly vaccine serotypes 6B, 14, 19F, and 23F), decreased carriage of vaccine-related serotype 19A, and small increases at later time points (ages 14–15 months) in non

  6. Rise in invasive serogroup W meningococcal disease in Australia 2013-2015.

    PubMed

    Martin, Nicolee V; Ong, Katherine S; Howden, Benjamin P; Lahra, Monica M; Lambert, Stephen B; Beard, Frank H; Dowse, Gary K; Saul, Nathan

    2016-12-24

    Since 2013, there has been an increase in the number of notified cases of invasive meningococcal disease (IMD) due to serogroup W (MenW) in Australia. In response to this observed increase, the Communicable Diseases Network Australia convened a working group in 2015 to collate and analyse the epidemiology of MenW disease nationally. Enhanced surveillance data collected by jurisdictions were collated and analysed, and whole genome sequencing (WGS) of MenW isolates assessed the genomic relatedness of strains between 2012 and 2015. This report describes that epidemiology. Since 2013, the incidence and proportion of MenW has increased in Australia, rising from an average of 2% of all IMD cases annually (range 0% to 5%) between 1991 and 2012; to 8% (12/149) of cases in 2013, 10% (17/169) in 2014, and 19% (34/182) in 2015. Victoria has been the main affected state, with 50% (17/34) of national cases in 2015. MenW has affected older populations, with a median age between 2003 and 2015 being 44 years. During this period, case fatality was 10.7% (17/159), 2.3 times higher than for all IMD serogroups combined (4.7%, 173/3720). There were 7 deaths due to MenW in 2015 (CFR 21%). WGS has found the majority of Australian isolates cluster within a group of W:P1.5,2:F1-1:ST11 isolates from the United Kingdom and South America, regions where rapid spread and endemic transmission has occurred since 2009. The recent increase in incidence of MenW in Australia is evolving and is being closely monitored. Lessons learned from the international experience will be important in informing the public health response.

  7. Refractory invasive aspergillosis controlled with posaconazole and pulmonary surgery in a patient with chronic granulomatous disease: case report.

    PubMed

    Kepenekli, Eda; Soysal, Ahmet; Kuzdan, Canan; Ermerak, Nezih Onur; Yüksel, Mustafa; Bakır, Mustafa

    2014-01-08

    Invasive aspergillosis is an important cause of morbidity and mortality in immunocompromised patients. Among primary immunodefiencies, chronic granulomatous disease (CGD) has the highest prevalence of invasive fungal diseases. Voriconazole is recommended for the primary treatment of invasive aspergillosis in most patients. In patients whose aspergillosis is refractory to voriconazole, therapeutic options include changing class of antifungal, for example using an amphotericin B formulation, an echinocandin, combination therapy, or further use of azoles. Posaconazole is a triazole derivative which is effective in Aspergillosis prophylaxis and treatment. Rarely, surgical therapy may be needed in some patients. Lesions those are contiguous with the great vessels or the pericardium, single cavitary lesion that cause hemoptysis, lesions invading the chest wall, aspergillosis that involves the skin and the bone are the indications for surgical therapy.Chronic granulomatous disease (CGD) is an inherited immundeficiency caused by defects in the phagocyte nicotinamide adenine dinucleotidephosphate (NADPH) oxidase complex which is mainstay of killing microorganisms. CGD is characterized by recurrent life-threatening bacterial and fungal infections and by abnormally exuberant inflammatory responses leading to granuloma formation, such as granulomatous enteritis, genitourinary obstruction, and wound dehiscence. The diagnosis is made by neutrophil function testing and the genotyping.Herein, we present a case with CGD who had invasive pulmonary aspergillosis refractory to voriconazole and liposomal amphotericine B combination therapy that was controlled with posaconazole treatment and pulmonary surgery.

  8. A Pneumococcal Protein Array as a Platform to Discover Serodiagnostic Antigens Against Infection*

    PubMed Central

    Olaya-Abril, Alfonso; Jiménez-Munguía, Irene; Gómez-Gascón, Lidia; Obando, Ignacio; Rodríguez-Ortega, Manuel J.

    2015-01-01

    Pneumonia is one of the most common and severe diseases associated with Streptococcus pneumoniae infections in children and adults. Etiological diagnosis of pneumococcal pneumonia in children is generally challenging because of limitations of diagnostic tests and interference with nasopharyngeal colonizing strains. Serological assays have recently gained interest to overcome some problems found with current diagnostic tests in pediatric pneumococcal pneumonia. To provide insight into this field, we have developed a protein array to screen the antibody response to many antigens simultaneously. Proteins were selected by experimental identification from a collection of 24 highly prevalent pediatric clinical isolates in Spain, using a proteomics approach consisting of “shaving” the cell surface with proteases and further LC/MS/MS analysis. Ninety-five proteins were recombinantly produced and printed on an array. We probed it with a collection of sera from children with pneumococcal pneumonia. From the set of the most seroprevalent antigens, we obtained a clear discriminant response for a group of three proteins (PblB, PulA, and PrtA) in children under 4 years old. We validated the results by ELISA and an immunostrip assay showed the translation to easy-to-use, affordable tests. Thus, the protein array here developed presents a tool for broad use in serodiagnostics. PMID:26183717

  9. A novel flow cytometry-based assay for the quantification of antibody-dependent pneumococcal agglutination

    PubMed Central

    van der Gaast—de Jongh, Christa E.; Diavatopoulos, Dimitri A.; de Jonge, Marien I.

    2017-01-01

    The respiratory pathogen Streptococcus pneumoniae is a major cause of diseases such as otitis media, pneumonia, sepsis and meningitis. The first step towards infection is colonization of the nasopharynx. Recently, it was shown that agglutinating antibodies play an important role in the prevention of mucosal colonization with S. pneumoniae. Here, we present a novel method to quantify antibody-dependent pneumococcal agglutination in a high-throughput manner using flow cytometry. We found that the concentration of agglutinating antibodies against pneumococcal capsule are directly correlated with changes in the size and complexity of bacterial aggregates, as measured by flow cytometry and confirmed by light microscopy. Using the increase in size, we determined the agglutination index. The cutoff value was set by measuring a series of non-agglutinating antibodies. With this method, we show that not only anti-polysaccharide capsule antibodies are able to induce agglutination but that also anti-PspA protein antibodies have agglutinating capabilities. In conclusion, we have described and validated a novel method to quantify pneumococcal agglutination, which can be used to screen sera from murine or human vaccination studies, in a high-throughput manner. PMID:28288168

  10. Increased utilization of influenza and pneumococcal vaccines in an elderly hospitalized population.

    PubMed

    Bloom, H G; Bloom, J S; Krasnoff, L; Frank, A D

    1988-10-01

    This study compared three interventions designed to increase acceptance of influenza and pneumococcal vaccines among elderly hospitalized patients. All individuals 65 and older able to give informed consent (73 patients) who were admitted to one medical floor of an acute care hospital were randomized to one of three groups. All groups received informational pamphlets explaining influenza and pneumococcal disease, their respective vaccines, and indications for their use. The first group received pamphlets only, the second received nursing follow-up, and the third received trained volunteer follow-up. Patients on another medical floor served as controls. The results showed a significant improvement in vaccine acceptance in all three study groups compared to controls for both influenza (78% vs 0%) and pneumococcal (75% vs 0%) vaccines. The differences among the three groups were not significant. No significant differences were found among patients accepting or refusing vaccination with regard to diagnosis, age, length of stay, sex, or having a private physician. We conclude that a simple educational program followed by offering vaccination before hospital discharge can be easily implemented, and dramatically increase immunization rates in this high risk group.

  11. Cannabidiol reduces host immune response and prevents cognitive impairments in Wistar rats submitted to pneumococcal meningitis.

    PubMed

    Barichello, Tatiana; Ceretta, Renan A; Generoso, Jaqueline S; Moreira, Ana Paula; Simões, Lutiana R; Comim, Clarissa M; Quevedo, João; Vilela, Márcia Carvalho; Zuardi, Antonio Waldo; Crippa, José A; Teixeira, Antônio Lucio

    2012-12-15

    Pneumococcal meningitis is a life-threatening disease characterized by an acute infection affecting the pia matter, arachnoid and subarachnoid space. The intense inflammatory response is associated with a significant mortality rate and neurologic sequelae, such as, seizures, sensory-motor deficits and impairment of learning and memory. The aim of this study was to evaluate the effects of acute and extended administration of cannabidiol on pro-inflammatory cytokines and behavioral parameters in adult Wistar rats submitted to pneumococcal meningitis. Male Wistar rats underwent a cisterna magna tap and received either 10μl of sterile saline as a placebo or an equivalent volume of S. pneumoniae suspension. Rats subjected to meningitis were treated by intraperitoneal injection with cannabidiol (2.5, 5, or 10mg/kg once or daily for 9 days after meningitis induction) or a placebo. Six hours after meningitis induction, the rats that received one dose were killed and the hippocampus and frontal cortex were obtained to assess cytokines/chemokine and brain-derived neurotrophic factor levels. On the 10th day, the rats were submitted to the inhibitory avoidance task. After the task, the animals were killed and samples from the hippocampus and frontal cortex were obtained. The extended administration of cannabidiol at different doses reduced the TNF-α level in frontal cortex. Prolonged treatment with canabidiol, 10mg/kg, prevented memory impairment in rats with pneumococcal meningitis. Although descriptive, our results demonstrate that cannabidiol has anti-inflammatory effects in pneumococcal meningitis and prevents cognitive sequel.

  12. 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

    ERIC Educational Resources Information Center

    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…

  13. Improved survival with an ambulatory model of non-invasive ventilation implementation in motor neuron disease.

    PubMed

    Sheers, Nicole; Berlowitz, David J; Rautela, Linda; Batchelder, Ian; Hopkinson, Kim; Howard, Mark E

    2014-06-01

    Non-invasive ventilation (NIV) increases survival and quality of life in motor neuron disease (MND). NIV implementation historically occurred during a multi-day inpatient admission at this institution; however, increased demand led to prolonged waiting times. The aim of this study was to evaluate the introduction of an ambulatory model of NIV implementation. A prospective cohort study was performed. Inclusion criteria were referral for NIV implementation six months pre- or post-commencement of the Day Admission model. This model involved a 4-h stay to commence ventilation with follow-up in-laboratory polysomnography titration and outpatient attendance. Outcome measures included waiting time, hospital length of stay, adverse events and polysomnography data. Results indicated that after changing to the Day Admission model the median waiting time fell from 30 to 13.5 days (p < 0.04) and adverse events declined (4/17 pre- (three deaths, one acute admission) vs. 0/12 post-). Survival was also prolonged (median (IQR) 278 (51-512) days pre- vs 580 (306-1355) days post-introduction of the Day Admission model; hazard ratio 0.41, p = 0.04). Daytime PaCO2 was no different. In conclusion, reduced waiting time to commence ventilation and improved survival were observed following introduction of an ambulatory model of NIV implementation in people with MND, with no change in the effectiveness of ventilation.

  14. Non-invasive brain stimulation in Parkinson's disease: Exploiting crossroads of cognition and mood.

    PubMed

    Dinkelbach, Lars; Brambilla, Michela; Manenti, Rosa; Brem, Anna-Katharine

    2017-04-01

    Cognitive impairments and depression are common non-motor manifestations in Parkinson's disease (PD). Recent evidence suggests that both partially arise via the same frontostriatal network, opening the opportunity for concomitant treatment with non-invasive brain stimulation (NIBS) techniques such as repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS). In this systematic review, we evaluate the effects of NIBS on cognition and/or mood in 19 placebo-controlled studies involving 561 PD patients. Outcomes depended on the area stimulated and the technique used. rTMS over the dorsolateral-prefrontal cortex (DLPFC) resulted in significant reductions in scores of depressive symptoms with moderate to large effect sizes along with increased performance in several tests of cognitive functions. tDCS over the DLPFC improved performance in several cognitive measures, including executive functions with large effect sizes. Additional effects of tDCS on mood were not detectable; however, only non-depressed patients were assessed. Further confirmatory research is needed to clarify the contribution that NIBS could make in the care of PD patients.

  15. Invasive pulmonary fungal infections in patients with connective tissue disease: a retrospective study from northern China

    PubMed Central

    Ge, H.F.; Liu, X.Q.; Zhu, Y.Q.; Chen, H.Q.; Chen, G.Z.

    2016-01-01

    Invasive pulmonary fungal infection (IPFI) is a potentially fatal complication in patients with connective tissue disease (CTD). The current study aimed to uncover the clinical characteristics and risk factors of patients with IPFI-CTD. The files of 2186 CTD patients admitted to a single center in northern China between January 2011 and December 2013 were retrospectively reviewed. A total of 47 CTD patients with IPFI were enrolled into this study and assigned to the CTD-IPFI group, while 47 uninfected CTD patients were assigned to the control group. Clinical manifestations were recorded, and risk factors of IPFI were calculated by stepwise logistical regression analysis. Forty-seven (2.15%) CTD patients developed IPFI. Systemic lupus erythematosus patients were responsible for the highest proportion (36.17%) of cases with IPFI. Candida albicans (72.3%) accounted for the most common fungal species. CTD-IPFI patients had significantly elevated white blood cell count, erythrocyte sedimentation rate, C-reactive protein and fasting glucose values compared to controls (P<0.05). Cough, sputum and blood in phlegm were the most common symptoms. Risk factors of IPFI in CTD included maximum prednisone dose ≥30 mg/day within 3 months prior to infection, anti-microbial drug therapy, and interstitial pneumonia. CTD patients who have underlying interstitial pneumonia, prior prednisone or multiple antibiotics, were more likely to develop IPFI. PMID:27683823

  16. Molecular diagnostic methods for invasive fungal disease: the horizon draws nearer?

    PubMed

    Halliday, C L; Kidd, S E; Sorrell, T C; Chen, S C-A

    2015-04-01

    Rapid, accurate diagnostic laboratory tests are needed to improve clinical outcomes of invasive fungal disease (IFD). Traditional direct microscopy, culture and histological techniques constitute the 'gold standard' against which newer tests are judged. Molecular diagnostic methods, whether broad-range or fungal-specific, have great potential to enhance sensitivity and speed of IFD diagnosis, but have varying specificities. The use of PCR-based assays, DNA sequencing, and other molecular methods including those incorporating proteomic approaches such as matrix-assisted laser desorption ionisation-time of flight mass spectroscopy (MALDI-TOF MS) have shown promising results. These are used mainly to complement conventional methods since they require standardisation before widespread implementation can be recommended. None are incorporated into diagnostic criteria for defining IFD. Commercial assays may assist standardisation. This review provides an update of molecular-based diagnostic approaches applicable to biological specimens and fungal cultures in microbiology laboratories. We focus on the most common pathogens, Candida and Aspergillus, and the mucormycetes. The position of molecular-based approaches in the detection of azole and echinocandin antifungal resistance is also discussed.

  17. Pneumococcal Colonization Rates in Patients Admitted to a United Kingdom Hospital with Lower Respiratory Tract Infection: a Prospective Case-Control Study

    PubMed Central

    Johnstone, Catherine M. K.; Gritzfeld, Jenna F.; Banyard, Antonia; Hancock, Carole A.; Wright, Angela D.; Macfarlane, Laura; Ferreira, Daniela M.

    2016-01-01

    Current diagnostic tests are ineffective for identifying the etiological pathogen in hospitalized adults with lower respiratory tract infections (LRTIs). The association of pneumococcal colonization with disease has been suggested as a means to increase the diagnostic precision. We compared the pneumococcal colonization rates and the densities of nasal pneumococcal colonization by (i) classical culture and (ii) quantitative real-time PCR (qPCR) targeting lytA in patients with LRTIs admitted to a hospital in the United Kingdom and control patients. A total of 826 patients were screened for inclusion in this prospective case-control study. Of these, 38 patients were recruited, 19 with confirmed LRTIs and 19 controls with other diagnoses. Nasal wash (NW) samples were collected at the time of recruitment. Pneumococcal colonization was detected in 1 patient with LRTI and 3 controls (P = 0.6) by classical culture. By qPCR, pneumococcal colonization was detected in 10 LRTI patients and 8 controls (P = 0.5). Antibiotic usage prior to sampling was significantly higher in the LRTI group than in the control group (19 versus 3; P < 0.001). With a clinically relevant cutoff of >8,000 copies/ml on qPCR, pneumococcal colonization was found in 3 LRTI patients and 4 controls (P > 0.05). We conclude that neither the prevalence nor the density of nasal pneumococcal colonization (by culture and qPCR) can be used as a method of microbiological diagnosis in hospitalized adults with LRTI in the United Kingdom. A community-based study recruiting patients prior to antibiotic therapy may be a useful future step. PMID:26791364

  18. A Risk Prediction Score for Invasive Mold Disease in Patients with Hematological Malignancies

    PubMed Central

    Stanzani, Marta; Lewis, Russell E.; Fiacchini, Mauro; Ricci, Paolo; Tumietto, Fabio; Viale, Pierluigi; Ambretti, Simone; Baccarani, Michele; Cavo, Michele; Vianelli, Nicola

    2013-01-01

    Background A risk score for invasive mold disease (IMD) in patients with hematological malignancies could facilitate patient screening and improve the targeted use of antifungal prophylaxis. Methods We retrospectively analyzed 1,709 hospital admissions of 840 patients with hematological malignancies (2005-2008) to collect data on 17 epidemiological and treatment-related risk factors for IMD. Multivariate regression was used to develop a weighted risk score based on independent risk factors associated with proven or probable IMD, which was prospectively validated during 1,746 hospital admissions of 855 patients from 2009-2012. Results Of the 17 candidate variables analyzed, 11 correlated with IMD by univariate analysis, but only 4 risk factors (neutropenia, lymphocytopenia or lymphocyte dysfunction in allogeneic hematopoietic stem cell transplant recipients, malignancy status, and prior IMD) were retained in the final multivariate model, resulting in a weighted risk score 0-13. A risk score of < 6 discriminated patients with low (< 1%) versus higher incidence rates (> 5%) of IMD, with a negative predictive value (NPV) of 0.99, (95% CI 0.98-0.99). During 2009-2012, patients with a calculated risk score at admission of < 6 had significantly lower 90-day incidence rates of IMD compared to patients with scores > 6 (0.9% vs. 10.6%, P <0.001). Conclusion An objective, weighted risk score for IMD can accurately discriminate patients with hematological malignancies at low risk for developing mold disease, and could possibly facilitate “screening-out” of low risk patients less likely to benefit from intensive diagnostic monitoring or mold-directed antifungal prophylaxis. PMID:24086555

  19. Invasive Haemophilus influenzae disease in the vaccine era in Rio de Janeiro, Brazil

    PubMed Central

    Tuyama, Mari; Corrêa-Antônio, Jessica; Schlackman, Jessica; Marsh, Jane W; Rebelo, Maria C; Cerqueira, Elaine O; Nehab, Márcio; Kegele, Fabíola; Carmo, Getúlio F; Thielmann, Dominique CA; Barroso, Paulo F; Harrison, Lee H; Barroso, David E

    2017-01-01

    BACKGROUND Haemophilus influenzae (Hi) serotype b (Hib) conjugate vaccine was incorporated into the infant immunisation schedule in Brazil in 1999, where Hib was one of the major etiologic sources of community-acquired bacterial meningitis. OBJECTIVES The purpose of this study is to describe the molecular epidemiology of invasive Hi disease in Rio de Janeiro state, Brazil, before and after vaccine introduction. METHODS Surveillance data from 1986 to 2014 were analysed. Hi isolates recovered from cerebrospinal fluid (CSF) or blood from 1993 to 2014 were serotyped by slide agglutination, genotyped by multilocus sequence typing (MLST), and the capsule type evaluation, differentiation of serologically non-typeable isolates, and characterisation of the capsule (cap) locus was done by polymerase chain reaction. Antimicrobial susceptibility testing was performed using E-test. FINDINGS From 1986 to 1999 and from 2000 to 2014, 2580 and 197 (42% without serotype information) confirmed cases were reported, respectively. The case fatality rate was 17% and did not correlate with the strain. Hib and b- variant isolates belonged to ST-6, whereas serotype a isolates belonged to the ST-23 clonal complex. Serotype a appeared to emerge during the 2000s. Non-encapsulated isolates were non-clonal and distinct from the encapsulated isolates. Ampicillin-resistant isolates were either of serotype b or were non-encapsulated, and all of them were β-lactamase-positive but amoxicillin-clavulanic acid susceptible. MAIN CONCLUSIONS Although Hi meningitis became a relatively rare disease in Rio de Janeiro after the introduction of the Hib conjugate vaccine, the isolates recovered from patients have become more diverse. These results indicate the need to implement an enhanced surveillance system to continue monitoring the impact of the Hib conjugate vaccine. PMID:28225904

  20. Decline in pneumococcal meningitis after the introduction of the heptavalent‐pneumococcal conjugate vaccine in northern France

    PubMed Central

    Dubos, F; Marechal, I; Husson, M O; Courouble, C; Aurel, M; Martinot, A