Science.gov

Sample records for pneumococcal invasive disease

  1. Pneumococcal Disease

    MedlinePlus

    ... pneumococcal disease. Quick Facts About Pneumococcal Disease and Vaccination According to WHO, pneumococcal pneumonia and meningitis are ... of antibiotic treatment. (9, 10, 11) Conjugate pneumococcal vaccination is safe and effective for preventing severe childhood ...

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

    PubMed

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

    2016-08-01

    Using a novel porcine model of intravenous Streptococcus pneumoniae infection, we showed that invasive pneumococcal infections induce marked platelet activation and hyperreactivity. This may contribute to the vascular complications seen in pneumococcal infection. PMID:27322088

  3. Invasive pneumococcal disease in Australia, 2009 and 2010.

    PubMed

    Bareja, Chritina; Toms, Cindy; Lodo, Kerryn; de Kluyver, Rachel

    2015-06-01

    Enhanced surveillance for invasive pneumococcal disease (IPD) was conducted in all Australian states and territories in 2009 and 2010 with comprehensive comparative data available since 2002. There were 1,556 cases of IPD notified to the National Notifiable Diseases Surveillance System in Australia in 2009, a notification rate of 7.2 cases per 100,000 population. In 2010 there were 1,640 cases, a notification rate of 7.4 cases per 100,000. The overall rate of IPD in Indigenous Australians was almost 6 times the rate in non-Indigenous Australians in both 2009 and 2010. In 2009 and 2010, notification rates of IPD caused by serotypes included in the 7-valent pneumococcal conjugate vaccine (7vPCV) continued to decrease across all age groups. Rates of IPD caused by non-7vPCV serotypes continued to show an increasing trend in both Indigenous and non-Indigenous children aged less than 5 years. In Indigenous adults (≥50 years), rates of IPD caused by both 23-valent pneumococcal polysaccharide vaccine (23vPPV) serotypes and non-23vPPV serotypes continued to show an overall increase, particularly in 2010. There were 110 deaths attributed to IPD in 2009 and 137 in 2010, although it should be noted that deaths may be under-reported. The number of invasive pneumococcal isolates with reduced penicillin susceptibility remained low and reduced susceptibility to third generation cephalosporins was rare. PMID:26234260

  4. Microarray Analysis of Pneumococcal Gene Expression during Invasive Disease

    PubMed Central

    Orihuela, Carlos J.; Radin, Jana N.; Sublett, Jack E.; Gao, Geli; Kaushal, Deepak; Tuomanen, Elaine I.

    2004-01-01

    Streptococcus pneumoniae is a leading cause of invasive bacterial disease. This is the first study to examine the expression of S. pneumoniae genes in vivo by using whole-genome microarrays available from The Institute for Genomic Research. Total RNA was collected from pneumococci isolated from infected blood, infected cerebrospinal fluid, and bacteria attached to a pharyngeal epithelial cell line in vitro. Microarray analysis of pneumococcal genes expressed in these models identified body site-specific patterns of expression for virulence factors, transporters, transcription factors, translation-associated proteins, metabolism, and genes with unknown function. Contributions to virulence predicted for several unknown genes with enhanced expression in vivo were confirmed by insertion duplication mutagenesis and challenge of mice with the mutants. Finally, we cross-referenced our results with previous studies that used signature-tagged mutagenesis and differential fluorescence induction to identify genes that are potentially required by a broad range of pneumococcal strains for invasive disease. PMID:15385455

  5. Risk Factors for Death from Invasive Pneumococcal Disease, Europe, 2010

    PubMed Central

    Dias, Joana Gomes; Hruba, Frantiska; Lopalco, Pier Luigi; Pastore-Celentano, Lucia; Gauci, Andrew J. Amato

    2015-01-01

    We studied the possible association between patient age and sex, clinical presentation, Streptococcus pneumoniae serotype, antimicrobial resistance, and death in invasive pneumococcal disease cases reported by 17 European countries during 2010. The study sample comprised 2,921 patients, of whom 56.8% were men and 38.2% were >65 years of age. Meningitis occurred in 18.5% of cases. Death was reported in 264 (9.0%) cases. Older age, meningitis, and nonsusceptibility to penicillin were significantly associated with death. Non–pneumococcal conjugate vaccine (PCV) serotypes among children <5 years of age and 7-valent PCV serotypes among persons 5–64 years of age were associated with increased risk for death; among adults >65 years of age, risk did not differ by serotype. These findings highlight differences in case-fatality rates between serotypes and age; thus, continued epidemiologic surveillance across all ages is crucial to monitor the long-term effects of PCVs. PMID:25693604

  6. Invasive pneumococcal disease in Australia, 2011 and 2012.

    PubMed

    Toms, Cindy; de Kluyver, Rachel

    2016-01-01

    In Australia, there were 1,883 cases (8.3 per 100,000 population) of invasive pneumococcal disease (IPD) notified to the National Notifiable Diseases Surveillance System (NNDSS) in 2011 and 1,823 cases (8.0 per 100,000) in 2012. The overall rate of IPD in Indigenous Australians was 9 times the rate of IPD in non-Indigenous Australians in 2011 and 7 times in 2012. Following the July 2011 introduction of the 13-valent pneumococcal conjugate vaccine (13vPCV) to the National Immunisation Program, rates of IPD in children aged less than 5 years decreased from 19.5 per 100,000 in 2011 to 12.6 per 100,000 in 2012. In Indigenous adults aged 50 years or over the rates of IPD caused by serotypes included in the 23-valent pneumococcal polysaccharide vaccine (23vPPV) continued to increase in both 2011 (47.2 per 100,000) and 2012 (51.2 per 100,000). The rates of IPD in non-Indigenous adults aged 65 years or over caused by serotypes included in the 23vPPV also increased in 2011 (10.1 per 100,000) and 2012 (11.2 per 100,000). There were 134 deaths attributable to IPD in 2011 and 126 in 2012, although it should be noted that deaths may be under-reported. The number of invasive pneumococcal isolates with reduced penicillin susceptibility remained low and reduced susceptibility to ceftriaxone/cefotaxime continued to be rare. PMID:27522138

  7. Invasive Pneumococcal Disease in Children Can Reveal a Primary Immunodeficiency

    PubMed Central

    Gaschignard, Jean; Levy, Corinne; Chrabieh, Maya; Boisson, Bertrand; Bost-Bru, Cécile; Dauger, Stéphane; Dubos, François; Durand, Philippe; Gaudelus, Joël; Gendrel, Dominique; Gras Le Guen, Christèle; Grimprel, Emmanuel; Guyon, Gaël; Jeudy, Catherine; Jeziorski, Eric; Leclerc, Francis; Léger, Pierre-Louis; Lesage, Fabrice; Lorrot, Mathie; Pellier, Isabelle; Pinquier, Didier; de Pontual, Loïc; Sachs, Philippe; Thomas, Caroline; Tissières, Pierre; Valla, Frédéric V.; Desprez, Philippe; Frémeaux-Bacchi, Véronique; Varon, Emmanuelle; Bossuyt, Xavier; Cohen, Robert; Abel, Laurent; Casanova, Jean-Laurent; Puel, Anne; Picard, Capucine

    2014-01-01

    Background. About 10% of pediatric patients with invasive pneumococcal disease (IPD) die from the disease. Some primary immunodeficiencies (PIDs) are known to confer predisposition to IPD. However, a systematic search for these PIDs has never been carried out in children presenting with IPD. Methods. We prospectively identified pediatric cases of IPD requiring hospitalization between 2005 and 2011 in 28 pediatric wards throughout France. IPD was defined as a positive pneumococcal culture, polymerase chain reaction result, and/or soluble antigen detection at a normally sterile site. The immunological assessment included abdominal ultrasound, whole-blood counts and smears, determinations of plasma immunoglobulin and complement levels, and the evaluation of proinflammatory cytokines. Results. We included 163 children with IPD (male-to-female ratio, 1.3; median age, 13 months). Seventeen children had recurrent IPD. Meningitis was the most frequent type of infection (87%); other infections included pleuropneumonitis, isolated bloodstream infection, osteomyelitis, endocarditis, and mastoiditis. One patient with recurrent meningitis had a congenital cerebrospinal fluid fistula. The results of immunological explorations were abnormal in 26 children (16%), and a PID was identified in 17 patients (10%), including 1 case of MyD88 deficiency, 3 of complement fraction C2 or C3 deficiencies, 1 of isolated congenital asplenia, and 2 of Bruton disease (X-linked agammaglobulinemia). The proportion of PIDs was much higher in children aged >2 years than in younger children (26% vs 3%; P < .001). Conclusions. Children with IPD should undergo immunological investigations, particularly those aged >2 years, as PIDs may be discovered in up to 26% of cases. PMID:24759830

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

    PubMed Central

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

    2010-01-01

    Invasive pneumococcal disease (IPD) in children with sickle cell disease (SCD) has decreased with prophylactic penicillin, pneumococcal polysaccharide vaccine, and pneumococcal protein-conjugate vaccine (PCV7) usage. We report 10 IPD cases since PCV7 licensure, including a recent surge of non-vaccine serotypes. IPD continues to be a serious risk in SCD. PMID:21193205

  9. Invasive pneumococcal disease in patients with haematological malignancies before routine use of conjugate vaccines in Finland.

    PubMed

    Lindström, Vesa; Aittoniemi, Janne; Lyytikäinen, Outi; Klemets, Peter; Ollgren, Jukka; Silvennoinen, Raija; Nuorti, J Pekka; Sinisalo, Marjatta

    2016-05-01

    The baseline national invasive pneumococcal disease (IPD) incidence rate, serotype distribution and serotype coverage of pneumococcal vaccines were evaluated in patients with Hodgkin's and non-Hodgkin's lymphomas, myeloma and leukaemia within 1 year after haematological diagnosis during 1995-2002, before introduction of pneumococcal conjugate vaccines. Pneumococcal serotype distribution among these patients was different from serotypes causing IPD in the general population. The serotype coverages of PCV13 and PPSV23 were 57% and 64%, respectively, lower than in the general population. This reflects a higher predisposition to IPD in vaccinated patients with haematological malignancies and possibly less benefit of herd immunity gained with the wide use of pneumococcal conjugate vaccines in the general population. This data will be useful as a baseline for determining the future role of adult PCV vaccination in these patient groups. PMID:26635103

  10. Risk factors for invasive pneumococcal disease among Navajo adults.

    PubMed

    Watt, James P; O'Brien, Katherine L; Benin, Andrea L; McCoy, Sandra I; Donaldson, Connie M; Reid, Raymond; Schuchat, Anne; Zell, Elizabeth R; Hochman, Michael; Santosham, Mathuram; Whitney, Cynthia G

    2007-11-01

    Invasive pneumococcal disease (IPD) is 3-5 times more common among Navajo adults than in the general US population. The authors conducted a case-control study to identify risk factors for IPD among Navajo adults. Navajos aged > or =18 years with IPD were identified through prospective, population-based active laboratory surveillance (December 1999-February 2002). Controls matched to cases on age, gender, and neighborhood were selected. Risk factors were identified through structured interviews and medical record reviews. The authors conducted a matched analysis based on 118 cases and 353 controls. Risk factors included in the final multivariable analysis were chronic renal failure (odds ratio (OR) = 2.6, 95% confidence interval (CI): 0.9, 7.7), congestive heart failure (OR = 5.6, 95% CI: 2.2, 14.5), self-reported alcohol use or alcoholism (OR = 2.9, 95% CI: 1.5, 5.4), body mass index (weight (kg)/height (m)(2)) <5th (OR = 3.2, 95% CI: 1.0, 10.6) or >95th (OR = 2.8, 95% CI: 1.0, 8.0) percentile, and unemployment (OR = 2.6, 95% CI: 1.2, 5.5). The population attributable fractions were 10% for chronic renal failure, 18% for congestive heart failure, 30% for self-reported alcohol use or alcoholism, 6% for body mass index, and 20% for unemployment. Several modifiable risk factors for IPD in Navajos were identified. The high prevalence of renal failure, alcoholism, and unemployment among Navajo adults compared with the general US population may explain some of their increased risk of IPD. PMID:17693393

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

    PubMed

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

    2015-07-01

    Streptococcus pneumoniae, a gram-positive diplococcus, is the causative agent of invasive pneumococcal diseases (IPDs) characterized by severe infections such as bacteraemia, sepsis and meningitis. S.pneumoniae and IPDs are situated in the focus of the vaccine studies because of being encompassed of a significant burden of disease in the world, severe mortality and morbidities, and location in vaccine-preventable diseases group. Although S.pneumoniae has more than 90 defined serotypes, certain serotypes are often identified as the cause of IPDs. Individuals with comorbid and chronic diseases, primary or secondary immune deficiencies, and <2 years or >65 years of age are at increased risk for IPDs. Currently, a 23-valent polysaccharide vaccine and also 7, 10 and 13 valent pneumococcal conjugated vaccines (PCV) have been produced for pneumococci. Phase studies of protein based vaccines, which will provide protection independent of serotypes, and 15-valent pneumococcal conjugated vaccine are still ongoing. In Turkey, in November 2008 PCV7 and in April 2011 PCV13 have been implemented in the national immunization program. First case of the pneumococcal unvaccinated cases presented in this report was a 6-year-old girl patient with pneumonia and pleural empyema due to S.pneumoniae serotype 1, without any underlying risk factors. The other case is a 52-days-old male patient, who had a history of pneumococcal septicemia in the newborn period and was followed for bacteremia associated S.pneumoniae serotype 12B and diagnosed as complement deficiency on follow-up. S.pneumoniae serotype 1 is within serotypes covered by 10 and 13 valent pneumococcal conjugate vaccines and pneumococcal polysaccharide vaccine that are in use today, and is a highly invasive strain often isolated in pneumococcal lobar pneumonia and empyema. S.pneumoniae serotype 12B is a non-vaccine serotype not included in any of conjugate and polysaccharide vaccines, and usually obtained in respiratory infections

  12. Passive Cigarette Smoke Exposure and Other Risk Factors for Invasive Pneumococcal Disease in Children: A Case-Control Study

    PubMed Central

    Chun, Colleen S; Weinmann, Sheila; Riedlinger, Karen; Mullooly, John P

    2015-01-01

    Objective: To investigate whether passive cigarette smoke exposure increases the risk of invasive pneumococcal disease in children. Methods: In a population-based case-control study, 171 children aged 0 to 12 years with culture-confirmed invasive pneumococcal disease during the years 1994 to 2004 were identified. Two controls were matched to each case on age and patterns of Health Plan membership. We reviewed medical records of subjects and family members for information on household cigarette smoke exposure within 2 years of the diagnosis of invasive pneumococcal disease. We collected information on sex, race, pneumococcal vaccination, selected medical conditions, and medications in the 3 months before the diagnosis. Results: Similar proportions of cases (25%) and controls (30%) had definite or probable passive smoke exposure (odds ratio [OR] = 0.76, 95% confidence interval [CI] = 0.47–1.2). Cases of invasive pneumococcal disease were more likely to be nonwhite than controls (OR = 4.4, 95% CI = 2.3–8.2). Elevated risk of invasive pneumococcal disease was found in subjects with recent pulmonary diagnoses (OR = 2.2, 95% CI = 1.2–4.0) and recent antibiotic use (OR = 1.6, 95% CI = 1.1–2.3). Conclusions: Passive cigarette smoke exposure was not associated with invasive pneumococcal disease in this pediatric population. Invasive pneumococcal disease was associated with recent pulmonary diagnoses and recent antibiotic use. PMID:25431997

  13. Overview of the disease burden of invasive pneumococcal disease in Asia.

    PubMed

    Bravo, L C

    2009-12-01

    This paper represents a collaborative effort by the Asian Strategic Alliance for Pneumococcal Disease Prevention (ASAP) Working Group to collate data on the disease burden due to invasive pneumococcal disease (IPD) in participating Asian countries and territories; namely, Hong Kong, India, Indonesia, Korea, Macau, Malaysia, Pakistan, the Philippines, Singapore, Sri Lanka, Taiwan and Thailand. A review of both published and unpublished data revealed that the incidence of IPD in some countries is well documented by way of large, long-duration studies, while in other countries, much of the available data have been extrapolated from international studies or have come from small population studies of limited geographical coverage. This paper confirms that data regarding the incidence of IPD in Asia are grossly lacking and reinforces the need for urgent and more substantial studies. PMID:19393708

  14. Clinical Implications of Pneumococcal Serotypes: Invasive Disease Potential, Clinical Presentations, and Antibiotic Resistance

    PubMed Central

    Nahm, Moon H.; Moseley, M. Allen

    2013-01-01

    Streptococcus pneumoniae can asymptomatically colonize the nasopharynx and cause a diverse range of illnesses. This clinical spectrum from colonization to invasive pneumococcal disease (IPD) appears to depend on the pneumococcal capsular serotype rather than the genetic background. According to a literature review, serotypes 1, 4, 5, 7F, 8, 12F, 14, 18C, and 19A are more likely to cause IPD. Although serotypes 1 and 19A are the predominant causes of invasive pneumococcal pneumonia, serotype 14 remains one of the most common etiologic agents of non-bacteremic pneumonia in adults, even after 7-valent pneumococcal conjugate vaccine (PCV7) introduction. Serotypes 1, 3, and 19A pneumococci are likely to cause empyema and hemolytic uremic syndrome. Serotype 1 pneumococcal meningitis is prevalent in the African meningitis belt, with a high fatality rate. In contrast to the capsule type, genotype is more closely associated with antibiotic resistance. CC320/271 strains expressing serotype 19A are multidrug-resistant (MDR) and prevalent worldwide in the era of PCV7. Several clones of MDR serotype 6C pneumococci emerged, and a MDR 6D clone (ST282) has been identified in Korea. Since the pneumococcal epidemiology of capsule types varies geographically and temporally, a nationwide serosurveillance system is vital to establishing appropriate vaccination strategies for each country. PMID:23341706

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

    PubMed Central

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

    2011-01-01

    Defining the propensity of Streptoccocus pneumoniae (SP) serotypes to invade sterile body sites following nasopharyngeal (NP) acquisition has the potential to inform about how much invasive pneumococcal disease (IPD) may occur in a typical population with a given distribution of carriage serotypes. Data from enhanced surveillance for IPD in Massachusetts children ≤7 years in 2003/04, 2006/07 and 2008/09 seasons and surveillance of SP NP carriage during the corresponding respiratory seasons in 16 Massachusetts communities in 2003/04 and 8 of the 16 communities in both 2006/07 and 2008/09 were used to compute a serotype specific “invasive capacity (IC)” by dividing the incidence of IPD due to serotype x by the carriage prevalence of that same serotype in children of the same age. A total of 206 IPD and 806 NP isolates of SP were collected during the study period. An approximate 50-fold variation in the point estimates between the serotypes having the highest (18C, 33F, 7F, 19A, 3 and 22F) and lowest (6C, 23A, 35F, 11A, 35B, 19F, 15A, and 15BC) IC was observed. Point estimates of IC for most of the common serotypes currently colonizing children in Massachusetts were low and likely explain the continued reduction in IPD from the pre-PCV era in the absence of specific protection against these serotypes. Invasive capacity differs among serotypes and as new pneumococcal conjugate vaccines are introduced, ongoing surveillance will be essential to monitor whether serotypes with high invasive capacity emerge (e.g. 33F, 22F) as successful colonizers resulting in increased IPD incidence due to replacement serotypes. PMID:21029807

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

    PubMed Central

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

    2015-01-01

    Invasive pneumococcal disease (IPD) and pneumonia are the major causes of morbidity and deaths in children in the world. The management of IPD and pneumonia is an important economic burden on healthcare systems and families. The aim of this study was to assess the economic burden of IPD and pneumonia among younger children in Taiwan. We used a cost-illness approach to identify the cost categories for analysis in this study according to various perspectives. We obtained data of admission, outpatient, and emergency department visit data from the National Health Insurance Research (NHIR) database for children <5 y of age between January 2008 and December 2008. A prospective survey was administered to the families of patients to obtain detailed personal costs. All costs are presented in US dollars and were estimated by extrapolating 2008 cost data to 2013 price levels. We estimated the number of pneumococcal disease cases that were averted if the PCV-13 vaccine had been available in 2008. The total annual social and hospital costs for IPD were US $4.3 million and US $926,000, respectively. The total annual social and hospital costs for pneumonia were US $150 million and US $17 million, respectively. On average, families spent US $653 or US $218 when their child was diagnosed with IPD or pneumonia, respectively. This cost is approximately 27%–81% of the monthly salary of an unskilled worker. In conclusion, a safe and effective pediatric pneumococcal vaccine is needed to reduce the economic burden caused by pneumococcal infection. PMID:25874476

  17. Pneumococcal serotypes associated with invasive disease in under five children in India & implications for vaccine policy

    PubMed Central

    Balaji, V.; Jayaraman, Ranjith; Verghese, Valsan Philip; Baliga, P.R.; Kurien, T.

    2015-01-01

    Background & objectives: Streptococcus pneumoniae is a major cause of morbidity and mortality especially in children less than five years, particularly in India. We present data on S. pneumoniae infections in children less than five years age group, with response to its serotype distribution, antibiotic resistance profile and available vaccines expected coverage. Methods: Children aged less than five, who were suspected for invasive pneumococcal disease were included in the study and their sterile body fluids were investigated for the presence of S. pneumoniae. Invasive S. pneumoniae isolates from sterile body fluids were identified by bile solubility and optochin susceptibility test. Pneumococcal serotyping was performed with co-agglutination technique and reconfirmed with multiplex PCR. Results: The most common pneumococcal serotypes causing invasive infections in children less than five years of age were 14, 19F, 5, 6A and 6B. Of the 114 S. pneumoniae isolates studied, 110 (96.4%) were non-susceptible to co-trimoxazole and 30 per cent were non-susceptible to erythromycin, 5.2 per cent of the isolates were non-susceptible to penicillin and only 0.8 per cent was non-susceptible to cefotaxime. Interpretation & conclusions: Our results indicate that PCV-10 can protect against 64 per cent of serotypes causing invasive pneumococcal infections. Use of PCV-13 in this region can provide increase in protection upto 74.6 per cent against serotypes causing invasive pneumococcal infections. Incorporating PCV-13 in the Universal Immunization Programme may provide incremental protection against IPD serotypes in the southern region of the country. PMID:26458344

  18. Effectiveness of the 23-valent polysaccharide vaccine against invasive pneumococcal disease in Navajo adults.

    PubMed

    Benin, Andrea L; O'Brien, Katherine L; Watt, James P; Reid, Raymond; Zell, Elizabeth R; Katz, Scott; Donaldson, Connie; Parkinson, Alan; Schuchat, Anne; Santosham, Mathuram; Whitney, Cynthia G

    2003-07-01

    Invasive pneumococcal disease occurs 2-3-fold more often among Navajo adults than among adults in the general United States population. The objective of this observational study was to determine the effectiveness of the 23-valent pneumococcal polysaccharide vaccine (PPV23) among Navajo adults. Active surveillance identified cases of invasive pneumococcal disease during 1996-1997. Three control patients per case patient were matched according to underlying medical conditions, sex, age, and location of medical care. Effectiveness was calculated by regression analysis of case-control sets and by indirect cohort methodology. Diabetes and alcoholism occurred in 41% and 43% of 108 case patients, respectively; 62% of case patients and 64% of control patients were immunized. Overall vaccine effectiveness was 26% (95% confidence interval [CI], -29% to 58%); 15% (95% CI, -116% to 67%) for patients with diabetes and -5% (95% CI, -141% to 54%) for patients with alcoholism. Overall vaccine effectiveness, as determined by use of the indirect cohort methodology, was 35% (95% CI, -33% to 69%). PPV23 was not significantly effective among Navajo adults and may be inadequate to prevent serious pneumococcal disease in this population. PMID:12825175

  19. Recurrent Invasive Pneumococcal Disease Serotype 12F in a Vaccinated Splenectomized Patient

    PubMed Central

    Blaabjerg, Anne Katrine; Schumacher, Anna Holst; Kantsø, Bjørn; Kristensen, Lena Hagelskjær; Schumacher, Helga

    2016-01-01

    This is the first case report of recurrent invasive pneumococcal disease (IPD), specifically, due to serotype 12F. The patient described here was vaccinated with the 23-valent pneumococcal polysaccharide vaccine (PPV23) due to previous splenectomy, and an anti-pneumococcal IgG test concluded that she had responded sufficiently to vaccination. Still, she had a fulminate recurrent infection with PPV23 serotype 12F. We investigated the anti-pneumococcal IgG test, and it turned out that it is based on the geometric mean value of only 12 of the serotypes included in PPV23; 12F is none of them. The reason is that there are no titer cut-offs available for 11 of the PPV23 serotypes, including 12F, neither nationally nor internationally. Yet, this is not specified in the answer to the clinicians. This case illustrates the need for titer cut-offs for the remaining pneumococcal serotypes in available vaccines, in order to get a more accurate estimation of the vaccination coverage for the individual patient. Therefore, more research on this area is warranted, along with a discussion of whether the laboratory answers to the clinicians should be more detailed. PMID:27141317

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

    PubMed

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

    2016-06-01

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

  1. Type I Interferon Protects against Pneumococcal Invasive Disease by Inhibiting Bacterial Transmigration across the Lung

    PubMed Central

    LeMessurier, Kim S.; Häcker, Hans; Chi, Liying; Tuomanen, Elaine; Redecke, Vanessa

    2013-01-01

    Streptococcus pneumoniae infection is a leading cause of bacterial pneumonia, sepsis and meningitis and is associated with high morbidity and mortality. Type I interferon (IFN-I), whose contribution to antiviral and intracellular bacterial immunity is well established, is also elicited during pneumococcal infection, yet its functional significance is not well defined. Here, we show that IFN-I plays an important role in the host defense against pneumococci by counteracting the transmigration of bacteria from the lung to the blood. Mice that lack the type I interferon receptor (Ifnar1−/−) or mice that were treated with a neutralizing antibody against the type I interferon receptor, exhibited enhanced development of bacteremia following intranasal pneumococcal infection, while maintaining comparable bacterial numbers in the lung. In turn, treatment of mice with IFNβ or IFN-I-inducing synthetic double stranded RNA (poly(I:C)), dramatically reduced the development of bacteremia following intranasal infection with S. pneumoniae. IFNβ treatment led to upregulation of tight junction proteins and downregulation of the pneumococcal uptake receptor, platelet activating factor receptor (PAF receptor). In accordance with these findings, IFN-I reduced pneumococcal cell invasion and transmigration across epithelial and endothelial layers, and Ifnar1−/− mice showed overall enhanced lung permeability. As such, our data identify IFN-I as an important component of the host immune defense that regulates two possible mechanisms involved in pneumococcal invasion, i.e. PAF receptor-mediated transcytosis and tight junction-dependent pericellular migration, ultimately limiting progression from a site-restricted lung infection to invasive, lethal disease. PMID:24244159

  2. Temporal Variations among Invasive Pneumococcal Disease Serotypes in Children and Adults in Germany (1992–2008)

    PubMed Central

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

    2010-01-01

    Nationwide surveillance of invasive pneumococcal disease has been conducted in Germany since 1992. From 1992 to 2008, a total of 12,137 isolates from invasive pneumococcal disease were collected. Data on serotypes were available for 9,394 invasive isolates. The leading serotypes were serotypes 14 (16.5%), 3 (8.0%), 7F (7.6%), 1 (7.3%), and 23F (6.0%). Variations in serotype distribution over the years are particularly extensive, especially concerning serotype 14 (min 7.4%, max 33.5%) with the highest percentages among the isolates serotyped from around 1997 to 2006. Serotypes 1 and 7F increased over the last decade. No increase was observed concerning serotype 19A. Higher pneumococcal conjugate vaccine coverages were observed among children (7v, 57.3%; 10v, 72.8%; 13v, 83.5%) than among adults (7v, 39.9%; 10v, 55.5%; 13v, 73.5%). The temporal variations in serotype distribution have to be kept in mind when interpreting vaccine coverages reported in epidemiological studies. PMID:20671944

  3. Minimum Incidence of Adult Invasive Pneumococcal Disease in Blantyre, Malawi an Urban African Setting: A Hospital Based Prospective Cohort Study

    PubMed Central

    Bar-Zeev, Naor; Mtunthama, Neema; Gordon, Stephen B; Mwafulirwa, Gershom; French, Neil

    2015-01-01

    Invasive pneumococcal disease causes substantial morbidity and mortality in Africa. Evaluating population level indirect impact on adult disease of pneumococcal conjugate vaccine (PCV) programmes in infants requires baseline population incidence rates but these are often lacking in areas with limited disease surveillance. We used hospital based blood culture and cerebrospinal fluid surveillance to calculate minimal incidence of invasive pneumococcal disease in the adult (≥15 years old) population of Blantyre, a rapidly growing urban centre in southern Malawi, in the period preceding vaccine introduction. Invasive pneumococcal disease incidence in Blantyre district was high, mean 58.1 (95% confidence interval (CI): 53.7, 62.7) per 100,000 person years and peaking among 35 to 40 year olds at 108.8 (95%CI: 89.0, 131.7) mirroring the population age prevalence of HIV infection. For pneumococcal bacteraemia in urban Blantyre, mean incidence was 60.6 (95% CI: 55.2, 66.5) per 100,000 person years, peaking among 35 to 40 year olds at 114.8 (95%CI: 90.3, 143.9). We suspected that our surveillance may under-ascertain the true burden of disease, so we used location data from bacteraemic subjects and projected population estimates to calculate local sub-district incidence, then examined the impact of community level socio-demographic covariates as possible predictors of local sub-district incidence of pneumococcal and non-pneumococcal pathogenic bacteraemia. Geographic heterogeneity in incidence was marked with localised hotspots but ward level covariates apart from prison were not associated with pneumococcal bacteraemia incidence. Modelling suggests that the current sentinel surveillance system under-ascertains the true burden of disease. We outline a number of challenges to surveillance for pneumococcal disease in our low-resource setting. Subsequent surveillance in the vaccine era will have to account for geographic heterogeneity when evaluating population level indirect

  4. Minimum incidence of adult invasive pneumococcal disease in Blantyre, Malawi an urban african setting: a hospital based prospective cohort study.

    PubMed

    Bar-Zeev, Naor; Mtunthama, Neema; Gordon, Stephen B; Mwafulirwa, Gershom; French, Neil

    2015-01-01

    Invasive pneumococcal disease causes substantial morbidity and mortality in Africa. Evaluating population level indirect impact on adult disease of pneumococcal conjugate vaccine (PCV) programmes in infants requires baseline population incidence rates but these are often lacking in areas with limited disease surveillance. We used hospital based blood culture and cerebrospinal fluid surveillance to calculate minimal incidence of invasive pneumococcal disease in the adult (≥15 years old) population of Blantyre, a rapidly growing urban centre in southern Malawi, in the period preceding vaccine introduction. Invasive pneumococcal disease incidence in Blantyre district was high, mean 58.1 (95% confidence interval (CI): 53.7, 62.7) per 100,000 person years and peaking among 35 to 40 year olds at 108.8 (95%CI: 89.0, 131.7) mirroring the population age prevalence of HIV infection. For pneumococcal bacteraemia in urban Blantyre, mean incidence was 60.6 (95% CI: 55.2, 66.5) per 100,000 person years, peaking among 35 to 40 year olds at 114.8 (95%CI: 90.3, 143.9). We suspected that our surveillance may under-ascertain the true burden of disease, so we used location data from bacteraemic subjects and projected population estimates to calculate local sub-district incidence, then examined the impact of community level socio-demographic covariates as possible predictors of local sub-district incidence of pneumococcal and non-pneumococcal pathogenic bacteraemia. Geographic heterogeneity in incidence was marked with localised hotspots but ward level covariates apart from prison were not associated with pneumococcal bacteraemia incidence. Modelling suggests that the current sentinel surveillance system under-ascertains the true burden of disease. We outline a number of challenges to surveillance for pneumococcal disease in our low-resource setting. Subsequent surveillance in the vaccine era will have to account for geographic heterogeneity when evaluating population level indirect

  5. Which individuals are at increased risk of pneumococcal disease and why? Impact of COPD, asthma, smoking, diabetes, and/or chronic heart disease on community-acquired pneumonia and invasive pneumococcal disease.

    PubMed

    Torres, Antoni; Blasi, Francesco; Dartois, Nathalie; Akova, Murat

    2015-10-01

    Pneumococcal disease (including community-acquired pneumonia and invasive pneumococcal disease) poses a burden to the community all year round, especially in those with chronic underlying conditions. Individuals with COPD, asthma or who smoke, and those with chronic heart disease or diabetes mellitus have been shown to be at increased risk of pneumococcal disease compared with those without these risk factors. These conditions, and smoking, can also adversely affect patient outcomes, including short-term and long-term mortality rates, following pneumonia. Community-acquired pneumonia, and in particular pneumococcal pneumonia, is associated with a significant economic burden, especially in those who are hospitalised, and also has an impact on a patient's quality of life. Therefore, physicians should target individuals with COPD, asthma, heart disease or diabetes mellitus, and those who smoke, for pneumococcal vaccination at the earliest opportunity at any time of the year. PMID:26219979

  6. Which individuals are at increased risk of pneumococcal disease and why? Impact of COPD, asthma, smoking, diabetes, and/or chronic heart disease on community-acquired pneumonia and invasive pneumococcal disease

    PubMed Central

    Torres, Antoni; Blasi, Francesco; Dartois, Nathalie; Akova, Murat

    2015-01-01

    Pneumococcal disease (including community-acquired pneumonia and invasive pneumococcal disease) poses a burden to the community all year round, especially in those with chronic underlying conditions. Individuals with COPD, asthma or who smoke, and those with chronic heart disease or diabetes mellitus have been shown to be at increased risk of pneumococcal disease compared with those without these risk factors. These conditions, and smoking, can also adversely affect patient outcomes, including short-term and long-term mortality rates, following pneumonia. Community-acquired pneumonia, and in particular pneumococcal pneumonia, is associated with a significant economic burden, especially in those who are hospitalised, and also has an impact on a patient's quality of life. Therefore, physicians should target individuals with COPD, asthma, heart disease or diabetes mellitus, and those who smoke, for pneumococcal vaccination at the earliest opportunity at any time of the year. PMID:26219979

  7. Effects of PCV7 and PCV13 on invasive pneumococcal disease and carriage in Stockholm, Sweden.

    PubMed

    Galanis, Ilias; Lindstrand, Ann; Darenberg, Jessica; Browall, Sarah; Nannapaneni, Priyanka; Sjöström, Karin; Morfeldt, Eva; Naucler, Pontus; Blennow, Margareta; Örtqvist, Åke; Henriques-Normark, Birgitta

    2016-04-01

    The effects of pneumococcal conjugated vaccines (PCVs) need to be investigated. In Stockholm County, Sweden, PCV7 was introduced in the childhood immunisation programme in 2007 and changed to PCV13 in 2010.Over 90% of all invasive isolates during 2005-2014 (n=2336) and carriage isolates, 260 before and 647 after vaccine introduction, were characterised by serotyping, molecular typing and antibiotic susceptibility, and serotype diversity was calculated. Clinical information was collected for children and adults with invasive pneumococcal disease (IPD).The IPD incidence decreased post-PCV7, but not post-PCV13, in vaccinated children. Beneficial herd effects were seen in older children and adults, but not in the elderly. The herd protection was more pronounced post-PCV7 than post-PCV13. PCV7 serotypes decreased. IPD caused by PCV13 serotypes 3 and 19A increased post-PCV7. Post-PCV13, serotypes 6A and 19A, but not serotype 3, decreased. The serotype distribution changed in carriage and IPD to nonvaccine types, also in nonvaccinated populations. Expansion of non-PCV13 serotypes was largest following PCV13 introduction. Serotype diversity increased and nonvaccine clones emerged, such as CC433 (serotype 22F) in IPD and CC62 (serotype 11A) in carriage. In young children, meningitis, septicaemia and severe rhinosinusitis, but not bacteraemic pneumonia, decreased.Pneumococcal vaccination leads to expansion of new or minor serotypes/clones, also in nonvaccinated populations. PMID:26797033

  8. Effects of PCV7 and PCV13 on invasive pneumococcal disease and carriage in Stockholm, Sweden

    PubMed Central

    Galanis, Ilias; Lindstrand, Ann; Darenberg, Jessica; Browall, Sarah; Nannapaneni, Priyanka; Sjöström, Karin; Morfeldt, Eva; Naucler, Pontus; Blennow, Margareta; Örtqvist, Åke

    2016-01-01

    The effects of pneumococcal conjugated vaccines (PCVs) need to be investigated. In Stockholm County, Sweden, PCV7 was introduced in the childhood immunisation programme in 2007 and changed to PCV13 in 2010. Over 90% of all invasive isolates during 2005–2014 (n=2336) and carriage isolates, 260 before and 647 after vaccine introduction, were characterised by serotyping, molecular typing and antibiotic susceptibility, and serotype diversity was calculated. Clinical information was collected for children and adults with invasive pneumococcal disease (IPD). The IPD incidence decreased post-PCV7, but not post-PCV13, in vaccinated children. Beneficial herd effects were seen in older children and adults, but not in the elderly. The herd protection was more pronounced post-PCV7 than post-PCV13. PCV7 serotypes decreased. IPD caused by PCV13 serotypes 3 and 19A increased post-PCV7. Post-PCV13, serotypes 6A and 19A, but not serotype 3, decreased. The serotype distribution changed in carriage and IPD to nonvaccine types, also in nonvaccinated populations. Expansion of non-PCV13 serotypes was largest following PCV13 introduction. Serotype diversity increased and nonvaccine clones emerged, such as CC433 (serotype 22F) in IPD and CC62 (serotype 11A) in carriage. In young children, meningitis, septicaemia and severe rhinosinusitis, but not bacteraemic pneumonia, decreased. Pneumococcal vaccination leads to expansion of new or minor serotypes/clones, also in nonvaccinated populations. PMID:26797033

  9. Pneumococcal Disease

    MedlinePlus

    ... is a very serious infection that causes pneumonia, meningitis, and bloodstream infection (sepsis). About one million US ... will die from it. Fewer will get pneumococcal meningitis or sepsis, but the mortality rate in this ...

  10. Effectiveness of a 2+1 dose schedule pneumococcal conjugate vaccination programme on invasive pneumococcal disease among children in Norway.

    PubMed

    Vestrheim, Didrik F; Løvoll, Oistein; Aaberge, Ingeborg S; Caugant, Dominique A; Høiby, E Arne; Bakke, Hilde; Bergsaker, Marianne R

    2008-06-19

    The 7-valent pneumococcal conjugate vaccine (PCV-7) was licensed in Norway in 2001. In July 2006, PCV-7 was introduced in the Norwegian Childhood Vaccination Programme in a 2+1 dose schedule, with immunizations administered at 3, 5 and 12 months of age. PCV-7 was offered through the vaccination programme to all children born from January 2006, i.e. a catch-up for children aged 3-6 months. Prior to 2006 the use of PCV-7 was negligible. The effectiveness of the PCV-7 vaccination programme was assessed using data on invasive pneumococcal disease (IPD) incidence obtained from the Norwegian Surveillance System for Communicable Diseases, serotype distribution from the National Reference Laboratory for Pneumococci, and vaccine coverage and vaccination status from the Norwegian National Vaccination Register. Vaccine coverage quickly reached high levels; 95% of children >3 months born from January 2006 had received at least one immunization with PCV-7. The incidence rate of IPD among children <2 years rapidly declined; the rate of vaccine serotype IPD in this age group fell from an average of 47.1 cases/100,000 population in the 2 years prior to PCV-7 introduction to 13.7 cases/100,000 population in 2007. The incidence rate of nonvaccine serotype IPD remained stable. The vaccine programme effectiveness was estimated to be 74% (95% CI 57-85%). No vaccine failure was seen after complete primary immunization with two vaccine doses. Our findings indicate that PCV-7 provides highly effective protection against vaccine serotype IPD when administered in a 2+1 dose schedule. PMID:18456376

  11. Using pneumococcal carriage data to monitor postvaccination changes in invasive disease.

    PubMed

    Weinberger, Daniel M; Bruden, Dana T; Grant, Lindsay R; Lipsitch, Marc; O'Brien, Katherine L; Pelton, Stephen I; Sanders, Elisabeth A M; Feikin, Daniel R

    2013-11-01

    Pneumococcal conjugate vaccines (PCVs) have been introduced worldwide. However, few developing countries have high-quality surveillance systems available for monitoring vaccine impact. We evaluated whether data from nasopharyngeal carriage studies can be used to accurately monitor post-PCV changes in the incidence of invasive pneumococcal disease (IPD) among children under 5 years of age. For various dates during 1991-2010, data on nasopharyngeal pneumococcal carriage and on IPD before and after administration of 7-valent PCV (PCV7) were available from England and Wales, the Netherlands, the Navajo and White Mountain Apache American Indian populations, and the US states of Massachusetts and Alaska. We estimated the change in carriage prevalence for each serotype in each study and then either calculated the average change (inverse variance-weighted) among vaccine and nonvaccine serotypes (model 1) or used mixed-effects models to estimate the change for each serotype individually, pooling serotype data within or between studies (models 2 and 3). We then multiplied these values by the proportion of IPD caused by each serotype during the pre-PCV7 period to obtain an estimate of post-PCV7 disease incidence. Model 1 accurately captured overall changes in IPD incidence following PCV7 introduction for most studies, while the more detailed models, models 2 and 3, were less accurate. Carriage data can be used in this simple model to estimate post-PCV changes in IPD incidence. PMID:24013204

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

    PubMed

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

    2016-06-01

    This study evaluated the incidence, serotype distribution, and antimicrobial susceptibility of invasive pneumococcal disease (IPD) in Saudi Arabian children. This multicenter, prospective, clinical surveillance study included children under 5years of age, residents of one of the seven study health areas, who were brought to a study hospital with suspicion of IPD. Bacterial isolates from sterile site samples, collected less than 24h after hospital visit/admission, were identified, serotyped, and tested for antibiotic susceptibility. Between June 2007 and January 2009, 631 episodes of suspected IPD were recorded, and 623 were included in the analysis. One child (0.2%) had previously received one dose of a pneumococcal vaccine. Forty-seven episodes were positive for Streptococcus pneumoniae and three for Haemophilus influenzae. The incidence of confirmed IPD cases was estimated to be 2.5-21.6 per 100,000 children (<5years). Among the 46 S. pneumoniae isolates serotyped and tested for antibiotic susceptibility, the most common serotypes were 5 and 23F (20% each), 6B (17%), and 1 and 14 (11% each). Sixty-three percent of isolates were multidrug-resistant. Vaccination of Saudi Arabian children with expanded-coverage conjugate pneumococcal vaccines containing serotypes 1 and 5 could have a substantial impact to prevent IPD in this population. PMID:26368823

  13. 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. PMID:26610421

  14. 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

  15. Epidemiology of Serotype 1 Invasive Pneumococcal Disease, South Africa, 2003–2013

    PubMed Central

    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

    2016-01-01

    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. PMID:26812214

  16. 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. PMID:26812214

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

    PubMed

    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

    2016-03-01

    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

  18. 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

  19. Host Factors and Biomarkers Associated with Poor Outcomes in Adults with Invasive Pneumococcal Disease

    PubMed Central

    Hanada, Shigeo; Iwata, Satoshi; Kishi, Kazuma; Morozumi, Miyuki; Chiba, Naoko; Wajima, Takeaki; Takata, Misako; Ubukata, Kimiko

    2016-01-01

    Background Invasive pneumococcal disease (IPD) causes considerable morbidity and mortality. We aimed to identify host factors and biomarkers associated with poor outcomes in adult patients with IPD in Japan, which has a rapidly-aging population. Methods In a large-scale surveillance study of 506 Japanese adults with IPD, we investigated the role of host factors, disease severity, biomarkers based on clinical laboratory data, treatment regimens, and bacterial factors on 28-day mortality. Results Overall mortality was 24.1%, and the mortality rate increased from 10.0% in patients aged ˂50 years to 33.1% in patients aged ≥80 years. Disease severity also increased 28-day mortality, from 12.5% among patients with bacteraemia without sepsis to 35.0% in patients with severe sepsis and 56.9% with septic shock. The death rate within 48 hours after admission was high at 54.9%. Risk factors for mortality identified by multivariate analysis were as follows: white blood cell (WBC) count <4000 cells/μL (odds ratio [OR], 6.9; 95% confidence interval [CI], 3.7–12.8, p < .001); age ≥80 years (OR, 6.5; 95% CI, 2.0–21.6, p = .002); serum creatinine ≥2.0 mg/dL (OR, 4.5; 95% CI, 2.5–8.1, p < .001); underlying liver disease (OR, 3.5; 95% CI, 1.6–7.8, p = .002); mechanical ventilation (OR, 3.0; 95% CI, 1.7–5.6, p < .001); and lactate dehydrogenase ≥300 IU/L (OR, 2.4; 95% CI, 1.4–4.0, p = .001). Pneumococcal serotype and drug resistance were not associated with poor outcomes. Conclusions Host factors, disease severity, and biomarkers, especially WBC counts and serum creatinine, were more important determinants of mortality than bacterial factors. PMID:26815915

  20. Serotype Changes and Drug Resistance in Invasive Pneumococcal Diseases in Adults after Vaccinations in Children, Japan, 2010-2013.

    PubMed

    Ubukata, Kimiko; Chiba, Naoko; Hanada, Shigeo; Morozumi, Miyuki; Wajima, Takeaki; Shouji, Michi; Iwata, Satoshi

    2015-11-01

    After 7-valent pneumococcal conjugate vaccine (PCV) for children was introduced in Japan in November 2010, we examined changes in Streptococcus pneumoniae serotypes and in genetic antimicrobial drug resistance of isolates from adults with invasive pneumococcal diseases. During April 2010-March 2013, a total of 715 isolates were collected from adults with invasive pneumococcal diseases. Seven-valent PCV serotypes in adults decreased from 43.3% to 23.8%, most noticeably for serotype 6B. Concomitantly, 23-valent pneumococcal polysaccharide vaccine (PPSV23) serotypes decreased from 82.2% to 72.2%; non-PPSV23 serotypes increased from 13.8% to 25.1%. Parallel with serotype changes, genotypic penicillin-resistant S. pneumoniae decreased from 32.4% to 21.1%, and 6 non-PPSV23 serotypes emerged (6D, 15A, 15C, 16F, 23A, and 35B). Respective vaccine coverage rates for 13-valent PCV and PPSV23 differed by disease: 73.9% and 84.3% for patients with pneumonia, 56.4% and 69.2% for patients with bacteremia and sepsis, and 45.7% and 69.3% for patients with meningitis. PMID:26485679

  1. Serotype Changes and Drug Resistance in Invasive Pneumococcal Diseases in Adults after Vaccinations in Children, Japan, 2010–2013

    PubMed Central

    Chiba, Naoko; Hanada, Shigeo; Morozumi, Miyuki; Wajima, Takeaki; Shouji, Michi; Iwata, Satoshi

    2015-01-01

    After 7-valent pneumococcal conjugate vaccine (PCV) for children was introduced in Japan in November 2010, we examined changes in Streptococcus pneumoniae serotypes and in genetic antimicrobial drug resistance of isolates from adults with invasive pneumococcal diseases. During April 2010–March 2013, a total of 715 isolates were collected from adults with invasive pneumococcal diseases. Seven-valent PCV serotypes in adults decreased from 43.3% to 23.8%, most noticeably for serotype 6B. Concomitantly, 23-valent pneumococcal polysaccharide vaccine (PPSV23) serotypes decreased from 82.2% to 72.2%; non-PPSV23 serotypes increased from 13.8% to 25.1%. Parallel with serotype changes, genotypic penicillin-resistant S. pneumoniae decreased from 32.4% to 21.1%, and 6 non-PPSV23 serotypes emerged (6D, 15A, 15C, 16F, 23A, and 35B). Respective vaccine coverage rates for 13-valent PCV and PPSV23 differed by disease: 73.9% and 84.3% for patients with pneumonia, 56.4% and 69.2% for patients with bacteremia and sepsis, and 45.7% and 69.3% for patients with meningitis. PMID:26485679

  2. Factors predicting mortality in invasive pneumococcal disease in adults in Alberta.

    PubMed

    Marrie, Thomas James; Tyrrell, Gregory J; Garg, Sipi; Vanderkooi, Otto G

    2011-05-01

    To define the factors associated with 30-day mortality among adult patients with invasive pneumococcal disease (IPD), we conducted a retrospective review of all cases of IPD in Alberta from 2000 to 2004. We hypothesized that multiple factors would be predictive of such mortality. We also examined the factors predictive of early (within 5 days of admission) mortality. We identified 1154 patients who met our inclusion criteria, 163 (14.1%) of whom died within 30 days. Over half (62.6%) of the deaths occurred within 5 days of admission. Ten factors were independently associated with increased 30-day mortality: 3 comorbidity factors-cancer within 5 years of diagnosis of IPD, diabetes, and cirrhosis; 4 complications-requirement for supplemental oxygen, mechanical ventilation, alteration of mental status, and cardiac arrest; 2 microorganism-related factors-infection with high- or infection with intermediate-mortality serotypes; and 1 treatment-related factor-treatment with a single antibiotic. Age 18-40 years and treatment with 2 antibiotics concurrently were associated with lower 30-day mortality. Comorbid illnesses were not contributory to early mortality (within 5 days of admission); instead, complications (alteration of mental status, requirement for supplemental oxygen, mechanical ventilation, and cardiac arrest) as well as infection with high-mortality serotypes and treatment with a single antibiotic were important. Age 18-40 years, infection with serotypes in the polysaccharide vaccine, and treatment with 2 or more than 2 antibiotics were associated with decreased early mortality. Early mortality accounted for 62.6% of the deaths. In conclusion, we found that mortality in IPD is multifactorial, the factors differ for 5- and 30-day mortality, and mortality is associated with host (age and complications), microorganism (pneumococcal serotypes), and therapeutic factors. Our data indicate that treatment with 2 or more antibiotics effective against Streptococcus

  3. 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

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

    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

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

    PubMed

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

    2015-07-01

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

  6. Serotype-specific differences in short- and longer-term mortality following invasive pneumococcal disease.

    PubMed

    Hughes, G J; Wright, L B; Chapman, K E; Wilson, D; Gorton, R

    2016-09-01

    Invasive pneumococcal disease (IPD), caused by infection with Streptococcus pneumoniae, has a substantial global burden. There are over 90 known serotypes of S. pneumoniae with a considerable body of evidence supporting serotype-specific mortality rates immediately following IPD. This is the first study to consider the association between serotype and longer-term mortality following IPD. Using enhanced surveillance data from the North East of England we assessed both the short-term (30-day) and longer-term (⩽7 years) independent adjusted associations between individual serotypes and mortality following IPD diagnosis using logistic regression and extended Cox proportional hazards models. Of the 1316 cases included in the analysis, 243 [18·5%, 95% confidence interval (CI) 16·4-20·7] died within 30 days of diagnosis. Four serotypes (3, 6A, 9N, 19 F) were significantly associated with overall increased 30-day mortality. Effects were observable only for older adults (⩾60 years). After extension of the window to 12 months and 36 months, one serotype was associated with significantly increased mortality at 12 months (19 F), but no individual serotypes were associated with increased mortality at 36 months. Two serotypes had statistically significant hazard ratios (HR) for longer-term mortality: serotype 1 for reduced mortality (HR 0·51, 95% CI 0·30-0·86) and serotype 9N for increased mortality (HR 2·30, 95% CI 1·29-4·37). The association with serotype 9N was no longer observed after limiting survival analysis to an observation period starting 30 days after diagnosis. This study supports the evidence for associations between serotype and short-term (30-day) mortality following IPD and provides the first evidence for the existence of statistically significant associations between individual serotypes and longer-term variation in mortality following IPD. PMID:27193457

  7. 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

  8. Molecular epidemiology of penicillin-non-susceptible Streptococcus pneumoniae isolates from children with invasive pneumococcal disease in Germany.

    PubMed

    Reinert, R R; van der Linden, M; Seegmüller, I; Al-Lahham, A; Siedler, A; Weissmann, B; Toschke, A M; von Kries, R

    2007-04-01

    A population-based nationwide surveillance of antibiotic resistance associated with invasive pneumococcal disease (IPD) in children and adolescents (aged<16 years) was performed in Germany between 1997 and 2004. In total, 1517 isolates were collected, of which 5.1% and 1.1% were intermediately- or fully-resistant, respectively, to penicillin G. During the 8-year study period, an increase in resistance to both penicillin G and erythromycin A was observed, and the frequency of isolates exhibiting reduced susceptibility to penicillin G or erythromycin A increased from 1.4% and 11.1%, respectively, in 1997, to 8.7% and 29.0%, respectively, in 2004. Among the penicillin non-susceptible pneumococcal isolates, serotypes 14 (24.5% of isolates), 23F (16.0%) and 6B (16.0%) were found most frequently. Multilocus sequence typing of 58 (62%) penicillin G non-susceptible isolates revealed that sequence type (ST) 156 (Spain9V-3 clone) and its single-locus variant ST 557 were widespread in Germany. Moreover, 17 new penicillin G non-susceptible STs were defined for the first time. The study illustrated the genetic heterogeneity of antibiotic-resistant pneumococcal isolates in Germany. PMID:17359319

  9. Invasive Pneumococcal Disease Among Children With and Without Sickle Cell Disease in the United States, 1998 to 2009

    PubMed Central

    Payne, Amanda B.; Link-Gelles, Ruth; Azonobi, Ijeoma; Hooper, W. Craig; Beall, Bernard W.; Jorgensen, James H.; Juni, Billie; Moore, Matthew

    2015-01-01

    Background Children with sickle cell disease (SCD) are at increased risk of illness and death from invasive pneumococcal disease (IPD). The introduction in 2000 of the 7-valent pneumococcal conjugate vaccine (PCV7) and penicillin prophylaxis for children with SCD has greatly reduced the incidence of IPD in this population. However, a recent report suggested an increase in cases of IPD in children with SCD. Methods Using data from Active Bacterial Core surveillance (ABCs), we analyzed trends in hospitalizations, mortality, and serotype among children with SCD compared with other children. We used neonatal screening data to estimate SCD population denominators for each ABCs site. Results From 1998–2009, 3,069 cases of IPD occurred among African-American children less than 18 years of age in the ABCs catchment area. Of these, 127 (4.1%) had SCD identified by medical chart review and 185 (6.0%) had one or more IPD risk factors, excluding SCD. Rates of IPD among children with SCD declined by 53% (1,118 versus 530 per 100,000) while the overall rates among African-American children declined by 74% (54 to 14 per 100,000). For all time periods, children with SCD and IPD were more likely to be hospitalized (84%–92% versus 31%–56%) and more likely to die (6%–17% versus 1%–2%) than children with no risk factors. Conclusions While the rate of IPD in children with SCD has dropped dramatically since PCV7 introduction, the rate of IPD in children with SCD remains higher than that of the general population of African-American children, pointing to the need for more effective prevention efforts to prevent IPD in children with SCD. PMID:23811745

  10. 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

  11. 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

    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

  12. Prompt effect of replacing the 7-valent pneumococcal conjugate vaccine with the 13-valent vaccine on the epidemiology of invasive pneumococcal disease in Norway.

    PubMed

    Steens, Anneke; Bergsaker, Marianne A Riise; Aaberge, Ingeborg S; Rønning, Karin; Vestrheim, Didrik F

    2013-12-16

    The introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) in the childhood immunisation programme in Norway in 2006 substantially decreased the incidence of vaccine-type (VT) invasive pneumococcal disease (IPD) in all age groups. Additionally, a slight increase in the non-vaccine (NVT) serotype IPD incidence (serotype replacement) was observed. After replacing PCV7 with PCV13 in 2011, a further decrease in IPD incidence is expected. However, the protection by the six additional serotypes opens new nasopharyngeal niches for colonisation, which favours conditions for serotype replacement. Close monitoring of IPD therefore remains important in order to quickly detect changes. In this observational retrospective population-based cohort study we used data notified nationally between 1 January 2004 and 31 December 2012 to determine the VT- and NVT-IPD incidences. The diversity in serotype distribution per year was analysed using the Simpson's index of diversity. Immunisation history of young children was obtained from the Norwegian Vaccination Registry to determine vaccine failure. The incidence of VT-IPD decreased in the targeted (<5 years) and non-targeted (≥5) age groups since PCV7 introduction and further decreased after the replacement with PCV13. Only two cases of vaccine failure were identified. This indicates very high effectiveness of the 2+1 schedules with PCV7 or PCV13 and suggests that non-vaccinated individuals profit through indirect protection. The decrease in incidence of PCV7-IPD in non-targeted age groups became larger in later years, indicating a lag phase for the indirect effects, and suggests that the indirect protection of PCV13 will increase in coming years. The incidence of some NVT, specifically serotypes 23B and 15A, increased after PCV13 introduction. This coincided with an increased Simpson's index of diversity in the targeted age group. As this suggests that serotype replacement is again occurring, continues monitoring of IPD

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

    PubMed Central

    Meiring, Susan; Cohen, Cheryl; Quan, Vanessa; de Gouveia, Linda; Feldman, Charles; Karstaedt, Alan; Klugman, Keith P.; Madhi, Shabir A.; Rabie, Helene; Sriruttan, Charlotte; von Gottberg, Anne

    2016-01-01

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

  14. Effectiveness of Pneumococcal Conjugate Vaccines (PCV7 and PCV13) against Invasive Pneumococcal Disease among Children under Two Years of Age in Germany

    PubMed Central

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

    2016-01-01

    Background In this study we calculate the effectiveness of pneumococcal conjugate vaccines (PCV) against invasive pneumococcal disease (IPD) among children under the age of two years using the indirect cohort method. We also discuss the timeliness of vaccination and the residual cases of vaccine type IPD. Methods and Findings From July 2006 until June 2015, 921 IPD cases were reported and for 618 children (67.1%), the vaccination status at the time of infection could be accurately determined. Of these, 379 (61.3%) were vaccinated and 239 (38.7%) were not vaccinated. The adjusted vaccine effectiveness (VE) of PCV7 for all included serotypes + 6A was 80% (95% CI: 63–89) for at least one dose, 97% (89–100) after three primary doses (post primary) and 95% (57–100) post booster. The adjusted overall VE of PCV13 was 86% (74–93) for at least one dose, 85% (62–94) post primary and 91% (61–99) post booster. For the additional serotypes included in PCV13, the adjusted VE was 82% (66–91), 80% (46–93) and 90% (54–98) respectively. The serotype specific VE for at least one dose was high for serotypes 1 (83%; 15–97), 3 (74%; 2–93), 7F (84%; 18–98) and 19A (77%; 47–90). Only 39.5% of children with IPD obtained their first dose of PCV7 according to schedule (2nd dose: 32.9%, 3rd dose: 22.0%, booster dose: 63.6%). For children vaccinated with PCV13 values were slightly better: 43.8%, 33.5%, 26.3% and 74.3% respectively. Among 90 residual cases with PCV7 serotypes, 73 (81.1%) were in unvaccinated children, and 15 (16.7%) in children who had not obtained the number of doses recommended for their age, and only two (2.2%) in children vaccinated according to age. Of 82 cases with PCV13 serotypes occurring after the switch from PCV7 to PCV13, 56 (68.3%) were not vaccinated, 22 (26.8%) were incompletely vaccinated, and four (4.9%) were vaccinated according to age. Conclusions Our data show a high effectiveness of pneumococcal conjugate vaccination in Germany

  15. 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

    2014-05-01

    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. PMID:24674661

  16. Invasive pneumococcal diseases in children and adolescents– a single centre experience

    PubMed Central

    2014-01-01

    Background S. pneumoniae is a major cause of meningitis, pneumonia and sepsis in children. In 2006 universal pneumococcal vaccination was recommended in Germany for all children up to their second birthday. We have compared the prevalence and outcome of IPD at a single hospital before and after the introduction of vaccination. Findings 55 cases of IPD were identified over an 11 year period. Almost half of the patients were younger than 2 years of age. Most of the children were affected by pneumonia. The second highest incidence seen was for meningitis and sepsis. 17 patients exhibited additional complications. Significant pre-existing and predisposing disorders, such as IRAK 4 defect, ALPS or SLE were identified in 4 patients. Complete recovery was seen in 78% of affected children; 11% had a fatal outcome and 11% suffered from long term complications. Only 31% overall had been vaccinated. The most common serotype was 14. Serotypes not covered by any of the current vaccines were also found. Antibiotic treatment commenced with cephalosporins in over 90%. Conclusion Frequency of IPD in our hospital did not decrease after initiation of the pneumococcal vaccination. This might be due to vaccinations not being administered satisfactorily as well as to poor education about the need of the vaccination. Pre-existing diseases must be monitored and treated accordingly and rare deficiencies taken into account when IPD takes a foudroyant course. In addition, antibiotic stewardship has been initiated at this hospital centre as a consequence of the high cephalosporin use detected in this study. PMID:24625087

  17. Burden of Invasive Pneumococcal Disease in Children Aged 1 Month to 12 Years Living in South Asia: A Systematic Review

    PubMed Central

    Jaiswal, Nishant; Singh, Meenu; Thumburu, Kiran Kumar; Bharti, Bhavneet; Agarwal, Amit; Kumar, Ajay; Kaur, Harpreet; Chadha, Neelima

    2014-01-01

    Objective The primary objective was to estimate the burden of invasive pneumococcal disease (IPD) in children aged 1 month to 12 years in South Asian countries. Methods We searched three electronic databases (PubMed, Embase and the Cochrane Library) using a comprehensive search strategy, we manually searched published databases (Index Medicus and Current Contents) and we also searched the bibliographies of the included studies and retrieved reviews. The searches were current through June 2013. Eligible studies (community-based and hospital-based) were pooled and a separate analysis for India was also completed. A meta-regression analysis and heterogeneity analysis were performed. The protocol was registered with PROSPERO registration number CRD42013004483. Results A total of 22 studies surveying 36,714 children were included in the systematic review. Hospital-based prospective studies from South Asia showed that 3.57% of children had IPD, and 15% of all bacterial pneumonia cases were due to Streptococcus pneumoniae. Indian studies showed that the incidence of IPD was 10.58% in children admitted to hospitals with suspected invasive bacterial diseases, and 24% of all bacterial pneumonia cases were due to S. pneumonia. Population-based studies from South Asian countries showed that 12.8% of confirmed invasive bacterial diseases were caused by S. pneumonia whereas retrospective hospital-based studies showed that 28% of invasive bacterial diseases were due to S. pneumoniae. Meta-regression showed that there was a significant influence of the antigen testing method for diagnosing IPD on IPD prevalence. Conclusion S. pneumoniae is responsible for a substantial bacterial disease burden in children of South Asian countries including India despite the presence of high heterogeneity in this meta-analysis. Treatment guidelines must be formulated, and preventive measures like vaccines must also be considered. PMID:24798424

  18. Changing epidemiology of invasive pneumococcal disease following increased coverage with the heptavalent conjugate vaccine in Navarre, Spain.

    PubMed

    Guevara, M; Barricarte, A; Gil-Setas, A; García-Irure, J J; Beristain, X; Torroba, L; Petit, A; Polo Vigas, M E; Aguinaga, A; Castilla, J

    2009-11-01

    The present study evaluated changes in the incidence of invasive pneumococcal disease (IPD) and the pattern of serotypes isolated in Navarre, Spain, after the introduction and increased coverage of the heptavalent pneumococcal conjugate vaccine (PCV7). All cases with isolation of pneumococcus from normally sterile bodily fluids were included. The incidence of IPD in children and adults was compared for the periods 2001-2002 and 2006-2007. By the end of 2002, only 11% of children aged <5 years had received any dose of PCV7, whereas, beginning in 2007, the proportion exceeded 50%. Among the cases of IPD aged <5 years, the percentage of those vaccinated increased from 7% during 2001-2002 to 53% during 2006-2007 (p <0.001). The incidence of IPD from PCV7-serotypes decreased by 85% in children <5 years (p <0.001), by 45% in the population aged 5-64 years (p 0.10) and by 68% in those >or=65 years (p 0.004). By contrast, the incidence of IPD from non-PCV7 serotypes increased by 40% overall (p 0.006). The incidence of IPD from all serotypes did not change significantly in children <5 years (from 83 to 72 per 100 000) or in the total population (from 15.8 to 16.3 per 100 000). The percentage of cases as a result of serotypes 7 and 19A increased significantly in both children and adults. No significant changes were seen in the clinical forms of IPD. The pattern of serotypes causing IPD has changed, in both children and adults, following the increased coverage of PCV7, although the incidence has been reduced only slightly. PMID:19673968

  19. [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. PMID:25107494

  20. 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

    2016-02-01

    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

  1. 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. PMID:26647277

  2. The Serotype Distribution among Healthy Carriers before Vaccination Is Essential for Predicting the Impact of Pneumococcal Conjugate Vaccine on Invasive Disease

    PubMed Central

    Flasche, Stefan; Le Polain de Waroux, Olivier; O’Brien, Katherine L.; Edmunds, W. John

    2015-01-01

    Pneumococcal conjugate vaccines (PCVs) have substantially reduced morbidity and mortality of pneumococcal disease. The impact of the 7-valent PCV on all-serotype invasive pneumococcal disease (IPD) among children was reported to vary between high-income countries. We investigate the ability to predict this heterogeneity from pre-vaccination data. We propose a parsimonious model that predicts the impact of PCVs from the odds of vaccine serotype (VT) among carriers and IPD cases in the pre-PCV period, assuming that VT are eliminated in a mature PCV programme, that full serotype replacement occurs in carriage and that invasiveness of the NVT group is unchanged. We test model performance against the reported impact of PCV7 on childhood IPD in high-income countries from a recent meta-analysis. The odds of pre-PCV7 VT IPD, PCV schedule, PCV coverage and whether a catch up campaign was used for introduction was gathered from the same analysis. We conducted a literature review and meta-analysis to obtain the odds of pre-PCV7 VT carriage in the respective settings. The model predicted the reported impact on childhood IPD of mature PCV programmes; the ratio of predicted and observed incidence risk ratios was close to 1 in all settings. In the high income settings studied differences in schedule, coverage, and catch up campaigns were not associated with the observed heterogeneity in impact of PCV7 on childhood all-serotype IPD. The pre-PCV7 proportion of VT IPD alone also had limited predictive value. The pre-PCV7 proportion of VT carriage and IPD are the main determinants for the impact of PCV7 on childhood IPD and can be combined in a simple model to provide predictions of the vaccine preventable burden of IPD. PMID:25879748

  3. Surveillance of pneumococcal diseases in Central and Eastern Europe

    PubMed Central

    Ceyhan, Mehmet; Dagan, Ron; Sayiner, Abdullah; Chernyshova, Liudmyla; Dinleyici, Ener Çağrı; Hryniewicz, Waleria; Kulcsár, Andrea; Mad'arová, Lucia; Pazdiora, Petr; Sidorenko, Sergey; Streinu-Cercel, Anca; Tambić-Andrašević, Arjana; Yeraliyeva, Lyazzat

    2016-01-01

    ABSTRACT Pneumococcal infection is a major cause of morbidity and mortality worldwide. The burden of disease associated with S. pneumoniae is largely preventable through routine vaccination. Pneumococcal conjugate vaccines (e.g. PCV7, PCV13) provide protection from invasive pneumococcal disease as well as non-invasive infection (pneumonia, acute otitis media), and decrease vaccine-type nasopharyngeal colonisation, thus reducing transmission to unvaccinated individuals. PCVs have also been shown to reduce the incidence of antibiotic-resistant pneumococcal disease. Surveillance for pneumococcal disease is important to understand local epidemiology, serotype distribution and antibiotic resistance rates. Surveillance systems also help to inform policy development, including vaccine recommendations, and monitor the impact of pneumococcal vaccination. National pneumococcal surveillance systems exist in a number of countries in Central and Eastern Europe (such as Croatia, Czech Republic, Hungary, Poland, Romania and Slovakia), and some have introduced PCVs (Czech Republic, Hungary, Kazakhstan, Russia, Slovakia and Turkey). Those countries without established programs (such as Kazakhstan, Russia and Ukraine) may be able to learn from the experiences of those with national surveillance systems. The serotype distributions and impact of PCV13 on pediatric pneumococcal diseases are relatively similar in different parts of the world, suggesting that approaches to vaccination used elsewhere are also likely to be effective in Central and Eastern Europe. This article briefly reviews the epidemiology of pneumococcal disease, presents the latest surveillance data from Central and Eastern Europe, and discusses any similarities and differences in these data as well the potential implications for vaccination policies in the region. PMID:27096714

  4. 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

  5. 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

  6. 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

    2016-04-01

    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. PMID:27103428

  7. Directed vaccination against pneumococcal disease.

    PubMed

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

    2016-06-21

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

  8. 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

    2016-04-01

    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

  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. Pneumococcal Disease: Risk Factors and Transmission

    MedlinePlus

    ... Foundation for Infectious Diseases Sepsis Risk Factors and Transmission Recommend on Facebook Tweet Share Compartir On this ... the brain and spinal cord) Who smoke cigarettes Transmission Pneumococcal bacteria spread from person-to-person by ...

  11. Changing epidemiology of invasive pneumococcal disease in central Australia prior to conjugate vaccine: a 16-year study.

    PubMed

    Torzillo, Paul J; Morey, Frances; Gratten, Mike; Murphy, Denise; Matters, Rex; Dixon, Jeannette

    2007-03-22

    This study reports a 16-year prospective surveillance of invasive disease isolates in central Australian Aborigines. There were 621 (89.6% of total) isolates recovered from Aborigines. The mortality in children less than 5 years of age was 4% but rose to 34.5% in those over 49 years of age. The study documented continuing high rates of disease overall, but with significant reductions in incidence rates for children. In children under 2 years of age, the incidence fell by 32% from 2053 per 100,000 in the period 1985-1990 to 1184 per 100,000 in the period 1996-2000. Rates of disease in adults showed no reduction despite an adult immunisation programme with 23 valent vaccine which occurred in the 1990s. Epidemics of serotypes 1, 5 and 12F were documented during the study period. PMID:17030079

  12. Serotype Distribution and Antimicrobial Resistance of Streptococcus pneumoniae Isolates Causing Invasive and Noninvasive Pneumococcal Diseases in Korea from 2008 to 2014

    PubMed Central

    Bae, Il Kwon; Park, Dongchul; Kim, Na Young; Song, Sae Am; Urm, Sang-Hwa; Shin, Jeong Hwan

    2016-01-01

    Introduction. Streptococcus pneumoniae is an important pathogen with high morbidity and mortality rates. The aim of this study was to evaluate the distribution of common serotypes and antimicrobial susceptibility of S. pneumoniae in Korea. Methods. A total of 378 pneumococcal isolates were collected from 2008 through 2014. We analyzed the serotype and antimicrobial susceptibility for both invasive and noninvasive isolates. Results. Over the 7 years, 3 (13.5%), 35 (10.8%), 19A (9.0%), 19F (6.6%), 6A (6.1%), and 34 (5.6%) were common serotypes/serogroups. The vaccine coverage rates of PCV7, PCV10, PCV13, and PPSV23 were 21.4%, 23.3%, 51.9%, and 62.4% in all periods. The proportions of serotypes 19A and 19F decreased and nonvaccine serotypes increased between 2008 and 2010 and 2011 and 2014. Of 378 S. pneumoniae isolates, 131 (34.7%) were multidrug resistant (MDR) and serotypes 19A and 19F were predominant. The resistance rate to levofloxacin was significantly increased (7.2%). Conclusion. We found changes of pneumococcal serotype and antimicrobial susceptibility during the 7 years after introduction of the first pneumococcal vaccine. It is important to continuously monitor pneumococcal serotypes and their susceptibilities. PMID:27314035

  13. Rare Variants in MYD88, IRAK4 and IKBKG and Susceptibility to Invasive Pneumococcal Disease: A Population-Based Case-Control Study

    PubMed Central

    Ellis, Magda K.; Elliott, Katherine S.; Rautanen, Anna; Crook, Derrick W.; Hill, Adrian V. S.; Chapman, Stephen J.

    2015-01-01

    Although rare variants within the Toll-like receptor signalling pathway genes have been found to underlie human primary immunodeficiencies associated with selective predisposition to invasive pneumococcal disease (IPD), the contribution of variants in these genes to IPD susceptibility at the population level remains unknown. Complete re-sequencing of IRAK4, MYD88 and IKBKG genes was undertaken in 164 IPD cases from the UK and 164 geographically-matched population-based controls. 233 single-nucleotide variants (SNVs) were identified, of which ten were in coding regions. Four rare coding variants were predicted to be deleterious, two variants in MYD88 and two in IRAK4. The predicted deleterious variants in MYD88 were observed as two heterozygote cases but not seen in controls. Frequencies of predicted deleterious IRAK4 SNVs were the same in cases and controls. Our findings suggest that rare, functional variants in MYD88, IRAK4 or IKBKG do not significantly contribute to IPD susceptibility in adults at the population level. PMID:25886387

  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. 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. PMID:27379023

  16. Pneumococcal Disease: Symptoms and Complications

    MedlinePlus

    ... bacteremia and sepsis are blood infections. Symptoms include: Fever Chills Low alertness Pneumococcus bacteria causes up to half of middle ear infections (otitis media). Symptoms include: Ear pain A red, swollen ear drum Fever Sleepiness  Top of Page Complications Some pneumococcal ...

  17. 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

  18. Secular trends (1990-2013) in serotypes and associated non-susceptibility of S. pneumoniae isolates causing invasive disease in the pre-/post-era of pneumococcal conjugate vaccines in Spanish regions without universal paediatric pneumococcal vaccination.

    PubMed

    Fenoll, Asunción; Granizo, Juan-José; Giménez, María-José; Yuste, José; Aguilar, Lorenzo

    2015-10-13

    This study analyzed temporal trends of non-susceptibility/serotypes in invasive pneumococci from Spanish regions where pneumococcal conjugate vaccines (PCVs) were not included in paediatric immunization programmes. All invasive pneumococcal isolates voluntarily sent to the Spanish Reference Laboratory for Pneumococci (January 1990-December 2013) from hospitals located in target study regions were analyzed by age group. The PCV estimated coverage in children <24 months was correlated with 13-valent PCV (PCV13) serotypes trends. A total of 28,124 invasive isolates were analyzed: 3138 (11.2%) from children <24 months, 2161 (7.7%) from children 24-59 months, 781 (2.8%) from children 5-14 years, and 22,044 (78.4%) from adults. The estimated coverage increased from 17.6% (2002) to around 40% (2010-2013). The percentage of PCV13 serotypes among all isolates over time followed a cubic significant trend (R(2)=0.884), with an increasing trend up to 2001 followed by a decrease (more prominent from 2010 onwards). The estimated PCVs coverage was significantly correlated with the decrease in the percentage of PCV13 isolates in children <24 months (r(2)=0.824) and in adults (r(2)=0.786), mainly due to decreases in serotypes 1 and 7F in adults, and in serogroup 6 and serotypes 7F and 19A in children <24 months. None of the non-PCV13 serotypes stood out with substantial increases in the last period. This study showed that the different serotypes (and its associated non-susceptibility trends) were not equally affected by low PCVs disposition. Lack of impact in certain serotypes as serotype 1 (in children 24-59 months), 6C (in all age groups), and 19A (in adults) suggests the need for increasing vaccine coverage in the target vaccine population to increase direct and indirect protection. PMID:26341563

  19. A current and historical perspective on disparities in US childhood pneumococcal conjugate vaccine adherence and in rates of invasive pneumococcal disease: Considerations for the routinely-recommended, pediatric PCV dosing schedule in the United States.

    PubMed

    McLaughlin, John M; Utt, Eric A; Hill, Nina M; Welch, Verna L; Power, Edward; Sylvester, Gregg C

    2016-01-01

    Previous research has suggested that reducing the US 4-dose PCV13 schedule to a 3-dose schedule may provide cost savings, despite more childhood pneumococcal disease. The study also stressed that dose reduction should be coupled with improved PCV adherence, however, US PCV uptake has leveled-off since 2008. An estimated 24-36% of US children aged 5-19 months are already receiving a reduced PCV schedule (i.e., missing ≥1 dose). This raises a practical concern that, under a reduced, 3-dose schedule, a similar proportion of children may receive ≤2 doses. It is also unknown if a reduced, 3-dose PCV schedule in the United States will afford the same disease protection as 3-dose schedules used elsewhere, given lower US PCV adherence. Finally, more assurance is needed that, under a reduced schedule, racial, socioeconomic, and geographic disparities in PCV adherence will not correspond with disproportionately higher rates of pneumococcal disease among poor or minority children. PMID:26376039

  20. Decreasing incidence and changes in serotype distribution of invasive pneumococcal disease in persons aged under 18 years since introduction of 10-valent and 13-valent conjugate vaccines in Portugal, July 2008 to June 2012.

    PubMed

    Aguiar, S I; Brito, M J; Horacio, A N; Lopes, J P; Ramirez, M; Melo-Cristino, J

    2014-01-01

    The 10-valent pneumococcal conjugate vaccine (PCV10) became available in Portugal in mid-2009 and the 13-valent vaccine (PCV13) in early 2010. The incidence of invasive pneumococcal disease (IPD) in patients aged under 18 years decreased from 8.19 cases per 100,000 in 2008–09 to 4.52/100,000 in 2011–12. However, IPD incidence due to the serotypes included in the 7-valent conjugate vaccine (PCV7) in children aged under two years remained constant. This fall resulted from significant decreases in the number of cases due to: (i) the additional serotypes included in PCV10 and PCV13 (1, 5, 7F; from 37.6% to 20.6%), particularly serotype 1 in older children; and (ii) the additional serotypes included in PCV13 (3, 6A, 19A; from 31.6% to 16.2%), particularly serotype 19A in younger children. The decrease in serotype 19A before vaccination indicates that it was not triggered by PCV13 administration. The decrease of serotype 1 in all groups, concomitant with the introduction of PCV10, is also unlikely to have been triggered by vaccination, although PCVs may have intensified and supported these trends. PCV13 serotypes remain major causes of IPD, accounting for 63.2% of isolates recovered in Portugal in 2011–12, highlighting the potential role of enhanced vaccination in reducing paediatric IPD in Portugal. PMID:24698140

  1. Pneumococcal Vaccination Strategies. An Update and Perspective.

    PubMed

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

    2016-06-01

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

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

    PubMed Central

    Whitney, Cynthia G.

    2015-01-01

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

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

    PubMed Central

    2012-01-01

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

  4. Role of pneumococcal vaccination in prevention of pneumococcal disease among adults in Singapore.

    PubMed

    Eng, Philip; Lim, Lean Huat; Loo, Chian Min; Low, James Alvin; Tan, Carol; Tan, Eng Kiat; Wong, Sin Yew; Setia, Sajita

    2014-01-01

    The burden of disease associated with Streptococcus pneumoniae infection in adults can be considerable but is largely preventable through routine vaccination. Although substantial progress has been made with the recent licensure of the new vaccines for prevention of pneumonia in adults, vaccine uptake rates need to be improved significantly to tackle adult pneumococcal disease effectively. Increased education regarding pneumococcal disease and improved vaccine availability may contribute to a reduction in pneumococcal disease through increased vaccination rates. The increase in the elderly population in Singapore as well as globally makes intervention in reducing pneumococcal disease an important priority. Globally, all adult vaccines remain underused and family physicians give little priority to pneumococcal vaccination for adults in daily practice. Family physicians are specialists in preventive care and can be leaders in ensuring that adult patients get the full benefit of protection against vaccine-preventable diseases. They can play a key role in the immunization delivery of new and routine vaccines by educating the public on the risks and benefits associated with vaccines. Local recommendations by advisory groups on vaccination in adults will also help to tackle vaccine preventable diseases in adults. PMID:24729726

  5. Should Pneumococcal Vaccines Eliminate Nasopharyngeal Colonization?

    PubMed

    McDaniel, Larry S; Swiatlo, Edwin

    2016-01-01

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

  6. Should Pneumococcal Vaccines Eliminate Nasopharyngeal Colonization?

    PubMed Central

    Swiatlo, Edwin

    2016-01-01

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

  7. Effective management in clusters of pneumococcal disease: a systematic review.

    PubMed

    Basarab, Marina; Ihekweazu, Chikwe; George, Robert; Pebody, Richard

    2011-02-01

    Outbreaks of serious pneumococcal disease can occur with high attack rates in certain settings. We systematically reviewed studies of interventions implemented in pneumococcal clusters and those reporting the effect of antibiotics on carriage reduction to assess the effectiveness of interventions. Evidence was graded according to the Scottish Intercollegiate Guidelines Network system. Of 28 identified cluster reports, one showed that administration of antibiotics to close contacts reduced risk of pneumococcal disease. In three of four clusters where rifampicin chemoprophylaxis was used and in four of five clusters where penicillin was used no further cases were seen after intervention. In clusters where pneumococcal polysaccharide vaccine was used, subsequent cases occurred, all within around 2 weeks of vaccination, which suggests delayed benefit with this approach (evidence grade D). Use of infection control measures alone was reported in eight clusters, with no further cases being reported in seven (grade D). From 21 selected carriage studies, large carriage reductions were observed consistently with use of penicillin and azithromycin, with median values being 90% and 73%, respectively (grade C). The findings were presented to a working group for pneumococcal cluster guidelines and used to develop key recommendations on the management of clusters that supported prompt use of amoxicillin or azithromycin chemoprophylaxis, pneumococcal vaccination for close contacts, and implementation of infection control measures. PMID:21272792

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

    PubMed

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

    2014-01-01

    Although Streptococcus pneumoniae is a leading cause of childhood disease in South East Asia, little has previously been reported regarding the epidemiology of invasive pneumococcal disease in Malaysia and very few studies have explored pneumococcal epidemiology using multilocus sequence typing (MLST). Here we describe serotype, multilocus sequence type (ST), and penicillin susceptibility of thirty pneumococcal invasive disease isolates received by the University of Malaya Medical Centre between February 2000 and January 2007 and relate this to the serotypes included in current pneumococcal conjugate vaccines. A high level of diversity was observed; fourteen serotypes and 26 sequence types (ST), (11 of which were not previously described) were detected from 30 isolates. Penicillin non-susceptible pneumococci accounted for 33% of isolates. The extent of molecular heterogeneity within carried and disease-causing Malaysian pneumococci remains unknown. Larger surveillance and epidemiological studies are now required in this region to provide robust evidence on which to base future vaccine policy. PMID:24941079

  9. Development of a conjugate vaccine against invasive pneumococcal disease based on capsular polysaccharides coupled with PspA/family 1 protein of Streptococcus pneumoniae.

    PubMed

    Lin, Haiying; Peng, Yonghui; Lin, ZiLin; Zhang, Shuangling; Guo, Yanghao

    2015-01-01

    The efforts were focused on exploring alternative pneumococcal vaccine strategies, aimed at addressing the shortcomings of existing formulations, without compromising efficacy. Our strategy involved the use of the carrier protein, pneumococcal surface protein A (PspA), conjugated with capsular polysaccharides (CPS), to provide effective and non-serotype-dependent protection. In this study, we generated a stable Escherichia coli construct expressing functional PspA from a capsular serotype 6B strain and confirmed it belonging to family 1, which was conjugated with CPS. The distribution of anti-CPS antibody response was almost completely of IgG2a subclass followed by IgG3 and low level of IgG1 subclass, but that of anti-PspA IgG subclass antibodies was almost equal IgG1 and IgG2a subclasses. Though PspA was less conspicuous on the surface of pneumococci than the capsule, the antibodies induced with CPS-rPspA conjugate possessed more accessibility to the surface of Streptococcus pneumoniae serotype 6B and 19F (the same family 1 PspA). By survival experiment, the result suggested that the level of cross-protection after immunized with the conjugate was more measurable within the same family 1. The CPS-rPspA conjugate not only induced CPS-specific protection but also provided PspA specific cross-protection. PMID:25959527

  10. Pneumococcal Polysaccharide Vaccine

    MedlinePlus

    Pneumococcal polysaccharide vaccine (PPSV)Treatment of pneumococcal infections with penicillin and other drugs used to be more effective. But ... the disease, through vaccination, even more important. Pneumococcal polysaccharide vaccine (PPSV) protects against 23 types of pneumococcal ...

  11. Early Changes in the Serotype Distribution of Invasive Pneumococcal Isolates from Children after the Introduction of Extended-valent Pneumococcal Conjugate Vaccines in Korea, 2011-2013

    PubMed Central

    2016-01-01

    This study was performed to measure early changes in the serotype distribution of pneumococci isolated from children with invasive disease during the 3-year period following the introduction of 10- and 13-valent pneumococcal conjugate vaccines (PCVs) in Korea. From January 2011 to December 2013 at 25 hospitals located throughout Korea, pneumococci were isolated among children who had invasive pneumococcal disease (IPD). Serotypes were determined using the Quellung reaction, and the change in serotype distribution was analyzed. Seventy-five cases of IPD were included. Eighty percent of patients were aged 3-59 months, and 32% had a comorbidity that increased the risk of pneumococcal infection. The most common serotypes were 19A (32.0%), 10A (8.0%), and 15C (6.7%). The PCV7 serotypes (4, 6B, 9V, 14, 18C, 19F, 23F, and 6A) accounted for 14.7% of the total isolates and the PCV13 minus PCV7 types (1, 3, 5, 7F and 19A) accounted for 32.0% of the total isolates. Serotype 19A was the only serotype in the PCV13 minus PCV7 group. The proportion of serotype 19A showed decreasing tendency from 37.5% in 2011 to 22.2% in 2013 (P = 0.309), while the proportion of non-PCV13 types showed increasing tendency from 45.8% in 2011 to 72.2% in 2013 (P = 0.108). Shortly after the introduction of extended-valent PCVs in Korea, serotype 19A continued to be the most common serotype causing IPD in children. Subsequently, the proportion of 19A decreased, and non-vaccine serotypes emerged as an important cause of IPD. The impact of extended-valent vaccines must be continuously monitored. PMID:27366006

  12. Early Changes in the Serotype Distribution of Invasive Pneumococcal Isolates from Children after the Introduction of Extended-valent Pneumococcal Conjugate Vaccines in Korea, 2011-2013.

    PubMed

    Cho, Eun Young; Choi, Eun Hwa; Kang, Jin Han; Kim, Kyung-Hyo; Kim, Dong Soo; Kim, Yae-Jean; Ahn, Young Min; Eun, Byung Wook; Oh, Sung Hee; Cha, Sung-Ho; Cho, Hye-Kyung; Hong, Young Jin; Kim, Kwang Nam; Kim, Nam Hee; Kim, Yun-Kyung; Kim, Jong-Hyun; Lee, Hyunju; Lee, Taekjin; Kim, Hwang Min; Lee, Kun Song; Kim, Chun Soo; Park, Su Eun; Kim, Young Mi; Oh, Chi Eun; Ma, Sang Hyuk; Jo, Dae Sun; Choi, Young Youn; Lee, Jina; Bae, Geun-Ryang; Park, Ok; Park, Young-Joon; Kim, Eun Seong; Lee, Hoan Jong

    2016-07-01

    This study was performed to measure early changes in the serotype distribution of pneumococci isolated from children with invasive disease during the 3-year period following the introduction of 10- and 13-valent pneumococcal conjugate vaccines (PCVs) in Korea. From January 2011 to December 2013 at 25 hospitals located throughout Korea, pneumococci were isolated among children who had invasive pneumococcal disease (IPD). Serotypes were determined using the Quellung reaction, and the change in serotype distribution was analyzed. Seventy-five cases of IPD were included. Eighty percent of patients were aged 3-59 months, and 32% had a comorbidity that increased the risk of pneumococcal infection. The most common serotypes were 19A (32.0%), 10A (8.0%), and 15C (6.7%). The PCV7 serotypes (4, 6B, 9V, 14, 18C, 19F, 23F, and 6A) accounted for 14.7% of the total isolates and the PCV13 minus PCV7 types (1, 3, 5, 7F and 19A) accounted for 32.0% of the total isolates. Serotype 19A was the only serotype in the PCV13 minus PCV7 group. The proportion of serotype 19A showed decreasing tendency from 37.5% in 2011 to 22.2% in 2013 (P = 0.309), while the proportion of non-PCV13 types showed increasing tendency from 45.8% in 2011 to 72.2% in 2013 (P = 0.108). Shortly after the introduction of extended-valent PCVs in Korea, serotype 19A continued to be the most common serotype causing IPD in children. Subsequently, the proportion of 19A decreased, and non-vaccine serotypes emerged as an important cause of IPD. The impact of extended-valent vaccines must be continuously monitored. PMID:27366006

  13. 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

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

    PubMed

    Hathaway, Lucy J; Grandgirard, Denis; Valente, Luca G; Täuber, Martin G; Leib, Stephen L

    2016-03-01

    Streptococcus pneumoniaebacteria 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

  15. Pneumococcal Vaccines: Understanding Centers for Disease Control and Prevention Recommendations

    PubMed Central

    Schraufnagel, Dean E.

    2014-01-01

    Streptococcus pneumoniae infection is a common and serious health problem that is best prevented by the pneumococcal vaccine. The first vaccine approved by the U.S. Federal Drug Administration in 1977 contained 14 polysaccharide antigens. An improved vaccine introduced in 1983 included 23 polysaccharide antigens. Both vaccines were effective for immunocompetent adults; however, young children and immunocompromised adults remained susceptible. A pediatric vaccine was developed consisting of the capsular antigens of seven pneumococcal serotypes commonly found in children. The antigens in this preparation are covalently conjugated to diphtheria protein to make them more antigenic. The conjugate vaccine was expanded to include 13 serotypes by 2010. Although more immunogenic, the conjugate vaccine has fewer serotypes than the older 23-valent vaccine. The U.S. Centers for Disease Control and Prevention recommend that children at risk for pneumococcal pneumonia as defined by the presence of chronic disease should receive the 13-valent conjugated vaccine. Adults at risk for pneumococcal pneumonia, which includes those over 65 years of age and those who have a chronic disease, should receive the 23-polysaccharide vaccine. Immunosuppressed patients of any age should receive both vaccines. Adults should be revaccinated once at age 65 years or older with the 23-polysaccharide vaccine provided that at least 5 years have elapsed since the previous vaccination. PMID:25032872

  16. Relating Pneumococcal Carriage Among Children to Disease Rates Among Adults Before and After the Introduction of Conjugate Vaccines.

    PubMed

    Weinberger, Daniel M; Grant, Lindsay R; Weatherholtz, Robert C; Warren, Joshua L; O'Brien, Katherine L; Hammitt, Laura L

    2016-06-01

    The use of pneumococcal conjugate vaccines (PCVs) in children has a strong indirect effect on disease rates in adults. When children are vaccinated with PCVs, other serotypes that are not targeted by the vaccine can increase in frequency (serotype replacement) and reduce the direct and indirect benefits of the vaccine. To understand and predict the likely impacts of serotype replacement, it is important to know how patterns in the transmission of serotypes among children relate to disease rates in adults. We used data on pneumococcal carriage and disease from Navajo Nation children and adults collected before and after the routine use of PCVs (1998-2012). Using regression models within a Bayesian framework, we found that serotype-specific carriage and invasiveness (disease incidence divided by carriage prevalence) had similar patterns in children and adults. Moreover, carriage in children, invasiveness in children, and a serotype-specific random intercept (which captured additional variation associated with the serotypes) could predict the incidence serotype-specific pneumococcal disease in adults 18-39 years of age and those 40 years of age or older in the era of routine use of PCVs. These models could help us predict the effects of future pneumococcal vaccine use in children on disease rates in adults, and the modeling approach developed here could be used to test these findings in other settings. PMID:27188949

  17. Invasive pneumococcal bacteremia in a 9-year-old boy caused by serotype 1: course, treatment and costs.

    PubMed

    Jackowska, Teresa; Zaleska-Ponganis, Joanna; Dziurda, Dominik

    2013-01-01

    Streptococcus pneumoniae is a leading cause of bacteremia, sepsis, meningitis, pneumonia, sinusitis, and acute otitis media in young children. Some serotypes are associated with particular disease syndromes, such as complicated pneumonias in children, or with higher rates of hospitalization in children and are consistently responsible for outbreaks in certain populations. In this report we describe a case of a nine-year-old boy who developed an abscess of pleura and invasive pneumococcal bacteremia. The boy was admitted to the hospital with abdominal pain and vomiting, accompanied by mild cough and fever. Chest X-ray revealed lower left lobe consolidation with pleural inflammation and chest CT showed extensive interstitial-alveolar changes in the left lung with atelectasis and pleural effusion causing a reduction in lung volume up to the fourth rib. From the 6(th) day of hospitalization on, suction drainage and intrapleural administration of alteplase were continued for 5 days. Intravenous antibiotics were administered for subsequent 32 days. The course of disease was complicated with labial herpes and acute adenoviral gastroenteritis. The costs of diagnosis (11.7%), pharmacotherapy (55.2%), hospitalization (30.7%) and additional procedures (2.4%) were about 4,444, while the cost of treatment from the perspective of the National Health Fund was only 1,508. The costs of treating the boy with sepsis caused by S. pneumoniae serotype 1 were thus about three times higher than those from the perspective of providers of the National Health Fund. Administration of a new pneumococcal conjugated vaccine containing serotype 1 (PHiD-CV10 or PCV13) could have prevented invasive pneumococcal disease in the described patient. PMID:22826075

  18. 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

  19. Natural human antibodies to pneumococcus have distinctive molecular characteristics and protect against pneumococcal disease

    PubMed Central

    Baxendale, H E; Johnson, M; Stephens, R C M; Yuste, J; Klein, N; Brown, J S; Goldblatt, D

    2008-01-01

    The molecular and functional characteristics of natural antibody from the preimmune repertoire have not been explored in detail in man. We describe seven human IgM monoclonal antibodies selected on the basis of pneumococcal polysaccharide binding that share both molecular and functional characteristics with natural antibody, suggesting a common B cell lineage origin. Unlike class-switched antibodies, which are serotype-specific, the antibodies were polyreactive and bound all pneumococcal polysaccharide capsular serotypes tested. Some bound endogenous antigens, including blood group antigens and intermediate filament proteins. All the antibodies used unmutated heavy chain V (IGHV) that are expressed at an increased frequency in the elderly and in the preimmune repertoire. The CDR3 was characterized by long length (mean aa 18·4 (±4·2) and selective use of IGHD6 (P < 0·001) and IGHJ6 (P < 0·01) family genes. The clones expressing IGHV1-69 and IGHV 3-21 provided significant passive protection against invasive pneumococcal disease in vivo. PMID:17983446

  20. Assessing the Immunogenic Response of a Single Center's Pneumococcal Vaccination Protocol in Sickle Cell Disease.

    PubMed

    Santoro, Jonathan D; Myers, Leann; Kanter, Julie

    2016-04-01

    Sickle cell disease (SCD) is the most common inherited hematologic disorder in the United States. Patients with SCD are at increased risk of invasive pneumococcal disease and are reliant on both early penicillin prophylaxis and antipneumococcal vaccination for prevention of infection. Although studies examining vaccine response have demonstrated a drop-off of titer response after 3 years, an optimal vaccination regimen has not been identified. Our study sought to assess the immunogenicity of our center's pneumococcal vaccination strategy, which included Prevnar (PCV-7) (before the introduction of PCV-13) followed by Pneumovax (PPV-23) given routinely at 2 and 5 years of age and then every 5 years thereafter. Our goal was to assess vaccine response in a population of patients with SCD who had received vaccines according to this regimen using multiplex bead analysis. Our study demonstrated a significant percentage of persons with SCD do not maintain a sufficient vaccination response to PPV-23 for 5 years. Our study revealed that only 36% of patients had protective levels of antipneumococcal antibody titers at an average of 37 months after vaccination. Most alarmingly, within the group of patients with subtherapeutic titers, 64% demonstrated vaccine response to <25% of the tested serotypes. These findings were significantly associated with duration of time since last vaccine administration, but the mean age of lack of response was below the 3-year window where vaccine response was previously reported to wane. Our results indicate antipneumococcal immunity may not be optimally maintained using this vaccination strategy in patients with SCD leaving them vulnerable to invasive pneumococcal disease. Many pediatric hematologists stop prophylactic penicillin at 5 years of age making these results alarming. We recommend further investigation into an optimal vaccine schedule and monitoring of antipneumococcal titers in at-risk patients. PMID:26886376

  1. 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

  2. A Virtual Clinic Improves Pneumococcal Vaccination for Asplenic Veterans at High Risk for Pneumococcal Disease

    PubMed Central

    Jump, Robin L.; Banks, Richard; Wilson, Brigid; Montpetite, Michelle M.; Carter, Rebecca; Phillips, Susan; Perez, Federico

    2015-01-01

    We developed a “virtual clinic” to improve pneumococcal vaccination among asplenic adults. Using an electronic medical record, we identified patients, assessed their vaccination status, entered orders, and notified patients and providers. Within 180 days, 38 of 76 patients (50%) received a pneumococcal vaccination. A virtual clinic may optimize vaccinations among high-risk patients. PMID:26668815

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

    PubMed

    van den Bosch, W J H M

    2002-05-01

    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. PMID:12038219

  4. 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

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

    PubMed

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

    2016-07-01

    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

  6. Intranasal immunization with pneumococcal polysaccharide conjugate vaccines with nontoxic mutants of Escherichia coli heat-labile enterotoxins as adjuvants protects mice against invasive pneumococcal infections.

    PubMed

    Jakobsen, H; Schulz, D; Pizza, M; Rappuoli, R; Jónsdóttir, I

    1999-11-01

    Host defenses against Streptococcus pneumoniae depend largely on phagocytosis following opsonization by polysaccharide-specific immunoglobulin G (IgG) antibodies and complement. Since colonization of the respiratory mucosa is the first step in pneumococcal pathogenesis, mucosal immune responses may play a significant role. In addition to inducing systemic immune responses, mucosal vaccination with an effective adjuvant has the advantage of inducing mucosal IgA antibodies. The heat-labile enterotoxin (LT) of Escherichia coli is a well-studied mucosal adjuvant, and adjuvant activity of nontoxic LT mutants has been demonstrated for several protein antigens. We investigated the immunogenicity of pneumococcal polysaccharide conjugate vaccines (PNC) of serotypes 1 and 3 in mice after intranasal (i.n.) immunization by using as an adjuvant the nontoxic LT mutant LT-K63 or LT-R72, which has minimal residual toxicity. Pneumococcal serotype-specific antibodies were measured in serum (IgM, IgG, and IgA) and saliva (IgA), and vaccine-induced protection was evaluated by i.n. challenge with virulent pneumococci of the homologous serotype. When administered with LT mutants, i.n. immunization with both conjugates induced systemic and mucosal immune responses, and serum IgG antibody levels were significantly higher than after subcutaneous immunization. All mice immunized i.n. with PNC-1 and LT mutants were protected against bacteremia and cleared the pneumococci from the lung 24 h after i.n. challenge; pneumococcal density correlated significantly with serum IgG antibody levels. Similarly, the survival of mice immunized i.n. with PNC-3 and LT mutants was significantly prolonged. These results demonstrate that i.n. vaccination with PNC and potent adjuvants can protect mice against invasive and lethal pneumococcal infections, indicating that mucosal vaccination with PNC may be an alternative vaccination strategy for humans. PMID:10531245

  7. Postvaccination increase in serotype 19A pneumococcal disease in Norway is driven by expansion of penicillin-susceptible strains of the ST199 complex.

    PubMed

    Vestrheim, Didrik F; Steinbakk, Martin; Aaberge, Ingeborg S; Caugant, Dominique A

    2012-03-01

    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

  8. 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

  9. Pneumococcal Vaccine in Diabetes: Relevance in India.

    PubMed

    Shashank, R Joshi; Samika, S Joshi; Siddharth, N Shah

    2015-04-01

    Currently we have more than 65 million Diabetes patients in India with estimated 80 million prediabetics. Diabetes is a immunologically vulnerable population to develop all types of microbial infections. Pneumoccocal infections do have a substantial morbidity and mortality burden in the community. India has a large geriatric pool now which has substantially increased pneumococcal disease burden. Diabetes is a well-known risk factor for pneumococcal infection and predisposes individuals to nasopharyngeal colonization with the pneumococcus which is associated with invasive infection. In diabetics who are elderly, with chronic kidney or pulmonary disease and long standing duration of the disease with poor glycemic control are the highest risk group susceptible to invasive pneumococcal disease. With now availibilty of Pneumoccal vaccine in India, now it may be an preventive option which can be offered. Most global organisations recommend pneumococcal vaccination to diabetics. PMID:26562963

  10. 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. PMID:22384845

  11. 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

  12. South Asia symposium on pneumococcal disease and the promise of vaccines - Meeting report.

    PubMed

    Kumar, Rakesh; Arora, Narendra; Santosham, Mathuram

    2016-05-17

    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

  13. Non-invasive pneumococcal pneumonia in Portugal--serotype distribution and antimicrobial resistance.

    PubMed

    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

  14. Pneumococcal hemolytic uremic syndrome and steroid resistant nephrotic syndrome.

    PubMed

    Groves, Andrew P; Reich, Patrick; Sigdel, Binayak; Davis, T Keefe

    2016-08-01

    Pneumococcal-associated hemolytic uremic syndrome (pHUS) is a rare but severe complication of invasive Streptococcus pneumoniae infection. We report the case of a 12-year-old female with steroid-resistant nephrotic syndrome treated with adrenocorticotrophic hormone (H.P. Acthar(®) Gel), who developed pneumococcal pneumonia and subsequent pHUS. While nephrotic syndrome is a well-known risk factor for invasive pneumococcal disease, this is the first reported case of pHUS in an adolescent patient with nephrotic syndrome, and reveals novel challenges in the diagnosis, treatment and potential prevention of this complication. PMID:27478599

  15. 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. PMID:23025421

  16. Evolving role of 13-valent pneumococcal conjugate vaccine in clinical practice.

    PubMed

    Azzari, Chiara; Martinón-Torres, Federico; Schmitt, Heinz-Josef; Dagan, Ron

    2014-08-01

    Since the introduction of 7-valent pneumococcal conjugate vaccine (PCV7), PCVs with extended coverage have become available, and there is emerging global evidence that these vaccines, in particular PCV13, have further reduced rates of invasive pneumococcal disease compared with PCV7. The present article aims to address emerging topics related to PCV13 use in routine clinical practice; specifically: (1) the potential role of high-valent PCVs in reducing pneumococcal disease burden; (2) the impact of PCVs on nasopharyngeal carriage and how this may contribute to reductions in otitis media and pneumonia, as well as the prevalence of resistant pneumococcal strains; (3) new PCV13 indications and (4) importance of schedule adherence for PCV in the prevention of cases of vaccine serotype-specific invasive pneumococcal disease. The beneficial effects of PCVs in protecting individuals from a wide spectrum of pneumococcal diseases can be increased by improving the vaccine coverage and adhering to the recommended vaccination schedules. There is increasing evidence that PCV13 has reduced much of the post-PCV7 burden of pneumococcal diseases in the pediatric community, including reducing pneumococcal colonization and the incidence of invasive pneumococcal disease and mucosal diseases. This has also led to a reduction in antibiotic-resistant pneumococcal diseases. The role of PCV13 in clinical practice is evolving, with PCV13 now available for children and adolescents between the ages of 6 weeks and 17 years, thus ensuring that children in all age groups can be protected against vaccine-serotype pneumococcal diseases. Continued surveillance is warranted to monitor the impact of PCV13 on disease burden. PMID:24618937

  17. Theory and strategy for Pneumococcal vaccines in the elderly.

    PubMed

    Namkoong, Ho; Ishii, Makoto; Funatsu, Yohei; Kimizuka, Yoshifumi; Yagi, Kazuma; Asami, Takahiro; Asakura, Takanori; Suzuki, Shoji; Kamo, Testuro; Fujiwara, Hiroshi; Tasaka, Sadatomo; Betsuyaku, Tomoko; Hasegawa, Naoki

    2016-01-01

    Pneumonia is the fourth-leading cause of death globally, and Streptococcus pneumoniae is the most important causative pathogen. Because the incidence of pneumococcal diseases is likely to increase with the aging society, we should determine an optimal strategy for pneumococcal vaccination. While consensus indicates that 23-valent pneumococcal polysaccharide vaccine prevents invasive pneumococcal diseases (IPD), its effects on community-acquired pneumonia (CAP) remain controversial. Recently, a 13-valent pneumococcal conjugate vaccine (PCV13) was released. The latest clinical study (CAPiTA study) showed that PCV13 reduced vaccine-type CAP and IPD. Based on these results, the Advisory Committee on Immunization Practices recommended initial vaccination with PCV13 for the elderly. Scientific evidence regarding immunosenescence is needed to determine a more ideal vaccination strategy for the elderly with impaired innate and adaptive immunity. Continuing research on the cost effectiveness of new vaccine strategies considering constantly changing epidemiology is also warranted. PMID:26406267

  18. [Pneumococcal vaccination for children and adults].

    PubMed

    Albrich, Werner

    2016-01-01

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

  19. Serotype-Specific Pneumococcal Status prior to PCV 13 Administration in Children and Adolescents with Inflammatory Bowel Disease.

    PubMed

    Banaszkiewicz, Aleksandra; Targońska, Brygida; Kowalska-Duplaga, Kinga; Karolewska-Bochenek, Katarzyna; Sieczkowska, Agnieszka; Gawrońska, Agnieszka; Grzybowska-Chlebowczyk, Urszula; Krzesiek, Elzbieta; Łazowska-Przeorek, Izabella; Kotowska, Maria; Sienkiewicz, Edyta; Walkowiak, Jarosław; Gregorek, Hanna; Radzikowski, Andrzej; Albrecht, Piotr

    2016-01-01

    The aim of this study was to evaluate the serotype-specific pneumococcal status of children and adolescents with inflammatory bowel disease (IBD) who were naïve to pneumococcal vaccination before administering the 13-valent pneumococcal conjugate vaccine (PCV 13). This was an open, prospective study on children and adolescents aged 5-18 years who had IBD and were naïve to pneumococcal vaccination. A single dose of PCV 13 was administered to each patient. The geometric mean concentrations (GMCs) were measured for all 13 serotypes. A total of 122 subjects completed the study. Prevaccination GMCs ranged from 0.55 μg/ml (serotype 4) to 4.26 μg/mI (serotype 19A). Prior to the administration of PCV 13, high GMCs were detected in older children and adolescents who had IBD and were naïve to pneumococcal vaccination. PMID:27281998

  20. Pneumococcal Conjugate Vaccine (PCV13)

    MedlinePlus

    ... to protect infants and toddlers, and some older children and adults with certain health conditions, from pneumococcal disease.Pneumococcal disease is caused by infection with Streptococcus pneumoniae bacteria. These bacteria can spread from person ...

  1. Infiltrated Macrophages Die of Pneumolysin-Mediated Necroptosis following Pneumococcal Myocardial Invasion.

    PubMed

    Gilley, Ryan P; González-Juarbe, Norberto; Shenoy, Anukul T; Reyes, Luis F; Dube, Peter H; Restrepo, Marcos I; Orihuela, Carlos J

    2016-05-01

    Streptococcus pneumoniae (the pneumococcus) is capable of invading the heart. Herein we observed that pneumococcal invasion of the myocardium occurred soon after development of bacteremia and was continuous thereafter. Using immunofluorescence microscopy (IFM), we observed that S. pneumoniae replication within the heart preceded visual signs of tissue damage in cardiac tissue sections stained with hematoxylin and eosin. Different S. pneumoniae strains caused distinct cardiac pathologies: strain TIGR4, a serotype 4 isolate, caused discrete pneumococcus-filled microscopic lesions (microlesions), whereas strain D39, a serotype 2 isolate, was, in most instances, detectable only using IFM and was associated with foci of cardiomyocyte hydropic degeneration and immune cell infiltration. Both strains efficiently invaded the myocardium, but cardiac damage was entirely dependent on the pore-forming toxin pneumolysin only for D39. Early microlesions caused by TIGR4 and microlesions formed by a TIGR4 pneumolysin-deficient mutant were infiltrated with CD11b(+) and Ly6G-positive neutrophils and CD11b(+) and F4/80-positive (F4/80(+)) macrophages. We subsequently demonstrated that macrophages in TIGR4-infected hearts died as a result of pneumolysin-induced necroptosis. The effector of necroptosis, phosphorylated mixed-lineage kinase domain-like protein (MLKL), was detected in CD11b(+) and F4/80(+) cells associated with microlesions. Likewise, treatment of infected mice and THP-1 macrophages in vitro with the receptor-interacting protein 1 kinase (RIP1) inhibitor necrostatin-5 promoted the formation of purulent microlesions and blocked cell death, respectively. We conclude that pneumococci that have invaded the myocardium are an important cause of cardiac damage, pneumolysin contributes to cardiac damage in a bacterial strain-specific manner, and pneumolysin kills infiltrated macrophages via necroptosis, which alters the immune response. PMID:26930705

  2. Rationale and prospects for novel pneumococcal vaccines.

    PubMed

    Moffitt, Kristin; Malley, Richard

    2016-01-01

    Streptococcus pneumoniae remains one of the most frequent bacterial causes of morbidity and mortality worldwide. National immunization programs implementing pneumococcal polysaccharide conjugate vaccines (PCVs) have successfully reduced rates of vaccine-type invasive disease and colonization both via direct effects in immunized children and, in some settings, indirect effects in unimmunized individuals. Limitations of the current PCV approach include the emergence of non-vaccine serotypes contributing to carriage and invasive disease in high-PCV coverage settings and the high cost of goods of PCVs which limits their accessibility in developing countries where the burden of disease remains highest. Furthermore, the distribution of serotypes causing disease varies geographically and includes more serotypes than are currently covered in a single PCV formulation. Researchers have long been exploring the potential of genetically conserved non-capsular pneumococcal antigens as vaccine candidates that might overcome such limitations. To better evaluate the rationale of such approaches, an understanding of the mechanisms of immunity to the various phases of pneumococcal infection is of paramount importance. Herein we will review the evolving understanding of both vaccine-induced and naturally acquired immunity to pneumococcal colonization and infection and discuss how this informs current approaches using serotype-independent pneumococcal vaccine candidates. We will then review the alternative vaccine candidates that have been or are currently under evaluation in clinical trials. PMID:26535755

  3. Call to action on pneumococcal disease: review of vaccination evidence and outcomes of webcast programs.

    PubMed

    Grogg, Stanley E; Schultz, Jan

    2015-06-01

    In 2015, the Advisory Committee on Immunization Practices issued updated recommendations for the use of 13-valent pneumococcal conjugate vaccine (PCV13) and 23-valent pneumococcal polysaccharide vaccine (PPSV23) to immunize adults aged 19 to 64 years with risk factors and all adults aged 65 years or older. Despite these recommendations, rates of vaccination among adults remain low. Federal and state initiatives have been launched to encourage health care providers to incorporate vaccination screening and recommendations in practice. Several resources are available to improve vaccination rates, including implementing electronic medical records; engaging non-physician staff in assessing vaccination history and administering immunizations; adopting standing order protocols; and implementing strong recommendations to patients regarding needed immunizations. However, even in the face of compelling evidence-based research, implementing changes in practice is challenging. The American Osteopathic Association implemented a 2-part Web program called the Call to Action on Pneumococcal Disease. Although some changes in attitudes and intent to change were demonstrated by this initiative, there were no statistically significant increases in self-reported actual adoption of standing order protocols or increases in adult pneumococcal immunization. Nonetheless, some lessons were learned, and these results support the need for ongoing efforts in this area of medicine. PMID:26000904

  4. Density and duration of experimental human pneumococcal carriage

    PubMed Central

    Gritzfeld, J F; Cremers, A J H; Ferwerda, G; Ferreira, D M; Kadioglu, A; Hermans, P W M; Gordon, S B

    2014-01-01

    The density and duration of pneumococcal carriage are considered to affect the likelihood of transmission and invasive disease. Because of its importance in both spreading and causing disease, carriage has been suggested as an endpoint in future vaccine studies. Culture is the current gold standard for detection, but may not be sensitive enough to detect changes at low density. Healthy adult volunteers received an intranasal inoculation of Streptococcus pneumoniae serotype 6B. Pneumococcal density in nasal washes collected at six time-points post-inoculation was determined by culture and quantitative PCR (qPCR). Natural pneumococcal carriers detected at initial screening were followed in parallel. In 331 nasal washes from 79 volunteers, the sensitivity and specificity of pneumococcal detection by qPCR, as compared with culture, were 92.3% and 75.9%. The estimation of pneumococcal density by culture and qPCR was highly correlated (rs = 0.73, p <0.0001), although qPCR had a lower detection limit. Pneumococcal density fluctuated within a carriage episode, and occasionally fell below the detection limit of both methods. The duration of carriage episodes was underestimated when only one method was used. Similar fluctuations in density were observed in natural carriers. Pneumococcal carriage is a dynamic event. Culture and qPCR are complementary for surveying the density and duration of pneumococcal carriage episodes. PMID:24995531

  5. Levofloxacin-resistant invasive Streptococcus pneumoniae in the United States: evidence for clonal spread and the impact of conjugate pneumococcal vaccine.

    PubMed

    Pletz, Mathias W R; McGee, Lesley; Jorgensen, James; Beall, Bernard; Facklam, Richard R; Whitney, Cynthia G; Klugman, Keith P

    2004-09-01

    The emergence of fluoroquinolone resistance in sterile-site isolates of Streptococcus pneumoniae is documented in this study characterizing all invasive levofloxacin-resistant (MIC, > or = 8 mg/liter) S. pneumoniae isolates (n = 50) obtained from the Centers for Disease Control and Prevention Active Bacterial Core Surveillance from 1998 to 2002. Resistance among all isolates increased from 0.1% in 1998 to 0.6% in 2001 (P = 0.008) but decreased to 0.4% in 2002, while resistance among vaccine serotypes continued to increase from 0.3% in 1998 to 1.0% in 2002, suggesting that fluoroquinolones continue to exert selective pressure on these vaccine serotypes. Only 22% of resistant isolates were not covered by the conjugate vaccine serogroups. Multilocus sequence typing revealed that 58% of resistant strains were related to five international clones identified by the Pneumococcal Molecular Epidemiology Network, with the Spain(23F)-1 clone being most frequent (16% of all isolates). Thirty-six percent of the isolates were coresistant to penicillin, 44% were coresistant to macrolides, and 28% were multiresistant to penicillin, macrolides, and fluoroquinolones. Fifty percent of the isolates were resistant to any three drug classes. Ninety-four percent of the isolates had multiple mutations in the quinolone resistance-determining regions of the gyrA, gyrB, parC, and parE genes. In 16% of the isolates, there was evidence of an active efflux mechanism. An unusual isolate was found that showed only a single parE mutation and for which the ciprofloxacin MIC was lower (2 mg/liter) than that of levofloxacin (8 mg/liter). Our results suggest that invasive pneumococcal isolates resistant to levofloxacin in the United States show considerable evidence of multiple resistance and of clonal spread. PMID:15328116

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

    PubMed

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

    2016-06-01

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

  7. Long-term Comparative Immunogenicity of Protein Conjugate and Free Polysaccharide Pneumococcal Vaccines in Chronic Obstructive Pulmonary Disease

    PubMed Central

    Dransfield, Mark T.; Harnden, Sarah; Burton, Robert L.; Albert, Richard K.; Bailey, William C.; Casaburi, Richard; Connett, John; Cooper, J. Allen D.; Criner, Gerard J.; Curtis, Jeffrey L.; Han, MeiLan K.; Make, Barry; Marchetti, Nathaniel; Martinez, Fernando J.; McEvoy, Charlene; Nahm, Moon H.; Niewoehner, Dennis E.; Porszasz, Janos; Reilly, John; Scanlon, Paul D.; Scharf, Steven M.; Sciurba, Frank C.; Washko, George R.; Woodruff, Prescott G.; Lazarus, Stephen C.

    2012-01-01

    Background. Although the 23-valent pneumococcal polysaccharide vaccine (PPSV23) protects against invasive disease in young healthy persons, randomized controlled trials in chronic obstructive pulmonary disease (COPD) have demonstrated no benefit in the intention-to-treat population. We previously reported that the 7-valent diphtheria-conjugated pneumococcal polysaccharide vaccine (PCV7) is safe and induced greater serotype-specific immunoglobulin G (IgG) and functional antibody than did PPSV23 1 month after vaccination. We hypothesized that these advantages would persist at 1 and 2 years. Methods. One hundred eighty-one patients with moderate to severe COPD were randomized to receive PPSV23 (n = 90) or PCV7 (1.0 mL; n = 91). We measured IgG by enzyme-linked immunosorbent assay and assessed functional antibody activity by a standardized opsonophagocytosis assay, reported as a killing index (OPK). We determined differences in IgG and OPK between vaccine groups at 1 and 2 years. Results. Relative to PPSV23, PCV7 induced greater OPK at both 1 and 2 years for 6 of 7 serotypes (not 19F). This response was statistically greater for 5 of 7 serotypes at 1 year and 4 of 7 at 2 years. Comparable differences in IgG were observed but were less often statistically significant. Despite meeting Centers for Disease Control and Prevention criteria for PPSV23 administration, almost 50% of individuals had never been vaccinated. No differences in the frequency of acute exacerbations, pneumonia, or hospitalization were observed. Conclusions. PCV7 induces a greater functional antibody response than PPSV23 in patients with COPD that persists for 2 years after vaccination. This superior functional response supports testing of conjugate vaccination in studies examining clinical end points. Clinical Trials Registration: NCT00457977. PMID:22652582

  8. A Case of Waterhouse-Friderichsen Syndrome Resulting from an Invasive Pneumococcal Infection in a Patient with a Hypoplastic Spleen

    PubMed Central

    Emori, Kazumasa; Takeuchi, Nobuhiro; Soneda, Junichi

    2016-01-01

    A 50-year-old male was brought to our emergency department by ambulance with complaints of pain and numbness in both legs. At arrival, purple spots were evident on his neck and face. Examination of the vital sign indicated septic shock. Laboratory data and blood gas analysis revealed disseminated intravascular coagulation, multiple organ failure, and metabolic acidosis. Peripheral blood smears revealed Howell-Jolly bodies, indicating decreased splenic function. A rapid urinary pneumococcal antigen test was also found to be positive. After admission to the intensive care unit, extensive treatment, including polymyxin-B direct hemoperfusion and administration of methylprednisolone and broad spectrum antibiotics was immediately initiated. Despite of our efforts to save his life, the patient died six hours after the arrival. The following day, blood cultures revealed the presence of Streptococcus pneumoniae. An autopsy revealed a hypoplastic spleen and a bilateral adrenal hemorrhage, indicating acute adrenal insufficiency caused by sepsis. Finally, the patient was diagnosed with Waterhouse-Friderichsen syndrome. Although severe infection may be seen in the splenectomized patients, it should be noted that patients with a hypoplastic spleen may have acute severe infections. We, therefore, report a case of Waterhouse-Friderichsen syndrome resulting from an invasive pneumococcal infection in a patient with a hypoplastic spleen. PMID:26942021

  9. A Case of Waterhouse-Friderichsen Syndrome Resulting from an Invasive Pneumococcal Infection in a Patient with a Hypoplastic Spleen.

    PubMed

    Emori, Kazumasa; Takeuchi, Nobuhiro; Soneda, Junichi

    2016-01-01

    A 50-year-old male was brought to our emergency department by ambulance with complaints of pain and numbness in both legs. At arrival, purple spots were evident on his neck and face. Examination of the vital sign indicated septic shock. Laboratory data and blood gas analysis revealed disseminated intravascular coagulation, multiple organ failure, and metabolic acidosis. Peripheral blood smears revealed Howell-Jolly bodies, indicating decreased splenic function. A rapid urinary pneumococcal antigen test was also found to be positive. After admission to the intensive care unit, extensive treatment, including polymyxin-B direct hemoperfusion and administration of methylprednisolone and broad spectrum antibiotics was immediately initiated. Despite of our efforts to save his life, the patient died six hours after the arrival. The following day, blood cultures revealed the presence of Streptococcus pneumoniae. An autopsy revealed a hypoplastic spleen and a bilateral adrenal hemorrhage, indicating acute adrenal insufficiency caused by sepsis. Finally, the patient was diagnosed with Waterhouse-Friderichsen syndrome. Although severe infection may be seen in the splenectomized patients, it should be noted that patients with a hypoplastic spleen may have acute severe infections. We, therefore, report a case of Waterhouse-Friderichsen syndrome resulting from an invasive pneumococcal infection in a patient with a hypoplastic spleen. PMID:26942021

  10. Pathogenesis and Pathophysiology of Pneumococcal Meningitis

    PubMed Central

    Mook-Kanamori, Barry B.; Geldhoff, Madelijn; van der Poll, Tom; van de Beek, Diederik

    2011-01-01

    Summary: Pneumococcal meningitis continues to be associated with high rates of mortality and long-term neurological sequelae. The most common route of infection starts by nasopharyngeal colonization by Streptococcus pneumoniae, which must avoid mucosal entrapment and evade the host immune system after local activation. During invasive disease, pneumococcal epithelial adhesion is followed by bloodstream invasion and activation of the complement and coagulation systems. The release of inflammatory mediators facilitates pneumococcal crossing of the blood-brain barrier into the brain, where the bacteria multiply freely and trigger activation of circulating antigen-presenting cells and resident microglial cells. The resulting massive inflammation leads to further neutrophil recruitment and inflammation, resulting in the well-known features of bacterial meningitis, including cerebrospinal fluid pleocytosis, cochlear damage, cerebral edema, hydrocephalus, and cerebrovascular complications. Experimental animal models continue to further our understanding of the pathophysiology of pneumococcal meningitis and provide the platform for the development of new adjuvant treatments and antimicrobial therapy. This review discusses the most recent views on the pathophysiology of pneumococcal meningitis, as well as potential targets for (adjunctive) therapy. PMID:21734248

  11. Pathogenesis and pathophysiology of pneumococcal meningitis.

    PubMed

    Mook-Kanamori, Barry B; Geldhoff, Madelijn; van der Poll, Tom; van de Beek, Diederik

    2011-07-01

    Pneumococcal meningitis continues to be associated with high rates of mortality and long-term neurological sequelae. The most common route of infection starts by nasopharyngeal colonization by Streptococcus pneumoniae, which must avoid mucosal entrapment and evade the host immune system after local activation. During invasive disease, pneumococcal epithelial adhesion is followed by bloodstream invasion and activation of the complement and coagulation systems. The release of inflammatory mediators facilitates pneumococcal crossing of the blood-brain barrier into the brain, where the bacteria multiply freely and trigger activation of circulating antigen-presenting cells and resident microglial cells. The resulting massive inflammation leads to further neutrophil recruitment and inflammation, resulting in the well-known features of bacterial meningitis, including cerebrospinal fluid pleocytosis, cochlear damage, cerebral edema, hydrocephalus, and cerebrovascular complications. Experimental animal models continue to further our understanding of the pathophysiology of pneumococcal meningitis and provide the platform for the development of new adjuvant treatments and antimicrobial therapy. This review discusses the most recent views on the pathophysiology of pneumococcal meningitis, as well as potential targets for (adjunctive) therapy. PMID:21734248

  12. Meningitis - pneumococcal

    MedlinePlus

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

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

    PubMed Central

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

    2014-01-01

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

  14. [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. PMID:27598280

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

    PubMed Central

    Daniels, Calvin C.; Rogers, P. David

    2016-01-01

    This review describes development of currently available pneumococcal vaccines, provides summary tables of current pneumococcal vaccine recommendations in children and adults, and describes new potential vaccine antigens in the pipeline. Streptococcus pneumoniae, the bacteria responsible for pneumonia, otitis media, meningitis and bacteremia, remains a cause of morbidity and mortality in both children and adults. Introductions of unconjugated and conjugated pneumococcal polysaccharide vaccines have each reduced the rate of pneumococcal infections caused by the organism S. pneumoniae. The first vaccine developed, the 23-valent pneumococcal polysaccharide vaccine (PPSV23), protected adults and children older than 2 years of age against invasive disease caused by the 23 capsular serotypes contained in the vaccine. Because PPSV23 did not elicit a protective immune response in children younger than 2 years of age, the 7-valent pneumococcal conjugate vaccine (PCV7) containing seven of the most common serotypes from PPSV23 in pediatric invasive disease was developed for use in children younger than 2 years of age. The last vaccine to be developed, the 13-valent pneumococcal conjugate vaccine (PCV13), contains the seven serotypes in PCV7, five additional serotypes from PPSV23, and a new serotype not contained in PPSV23 or PCV7. Serotype replacement with virulent strains that are not contained in the polysaccharide vaccines has been observed after vaccine implementation and stresses the need for continued research into novel vaccine antigens. We describe eight potential protein antigens that are in the pipeline for new pneumococcal vaccines. PMID:26997927

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

    PubMed

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

    2016-01-01

    This review describes development of currently available pneumococcal vaccines, provides summary tables of current pneumococcal vaccine recommendations in children and adults, and describes new potential vaccine antigens in the pipeline. Streptococcus pneumoniae, the bacteria responsible for pneumonia, otitis media, meningitis and bacteremia, remains a cause of morbidity and mortality in both children and adults. Introductions of unconjugated and conjugated pneumococcal polysaccharide vaccines have each reduced the rate of pneumococcal infections caused by the organism S. pneumoniae. The first vaccine developed, the 23-valent pneumococcal polysaccharide vaccine (PPSV23), protected adults and children older than 2 years of age against invasive disease caused by the 23 capsular serotypes contained in the vaccine. Because PPSV23 did not elicit a protective immune response in children younger than 2 years of age, the 7-valent pneumococcal conjugate vaccine (PCV7) containing seven of the most common serotypes from PPSV23 in pediatric invasive disease was developed for use in children younger than 2 years of age. The last vaccine to be developed, the 13-valent pneumococcal conjugate vaccine (PCV13), contains the seven serotypes in PCV7, five additional serotypes from PPSV23, and a new serotype not contained in PPSV23 or PCV7. Serotype replacement with virulent strains that are not contained in the polysaccharide vaccines has been observed after vaccine implementation and stresses the need for continued research into novel vaccine antigens. We describe eight potential protein antigens that are in the pipeline for new pneumococcal vaccines. PMID:26997927

  17. The surface-anchored NanA protein promotes pneumococcal brain endothelial cell invasion.

    PubMed

    Uchiyama, Satoshi; Carlin, Aaron F; Khosravi, Arya; Weiman, Shannon; Banerjee, Anirban; Quach, Darin; Hightower, George; Mitchell, Tim J; Doran, Kelly S; Nizet, Victor

    2009-08-31

    In humans, Streptococcus pneumoniae (SPN) is the leading cause of bacterial meningitis, a disease with high attributable mortality and frequent permanent neurological sequelae. The molecular mechanisms underlying the central nervous system tropism of SPN are incompletely understood, but include a primary interaction of the pathogen with the blood-brain barrier (BBB) endothelium. All SPN strains possess a gene encoding the surface-anchored sialidase (neuraminidase) NanA, which cleaves sialic acid on host cells and proteins. Here, we use an isogenic SPN NanA-deficient mutant and heterologous expression of the protein to show that NanA is both necessary and sufficient to promote SPN adherence to and invasion of human brain microvascular endothelial cells (hBMECs). NanA-mediated hBMEC invasion depends only partially on sialidase activity, whereas the N-terminal lectinlike domain of the protein plays a critical role. NanA promotes SPN-BBB interaction in a murine infection model, identifying the protein as proximal mediator of CNS entry by the pathogen. PMID:19687228

  18. Overview of Community-Acquired Pneumonia and the Role of Inflammatory Mechanisms in the Immunopathogenesis of Severe Pneumococcal Disease

    PubMed Central

    Steel, Helen C.; Anderson, Ronald; Feldman, Charles

    2013-01-01

    Community-acquired pneumonia (CAP) remains a leading cause of morbidity and mortality among the infectious diseases. Despite the implementation of national pneumococcal polyvalent vaccine-based immunisation strategies targeted at high-risk groups, Streptococcus pneumoniae (the pneumococcus) remains the most common cause of CAP. Notwithstanding the HIV pandemic, major challenges confronting the control of CAP include the range of bacterial and viral pathogens causing this condition, the ever-increasing problem of antibiotic resistance worldwide, and increased vulnerability associated with steadily aging populations in developed countries. These and other risk factors, as well as diagnostic strategies, are covered in the first section of this review. Thereafter, the review is focused on the pneumococcus, specifically the major virulence factors of this microbial pathogen and their role in triggering overexuberant inflammatory responses which contribute to the immunopathogenesis of invasive disease. The final section of the review is devoted to a consideration of pharmacological, anti-inflammatory strategies with adjunctive potential in the antimicrobial chemotherapy of CAP. This is focused on macrolides, corticosteroids, and statins with respect to their modes of anti-inflammatory action, current status, and limitations. PMID:24453422

  19. Prevention of early episodes of otitis media by pneumococcal vaccines might reduce progression to complex disease.

    PubMed

    Dagan, Ron; Pelton, Stephen; Bakaletz, Lauren; Cohen, Robert

    2016-04-01

    Otitis media is a common childhood infection of the middle ear and a major cause of morbidity. This multifactorial disease manifests as a spectrum of clinical syndromes from uncomplicated acute otitis media to more complex recurrent and chronic cases (frequently polymicrobial), with the major pathogens involved being Streptococcus pneumoniae and non-typeable Haemophilus influenzae. Pneumococcal conjugate vaccines (PCVs) target only a few serotypes that cause otitis media; however, results from studies suggest that existing PCVs can prevent early episodes of disease associated with vaccine serotypes, resulting in a reduction of subsequent complex cases caused by non-vaccine serotypes and other otopathogens, which contribute considerably to the disease burden. In this Review, we discuss the role of pneumococcus in the disease continuum and assess clinical evidence showing the effect of prevention of early episodes on the complex interplay between bacterial species implicated in otitis media. PMID:27036355

  20. 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

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

    PubMed

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

    2016-05-27

    Brazil introduced the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV, Synflorix™, GSK Vaccines) in the routine childhood immunization program in 2010 with a 3+1 schedule (with catch-up for children <2 years-old). This review represents the first analysis of the overall impact of a second-generation pneumococcal conjugate vaccine on nasopharyngeal carriage and all the major pneumococcal disease manifestations in a single, pneumococcal conjugate vaccine-naïve, developing country. A total of 15 published articles and 13 congress abstracts were included in the analysis. In children <5 years-old, studies showed a positive impact of PHiD-CV on the incidence of vaccine-type and any-type invasive pneumococcal disease (including decreases in pneumococcal meningitis morbidity and mortality), on pneumonia incidence and mortality, and on otitis media. Nasopharyngeal carriage of vaccine-type and any-type pneumococci decreased after the primary doses, with no early signs of replacement with other pathogens. Finally, herd protection against vaccine-type invasive pneumococcal disease and pneumonia in unvaccinated subjects was shown in some studies for some age groups. In conclusion, pneumococcal disease decreased after the introduction of PHiD-CV into the Brazilian national immunization program. Further follow-up is needed to evaluate the long-term overall impact of PHiD-CV in the Brazilian population. PMID:27113162

  2. Molecular analysis of Streptococcus pneumoniae clones causing invasive disease in children in Singapore.

    PubMed

    Jefferies, J M C; Tee, W S N; Clarke, S C

    2011-06-01

    Streptococcus pneumoniae remains a leading cause of serious paediatric disease. However, there are few published epidemiological data regarding invasive pneumococcal disease (IPD) in many countries in South East Asia, including Singapore. Baseline data for IPD are essential to inform policy regarding pneumococcal conjugate vaccine (PCV) use in Singapore. To our knowledge, this is the first study to use multilocus sequence typing (MLST) to investigate clonal relationships among Singaporean IPD isolates. We characterized 86 invasive pneumococci isolated from Singaporean children between 2001 and 2006 using serotyping and MLST. The objectives were to compare Singaporean MLST data to worldwide data and to assess serotype distribution in relation to current PCV formulations. We observed 50 sequence types (STs), a high proportion of which (n = 16) were novel STs. Despite the presence of these novel STs, serotype distribution was similar to that observed elsewhere. Serotypes 14, 6B, 19A and 19F accounted for 85 % of IPD cases. PCV7, PCV10 and PCV13 covered 85 %, 86 % and 97 % of IPD isolates, respectively. We have demonstrated a pressing need for larger studies to determine the molecular epidemiology and antibiotic susceptibility of circulating pneumococcal clones from both carriage and disease in Singapore. PMID:21330410

  3. Pneumococcal meningitis in an adolescent with fever and foot ache.

    PubMed

    Dias, Catarina; Pedrosa, Cláudia; Romariz, Jorge; Santos, Mafalda; Rodrigues, Lúcia

    2013-01-01

    Invasive pneumococcal disease predominantly affects younger children, elderly, and immunocompromised patients. Pneumococcal meningitis is a particularly important form of presentation, considering its high rate of morbimortality. We present the case of a previously healthy 12-year-old adolescent male who was hospitalized due to suspicion of osteoarticular infection in his left foot. A few hours later, he developed meningeal signs, exhibiting slight pleocytosis and Streptococcus pneumoniae isolates in both cerebrospinal fluid and blood. Imaging studies were inconclusive regarding the nature of the foot disorder. We considered the hypothesis of osteomyelitis of the navicular bone as the most likely, for which he completed six weeks of antibiotic therapy. There was a favorable clinical evolution, along with complete absence of osteoarticular or neurological sequelae. The relevance of this clinical case resides in the unusual presentation of invasive pneumococcal disease in this age group, as well as in the rare form of orthopedic involvement. PMID:23956909

  4. Pneumococcal Meningitis in an Adolescent with Fever and Foot Ache

    PubMed Central

    Dias, Catarina; Pedrosa, Cláudia; Romariz, Jorge; Santos, Mafalda; Rodrigues, Lúcia

    2013-01-01

    Invasive pneumococcal disease predominantly affects younger children, elderly, and immunocompromised patients. Pneumococcal meningitis is a particularly important form of presentation, considering its high rate of morbimortality. We present the case of a previously healthy 12-year-old adolescent male who was hospitalized due to suspicion of osteoarticular infection in his left foot. A few hours later, he developed meningeal signs, exhibiting slight pleocytosis and Streptococcus pneumoniae isolates in both cerebrospinal fluid and blood. Imaging studies were inconclusive regarding the nature of the foot disorder. We considered the hypothesis of osteomyelitis of the navicular bone as the most likely, for which he completed six weeks of antibiotic therapy. There was a favorable clinical evolution, along with complete absence of osteoarticular or neurological sequelae. The relevance of this clinical case resides in the unusual presentation of invasive pneumococcal disease in this age group, as well as in the rare form of orthopedic involvement. PMID:23956909

  5. Vaccines against invasive Salmonella disease

    PubMed Central

    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. PMID:24804797

  6. The Saudi Thoracic Society pneumococcal vaccination guidelines-2016.

    PubMed

    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

  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. Serotype changes in adult invasive pneumococcal infections in Portugal did not reduce the high fraction of potentially vaccine preventable infections.

    PubMed

    Horácio, Andreia N; Diamantino-Miranda, Jorge; Aguiar, Sandra I; Ramirez, Mário; Melo-Cristino, José

    2012-01-01

    We determined the serotype and antimicrobial susceptibility of 1100 isolates responsible for adult invasive pneumococcal infections (IPD) in Portugal between 2006 and 2008. Serotypes 3 (13%), 1 (12%), 7F (11%), 19A (10%) and 14 (7%) were the most frequent causes of IPD and the two later serotypes accounted for the majority of erythromycin and penicillin nonsusceptible isolates. Serotype 1 was associated with younger adults whereas serotype 3 was associated with older adults. Despite the availability of the 23-valent polysaccharide vaccine (PPV23) in Portugal since 1996, the proportion of PPV23 preventable IPD remained stable and above 80%. Comparing with previous data from Portugal, we showed a continued decline of the serotypes included in the 7-valent conjugate vaccine (PCV7) in adult IPD and a rise of serotypes included in the 13-valent conjugate vaccine, increasing its potential coverage of adult IPD to 70% in 2008. Penicillin non-susceptibility remained stable (17%) whereas erythromycin resistance (18%) has continued to rise in the post-PCV7 years. PMID:22100892

  9. Genetic Variation in NFKBIE Is Associated With Increased Risk of Pneumococcal Meningitis in Children

    PubMed Central

    Lundbo, Lene F.; Harboe, Zitta Barrella; Clausen, Louise N.; Hollegaard, Mads V.; Sørensen, Henrik T.; Hougaard, David M.; Konradsen, Helle B.; Nørgaard, Mette; Benfield, Thomas

    2015-01-01

    Background Streptococcus pneumoniae and Neisseria meningitidis are frequent pathogens in life-threatening infections. Genetic variation in the immune system may predispose to these infections. Nuclear factor-κB is a key component of the TLR-pathway, controlled by inhibitors, encoded by the genes NFKBIA, NFKBIE and NFKBIZ. We aimed to replicate previous findings of genetic variation associated with invasive pneumococcal disease (IPD), and to assess whether similar associations could be found in invasive meningococcal disease (IMD). Methods Cases with IPD and IMD and controls were identified by linking Danish national registries. DNA was obtained from the Danish Neonatal Screening Biobank. The association between SNPs and susceptibility to IPD and IMD, mortality and pneumococcal serotypes was investigated. Results 372 children with pneumococcal meningitis, 907 with pneumococcal bacteremia and 1273 controls were included. We included 406 cases with meningococcal meningitis, 272 with meningococcal bacteremia, and 672 controls. The NFKBIE SNP was associated with increased risk of pneumococcal meningitis (aOR 1.68; 95% CI: 1.20–2.36), but not bacteremia (aOR 1.08; 95% CI: 0.86–1.35). The remaining SNPs were not associated with susceptibility to invasive disease. None of the SNPs were associated with risk of IMD or mortality. Conclusions A NFKBIE polymorphism was associated with increased risk of pneumococcal meningitis. PMID:26870821

  10. Pneumococcal vaccination: what have we learnt so far and what can we expect in the future?

    PubMed

    Torres, A; Bonanni, P; Hryniewicz, W; Moutschen, M; Reinert, R R; Welte, T

    2015-01-01

    Individuals <2 years and ≥ 50 years of age, as well as those with other specific risk factors, are especially vulnerable to invasive pneumococcal disease (IPD). Conjugate vaccines have been developed against encapsulated bacteria such as Streptococcus pneumoniae to provide improved immune responses. The 7-valent pneumococcal conjugate vaccine (PCV7) has significantly reduced the burden of vaccine-type pneumococcal diseases in children, including invasive disease and pneumonia and acute otitis media. There have also been significant declines in antimicrobial resistance in 7-valent vaccine serotypes and carriage of S. pneumoniae in the post-PCV7 era. Two to three years after the introduction of PCV13, there is emerging, global evidence of a reduced burden of pneumococcal diseases in children, including declines in IPD (UK and Germany) and nasopharyngeal carriage of PCV13 serotypes (Portugal and France). The functional immunogenicity of PCV13 in individuals ≥ 50 years of age has been demonstrated in clinical trials in comparison with the 23-valent pneumococcal polysaccharide vaccine and for children and adults 6 to 49 years of age. Between 2011 and 2013, PCV13 received market authorisation by the European Medicines Agency (EMA) for these additional age groups and is now available in Europe for the prevention of pneumococcal disease in all age groups. PMID:25149825

  11. Population-based study of the association between asthma and pneumococcal disease in children

    PubMed Central

    Shea, Kimberly M; Lash, Timothy L; Antonsen, Sussie; Jick, Susan S; Sørensen, Henrik T

    2015-01-01

    Background Although asthma has recently been established as a risk factor for pneumococcal disease (PD), few studies have specifically evaluated this association in children. Methods We conducted a nation-wide population-based cohort study of the effect of asthma on childhood PD among all singleton live births in Denmark from 1994 to 2007, before the introduction of the 7-valent pneumococcal conjugate vaccine. All data were abstracted from Danish medical registries. Because underlying comorbidity substantially increases the PD risk in children, standard methods were used to assess the evidence of biologic interaction between comorbidity and asthma on the risk of PD. Results There were 2,253 cases of childhood PD among 888,655 children born in Denmark from 1994 to 2007. The adjusted incidence rate ratio of the effect of asthma on childhood PD was 2.2 (95% confidence interval [CI]: 2.0, 2.5). Age-stratified incidence rate ratios were 2.1 (95% CI: 1.8, 2.9) in children 6 months to <24 months, 4.1 (95% CI: 3.3, 5.1) in children 24 months to <60 months, and 2.3 (95% CI: 1.6, 3.2) in children ≥60 months. Evaluation of the biologic interaction between asthma and comorbidity in older children revealed that 55% (24 months to <60 months) to 73% (≥60 months) of cases among asthma-exposed children can be accounted for by the interaction between asthma and comorbidity. Conclusion These results confirm that asthma is an important risk factor for PD in children and suggest that children with underlying comorbidities are more sensitive to the effect of asthma on PD than children without comorbidities. PMID:26203278

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

    PubMed

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

    2016-05-17

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

  13. Prospects for use of interleukin-12 as a mucosal adjuvant for vaccination of humans to protect against respiratory pneumococcal infection.

    PubMed

    Wright, A K A; Briles, D E; Metzger, D W; Gordon, S B

    2008-09-01

    Mucosal vaccination against pneumococcal disease offers potential protection against otitis media, pneumonia and invasive disease, including providing herd benefit by reducing pathogen carriage. The major obstacle, however, remains the lack of a suitable adjuvant for use in humans. Animal models have demonstrated success of interleukin-12 (IL-12) as an adjuvant for mucosal vaccines using recombinant pneumococcal protein antigens. This review examines the biology of the IL-12 cytokine family, the toxicity of IL-12 in human studies and suggests approaches by which IL-12 could be developed as a mucosal adjuvant with pneumococcal protein based vaccines, for use in humans. PMID:18602438

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

    PubMed Central

    Rogers, Kara; Cotte, Christina; Adami, Alexander J.; Bracken, Sonali J.; Salmon, Sharon; Secor, Eric R.; Thrall, Roger S.; Andemariam, Biree; Metzger, Dennis W.

    2016-01-01

    Background One of the most common causes of morbidity and mortality in children with sickle cell disease (SCD) is infection with the pneumococcal bacterium (Streptococcus pneumoniae). Unfortunately, the polysaccharide-conjugate vaccine appears to be less effective in individuals with SCD when compared to the general population. We sought to better understand the relative efficacy of pneumococcal vaccination in a SCD mouse challenge model. Methods Transgenic control and SCD mice were monitored for mortality after intranasal pneumococcal infection or pneumococcal vaccination with Prevnar-13 and type-matched challenge. Anti-pneumococcal antibody titers were measured by ELISA and opsonophagocytosis was measured in vitro. Results Mortality after pneumococcal infection was similar between control and SCD mice. However, after three intramuscular polysaccharide-conjugate vaccinations, all control mice were protected following high-dose intranasal infection, whereas 60% of SCD mice died. Anti-pneumococcal antibody titers showed initial IgG and IgM responses in both groups, but waning titers were observed in the SCD group, even after boosting. When functionally assayed in vitro, serum from SCD mice 13 weeks after a second booster shot maintained little to no ability to opsonize pneumococci, while serum from control mice sustained a significantly higher capacity opsonization. Thus, it appears that SCD mice do not maintain antibody responses to pneumococcal polysaccharides after Prevnar-13 vaccination, thereby leaving them susceptible to mortality after type-matched infection. Conclusion Our results emphasize the need to better understand the correlates of immune protection in SCD so that pneumococcal vaccines can be improved and mortality reduced in this susceptible population. PMID:26910228

  15. 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 SiglecFlow Alveolar Macrophages

    PubMed Central

    Sanfilippo, Alan M.; Furuya, Yoichi; Roberts, Sean; Salmon, Sharon L.

    2015-01-01

    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 SiglecFlow 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. PMID:25964474

  16. 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. PMID:25964474

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

    PubMed Central

    Pangonis, Scott; Patamasucon, Pisespong; Fitzpatrick, Ellen

    2016-01-01

    Streptococcus pneumoniae is an invasive organism that causes a wide range of common diseases, including sinusitis, acute otitis media, and pneumonia. Splenic abscesses and purpura fulminans (PF) are rare complications of pneumococcal disease. Splenic abscesses caused by S pneumoniae have only been reported in the adult literature. PF has been described in the pediatric population as a rare complication in patients with invasive pneumococcal disease (IPD) with and without underlying immunological disorders such as asplenia. Here, we report a patient with IPD complicated by splenic abscesses and PF. Our patient initially presented with bacteremia, septic shock, and disseminated intravascular coagulation. She subsequently developed PF and splenic abscesses. She survived her illness after receiving a total of 8 weeks of antibiotic therapy. This case highlights 2 rare complications of IPD and demonstrates the need to keep pneumococcal disease in the differential diagnosis even in children whose vaccination status is up to date. PMID:27006958

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

    PubMed

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

    2016-05-27

    The introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) followed by PCV13 resulted in a dramatic reduction in carriage and disease rates of Streptococcus pneumoniae (Sp) serotype 6B (Sp6B) and Sp6A. The structural modifications of the capsule of Sp6A and Sp6B to become Sp6C and Sp6D, respectively, raised a concern that eradication of Sp6A/Sp6B by PCV could be accompanied by an increase in Sp6C/Sp6D. This study examines the dynamics and clonal distribution of Sp6C/Sp6D relative to Sp6A/Sp6B during 1999-2014, pre- and post-PCV implementation. Sp were cultured from Blood/CSF and MEF of children <2 years, and from conjunctiva and nasopharynx of children <5 years. PCR was applied for Sp6C and Sp6D identification. Clonality was determined by PFGE and MLST. PCV introduction resulted in decreased carriage rates and conjunctivitis caused by serogroup 6 serotypes. Incidence of Sp6A, Sp6B and Sp6D in otitis media dropped gradually along with PCV7/13 introduction, whereas Sp6C rates increased in the PCV7 period and then decreased following PCV13 implementation. In invasive pneumococcal disease, complete elimination of serogroup 6 was found in the PCV era. Similar clonal composition was found for Sp6C and Sp6D pre- and post-PCV. We conclude that Sp6C and Sp6D do not act as replacement serotypes for Sp6A and Sp6B following vaccination with PCV13. The major Sp6C and Sp6D clones present pre-PCV persisted also post-PCV implementation, suggesting that these clones possess an advantage retained post-vaccination. PMID:27113163

  19. 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. PMID:26325175

  20. Pneumococcal Infections

    MedlinePlus

    ... blood, imaging, or lab tests. Treatment is with antibiotics. Vaccines can prevent pneumococcal infections. There are two vaccines. One is for infants and young children. The other is for people ...

  1. Pneumococcal Polysaccharide Vaccine: What You Need to Know

    MedlinePlus

    ... children and younger adults) from pneumococcal disease . Pneumococcal disease is caused by bacteria that can spread from person to person through close contact. It can cause ear infections, and it can also lead to more serious infections of ... can get pneumococcal disease, but children under 2 years of age, people ...

  2. The multifaceted impact of pneumococcal conjugate vaccine implementation in children in France between 2001 to 2014.

    PubMed

    Cohen, Robert; Biscardi, Sandra; Levy, Corinne

    2016-02-01

    In 2003, France was the first European country to recommend 7-valent pneumococcal conjugate vaccine (PCV7) for a large proportion of healthy children. With complicated recommendations, the vaccine coverage during the first 4 y of implementation was low, then progressively increased to reach 90% in 2008. The aim of this review was to describe the particular impact of PCVs in a country where the vaccine coverage was initially suboptimal. After PCV7 implementation, the PCV7 serotypes nearly disappeared among pneumococci isolated from meningitis (-73%), other invasive pneumococcal disease (IPD; -90%) and pneumococcal carriage (-97%). Consequently, the rates of penicillin-resistant strains declined. However, because of important serotype replacement, the global effect on the incidence of meningitis (-31%) or other IPD (-14%) was modest and observed only in young children < 2 y old. After PCV13 transition, with immediate high vaccine coverage, the vaccine had an important impact on all pneumococcal disease: reduction of -20% for pneumococcal meningitis, -36% for non-meningitis IPD, -32% for community acquired pneumonia and -15% for S. pneumoniae carriage. These findings underline the complexity of pneumococcal epidemiology and the importance of high and fast vaccination coverage to obtain the optimal effect of PCVs. PMID:26905678

  3. [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

  4. Pneumococcal conjugate vaccine (PCV13) - What you need to know

    MedlinePlus

    ... www.cdc.gov/vaccines/hcp/vis/vis-statements/pcv13.html CDC review information for Pneumococcal Conjugate VIS: ... the disease, through vaccination, even more important. 2. PCV13 vaccine Pneumococcal conjugate vaccine (called PCV13) protects against ...

  5. Invasive Disease Caused by Nontypeable Haemophilus influenzae

    PubMed Central

    de Jonge, Marien I.

    2015-01-01

    The incidence of severe Haemophilus influenza infections, such as sepsis and meningitis, has declined substantially since the introduction of the H. influenzae serotype b vaccine. However, the H. influenzae type b vaccine fails to protect against nontypeable H. influenzae strains, which have become increasingly frequent causes of invasive disease, especially among children and the elderly. We summarize recent literature supporting the emergence of invasive nontypeable H. influenzae and describe mechanisms that may explain its increasing prevalence over the past 2 decades. PMID:26407156

  6. 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

  7. The majority of adult pneumococcal invasive infections in Portugal are still potentially vaccine preventable in spite of significant declines of serotypes 1 and 5.

    PubMed

    Horácio, Andreia N; Diamantino-Miranda, Jorge; Aguiar, Sandra I; Ramirez, Mário; Melo-Cristino, José

    2013-01-01

    In Portugal, pneumococcal conjugate vaccines have been administered to children outside of the national immunization plan since 2001. We determined the serotype and antimicrobial susceptibility of 1265 isolates responsible for adult invasive pneumococcal infections (IPD) between 2009 and 2011 and compared the results with previously published data from 1999 to 2008. Serotypes 3 (12.6%), 7F (10.0%), 19A (9.1%), 14 (8.4%), 1 (6.9%) and 8 (6.2%) were the most frequent and together accounted for 53.2% of adult IPD. Serotypes 1 and 5 declined significantly while serotype 34, not included in any vaccine, increased. Taken together, the serotypes included in the 13-valent conjugate vaccine (PCV13) peaked among adult IPD isolates in 2008 (70.2%) and declined since then reaching 53.5% in 2011. The decline in the serotypes included in the 23-valent polysaccharide vaccine since 2007 was also significant but much more modest with 79.2% of the isolates causing IPD in 2011 expressing these serotypes. Since the changes in serotypes causing IPD in adults coincided with the 10-valent and PCV13 introduction in children, it is unlikely that vaccination triggered these changes although it may have accelerated them. The proportion of IPD caused by serotypes included in the 7-valent conjugate vaccine remained stable (19.0%). Both penicillin non-susceptibility and erythromycin resistance increased in the study period, with serotypes 14 and 19A accounting for the majority of resistant isolates. PMID:24066064

  8. Persisting high prevalence of pneumococcal carriage among HIV-infected adults receiving antiretroviral therapy in Malawi: a cohort study

    PubMed Central

    Heinsbroek, Ellen; Tafatatha, Terence; Phiri, Amos; Ngwira, Bagrey; Crampin, Amelia C.; Read, Jonathan M.; French, Neil

    2015-01-01

    Objective: HIV-infected adults have high rates of pneumococcal carriage and invasive disease. We investigated the effect of antiretroviral therapy (ART) on pneumococcal carriage in HIV-infected adults prior to infant pneumococcal conjugate vaccine (PCV) rollout. Design: Observational cohort study. Methods: We recruited HIV-infected adults newly attending a rural HIV clinic in northern Malawi between 2008 and 2010. Nasopharyngeal samples were taken at baseline and after 6, 12, 18 and 24 months. We compared pneumococcal carriage by ART status using generalized estimated equation models adjusted for CD4+ cell count, sex, seasonality, and other potential confounders. Results: In total, 336 individuals were included, of which 223 individuals started ART during follow-up. Individuals receiving ART had higher pneumococcal carriage than individuals not receiving ART (25.9 vs. 19.8%, P = 0.03) particularly for serotypes not included in PCV13 (16.1 vs. 9.6% P = 0.003). Following adjustment, increased carriage of non-PCV13 serotypes was still observed for individuals on ART, but results for all serotypes were nonsignificant [all serotypes: adjusted risk ratio (aRR) 1.22 (0.95–1.56); non-PCV13 serotypes: aRR 1.72, 95% CI 1.13–2.62]. Conclusion: Pneumococcal carriage in HIV-infected adults in Malawi remained high despite use of ART, consistent with failure of mucosal immune reconstitution in the upper respiratory tract. There was evidence of increased carriage of non-PCV13 serotypes. HIV-infected adults on ART could remain an important reservoir for pneumococcal diversity post infant pneumococcal vaccine introduction. Control of pneumococcal disease in African HIV remains a priority. PMID:26218599

  9. Pneumococcal Infections - Multiple Languages: MedlinePlus

    MedlinePlus

    ... Coalition; Centers for Disease Control and Prevention Pneumococcal Polysaccharide Vaccine (PPV23) English 肺炎球菌多糖疫苗 - 繁體中文 (Chinese - Traditional) PDF ... Coalition; Centers for Disease Control and Prevention Pneumococcal Polysaccharide Vaccine (PPV23) English Русский (Russian) PDF Immunization Action ...

  10. Optimising Assessments of the Epidemiological Impact in the Netherlands of Paediatric Immunisation with 13-Valent Pneumococcal Conjugate Vaccine Using Dynamic Transmission Modelling

    PubMed Central

    De Cao, Elisabetta; Melegaro, Alessia; Klok, Rogier; Postma, Maarten

    2014-01-01

    This work is the first attempt to quantify the overall effects of a 13-valent pneumococcal conjugate vaccine (PCV13) vaccination programme in the Dutch population taking into account all the direct and indirect effects of the vaccine on invasive pneumococcal disease. Using available Dutch data, a dynamic transmission model for the spread of pneumococci and potential subsequent invasive pneumococcal disease has been adapted to the Dutch setting. Overall, invasive pneumococcal disease cases in the Netherlands are predicted to decrease from a pre-vaccination level of 2623 cases annually to 2475, 2289, 2185, 2179, and 2178 cases annually 5-, 10-, 20-, 30-, and 40-years, respectively, post-vaccination. Therefore, vaccination with PCV13 in the Netherlands is predicted to lower invasive pneumococcal disease cases per year by up to 445 cases in the medium- to long-term. The results are quite robust for the sensitivity analyses performed on the parameters that regulate herd immunity and competition between vaccine and non-vaccine types. PMID:24694656

  11. 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

  12. 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

    2016-03-01

    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. PMID:26652736

  13. 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...

  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, 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...

  16. 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...

  17. 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...

  18. Invasive mucormycosis in chronic granulomatous disease.

    PubMed

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

    2016-05-01

    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

  19. 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

  20. 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

  1. Molecular epidemiology of pneumococcal isolates from children in China

    PubMed Central

    Kang, Li-Hua; Liu, Meng-Juan; Xu, Wen-Chun; Cui, Jing-Jing; Zhang, Xue-Mei; Wu, Kai-Feng; Zhang, Qun

    2016-01-01

    Objectives: To investigate the molecular epidemiology of pneumococcal isolates in Chongqing, China. Methods: In this cross-sectional study, 51 invasive Streptococcus pneumoniae (S. pneumoniae) strains were from children with invasive pneumococcal disease (IPD) and 32 carriage strains from healthy children from January 2010 to December 2013 at the Children’s Hospital of Chongqing Medical University, Chongqing, China. Multilocus sequence typing was used to identify the sequence types (STs). Capsular serotypes were determined by multiplex polymerase chain reaction. Drug susceptibility and resistance was determined by minimum inhibitory concentrations. Results: In this study, 11 serotypes were identified among the 83 S. pneumoniae clinical isolates tested. Prevalent serotypes were 19A (20.4%), 6A/B (20.4%), 19F (15.7%), 14 (14.5%), and 23F (10.8%). Serotype 19F was the most frequent carriage strain, and serotype 19A was the most frequent invasive strain. The ST983 was the most prevalent ST for carriage strains, and ST320 was the most prevalent ST for invasive strains. For gene analysis, psaA (99.5%) and piaA (98.6%) were present and much conserved in all pneumococci tested. The cps2A and pcsB genes were more frequent in invasive isolates than carriage strains. Antimicrobial resistance rates of invasive pneumococcal isolates to erythromycin, penicillin, meropenem, cefotaxime, and clindamycin were higher than the carriage isolates from children. Conclusion: Our epidemiological evidence shows that 19A, 6A/B, 19F, 14, and 23F remain the most prevalent serotypes, which can be targeted by PCV13. Genotypes and drug resistance varied between carriage and invasive strains. The PsaA and PiaA may be good protein vaccine candidates. PMID:27052283

  2. 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

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

    PubMed

    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

  4. Association of Secondhand Smoke Exposure with Pediatric Invasive Bacterial Disease and Bacterial Carriage: A Systematic Review and Meta-analysis

    PubMed Central

    Lee, Chien-Chang; Middaugh, Nicole A.; Howie, Stephen R. C.; Ezzati, Majid

    2010-01-01

    Background A number of epidemiologic studies have observed an association between secondhand smoke (SHS) exposure and pediatric invasive bacterial disease (IBD) but the evidence has not been systematically reviewed. We carried out a systematic review and meta-analysis of SHS exposure and two outcomes, IBD and pharyngeal carriage of bacteria, for Neisseria meningitidis (N. meningitidis), Haemophilus influenzae type B (Hib), and Streptococcus pneumoniae (S. pneumoniae). Methods and Findings Two independent reviewers searched Medline, EMBASE, and selected other databases, and screened articles for inclusion and exclusion criteria. We identified 30 case-control studies on SHS and IBD, and 12 cross-sectional studies on SHS and bacterial carriage. Weighted summary odd ratios (ORs) were calculated for each outcome and for studies with specific design and quality characteristics. Tests for heterogeneity and publication bias were performed. Compared with those unexposed to SHS, summary OR for SHS exposure was 2.02 (95% confidence interval [CI] 1.52–2.69) for invasive meningococcal disease, 1.21 (95% CI 0.69–2.14) for invasive pneumococcal disease, and 1.22 (95% CI 0.93–1.62) for invasive Hib disease. For pharyngeal carriage, summary OR was 1.68 (95% CI, 1.19–2.36) for N. meningitidis, 1.66 (95% CI 1.33–2.07) for S. pneumoniae, and 0.96 (95% CI 0.48–1.95) for Hib. The association between SHS exposure and invasive meningococcal and Hib diseases was consistent regardless of outcome definitions, age groups, study designs, and publication year. The effect estimates were larger in studies among children younger than 6 years of age for all three IBDs, and in studies with the more rigorous laboratory-confirmed diagnosis for invasive meningococcal disease (summary OR 3.24; 95% CI 1.72–6.13). Conclusions When considered together with evidence from direct smoking and biological mechanisms, our systematic review and meta-analysis indicates that SHS exposure may be

  5. A pneumococcal pilus influences virulence and host inflammatory responses.

    PubMed

    Barocchi, M A; Ries, J; Zogaj, X; Hemsley, C; Albiger, B; Kanth, A; Dahlberg, S; Fernebro, J; Moschioni, M; Masignani, V; Hultenby, K; Taddei, A R; Beiter, K; Wartha, F; von Euler, A; Covacci, A; Holden, D W; Normark, S; Rappuoli, R; Henriques-Normark, B

    2006-02-21

    Streptococcus pneumoniae (pneumococcus) is a major cause of morbidity and mortality world-wide. The initial event in invasive pneumococcal disease is the attachment of encapsulated pneumococci to epithelial cells in the upper respiratory tract. This work provides evidence that initial bacterial adhesion and subsequent ability to cause invasive disease is enhanced by pili, long organelles able to extend beyond the polysaccharide capsule, previously unknown to exist in pneumococci. These adhesive pili-like appendages are encoded by the pneumococcal rlrA islet, present in some, but not all, clinical isolates. Introduction of the rlrA islet into an encapsulated rlrA-negative isolate allowed pilus expression, enhanced adherence to lung epithelial cells, and provided a competitive advantage upon mixed intranasal challenge of mice. Furthermore, a pilus-expressing rlrA islet-positive clinical isolate was more virulent than a nonpiliated deletion mutant, and it out-competed the mutant in murine models of colonization, pneumonia, and bacteremia. Additionally, piliated pneumococci evoked a higher TNF response during systemic infection, compared with nonpiliated derivatives, suggesting that pneumococcal pili not only contribute to adherence and virulence but also stimulate the host inflammatory response. PMID:16481624

  6. A pneumococcal pilus influences virulence and host inflammatory responses

    PubMed Central

    Barocchi, M. A.; Ries, J.; Zogaj, X.; Hemsley, C.; Albiger, B.; Kanth, A.; Dahlberg, S.; Fernebro, J.; Moschioni, M.; Masignani, V.; Hultenby, K.; Taddei, A. R.; Beiter, K.; Wartha, F.; von Euler, A.; Covacci, A.; Holden, D. W.; Normark, S.; Rappuoli, R.; Henriques-Normark, B.

    2006-01-01

    Streptococcus pneumoniae (pneumococcus) is a major cause of morbidity and mortality world-wide. The initial event in invasive pneumococcal disease is the attachment of encapsulated pneumococci to epithelial cells in the upper respiratory tract. This work provides evidence that initial bacterial adhesion and subsequent ability to cause invasive disease is enhanced by pili, long organelles able to extend beyond the polysaccharide capsule, previously unknown to exist in pneumococci. These adhesive pili-like appendages are encoded by the pneumococcal rlrA islet, present in some, but not all, clinical isolates. Introduction of the rlrA islet into an encapsulated rlrA-negative isolate allowed pilus expression, enhanced adherence to lung epithelial cells, and provided a competitive advantage upon mixed intranasal challenge of mice. Furthermore, a pilus-expressing rlrA islet-positive clinical isolate was more virulent than a nonpiliated deletion mutant, and it out-competed the mutant in murine models of colonization, pneumonia, and bacteremia. Additionally, piliated pneumococci evoked a higher TNF response during systemic infection, compared with nonpiliated derivatives, suggesting that pneumococcal pili not only contribute to adherence and virulence but also stimulate the host inflammatory response. PMID:16481624

  7. Cost-effectiveness of vaccinating adults with the 23-valent pneumococcal polysaccharide vaccine (PPV23) in Germany.

    PubMed

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

    2012-10-01

    The introduction of routine infant vaccination against pneumococcal disease has resulted in a decreased overall invasive pneumococcal disease incidence in adults but also a change in invasive pneumococcal disease serotypes. This study aimed to assess the cost-effectiveness of 23-valent pneumococcal polysaccharide vaccine (PPV23) in Germany in this context. A population-based Markov model was developed. A cohort of adults currently eligible for vaccination was followed until death. Adult vaccination with PPV23 was associated with an incremental cost-effectiveness ratio of €17,065/quality-adjusted life years gained from the third-party payer's perspective. Univariate sensitivity analyses showed that the incremental cost-effectiveness ratio was below €50,000/quality-adjusted life years gained in most test scenarios. The model suggests that adult PPV23 vaccination is cost effective in Germany, due to its broad serotype coverage. This is despite epidemiological changes in Streptococcus pneumoniae serotypes caused by wider use of pneumococcal conjugate vaccines during childhood. PMID:23025422

  8. [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. PMID:27440038

  9. Serotypes and Clonal Diversity of Streptococcus pneumoniae Causing Invasive Disease in the Era of PCV13 in Catalonia, Spain.

    PubMed

    Del Amo, Eva; Esteva, Cristina; Hernandez-Bou, Susanna; Galles, Carmen; Navarro, Marian; Sauca, Goretti; Diaz, Alvaro; Gassiot, Paula; Marti, Carmina; Larrosa, Nieves; Ciruela, Pilar; Jane, Mireia; Sá-Leão, Raquel; Muñoz-Almagro, Carmen

    2016-01-01

    The aim of this study was to study the serotypes and clonal diversity of pneumococci causing invasive pneumococcal disease in Catalonia, Spain, in the era of 13-valent pneumococcal conjugate vaccine (PCV13). In our region, this vaccine is only available in the private market and it is estimated a PCV13 vaccine coverage around 55% in children. A total of 1551 pneumococcal invasive isolates received between 2010 and 2013 in the Molecular Microbiology Department at Hospital Sant Joan de Déu, Barcelona, were included. Fifty-two serotypes and 249 clonal types-defined by MLST-were identified. The most common serotypes were serotype 1 (n = 182; 11.7%), 3 (n = 145; 9.3%), 19A (n = 137; 8.8%) and 7F (n = 122; 7.9%). Serotype 14 was the third most frequent serotype in children < 2 years (15 of 159 isolates). PCV7 serotypes maintained their proportion along the period of study, 16.6% in 2010 to 13.4% in 2013, whereas there was a significant proportional decrease in PCV13 serotypes, 65.3% in 2010 to 48.9% in 2013 (p<0.01). This decrease was mainly attributable to serotypes 19A and 7F. Serotype 12F achieved the third position in 2013 (n = 22, 6.4%). The most frequent clonal types found were ST306 (n = 154, 9.9%), ST191 (n = 111, 7.2%), ST989 (n = 85, 5.5%) and ST180 (n = 80, 5.2%). Despite their decrease, PCV13 serotypes continue to be a major cause of disease in Spain. These results emphasize the need for complete PCV13 vaccination. PMID:26953887

  10. Serotypes and Clonal Diversity of Streptococcus pneumoniae Causing Invasive Disease in the Era of PCV13 in Catalonia, Spain

    PubMed Central

    del Amo, Eva; Esteva, Cristina; Hernandez-Bou, Susanna; Galles, Carmen; Navarro, Marian; Sauca, Goretti; Diaz, Alvaro; Gassiot, Paula; Marti, Carmina; Larrosa, Nieves; Ciruela, Pilar; Jane, Mireia; Sá-Leão, Raquel; Muñoz-Almagro, Carmen

    2016-01-01

    The aim of this study was to study the serotypes and clonal diversity of pneumococci causing invasive pneumococcal disease in Catalonia, Spain, in the era of 13-valent pneumococcal conjugate vaccine (PCV13). In our region, this vaccine is only available in the private market and it is estimated a PCV13 vaccine coverage around 55% in children. A total of 1551 pneumococcal invasive isolates received between 2010 and 2013 in the Molecular Microbiology Department at Hospital Sant Joan de Déu, Barcelona, were included. Fifty-two serotypes and 249 clonal types—defined by MLST—were identified. The most common serotypes were serotype 1 (n = 182; 11.7%), 3 (n = 145; 9.3%), 19A (n = 137; 8.8%) and 7F (n = 122; 7.9%). Serotype 14 was the third most frequent serotype in children < 2 years (15 of 159 isolates). PCV7 serotypes maintained their proportion along the period of study, 16.6% in 2010 to 13.4% in 2013, whereas there was a significant proportional decrease in PCV13 serotypes, 65.3% in 2010 to 48.9% in 2013 (p<0.01). This decrease was mainly attributable to serotypes 19A and 7F. Serotype 12F achieved the third position in 2013 (n = 22, 6.4%). The most frequent clonal types found were ST306 (n = 154, 9.9%), ST191 (n = 111, 7.2%), ST989 (n = 85, 5.5%) and ST180 (n = 80, 5.2%). Despite their decrease, PCV13 serotypes continue to be a major cause of disease in Spain. These results emphasize the need for complete PCV13 vaccination. PMID:26953887

  11. Impact of pneumococcal conjugate vaccination of infants on pneumonia and influenza hospitalization and mortality in all age groups in the United States.

    PubMed

    Simonsen, Lone; Taylor, Robert J; Young-Xu, Yinong; Haber, Michael; May, Larissa; Klugman, Keith P

    2011-01-01

    A seven-valent pneumococcal conjugate vaccine (PCV7) introduced in the United States in 2000 has been shown to reduce invasive pneumococcal disease (IPD) in both vaccinated children and adults through induction of herd immunity. We assessed the impact of infant immunization on pneumococcal pneumonia hospitalizations and mortality in all age groups using Health Care Utilization Project State Inpatient Databases (SID) for 1996 to 2006 from 10 states; SID contain 100% samples of ICD9-coded hospitalization data for the selected states. Compared to a 1996-1997 through 1998-1999 baseline, by the 2005-2006 season, both IPD and pneumococcal pneumonia hospitalizations and deaths had decreased substantially in all age groups, including a 47% (95% confidence interval [CI], 38 to 54%) reduction in nonbacteremic pneumococcal pneumonia (ICD9 code 481 with no codes indicating IPD) in infants <2 years old and a 54% reduction (CI, 53 to 56%) in adults ≥65 years of age. A model developed to calculate the total burden of pneumococcal pneumonia prevented by infant PCV7 vaccination in the United States from 2000 to 2006 estimated a reduction of 788,838 (CI, 695,406 to 875,476) hospitalizations for pneumococcal pneumonia. Ninety percent of the reduction in model-attributed pneumococcal pneumonia hospitalizations occurred through herd immunity among adults 18 years old and older; similar proportions were found in pneumococcal disease mortality prevented by the vaccine. In the first seasons after PCV introduction, when there were substantial state differences in coverage among <5-year-olds, states with greater coverage had significantly fewer influenza-associated pneumonia hospitalizations among children, suggesting that PCV7 use also reduces influenza-attributable pneumonia hospitalizations. PMID:21264063

  12. 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

  13. Effectiveness of 23-valent pneumococcal polysaccharide vaccine on diabetic elderly

    PubMed Central

    Kuo, Chia-Sheng; Lu, Chia-Wen; Chang, Yu-Kang; Yang, Kuen-Cheh; Hung, Shou-Hung; Yang, Ming-Ching; Chang, Hao-Hsiang; Huang, Chi-Ting; Hsu, Chih-Cheng; Huang, Kuo-Chin

    2016-01-01

    Abstract Diabetes mellitus is associated with increased risk of pneumonia, and 23-valent pneumococcal polysaccharide vaccine (PPV23) is recommended for prevention of pneumonia. However, the effectiveness of PPV23 remains unclear in the older diabetic patients who usually have compromised immune function. We used data extracted from the Taiwanese National Health Insurance Research Database (NHIRD) from 2000 to 2009 to conduct a population-based retrospective cohort study, comparing the incidence of pneumococcal diseases among PPV23-vaccinated and propensity-score matched PPV23-unvaccinated groups in diabetic elderly. The primary outcome was invasive pneumococcal diseases (IPDs), and the secondary outcomes were medical utilization. PPV23-vaccinated group had reduced risks of IPD (adjusted OR: 0.86, 95% CI: 0.78–0.94), respiratory failure (0.84, 0.77–0.93), and shorter length of hospitalization (−1.27 ± 0.19 days, P value: 0.0012). In flu-vaccinated group, subjects who received PPV23 had reduced risks of IPD, hospitalization, and respiratory failure; had shorter lengths of hospitalization; and less medical costs, than those without receiving PPV23. In not flu-vaccinated group, PPV23 vaccination was associated with reduced risks of IPD and respiratory failure. Receiving both vaccines could bring better protection in IPD, hospitalization, visits of emergency department, and respiratory failure. PPV23 vaccination was effective in prevention of pneumococcal diseases and reduction of medical utilization in diabetic elderly aged 75 and more. Receiving both vaccines resulted in better outcomes than PPV vaccination alone. PMID:27368047

  14. 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 ...

  15. Evolving pneumococcal serotypes and sequence types in relation to high antibiotic stress and conditional pneumococcal immunization

    PubMed Central

    Su, Lin-Hui; Kuo, An-Jing; Chia, Ju-Hsin; Li, Hsin-Chieh; Wu, Tsu-Lan; Feng, Ye; Chiu, Cheng-Hsun

    2015-01-01

    In Taiwan, beginning in 2013, the 13-valent pneumococcal conjugate vaccine (PCV13) was provided free of charge to children 2–5 years of age. In 2014, this was extended to children 1–5 years old. During 2012–2014, 953 cases of culture-confirmed pneumococcal disease (CCPD), including 104 invasive pneumococcal disease (IPD), were prospectively identified and analyzed at a 3,700-bed hospital in Taiwan. From 2012 to 2014, the incidence per 10,000 admissions decreased from 26.7 to 20.4 for CCPD (P < 0.001) and from 3.2 to 1.9 for IPD (P < 0.05). Significant reduction of PCV13 serotypes was firstly noted in children in 2013 and extended to both paediatric and adult populations in 2014. Simultaneously, the incidence per 10,000 admissions of non-PCV13 serotypes increased from 6.1 in 2012 to 9.3 in 2014 (P < 0.005). The most prevalent non-PCV13 serotypes were 15A, 15B, and 23A, each containing a predominant clone, ST6315A, ST8315B, and ST33823A. From 2012 to 2014, isolates with penicillin minimum inhibitory concentrations >2 mg/L decreased from 27.8% to 8.1% (P < 0.001) among all isolates. PCV13 immunization in young children demonstrated an early protective effect in all ages. However, in the elderly, the effect was compromised by an emergence of non-PCV13 serotypes. PMID:26522920

  16. 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. PMID:27009210

  17. The post-vaccine microevolution of invasive Streptococcus pneumoniae.

    PubMed

    Cremers, Amelieke J H; Mobegi, Fredrick M; de Jonge, Marien I; van Hijum, Sacha A F T; Meis, Jacques F; Hermans, Peter W M; Ferwerda, Gerben; Bentley, Stephen D; Zomer, Aldert L

    2015-01-01

    The 7-valent pneumococcal conjugated vaccine (PCV7) has affected the genetic population of Streptococcus pneumoniae in pediatric carriage. Little is known however about pneumococcal population genomics in adult invasive pneumococcal disease (IPD) under vaccine pressure. We sequenced and serotyped 349 strains of S. pneumoniae isolated from IPD patients in Nijmegen between 2001 and 2011. Introduction of PCV7 in the Dutch National Immunization Program in 2006 preluded substantial alterations in the IPD population structure caused by serotype replacement. No evidence could be found for vaccine induced capsular switches. We observed that after a temporary bottleneck in gene diversity after the introduction of PCV7, the accessory gene pool re-expanded mainly by genes already circulating pre-PCV7. In the post-vaccine genomic population a number of genes changed frequency, certain genes became overrepresented in vaccine serotypes, while others shifted towards non-vaccine serotypes. Whether these dynamics in the invasive pneumococcal population have truly contributed to invasiveness and manifestations of disease remains to be further elucidated. We suggest the use of whole genome sequencing for surveillance of pneumococcal population dynamics that could give a prospect on the course of disease, facilitating effective prevention and management of IPD. PMID:26492862

  18. The post-vaccine microevolution of invasive Streptococcus pneumoniae

    PubMed Central

    Cremers, Amelieke J. H.; Mobegi, Fredrick M.; de Jonge, Marien I.; van Hijum, Sacha A. F. T.; Meis, Jacques F.; Hermans, Peter W. M.; Ferwerda, Gerben; Bentley, Stephen D.; Zomer, Aldert L.

    2015-01-01

    The 7-valent pneumococcal conjugated vaccine (PCV7) has affected the genetic population of Streptococcus pneumoniae in pediatric carriage. Little is known however about pneumococcal population genomics in adult invasive pneumococcal disease (IPD) under vaccine pressure. We sequenced and serotyped 349 strains of S. pneumoniae isolated from IPD patients in Nijmegen between 2001 and 2011. Introduction of PCV7 in the Dutch National Immunization Program in 2006 preluded substantial alterations in the IPD population structure caused by serotype replacement. No evidence could be found for vaccine induced capsular switches. We observed that after a temporary bottleneck in gene diversity after the introduction of PCV7, the accessory gene pool re-expanded mainly by genes already circulating pre-PCV7. In the post-vaccine genomic population a number of genes changed frequency, certain genes became overrepresented in vaccine serotypes, while others shifted towards non-vaccine serotypes. Whether these dynamics in the invasive pneumococcal population have truly contributed to invasiveness and manifestations of disease remains to be further elucidated. We suggest the use of whole genome sequencing for surveillance of pneumococcal population dynamics that could give a prospect on the course of disease, facilitating effective prevention and management of IPD. PMID:26492862

  19. 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

  20. [Public health management in invasive meningococcal diseases].

    PubMed

    Ehrhard, I; Arndt, U

    2004-12-01

    At the 54(th) Scientific Congress of the German Professional Association of Public Health Service Physicians and Dentists in Marburg on 6th May 2004 the working group on meningococci (Arbeitsgemeinschaft Meningokokken, AGMK) organised the international workshop "Public Health Management of invasive Meningococcal Disease". In recent years significant changes in the epidemiology of meningococcal disease took place in Europe: in some countries and regions the number of disease caused by meningococci serogroup C has increased significantly. In the Netherlands this increase led to the introduction of an immunisation programme with conjugated meningococcal vaccines targeting children aged 1 up to 18 years. In Switzerland a peak in the number of reported meningococcal group C cases could be observed in some regions. Therefore, a regional vaccination programme has been introduced. Nevertheless, compared with Germany, the indications for vaccination against meningococci in Switzerland are more extensive. In the workshop, Professor Ulrich Vogel and Dr. Ingrid Ehrhard presented the epidemiological situation in Germany and the recommended prophylaxis regimen against meningococci. PMID:15609213

  1. Disease invasion risk in a growing population.

    PubMed

    Yuan, Sanling; van den Driessche, P; Willeboordse, Frederick H; Shuai, Zhisheng; Ma, Junling

    2016-09-01

    The spread of an infectious disease may depend on the population size. For simplicity, classic epidemic models assume homogeneous mixing, usually standard incidence or mass action. For standard incidence, the contact rate between any pair of individuals is inversely proportional to the population size, and so the basic reproduction number (and thus the initial exponential growth rate of the disease) is independent of the population size. For mass action, this contact rate remains constant, predicting that the basic reproduction number increases linearly with the population size, meaning that disease invasion is easiest when the population is largest. In this paper, we show that neither of these may be true on a slowly evolving contact network: the basic reproduction number of a short epidemic can reach its maximum while the population is still growing. The basic reproduction number is proportional to the spectral radius of a contact matrix, which is shown numerically to be well approximated by the average excess degree of the contact network. We base our analysis on modeling the dynamics of the average excess degree of a random contact network with constant population input, proportional deaths, and preferential attachment for contacts brought in by incoming individuals (i.e., individuals with more contacts attract more incoming contacts). In addition, we show that our result also holds for uniform attachment of incoming contacts (i.e., every individual has the same chance of attracting incoming contacts), and much more general population dynamics. Our results show that a disease spreading in a growing population may evade control if disease control planning is based on the basic reproduction number at maximum population size. PMID:26794321

  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

    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

    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. 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

  4. [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. PMID:21812250

  5. A review of the evidence to inform pneumococcal vaccine recommendations for risk groups aged 2 years and older.

    PubMed

    Steens, A; Vestrheim, D F; Aaberge, I S; Wiklund, B S; Storsaeter, J; Riise Bergsaker, M A; Rønning, K; Furuseth, E

    2014-12-01

    For decades, vaccination with the 23-valent polysaccharide pneumococcal vaccine (PPV23) has been available for risk groups aged ⩾2 years to prevent invasive pneumococcal disease (IPD). Recently, a 13-valent pneumococcal conjugated vaccine (PCV13) has been licensed for use in all age groups. PCV13 may induce better protection than PPV23 because of different immunogenic properties. This called for a revision of vaccine recommendations for risk groups. We therefore reviewed literature on risk groups for IPD, and effectiveness and safety of pneumococcal vaccines and supplemented that with information from public health institutes, expert consultations and data on IPD epidemiology. We included 187 articles. We discuss the implications of the heterogenic vulnerability for IPD within and between risk groups, large indirect effects of childhood immunization, and limited knowledge on additional clinical benefits of PCV13 in combination with PPV23 for the Norwegian recommendations. These are now step-wise and consider the need for vaccination, choice of pneumococcal vaccines, and re-vaccination interval by risk group. PMID:24932959

  6. Underestimation of Invasive Meningococcal Disease in Italy

    PubMed Central

    Nieddu, Francesco; Moriondo, Maria; Indolfi, Giuseppe; Canessa, Clementina; Ricci, Silvia; Bianchi, Leila; Serranti, Daniele; Poggi, Giovanni Maria; Resti, Massimo

    2016-01-01

    Knowing the incidence of invasive meningococcal disease (IMD) is essential for planning appropriate vaccination policies. However, IMD may be underestimated because of misdiagnosis or insufficiently sensitive laboratory methods. Using a national molecular surveillance register, we assessed the number of cases misdiagnosed and diagnoses obtained postmortem with real-time PCR (rPCR), and we compared sensitivity of rPCR versus culture-based testing. A total of 222 IMD cases were identified: 11 (42%) of 26 fatal cases had been misdiagnosed or undiagnosed and were reclassified as IMD after rPCR showed meningococcal DNA in all available specimens taken postmortem. Of the samples tested with both rPCR and culture, 58% were diagnosed by using rPCR alone. The underestimation factor associated with the use of culture alone was 3.28. In countries such as Italy, where rPCR is in limited use, IMD incidence may be largely underestimated; thus, assessments of benefits of meningococcal vaccination may be prone to error. PMID:26890305

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

    PubMed

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

    2016-05-01

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

  8. 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

  9. Nanogel-based PspA intranasal vaccine prevents invasive disease and nasal colonization by Streptococcus pneumoniae.

    PubMed

    Kong, Il Gyu; Sato, Ayuko; Yuki, Yoshikazu; Nochi, Tomonori; Takahashi, Haruko; Sawada, Shinichi; Mejima, Mio; Kurokawa, Shiho; Okada, Kazunari; Sato, Shintaro; Briles, David E; Kunisawa, Jun; Inoue, Yusuke; Yamamoto, Masafumi; Akiyoshi, Kazunari; Kiyono, Hiroshi

    2013-05-01

    To establish a safer and more effective vaccine against pneumococcal respiratory infections, current knowledge regarding the antigens common among pneumococcal strains and improvements to the system for delivering these antigens across the mucosal barrier must be integrated. We developed a pneumococcal vaccine that combines the advantages of pneumococcal surface protein A (PspA) with a nontoxic intranasal vaccine delivery system based on a nanometer-sized hydrogel (nanogel) consisting of a cationic cholesteryl group-bearing pullulan (cCHP). The efficacy of the nanogel-based PspA nasal vaccine (cCHP-PspA) was tested in murine pneumococcal airway infection models. Intranasal vaccination with cCHP-PspA provided protective immunity against lethal challenge with Streptococcus pneumoniae Xen10, reduced colonization and invasion by bacteria in the upper and lower respiratory tracts, and induced systemic and nasal mucosal Th17 responses, high levels of PspA-specific serum immunoglobulin G (IgG), and nasal and bronchial IgA antibody responses. Moreover, there was no sign of PspA delivery by nanogel to either the olfactory bulbs or the central nervous system after intranasal administration. These results demonstrate the effectiveness and safety of the nanogel-based PspA nasal vaccine system as a universal mucosal vaccine against pneumococcal respiratory infection. PMID:23460513

  10. Nanogel-Based PspA Intranasal Vaccine Prevents Invasive Disease and Nasal Colonization by Streptococcus pneumoniae

    PubMed Central

    Kong, Il Gyu; Sato, Ayuko; Nochi, Tomonori; Takahashi, Haruko; Sawada, Shinichi; Mejima, Mio; Kurokawa, Shiho; Okada, Kazunari; Sato, Shintaro; Briles, David E.; Kunisawa, Jun; Inoue, Yusuke; Yamamoto, Masafumi; Akiyoshi, Kazunari

    2013-01-01

    To establish a safer and more effective vaccine against pneumococcal respiratory infections, current knowledge regarding the antigens common among pneumococcal strains and improvements to the system for delivering these antigens across the mucosal barrier must be integrated. We developed a pneumococcal vaccine that combines the advantages of pneumococcal surface protein A (PspA) with a nontoxic intranasal vaccine delivery system based on a nanometer-sized hydrogel (nanogel) consisting of a cationic cholesteryl group-bearing pullulan (cCHP). The efficacy of the nanogel-based PspA nasal vaccine (cCHP-PspA) was tested in murine pneumococcal airway infection models. Intranasal vaccination with cCHP-PspA provided protective immunity against lethal challenge with Streptococcus pneumoniae Xen10, reduced colonization and invasion by bacteria in the upper and lower respiratory tracts, and induced systemic and nasal mucosal Th17 responses, high levels of PspA-specific serum immunoglobulin G (IgG), and nasal and bronchial IgA antibody responses. Moreover, there was no sign of PspA delivery by nanogel to either the olfactory bulbs or the central nervous system after intranasal administration. These results demonstrate the effectiveness and safety of the nanogel-based PspA nasal vaccine system as a universal mucosal vaccine against pneumococcal respiratory infection. PMID:23460513

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

    PubMed Central

    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. PMID:27279965

  12. 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. PMID:27279965

  13. 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

  14. Pneumococcal Infection among Children before Introduction of 13-Valent Pneumococcal Conjugate Vaccine, Cambodia

    PubMed Central

    Turner, Claudia; Suy, Kuong; Soeng, Sona; Ly, Sokeng; Miliya, Thyl; Goldblatt, David; Day, Nicholas P.J.

    2015-01-01

    Vaccination of children with pneumococcal conjugate vaccine (PCV13) was initiated in Cambodia in 2015. To determine baseline data, we collected samples from children in 2013 and 2014. PCV13 serotypes accounted for 62.7% of colonizing organisms in outpatients and 88.4% of invasive pneumococci overall; multidrug resistance was common. Thus, effectiveness of vaccination should be high. PMID:26488597

  15. Pneumococcal Infection among Children before Introduction of 13-Valent Pneumococcal Conjugate Vaccine, Cambodia.

    PubMed

    Turner, Paul; Turner, Claudia; Suy, Kuong; Soeng, Sona; Ly, Sokeng; Miliya, Thyl; Goldblatt, David; Day, Nicholas P J

    2015-11-01

    Vaccination of children with pneumococcal conjugate vaccine (PCV13) was initiated in Cambodia in 2015. To determine baseline data, we collected samples from children in 2013 and 2014. PCV13 serotypes accounted for 62.7% of colonizing organisms in outpatients and 88.4% of invasive pneumococci overall; multidrug resistance was common. Thus, effectiveness of vaccination should be high. PMID:26488597

  16. Vaccine Failures in Patients Properly Vaccinated with 13-Valent Pneumococcal Conjugate Vaccine in Catalonia, a Region with Low Vaccination Coverage.

    PubMed

    Moraga-Llop, Fernando; Garcia-Garcia, Juan-Jose; Díaz-Conradi, Alvaro; Ciruela, Pilar; Martínez-Osorio, Johanna; González-Peris, Sebastià; Hernández, Sergi; de Sevilla, Mariona Fernández; Uriona, Sonia; Izquierdo, Conchita; Selva, Laura; Campins, Magda; Codina, Gemma; Batalla, Joan; Esteva, Cristina; Domínguez, Àngela; Muñoz-Almagro, Carmen

    2016-04-01

    Vaccine failures occurring with 13-valent pneumococcal conjugate vaccine (PCV13) in 3 pediatric hospitals in Barcelona (2012-2013) are described. PCV13 vaccine failure was defined as the occurrence of an invasive pneumococcal infection in children properly vaccinated by PCV13. Among 84 patients with invasive pneumococcal infection, 32 had received at least one dose of PCV13. Seventeen of them had invasive pneumococcal infection produced by a PCV13 serotype. Among those, 9 patients were considered to have a PCV13 vaccine failure. Serotype 3 was isolated in 6 patients, serotype 19A in 2 and serotype 6B in 1. PMID:26658626

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

    PubMed

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

    2016-09-01

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

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

    PubMed

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

    2016-01-01

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

  19. 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. PMID:23278538

  20. Hearing loss in adults surviving pneumococcal meningitis is associated with otitis and pneumococcal serotype.

    PubMed

    Heckenberg, S G B; Brouwer, M C; van der Ende, A; Hensen, E F; van de Beek, D

    2012-09-01

    We assessed the incidence of hearing loss and its relationship with clinical characteristics and pneumococcal serotypes in adults surviving pneumococcal meningitis. We analysed hearing loss in 531 adults surviving pneumococcal meningitis included in two prospective nationwide cohort studies performed from April 1998 through to October 2002 and March 2006 through to January 2009. Hearing loss was evaluated on admission and discharge for all patients. Severe hearing loss was assessed by pure tone average on audiology and corrected for age, or by the combination of hearing loss on discharge and a score on the Glasgow Outcome Scale below 5, which could not be explained by other neurological sequelae. A total of 531 episodes of pneumococcal meningitis with non-lethal outcome were included. Predisposing conditions for pneumococcal meningitis were present in the majority of patients (64%), most commonly otitis (36%). Hearing loss was present at discharge in 116 patients (22%) and was classified as mild in 53% and severe in 47%. Hearing loss was related to otitis (odds ratio [OR], 2.58; 95% confidence interval [CI], 1.66-4.02; p < 0.001) and inversely related to serotype 23 F infection (OR, 0.36; 95% CI, 0.13-0.98; p = 0.025), but not with parameters of disease severity or indicators of cerebrospinal fluid inflammation severity. Meningitis due to pneumococcal serotype 3 was associated with the highest rate of hearing loss. Hearing loss frequently complicates pneumococcal meningitis. Risk factors for hearing loss were infection with pneumococcal serotype 23 F and otitis, but not disease severity. Otitis and resulting perilympathic inflammation contribute to meningitis-associated hearing loss. PMID:21958295

  1. Pneumococcal Disease Fast Facts

    MedlinePlus

    ... Vaccination For Clinicians Streptococcus pneumoniae Transmission Clinical Features Risk Factors Diagnosis & Management Prevention For Laboratorians Drug Resistance Surveillance & Reporting Global ...

  2. Anatomical site-specific contributions of pneumococcal virulence determinants

    PubMed Central

    Shenoy, Anukul T.; Orihuela, Carlos J.

    2016-01-01

    Streptococcus pneumoniae is an opportunistic pathogen globally associated with significant morbidity and mortality. It is capable of causing a wide range of diseases including sinusitis, conjunctivitis, otitis media, pneumonia, bacteraemia, sepsis, and meningitis. While its capsular polysaccharide is indispensible for invasive disease, and opsonising antibodies against the capsule are the basis for the current vaccines, a long history of biomedical research indicates that other components of this Gram-positive bacterium are also critical for virulence. Herein we review the contribution of pneumococcal virulence determinants to survival and persistence in the context of distinct anatomical sites. We discuss how these determinants allow the pneumococcus to evade mucociliary clearance during colonisation, establish lower respiratory tract infection, resist complement deposition and opsonophagocytosis in the bloodstream, and invade secondary tissues such as the central nervous system leading to meningitis. We do so in a manner that highlights both the critical role of the capsular polysaccharide and the accompanying and necessary protein determinants. Understanding the complex interplay between host and pathogen is necessary to find new ways to prevent pneumococcal infection. This review is an attempt to do so with consideration for the latest research findings.

  3. [PNEUMOCOCCAL VACCINE IN ADULTS REDUCES THE RISK OF INFECTIONS CAUSED BY STREPTOCOCCUS PNEUMONIAE].

    PubMed

    Belocerkovskaja, Ju G; Romanovskih, A G; Styrt, E A

    2016-01-01

    Streptococcus pneumoniae is a major cause of severe disease worldwide, particularly in the risk population. Two pneumococcal vaccines are currently available for specific prevention of pneumococcal infections among adults in Russia: a 23-valent pneumococcal polysaccharide vaccine (PPSV23) and a 13-valent pneumococcal conjugate vaccine (PCV13). The article describes modern views on the effectiveness and safety of two pneumococcal vaccines in adults with underlying medical conditions and adults aged ≥ 65 years and provides current recommendations for routine use of PPSV23 and PCV13 among persons included in the risk group. PMID:27172726

  4. [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. PMID:26474708

  5. Alcoholic leukopenic pneumococcal sepsis.

    PubMed

    Alraiyes, Abdul Hamid; Shaheen, Khaldoon; Alraies, M Chadi

    2013-04-01

    Alcohol abuse has been associated with an increased mortality and morbidity due to increased aspiration, delirium tremens, and seizures. The association of pneumococcal lung infections and leukopenia in the setting of alcohol abuse are rarely reported; however, when present, severe lung infections can happen with severe lung injury and poor response to conventional therapy and ultimately, death. We are reporting a case of 55-year-old-man presented with shortness of breath, cough and altered mental status and eventually found with severe pneumococcal lung infection in the setting of leukopenia and long-term alcohol abuse representing alcoholic leukopenic pneumococcal sepsis syndrome. PMID:23930244

  6. Fulminant pneumococcal infection

    PubMed Central

    Naito, Ryo; Miyazaki, Tetsuro; Kajino, Kazunori; Daida, Hiroyuki

    2014-01-01

    Summary Fulminant pneumococcal infection is a fatal pneumococcal infection that tends to occur in immunocompromised hosts, such as patients who are asplenic or on immunosuppressant therapy. We experienced a case of a 73-year-old Japanese man with a medical history of coronary stent implantation and catheter ablation for atrial flutter who presented with dyspnoea at rest. The patient was diagnosed with streptococcal pneumonia based on a urine antigen test and CT. Despite the use of effective antibiotics and systemic therapies, his clinical course was rapidly progressive and he died 18 h after admission. This case of fulminant pneumococcal infection is reported along with the autopsy findings. PMID:25150240

  7. Changes in Streptococcus pneumoniae Serotype 19A Invasive Infections in Children from 1993 to 2011

    PubMed Central

    Kaplan, Sheldon L.; Lamberth, Linda B.; Barson, William J.; Romero, José R.; Lin, Philana Ling; Bradley, John S.; Givner, Laurence B.; Tan, Tina Q.; Hoffman, Jill A.; Mason, Edward O.

    2013-01-01

    Among 594 Streptococcus pneumoniae serotype 19A invasive pneumococcal disease (IPD) isolates collected from 1993 to 2011, we identified 85 sequence types by multilocus sequence typing. CC320 was associated with multidrug resistance and reduced susceptibility to penicillin and ceftriaxone and still predominated among declining serotype 19A IPD isolates following PCV13 introduction. PMID:23390277

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

    PubMed

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

    2011-04-01

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

  9. Stable coronary artery disease: revascularisation and invasive strategies.

    PubMed

    Piccolo, Raffaele; Giustino, Gennaro; Mehran, Roxana; Windecker, Stephan

    2015-08-15

    Stable coronary artery disease is the most common clinical manifestation of ischaemic heart disease and a leading cause of mortality worldwide. Myocardial revascularisation is a mainstay in the treatment of symptomatic patients or those with ischaemia-producing coronary lesions, and reduces ischaemia to a greater extent than medical treatment. Documentation of ischaemia and plaque burden is fundamental in the risk stratification of patients with stable coronary artery disease, and several invasive and non-invasive techniques are available (eg, fractional flow reserve or intravascular ultrasound) or being validated (eg, instantaneous wave-free ratio and optical coherence tomography). The use of new-generation drug-eluting stents and arterial conduits greatly improve clinical outcome in patients undergoing percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). PCI is feasible, safe, and effective in many patients with stable coronary artery disease who remain symptomatic despite medical treatment. In patients with multivessel and left main coronary artery disease, the decision between PCI or CABG is guided by the local Heart Team (team of different cardiovascular specialists, including non-invasive and invasive cardiologists, and cardiac surgeons), who carefully judge the possible benefits and risks inherent to PCI and CABG. In specific subsets, such as patients with diabetes and advanced, multivessel coronary artery disease, CABG remains the standard of care in view of improved protection against recurrent ischaemic adverse events. PMID:26334162

  10. Pneumococcal Vaccines (PCV, PPSV)

    MedlinePlus

    ... Know About Zika & Pregnancy 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, ...

  11. [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. PMID:25434346

  12. 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

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

    PubMed

    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

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

    PubMed

    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

  15. 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

  16. Prevention of pneumococcal infections during mass gathering.

    PubMed

    Al-Tawfiq, Jaffar A; Memish, Ziad A

    2016-01-01

    The interest in mass gathering and its implications has been increasing due to globalization and international travel. The potential occurrence of infectious disease outbreaks during mass gathering is most feared. In this context, respiratory tract infections are of great concern due to crowding in a limited space which facilitates and magnifies the potential of disease spread among attendees. Pneumococcal disease is best described among pilgrims to Makkah and vaccination is one of the methods for the prevention of this disease. Pneumonia was described in a mass gathering with a prevalence of 4.8/100,000 pilgrims and contributes to 15-39% of hospitalizations. Various studies showed that 7-37% of pilgrims are 65 y of age or older. The uptake of pneumococcal vaccine among pilgrims is low at 5%. There is no available data to make strong recommendations for S. pneumoniae vaccination of all pilgrims, it is important that a high risk population receive the indicated vaccination. We reviewed the available literature on the burden of pneumococcal infections during mass gathering and evaluate the available literature on pneumococcal vaccinations for attendees of mass gathering. PMID:26176306

  17. MedlinePlus: Pneumococcal Infections

    MedlinePlus

    ... infections are Ear infections Sinus infections Pneumonia Sepsis Meningitis How the diagnosis is made depends upon where ... Article: The Earliest Success of Penicillin. Article: Pneumococcal meningitis outbreaks in sub-Saharan Africa. Pneumococcal Infections -- see ...

  18. Pediatric Pneumococcal Serotypes in 4 European Countries

    PubMed Central

    Kissling, Esther; Fenoll, Asuncion; George, Robert; Lepoutre, Agnes; Lernout, Tinne; Tarragó, David; Varon, Emmanuelle; Verhaegen, Jan

    2010-01-01

    After heptavalent pneumococcal conjugate vaccine (PCV7) was marketed in France, Spain, Belgium, and England and Wales (United Kingdom), invasive disease from non-PCV7 serotypes (NVT) increased. Adjusted serotype-specific incidences among children <15 years of age were compared between 1999–2002 (prevaccine) and 2005–2006 (postmarketing). Vaccine coverage increased to ≈32%–48% in France, Spain, and Belgium but remained <1% in England and Wales. Serotype 1 incidence rose in all age groups and countries (incidence rate ratio [IRR] 1.3–4.2; p<0.004), independently of PCV7 use, but incidence of serotypes 7F and 19A increased most in France, Spain, and Belgium (IRR 1.9–16.9 in children <5 years; p<0.001), where PCV7 coverage was greater. Vaccine-induced replacement of PCV7 serotypes possibly contributed to NVT increases, as did secular trends. New vaccines targeting these serotypes are available, but serotype dynamics needs further exploration that accounts for underreporting and prevaccine trends. PMID:20735928

  19. 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

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

    PubMed

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

    2015-11-01

    The Community-Acquired Pneumonia Immunization Trial in Adults (CAPiTA) demonstrated the efficacy of 13-valent pneumococcal conjugate vaccine (PCV13) in preventing vaccine-type community-acquired pneumonia and vaccine-type invasive pneumococcal disease in elderly subjects. We examined the cost-effectiveness of PCV13 vaccination in the Netherlands. Using a Markov-type model, incremental cost-effectiveness ratios (ICER) of PCV13 vaccination in different age- and risk-groups for pneumococcal disease were evaluated using a societal perspective. Estimates of quality-adjusted life-years (QALYs), costs, vaccine efficacy and epidemiological data were based on the CAPiTA study and other prospective studies. The base-case was PCV13 vaccination of adults aged 65-74 years compared to no vaccination, assuming no net indirect effects in base-case due to paediatric 10-valent pneumococcal conjugate vaccine use. Analyses for age- and risk-group specific vaccination strategies and for different levels of hypothetical herd effects from a paediatric PCV programme were also conducted. The ICER for base-case was €8650 per QALY (95% CI 5750-17,100). Vaccination of high-risk individuals aged 65-74 years was cost-saving and extension to medium-risk individuals aged 65-74 years yielded an ICER of €2900. Further extension to include medium- and high-risk individuals aged ≥18 years yielded an ICER of €3100.PCV13 vaccination is highly cost-effective in the Netherlands. The transferability of our results to other countries depends upon vaccination strategies already implemented in those countries. PMID:26160871

  1. 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. PMID:24804797

  2. Synchronous unilateral triple breast cancers composed of invasive ductal carcinoma, invasive lobular carcinoma, and Paget's disease.

    PubMed

    Onoe, Shunsuke; Tsuda, Hitoshi; Akashi-Tanaka, Sadako; Hasebe, Takahiro; Iwamoto, Eriko; Hojo, Takashi; Kinoshita, Takayuki

    2014-03-01

    We report a case of synchronous unilateral triple breast cancers comprising invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), and Paget's disease. A 57-year-old woman with a left breast mass was referred to our hospital. Mammography revealed only an isodense area with foci of microcalcification in the lateral area of the left breast. Ultrasonography revealed 2 hypoechoic masses in the outer lower and inner upper areas, and these 2 lesions were diagnosed by core needle biopsy as ILC and IDC, respectively. Left total mastectomy with sentinel lymph node biopsies was performed. In addition to the ILC and IDC, histological examination also identified Paget's disease. Breast cancer often manifests as multiple unilateral lesions; however, it is sometimes difficult to determine whether these tumors have developed multicentrically or have multifocally invaded from an intraductal carcinoma. This case was clearly diagnosed to have occurred multicentrically because of the absence of continuity among the 3 tumors, the presence of a non-invasive component in all 3 tumors, and different histopathological findings. The synchronous unilateral development of ILCs is well known. Cases of synchronous unilateral triple or more breast cancers were reviewed, and their histopathological characteristics, including the incidence of Paget's disease, is discussed. PMID:21140247

  3. Minimally invasive approaches for the treatment of inflammatory bowel disease

    PubMed Central

    Zoccali, Marco; Fichera, Alessandro

    2012-01-01

    Despite significant improvements in medical management of inflammatory bowel disease, many of these patients still require surgery at some point in the course of their disease. Their young age and poor general conditions, worsened by the aggressive medical treatments, make minimally invasive approaches particularly enticing to this patient population. However, the typical inflammatory changes that characterize these diseases have hindered wide diffusion of laparoscopy in this setting, currently mostly pursued in high-volume referral centers, despite accumulating evidences in the literature supporting the benefits of minimally invasive surgery. The largest body of evidence currently available for terminal ileal Crohn’s disease shows improved short term outcomes after laparoscopic surgery, with prolonged operative times. For Crohn’s colitis, high quality evidence supporting laparoscopic surgery is lacking. Encouraging preliminary results have been obtained with the adoption of laparoscopic restorative total proctocolectomy for the treatment of ulcerative colitis. A consensus about patients’ selection and the need for staging has not been reached yet. Despite the lack of conclusive evidence, a wave of enthusiasm is pushing towards less invasive strategies, to further minimize surgical trauma, with single incision laparoscopic surgery being the most realistic future development. PMID:23239913

  4. Molecular surveillance of nasopharyngeal carriage of Streptococcus pneumoniae in children vaccinated with conjugated polysaccharide pneumococcal vaccines.

    PubMed

    Wyllie, Anne L; Wijmenga-Monsuur, Alienke J; van Houten, Marlies A; Bosch, Astrid A T M; Groot, James A; van Engelsdorp Gastelaars, Jody; Bruin, Jacob P; Bogaert, Debby; Rots, Nynke Y; Sanders, Elisabeth A M; Trzciński, Krzysztof

    2016-01-01

    Following the introduction of pneumococcal conjugate vaccines (PCVs) for infants, surveillance studies on Streptococcus pneumoniae carriage have proven valuable for monitoring vaccine effects. Here, we compared molecular versus conventional diagnostic methods in prospective cross-sectional surveillances in vaccinated infants in the Netherlands. Nasopharyngeal samples (n = 1169) from 11- and 24-month-old children, collected during autumn/winter 2010/2011 and 2012/2013, were tested by conventional culture for S. pneumoniae. DNA extracted from all culture-plate growth was tested by qPCR for pneumococcal-specific genes (lytA/piaB) and selected serotypes (including PCV13-serotypes). qPCR significantly increased the number of carriers detected compared to culture (69% vs. 57%, p < 0.0001). qPCR assays targeting vaccine-serotypes 4 and 5 proved non-specific (results excluded). For serotypes reliably targeted by qPCR, the number of serotype-carriage events detected by qPCR (n = 709) was 1.68× higher compared to culture (n = 422). There was a strong correlation (rho = 0.980; p < 0.0001) between the number of serotypes detected using qPCR and by culture. This study demonstrates the high potential of molecular methods in pneumococcal surveillances, particularly for enhanced serotype detection. We found no evidence of a hidden circulation of vaccine-targeted serotypes, despite vaccine-serotypes still significantly contributing to invasive pneumococcal disease in unvaccinated individuals, supporting the presence of a substantial S. pneumoniae reservoir outside vaccinated children. PMID:27046258

  5. An analytical model applied to a multicenter pneumococcal enzyme-linked immunosorbent assay study.

    PubMed

    Plikaytis, B D; Goldblatt, D; Frasch, C E; Blondeau, C; Bybel, M J; Giebink, G S; Jonsdottir, I; Käyhty, H; Konradsen, H B; Madore, D V; Nahm, M H; Schulman, C A; Holder, P F; Lezhava, T; Elie, C M; Carlone, G M

    2000-06-01

    Pneumococcal conjugate vaccines will eventually be licensed after favorable results from phase III efficacy trials. After licensure of a conjugate vaccine for invasive pneumococcal disease in infants, new conjugate vaccines will likely be licensed primarily on the basis of immunogenicity data rather than clinical efficacy. Analytical methods must therefore be developed, evaluated, and validated to compare immunogenicity results accurately within and between laboratories for different vaccines. At present no analytical technique is uniformly accepted and used in vaccine evaluation studies to determine the acceptable level of agreement between a laboratory result and the assigned value for a given serum sample. This multicenter study describes the magnitude of agreement among 12 laboratories quantifying an identical series of 48 pneumococcal serum specimens from 24 individuals (quality-control sera) by a consensus immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) developed for this study. After provisional or trial antibody concentrations were assigned to the quality-control serum samples for this study, four methods for comparison of a series of laboratory-determined values with the assigned concentrations were evaluated. The percent error between assigned values and laboratory-determined concentrations proved to be the most informative of the four methods. We present guidelines that a laboratory may follow to analyze a series of quality-control sera to determine if it can reproduce the assigned antibody concentrations within an acceptable level of tolerance. While this study focused on a pneumococcal IgG ELISA, the methods that we describe are easily generalizable to other immunological assays. PMID:10834951

  6. Molecular surveillance of nasopharyngeal carriage of Streptococcus pneumoniae in children vaccinated with conjugated polysaccharide pneumococcal vaccines

    PubMed Central

    Wyllie, Anne L.; Wijmenga-Monsuur, Alienke J.; van Houten, Marlies A.; Bosch, Astrid A. T. M.; Groot, James A.; van Engelsdorp Gastelaars, Jody; Bruin, Jacob P.; Bogaert, Debby; Rots, Nynke Y.; Sanders, Elisabeth A. M.; Trzciński, Krzysztof

    2016-01-01

    Following the introduction of pneumococcal conjugate vaccines (PCVs) for infants, surveillance studies on Streptococcus pneumoniae carriage have proven valuable for monitoring vaccine effects. Here, we compared molecular versus conventional diagnostic methods in prospective cross-sectional surveillances in vaccinated infants in the Netherlands. Nasopharyngeal samples (n = 1169) from 11- and 24-month-old children, collected during autumn/winter 2010/2011 and 2012/2013, were tested by conventional culture for S. pneumoniae. DNA extracted from all culture-plate growth was tested by qPCR for pneumococcal-specific genes (lytA/piaB) and selected serotypes (including PCV13-serotypes). qPCR significantly increased the number of carriers detected compared to culture (69% vs. 57%, p < 0.0001). qPCR assays targeting vaccine-serotypes 4 and 5 proved non-specific (results excluded). For serotypes reliably targeted by qPCR, the number of serotype-carriage events detected by qPCR (n = 709) was 1.68× higher compared to culture (n = 422). There was a strong correlation (rho = 0.980; p < 0.0001) between the number of serotypes detected using qPCR and by culture. This study demonstrates the high potential of molecular methods in pneumococcal surveillances, particularly for enhanced serotype detection. We found no evidence of a hidden circulation of vaccine-targeted serotypes, despite vaccine-serotypes still significantly contributing to invasive pneumococcal disease in unvaccinated individuals, supporting the presence of a substantial S. pneumoniae reservoir outside vaccinated children. PMID:27046258

  7. 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. PMID:27134492

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

    PubMed Central

    Song, Jin-Su; Kim, Eui-Chong

    2016-01-01

    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. PMID:27134492

  9. 75 FR 48707 - Proposed Vaccine Information Materials for Pneumococcal Conjugate Vaccine and Human...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-11

    ... these materials is included in a December 17, 1999 Federal Register notice (64 FR 70914). Proposed... Vaccine: What You Need to Know 1. Pneumococcal Disease Infection with Streptococcus pneumoniae bacteria... risk for serious disease than older children. Pneumococcal bacteria are spread from person to...

  10. Influenza-induced inflammation drives pneumococcal otitis media.

    PubMed

    Short, Kirsty R; Reading, Patrick C; Brown, Lorena E; Pedersen, John; Gilbertson, Brad; Job, Emma R; Edenborough, Kathryn M; Habets, Marrit N; Zomer, Aldert; Hermans, Peter W M; Diavatopoulos, Dimitri A; Wijburg, Odilia L

    2013-03-01

    Influenza A virus (IAV) predisposes individuals to secondary infections with the bacterium Streptococcus pneumoniae (the pneumococcus). Infections may manifest as pneumonia, sepsis, meningitis, or otitis media (OM). It remains controversial as to whether secondary pneumococcal disease is due to the induction of an aberrant immune response or IAV-induced immunosuppression. Moreover, as the majority of studies have been performed in the context of pneumococcal pneumonia, it remains unclear how far these findings can be extrapolated to other pneumococcal disease phenotypes such as OM. Here, we used an infant mouse model, human middle ear epithelial cells, and a series of reverse-engineered influenza viruses to investigate how IAV promotes bacterial OM. Our data suggest that the influenza virus HA facilitates disease by inducing a proinflammatory response in the middle ear cavity in a replication-dependent manner. Importantly, our findings suggest that it is the inflammatory response to IAV infection that mediates pneumococcal replication. This study thus provides the first evidence that inflammation drives pneumococcal replication in the middle ear cavity, which may have important implications for the treatment of pneumococcal OM. PMID:23319557

  11. 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. PMID:26449937

  12. Invasive Haemophilus influenzae Disease, Europe, 1996–2006

    PubMed Central

    Slack, Mary P.E.; Heath, Paul T.; von Gottberg, Anne; Chandra, Manosree; Ramsay, Mary E.

    2010-01-01

    An international collaboration was established in 1996 to monitor the impact of routine Haemophilus influenzae type b (Hib) vaccination on invasive H. influenzae disease; 14 countries routinely serotype all clinical isolates. Of the 10,081 invasive H. influenzae infections reported during 1996–2006, 4,466 (44%, incidence 0.28 infections/100,000 population) were due to noncapsulated H. influenzae (ncHi); 2,836 (28%, 0.15/100,000), to Hib; and 690 (7%, 0.036/100,000), to non–b encapsulated H. influenzae. Invasive ncHi infections occurred in older persons more often than Hib (median age 58 years vs. 5 years, p<0.0001) and were associated with higher case-fatality ratios (12% vs. 4%, p<0.0001), particularly in infants (17% vs. 3%, p<0.0001). Among non-b encapsulated H. influenzae, types f (72%) and e (21%) were responsible for almost all cases; the overall case-fatality rate was 9%. Thus, the incidence of invasive non–type b H. influenzae is now higher than that of Hib and is associated with higher case fatality. PMID:20202421

  13. [State of the art in invasive diseases by filamentous fungi].

    PubMed

    Pemán, Javier; Quindós, Guillermo

    2014-01-01

    Invasive fungal infections have become a major cause of morbimortality in intensive care patients, persons suffering from cancer or immune deficiencies, and other diseases with impaired immunity. Candida albicans remains the most frequent fungal pathogen, but advances in the diagnosis, prevention and treatment of invasive candidiasis are leading to important etiological changes. Among the emerging invasive mycoses, are those caused by filamentous fungi, such as Aspergillus, Lomentospora/Scedosporium, Fusarium or the Mucorales. Invasive aspergillosis is difficult to diagnose, and although there are diagnostic tools available, their use is not widespread, and their effectiveness vary depending on the group of patients. Clinical suspicion in high-risk patients, radiological diagnosis and the use of biomarkers, such as 1,3-β-D-glucan and galactomannan, can be of great help. However, diagnostic resources are limited in other mycoses, but radiology, pathological studies and the microbiological diagnosis can be useful. The high mortality of these mycoses requires early empirical antifungal treatment in many cases. Voriconazole is the first choice for treatment of the majority of aspergillosis, scedosporiasis, fusariosis and other hyalohyphomycoses. The treatment of mucormycoses, Lomentospora prolificans infections or mycoses by dematiaceous fungi are more complicated. Amphotericin B is active against many mucoralean fungi, but the combination of two or more antifungal agents could be a therapeutic alternative in many amphotericin B-refractory mycoses. Current clinical challenges include improving the diagnosis and the treatment of these mycoses, along with improving the adequate prevention in patients at high risk of suffering from them. PMID:25449676

  14. Invasive and non-invasive methods for the assessment of fibrosis and disease progression in chronic liver disease.

    PubMed

    Castera, Laurent

    2011-04-01

    Chronic liver diseases represent a major public health problem, accounting for significant morbidity and mortality worldwide. Their prognosis and management greatly depend on the amount and progression of liver fibrosis with the risk of developing cirrhosis. Liver biopsy, traditionally considered as the reference standard for staging of fibrosis, has been challenged over the past decade by the development of novel non invasive methodologies. These methods rely on two distinct but complementary approaches: i) a 'biological' approach based on the dosage of serum biomarkers of fibrosis; ii) a 'physical' approach based on the measurement of liver stiffness using transient elastography (TE). Non invasive methods have been initially studied and validated in chronic hepatitis C but are now increasingly used in other chronic liver diseases, resulting in a significant decrease in the need for liver biopsy. However, they will likely not completely abolish the need for liver biopsy and they should rather be employed as an integrated system with liver biopsy. This review is aimed at discussing the advantages and inconveniences of non invasive methods in comparison with liver biopsy for the management of patients with chronic liver diseases. PMID:21497746

  15. Density and Duration of Pneumococcal Carriage Is Maintained by Transforming Growth Factor β1 and T Regulatory Cells

    PubMed Central

    Coward, William R.; Gritzfeld, Jenna F.; Richards, Luke; Garcia-Garcia, Francesc J.; Dotor, Javier; Gordon, Stephen B.

    2014-01-01

    Rationale: Nasopharyngeal carriage of Streptococcus pneumoniae is a prerequisite for invasive disease, but the majority of carriage episodes are asymptomatic and self-resolving. Interactions determining the development of carriage versus invasive disease are poorly understood but will influence the effectiveness of vaccines or therapeutics that disrupt nasal colonization. Objectives: We sought to elucidate immunological mechanisms underlying noninvasive pneumococcal nasopharyngeal carriage. Methods: Pneumococcal interactions with human nasopharyngeal and bronchial fibroblasts and epithelial cells were investigated in vitro. A murine model of nasopharyngeal carriage and an experimental human pneumococcal challenge model were used to characterize immune responses in the airways during carriage. Measurements and Main Results: We describe the previously unknown immunological basis of noninvasive carriage and highlight mechanisms whose perturbation may lead to invasive disease. We identify the induction of active transforming growth factor (TGF)-β1 by S. pneumoniae in human host cells and highlight the key role for TGF-β1 and T regulatory cells in the establishment and maintenance of nasopharyngeal carriage in mice and humans. We identify the ability of pneumococci to drive TGF-β1 production from nasopharyngeal cells in vivo and show that an immune tolerance profile, characterized by elevated TGF-β1 and high nasopharyngeal T regulatory cell numbers, is crucial for prolonged carriage of pneumococci. Blockade of TGF-β1 signaling prevents prolonged carriage and leads to clearance of pneumococci from the nasopharynx. Conclusions: These data explain the mechanisms by which S. pneumoniae colonize the human nasopharynx without inducing damaging host inflammation and provide insight into the role of bacterial and host constituents that allow and maintain carriage. PMID:24749506

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

    PubMed

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

    2015-05-01

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

  17. New Invasive Assessment Measures of Coronary Artery Disease Severity.

    PubMed

    Khanna, Neel; Subramanian, Kathir S; Khera, Sahil; Aronow, Wilbert S; Frishman, William H

    2016-01-01

    Ischemic heart disease is the leading cause of mortality worldwide. The assessment and treatment of patients with ischemic heart disease have advanced greatly over the past decade. Particular attention has been given recently to the recognition of lesions that cause ischemia or that are prone to plaque rupture. New invasive measures of coronary artery disease have been developed, including fractional flow reserve, intravascular ultrasound, optical coherence tomography, and most recently, near-infrared spectroscopy. These technologies have helped to guide the assessment of hemodynamically significant lesions and have shown particular promise in guiding percutaneous coronary interventions. However, mortality and the rate of revascularization have shown mixed results to date. This review seeks to investigate the use and potential benefit of these technologies, with particular attention to clinical end points. PMID:26751263

  18. Description of the Pathogenic Features of Streptococcus pyogenes Isolates from Invasive and Non-Invasive Diseases in Aichi, Japan.

    PubMed

    Matsumoto, Masakado; Yamada, Kazuhiro; Suzuki, Masahiro; Adachi, Hirokazu; Kobayashi, Shinichi; Yamashita, Teruo; Minagawa, Hiroko; Tatsuno, Ichiro; Hasegawa, Tadao

    2016-07-22

    We identified hypervirulent Streptococcus pyogenes in 27 and 420 isolates from patients with invasive and non-invasive diseases, respectively, in Aichi Prefecture, Japan, between 2003 and 2012, in an attempt to understand why the prevalence of streptococcal toxic shock syndrome (STSS) suddenly increased in this location during 2011. Hypervirulent strains belong to the emm1 genotype, with a mutation in the covR/S genes that regulate many other genes, encoding virulence determinants and resulting in the absence of the proteinase streptococcal exotoxin B and the production of virulence factors such as the superantigen streptococcal exotoxin A, the nuclease streptococcal DNase, the cytotoxin NAD-glycohydrolase, and the hemolysin streptolysin O. We found 1 strain from invasive disease and 1 from non-invasive disease with traits similar to those of hypervirulent strains, except that the sda1 gene was absent. We also found 1 non-emm1 strain with phenotypic and genetic traits identical to those of the emm1 hypervirulent strains except that it did not belong to emm1 genotype, from non-invasive diseases cases in 2011. These findings suggested that hypervirulent and hypervirulent-like strains from invasive and non-invasive disease cases could have at least partially contributed to the sudden increase in the number of patients with STSS in Aichi during 2011. PMID:26567838

  19. Pneumococcal Infections - Multiple Languages: MedlinePlus

    MedlinePlus

    ... please enable JavaScript. Chinese - Traditional (繁體中文) Farsi (فارسی) Russian (Русский) Spanish (español) Tagalog (Tagalog) Thai (ภาษาไทย) Vietnamese ( ... Action Coalition; Centers for Disease Control and Prevention Russian (Русский) Pneumococcal Conjugate Vaccine English Русский (Russian) PDF ...

  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. PMID:25245810

  1. Lactate Dehydrogenase Is the Key Enzyme for Pneumococcal Pyruvate Metabolism and Pneumococcal Survival in Blood

    PubMed Central

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

    2014-01-01

    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. PMID:25245810

  2. 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

  3. The Effects of CFTR and Mucoid Phenotype on Susceptibility and Innate Immune Responses in a Mouse Model of Pneumococcal Lung Disease

    PubMed Central

    Dennis, Evida A.; Coats, Mamie T.; Griffin, Sarah E.; Hale, Joanetha Y.; Novak, Lea; Briles, David E.; Crain, Marilyn J.

    2015-01-01

    Recent studies have reported the isolation of highly mucoid serotype 3 Streptococcus pneumoniae (Sp) from the respiratory tracts of children with cystic fibrosis (CF). Whether these highly mucoid Sp contribute to, or are associated with, respiratory failure among patients with CF remains unknown. Other mucoid bacteria, predominately Pseudomonas aeruginosa, are associated with CF respiratory decline. We used a mouse model of CF to study pneumococcal pneumonia with highly mucoid serotype 3 and non-mucoid serotype 19A Sp isolates. We investigated susceptibility to infection, survival, and bacterial counts from bronchoaviolar lavage samples and lung homogenates, as well as associated inflammatory cytokines at the site of infection, and lung pathology. Congenic CFTR–/– mice and wild-type (WT)-mice were infected intranasally with CHB756, CHB1126, and WU2 (highly mucoid capsular serotype 3, intermediately mucoid serotype 3, and less mucoid serotype 3, respectively), or CHB1058 (non-mucoid serotype 19A). BAL, lung homogenates, and blood were collected from mice 5 days post-infection. Higher CFU recovery and shorter survival were observed following infection of CFTR–/– mice with CHB756 compared to infection with CHB1126, WU2, or CHB1058 (P≤0.001). Additionally, CFTR–/– mice infected with CHB756 and CHB1126 were more susceptible to infection than WT-mice (P≤0.05). Between CFTR–/– mice and WT-mice, no significant differences in TNF-α, CXCL1/KC concentrations, or lung histopathology were observed. Our results indicate that highly mucoid type 3 Sp causes more severe lung disease than non-mucoid Sp, and does so more readily in the lungs of CFTR–/– than WT-mice. PMID:26469863

  4. Does high biodiversity reduce the risk of Lyme disease invasion?

    PubMed Central

    2013-01-01

    Background It has been suggested that increasing biodiversity, specifically host diversity, reduces pathogen and parasite transmission amongst wildlife (causing a “dilution effect”), whereby transmission amongst efficient reservoir hosts, (e.g. Peromyscus spp. mice for the agent of Lyme disease Borrelia burgdorferi) is reduced by the presence of other less efficient host species. If so, then increasing biodiversity should inhibit pathogen and parasite invasion. Methods We investigated this hypothesis by studying invasion of B. burgdorferi and its tick vector Ixodes scapularis in 71 field sites in southeastern Canada. Indices of trapped rodent host diversity, and of biodiversity of the wider community, were investigated as variables explaining the numbers of I. scapularis collected and B. burgdorferi infection in these ticks. A wide range of alternative environmental explanatory variables were also considered. Results The observation of low I. scapularis abundance and low B. burgdorferi infection prevalence in sites where I. scapularis were detected was consistent with early-stage invasion of the vector. There were significant associations between the abundance of ticks and season, year of study and ambient temperature. Abundance of host-seeking larvae was significantly associated with deer density, and abundance of host-seeking larvae and nymphs were positively associated with litter layer depth. Larval host infestations were lower where the relative proportion of non-Peromyscus spp. was high. Infestations of hosts with nymphs were lower when host species richness was higher, but overall nymphal abundance increased with species richness because Peromyscus spp. mouse abundance and host species richness were positively correlated. Nymphal infestations of hosts were lower where tree species richness was higher. B. burgdorferi infection prevalence in ticks varied significantly with an index of rates of migratory bird-borne vector and pathogen invasion. Conclusions

  5. Non-invasive investigation of inflammatory bowel disease

    PubMed Central

    Tibble, JA; Bjarnason, I

    2001-01-01

    The assessment of inflammatory activity in intestinal disease in man can be done using a variety of different techniques. These range from the use of non-invasive acute phase inflammatory markers measured in plasma such as C reactive protein (CRP) and the erythrocyte sedimentation rate (ESR) (both of which give an indirect assessment of disease activity) to the direct assessment of disease activity by intestinal biopsy performed during endoscopy in association with endoscopic scoring systems. Both radiology and endoscopy are conventional for the diagnosis of inflammatory bowel disease (IBD). However these techniques have severe limitations when it comes to assessing functional components of the disease such as activity and prognosis. Here we briefly review the value of two emerging intestinal function tests. Intestinal permeability, although ideally suited for diagnostic screening for small bowel Crohn’s disease, appears to give reliable predictive data for imminent relapse of small bowel Crohn’s disease and it can be used to assess responses to treatment. More significantly it is now clear that single stool assay of neutrophil specific proteins (calprotectin, lactoferrin) give the same quantitative data on intestinal inflammation as the 4-day faecal excretion of 111Indium labelled white cells. Faecal calprotectin is shown to be increased in over 95% of patients with IBD and correlates with clinical disease activity. It reliably differentiates between patients with IBD and irritable bowel syndrome. More importantly, at a given faecal calprotectin concentration in patients with quiescent IBD, the test has a specificity and sensitivity in excess of 85% in predicting clinical relapse of disease. This suggests that relapse of IBD is closely related to the degree of intestinal inflammation and suggests that targeted treatment at an asymptomatic stage of the disease may be indicated. PMID:11819811

  6. Improving Influenza and Pneumococcal Vaccination Rates in Ambulatory Specialty Practices

    PubMed Central

    Pennant, Keyana N.; Costa, John J.; Fuhlbrigge, Anne L.; Sax, Paul E.; Szent-Gyorgyi, Lara E.; Coblyn, Jonathan; Desai, Sonali P.

    2015-01-01

    Background. Influenza and pneumococcal vaccinations are recommended for elderly and high-risk patients; however, rates of adherence are low. We sought to implement influenza and pneumococcal vaccine initiatives in 4 different ambulatory specialty practices, using 3 unique approaches. Methods. Four specialties with high-risk patient populations were selected for intervention: allergy (asthma), infectious disease (ID) (human immunodeficiency virus), pulmonary (chronic lung disease), and rheumatology (immunocompromised). Allergy and ID focused on influenza vaccination, and pulmonary and rheumatology focused on pneumococcal vaccination. We used 3 strategies for quality improvement: physician reminders, patient letters, and a nurse-driven model. Physicians were provided their performance data on a monthly basis and presented trended data on a quarterly basis at staff meetings. Results. All 4 specialties developed processes for improving vaccination rates with all showing some increase. Higher rates were achieved with pneumococcal vaccine than influenza. Pneumococcal vaccine rates showed steady improvement from year to year while influenza vaccine rates remained relatively constant. Allergy's influenza rate was 59% in 2011 and 64% in the 2014 flu season. Infectious disease influenza rates moved from 74% in the 2011 flu season to 86% for the 2014 season. Pneumococcal vaccine in pulmonary patients' rate was 52% at the start of intervention in February 2009 and 79% as of January 2015. Rheumatology rates rose from 50% in February 2009 to 87% in January 2015. Conclusions. Integrated routine workflow and performance data sharing can effectively engage specialists and staff in vaccine adherence improvement. Influenza vaccination may require other approaches to achieve the rates seen with pneumococcal vaccine. PMID:26430697

  7. 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

    2016-01-01

    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. 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. PMID:27193124

  8. Low vaccination coverage for seasonal influenza and pneumococcal disease among adults at-risk and health care workers in Ireland, 2013: The key role of GPs in recommending vaccination.

    PubMed

    Giese, Coralie; Mereckiene, Jolita; Danis, Kostas; O'Donnell, Joan; O'Flanagan, Darina; Cotter, Suzanne

    2016-07-12

    The World Health Organization (WHO), and European Agencies recommend influenza vaccination for individuals at-risk due to age (≥65 years), underlying diseases, pregnancy and for health care workers (HCWs) in Europe. Pneumococcal vaccine is recommended for those at-risk of pneumococcal disease. In Ireland, vaccination uptake among at-risk adults is not routinely available. In 2013, we conducted a national survey among Irish residents ≥18 years of age, to estimate size and vaccination coverage of at-risk groups, and identify predictive factors for influenza vaccination. We used computer assisted telephone interviews to collect self-reported information on health, vaccination status, attitudes towards vaccination. We calculated prevalence and prevalence ratios (PR) using binomial regression. Overall, 1770 individuals participated. For influenza, among those aged 18-64 years, 22% (325/1485) [95%CI: 17%-20%] were at-risk; 28% [95%CI: 23%-33%] were vaccinated. Among those aged ≥65 years, 60% [95%CI: 54%-66%] were vaccinated. Influenza vaccine uptake among HCWs was 28% [95%CI: 21%-35%]. For pneumococcal disease, among those aged 18-64 years, 18% [95%CI: 16%-20%] were at-risk; 16% [95%CI: 12%-21%] reported ever-vaccination; among those aged ≥65 years, 36% [95%CI: 30%-42%] reported ever-vaccination. Main reasons for not receiving influenza vaccine were perceptions of not being at-risk, or not thinking of it; and among HCWs thinking that vaccination was not necessary or they were not at-risk. At-risk individuals were more likely to be vaccinated if their doctor had recommended it (PR 3.2; [95%CI: 2.4%-4.4%]) or they had access to free medical care or free vaccination services (PR 2.0; [95%CI: 1.5%-2.8%]). Vaccination coverage for both influenza and pneumococcal vaccines in at-risk individuals aged 18-64 years was very low. Influenza vaccination coverage among individuals ≥65 years was moderate. Influenza vaccination status was associated with GP vaccination

  9. 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. PMID:26767542

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

    PubMed Central

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

    2012-01-01

    Summary 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. PMID:22587967

  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. Diagnostic methods for invasive fungal diseases in patients with hematologic malignancies

    PubMed Central

    Riwes, Mary Mansour; Wingard, John R

    2013-01-01

    Invasive fungal disease is associated with increased morbidity and mortality in hematologic malignancy patients and hematopoietic stem cell transplant recipients. Timely recognition and treatment of invasive fungal diseases in these patients are essential and decrease mortality. However, conventional definitive diagnostic methods are difficult and time consuming. While conventional microbiological and histopathological methods are still needed for a definitive diagnosis of invasive fungal disease, new noninvasive diagnostic methods including serologic and molecular biomarkers are now available. These new diagnostic methods facilitate an early diagnosis of invasive fungal disease and allow for utilization of a pre-emptive treatment approach, which may ultimately lead to improved treatment outcomes and reduced toxicity. PMID:23216596

  13. Structure of Pneumococcal Peptidoglycan Hydrolase LytB Reveals Insights into the Bacterial Cell Wall Remodeling and Pathogenesis*

    PubMed Central

    Bai, Xiao-Hui; Chen, Hui-Jie; Jiang, Yong-Liang; Wen, Zhensong; Huang, Yubin; Cheng, Wang; Li, Qiong; Qi, Lei; Zhang, Jing-Ren; Chen, Yuxing; Zhou, Cong-Zhao

    2014-01-01

    Streptococcus pneumoniae causes a series of devastating infections in humans. Previous studies have shown that the endo-β-N-acetylglucosaminidase LytB is critical for pneumococcal cell division and nasal colonization, but the biochemical mechanism of LytB action remains unknown. Here we report the 1.65 Å crystal structure of the catalytic domain (residues Lys-375–Asp-658) of LytB (termed LytBCAT), excluding the choline binding domain. LytBCAT consists of three structurally independent modules: SH3b, WW, and GH73. These modules form a “T-shaped” pocket that accommodates a putative tetrasaccharide-pentapeptide substrate of peptidoglycan. Structural comparison and simulation revealed that the GH73 module of LytB harbors the active site, including the catalytic residue Glu-564. In vitro assays of hydrolytic activity indicated that LytB prefers the peptidoglycan from the lytB-deficient pneumococci, suggesting the existence of a specific substrate of LytB in the immature peptidoglycan. Combined with in vitro cell-dispersing and in vivo cell separation assays, we demonstrated that all three modules are necessary for the optimal activity of LytB. Further functional analysis showed that the full catalytic activity of LytB is required for pneumococcal adhesion to and invasion into human lung epithelial cells. Structure-based alignment indicated that the unique modular organization of LytB is highly conserved in its orthologs from Streptococcus mitis group and Gemella species. These findings provided structural insights into the pneumococcal cell wall remodeling and novel hints for the rational design of therapeutic agents against pneumococcal growth and thereby the related diseases. PMID:25002590

  14. Low Serum Fetuin-A as a Biomarker to Predict Pneumococcal Necrotizing Pneumonia and Hemolytic Uremic Syndrome in Children

    PubMed Central

    Janapatla, Rajendra Prasad; Hsu, Mei-Hua; Liao, Wan-Ting; Chien, Kun-Yi; Lee, Hao-Yuan; Chiu, Cheng-Hsun

    2016-01-01

    Abstract Streptococcus pneumoniae, a neuraminidase-producing pathogen, can cause invasive pneumococcal disease (IPD) with or without hemolytic uremic syndrome (HUS) in humans. We aimed to identify serum sialoglycoproteins that are targeted by neuraminidases in severe pneumococcal infection. We hypothesized that serum sialoglycoprotein such as fetuin-A can serve as a biomarker to predict IPD or HUS. We constructed serum sialoglycoprotein profiles before and after pneumococcal neuraminidase treatment using liquid chromatography-tandem mass spectrometry (LC-MS/MS), a proteomic approach. An observational study was conducted using clinical data and serum samples from pediatric patients with pneumococcal infection to verify the predictive role of fetuin-A in IPD. Serum fetuin-A levels were determined by enzyme-linked immunosorbent assay. The most abundant serum sialoglycoproteins identified by LC-MS/MS after neuraminidase treatment and peanut lectin capture were immunoglobulins, apolipoproteins, fibrinogens, keratins, complement system proteins, and fetuin-A. Serum fetuin-A levels in the HUS patients were significantly lower (207 ± 80 mg/L, P < 0.001) than in patients with lobar pneumonia (610 ± 190 mg/L) as well as the healthy controls (630 ± 250 mg/L). In comparing HUS with necrotizing pneumonia and lobar pneumonia, the ROC area under the curve was 0.842; a cutoff value of 298 mg/L yielded sensitivity of 92.9% (95% CI: 68.5–98.7%) and specificity of 71.9% (95% CI: 54.6–84.4%). This observational study with validation cohorts of patients with HUS, complicated pneumonia, and lobar pneumonia demonstrates the high performance of low serum fetuin-A levels as a biomarker to predict severe IPD and HUS in children. PMID:27043691

  15. Low Serum Fetuin-A as a Biomarker to Predict Pneumococcal Necrotizing Pneumonia and Hemolytic Uremic Syndrome in Children.

    PubMed

    Janapatla, Rajendra Prasad; Hsu, Mei-Hua; Liao, Wan-Ting; Chien, Kun-Yi; Lee, Hao-Yuan; Chiu, Cheng-Hsun

    2016-03-01

    Streptococcus pneumoniae, a neuraminidase-producing pathogen, can cause invasive pneumococcal disease (IPD) with or without hemolytic uremic syndrome (HUS) in humans.We aimed to identify serum sialoglycoproteins that are targeted by neuraminidases in severe pneumococcal infection. We hypothesized that serum sialoglycoprotein such as fetuin-A can serve as a biomarker to predict IPD or HUS.We constructed serum sialoglycoprotein profiles before and after pneumococcal neuraminidase treatment using liquid chromatography-tandem mass spectrometry (LC-MS/MS), a proteomic approach. An observational study was conducted using clinical data and serum samples from pediatric patients with pneumococcal infection to verify the predictive role of fetuin-A in IPD. Serum fetuin-A levels were determined by enzyme-linked immunosorbent assay.The most abundant serum sialoglycoproteins identified by LC-MS/MS after neuraminidase treatment and peanut lectin capture were immunoglobulins, apolipoproteins, fibrinogens, keratins, complement system proteins, and fetuin-A. Serum fetuin-A levels in the HUS patients were significantly lower (207 ± 80 mg/L, P < 0.001) than in patients with lobar pneumonia (610 ± 190 mg/L) as well as the healthy controls (630 ± 250 mg/L). In comparing HUS with necrotizing pneumonia and lobar pneumonia, the ROC area under the curve was 0.842; a cutoff value of 298 mg/L yielded sensitivity of 92.9% (95% CI: 68.5-98.7%) and specificity of 71.9% (95% CI: 54.6-84.4%).This observational study with validation cohorts of patients with HUS, complicated pneumonia, and lobar pneumonia demonstrates the high performance of low serum fetuin-A levels as a biomarker to predict severe IPD and HUS in children. PMID:27043691

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

    PubMed Central

    Morand, Philippe C; Veuillez, Veronique; Poyart, Claire; Abachin, Eric; Quesne, Gilles; Dupont, Bertrand; Berche, Patrick; Viard, Jean-Paul

    2003-01-01

    Background Streptococcus pneumoniae is a major cause of human disease, especially in pre-school children and elderly people, as well as in special risk groups such as asplenic, antibody deficient patients, or presenting disruption of natural barriers. The occurrence of pneumococcal disease has increased with the onset of the HIV epidemic and the emergence of drug-resistance. Case presentation We report the case of an HIV-1-infected patient who experienced three episodes of recurrent pneumococcal meningitis over a 4-year period, despite chemoprophylaxis and capsular vaccination. Conclusions Efficacy of anti-pneumococcal chemoprophylaxis and vaccination in HIV-infected patients are discussed in the light of this particular case. PMID:14613586

  17. 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. PMID:26000646

  18. [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. PMID:26062225

  19. Minimally invasive surgery for inflammatory bowel disease: Current perspectives.

    PubMed

    Shrestha, Badri

    2016-05-01

    The surgical management of complicated and recurrent inflammatory bowel disease (IBD), has remained a challenge. Minimally invasive surgery (MIS), in the form of laparoscopic resections, single port approach and robotic-assisted dissections in the management of IBD, have been examined in several prospective studies. All of them have shown advantages over open surgery in terms of reduction of physical trauma of surgery, recovery time, better cosmetic outcomes and shorter hospitalization. However, it is important to appreciate that not all patients with IBD are suitable for MIS, so a combination of both open and MIS should be adopted to achieve optimum outcomes. A review on this subject performed by Neumann et al in this issue of World Journal of Gastrointestinal Pharmacology and Therapeutics have provided evidence in support of the contemporary practice of MIS in the management of IBD and the accompanying commentary further critically evaluates their application in clinical practice. PMID:27158536

  20. Minimally invasive surgery for inflammatory bowel disease: Current perspectives

    PubMed Central

    Shrestha, Badri

    2016-01-01

    The surgical management of complicated and recurrent inflammatory bowel disease (IBD), has remained a challenge. Minimally invasive surgery (MIS), in the form of laparoscopic resections, single port approach and robotic-assisted dissections in the management of IBD, have been examined in several prospective studies. All of them have shown advantages over open surgery in terms of reduction of physical trauma of surgery, recovery time, better cosmetic outcomes and shorter hospitalization. However, it is important to appreciate that not all patients with IBD are suitable for MIS, so a combination of both open and MIS should be adopted to achieve optimum outcomes. A review on this subject performed by Neumann et al in this issue of World Journal of Gastrointestinal Pharmacology and Therapeutics have provided evidence in support of the contemporary practice of MIS in the management of IBD and the accompanying commentary further critically evaluates their application in clinical practice. PMID:27158536

  1. Invasive fungal diseases in patients with acute lymphoid leukemia.

    PubMed

    Nicolato, Andrea; Nouér, Simone A; Garnica, Marcia; Portugal, Rodrigo; Maiolino, Angelo; Nucci, Marcio

    2016-09-01

    Invasive fungal disease (IFD) represents an important complication in patients with acute lymphoid leukemia (ALL). The objectives of this study were to determine the prevalence of IFD in ALL patients with neutropenia, identify factors associated with IFD, and estimate the impact of IFD on the outcome. All patients with ALL who developed febrile neutropenia from 1987 to 2013 were evaluated. Cases of IFD were classified as proven or probable. Factors associated with IFD were evaluated by comparing episodes with and without a diagnosis of IFD. Among 350 episodes of febrile neutropenia, 31 IFDs were diagnosed (8.8%). Prolonged neutropenia was the only factor associated with IFD caused by yeasts. Factors associated with IFD caused by molds by multivariate analysis were the period after 2008, receipt of allogeneic transplant, relapsed ALL and prolonged neutropenia. Patients in relapse should receive induction chemotherapy in rooms with HEPA filter and receive antifungal prophylaxis. PMID:26949001

  2. Non-invasive diagnosis of alcoholic liver disease.

    PubMed

    Mueller, Sebastian; Seitz, Helmut Karl; Rausch, Vanessa

    2014-10-28

    Alcoholic liver disease (ALD) is the most common liver disease in the Western world. For many reasons, it is underestimated and underdiagnosed. An early diagnosis is absolutely essential since it (1) helps to identify patients at genetic risk for ALD; (2) can trigger efficient abstinence namely in non-addicted patients; and (3) initiate screening programs to prevent life-threatening complications such as bleeding from varices, spontaneous bacterial peritonitis or hepatocellular cancer. The two major end points of ALD are alcoholic liver cirrhosis and the rare and clinically-defined alcoholic hepatitis (AH). The prediction and early diagnosis of both entities is still insufficiently solved and usually relies on a combination of laboratory, clinical and imaging findings. It is not widely conceived that conventional screening tools for ALD such as ultrasound imaging or routine laboratory testing can easily overlook ca. 40% of manifest alcoholic liver cirrhosis. Non-invasive methods such as transient elastography (Fibroscan), acoustic radiation force impulse imaging or shear wave elastography have significantly improved the early diagnosis of alcoholic cirrhosis. Present algorithms allow either the exclusion or the exact definition of advanced fibrosis stages in ca. 95% of patients. The correct interpretation of liver stiffness requires a timely abdominal ultrasound and actual transaminase levels. Other non-invasive methods such as controlled attenuation parameter, serum levels of M30 or M65, susceptometry or breath tests are under current evaluation to assess the degree of steatosis, apoptosis and iron overload in these patients. Liver biopsy still remains an important option to rule out comorbidities and to confirm the prognosis namely for patients with AH. PMID:25356026

  3. Non-invasive diagnosis of alcoholic liver disease

    PubMed Central

    Mueller, Sebastian; Seitz, Helmut Karl; Rausch, Vanessa

    2014-01-01

    Alcoholic liver disease (ALD) is the most common liver disease in the Western world. For many reasons, it is underestimated and underdiagnosed. An early diagnosis is absolutely essential since it (1) helps to identify patients at genetic risk for ALD; (2) can trigger efficient abstinence namely in non-addicted patients; and (3) initiate screening programs to prevent life-threatening complications such as bleeding from varices, spontaneous bacterial peritonitis or hepatocellular cancer. The two major end points of ALD are alcoholic liver cirrhosis and the rare and clinically-defined alcoholic hepatitis (AH). The prediction and early diagnosis of both entities is still insufficiently solved and usually relies on a combination of laboratory, clinical and imaging findings. It is not widely conceived that conventional screening tools for ALD such as ultrasound imaging or routine laboratory testing can easily overlook ca. 40% of manifest alcoholic liver cirrhosis. Non-invasive methods such as transient elastography (Fibroscan), acoustic radiation force impulse imaging or shear wave elastography have significantly improved the early diagnosis of alcoholic cirrhosis. Present algorithms allow either the exclusion or the exact definition of advanced fibrosis stages in ca. 95% of patients. The correct interpretation of liver stiffness requires a timely abdominal ultrasound and actual transaminase levels. Other non-invasive methods such as controlled attenuation parameter, serum levels of M30 or M65, susceptometry or breath tests are under current evaluation to assess the degree of steatosis, apoptosis and iron overload in these patients. Liver biopsy still remains an important option to rule out comorbidities and to confirm the prognosis namely for patients with AH. PMID:25356026

  4. Global Burden of Invasive Nontyphoidal Salmonella Disease, 20101

    PubMed Central

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

    2015-01-01

    Nontyphoidal Salmonella is a major cause of bloodstream infections worldwide, and HIV-infected persons and malaria-infected and malnourished 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, had 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. PMID:25860298

  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

    2016-02-01

    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. PMID:26618243

  6. 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

  7. Impact of Pneumococcal Conjugate Vaccine Administration in Pediatric Older Age Groups in Low and Middle Income Countries: A Systematic Review

    PubMed Central

    Bonner, Kimberly; Welch, Emily; Elder, Kate; Cohn, Jennifer

    2015-01-01

    Introduction Pneumococcal conjugate vaccine (PCV) is included in the World Health Organization’s routine immunization schedule and is recommended by WHO for vaccination in high-risk children up to 60 months. However, many countries do not recommend vaccination in older age groups, nor have donors committed to supporting extended age group vaccination. To better inform decision-making, this systematic review examines the direct impact of extended age group vaccination in children over 12 months in low and middle income countries. Methods An a priori protocol was used. Using pre-specified terms, a search was conducted using PubMed, LILACS, Cochrane Infectious Diseases Group Specialized Register, Cochrane Central Register of Controlled Trials, CAB Abstracts, clinicaltrials.gov and the International Symposium on Pneumococci and Pneumococcal Diseases abstracts. The primary outcome was disease incidence, with antibody titers and nasopharyngeal carriage included as secondary outcomes. Results Eighteen studies reported on disease incidence, immune response, and nasopharyngeal carriage. PCV administered after 12 months of age led to significant declines in invasive pneumococcal disease. Immune response to vaccine type serotypes was significantly higher for those vaccinated at older ages than the unimmunized at the established 0.2ug/ml and 0.35ug/ml thresholds. Vaccination administered after one year of age significantly reduced VT carriage with odds ratios ranging from 0.213 to 0.69 over four years. A GRADE analysis indicated that the studies were of high quality. Discussion PCV administration in children over 12 months leads to significant protection. The direct impact of PCV administration, coupled with the large cohort of children missed in first year vaccination, indicates that countries should initiate or expand PCV immunization for extended age group vaccinations. Donors should support implementation of PCV as part of delayed or interrupted immunization for older

  8. 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. PMID:26972430

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

    PubMed

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

    2015-07-01

    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

  10. 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

  11. Streptococcus acidominimus causing invasive disease in humans: a case series

    PubMed Central

    2014-01-01

    Introduction Streptococcus acidominimus is a member of the viridans group streptococci and is rarely pathogenic in humans, making it difficult to assess its epidemiologic and clinical significance. Case presentation We report the cases of five Han Chinese patients with invasive diseases caused by S. acidominimus over a one-year time frame. Three of the patients developed continuous fever after surgery, consisting of a successful elective laparoscopic cholecystectomy (case 1), a laparoscopic esophageal resection and gastroesophageal anastomosis (case 2), and a liver transplant in a patient with liver cancer (case 3). For these three patients, cultures of the purulent drainage material grew S. acidominimus. Case 4 concerns a 52-year-old man who developed sepsis 48 hours after hospitalization for hepatitis, liver cirrhosis and hepatitis-related glomerulonephritis. Case 5 concerns a 55-year-old woman receiving regular hemodialysis who had low-grade fever for one month. For these two patients, blood cultures grew S. acidominimus. An antimicrobial susceptibility test revealed that S. acidominimus was resistant to clindamycin and, to some degree, beta-lactam or macrolides. The S. acidominimus from the patient on hemodialysis was resistant to multiple antibiotics. Conclusion S. acidominimus is an ever-increasing cause of disease, especially in patients who are critically ill. It is showing increased resistance to antimicrobial agents, so in patients with viridans group streptococci infections, it is necessary to identify the species to improve the clinical management of S. acidominimus. PMID:24529345

  12. Pneumococcal Vaccination: Who Needs It?

    MedlinePlus

    ... News and Media Resources News Newsletters Events Pneumococcal Vaccination: Who Needs It? Recommend on Facebook Tweet Share ... doses will depend on the child's age when vaccination begins. Ask your healthcare provider for details. Children ...

  13. 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. PMID:27021424

  14. Indirect effect of conjugate pneumococcal vaccination in a 2+1 dose schedule.

    PubMed

    Vestrheim, Didrik F; Høiby, E Arne; Bergsaker, Marianne R; Rønning, Karin; Aaberge, Ingeborg S; Caugant, Dominique A

    2010-03-01

    In 2006, the heptavalent pneumococcal conjugate vaccine (PCV7) was introduced in the Norwegian Childhood Vaccination Programme in a 2+1 dose schedule; immunisations are administered at 3, 5 and 12 months. Changes in invasive pneumococcal disease in all ages from the baseline years 2004-2005 to 2008 were assessed, focusing on the indirect effect in the unvaccinated population. Following the introduction of PCV7, incidence rates of IPD caused by vaccine serotypes declined across all age groups, the decline being statistically significant for the age groups <5 years, 5-19 years, 40-64 years and > or = 65 years. In the unvaccinated population aged > or = 5 years the incidence rate of IPD caused by PCV7 serotypes declined by 48% from 12.34 cases/100,000 population to 6.44 cases/100,000 population, accounting for 74% of prevented cases of IPD in 2008. Among the adults aged > or = 65 years the incidence rate of IPD caused by serotypes not included in PCV7 increased. No vaccine failure was identified, indicating a very high effectiveness of the 2+1 dose schedule vaccination programme. PMID:20056192

  15. Minimally invasive surgery for diaphragmatic diseases in neonates and infants.

    PubMed

    Fujishiro, Jun; Ishimaru, Tetsuya; Sugiyama, Masahiko; Arai, Mari; Suzuki, Keisuke; Kawashima, Hiroshi; Iwanaka, Tadashi

    2016-07-01

    Owing to recent advances in minimally invasive surgery (MIS), laparoscopic and thoracoscopic surgery have been gradually introduced for use in neonates and infants. This review focuses on two popular MIS procedures for diaphragmatic diseases in neonates and infants: congenital diaphragmatic hernia (CHD) repair and plication for diaphragmatic eventration. While several advantages of MIS are proposed for CDH repair in neonates, there are also some concerns, namely intraoperative hypercapnia and acidosis and a higher recurrence rate than open techniques. Thus, neonates with severe CDH, along with an unstable circulatory and respiratory status, may be unsuitable for MIS repair, and the use of selection criteria is, therefore, important in these patients. It is generally believed that a learning curve is associated with the higher recurrence rate. Contrary to CDH repair, no major disadvantages associated with the use of MIS for diaphragmatic eventration have been reported in the literature, other than technical difficulty. Thus, if technically feasible, all pediatric patients with diaphragmatic eventration requiring surgical treatment are potential candidates for MIS. Due to a shortage of studies on this procedure, the potential advantages of MIS compared to open techniques for diaphragmatic eventration, such as early recovery and more rapid extubation, need to be confirmed by further studies. PMID:27246508

  16. 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.

  17. Pneumococcal Disease: Types of Infection

    MedlinePlus

    ... Vaccination For Clinicians Streptococcus pneumoniae Transmission Clinical Features Risk Factors Diagnosis & Management Prevention For Laboratorians Drug Resistance Surveillance & Reporting Global ...

  18. Pneumococcal Disease: Diagnosis and Treatment

    MedlinePlus

    ... in 3 out of every 10 cases. Antibiotic sensitivity testing shows which antibiotics will be most successful ... ‘broad-spectrum’ antibiotics until results of antibiotic sensitivity testing are available. Broad-spectrum antibiotics work against ...

  19. Simultaneous Nasopharyngeal Carriage of Two Pneumococcal Multilocus Sequence Types with a Serotype 3 Phenotype

    PubMed Central

    Inverarity, Donald; Diggle, Mathew; Ure, Roisin; Santana-Hernandez, Diego; Altstadt, Peter; Mitchell, Timothy; Edwards, Giles

    2010-01-01

    Knowledge of the epidemiology of pneumococcal disease in Bolivia is sparse, and Multilocus Sequence Typing (MLST) of isolates has not been previously possible. Beni state has until recently been a geographically isolated region of the Bolivian Amazon basin and is a region of significant poverty. During June and July 2007, we performed a pneumococcal carriage study recruiting over 600 schoolchildren in two towns in the Beni state. Here, we describe the unique identification of simultaneous nasopharyngeal carriage of two pneumococcal multilocus sequence types with a serotype 3 phenotype within a single subject. PMID:21151653

  20. Invasion of two tick-borne diseases across New England: harnessing human surveillance data to capture underlying ecological invasion processes.

    PubMed

    Walter, Katharine S; Pepin, Kim M; Webb, Colleen T; Gaff, Holly D; Krause, Peter J; Pitzer, Virginia E; Diuk-Wasser, Maria A

    2016-06-15

    Modelling the spatial spread of vector-borne zoonotic pathogens maintained in enzootic transmission cycles remains a major challenge. The best available spatio-temporal data on pathogen spread often take the form of human disease surveillance data. By applying a classic ecological approach-occupancy modelling-to an epidemiological question of disease spread, we used surveillance data to examine the latent ecological invasion of tick-borne pathogens. Over the last half-century, previously undescribed tick-borne pathogens including the agents of Lyme disease and human babesiosis have rapidly spread across the northeast United States. Despite their epidemiological importance, the mechanisms of tick-borne pathogen invasion and drivers underlying the distinct invasion trajectories of the co-vectored pathogens remain unresolved. Our approach allowed us to estimate the unobserved ecological processes underlying pathogen spread while accounting for imperfect detection of human cases. Our model predicts that tick-borne diseases spread in a diffusion-like manner with occasional long-distance dispersal and that babesiosis spread exhibits strong dependence on Lyme disease. PMID:27252022

  1. US Pneumonia Hospitalizations, a Decade of Pneumococcal Conjugate Vaccine Use

    PubMed Central

    Griffin, Marie R.; Zhu, Yuwei; Moore, Matthew R.; Whitney, Cynthia G.; Grijalva, Carlos G.

    2016-01-01

    Background The introduction of 7-valent pneumococcal conjugate vaccine (PCV7) into the US childhood immunization schedule in 2000 has substantially reduced vaccine-serotype invasive pneumococcal disease (IPD) in both young children and unvaccinated older children and adults. All-cause pneumonia hospitalizations also markedly declined in young children by 2004. Because of concern about increases in disease caused by non-vaccine serotypes, we assessed whether the pneumonia reduction in young children was sustained through 2009 and whether pneumonia hospitalizations in older age groups also declined. Methods Annual all-cause pneumonia hospitalization rates were estimated using the Nationwide Inpatient Sample. Pneumonia hospitalizations were defined by pneumonia listed first or listed in another position if sepsis, meningitis or empyema was the first listed diagnosis. Average annual rates in pre-PCV7 (1997–1999) and late PCV7 years (2007–2009) were used to estimate annual declines in pneumonia hospitalizations. Results Annual pneumonia hospitalization rates declined by 551.1 (95% confidence interval 445.1–657.1) per 100,000 children aged <2 years, translating to 47,172 fewer hospitalizations annually compared to expected based on pre-PCV7 rates. The decline of 1300.8 (984.0–1617.6) pneumonia hospitalizations per 100,000 adults aged ≥85 years translated to 73,243 fewer hospitalizations annually. Pneumonia hospitalizations declined by 8.4 (0.6–16.2), 85.3 (7.0–163.6), and 359.8 (199.6–520.0) per 100,000 adults aged 18–39, 65–74 and 75–84 years, respectively. Overall, we estimated an age-adjusted annual reduction of 54.8 (41.1–68.5) per 100,000 or 168,182 fewer pneumonia hospitalizations annually. Conclusions Declines in childhood pneumonia were sustained during the decade since PCV7 introduction. Substantial reductions in pneumonia hospitalizations in adults were also observed. PMID:23841730

  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

    Kristian, Sascha A; Ota, Takayuki; Bubeck, Sarah S; 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. 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

  4. Pneumococcal carriage among indigenous Warao children in Venezuela: serotypes, susceptibility patterns, and molecular epidemiology.

    PubMed

    Rivera-Olivero, Ismar A; Bogaert, Debby; Bello, Teresita; del Nogal, Berenice; Sluijter, Marcel; Hermans, Peter W M; de Waard, Jacobus H

    2007-12-01

    Little attention has been paid to pneumococcal carriage and disease in Amerindians from Latin America. The Warao people, an indigenous population from Venezuela, live in the delta of the Orinoco River in geographically isolated communities with difficult access to medical care. To obtain insight into pneumococcal carriage and the theoretical coverage of pneumococcal vaccines in this population, we investigated pneumococcal colonization, serotype, and genotype distribution among Warao children in 9 distinct, geographically isolated communities in the Delta Amacuro area in the northeast of Venezuela. From April 2004 through January 2005, a total of 161 Streptococcus pneumoniae isolates were recovered from single nasopharyngeal swab samples obtained from 356 children aged 0-72 months. The overall pneumococcal carriage rate was 49%, ranging from 13% to 76%, depending on the community investigated and the age of the children (50% among children aged <2 years and 25% among children aged >2 years). The most frequent serotypes were 23F (19.5% of isolates), 6A (19.5%), 15B (10.4%), 6B (9.1%), and 19F (7.2%). The theoretical coverage of the 7-valent pneumococcal conjugate vaccine, including the cross-reactive nonvaccine serotype 6A, was 65%. A total of 26% of the isolates were resistant to first-line antibiotics, with 70% of these strains being covered by the 7-valent pneumococcal conjugate vaccine. Restriction fragment end labelling analysis revealed 65 different genotypes, with 125 (80%) of the isolates belonging to 27 different genetic clusters, suggesting a high degree of horizontal spread of pneumococcal strains in and between the villages. The high colonization rates and high (registered) acute respiratory tract infection morbidity and mortality in this part of Venezuela suggest that Warao children are at increased risk for pneumococcal disease and, therefore, benefit from vaccination. PMID:17990224

  5. Invasive pulmonary aspergillosis in patients with chronic obstructive pulmonary disease

    PubMed Central

    2013-01-01

    Background Invasive pulmonary aspergillosis (IPA) is an infection often occurring in neutropenic patients and has high mortality rates. In recent years, it has been reported that the incidence of IPA has also increased in patients with chronic obstructive pulmonary disease (COPD). The purpose of this study is to investigate the clinical and demographic characteristics and treatment responses of IPA in patients with COPD. Methods Seventy-one patients with a positive culture of Aspergillus from lower respiratory tract samples were examined retrospectively. Eleven (15.4%) of these patients, affected with grade 3 or 4 COPD, had IPA. Results Aspergillus hyphae were detected in lung biopsy in three (27.3%) out of 11 patients and defined as proven IPA; a pathological sample was not taken in the other eight (72.7%) patients, and these were defined as probable IPA. Aspergillus isolates were identified as six cases of Aspergillusfumigatus and three of Aspergillusniger in nine patients, while two isolates were not identified at species level. While five patients required intensive care unit admission, four of them received mechanical ventilation. The most common finding on chest X-ray and computed tomography (CT) (respectively 63.6%, 72.7%) was infiltration. Amphotericin B was the initial drug of choice in all patients and five patients were discharged with oral voriconazole after amphotericin B therapy. Six patients (54.5%) died before treatment was completed. Conclusions IPA should be taken into account in the differential diagnosis particularly in patients with severe and very severe COPD presenting with dyspnea exacerbation, poor clinical status, and a new pulmonary infiltrate under treatment with broad-spectrum antibiotics and steroids. PMID:24135224

  6. Genetic stability of pneumococcal isolates during 35 days of human experimental carriage

    PubMed Central

    Gladstone, R.A.; Gritzfeld, J.F.; Coupland, P.; Gordon, S.B.; Bentley, S.D.

    2015-01-01

    Background Pneumococcal carriage is a reservoir for transmission and a precursor to pneumococcal disease. The experimental human pneumococcal carriage model provides a useful tool to aid vaccine licensure through the measurement of vaccine efficacy against carriage (VEcol). Documentation of the genetic stability of the experimental human pneumococcal carriage model is important to further strengthen confidence in its safety and conclusions, enabling it to further facilitate vaccine licensure through providing evidence of VEcol. Methods 229 isolates were sequenced from 10 volunteers in whom experimental human pneumococcal carriage was established, sampled over a period of 35 days. Multiple isolates from within a single volunteer at a single time provided a deep resolution for detecting variation. HiSeq data from the isolates were mapped against a PacBio reference of the inoculum to call variable sites. Results The observed variation between experimental carriage isolates was minimal with the maximum SNP distance between any isolate and the reference being 3 SNPs. Conclusion The low-level variation described provides evidence for the stability of the experimental human pneumococcal carriage model over 35 days, which can be reliably and confidently used to measure VEcol and aid future progression of pneumococcal vaccination. PMID:26006086

  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. PMID:26508372

  8. Characterization of nontypeable Haemophilus influenzae collected from respiratory infections and invasive disease cases in Manitoba, Canada.

    PubMed

    Shuel, Michelle; Law, Dennis; Skinner, Stuart; Wylie, John; Karlowsky, James; Tsang, Raymond S W

    2010-03-01

    With the introduction of the Haemophilus influenzae serotype b (Hib) vaccine, invasive Hib disease has decreased substantially, but nontypeable H. influenzae (NT Hi) disease appears to be increasing. In order to understand the origin of NT Hi strains and their relationship with serotypeable strains, we analysed 125 NT Hi isolates collected from individual patients with either invasive disease (70 isolates) or respiratory tract infections (55 isolates). Serotype-specific and capsular transport genes were absent by PCR analysis, confirming their nonencapsulated status, which also suggested the NT Hi isolates were not encapsulated strains that shed their capsules. Multilocus sequence typing confirmed the NT Hi isolates did not have the same genetic background as serotypeable strains, including Hib. Despite the genetic heterogeneity found, two major genetic clusters were identified, both containing invasive and respiratory isolates. Fourteen invasive isolates and nine respiratory isolates produced beta-lactamase and were ampicillin resistant. More invasive (26.8%) than respiratory isolates (10.9%) showed decreased susceptibility towards ampicillin by a mechanism unrelated to beta-lactamase production. Besides a change in the capsule status of invasive Hi strains, the burden of invasive Hi disease, which used to be mainly a childhood disease, has now shifted to involve both adults and infants. PMID:20041949

  9. 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

  10. Invasive non-Typhi Salmonella disease in Africa

    PubMed Central

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

    2009-01-01

    Invasive non-Typhi Salmonella (NTS) is endemic in sub-Saharan Africa where it is a leading cause of bloodstream infection. Host risk factors have been established, but little is known about environmental reservoirs and predominant modes of transmission so prevention strategies are underdeveloped. While foodborne transmission from animals to humans predominates in high-income countries, it has been postulated that anthroponotic transmission both within and outside healthcare facilities may be important in sub-Saharan Africa. Antimicrobial resistance to ampicillin, trimethoprim-sulphamethoxazole and chloramphenicol is common; wider use of alternative agents may be warranted for empiric therapy. Vaccine development targeting the leading invasive NTS serotypes Typhimurium and Enteritidis shows promise. The clinical presentation of NTS bacteremia is non-specific and in the absence of blood culture may be confused with other febrile illnesses such as malaria. Much work remains to understand and control invasive NTS in sub-Saharan Africa. PMID:19591599

  11. Sialic Acid Transport Contributes to Pneumococcal Colonization ▿

    PubMed Central

    Marion, Carolyn; Burnaugh, Amanda M.; Woodiga, Shireen A.; King, Samantha J.

    2011-01-01

    Streptococcus pneumoniae is a major cause of pneumonia and meningitis. Airway colonization is a necessary precursor to disease, but little is known about how the bacteria establish and maintain colonization. Carbohydrates are required as a carbon source for pneumococcal growth and, therefore, for colonization. Free carbohydrates are not readily available in the naso-oropharynx; however, N- and O-linked glycans are common in the airway. Sialic acid is the most common terminal modification on N- and O-linked glycans and is likely encountered frequently by S. pneumoniae in the airway. Here we demonstrate that sialic acid supports pneumococcal growth when provided as a sole carbon source. Growth on sialic acid requires import into the bacterium. Three genetic regions have been proposed to encode pneumococcal sialic acid transporters: one sodium solute symporter and two ATP binding cassette (ABC) transporters. Data demonstrate that one of these, satABC, is required for transport of sialic acid. A satABC mutant displayed significantly reduced growth on both sialic acid and the human glycoprotein alpha-1. The importance of satABC for growth on human glycoprotein suggests that sialic acid transport may be important in vivo. Indeed, the satABC mutant was significantly reduced in colonization of the murine upper respiratory tract. This work demonstrates that S. pneumoniae is able to use sialic acid as a sole carbon source and that utilization of sialic acid is likely important during pneumococcal colonization. PMID:21189320

  12. Influenza promotes pneumococcal growth during co-infection by providing host sialylated substrates as a nutrient source

    PubMed Central

    Siegel, Steven J.; Roche, Aoife M.; Weiser, Jeffrey N.

    2014-01-01

    Summary Much of the mortality attributed to influenza virus is due to secondary bacterial pneumonia, particularly from Streptococcus pneumoniae. However, mechanisms underlying this co-infection are incompletely understood. We find that prior influenza infection enhances pneumococcal colonization of the murine nasopharynx, which in-turn promotes bacterial spread to the lungs. Influenza accelerates bacterial replication in vivo, and sialic acid, a major component of airway glycoconjugates, is identified as the host-derived metabolite that stimulates pneumococcal proliferation. Influenza infection increases sialic acid and sialylated mucin availability, and enhances desialylation of host glycoconjugates. Pneumococcal genes for sialic acid catabolism are required for influenza to promote bacterial growth. Decreasing sialic acid availability in vivo by genetic deletion of the major airway mucin Muc5ac or mucolytic treatment limits influenza-induced pneumococcal replication. Our findings suggest that higher rates of disease during co-infection could stem from influenza-provided sialic acid, which increases pneumococcal proliferation, colonization and aspiration. PMID:25011108

  13. Does a 10-valent pneumococcal-Haemophilus influenzae protein D conjugate vaccine prevent respiratory exacerbations in children with recurrent protracted bacterial bronchitis, chronic suppurative lung disease and bronchiectasis: protocol for a randomised controlled trial

    PubMed Central

    2013-01-01

    Background Recurrent protracted bacterial bronchitis (PBB), chronic suppurative lung disease (CSLD) and bronchiectasis are characterised by a chronic wet cough and are important causes of childhood respiratory morbidity globally. Haemophilus influenzae and Streptococcus pneumoniae are the most commonly associated pathogens. As respiratory exacerbations impair quality of life and may be associated with disease progression, we will determine if the novel 10-valent pneumococcal-Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) reduces exacerbations in these children. Methods A multi-centre, parallel group, double-blind, randomised controlled trial in tertiary paediatric centres from three Australian cities is planned. Two hundred six children aged 18 months to 14 years with recurrent PBB, CSLD or bronchiectasis will be randomised to receive either two doses of PHiD-CV or control meningococcal (ACYW135) conjugate vaccine 2 months apart and followed for 12 months after the second vaccine dose. Randomisation will be stratified by site, age (<6 years and ≥6 years) and aetiology (recurrent PBB or CSLD/bronchiectasis). Clinical histories, respiratory status (including spirometry in children aged ≥6 years), nasopharyngeal and saliva swabs, and serum will be collected at baseline and at 2, 3, 8 and 14 months post-enrolment. Local and systemic reactions will be recorded on daily diaries for 7 and 30 days, respectively, following each vaccine dose and serious adverse events monitored throughout the trial. Fortnightly, parental contact will help record respiratory exacerbations. The primary outcome is the incidence of respiratory exacerbations in the 12 months following the second vaccine dose. Secondary outcomes include: nasopharyngeal carriage of H. influenzae and S. pneumoniae vaccine and vaccine- related serotypes; systemic and mucosal immune responses to H. influenzae proteins and S. pneumoniae vaccine and vaccine-related serotypes; impact upon lung function

  14. [Invasive fungal disease due to Scedosporium, Fusarium and mucorales].

    PubMed

    Pemán, Javier; Salavert, Miguel

    2014-01-01

    The number of emerging organisms causing invasive fungal infections has increased in the last decades. These etiological agents include Scedosporium, Fusarium and mucorales. All of them can cause disseminated, virulent, and difficult-to treat infections in immunosuppressed patients, the most affected, due to their resistance to most available antifungal agents. Current trends in transplantation including the use of new immunosuppressive treatments, the common prescription of antifungal agents for prophylaxis, and new ecological niches could explain the emergence of these fungal pathogens. These pathogens can also affect immunocompetent individuals, especially after natural disasters (earthquakes, floods, tsunamis), combat wounds or near drowning. All the invasive infections caused by Scedosporium, Fusarium, and mucorales are potentially lethal and a favourable outcome is associated with rapid diagnosis by direct microscopic examination of the involved tissue, wide debridement of infected material, early use of antifungal agents including combination therapy, and an improvement in host defenses, especially neutropenia. PMID:25442383

  15. Antimicrobial resistance and management of invasive Salmonella disease

    PubMed Central

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

    2015-01-01

    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. PMID:25912288

  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. PMID:25912288

  17. Exome Array Analysis of Susceptibility to Pneumococcal Meningitis.

    PubMed

    Kloek, Anne T; van Setten, Jessica; van der Ende, Arie; Bots, Michiel L; Asselbergs, Folkert W; Valls Serón, Mercedes; 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

  18. 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

  19. Control of Invasive Salmonella Disease in Africa: Is There a Role for Human Challenge Models?

    PubMed Central

    Gibani, Malick M.; Jin, Celina; Darton, Thomas C.; Pollard, Andrew J.

    2015-01-01

    Invasive Salmonella disease in Africa is a major public health concern. With evidence of the transcontinental spread of the Salmonella Typhi H58 haplotype, improved estimates of the burden of infection and understanding of the complex interplay of factors affecting disease transmission are needed to assist with efforts aimed at disease control. In addition to Salmonella Typhi, invasive nontyphoidal Salmonella are increasingly recognized as an important cause of febrile illness and mortality in sub-Saharan Africa. Human experimental oral challenge studies with Salmonella can be used as a model to offer unique insights into host–pathogen interactions as well as a platform to efficiently test new diagnostic and vaccine candidates. In this article, we review the background and use of human challenge studies to date and discuss how findings from these studies may lead to progress in the control of invasive Salmonella disease in Africa. PMID:26449941

  20. 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

  1. High-Level Genetic Diversity among Invasive Streptococcus pneumoniae Isolates in Turkey.

    PubMed

    Guldemir, Dilek; Acar, Sumeyra; Otgun, Selin Nar; Unaldi, Ozlem; Gozalan, Aysegul; Ertek, Mustafa; Durmaz, Riza

    2016-05-20

    This study obtained information on the serotypes and molecular typing characteristics of Streptococcus pneumoniae strains causing invasive diseases in Turkey. Sixty-eight S. pneumoniae isolates causing invasive pneumococcal diseases were collected from different regions of Turkey from 2009 to 2011. The isolates were characterized by performing multilocus sequence typing (MLST), pulsed-field gel electrophoresis (PFGE), and capsular serotyping, and 25 different serotypes were identified. Serotypes 19F, 23F, 1, 14, and 7F were common and accounted for 52.9% of all the serotypes. In addition, 54 different PFGE profiles (pulsotypes) were observed. Twenty-three of the 68 (33.8%) isolates were clustered into 9 pulsotypes. MLST analysis yielded 36 sequence types, of which 12 (33.3%) were novel. A comparison of results with the global pneumococcal MLST database by performing eBURST analysis showed that our strains belonged to 20 different clonal complexes and 5 singletons. In addition, we identified 4 new alleles: 2 gdh, 1 xpt, and 1 ddl. Thus, the results of this study highlighted a high level of diversity among pneumococcal isolates. In addition, the study identified a case of possible capsular switching. PMID:26255730

  2. A neonatal case of chronic granulomatous disease, initially presented with invasive pulmonary aspergillosis.

    PubMed

    Saito, Sachiko; Oda, Arata; Kasai, Masashi; Minami, Kisei; Nagumo, Haruo; Shiohara, Masaaki; Ogiso, Yoshifumi; Kawakami, Yoshiyuki

    2014-03-01

    Chronic granulomatous disease (CGD) often presents with infectious illness, such as repeating bacterial and fungal infections, due to the inability to generate superoxide, which would destroy certain infectious pathogens, and is usually diagnosed in childhood. We describe a CGD case diagnosed in neonatal period, who initially presented with invasive aspergillosis. Neonatal invasive pulmonary aspergillosis is very rare and, to the best of our knowledge, this might be the youngest case in Japan. PMID:24674387

  3. Epidemiology of invasive Streptococcus pneumoniae infections in adults in Finland.

    PubMed Central

    Sankilampi, U.; Herva, E.; Haikala, R.; Liimatainen, O.; Renkonen, O. V.; Leinonen, M.

    1997-01-01

    Laboratory-based surveillance of invasive pneumococcal infections in adults in Finland from 1983 to 1992 identified 862 episodes of pneumococcal bacteraemia and 97 episodes of meningitis. The overall incidence of invasive pneumococcal infections was 9.1 per 100,000 for all adults per year, but 27.1, 35.8, and 44.5 per 100,000 in those aged 65 years or over, 75 years or over, and 85 years or over, respectively. Most (99.7%) of the pneumococcal strains were sensitive to penicillin. Ninety-five percent of the strains belonged to serogroups/types present in the 23-valent pneumococcal polysaccharide vaccine. Group/type distribution was different in patients aged 16-64 years compared to those 65 years or over (P < 0.001), in bacteraemia compared to meningitis (P < 0.001), and in the years 1983-7 compared to 1988-92 (P < 0.05). PMID:9042030

  4. Space-Time Cluster Analysis of Invasive Meningococcal Disease

    PubMed Central

    de Melker, Hester; Spanjaard, Lodewijk; Dankert, Jacob; Nagelkerke, Nico

    2004-01-01

    Clusters are recognized when meningococcal cases of the same phenotypic strain (markers: serogroup, serotype, and subtype) occur in spatial and temporal proximity. The incidence of such clusters was compared to the incidence that would be expected by chance by using space-time nearest-neighbor analysis of 4,887 confirmed invasive meningococcal cases identified in the 9-year surveillance period 1993–2001 in the Netherlands. Clustering beyond chance only occurred among the closest neighboring cases (comparable to secondary cases) and was small (3.1%, 95% confidence interval 2.1%–4.1%). PMID:15498165

  5. Lactococcus lactis as an adjuvant and delivery vehicle of antigens against pneumococcal respiratory infections

    PubMed Central

    Vintiñi, Elisa; Villena, Julio; Raya, Raul

    2010-01-01

    Most studies of Lactococcus lactis as delivery vehicles of pneumococcal antigens are focused on the effectiveness of mucosal recombinant vaccines against Streptococcus pneumoniae in animal models. At present, there are three types of pneumococcal vaccines: capsular polysaccharide pneumococcal vaccines (PPV), protein-polysaccharide conjugate pneumococcal vaccines (PCV) and protein-based pneumococcal vaccines (PBPV). Only PPV and PCV have been licensed. These vaccines, however, do not represent a definitive solution. Novel, safe and inexpensive vaccines are necessary, especially in developing countries. Probiotic microorganisms such as lactic acid bacteria (LAB) are an interesting alternative for their use as vehicles in pneumococcal vaccines due to their GRAS (Generally Recognized As Safe) status. Thus, the adjuvanticity of Lactococcus lactis by itself represents added value over the use of other bacteria, a question dealt with in this review. In addition, the expression of different pneumococcal antigens as well as the use of oral and nasal mucosal routes of administration of lactococcal vaccines is considered. The advantages of nasal live vaccines are evident; nonetheless, oral vaccines can be a good alternative when the adequate dose is used. Another point addressed here is the use of live versus inactivated vaccines. In this sense, few researchers have focused on inactivated strains to be used as vaccines against pneumoccoccus. The immunogenicity of live vaccines is better than the one afforded by inactivated ones; however, the probiotic-inactivated vaccine combination has improved this matter considerably. The progress made so far in the protective immune response induced by recombinant vaccines, the successful trials in animal models and the safety considerations of their application in humans suggest that the use of recombinant vaccines represents a good short-term option in the control of pneumococcal diseases. PMID:21326831

  6. Pneumococcal conjugate vaccine in adults: Let's see what happens.

    PubMed

    Paradiso, Peter R

    2016-07-01

    The recent recommendation for the use of the 13-valent pneumococcal conjugate vaccine (PCV13) in adults 65 y of age and older, provides a new tool for preventing disease in this at-risk population. The conjugate vaccine induces a T-cell dependent response, which distinguishes it from the polysaccharide vaccine and could provide the longer-term protection necessary to have a significant impact in this population. PMID:26901618

  7. Clinical and Microbiological Factors Associated with High Nasopharyngeal Pneumococcal Density in Patients with Pneumococcal Pneumonia

    PubMed Central

    Alpkvist, Helena; Athlin, Simon; Nauclér, Pontus; Herrmann, Björn; Abdeldaim, Guma; Slotved, Hans-Christian; Hedlund, Jonas; Strålin, Kristoffer

    2015-01-01

    Background We aimed to study if certain clinical and/or microbiological factors are associated with a high nasopharyngeal (NP) density of Streptococcus pneumoniae in pneumococcal pneumonia. In addition, we aimed to study if a high NP pneumococcal density could be useful to detect severe pneumococcal pneumonia. Methods Adult patients hospitalized for radiologically confirmed community-acquired pneumonia were included in a prospective study. NP aspirates were collected at admission and were subjected to quantitative PCR for pneumococcal DNA (Spn9802 DNA). Patients were considered to have pneumococcal etiology if S. pneumoniae was detected in blood culture and/or culture of respiratory secretions and/or urinary antigen test. Results Of 166 included patients, 68 patients had pneumococcal DNA detected in NP aspirate. Pneumococcal etiology was noted in 57 patients (84%) with positive and 8 patients (8.2%) with negative test for pneumococcal DNA (p<0.0001). The median NP pneumococcal density of DNA positive patients with pneumococcal etiology was 6.83 log10 DNA copies/mL (range 1.79–9.50). In a multivariate analysis of patients with pneumococcal etiology, a high pneumococcal density was independently associated with severe pneumonia (Pneumonia Severity Index risk class IV-V), symptom duration ≥2 days prior to admission, and a medium/high serum immunoglobulin titer against the patient’s own pneumococcal serotype. NP pneumococcal density was not associated with sex, age, smoking, co-morbidity, viral co-infection, pneumococcal serotype, or bacteremia. Severe pneumococcal pneumonia was noted in 28 study patients. When we studied the performance of PCR with different DNA cut-off levels for detection of severe pneumococcal pneumonia, we found sensitivities of 54–82% and positive predictive values of 37–56%, indicating suboptimal performance. Conclusions Pneumonia severity, symptom duration ≥2 days, and a medium/high serum immunoglobulin titer against the patient

  8. Pathological manifestations in murine Lyme disease: association with tissue invasion and spirochete persistence.

    PubMed

    Weis, J J; Yang, L; Seiler, K P; Silver, R M

    1997-07-01

    The clinical manifestations of human Lyme disease present with a spectrum of tissue or organ involvement and severity of symptoms. The murine model of Lyme disease has proved to be an accurate reflection of many of the human symptoms of disease and has been particularly useful for studying development of subacute arthritis and tendonitis. Direct tissue invasion by Borrelia burgdorferi and persistence of high levels of spirochetes in tissues are important components of arthritis development. The outer-surface lipoproteins contain a biologically active lipid-modified moiety with potent ability to stimulate inflammatory cytokine production and other inflammatory mediators such as nitric oxide. Localized inflammation stimulated by these lipoproteins may be the trigger for neutrophil infiltration, synovial proliferation, and other events associated with this arthritis. Invasion of maternal uterine tissue, but not direct invasion of fetal tissue, is associated with low levels of pregnancy loss in mice infected during gestation, consistent with the detrimental effect of inflammatory cytokines on pregnancy. PMID:9233659

  9. 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

  10. Invasive Haemophilus influenzae type b disease in elderly nursing home residents: two related cases.

    PubMed Central

    Heath, T. C.; Hewitt, M. C.; Jalaludin, B.; Roberts, C.; Capon, A. G.; Jelfs, P.; Gilbert, G. L.

    1997-01-01

    We investigated two fatal cases of invasive Haemophilus influenzae type b (Hib) infection in a community nursing home in western Sydney, Australia. Two elderly women had lived in the same room, and the onset of their illness was 5 days apart. Hib isolates from blood cultures showed identical profiles by pulsed field gel electrophoresis. These findings suggest that Hib infection was transmitted within this nursing home. Serious Hib disease may be underrecognized in this setting. Continued surveillance and serotyping of invasive H. influenzae disease is essential for identifying groups at increasing risk that may benefit from immunization against Hib. PMID:9204300

  11. 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.

  12. Disease invasion: impacts on biodiversity and human health

    PubMed Central

    Cunningham, Andrew A.; Dobson, Andrew P.; Hudson, Peter J.

    2012-01-01

    An introduction to the theme issue that includes papers that identify how, where and why infectious diseases in wildlife emerge, while also addressing their possible conservation impacts. PMID:22966135

  13. 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

  14. 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

    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, 9 V, 10A, 11A, 15 B, 18C, 19 A, 22 F and 33 F. 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

  15. Additive preventive effect of influenza and pneumococcal vaccines in the elderly

    PubMed Central

    Mahamat, Aba; Daurès, Jean-Pierre; de Wazières, Benoît

    2013-01-01

    Elderly people are at increased risk of influenza and pneumococcal diseases. Influenza increases clinical pneumococcal disease incidence. Pneumococcal vaccination could therefore be a supplement to influenza vaccination. This study evaluated all-cause mortality and antibiotic consumption according to elderly people’s influenza and pneumococcal vaccination status. Its goal was to demonstrate that vaccination with both Influenza and pneumococcal vaccines decrease all-cause mortality and antibiotic consumption. From 2004-10-01 to 2004-12-31 (3 mo), elderly people (≥ 65 y) who lived in the Gard department (South of France) were offered both vaccinations. Among the 68,897 subjects followed-up one year after this vaccination campaign, 21,303 (30.9%) were vaccinated with both vaccines, 18,651 (27.1%) with influenza vaccine alone, 3,769 (5.5%) with pneumococcal vaccine alone; 25,174 (36.5%) subjects were unvaccinated. Mortality rate (per 1,000 inhabitants-year) adjusted on gender, age and prior underlying chronic disease was 17.9 (95% CI: 16.3–19.6), 20.8 (19.0–22.8), 22.5 (19.0–26.6) and 24.7 (22.7–26.8), respectively. It was 42.1 (38.8–45.8) in elderly people with underlying chronic disease who received both vaccines vs. 58.1 (53.7–62.9) in unvaccinated elderly people. The decrease in mortality rate was 27.0% (20.0–34.0) in subjects who received both vaccines and 16.0% (6.0–24.0) in those who received influenza vaccine. No significant reduction in mortality rate was seen with the pneumococcal vaccine alone. Influenza and/or pneumococcal vaccinations did not decrease antibiotic consumption that drastically increases during the winter period. An additive effect was observed in the prevention of all-cause mortality with influenza and pneumococcal vaccines given together in elderly people, including in those with underlying chronic disease. PMID:23442587

  16. Long-term immune responses and comparative effectiveness of one or two doses of 7-valent pneumococcal conjugate vaccine (PCV7) in HIV-positive adults in the era of combination antiretroviral therapy

    PubMed Central

    Cheng, Aristine; Chang, Sui-Yuan; Tsai, Mao-Song; Su, Yi-Ching; Liu, Wen-Chun; Sun, Hsin-Yun; Hung, Chien-Ching

    2016-01-01

    Introduction HIV infection impairs maintenance of immunological memory, yet few studies of HIV-positive adults receiving 7-valent pneumococcal conjugate vaccine (PCV7) have followed them beyond the first year. We determined and compared the durability of serological responses and the clinical outcomes of HIV-positive adults annually for five years following vaccination with one or two doses of PCV7. Methods In this non-randomized clinical trial, 221 pneumococcal vaccine-naïve HIV-positive adults receiving one (n=109) or two doses four weeks apart (n=112) of PCV7 between 2008 and 2010 were longitudinally followed for evaluation of significant serological response and for episodes of pneumonia and invasive pneumococcal disease. Results At the time of vaccination, the two groups were well matched for age, risk factors, combination antiretroviral therapy (cART) coverage, CD4 count and plasma HIV RNA load (PVL). At the end of five years, the CD4 counts for the one- and two-dose groups had increased from 407 and 406 to 550 and 592 cells/µL, respectively, and 82.4 and 81.6% of the participants had fully suppressed PVL. Significant immune responses to ≥2 serotypes persisted for 67.9 vs 78.6%, 64.2 vs 71.4%, 66.1 vs 71.4%, 57.8 vs 69.6% in the second, third, fourth and fifth years after one and two doses of PCV7 in the intention-to-treat analysis, respectively. In multivariate analysis, immunization with two doses of PCV7 (odds ratio (OR) 1.71, 95% confidence interval (CI) 1.10 to 2.65, p=0.016), concurrent cART (OR 2.16, 95% CI 1.16 to 4.00, p=0.015) and CD4 proliferation (OR 1.12, 95% CI 1.01 to 1.27, p=0.031) were predictive of persistent serological responses in the fifth year. Only one patient in the one-dose group had documented pneumococcal pneumonia (non-bacteraemic) and none had invasive pneumococcal disease in the 6.5 years of follow-up. Conclusions One or two doses of PCV7 achieve durable seroprotective responses in HIV-treated participants; however, two

  17. The Role of Influenza and Parainfluenza Infections in Nasopharyngeal Pneumococcal Acquisition Among Young Children

    PubMed Central

    Grijalva, Carlos G.; Griffin, Marie R.; Edwards, Kathryn M.; Williams, John V.; Gil, Ana I.; Verastegui, Hector; Hartinger, Stella M.; Vidal, Jorge E.; Klugman, Keith P.; Lanata, Claudio F.

    2014-01-01

    Background. Animal models suggest that influenza infection favors nasopharyngeal acquisition of pneumococci. We assessed this relationship with influenza and other respiratory viruses in young children. Methods. A case-control study was nested within a prospective cohort study of acute respiratory illness (ARI) in Andean children <3 years of age (RESPIRA-PERU study). Weekly household visits were made to identify ARI and obtain nasal swabs for viral detection using real-time reverse-transcription polymerase chain reaction. Monthly nasopharyngeal (NP) samples were obtained to assess pneumococcal colonization. We determined whether specific respiratory viral ARI episodes occurring within the interval between NP samples increased the risk of NP acquisition of new pneumococcal serotypes. Results. A total of 729 children contributed 2128 episodes of observation, including 681 pneumococcal acquisition episodes (new serotype, not detected in prior sample), 1029 nonacquisition episodes (no colonization or persistent colonization with the same serotype as the prior sample), and 418 indeterminate episodes. The risk of pneumococcal acquisition increased following influenza-ARI (adjusted odds ratio [AOR], 2.19; 95% confidence interval [CI], 1.02–4.69) and parainfluenza-ARI (AOR, 1.86; 95% CI, 1.15–3.01), when compared with episodes without ARI. Other viral infections (respiratory syncytial virus, human metapneumovirus, human rhinovirus, and adenovirus) were not associated with acquisition. Conclusions. Influenza and parainfluenza ARIs appeared to facilitate pneumococcal acquisition among young children. As acquisition increases the risk of pneumococcal diseases, these observations are pivotal in our attempts to prevent pneumococcal disease. PMID:24621951

  18. Case Report Unicentric Castleman disease located in the anterior mediastinum misdiagnosed as invasive thymoma: a case report.

    PubMed

    Liu, Y; Xie, D Y; Lin, X M; Chi, C

    2015-01-01

    Castleman disease is a rare lymphoproliferative disorder of unknown etiology. The localized form, which usually presents as a slow-growing mass, is most commonly located in the mediastinum. Invasion of the vena anonyma by a mass has rarely been reported. We herein describe a case of initially misdiagnosed invasive thymoma in a 72-year-old woman, but postoperatively proven to have anterior mediastinal Castleman disease with invasion of the vena anonyma. PMID:26125875

  19. Development of poorly differentiated invasive squamous cell carcinoma in giant Bowen’s disease: a case report with dermatoscopy

    PubMed Central

    Akay, Bengu Nisa; Maden, Aysenur; Kocak, Oguzhan; Bostanci, Seher; Boyvat, Ayşe; Kocyigit, Pelin; Heper, Aylin Okcu

    2016-01-01

    Bowen’s disease (BD) is an in situ form of squamous cell carcinoma (SCC), often occurring in the chronically UV-damaged skin of elderly people. The risk of progression of BD to invasive SCC varies between 3% and 5%, and one-third of invasive tumors may metastasize. Herein we discuss the dermatoscopic findings of a case of giant Bowen’s disease, which progressed to poorly differentiated invasive SCC. PMID:27222765

  20. 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

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

    PubMed

    Neumann, Philipp-Alexander; Rijcken, Emile

    2016-05-01

    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

  2. Possible disease remission in patient with invasive bladder cancer with D-fraction regimen

    PubMed Central

    Rajamahanty, Srinivas; Louie, Brandon; O’Neill, Cormac; Choudhury, Muhammad; Konno, Sensuke

    2009-01-01

    Superficial bladder tumors are the most prevalent form of bladder cancers and transurethral resection is the primary surgical modality for those tumors. However, nearly 65% of patients will have tumor recurrence in five years while about 15% will have progression to muscle invasion. Thus, the primary therapeutic aim is to prevent multiple recurrences and progression to a more advanced, invasive disease. We here report an 87-year-old white male patient with invasive bladder cancer who received an unconventional oral regimen of D-fraction, the bioactive extract of Maitake mushroom (Grifola frondosa), following endoscopic transurethral resection of bladder tumor. Despite a high risk for disease recurrence, follow-up yet indicated no clinical evidence of progression of residual disease or recurrence of invasive cancer. It has been nearly two years but the patient remains remarkably well and appears to be in remission. To our knowledge, this is the first and only case report of possible disease remission in a bladder cancer patient after the two-year follow-up of D-fraction regimen, so that further studies with long terms are required for drawing a relevant conclusion. Nevertheless, it is conceivable that D-fraction is a natural agent that may have clinical implications in patients with superficial bladder tumors. PMID:20360882

  3. Cost-Effectiveness of Vaccinating Immunocompetent ≥65 Year Olds with the 13-Valent Pneumococcal Conjugate Vaccine in England

    PubMed Central

    van Hoek, Albert Jan; Miller, Elizabeth

    2016-01-01

    Background Recently a large clinical trial showed that the use of 13-valent pneumococcal conjugate vaccine (PCV13) among immunocompetent individuals aged 65 years and over was safe and efficacious. The aim of this study was to assess the cost-effectiveness of vaccinating immunocompetent 65 year olds with PCV13 vaccine in England. England is a country with universal childhood pneumococcal conjugate vaccination programme in place (7-valent (PCV7) since 2006 and PCV13 since 2010), as well as a 23-valent pneumococcal polysaccharide (PPV23) vaccination programme targeting clinical risk-groups and those ≥65 years. Method A static cohort cost-effectiveness model was developed to follow a cohort of 65 year olds until death, which will be vaccinated in the autumn of 2016 with PCV13. Sensitivity analysis was performed to test the robustness of the results. Results The childhood vaccination programme with PCV7 has induced herd protection among older unvaccinated age groups, with a resultant low residual disease burden caused by PCV7 vaccine types. We show similar herd protection effects for the 6 additional serotypes included in PCV13, and project a new low post-introduction equilibrium of vaccine-type disease in 2018/19. Applying these incidence projections for both invasive disease and community-acquired pneumonia (CAP), and using recent measures of vaccine efficacy against these endpoints for ≥65 year olds, we estimate that vaccination of a cohort of immunocompetent 65 year olds with PCV13 would directly prevent 26 cases of IPD, 69 cases of CAP and 15 deaths. The associated cost-effectiveness ratio is £257,771 per QALY gained (using list price of £49.10 per dose and £7.51 administration costs) and is therefore considered not cost-effective. To obtain a cost-effective programme the price per dose would need to be negative. The results were sensitive to disease incidence, waning vaccine protection and case fatality rate; despite this, the overall conclusion was robust

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

    PubMed

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

    2016-06-01

    The etiological diagnosis of infection by Streptococcus pneumoniae in children is difficult, and the use of indirect techniques is frequently warranted. We aimed to study the use of pneumococcal proteins for the serological diagnosis of pneumococcal infection in children with pneumonia. We analyzed paired serum samples from 13 Brazilian children with invasive pneumococcal pneumonia (positive control group) and 23 Finnish children with viral pharyngitis (negative control group), all aged <5years-old. Children with pharyngitis were evaluated for oropharyngeal colonization, and none of them carried S. pneumoniae. We used a multiplex bead-based assay with eight proteins: Ply, CbpA, PspA1 and 2, PcpA, PhtD, StkP and PcsB. The optimal cut-off for increase in antibody level for the diagnosis of pneumococcal infection was determined for each antigen by ROC curve analysis. The positive control group had a significantly higher rate of ≥2-fold rise in antibody levels against all pneumococcal proteins, except Ply, compared to the negative controls. The cut-off of ≥2-fold increase in antibody levels was accurate for pneumococcal infection diagnosis for all investigated antigens. However, there was a substantial increase in the accuracy of the test with a cut-off of ≥1.52-fold rise in antibody levels for PcpA. When using the investigated protein antigens for the diagnosis of pneumococcal infection, the detection of response against at least one antigen was highly sensitive (92.31%) and specific (91.30%). The use of serology with pneumococcal proteins is a promising method for the diagnosis of pneumococcal infection in children with pneumonia. The use of a ≥2-fold increase cut-off is adequate for most pneumococcal proteins. PMID:26928648

  5. 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. PMID:26807809

  6. Development of a TaqMan Array Card for Pneumococcal Serotyping on Isolates and Nasopharyngeal Samples.

    PubMed

    Pholwat, Suporn; Sakai, Fuminori; Turner, Paul; Vidal, Jorge E; Houpt, Eric R

    2016-07-01

    Streptococcus pneumoniae is both a commensal and a major pathogen that causes invasive disease in people of all ages. The introduction of serotype-specific pneumococcal vaccines has reduced the burden of disease but has also led to replacement with new strains; thus, serotyping remains important for vaccine-related disease surveillance. Conventional serotyping methods are laborious and expensive. We developed an easy-to-perform genotypic TaqMan array card (TAC) to identify S. pneumoniae strains, including lytA-based sequences, and 53 sequence-specific PCRs to identify 74 serotypes/serogroups covering all current vaccine types as well as prevalent nonvaccine types. The TAC method was evaluated on 146 clinical S. pneumoniae isolates and 13 nonpneumococcal species that naturally inhabit the upper respiratory tract and yielded 97% (142/146) sensitivity and 100% (13/13) specificity versus results of standard Quellung serotyping. The calculated limit of detection was 20 to 200 fg (∼8 to 84 genome equivalents) per reaction. On 23 blinded nasopharyngeal specimens that were pneumococcus culture positive, the TAC pan-pneumococcus lytA assay was positive in 21 (91% sensitivity versus culture). On TAC lytA-positive specimens, a serotype result was obtained on 86%, and the result was 95% accurate versus the subsequent culture's Quellung result. TAC also detected mixed serotypes in two specimens where Quellung detected only the predominant serotype. This TAC method yields fast and comprehensive serotyping compared to the standard method and may be useful on direct specimens. PMID:27170020

  7. Development of a TaqMan Array Card for Pneumococcal Serotyping on Isolates and Nasopharyngeal Samples

    PubMed Central

    Pholwat, Suporn; Sakai, Fuminori; Turner, Paul; Vidal, Jorge E.

    2016-01-01

    Streptococcus pneumoniae is both a commensal and a major pathogen that causes invasive disease in people of all ages. The introduction of serotype-specific pneumococcal vaccines has reduced the burden of disease but has also led to replacement with new strains; thus, serotyping remains important for vaccine-related disease surveillance. Conventional serotyping methods are laborious and expensive. We developed an easy-to-perform genotypic TaqMan array card (TAC) to identify S. pneumoniae strains, including lytA-based sequences, and 53 sequence-specific PCRs to identify 74 serotypes/serogroups covering all current vaccine types as well as prevalent nonvaccine types. The TAC method was evaluated on 146 clinical S. pneumoniae isolates and 13 nonpneumococcal species that naturally inhabit the upper respiratory tract and yielded 97% (142/146) sensitivity and 100% (13/13) specificity versus results of standard Quellung serotyping. The calculated limit of detection was 20 to 200 fg (∼8 to 84 genome equivalents) per reaction. On 23 blinded nasopharyngeal specimens that were pneumococcus culture positive, the TAC pan-pneumococcus lytA assay was positive in 21 (91% sensitivity versus culture). On TAC lytA-positive specimens, a serotype result was obtained on 86%, and the result was 95% accurate versus the subsequent culture's Quellung result. TAC also detected mixed serotypes in two specimens where Quellung detected only the predominant serotype. This TAC method yields fast and comprehensive serotyping compared to the standard method and may be useful on direct specimens. PMID:27170020

  8. Global incidence of serogroup B invasive meningococcal disease: a systematic review.

    PubMed

    Sridhar, Shruti; Greenwood, Brian; Head, Christopher; Plotkin, Stanley A; Sáfadi, Marco A; Saha, Samir; Taha, Muhamed-Kheir; Tomori, Oyewale; Gessner, Bradford D

    2015-11-01

    Use of recently licensed vaccines against Neisseria meningitidis serogroup B (NmB) will depend partly on disease burden estimates. We systematically reviewed NmB incidence and mortality worldwide between January, 2000, and March, 2015, incorporating data from 37 articles and 12 websites. Most countries had a yearly invasive NmB incidence of less than 2 per 100,000 people. Within these relatively low incidence rates (compared with common causes of invasive bacterial diseases), substantial variation was detected between countries, with a notably higher incidence in Australia, Europe, North America, and South America. China and India had reports only of sporadic cases, and except for South Africa, sub-Saharan Africa showed a near absence of disease. In countries with consistently collected data, NmB incidence has tended to decrease, even as the proportion of invasive meningococcal disease cases caused by serogroup B has increased. With few exceptions, case-fatality ratios were fairly consistent, ranging between 3% and 10%. In high-income countries, incidence rates of NmB were relatively low compared with other vaccine-preventable diseases and might be decreasing. High case-fatality ratios, substantial disease-related morbidity, and the threat of outbreaks could nevertheless make NmB an attractive target for preventive and reactive immunisation programmes. The low availability of data from low-income and middle-income countries suggests the need for improved surveillance before vaccination strategies are designed. PMID:26453240

  9. 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

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

    PubMed

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

    2014-01-01

    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

  11. 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

  12. Force Matters: Biomechanical Regulation of Cell Invasion and Migration in Disease.

    PubMed

    Kai, FuiBoon; Laklai, Hanane; Weaver, Valerie M

    2016-07-01

    Atherosclerosis, cancer, and various chronic fibrotic conditions are characterized by an increase in the migratory behavior of resident cells and the enhanced invasion of assorted exogenous cells across a stiffened extracellular matrix (ECM). This stiffened scaffold aberrantly engages cellular mechanosignaling networks in cells, which promotes the assembly of invadosomes and lamellae for cell invasion and migration. Accordingly, deciphering the conserved molecular mechanisms whereby matrix stiffness fosters invadosome and lamella formation could identify therapeutic targets to treat fibrotic conditions, and reducing ECM stiffness could ameliorate disease progression. PMID:27056543

  13. Non-Invasive Therapy of Peripheral Arterial Disease.

    PubMed

    Marcial, José M; Pérez, Reynerio; Vargas, Pedro; Franqui-Rivera, Hilton

    2015-01-01

    Peripheral arterial disease (PAD) is a significant cause of morbidity and mortality worldwide. Lifestyle changes, like the cessation of the use of tobacco as well as a modification of dietary and exercise habits, can be the most cost-effective interventions in patients with PAD. Smocking cessation is the most important intervention, since it increases survival in these patients. Antiplatelet therapy is an essential component in the treatment of peripheral arterial disease (PAD) of the lower extremities. In addition to delaying arterial obstructive progression, these agents are most usefull in reducing adverse cardiovascular events such as non-fatal myocardial infarction (MI), stroke and vascular death. Mainstay of treatment continues to be aspirin monotherapy (75-325mg daily). Current treatment for lower extremity PAD is directed towards the relief of symptoms and improvement in QoL. The two agents which have consistently been found to be most efficient in achieving these goals are cilostazol and naftidrofuryl oxalate. Naftidrofuryl oxalate may emerge as the most efficient and cost-effective treatment for symptom relief. PMID:26742197

  14. Impact of bacterial coinfection on clinical outcomes in pneumococcal pneumonia.

    PubMed

    Kumagai, S; Ishida, T; Tachibana, H; Ito, Y; Ito, A; Hashimoto, T

    2015-09-01

    The aim of this study was to investigate the influence of bacterial coinfection on patients with pneumococcal pneumonia. We retrospectively analyzed the incidence, clinical features, microbial distributions, and outcomes of patients with bacterial coinfection in a cohort of 433 hospitalized patients with pneumococcal pneumonia. Eighty-five patients (19.6 %) were diagnosed with bacterial coinfection; the most frequent pathogens were Haemophilus influenzae (25 patients, 33.3 %), methicillin-susceptible Staphylococcus aureus (MSSA) (15 patients, 20.0 %), and Moraxella catarrhalis (13 patients, 17.3 %). The CURB-65 score and pneumonia severity index (PSI) were significantly higher in patients with bacterial coinfection (both P < 0.001). In addition, the proportion of patients with bacterial coinfection who met the Infectious Disease Society of America (IDSA)/American Thoracic Society (ATS) severe pneumonia criteria was significantly higher (P < 0.001). Multivariate logistic regression analysis identified three risk factors for bacterial coinfection in patients with pneumococcal pneumonia: alcoholism (odds ratio [OR], 5.12; 95 % confidence interval (95 % CI), 1.60-16.4; P = 0.006), hospitalization for 2 days or more within 90 days preceding admission (OR, 2.02; 95 % CI, 1.03-3.98; P = 0.041), and residence in a nursing home or extended care facility (OR, 3.22; 95 % CI, 1.48-6.97; P = 0.003). Multivariate analysis for 30-day mortality showed that bacterial coinfection was a significant adverse prognostic factor (OR, 2.50; 95 % CI, 1.13-5.53; P = 0.023), independent of IDSA/ATS severe pneumonia, PSI, or healthcare-associated pneumonia. In conclusion, bacterial coinfection may have an adverse impact on severity and outcomes of pneumococcal pneumonia. PMID:26059041

  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. 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

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

    PubMed Central

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

    2015-01-01

    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. PMID:26311246

  18. Review on the association of Group B Streptococcus capsular antibody and protection against invasive disease in infants.

    PubMed

    Dangor, Ziyaad; Kwatra, Gaurav; Izu, Alane; Lala, Sanjay G; Madhi, Shabir A

    2015-01-01

    A trivalent Group B streptococcus (GBS) polysaccharide-protein conjugate vaccine for vaccination of pregnant women is under development to protect their newborns against invasive GBS disease. Establishing sero-correlates of protection against invasive GBS disease in infants could expedite the licensure pathway of polysaccharide-protein conjugate vaccine. A systematic review of studies reporting on the association of capsular antibodies and invasive GBS disease in infants and colonization in women or newborns was undertaken. Most studies that described maternal and/or infant capsular antibody levels in infants with invasive GBS disease identified an association between low capsular antibody levels in invasive GBS cases compared to controls. Different assay methods and the lack of standardized reference ranges for serotype-specific antibody levels makes it difficult to select an antibody level that may be used as a reliable sero-correlate of protection. Further studies using standardized methods are warranted. PMID:25242617

  19. 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. PMID:23531056

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

    PubMed

    Quan, Vanessa; Verani, Jennifer R; 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 probe to better

  1. 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

  2. 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

  3. 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

    2016-02-01

    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

  4. Variation in Inflammatory Response during Pneumococcal Infection Is Influenced by Host-Pathogen Interactions but Associated with Animal Survival

    PubMed Central

    Escudero, Laura; Sylvius, Nicolas; Norman, Martin; Henriques-Normark, Birgitta

    2016-01-01

    Inflammation is a crucial part of innate immune responses but, if imbalanced, can lead to serious clinical conditions or even death. Cytokines regulate inflammation, and studies report their impact on clinical outcome. However, host and pathogen genetic backgrounds influence cytokine production, making it difficult to evaluate which inflammatory profiles (if any) relate to improved prognosis. Streptococcus pneumoniae is a common human pathogen associated with asymptomatic nasopharyngeal carriage. Infrequently, it can lead to a wide range of diseases with high morbidity and mortality rates. Studies show that both pneumococcal serotype and host genetic background affect the development of disease and contribute to variation in inflammatory responses. In this study, we investigated the impact of the host and pneumococcal genetic backgrounds on pulmonary cytokine responses and their relationship to animal survival. Two inbred mouse strains, BALB/c and CBA/Ca, were infected with 10 pneumococcal strains, and the concentrations of six pulmonary cytokines were measured at 6 h and 24 h postinfection. Collected data were analyzed by principal-component analysis to identify whether there is any pattern in the observed cytokine variation. Our results show that host-pneumococcus combination was at the core of observed variation in cytokine responses, yet the resulting cytokine profile discriminated only between survivors and fatalities but not mouse or pneumococcal strains used during infection. Therefore, our results indicate that although alternative inflammatory profiles are generated during pneumococcal infection, a common pattern emerged, which determined the clinical outcome of pneumococcal infections. PMID:26787718

  5. Variation in Inflammatory Response during Pneumococcal Infection Is Influenced by Host-Pathogen Interactions but Associated with Animal Survival.

    PubMed

    Jonczyk, Magda S; Escudero, Laura; Sylvius, Nicolas; Norman, Martin; Henriques-Normark, Birgitta; Andrew, Peter W

    2016-04-01

    Inflammation is a crucial part of innate immune responses but, if imbalanced, can lead to serious clinical conditions or even death. Cytokines regulate inflammation, and studies report their impact on clinical outcome. However, host and pathogen genetic backgrounds influence cytokine production, making it difficult to evaluate which inflammatory profiles (if any) relate to improved prognosis.Streptococcus pneumonia is a common human pathogen associated with asymptomatic nasopharyngeal carriage. Infrequently, it can lead to a wide range of diseases with high morbidity and mortality rates. Studies show that both pneumococcal serotype and host genetic background affect the development of disease and contribute to variation in inflammatory responses. In this study, we investigated the impact of the host and pneumococcal genetic backgrounds on pulmonary cytokine responses and their relationship to animal survival. Two inbred mouse strains, BALB/c and CBA/Ca, were infected with 10 pneumococcal strains, and the concentrations of six pulmonary cytokines were measured at 6 h and 24 h postinfection. Collected data were analyzed by principal-component analysis to identify whether there is any pattern in the observed cytokine variation. Our results show that host-pneumococcus combination was at the core of observed variation in cytokine responses, yet the resulting cytokine profile discriminated only between survivors and fatalities but not mouse or pneumococcal strains used during infection. Therefore, our results indicate that although alternative inflammatory profiles are generated during pneumococcal infection, a common pattern emerged, which determined the clinical outcome of pneumococcal infections. PMID:26787718

  6. Identification and Characterization of a Novel Family of Pneumococcal Proteins That Are Protective against Sepsis

    PubMed Central

    Adamou, John E.; Heinrichs, Jon H.; Erwin, Alice L.; Walsh, William; Gayle, Tony; Dormitzer, Melissa; Dagan, Ron; Brewah, Yambasu A.; Barren, Philip; Lathigra, Raju; Langermann, Solomon; Koenig, Scott; Johnson, Syd

    2001-01-01

    Four pneumococcal genes (phtA, phtB, phtD, and phtE) encoding a novel family of homologous proteins (32 to 87% identity) were identified from the Streptococcus pneumoniae genomic sequence. These open reading frames were selected as potential vaccine candidates based upon their possession of hydrophobic leader sequences which presumably target these proteins to the bacterial cell surface. Analysis of the deduced amino acid sequences of these gene products revealed the presence of a histidine triad motif (HxxHxH), termed Pht (pneumococcal histidine triad) that is conserved and repeated several times in each of the four proteins. The four pht genes (phtA, phtB, phtD, and a truncated version of phtE) were expressed in Escherichia coli. A flow cytometry-based assay confirmed that PhtA, PhtB, PhtD and, to a lesser extent, PhtE were detectable on the surface of intact bacteria. Recombinant PhtA, PhtB, and PhtD elicited protection against certain pneumococcal capsular types in a mouse model of systemic disease. These novel pneumococcal antigens may serve as effective vaccines against the most prevalent pneumococcal serotypes. PMID:11159990

  7. 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

  8. Invasion Ability and Disease Dynamics of Environmentally Growing Opportunistic Pathogens under Outside-Host Competition

    PubMed Central

    Merikanto, Ilona; Laakso, Jouni T.; Kaitala, Veijo

    2014-01-01

    Most theories of the evolution of virulence concentrate on obligatory host-pathogen relationship. Yet, many pathogens replicate in the environment outside-host where they compete with non-pathogenic forms. Thus, replication and competition in the outside-host environment may have profound influence on the evolution of virulence and disease dynamics. These environmentally growing opportunistic pathogens are also a logical step towards obligatory pathogenicity. Efficient treatment methods against these diseases, such as columnaris disease in fishes, are lacking because of their opportunist nature. We present a novel epidemiological model in which replication and competition in the outside-host environment influences the invasion ability of a novel pathogen. We also analyze the long-term host-pathogen dynamics. Model parameterization is based on the columnaris disease, a bacterial fresh water fish disease that causes major losses in fish farms worldwide. Our model demonstrates that strong competition in the outside-host environment can prevent the invasion of a new environmentally growing opportunist pathogen and long-term disease outbreaks. PMID:25415341

  9. 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.

  10. Comparative phylogenomics of Streptococcus pneumoniae isolated from invasive disease and nasopharyngeal carriage from West Africans

    PubMed Central

    2012-01-01

    Background We applied comparative phylogenomics (whole genome comparisons of microbes using DNA microarrays combined with Bayesian-based phylogenies) to investigate S. pneumoniae isolates from West Africa, with the aim of providing insights into the pathogenicity and other features related to the biology of the organism. The strains investigated comprised a well defined collection of 58 invasive and carriage isolates that were sequenced typed and included eight different S. pneumoniae serotypes (1, 3, 5, 6A, 11, 14, 19 F and 23 F) of varying invasive disease potential. Results The core genome of the isolates was estimated to be 38% and was mainly represented by gene functional categories associated with housekeeping functions. Comparison of the gene content of invasive and carriage isolates identified at least eleven potential genes that may be important in virulence including surface proteins, transport proteins, transcription factors and hypothetical proteins. Thirteen accessory regions (ARs) were also identified and did not show any loci association with the eleven virulence genes. Intraclonal diversity (isolates of the same serotype and MLST but expressing different patterns of ARs) was observed among some clones including ST 1233 (serotype 5), ST 3404 (serotype 5) and ST 3321 (serotype 14). A constructed phylogenetic tree of the isolates showed a high level of heterogeneity consistent with the frequent S. pneumoniae recombination. Despite this, a homogeneous clustering of all the serotype 1 strains was observed. Conclusions Comparative phylogenomics of invasive and carriage S. pneumoniae isolates identified a number of putative virulence determinants that may be important in the progression of S. pneumoniae from the carriage phase to invasive disease. Virulence determinants that contribute to S. pneumoniae pathogenicity are likely to be distributed randomly throughout its genome rather than being clustered in dedicated loci or islands. Compared to other S

  11. RrgB321, a Fusion Protein of the Three Variants of the Pneumococcal Pilus Backbone RrgB, Is Protective In Vivo and Elicits Opsonic Antibodies

    PubMed Central

    Harfouche, Carole; Filippini, Sara; Gianfaldoni, Claudia; Ruggiero, Paolo; Moschioni, Monica; Maccari, Silvia; Pancotto, Laura; Arcidiacono, Letizia; Galletti, Bruno; Censini, Stefano; Mori, Elena; Giuliani, Marzia; Facciotti, Claudia; Cartocci, Elena; Savino, Silvana; Doro, Francesco; Pallaoro, Michele; Nocadello, Salvatore; Mancuso, Giuseppe; Haston, Mitch; Goldblatt, David; Barocchi, Michèle A.; Pizza, Mariagrazia; Rappuoli, Rino

    2012-01-01

    Streptococcus pneumoniae pilus 1 is present in 30 to 50% of invasive disease-causing strains and is composed of three subunits: the adhesin RrgA, the major backbone subunit RrgB, and the minor ancillary protein RrgC. RrgB exists in three distinct genetic variants and, when used to immunize mice, induces an immune response specific for each variant. To generate an antigen able to protect against the infection caused by all pilus-positive S. pneumoniae strains, we engineered a fusion protein containing the three RrgB variants (RrgB321). RrgB321 elicited antibodies against proteins from organisms in the three clades and protected mice against challenge with piliated pneumococcal strains. RrgB321 antisera mediated complement-dependent opsonophagocytosis of piliated strains at levels comparable to those achieved with the PCV7 glycoconjugate vaccine. These results suggest that a vaccine composed of RrgB321 has the potential to cover 30% or more of all pneumococcal strains and support the inclusion of this fusion protein in a multicomponent vaccine against S. pneumoniae. PMID:22083702

  12. The Association between Invasive Group A Streptococcal Diseases and Viral Respiratory Tract Infections

    PubMed Central

    Herrera, Andrea L.; Huber, Victor C.; Chaussee, Michael S.

    2016-01-01

    Viral infections of the upper respiratory tract are associated with a variety of invasive diseases caused by Streptococcus pyogenes, the group A streptococcus, including pneumonia, necrotizing fasciitis, toxic shock syndrome, and bacteremia. While these polymicrobial infections, or superinfections, are complex, progress has been made in understanding the molecular basis of disease. Areas of investigation have included the characterization of virus-induced changes in innate immunity, differences in bacterial adherence and internalization following viral infection, and the efficacy of vaccines in mitigating the morbidity and mortality of superinfections. Here, we briefly summarize viral-S. pyogenes superinfections with an emphasis on those affiliated with influenza viruses. PMID:27047460

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

    PubMed

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

    2016-08-01

    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

  14. Invasive Non-typhoidal Salmonella Disease – epidemiology, pathogenesis and diagnosis

    PubMed Central

    Gordon, Melita A

    2012-01-01

    Purpose of review To highlight and discuss important publications over the past 12 months providing new insights on invasive non-typhoidal Salmonella disease (iNTS). Recent findings There have been informative new estimates of the burden of iNTS in Asia and in high-resource low-incidence settings. Important information has emerged in the last year about the relationships between HIV, malaria, iNTS and typhoid fever in adults and children in Africa. HIV causes susceptibility to iNTS disease, but has been shown to be protective against typhoid fever. Clinical guidelines for presumptive diagnosis frequently fail to identify iNTS disease in Africa, and there remains a need for improved diagnostic tools. Experimental studies in humans have helped us to understand the intracellular pathogenesis of iNTS and to direct the search for appropriate protein vaccine targets. Summary The most important remaining gap in our knowledge is probably an understanding of how NTS are transmitted, and the nature of the relationship between diarrhoeal disease, carriage and invasive disease in Africa, so that diagnostic and prevention tools can be appropriately directed. PMID:21844803

  15. 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

  16. 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

  17. Pneumococcal polysaccharide vaccine - what you need to know

    MedlinePlus

    ... taken in its entirety from the CDC Pneumococcal Polysaccharide Vaccine Information Statement (VIS): www.cdc.gov/vaccines/ ... statements/ppv.html CDC review information for Pneumococcal Polysaccharide VIS: Page last reviewed: April 24, 2015 Page ...

  18. 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

  19. Disease-specific survival of patients with invasive cribriform and intraductal prostate cancer at diagnostic biopsy.

    PubMed

    Kweldam, Charlotte F; Kümmerlin, Intan P; Nieboer, Daan; Verhoef, Esther I; Steyerberg, Ewout W; van der Kwast, Theodorus H; Roobol, Monique J; van Leenders, Geert J

    2016-06-01

    Invasive cribriform and intraductal carcinoma in radical prostatectomy specimens have been associated with an adverse clinical outcome. Our objective was to determine the prognostic value of invasive cribriform and intraductal carcinoma in pre-treatment biopsies on time to disease-specific death. We pathologically revised the diagnostic biopsies of 1031 patients from the first screening round of the European Randomized Study of Screening for Prostate Cancer (1993-2000). Ninety percent of all patients (n=923) had received active treatment, whereas 10% (n=108) had been followed by watchful waiting. The median follow-up was 13 years. Patients who either had invasive cribriform growth pattern or intraductal carcinoma were categorized as CR/IDC+. The outcome was disease-specific survival. Relationships with outcome were analyzed using multivariable Cox regression and log-rank analysis. In total, 486 patients had Gleason score 6 (47%) and 545 had ≥7 (53%). The 15-year disease-specific-survival probabilities were 99% in Gleason score 6 (n=486), 94% in CR/IDC- Gleason score ≥7 (n=356) and 67% in CR/IDC+ Gleason score ≥7 (n=189). CR/IDC- Gleason score 3+4=7 patients did not have statistically different survival probabilities from those with Gleason score 6 (P=0.30), while CR/IDC+ Gleason score 3+4=7 patients did (P<0.001). In multivariable analysis, CR/IDC+ status was independently associated with a poorer disease-specific survival (HR 2.6, 95% CI 1.4-4.8, P=0.002). We conclude that CR/IDC+ status in prostate cancer biopsies is associated with a worse disease-specific survival. Our findings indicate that men with biopsy CR/IDC- Gleason score 3+4=7 prostate cancer could be candidates for active surveillance, as these patients have similar survival probabilities to those with Gleason score 6. PMID:26939875

  20. Perineural Invasion is a Marker for Pathologically Advanced Disease in Localized Prostate Cancer

    SciTech Connect

    Lee, Irwin H. . E-mail: irwinlee@med.umich.edu; Roberts, Rebecca; Shah, Rajal B.; Wojno, Kirk J.; Wei, John T.; Sandler, Howard M.

    2007-07-15

    Purpose: To determine if perineural invasion (PNI) should be included in addition to prostate-specific antigen (PSA), biopsy Gleason score, and clinical T-stage for risk-stratification of patients with localized prostate cancer. Methods and Materials: We analyzed prostatectomy findings for 1550 patients, from a prospectively collected institutional database, to determine whether PNI was a significant predictor for upgrading of Gleason score or pathologic T3 disease after patients were stratified into low-, intermediate-, and high-risk groups (on the basis of PSA, biopsy Gleason score, and clinical T-stage). Results: For the overall population, PNI was associated with a significantly increased frequency of upgrading and of pathologic T3 disease. After stratification, PNI was still associated with significantly increased odds of pathologic T3 disease within each risk group. In particular, for low-risk patients, there was a markedly increased risk of extraprostatic extension (23% vs. 7%), comparable to that of intermediate-risk patients. Among high-risk patients, PNI was associated with an increased risk of seminal vesicle invasion and lymph node involvement. Furthermore, over 80% of high-risk patients with PNI were noted to have an indication for postoperative radiation. Conclusions: Perineural invasion may be useful for risk-stratification of prostate cancer. Our data suggest that low-risk patients with PNI on biopsy may benefit from treatment typically reserved for those with intermediate-risk disease. In addition, men with high-risk disease and PNI, who are contemplating surgery, should be informed of the high likelihood of having an indication for postoperative radiation therapy.

  1. 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

  2. Epidemiology of Invasive Group B Streptococcal Disease in Alberta, Canada, from 2003 to 2013.

    PubMed

    Alhhazmi, Areej; Hurteau, Donna; Tyrrell, Gregory J

    2016-07-01

    Group B streptococci (GBS) cause severe invasive disease in both neonates and adults. Understanding the epidemiology of GBS provides information that can include determining disease prevalence rates in defined populations and geographic regions, documenting the success of GBS screening programs, and understanding antimicrobial susceptibility patterns. In Alberta, only neonatal invasive GBS (iGBS) disease is notifiable to health authorities. We performed a surveillance study of iGBS in Alberta, Canada, from 2003 to 2013. Over the 11-year period, the disease incidence rate increased from a low of 3.92 cases/100,000 population to a high of 5.99 cases/100,000 population. The capsular polysaccharide serotypes (CPSs) found were CPS III (20.3%), CPS V (19.1%), CPS Ia (18.9%), CPS Ib (12.7%), CPS II (11.1%), CPS IV (6.3%), and nontypeable GBS (9.4%). Rates of early-onset disease (0 to 7 days) increased from 0.15 cases/1,000 live births (in 2003) to 0.34 cases/1,000 live births (in 2013). Rates of late-onset disease (>7 to 90 days) also rose, from 0.15 cases/1,000 live births (in 2003) to 0.39 cases/1,000 live births (in 2013). Alberta also experienced an increase in CPS IV isolates, from 2 cases (in 2003) to 24 cases (in 2013), of which the majority were hvgA positive (86.6%). The predominant sequence type (ST) in 2013 was ST459. Erythromycin resistance rose from 23.6% to 43.9% (in 2013). Clindamycin resistance also increased, from 12.2% to 32.5%. In summary, Alberta, Canada, has experienced an increase in GBS disease; the increase includes both neonatal and adult disease. CPS IV cases also notably increased during the surveillance period, as did resistance to erythromycin and clindamycin. PMID:27098960

  3. 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. PMID:26742762

  4. Recombinant Bactericidal/Permeability-Increasing Protein rBPI21 Protects against Pneumococcal Disease▿

    PubMed Central

    Srivastava, Amit; Casey, Heather; Johnson, Nathaniel; Levy, Ofer; Malley, Richard

    2007-01-01

    Bactericidal/permeability-increasing (BPI) protein has been shown to play an important role in innate immunity to gram-negative bacteria, by direct microbicidal as well as endotoxin-neutralizing action. Here we examined potential interactions between a recombinant 21-kDa bioactive fragment of BPI, rBPI21, and the gram-positive pathogen Streptococcus pneumoniae. rBPI21 bound to pneumococci and pneumolysin (Ply) in a direct and specific fashion. We observed an enhanced inflammatory response in mouse macrophages when rBPI21 was combined with killed pneumococci or supernatant from overnight growth of pneumococci. In addition, rBPI21 augmented the proapoptotic activity of Ply+ (but not Ply−) pneumococci in TLR4-defective murine macrophages (known to be defective also in their apoptotic response to pneumolysin) in a tumor necrosis factor alpha-dependent manner. rBPI21 also enhanced the association of pneumococci with murine macrophages. In a model of invasive pneumococcal disease in TLR4-defective mice, the intranasal administration of rBPI21 following intranasal inoculation of Ply+ pneumococci both enhanced upper respiratory tract cell apoptosis and prolonged survival. We have thus discovered a novel interaction between pneumococcus and rBPI21, a potent antimicrobial peptide previously considered to target only gram-negative bacteria. PMID:17101667

  5. A random six-phase switch regulates pneumococcal virulence via global epigenetic changes

    PubMed Central

    Manso, Ana Sousa; Chai, Melissa H.; Atack, John M.; Furi, Leonardo; De Ste Croix, Megan; Haigh, Richard; Trappetti, Claudia; Ogunniyi, Abiodun D.; Shewell, Lucy K.; Boitano, Matthew; Clark, Tyson A.; Korlach, Jonas; Blades, Matthew; Mirkes, Evgeny; Gorban, Alexander N.; Paton, James C.; Jennings, Michael P.; Oggioni, Marco R.

    2014-01-01

    Streptococcus pneumoniae (the pneumococcus) is the world’s foremost bacterial pathogen in both morbidity and mortality. Switching between phenotypic forms (or ‘phases’) that favour asymptomatic carriage or invasive disease was first reported in 1933. Here, we show that the underlying mechanism for such phase variation consists of genetic rearrangements in a Type I restriction-modification system (SpnD39III). The rearrangements generate six alternative specificities with distinct methylation patterns, as defined by single-molecule, real-time (SMRT) methylomics. The SpnD39III variants have distinct gene expression profiles. We demonstrate distinct virulence in experimental infection and in vivo selection for switching between SpnD39III variants. SpnD39III is ubiquitous in pneumococci, indicating an essential role in its biology. Future studies must recognize the potential for switching between these heretofore undetectable, differentiated pneumococcal subpopulations in vitro and in vivo. Similar systems exist in other bacterial genera, indicating the potential for broad exploitation of epigenetic gene regulation. PMID:25268848

  6. Epidemiological analysis of pneumococcal serotype 19A in healthy children following PCV7 vaccination.

    PubMed

    Tóthpál, A; Laub, K; Kardos, S; Tirczka, T; Kocsis, A; VAN DER Linden, M; Dobay, O

    2016-05-01

    After the introduction of conjugate vaccines, a strong rearrangement of pneumococcal serotypes was observed globally. Probably most concerning was the emergence of serotype 19A, which has not only high invasive disease potential, but also high antibiotic resistance. In the current study we focused on the increased prevalence of serotype 19A after the PCV vaccination rate became widely used in Hungary. A total of 2262 children aged 3-6 years were screened for pneumococcus carriage using nasal swabs. Children were divided into two groups according to the vaccination rates, low level (group 1) vs. high level (group 2). While the carriage rate did not change over time (average 32·9%), the serotype distribution differed greatly in the two groups. The prevalence of serotype 19A increased >eightfold. Almost all 19A isolates had high-level macrolide resistance and elevated penicillin minimum inhibitory concentrations. Genotyping methods revealed that these new 19A isolates are different from the previously frequent Hungary19A-6 PMEN clone. Both the carriage rate and the overall penicillin and macrolide resistance remained stable over time, but while several serotypes were represented in group 1, serotype 19A alone was clearly dominant in group 2. PMID:26548594

  7. Identification of a novel pneumococcal vaccine antigen preferentially expressed during meningitis in mice

    PubMed Central

    Mahdi, Layla K.; Wang, Hui; Van der Hoek, Mark B.; Paton, James C.; Ogunniyi, Abiodun D.

    2012-01-01

    Streptococcus pneumoniae is the most common cause of severe bacterial meningitis in children, the elderly, and immunocompromised individuals. To identify virulence factors preferentially expressed during meningitis, we conducted niche-specific genome-wide in vivo transcriptomic analysis after intranasal infection of mice with serotype 4 or 6A pneumococci. The expression of 34 bacterial genes was substantially altered in brain tissue of mice infected with either of the 2 strains. Ten upregulated genes were common to both strains, 7 of which were evaluated for their role in the development of meningitis. One previously uncharacterized protein, α-glycerophosphate oxidase (GlpO), was cytotoxic for human brain microvascular endothelial cells (HBMECs) via generation of H2O2. A glpO deletion mutant was defective in adherence to HBMECs in vitro as well as in progression from the blood to the brain in vivo. Mutant bacteria also induced markedly reduced meningeal inflammation and brain pathology compared with wild type, despite similar levels of bacteremia. Immunization of mice with GlpO protected against invasive pneumococcal disease and provided additive protection when formulated with pneumolysin toxoid. Our results provide the basis of a strategy that can be adapted to identify genes that contribute to the development of meningitis caused by other pathogens. PMID:22622042

  8. Burden of Invasive Group B Streptococcus Disease and Early Neurological Sequelae in South African Infants

    PubMed Central

    Dangor, Ziyaad; Lala, Sanjay G.; Cutland, Clare L.; Koen, Anthonet; Jose, Lisa; Nakwa, Firdose; Ramdin, Tanusha; Fredericks, Joy; Wadula, Jeannette; Madhi, Shabir A.

    2015-01-01

    Introduction Group B Streptococcus (GBS) is a leading cause of neonatal sepsis and meningitis. We aimed to evaluate the burden of invasive early-onset (0–6 days of life, EOD) and late-onset (7–89 days, LOD) GBS disease and subsequent neurological sequelae in infants from a setting with a high prevalence (29.5%) of HIV among pregnant women. Methods A case-control study was undertaken at three secondary-tertiary care public hospitals in Johannesburg. Invasive cases in infants <3 months age were identified by surveillance of laboratories from November 2012 to February 2014. Neurodevelopmental screening was done in surviving cases and controls at 3 and 6 months of age. Results We identified 122 cases of invasive GBS disease over a 12 month period. Although the incidence (per 1,000 live births) of EOD was similar between HIV-exposed and HIV-unexposed infants (1.13 vs. 1.46; p = 0.487), there was a 4.67-fold (95%CI: 2.24–9.74) greater risk for LOD in HIV-exposed infants (2.27 vs. 0.49; p<0.001). Overall, serotypes Ia, Ib and III constituted 75.8% and 92.5% of EOD and LOD, respectively. Risk factors for EOD included offensive draining liquor (adjusted Odds Ratio: 27.37; 95%CI: 1.94–386.50) and maternal GBS bacteriuria (aOR: 8.41; 95%CI: 1.44–49.15), which was also a risk-factor for LOD (aOR: 3.49; 95%CI: 1.17–10.40). The overall case fatality rate among cases was 18.0%. The adjusted odds for neurological sequelae at 6 months age was 13.18-fold (95%CI: 1.44–120.95) greater in cases (13.2%) than controls (0.4%). Discussion The high burden of invasive GBS disease in South Africa, which is also associated with high case fatality rates and significant neurological sequelae among survivors, is partly due to the heightened risk for LOD in infants born to HIV-infected women. An effective trivalent GBS conjugate vaccine targeted at pregnant women could prevent invasive GBS disease in this setting. PMID:25849416

  9. Ultrastructural observations on bacterial invasion in cementum and radicular dentin of periodontally diseased human teeth.

    PubMed

    Adriaens, P A; Edwards, C A; De Boever, J A; Loesche, W J

    1988-08-01

    In this study the bacterial invasion in root cementum and radicular dentin of periodontally diseased, caries-free human teeth was examined. In addition, structural changes in these tissues, which could be related to the bacterial invasion, were reported. Twenty-one caries-free human teeth with extensive periodontal attachment loss were studied by light and scanning electron microscopy. At the base of the gingival pocket, bacteria were found in the spaces between remnants of Sharpey's fibers and their point of insertion in the cementum. In teeth that had been scaled and root planed, most of the root cementum had been removed. Bacterial invasion was found in the remaining root cementum. The invasion seemed to start as a localized process, often involving only one bacterium. In other areas bacteria were present in lacunar defects in the cementum. These lacunae extended into the radicular dentin. In 11 teeth bacteria had invaded the dentinal tubules. Most bacteria were located in the outer 300 microns of the dentinal tubules, although occasionally they were found in deeper parts. In two of the nontreated teeth, bacteria were detected on the pulpal wall. No correlation was found between the presence of bacterial invasion and the absence of radicular cementum. No bacteria were found in the portion of the root located apically to the epithelial attachment. These data are in agreement with our results from cultural studies of the bacterial flora in these structures. It was also demonstrated that in spite of meticulous scaling and root planning and personal oral hygiene, bacterial plaque remained present on radicular surfaces. Both the invaded dentinal tubules and the lacunae could act as bacterial reservoirs from which recolonization of treated root surfaces occurs. From these reservoirs bacteria could also induce pulpal pathoses. Since these bacterial reservoirs are not eliminated by conventional mechanical periodontal treatment, it seems appropriate to combine mechanical

  10. Small bowel transplantation complicated by cytomegalovirus tissue invasive disease without viremia.

    PubMed

    Avsar, Yesim; Cicinnati, Vito R; Kabar, Iyad; Wolters, Heiner; Anthoni, Christoph; Schmidt, Hartmut H J; Beckebaum, Susanne

    2014-06-01

    We report on a small bowel transplant patient, donor/recipient seropositive (D+/R+) for cytomegalovirus (CMV), with a clinical course complicated by CMV disease. Anti-CMV prophylaxis was given for 100 days. Immunosuppression consisted of alemtuzumab, tacrolimus, mycophenolate mofetil and prednisolone. Five months posttransplant, CMV tissue invasive disease of the upper gastrointestinal tract was evident without the presence of viremia, tested by quantitative polymerase chain reaction (PCR). Complete viral load suppression was achieved with intravenous ganciclovir, followed by valganciclovir for secondary prophylaxis. Mycophenolate mofetil and prednisolone were discontinued. Shortly thereafter the patient presented with recurrent CMV and candida esophagitis. While on ganciclovir and caspofungin, the patient developed CMV tissue invasive disease of the ileal graft, with persistent absence of viremia. Foscarnet and CMV immunoglobulin were added. Viral load declined to undetectable levels; however, clinical improvement did not occur due to occurrence of graft rejection. Despite infliximab and high dose prednisolone, graft rejection was progressive, requiring surgical explantation of the graft. This case highlights the importance of additional diagnostic tools such as endoscopy including PCR analysis of tissue samples. Extension of primary antiviral prophylaxis interval up to 6 months and prolonged retreatment for recurrent CMV disease may be useful to avoid severe CMV-related complications. PMID:24703746

  11. Relationship between invasion of the periodontium by periodontal pathogens and periodontal disease: a systematic review.

    PubMed

    Mendes, Luzia; Azevedo, Nuno Filipe; Felino, António; Pinto, Miguel Gonçalves

    2015-01-01

    Bacterial invasion of the periodontal tissues has been suggested as a relevant step in the etiopathogenesis of periodontal disease. However, its exact importance remains to be defined. The present systematic review assessed the scientific evidence concerning the relationship between the quality or quantity of periodontal microbiota in periodontal tissues and development of periodontal disease. The databases Medline-PubMed, Cochrane-CENTRAL, ISI Web of Knowledge and SCOPUS were searched, up to January 2014. Studies that reported evaluation of periodontal pathogens invasion on human tissues were selected. The screening of 440 title/abstracts elected 26 papers for full-text reading. Twenty three papers were subsequently excluded because of insufficient data or a study protocol not related to the objectives of this systematic review. All included studies were case-control studies that evaluated intracellular or adherent bacteria to epithelial cells from periodontal pockets versus healthy sulci. Study protocols presented heterogeneity regarding case and control definitions and methodological approaches for microbial identification. No consistent significant differences were found related to the presence/absence or proportion of specific periopathogens across the studies, as only one study found statistically significant differences regarding the presence of A. actinomycetemcomitans (p = 0.043), T. forsythia (P < 0.001), P. intermedia (P < 0.001), C. ochracea (P < 0.001) and C. rectus (P = 0.003) in epithelial cells from periodontal pockets vs. healthy sulci. All studies reported a larger unspecific bacterial load in or on the epithelial cells taken from a diseased site compared to a healthy sulcus. The current available data is of low to moderate quality and inconsistent mainly due to study design, poor reporting and methodological diversity. As so, there is insufficient evidence to support or exclude the invasion by periodontal pathogens as a key step in the

  12. Relationship between invasion of the periodontium by periodontal pathogens and periodontal disease: a systematic review

    PubMed Central

    Mendes, Luzia; Azevedo, Nuno Filipe; Felino, António; Pinto, Miguel Gonçalves

    2015-01-01

    Bacterial invasion of the periodontal tissues has been suggested as a relevant step in the etiopathogenesis of periodontal disease. However, its exact importance remains to be defined. The present systematic review assessed the scientific evidence concerning the relationship between the quality or quantity of periodontal microbiota in periodontal tissues and development of periodontal disease. The databases Medline-PubMed, Cochrane-CENTRAL, ISI Web of Knowledge and SCOPUS were searched, up to January 2014. Studies that reported evaluation of periodontal pathogens invasion on human tissues were selected. The screening of 440 title/abstracts elected 26 papers for full-text reading. Twenty three papers were subsequently excluded because of insufficient data or a study protocol not related to the objectives of this systematic review. All included studies were case-control studies that evaluated intracellular or adherent bacteria to epithelial cells from periodontal pockets versus healthy sulci. Study protocols presented heterogeneity regarding case and control definitions and methodological approaches for microbial identification. No consistent significant differences were found related to the presence/absence or proportion of specific periopathogens across the studies, as only one study found statistically significant differences regarding the presence of A. actinomycetemcomitans (p = 0.043), T. forsythia (P < 0.001), P. intermedia (P < 0.001), C. ochracea (P < 0.001) and C. rectus (P = 0.003) in epithelial cells from periodontal pockets vs. healthy sulci. All studies reported a larger unspecific bacterial load in or on the epithelial cells taken from a diseased site compared to a healthy sulcus. The current available data is of low to moderate quality and inconsistent mainly due to study design, poor reporting and methodological diversity. As so, there is insufficient evidence to support or exclude the invasion by periodontal pathogens as a key step in the

  13. 220D-F2 from Rubus ulmifolius Kills Streptococcus pneumoniae Planktonic Cells and Pneumococcal Biofilms

    PubMed Central

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

    2014-01-01

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

  14. 220D-F2 from Rubus ulmifolius kills Streptococcus pneumoniae planktonic cells and pneumococcal biofilms.

    PubMed

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

    2014-01-01

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

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

    PubMed

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

    2015-01-01

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

  16. Multivalent Pneumococcal Protein Vaccines Comprising Pneumolysoid with Epitopes/Fragments of CbpA and/or PspA Elicit Strong and Broad Protection.

    PubMed

    Chen, Austen; Mann, Beth; Gao, Geli; Heath, Richard; King, Janice; Maissoneuve, Jeff; Alderson, Mark; Tate, Andrea; Hollingshead, Susan K; Tweten, Rodney K; Briles, David E; Tuomanen, Elaine I; Paton, James C

    2015-10-01

    Immunization with the pneumococcal proteins pneumolysin (Ply), choline binding protein A (CbpA), or pneumococcal surface protein A (PspA) elicits protective responses against invasive pneumococcal disease in animal models. In this study, we used different mouse models to test the efficacy of a variety of multivalent protein-based vaccines that comprised various combinations of full-length or peptide regions of the immunogens Ply, CbpA, or PspA: Ply toxoid with the L460D substitution (referred to herein as L460D); L460D fused with protective peptide epitopes from CbpA (YPT-L460D-NEEK [YLN]); L460D fused with the CD2 peptide containing the proline-rich region (PRR) of PspA (CD2-L460D); a combination of L460D and H70 (L460D+H70), a slightly larger PspA-derived peptide containing the PRR and the SM1 region; H70+YLN; and other combinations. Each mouse was immunized either intraperitoneally (i.p.) or subcutaneously (s.c.) with three doses (at 2-week intervals) of the various antigen combinations in alum adjuvant and then challenged in mouse models featuring different infection routes with multiple Streptococcus pneumoniae strains. In the i.p. infection sepsis model, H70+YLN consistently provided significant protection against three different challenge strains (serotypes 1, 2, and 6A); the CD2+YLN and H70+L460D combinations also elicited significant protection. Protection against intravenous (i.v.) sepsis (type 3 and 6A challenge strains) was largely dependent on PspA-derived antigen components, and the most protection was elicited by H70 with or without L460D or YLN. In a type 4 intratracheal (i.t.) challenge model that results in progression to meningitis, antigen combinations that contained YLN elicited the strongest protection. Thus, the trivalent antigen combination of H70+YLN elicited the strongest and broadest protection in diverse pneumococcal challenge models. PMID:26245351

  17. Nasopharyngeal colonization of Gambian infants by Staphylococcus aureus and Streptococcus pneumoniae before the introduction of pneumococcal conjugate vaccines

    PubMed Central

    Usuf, E.; Bojang, A.; Hill, P.C.; Bottomley, C.; Greenwood, B.; Roca, A.

    2015-01-01

    Staphylococcus aureus and Streptococcus pneumoniae commonly colonize the upper respiratory tract and can cause invasive disease. Several studies suggest an inverse relationship between these two bacteria in the nasopharynx. This association is of particular concern as the introduction of pneumococcal conjugate vaccines (PCVs) that affect pneumococcal nasopharyngeal carriage become widespread. A cohort of children in rural Gambia were recruited at birth and followed for 1 year, before the introduction of PCV into the routine immunization program. Nasopharyngeal swabs were taken immediately after birth, every 2 weeks for the first 6 months and then every other month. The presence of S. aureus and S. pneumoniae was determined using conventional microbiologic methods. Prevalence of S. aureus carriage was 71.6% at birth, decreasing with age to reach a plateau at approximately 20% between 10 to 20 weeks of age. Carriage with any S. pneumoniae increased during the first 10 weeks of life to peak at approximately 90%, mostly of PCV13 serotypes. Although in the crude analysis S. aureus carriage was inversely associated with carriage of any S. pneumoniae and PCV13 serotypes, after adjusting by age and season, there was a positive association with any carriage (odds ratio 1.32; 95% confidence interval 1.07–1.64; p 0.009) and no association with carriage of PCV13 serotypes (odds ratio 0.99; 95% confidence interval 0.70–1.41; p 0.973). Among Gambian infants, S. aureus and S. pneumoniae are not inversely associated in nasopharyngeal carriage after adjustment for age. Further carriage studies following the introduction of PCV are needed to better understand the relationship between the two bacteria. PMID:26909154

  18. Nasopharyngeal colonization of Gambian infants by Staphylococcus aureus and Streptococcus pneumoniae before the introduction of pneumococcal conjugate vaccines.

    PubMed

    Usuf, E; Bojang, A; Hill, P C; Bottomley, C; Greenwood, B; Roca, A

    2016-03-01

    Staphylococcus aureus and Streptococcus pneumoniae commonly colonize the upper respiratory tract and can cause invasive disease. Several studies suggest an inverse relationship between these two bacteria in the nasopharynx. This association is of particular concern as the introduction of pneumococcal conjugate vaccines (PCVs) that affect pneumococcal nasopharyngeal carriage become widespread. A cohort of children in rural Gambia were recruited at birth and followed for 1 year, before the introduction of PCV into the routine immunization program. Nasopharyngeal swabs were taken immediately after birth, every 2 weeks for the first 6 months and then every other month. The presence of S. aureus and S. pneumoniae was determined using conventional microbiologic methods. Prevalence of S. aureus carriage was 71.6% at birth, decreasing with age to reach a plateau at approximately 20% between 10 to 20 weeks of age. Carriage with any S. pneumoniae increased during the first 10 weeks of life to peak at approximately 90%, mostly of PCV13 serotypes. Although in the crude analysis S. aureus carriage was inversely associated with carriage of any S. pneumoniae and PCV13 serotypes, after adjusting by age and season, there was a positive association with any carriage (odds ratio 1.32; 95% confidence interval 1.07-1.64; p 0.009) and no association with carriage of PCV13 serotypes (odds ratio 0.99; 95% confidence interval 0.70-1.41; p 0.973). Among Gambian infants, S. aureus and S. pneumoniae are not inversely associated in nasopharyngeal carriage after adjustment for age. Further carriage studies following the introduction of PCV are needed to better understand the relationship between the two bacteria. PMID:26909154

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

    PubMed

    Van Steenkiste, M

    2013-03-01

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

  20. Cell-derived extracellular vesicles as a platform to identify low-invasive disease biomarkers.

    PubMed

    González, Esperanza; Falcón-Pérez, Juan Manuel

    2015-01-01

    Biomarkers are of great importance for prediction, diagnosis and monitoring the progression and therapeutic success of a disease. Whole body fluids, such as blood or urine, constitute the main desired biological source to identify these markers, mostly due to the minimally invasive procedures used to collect them. An additional benefit of studying these biological fluids that has been demonstrated by many different groups is that they contain cell-released extracellular vesicles, carrying a cargo of lipids, proteins and nucleic acids that reflects cell/tissue origin and, remarkably, cellular status. In this review, the information obtained from the characterization of this body fluid compartment in human samples is discussed in the context of its usefulness as diagnostic resource for several pathologies, including cancer, inflammatory, vascular and metabolic diseases. The review shows the great variety of methods used for this purpose as well as the different types of molecules that could serve as specific or common disease markers. PMID:25948243

  1. Resting-state networks link invasive and noninvasive brain stimulation across diverse psychiatric and neurological diseases.

    PubMed

    Fox, Michael D; Buckner, Randy L; Liu, Hesheng; Chakravarty, M Mallar; Lozano, Andres M; Pascual-Leone, Alvaro

    2014-10-14

    Brain stimulation, a therapy increasingly used for neurological and psychiatric disease, traditionally is divided into invasive approaches, such as deep brain stimulation (DBS), and noninvasive approaches, such as transcranial magnetic stimulation. The relationship between these approaches is unknown, therapeutic mechanisms remain unclear, and the ideal stimulation site for a given technique is often ambiguous, limiting optimization of the stimulation and its application in further disorders. In this article, we identify diseases treated with both types of stimulation, list the stimulation sites thought to be most effective in each disease, and test the hypothesis that these sites are different nodes within the same brain network as defined by resting-state functional-connectivity MRI. Sites where DBS was effective were functionally connected to sites where noninvasive brain stimulation was effective across diseases including depression, Parkinson's disease, obsessive-compulsive disorder, essential tremor, addiction, pain, minimally conscious states, and Alzheimer's disease. A lack of functional connectivity identified sites where stimulation was ineffective, and the sign of the correlation related to whether excitatory or inhibitory noninvasive stimulation was found clinically effective. These results suggest that resting-state functional connectivity may be useful for translating therapy between stimulation modalities, optimizing treatment, and identifying new stimulation targets. More broadly, this work supports a network perspective toward understanding and treating neuropsychiatric disease, highlighting the therapeutic potential of targeted brain network modulation. PMID:25267639

  2. Resting-state networks link invasive and noninvasive brain stimulation across diverse psychiatric and neurological diseases

    PubMed Central

    Fox, Michael D.; Buckner, Randy L.; Liu, Hesheng; Chakravarty, M. Mallar; Lozano, Andres M.; Pascual-Leone, Alvaro

    2014-01-01

    Brain stimulation, a therapy increasingly used for neurological and psychiatric disease, traditionally is divided into invasive approaches, such as deep brain stimulation (DBS), and noninvasive approaches, such as transcranial magnetic stimulation. The relationship between these approaches is unknown, therapeutic mechanisms remain unclear, and the ideal stimulation site for a given technique is often ambiguous, limiting optimization of the stimulation and its application in further disorders. In this article, we identify diseases treated with both types of stimulation, list the stimulation sites thought to be most effective in each disease, and test the hypothesis that these sites are different nodes within the same brain network as defined by resting-state functional-connectivity MRI. Sites where DBS was effective were functionally connected to sites where noninvasive brain stimulation was effective across diseases including depression, Parkinson's disease, obsessive-compulsive disorder, essential tremor, addiction, pain, minimally conscious states, and Alzheimer’s disease. A lack of functional connectivity identified sites where stimulation was ineffective, and the sign of the correlation related to whether excitatory or inhibitory noninvasive stimulation was found clinically effective. These results suggest that resting-state functional connectivity may be useful for translating therapy between stimulation modalities, optimizing treatment, and identifying new stimulation targets. More broadly, this work supports a network perspective toward understanding and treating neuropsychiatric disease, highlighting the therapeutic potential of targeted brain network modulation. PMID:25267639

  3. Desialylation of airway epithelial cells during influenza virus infection enhances pneumococcal adhesion via galectin binding

    PubMed Central

    Nita-Lazar, Mihai; Banerjee, Aditi; Feng, Chiguang; Amin, Mohammed N.; Frieman, Matthew B.; Chen, Wilbur H.; Cross, Alan S.; Wang, Lai-Xi; Vasta, Gerardo R.

    2015-01-01

    The continued threat of worldwide influenza pandemics, together with the yearly emergence of antigenically drifted influenza A virus (IAV) strains, underscore the urgent need to elucidate not only the mechanisms of influenza virulence, but also those mechanisms that predispose influenza patients to increased susceptibility to subsequent infection with Streptococcus pneumoniae. Glycans displayed on the surface of epithelia that are exposed to the external environment play important roles in microbial recognition, adhesion, and invasion. It is well established that the IAV hemagglutinin and pneumococcal adhesins enable their attachment to the host epithelia. Reciprocally, the recognition of microbial glycans by host carbohydrate-binding proteins (lectins) can initiate innate immune responses, but their relevance in influenza or pneumococcal infections is poorly understood. Galectins are evolutionarily conserved lectins characterized by affinity for β-galactosides and a unique sequence motif, with critical regulatory roles in development and immune homeostasis. In this study, we examined the possibility that galectins expressed in the airway epithelial cells might play a significant role in viral or pneumococcal adhesion to airway epithelial cells. Our results in a mouse model for influenza and pneumococcal infection revealed that the murine lung expresses a diverse galectin repertoire, from which selected galectins, including galectin 1 (Gal1) and galectin 3 (Gal3), are released to the bronchoalveolar space. Further, the results showed that influenza and subsequent S. pneumoniae infections significantly alter the glycosylation patterns of the airway epithelial surface and modulate galectin expression. In vitro studies on the human airway epithelial cell line A549 were consistent with the observations made in the mouse model, and further revealed that both Gal1 and Gal3 bind strongly to IAV and S. pneumoniae, and that exposure of the cells to viral neuraminidase or

  4. Epidemiology of invasive fungal diseases on the basis of autopsy reports.

    PubMed

    Dignani, María Cecilia

    2014-01-01

    Invasive fungal diseases (IFDs) are a major cause of morbidity and mortality among immunocompromised patients and cost to health services. They are difficult to prevent, diagnose, and treat. This difficulty in diagnosis leads us to treat them empirically by using several tools, including epidemiological data, non-culture methods and images. Most of the available epidemiological information may not be accurate because we are dealing with a disease that only has an estimated 50% chance of being diagnosed before death. Therefore, autopsy reports become a valuable tool, not only to define the real epidemiology, but also to address the trend in pre-mortem diagnosis, which is the best marker available to prove the efficiency of the research in IFD. This article reviews and analyzes the data on IFD obtained from 11 single-center, multi-center and nationwide autopsy reports published between 2008 and 2013, and also discusses the issues we need to address in order to improve the quality of the epidemiological data on invasive fungal disease obtained from autopsy reports. PMID:25343038

  5. Epidemiology of invasive fungal diseases on the basis of autopsy reports

    PubMed Central

    2014-01-01

    Invasive fungal diseases (IFDs) are a major cause of morbidity and mortality among immunocompromised patients and cost to health services. They are difficult to prevent, diagnose, and treat. This difficulty in diagnosis leads us to treat them empirically by using several tools, including epidemiological data, non-culture methods and images. Most of the available epidemiological information may not be accurate because we are dealing with a disease that only has an estimated 50% chance of being diagnosed before death. Therefore, autopsy reports become a valuable tool, not only to define the real epidemiology, but also to address the trend in pre-mortem diagnosis, which is the best marker available to prove the efficiency of the research in IFD. This article reviews and analyzes the data on IFD obtained from 11 single-center, multi-center and nationwide autopsy reports published between 2008 and 2013, and also discusses the issues we need to address in order to improve the quality of the epidemiological data on invasive fungal disease obtained from autopsy reports. PMID:25343038

  6. 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

  7. 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. PMID:19787407

  8. Survey of Obstetrics and Gynecology Residents Regarding Pneumococcal Vaccination in Pregnancy: Education, Knowledge, and Barriers to Vaccination.

    PubMed

    Fay, Emily E; Hoppe, Kara K; Schulkin, Jay; Eckert, Linda O

    2016-01-01

    Objective. The 23-valent pneumococcal vaccine is recommended for adults over 65 years of age and younger adults with certain medical conditions. The Centers for Disease Control and Prevention (CDC) state insufficient evidence to recommend routine pneumococcal vaccination during pregnancy, but the vaccine is indicated for pregnant women with certain medical conditions. We designed this project to gauge obstetrics and gynecology (OB/GYN) resident knowledge of maternal pneumococcal vaccination. Methods. We administered a 22-question survey to OB/GYN residents about maternal pneumococcal vaccination. We performed descriptive analysis for each question. Results. 238 OB/GYN residents responded. Overall, 69.3% of residents reported receiving vaccination education and 86.0% reported having ready access to vaccine guidelines and safety data. Most residents knew that asplenia (78.2%), pulmonary disease (77.3%), and HIV/AIDS (69.4%) are indications for vaccination but less knew that cardiovascular disease (45.0%), diabetes (35.8%), asthma (42.8%), nephrotic syndrome (19.7%), and renal failure (33.6%) are also indications for vaccination. Conclusion. OB/GYN residents are taught about vaccines and have ready access to vaccine guidelines and safety data. However, knowledge of indications for pneumococcal vaccination in pregnancy is lacking. Likely, the opportunity to vaccinate at-risk pregnant patients is being missed. PMID:26949324

  9. Survey of Obstetrics and Gynecology Residents Regarding Pneumococcal Vaccination in Pregnancy: Education, Knowledge, and Barriers to Vaccination

    PubMed Central

    Fay, Emily E.; Hoppe, Kara K.; Schulkin, Jay; Eckert, Linda O.

    2016-01-01

    Objective. The 23-valent pneumococcal vaccine is recommended for adults over 65 years of age and younger adults with certain medical conditions. The Centers for Disease Control and Prevention (CDC) state insufficient evidence to recommend routine pneumococcal vaccination during pregnancy, but the vaccine is indicated for pregnant women with certain medical conditions. We designed this project to gauge obstetrics and gynecology (OB/GYN) resident knowledge of maternal pneumococcal vaccination. Methods. We administered a 22-question survey to OB/GYN residents about maternal pneumococcal vaccination. We performed descriptive analysis for each question. Results. 238 OB/GYN residents responded. Overall, 69.3% of residents reported receiving vaccination education and 86.0% reported having ready access to vaccine guidelines and safety data. Most residents knew that asplenia (78.2%), pulmonary disease (77.3%), and HIV/AIDS (69.4%) are indications for vaccination but less knew that cardiovascular disease (45.0%), diabetes (35.8%), asthma (42.8%), nephrotic syndrome (19.7%), and renal failure (33.6%) are also indications for vaccination. Conclusion. OB/GYN residents are taught about vaccines and have ready access to vaccine guidelines and safety data. However, knowledge of indications for pneumococcal vaccination in pregnancy is lacking. Likely, the opportunity to vaccinate at-risk pregnant patients is being missed. PMID:26949324

  10. Development of a non-invasive murine infection model for acute otitis media.

    PubMed

    Stol, K; van Selm, S; van den Berg, S; Bootsma, H J; Blokx, W A M; Graamans, K; Tonnaer, E L G M; Hermans, P W M

    2009-12-01

    Otitis media (OM) is one of the most frequent diseases in childhood, and Streptococcus pneumoniae is among the main causative bacterial agents. Since current experimental models used to study the bacterial pathogenesis of OM have several limitations, such as the invasiveness of the experimental procedures, we developed a non-invasive murine OM model. In our model, adapted from a previously developed rat OM model, a pressure cabin is used in which a 40 kPa pressure increase is applied to translocate pneumococci from the nasopharyngeal cavity into both mouse middle ears. Wild-type pneumococci were found to persist in the middle ear cavity for 144 h after infection, with a maximum bacterial load at 96 h. Inflammation was confirmed at 96 and 144 h post-infection by IL-1beta and TNF-alpha cytokine analysis and histopathology. Subsequently, we investigated the contribution of two surface-associated pneumococcal proteins, the streptococcal lipoprotein rotamase A (SlrA) and the putative proteinase maturation protein A (PpmA), to experimental OM in our model. Pneumococci lacking the slrA gene, but not those lacking the ppmA gene, were significantly reduced in virulence in the OM model. Importantly, pneumococci lacking both genes were significantly more attenuated than the DeltaslrA single mutant. This additive effect suggests that SlrA and PpmA exert complementary functions during experimental OM. In conclusion, we have developed a highly reproducible and non-invasive murine infection model for pneumococcal OM using a pressure cabin, which is very suitable to study pneumococcal pathogenesis and virulence in vivo. PMID:19762437

  11. The clinical features and long-term sequelae of invasive meningococcal disease in children.

    PubMed

    Stein-Zamir, Chen; Shoob, Hanna; Sokolov, Irina; Kunbar, Amin; Abramson, Nitza; Zimmerman, Deena

    2014-07-01

    We evaluated the outcome of invasive meningococcal disease in children <15 years of age (n = 181). Neisseria meningitidis serogroup B comprised 78% of bacterial isolates. Case fatality rate was 11.6%. In follow-up interviews (115/160 survivors, 72%), at least 1 long-term sequela was reported in 38/115 children (33%), including learning-academic difficulties (22.6%), hearing impairment (7%), neurologic (12.2%), behavioral (14.8%) and motor (10.4%) deficits. PMID:24622347

  12. 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

  13. 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

  14. 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. PMID:27273325

  15. Disease Burden of Invasive Listeriosis and Molecular Characterization of Clinical Isolates in Taiwan, 2000-2013.

    PubMed

    Huang, Yu-Tsung; Ko, Wen-Chien; Chan, Yu-Jiun; Lu, Jang-Jih; Tsai, Hsih-Yeh; Liao, Chun-Hsing; Sheng, Wang-Huei; Teng, Lee-Jene; Hsueh, Po-Ren

    2015-01-01

    The information about disease burden and epidemiology of invasive listeriosis in Asia is scarce. From 2000 to 2013, a total of 338 patients with invasive listeriosis (bacteremia, meningitis, and peritonitis) were treated at four medical centers in Taiwan. The incidence (per 10,000 admissions) of invasive listeriosis increased significantly during the 14-year period among the four centers (0.15 in 2000 and >1.25 during 2010-2012) and at each of the four medical centers. Among these patients, 45.9% were elderly (>65 years old) and 3.3% were less than one year of age. More than one-third (36.7%) of the patients acquired invasive listeriosis in the spring (April to June). Among the 132 preserved Listeria monocytogenes isolates analyzed, the most frequently isolated PCR serogroup-sequence type (ST) was IIb-ST87 (23.5%), followed by IIa-ST378 (19.7%) and IIa-ST155 (12.1%). Isolation of PCR serogroups IIb and IVb increased significantly with year, with a predominance of IIb-ST87 isolates (23.5%) and IIb-ST 228 isolates emerging in 2013. A total of 12 different randomly amplified polymorphic DNA (RAPD) patterns (Patterns I to XII) were identified among the 112 L. monocytogenes isolates belonging to eight main PCR serogroup-STs. Identical RAPD patterns were found among the isolates exhibiting the same PCR serogroup-ST. In conclusion, our study revealed that during 2000-2013, listeriosis at four medical centers in Taiwan was caused by heterogeneous strains and that the upsurge in incidence beginning in 2005 was caused by at least two predominant clones. PMID:26555445

  16. Cytokine Profiles during Invasive Nontyphoidal Salmonella Disease Predict Outcome in African Children.

    PubMed

    Gilchrist, James J; Heath, Jennifer N; Msefula, Chisomo L; Gondwe, Esther N; Naranbhai, Vivek; Mandala, Wilson; MacLennan, Jenny M; Molyneux, Elizabeth M; Graham, Stephen M; Drayson, Mark T; Molyneux, Malcolm E; MacLennan, Calman A

    2016-07-01

    Nontyphoidal Salmonella is a leading cause of sepsis in African children. Cytokine responses are central to the pathophysiology of sepsis and predict sepsis outcome in other settings. In this study, we investigated cytokine responses to invasive nontyphoidal Salmonella (iNTS) disease in Malawian children. We determined serum concentrations of 48 cytokines with multiplexed immunoassays in Malawian children during acute iNTS disease (n = 111) and in convalescence (n = 77). Principal component analysis and logistic regression were used to identify cytokine signatures of acute iNTS disease. We further investigated whether these responses are altered by HIV coinfection or severe malnutrition and whether cytokine responses predict inpatient mortality. Cytokine changes in acute iNTS disease were associated with two distinct cytokine signatures. The first is characterized by increased concentrations of mediators known to be associated with macrophage function, and the second is characterized by raised pro- and anti-inflammatory cytokines typical of responses reported in sepsis secondary to diverse pathogens. These cytokine responses were largely unaltered by either severe malnutrition or HIV coinfection. Children with fatal disease had a distinctive cytokine profile, characterized by raised mediators known to be associated with neutrophil function. In conclusion, cytokine responses to acute iNTS infection in Malawian children are reflective of both the cytokine storm typical of sepsis secondary to diverse pathogens and the intramacrophage replicative niche of NTS. The cytokine profile predictive of fatal disease supports a key role of neutrophils in the pathogenesis of NTS sepsis. PMID:27170644

  17. Escherichia coli in chronic inflammatory bowel diseases: An update on adherent invasive Escherichia coli pathogenicity

    PubMed Central

    Martinez-Medina, Margarita; Garcia-Gil, Librado Jesus

    2014-01-01

    Escherichia coli (E. coli), and particularly the adherent invasive E. coli (AIEC) pathotype, has been increasingly implicated in the ethiopathogenesis of Crohn’s disease (CD). E. coli strains with similar pathogenic features to AIEC have been associated with other intestinal disorders such as ulcerative colitis, colorectal cancer, and coeliac disease, but AIEC prevalence in these diseases remains largely unexplored. Since AIEC was described one decade ago, substantial progress has been made in deciphering its mechanisms of pathogenicity. However, the molecular bases that characterize the phenotypic properties of this pathotype are still not well resolved. A review of studies focused on E. coli populations in inflammatory bowel disease (IBD) is presented here and we discuss about the putative role of this species on each IBD subtype. Given the relevance of AIEC in CD pathogenesis, we present the latest research findings concerning AIEC host-microbe interactions and pathogenicity. We also review the existing data regarding the prevalence and abundance of AIEC in CD and its association with other intestinal diseases from humans and animals, in order to discuss the AIEC disease- and host-specificity. Finally, we highlight the fact that dietary components frequently found in industrialized countries may enhance AIEC colonization in the gut, which merits further investigation and the implementation of preventative measures. PMID:25133024

  18. Cytokine Profiles during Invasive Nontyphoidal Salmonella Disease Predict Outcome in African Children

    PubMed Central

    Gilchrist, James J.; Heath, Jennifer N.; Msefula, Chisomo L.; Gondwe, Esther N.; Naranbhai, Vivek; Mandala, Wilson; MacLennan, Jenny M.; Molyneux, Elizabeth M.; Graham, Stephen M.; Drayson, Mark T.; Molyneux, Malcolm E.

    2016-01-01

    Nontyphoidal Salmonella is a leading cause of sepsis in African children. Cytokine responses are central to the pathophysiology of sepsis and predict sepsis outcome in other settings. In this study, we investigated cytokine responses to invasive nontyphoidal Salmonella (iNTS) disease in Malawian children. We determined serum concentrations of 48 cytokines with multiplexed immunoassays in Malawian children during acute iNTS disease (n = 111) and in convalescence (n = 77). Principal component analysis and logistic regression were used to identify cytokine signatures of acute iNTS disease. We further investigated whether these responses are altered by HIV coinfection or severe malnutrition and whether cytokine responses predict inpatient mortality. Cytokine changes in acute iNTS disease were associated with two distinct cytokine signatures. The first is characterized by increased concentrations of mediators known to be associated with macrophage function, and the second is characterized by raised pro- and anti-inflammatory cytokines typical of responses reported in sepsis secondary to diverse pathogens. These cytokine responses were largely unaltered by either severe malnutrition or HIV coinfection. Children with fatal disease had a distinctive cytokine profile, characterized by raised mediators known to be associated with neutrophil function. In conclusion, cytokine responses to acute iNTS infection in Malawian children are reflective of both the cytokine storm typical of sepsis secondary to diverse pathogens and the intramacrophage replicative niche of NTS. The cytokine profile predictive of fatal disease supports a key role of neutrophils in the pathogenesis of NTS sepsis. PMID:27170644

  19. Pneumococcal components induce regulatory T cells that attenuate the development of allergic airways disease by deviating and suppressing the immune response to allergen.

    PubMed

    Thorburn, Alison N; Brown, Alexandra C; Nair, Prema M; Chevalier, Nina; Foster, Paul S; Gibson, Peter G; Hansbro, Philip M

    2013-10-15

    The induction of regulatory T cells (Tregs) to suppress aberrant inflammation and immunity has potential as a therapeutic strategy for asthma. Recently, we identified key immunoregulatory components of Streptococcus pneumoniae, type 3 polysaccharide and pneumolysoid (T+P), which suppress allergic airways disease (AAD) in mouse models of asthma. To elucidate the mechanisms of suppression, we have now performed a thorough examination of the role of Tregs. BALB/c mice were sensitized to OVA (day 0) i.p. and challenged intranasal (12-15 d later) to induce AAD. T+P was administered intratracheally at the time of sensitization in three doses (0, 12, and 24 h). T+P treatment induced an early (36 h-4 d) expansion of Tregs in the mediastinal lymph nodes, and later (12-16 d) increases in these cells in the lungs, compared with untreated allergic controls. Anti-CD25 treatment showed that Treg-priming events involving CD25, CCR7, IL-2, and TGF-β were required for the suppression of AAD. During AAD, T+P-induced Tregs in the lungs displayed a highly suppressive phenotype and had an increased functional capacity. T+P also blocked the induction of IL-6 to prevent the Th17 response, attenuated the expression of the costimulatory molecule CD86 on myeloid dendritic cells (DCs), and reduced the number of DCs carrying OVA in the lung and mediastinal lymph nodes. Therefore, bacterial components (T+P) drive the differentiation of highly suppressive Tregs, which suppress the Th2 response, prevent the Th17 response and disable the DC response resulting in the effective suppression of AAD. PMID:24048894

  20. Impact of the Hajj on pneumococcal transmission.

    PubMed

    Memish, Z A; Assiri, A; Almasri, M; Alhakeem, R F; Turkestani, A; Al Rabeeah, A A; Akkad, N; Yezli, S; Klugman, K P; O'Brien, K L; van der Linden, M; Gessner, B D

    2015-01-01

    Over two million Muslim pilgrims assemble annually in Mecca and Medina, Saudi Arabia, to complete the Hajj. The large number of people in a crowded environment increases the potential for pneumococcal carriage amplification. We evaluated pneumococcal carriage prevalence with four cross-sectional studies conducted at beginning-Hajj (Mecca) and end-Hajj (Mina) during 2011 and 2012. A questionnaire was administered and a nasopharyngeal swab was collected. The swab was tested for pneumococcus, serotype and antibiotic resistance. A total of 3203 subjects (1590 at beginning-Hajj and 1613 at end-Hajj) originating from 18 countries in Africa or Asia were enrolled. The overall pneumococcal carriage prevalence was 6.0%. There was an increase in carriage between beginning-Hajj and end-Hajj cohorts for: overall carriage (4.4% versus 7.5%, prevalence ratio (PR) 1.7, 95% CI 1.3-2.3), and carriage of 23-valent pneumococcal polysaccharide vaccine serotypes (2.3% versus 4.1%, PR 1.8, 95% CI 1.2-2.7), 13-valent pneumococcal conjugate vaccine (PCV) serotypes (1.1% versus 3.6%, PR 3.2, 95% CI 1.9-5.6), 10-valent PCV serotypes (0.6% versus 1.6%, PR 2.6, 95% CI 1.2-5.3), antibiotic non-susceptible isolates (2.5% versus 6.1%, PR 2.5, 95% CI 1.7-3.6) and multiple non-susceptible isolates (0.6% versus 2.2%, PR 3.8, 95% CI 1.8-7.9). Fifty-two different serotypes were identified, most commonly serotypes 3 (17%), 19F (5%) and 34 (5%). These results suggest that the Hajj may increase pneumococcal carriage-particularly conjugate vaccine serotypes and antibiotic non-susceptible strains, although the exact mechanism remains unknown. The Hajj may therefore provide a mechanism for the global distribution of pneumococci. PMID:25636939

  1. Factors Predicting and Reducing Mortality in Patients with Invasive Staphylococcus aureus Disease in a Developing Country

    PubMed Central

    Nickerson, Emma K.; Wuthiekanun, Vanaporn; Wongsuvan, Gumphol; Limmathurosakul, Direk; Srisamang, Pramot; Mahavanakul, Weera; Thaipadungpanit, Janjira; Shah, Krupal R.; Arayawichanont, Arkhom; Amornchai, Premjit; Thanwisai, Aunchalee; Day, Nicholas P.; Peacock, Sharon J.

    2009-01-01

    Background Invasive Staphylococcus aureus infection is increasingly recognised as an important cause of serious sepsis across the developing world, with mortality rates higher than those in the developed world. The factors determining mortality in developing countries have not been identified. Methods A prospective, observational study of invasive S. aureus disease was conducted at a provincial hospital in northeast Thailand over a 1-year period. All-cause and S. aureus-attributable mortality rates were determined, and the relationship was assessed between death and patient characteristics, clinical presentations, antibiotic therapy and resistance, drainage of pus and carriage of genes encoding Panton-Valentine Leukocidin (PVL). Principal Findings A total of 270 patients with invasive S. aureus infection were recruited. The range of clinical manifestations was broad and comparable to that described in developed countries. All-cause and S. aureus-attributable mortality rates were 26% and 20%, respectively. Early antibiotic therapy and drainage of pus were associated with a survival advantage (both p<0.001) on univariate analysis. Patients infected by a PVL gene-positive isolate (122/248 tested, 49%) had a strong survival advantage compared with patients infected by a PVL gene-negative isolate (all-cause mortality 11% versus 39% respectively, p<0.001). Multiple logistic regression analysis using all variables significant on univariate analysis revealed that age, underlying cardiac disease and respiratory infection were risk factors for all-cause and S. aureus-attributable mortality, while one or more abscesses as the presenting clinical feature and procedures for infectious source control were associated with survival. Conclusions Drainage of pus and timely antibiotic therapy are key to the successful management of S. aureus infection in the developing world. Defining the presence of genes encoding PVL provides no practical bedside information and draws attention

  2. Cortical plasticity in patients with Parkinson's disease a window for therapeutic non-invasive neuromodulation.

    PubMed

    Quartarone, Angelo; Rizzo, Vincenzo; Terranova, Carmen; Bruschetta, Daniele; Milardi, Demetrio; Girlanda, Paolo; Ghilardi, Maria Felice

    2014-12-01

    Several evidences in animal models have consistently an alteration of cortico-striatal plasticity, which is related to the degeneration of the substantia nigra. An alteration of plasticity have also been reported in humans by recording evoked field potentials in the substantia nigra pars reticulata of PD patients undergoing subthalamic nucleus (STN) stimulation where high-frequency (HF) in the OFF state did not induce a lasting change in field potential amplitude in the substantia nigra. In addition protocols of non-invasive brain stimulation, such as paired associative stimulation (PAS) and theta-burst stimulation (TBS), can be used to investigate cortical plasticity of the human primary motor cortex. Despite data reported in literature are apparently controversial with some studies showing a reduced or increased or even normal LTP and LTD like plasticity, recent evidences suggest the hypothesis that these different pat- terns of cortical plasticity likely depend on the stage of the disease and on the concomitant administration of L-DOPA. The current review will provide an up-to-date of these issues on cortical plasticity in PD discussing the clinical implications in rehabilitation. In addition in the last section we will review the state of art of non invasive neuro- modulation as adjuvant treatment in the advanced stage of the disease. PMID:25987183

  3. Comparing Supervised Exercise Therapy to Invasive Measures in the Management of Symptomatic Peripheral Arterial Disease

    PubMed Central

    Aherne, Thomas; McHugh, Seamus; Kheirelseid, Elrasheid A.; Lee, Michael J.; McCaffrey, Noel; Moneley, Daragh; Leahy, Austin L.; Naughton, Peter

    2015-01-01

    Peripheral arterial disease (PAD) is associated with considerable morbidity and mortality. Consensus rightly demands the incorporation of supervised exercise training (SET) into PAD treatment protocols. However, the exact role of SET particularly its relationship with intervention requires further clarification. While supervised exercise is undoubtedly an excellent tool in the conservative management of mild PAD its use in more advanced disease as an adjunct to open or endovascular intervention is not clearly defined. Indeed its use in isolation in this cohort is incompletely reported. The aim of this review is to clarify the exact role of SET in the management of symptomatic PAD and in particular to assess its role in comparison with or as an adjunct to invasive intervention. A systematic literature search revealed a total 11 randomised studies inclusive of 969 patients. All studies compared SET and intervention with monotherapy. Study results suggest that exercise is a complication-free treatment. Furthermore, it appears to offer significant improvements in patients walk distances with a combination of both SET and intervention offering a superior walking outcome to monotherapy in those requiring invasive measures. PMID:26601122

  4. 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. PMID:26677751

  5. Effectiveness of 23-valent pneumococcal polysaccharide vaccine in adults aged 60 years and over in the Region of Madrid, Spain, 2008-2011.

    PubMed

    Gutierrez Rodriguez, M A; Ordobas Gavin, M A; Garcia-Comas, L; Sanz Moreno, J C; Cordoba Deorador, E; Lasheras Carbajo, M D; Taveira Jimenez, J A; Martin Martinez, F; Iniesta Fornies, D; Arce Arnaez, A

    2014-01-01

    Invasive pneumococcal disease (IPD) is a notifiable disease in the Region of Madrid. The 23-valent pneumococcal polysaccharide vaccine (PPV23) is recommended for children and adults aged two years or over with a high risk of disease, and for all adults aged 60 and over. We describe the evolution of IPD incidence from 2008 to 2011 in people aged 60 years and over and PPV23 vaccine effectiveness (VE). VE is estimated using both the screening method and indirect cohort method. The incidence of IPD varied from 20.0 in 2008 to 15.2 per 100,000 inhabitants in 2011 (RR: 0.8; 95% CI: 0.6–0.9). Adjusted VE estimated with the screening method was 68.2% (95% CI: 56.2–76.9). VE with the Broome method was 44.5% (95% CI: 23.8–59.6) for all PPV23 serotypes, and 64.4% (95% CI: 45.2–76.8) for PPV23 serotypes not included in conjugate vaccines. VE was lower in patients aged 80 years and older (25.5%; 95% CI:-23.2 to 55.0) and those with highrisk medical conditions (31.7%; 95% CI: -2.2 to -54.4). Adjusted VE was 44.5% (95% CI: 19.4-61.8) within 5 years of vaccination and 32.5% (95% CI: -5.6 to 56.9) after 5 years. These results are compatible with current recommendations for PPV23. PMID:25323079

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

    PubMed Central

    Hollingshead, Susan K.; Briles, David E.; Yamanaka, Noboru

    2011-01-01

    Pathogen-specific antibody plays an important role in protection against pneumococcal carriage and infections. However, neonates and infants exhibit impaired innate and adaptive immune responses, which result in their high susceptibility to pneumococci. To protect neonates and infants against pneumococcal infection it is important to elicit specific protective immune responses at very young ages. In this study, we investigated the protective immunity against pneumococcal carriage, pneumonia, and sepsis induced by maternal immunization with pneumococcal surface protein A (PspA). Mother mice were intranasally immunized with recombinant PspA (rPspA) and cholera toxin B subunit (CTB) prior to being mated. Anti-PspA specific IgG, predominantly IgG1, was present at a high level in the serum and milk of immunized mothers and in the sera of their pups. The pneumococcal densities in washed nasal tissues and in lung homogenate were significantly reduced in pups delivered from and/or breast-fed by PspA-immunized mothers. Survival after fatal systemic infections with various types of pneumococci was significantly extended in the pups, which had received anti-PspA antibody via the placenta or through their milk. The current findings strongly suggest that maternal immunization with PspA is an attractive strategy against pneumococcal infections during early childhood. (191 words) PMID:22073127

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

    PubMed

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

    2011-01-01

    Pathogen-specific antibody plays an important role in protection against pneumococcal carriage and infections. However, neonates and infants exhibit impaired innate and adaptive immune responses, which result in their high susceptibility to pneumococci. To protect neonates and infants against pneumococcal infection it is important to elicit specific protective immune responses at very young ages. In this study, we investigated the protective immunity against pneumococcal carriage, pneumonia, and sepsis induced by maternal immunization with pneumococcal surface protein A (PspA). Mother mice were intranasally immunized with recombinant PspA (rPspA) and cholera toxin B subunit (CTB) prior to being mated. Anti-PspA specific IgG, predominantly IgG1, was present at a high level in the serum and milk of immunized mothers and in the sera of their pups. The pneumococcal densities in washed nasal tissues and in lung homogenate were significantly reduced in pups delivered from and/or breast-fed by PspA-immunized mothers. Survival after fatal systemic infections with various types of pneumococci was significantly extended in the pups, which had received anti-PspA antibody via the placenta or through their milk. The current findings strongly suggest that maternal immunization with PspA is an attractive strategy against pneumococcal infections during early childhood. PMID:22073127

  8. 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 ...

  9. Pneumococcal phosphoglycerate kinase interacts with plasminogen and its tissue activator.

    PubMed

    Fulde, M; Bernardo-García, N; Rohde, M; Nachtigall, N; Frank, R; Preissner, K T; Klett, J; Morreale, A; Chhatwal, G S; Hermoso, J A; Bergmann, S

    2014-03-01

    Streptococcus pneumoniae is not only a commensal of the nasopharyngeal epithelium, but may also cause life-threatening diseases. Immune-electron microscopy studies revealed that the bacterial glycolytic enzyme, phosphoglycerate kinase (PGK), is localised on the pneumococcal surface of both capsulated and non-capsulated strains and colocalises with plasminogen. Since pneumococci may concentrate host plasminogen (PLG) together with its activators on the bacterial cell surface to facilitate the formation of plasmin, the involvement of PGK in this process was studied. Specific binding of human or murine PLG to strain-independent PGK was documented, and surface plasmon resonance analyses indicated a high affinity interaction with the kringle domains 1-4 of PLG. Crystal structure determination of pneumococcal PGK together with peptide array analysis revealed localisation of PLG-binding site in the N-terminal region and provided structural motifs for the interaction with PLG. Based on structural analysis data, a potential interaction of PGK with tissue plasminogen activator (tPA) was proposed and experimentally confirmed by binding studies, plasmin activity assays and thrombus degradation analyses. PMID:24196407

  10. Collective migration models: Dynamic monitoring of leader cells in migratory/invasive disease processes

    NASA Astrophysics Data System (ADS)

    Dean, Zachary Steven

    Leader cells are a fundamental biological process that have only been investigated since the early 2000s. These cells have often been observed emerging at the edge of an artificial wound in 2D epithelial cell collective invasion, created with either a mechanical scrape from a pipette tip or from the removal of a plastic, physical blocker. During migration, the moving cells maintain cell-cell contacts, an important quality of collective migration; the leader cells originate from either the first or the second row, they increase in size compared to other cells, and they establish ruffled lamellipodia. Recent studies in 3D have also shown that cells emerging from an invading collective group that also exhibit leader-like properties. Exactly how leader cells influence and interact with follower cells as well as other cells types during collective migration, however, is another matter, and is a subject of intense investigation between many different labs and researchers. The majority of leader cell research to date has involved epithelial cells, but as collective migration is implicated in many different pathogenic diseases, such as cancer and wound healing, a better understanding of leader cells in many cell types and environments will allow significant improvement to therapies and treatments for a wide variety of disease processes. In fact, more recent studies on collective migration and invasion have broadened the field to include other cell types, including mesenchymal cancer cells and fibroblasts. However, the proper technology for picking out dynamic, single cells within a moving and changing cell population over time has severely limited previous investigation into leader cell formation and influence over other cells. In line with these previous studies, we not only bring new technology capable of dynamically monitoring leader cell formation, but we propose that leader cell behavior is more than just an epithelial process, and that it is a critical physiological

  11. 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

  12. γδ Intraepithelial Lymphocyte Migration Limits Transepithelial Pathogen Invasion and Systemic Disease in Mice

    PubMed Central

    Edelblum, Karen L.; Singh, Gurminder; Odenwald, Matthew A.; Lingaraju, Amulya; El Bissati, Kamal; McLeod, Rima; Sperling, Anne I.; Turner, Jerrold R.

    2015-01-01

    Background & Aims Intraepithelial lymphocytes that express the γδ T cell receptor (γδ IELs) limit pathogen translocation across the intestinal epithelium by unknown mechanisms. We investigated whether γδ IEL migration and interaction with epithelial cells promote mucosal barrier maintenance during enteric infection. Methods Salmonella typhimurium or Toxoplasma gondii were administered to γδ T cell-deficient (Tcrd KO), CD103-deficient (CD103 KO), or control TcrdEGFP C57BL/6 reporter mice. Intravital microscopy was used to visualize migration of GFP-tagged γδ T cells within the small intestinal mucosa of mice infected with DsRed-labeled S typhimurium. Mixed bone marrow chimeras were generated to assess the effects of γδ IEL migration on early pathogen invasion and chronic systemic infection. Results Morphometric analyses of intravital video microscopy data showed that γδ IELs rapidly localized to and remained near epithelial cells in direct contact with bacteria. Within 1 hr, greater numbers of T gondii or S typhimurium were present within mucosae of mice with migration-defective occludin KO γδ T cells, compared with controls. Pathogen invasion in Tcrd KO mice was quantitatively similar to that in mice with occludin-deficient γδ T cells, whereas invasion in CD103 KO mice, which have increased migration of γδ T cells into the lateral intercellular space, was reduced by 63%. Consistent with a role of γδ T cell migration in early host defense, systemic salmonellosis developed more rapidly and with greater severity in mice with occludin-deficient γδ IELs, relative to those with wild-type or CD103 KO γδ IELs. Conclusions In mice, intraepithelial migration to epithelial cells in contact with pathogens is essential to γδ IEL surveillance and immediate host defense. γδ IEL occludin is required for early surveillance that limits systemic disease. PMID:25747597

  13. Epidemiology of serogroup B invasive meningococcal disease in Ontario, Canada, 2000 to 2010

    PubMed Central

    2012-01-01

    Background Invasive meningococcal disease (IMD) caused by serogroup B is the last major serogroup in Canada to become vaccine-preventable. The anticipated availability of vaccines targeting this serogroup prompted an assessment of the epidemiology of serogroup B disease in Ontario, Canada. Methods We retrieved information on confirmed IMD cases reported to Ontario’s reportable disease database between January 1, 2000 and December 31, 2010 and probabilistically-linked these cases to Public Health Ontario Laboratory records. Rates were calculated with denominator data obtained from Statistics Canada. We calculated a crude number needed to vaccinate using the inverse of the infant (<1 year) age-specific incidence multiplied by expected vaccine efficacies between 70% and 80%, and assuming only direct protection (no herd effects). Results A total of 259 serogroup B IMD cases were identified in Ontario over the 11-year period. Serogroup B was the most common cause of IMD. Incidence ranged from 0.11 to 0.27/100,000/year, and fluctuated over time. Cases ranged in age from 13 days to 101 years; 21.4% occurred in infants, of which 72.7% were <6 months. Infants had the highest incidence (3.70/100,000). Case-fatality ratio was 10.7% overall. If we assume that all infant cases would be preventable by vaccination, we would need to vaccinate between 33,784 and 38,610 infants to prevent one case of disease. Conclusions Although rare, the proportion of IMD caused by serogroup B has increased and currently causes most IMD in Ontario, with infants having the highest risk of disease. Although serogroup B meningococcal vaccines are highly anticipated, our findings suggest that decisions regarding publicly funding serogroup B meningococcal vaccines will be difficult and may not be based on disease burden alone. PMID:22928839

  14. Minimally invasive treatment of pilonidal disease: crystallized phenol and laser depilation.

    PubMed

    Girgin, Mustafa; Kanat, Burhan Hakan; Ayten, Refik; Cetinkaya, Ziya; Kanat, Zekiye; Bozdağ, Ahmet; Turkoglu, Ahmet; Ilhan, Yavuz Selim

    2012-01-01

    Pilonidal disease has been treated surgically and by various other methods for many years. The most important problem associated with such treatment is recurrence, but cosmetic outcome is another important issue that cannot be ignored. Today, crystallized phenol is recognized as a treatment option associated with good medical and cosmetic outcomes. We hypothesized that the addition of laser depilation to crystallized phenol treatment of pilonidal disease might increase the rate of success, and this study aimed to determine if the hypothesis was true. Patients who were treated with crystallized phenol and 755-nm alexandrite laser depilation were retrospectively analyzed. In total, 42 (31 male and 11 female) patients were treated with crystallized phenol and alexandrite laser depilation and were followed up between January 2009 and January 2012. In all, 38 patients (90.5%) had chronic disease and 4 (9.5%) had recurrent disease. Among the patients, 26 (61.9%) recovered following 1 crystallized phenol treatment, and the remaining patients had complete remission following repeated treatment. Some patients needed multiple treatments, even up to 8 times. None of the patients had a recurrence during a mean 24 months (range, 6-30 months) of follow-up. Whatever method of treatment is used for pilonidal disease, hair cleaning positively affects treatment outcome. The present results support the hypothesis that the addition of laser depilation (which provides more permanent and effective depilation than other methods) to crystallized phenol treatment (a non-radical, minimally invasive method associated with very good cosmetic results) can increase the effectiveness of the treatment and also reduce the recurrence rate of the disease. PMID:23294066

  15. 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

  16. 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. PMID:24062235

  17. Safety, tolerability, and immunologic noninferiority of a 13-valent pneumococcal conjugate vaccine compared to a 7-valent pneumococcal conjugate vaccine given with routine pediatric vaccinations in Germany.

    PubMed

    Kieninger, Dorothee M; Kueper, Kathrin; Steul, Katrin; Juergens, Christine; Ahlers, Norbert; Baker, Sherryl; Jansen, Kathrin U; Devlin, Carmel; Gruber, William C; Emini, Emilio A; Scott, Daniel A

    2010-06-01

    13-valent pneumococcal conjugate vaccine (PCV13) was compared to PCV7 in infants administered 4 doses. For the 7 common serotypes, PCV13- and PCV7-elicited responses showed comparable percent responders achieving 0.35mug/mL IgG threshold (exception 6B, 77.5% versus 87.1%, respectively) and OPA titers of 1:8; IgGs were lower than PCV7 but functional responses were generally comparable. For the 6 additional serotypes, PCV13-elicited IgG and functional OPA responses were notably greater than PCV7. The toddler dose boosted immune responses. Vaccines were comparable with regard to safety. PCV13 should be as effective as PCV7 in preventing pneumococcal disease caused by the common serotypes and may provide protection against the additional serotypes. PMID:20417262

  18. Understanding Host-Adherent-Invasive Escherichia coli Interaction in Crohn's Disease: Opening Up New Therapeutic Strategies

    PubMed Central

    Massier, Sébastien; Darfeuille-Michaud, Arlette; Billard, Elisabeth; Barnich, Nicolas

    2014-01-01

    A trillion of microorganisms colonize the mammalian intestine. Most of them have coevolved with the host in a symbiotic relationship and some of them have developed strategies to promote their replication in the presence of competing microbiota. Recent evidence suggests that perturbation of the microbial community favors the emergence of opportunistic pathogens, in particular adherent-invasive Escherichia coli (AIEC) that can increase incidence and severity of gut inflammation in the context of Crohn's disease (CD). This review will report the importance of AIEC as triggers of intestinal inflammation, focusing on their impact on epithelial barrier function and stimulation of mucosal inflammation. Beyond manipulation of immune response, restoration of gut microbiota as a new treatment option for CD patients will be discussed. PMID:25580435

  19. 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. PMID:18975486

  20. Update on Pharmaceutical and Minimally Invasive Management Strategies for Chronic Obstructive Pulmonary Disease

    PubMed Central

    Rafii, Rokhsara; Albertson, Timothy E.; Louie, Samuel; Chan, Andrew L.

    2011-01-01

    Chronic obstructive pulmonary disease (COPD) is a debilitating pulmonary disorder with systemic effects, and it is the fourth leading cause of death in the United States. COPD patients not only develop respiratory limitations, but can also demonstrate systemic wasting, features of depression, and can succumb to social isolation. Smoking cessation is crucial, and pharmacotherapy with bronchodilators is helpful in symptom management. Inhaled corticosteroids may be beneficial in some patients. In addition, pulmonary rehabilitation and palliative care are important components under the right clinical circumstance. This review highlights current guidelines and management strategies for COPD and emphasizes novel pharmacotherapy and minimally invasive (nonsurgical) lung-volume reduction interventions that may prove to be of significant benefit in the future. PMID:21660228

  1. Breakthrough invasive fungal diseases during echinocandin treatment in high-risk hospitalized hematologic patients.

    PubMed

    Chan, Thomas S Y; Gill, Harinder; Hwang, Yu-Yan; Sim, Joycelyn; Tse, Alan C T; Loong, Florence; Khong, Pek-Lan; Tse, Eric; Leung, Anskar Y H; Chim, Chor-Sang; Lie, Albert K W; Kwong, Yok-Lam

    2014-03-01

    The frequency of breakthrough invasive fungal diseases (IFDs) during echinocandin therapy is unclear. We retrospectively analyzed 534 hematologic patients treated with echinocandin (caspofungin, N = 55; micafungin, N = 306; anidulafungin, N = 173). Four proven IFDs were found, caused by Candida parapsilosis (N = 2), C. parapsilosis and Candida glabrata (N = 1), and Fusarium species (N = 1). Four cases of possible IFDs were observed, all showing pulmonary infection. One case showed features suggestive of hepatosplenic candidiasis. Six of these eight cases had previously received the purine analog clofarabine. Breakthrough IFD during echinocandin treatment occurred infrequently (1.5 %), caused predominantly by Candida species. Clofarabine usage was an important risk factor. PMID:23949318

  2. 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.

  3. Non-invasive methods for the diagnosis of nonalcoholic fatty liver disease

    PubMed Central

    Papagianni, Marianthi; Sofogianni, Areti; Tziomalos, Konstantinos

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) is the commonest chronic liver disease and includes simple steatosis and nonalcoholic steatohepatitis (NASH). Since NASH progresses to cirrhosis more frequently and increases liver-related and cardiovascular disease risk substantially more than simple steatosis, there is a great need to differentiate the two entities. Liver biopsy is the gold standard for the diagnosis of NAFLD but its disadvantages, including the risk of complications and sampling bias, stress the need for developing alternative diagnostic methods. Accordingly, several non-invasive markers have been evaluated for the diagnosis of simple steatosis and NASH, including both serological indices and imaging methods. The present review summarizes the current knowledge on the role of these markers in the diagnosis of NAFLD. Current data suggest that ultrasound and the fibrosis-4 score are probably the most appealing methods for detecting steatosis and for distinguishing NASH from simple steatosis, respectively, because of their low cost and relatively high accuracy. However, currently available methods, both serologic and imaging, cannot obviate the need for liver biopsy for diagnosing NASH due to their substantial false positive and false negative rates. Therefore, the current role of these methods is probably limited in patients who are unwilling or have contraindications for undergoing biopsy. PMID:25866601

  4. Phylogenetic Analysis of Invasive Serotype 1 Pneumococcus in South Africa, 1989 to 2013.

    PubMed

    du Plessis, Mignon; 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

    2016-05-01

    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

  5. 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

  6. 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

  7. 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...

  8. 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

  9. Recurrent Staphylococcus aureus abscess and fatal pneumococcal septicemia due to IRAK-4 deficiency.

    PubMed

    Shichijo, Koichi; Ogose, Takeshi; Kubota, Mari; Tomimoto, Ayumi; Kondo, Rieko; Taniguchi, Takako; Takahashi, Akiyoshi; Nakatsu, Tadanori; Urano, Yoshio; Watanabe, Tsutomu

    2015-12-01

    We describe the case of an infant with recurrent episodes of staphylococcal skin abscess and subsequent lethal pneumococcal meningitis/septicemia due to interleukin-1 receptor-associated kinase 4 (IRAK-4) deficiency. In this case, systemic signs of inflammatory response were poor and delayed. Among all other reported cases of IRAK-4 deficiency, none involved severe viral or fungal disease, and the range of infecting bacteria was narrow. PMID:26711917

  10. [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. PMID:27450526

  11. 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. PMID:21942868

  12. Invasive and Noninvasive Streptococcus pneumoniae Capsule and Surface Protein Diversity following the Use of a Conjugate Vaccine

    PubMed Central

    Croney, Christina M.; Nahm, Moon H.; Juhn, Steven K.; Briles, David E.

    2013-01-01

    The 13-valent pneumococcal conjugate vaccine (PCV13) was introduced in the United States in 2010 for the prevention of invasive pneumococcal disease (IPD) and otitis media. While many studies have reported its potential efficacy for IPD, not much is known about the epidemiology of noninvasive disease following its introduction. We characterized the capsular types and surface protein genes of noninvasive pediatric pneumococcal isolates collected between 2002 and 2010 (n = 1,058) at Children's of Alabama following the introduction of PCV7 and tested a subset of noninvasive and previously characterized IPD isolates for the presence of the pspA, pspC, and rrgC genes, which encode protection-eliciting proteins. PCV7 serotypes had dramatically decreased by 2010 (P < 0.0001), and only 50% of all noninvasive infections were caused by the PCV13 capsular serotypes. Serotype 19A accounted for 32% of the noninvasive isolates, followed by serotypes 35B (9%), 19F (7%), and 6C (6%). After 7 years of PCV7 usage, there were no changes in the frequencies of the pspA or pspC genes; 96% of the strains were positive for family 1 or 2 pspA genes, and 81% were also positive for pspC. Unexpectedly, more noninvasive than invasive strains were positive for rrgC (P < 0.0001), and the proportion of rrgC-positive strains in 2008 to 2010 was greater than that in 2002 to 2008 (IPD, P < 0.02; noninvasive, P < 0.001). Serotypes 19F, 19A, and 35B were more frequently rrgC positive (P < 0.005) than other serotypes. A vaccine containing antigens, such as PspA, PspC, and/or RrgC, can provide coverage against most non-PCV13-type pneumococci. Continued surveillance is critical for optimal future vaccine development. PMID:24006139

  13. 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

  14. Incidence of Pneumococcal Pneumonia Among Adults in Rural Thailand, 2006-2011: Implications for Pneumococcal Vaccine Considerations.

    PubMed

    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

    2015-12-01

    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

  15. IRAK-4 deficiency as a cause for familial fatal invasive infection by Streptococcus pneumoniae.

    PubMed

    Grazioli, Serge; Hamilton, Sara J; McKinnon, Margaret L; Del Bel, Kate L; Hoang, Linda; Cook, Victoria E; Hildebrand, Kyla J; Junker, Anne K; Turvey, Stuart E

    2016-02-01

    In this Letter to the Editor we report the case of two siblings with fatal pneumococcal meningitis as the initial manifestation of IRAK-4 deficiency caused by previously undescribed mutations in IRAK4. The letter also highlights the importance of invasive pneumococcal infection as a critical 'red flag' warning of the potential for an underlying primary immunodeficiency and identifies some of the challenges in making the clinical diagnosis of IRAK-4 deficiency. PMID:26698383

  16. Mucosal immunization with PsaA protein, using chitosan as a delivery system, increases protection against acute otitis media and invasive infection by Streptococcus pneumoniae.

    PubMed

    Xu, J-H; Dai, W-J; Chen, B; Fan, X-Y

    2015-03-01

    As infection with Streptococcus pneumoniae (mainly via the mucosal route) is a leading cause of acute otitis media, sinus and bacterial pneumonia, the mucosal immunity plays an important role in the prevention of pneumococcal diseases. Therefore, intranasal vaccination may be an effective immunization strategy, but requires appropriate mucosal vaccine delivery systems. In this work, chitosan was used as a mucosal delivery system to form chitosan-PsaA nanoparticles based on ionotropic gelation methods and used to immunize BALB/c mice intranasally. Compared to mice immunized with naked PsaA, levels of IFN-γ, IL-17A and IL-4 in spleen lymphocytes, the systemic (IgG in serum) and mucosal (IgA in mucosal lavage) specific antibodies were enhanced significantly in mice inoculated with chitosan-PsaA. Furthermore, increased protection against acute otitis media following middle ear challenge with pneumococcus serotype 14, and improved survival following intraperitoneal challenge with pneumococcus serotype 3 or serotype 14, was found in the mice immunized with chitosan-PsaA nanoparticles. Thus, intranasal immunization with chitosan-PsaA can successfully induce mucosal and systemic immune responses and increase protection against pneumococcal acute otitis media and invasive infections. Hence, intranasal immunization with PsaA protein, based on chitosan as a delivery system, is an efficient immunization strategy for preventing pneumococcal infections. PMID:25565478

  17. Pneumococcal conjugate vaccine use in adults.

    PubMed

    Isturiz, Raul E; Schmoele-Thoma, Beate; Scott, Daniel A; Jodar, Luis; Webber, Chris; Sings, Heather L; Paradiso, Peter

    2016-03-01

    Streptococcus pneumoniae is a leading cause of illness and death in adults. A polysaccharide vaccine has been available for over 30 years, but despite significant use, the public health impact of this vaccine has been limited. The 13-valent pneumococcal conjugate vaccine (PCV13) has been licensed by the US Food and Drug Administration and other international regulatory authorities with the assumption that induction of a T cell-dependent immune response and noninferior immunogenicity to vaccine antigens when compared with the polysaccharide vaccine would be important to satisfy a significant unmet medical need. PCV13 efficacy against vaccine-type pneumococcal community-acquired pneumonia was confirmed in a large randomized controlled trial in older adults and its use is now increasingly recommended globally. PMID:26651847

  18. 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

    2014-01-01

    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. PMID:24401677

  19. Overwhelming pneumococcal infection in a hyposplenic adult.

    PubMed Central

    Hatch, J. P.; Sibbald, W. J.; Austin, T. W.

    1983-01-01

    In a woman with an atrophic, apparently nonfunctioning spleen pneumococcal septicemia led to death within 72 hours of admission. As in five previously described adults, the patient's presentation and subsequent clinical course were identical to those of the syndrome of overwhelming postsplenectomy infection, except that there was no history of splenectomy. Patients without spleens may be given penicillin prophylaxis for an indefinite period, vaccinated against pneumococci or both. PMID:6616391

  20. Cost-effectiveness analysis of pneumococcal polysaccharide vaccination from age 60 in São Paulo State, Brazil