Benfield, Thomas; Skovgaard, Marlene; Schønheyder, Henrik Carl;
There is limited knowledge of serotypes that cause non-bacteremic pneumococcal pneumonia (NBP). Here we report serotypes, their associated disease potential and coverage of pneumococcal conjugate vaccines (PCV) in adults with NBP and compare these to bacteremic pneumonia (BP)....
MANNES, GPM; BOERSMA, WG; BAUR, CHJM; POSTMUS, PE
We describe a patient, who had no pre-existing disease, with bacteraemic pneumococcal pneumonia and adult respiratory distress syndrome (ARDS), a rare complication. In spite of the use of antibiotics and intensive treatment the mortality rate of this kind of infection remains high. Streptococcus pne
J. H. Gentile; M. D. Sparo; M. E. Mercapide; C. M. Luna
Our objective was to describe incidence, clinical, radiographic and microbiological features of bacteremic pneumococcal pneumonia (BPP) in our environment. A total of 101 patients (7 were treated as outpatients), older than 18 years of age suffering BPP were prospectively evaluated. The incidence was 2.8 cases per 1000 admissions, 50 were males, mean age was 59.9 years (19-97), mortality was 11.8%. Eighty three percent of fatalities occurred within 3 days of admission. Mortality rate increase...
IrohTam, Pui-Ying; Hanisch, Benjamin R.; Forward, Brennan
We report a case of bacteremic pneumococcal pneumonia due to serotype 19A in a child who had received four doses of the 13-valent pneumococcal conjugate vaccine, and review the literature on effectiveness of this vaccine. Pediatricians should be alert to the fact that up-to-date immunization status with pneumococcal vaccine does not preclude illness from invasive disease caused by a vaccine serotype.
Maria Regina Alves Cardoso
Full Text Available We compared bacteremic pneumococcal pneumonia (BPP and pneumococcal empyema (PE, in terms of clinical, radiological, and laboratory findings, in under-fives. A cross-sectional nested cohort study, involving under-fives (102 with PE and 128 with BPP, was conducted at 12 centers in Argentina, Brazil, and the Dominican Republic. Among those with PE, mean age was higher; disease duration was longer; and tachypnea, dyspnea, and high leukocyte counts were more common. Among those with BPP, fever and lethargy were more common. It seems that children with PE can be distinguished from those with BPP on the basis of clinical and laboratory findings. Because both conditions are associated with high rates of morbidity and mortality, prompt diagnosis is crucial.
Full Text Available AIMS: Bacteremic pneumococcal pneumonia (BPP is a severe condition. To evaluate seasonal distribution, mortality, serotype frequencies, antimicrobial susceptibility, and different severity scores among patients with BPP. PATIENTS AND METHODS: Patients were identified by laboratory data and restricted to adulthood. Standard methods were used for serotyping and antimicrobial susceptibility. Risk factors were analyzed by univariate and multivariate methods. Severity scores (APACHE II, CURB-65 and CAP PIRO were compared using ROC curves. RESULTS: Sixty events of community-acquired BPP occurred between 2005 and 2010. A seasonal pattern was detected. Mean age was 72.1 years old (81.4% >60 years. All had a predisposing factor. Previous influenza (3.3% or pneumococcal immunization (1.7% was infrequent. Admission to critical units was required by 51.7%. Twenty-two serotypes were identified among 59 strains. Only one strain had intermediate resistance to penicillin (1.7%. In-hospital mortality reached 33.3%. Multivariate analysis identified a CAP PIRO score>3 (OR 29.7; IC95 4.7-187, age >65 years (OR 42.1; IC95 2.2-796, and a platelet count<100,000/μL (OR 10.9; IC95 1.2-96 as significant independent factors associated with death. ROC curve analysis did not reveal statistical differences between the three severity scores to predict death (AUC 0.77-0.90. The prognostic yield for all of them was limited (Positive Likelihood Ratio: 1.5-3.8. CONCLUSIONS: BPP had a high case-fatality rate in this group of adult patients with no association to resistant isolates, and a low immunization record. Three independent factors were related to death and the prognostic yield of different severity scores was low.
J. H. Gentile
Full Text Available Our objective was to describe incidence, clinical, radiographic and microbiological features of bacteremic pneumococcal pneumonia (BPP in our environment. A total of 101 patients (7 were treated as outpatients, older than 18 years of age suffering BPP were prospectively evaluated. The incidence was 2.8 cases per 1000 admissions, 50 were males, mean age was 59.9 years (19-97, mortality was 11.8%. Eighty three percent of fatalities occurred within 3 days of admission. Mortality rate increased with advancing age. Fever, cough and chest pain were the commonest presenting symptoms and 44% of patients had extrapulmonary manifestations. Cigarette smoking, chronic obstructive lung disease, alcoholism and congestive heart failure (CHF were the commonest underlying conditions. CHF was more frequent in non-survivors (p = 0.002. A lobar pattern at chest radiograph predominated in survivors and a diffuse pattern in non-survivors (p = 0.007. Pleural effusion (20.7%, empyema (7.9% and respiratory failure (7.9% were the main complications. Underlying diseases were present in 100% of non-survivors (p = 0.03. Ninety four percent of patients were treated with beta-lactam antibiotics. Streptococcus pneumoniae was isolated from sputum in 6 cases. Three out of 101 S. pneumoniae isolates recovered from blood samples (one from each patient presented organisms resistant to penicillin. We observed an incidence of BPP that is similar to the observed in other countries. There are clinical and radiographic differences between survivors and non-survivors. Penicillin-resistant S. pneumoniae is still an unusual problem in our area.Se evaluaron en forma prospectiva 101 pacientes > 18 años admitidos al hospital con diagnóstico de NNB. El objetivo fue conocer la incidencia y describir las características de la enfermedad, así como la susceptibilidad antibiótica de cepas invasivas de Streptococcus pneumoniae. Se halló una incidencia de 2.8 casos/1000 admisiones; 50 fueron
Pletz, Mathias W; Ewig, Santiago; Rohde, Gernot; Schuette, Hartwig; Rupp, Jan; Welte, Tobias; Suttorp, Norbert; Forstner, Christina
The aim of the study was to compare the distribution of the vaccine-serotypes covered by pneumococcal conjugate vaccines (PCV7 and PCV13) in adult patients with pneumococcal community-acquired pneumonia in Germany between the periods 2002-2006 and 2007-2011 using a novel serotype-specific multiplex urinary antigen detection assay (SSUA). Vaccination of children started with PCV7 in 2007, which was replaced by PCV13 in 2010. Following confirmation of the accuracy of SSUA in long-term stored urine samples from 112 patients with confirmed pneumonia and known pneumococcal serotype, urine samples of 391 CAPNETZ patients with documented pneumococcal pneumonia (i.e. positive BinaxNOW(®) Streptococcus pneumoniae urine antigen test) but unknown serotype were tested for the 13 vaccine-serotypes using SSUA. The proportion of PCV7-serotypes significantly decreased in adult patients with pneumonia from 30.6% (2002-6) to 13.3% (2007-11, ppneumococcal serotypes included by PCV13 remained stable during study period with a coverage of 61.5% (2002-06) and 59.7% (2007-11) in non-bacteremic pneumonia and 79% (for both periods) in bacteremic pneumonia, mainly due to an increase in pneumococcal serotypes 1, 3 and 7F during the second period. Thus, implementation of PCV7 in children in Germany in 2007 was associated with a significant decrease in vaccine-serotypes covered by PCV7 in adult patients with non-bacteremic pneumococcal pneumonia and with an elimination of PCV7 vaccine-serotypes in bacteremic pneumococcal pneumonia. PCV13 coverage remained high up to 2011, mainly due to an increase in serotypes 1, 3 and 7F. German Clinical Trials Register: DRKS00005274. PMID:27016653
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
Cremers, Amelieke Jh; Zomer, Aldert L; Gritzfeld, Jenna F; Ferwerda, Gerben; van Hijum, Sacha Aft; Ferreira, Daniela M; Shak, Joshua R; Klugman, Keith P; Boekhorst, Jos; Timmerman, Harro M; de Jonge, Marien I; Gordon, Stephen B; Hermans, Peter Wm
BACKGROUND: Several cohort studies have indicated associations between S. pneumoniae and other microbes in the nasopharynx. To study causal relationships between the nasopharyngeal microbiome and pneumococcal carriage, we employed an experimental human pneumococcal carriage model. Healthy adult volu
Paradiso, Peter R
A 13-valent pneumococcal conjugate vaccine has been studied in adults aged ≥50 years to compare the immune response to that induced by the 23-valent pneumococcal polysaccharide vaccine, which has been the standard of care over the past 30 years. The results demonstrate that adults, regardless of whether they are naive or previously vaccinated with the polysaccharide vaccine, have an overall superior antibody response when vaccinated with the conjugate vaccine compared with the pneumococcal po...
Fedson, David S; Guppy, Martin J.
Invasive pneumococcal disease continues to be important problem for older adults. Pneumococcal polysaccharide vaccine (PPV23) has a clinical effectiveness of 43–81%, and following primary vaccination and revaccination, antibody responses last 5–10 y. Hyporesponsiveness to a second dose of vaccine has not been shown to be a significant problem. The use of pneumococcal conjugate vaccines (initially PCV7; more recently PCV13) has led to a dramatic fall in the incidence of conjugate vaccine-type ...
Full Text Available Philip Eng,1 Lean Huat Lim,2 Chian Min Loo,3 James Alvin Low,4 Carol Tan,5 Eng Kiat Tan,6 Sin Yew Wong,7 Sajita Setia8 1Philip Eng Respiratory and Medical Clinic, Mount Elizabeth Medical Center, 2Dr Lim Lean Huat and Associates Pte Ltd, 3Department of Respiratory and Critical Care Medicine, Singapore General Hospital, 4Department of Geriatric Medicine, Khoo Teck Puat Hospital, 5Rophi Clinic, Mount Elizabeth Novena Specialist Centre, Singapore, 6Kevin Tan Clinic for Diabetes, Thyroid, and Hormones, Mount Elizabeth Medical Center, 7Infectious Disease Partners Pte Ltd, Gleneagles Medical Center, 8Medical Affairs Department, Pfizer Pte Ltd, SingaporeAbstract: 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
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
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
Full Text Available Streptococcus pneumoniae is the commonest cause of bacteremic pneumonia among HIV-infected persons. As more countries with high HIV prevalence are implementing infant pneumococcal conjugate vaccine (PCV programs, we aimed to describe the baseline clinical characteristics of adult invasive pneumococcal disease (IPD in the pre-PCV era in South Africa in order to interpret potential indirect effects following vaccine use.National, active, laboratory-based surveillance for IPD was conducted in South Africa from 1 January 2003 through 31 December 2008. At 25 enhanced surveillance (ES hospital sites, clinical data, including HIV serostatus, were collected from IPD patients ≥ 5 years of age. We compared the clinical characteristics of individuals with IPD in those HIV-infected and -uninfected using multivariable analysis. PCV was introduced into the routine South African Expanded Program on Immunization (EPI in 2009.In South Africa, from 2003-2008, 17 604 cases of IPD occurred amongst persons ≥ 5 years of age, with an average incidence of 7 cases per 100 000 person-years. Against a national HIV-prevalence of 18%, 89% (4190/4734 of IPD patients from ES sites were HIV-infected. IPD incidence in HIV-infected individuals is 43 times higher than in HIV-uninfected persons (52 per 100 000 vs. 1.2 per 100 000, with a peak in the HIV-infected elderly population of 237 per 100 000 persons. Most HIV-infected individuals presented with bacteremia (74%, 3 091/4 190. HIV-uninfected individuals were older; and had more chronic conditions (excluding HIV than HIV-infected persons (39% (210/544 vs. 19% (790/4190, p<0.001. During the pre-PCV immunization era in South Africa, 71% of serotypes amongst HIV-infected persons were covered by PCV13 vs. 73% amongst HIV-uninfected persons, p = 0.4, OR 0.9 (CI 0.7-1.1.Seventy to eighty-five percent of adult IPD in the pre-PCV era were vaccine serotypes and 93% of cases had recognized risk factors (including HIV-infection for
Paradiso, Peter R
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
... 000 adults age 65 years and older. Pneumococcal disease can cause serious illness and lifelong complications. Pneumococcal meningitis can cause hearing loss, seizures, blindness, and paralysis. Serious heart problems are ... its worst forms, pneumococcal disease kills one in every four to five people ...
Ballegaard, Vibe C; Schejbel, Lone; Hoffmann, Steen;
condition was found. Despite immunization against S. pneumoniae and measurement of what was interpreted as protective levels of serotype-specific IgG antibodies after vaccination, the patient suffered from a third episode of IPD. CONCLUSIONS: Individuals with predisposing medical conditions or a history of......BACKGROUND: The risk of life-threatening and invasive infections with encapsulated bacteria is increased in patients with hyposplenia or asplenia. We report a case of recurrent invasive pneumococcal meningitis in a woman with previous unknown hyposplenia. She was vaccinated after the first episode...... of meningitis and developed sufficient levels of pneumococcal antibodies. The pneumococcal strains isolated were serotype 7 F and 17 F. To our knowledge, there has been no previously reported case of recurrent invasive pneumococcal disease in a pneumococcal vaccinated adult with hyposplenia and...
Hampton, Lee M; Bigogo, Godfrey; Jagero, Geofrey; da Gloria Carvalho, Maria; Pimenta, Fabiana; Junghae, Muthoni; Breiman, Robert F; Whitney, Cynthia G; Feikin, Daniel R; Conklin, Laura M
When used in an area of rural western Kenya, the BinaxNOW® urine antigen test had a sensitivity of 67% (95% Confidence Interval [CI]: 43-85%) among 21 adults ≥15 years old with acute respiratory illnesses and pneumococcal bacteremia and a specificity of 98% (95% CI: 96-99%) among 660 adults ≥15 years old without fever or cough. The specificity of the test was not significantly affected by pneumococcal colonization, regardless of patients' HIV status, age, or sex. Use of the pneumococcal urine antigen test in clinical assessments of adults in Africa with acute respiratory illness is a viable option regardless of whether a patient is colonized by pneumococci, even among HIV-infected adults, although the moderate sensitivity of the urine antigen test indicates that the test is probably best used clinically as part of a panel with other tests that can detect pneumococci. PMID:27220607
Park, Nina J; Sklaroff, Laura Myerchin; Gross-Schulman, Sandra; Hoang, Khathy; Tran, Helen; Campa, David; Scheib, Geoffrey; Guterman, Jeffrey J
Streptococcus pneumoniae is a principal cause of serious illness, including bacteremia, meningitis, and pneumonia, worldwide. Pneumococcal immunization is proven to reduce morbidity and mortality in high-risk adult and elderly populations. Current pneumococcal vaccination practices are suboptimal in part because of recommendation complexity, the high cost of provider-driven immunization interventions, and outreach methods that are not patient-centric. These barriers are amplified within the safety net. This paper identifies efforts by the Los Angeles County Department of Health Services to increase pneumococcal immunization rates for adult indigent patient populations. A 4-part approach will be used to increase vaccination rates: (1) protocol driven care, (2) staff education, (3) electronic identification of eligible patients, and (4) automated patient outreach and scheduling. The proposed analytics plan and potential for scalability are described. (Population Health Management 2016;19:240-247). PMID:26824148
Ridda, Iman; Musher, Daniel M.
Longstanding controversy over the efficacy of 23-valent pneumococcal polysaccharide vaccine (PPV23) led to a recommendation by the Joint Committee on Vaccination and Immunisation (JCVI) of the United Kingdom in March 2011, to discontinue routine use of PPV23 in older adults.1 Following careful review of the evidence and feedback from stakeholders, the JCVI decided to retain the original policy of uniform vaccination of adults >65 years of age, while keeping the subject under continued review....
Sadlier, C.; O’Dea, S.; Bennett, K.; Dunne, J.; Conlon, N.; Bergin, C.
The aim of this study was to compare the immunologic response to a prime-boost immunization strategy combining the 13-valent conjugate pneumococcal vaccine (PCV13) with the 23-valent polysaccharide pneumococcal vaccine (PPSV23) versus the PPSV23 alone in HIV-infected adults. HIV-infected adults were randomized to receive PCV13 at week 0 followed by PPSV23 at week 4 (n = 31, prime-boost group) or PPSV23 alone at week 4 (n = 33, PPSV23-alone group). Serotype specific IgG geometric mean concentration (GMC) and functional oposonophagocytic (OPA) geometric mean titer (GMT) were compared for 12 pneumococcal serotypes shared by both vaccines at week 8 and week 28. The prime-boost vaccine group were more likely to achieve a ≥2-fold increase in IgG GMC and a GMC >1 ug/ml at week 8 (odds ratio (OR) 2.00, 95% confidence interval (CI) 1.46–2.74, p < 0.01) and week 28 (OR 1.95, 95% CI 1.40–2.70, p < 0.01). Similarly, the prime-boost vaccine group were more likely to achieve a ≥4-fold increase in GMT at week 8 (OR 1.71, 95% CI 1.22–2.39, p < 0.01) and week 28 (OR 1.6, 95% CI 1.15–2.3, p < 0.01). This study adds to evidence supporting current pneumococcal vaccination recommendations combining the conjugate and polysaccharide pneumococcal vaccines in the United States and Europe for HIV-infected individuals. PMID:27580688
Full Text Available 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
Bar-Zeev, Naor; Mtunthama, Neema; Gordon, Stephen B; Mwafulirwa, Gershom; French, Neil
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
Rose, M A; Buess, J; Ventur, Y; Zielen, S; Herrmann, E; Schulze, J; Schubert, R
Pneumococcal antibodies represent the acquisition of natural immunity. Determination of pneumococcal antibodies is an important screening tool for immunodeficiencies. Our study generated reference ranges and cutoff levels for pneumococcal antibody global serum assays correlated to a specific pneumococcal antibody ELISA. Specific pneumococcal antibody levels were measured from 457 children undergoing elective surgery and 46 healthy adult volunteers (88 with previous pneumococcal immunization from both groups), 22 severe immunodeficient subjects with ataxia telangiectasia (A-T, negative controls), and age-matched 36 healthy allergic asthmatics. We determined a representative panel of serotype-specific pneumococcal antibodies (serotype 4, 5, 6B, 7F, 14, 18C, 19F, 23F) by ELISA and global pneumococcal IgG and IgG2 antibodies by EIA. In vaccine-naïve healthy subjects, initial pneumococcal IgG geometric mean concentrations of 13.1 μg/ml were low in the first year of life and increased over the time, reaching adult levels (70.5 μg/ml) at age 8-12 years. In parallel, IgG2 antibodies increased from 20.7 % (0.5-1 year old) to adult proportions (>30 %) in preschoolers. Correlation between the pneumococcal IgG screening assay and specific pneumococcal antibody levels was acceptable (Pearson's coefficient r = 0.4455; p = 0.001). Cutoff levels showed high sensitivity, whereas specificity was high to moderate calculated from correlations with the specific ELISA. We provide reference ranges and cutoff levels for the interpretation of specific antibody determinations in the clinical setting. The global pneumococcal IgG/IgG2 assay is a suitable screening tool and correlates with the ELISA serotype-specific pneumococcal antibodies. However, results below our cutoff values should be re-evaluated by serotype-specific ELISA testing. PMID:23529214
Weinberger, Daniel M; Grant, Lindsay R; Weatherholtz, Robert C; Warren, Joshua L; O'Brien, Katherine L; Hammitt, Laura L
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
Full Text Available 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.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.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.Host factors, disease severity, and biomarkers, especially WBC counts and serum creatinine, were more important determinants of mortality than bacterial factors.
... and older People at high risk for pneumococcus infection Alternative Names Pneumococcal meningitis Images Pneumococci organism Pneumococcal pneumonia References Swartz MN. Meningitis: bacterial, ...
Guchev, I A; Klochkov, O I; Sinopalnikov, A I
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
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
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
Berical, Andrew C; Harris, Drew; Dela Cruz, Charles S; Possick, Jennifer D
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
Full Text Available BACKGROUND: Adult invasive pneumococcal disease (IPD occurs mainly in the elderly and patients with co-morbidities. Little is known about the clinical characteristics, serotypes and genotypes causing IPD in healthy adults. METHODS: We studied 745 culture-proven cases of IPD in adult patients aged 18-64 years (1996-2010. Patients were included in two groups: 1. adults with co-morbidities, and 2. healthy adults, who had no prior or coincident diagnosis of a chronic or immunosuppressive underlying disease. Microbiological studies included pneumococcal serotyping and genotyping. RESULTS: Of 745 IPD episodes, 525 (70% occurred in patients with co-morbidities and 220 (30% in healthy adults. The healthy adults with IPD were often smokers (56% or alcohol abusers (18%. As compared to patients with co-morbidities, the healthy adults had (P<0.05: younger age (43.5+/-13.1 vs. 48.7+/-11.3 years; higher proportions of women (45% vs. 24%, pneumonia with empyema (15% vs. 7% and infection with non-PCV7 serotypes including serotypes 1 (25% vs. 5%, 7F (13% vs. 4%, and 5 (7% vs. 2%; and lower mortality (5% vs. 20%. Empyema was more frequently caused by serotype 1. No death occurred among 79 patients with serotype 1 IPD. There was an emergence of virulent clonal-types Sweden(1-ST306 and Netherlands(7F-ST191. The vaccine serotype coverage with the PCV13 was higher in healthy adults than in patients with co-morbidities: 82% and 56%, respectively, P<0.001. CONCLUSION: In this clinical study, one-third of adults with IPD had no underlying chronic or immunosuppressive diseases (healthy adults. They were often smokers and alcohol abusers, and frequently presents with pneumonia and empyema caused by virulent clones of non-PCV7 serotypes such as the Sweden(1-ST306. Thus, implementing tobacco and alcohol abuse-cessation measures and a proper pneumococcal vaccination, such as PCV13 policy, in active smokers and alcohol abusers may diminish the burden of IPD in adults.
Leah J Ricketson
Full Text Available BACKGROUND: Invasive pneumococcal disease continues to be an important cause of mortality. In Calgary, 60% of deaths occur within 5 days of presenting to hospital. This proportion has not changed since before the era of penicillin. The purpose of this study was to investigate what factors may influence death within 5 days of presentation with pneumococcal disease. METHODS AND FINDINGS: Demographic and clinical data from the CASPER (Calgary Area Streptococcus pneumoniae Epidemiology Research study on 1065 episodes of invasive pneumococcal disease in adults (≥18 years from 2000 to 2010 were analyzed. Adjusted multinomial regression was performed to analyze 3 outcomes: early mortality (<5 days post-presentation, late mortality (5-30 days post-presentation, and survival, generating relative risk ratios (RRR. Patients with severe disease had increased risk of early and late death. In multinomial regression with survivors as baseline, the risk of early death increased in those with a Charlson index ≥2 (RRR: 6.3, 95% CI: 1.8-21.9; the risk of late death increased in those with less severe disease and a Charlson ≥2 (RRR: 6.1, 95% CI: 1.4-27.7. Patients who never received appropriate antibiotics had 5.6X (95% CI: 2.4-13.1 the risk of early death. Risk of both early and late death increased by a RRR of 1.3 (95% CI: 1.2-1.4 per 5-year increase in age. In multinomial regression, there were no significant differences in the effects of the factors tested between early and late mortality. CONCLUSIONS: Presenting with severe invasive pneumococcal disease, multiple comorbidities, and older age increases the risk of both early and late death. Patients who died early often presented too late for effective antibiotic therapy, highlighting the need for an effective vaccine.
Oluwadamilola H Iwajomo
Full Text Available Pneumococcal disease is associated with a particularly high morbidity and mortality amongst adults in HIV endemic countries. Our previous findings implicating a B-cell defect in HIV-infected children from the same population led us to comprehensively characterize B-cell subsets in minimally symptomatic HIV-infected Malawian adults and investigate the isotype-switched IgG memory B-cell immune response to the pneumococcus. We show that similar to vertically acquired HIV-infected Malawian children, horizontally acquired HIV infection in these adults is associated with IgM memory B-cell (CD19(+ CD27(+ IgM(+ IgD(+ depletion, B-cell activation and impairment of specific IgG B-cell memory to a range of pneumococcal proteins. Our data suggest that HIV infection affects both T-cell independent and T-cell dependent B-cell maturation, potentially leading to impairment of humoral responses to extracellular pathogens such as the pneumococcus, and thus leaving this population susceptible to invasive disease.
Is 13-Valent Pneumococcal Conjugate Vaccine (PCV13) Combined With 23-Valent Pneumococcal Polysaccharide Vaccine (PPSV23) Superior to PPSV23 Alone for Reducing Incidence or Severity of Pneumonia in Older Adults? A Clin-IQ
Hayward, Starla; Thompson, Lou Ann; McEachern, Andrea
Pneumonia infection is a significant cause of morbidity and mortality worldwide. In addition to the public health concerns, pneumonia also accounts for a significant cost to the health care system. Currently there are two leading vaccines targeted against S. pneumoniae: 23-valent pneumococcal polysaccharide vaccine (PPSV23) and 13-valent pneumococcal conjugate vaccine (PCV13). Until recently the recommendation for adult pneumonia vaccination has been a single dose of PPSV23 for all adults 65 years and older. However, concerns were raised regarding the vaccine’s efficacy due to the persistent burden of pneumococcal disease in the elderly population. This paper focuses on two trials which evaluate the safety and efficacy of PCV13 in the adult population. The first study reveals improved immune response with the addition of PCV13 to PPSV23, while the second shows PCV13 was effective in the prevention of vaccine-type community-acquired pneumonia. The two studies observed adequate safety profiles for PCV13 in series with PPSV23 and with PCV13 compared to placebo. PMID:27376105
Is 13-Valent Pneumococcal Conjugate Vaccine (PCV13 Combined With 23-Valent Pneumococcal Polysaccharide Vaccine (PPSV23 Superior to PPSV23 Alone for Reducing Incidence or Severity of Pneumonia in Older Adults? A Clin-IQ
Full Text Available Pneumonia infection is a significant cause of morbidity and mortality worldwide. In addition to the public health concerns, pneumonia also accounts for a significant cost to the health care system. Currently there are two leading vaccines targeted against Streptococcus pneumoniae: 23-valent pneumococcal polysaccharide vaccine (PPSV23 and 13-valent pneumococcal conjugate vaccine (PCV13. Until recently, the recommendation for adult pneumonia vaccination has been a single dose of PPSV23 for all adults aged 65 years or older. However, concerns were raised regarding the vaccine’s efficacy due to the persistent burden of pneumococcal disease in the elderly population. This paper focuses on two trials that evaluated the safety and efficacy of PCV13 in the adult population. The first study reveals improved immune response with the addition of PCV13 to PPSV23, while the second shows PCV13 was effective in the prevention of vaccine-type community-acquired pneumonia. Both studies observed adequate safety profiles for PCV13 in series with PPSV23 and with PCV13 compared to placebo.
Thomas G Johannesson
Full Text Available Untreated HIV infection results in severe perturbations of the B-cell population and hyporesponsiveness to vaccination. We studied associations between circulating B-cell subsets and antibody response to pneumococcal conjugate vaccine in treated and untreated HIV patients.Ninety-five HIV-infected adults were grouped according to antiretroviral therapy (ART and CD4+ cell count as follows: 20 ART-naïve (no prior ART, 62 ART-responders (received ART, and CD4 count >500 cells/µl, and 13 impaired responders (received ART for more than 3 years, and CD4 count <500 cells/µl. All subjects were immunized twice with double-dose 7-valent pneumococcal conjugate vaccine with or without 1 mg CPG 7909 (toll-like receptor 9 agonist at baseline and after three months. Pre-vaccination B-cell subpopulations were assessed by flow cytometry. Serum IgG concentrations for vaccine serotypes were quantified by ELISA at baseline and 3, 4, and 9 months post-vaccination. ART responders had more isotype-switched memory B cells and more marginal-zone (MZ-like B cells compared with impaired responders. Furthermore, ART-naïve patients had higher concentration of transitional B cells and plasmablasts compared with B cells of other patient groups. The concentration of MZ-like, isotype switched memory cells and plasmablasts correlated positively with post-vaccination IgG concentration at 3, 4, and 9 months. Low concentrations of isotype-switched memory B cells was the strongest independent predictor of poor pneumococcal conjugate vaccine responsiveness, emphasizing that B-cell subset disturbances are associated with poor vaccine response among HIV-infected patients.
Belongia Edward A
Full Text Available Abstract Background Pneumococcal polysaccharide vaccine (PPV is recommended for all adults 65 years of age and older and for younger adults with high-risk conditions. While data from national surveys provide information on the proportion of adults 65 years of age and older reporting ever receipt of PPV they do not collect more detailed information, such as age at vaccination or the total number of vaccinations received. In addition, there is relatively little information available on PPV coverage in younger adults with chronic conditions. To assess contemporary patterns of pneumococcal vaccination and revaccination of adults, we conducted a cross-sectional study of adults enrolled in medical care organizations (MCOs participating in the Vaccine Safety Datalink project. Methods The study population included 1.5 million adults 25 years of age and older enrolled in the four participating MCOs on December 1, 2006. PPVs administered to members of the study population prior to that date were identified from computerized immunization registries maintained by the MCOs. Results Among the general population of adults 25 through 64 years of age, vaccine coverage increased from 2% in the 25–29 year old age-group to 26% in the 60–64 year old age-group. In all age-groups, coverage was substantially higher in persons defined as having a chronic high risk condition. This was particularly true for diabetes mellitus, with vaccine coverage of over 50% in the lower age-groups and 75% in those 60–64 years of age. Among adults 65 years of age and older, 82% had received at least one PPV and 18% had received two or more PPVs. Conclusion We found higher levels of PPV coverage among adults 65 years of age and older and among younger adults with diabetes mellitus than reported by national surveys and for those groups PPV coverage approached the Healthy People 2010 national objectives. These results suggest that achieving those objectives for PPV is possible and
Chen-Fang Ho; Tzou-Yien Lin
Streptococcus pneumoniae is the leading bacterial pathogen of infectious diseases inchildren and adolescents. The 23-valent pneumococcal polysaccharide vaccine could preventinvasive pneumococcal infection with broader serotype coverage but still has some limitations.On the other hand, 7-valent pneumococcal conjugate vaccine has been shown todecrease cases of nasopharyngeal acquired S. pneumoniae vaccine serotypes and provedherd immunity. The safety and efficacy against vaccine serotype pneumo...
Conclusions: The ORs for CAP and IPD of patients with two or more comorbidities, with or without smoking, were found to be similar to the ORs for CAP and IPD described in the literature for patients currently classified as high risk. The potential impact of multiple, stacking comorbidities is underestimated and there is a need for the risk categories for pneumococcal disease to be redefined.
Full Text Available Introduction: Coeliac disease can be associated with hyposplenism and splenic atrophy, which may increase the patient’s risk for fatal infections caused by Streptococcus pneumoniae or Pneumococcus. It is general opinion that many more patients with coeliac disease have died from hyposplenism-related infections than those reported in literature. Case report: A 62-year-old woman with recently diagnosed coeliac disease was hospitalized with high fever, disorientation, and nuchal rigidity. Cerebral computed tomography was negative. Laboratory tests showed an elevated leukocyte count and very high levels of C reactive protein. The cerebrospinal fluid (CSF contained an increased number of mononuclear cells associated with a low glucose level and high protein concentrations. The CSF culture was positive for Streptococcus pneumoniae. Neurological conditions rapidly deteriorated with the onset of coma, and magnetic resonance imaging of the brain revealed initial signs of encephalitis extending above and below the tentorium. Abdominal ultrasonography disclosed splenic hypotrophy that raised the suspicion of hyposplenism. The diagnosis of hyposplenism was confirmed by demonstration of Howell-Jolly bodies in a peripheral blood smear. Discussion: This is the first reported case of pneumococcal meningoencephalitis caused by splenic hypofunction in a patient with coeliac disease. When coeliac disease is diagnosed with a marked delay in an elderly patient, spleen function should always be assessed. If impaired, the patient should undergo vaccination with pneumococcal conjugate vaccine to prevent pneumococcal infections.
Sónia T Almeida
Full Text Available Pneumococcal disease is frequent at the extremes of age. While several studies have looked at colonization among young children, much less is known among the elderly. We aimed to evaluate pneumococcal carriage among elderly adults living in Portugal. Between April 2010 and December 2012, nasopharyngeal and oropharyngeal swabs of adults over 60 years of age, living in an urban area (n = 1,945 or in a rural area (n = 1,416, were obtained. Pneumococci were isolated by culture-based standard procedures, identified by optochin susceptibility, bile solubility and PCR screening for lytA and cpsA, and characterized by antibiotype, serotype, and MLST. Associations between pneumococcal carriage, socio-demographic and clinical characteristics were evaluated by univariate analysis and multiple logistic regression. The global prevalence of carriage was 2.3% (95% CI: 1.8-2.8. In the multiple logistic regression analysis, smoking, being at a retirement home, and living in a rural area increased the odds of being a pneumococcal carrier by 4.4-fold (95% CI: 1.9-9.2, 2.0-fold (95% CI: 1.1-3.6 and 2.0-fold (95% CI: 1.2-3.5, respectively. Among the 77 pneumococcal isolates, 26 serotypes and 40 STs were identified. The most prevalent serotypes were (in decreasing order 19A, 6C, 22F, 23A, 35F, 11A, and 23B, which accounted, in total, for 60.0% of the isolates. Most isolates (93.5% had STs previously described in the MLST database. Resistance to macrolides, non-susceptibility to penicillin and multidrug resistance were found in 19.5%, 11.7%, and 15.6% of the isolates, respectively. We conclude that the prevalence of pneumococcal carriage in the elderly, in Portugal, as determined by culture-based methods, is low. Serotype and genotype diversity is high. Living in a rural area, in a retirement home, and being a smoker increased the risk of pneumococcal carriage. This study contributes to the establishment of a baseline that may be used to monitor how novel
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.
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 children in the U.S. Serotypes 19A and 7F, which emerged after PCV7 introduction, have been effectively controlled. PMID:25656600
Full Text Available Abstract Background Although causing substantial morbidity, the burden of pneumococcal disease among older children and adults in Africa, particularly in rural settings, is not well-characterized. We evaluated pneumococcal bacteremia among 21,000 persons ≥5 years old in a prospective cohort as part of population-based infectious disease surveillance in rural western Kenya from October 2006-September 2008. Methods Blood cultures were done on patients meeting pre-defined criteria - severe acute respiratory illness (SARI, fever, and admission for any reason at a referral health facility within 5 kilometers of all 33 villages where surveillance took place. Serotyping of Streptococcus pneumoniae was done by latex agglutination and quellung reaction and antibiotic susceptibility testing was done using broth microdilution. We extrapolated incidence rates based on persons with compatible illnesses in the surveillance population who were not cultured. We estimated rates among HIV-infected persons based on community HIV prevalence. We projected the national burden of pneumococcal bacteremia cases based on these rates. Results Among 1,301 blood cultures among persons ≥5 years, 52 (4% yielded pneumococcus, which was the most common bacteria isolated. The yield was higher among those ≥18 years than 5-17 years (6.9% versus 1.6%, p 95%. The crude rate of pneumococcal bacteremia was 129/100,000 person-years, and the adjusted rate was 419/100,000 person-years. Nineteen (61% of 31 patients with HIV results were HIV-positive. The adjusted rate among HIV-infected persons was 2,399/100,000 person-years (Rate ratio versus HIV-negative adults, 19.7, 95% CI 12.4-31.1. We project 58,483 cases of pneumococcal bacteremia will occur in Kenyan adults in 2010. Conclusions Pneumococcal bacteremia rates were high among persons ≥5 years old, particularly among HIV-infected persons. Ongoing surveillance will document if expanded use of highly-active antiretroviral
Lombardi, Francesca; Belmonti, Simone; Fabbiani, Massimiliano; Morandi, Matteo; Rossetti, Barbara; Tordini, Giacinta; Cauda, Roberto; De Luca, Andrea; Di Giambenedetto, Simona; Montagnani, Francesca
Objectives Definition of the optimal pneumococcal vaccine strategy in HIV-infected adults is still under evaluation. We aimed to compare immunogenicity and safety of the 13-valent pneumococcal conjugate vaccine (PCV13) versus the 23-valent polysaccharide vaccine (PPSV23) in HIV-infected adults. Methods We performed a pilot, prospective controlled study enrolling HIV-infected pneumococcal vaccine-naïve outpatients, aged 18–65 years with CD4 counts ≥200 cells/μL. Eligible subjects were recruited into two parallel groups: group 1 (n = 50) received two doses of PCV13 eight weeks apart, and group 2 (n = 50) received one dose of PPSV23, as part of their standard of care. Anti-pneumococcal capsular polysaccharide immunoglobulin G concentrations were quantified by ELISA at baseline, 8, 24 and 48 weeks. Clinical and viro-immunological follow-up was performed at the same time points. Unvaccinated, age-matched HIV-negative adults (n = 100) were also enrolled as baseline controls. Results Pre-vaccination specific IgG titers for each pneumococcal antigen did not differ between study groups but they were constantly lower than those from the HIV-negative controls. After immunization, significant increases in IgG titers were observed in both study groups at each time point compared to baseline, but response to serotype 3 was blunted in group 1. Antibody titers for each antigen did not differ between study groups at week 48. Overall, the proportion of subjects achieving seroprotection and seroconversion to all serotypes was comparable between groups. A marked decrease in IgG levels over time was observed with both vaccines. No relevant adverse reactions were reported in either group. Conclusions In this population with favorable immune profile, no relevant differences were observed in immunogenicity between PCV13 and PPSV23. Both vaccines were safe and well tolerated. Trial Registration ClinicalTrials.gov NCT02123433 PMID:27258647
Full Text Available Definition of the optimal pneumococcal vaccine strategy in HIV-infected adults is still under evaluation. We aimed to compare immunogenicity and safety of the 13-valent pneumococcal conjugate vaccine (PCV13 versus the 23-valent polysaccharide vaccine (PPSV23 in HIV-infected adults.We performed a pilot, prospective controlled study enrolling HIV-infected pneumococcal vaccine-naïve outpatients, aged 18-65 years with CD4 counts ≥200 cells/μL. Eligible subjects were recruited into two parallel groups: group 1 (n = 50 received two doses of PCV13 eight weeks apart, and group 2 (n = 50 received one dose of PPSV23, as part of their standard of care. Anti-pneumococcal capsular polysaccharide immunoglobulin G concentrations were quantified by ELISA at baseline, 8, 24 and 48 weeks. Clinical and viro-immunological follow-up was performed at the same time points. Unvaccinated, age-matched HIV-negative adults (n = 100 were also enrolled as baseline controls.Pre-vaccination specific IgG titers for each pneumococcal antigen did not differ between study groups but they were constantly lower than those from the HIV-negative controls. After immunization, significant increases in IgG titers were observed in both study groups at each time point compared to baseline, but response to serotype 3 was blunted in group 1. Antibody titers for each antigen did not differ between study groups at week 48. Overall, the proportion of subjects achieving seroprotection and seroconversion to all serotypes was comparable between groups. A marked decrease in IgG levels over time was observed with both vaccines. No relevant adverse reactions were reported in either group.In this population with favorable immune profile, no relevant differences were observed in immunogenicity between PCV13 and PPSV23. Both vaccines were safe and well tolerated.ClinicalTrials.gov NCT02123433.
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 ...
Offersen, Rasmus; Melchjorsen, Jesper; Paludan, Søren R; Østergaard, Lars; Tolstrup, Martin; Søgaard, Ole S.
HIV-patients have excess of pneumococcal infection. We immunized 40 HIV-patients twice with pneumococcal conjugate vaccine (Prevnar, Pfizer) +/− a TLR9 agonist (CPG 7909). Peripheral blood mononuclear cells were stimulated with pneumococcal polysaccharides and cytokine concentrations measured. The CPG 7909 adjuvant group had significantly higher relative cytokine responses than the placebo group for IL-1β, IL-2R, IL-6, IFN-γ and MIP-β, which, did not correlate with IgG antibody responses. The...
Streptococcus pneumoniae is a frequent cause of pneumonia and meningitis. This article looks at the pneumococcal vaccine, its uses, efficacy, and adverse effects and how vaccination may be improved. We also look at the role of the new conjugate vaccines.
Ariza-Prota, Miguel Angel; Pando-Sandoval, Ana; García-Clemente, Marta; Fole-Vázquez, David; Casan, Pere
Moraxella (formerly Branhamella) catarrhalis was discovered at the end of the nineteenth century, and for many decades it was considered to be a harmless commensal of the upper respiratory tract. It is a Gram-negative, aerobic diplococcus considered to be the third most common pathogen isolated in childhood sinusitis and otitis media and in adult chronic lower respiratory disease, as well as an etiological agent of pneumonia in immunosuppressed patients or those with chronic obstructive pulmonary disease. Moraxella catarrhalis pneumonia is rarely associated with bacteremia. Here, we present two cases of community-acquired Moraxella catarrhalis bacteremic pneumonia. PMID:26989548
Full Text Available Abstract Background The systematic vaccination with 23-valent polysaccharide pneumococcal vaccine (PPV was introduced as a strategic objective of health for all the people over 65 in Catalonia in 1999. We analysed the evolution of the pneumococcal vaccination rates from 2000 to 2003. Methods We conducted a retrospective population-based study including all the individuals 65 years or older assigned to 8 Primary Care Centres (PCCs in Tarragona (Catalonia, Spain, who figured in the administrative population databases on 31 December 2003 (n = 10,410 persons. We assessed whether every person had received PPV during the last four years (2000 to 2003 or whether they had received it before January 2000. Data sources were the computerised clinical records of the 8 participating PCCs, which included adult vaccination registries and diagnoses coded of International Classification of Diseases 9th Review Results The overall vaccination uptake increased to 38.6% at the end of 2000. Global accumulated coverages increased more slowly the following years: 44.4% in 2001, 50.9% in 2002, and 53.1% at the end of 2003. Vaccine uptake varied significantly according to age (46.7% in people 65–74 years-old, 60.9% in people 75 years or more; p Discussion The pneumococcal vaccination coverage increased quickly after the introduction of the recommendation for free vaccination in all the elderly people (with and without risk factors, but two years after the improvement the coverage became stable and increased slowly.
Full Text Available Purified polysaccharide and conjugate vaccines are widely used for preventing infections in adults and in children against the Gram-positive bacterium Streptococcus pneumoniae, a pathogen responsible for high morbidity and mortality rates, especially in developing countries. However, these polysaccharide-based vaccines have some important limitations, such as being serotype-dependent, being subjected to losing efficacy because of serotype replacement and high manufacturing complexity and cost. It is expected that protein-based vaccines will overcome these issues by conferring a broad coverage independent of serotype and lowering production costs. In this study, we have applied the "shaving" proteomic approach, consisting of the LC/MS/MS analysis of peptides generated by protease treatment of live cells, to a collection of 16 pneumococcal clinical isolates from adults, representing the most prevalent strains circulating in Spain during the last years. The set of unique proteins identified in all the isolates, called "pan-surfome", consisted of 254 proteins, which included most of the protective protein antigens reported so far. In search of new candidates with vaccine potential, we identified 32 that were present in at least 50% of the clinical isolates analyzed. We selected four of them (Spr0012, Spr0328, Spr0561 and SP670_2141, whose protection capacity has not yet been tested, for assaying immunogenicity in human sera. All of them induced the production of IgM antibodies in infected patients, thus indicating that they could enter the pipeline for vaccine studies. The pan-surfomic approach shows its utility in the discovery of new proteins that can elicit protection against infectious microorganisms.
Pneumococci are a type of streptococcus bacteria. The bacteria spread through contact with people who are ill or by healthy people who carry the bacteria in the back of their nose. Pneumococcal infections can be mild or severe. The most common types of infections are Ear infections Sinus infections ...
Full Text Available BACKGROUND: PCV7 was introduced as universal childhood vaccination in Israel in July 2009 and PCV13 in November 2010. Here we report data on adult invasive pneumococcal disease (IPD, two years post PCV7 implementation and before an expected effect of PCV13. METHODS: An ongoing nationwide active-surveillance (all 27 laboratories performing blood cultures in Israel, providing all blood & CSF S. pneumoniae isolates from persons >18 y was initiated in July 2009. Capture-recapture method assured reporting of >95% cases. All isolates were serotyped in one central laboratory. IPD outcome and medical history were recorded in 90%. Second year post PCV implementation is compared to the first year. RESULTS: During July 2009 to June 2011, 970 IPD cases were reported (annual incidence [/100,000] of 9.17 and 10.16 in the two consecutive years, respectively. Respective case fatality rates (CFRs were 20% and 19.1%. Incidence of IPD and CFR increased with age and number of comorbidities. Incidence rate was significantly greater during the second winter, 7.79/100,000 vs. 6.14/100,000 in first winter, p = 0.004, with a non-significant decrease during summer months (3.02 to 2.48/100,000. The proportion of IPD cases due to PCV7-serotypes decreased from 27.5% to 13.1% (first to second year (p64 y. Among younger/healthier patients serotype 5 was the major increasing serotype. Penicillin and ceftriaxone resistance decreased significantly in the second year. CONCLUSIONS: While overall annual incidence of IPD did not change, the indirect effect of PCV7 vaccination was evident by the significant decrease in PCV7 serotypes across all age groups. Increase in non-VT13 strains was significant in immunocompromised patients. A longer follow-up is required to appreciate the full effect of infant vaccination on annual IPD.
Daniels, Calvin C.; Rogers, P. David; Shelton, Chasity M.
This review describes development of currently available pneumococcal vaccines, provides summary tables of current pneumococcal vaccine recommendations in children and adults, and describes new potential vaccine antigens in the pipeline. Streptococcus pneumoniae, the bacteria responsible for pneumonia, otitis media, meningitis and bacteremia, remains a cause of morbidity and mortality in both children and adults. Introductions of unconjugated and conjugated pneumococcal polysaccharide vaccine...
Anselm Chi-wai Lee; Nellie Dawn Siao-ping Ong
Bacteremia following febrile neutropenia is a serious complication in children with malignancies. Preventive measures are currently targeted at antimicrobial prophylaxis, amelioration of drug-induced neutropenia, and nosocomial spread of pathogens, with little attention to community-acquired infections. A retrospective study was conducted at a pediatric oncology center during a 3-year period to identify probable cases of food-borne infections with bacteremia. Twenty-one bacteremic illnesses a...
Conclusions: Although a reduction in infections due to vaccine serotypes was observed, close to half of infections in adult patients were caused by PCV-13 serotypes. Even after pediatric vaccination with PCV-13, vaccine serotypes were still responsible for most pneumonia and invasive disease, underscoring the importance of implementing current guidelines and extending vaccination to other risk groups.
Anneke Steens; Vestrheim, Didrik F.; Birgitte Freiesleben de Blasio
Two different vaccines, a 23-valent polysaccharide vaccine (PPV23) and a 13-valent conjugate vaccine (PCV13), are available for prevention of invasive pneumococcal disease (IPD) in the population aged 65 years and older (65+). The IPD epidemiology in the 65+ is undergoing change due to indirect effects of childhood immunisation. Vaccine recommendations for the 65+ must take into account these trends in epidemiology. We therefore explored the preventive potential of vaccination strategies to p...
Harboe, Zitta B; Thomsen, Reimar W; Riis, Anders;
BACKGROUND: Pneumococcal disease is a leading cause of morbidity and mortality worldwide. The aim of this study was to investigate the association between specific pneumococcal serotypes and mortality from invasive pneumococcal disease (IPD). METHODS AND FINDINGS: In a nationwide population......-based cohort study of IPD in Denmark during 1977-2007, 30-d mortality associated with pneumococcal serotypes was examined by multivariate logistic regression analysis after controlling for potential confounders. A total of 18,858 IPD patients were included. Overall 30-d mortality was 18%, and 3% in children...... compared with serotype 1 (all: adjusted odds ratio >or=3, p<0.001). In children younger than 5 y, associations between serotypes and mortality were different than in adults but statistical precision was limited because of low overall childhood-related mortality. CONCLUSIONS: Specific pneumococcal serotypes...
Several years after the seven-valent pneumococcal conjugate vaccine (PCV7) was introduced in Canada and elsewhere, routine infant vaccination has led to near eradication of invasive pneumococcal disease caused by vaccine serotype strains in both children and adults. There have also been significant declines in pneumococcal-related disease including lobar pneumonia and otitis media. These declines have been offset, to some extent, by increases in nonvaccine serotype disease. Serotype 19A, whic...
Marta C Nunes
Full Text Available BACKGROUND: Highly active antiretroviral treatment (HAART programs have been associated with declines in the burden of invasive pneumococcal disease (IPD in industrialized countries. The aim of this study was to evaluate trends in IPD hospitalizations in HIV-infected adults in Soweto, South Africa, associated with up-scaling of the HAART program from 2003 to 2008. METHODS: Laboratory-confirmed IPD cases were identified from 2003 through 2008 through an existing surveillance program. The period 2003-04 was designated as the early-HAART era, 2005-06 as the intermediate-HAART era and 2007-08 as the established-HAART era. The incidence of IPD was compared between the early-HAART and established-HAART eras in HIV-infected and-uninfected individuals. RESULTS: A total of 2,567 IPD cases among individuals older than 18 years were reported from 2003 through 2008. Overall incidence of IPD (per 100,000 did not change during the study period in HIV-infected adults (207.4 cases in the early-HAART and 214.0 cases in the established-HAART era; p = 0.55. IPD incidence, actually increased 1.16-fold (95% CI: 1.01; 1.62 in HIV-infected females between the early-and established-HAART eras (212.1 cases and 246.2 cases, respectively; p = 0.03. The incidence of IPD remained unchanged in HIV-uninfected adults across the three time periods. CONCLUSION: Despite a stable prevalence of HIV and the increased roll-out of HAART for treatment of AIDS patients in our setting, the burden of IPD has not decreased among HIV-infected adults. The study indicates a need for ongoing monitoring of disease and HAART program effectiveness to reduce opportunistic infections in African adults with HIV/AIDS, as well as the need to consider alternate strategies including pneumococcal conjugate vaccine immunization for the prevention of IPD in HIV-infected adults.
Julie M Okapuu
Full Text Available BACKGROUND: The American Advisory Committee on Immunization Practices recommended the inclusion of adults with asthma in the high-risk category for pneumococcal vaccination based on a twofold increase in risk of invasive pneumococcal disease (IPD.
Macfarlane, J T; Miller, A C; Roderick Smith, W H; Morris, A. H.; Rose, D. H.
The features of the chest radiographs of 49 adults with legionnaires' disease were compared with those of 91 adults with pneumococcal pneumonia (31 of whom had bacteraemia or antigenaemia), 46 with mycoplasma pneumonia, and 10 with psittacosis pneumonia. No distinctive pattern was seen for any group. Homogeneous shadowing was more frequent in legionnaires' disease (40/49 cases) (p less than 0.005), bacteraemic pneumococcal pneumonia (25/31) (p less than 0.01) and non-bacteraemic pneumococcal ...
Full Text Available 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
Full Text Available Two different vaccines, a 23-valent polysaccharide vaccine (PPV23 and a 13-valent conjugate vaccine (PCV13, are available for prevention of invasive pneumococcal disease (IPD in the population aged 65 years and older (65+. The IPD epidemiology in the 65+ is undergoing change due to indirect effects of childhood immunisation. Vaccine recommendations for the 65+ must take into account these trends in epidemiology. We therefore explored the preventive potential of vaccination strategies to prevent IPD in the 65+, including PPV23, PCV13 or PCV13 + PPV23 in 2014–2019. Quasi-Poisson regression models were fitted to 2004–2014 population-wide surveillance data and used to predict incidences for vaccine-type and non-vaccine type IPD. We determined the number of people needed to be vaccinated to prevent one case per season (NNV for each strategy and estimated the public health impact on the IPD case counts from increasing the vaccine uptake to 28–45%. Our results indicate that PCV13-IPD will decrease by 71% from 58 (95% prediction interval 55–61 cases in 2014/15 to 17 (6–52 in 2018/19 and PPV23-IPD by 32% from 168 (162–175 to 115 (49–313 cases. The NNV will increase over time for all strategies because of a decreasing vaccine-type IPD incidence. In 2018/19, the PCV13-NNV will be 5.3 times higher than the PPV23-NNV. Increasing the vaccine uptake will lead to a larger public health impact for all scenarios. Combining PCV13 and PPV23 is most effective, but the additional effect of PCV13 will decrease and is only marginal in 2018/19. Our study demonstrates the importance of increasing PPV23 uptake and of developing vaccines that confer broader immunity.
Steens, Anneke; Vestrheim, Didrik F; de Blasio, Birgitte Freiesleben
Two different vaccines, a 23-valent polysaccharide vaccine (PPV23) and a 13-valent conjugate vaccine (PCV13), are available for prevention of invasive pneumococcal disease (IPD) in the population aged 65 years and older (65+). The IPD epidemiology in the 65+ is undergoing change due to indirect effects of childhood immunisation. Vaccine recommendations for the 65+ must take into account these trends in epidemiology. We therefore explored the preventive potential of vaccination strategies to prevent IPD in the 65+, including PPV23, PCV13 or PCV13 + PPV23 in 2014-2019. Quasi-Poisson regression models were fitted to 2004-2014 population-wide surveillance data and used to predict incidences for vaccine-type and non-vaccine type IPD. We determined the number of people needed to be vaccinated to prevent one case per season (NNV) for each strategy and estimated the public health impact on the IPD case counts from increasing the vaccine uptake to 28-45%. Our results indicate that PCV13-IPD will decrease by 71% from 58 (95% prediction interval 55-61) cases in 2014/15 to 17 (6-52) in 2018/19 and PPV23-IPD by 32% from 168 (162-175) to 115 (49-313) cases. The NNV will increase over time for all strategies because of a decreasing vaccine-type IPD incidence. In 2018/19, the PCV13-NNV will be 5.3 times higher than the PPV23-NNV. Increasing the vaccine uptake will lead to a larger public health impact for all scenarios. Combining PCV13 and PPV23 is most effective, but the additional effect of PCV13 will decrease and is only marginal in 2018/19. Our study demonstrates the importance of increasing PPV23 uptake and of developing vaccines that confer broader immunity. PMID:25979279
Alraiyes, Abdul Hamid; Shaheen, Khaldoon; Alraies, M Chadi
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
Lee, Anselm Chi-Wai; Siao-Ping Ong, Nellie Dawn
Bacteremia following febrile neutropenia is a serious complication in children with malignancies. Preventive measures are currently targeted at antimicrobial prophylaxis, amelioration of drug-induced neutropenia, and nosocomial spread of pathogens, with little attention to community-acquired infections. A retrospective study was conducted at a pediatric oncology center during a 3-year period to identify probable cases of food-borne infections with bacteremia. Twenty-one bacteremic illnesses affecting 15 children receiving chemotherapy or hematopoietic stem cell transplantation were reviewed. Three (14%) episodes were highly suspected of a food-borne origin: a 17-year-old boy with osteosarcoma contracted Sphingomonas paucimobilis septicemia after consuming nasi lemak bought from a street hawker; a 2-year-old boy with acute lymphoblastic leukemia developed Chryseobacterium meningosepticum septicemia after a sushi dinner; a 2-year-old girl was diagnosed with acute lymphoblastic leukemia and Lactobacillus bacteremia suspected to be of probiotic origin. All of them were neutropenic at the time of the infections and the bacteremias were cleared with antibiotic treatment. Food-borne sepsis may be an important, but readily preventable, cause of bloodstream infections in pediatric oncology patients, especially in tropical countries with an abundance of culinary outlets. PMID:22184532
Anselm Chi-wai Lee
Full Text Available Bacteremia following febrile neutropenia is a serious complication in children with malignancies. Preventive measures are currently targeted at antimicrobial prophylaxis, amelioration of drug-induced neutropenia, and nosocomial spread of pathogens, with little attention to community-acquired infections. A retrospective study was conducted at a pediatric oncology center during a 3-year period to identify probable cases of food-borne infections with bacteremia. Twenty-one bacteremic illnesses affecting 15 children receiving chemotherapy or hematopoietic stem cell transplantation were reviewed. Three (14% episodes were highly suspected of a food-borne origin: a 17-year-old boy with osteosarcoma contracted Sphingomonas paucimobilis septicemia after consuming nasi lemak bought from a street hawker; a 2-year-old boy with acute lymphoblastic leukemia developed Chryseobacterium meningosepticum septicemia after a sushi dinner; a 2-year-old girl was diagnosed with acute lymphoblastic leukemia and Lactobacillus bacteremia suspected to be of probiotic origin. All of them were neutropenic at the time of the infections and the bacteremias were cleared with antibiotic treatment. Food-borne sepsis may be an important, but readily preventable, cause of bloodstream infections in pediatric oncology patients, especially in tropical countries with an abundance of culinary outlets.
Full Text Available An association between pneumococcal serotypes and mortality has been suggested. We aimed to investigate this among individuals aged ≥15 years with invasive pneumococcal disease (IPD in South Africa.IPD cases were identified through national laboratory-based surveillance at 25 sites, pre-pneumococcal conjugate vaccine (PCV introduction, from 2003-2008. We assessed the association between the 20 commonest serotypes and in-hospital mortality using logistic regression with serotype 4 (the third commonest serotype with intermediate case-fatality ratio (CFR as referent.Among 3953 IPD cases, CFR was 55% (641/1166 for meningitis and 23% (576/2484 for bacteremia (p<0.001. Serotype 19F had the highest CFR (48%, 100/207, followed by serotype 23F (39%, 99/252 and serotype 1 (38%, 246/651. On multivariable analysis, factors independently associated with mortality included serotype 1 (OR 1.9, 95%CI 1.1-3.5 and 19F (OR 2.9, 95%CI 1.4-6.1 vs. serotype 4; increasing age (25-44 years, OR 1.8, 95%CI 1.0-3.0; 45-64 years, OR 3.6, 95%CI 2.0-6.4; ≥65 years, OR 5.2, 95%CI 1.9-14.1; vs. 15-24 years; meningitis (OR 4.1, 95%CI 3.0-5.6 vs. bacteremic pneumonia; and HIV infection (OR1.7, 95%CI 1.0-2.8. On stratified multivariate analysis, serotype 19F was associated with increased mortality amongst bacteremic pneumococcal pneumonia cases, while no serotype was associated with increased mortality in meningitis cases.Mortality was increased in HIV-infected individuals, which may be reduced by increased antiretroviral therapy availability. Serotypes associated with increased mortality are included in the 10-and-13-valent PCV and may become less common in adults due to indirect effects following routine infant immunization.
Klugman, Keith P.
Pneumonia is the leading cause of mortality in children in developing countries and is also the leading infectious cause of death in adults. The most important cause of pneumonia is the Gram-positive bacterial pathogen, Streptococcus pneumoniae, also known as the pneumococcus. It has thus become the leading vaccine-preventable cause of death and is a successful and diverse human pathogen. The development of conjugate pneumococcal vaccines has made possible the prevention of pneumococcal disea...
Kristin L Moffitt; Malley, Richard
Currently licensed pneumococcal vaccines are based on the generation of antibodies to the pneumococcal polysaccharide, of which there are more than 90 different types. While these vaccines are highly effective against the serotypes included, their high cost and limited serotype coverage limits their usefulness worldwide, particularly in low resources areas. Thus alternative or adjunctive options are being actively pursued. This review will present these various approaches, including variation...
Walker, Melissa M; Novak, Lea; Widener, Rebecca; Grubbs, James Aaron; King, Janice; Hale, Joanetha Y; Ochs, Martina M; Myers, Lisa E; Briles, David E; Deshane, Jessy
We used two different infection models to investigate the kinetics of the PcpA-dependent pneumococcal disease in mice. In a bacteremic pneumonia model, we observed a PcpA-dependent increase in bacterial burden in the lungs, blood, liver, bronchoalveolar lavage, and spleens of mice at 24 h postinfection. This PcpA-dependent effect on bacterial burden appeared earlier (within 12 h) in the focal pneumonia model, which lacks bacteremia or sepsis. Histological changes show that the ability of pneumococci to make PcpA was associated with unresolved inflammation in both models of infection. Using our bacteremic pneumonia model we further investigated the effects of PcpA on recruitment of innate immune regulatory cells. The presence of PcpA was associated with increased IL-6 levels, suppressed production of TRAIL, and reduced infiltration of polymorphonuclear cells. The ability of pneumococci to make PcpA negatively modulated both the infiltration and apoptosis of macrophages and the recruitment of myeloid-derived suppressor-like cells. The latter have been shown to facilitate the clearance and control of bacterial pneumonia. Taken together, the ability to make PcpA was strongly associated with increased bacterial burden, inflammation, and negative regulation of innate immune cell recruitment to the lung tissue during bacteremic pneumonia. PMID:26829988
Andersen, Christian Østergaard; Leib, S.L.; Rowland, Ian J;
ABSTRACT: BACKGROUND: Bacteremia and systemic complications both play important roles in brain pathophysiological alterations and the outcome of pneumococcal meningitis. Their individual contributions to the development of brain damage, however, still remain to be defined. METHODS: Using an adult...... rat pneumococcal meningitis model, the impact of bacteremia accompanying meningitis on the development of hippocampal injury was studied. The study comprised of the three groups: I. Meningitis (n=11), II. meningitis with attenuated bacteremia resulting from iv injection of serotype......-specific pneumococcal antibodies (n=14), and III. uninfected controls (n=6). RESULTS: Pneumococcal meningitis resulted in a significantly higher apoptosis score 0.22 (0.18-0.35) compared to uninfected controls (0.02 (0.00-0.02), Mann Whitney test, P=0.0003). Also, meningitis with an attenuation of bacteremia by...
Giese, Coralie; Mereckiene, Jolita; Danis, Kostas; O'Donnell, Joan; O'Flanagan, Darina; Cotter, Suzanne
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
Jansen, Wouter T. M.; Väkeväinen-Anttila, Merja; Käyhty, Helena; Nahm, Moon; Bakker, N.; Verhoef, Jan; Snippe, Harm; Verheul, André F. M.
Antibody- and complement-mediated phagocytosis is the main defense mechanism against Streptococcus pneumoniae. A standardized, easy to perform phagocytosis assay for pneumococci would be a great asset for the evaluation of the potential efficacy of (experimental) pneumococcal vaccines. Such an assay could replace the laborious phagocytosis assay of viable pneumococci (classical killing assay). Therefore, a newly developed phagocytosis assay based on flow cytometry (flow assay) was compared wi...
This study examined whether alterations in cellular Ca2+ regulation contribute to previously observed changes in skeletal muscle sugar transport during bacteremia. Fasted male rats received saline (control) or bacteria (4 X 10(10) Escherichia coli/kg) intraperitoneally. Twelve hours later, basal and insulin-mediated 3-O-methylglucose (3MG) transport was measured in isolated soleus muscles. Measurements of 3MG transport in the presence of cytochalasin b or at a low temperature (0.5 degree C) indicated that altered sugar transport in bacteremic rat muscles was not due to nonspecific membrane permeability changes. To determine the role of Ca2+ in the pathogenesis of altered sugar transport during bacteremia, rats were treated with the Ca2+ antagonist diltiazem (DZ, 0.6-2.4 mg/kg) at various times (0, 0 + 7.5, 10 h) after saline or bacterial injection. In bacteremic rats given 2.4 mg/kg DZ at 10 h, basal and insulin-mediated transport were similar to control values. This dose of DZ had little effect on control muscles. The addition of 20 microM DZ to the incubation media did not affect basal or insulin-mediated 3MG transport in bacteremic rat muscles. Addition of the Ca2+ agonist BAY K 8644 to the incubation media had no effect on sugar transport in bacteremic rat muscles but caused alterations in control rat muscles that were comparable to those observed in bacteremia. These results suggest that alterations in Ca2+ regulation could contribute to the previously observed changes in sugar transport in skeletal muscles from bacteremic rats
Park So-Youn; Park Hyun; Moon Song; Park Ki-Ho; Chong Yong; Kim Mi-Na; Kim Sung-Han; Lee Sang-Oh; Kim Yang; Woo Jun; Choi Sang-Ho
Abstract Background Pseudomonas aeruginosa has gained an increasing amount of attention in the treatment of patients with pneumonia. However, the benefit of empirical combination therapy for pneumonia remains unclear. We evaluated the effects of adequate empirical combination therapy and multidrug-resistance in bacteremic Pseudomonas pneumonia on the mortality. Methods A retrospective cohort study was performed at the 2,700-bed tertiary care university hospital. We reviewed the medical record...
Imöhl, Matthias; Reinert, Ralf René; van der Linden, Mark
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 importance, particularly with respect to antibiotic resistance. However, concerning antibiotic non-susceptibility the most outstanding change over the years is the decline in macrolide resistance, especially among children. PMID:26324014
Serologic response to primary vaccination with 7-valent pneumococcal conjugate vaccine is better than with 23-valent pneumococcal polysaccharide vaccine in HIV-infected patients in the era of combination antiretroviral therapy
Lu, Ching-Lan; Hung, Chien-Ching; Chuang, Yu-Chung; Liu, Wen-Chun; Su, Chin-Ting; Su, Yi-Ching; Chang, Shu-Fang; Chang, Sui-Yuan; Chang, Shan-Chwen
Objectives: The objectives of this study were to compare the serologic responses at week 48 to primary vaccination with 23-valent pneumococcal polysaccharide vaccine (PPV) vs. 7-valent pneumococcal conjugate vaccine (PCV); and to identify factors associated with serologic response in HIV-infected adult patients with access to combination antiretroviral therapy (cART).
Jean-Baptiste Le Meur
Full Text Available Background: In 2000, an outbreak of severe pneumonia caused by a virulent clone of serotype 1 Streptococcus pneumoniae was detected in the Nunavik region of Quebec. A mass immunization campaign was implemented in the spring of 2002, targeting persons ≥5 years of age and using the 23-valent pneumococcal polysaccharide vaccine (PPSV23. At the same time, the 7-valent pneumococcal conjugate vaccine (PCV7 was introduced into the routine immunization programme of infants, with catch-up for children up to 4 years of age. Objectives: To describe the epidemiology of invasive pneumococcal disease (IPD in relation to PPSV23 and PCV7 use. Study design and methods: Retrospective analysis of IPD cases identified by the Quebec public health laboratory during the period 1997–2010. Results: A total of 82 IPD cases were identified during the study period. In adults, serotype 1 incidence decreased following the 2002 PPSV23 mass campaign but breakthrough cases continued to occur. Following PCV7 use in children, there was a decrease in the incidence of vaccine-type IPD and replacement by other serotypes in adults. In children, a marked decrease in the annual incidence of serotypes included in PCV7 was observed following PCV7 introduction: 162/100,000 in 1997–2001 vs. 10/100,000 in 2004–2010 (p<0.01. Concomitantly, the incidence of IPD caused by serotypes not included in PCV7 increased from 29/100,000 to 109/100,000 (p=0.11. Conclusion: The mass immunization campaign using the PPSV23 in 2002 and the introduction of PCV7 for the routine immunization of infants induced important modifications in the epidemiology of IPD. IPD rates in Nunavik remain much higher than in the southern part of the province both in children and adults. More effective pneumococcal vaccines are needed to eliminate geographic disparities in IPD risk.
Dransfield, Mark T.; Nahm, Moon H.; Han, MeiLan K.; Harnden, Sarah; Criner, Gerard J.; Fernando J Martinez; Scanlon, Paul D.; Woodruff, Prescott G.; Washko, George R.; Connett, John E.; Anthonisen, Nicholas R.; Bailey, William C.
Rationale: Debate exists about the immunogenicity and protective efficacy of antibodies produced by the 23-valent pneumococcal polysaccharide vaccine (PPSV23) in chronic obstructive pulmonary disease (COPD). The 7-valent diphtheria-conjugated pneumococcal polysaccharide vaccine (PCV7) induces a more robust immune response than PPSV23 in healthy elderly adults.
Full Text Available Abstract Background Bacterial meningitis in children causes high rates of mortality and morbidity. In a recent clinical trial, oral glycerol significantly reduced severe neurological sequelae in paediatric meningitis caused by Haemophilus influenzae type b, and a tendency towards a benefit of adjunctive glycerol was seen in pneumococcal meningitis. Methods Here we examined the effects of glycerol in pneumococcal meningitis of infant rats and adult mice. All animals received ceftriaxone, and glycerol or placebo. Brain damage, hearing loss, and inflammatory parameters were assessed. Results Clinically and by histopathology, animals treated with glycerol or placebo did not differ. While both groups showed equally high levels of matrix metalloproteinase-9 at 24 h after infection, a significant difference in favour of glycerol was observed at 40 h after infection. However, this difference in matrix metalloproteinase-9 in late disease did not result in an improvement of histopathologic parameters. Conclusion No benefit of adjunctive glycerol was found in these models of pneumococcal meningitis.
Kapetanovic, Meliha Crnkic; Roseman, Carmen; Jönsson, Göran; Truedsson, Lennart
The objectives of the study were to compare antibody response in immunosuppressed patients with rheumatoid arthritis (RA) after vaccination with heptavalent pneumococcal conjugate vaccine (PCV7) to that of RA patients and healthy controls vaccinated with 23-valent polysaccharide vaccine (PPV23) and to study the impact of disease and/or treatment characteristics and type of vaccine on antibody response following pneumococcal vaccination in patients with RA. In total, 253 RA patients treated with methotrexate (MTX), anti-TNF blockers as monotherapy or anti-TNF + MTX were vaccinated with a single dose (0.5 ml) of PCV7. In addition, 149 RA patients receiving corresponding treatments and 47 healthy controls were vaccinated with a single dose (0.5 ml) of PPV23. Serotype-specific IgG to 23F and 6B were measured at vaccination and 4-6 weeks after vaccination using ELISA. Antibody response ratio (ARR), i.e. ratio between post-/prevaccination antibody levels, was compared between corresponding treatment groups. Differences in ARR were analysed using analysis of variance. Positive antibody response (posAR) was defined as equal to or greater than twofold increase in prevaccination antibody levels. Possible predictors of posAR were analysed using logistic regression model. Corresponding RA treatment groups showed similar ARR and posAR for both serotypes regardless of vaccine type. Higher age at vaccination and concomitant MTX were identified as predictors of impaired posAR for both serotypes tested, whereas type of vaccine did not influence posAR significantly. PCV7 elicits similar antibody response as PPV23 in patients with RA receiving immunosuppressive treatment. In RA patients, higher age and MTX treatment but not type of vaccine predicted impaired posAR. PMID:21956234
... Resources News Newsletters Events Pneumococcal Vaccination: Who Needs It? Recommend on Facebook Tweet Share Compartir There are ... healthy, do not need to get PPSV23 because it is not effective against those conditions. For additional ...
Eun Hwa Choi; Kyung Hyo Kim; Yae Jean Kim; Jong Hyun Kim; Su Eun Park; Hoan Jong Lee; Byung Wook Eun; Dae Sun Jo; Kyong Min Choi; Young Jin Hong
Streptococcus pneumoniae remains a leading cause of invasive infections including bacteremia and meningitis, as well as mucosal infections such as otitis media and pneumonia among children and adults. The 7-valent pneumococcal conjugate vaccine (PCV7) was licensed for use among infants and young children in many countries including Korea. The routine use of PCV7 has resulted in a decreased incidence of invasive pneumococcal disease (IPD) by the vaccine serotypes among the vaccinees and substa...
Helferty, Melissa; Rotondo, Jenny L.; Martin, Irene; Desai, Shalini
Introduction. The International Circumpolar Surveillance network is a population-based surveillance system that collects data on invasive pneumococcal disease (IPD) in Northern Canada. A 7-valent pneumococcal conjugate vaccine was first introduced in some regions of Northern Canada in 2002, followed by 10-valent (2009) and 13-valent (PCV-13) vaccines (2010). A 23-valent polysaccharide (PPV-23) vaccine was first introduced in 1988 for special populations and adults aged 65 years and older. To ...
Carina Valente; Jason Hinds; Francisco Pinto; Brugger, Silvio D.; Katherine Gould; Kathrin Mühlemann; Hermínia de Lencastre; Raquel Sá-Leão
Understanding the epidemiology of pneumococcal co-colonization is important for monitoring vaccine effectiveness and the occurrence of horizontal gene transfer between pneumococcal strains. In this study we aimed to evaluate the impact of the seven-valent pneumococcal conjugate vaccine (PCV7) on pneumococcal co-colonization among Portuguese children. Nasopharyngeal samples from children up to 6 years old yielding a pneumococcal culture were clustered into three groups: pre-vaccine era (n = 17...
朱朗; 陈磊; 林纪胜; 高强; 王见冬; 王新立; 蔡芳
Streptococcus pneumoniae is an important pathogen causing serious diseases such as pneumonia, septicemia and meningitis in people of all ages, especially in young children and the eldly worldwide.These diseases can be prevented by pneumococcal vaccines.In countries where pneumococcal vaccines have been introduced in national immunization program, the incidence of pneumococcal diseases and the carriage of pneumococcal vaccine serotypes decreased dramatically in children, and indirect herd protection was developed among unvaccinated people.The utilization of 23-valent pneumococcal polysaccharide vaccine and 13-valent pneumococcal conjugate vaccine are discussed in this article.%肺炎链球菌是引起全球不同年龄人群,尤其是幼儿和老年人肺炎、败血症和脑膜炎等严重疾病的重要病原菌,由肺炎链球菌导致的这些疾病可以通过疫苗进行预防.在将肺炎链球菌疫苗纳入国家免疫计划的国家,儿童肺炎链球菌病的发病率以及疫苗型肺炎链球菌的携带率大大降低,且可在未免疫人群中产生间接保护作用.此文对23价肺炎链球菌多糖疫苗和1 3价肺炎链球菌结合疫苗在成年人中的应用进行探讨.
McDaniel, Larry S.; Swiatlo, Edwin
ABSTRACT Streptococcus pneumoniae remains an important human pathogen. For more than 100 years, there have been vaccine efforts to prevent pneumococcal infection. The pneumococcal conjugate vaccines have significantly reduced invasive disease. However, these vaccines have changed pneumococcal ecology within the human nasopharynx. We suggest that elimination of the pneumococcus from the human nasopharynx can have consequences that should be considered as the next generation of pneumococcal va...
Madhi, Shabir A; Heera, Jayvant R.; Locadiah Kuwanda; Klugman, Keith P.
BACKGROUND: Pneumonia remains the leading cause of death in young children. The poor specificity of chest radiographs (CXRs) to diagnose pneumococcal pneumonia may underestimate the efficacy of pneumococcal conjugate vaccine in preventing pneumococcal pneumonia. METHODS AND FINDINGS: The efficacy of nine-valent pneumococcal conjugate vaccine among children not infected with HIV (21%; 95% confidence interval, 1%-37%) increased when CXR-confirmed pneumonia was associated with serum C-reactive p...
McDaniel, Larry S; Swiatlo, Edwin
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
Eun Hwa Choi
Full Text Available Streptococcus pneumoniae remains a leading cause of invasive infections including bacteremia and meningitis, as well as mucosal infections such as otitis media and pneumonia among children and adults. The 7-valent pneumococcal conjugate vaccine (PCV7 was licensed for use among infants and young children in many countries including Korea. The routine use of PCV7 has resulted in a decreased incidence of invasive pneumococcal disease (IPD by the vaccine serotypes among the vaccinees and substantial declines in IPD among unvaccinated populations such as older children and adults as well. In addition, there are increasing evidences to suggest that routine immunization with PCV7 is changing the epidemiology of pneumococcal diseases such as serotype distribution of IPD, nasopharyngeal colonization, and antibiotic resistance patterns. In contrast, there is an increase in the number of IPDs caused by nonvaccine serotypes, though it is much smaller than overall declines of vaccine serotype diseases. Several vaccines containing additional serotypes have been developed and tested clinically in order to expand the range of serotypes of Streptococcus pneumoniae. Recently two new pneumococcal protein conjugate vaccines, 10-valent pneumococcal conjugate vaccine (PCV10 and 13-valent pneumococcal conjugate vaccine (PCV13, have been approved for use in several countries including Korea. This report summarizes the recommendations approved by the Committee on Infectious Diseases, the Korean Pediatric Society.
Full Text Available Abstract Background Polysaccharide pneumococcal vaccine is recommended for use in HIV-infected adults in Brazil but there is uncertainty about its effectiveness in this patient population. The main objective of this study was to assess the effectiveness of the 23-valent polysaccharide pneumococcal vaccine against invasive pneumococcal infection among HIV-infected adult patients in São Paulo, Brazil. Methods A case-control study of 79 cases and 242 controls matched on CD4+ cell count and health care setting was conducted. Among HIV-infected adults in São Paulo, Brazil, with and without S. pneumoniae recovered from a normally sterile site; prior receipt of 23 valent polysaccharide pneumococcal vaccine was determined by review of medical records and patient interview. Results After adjustment for confounding factors, the point estimate for the effectiveness of 23 valent polysaccharide vaccine among HIV-infected adults against all invasive pneumococcal infection was 18% (95% CI: Conclusion We were unable to demonstrate a statistically significant protective effect of 23 valent polysaccharide against invasive pneumococcal infection vaccine among HIV-infected adults in Brazil. While the vaccine is relatively inexpensive and safe, its effectiveness among HIV-infected adults in Brazil is uncertain.
Full Text Available India is today facing a diabetes epidemic and has the maximum number of patients with diabetes in the world. People with diabetes are more prone to develop all types of infections. Pneumococcal infections are a common cause of morbidity and mortality, and people with diabetes are more prone to develop pneumococcal infections. With the availability of the pneumococcal vaccine, most international organizations now recommend that people with diabetes should be vaccinated against pneumococcal disease. This article tries to provide a balanced review of the place of pneumococcal vaccination in Indian diabetic patients.
Santibanez, Tammy A.; Zimmerman, Richard Kent; Nowalk, Mary Patricia; Katz Jewell, Ilene; Bardella, Inis J.
BACKGROUND Barriers to adult immunizations persist as current rates for pneumococcal polysaccharide vaccine (PPV) receipt among eligible adults remain below national goals. This study investigated potential barriers to patients receiving the PPV, including predisposing, enabling, environmental and reinforcing factors among physicians from a variety of practice and geographic settings.
Knol, Mirjam J.; Wagenvoort, Gertjan H.J.; Sanders, Elisabeth A. M.; Elberse, Karin; Vlaminckx, Bart J.; Hester E. de Melker; van der Ende, Arie
Three years after a 7-valent pneumococcal conjugate vaccine was replaced by a 10-valent pneumococcal conjugate vaccine in the Netherlands, we observed a decrease in incidence of invasive pneumococcal disease caused by Streptococcus pneumoniae serotypes 1, 5, and 7F. Our data do not support or exclude cross-protection against serotype 19A.
Disappearance of Vaccine-Type Invasive Pneumococcal Disease and Emergence of Serotype 19A in a Minority Population with a High Prevalence of Human Immunodeficiency Virus and Low Childhood Immunization Rates▿
Tasslimi, Azadeh; Sison, Erica J.; Story, Elizabeth; Alland, David; Burday, Michele; Morrison, Susan; Nalmas, Sandhya; Smith, Stephen; Thomas, Pauline A.; Wenger, Peter; Sinha, Anushua
We analyzed the epidemiology of invasive pneumococcal disease (IPD) following introduction of pneumococcal conjugated vaccine in an urban population with a 2% human immunodeficiency virus (HIV) prevalence and history of low childhood immunization rates. We observed near-elimination of vaccine-type IPD. Substantial disease remains due to non-vaccine-type pneumococci, highlighting the need to increase pneumococcal immunization among HIV-infected adults.
Full Text Available Abstract Background S. pneumoniae is the most common causative agent of meningitis, and is associated with high morbidity and mortality. We aimed to develop an integrated and representative pneumococcal meningitis mouse model resembling the human situation. Methods Adult mice (C57BL/6 were inoculated in the cisterna magna with increasing doses of S. pneumoniae serotype 3 colony forming units (CFU; n = 24, 104, 105, 106 and 107 CFU and survival studies were performed. Cerebrospinal fluid (CSF, brain, blood, spleen, and lungs were collected. Subsequently, mice were inoculated with 104 CFU S. pneumoniae serotype 3 and sacrificed at 6 (n = 6 and 30 hours (n = 6. Outcome parameters were bacterial outgrowth, clinical score, and cytokine and chemokine levels (using Luminex® in CSF, blood and brain. Meningeal inflammation, neutrophil infiltration, parenchymal and subarachnoidal hemorrhages, microglial activation and hippocampal apoptosis were assessed in histopathological studies. Results Lower doses of bacteria delayed onset of illness and time of death (median survival CFU 104, 56 hrs; 105, 38 hrs, 106, 28 hrs. 107, 24 hrs. Bacterial titers in brain and CSF were similar in all mice at the end-stage of disease independent of inoculation dose, though bacterial outgrowth in the systemic compartment was less at lower inoculation doses. At 30 hours after inoculation with 104 CFU of S. pneumoniae, blood levels of KC, IL6, MIP-2 and IFN- γ were elevated, as were brain homogenate levels of KC, MIP-2, IL-6, IL-1β and RANTES. Brain histology uniformly showed meningeal inflammation at 6 hours, and, neutrophil infiltration, microglial activation, and hippocampal apoptosis at 30 hours. Parenchymal and subarachnoidal and cortical hemorrhages were seen in 5 of 6 and 3 of 6 mice at 6 and 30 hours, respectively. Conclusion We have developed and validated a murine model of pneumococcal meningitis.
Jonathan F Mosser
Full Text Available BACKGROUND: Young children played a major role in pneumococcal nasopharyngeal carriage, acquisition, and transmission in the era before pneumococcal conjugate vaccine (PCV use. Few studies document pneumococcal household dynamics in the routine-PCV7 era. METHODS: We investigated age-specific acquisition, household introduction, carriage clearance, and intra-household transmission in a prospective, longitudinal, observational cohort study of pneumococcal nasopharyngeal carriage in 300 American Indian households comprising 1,072 participants between March 2006 and March 2008. RESULTS: Pneumococcal acquisition rates were 2-6 times higher in children than adults. More household introductions of new pneumococcal strains were attributable to children <9 years than adults ≥17 years (p<0.001, and older children (2-8 years than younger children (<2 years (p<0.008. Compared to children <2 years, carriage clearance was more rapid in older children (2-4 years, HRclearance 1.53 [95% CI: 1.22, 1.91]; 5-8 years, HRclearance 1.71 [1.36, 2.15] and adults (HRclearance 1.75 [1.16, 2.64]. Exposure to serotype-specific carriage in older children (2-8 years most consistently increased the odds of subsequently acquiring that serotype for other household members. CONCLUSIONS: In this community with a high burden of pneumococcal colonization and disease and routine PCV7 use, children (particularly older children 2-8 years drive intra-household pneumococcal transmission: first, by acquiring, introducing, and harboring pneumococcus within the household, and then by transmitting acquired serotypes more efficiently than household members of other ages.
Full Text Available Abstract Background Community-acquired pneumonia (CAP has large impact on direct healthcare costs, especially those derived from hospitalization. This study determines impact, clinical characteristics, outcome and economic consequences of CAP in the adult (≥18 years population attended in 6 primary-care centers and 2 hospitals in Badalona (Spain over a two-year period. Methods Medical records were identified by codes from the International Classification of Diseases in databases (January 1st 2008-December 31st 2009. Results A total of 581 patients with CAP (55.6% males, mean age 57.5 years were identified. Prevalence: 0.64% (95% CI: 0.5%-0.7%; annual incidence: 3.0 cases/1,000 inhabitants (95% CI: 0.2-0.5. Up to 241 (41.5% required hospitalization. Hospital admission was associated (pS pneumoniae was identified in 57.5% cases. Time to recovery was 29.9±17.2 days. Up to 7.5% inpatients presented complications, 0.8% required ICU admission and 19.1% readmission. Inhospital mortality rate was 2.5%. Adjusted mean total cost was €2,332.4/inpatient and €698.6/outpatient (p Conclusions Strategies preventing CAP, thus reducing hospital admissions could likely produce substantial costs savings in addition to the reduction of CAP burden.
Rai, Aswathy N; Thornton, Justin A; Stokes, John; Sunesara, Imran; Swiatlo, Edwin; Nanduri, Bindu
Streptococcus pneumoniae is the most common bacterial etiology of pneumococcal pneumonia in adults worldwide. Genomic plasticity, antibiotic resistance and extreme capsular antigenic variation complicates the design of effective therapeutic strategies. Polyamines are ubiquitous small cationic molecules necessary for full expression of pneumococcal virulence. Polyamine transport system is an attractive therapeutic target as it is highly conserved across pneumococcal serotypes. In this study, we compared an isogenic deletion strain of S. pneumoniae TIGR4 in polyamine transport operon (ΔpotABCD) with the wild type in a mouse model of pneumococcal pneumonia. Our results show that the wild type persists in mouse lung 24 h post infection while the mutant strain is cleared by host defense mechanisms. We show that intact potABCD is required for survival in the host by providing resistance to neutrophil killing. Comparative proteomics analysis of murine lungs infected with wild type and ΔpotABCD pneumococci identified expression of proteins that could confer protection to wild type strain and help establish infection. We identified ERM complex, PGLYRP1, PTPRC/CD45 and POSTN as new players in the pathogenesis of pneumococcal pneumonia. Additionally, we found that deficiency of polyamine transport leads to up regulation of the polyamine synthesis genes speE and cad in vitro. PMID:27247105
Frederiksen, B.; Specht, L.; Henrichsen, J.;
Antibody response to pneumococcal vaccination was studied in 76 patients with Hodgkin's disease (HD) before, during and at different time intervals after cessation of therapy. All patients were in pathological stage I and II following explorative laparatomy with splenectomy. The increase in...... antibody response was compared to the findings in 12 healthy volunteers with the aim of establishing the optimal time for vaccination. Serum antibodies against 6 of the pneumococcal polysaccharide antigens (types 1, 4, 7F, 14, 18C and 23F) contained in the vaccine were determined by an ELISA. Antibody...... response to pneumococcal type antigens was similar in healthy adults and in patients with early stage HD before therapy. After treatment, postvaccination antibody response became negligible. Even up to 7 years after cessation of therapy patients were not able to raise a significant antibody response...
Frederiksen, B; Specht, L; Henrichsen, J;
Antibody response to pneumococcal vaccination was studied in 76 patients with Hodgkin's disease (HD) before, during and at different time intervals after cessation of therapy. All patients were in pathological stage I and II following explorative laparatomy with splenectomy. The increase in...... antibody response was compared to the findings in 12 healthy volunteers with the aim of establishing the optimal time for vaccination. Serum antibodies against 6 of the pneumococcal polysaccharide antigens (types 1, 4, 7F, 14, 18C and 23F) contained in the vaccine were determined by an ELISA. Antibody...... response to pneumococcal type antigens was similar in healthy adults and in patients with early stage HD before therapy. After treatment, postvaccination antibody response became negligible. Even up to 7 years after cessation of therapy patients were not able to raise a significant antibody response....
Hoogman, M.; Beek, D. van de; Weisfelt, M.; Gans, J. de; Schmand, B.
OBJECTIVE: To evaluate cognitive outcome in adult survivors of bacterial meningitis. METHODS: Data from three prospective multicentre studies were pooled and reanalysed, involving 155 adults surviving bacterial meningitis (79 after pneumococcal and 76 after meningococcal meningitis) and 72 healthy c
Harboe, Zitta B; Benfield, Thomas L; Valentiner-Branth, Palle;
BACKGROUND: Pneumococcal infections have historically played a major role in terms of morbidity and mortality. We explored historical trends of invasive pneumococcal disease (IPD) and pneumococcal serotypes in a population exposed to limited antibiotic selective pressure and conjugate pneumococcal...... vaccination (PCV). METHODS: Retrospective cohort study based on nationwide laboratory surveillance data on IPD collected uninterruptedly in Denmark during 1938-2007. Changes in the reported incidence and trends of pneumococcal serotypes were explored using nonlinear regression analysis. RESULTS: There were 25...... serotype 19A increased before introduction of PCV. Between 1993 and 2007, the level of resistance to macrolides and beta-lactams was 6%. CONCLUSIONS: The epidemiology of IPD and single serotypes has constantly changed over the past 7 decades. PCV serotypes appeared to dominate the pneumococcal population....
Tin Tin Htar, Myint; Madhava, Harish; Balmer, Paul; Christopoulou, Dina; Menegas, Damianos; Bonnet, Eric
Introduction Streptococcus pneumoniae is the leading cause of bacterial meningitis. Young children, the elderly and those who are immunocompromised or who suffer from chronic diseases have the highest risk of developing pneumococcal meningitis. A 7-valent pneumococcal conjugate vaccine (PCV7) was licensed in 2000 in the US and in 2001 in Europe. Methods A literature search was performed in PubMed to identify studies assessing the impact of routine childhood PCV7 vaccination on pneumococcal di...
Masamitsu Kono; Muneki Hotomi; Hollingshead, Susan K.; Briles, David E.; Noboru Yamanaka
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, ...
Shelly A. McNeil
Full Text Available Background. Routine vaccination against Streptococcus pneumoniae is recommended in Canada for infants, the elderly, and individuals with chronic comorbidity. National incidence and burden of all-cause and pneumococcal pneumonia in Canada (excluding Quebec were assessed. Methods. Incidence, length of stay, and case-fatality rates of hospitalized all-cause and pneumococcal pneumonia were determined for 2004–2010 using ICD-10 discharge data from the Canadian Institutes for Health Information Discharge Abstract Database. Population-at-risk data were obtained from the Statistics Canada census. Temporal changes in pneumococcal and all-cause pneumonia rates in adults ≥65 years were analyzed by logistic regression. Results. Hospitalization for all-cause pneumonia was highest in children 70 years and declined significantly from 1766/100,000 to 1537/100,000 per year in individuals aged ≥65 years (P<0.001. Overall hospitalization for pneumococcal pneumonia also declined from 6.40/100,000 to 5.08/100,000 per year. Case-fatality rates were stable (11.6% to 12.3%. Elderly individuals had longer length of stay and higher case-fatality rates than younger groups. Conclusions. All-cause and pneumococcal pneumonia hospitalization rates declined between 2004 and 2010 in Canada (excluding Quebec. Direct and indirect effects from pediatric pneumococcal immunization may partly explain some of this decline. Nevertheless, the burden of disease from pneumonia remains high.
Kronborg, Gitte; Madsen, Hans O; Pedersen, Svend S;
Invasive pneumococcal disease is a serious infection that primarily affects very young children and elderly or immunocompromised individuals but also affects previously healthy people. Variant mannose-binding lectin (MBL) alleles are associated with recurrent infections and may be a risk factor for...... pneumococcal infections. To assess the influence of MBL genotypes on the course and outcome of invasive pneumococcal disease, clinical data for 141 adult patients were collected prospectively and their genotypes were determined. All patients included had positive blood cultures for Streptococcus pneumoniae....... The distribution of variant MBL alleles related to low MBL serum concentrations was similar among the patients and healthy individuals, and MBL genotype was not associated with infection outcome. Thus, in a random adult population with invasive pneumococcal infection, MBL does not seem to play a role...
U.S. Department of Health & Human Services — NNDSS - Table II. Invasive Pneumococcal to Legionellosis - 2016. In this Table, provisional* cases of selectedâ notifiable diseases (â¥1,000 cases reported during...
U.S. Department of Health & Human Services — NNDSS - Table II. Invasive Pneumococcal to Legionellosis - 2015.In this Table, provisional cases of selected notifiable diseases (â¥1,000 cases reported during the...
U.S. Department of Health & Human Services — NNDSS - Table II. Invasive Pneumococcal to Legionellosis - 2014.In this Table, all conditions with a 5-year average annual national total of more than or equals...
Aim: Resistance to antibiotics is better. Between should not be in capitals. Antibiotics resistant has been increasing in pneumococci that cause serious diseases such as pneumonia, meningitis in recent years. The resistance rates vary between geographic regions. In this study, we aimed to determine antibiotic resistance rates in pneumococcal infections in our region. Material and Method: This study included 31 pneumococcal strains isolated from blood, CSF and urine samples of patients with me...
Francesca Fortunato; Domenico Martinelli; Maria Giovanna Cappelli; Vanessa Cozza; Rosa Prato
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
... 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 ...
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
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
Lee, Hyunju; Choi, Eun Hwa; Lee, Hoan Jong
The 7-valent pneumococcal protein conjugate vaccine (PCV7) has been shown to be highly efficacious against invasive pneumococcal diseases and effective against pneumonia and in reducing otitis media. The introduction of PCV7 has resulted in major changes in the epidemiology of pneumococcal diseases. However, pneumococcal vaccines induce serotype-specific immunity, and a relative increase in non-vaccine serotypes has been reported following the widespread use of PCV7, leading to a need for ext...
Sarah J Glennie; Banda, Dominic; Mulwafu, Wakisa; Nkhata, Rose; Neil A Williams; Heyderman, Robert S.
Worldwide, invasive pneumococcal disease caused by Streptococcus pneumoniae is most common in young children. In adults, disease rates decline following intermittent colonization and the acquisition of naturally acquired immunity. We characterized mucosal and systemic pneumococcal-specific T-cell responses in African children and adults who contend with intense rates of colonization, up to 100% and 60% respectively. We find most Malawian children have high pneumococcal-specific T-cell respons...
Bogaert, D.; Veenhoven, R.H.; Sluijter, M.; Wannet, W. J. W.; Rijkers, G.T.; Mitchell, T J; Clarke, S. C.; Goessens, W.H.F.; Schilder, A. G.; Sanders, E. A. M.; de Groot, R.; Hermans, P. W. M.
A randomized double-blind trial with a 7-valent pneumococcal conjugate vaccine was conducted in The Netherlands among 383 children, aged 1 to 7 years, with a history of recurrent acute otitis media. No effect of vaccination on the pneumococcal colonization rate was found. However, a shift in serotype distribution was clearly observed (R. Veenhoven et al., Lancet 361:2189-2195, 2003). We investigated the molecular epidemiology of 921 pneumococcal isolates retrieved from both the pneumococcal v...
Carolina Regis Leite; Jailton Azevedo; Vivian Santos Galvão; Otávio Moreno-Carvalho; Joice Neves Reis; Cristiana Nascimento-Carvalho
Abstract Invasive pneumococcal disease is a relevant public health problem in Brazil, especially among children and the elderly. In July/2010 a 10-valent pneumococcal conjugate vaccine was introduced to the immunization schedule of Brazilian children under two years of age. Between July/2010 and December/2013 we conducted a case-series study on invasive pneumococcal disease in Salvador, Brazil to describe the clinical and bacteriological profile of invasive pneumococcal disease cases during t...
Harboe, Zitta B; Valentiner-Branth, Palle; Benfield, Thomas;
In order to provide an estimation of the direct and indirect benefits of pneumococcal vaccination with three protein-conjugate pneumococcal vaccines (PCV) we described the epidemiology and mortality from invasive pneumococcal disease (IPD) in Denmark between 2000 and 2005. Approximately 1080 case...
Harboe, Z.B.; Valentiner-Branth, P.; Benfield, T.L.;
In order to provide an estimation of the direct and indirect benefits of pneumococcal vaccination with three protein-conjugate pneumococcal vaccines (PCV) we described the epidemiology and mortality from invasive pneumococcal disease (IPD) in Denmark between 2000 and 2005. Approximately 1080 cases...
Papadatou, Ioanna; Spoulou, Vana
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
Richard, C; Le Garlantezec, P; Lamand, V; Rasamijao, V; Rapp, C
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
Öbrink-Hansen, Kristina; Søgaard, Ole S; Harboe, Zitta B;
(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......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...
Kim, K H; Seoh, J. Y.
Antibodies to a capsular polysaccharide (PS) provide protection against Streptococcus pneumoniae which express the homologous capsular serotype, and pneumococcal vaccines are designed to induce antibodies in the capsular PS. Levels and opsonophagocytic capacity of antibodies to the capsular PS of S. pneumoniae serotype 19F were determined by sera from adults immunized with 23-valent S. pneumoniae capsular PS vaccines. Geometric means of IgG anti-19F antibody level and specific opsonic titer r...
Ingels, Helene; Lambertsen, Lotte; Harboe, Zitta B;
Abstract Background: Pneumococcal diseases play a major role in human morbidity and mortality. We present the results of a Danish nationwide study of recurrent paediatric invasive pneumococcal disease (rIPD) focusing on the epidemiological, microbiological, and clinical aspects. Methods: All......%, and 78% of the cases would have been covered by the 7-, 10-, and 13-valent pneumococcal conjugate vaccines, respectively. Conclusions: Of children with an IPD episode, 2.4% experienced rIPD, and an underlying disease was documented in 66% of these children. Investigation of underlying conditions is...... positive culture. Clinical data were obtained for all children with rIPD. Results: Of all children with IPD, 2.4% (59/2418) experienced at least 1 episode of rIPD, and an underlying condition was documented in 39 (66%). Immune deficiency due to transplantation (n = 9) was the most common disease; however...
Yu. V. Lobzin
Full Text Available First in Russia prospective non-interventional hospital-based study on Streptococcus pneumoniae serotypes causing meningitis and acute otitis media (AOM in children and community-acquired pneumonia (CAP in children and adults, as well as serotype coverage by pneumococcal conjugate vaccines (PCV’s of different composition has been conducted. Serotypes 19F, 14 and serogroup 6 are the leading in meningitis; serotype coverage is 70,6% for PCV7, and 76,5% – for PCV10 and PCV13. Among S. pneumoniae serotypes causing AOM 19F, 3, 23F and serogroup 6 have been the most prevalent in Saint Petersburg. PCV7 and PCV10 provide equal serotypes coverage in AOM – 63,2% among children 0–2 years old, and 32,5% among children 5–17 years old. PCV13 covers up to 79% of serotypes in infants. In CAP PCV7 and PCV10 provide 57,1% serotype coverage in children and 56,1% – in adults. Serotype coverage in CAP for PCV13 has been 14,3% and 34,5% higher for children and adults, correspondingly. Obtained data supports PCV inclusion in children immunization program in Saint Petersburg, whereas PCV13 provides the broadest serotype coverage. In the course PCV’s implementation continued pneumococcal infection surveillance is advisable.
Møller, Holger Jon; Moestrup, Søren K; Weis, Nina;
probability of survival when sCD163 and CRP were known (p = .25). CONCLUSIONS: Macrophage marker response in pneumococcal bacteremia was compromised in old age. In patients <75 yrs old, sCD163 was superior to other markers, including C-reactive protein, in predicting fatal disease outcome....... pneumococcal bacteremia. DESIGN: Observational cohort study. SETTING: Five university hospitals in Denmark. PATIENTS: A total of 133 patients with Streptococcus pneumoniae bacteremia (positive blood culture) and 133 age- and gender-matched controls. INTERVENTIONS: Samples were collected for biochemical...
Harboe, Zitta Barrella; Dalby, Tine; Weinberger, Daniel M;
BACKGROUND: The impact of the 13-valent pneumococcal conjugate vaccine (PCV13) at the population level is unclear. We explored PCV13's effect in reducing invasive pneumococcal disease (IPD)-related morbidity and mortality, and whether serotype-specific changes were attributable to vaccination or...... expected as a part of natural, cyclical variations. METHODS: This was a Danish nationwide population-based cohort study based on the linkage of laboratory surveillance data and the Danish Civil Registration System. Changes in IPD incidence and mortality during baseline (2000-2007), 7-valent pneumococcal...... the shift from PCV7 to PCV13 in the national immunization program. This decline was accompanied by a substantial population-level decline in pneumococcal-related mortality of nearly 30% among nonvaccinated persons....
Ifedayo M O Adetifa
Full Text Available BACKGROUND: Introduction of pneumococcal vaccines in Nigeria is a priority as part of the Accelerated Vaccine Introduction Initiative (AVI of the Global Alliance for Vaccines and Immunisation (GAVI. However, country data on the burden of pneumococcal disease (IPD is limited and coverage by available conjugate vaccines is unknown. This study was carried out to describe the pre vaccination epidemiology and population biology of pneumococcal carriage in Nigeria. METHODS: This was a cross sectional survey. Nasopharyngeal swabs (NPS were obtained from a population sample in 14 contiguous peri-urban Nigerian communities. Data on demographic characteristics and risk factor for carriage were obtained from all study participants. Pneumococci isolated from NPS were characterised by serotyping, antimicrobial susceptibility and Multi Locus Sequencing Typing (MLST. RESULTS: The prevalence of pneumococcal carriage was 52.5%. Carriage was higher in children compared to adults (67.4% vs. 26%, highest (≈90% in infants aged <9 months and reduced significantly with increasing age (P<0.001. Serotypes 19F (18.6% and 6A (14.4% were most predominant. Potential vaccine coverage was 43.8%, 45.0% and 62% for PCV-7, PCV-10 and PCV-13 respectively. There were 16 novel alleles, 72 different sequence types (STs from the isolates and 3 Sequence Types (280, 310 and 5543 were associated with isolates of more than one serotype indicative of serotype switching. Antimicrobial resistance was high for cotrimoxazole (93% and tetracycline (84%, a third of isolates had intermediate resistance to penicillin. Young age was the only risk factor significantly associated with carriage. CONCLUSIONS: Pneumococcal carriage and serotype diversity is highly prevalent in Nigeria especially in infants. Based on the coverage of serotypes in this study, PCV-13 is the obvious choice to reduce disease burden and prevalence of drug resistant pneumococci. However, its use will require careful
Breukels, Mijke A.; Zandvoort, Andre; van den Dobbelsteen, Germie P. J. M.; van den Muijsenberg, Adrie; Lodewijk, Monique E.; Beurret, Michel; Pieter A Klok; Timens, Wim; Rijkers, Ger T.
Protection against infections with Streptococcus pneumoniae depends on the presence of antibodies against capsular polysaccharides that facilitate phagocytosis. Asplenic patients are at increased risk for pneumococcal infections, since both phagocytosis and the initiation of the antibody response to polysaccharides take place in the spleen. Therefore, vaccination with pneumococcal polysaccharide vaccines is recommended prior to splenectomy, which, as in the case of trauma, is not always feasi...
Full Text Available In Italy, the effectiveness of pneumococcal universal vaccination in preventing vaccine-type invasive pneumococcal disease (IPD in the PCV7/PCV13 shifting period was estimated to be 84.3% (95% CI: 84.0–84.6% in children <5 years. This study aims at corroborating the estimation of both the effectiveness (VE of PCVs and its impact in reducing pneumococcal diseases. A 1 : 3 matched-case-control study was conducted among children <5 years old hospitalized for IPD or pneumococcal pneumonia (PP between 2006 and 2012 in the Puglia region. Moreover, hospitalizations for pneumococcal outcomes in the pre- and postvaccination period and the hospitalization risk ratios (HRRs with 95% CIs were computed in Italy and in the first eight regions that introduced PCVs in 2006. The overall effectiveness of PCVs was 75% (95% CI: 61%–84%; it was 69% (95% CI: 30%–88% against IPD and 77% (95% CI: 61%–87% against PP. PCVs showed a significant impact on IPD and acute otitis media either at a national level or in those regions with a longer vaccination history, with a nearly 40% reduction of hospitalizations for both outcomes. Our findings provide further evidence of the effectiveness of PCVs against pneumococcal diseases and its impact on nasopharyngeal carriage in children <5 years, indicating the importance of maintaining high immunization coverage.
Full Text Available Pathogen-specific antibody plays an important role in protection against pneumococcal carriage and infections. However, neonates and infants exhibit impaired innate and adaptive immune responses, which result in their high susceptibility to pneumococci. To protect neonates and infants against pneumococcal infection it is important to elicit specific protective immune responses at very young ages. In this study, we investigated the protective immunity against pneumococcal carriage, pneumonia, and sepsis induced by maternal immunization with pneumococcal surface protein A (PspA. Mother mice were intranasally immunized with recombinant PspA (rPspA and cholera toxin B subunit (CTB prior to being mated. Anti-PspA specific IgG, predominantly IgG1, was present at a high level in the serum and milk of immunized mothers and in the sera of their pups. The pneumococcal densities in washed nasal tissues and in lung homogenate were significantly reduced in pups delivered from and/or breast-fed by PspA-immunized mothers. Survival after fatal systemic infections with various types of pneumococci was significantly extended in the pups, which had received anti-PspA antibody via the placenta or through their milk. The current findings strongly suggest that maternal immunization with PspA is an attractive strategy against pneumococcal infections during early childhood.
Van Steenkiste, M
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
Al-Tawfiq, Jaffar A; Memish, Ziad A
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
Full Text Available Abstract Background Pneumococcal disease is the leading cause of vaccine-preventable death in children younger than 5 years of age worldwide. The World Health Organization recommends pneumococcal conjugate vaccine as a priority for inclusion into national childhood immunization programmes. Pneumococcal vaccine has yet to be included as part of the national vaccination programme in Malaysia although it has been available in the country since 2005. This study sought to estimate the disease burden of pneumococcal disease in Malaysia and to assess the cost effectiveness of routine infant vaccination with PCV7. Methods A decision model was adapted taking into consideration prevalence, disease burden, treatment costs and outcomes for pneumococcal disease severe enough to result in a hospital admission. Disease burden were estimated from the medical records of 6 hospitals. Where local data was unavailable, model inputs were obtained from international and regional studies and from focus group discussions. The model incorporated the effects of herd protection on the unvaccinated adult population. Results At current vaccine prices, PCV7 vaccination of 90% of a hypothetical 550,000 birth cohort would incur costs of RM 439.6 million (US$128 million. Over a 10 year time horizon, vaccination would reduce episodes of pneumococcal hospitalisation by 9,585 cases to 73,845 hospitalisations with cost savings of RM 37.5 million (US$10.9 million to the health system with 11,422.5 life years saved at a cost effectiveness ratio of RM 35,196 (US$10,261 per life year gained. Conclusions PCV7 vaccination of infants is expected to be cost-effective for Malaysia with an incremental cost per life year gained of RM 35,196 (US$10,261. This is well below the WHO's threshold for cost effectiveness of public health interventions in Malaysia of RM 71,761 (US$20,922.
Sankilampi, U.; Herva, E.; Haikala, R.; Liimatainen, O.; Renkonen, O. V.; Leinonen, M.
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
Susanna Esposito; Nicola Principi
Applications of the heptavalent pneumococcal conjugate vaccine (PCV7) in the pediatric immunization schedule have dramatically reduced the incidence of pneumococcal diseases in both vaccinated children and unvaccinated individuals of all ages. However, increased infections caused by non-PCV7 serotypes have been reported by several groups. To overcome this problem, new vaccines covering more serotypes including the emerging serotypes have been developed. The 13-valent pneumococcal conjugate va...
Irma Gabriela Echániz Avilés; Fortino Solórzano Santos
Streptococcus pneumoniae is one of the leading causes of both invasive and noninvasive diseases in the pediatric population and continues to represent a significant public health burden worldwide. The increasing incidence of antibioticresistant strains of the pathogen has complicated treatment and management of the various pneumococcal disease manifestations. Thus, the best management strategy may be the prevention of pneumococcal diseases through vaccination. Although several pneumococcal co...
Käyhty, H; Eskola, J.
Streptococcus pneumoniae is a major cause of acute otitis media, pneumonia, bacteremia, and meningitis. Because in recent years antibiotic-resistant pneumococcal strains have been emerging throughout the world, vaccination against pneumococcal infections has become more urgent. The capsular polysaccharide vaccine that has been available is neither immunogenic nor protective in young children and other immunocompromised patients. Several pneumococcal proteins have been proposed as candidate va...
Tvedebrink, Torben; Lundbye-Christensen, Søren; Thomsen, Reimar W.;
The seasonal nature of invasive pneumococcal disease with peak incidences during winter months is well recognized (Dowell 2003, Talbot 2005, Watson 2006). However few detailed studies of the temporal relationship between actual climatic changes and subsequent pneumococcal disease are available. We...... perform an 8-year longitudinal population-based ecological study in a Danish county to examine whether foregoing changes in meteorological parameters, including temperature, relative humidity, precipitation, and wind velocity, predicted variations in pneumococcal bacteremia (PB) incidence....
Hillegonda Maria Dutilh Novaes
Full Text Available OBJECTIVE: To estimate hospitalization rates for pneumococcal disease based on the Brazilian Hospital Information System (SIH. METHODS: Descriptive study based on the Hospital Information System of Brazilian National Health System data from January 2004 to December 2006: number of hospitalizations and deaths for pneumococcal meningitis, pneumococcal sepsis, pneumococcal pneumonia and Streptococcus pneumoniae as the cause of diseases reported in Brazil. Data from the 2003 Brazilian National Household Survey were used to estimate events in the private sector. Pneumococcal meningitis cases and deaths reported to the Notifiable Diseases Information System during the study period were also analyzed. RESULTS: Pneumococcal disease accounted for 34,217 hospitalizations in the Brazilian National Health System (0.1% of all hospitalizations in the public sector. Pneumococcal pneumonia accounted for 64.8% of these hospitalizations. The age distribution of the estimated hospitalization rates for pneumococcal disease showed a "U"-shape curve with the highest rates seen in children under one (110 to 136.9 per 100,000 children annually. The highest hospital case-fatality rates were seen among the elderly, and for sepsis and meningitis. CONCLUSIONS: PD is a major public health problem in Brazil. The analysis based on the SIH can provide an important input to pneumococcal disease surveillance and the impact assessment of immunization programs.
Adrienne Morrow; Philippe De Wals; Geneviève Petit; Maryse Guay; Lonny James Erickson
BACKGROUND: In the United States, implementation of the seven-valent conjugate vaccine into childhood immunization schedules has had an effect on the burden of pneumococcal disease in all ages of the population. To evaluate the impact in Canada, it is essential to have an estimate of the burden of pneumococcal disease before routine use of the vaccine.METHODS: The incidence and costs of pneumococcal disease in the Canadian population in 2001 were estimated from various sources, including publ...
Zielen, S; Bühring, I.; Strnad, N.; Reichenbach, J; Hofmann, D.
There is still a lack of effective vaccination strategies for patients with a deficient antibody response to bacterial polysaccharide antigens. In an open trial, we evaluated the immunogenicity and tolerance of a new 7-valent pneumococcal conjugate vaccine in 22 infection-prone nonresponders to pneumococcal polysaccharide vaccine and 21 controls. In the patient group, nonresponsiveness was confirmed by repeated vaccination with a 23-valent pneumococcal polysaccharide vaccine. The study protoc...
Song, Joon Young; Cheong, Hee Jin; Heo, Jung Yeon; Noh, Ji Yun; Seo, Yu Bin; Kim, In Seon; Choi, Won Suk; Kim, Woo Joo
Purpose Despite the ready availability of pneumococcal vaccine, vaccination rates are quite low in South Korea. This study was designed to assess perceptions and awareness about pneumococcal vaccines among subjects at risk and find strategies to increases vaccine coverage rates. Materials and Methods A cross sectional, community-based survey was conducted to assess perceptions about the pneumococcal vaccine at a local public health center. In a tertiary hospital, an outpatient-based pneumococ...
Winther, Thilde N; Kristensen, Tim D; Kaltoft, Margit S;
Aim: The aim of this study was to document the epidemiology, microbiology and outcome of invasive pneumococcal disease (IPD) among children <16 years with quality surveillance data, just prior to the introduction of the heptavalent pneumococcal conjugate vaccine (PCV7) into the Danish routine......, but considerably higher, 62 per 100 000, in children <2 years. Additionally, of the children with pneumococcal meningitis 86% were <2 years. We observed no fatalities. A total of 10% developed sequelae, but of the patients with pneumococcal meningitis 27% developed sequelae. Nine patients had known...... all IPD cases among children <2 years are caused by PCV7 serotypes and might therefore be prevented by PCV7 vaccination....
Winther, Thilde N; Kristensen, Tim D; Kaltoft, Margit S;
Aim: The aim of this study was to document the epidemiology, microbiology and outcome of invasive pneumococcal disease (IPD) among children <16 years with quality surveillance data, just prior to the introduction of the heptavalent pneumococcal conjugate vaccine (PCV7) into the Danish routine......, but considerably higher, 62 per 100 000, in children <2 years. Additionally, of the children with pneumococcal meningitis 86% were <2 years. We observed no fatalities. A total of 10% developed sequelae, but of the patients with pneumococcal meningitis 27% developed sequelae. Nine patients had known...
Griffin, Marie R.; Zhu, Yuwei; Moore, Matthew R.; Whitney, Cynthia G.; Grijalva, Carlos G.
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
Brandt, Christian; Frimodt-Moller, N; Lundgren, Jens Dilling;
OBJECTIVE: Bacteraemia concomitant with meningitis has been shown to greatly affect outcome. Consequently, the efficacy of serotype-specific anti-pneumococcal antiserum (APAS) was investigated in a rat model of pneumococcal meningitis. METHODS: Rats were infected with Streptococcus pneumoniae...... serotype 3. All rats received ceftriaxone starting 26 h post-infection. APAS was administered either at the time of infection or 26 h post-infection and effects were compared with rats treated with antibiotics only. RESULTS AND CONCLUSION: A significant clinical benefit was found when APAS was given at the...... time of infection whereas no effect was found when administered 26 h after infection. This work indicates that the clinical value of using APAS in pneumococcal meningitis may be limited...
Findlay, P.; Gibbons, Y; Primrose, W; Ellis, G.; Downie, G
The efficacy of the influenza vaccine in reducing mortality and hospital admissions is established, particularly in the elderly. However, up to 50% of those at risk do not receive the vaccine. These patients are also at risk from pneumococcal infection and there is considerable overlap between the target group for each vaccine. This study sought to identify at risk individuals from consecutive admissions to an acute geriatric unit and to gain an insight into their perceptions with regard to v...
Daniel M. Musher
Full Text Available Longstanding controversy over the efficacy of 23‐valentpneumococcal polysaccharide vaccine (PPV23 led to arecommendation by the Joint Committee on Vaccinationand Immunisation (JCVI of the United Kingdom in March2011, to discontinue routine use of PPV23 in older adults.1Following careful review of the evidence and feedbackfrom stakeholders, the JCVI decided to retain the originalpolicy of uniform vaccination of adults >65 years of age,while keeping the subject under continued review. In theUnited States, the Advisory Committee on ImmunizationPractices (ACIP which is also concerned about the efficacyof PPV23 is currently considering a different strategy, i.e.adding 13‐valent pneumococcal protein‐conjugate vaccine(PCV13 for recommended use in adults, following recentFood and Drug Administration (FDA approval for thispurpose in adults over 50 years of age. It is thereforetimely to review the options for prevention ofpneumococcal disease in adults.
Full Text Available Aim: Resistance to antibiotics is better. Between should not be in capitals. Antibiotics resistant has been increasing in pneumococci that cause serious diseases such as pneumonia, meningitis in recent years. The resistance rates vary between geographic regions. In this study, we aimed to determine antibiotic resistance rates in pneumococcal infections in our region. Material and Method: This study included 31 pneumococcal strains isolated from blood, CSF and urine samples of patients with meningitis, sepsis and urinary tract infections who admitted Dicle University Medicine School Children Clinic and Diyarbakir Pediatric Hospital Between December 2004-April 2007. Reproducing clinical specimens with alpha-hemolysis, optochin-sensitive, bile soluble and gram-positive diplococci morphology was defined as S. pneumoniae. The antimicrobial susceptibilities of strains were measured by the E-test method. MIC values of penicillin against pneumococci was accepted as <0.06 mg / ml value of the sensitive, 0.12-1μg/ml mid-level resistance, ≥ 2 mg / ml value of the high-level resistance. Results: It was found 16% mid-level penicillin resistance and 3.2% high-level penicillin resistance by E-test method. 80.7% of Strains were percent of the penicillin-sensitive. Seftiriakson resistance was found as 3.2%. there was not Vancomycin resistance. Discussion: We think penicillin therapy is enough effective for pneumococcal infections except serious conditions such as meningitis and sepsis. Also we think it should be supported by multicenter studies.
Julie Y. Zhou
Full Text Available Nasopharyngeal (NP pneumococcal carriage predisposes children to pneumococcal infections. Defining the proportion of pneumococcal isolates that are antibiotic-resistant enables the appropriate choice of empiric therapies. The antibiogram of NP carriage isolates derived from a pediatric population following the introduction of the 13-valent pneumococcal conjugate vaccine was defined in this study.
Full Text Available The 7-valent pneumococcal conjugate vaccine (PCV7 is currently being introduced in the vaccine schedule of over 90 countries around the world. After the introduction of the PCV7 vaccine in the United States, a reduction of more than 90% of invasive pneumococcal disease (IPD was reported in vaccinated children under the age of 5 years. Similar findings were reported from other countries. A reduction in community-acquired pneumonia (CAP of > 40% has also been reported. In children under the age of 5 years, the number of primary medical visits and antibiotic usage for acute otitis media (AOM decreased by more than 40%. In adults over 65 years of age a significant reduction of 90% in IPD caused by PCV7 serotypes was reported as well. However, after the introduction of PCV7 there were reports of increase of serotypes not included in the vaccine, such as serotype 19A in various Streptococcus pneumoniae-related diseases such as invasive disease, AOM and pneumonia. In addition, serotypes 1, 5, 7F and 19A were more prevalent in complicated cases of CAP. Recently, new vaccines covering additional serotypes such as the 10-valent pneumococcal conjugate vaccine (PCV10 and 13-valent pneumococcal conjugate vaccine (PCV13 were introduced, and are expected to reduce S. pneumoniae-related diseases furthermore.
... 42 Public Health 2 2010-10-01 2010-10-01 false Pneumococcal vaccine and flu vaccine. 410.57 Section 410.57 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES MEDICARE PROGRAM SUPPLEMENTARY MEDICAL INSURANCE (SMI) BENEFITS Medical and Other Health Services § 410.57 Pneumococcal vaccine and flu...
Sparding, Nadja; Dayie, Nicholas Tete Kwaku Dzifa; Mills, Richael O.;
Streptococcus pneumoniae is a major cause of morbidity and mortality worldwide. Pneumococcal strains are classified according to their capsular polysaccharide and more than 90 different serotypes are currently known. In this project, three distinct groups of pneumococcal carriage isolates from Gh...
Sarah J Glennie
Full Text Available Worldwide, invasive pneumococcal disease caused by Streptococcus pneumoniae is most common in young children. In adults, disease rates decline following intermittent colonization and the acquisition of naturally acquired immunity. We characterized mucosal and systemic pneumococcal-specific T-cell responses in African children and adults who contend with intense rates of colonization, up to 100% and 60% respectively. We find most Malawian children have high pneumococcal-specific T-cell responses in tonsil tissue and peripheral blood. In addition, frequent commensalism generates CD25(hi (Tregs which modulate mucosal pneumococcal-specific T-cell responses in some children and ≥50% of adults. We propose that immune regulation may prolong pneumococcal colonization and predispose vulnerable individuals to disease.
Harboe, Zitta Barrella; Larsen, Mette Vang; Ladelund, Steen;
BACKGROUND: Invasive pneumococcal disease (IPD) is an important cause of morbidity among HIV-infected individuals. We described incidence and risk factors for IPD in HIV-infected and uninfected individuals. METHODS: Nationwide population-based cohort study of HIV-infected adults treated at all...
Full Text Available BACKGROUND: Introduction of pneumococcal conjugate vaccines (PCVs of limited valency is justified in Africa by the high burden of pneumococcal disease. Long-term beneficial effects of PCVs may be countered by serotype replacement. We aimed to determine the impact of PCV-7 vaccination on pneumococcal carriage in rural Gambia. METHODS AND FINDINGS: A cluster-randomized (by village trial of the impact of PCV-7 on pneumococcal nasopharyngeal carriage was conducted in 21 Gambian villages between December 2003 to June 2008 (5,441 inhabitants in 2006. Analysis was complemented with data obtained before vaccination. Because efficacy of PCV-9 in young Gambian children had been shown, it was considered unethical not to give PCV-7 to young children in all of the study villages. PCV-7 was given to children below 30 mo of age and to those born during the trial in all study villages. Villages were randomized (older children and adults to receive one dose of PCV-7 (11 vaccinated villages or meningococcal serogroup C conjugate vaccine (10 control villages. Cross-sectional surveys (CSSs to collect nasopharyngeal swabs were conducted before vaccination (2,094 samples in the baseline CSS, and 4-6, 12, and 22 mo after vaccination (1,168, 1,210, and 446 samples in CSS-1, -2, and -3, respectively. A time trend analysis showed a marked fall in the prevalence of vaccine-type pneumococcal carriage in all age groups following vaccination (from 23.7% and 26.8% in the baseline CSS to 7.1% and 8.5% in CSS-1, in vaccinated and control villages, respectively. The prevalence of vaccine-type pneumococcal carriage was lower in vaccinated than in control villages among older children (5 y to <15 y of age and adults (≥15 y of age at CSS-2 (odds ratio [OR] = 0.15 [95% CI 0.04-0.57] and OR = 0.32 [95% CI 0.10-0.98], respectively and at CSS-3 (OR = 0.37 [95% CI 0.15-0.90] for older children, and 0% versus 7.6% for adults in vaccinated and control villages, respectively
Medina, Marcela; Vintiñi, Elisa; Villena, Julio; Raya, Raul; Alvarez, Susana
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...
Hodges, G R; Worley, S E; Degener, C E; Clark, G M
The response to type 3 pneumococcal polysaccharide vaccination, the protective effect of type 3 pneumococcal polysaccharide vaccination, and the ability of hemagglutinating antibody to type 3 pneumococcal polysaccharide to cross the blood-brain barrier were studied in rats. Hemagglutinating antibody response to vaccination with type 3 pneumococcal polysaccharide was found to be dependent on the dose and route of inoculation. Intraperitoneal vaccination with type 3 pneumococcal polysaccharide ...
Harboe, Zitta B.; Valentiner-Branth, Palle; Benfield, Thomas;
We evaluated the effectiveness of the heptavalent pneumococcal conjugate vaccine (PCV7) on invasive pneumococcal disease (IPD) 1 year after PCV7's introduction in the childhood immunization programme through a nationwide cohort study based on laboratory surveillance data. There was a decline in the...
Bogaert, D.; Veenhoven, R.H.; Sluijter, M.; Wannet, W.J.B.; Rijkers, G.T.; Mitchell, T.J.; Clarke, S.C.; Goessens, W.H.F.; Schilder, A.G.M.; Sanders, E.A.M.; Groot, R. de; Hermans, P.W.M.
A randomized double-blind trial with a 7-valent pneumococcal conjugate vaccine was conducted in The Netherlands among 383 children, aged 1 to 7 years, with a history of recurrent acute otitis media. No effect of vaccination on the pneumococcal colonization rate was found. However, a shift in serotyp
Turner, Paul; Turner, Claudia; Suy, Kuong; Soeng, Sona; Ly, Sokeng; Miliya, Thyl; Goldblatt, David; Day, Nicholas P. J.
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.
Turner, Paul; Turner, Claudia; Suy, Kuong; Soeng, Sona; Ly, Sokeng; Miliya, Thyl; Goldblatt, David; Day, Nicholas P J
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
Tatiane E. Hirose
Full Text Available OBJECTIVES: To evaluate the possible effects of the introduction of the pneumococcal conjugate 10-valent vaccine schedule in the state of Parana on pneumococcal meningitis cases and to assess the distribution of serotypes among cases. METHOD: Cross-sectional study with retrospective data collection of cases of pneumococcal meningitis in the state of Paraná reported to Sistema de Informação de Agravos de Notificação (SINAN, from 1998 to 2011. A total of 1,339 cases of pneumococcal meningitis were analyzed; 1,205 cases from the pre-vaccine period (1998-2009 were compared to 134 cases from the post-vaccine period (2010-2011. Descriptive and comparative statistical analyses (chi-squared test and prevalence ratio were performed using JMP 5.1.2 statistical software (JMP Statistical Discovery, North Carolina, USA and EPI INFO 6 (Centers for Disease Control and Prevention, Georgia, EUA. RESULTS: There was a significant reduction in the mean rates of incidence and mortality in the general population. The analysis of cases in the pre- and post-vaccination periods in the age groups covered by vaccination (younger than 2 years showed significant reductions in incidence rates (6.01 cases/100,000 to 2.49 cases/100,000 individuals and mortality (1.85 cases/100,000 population to 0.47 cases/100,000 population, while the mean lethality rate did not change significantly. There was a significant reduction in cases whose serotypes are included in the vaccine (80.7% to 53.3%. CONCLUSION: Even after a short time of use, the 10-valent pneumococcal conjugate vaccine has already had a significant impact in reducing the incidence and mortality of meningitis cases among infants, as well as the reduction of cases whose serotypes are included in the vaccine.
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.
Simell, Birgit; Nurkka, Anu; Lahdenkari, Mika; Givon-Lavi, Noga; Käyhty, Helena; Dagan, Ron; Jokinen, Jukka
Association of pneumococcal nasopharyngeal carriage with the concentration and opsonophagocytic activity (OPA) of serum serotype-specific antibodies was determined for toddlers 1 month after immunization with a 9-valent pneumococcal conjugate vaccine. Higher anti-serotype 14 and anti-serotype 19F IgG and anti-serotype 14 IgM correlated with a lowered probability of pneumococcal acquisition. Postvaccination OPA did not correlate with pneumococcal carriage.
Francis, Jacinta P.; Peter C Richmond; Pomat, William S.; Michael, Audrey; Keno, Helen; Phuanukoonnon, Suparat; Nelson, Jan B.; Whinnen, Melissa; Heinrich, Tatjana; Smith, Wendy-Anne; Prescott, Susan L.; Holt, Patrick G; Siba, Peter M.; Lehmann, Deborah; Anita H J van den Biggelaar
Immunization of pregnant women can be an efficient strategy to induce early protection in infants in developing countries. Pneumococcal protein-based vaccines may have the capacity to induce pneumococcal serotype-independent protection. To understand the potential of maternal pneumococcal protein-specific antibodies in infants in high-risk areas, we studied the placental transfer of naturally acquired antibodies to pneumolysin (Ply) and pneumococcal surface protein A family 1 and 2 (PspA1 and...
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
Host genetic variability may contribute to susceptibility of bacterial meningitis, but which genes contribute to the susceptibility to this complex disease remains undefined. We performed a genetic association study in 469 community-acquired pneumococcal meningitis cases and 2072 population-based controls from the Utrecht Health Project in order to find genetic variants associated with pneumococcal meningitis susceptibility. A HumanExome BeadChip was used to genotype 102,097 SNPs in the collected DNA samples. Associations were tested with the Fisher exact test. None of the genetic variants tested reached Bonferroni corrected significance (p-value pathophysiology of pneumococcal meningitis. PMID:27389768
Full Text Available Despite good cover with 7-valent vaccination, invasive pneumococcal infections may still be misdiagnosed and may lead to lifethreatening situations or death in young children. New serotypes are emerging and, therefore, clinicians must keep a high level of suspicion in young children regardless of their vaccination status. We report three cases of invasive pneumococcal infection due to new serotypes not covered by the 7-valent conjugated vaccine, two of which led children to death.
Daniel R Feikin
Full Text Available BACKGROUND: Vaccine-serotype (VT invasive pneumococcal disease (IPD rates declined substantially following introduction of 7-valent pneumococcal conjugate vaccine (PCV7 into national immunization programs. Increases in non-vaccine-serotype (NVT IPD rates occurred in some sites, presumably representing serotype replacement. We used a standardized approach to describe serotype-specific IPD changes among multiple sites after PCV7 introduction. METHODS AND FINDINGS: Of 32 IPD surveillance datasets received, we identified 21 eligible databases with rate data ≥ 2 years before and ≥ 1 year after PCV7 introduction. Expected annual rates of IPD absent PCV7 introduction were estimated by extrapolation using either Poisson regression modeling of pre-PCV7 rates or averaging pre-PCV7 rates. To estimate whether changes in rates had occurred following PCV7 introduction, we calculated site specific rate ratios by dividing observed by expected IPD rates for each post-PCV7 year. We calculated summary rate ratios (RRs using random effects meta-analysis. For children <5 years old, overall IPD decreased by year 1 post-PCV7 (RR 0.55, 95% CI 0.46-0.65 and remained relatively stable through year 7 (RR 0.49, 95% CI 0.35-0.68. Point estimates for VT IPD decreased annually through year 7 (RR 0.03, 95% CI 0.01-0.10, while NVT IPD increased (year 7 RR 2.81, 95% CI 2.12-3.71. Among adults, decreases in overall IPD also occurred but were smaller and more variable by site than among children. At year 7 after introduction, significant reductions were observed (18-49 year-olds [RR 0.52, 95% CI 0.29-0.91], 50-64 year-olds [RR 0.84, 95% CI 0.77-0.93], and ≥ 65 year-olds [RR 0.74, 95% CI 0.58-0.95]. CONCLUSIONS: Consistent and significant decreases in both overall and VT IPD in children occurred quickly and were sustained for 7 years after PCV7 introduction, supporting use of PCVs. Increases in NVT IPD occurred in most sites, with variable magnitude. These findings may not
Basarab, Marina; Ihekweazu, Chikwe; George, Robert; Pebody, Richard
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
Kantsø, Bjørn; Green, Nicola; Goldblatt, David;
BACKGROUND: Human immunodeficiency virus (HIV)-infected individuals are at increased risk of invasive pneumococcal disease (IPD). In order to assess the immunogenicity of pneumococcal proteins and polysaccharide, we investigated protein and serotype-specific antibody responses after HIV......-associated IPD. METHODS: Specific antipneumococcal immunoglobulin G to 27 pneumococcal protein antigens and 30 serotype polysaccharides was measured in plasma before and after IPD in HIV-infected individuals and compared to HIV-infected individuals without IPD. RESULTS: Over time, 81% of IPD cases responded to...... HIV-infected individuals with IPD had a serotype-specific antibody response. Younger age at the time of IPD was the only predictor of a serotype-specific pneumococcal antibody response, whereas we did not identify predictors of a protein-specific antibody response. CONCLUSIONS: Antibody responses...
Ota, Martin O. C.; Anna Roca; Christian Bottomley; Philip C. Hill; Uzochukwu Egere; Brian Greenwood; Adegbola, Richard A.
BACKGROUND A recent trial with PCV-7 in a rural Gambian community showed reduced vaccine-type pneumococcal carriage in fully vaccinated compared with control communities. We measured pneumococcal polysaccharide antibody concentrations in this trial to understand further the mechanisms underlying the observed changes. METHODS A single-blind, cluster-randomized (by village) trial was conducted in 21 Gambian villages. In 11 villages, all residents received PCV-7 (Vaccine group); in 10 contr...
Cremers, A.J.H.; Kokmeijer, I.; Groh, L.; Jonge, M.I. de; Ferwerda, G.
INTRODUCTION: The clinical severity and course of invasive pneumococcal disease (IPD) differs substantially between patients. Streptococcus pneumoniae harbors large genetic variability. Zinc metalloproteinase C (ZmpC), a secreted pneumococcal protein involved in neutrophil extravasation, inflammatio
Full Text Available Monocyte phenotype and output changes with age, but why this occurs and how it impacts anti-bacterial immunity are not clear. We found that, in both humans and mice, circulating monocyte phenotype and function was altered with age due to increasing levels of TNF in the circulation that occur as part of the aging process. Ly6C+ monocytes from old (18-22 mo mice and CD14+CD16+ intermediate/inflammatory monocytes from older adults also contributed to this "age-associated inflammation" as they produced more of the inflammatory cytokines IL6 and TNF in the steady state and when stimulated with bacterial products. Using an aged mouse model of pneumococcal colonization we found that chronic exposure to TNF with age altered the maturity of circulating monocytes, as measured by F4/80 expression, and this decrease in monocyte maturation was directly linked to susceptibility to infection. Ly6C+ monocytes from old mice had higher levels of CCR2 expression, which promoted premature egress from the bone marrow when challenged with Streptococcus pneumoniae. Although Ly6C+ monocyte recruitment and TNF levels in the blood and nasopharnyx were higher in old mice during S. pneumoniae colonization, bacterial clearance was impaired. Counterintuitively, elevated TNF and excessive monocyte recruitment in old mice contributed to impaired anti-pneumococcal immunity since bacterial clearance was improved upon pharmacological reduction of TNF or Ly6C+ monocytes, which were the major producers of TNF. Thus, with age TNF impairs inflammatory monocyte development, function and promotes premature egress, which contribute to systemic inflammation and is ultimately detrimental to anti-pneumococcal immunity.
Balmer, Paul; Cant, Andrew J.; Borrow, Ray
Measuring and interpretation of the immune response to pneumococcal polysaccharides is a complex field, owing to the diversity of the pneumococcal polysaccharide capsular types, different vaccine formulations including both polysaccharide and conjugate vaccines, diverse pneumococcal serological assays, lack of immunogenicity data for the conjugate in a number of at‐risk groups and complex vaccine schedules. Even the reasons for performing pneumococcal serology can be complex, as assays may be...
Gladstone, R.A.; Gritzfeld, J.F.; Coupland, P.; S. B. Gordon; Bentley, S.D.
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 ...
Age-Stratified Prevalences of Pneumococcal-Serotype-Specific Immunoglobulin G in England and Their Relationship to the Serotype-Specific Incidence of Invasive Pneumococcal Disease Prior to the Introduction of the Pneumococcal 7-Valent Conjugate Vaccine▿
Balmer, Paul; Borrow, Ray; Findlow, Jamie; Warrington, Rosalind; Frankland, Sarah; Waight, Pauline; George, Robert; Andrews, Nick; Miller, Elizabeth
Recent changes to the childhood immunization schedule in the United Kingdom have resulted in the inclusion of the 7-valent pneumococcal conjugate vaccine. However, the seroprevalence of pneumococcal antibodies in the population was unknown. To address this, we measured pneumococcal, age-specific immunoglobulin G (IgG) concentrations specific for nine serotypes by an assay run on the Bioplex platform, using 2,664 serum samples collected in England from 2000 to 2004. The lowest concentrations o...
Full Text Available Introduction . The International Circumpolar Surveillance network is a population-based surveillance system that collects data on invasive pneumococcal disease (IPD in Northern Canada. A 7-valent pneumococcal conjugate vaccine was first introduced in some regions of Northern Canada in 2002, followed by 10-valent (2009 and 13-valent (PCV-13 vaccines (2010. A 23-valent polysaccharide (PPV-23 vaccine was first introduced in 1988 for special populations and adults aged 65 years and older. To describe the epidemiology in the context of pneumococcal vaccination programs, we analysed surveillance data from Northern Canada from 1999 to 2010. Methods . A standardized case report form capturing demographic and clinical information was completed for all IPD cases in Northern Canada meeting the national case definition. Isolates were sent to a reference laboratory for confirmation, serotyping and antimicrobial resistance testing. Both laboratory and epidemiological data were sent to the Public Health Agency of Canada for analysis. Population denominators were obtained from Statistics Canada. Results . From 1999 to 2010, 433 IPD cases were reported (average 36 cases per year. Incidence was greatest among infants aged <2 years and among those aged 65 years and older, with an average annual incidence of 133 and 67 cases per 100,000 population, respectively. After a peak in incidence in 2008, rates among infants have declined. Incidence rates varied from 2 to 16 times greater, depending on the year, among Aboriginals compared to non-Aboriginals. Hospitalization was reported in 89% of all cases and the case fatality ratio was 6.0%. Clinical manifestations varied, with some patients reporting >1 manifestation. Pneumonia was the most common (70%, followed by bacteremia/septicaemia (30% and meningitis (8%. Approximately, 42% of cases aged <2 years in 2009 and 2010 had serotypes covered by the PCV-13. In addition, the majority (89% of serotypes isolated in cases
Echániz-Avilés Irma Gabriela
Full Text Available Streptococcus pneumoniae is one of the leading causes of both invasive and noninvasive diseases in the pediatric population and continues to represent a significant public health burden worldwide. The increasing incidence of antibioticresistant strains of the pathogen has complicated treatment and management of the various pneumococcal disease manifestations. Thus, the best management strategy may be the prevention of pneumococcal diseases through vaccination. Although several pneumococcal conjugate vaccines have been clinically studied in infants and children, only a 7-valent conjugate vaccine (PNCRM7; Prevnar®/Prevenar® is currently approved for the prevention of invasive disease. Vaccination with PNCRM7 is safe and effective in infants and young children. Routine vaccination with the conjugate vaccine could improve outcomes by safeguarding against the development of antibiotic-resistant strains of S. pneumoniae, thus simplifying the management of pneumococcal disease. Additionally, the overall costs associated with the treatment of pneumococcal diseases could be substantially reduced, particularly in developing countries. The time has come for fully applying this new advancement against S. pneumoniae, to benefit the children of the world. The Spanish version of this paper is available at: http://www.insp.mx/salud/index.html
Vestrheim, Didrik F; Høiby, E Arne; Bergsaker, Marianne R; Rønning, Karin; Aaberge, Ingeborg S; Caugant, Dominique A
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 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
Full Text Available Abstract Background Streptococcus pneumoniae is a major cause of human disease, especially in pre-school children and elderly people, as well as in special risk groups such as asplenic, antibody deficient patients, or presenting disruption of natural barriers. The occurrence of pneumococcal disease has increased with the onset of the HIV epidemic and the emergence of drug-resistance. Case presentation We report the case of an HIV-1-infected patient who experienced three episodes of recurrent pneumococcal meningitis over a 4-year period, despite chemoprophylaxis and capsular vaccination. Conclusions Efficacy of anti-pneumococcal chemoprophylaxis and vaccination in HIV-infected patients are discussed in the light of this particular case.
Engelen-Lee, Joo-Yeon; Brouwer, Matthijs C.; Aronica, Eleonora; de Beek, Diederik van
Pneumococcal meningitis is associated with substantial mortality and morbidity. We systematically assessed brain histopathology of 31 patients who died of pneumococcal meningitis from a nationwide study (median age 67 years; 21 (67 %) were male) using a pathology score including inflammation and vascular damage. Of the 27 patients with known time from the admission to death, 14 patients died within 7 days of admission and 13 after 7 days of admission. Eleven of 25 (44 %) patients had been tre...
Full Text Available Abstract Background Conflicting results have been recently reported evaluating the relationship between pneumococcal vaccination and the risk of thrombotic vascular events. This study assessed the clinical effectiveness of the 23-valent polysaccharide pneumococcal vaccine (PPV23 against acute myocardial infarction and ischaemic stroke in older adults. Methods Population-based prospective cohort study conducted from December 1, 2008 until November 30, 2009, including all individuals ≥ 60 years-old assigned to nine Primary Care Centres in Tarragona, Spain (N = 27,204 individuals. Primary outcomes were hospitalisation for acute myocardial infarction and/or ischaemic stroke. All cases were validated by checking clinical records. The association between pneumococcal vaccination and the risk of each outcome was evaluated by Multivariable Cox proportional-hazard models (adjusted by age, sex, influenza vaccine status, presence of comorbidities and cardiovascular risk factors. Results Cohort members were followed for a total of 26,444 person-years, of which 34% were for vaccinated subjects. Overall incidence rates (per 1000 person-years were 4.9 for myocardial infarction and 4.6 for ischaemic stroke. In the multivariable analysis, vaccination was associated with a marginally significant 35% lower risk of stroke (hazard ratio [HR]: 0.65; 95% confidence interval [CI]: 0.42-0.99; p = 0.046. We found no evidence for an association between pneumococcal vaccination and reduced risk of myocardial infarction (HR: 0.83; 95% CI: 0.56-1.22; p = 0.347. Conclusions Our data supports a benefit of PPV23 against ischaemic stroke among the general population over 60 years, suggesting a possible protective role of pneumococcal vaccination against some acute thrombotic events.
Martin O C Ota
Full Text Available BACKGROUND: A recent trial with PCV-7 in a rural Gambian community showed reduced vaccine-type pneumococcal carriage in fully vaccinated compared with control communities. We measured pneumococcal polysaccharide antibody concentrations in this trial to understand further the mechanisms underlying the observed changes. METHODS: A single-blind, cluster-randomized (by village trial was conducted in 21 Gambian villages. In 11 villages, all residents received PCV-7 (Vaccine group; in 10 control villages only children 5.0 µg/mL for all but serotype 9V of the PCV-7 serotypes in the older group, but not in the younger age group. CONCLUSION: Higher antibodies in vaccinated communities provide an explanation for the lower pneumococcal carriage rates in fully vaccinated compared to control communities. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN51695599 51695599.
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
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 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
Ingels, Helene; Schejbel, Lone; Lundstedt, A C;
BACKGROUND: Recurrent invasive pneumococcal disease (rIPD) occurs mostly in children with an underlying disease, but some cases remain unexplained. Immunodeficiency has been described in children with rIPD, but the prevalence is unknown. We used a nationwide registry of all laboratory-confirmed c...
Dr. George Nelson, a CDC medical officer, discusses the relationship between pneumococcal pneumonia and Pandemic H1N1. Created: 6/6/2012 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID). Date Released: 6/6/2012.
Full Text Available Abstract Background Streptococcus pneumoniae is the leading cause of bacterial meningitis. Pneumococcal meningitis is associated with the highest mortality among bacterial meningitis and it may also lead to neurological sequelae despite the use of antibiotic therapy. Experimental animal models of pneumococcal meningitis are important to study the pathogenesis of meningitis, the host immune response induced after infection, and the efficacy of novel drugs and vaccines. Results In the present work, we describe in detail a simple, reproducible and efficient method to induce pneumococcal meningitis in outbred mice by using the intracranial subarachnoidal route of infection. Bacteria were injected into the subarachnoid space through a soft point located 3.5 mm rostral from the bregma. The model was tested with several doses of pneumococci of three capsular serotypes (2, 3 and 4, and mice survival was recorded. Lethal doses killing 50 % of animals infected with type 2, 3 and 4 S. pneumoniae were 3.2 × 10, 2.9 × 10 and 1.9 × 102 colony forming units, respectively. Characterisation of the disease caused by the type 4 strain showed that in moribund mice systemic dissemination of pneumococci to blood and spleen occurred. Histological analysis of the brain of animals infected with type 4 S. pneumoniae proved the induction of meningitis closely resembling the disease in humans. Conclusions The proposed method for inducing pneumococcal meningitis in outbred mice is easy-to-perform, fast, cost-effective, and reproducible, irrespective of the serotype of pneumococci used.
Engelen-Lee, Joo-Yeon; Brouwer, Matthijs C; Aronica, Eleonora; van de Beek, Diederik
Pneumococcal meningitis is associated with substantial mortality and morbidity. We systematically assessed brain histopathology of 31 patients who died of pneumococcal meningitis from a nationwide study (median age 67 years; 21 (67 %) were male) using a pathology score including inflammation and vascular damage. Of the 27 patients with known time from the admission to death, 14 patients died within 7 days of admission and 13 after 7 days of admission. Eleven of 25 (44 %) patients had been treated with adjunctive dexamethasone therapy. Observed pathological processes were inflammation of medium-large arteries in 30 brains (97 %), cerebral haemorrhage in 24 (77 %), cerebritis in 24 (77 %), thrombosis in 21 (68 %), infarction in 19 (61 %) and ventriculitis in 19 (of 28 cases, 68 %). Inflammation of medium-large arteries led to obstruction of the vascular lumen in 14 (of 31 cases, 45 %). Vascular inflammation was associated with infarction and thrombosis of brain parenchymal vessels. Hippocampal dentate gyrus apoptosis between patients treated with and without dexamethasone was similar (p = 0.66); however, dexamethasone treated patients had higher total pathology score than non-dexamethasone treated patients (p = 0.003). Our study shows that vascular damage is key in the process of brain damage in pneumococcal meningitis. Data and material of this study will be made open-access for translational research in pneumococcal meningitis (MeninGene-Path). PMID:27001057
Full Text Available BACKGROUND: Recently, the 13-valent pneumococcal conjugate vaccine (PCV13 has been recommended for adults. We analyzed the epidemiology of invasive pneumococcal disease (IPD in older adults in Spain before PCV13 introduction. METHODOLOGY/PRINCIPAL FINDINGS: IPD episodes, defined as clinical findings together with an invasive pneumococcal isolate, were prospectively collected from patients aged over 65 years in three hospitals in Spain from 2007 to 2009. A total of 335 IPD episodes were collected. Pneumonia was the main clinical syndrome, while chronic obstructive pulmonary disease, diabetes mellitus and cancer were the main underlying diseases. Pneumococcal isolates were serotyped and the molecular typing was performed by PFGE/MLST. PCV13 serotypes accounted for 59.3% of isolates, the most prevalent being serotypes 19A (15.1%, 3 (9.6%, 7F (7.5%, 14 (6.9% and 1 (5.4%. The most frequent non-PCV13 serotypes were serotypes 16F (4.5%, 22F (3.6%, 24F (3.3% and 6C (2.1%. The most common genotypes were CC230 (8.5%, serotypes 19A and 24F, CC156 (8.2%, serotypes 9V and 14, ST191 (7.9%, serotype 7F, CC260 (6.6%, serotype 3, ST306 (5.2%, serotype 1, CC30 (4.6%, serotype 16F and ST433 (3.6%, serotype 22F. Comparing the 335 IPD isolates to 174 invasive pneumococci collected at the same hospitals in 1999-2000, PCV7 serotypes decreased (45.4% vs 18.4%,p<0.001, non-PCV7 serotypes included in PCV13 increased (26.4% vs 41.0%,p = 0.001 and two non-PCV13 serotypes increased (serotype 6C 0% vs 2.1%, p = 0.05; serotype 24F 0.6% vs 3.3%, p = 0.04,. CONCLUSION: In our older adult population two serotypes (19A and 3 included in PCV13 accounted for about a quarter of IPD episodes in people ≥65 years. Non-PCV13 emerging serotypes should be carefully monitored in future surveillance studies.
Schaballie, H; Wuyts, G; Dillaerts, D; Frans, G; Moens, L; Proesmans, M; Vermeulen, F; De Boeck, K; Meyts, I; Bossuyt, X
During the past 10 years, pneumococcal conjugate vaccine (PCV) has become part of the standard childhood vaccination programme. This may impact upon the diagnosis of polysaccharide antibody deficiency by measurement of anti-polysaccharide immunoglobulin (Ig)G after immunization with unconjugated pneumococcal polysaccharide vaccine (PPV). Indeed, contrary to PPV, PCV induces a T-dependent, more pronounced memory response. The antibody response to PPV was studied retrospectively in patients referred for suspected humoral immunodeficiency. The study population was divided into four subgroups based on age (2-5 years versus ≥ 10 years) and time tested (1998-2005 versus 2010-12). Only 2-5-year-old children tested in 2010-12 had been vaccinated with PCV prior to PPV. The PCV primed group showed higher antibody responses for PCV-PPV shared serotypes 4 and 18C than the unprimed groups. To a lesser extent, this was also found for non-PCV serotype 9N, but not for non-PCV serotypes 19A and 8. Furthermore, PCV-priming elicited a higher IgG2 response. In conclusion, previous PCV vaccination affects antibody response to PPV for shared serotypes, but can also influence antibody response to some non-PCV serotypes (9N). With increasing number of serotypes included in PCV, the diagnostic assessment for polysaccharide antibody deficiency requires careful selection of serotypes that are not influenced by prior PCV (e.g. serotype 8). Further research is needed to identify more serotypes that are not influenced. PMID:26939935
Tsigrelis, Constantine; Tleyjeh, Imad M.; Huskins, W. Charles; Lahr, Brian D.; Nyre, Lisa M.; Virk, Abinash; Baddour, Larry M.
OBJECTIVE: To examine the effect of the 7-valent pneumococcal conjugate vaccine in a well-characterized population in Olmsted County, Minnesota, with a combination of urban and rural residents likely to have a relatively low risk of invasive pneumococcal disease (IPD).
Gladstone, R.A.; Jefferies, J. M.; Faust, S. N.; Clarke, S. C.
Streptococcus pneumoniae, also known as the pneumococcus, is an important cause of morbidity and mortality in the developed and developing world. Pneumococcal conjugate vaccines were first introduced for routine use in the USA in 2000, although the seven-valent pneumococcal conjugate vaccine (PCV7) was not introduced into the UK's routine childhood immunization programme until September 2006. After its introduction, a marked decrease in the incidence of pneumococcal disease was observed, both...
Rozenbaum, Mark H.; Van Hoek, Albert Jan; Fleming, Douglas; Caroline L Trotter; Miller, Elizabeth; Edmunds, W John
Objective To estimate the cost effectiveness of vaccinating people with high risk conditions against invasive pneumococcal disease using the 13 valent pneumococcal conjugate vaccine. Design Economic evaluation using a cohort model from the perspective of healthcare providers. Setting England. Participants People aged 2 years and older at increased risk of invasive pneumococcal disease due to chronic kidney disease; splenic dysfunction; HIV infection; a compromised immune system; chronic heart...
Zhang, Xiaochun; Simmerman, Kelly; Yen-Lieberman, Belinda; Daly, Thomas M.
The response to pneumococcal vaccination can be used to assess a patient's humoral immune response to polysaccharide antigens. Multiplex assays measuring serotype-specific levels of pneumococcal antibodies are often used for this purpose, and clinical algorithms have been published to assist in the definition of an adequate immune response. We evaluated whether interlaboratory variability in multiplex pneumococcal serology assays would affect the clinical classification of the immune response...
This thesis describes the chemical structures of the capsular polysaccharides from Streptococcus pneumoniae types 18B, 32F, and 32A. The structure of the pneumococcal common antigen, C-polysaccharide, from a non-capsulated pneumococcal strain, CSR SCS2, is described and the structure of the C-polysaccharide associated with pneumococcal types 18B, 32F, and 32A. Two distinct forms of C-polysaccharide were demonstrated, mono- or disubstituted with phosphorylcholine. In addi...
Coats, Mamie T.; Murphy, Trudy; James C Paton; Gray, Barry; Briles, David E.
Pneumococcal hemolytic uremic syndrome is recognized in a small portion of otherwise healthy children who have or have recently had Streptococcus pneumoniae infections, including severe pneumonia, meningitis, and bacteremia. As in other types of hemolytic uremic syndrome (HUS), pneumococcal HUS is characterized by microangiopathic hemolytic anemia, and thrombocytopenia, usually with extensive kidney damage. Although not demonstrated in vivo, the pathogenesis of pneumococcal HUS has been attri...
Full Text Available UNLABELLED: Renal transplant recipients are at increased risk of developing invasive pneumococcal diseases but may have poor response to the 23-valent pneumococcal polysaccharide vaccine (PPV. It may be possible to enhance immunogenicity by priming with 7-valent pneumococcal conjugate vaccine (7vPnC and boosting with PPV 1 year later. In a randomized single-blind, controlled study, adult recipients of renal transplants received either 7nPVC or PPV followed by PPV 1 year later. The vaccine response was defined as 2-fold increase in antibody concentration from baseline and an absolute post-vaccination values ≥1 µg/ml. The primary endpoint was vaccine response of the primed group (7vPnC/PPV compared with single PPV vaccination. Antibody concentrations for 10 serotypes were measured at baseline, 8 weeks after first vaccination, before second vaccination, and 8 weeks after second vaccination. Of 320 screened patients, 80 patients were randomized and 62 completed the study. Revaccination with PPV achieved no significant increase of immune response in the 7vPnC/PPV group compared with the single PPV recipients A response to at least 1 serotype was seen in 77.1% of patients who received 7vPnC and 93.1% of patients who received PPV (P = 0.046. After second vaccination response to at least 1 serotype was seen in 87.5% patients of 7vPnC/PPV group and 87.1% patients of PPV group (non significant p. The median number of serotypes eliciting a response was 3.5 (95% CI 2.5-4.5 in the 7vPnC/PPV group versus 5 (95% CI 3.9-6.1 in the PPV group (non-significant p. Immunogenicity of pneumococcal vaccination was not enhanced by the prime-boost strategy compared with vaccination with PPV alone. Administration of a single dose of PPV should continue to be the standard of care for adult recipients of renal transplants. TRIAL REGISTRATION: EudraCT 2007-004590-25.
Scott, Jennifer R.; Millar, Eugene V.; Lipsitch, Marc; Moulton, Lawrence H.; Weatherholtz, Robert; Perilla, Mindy J.; Jackson, Delois M.; Beall, Bernard; Craig, Mariddie J.; Reid, Raymond; Santosham, Mathuram; O’Brien, Katherine L.
Background. We assessed the impact of 12 years of pneumococcal conjugate vaccine (PCV7) use on pneumococcal nasopharyngeal carriage and serotype-specific invasive disease potential among Native Americans.
Full Text Available Abstract Background Epidemiological studies suggest that inhalation of carbonaceous particulate matter from biomass combustion increases susceptibility to bacterial pneumonia. In vitro studies report that phagocytosis of carbon black by alveolar macrophages (AM impairs killing of Streptococcus pneumoniae. We have previously reported high levels of black carbon in AM from biomass smoke-exposed children and adults. We therefore aimed to use a mouse model to test the hypothesis that high levels of carbon loading of AM in vivo increases susceptibility to pneumococcal pneumonia. Methods Female outbred mice were treated with either intranasal phosphate buffered saline (PBS or ultrafine carbon black (UF-CB in PBS; 500 μg on day 1 and day 4, and then infected with S. pneumoniae strain D39 on day 5. Survival was assessed over 72 h. The effect of UF-CB on AM carbon loading, airway inflammation, and a urinary marker of pulmonary oxidative stress was assessed in uninfected animals. Results Instillation of UF-CB in mice resulted a pattern of AM carbon loading similar to that of biomass-smoke exposed humans. In uninfected animals, UF-CB treated animals had increased urinary 8-oxodG (P = 0.055, and an increased airway neutrophil differential count (P . pneumoniae, whereas morbidity and mortality after infection was reduced in UF-CB treated animals (median survival 48 h vs. 30 h, P . pneumoniae colony forming unit counts, and lower airway levels of keratinocyte-derived chemokine/growth-related oncogene (KC/GRO, and interferon gamma. Conclusion Acute high level loading of AM with ultrafine carbon black particles per se does not increase the susceptibility of mice to pneumococcal infection in vivo.
Full Text Available Abstract Background The 23-valent pneumococcal polysaccharide vaccine (PPV23 is recommended for persons aged Methods Population-based data on all episodes of IPD (positive blood or cerebrospinal fluid culture reported by Finnish clinical microbiology laboratories during 1995–2002 were linked to data in national health care registries and vital statistics to obtain information on the patient's preceding hospitalisations, co-morbidities, and outcome of illness. Results Overall, 4357 first episodes of IPD were identified in all age groups (average annual incidence, 10.6/100,000. Patients aged 18–49 and 50–64 years accounted for 1282 (29% and 934 (21% of IPD cases, of which 372 (29% and 427 (46% had a current PPV23 indication, respectively. Overall, 536 (12% IPD patients died within one month of first positive culture. Persons aged 18–64 years accounted for 254 (47% of all deaths (case-fatality proportion, 12%. Of those who died 117 (46% did not have a vaccine indication. In a survival model, patients with alcohol-related diseases, non-haematological malignancies, and those aged 50–64 years were most likely to die. Conclusion In the general population of non-elderly adults, almost two-thirds of IPD and half of fatal cases occurred in persons without a recognised PPV23 indication. Policymakers should consider additional prevention strategies such as lowering the age of universal PPV23 vaccination and introducing routine childhood pneumococcal conjugate immunisation which could provide substantial health benefits to this population through indirect vaccine effects.
Christa Claes; Johann-Matthias Graf von der Schulenburg
Background: The introduction of the conjugate vaccine PnC-7 implies that a pneumococcal vaccine is available, for the first time, which also gives children under the age of 2 years reliable protection against invasive pneumococcal infections and offers some protection against non-invasive pneumococcal infections. Objective and perspective: In the context of a multiple-period Markov model, a cost-effectiveness analysis of a recommendation for general pneumococcal vaccination in Germany for inf...
Dias, Joana Gomes; Hruba, Frantiska; Lopalco, Pier Luigi; Pastore-Celentano, Lucia; Gauci, Andrew J. Amato
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 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
Song, Joon Young; Nahm, Moon H.; Cheong, Hee Jin; Kim, Woo Joo
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
McCavit, Timothy L.; Quinn, Charles T.; Techasaensiri, Chonnamet; Rogers, Zora R.
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.
Brandt, Christian; Peters, David Alberg; Liptrot, Matthew George;
Background. Bacteremia plays a major role in the outcome of pneumococcal meningitis. This experimental study investigated how bacteremia influences the pathophysiologic profile of the brain. Methods. Rats with Streptococcus pneumoniae meningitis were randomized to 1 of 3 groups of infected study ....... The different end points affected by the systemic and local infectious processes should be addressed in future studies. © 2008 by the Infectious Diseases Society of America. All rights reserved....
Pallarés Giner, Roman; Viladrich, P F; Liñares Louzao, Josefina; Cabellos Mínguez, Ma. Carmen; Gudiol i Munté, Francesc
Over the past three decades, penicillin-resistant pneumococci have emerged worldwide. In addition, penicillin-resistant strains have also decreased susceptibility to other β-lactams (including cephalosporins) and these strains are often resistant to other antibiotic groups, making the treatment options much more difficult. Nevertheless, the present in vitro definitions of resistance to penicillin and cephalosporins in pneumococci could not be appropriated for all types of pneumococcal infecti...
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.
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 adhesi...
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.
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
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
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
Mitchell William S
Full Text Available Abstract Background Influenza and pneumococcal vaccination are recommended for a number of clinical risk groups including patients treated with major immunosuppressant disease modifying anti-rheumatic drugs. Such immunisation is not only safe but immunogenic in patients with rheumatic diseases. We sought to establish dual vaccination rates and significant influencing factors amongst our hospital rheumatology outpatients. Method We audited a sample of 101 patients attending hospital rheumatology outpatient clinics on any form of disease modifying treatment by clinical questionnaire and medical record perusal. Further data were collected from the local immunisation coordinating agency and analysed by logistic regression modelling. Results Although there was a high rate of awareness with regard to immunisation, fewer patients on major immunosuppressants were vaccinated than patients with additional clinical risk factors against influenza (53% vs 93%, p Conclusion Influenza and pneumococcal immunisation is suboptimal amongst patients on current immunosuppressant treatments attending rheumatology outpatient clinics. Raising awareness amongst patients may not be sufficient to improve vaccination rates and alternative strategies such as obligatory pneumococcal vaccination prior to treatment initiation and primary care provider education need to be explored.
Full Text Available Streptococcus pneumoniae is an important cause of morbidity and mortality in Southeast Asia, but regional data is limited. Updated burden estimates are critical as pneumococcal conjugate vaccine (PCV is highly effective, but not yet included in the Expanded Program on Immunization of Thailand or neighboring countries.We implemented automated blood culture systems in two rural Thailand provinces as part of population-based surveillance for bacteremia. Blood cultures were collected from hospitalized patients as clinically indicated.From May 2005- March 2010, 196 cases of pneumococcal bacteremia were confirmed in hospitalized patients. Of these, 57% had clinical pneumonia, 20% required mechanical ventilation, and 23% (n = 46 died. Antibiotic use before blood culture was confirmed in 25% of those with blood culture. Annual incidence of hospitalized pneumococcal bacteremia was 3.6 per 100,000 person-years; rates were higher among children aged <5 years at 11.7 and adults ≥65 years at 14.2, and highest among infants <1 year at 33.8. The median monthly case count was higher during December-March compared to the rest of the year 6.0 vs. 1.0 (p<0.001. The most common serotypes were 23F (16% and 14 (14%; 61% (74% in patients <5 years were serotypes in the 10-valent PCV (PCV 10 and 82% (92% in <5 years in PCV 13. All isolates were sensitive to penicillin, but non-susceptibility was high for co-trimoxazole (57%, erythromycin (30%, and clindamycin (20%.We demonstrated a high pneumococcal bacteremia burden, yet underestimated incidence because we captured only hospitalized cases, and because pre-culture antibiotics were frequently used. Our findings together with prior research indicate that PCV would likely have high serotype coverage in Thailand. These findings will complement ongoing cost effectiveness analyses and support vaccine policy evaluation in Thailand and the region.
John J. Murray; Joseph Akamah; Oghenerukevwe Odiete; Olagoke Akinwande
Following the development of penicillin, complications from streptococcus pneumonia such as endocarditis have become rare. However, certain independent risk factors such as cigarette smoking and being of African-American (AA) decent have been associated with a higher incidence of invasive pneumococcal disease, but only cigarette smoking has been targeted by current recommendations from the Advisory Committee on Immunological Practices (ACIPs). We report a case of a young AA smoker, who develo...
Abdoulie Bojang; James Jafali; Uzochukwu E Egere; Hill, Phillip C.; Martin Antonio; David Jeffries; Greenwood, Brian M.; Anna Roca
Background We conducted an ancillary study among individuals who had participated in a PCV-7 trial in rural Gambia, to determine the influence of season on the prevalence of pneumococcal carriage. Methods 636 individuals above 30 months of age were followed from 4 to 20 months after vaccination with PCV-7 or meningococcal-conjugate-vaccine. Nasopharyngeal swabs were collected periodically between November 2006 and June 2008. Overall, 4,495 NPS were collected. Results Prevalence of pneumococca...
肺炎链球菌(即肺炎球菌)导致的疾病在世界各地都是严重的公共健康问题,包括肺炎、脑膜炎、发热性菌血症、中耳炎、鼻窦炎、气管炎等感染.体内外研究显示,肺炎球菌多糖疫苗对成年人肺炎球菌引发的疾病能起到积极的预防作用,但由于多糖疫苗无法刺激产生持续的抗体应答,所以不适用于2岁以下的婴幼儿;而将荚膜多糖与载体蛋白耦联的结合型肺炎球菌疫苗对2岁以下的婴幼儿或免疫缺陷的人群起到积极的保护作用,扩大了使用范围,提高了保护力.本文阐述了预防肺炎球菌疾病疫苗的研究进展,从全菌体疫苗、以菌体荚膜多糖为成分的多糖疫苗直到多糖结合疫苗的发展过程.同时总结了目前国内外结合疫苗的研究现状,认为应将开发安全、有效、价格合理、对肺炎球菌性疾病保护范围广的肺炎球菌疫苗作为高度优先的研究项目.%The diseases caused by Streptococcus pneumoniae (pneumococcus) are serious public health problems around the world, including pneumonia, meningitis, febrile bacteraemia, otitis media,sinusitis and bronchitis. In vivo studies have shown that pneumococcal polysaccharide vaccine can play an active role in prevention of pneumococcal diseases in adults. Because polysaccharide vaccine can not stimulate to produce sustained antibody response,it dose not refer to infants under two years old. And the conjugated pneumococcal vaccine of capsular polysaccharides and carrier protein plays an actively protective role for infants under two years old or immunocompromised people,expands the scope of use,and improves the protection force. This article reports the research progress of pneumococcal vaccine,the development from the whole bacterial vaccine, polysaccharide vaccine composed by bacterial capsular polysaccharide to polysaccharide conjugate vaccine. This review also summarizes the current research status of vaccine at home and
Roed, Casper; Engsig, Frederik Neess; Omland, Lars; Skinhøj, Peter; Obel, Niels
The objective of the study was to determine the long-term mortality and the causes of death in patients diagnosed with pneumococcal meningitis. The authors performed a nationwide, population-based cohort study including all Danish patients diagnosed with pneumococcal meningitis from 1977 through ...
Pneumococcal glycoconjugate vaccines are now used in infant immunization schedules, globally. Pneumococcal polysaccharide vaccines are still, however, advised from the second year of life to provide broader serotype coverage. The use of these polysaccharide vaccines has been under review, especially for children.
Ostrowska, KI; Rotstein, C.; Thornley, JH; Mandell, LA
The first case of pneumococcal endometritis with peritonitis in a woman using tampons is described. The patient responded to removal of the tampon and administration of broad spectrum antibiotics. The pathogenesis of pneumococcal endometritis and peritonitis and the potential significance of a tampon in situ are discussed.
Bello Gonzalez, T.; Rivera-Olivero, I.A.; Pocaterra, L.; Spadola, E.; Araque, M.; Hermans, P.W.M.; Waard, J.H. de
In North America, the indigenous groups have been identified as a population with increased risk of pneumococcal colonization and pneumococcal invasive disease. However, little information is available from South American natives. In the present study we evaluated the nasopharyngeal carriage and ser
Mirsaeidi, Mehdi; Ebrahimi, Golnaz; Allen, Mary Beth; Aliberti, Stefano
Chronic pulmonary diseases describe chronic diseases that affect the airways and lung parenchyma. Examples of common chronic pulmonary diseases include asthma, bronchiectasis, chronic obstructive lung disease, lung fibrosis, sarcoidosis, pulmonary hypertension and cor pulmonale. Pulmonary infection is considered a significant cause of mortality in patients with chronic pulmonary diseases. Streptococcus pneumoniae is the leading isolated bacteria from adult patients with community-acquired pne...
Indianara Maria Grando
Full Text Available The objective of this study was to analyze the impact of vaccination against Streptococcus pneumoniae on the morbidity and mortality from pneumococcal meningitis in children ≤ 2 years in Brazil, from 2007 to 2012. This is a descriptive study and ecological analysis using data from the Information System on Notifiable Diseases. Pre-vaccination (2007-2009 and post-vaccination (2011-2012 periods were defined to compare incidence rates and mortality. A total of 1,311 cases and 430 deaths were reported during the study period. Incidence decreased from 3.70/100,000 in 2007 to 1.84/100,000 in 2012, and mortality decreased from 1.30/100,000 to 0.40/100,000, or 50% and 69% respectively, with the greatest impact in the 6-11 month age group. This decrease in Pneumococcal meningitis morbidity and mortality rates two years after introduction of the 10-valent pneumococcal conjugate vaccine suggests its effectiveness.
Guevara, Marcela; Ezpeleta, Carmen; Gil-Setas, Alberto; Torroba, Luis; Beristain, Xabier; Aguinaga, Aitziber; García-Irure, José Javier; Navascués, Ana; García-Cenoz, Manuel; Castilla, Jesús
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
Blaabjerg, Anne Katrine; Schumacher, Anna Holst; Kantsø, Bjørn;
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...
Lundbo, Lene F; Harboe, Zitta Barrella; Clausen, Louise N;
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...... 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....... 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...
Pneumococcal disease is an important reason of morbidity and hospitalization among adults and children. Among 91 serotypes of pneumococcus, approximately 20 serotypes are responsible for >85% of invasive pneumococcal disease in all age groups. 23-valent pneumococcal polysaccharide vaccine ( PPV23) , which contains 23 serotypes that collectively accounted for most cases (85% ~90% ) of invasive pneumococcal disease (IPD) a-mong adults, is considered safe and with high efficacy. Effectiveness of PPV23 generally has shown that the vaccine was 50% ～ 80% effective in preventing IPD among immunocompetent adults and individuals with various underlying illnesses who are not severely immunosuppressed. The cost-benefit studies show that PPV23 immunization is valuable for children and adult. Vaccination of PPV23 is recommended for children with immunodeficiency, elderly group aged＞60 years, and adult with chronic disease. This paper mainly reviewed the safety, immunological reaction, protective rate, cost-benefit, effect among special population and immunization strategy of PPV23.%肺炎球菌是导致成人和儿童罹患肺炎疾病住院甚至死亡的重要原因.肺炎球菌的91个血清型中有20种血清型与各年龄组超过85％的侵袭性肺炎球菌感染有关.根据23种引起85％ - 90％的引起肺炎球菌感染疾病的血清型研制而成的23价肺炎球菌多糖疫苗,具有很好的安全性,成人和＞2岁儿童接种后会产生可靠的免疫力,在人群中保护率达50％～80％,具有较好的成本效益比,是儿童和成人预防肺炎球菌感染的有效措施,推荐用于60岁以上老年人和2岁以上体弱儿童和慢性疾病患者.本文主要对23价肺炎球菌多糖疫苗的安全性、免疫反应、保护率及成本效益、对特殊健康状况人群的保护效果和免疫策略作一综述.
Streptococcus pneumoniae colonisation in children and adolescents with asthma: impact of the heptavalent pneumococcal conjugate vaccine and evaluation of potential effect of thirteen-valent pneumococcal conjugate vaccine
Esposito, S.; L. Terranova; M.F. Patria; Marseglia, G L; Miraglia del Giudice, M; Bodini, A; Martelli, A.; Baraldi, E; O. Mazzina; Tagliabue, C.; A. Licari; V. Ierardi; M. Lelii; Principi, N
Background The main aim of this study was to evaluate Streptococcus pneumoniae carriage in a group of school-aged children and adolescents with asthma because these results might indicate the theoretical risk of invasive pneumococcal disease (IPD) of such patients and the potential protective efficacy of the 13-valent pneumococcal conjugate vaccine (PCV13). Methods Oropharyngeal samples were obtained from 423 children with documented asthma (300 males, 70.9 %), and tested for the autolysin-A-...
Fortuin-de Smit, Melony; Madhi, Shabir A.; O'Brien, Katherine L.; Zell, Elizabeth R; Whitney, Cynthia G.; Moore, David; Verwey, Charl; Varughese, Sheeba; Archary, Moherndran; Naby, Fathima; Dawood, Khathija; Naidoo, Ramola; Elliott, Gene; Hallbauer, Ute; Eley, Brian
Background. South Africa introduced 7-valent pneumococcal conjugate vaccine (PCV7) in April 2009 using a 2 + 1 schedule (6 and 14 weeks and 9 months). We estimated the effectiveness of ≥2 PCV7 doses against invasive pneumococcal disease (IPD) in human immunodeficiency virus (HIV)–infected and -uninfected children. Methods. IPD (pneumococcus identified from a normally sterile site) cases were identified through national laboratory-based surveillance. Specimens were serotyped by Quellung or p...
Reinert, Ralf; Taysi, Bulent
A new WHO position paper has been published recently stressing the high priority of the inclusion of PCVs in childhood immunization programs worldwide. Planning for national use of pneumococcal vaccines should take besides other factors the distribution of pneumococcal serotypes in different age groups into consideration. In addition to the serotypes included in PCV7, PCV13 contains serotypes 1, 3, 5, 6A, 7F and 19A and this vaccine provides the broadest serotype coverage of PCVs globally. In...
Faye Janice Lim
Full Text Available Australian Aboriginal people have among the highest rates of invasive pneumococcal disease (IPD worldwide. We investigated clinical diagnosis, risk factors, comorbidities and vaccine coverage in Aboriginal and non-Aboriginal IPD cases. Using enhanced surveillance, we identified IPD cases in Western Australia, Australia, between 1997 and 2007. We calculated the proportion with risk factors and comorbidities in children (<5 years and adults (≥15 years, as well as adults living in metropolitan and non-metropolitan regions. We then calculated the proportion of cases eligible for vaccination who were vaccinated before contracting IPD. Of the 1,792 IPD cases that were reported, 355 (20% were Aboriginal and 1,155 (65% were adults. Pneumonia was the most common diagnosis (61% of non-Aboriginal and 49% of Aboriginal adult IPD cases in 2001-2007. Congenital abnormality was the most frequent comorbidity in non-Aboriginal children (11%. In Aboriginal children, preterm delivery was most common (14%. Ninety-one percent of non-Aboriginal and 96% of Aboriginal adults had one or more risk factors or comorbidities. In non-Aboriginal adults, cardiovascular disease (34% was the predominant comorbidity whilst excessive alcohol use (66% was the most commonly reported risk factor in Aboriginal adults. In adults, comorbidities were more frequently reported among those in metropolitan regions than those in non-metropolitan regions. Vaccination status was unknown for 637 of 1,082 cases post-July 2001. Forty-one percent of non-Aboriginal and 60% of Aboriginal children were eligible for vaccination but were not vaccinated. Among adults with risk factors who were eligible for vaccination and with known vaccination status, 75% Aboriginal and 94% non-Aboriginal were not vaccinated. An all-of-life immunisation register is needed to evaluate vaccine coverage and effectiveness in preventing IPD in adults.
Full Text Available Abstract Background Pneumococcal meningitis is associated with high mortality (~30% and morbidity. Up to 50% of survivors are affected by neurological sequelae due to a wide spectrum of brain injury mainly affecting the cortex and hippocampus. Despite this significant disease burden, the genetic program that regulates the host response leading to brain damage as a consequence of bacterial meningitis is largely unknown. We used an infant rat model of pneumococcal meningitis to assess gene expression profiles in cortex and hippocampus at 22 and 44 hours after infection and in controls at 22 h after mock-infection with saline. To analyze the biological significance of the data generated by Affymetrix DNA microarrays, a bioinformatics pipeline was used combining (i a literature-profiling algorithm to cluster genes based on the vocabulary of abstracts indexed in MEDLINE (NCBI and (ii the self-organizing map (SOM, a clustering technique based on covariance in gene expression kinetics. Results Among 598 genes differentially regulated (change factor ≥ 1.5; p ≤ 0.05, 77% were automatically assigned to one of 11 functional groups with 94% accuracy. SOM disclosed six patterns of expression kinetics. Genes associated with growth control/neuroplasticity, signal transduction, cell death/survival, cytoskeleton, and immunity were generally upregulated. In contrast, genes related to neurotransmission and lipid metabolism were transiently downregulated on the whole. The majority of the genes associated with ionic homeostasis, neurotransmission, signal transduction and lipid metabolism were differentially regulated specifically in the hippocampus. Of the cell death/survival genes found to be continuously upregulated only in hippocampus, the majority are pro-apoptotic, while those continuously upregulated only in cortex are anti-apoptotic. Conclusion Temporal and spatial analysis of gene expression in experimental pneumococcal meningitis identified potential
Full Text Available Streptococcus pneumoniae is a common cause of bacterial meningitis, frequently resulting in severe neurological impairment. A seven-month-old child presenting with Streptococcus pneumoniae meningoencephalitis developed right basal ganglia and hypothalamic infarctions. Daily episodes of agitation, hypertension, tachycardia, diaphoresis, hyperthermia, and decerebrate posturing were observed. The diagnosis of paroxysmal autonomic instability with dystonia was established. The patient responded to clonidine, baclofen, and benzodiazepines. Although this entity has been reported in association with traumatic brain injury, and as a sequel to some nervous system infections, this is the first case, to our knowledge, associated with pneumococcal meningoencephalitis.
Full Text Available 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.
Vestrheim, Didrik F.; Høiby, E. Arne; Aaberge, Ingeborg S; Dominique A. Caugant
In July 2006, the seven-valent pneumococcal conjugate vaccine (PCV7) was introduced in Norway with a reduced (2 doses + 1 boost) dose schedule. Post-PCV7 shifts in pneumococcal reservoirs were assessed by two point prevalence studies of nasopharyngeal colonization among children in day care centers, before (2006) and after (2008) widespread use of PCV7. Nasopharyngeal swabs were obtained from 1,213 children, 611 in 2006 and 602 in 2008. A total of 1,102 pneumococcal isolates were recovered. S...
Kanık Yüksek, Saliha; Gülhan, Belgin; Tezer, Hasan; Özkaya Parlakay, Aslınur; Uzun Kenan, Bahriye; Sayed Oskovi, Hülya; Nar Ötgün, Selin
Streptococcus pneumoniae, a gram-positive diplococcus, is the causative agent of invasive pneumococcal diseases (IPDs) characterized by severe infections such as bacteraemia, sepsis and meningitis. S.pneumoniae and IPDs are situated in the focus of the vaccine studies because of being encompassed of a significant burden of disease in the world, severe mortality and morbidities, and location in vaccine-preventable diseases group. Although S.pneumoniae has more than 90 defined serotypes, certain serotypes are often identified as the cause of IPDs. Individuals with comorbid and chronic diseases, primary or secondary immune deficiencies, and 65 years of age are at increased risk for IPDs. Currently, a 23-valent polysaccharide vaccine and also 7, 10 and 13 valent pneumococcal conjugated vaccines (PCV) have been produced for pneumococci. Phase studies of protein based vaccines, which will provide protection independent of serotypes, and 15-valent pneumococcal conjugated vaccine are still ongoing. In Turkey, in November 2008 PCV7 and in April 2011 PCV13 have been implemented in the national immunization program. First case of the pneumococcal unvaccinated cases presented in this report was a 6-year-old girl patient with pneumonia and pleural empyema due to S.pneumoniae serotype 1, without any underlying risk factors. The other case is a 52-days-old male patient, who had a history of pneumococcal septicemia in the newborn period and was followed for bacteremia associated S.pneumoniae serotype 12B and diagnosed as complement deficiency on follow-up. S.pneumoniae serotype 1 is within serotypes covered by 10 and 13 valent pneumococcal conjugate vaccines and pneumococcal polysaccharide vaccine that are in use today, and is a highly invasive strain often isolated in pneumococcal lobar pneumonia and empyema. S.pneumoniae serotype 12B is a non-vaccine serotype not included in any of conjugate and polysaccharide vaccines, and usually obtained in respiratory infections and
Vestrheim, Didrik F; Gaustad, Peter; Aaberge, Ingeborg S; Caugant, Dominique A
Genetic diversity in the species Streptococcus pneumoniae is mainly driven by horizontal gene transfer. S. pneumoniae is naturally competent for transformation. Competence is induced by a pheromone termed competence stimulating peptide (CSP) by a quorum-sensing mechanism. Two CSP pherotypes predominate amongst clinical isolates of S. pneumoniae, CSP-1 and CSP-2, with ability to trigger competence in bacteria of the homologue pherotype. Opposing theories on the effect of pherotypes on speciation have been proposed, either as a barrier for intra-pherotype gene transfer, or as a mechanism for fratricide resulting in lysis of non-competent bacterial cells. The aim of the present study was to determine pherotype distribution in strains of S. pneumococci isolated from the nasopharynges of healthy children. We sequenced the locus encoding CSP, comC, in sets of strains obtained from children colonised by multiple pneumococcal strains simultaneously. The impact of pherotype on co-colonisation was determined by comparing the observed distribution of pherotypes in co-colonising strains with the estimated pair-wise probability based on the overall pherotype distribution in the sample set. Five distinct comC alleles were identified, encoding CSP belonging to the two dominating pherotypes, CSP-1 (62.7%) and CSP-2 (37.3%). The observed distribution of pherotypes in sets of co-colonising pneumococcal strains did not differ from the probability estimate. Thus, co-colonisation of S. pneumoniae in healthy children is not restricted by pherotype. PMID:21763465
Full Text Available Abstract Background Streptococcus pneumoniae can be carried asymptomatically in the nasopharynx of its human host but can also cause a wide range of infections. A role for pneumococcal phase variants in the different lifestyles of this bacterium has been suggested but no systematic survey of the colony phenotypes of isolates associated with human infections has been undertaken. Results We report the colony opacity phenotypes of a genetically diverse set of 304 invasive isolates representing 10 serotypes. Over half of the isolates (52% presented the opaque phenotype whereas transparent variants accounted for only 26% of the total. However, the frequency of recovery of each phase variant was not uniform, while serotypes 1, 4, 12B and 23F presented the opaque phenotype more frequently than expected by chance, serotypes 3 and 14 where less frequently associated with this phenotype. Conclusion The opaque phenotype was the most frequent phenotype found among invasive isolates. An unexpected and equally important finding is the variability of the dominant opacity phenotype found among serotypes. This observation highlights the heterogeneity of opacity phenotypes in invasive isolates and lends further support to the proposal that other factors, in addition to the site of isolation, determine the opacity phenotype of a given isolate. The association between serotype and colonial opacity could help explain epidemiological differences observed among pneumococcal serotypes such as a higher invasive disease potential.
V. V. Pilipenko
Full Text Available Morphological displays of cerebral microcirculation derangements in a brain cortex with their semiquantitative estimation have been studied in experimental mice model of the first 24-72 hours period of pneumococcal meningitis.Also displays oxidative stress and activity antioxidative protectional system by means of definition of markers of these processes – malondialdehide, reduced glutathione and glucose-6-phosphate-dehydrogenase activity have been investigated. The received results testify to morphological signs of the expressed derangements of cerebral microcirculation in a brain cortex already by first 24 hour of an experimental meningitis. The maximum expressiveness oxidative stress and activity antioxidative protectional system of reduced glutathione with the max activity of glucose-6-phosphatedehydrogenase in a mice brain cortex was noted at first 48hour durations of experimental disease. Signs of irreversible changes of mice cortex neurons are not revealed at 24–72-hour duration of experimental pneumococcal meningitis.
The antibody response after immunization with capsular polysaccharides of Streptococcus pneumoniae of patients with Hodgkin's disease or with carcinoma of the head and neck was studied. Patients with Hodgkin's disease who were immunized prior to the institution of immunosuppressive therapy were capable of responding to each of the pneumococcal polysaccharides evaluated. The level of antibody achieved by the patients is lower than that of normal control subjects. Nevertheless, absolute values were in the range that would be expected to result in protection. The duration of antibody response was not evaluated. Patients with carcinoma of the head and neck did not demonstrate a significant increase in antibody levels after vaccination, which was done at the time of radiation therapy. Two years after immunization antibody levels were lower with recovery at three years. However, these changes were not statistically significant. Decreased levels of antibody to pneumococcal polysaccharide types not present in the vaccine were observed. Studies of patients with carcinoma of the heat and neck demonstrated that radiation therapy has a profound immunosuppressive effect on antibody levels. More selective immunosuppressive therapy and/or an increase in the immunogenicity of the polysaccharides in the vaccine are required for protection of patients with malignancy
Ammann, A.J.; Schiffman, G.; Addiego, J.E.; Wara, W.M.; Wara, D.W.
The antibody response after immunization with capsular polysaccharides of Streptococcus pneumoniae of patients with Hodgkin's disease or with carcinoma of the head and neck was studied. Patients with Hodgkin's disease who were immunized prior to the institution of immunosuppressive therapy were capable of responding to each of the pneumococcal polysaccharides evaluated. The level of antibody achieved by the patients is lower than that of normal control subjects. Nevertheless, absolute values were in the range that would be expected to result in protection. The duration of antibody response was not evaluated. Patients with carcinoma of the head and neck did not demonstrate a significant increase in antibody levels after vaccination, which was done at the time of radiation therapy. Two years after immunization antibody levels were lower with recovery at three years. However, these changes were not statistically significant. Decreased levels of antibody to pneumococcal polysaccharide types not present in the vaccine were observed. Studies of patients with carcinoma of the heat and neck demonstrated that radiation therapy has a profound immunosuppressive effect on antibody levels. More selective immunosuppressive therapy and/or an increase in the immunogenicity of the polysaccharides in the vaccine are required for protection of patients with malignancy.
J.R. Piet; M. Geldhoff; B.D.C. van Schaik; M.C. Brouwer; M. Valls Seron; M.E. Jakobs; K. Schipper; Y. Pannekoek; A.H. Zwinderman; T. van der Poll; A.H.C. van Kampen; F. Baas; A van der Ende; D. van de Beek
Streptococcus pneumoniae (pneumococcus) is a major human pathogen causing pneumonia, sepsis and bacterial meningitis. Using a clinical phenotype based approach with bacterial whole-genome sequencing we identified pneumococcal arginine biosynthesis genes to be associated with outcome in patients with
Worsøe, Lise Lotte; Brandt, C.T.; Lund, S.P.;
Sensorineural hearing loss is a common complication of pneumococcal meningitis. Treatment with corticosteroids reduces inflammatory response and may thereby reduce hearing loss. However, both experimental studies and clinical trials investigating the effect of corticosteroids on hearing loss have...
Bergman, Annika; Hjelmgren, Jonas; Ortqvist, Ake;
The 7-valent pneumococcal conjugate vaccine (PCV-7) has proved to be highly effective against invasive pneumococcal disease and has also provided some protection against all-cause pneumonia and acute otitis media. The objective of this study was to evaluate the projected health benefits, costs and...... cost-effectiveness of vaccination with the 7-valent conjugated pneumococcal vaccine compared with no vaccination, in all infants in Sweden, taking herd immunity into account. A Markov model was used and a hypothetical birth cohort was simulated for a lifelong perspective. The results show that...... vaccination of 1 cohort could potentially prevent 9 cases of pneumococcal meningitis, 22 cases of pneumococcal septicaemia, 509 cases of hospitalized pneumonia, 7812 cases of acute otitis media, and 2.7 fatalities, among children 0-4 y of age and 6 episodes of pneumococcal meningitis and 167 cases of...
Fletcher, Mark A.; Bernard Fritzell
Streptococcus pneumoniae is the predominant otitis media pathogen and its prevention through effective vaccination could diminish childhood illness and antibiotic use. This paper reviews 5 pneumococcal conjugate vaccine (PCV) trials that used otitis media as an endpoint: Northern California Kaiser Permanente (NCKP; vaccine, 7-valent PCV [PCV7]-CRM); Finnish Otitis Media (FinOM; vaccines, PCV7-CRM or PCV7-OMPC); Native American Trial (vaccine, PCV7-CRM); Pneumococcal Otitis Efficacy Trial (POE...
FIORE, A. E.; Levine, O S; Elliott, J A; Facklam, R R; Butler, J.C.
To estimate the effectiveness of pneumococcal polysaccharide vaccine, we serotyped isolates submitted to the Pneumococcal Sentinel Surveillance System from 1984 to 1996 from 48 vaccinated and 125 unvaccinated children 2 to 5 years of age. Effectiveness against invasive disease caused by serotypes included in the vaccine was 63%. Effectiveness against serotypes in the polysaccharide vaccine but not in a proposed seven-valent protein conjugate vaccine was 94%.
Daly, Thomas M.; Hill, Harry R.
Pneumococcal vaccination is a commonly used technique for assessing the humoral immune status of a patient suspected of having immunodeficiency. Interpretation of what constitutes an adequate response, however, can be challenging. This is due to the complexity of the data generated from serotype-specific assays, historical variations in the assays used to measure pneumococcal antibodies, and varying recommendations on the relevant cut points that define response. In this review, we summarize ...
Dunne, Eileen M.; Toh, Zheng Q.; John, Mary; Manning, Jayne; Satzke, Catherine; Licciardi, Paul
Adherence of Streptococcus pneumoniae (the pneumococcus) to the epithelial lining of the nasopharynx can result in colonization and is considered a prerequisite for pneumococcal infections such as pneumonia and otitis media. In vitro adherence assays can be used to study the attachment of pneumococci to epithelial cell monolayers and to investigate potential interventions, such as the use of probiotics, to inhibit pneumococcal colonization. The protocol described here is used to investigate t...
Leeming, John P.; Cartwright, Keith; Morris, Rhonwen; Martin, Siobhan A.; Smith, Michael D.
Widespread use of conjugate pneumococcal polysaccharide-protein vaccines may alter the spectrum of pneumococci producing invasive disease. Novel sensitive diagnostic methods would be valuable for monitoring the epidemiology of pneumococcal disease within populations and vaccine recipients. Ideally, these methods should allow determination of the serotype of the infecting clone. Serotype-specific enzyme-linked immunosorbent assays (ELISA) for 13 capsular polysaccharides (types 1, 3, 4, 5, 6A, ...
PURPOSE AND OBJECTIVES: The patients using immunosuppressive agents are considered at high risk for acquiring different infections. Accordingly, international guidelines recommend vaccinating such patients against influenza and pneumococcal organisms. The aims of this study were two-fold: (1) to assess the influenza and pneumococcal vaccination uptake among our rheumatology outpatients who are immunosuppressed; (2) to identify the factors influencing immunisation uptake among our sample of patients.
Salt, Penny; Banner, Carly; Oh, Sarah; Yu, Ly-Mee; Lewis, Susan; Pan, DingXin; Griffiths, David; Ferry, Berne; Pollard, Andrew
Children who have siblings and/or who attend day care have higher rates of nasopharyngeal colonization with pneumococci than lone children do. Pneumococcal colonization is usually asymptomatic but is a prerequisite for invasive disease. We studied the effect of social mixing with other children on immunity to a pneumococcal vaccine. One hundred sixty children aged 1 year were immunized with a 7-valent conjugate pneumococcal vaccine. A blood sample was obtained before and 9 to 11 days after th...
Full Text Available Abstract Background Gambia is the second GAVI support-eligible country to introduce the 7-valent pneumococcal conjugate vaccine (PCV7, but a country-specific cost-effectiveness analysis of the vaccine is not available. Our objective was to assess the potential impact of PCVs of different valences in The Gambia. Methods We synthesized the best available epidemiological and cost data using a state-transition model to simulate the natural histories of various pneumococcal diseases. For the base-case, we estimated incremental cost (in 2005 US dollars per disability-adjusted life year (DALY averted under routine vaccination using PCV9 compared to no vaccination. We extended the base-case results for PCV9 to estimate the cost-effectiveness of PCV7, PCV10, and PCV13, each compared to no vaccination. To explore parameter uncertainty, we performed both deterministic and probabilistic sensitivity analyses. We also explored the impact of vaccine efficacy waning, herd immunity, and serotype replacement, as a part of the uncertainty analyses, by assuming alternative scenarios and extrapolating empirical results from different settings. Results Assuming 90% coverage, a program using a 9-valent PCV (PCV9 would prevent approximately 630 hospitalizations, 40 deaths, and 1000 DALYs, over the first 5 years of life of a birth cohort. Under base-case assumptions ($3.5 per vaccine, compared to no intervention, a PCV9 vaccination program would cost $670 per DALY averted in The Gambia. The corresponding values for PCV7, PCV10, and PCV13 were $910, $670, and $570 per DALY averted, respectively. Sensitivity analyses that explored the implications of the uncertain key parameters showed that model outcomes were most sensitive to vaccine price per dose, discount rate, case-fatality rate of primary endpoint pneumonia, and vaccine efficacy against primary endpoint pneumonia. Conclusions Based on the information available now, infant PCV vaccination would be expected to reduce
Gouveia Edilane L
Full Text Available Abstract Background Prior to the availability of generic third-generation cephalosporins, penicillins were widely used for treatment of pneumococcal meningitis in developing countries despite concerns about rising levels of penicillin resistance among pneumococcal isolates. We examined the impact of penicillin resistance on outcomes of pneumococcal meningitis over a ten year period in an infectious diseases hospital in Brazil. Methods Clinical presentation, antimicrobial therapy and outcomes were reviewed for 548 patients with culture-confirmed pneumococcal meningitis from December, 1995, to November, 2005. Pneumococcal isolates from meningitis patients were defined as penicillin-resistant if Minimum Inhibitory Concentrations for penicillin were greater than 0.06 μg/ml. Proportional hazards regression was used to identify risk factors for fatal outcomes. Results During the ten-year period, ceftriaxone replaced ampicillin as first-line therapy for suspected bacterial meningitis. In hospital case-fatality for pneumococcal meningitis was 37%. Of 548 pneumococcal isolates from meningitis cases, 92 (17% were resistant to penicillin. After controlling for age and severity of disease at admission, penicillin resistance was associated with higher case-fatality (Hazard Ratio [HR], 1.62; 95% Confidence Interval [CI], 1.08-2.43. Penicillin-resistance remained associated with higher case-fatality when initial therapy included ceftriaxone (HR, 1.68; 95% CI 1.02-2.76. Conclusions Findings support the use of third generation cephalosporin antibiotics for treatment of suspected pneumococcal meningitis even at low prevalence of pneumococcal resistance to penicillins.
Full Text Available Abstract Background In Australia in June 2001, a unique pneumococcal vaccine schedule commenced for Indigenous infants; seven-valent pneumococcal conjugate vaccine (7PCV given at 2, 4, and 6 months of age and 23-valent pneumococcal polysaccharide vaccine (23PPV at 18 months of age. This study presents carriage serotypes following this schedule. Methods We conducted cross sectional surveys of pneumococcal carriage in Aboriginal children 0 to 6 years of age living in remote Aboriginal communities (RACs in 2003 and 2005. Nasal secretions were collected and processed according to published methods. Results 902 children (mean age 25 months living in 29 communities in 2003 and 818 children (mean age 35 months in 17 communities in 2005 were enrolled. 87% children in 2003 and 96% in 2005 had received two or more doses of 7PCV. From 2003 to 2005, pneumococcal carriage was reduced from 82% to 76% and reductions were apparent in all age groups; 7PCV-type carriage was reduced from 11% to 8%, and 23PPV-non-7PCV-type carriage from 31% to 25% respectively. Thus non-23PPV-type carriage increased from 57% to 67%. All these changes were statistically significant, as were changes for some specific serotypes. Shifts could not be attributed to vaccination alone. The top 10 of 40 serotypes identified were (in descending order 16F, 19A, 11A, 6C, 23B, 19F, 6A, 35B, 6B, 10A and 35B. Carriage of penicillin non-susceptible (MIC > = 0.12 μg/mL strains (15% overall was detected in serotypes (descending order 19A, 19F, 6B, 16F, 11A, 9V, 23B, and in 4 additional serotypes. Carriage of azithromycin resistant (MIC > = 2 μg/mL strains (5% overall, was detected in serotypes (descending order 23B, 17F, 9N, 6B, 6A, 11A, 23F, and in 10 additional serotypes including 6C. Conclusion Pneumococcal carriage remains high (~80% in this vaccinated population. Uptake of both pneumococcal vaccines increased, and carriage was reduced between 2003 and 2005. Predominant serotypes in combined
Ortika Belinda D
Full Text Available Abstract Background The current ‘gold standard’ for serotyping pneumococci is the Quellung test. This technique is laborious and requires a certain level of training to correctly perform. Commercial pneumococcal latex agglutination serotyping reagents are available, but these are expensive. In-house production of latex agglutination reagents can be a cost-effective alternative to using commercially available reagents. This paper describes a method for the production and quality control (QC of latex reagents, including problem solving recommendations, for pneumococcal serotyping. Results Here we describe a method for the production of latex agglutination reagents based on the passive adsorption of antibodies to latex particles. Sixty-five latex agglutination reagents were made using the PneuCarriage Project (PCP method, of which 35 passed QC. The other 30 reagents failed QC due to auto-agglutination (n=2, no reactivity with target serotypes (n=8 or cross-reactivity with non-target serotypes (n=20. Dilution of antisera resulted in a further 27 reagents passing QC. The remaining three reagents passed QC when prepared without centrifugation and wash steps. Protein estimates indicated that latex reagents that failed QC when prepared using the PCP method passed when made with antiserum containing ≤ 500 μg/ml of protein. Sixty-one nasopharyngeal isolates were serotyped with our in-house latex agglutination reagents, with the results showing complete concordance with the Quellung reaction. Conclusions The method described here to produce latex agglutination reagents allows simple and efficient serotyping of pneumococci and may be applicable to latex agglutination reagents for typing or identification of other microorganisms. We recommend diluting antisera or removing centrifugation and wash steps for any latex reagents that fail QC. Our latex reagents are cost-effective, technically undemanding to prepare and remain stable for long periods of
Sylvan Staffan PE
Full Text Available Abstract Background The present prospective study was conducted from 2003–2005, among all individuals 65 years and older in Uppsala County, a region with 300 000 inhabitants situated close to the Stockholm urban area. The objective of this study was to assess the preventive effect of influenza and pneumococcal vaccination in reducing hospitalisation and length of hospital stay (LOHS even during periods of low influenza activity. The specificity of the apparent vaccine associations were evaluated in relation to the influenza seasons. Results In 2003, the total study population was 41,059, of which 12,907 (31% received influenza vaccine of these, 4,447 (11% were administered the pneumococcal vaccine. In 2004, 14,799 (34% individuals received the influenza vaccine and 8,843 (21% the pneumococcal vaccine and in 2005 16,926 (39% individuals were given the influenza vaccine and 12,340 (28% the pneumococcal vaccine. Our findings indicated that 35% of the vaccinated cohort belonged to a medical risk category (mainly those persons that received the pneumococcal vaccine. Data on hospitalisation and mortality during the 3-year period were obtained from the administrative database of the Uppsala county council. During the influenza seasons, reduction of hospital admissions and significantly shorter in-hospital stay for influenza was observed in the vaccinated cohort (below 80 years of age. For individuals who also had received the pneumococcal vaccine, a significant reduction of hospital admissions and of in-hospital stay was observed for invasive pneumococcal disease and for pneumococcal pneumonia. Effectiveness was observed for cardiac failure even in persons that also had received the pneumococcal vaccine, despite that the pneumococcal vaccinated mainly belonged to a medical risk category. Reduction of death from all causes was observed during the influenza season of 2004, in the 75–84-year old age group and in all age-groups during the influenza
Full Text Available Background: Invasive pneumococcal disease (IPD is a serious bacterial disease. Vaccination can prevent disease for many of the current serotypes. The aim of this investigation was to describe the notification rates of IPD in a regional area of Australia, explore changes in rates since the introduction of the population vaccine programmes in 2005 and to describe changes in the distribution of serotypes in relation to the available vaccines after three years.Methods: Annualized IPD notification rates were calculated for residents of a regional area in northern New South Wales. Rates were analysed according to serotypes covered by available vaccines. Changes in serotypes were compared for the periods 2002–2004 and 2008–2010.Results: The annualized notification rate of IPD in all ages for the period 2002–2004 was 13.7 per 100 000 population and 8.3 per 100 000 population for the period 2008–2010 (rate ratio [RR], 0.61, confidence interval [CI]: 0.51–0.72. The largest decline was observed in 7-valent pneumococcal conjugate vaccine (7vPCV types across all age groups (RR, 0.17, CI: 0.12–0.24 and in the zero to four year age group (RR, 0.03, CI: 0.01–0.11. The six serotypes included in the new 13-valent pneumococcal conjugate vaccine, but not in the 7vPCV, accounted for 40.6% of IPD cases in the zero to four year age group during the period of 2008–2010.Discussion: The introduction of 7vPCV significantly reduced the overall notification rate of IPD caused by the serotypes contained in this vaccine. This decline in IPD rates in children can be directly attributed to the use of 7vPCV, and in adults it is most likely an indirect effect of the 7vPCV programme in children.
Auranen, Kari; Mehtälä, Juha; Tanskanen, Antti; S. Kaltoft, Margit
The state of pneumococcal carriage—that is, pneumococcal colonization in the nasopharynx of healthy persons—represents a reservoir for the spread of pneumococci among individuals. In light of the introduction of new pneumococcal conjugate vaccines, further knowledge on the dynamics of pneumococcal carriage is important. Different serotypes (strains) of pneumococcus are known to compete with each other in colonizing human hosts. Understanding the strength and mode of between-serotype competiti...
Vestrheim, Didrik F; Løvoll, Oistein; Aaberge, Ingeborg S; Caugant, Dominique A; Høiby, E Arne; Bakke, Hilde; Bergsaker, Marianne R
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
Jakobsen, Håvard; Sigurdsson, Viktor D.; Sigurdardottir, Sigurveig; Schulz, Dominique; Jonsdottir, Ingileif
Immunization with a pneumococcal conjugate vaccine (PNC) containing serotype 19F induces cross-reactive antibodies to 19A in mice and human infants. Active immunization with PNC and passive immunization with serum samples from infants vaccinated with PNC containing serotype 19F, but not serotype 19A, protected against lung infection caused by both serotypes in a murine model.
Maria Leonor S Oliveira
Full Text Available Streptococcus pneumoniae is the leading cause of respiratory acute infections around the world. In Latin America, approximately 20,000 children under 5 years of age die of pneumococcal diseases annually. Pneumococcal surface protein A (PspA is among the best-characterized pneumococcal antigens that confer protection in animal models of pneumococcal infections and, as such, is a good alternative for the currently available conjugated vaccines. Efficient immune responses directed to PspA in animal models have already been described. Nevertheless, few low cost adjuvants for a subunit pneumococcal vaccine have been proposed to date. Here, we have tested the adjuvant properties of the whole cell Bordetella pertussis vaccine (wP that is currently part of the DTP (diphtheria-tetanus-pertussis vaccine administrated to children in several countries, as an adjuvant to PspA. Nasal immunization of BALB/c mice with a combination of PspA5 and wP or wP(low--a new generation vaccine that contains low levels of B. pertussis LPS--conferred protection against a respiratory lethal challenge with S. pneumoniae. Both PspA5-wP and PspA5-wP(low vaccines induced high levels of systemic and mucosal antibodies against PspA5, with similar profile, indicating no essential requirement for B. pertussis LPS in the adjuvant properties of wP. Accordingly, nasal immunization of C3H/HeJ mice with PspA5-wP conferred protection against the pneumococcal challenge, thus ruling out a role for TLR4 responses in the adjuvant activity and the protection mechanisms triggered by the vaccines. The high levels of anti-PspA5 antibodies correlated with increased cross-reactivity against PspAs from different clades and also reflected in cross-protection. In addition, passive immunization experiments indicated that antibodies played an important role in protection in this model. Finally, subcutaneous immunization with a combination of PspA5 with DTP(low protected mice against challenge with two
Moreira, Marta; Cintra, Otavio; Harriague, Julie; Hausdorff, William P; Hoet, Bernard
Brazil introduced the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV, Synflorix™, GSK Vaccines) in the routine childhood immunization program in 2010 with a 3+1 schedule (with catch-up for children pneumococcal conjugate vaccine on nasopharyngeal carriage and all the major pneumococcal disease manifestations in a single, pneumococcal conjugate vaccine-naïve, developing country. A total of 15 published articles and 13 congress abstracts were included in the analysis. In children vaccine-type and any-type invasive pneumococcal disease (including decreases in pneumococcal meningitis morbidity and mortality), on pneumonia incidence and mortality, and on otitis media. Nasopharyngeal carriage of vaccine-type and any-type pneumococci decreased after the primary doses, with no early signs of replacement with other pathogens. Finally, herd protection against vaccine-type invasive pneumococcal disease and pneumonia in unvaccinated subjects was shown in some studies for some age groups. In conclusion, pneumococcal disease decreased after the introduction of PHiD-CV into the Brazilian national immunization program. Further follow-up is needed to evaluate the long-term overall impact of PHiD-CV in the Brazilian population. PMID:27113162
Nierop Groot, M.N.; Godefrooij, J.; Kleerebezem, M.
The pneumococcal serotype 14 polysaccharide was produced in Lactococcus lactis by coexpressing pneumococcal polysaccharide type 14-specific genes (cpsFGHIJKL(14)) with the lactococcal regulatory and priming glucosyltransferase-encoding genes specific for B40 polysaccharide (epsABCD(B40)). The polysaccharide produced by Lactococcus was secreted in the medium, simplifying downstream processing and polysaccharide isolation from culture broth
Full Text Available Abstract Background The burden of invasive pneumococcal disease in young children decreased dramatically following introduction of the 7-valent pneumococcal conjugate vaccine (PCV7. The epidemiology of S. pneumoniae now reflects infections caused by serotypes not included in PCV7. Recently introduced higher valency pneumococcal vaccines target the residual burden of invasive and non-invasive infections, including those caused by serotypes not included in PCV7. This review is based on presentations made at the European Society of Pediatric Infectious Diseases in June 2011. Discussion Surveillance data show increased circulation of the non-PCV7 vaccine serotypes 1, 3, 6A, 6C, 7 F and 19A in countries with routine vaccination. Preliminary evidence suggests that broadened serotype coverage offered by higher valency vaccines may be having an effect on invasive disease caused by some of those serotypes, including 19A, 7 F and 6C. Aetiology of community acquired pneumonia remains a difficult clinical diagnosis. However, recent reports indicate that pneumococcal vaccination has reduced hospitalisations of children for vaccine serotype pneumonia. Variations in serotype circulation and occurrence of complicated and non-complicated pneumonia caused by non-PCV7 serotypes highlight the potential of higher valency vaccines to decrease the remaining burden. PCVs reduce nasopharyngeal carriage and acute otitis media (AOM caused by vaccine serotypes. Recent investigations of the interaction between S. pneumoniae and non-typeable H. influenzae suggest that considerable reduction in severe, complicated AOM infections may be achieved by prevention of early pneumococcal carriage and AOM infections. Extension of the vaccine serotype spectrum beyond PCV7 may provide additional benefit in preventing the evolution of AOM. The direct and indirect costs associated with pneumococcal disease are high, thus herd protection and infections caused by non-vaccine serotypes
Vestrheim, Didrik F.; Høiby, E. Arne; Aaberge, Ingeborg S.; Caugant, Dominique A.
In July 2006, the seven-valent pneumococcal conjugate vaccine (PCV7) was introduced in Norway with a reduced (2 doses + 1 boost) dose schedule. Post-PCV7 shifts in pneumococcal reservoirs were assessed by two point prevalence studies of nasopharyngeal colonization among children in day care centers, before (2006) and after (2008) widespread use of PCV7. Nasopharyngeal swabs were obtained from 1,213 children, 611 in 2006 and 602 in 2008. A total of 1,102 pneumococcal isolates were recovered. Serotyping, multilocus sequence typing, and antimicrobial drug susceptibility testing were performed on all isolates. Although carriage of PCV7 serotypes decreased among both vaccinated and unvaccinated children, the overall prevalence of pneumococcal carriage remained high (80.4%) after vaccine introduction. The pneumococcal populations were diverse, and in the shift toward non-PCV7 serotypes, expansion of a limited number of established clonal complexes was observed. While non-antimicrobial-susceptible clones persisted among PCV7 serotypes, antimicrobial resistance did not increase among non-PCV7 serotypes. Direct and indirect protection of PCV7 against nasopharyngeal colonization was inferred from an overall decrease in carriage of PCV7 serotypes. No preference was found for nonsusceptible clones among the replacing non-PCV7 serotypes. PMID:20107006
Vestrheim, Didrik F; Høiby, E Arne; Aaberge, Ingeborg S; Caugant, Dominique A
In July 2006, the seven-valent pneumococcal conjugate vaccine (PCV7) was introduced in Norway with a reduced (2 doses + 1 boost) dose schedule. Post-PCV7 shifts in pneumococcal reservoirs were assessed by two point prevalence studies of nasopharyngeal colonization among children in day care centers, before (2006) and after (2008) widespread use of PCV7. Nasopharyngeal swabs were obtained from 1,213 children, 611 in 2006 and 602 in 2008. A total of 1,102 pneumococcal isolates were recovered. Serotyping, multilocus sequence typing, and antimicrobial drug susceptibility testing were performed on all isolates. Although carriage of PCV7 serotypes decreased among both vaccinated and unvaccinated children, the overall prevalence of pneumococcal carriage remained high (80.4%) after vaccine introduction. The pneumococcal populations were diverse, and in the shift toward non-PCV7 serotypes, expansion of a limited number of established clonal complexes was observed. While non-antimicrobial-susceptible clones persisted among PCV7 serotypes, antimicrobial resistance did not increase among non-PCV7 serotypes. Direct and indirect protection of PCV7 against nasopharyngeal colonization was inferred from an overall decrease in carriage of PCV7 serotypes. No preference was found for nonsusceptible clones among the replacing non-PCV7 serotypes. PMID:20107006
Basset, Alan; Trzcinski, Krzysztof; Hermos, Christina; O'Brien, Katherine L; Reid, Raymond; Santosham, Mathuram; McAdam, Alexander J; Lipsitch, Marc; Malley, Richard
The recent discovery of a mobile genetic element encoding a pilus-like structure in Streptococcus pneumoniae and the demonstration of a role for the pilus in virulence in mice have led to the proposal of the use of the pilus as a candidate pneumococcal vaccine. We examined the frequency of occurrence of the pneumococcal pilus, as determined by the presence of the rrgC gene, and analyzed its association with virulence, capsular serotypes, and multilocus sequence types in the American Indian pneumococcal collection and isolates of S. pneumoniae from blood cultures collected at Children's Hospital Boston. Overall, 21.4% of strains in the American Indian collection had the rrgC gene, but there was no difference between isolates obtained from the nasopharynx and those obtained from sterile sites (blood or cerebrospinal fluid). Vaccine-type strains were significantly more likely than non-vaccine-type strains to have this pilus gene (P types, there was a high concordance (95%) between the multilocus sequence type and the presence or the absence of rrgC. Finally, in the era of the pneumococcal conjugate vaccine, the frequency of rrgC in isolates from Children's Hospital Boston has decreased significantly (42.8% before 2000 versus 21.3% after 2000; P = 0.019). Therefore, our data show that the pilus is present in a minority of strains and is associated with certain serotypes and that its frequency has been reduced by the conjugate pneumococcal vaccine. PMID:17392439
Kumar, Rakesh; Arora, Narendra; Santosham, Mathuram
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
Kumar, Rakesh; Arora, Narendra; Santosham, Mathuram
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
Daudin, M; Tattevin, P; Lelong, B; Flecher, E; Lavoué, S; Piau, C; Ingels, A; Chapron, A; Daubert, J-C; Revest, M
Case series have suggested that pneumococcal endocarditis is a rare disease, mostly reported in patients with co-morbidities but no underlying valve disease, with a rapid progression to heart failure, and high mortality. We performed a case-control study of 28 patients with pneumococcal endocarditis (cases), and 56 patients with non-pneumococcal endocarditis (controls), not matched for sex and age, during the years 1991-2013, in one referral centre. Alcoholism (39.3% versus 10.7%; p endocarditis. Cardiac surgery was required in 64.3% of patients with pneumococcal endocarditis, much earlier than in patients with non-pneumococcal endocarditis (mean time from symptom onset, 14.1 ± 18.2 versus 69.0 ± 61.1 days). In-hospital mortality rates were similar (7.1% versus 12.5%). Streptococcus pneumoniae causes rapidly progressive endocarditis requiring life-saving early cardiac surgery in most cases. PMID:27021424
Full Text Available Abstract Background Previous studies have shown influenza vaccine uptake in UK nursing home residents to be low. Very little information exists regarding the uptake of pneumococcal vaccine in this population. The formulation of policies relating to the vaccination of residents has been proposed as a simple step that may help improve vaccine uptake in care homes. Methods A postal questionnaire was sent to matrons of all care homes with nursing within the Greater Nottingham area in January 2006. Non respondents were followed up with up to 3 phone calls. Results 30% (16/53 of respondents reported having a policy addressing influenza vaccination and 15% (8/53 had a policy addressing pneumococcal vaccination. Seasonal influenza vaccine coverage in care homes with a vaccination policy was 87% compared with 84% in care homes without a policy (p = 0.47. The uptake of pneumococcal vaccination was found to be low, particularly in care homes with no vaccination policy. Coverage was 60% and 32% in care homes with and without a vaccination policy respectively (p = 0.06. This result was found to be statistically significant on multivariate analysis (p = 0.03, R = 0.46 Conclusion The uptake of influenza vaccine among care home residents in the Nottingham region is relatively high, although pneumococcal vaccine uptake is low. This study shows that there is an association between pneumococcal vaccine uptake and the existence of a vaccination policy in care homes, and highlights that few care homes have vaccination policies in place.
Blaabjerg, Anne Katrine; Schumacher, Anna Holst; Kantsø, Bjørn; Kristensen, Lena Hagelskjær; Schumacher, Helga
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.
Pneumococcal vaccination is one of the most important strategies against pneumococcal diseases.This article reviews the clinical and epidemiological features of pneumococcal diseases in the post-7-valent pneumococcal conjugate vaccine era,application of two new approved pneumococcal conjugate vaccines and current developing status of protein-based vaccines.%肺炎链球菌疫苗接种是抵抗肺炎链球菌病的最主要策略之一.此文阐述了后7价肺炎链球菌结合疫苗接种时代的肺炎链球菌病的临床和流行特征、新批准的2种肺炎链球菌结合疫苗的应用以及基于蛋白的肺炎链球菌疫苗的研发现状.
Hughes, G J; Wright, L B; Chapman, K E; Wilson, D; Gorton, R
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
Mark van der Linden
Full Text Available BACKGROUND: Between 1986 and 2008 Streptococcus pneumoniae was isolated from 41 pets/zoo animals (guinea pigs (n = 17, cats (n = 12, horses (n = 4, dogs (n = 3, dolphins (n = 2, rat (n = 2, gorilla (n = 1 treated in medical veterinary laboratories and zoos, and 44 laboratory animals (mastomys (multimammate mice; n = 32, mice (n = 6, rats (n = 4, guinea pigs (n = 2 during routine health monitoring in an animal facility. S. pneumoniae was isolated from nose, lung and respiratory tract, eye, ear and other sites. METHODOLOGY/PRINCIPAL FINDINGS: Carriage of the same isolate of S. pneumoniae over a period of up to 22 weeks was shown for four mastomys. Forty-one animals showed disease symptoms. Pneumococcal isolates were characterized by optochin sensitivity, bile solubility, DNA hybridization, pneumolysin PCR, serotyping and multilocus sequence typing. Eighteen of the 32 mastomys isolates (56% were optochin resistant, all other isolates were optochin susceptible. All mastomys isolates were serotype 14, all guinea pig isolates serotype 19F, all horse isolates serotype 3. Rats had serotypes 14 or 19A, mice 33A or 33F. Dolphins had serotype 23F, the gorilla serotype 14. Cats and dogs had many different serotypes. Four isolates were resistant to macrolides, three isolates also to clindamycin and tetracycline. Mastomys isolates were sequence type (ST 15 (serotype 14, an ST/serotype combination commonly found in human isolates. Cats, dogs, pet rats, gorilla and dolphins showed various human ST/serotype combinations. Lab rats and lab mice showed single locus variants (SLV of human STs, in human ST/serotype combinations. All guinea pig isolates showed the same completely new combination of known alleles. The horse isolates showed an unknown allele combination and three new alleles. CONCLUSIONS/SIGNIFICANCE: The isolates found in mastomys, mice, rats, cats, dogs, gorilla and dolphins are most likely identical to human pneumococcal isolates. Isolates from
Faber, Tina E; Schuurs, Theo A; Veeger, Nic J G M; Hennus, Marije P; Bont, Louis J
The effect of viral infection on nasopharyngeal carriage of Streptococcus pneumoniae during childhood is not well known. We studied dynamics of pneumococcal colonization by quantitative PCR during the natural course of viral bronchiolitis. At time of admission, 47 (47%) of 100 patients with bronchiolitis carried pneumococci. In patients with viral bronchiolitis who did not receive antibiotics, pneumococcal load decreased from time of admission to discharge (n = 35, cycle threshold 23 vs. 25, P = 0.0017) and from discharge to follow-up (n = 22, cycle threshold 25 vs. 40, P = 0.003). We conclude that viral respiratory infection is negatively associated with pneumococcal colonization of the upper airways. Pediatr Pulmonol. 2016;51:863-867. © 2016 Wiley Periodicals, Inc. PMID:26859410
Worsøe, Lise Lotte; Caye-Thomasen, P.; Brandt, C.T.;
pneumococcal serotype) for development of hearing loss. Methods. Results of blood and cerebrospinal fluid (CSF) biochemistry, bacterial serotyping, follow-up audiological examinations, and medical records were collected, and disease-related risk factors for hearing loss were identified. The mean pure......Background. On the basis of a nationwide registration during a 5-year period (1999-2003), the frequency and severity of hearing loss was investigated retrospectively in 343 consecutive Danish patients who survived pneumococcal meningitis, to identify important risk factors (including the...... hearing loss, and another 16 (7%) had bilateral profound hearing loss. Significant risk factors for hearing loss were advanced age, the presence of comorbidity, severity of meningitis, a low CSF glucose level, a high CSF protein level, and a certain pneumococcal serotype (P <.05). By applying multivariate...
Sharmila J Talekar
Full Text Available Streptococcus pneumoniae (pneumococcus forms organized biofilms to persist in the human nasopharynx. This persistence allows the pneumococcus to produce severe diseases such as pneumonia, otitis media, bacteremia and meningitis that kill nearly a million children every year. While bacteremia and meningitis are mediated by planktonic pneumococci, biofilm structures are present during pneumonia and otitis media. The global emergence of S. pneumoniae strains resistant to most commonly prescribed antibiotics warrants further discovery of alternative therapeutics. The present study assessed the antimicrobial potential of a plant extract, 220D-F2, rich in ellagic acid, and ellagic acid derivatives, against S. pneumoniae planktonic cells and biofilm structures. Our studies first demonstrate that, when inoculated together with planktonic cultures, 220D-F2 inhibited the formation of pneumococcal biofilms in a dose-dependent manner. As measured by bacterial counts and a LIVE/DEAD bacterial viability assay, 100 and 200 µg/ml of 220D-F2 had significant bactericidal activity against pneumococcal planktonic cultures as early as 3 h post-inoculation. Quantitative MIC's, whether quantified by qPCR or dilution and plating, showed that 80 µg/ml of 220D-F2 completely eradicated overnight cultures of planktonic pneumococci, including antibiotic resistant strains. When preformed pneumococcal biofilms were challenged with 220D-F2, it significantly reduced the population of biofilms 3 h post-inoculation. Minimum biofilm inhibitory concentration (MBIC50 was obtained incubating biofilms with 100 µg/ml of 220D-F2 for 3 h and 6 h of incubation. 220D-F2 also significantly reduced the population of pneumococcal biofilms formed on human pharyngeal cells. Our results demonstrate potential therapeutic applications of 220D-F2 to both kill planktonic pneumococcal cells and disrupt pneumococcal biofilms.
Talekar, Sharmila J; Chochua, Sopio; Nelson, Katie; Klugman, Keith P; Quave, Cassandra L; Vidal, Jorge E
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
Full Text Available BACKGROUND: The degree and time frame of indirect effects of vaccination (serotype replacement and herd immunity are key determinants in assessing the net effectiveness of vaccination with pneumococcal conjugate vaccines (PCV in control of pneumococcal disease. Using modelling, we aimed to quantify these effects and their dependence on coverage of vaccination and the vaccine's efficacy against susceptibility to pneumococcal carriage. METHODS AND FINDINGS: We constructed an individual-based simulation model that explores the effects of large-scale PCV programmes and applied it in a developed country setting (Finland. A population structure with transmission of carriage taking place within relevant mixing groups (families, day care groups, schools and neighbourhoods was considered in order to properly assess the dependency of herd immunity on coverage of vaccination and vaccine efficacy against carriage. Issues regarding potential serotype replacement were addressed by employing a novel competition structure between multiple pneumococcal serotypes. Model parameters were calibrated from pre-vaccination data about the age-specific carriage prevalence and serotype distribution. The model predicts that elimination of vaccine-type carriage and disease among those vaccinated and, due to a substantial herd effect, also among the general population takes place within 5-10 years since the onset of a PCV programme with high (90% coverage of vaccination and moderate (50% vaccine efficacy against acquisition of carriage. A near-complete replacement of vaccine-type carriage by non-vaccine-type carriage occurs within the same time frame. CONCLUSIONS: The changed patterns in pneumococcal carriage after PCV vaccination predicted by the model are unequivocal. The overall effect on disease incidence depends crucially on the magnitude of age- and serotype-specific case-to-carrier ratios of the remaining serotypes relative to those of the vaccine types. Thus the
Full Text Available There is a lack of information on supply-side determinants, their utilization, and the access to pneumococcal vaccination in India. The objective of this exploratory study was to document the perceptions and perspectives of practicing pediatricians with regard to pneumococcal conjugate vaccines (PCVs in selected metropolitan areas of India. A qualitative study was conducted to generate evidence on the perspective of pediatricians practicing in the private sector regarding pneumococcal vaccination. The pediatricians were identified from 11 metropolitan areas on the basis of PCV vaccine sales in India through multilevel stratified sampling method. Relevant information was collected through in-depth personal interviews. Finally, qualitative data analysis was carried out through standard techniques such as the identification of key domains, words, phrases, and concepts from the respondents. We observed that the majority (67.7% of the pediatricians recommended pneumococcal vaccination to their clients, whereas 32.2% recommended it to only those who could afford it. More than half (62.9% of the pediatricians had no preference for any brand and recommended both a 10-valent pneumococcal conjugate vaccine (PCV10 and a 13-valent PCV (PCV13, whereas 8.0% recommended none. An overwhelming majority (97.3% of the pediatricians reported that the main reason for a patient not following the pediatrician′s advice for pneumococcal vaccination was the price of PCV. To reduce childhood pneumonia-related burden and mortality, pediatricians should use every opportunity to increase awareness about vaccine-preventable diseases, especially vaccine-preventable childhood pneumonia among their patients.
Zodpey, Sanjay; Farooqui, Habib Hasan; Chokshi, Maulik; Kumar, Balu Ravi; Thacker, Naveen
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
Hathaway, Lucy J; Grandgirard, Denis; Valente, Luca G; Täuber, Martin G; Leib, Stephen L
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
Alonso Palacio, J; Madrigal Díez, V; García Fuentes, M
A retrospective study of pneumococcal meningitis was carried out. This study included 22 cases of this illness that occurred in 17 pediatric patients in Cantabria between 1977 and 1990, inclusive. Three children suffered from recurrent meningitis. The age range of the patients was 0.3-14 years, with a mean age of 4 years. Of these cases, 77.4% occurred in the winter or spring. In 14 cases of meningitis (63.6%), corresponding to 9 patients, underlying pathology was observed: cranial fracture, occipital dermoid cyst, splenectomy, congenital cardiopathy, epilepsy and gastroduodenal "situs inversus". The isolated pneumococci were found to be resistant to penicillin and chloramphenicol in 4 cases. One patient suffered from septic shock. The outcome was complete recovery in 19 cases (86.4%), recovery with sequelae (deafness and epilepsy, respectively) in 2 cases (9.1%) and death in another 2 cases. CSF protein levels elevated above 150 mg/dl and the absence of glucose in the CSF were found to be the most useful analytical indicators of the seriousness of the illness. PMID:1497225
Nicholas J Croucher
Full Text Available Streptococcus pneumoniae isolates typically express one of over 90 immunologically distinguishable polysaccharide capsules (serotypes, which can be classified into "serogroups" based on cross-reactivity with certain antibodies. Pneumococci can alter their serotype through recombinations affecting the capsule polysaccharide synthesis (cps locus. Twenty such "serotype switching" events were fully characterised using a collection of 616 whole genome sequences from systematic surveys of pneumococcal carriage. Eleven of these were within-serogroup switches, representing a highly significant (p < 0.0001 enrichment based on the observed serotype distribution. Whereas the recombinations resulting in between-serogroup switches all spanned the entire cps locus, some of those that caused within-serogroup switches did not. However, higher rates of within-serogroup switching could not be fully explained by either more frequent, shorter recombinations, nor by genetic linkage to genes involved in β-lactam resistance. This suggested the observed pattern was a consequence of selection for preserving serogroup. Phenotyping of strains constructed to express different serotypes in common genetic backgrounds was used to test whether genotypes were physiologically adapted to particular serogroups. These data were consistent with epistatic interactions between the cps locus and the rest of the genome that were specific to serotype, but not serogroup, meaning they were unlikely to account for the observed distribution of capsule types. Exclusion of these genetic and physiological hypotheses suggested future work should focus on alternative mechanisms, such as host immunity spanning multiple serotypes within the same serogroup, which might explain the observed pattern.
Schlottmann, Sonela A; Jain, Neil; Chirmule, Narendra; Esser, Mark T
Here we describe a novel method to conjugate pneumococcal polysaccharides (PnPS) to Luminex microspheres for use in serological assays. 4-(4,6-dimethoxy[1,3,5]triazin-2-yl)-4-methyl-morpholinium (DMTMM) modification of PnPS and conjugation to carboxyl functional groups on Luminex microspheres (COOH-DMTMM method) was shown to be a reproducible chemistry that efficiently conjugated PnPS to Luminex microspheres without affecting the antigenicity of a broad set of PnPS. The COOH-DMTMM method was compared to three other methods for robustness, reproducibility and effect on PnPS antigenicity in a multiplexed assay format. The other methods examined included adsorption of the unmodified PnPS to Luminex microspheres, oxidation of the PnPS to conjugate them to amino-modified microspheres using carbodiimide chemistry and poly-l-lysine modification of the PnPS before conjugating to carboxy Luminex microspheres using carbodiimide chemistry. Of the four methods, the COOH-DMTMM chemistry was shown to be a robust methodology, producing stable PnPS coupled microspheres with a 4-log dynamic range and low cross-reactivity when used in a PnPS-specific IgG serology assay. This novel chemistry should be useful for developing serological assays to measure antibodies to polysaccharides for use in vaccine and epidemiology studies. PMID:16448665
Basset, Alan; Trzcinski, Krzysztof; Hermos, Christina; O'Brien, Katherine L.; Reid, Raymond; Santosham, Mathuram; McAdam, Alexander J.; Lipsitch, Marc; Malley, Richard
The recent discovery of a mobile genetic element encoding a pilus-like structure in Streptococcus pneumoniae and the demonstration of a role for the pilus in virulence in mice have led to the proposal of the use of the pilus as a candidate pneumococcal vaccine. We examined the frequency of occurrence of the pneumococcal pilus, as determined by the presence of the rrgC gene, and analyzed its association with virulence, capsular serotypes, and multilocus sequence types in the American Indian pn...
Gerwin D Rodenburg; Sabine C de Greeff; Jansen, Angelique G. C. S.; Hester E. de Melker; Leo M Schouls; Hak, Eelko; Spanjaard, Lodewijk; Sanders, Elisabeth A. M.; van der Ende, Arie
In the Netherlands, the 7-valent pneumococcal conjugate vaccine (PCV-7) was implemented in a 3+1-dose schedule in the national immunization program for infants born after April 1, 2006. To assess the vaccine’s effectiveness, we compared disease incidence before and after vaccine implementation (June 2004–June 2006 and June 2006–June 2008, respectively). We serotyped 2,552 invasive pneumococcal isolates from throughout the Netherlands, covering 25% of the country’s population. Clinical charact...
Møller, Holger Jon; K. Moestrup, Søren; Wejse, Christian;
probability of survival when sCD163 and CRP were known (p = .25). CONCLUSIONS: Macrophage marker response in pneumococcal bacteremia was compromised in old age. In patients <75 yrs old, sCD163 was superior to other markers, including C-reactive protein, in predicting fatal disease outcome....... pneumococcal bacteremia. DESIGN: Observational cohort study. SETTING: Five university hospitals in Denmark. PATIENTS: A total of 133 patients with Streptococcus pneumoniae bacteremia (positive blood culture) and 133 age- and gender-matched controls. INTERVENTIONS: Samples were collected for biochemical...
Wright, A K A; Briles, D E; Metzger, D W; Gordon, S B
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
Jefferies, J. M.; Smith, A. J.; Edwards, G.F.S.; McMenamin, J.; Mitchell, T J; Clarke, S. C.
In September 2006, the seven-valent pneumococcal conjugate vaccine (PCV7; Prevenar) was introduced into the childhood vaccination schedule in the United Kingdom. We monitored the population of invasive pneumococci in Scotland in the 5 years preceding the introduction of PCV7 by using serogrouping, multilocus sequence typing (MLST), and eBURST analysis. Here, we present a unique analysis of a complete national data set of invasive pneumococci over this time. We observed an increase in invasive...
Swiatlo, E.; J. King; Nabors, G S; Mathews, B; Briles, D. E.
Pneumococcal surface protein A (PspA) is an immunogenic protein expressed on the surface of all strains of Streptococcus pneumoniae (pneumococcus) and induces antibodies which protect against invasive infection in mice. Pneumococci used for infectious challenge in protection studies are typically collected from cultures grown in semisynthetic medium in vitro. The purpose of these studies is to confirm that PspA is expressed by pneumococci during growth in vivo at ...
Full Text Available Abstract Background Most guidelines have been proposing, for more than 15 years, a β-lactam combined with either a quinolone or a macrolide as empirical, first-line therapy of severe community acquired pneumonia (CAP requiring ICU admission. Our goal was to evaluate the outcome of patients with severe CAP, focusing on the impact of new rather than old fluoroquinolones combined with β-lactam in the empirical antimicrobial treatments. Methods Retrospective study of consecutive patients admitted in a 16-bed general intensive care unit (ICU, between January 1996 and January 2009, for severe (Pneumonia Severity Index > or = 4 community-acquired pneumonia due to non penicillin-resistant Streptococcus pneumoniae and treated with a β-lactam combined with a fluoroquinolone. Results We included 70 patients of whom 38 received a β-lactam combined with ofloxacin or ciprofloxacin and 32 combined with levofloxacin. Twenty six patients (37.1% died in the ICU. Three independent factors associated with decreased survival in ICU were identified: septic shock on ICU admission (AOR = 10.6; 95% CI 2.87-39.3; p = 0.0004, age > 70 yrs. (AOR = 4.88; 95% CI 1.41-16.9; p = 0.01 and initial treatment with a β-lactam combined with ofloxacin or ciprofloxacin (AOR = 4.1; 95% CI 1.13-15.13; p = 0.03. Conclusion Our results suggest that, when combined to a β-lactam, levofloxacin is associated with lower mortality than ofloxacin or ciprofloxacin in severe pneumococcal community-acquired pneumonia.
Full Text Available Streptococcus pneumoniae is a leading cause of bacterial pneumonia worldwide. Given the critical role of dendritic cells (DCs in regulating and modulating the immune response to pathogens, we investigated here the role of DCs in S. pneumoniae lung infections. Using a well-established transgenic mouse line which allows the conditional transient depletion of DCs, we showed that ablation of DCs resulted in enhanced resistance to intranasal challenge with S. pneumoniae. DC-depleted mice exhibited delayed bacterial systemic dissemination, significantly reduced bacterial loads in the infected organs and lower levels of serum inflammatory mediators than non-depleted animals. The increased resistance of DC-depleted mice to S. pneumoniae was associated with a better capacity to restrict pneumococci extrapulmonary dissemination. Furthermore, we demonstrated that S. pneumoniae disseminated from the lungs into the regional lymph nodes in a cell-independent manner and that this direct way of dissemination was much more efficient in the presence of DCs. We also provide evidence that S. pneumoniae induces expression and activation of matrix metalloproteinase-9 (MMP-9 in cultured bone marrow-derived DCs. MMP-9 is a protease involved in the breakdown of extracellular matrix proteins and is critical for DC trafficking across extracellular matrix and basement membranes during the migration from the periphery to the lymph nodes. MMP-9 was also significantly up-regulated in the lungs of mice after intranasal infection with S. pneumoniae. Notably, the expression levels of MMP-9 in the infected lungs were significantly decreased after depletion of DCs suggesting the involvement of DCs in MMP-9 production during pneumococcal pneumonia. Thus, we propose that S. pneumoniae can exploit the DC-derived proteolysis to open tissue barriers thereby facilitating its own dissemination from the local site of infection.
Zwijnenburg, P.J.G.; Poll, van der T.; Florquin, S; Akira, S; Takeda, K; Roord, J.J.; Furth, van A.M.
To determine the role of endogenous interleukin-18 (IL-18) in pneumococcal meningitis, meningitis was induced in IL-18 gene-deficient (IL-18(-/-)) and wild-type (WT) mice by intranasal inoculation of Streptococcus pneumoniae with hyaluronidase. Induction of meningitis resulted in an upregulation of
Vandenbos, F; Roth, S; Montagne, N
We report a case of mitral endocarditis caused by Streptococcus pneumoniae in a 43 year old man with history of alcohol abuse and cigarette smoking. The pneumococcal endocarditis was associated with pneumonia, meningitis and brain abscess. Only transesophageal echocardiography could confirm the presence of vegetation. The patient was treated medically with good results. PMID:11887774
McEllistrem, M. Catherine; Nahm, Moon H.
The discovery of serotypes 6C and 6D, the former of which expanded in the 7-valent pneumococcal protein conjugate vaccine era, illustrates a previously unrecognized limitation of conjugate vaccines: the expansion of unrecognized serotypes could erode the efficacy of a serotype-specific vaccine.
Wiese, Andrew D; Grijalva, Carlos G; Zhu, Yuwei; Mitchel, Edward F; Griffin, Marie R
Introduction of pneumococcal conjugate vaccines in the childhood immunization schedule was associated with decreases in all-cause pneumonia hospitalizations among black and white children in Tennessee, USA. Although racial disparities that existed before introduction of these vaccines have been substantially reduced, rates remain higher in boys than in girls among young children. PMID:27197048
Troldborg, Anne; Deleuran, Bent; Storgaard, Merete
Autosplenectomy is a rare phenomenon in patients with systemic lupus erythematosus (SLE). We present a case of pneumococcal septicaemia in an SLE patient. A CT-scan of the abdomen showed complete autosplenectomy, but a CT scan from years prior showed a normal size spleen. SLE patients have an...
Vassal-Stermann, Emilie; Lacroix, Monique; Gout, Evelyne;
clinical isolates, but its ligands and especially its molecular specificity remain to be identified. Using solid-phase binding assays, serum and recombinant L-ficolins were shown to interact with serotype 2 pneumococcal strain D39 and its unencapsulated R6 derivative. Incubation of both strains with serum...
Harboe, Zitta B; Valentiner-Branth, Palle; Ingels, Helene;
A seven-valent pneumococcal conjugate vaccine (PCV7) was introduced in the Danish childhood immunization program (2+1 schedule) in October 2007, followed by PCV13 starting from April 2010. The nationwide incidence of IPD among children younger than 5 years nearly halved after the introduction of ...
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
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
Worsøe, Lise Lotte; Caye-Thomasen, P.; Brandt, C.T.; Thomsen, J.; Andersen, Christian Østergaard
Background. On the basis of a nationwide registration during a 5-year period (1999-2003), the frequency and severity of hearing loss was investigated retrospectively in 343 consecutive Danish patients who survived pneumococcal meningitis, to identify important risk factors (including the pneumoco...
Wang, Erjian; Simard, Marie; Ouellet, Nathalie; Bergeron, Yves; Beauchamp, Denis; Bergeron, Michel G.
Streptococcus pneumoniae pneumonia frequently occurs in leukopenic hosts, and most patients subsequently develop lung injury and septicemia. However, few correlations have been made so far between microbial growth, inflammation, and histopathology of pneumonia in specific leukopenic states. In the present study, the pathogenesis of pneumococcal pneumonia was investigated in mice rendered leukopenic by the immunosuppressor antineoplastic drug cyclophosphamide. Compared to the immunocompetent s...
Grijalva, Carlos G.; Zhu, Yuwei; Mitchel, Edward F.; Griffin, Marie R.
Introduction of pneumococcal conjugate vaccines in the childhood immunization schedule was associated with decreases in all-cause pneumonia hospitalizations among black and white children in Tennessee, USA. Although racial disparities that existed before introduction of these vaccines have been substantially reduced, rates remain higher in boys than in girls among young children. PMID:27197048
M. Schouten; C. van 't Veer; J.J.T.H. Roelofs; B. Gerlitz; B.W. Grinnell; M. Levi; T. van der Poll
Recombinant human activated protein C (APC), which has both anticoagulant and anti-inflammatory properties, improves survival of patients with severe sepsis. This beneficial effect is especially apparent in patients with pneumococcal pneumonia. Earlier treatment with APC in sepsis has been associate
Full Text Available Abstract Background Streptococcus pneumoniae infections, which place a considerable burden on healthcare resources, can be reduced in a cost-effective manner using a 7-valent pneumococcal conjugate vaccine (PCV-7. We compare the cost effectiveness of a 13-valent PCV (PCV-13 and a 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV with that of PCV-7 in Turkey. Methods A cost-utility analysis was conducted and a decision analytical model was used to estimate the proportion of the Turkish population Results PCV-13 and PHiD-CV are projected to have a substantial impact on pneumococcal disease in Turkey versus PCV-7, with 2,223 and 3,156 quality-adjusted life years (QALYs and 2,146 and 2,081 life years, respectively, being saved under a 3+1 schedule. Projections of direct medical costs showed that a PHiD-CV vaccination programme would provide the greatest cost savings, offering additional savings of US$11,718,813 versus PCV-7 and US$8,235,010 versus PCV-13. Probabilistic sensitivity analysis showed that PHiD-CV dominated PCV-13 in terms of QALYs gained and cost savings in 58.3% of simulations. Conclusion Under the modeled conditions, PHiD-CV would provide the most cost-effective intervention for reducing pneumococcal disease in Turkish children.
Yasir Alhamdi; Neill, Daniel R.; Abrams, Simon T.; Malak, Hesham A.; Reham Yahya; Richard Barrett-Jolley; Guozheng Wang; Aras Kadioglu; Cheng-Hock Toh
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 ...
Full Text Available A nonneutropenic patient with treated low-grade non-Hodgkin’s (Follicular lymphoma and secondary hypogammaglobulinemia recovered from pneumococcal pneumonia and septicemia (serotype 7F; ST191 subsequent to influenza A H1N1 (2009. Both infections were potentially vaccine preventable. The patient then developed pneumococcal meningitis due to a serotype 35F pneumococcus with a unique Multilocus Sequence Type (ST7004 which was not vaccine preventable. Patient management was influenced by host predisposition to pneumococcal infection, antibiotic intolerance, and poor response to polysaccharide pneumococcal vaccine. Indirect immunofluorescence with anti-human immunoglobulin confirmed a poor or intermediate response to Pneumovax II. Prophylactic erythromycin was initiated, and immunoglobulin transfusions were also commenced as a preventive strategy. ST7004 is a single locus variant of ST1635 which has been associated with the serotype 35F capsule in England. The spi gene in ST7004, which differentiates it from ST1635, is the same as the spi gene present in ST191 which could have arisen from the first disease episode suggesting that horizontal gene transfer may have occurred between different populations of pneumococci present within the patient in an attempt to evade vaccination selection pressure.
Kantsø, Bjørn; Simonsen, Jacob; Hoffmann, Steen;
OBJECTIVES: Inflammatory bowel disease (IBD), Crohn's disease (CD), and ulcerative colitis (UC) are chronic diseases characterized by an inappropriate immune response, which may also increase the risk of infections. We investigated the risk of invasive pneumococcal disease (IPD) before and after...
Economic Evaluation of Immunisation Programme of 23-Valent Pneumococcal Polysaccharide Vaccine and the Inclusion of 13-Valent Pneumococcal Conjugate Vaccine in the List for Single-Dose Subsidy to the Elderly in Japan.
Full Text Available Currently in Japan, both 23-valent pneumococcal polysaccharide vaccine (PPSV-23 and 13-valent pneumococcal conjugate vaccine (PCV-13 are available for the elderly for the prevention of S. pneumoniae-related diseases. PPSV-23 was approved in 1988, while the extended use of PCV-13 was approved for adults aged 65 and older in June 2014. Despite these two vaccines being available, the recently launched national immunisation programme for the elderly only subsidised PPSV-23. The framework of the current immunisation programme lasts for five years. The elderly population eligible for the subsidised PPSV-23 shot for the 1st year are those aged 65, 70, 75, 80, 85, 90, 95 and ≥ 100. While from the 2nd year to the 5th year, those who will age 65, 70, 75, 80, 85, 90, 95 and 100 will receive the same subsidised shot.We performed economic evaluations to (1 evaluate the efficiency of alternative strategies of PPSV-23 single-dose immunisation programme, and (2 investigate the efficiency of PCV-13 inclusion in the list for single-dose pneumococcal vaccine immunisation programme. Three alternative strategies were created in this study, namely: (1 current PPSV-23 strategy, (2 65 to 80 (as "65-80 PPSV-23 strategy", and (3 65 and older (as "≥ 65 PPSV-23 strategy". We constructed a Markov model depicting the S. pneumoniae-related disease course pathways. The transition probabilities, utility weights to estimate quality adjusted life year (QALY and disease treatment costs were either calculated or cited from literature. Cost of per shot of vaccine was ¥ 8,116 (US$74; US$1 = ¥ 110 for PPSV-23 and ¥ 10,776 (US$98 for PCV-13. The model runs for 15 years with one year cycle after immunisation. Discounting was at 3%.Compared to current PPSV-23 strategy, 65-80 PPSV-23 strategy cost less but gained less, while the incremental cost-effectiveness ratios (ICERs of ≥ 65 PPSV-23 strategy was ¥ 5,025,000 (US$45,682 per QALY gained. PCV-13 inclusion into the list for
Nieto, Pamela A; Peñaloza, Hernán F; Salazar-Echegarai, Francisco J; Castellanos, Raquel M; Opazo, Maria Cecilia; Venegas, Luis; Padilla, Oslando; Kalergis, Alexis M; Riedel, Claudia A; Bueno, Susan M
Maternal thyroid hormones are essential for proper fetal development. A deficit of these hormones during gestation has enduring consequences in the central nervous system of the offspring, including detrimental learning and impaired memory. Few studies have shown that thyroid hormone deficiency has a transient effect in the number of T and B cells in the offspring gestated under hypothyroidism; however, there are no studies showing whether maternal hypothyroidism during gestation impacts the response of the offspring to infections. In this study, we have evaluated whether adult mice gestated in hypothyroid mothers have an altered response to pneumococcal pneumonia. We observed that female mice gestated in hypothyroidism have increased survival rate and less bacterial dissemination to blood and brain after an intranasal challenge with Streptococcus pneumoniae. Further, these mice had higher amounts of inflammatory cells in the lungs and reduced production of cytokines characteristic of sepsis in spleen, blood, and brain at 48 hours after infection. Interestingly, mice gestated in hypothyroid mothers had basally increased vascular permeability in the lungs. These observations suggest that gestational hypothyroidism alters the immune response and the physiology of lungs in the offspring, increasing the resistance to respiratory bacterial infections. PMID:27035652
Serotype Distribution and Antimicrobial Resistance of Streptococcus pneumoniae prior to Introduction of the 10-Valent Pneumococcal Conjugate Vaccine in Brazil, 2000-2007: Pneumococcal Serotypes Prior to Conjugate Vaccine Introduction
Menezes, Ana Paula de O.; Campos, Leila C.; dos Santos, Milena S.; Azevedo, Jailton; dos Santos, Renan Cardoso Nery; Carvalho, Maria da Gloria S.; Beall, Bernard W.; Martin, Stacey W.; Salgado, Katia; Reis, Mitermayer G.; Ko, Albert I.; Reis, Joice N
This study describes the serotype distribution and antibiotic resistance patterns among 397 S. pneumoniae meningitis case isolates recovered in Salvador, Brazil, during the period of 2000-2007, before introduction of the 10-valent pneumococcal conjugate vaccine.
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
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
van der Linden Mark
Full Text Available Abstract Background This study presents an analysis of 159 serotype 19A isolates from IPD in children before and after the general recommendation for childhood pneumococcal conjugate vaccination in Germany in July 2006. Vaccination formulations used were PCV7, PCV10 (from April 2009 and PCV13 (from Dec. 2009, replacing PCV7. Methods Isolates from invasive pneumococcal disease in children were serotyped using the Quellung reaction, tested for antibiotic susceptibility and analysed for their multi locus sequence type. Results In an analysis of 3328 isolates from invasive pneumococcal disease (IPD in children that were sent to the German National Reference Center for Streptococci between July 1997 and June 2011, we show that the proportion of 19A isolates ranged between 1.7 and 4.2% in the period 1997 to 2006. After the recommendation for pneumococcal conjugate childhood vaccination, which was issued in July 2006, the proportion of 19A isolates increased significantly to 15.0% in 2010/11. Eight clonal complexes (CC and groups accounted for 77.2% and 65.3% of all serotype 19A isolates before and after vaccination, respectively. While three CCs and several STs were not detected after vaccine introduction, four CCs and several STs first appeared after vaccination, including three ST320 isolates that could be traced to recent imports from the US, UK and India. The proportion of penicillin-nonsusceptible and of multidrug-resistant 19A isolates moderately increased after vaccine introduction. A significant increase in the use of cephalosporins and azithromycin was noted post-vaccination (p=0.00001 and p=0.0013 respectively. Conclusions The prevalence of serotype 19A in Germany has increased significantly between July 2007 and June 2011. Possible reasons for this are the introduction of pneumococcal conjugate vaccination, increased use of cephalosporins and azithromycin, import of multidrug-resistant isolates and increased reporting.
Kim S LeMessurier
Full Text Available 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.
Balloch, Anne; Licciardi, Paul V.; Russell, Fiona M.; Edward K Mulholland; Tang, Mimi L. K.
This is the first study examining serotype-specific IgG responses following immunization with the polysaccharide vaccine Pneumovax® in infants aged 12 months in the absence of prior pneumococcal conjugate vaccine priming.
van Gils, E.J.M.; Hak, E.; Veenhoven, R.H.; Rodenburg, G.D.; Bogaert, D.; Bruin, J.P.; van Alphen, L.; Sanders, E.A.M.
Background: Heptavalent pneumococcal conjugate vaccine (PCV7) shifts nasopharyngeal colonisation with vaccine serotype pneumococci towards nonvaccine serotypes. Because of the reported negative association of vaccine serotype pneumococci and Staphylococcus aureus in the nasopharynx, we explored the
C. Azzari; M. Moriondo; G. INDOLFI; CORTIMIGLIA M; Canessa, C; BECCIOLINI L; F. Lippi; Martino, M; Resti, M
Background Pneumococcal serotyping is usually performed by Quellung reaction, considered the gold standard test. However the method cannot be used on culture-negative samples. Molecular methods can be a useful alternative. The aim of the study was to evaluate the use of Multiplex-sequential-PCR (MS-PCR) or Realtime-PCR on blood samples for diagnosis and serotyping of invasive pneumococcal disease (IPD) in a pediatric clinical setting. Methodology/Principal Findings Sensitivity and specificity...
Tigoi, Caroline C.; Gatakaa, Hellen; Karani, Angela; Mugo, Daisy; Kungu, Stella; Wanjiru, Eva; Jomo, Jane; Musyimi, Robert; Ojal, John; Glass, Nina E.; Abdullahi, Osman; Scott, J Anthony G
Background. Herd protection and serotype replacement disease following introduction of pneumococcal conjugate vaccine (PCV) are attributable to the vaccine's impact on colonization. Prior to vaccine introduction in Kenya, we did an epidemiological study to estimate the rate of pneumococcal acquisition, by serotype, in an uncolonized population. Methods. Nasopharyngeal swab specimens were taken from newborns aged ≤7 days and weekly thereafter for 13 weeks. Parents, and siblings aged
Dagan, Ron; Shriker, Ofra; Hazan, Inbal; Leibovitz, Eugene; Greenberg, David; Schlaeffer, Francis; Levy, Rachel
We undertook a prospective study to evaluate the accuracy of PCR of serum (aimed at the pneumococcal pneumolysin gene) at detecting pneumococcal infections in infants and children. The assay was positive for all blood and cerebrospinal fluid culture-positive samples and for 38 and 44% of patients with lobar pneumonia and acute otitis media, respectively. It was positive for 17% of healthy controls. There was a marked effect of age on the rate of positivity among healthy controls, with the hig...
Perciani, Catia T.; Barazzone, Giovana C.; Goulart, Cibelly; Carvalho, Eneas; Cabrera-Crespo, Joaquin; Gonçalves, Viviane M.; Luciana C. C. Leite; Tanizaki, Martha M.
Despite the substantial beneficial effects of incorporating the 7-valent pneumococcal conjugate vaccine (PCV7) into immunization programs, serotype replacement has been observed after its widespread use. As there are many serotypes currently documented, the use of a conjugate vaccine relying on protective pneumococcal proteins as active carriers is a promising alternative to expand PCV coverage. In this study, capsular polysaccharide serotype 6B (PS6B) and recombinant pneumococcal surface pro...
Lipsitch, Marc; O’Neill, Keith; Cordy, Derrick; Bugalter, Boris; Trzcinski, Krzysztof; Thompson, Claudette M; Goldstein, Richard; Pelton, Stephen; Huot, Heather; Bouchet, Valerie; Reid, Raymond; Santosham, Mathuram; O’Brien, Katherine L.
Widespread use of 7-valent pneumococcal conjugate vaccine (PCV7) has led to significant reductions in disease while changing pneumococcal population dynamics via herd immunity and serotype replacement. We performed multilocus sequence typing (MLST) on 590 pneumococcal isolates obtained during the American Indian clinical trial of PCV7, in which communities were randomized for eligible children to receive either PCV7 or a meningococcal conjugate vaccine (MCV). Sequence types (STs) were analyze...
Jonczyk, Magda S; Escudero, Laura; Sylvius, Nicolas; Norman, Martin; Henriques-Normark, Birgitta; Andrew, Peter W
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 pneumoniaeis 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
M. Teresa Valenzuela B.
Full Text Available S. pneumoniae is a significant cause of community-acquired pneumonia in the elderly, and accounts for the majority of the pneumonia deaths among the elderly. We conducted this randomized double-blind study to evaluate the immune response to a 23-valent pneumococcal polysaccharide vaccine and the persistence of antibodies two years after the vaccination in an elderly population in Santiago, Chile. A total of 118 elderly nursing home residents received either the pneumococcal or a tetanus control vaccine. Serum samples were taken at enrolment, at two months, and at two years post-vaccination. Pre-vaccination anti-pneumococcal antibody geometric mean concentrations (GMC were similar in both study groups, with increased levels of antibodies found only against serotype 14. The pneumococcal vaccine was highly immunogenic at 2 months, and titers remained high two years after the vaccination for the 10 serotypes studied in this elderly population. The results thus support the benefits of this pneumococcal vaccine in this elderly population who are at increased risk of invasive pneumococcal disease.
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
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
Pride, Michael W; Huijts, Susanne M; Wu, Kangjian; Souza, Victor; Passador, Sherry; Tinder, Chunyan; Song, Esther; Elfassy, Arik; McNeil, Lisa; Menton, Ronald; French, Roger; Callahan, Janice; Webber, Chris; Gruber, William C; Bonten, Marc J M; Jansen, Kathrin U
To improve the clinical diagnosis of pneumococcal infection in bacteremic and nonbacteremic community-acquired pneumonia (CAP), a Luminex technology-based multiplex urinary antigen detection (UAD) diagnostic assay was developed and validated. The UAD assay can simultaneously detect 13 different serotypes of Streptococcus pneumoniae by capturing serotype-specific S. pneumoniae polysaccharides (PnPSs) secreted in human urine. Assay specificity is achieved by capturing the polysaccharides with serotype-specific monoclonal antibodies (MAbs) on spectrally unique microspheres. Positivity for each serotype was based on positivity cutoff values calculated from a standard curve run on each assay plate together with positive- and negative-control urine samples. The assay is highly specific, since significant signals are detected only when each PnPS was paired with its homologous MAb-coated microspheres. Validation experiments demonstrated excellent accuracy and precision. The UAD assay and corresponding positivity cutoff values were clinically validated by assessing 776 urine specimens obtained from patients with X-ray-confirmed CAP. The UAD assay demonstrated 97% sensitivity and 100% specificity using samples obtained from patients with bacteremic, blood culture-positive CAP. Importantly, the UAD assay identified Streptococcus pneumoniae (13 serotypes) in a proportion of individuals with nonbacteremic CAP, a patient population for which the pneumococcal etiology of CAP was previously difficult to assess. Therefore, the UAD assay provides a specific, noninvasive, sensitive, and reproducible tool to support vaccine efficacy as well as epidemiological evaluation of pneumococcal disease, including CAP, in adults. PMID:22675155
Diana C Otczyk
Full Text Available Pneumonia in childhood is endemic in large parts of the world and in particular, in developing countries, as well as in many indigenous communities within developed nations. Haemophilus influenzae type b and Streptococcus pneumoniae conjugate vaccines are currently available against the leading bacterial causes of pneumonia. The use of the vaccines in both industrialised and developing countries have shown a dramatic reduction in the burden of pneumonia and invasive disease in children. However, the greatest threat facing pneumococcal conjugate vaccine effectiveness is serotype replacement. The current vaccines provide serotype-specific, antibody–mediated protection against only a few of the 90+ capsule serotypes. Therefore, there has been a focus in recent years to rapidly advance technologies that will result in broader disease coverage and more affordable vaccines that can be used in developing countries. The next generation of pneumococcal vaccines have advanced to clinical trials.
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
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
Prasanth, Sudhakaran; Shaji, Velayudhan Cheruvallil; Lyla, Chacko; Jayalakshmi, Vasudevapanicker
Pneumococcal meningitis remains a life-threatening infection, with varied presentations. A 3 month-old-baby with pneumococcal meningitis presented with clusters of seizures evolving into refractory status epilepticus despite standard antibiotic and aggressive anticonvulsant therapy. Progressive illness despite antibiotic initially suggested possible antibiotic resistance and resulted in addition of another antibiotic. Nonresponse to standard treatment and previous history of abscess in the back of neck pointed to some underlying congenital immunodeficiency. Further evaluation showed a deficiency of complement factor C3. This case underlines the need to consider underlying immunodeficiency in cases of refractory status epilepticus due to bacterial meningitis. Gram-staining of cerebrospinal fluid sample showing plenty of Gram-positive bacteria and comparatively fewer pus cells is a clue regarding some underlying immunodeficiency.
M. Weisfelt; D. van de Beek; J. de Gans
In experimental meningitis, adjunctive treatment with steroids reduces cerebrospinal fluid inflammation and thereby improves neurological outcome. On the basis of these findings, several clinical trials have assessed treatment with adjunctive steroids in bacterial meningitis, with conflicting result
... HIV Chronic renal failure Nephrotic syndrome Leukemia Lymphoma Hodgkin disease Generalized malignancy Iatrogenic immunosuppression 5 Solid organ transplant Multiple myeloma PCV13 Administer PCV13 doses needed to complete series to children through age 71 months X X X X ...
Reppe, Katrin; Radünzel, Peter; Dietert, Kristina; Tschernig, Thomas; Wolff, Thorsten; Hammerschmidt, Sven; Gruber, Achim D; Suttorp, Norbert; Witzenrath, Martin
Pulmonary infection with influenza virus is frequently complicated by bacterial superinfection, with Streptococcus pneumoniae being the most prevalent causal pathogen and hence often associated with high morbidity and mortality rates. Local immunosuppression due to pulmonary influenza virus infection has been identified as a major cause of the pathogenesis of secondary bacterial lung infection. Thus, specific local stimulation of the pulmonary innate immune system in subjects with influenza virus infection might improve the host defense against secondary bacterial pathogens. In the present study, we examined the effect of pulmonary immunostimulation with Toll-like receptor 2 (TLR-2)-stimulating macrophage-activating lipopeptide 2 (MALP-2) in influenza A virus (IAV)-infected mice on the course of subsequent pneumococcal superinfection. Female C57BL/6N mice infected with IAV were treated with MALP-2 on day 5 and challenged with S. pneumoniae on day 6. Intratracheal MALP-2 application increased proinflammatory cytokine and chemokine release and enhanced the recruitment of leukocytes, mainly neutrophils, into the alveolar space of IAV-infected mice, without detectable systemic side effects. Local pulmonary instillation of MALP-2 in IAV-infected mice 24 h before transnasal pneumococcal infection considerably reduced the bacterial number in the lung tissue without inducing exaggerated inflammation. The pulmonary viral load was not altered by MALP-2. Clinically, MALP-2 treatment of IAV-infected mice increased survival rates and reduced hypothermia and body weight loss after pneumococcal superinfection compared to those of untreated coinfected mice. In conclusion, local immunostimulation with MALP-2 in influenza virus-infected mice improved pulmonary bacterial elimination and increased survival after subsequent pneumococcal superinfection. PMID:26371127
Biesbroek, G.; Wang, X.; Keijser, B.J.F.; Eijkemans, R.M.J.; Trzciński, K.; Rots, N.Y.; Veenhoven, R.H.; Sanders, E. A. M.; Bogaert, D.
Seven-valent pneumococcal conjugate vaccine (PCV- 7) is effective against vaccine serotype disease and carriage. Nevertheless, shifts in colonization and disease toward nonvaccine serotypes and other potential pathogens have been described. To understand the extent of these shifts, we analyzed nasopharyngeal microbial profiles of 97 PCV-7-vaccinated infants and 103 control infants participating in a randomized controlled trial in the Netherlands. PCV-7 immunization resulted in a temporary shi...
Full Text Available Pneumonia is considered to be one of the leading causes of death worldwide. The outcome depends on both, proper antibiotic treatment and the effectivity of the immune response of the host. However, due to the complexity of the immunologic cascade initiated during infection, the latter cannot be predicted easily. We construct a biomathematical model of the murine immune response during infection with pneumococcus aiming at predicting the outcome of antibiotic treatment. The model consists of a number of non-linear ordinary differential equations describing dynamics of pneumococcal population, the inflammatory cytokine IL-6, neutrophils and macrophages fighting the infection and destruction of alveolar tissue due to pneumococcus. Equations were derived by translating known biological mechanisms and assuming certain response kinetics. Antibiotic therapy is modelled by a transient depletion of bacteria. Unknown model parameters were determined by fitting the predictions of the model to data sets derived from mice experiments of pneumococcal lung infection with and without antibiotic treatment. Time series of pneumococcal population, debris, neutrophils, activated epithelial cells, macrophages, monocytes and IL-6 serum concentrations were available for this purpose. The antibiotics Ampicillin and Moxifloxacin were considered. Parameter fittings resulted in a good agreement of model and data for all experimental scenarios. Identifiability of parameters is also estimated. The model can be used to predict the performance of alternative schedules of antibiotic treatment. We conclude that we established a biomathematical model of pneumococcal lung infection in mice allowing predictions regarding the outcome of different schedules of antibiotic treatment. We aim at translating the model to the human situation in the near future.
Kihara Michael; de Haan Michelle; Were Eugene O; Garrashi Harrun H; Neville Brian GR; Newton Charles RJC
Abstract Background Pneumococcal meningitis (PM) is a severe and life-threatening disease that is associated with cognitive impairment including learning difficulties, cognitive slowness, short-term memory deficits and poor academic performance. There are limited data on cognitive outcomes following exposure to PM from Africa mainly due to lack of culturally appropriate tools. We report cognitive processes of exposed children as measured by auditory and visual event-related potentials. Method...
Solano-Collado, Virtu; Espinosa, Manuel; Bravo, Alicia
Global transcriptional regulators that respond to specific environmental signals are crucial in bacterial pathogenesis. In the case of the Gram-positive pathogen Streptococcus pneumoniae (the pneumococcus), the sp1800 gene of the clinical isolate TIGR4 encodes a protein that exhibits homology to the Mga “stand-alone” response regulator of the group A Streptococcus. Such a pneumococcal protein was shown to play a significant role in both nasopharyngeal colonization and development of pneumonia...
M. S. Naumtseva
Full Text Available Objective: to study the clinical efficacy, immunogenicity, and safety of a 23-valent pneumococcal vaccine in patients with rheumatoid arthritis (RA. Subjects and methods. The investigation enrolled 70 patients (55 women and 15 men aged 23–70 years, including 40 patients with RA and 30 people without systemic inflammatory rheumatic diseases (a control group who had a recent history of 2 and more cases of lower respiratory tract infections (bronchitis, pneumonia. When included, all the patients received anti-inflammatory therapy with methotrexate (MT (n = 24, leflunomide (LEF (n = 6, or MT + tumor necrosis factor-α (TNF-α inhibitors (n = 10. A single 0.5-ml dose of the 23-valent pneumococcal vaccine Pneumo-23 (Sanofi Pasteur was administered subcutaneously or intramuscularly during continuous MT or LEF therapy for the underlying disease or 3–4 weeks before the use of a TNF-α inhibitor. During control visits (1 and 3 months and 1 year after administration of the vaccine, the patients underwent physical examination and routine clinical and laboratory studies. Results. No clinical and radiological symptoms of pneumonia were recorded in any case during a 12-month follow-up. The RA and control groups showed a more than 2-fold increase in anti-pneumococcal antibody levels 1 year after vaccination. The vaccine was well tolerated by 50 patients. Sixteen patients were observed to have pain, cutaneous swelling and hyperemia and 4 had subfebrility. There were neither episodes of RA exacerbation nor new autoimmune disorders during the follow-up. Conclusion. The findings suggest that 23-valent pneumococcal vaccine shows a good clinical efficacy, adequate immunogenicity, and good tolerability in the patients with RA.
Hirohito Kita; Juhn, Young J.; Robin Patel; Rouse, Mark S.; Cheol-In Kang; Hongxia Zhao
Interleukin- (IL-) 17 is important in the development of asthma and host defense against pneumococci. We determined the role of IL-17 in the risk of pneumococcal pneumonia. We challenged mice intranasally with a bioluminescent Streptococcus pneumoniae strain after sensitization and challenge with ovalbumin (OVA). We measured the levels of cytokines, including IL-17 (pg/mL), in the lung homogenate in experimental mice with and without OVA sensitization/challenge, as well as those with and with...
Doddi Sudeendra; Singhal Tarun; Sinha Prakash
Abstract Introduction Acute compartment syndrome is a surgical emergency requiring immediate fasciotomy. Spontaneous onset of acute compartment syndrome of the lower limbs is rare. We present a very rare case of pneumococcal sepsis leading to spontaneous acute compartment syndrome. Case presentation A 40-year-old Caucasian man presented as an emergency with spontaneous onset of pain in both legs and signs of compartment syndrome. This was confirmed on fasciotomy. Blood culture grew Streptococ...
Wei Feifei; Xu Stanley; France Eric K; Yu Xian-Jie; Chan K Arnold; Kleinman Ken; Lin Nancy D; Mullooly John; Santoli Jeanne; Lieu Tracy A
Abstract Background The introduction of pneumococcal conjugate vaccine (PCV) to the U.S. recommended childhood immunization schedule in the year 2000 added three injections to the number of vaccinations a child is expected to receive during the first year of life. Surveys have suggested that the addition of PCV has led some immunization providers to move other routine childhood vaccinations to later ages, which could increase the possibility of missing these vaccines. The purpose of this stud...
Brown, E J; Hosea, S W; Hammer, C H; Burch, C G; Frank, M M
The mechanism of protection of type-specific antipneumococcal antibody and complement in bacteremia was investigated with purified rabbit antibody and a guinea pig model of pneumococcal bacteremia. IgG and IgM were isolated from the sera of rabbits immunized with type 7 pneumococci (Pn), and their binding to Pn was quantitated. The number of antibody-binding sites on the pnuemococcal capsule was also determined. Pn were incubated with various amounts of the immunoglobulin preparations before ...
Gallagher, Stephen; Phillips, Anna C; Ferraro, Alastair J.; Drayson, Mark T.; Carroll, Douglas
Evidence shows that psychosocial factors are associated with immunoglobulin G response to medical vaccinations. As yet, there are no reports of whether the earlier immunoglobulin M response is similarly susceptible. This study examined the association between psychological stress, social support and the immunoglobulin M response to vaccination with pneumococcal capsular polysaccharides. Stressful life events in the previous year and customary social support were measured by standard questionn...
Pneumonia causes about three million deaths a year in young children, nearly all of which are in developing countries. Streptococcus pneumoniae (the pneumococcus) is the most important bacterial cause of pneumonia in young children and so is likely to be responsible for a high proportion of these deaths. The pneumococcus is also responsible for a substantial proportion of the 100,000-500,000 deaths that occur from meningitis in children each year. The incidence of invasive pneumococcal diseas...
Lynch, Joyce M.; Briles, David E.; Metzger, Dennis W.
Streptococcus pneumoniae is a common cause of respiratory tract infections, its main entry route being the nasal mucosa. The recent development of pneumococcal polysaccharide conjugate vaccines has led to a dramatic improvement in protection against invasive disease in infants and children, but these vaccines have been found to be only 50 to 60% protective against bacterial carriage. In this study, we investigated the efficacy of intranasal (i.n.) conjugate vaccine delivery using interleukin-...
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
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
Eisen, Damon P; Dean, Melinda M; Boermeester, Marja A;
MBL-deficient patients with Streptococcus pneumoniae infection (odds ratio, 5.62; 95% confidence interval, 1.27-24.92) after adjustment for bacteremia, comorbidities, and age. CONCLUSIONS: We defined a serum level for MBL deficiency that can be used with confidence in future studies of MBL disease...... associations. The risk of death was increased among MBL-deficient patients with severe pneumococcal infection, highlighting the pathogenic significance of this innate immune defence protein....
Angela B Brueggemann
Full Text Available The heptavalent pneumococcal conjugate vaccine (PCV7 was introduced in the United States (US in 2000 and has significantly reduced invasive pneumococcal disease; however, the incidence of nonvaccine serotype invasive disease, particularly due to serotype 19A, has increased. The serotype 19A increase can be explained in part by expansion of a genotype that has been circulating in the US prior to vaccine implementation (and other countries since at least 1990, but also by the emergence of a novel "vaccine escape recombinant" pneumococcal strain. This strain has a genotype that previously was only associated with vaccine serotype 4, but now expresses a nonvaccine serotype 19A capsule. Based on prior evidence for capsular switching by recombination at the capsular locus, the genetic event that resulted in this novel serotype/genotype combination might be identifiable from the DNA sequence of individual pneumococcal strains. Therefore, the aim of this study was to characterise the putative recombinational event(s at the capsular locus that resulted in the change from a vaccine to a nonvaccine capsular type. Sequencing the capsular locus flanking regions of 51 vaccine escape (progeny, recipient, and putative donor pneumococci revealed a 39 kb recombinational fragment, which included the capsular locus, flanking regions, and two adjacent penicillin-binding proteins, and thus resulted in a capsular switch and penicillin nonsusceptibility in a single genetic event. Since 2003, 37 such vaccine escape strains have been detected, some of which had evolved further. Furthermore, two new types of serotype 19A vaccine escape strains emerged in 2005. To our knowledge, this is the first time a single recombinational event has been documented in vivo that resulted in both a change of serotype and penicillin nonsusceptibility. Vaccine escape by genetic recombination at the capsular locus has the potential to reduce PCV7 effectiveness in the longer term.
Yildirim, Inci; William P Hanage; Lipsitch, Marc; Shea, Kimberly M.; STEVENSON, ABBIE; Finkelstein, Jonathan; Huang, Susan S.; Grace M Lee; Kleinman, Ken; Pelton, SI
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...
Murdoch, I A; Anjos, R D; Mitchell, A
A 22 month old male infant with isomerism of the right atrial appendages (associated with a complete atrioventricular septal defect, double outlet right ventricle, and pulmonary valve stenosis) died from pneumococcal septicaemia after a 36 hour illness. He had not been given penicillin prophylaxis. Asplenia was confirmed at necropsy. In a survey of 50 paediatric cardiologists in the United Kingdom, 13 (33%) of the 40 (80%) who replied did not advise any prophylactic measures against pneumococ...
Täuber, M G; Kennedy, S L; Tureen, J H; Lowenstein, D. H.
We examined whether experimental pneumococcal meningitis induced the 72-kd heat shock protein (HSP72), a sensitive marker of neuronal stress in other models of central nervous system (CNS) injury. Brain injury was characterized by vasculitis, cerebritis, and abscess formation in the cortex of infected animals. The extent of these changes correlated with the size of the inoculum (P less than 0.003) and with pathophysiologic parameters of disease severity, i.e., cerebrospinal fluid (CSF) lactat...
Farooqui, H; Jit, M.; Heymann, DL; Zodpey, S.
The burden of severe pneumonia in terms of morbidity and mortality is unknown in India especially at sub-national level. In this context, we aimed to estimate the number of severe pneumonia episodes, pneumococcal pneumonia episodes and pneumonia deaths in children younger than 5 years in 2010. We adapted and parameterized a mathematical model based on the epidemiological concept of potential impact fraction developed CHERG for this analysis. The key parameters that determine the distribution ...
Hotomi, Muneki; Yuasa, Jun; Briles, David E; Yamanaka, Noboru
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
Almazrou, Yagob; Shibl, Atef M; Alkhlaif, Riyadh; Pirçon, Jean-Yves; Anis, Sameh; Kandeil, Walid; Hausdorff, William P
This study evaluated the incidence, serotype distribution, and antimicrobial susceptibility of invasive pneumococcal disease (IPD) in Saudi Arabian children. This multicenter, prospective, clinical surveillance study included children under 5years of age, residents of one of the seven study health areas, who were brought to a study hospital with suspicion of IPD. Bacterial isolates from sterile site samples, collected less than 24h after hospital visit/admission, were identified, serotyped, and tested for antibiotic susceptibility. Between June 2007 and January 2009, 631 episodes of suspected IPD were recorded, and 623 were included in the analysis. One child (0.2%) had previously received one dose of a pneumococcal vaccine. Forty-seven episodes were positive for Streptococcus pneumoniae and three for Haemophilus influenzae. The incidence of confirmed IPD cases was estimated to be 2.5-21.6 per 100,000 children (Vaccination of Saudi Arabian children with expanded-coverage conjugate pneumococcal vaccines containing serotypes 1 and 5 could have a substantial impact to prevent IPD in this population. PMID:26368823
McCarthy, E M
Patients with inflammatory arthritis are at increased risk of vaccine preventable infections. This risk is increased by immunomodulatory therapies. Vaccination for influenza and pneumococcal disease reduces the risk. Severe cases of varicella infection have occurred in patients on biologic therapies. We sought to identify vaccination rates for commonly acquired infections and to ascertain varicella immune status in patients with inflammatory arthritis. 100 patients with inflammatory arthritis were administered a standardised questionnaire. Data collected included age, diagnosis, vaccination history, history of varicella, treatment and the presence of other indications for vaccination. 58 patients (58%) had not received the influenza vaccine in the past year. Only 19 patients (19%) had ever received pneumococcal vaccine. Anti TNF use did not predict vaccination (p = .46). An increasing number of co morbid conditions predicted both pneumococcal (p < 0.003) and influenza vaccine (p < 0.03) administration. Nineteen patients (19%) gave no history of varicella infection, none having had varicella titres checked pre treatment. Immunisation rates in patients with inflammatory arthritis on immunosuppressive therapies are low. Immunisation schedules should be available for each patient during rheumatology and general practice consultations.
Malone, Kathryn; Clark, Stephanie; Palmer, Jo Ann; Lopez, Sonya; Pradhan, Madhura; Furth, Susan; Kim, Jason; Fisher, Brian; Laskin, Benjamin
Pneumococcal vaccination rates among children receiving a kidney transplant remain suboptimal. Current practice guidelines in the United States recommend giving the PPSV23 after priming with the PCV13. We conducted a QI initiative to increase pneumococcal vaccine rates in our kidney transplant recipients by developing an age-based vaccine algorithm, obtaining vaccine records, and generating reminders for patients and clinicians. A monthly report from the EHR tracked outcomes. The process metric was missed vaccine opportunities, and the overall objective was to improve coverage with both the PCV13 and PPSV23. Over the first six months, we increased the percentage of visits where the vaccine was given from a baseline of 4% to 33%. However, by the end of the 12-month period, the percentage of eligible visits where the vaccine was given decreased to 8.7%. Nevertheless, over the 12-month observation period, we were able to increase the percentage of transplant patients receiving the PCV13 and PPSV23 from 6% to 52%. Utilizing an age-based algorithm and the electronic medical record, vaccine champions can track both missed visit opportunities and the number of vaccinated patients to improve pneumococcal immunization coverage for these high-risk patients. PMID:27334506
Yamamoto, Natsuo; Kerfoot, Steven M; Hutchinson, Andrew T; Dela Cruz, Charles S; Nakazawa, Naomi; Szczepanik, Marian; Majewska-Szczepanik, Monika; Nazimek, Katarzyna; Ohana, Noboru; Bryniarski, Krzysztof; Mori, Tsutomu; Muramatsu, Masamichi; Kanemitsu, Keiji; Askenase, Philip W
We describe a protective early acquired immune response to pneumococcal pneumonia that is mediated by a subset of B1a cells. Mice deficient in B1 cells (xid), or activation-induced cytidine deaminase (AID(-/-) ), or invariant natural killer T (iNKT) cells (Jα18(-/-) ), or interleukin-13 (IL-13(-/-) ) had impaired early clearance of pneumococci in the lung, compared with wild-type mice. In contrast, AID(-/-) mice adoptively transferred with AID(+/+) B1a cells, significantly cleared bacteria from the lungs as early as 3 days post infection. We show that this early bacterial clearance corresponds to an allergic contact sensitivity-like cutaneous response, probably due to a subpopulation of initiating B1a cells. In the pneumonia model, these B1a cells were found to secrete higher affinity antigen-specific IgM. In addition, as in contact sensitivity, iNKT cells were required for the anti-pneumococcal B1a cell initiating response, probably through early production of IL-13, given that IL-13(-/-) mice also failed to clear infection. Our study is the first to demonstrate the importance of AID in generating an appropriate B1a cell response to pathogenic bacteria. Given the antibody affinity and pneumonia resistance data, natural IgM produced by conventional B1a cells are not responsible for pneumonia clearance compared with the AID-dependent subset. PMID:26456931
Spijkerman, Judith; Prevaes, Sabine M. P. J.; van Gils, Elske J. M.; Veenhoven, Reinier H.; Bruin, Jacob P.; Bogaert, Debby; Wijmenga-Monsuur, Alienke J.; van den Dobbelsteen, Germie P. J. M.; Sanders, Elisabeth A. M.
Background: Shifts in pneumococcal serotypes following introduction of 7-valent pneumococcal conjugate vaccine (PCV-7) may alter the presence of other bacterial pathogens co-inhabiting the same nasopharyngeal niche. Methodology/Principal Findings: Nasopharyngeal prevalence rates of S. pneumoniae, S.
Skovgaard, Marlene; Schønheyder, Henrik C; Benfield, Thomas Lars Vibe;
Little is known about the clinical presentation and outcome of pneumococcal lower respiratory tract infection (LRTI) without positive chest X-ray findings and blood cultures. We investigated the prognostic impact of a pulmonary infiltrate and bacteraemia on the clinical course of hospitalized...... patients with confirmed pneumococcal LRTI....
Full Text Available BACKGROUND: The epidemiology of pneumococcal meningitis in the African 'meningitis belt' is poorly studied. In order to ensure an effective vaccination strategy and post-vaccination surveillance, we examined the serotype distribution patterns of pneumococcal meningitis in Niger over the period 2003-2011. METHODS: Cerebrospinal fluid (CSF samples were collected from different health facilities throughout Niger in the frame of the national microbiological surveillance of meningitis. Determination of the serotype of CSF positive for pneumococci was performed using a sequential multiplex PCR method (SM-PCR adapted with a national algorithm in which 32 different serotypes were covered and grouped into eight consecutive PCR. RESULTS: The SM-PCR assay could predict the Sp serotype for 779 CSF (88.7%, 98 CSF (11.3% were not-typeable in our national-adapted algorithm. In total, 26 different serotypes were identified. Serotype 1 (n = 393 was the most prevalent and accounted for 45.3% of infections, followed by serogroups/serotypes 12F/(12A/(44/(46 (7.3%, 6/(6A/6B/6C/6D (5.4%, 14 (5.2%, 5 (4.6%, 23F (4.2%, 45 (3.6%, 2 (3.1%, 18/(18A/18B/18C/18F (2.9% and 17 others serotypes with a prevalence of less than 2%. The proportion of serotype 1 in infants(<2 years old represented only 4.3% of the cases affected by this serotype. In contrast, serotypes 5, 6, 14, 19A and 23F were only detected in very young children. CONCLUSIONS: The proportion of serotype 1 in the pneumococcal meningitis cases and the theoretical vaccine coverage across all age groups advocates for the introduction of a conjugate vaccine (PCV10 or 13 into the Expanded Programme on Immunization (EPI in Niger. Post-vaccine introduction surveillance supported by molecular approaches will be essential to provide a comprehensive picture of the impact of the vaccine on the burden reduction of pneumococcal meningitis and on pneumococcal serotype distribution.
Alhamdi, Yasir; Neill, Daniel R; Abrams, Simon T; Malak, Hesham A; Yahya, Reham; Barrett-Jolley, Richard; Wang, Guozheng; Kadioglu, Aras; Toh, Cheng-Hock
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
Full Text Available Streptococcus pneumoniae accounts for more deaths worldwide than any other single pathogen through diverse disease manifestations including pneumonia, sepsis and meningitis. Life-threatening acute cardiac complications are more common in pneumococcal infection compared to other bacterial infections. Distinctively, these arise despite effective antibiotic therapy. Here, we describe a novel mechanism of myocardial injury, which is triggered and sustained by circulating pneumolysin (PLY. Using a mouse model of invasive pneumococcal disease (IPD, we demonstrate that wild type PLY-expressing pneumococci but not PLY-deficient mutants induced elevation of circulating cardiac troponins (cTns, well-recognized biomarkers of cardiac injury. Furthermore, elevated cTn levels linearly correlated with pneumococcal blood counts (r=0.688, p=0.001 and levels were significantly higher in non-surviving than in surviving mice. These cTn levels were significantly reduced by administration of PLY-sequestering liposomes. Intravenous injection of purified PLY, but not a non-pore forming mutant (PdB, induced substantial increase in cardiac troponins to suggest that the pore-forming activity of circulating PLY is essential for myocardial injury in vivo. Purified PLY and PLY-expressing pneumococci also caused myocardial inflammatory changes but apoptosis was not detected. Exposure of cultured cardiomyocytes to PLY-expressing pneumococci caused dose-dependent cardiomyocyte contractile dysfunction and death, which was exacerbated by further PLY release following antibiotic treatment. We found that high PLY doses induced extensive cardiomyocyte lysis, but more interestingly, sub-lytic PLY concentrations triggered profound calcium influx and overload with subsequent membrane depolarization and progressive reduction in intracellular calcium transient amplitude, a key determinant of contractile force. This was coupled to activation of signalling pathways commonly associated with
Steens, A; Vestrheim, D F; Aaberge, I S; Wiklund, B S; Storsaeter, J; Riise Bergsaker, M A; Rønning, K; Furuseth, E
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
Bowman, Jacinta; Jones, Jade; Stemberger, Natalie A.; Richmond, Peter C.; Leach, Amanda J.; Lehmann, Deborah
Background Invasive pneumococcal disease (IPD) continues to occur at high rates among Australian Aboriginal people. The seven-valent pneumococcal conjugate vaccine (7vPCV) was given in a 2-4-6-month schedule from 2001, with a 23-valent pneumococcal polysaccharide vaccine (23vPPV) booster at 18 months, and replaced with 13vPCV in July 2011. Since carriage surveillance can supplement IPD surveillance, we have monitored pneumococcal carriage in western Australia (WA) since 2008 to assess the impact of the 10-year 7vPCV program. Methods We collected 1,500 nasopharyngeal specimens from Aboriginal people living in varied regions of WA from August 2008 until June 2011. Specimens were cultured on selective media. Pneumococcal isolates were serotyped by the quellung reaction. Results Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis were carried by 71.9%, 63.2% and 63.3% respectively of children Aboriginal Australian children, 7vPCV serotypes account for a small proportion of carried pneumococci. A large proportion of circulating serotypes are not covered by any currently licensed vaccine. PMID:24349245
Evaluation of components of X-ray irradiated 7-valent pneumococcal conjugate vaccine and pneumococcal vaccine polyvalent and X-ray and gamma-ray irradiated acellular pertussis component of DTaP vaccine products
May, J. C.; Rey, L.; Lee, Chi-Jen; Arciniega, Juan
Samples of pneumococcal vaccine polyvalent, 7-valent pneumococcal conjugate vaccine, and two different diphtheria and tetanus toxoids and acellular pertussis vaccines adsorbed were irradiated with X-rays and/or gamma-rays (Co-60). Mouse IgG and IgM antibody responses (ELISA) for types 9V, 14, 18C, and 19F pneumococcal polysaccharides and conjugates indicated that the polysaccharides were more tolerant of the radiation than the conjugates. The mouse antibody response for the detoxified pertussis toxin (PT) antigen, filamentous hemagglutinin antigen (FHA), pertactin (PRN), and fimbriae types 2 and 3 (FIM) antigens for the appropriate vaccine type indicated that the antibody response was not significantly changed in the 25 kGy X-ray irradiated vaccines frozen in liquid nitrogen compared to the control vaccine.
Evaluation of components of X-ray irradiated 7-valent pneumococcal conjugate vaccine and pneumococcal vaccine polyvalent and X-ray and gamma-ray irradiated acellular pertussis component of DTaP vaccine products
Samples of pneumococcal vaccine polyvalent, 7-valent pneumococcal conjugate vaccine, and two different diphtheria and tetanus toxoids and acellular pertussis vaccines adsorbed were irradiated with X-rays and/or gamma-rays (Co-60). Mouse IgG and IgM antibody responses (ELISA) for types 9V, 14, 18C, and 19F pneumococcal polysaccharides and conjugates indicated that the polysaccharides were more tolerant of the radiation than the conjugates. The mouse antibody response for the detoxified pertussis toxin (PT) antigen, filamentous hemagglutinin antigen (FHA), pertactin (PRN), and fimbriae types 2 and 3 (FIM) antigens for the appropriate vaccine type indicated that the antibody response was not significantly changed in the 25 kGy X-ray irradiated vaccines frozen in liquid nitrogen compared to the control vaccine
Evaluation of components of X-ray irradiated 7-valent pneumococcal conjugate vaccine and pneumococcal vaccine polyvalent and X-ray and gamma-ray irradiated acellular pertussis component of DTaP vaccine products
May, J.C. E-mail: firstname.lastname@example.org; Rey, L. E-mail: email@example.com; Lee, C.-J.; Arciniega, Juan
Samples of pneumococcal vaccine polyvalent, 7-valent pneumococcal conjugate vaccine, and two different diphtheria and tetanus toxoids and acellular pertussis vaccines adsorbed were irradiated with X-rays and/or gamma-rays (Co-60). Mouse IgG and IgM antibody responses (ELISA) for types 9V, 14, 18C, and 19F pneumococcal polysaccharides and conjugates indicated that the polysaccharides were more tolerant of the radiation than the conjugates. The mouse antibody response for the detoxified pertussis toxin (PT) antigen, filamentous hemagglutinin antigen (FHA), pertactin (PRN), and fimbriae types 2 and 3 (FIM) antigens for the appropriate vaccine type indicated that the antibody response was not significantly changed in the 25 kGy X-ray irradiated vaccines frozen in liquid nitrogen compared to the control vaccine.
Andrade, Dafne Carvalho; Borges, Igor Carmo; Ivaska, Lauri; Peltola, Ville; Meinke, Andreas; Barral, Aldina; Käyhty, Helena; Ruuskanen, Olli; Nascimento-Carvalho, Cristiana Maria
The etiological diagnosis of infection by Streptococcus pneumoniae in children is difficult, and the use of indirect techniques is frequently warranted. We aimed to study the use of pneumococcal proteins for the serological diagnosis of pneumococcal infection in children with pneumonia. We analyzed paired serum samples from 13 Brazilian children with invasive pneumococcal pneumonia (positive control group) and 23 Finnish children with viral pharyngitis (negative control group), all aged pharyngitis were evaluated for oropharyngeal colonization, and none of them carried S. pneumoniae. We used a multiplex bead-based assay with eight proteins: Ply, CbpA, PspA1 and 2, PcpA, PhtD, StkP and PcsB. The optimal cut-off for increase in antibody level for the diagnosis of pneumococcal infection was determined for each antigen by ROC curve analysis. The positive control group had a significantly higher rate of ≥2-fold rise in antibody levels against all pneumococcal proteins, except Ply, compared to the negative controls. The cut-off of ≥2-fold increase in antibody levels was accurate for pneumococcal infection diagnosis for all investigated antigens. However, there was a substantial increase in the accuracy of the test with a cut-off of ≥1.52-fold rise in antibody levels for PcpA. When using the investigated protein antigens for the diagnosis of pneumococcal infection, the detection of response against at least one antigen was highly sensitive (92.31%) and specific (91.30%). The use of serology with pneumococcal proteins is a promising method for the diagnosis of pneumococcal infection in children with pneumonia. The use of a ≥2-fold increase cut-off is adequate for most pneumococcal proteins. PMID:26928648
McLaughlin, John M; McGinnis, Justin J; Tan, Litjen; Mercatante, Annette; Fortuna, Joseph
Low uptake of routinely recommended adult immunizations is a public health concern. Using data from the peer-reviewed literature, government disease-surveillance programs, and the US Census, we developed a customizable model to estimate human and economic burden caused by four major adult vaccine-preventable diseases (VPD) in 2013 in the United States, and for each US state individually. To estimate the number of cases for each adult VPD for a given population, we multiplied age-specific incidence rates obtained from the literature by age-specific 2013 Census population data. We then multiplied the estimated number of cases for a given population by age-specific, estimated medical and indirect (non-medical) costs per case. Adult VPDs examined were: (1) influenza, (2) pneumococcal disease (both invasive disease and pneumonia), (3) herpes zoster (shingles), and (4) pertussis (whooping cough). Sensitivity analyses simulated the impact of various epidemiological scenarios on the total estimated economic burden. Estimated US annual cost for the four adult VPDs was $26.5 billion (B) among adults aged 50 years and older, $15.3B (58 %) of which was attributable to those 65 and older. Among adults 50 and older, influenza, pneumococcal disease, herpes zoster, and pertussis made up $16.0B (60 %), $5.1B (19 %), $5.0B (19 %), and $0.4B (2 %) of the cost, respectively. Among those 65 and older, they made up $8.3B (54 %), $3.8B (25 %), $3.0B (20 %), and 0.2B (1 %) of the cost, respectively. Most (80-85 %) pneumococcal costs stemmed from nonbacteremic pneumococcal pneumonia (NPP). Cost attributable to adult VPD in the United States is substantial. Broadening adult immunization efforts beyond influenza only may help reduce the economic burden of adult VPD, and a pneumococcal vaccination effort, primarily focused on reducing NPP, may constitute a logical starting place. Sensitivity analyses revealed that a pandemic influenza season or change in size of the US elderly population
Boelsen, Laura K; Dunne, Eileen M; Lamb, Karen E; Bright, Kathryn; Cheung, Yin Bun; Tikoduadua, Lisi; Russell, Fiona M; Mulholland, E Kim; Licciardi, Paul V; Satzke, Catherine
Previously, the Fiji Pneumococcal Project (FiPP) evaluated reduced dose immunization schedules that incorporated pneumococcal protein conjugate and/or polysaccharide vaccine (PCV7 and 23vPPV, respectively). Immune hyporesponsiveness was observed in children vaccinated with 23vPPV at 12 months of age compared with children who did not receive 23vPPV. Here we assess the long-term impact of 23vPPV vaccination on nasopharyngeal carriage rates and densities of Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus and Moraxella catarrhalis. Nasopharyngeal swabs (n=194) were obtained from healthy children who participated in FiPP (now aged 5-7 years). S. pneumoniae were isolated and identified by standard culture-based methods, and serotyped using latex agglutination and the Quellung reaction. Carriage rates and densities of S. pneumoniae, H. influenzae, S. aureus and M. catarrhalis were determined using real-time quantitative PCR. There were no differences in the rate or density of S. pneumoniae, H. influenzae or M. catarrhalis carriage by PCV7 dose or 23vPPV vaccination in the vaccinated participants overall. However, differences were observed between the two main ethnic groups: Fijian children of Indian descent (Indo-Fijian) were less likely to carry S. pneumoniae, H. influenzae and M. catarrhalis, and there was evidence of a higher carriage rate of S. aureus compared with indigenous Fijian (iTaukei) children. Polysaccharide vaccination appeared to have effects that varied between ethnic groups, with 23vPPV vaccination associated with a higher carriage rate of S. aureus in iTaukei children, while there was a lower carriage rate of S. pneumoniae associated with 23vPPV vaccination in Indo-Fijian children. Overall, polysaccharide vaccination had no long-term impact on pneumococcal carriage, but may have impacted on S. aureus carriage and have varying effects in ethnic groups, suggesting current WHO vaccine schedule recommendations against the use of 23v
Brandt, Christian T; Lundgren, Jens D; Frimodt-Møller, Niels;
damage and outcome in pneumococcal meningitis in rats treated with ceftriaxone from 28 h after infection. Rats treated with fucoidin from time of infection had an excess risk of a fatal outcome compared to rats not receiving fucoidin (25/63 versus 5/34, p=0.012), whereas the risk of cortical damage in......, blocking leukocyte entry to the central nervous system in experimental pneumococcal meningitis compromises the survival prognosis but does not affect the risk of brain damage or level of infection in this compartment. Conversely, poorer prognosis was associated with an increase in bacterial load in blood...
Full Text Available Background: An alarming increase in infections due to penicillin non-susceptible pneumococci (PNSP has been documented in nearly all countries. Increasingly, PNSP are also resistant to other antibiotics, and a growing number of clinical failures following the use of these agents have been reported. Aims: To determine the resistance pattern of pneumococcal isolates from patients with invasive pneumococcal infection in North West Nigeria. Materials and Methods: In a cross-sectional study clinical specimens were obtained from patients with community acquired pneumonia (CAP, meningitis and bacteraemia over a 2 year period. Pneumococcus strains were identified. Isolates were tested against a panel of antibiotics using E-test strips, and interpreted according to the CLSI criteria. 0.06 ΅g/ml was used as break point for penicillin. Analysis was carried out using descriptive statistics; relationships determined using chi-squared or Fisher′s exact tests, with P < 0.05 regarded as significant. Results: Total number of isolates was 132. Twenty-two (16.7% of the isolates were fully sensitive to penicillin while 73 (55.3% and 37 (28.0% were intermediately and fully resistant, respectively. One hundred and twenty-seven (96.2% of the isolates were fully resistant to trimethoprim-sulphamethoxazole. Eleven (8.5% were fully resistant to amoxicillin and 104 (78.8% and 17 (12.9% were intermediately resistant and fully susceptible. One hundred and six (80.3% of the isolates were fully susceptible to chloramphenicol. Resistance to penicillin was shown to infer resistance to other antibiotics. Conclusions: Pneumococcal resistance is common in North West Nigeria. Ceftriaxone retains excellent activity against most of the invasive isolate, while trimethoprim-sulphamethoxazole is almost uniformly resistant.
Full Text Available PURPOSE: Etiological diagnosis of pneumococcal pneumonia is difficult in small children in whom blood culture cannot be done or who have already been started on antibiotics. A simple technique which can be applied at the bedside or in the outpatient department may help in obviating this problem. Detection of pneumolysin, a product of invasive pneumococci is being exploited as a diagnostic tool. METHODS: An attempt was made to detect this protein in urine of seventy children, clinically suspected and radiologically diagnosed cases of pneumonia. Seventy age and sex matched controls were included in the study. Purified pneumolysin was prepared from clinical isolates of invasive pneumococcal infections. This was used to raise polyclonal antisera in rabbits. The antisera was used to sensitise Cowan 1 Staphylococcus aureus (CoA. A slide agglutination was performed with 25 µL urine and equal quantity of the reagent. RESULTS: Results were compared with CoA reagent sensitised with antisera raised against a genetically derived pneumolysoid and capsular polysaccharide for antigen detection in the urine. Pneumolysin could be detected in 42.9% (30/70 urine samples from cases with pneumonia by the genetically derived antigen and in 37.1% samples by the in house prepared antigen, in contrast to 2.1% in healthy controls and 4.2% in children with infections other than pneumonia. The result was statistically significant. Detection of pneumolysin was slightly better than detection of capsular polysaccharide antigen in urine although the result was not statistically significant. Blood culture proved to be positive in only 29.5% cases. CONCLUSIONS: Pneumolysin detection in urine showed promising results and was found to be simple and rapid. It will help in quickening the diagnosis of pneumococcal pneumonia.
Full Text Available Abstract Background PspA is recognized as a major pneumococcal virulence factor and a possible vaccine candidate. The aim of this study was to analyze the PspA family and clade distribution among 112 Spanish pneumococci representatives of dominant clones among patients with invasive disease (n = 66 and nasopharyngeal healthy carriage in children (n = 46. Results PspA family 2 was predominant among invasive (63.6% and carriage (54.3% pneumococcal isolates. No PspA family 3 isolates were detected and only one strain was PspA negative. Although four clonal complexes contained strains of different clades, a clear association between clade and multi locus sequence typing results was found. Clades 1, 3 and 4 were associated with a wide variety of sequence types (ST related to multiresistant and antibiotic-susceptible worldwide-disseminated clones. Clade 1 was associated with Spain6B-ST90, Spain14-ST18, Colombia5-ST289, Sweden1-ST306, Denmark14-ST230 and Sweden1-ST304 clones. Clade 3 was associated with Spain23F-ST81, Spain9V-ST156, Tennessee14-ST67, Netherlands3-ST180 and Netherlands7F-ST191 clones. Clade 4 was related to Sweden15A-ST63, Netherlands18C-ST113 and Greece21-ST193 clones. In contrast, PspA clade was not related to serotype, age or clinical origin of the isolates. Conclusion PspA clades were associated with genotypes. PspA family 2 and family 1 were dominant among major Spanish pneumococcal clones isolated from patients with invasive disease and nasopharyngeal carriage in children.
Steens, Anneke; Bergsaker, Marianne A Riise; Aaberge, Ingeborg S; Rønning, Karin; Vestrheim, Didrik F
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
Cho, Hye-Kyung; Park, In Ho; Burton, Robert L; Kim, Kyung-Hyo
Although it is well known that pneumococcal conjugate vaccines provide cross-protection against some vaccine-related serotypes, these mechanisms are still unclear. This study was performed to investigate the role of cross-protective IgM antibodies against vaccine-related serotypes 6A, 6C, and 19A induced in children aged 12-23 months after immunization with 7-valent pneumococcal conjugate vaccine (PCV7). We obtained serum samples from 18 Korean children aged 12-23 months after a PCV7 booster immunization. The serum IgG and IgM concentrations of serotypes 6B and 19F were measured by enzyme-linked immunosorbent assay (ELISA) in serum. The opsonic indices (OIs) against vaccine serotypes 6B and 19F and vaccine-related serotypes 6A, 6C, and 19A were determined by an opsonophagocytic killing assay (OPA) in IgM-depleted and control serum. Both IgG and IgM antibodies in ELISA and opsonic indices in OPA against serotypes 6B and 19F were demonstrated in the immune serum. IgM depletion decreased the OIs against vaccine serotypes 6B (geometric means of OIs (GMIs) of 3,009 vs. 1,396, 38% reduction) and 19F (1,117 vs. 750, 36% reduction). In addition, IgM depletion markedly decreased the OIs against vaccine-related serotypes 6A (GMIs of 961 vs. 329, 70% reduction), 6C (432 vs. 185, 72% reduction), and 19A (301 vs. 166, 58% reduction). The booster immunization PCV7 induced protective antibodies in the form of both IgG and IgM isotypes. IgM antibodies contributed to eliciting cross-protection against vaccine-related serotypes as well as against vaccine serotypes. PMID:27247505
Full Text Available Pneumococcal infections are a major cause of morbidity and mortality in developing countries. The introduction of pneumococcal conjugate vaccines (PCVs has dramatically reduced the incidence of pneumococcal diseases. PCVs are not currently being used in Algeria. We conducted a prospective study from 2005 to 2012 in Algeria to determine antimicrobial drug resistance and serotype distribution of Streptococcus pneumoniae from children with pneumococcal disease. Among 270 isolated strains from children, 97 (36% were invasive disease; of these, 48% were not susceptible to penicillin and 53% not susceptible to erythromycin. A high rate of antimicrobial nonsusceptibility was observed in strains isolated from children with meningitis. The serotype distribution from pneumococci isolated from children with invasive infections was (by order of prevalence: 14, 1, 19F, 19A, 6B, 5, 3, 6A and 23F. Multidrug resistance was observed in serotypes 14, 19F, 19A and 6B. The vaccine coverage of serotypes isolated from children aged <5 years was 55.3% for PCV7, 71.1% for PCV10 and 86.8% for PCV13. Our results highlight the burden of pneumococcal disease in Algeria and the increasing S. pneumoniae antibiotic resistance. The current pneumococcal vaccines cover a high percentage of the circulating strains. Therefore, vaccination would reduce the incidence of pneumococcal disease in Algeria.
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
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
Auranen, Kari; Mehtälä, Juha; Tanskanen, Antti; S Kaltoft, Margit
The state of pneumococcal carriage-that is, pneumococcal colonization in the nasopharynx of healthy persons-represents a reservoir for the spread of pneumococci among individuals. In light of the introduction of new pneumococcal conjugate vaccines, further knowledge on the dynamics of pneumococcal carriage is important. Different serotypes (strains) of pneumococcus are known to compete with each other in colonizing human hosts. Understanding the strength and mode of between-serotype competition is important because of its implications for vaccine-induced changes in the ecology of pneumococcal carriage. Competition may work through reduced acquisition of new serotypes, due to concurrent carriage in the individual, or through enhanced clearance of serotypes in carriers who harbor more than 1 serotype simultaneously. The authors employed longitudinal data (1999-2001) on pneumococcal carriage in Danish day-care children to analyze between-serotype competition. The data included observations of carriage in children who had not been vaccinated against pneumococcus, and the level of pneumococcal antibiotic resistance and antibiotic usage in the community was very low. Clearance of any single serotype was not affected by simultaneous carriage of other serotypes. In contrast, acquisition of other serotypes in already-colonized hosts was weak (relative rate of acquisition = 0.09, 95% credible interval: 0.05, 0.15). PMID:19969530
A soluble membrane component of type III pneumococcal polysaccharide- coupled spleen cells (S3-SCSM) induces S3-specific suppressor T cells (Ts) in mice. These Ts can be detected only if mice are pretreated with cyclophosphamide (Cy) or if cells adherent to the lectin Vicia villosa are removed from the spleen cell population prior to transfer. The V. villosa-adherent spleen cells from mice injected with S3-SCSM could abrogate suppression mediated by Ts induced by S3-SCSM in Cy-treated mice. T...
Dunne, E M; Tikkanen, L; Balloch, A; Gould, K; Yoannes, M; Phuanukoonnon, S; Licciardi, P V; Russell, F M; Mulholland, E K; Satzke, C; Hinds, J
Molecular identification of Streptococcus pneumoniae serotype 19F is routinely performed by PCR targeting the wzy gene of the capsular biosynthetic locus. However, 19F isolates with genetic similarity to 19A have been reported in the United States and Brazil. We screened 78 pneumococcal carriage isolates and found six 19F wzy variants that originated from children in Papua New Guinea and Fiji. Isolates were characterized using multilocus sequence typing and opsonophagocytic assays. The 19F wzy variants displayed similar susceptibility to anti-19F IgG antibodies compared to standard 19F isolates. Our findings indicate that these 19F variants may be more common than previously believed. PMID:26339490
Kontiokari, T; Svanberg, M; Mattila, P; Leinonen, M; Uhari, M
Xylitol possesses anti-bacterial effects on pneumococci in vitro. To study the effect in vivo, the nostrils of 80 rats were inoculated with pneumococci. Intervention groups (n = 20) received either a xylitol diet or xylitol nasal sprays. The control groups were on a normal diet or had saline sprays. After 3 days, a quantitative bacterial culture and a PCR were done from the mucosal suspension. Neither the mean colony-forming unit counts nor the PCR counts differed statistically significant between the xylitol and control groups. Thus, we found that xylitol had no significant effect on pneumococcal mucosal colonisation. PMID:10499281
Full Text Available Abstract Introduction Acute compartment syndrome is a surgical emergency requiring immediate fasciotomy. Spontaneous onset of acute compartment syndrome of the lower limbs is rare. We present a very rare case of pneumococcal sepsis leading to spontaneous acute compartment syndrome. Case presentation A 40-year-old Caucasian man presented as an emergency with spontaneous onset of pain in both legs and signs of compartment syndrome. This was confirmed on fasciotomy. Blood culture grew Streptococcus pneumoniae. Conclusion Sepsis should be strongly suspected in bilateral acute compartment syndrome of spontaneous onset.
McCool, T. L.; Schreiber, J R; Greenspan, N S
CBA/J mice immunized with pneumococcal 23F-CRM197 vaccine produce significantly lower titers of 23F-specific antibodies and fewer 23F-specific antibody-secreting cells (ASC) than did BALB/c or (CBA/J × BALB/c)F1 (CCBAF1) mice. The reduced 23F-specific titers of CBA/J versus BALB/c or CCBAF1 mice are presumably related to lower frequencies of 23F-specific ASC influenced by genetic variation.
Tatiana Barichello; Santos, Ana Lucia B.; Cintia Silvestre; Generoso, Jaqueline S.; Cipriano, Andreza L.; Fabricia Petronilho; Felipe Dal-Pizzol; Comim, Clarissa M.; João Quevedo
Pneumococcal meningitis is associated with a significant mortality rate and neurologic sequelae. The animals received either 10 μ L of saline or a S. pneumoniae suspension and were randomized into different groups: sham: placebo with dexamethasone 0.7 mg/kg/1 day; placebo with dexamethasone 0.2 mg/kg/7 days; meningitis groups: dexamethasone 0.7 mg/kg/1 day and dexamethasone 0.2 mg/kg/7 days. Ten days after induction we evaluated memory and oxidative stress parameters in hippocampus and corte...
Ricketson, Leah J; Otto G Vanderkooi; Wood, Melissa L; Jenine Leal; Kellner, James D
BACKGROUND: Streptoccocus pneumoniae serotype 19A (ST19A) became an important cause of invasive pneumococcal disease (IPD) after the introduction of the conjugate vaccine.OBJECTIVE: To examine the severity and outcome of ST19A IPD compared with non-ST19A IPD.METHODS: The Calgary Area Streptococcus pneumoniae Epidemiology Research (CASPER) study collects clinical and laboratory data on all IPD cases in Calgary, Alberta. Analysis was performed on data from 2000 to 2010 comparing ST19A and non-S...
Steven M Szczepanek
Full Text Available One of the most common causes of morbidity and mortality in children with sickle cell disease (SCD is infection with the pneumococcal bacterium (Streptococcus pneumoniae. Unfortunately, the polysaccharide-conjugate vaccine appears to be less effective in individuals with SCD when compared to the general population. We sought to better understand the relative efficacy of pneumococcal vaccination in a SCD mouse challenge model.Transgenic control and SCD mice were monitored for mortality after intranasal pneumococcal infection or pneumococcal vaccination with Prevnar-13 and type-matched challenge. Anti-pneumococcal antibody titers were measured by ELISA and opsonophagocytosis was measured in vitro.Mortality after pneumococcal infection was similar between control and SCD mice. However, after three intramuscular polysaccharide-conjugate vaccinations, all control mice were protected following high-dose intranasal infection, whereas 60% of SCD mice died. Anti-pneumococcal antibody titers showed initial IgG and IgM responses in both groups, but waning titers were observed in the SCD group, even after boosting. When functionally assayed in vitro, serum from SCD mice 13 weeks after a second booster shot maintained little to no ability to opsonize pneumococci, while serum from control mice sustained a significantly higher capacity opsonization. Thus, it appears that SCD mice do not maintain antibody responses to pneumococcal polysaccharides after Prevnar-13 vaccination, thereby leaving them susceptible to mortality after type-matched infection.Our results emphasize the need to better understand the correlates of immune protection in SCD so that pneumococcal vaccines can be improved and mortality reduced in this susceptible population.
Yoon Hong Choi
Full Text Available INTRODUCTION: England and Wales recently replaced the 7-valent pneumococcal conjugate vaccine (PCV7 with its 13-valent equivalent (PCV13, partly based on projections from mathematical models of the long-term impact of such a switch compared to ceasing pneumococcal conjugate vaccination altogether. METHODS: A compartmental deterministic model was used to estimate parameters governing transmission of infection and competition between different groups of pneumococcal serotypes prior to the introduction of PCV13. The best-fitting parameters were used in an individual based model to describe pneumococcal transmission dynamics and effects of various options for the vaccination programme change in England and Wales. A number of scenarios were conducted using (i different assumptions about the number of invasive pneumococcal disease cases adjusted for the increasing trend in disease incidence prior to PCV7 introduction in England and Wales, and (ii a range of values representing serotype replacement induced by vaccination of the additional six serotypes in PCV13. RESULTS: Most of the scenarios considered suggest that ceasing pneumococcal conjugate vaccine use would cause an increase in invasive pneumococcal disease incidence, while replacing PCV7 with PCV13 would cause an overall decrease. However, the size of this reduction largely depends on the level of competition induced by the additional serotypes in PCV13. The model estimates that over 20 years of PCV13 vaccination, around 5000-62000 IPD cases could be prevented compared to stopping pneumococcal conjugate vaccination altogether. CONCLUSION: Despite inevitable uncertainty around serotype replacement effects following introduction of PCV13, the model suggests a reduction in overall invasive pneumococcal disease incidence in all cases. Our results provide useful evidence on the benefits of PCV13 to countries replacing or considering replacing PCV7 with PCV13, as well as data that can be used to
de Andrade, Ana Lucia Sampaio Sgambatti; Pimenta, Fabiana Cristina; Brandileone, Maria Cristina C.; Laval, Cristina Aparecida; Guerra, Maria Luiza; de Andrade, João Guimarães; Di Fabio, Jose Luis
The molecular epidemiology of Streptococcus pneumoniae isolates from carriage and cerebrospinal fluid (CSF) concurrently recovered from the same individual has not yet been reported. By using pulsed-field gel electrophoresis, we demonstrated the genetic linkage among strains from CSF and nasopharynges of two children with pneumococcal meningitis. PMID:12904432
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
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
Kemp, Kåre; Bruunsgaard, Helle; Skinhøj, Peter;
, little is known regarding the T-cell response during in vivo infections in humans. The purpose of this study was to test the hypothesis that activated T cells producing type 1 cytokines were engaged in the host response to pneumococcal infections. The phenotype and function of T cells were studied in 22...
Lundbo, Lene Fogt; Harboe, Zitta Barrella; Clausen, Louise Nygaard;
BACKGROUND: Most children are transiently colonized with Streptococcus pneumoniae, but very few develop invasive pneumococcal disease (IPD). Host genetic variation of innate immunity may predispose to IPD. We investigated the effect of genetic variation in the mannose-binding lectin gene, MBL2, on...
Ingels, Helene; Rasmussen, Jeppe; Andersen, Peter Henrik;
BACKGROUND AND AIMS: The 7-valent pneumococcal conjugate vaccine (PCV7) was introduced in Denmark in October 2007 in a 2+1 schedule with a catch-up programme for children up to 17 months of age. To assess the impact of PCV we evaluated on the whole population: (1) direct and indirect effects on...
Kristin L Moffitt
Full Text Available Mucosal or parenteral immunization with a killed unencapsulated pneumococcal whole cell antigen (WCA with an adjuvant protects mice from colonization by a T(H17 CD4+ cell-mediated mechanism. Using preparative SDS gels, we separated the soluble proteins that compose the WCA in order to identify fractions that were immunogenic and protective. We screened these fractions for their ability to stimulate IL-17A secretion from splenocytes obtained from mice immunized with WCA and adjuvant. We identified 12 proteins within the stimulatory fractions by mass spectrometry; these proteins were then cloned, recombinantly expressed and purified using an Escherichia coli expression system. The ability of these proteins to induce IL-17A secretion was then evaluated by stimulation of mouse splenocytes. Of the four most stimulatory proteins, three were protective in a mouse pneumococcal serotype 6B colonization model. This work thus describes a method for identifying immunogenic proteins from the soluble fraction of pneumococcus and shows that several of the proteins identified protect mice from colonization when used as mucosal vaccines. We propose that, by providing protection against pneumococcal colonization, one or more of these proteins may serve as components of a multivalent pneumococcal vaccine.
Bogaert, D.; Veenhoven, R.H.; Ramdin, R.; Luijendijk, I.H.; Rijkers, G.T.; Sanders, E.A.M.; Groot, R. de; Hermans, P.W.M.
AIM: In a prospective controlled study in young children with a history of recurrent acute otitis media, we analyzed the salivary IgA and IgG antibody titers upon vaccination with a 7-valent pneumococcal conjugate vaccine (PCV) given once or twice, followed by a 23-valent polysaccharide booster vacc
Brandt, CT; Caye-Thomsen, P; Lund, SP;
augmented neutrophil response on the development of hearing loss and cochlear damage in a model of experimental pneumococcal meningitis in rats. Hearing loss and cochlear damage were assessed by distortion product oto-acoustic emissions (DPOAE), auditory brainstem response (ABR) and histopathology in rats...
Paul, Sourabh; Sahoo, Jyotiranjan
Immunization is the process whereby a person is made immune or resistant to an infectious disease, typically by the administration of a vaccine. The Expanded Program on Immunization (EPI) was flagged off in India in 1978. According to the recommendation of National technical advisory group of India (NATGI), Government of India is going to include four new vaccines in the UIP for whole India. The four new vaccines are Inactivated Poliomyelitis Vaccine (IPV) for polio, rota viral vaccine, vaccine against rubella, and Japanese encephalitis vaccine (179 districts in India). Here, authors have tried to show a comparative descriptive analysis of the hemophilus influenza and pneumococcal pneumonia with rota virus, so that in near future Government of India can also consider their inclusion in the national UIP. In India, 39.2% of all diarrheal death are due to rota virus, whereas 0.72 million deaths are due to hemophilus influenza B and 1.3 million are due to pneumococcal pneumonia in UIP which will save millions of poor children's life. PMID:25810981
Renko, Marjo; Valkonen, Päivi; Tapiainen, Terhi; Kontiokari, Tero; Mattila, Pauli; Knuuttila, Matti; Svanberg, Martti; Leinonen, Maija; Karttunen, Riitta; Uhari, Matti
Background Xylitol has antiadhesive effects on Streptococcus pneumoniae and inhibits its growth, and has also been found to be effective in preventing acute otitis media and has been used in intensive care as a valuable source of energy. Results We evaluated the oxidative burst of neutrophils in rats fed with and without xylitol. The mean increase in the percentage of activated neutrophils from the baseline was higher in the xylitol-exposed group than in the control group (58.1% vs 51.4%, P = 0.03 for the difference) and the mean induced increase in the median strength of the burst per neutrophil was similarly higher in the xylitol group (159.6 vs 140.3, P = 0.04). In two pneumococcal sepsis experiments rats were fed either a basal powder diet (control group) or the same diet supplemented with 10% or 20% xylitol and infected with an intraperitoneal inoculation of S. pneumoniae after two weeks. The mean survival time was 48 hours in the xylitol groups and 34 hours in the control groups (P < 0.001 in log rank test). Conclusion Xylitol has beneficial effects on both the oxidative killing of bacteria in neutrophilic leucocytes and on the survival of rats with experimental pneumococcal sepsis. PMID:18334022
Nelson Alvis Guzmán
Full Text Available Objective: To estimate the economic impact of the introduction of heptavalent pneumococcal conjugate vaccine (PCV-7 in high risk populations of Colombia.Methods: A full economic evaluation was done regarding potential introduction of PCV-7. A cost-effectiveness study from the perspective of the third payer was done using a Decision Model. The model considered two alternatives: with and without vaccination. As measurement of results the avoided events were taken [cases, hospitalizations, deaths and Life-Years Saved (LYS]. In addition the net costs and the incremental cost-effectiveness ratio (ICER were evaluated.Results: In a cohort of 70 thousand children of under 2 years old in situation of high risk, can generate 532 deaths that would produce a little more than 21 thousand Years of Life Lost (YLL with costs between 7.7 and 13.3 million dollars. If we vaccinate this same cohort the deaths can be reduced to 355, and the costs of burden of disease would be between 5.7 and 10 million dollars. It is estimated a reduction of 25% of the costs of burden of disease and of 33% of the deaths. In addition the ICER by YLS would be between 590 and 762 dollars.Conclusion: The introduction of the Heptavalent Pneumococcal Conjugate Vaccine in populations of high risk is highly cost effective in Colombia.
Johnston, Calum; Hauser, Christoph; Hermans, Peter W M; Martin, Bernard; Polard, Patrice; Bootsma, Hester J; Claverys, Jean-Pierre
The human pathogen Streptococcus pneumoniae (the pneumococcus) is rare in having a strict requirement for the amino alcohol choline, which decorates pneumococcal teichoic acids. This process relies on the lic locus, containing the lic1 and lic2 operons. These operons produce eight proteins that import and metabolize choline, generate teichoic acid precursors and decorate these with choline. Three promoters control expression of lic operons, with Plic1P1 and Plic1P2 controlling lic1 and Plic2 controlling lic2. To investigate the importance of lic regulation for pneumococci, we assayed the activity of transcriptional fusions of the three lic promoters to the luciferase reporter gene. Plic1P1 , whose activity depends on the response regulator CiaR, responded to fluctuations in extracellular choline, with activity increasing greatly upon choline depletion. We uncovered a complex regulatory mechanism controlling Plic1P1 , involving activity driven by CiaR, repression by putative repressor LicR in the presence of choline, and derepression upon choline depletion mediated by LicC, a choline metabolism enzyme. Finally, the ability to regulate Plic1P1 in response to choline was important for pneumococcal colonization. We suggest that derepression of Plic1P1 upon choline depletion maximizing choline internalization constitutes an adaptive response mechanism allowing pneumococci to optimize growth and survival in environments where choline is scarce. PMID:26919406
Full Text Available Abstract Background Xylitol has antiadhesive effects on Streptococcus pneumoniae and inhibits its growth, and has also been found to be effective in preventing acute otitis media and has been used in intensive care as a valuable source of energy. Results We evaluated the oxidative burst of neutrophils in rats fed with and without xylitol. The mean increase in the percentage of activated neutrophils from the baseline was higher in the xylitol-exposed group than in the control group (58.1% vs 51.4%, P = 0.03 for the difference and the mean induced increase in the median strength of the burst per neutrophil was similarly higher in the xylitol group (159.6 vs 140.3, P = 0.04. In two pneumococcal sepsis experiments rats were fed either a basal powder diet (control group or the same diet supplemented with 10% or 20% xylitol and infected with an intraperitoneal inoculation of S. pneumoniae after two weeks. The mean survival time was 48 hours in the xylitol groups and 34 hours in the control groups (P Conclusion Xylitol has beneficial effects on both the oxidative killing of bacteria in neutrophilic leucocytes and on the survival of rats with experimental pneumococcal sepsis.
Lin, Te-Yu; Chen, Yu-Guang; Lin, Cheng-Li; Kao, Chia-Hung
Purpose Pneumococcal disease leads to renal complications ranging from persistent proteinuria to end-stage renal disease. Studies on the association between pneumococcal pneumonia (PP) and acute kidney injury (AKI) are scant. This study assessed the relationship between PP and risk of AKI. Methods This nationwide population-based cohort study examined data from the Taiwan National Health Insurance Research Database for the period 2000–2011. We identified inpatients with newly diagnosed PP according to the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes. In addition, we selected a comparison cohort from inpatient claims without the diagnosis of PP that was randomly frequency-matched with the PP cohort according to age, sex, index year and comorbidities. We analyzed the risks of AKI by using Cox proportional hazards regression models, adjusted for sex, age, and comorbidities. Results A total of 10,069 patients with PP and 10,069 controls were enrolled in this study. After adjustments for age, sex, and comorbidities, patients with PP had a 1.11-fold risk of developing AKI compared with the comparison cohort. Conclusion This study indicates that AKI risks are higher in patients with PP compared with the comparison cohort. Careful follow-up observation and aggressive treatment are necessary for patients with PP to reduce the risk of AKI. PMID:27362355
Rabes, Anne; Suttorp, Norbert; Opitz, Bastian
Streptococcus pneumoniae frequently colonizes the upper respiratory tract of healthy individuals, but also commonly causes severe invasive infections such as community-acquired pneumonia and meningitis. One of the key virulence factors of pneumococci is the pore-forming toxin pneumolysin which stimulates cell death and is involved in the evasion of some defense mechanisms. The immune system, however, employs different inflammasomes to sense pneumolysin-induced pore formation, cellular membrane damage, and/or subsequent leakage of bacterial nucleic acid into the host cell cytosol. Canonical inflammasomes are cytosolic multiprotein complexes consisting of a receptor molecule such as NLRP3 or AIM2, the adapter ASC, and caspase-1. NLRP3 and AIM2 inflammasomes mediate cell death and production of important IL-1 family cytokines to recruit leukocytes and defend against S. pneumoniae. Here, we review recent evidence that highlights inflammasomes as critical sensors of S. pneumoniae-induced cellular perturbations, summarize their role in pneumococcal infections, and discuss potential evasion strategies of some emerging pneumococcal strains. PMID:27460812
Earnshaw Stephanie R
Full Text Available Abstract Background Thirteen-valent pneumococcal conjugate vaccine (PCV13 and 10-valent pneumococcal conjugate vaccine (PCV10 are two recently approved vaccines for the active immunization against Streptococcus pneumoniae causing invasive pneumococcal disease in infants and children. PCV13 offers broader protection against Streptococcus pneumoniae; however, PCV10 offers potential protection against non-typeable Haemophilus influenza (NTHi. We examined public health and economic impacts of a PCV10 and PCV13 pediatric national immunization programs (NIPs in Canada. Methods A decision-analytic model was developed to examine the costs and outcomes associated with PCV10 and PCV13 pediatric NIPs. The model followed individuals over the remainder of their lifetime. Recent disease incidence, serotype coverage, population data, percent vaccinated, costs, and utilities were obtained from the published literature. Direct and indirect effects were derived from 7-valent pneumococcal vaccine. Additional direct effect of 4% was attributed to PCV10 for moderate to severe acute otitis media to account for potential NTHi benefit. Annual number of disease cases and costs (2010 Canadian dollars were presented. Results In Canada, PCV13 was estimated to prevent more cases of disease (49,340 when considering both direct and indirect effects and 7,466 when considering direct effects only than PCV10. This translated to population gains of 258 to 13,828 more quality-adjusted life-years when vaccinating with PCV13 versus PCV10. Annual direct medical costs (including the cost of vaccination were estimated to be reduced by $5.7 million to $132.8 million when vaccinating with PCV13. Thus, PCV13 dominated PCV10, and sensitivity analyses showed PCV13 to always be dominant or cost-effective versus PCV10. Conclusions Considering the epidemiology of pneumococcal disease in Canada, PCV13 is shown to be a cost-saving immunization program because it provides substantial public
Gisselsson-Solén, Marie; Henriksson, Gunnel; Hermansson, Ann; Melhus, Åsa
Abstract Conclusion: Although children vaccinated with heptavalent pneumococcal conjugate vaccine (PCV) had fewer episodes of acute otitis media (AOM), this trial was unable to prove a simultaneous decrease in nasopharyngeal carriage.
Carvalho, Sandra M.; Kuipers, Oscar P.; Neves, Ana Rute; Horsburgh, Malcolm James
Links between carbohydrate metabolism and virulence in Streptococcus pneumoniae have been recurrently established. To investigate these links further we developed a chemically defined medium (CDM) and standardized growth conditions that allowed for high growth yields of the related pneumococcal stra
Lancelot W H Mui
Full Text Available OBJECTIVE: To study the attitudes among general practitioners towards pneumococcal vaccination for middle-aged (50-64 and elderly population (over 65 in Hong Kong and the factors affecting their decision to advise pneumococcal vaccination for those age groups. DESIGN: Cross-sectional study of general practitioners in private practice in Hong Kong. PARTICIPANTS: Members of Hong Kong Medical Association delivering general practice services in private sector. MEASURING TOOL: Self-administered questionnaire. MAIN OUTCOME MEASURES: Intention to recommend pneumococcal vaccination, barriers against pneumococcal vaccination. RESULTS: 53.4% of the respondents would actively recommend pneumococcal vaccination to elderly patients but only 18.8% would recommend for middle-aged patients. Consultation not related to pneumococcal vaccine was the main reason for not recommending pneumococcal vaccine (43.6%. Rarity of pneumonia in their daily practice was another reason with 68.4% of respondents attending five or less patients with pneumonia each year. In multivariate analysis, factors such as respondents would get vaccination when reaching age 50 (ORm 10.1, and attending 6 pneumonia cases or more per year (ORm 2.28 were found to be associated with increasing likelihood for recommending vaccination to the middle-aged. While concerns of marketing a product (ORm 0.41, consultation not related to vaccination (ORm 0.45 and limited time (ORm 0.38 were factors that reduced the likelihood. CONCLUSION: Public policy is needed to increase the awareness of impact of pneumococcal pneumonia and the availability of preventive measures.
Vestrheim, Didrik F.; Steinbakk, Martin; Aaberge, Ingeborg S; Dominique A. Caugant
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, se...
Lebensburger, Jeffrey D.; Howard, Thad; Hu, Yunming; Pestina, Tamara I.; Gao, Geli; Johnson, Melissa; Zakharenko, Stanislav S.; Ware, Russell E.; Tuomanen, Elaine I.; Persons, Derek A; Rosch, Jason W.
Sickle cell anemia is characterized by chronic hemolysis coupled with extensive vascular inflammation. This inflammatory state also mechanistically promotes a high risk of lethal, invasive pneumococcal infection. Current treatments to reduce vaso-occlusive complications include chronic hydroxyurea therapy to induce fetal hemoglobin. Because hydroxyurea also reduces leukocytosis, an understanding of the impact of this treatment on pneumococcal pathogenesis is needed. Using a sickle cell mouse ...
Tregnaghi, Miguel W.; Sáez-Llorens, Xavier; López, Pio; Abate, Hector; Smith, Enrique; Pósleman, Adriana; Calvo, Arlene; Wong, Digna; Cortes-Barbosa, Carlos; Ceballos, Ana; Tregnaghi, Marcelo; Sierra, Alexandra; Rodriguez, Mirna; Troitiño, Marisol; Carabajal, Carlos
Editors' Summary Background Pneumococcal diseases are illnesses caused by Streptococcus pneumoniae bacteria, pathogens (disease-causing organisms) that are transmitted through contact with infected respiratory secretions. S. pneumoniae causes mucosal diseases–infections of the lining of the body cavities that are connected to the outside world–such as community-acquired pneumonia (CAP; lung infection) and acute otitis media (AOM; middle-ear infection). It also causes invasive pneumococcal dis...
Gabriela García Gabarrot
Full Text Available In 2008, a 7-valent pneumococcal conjugate vaccine (PCV7 was introduced into the routine childhood immunization program in Uruguay, with a 2+1 schedule. In 2010, PCV13 replaced PCV7, and the same 2+1 schedule was used. The effect of these pneumococcal vaccines on the incidence of invasive pneumococcal infections (IPD and on serotype distribution was analyzed retrospectively, based on passive national laboratory surveillance.Data from 1,887 IPD isolates from 5 years before and 5 years after PCV7 introduction (7 before and 3 after PCV13 introduction was examined to assess the incidence rate per 100,000 age-specific population of all IPD, PCV7-serotypes, and PCV13-serotypes associated IPD among children < 2 years and 2 to 4 years old, and patients ≥ 5 years old. Trends of frequency for each serotype were also analyzed.Comparison of pre-vaccination (2003-2007 and post-vaccination (2008-2012 periods showed a significant decrease in IPD incidence among children < 2 years old (IR 68.7 to IR 29.6, p<0.001 and children 2 to 4 years (p < 0.04. IPD caused by serotypes in PCV7 was reduced by 95.6% and IPD caused by 6 serotypes added in PCV13 was reduced by 83.9% in children <5 years old. Indirect effects of both conjugate vaccines were observed among patients ≥ 5 years old one year after the introduction of each vaccine, in 2010 for PCV7 and in 2012 for PCV13. Nevertheless, for reasons that still need to be explained, perhaps due to ascertainment bias, total IPD in this group increased after 2007. In 2012, the relative frequency of vaccine serotypes among vaccinated and unvaccinated population declined, except for serotype 3. Non vaccine serotypes with increasing frequency were identified, in rank order: 12F, 8, 24F, 22F, 24A, 15C, 9N, 10A and 33.Consecutive immunization with PCV7 and PCV13 has significantly reduced IPD in children < 5 years of age in Uruguay.
Deirdre A Collins
Full Text Available BACKGROUND: Invasive pneumococcal disease (IPD continues to occur at high rates among Australian Aboriginal people. The seven-valent pneumococcal conjugate vaccine (7vPCV was given in a 2-4-6-month schedule from 2001, with a 23-valent pneumococcal polysaccharide vaccine (23vPPV booster at 18 months, and replaced with 13vPCV in July 2011. Since carriage surveillance can supplement IPD surveillance, we have monitored pneumococcal carriage in western Australia (WA since 2008 to assess the impact of the 10-year 7vPCV program. METHODS: We collected 1,500 nasopharyngeal specimens from Aboriginal people living in varied regions of WA from August 2008 until June 2011. Specimens were cultured on selective media. Pneumococcal isolates were serotyped by the quellung reaction. RESULTS: Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis were carried by 71.9%, 63.2% and 63.3% respectively of children <5 years of age, and 34.6%, 22.4% and 27.2% of people ≥5 years. Of 43 pneumococcal serotypes identified, the most common were 19A, 16F and 6C in children <5 years, and 15B, 34 and 22F in older people. 7vPCV serotypes accounted for 14.5% of all serotypeable isolates, 13vPCV for 32.4% and 23vPPV for 49.9%, with little variation across all age groups. Serotypes 1 and 12F were rarely identified, despite causing recent IPD outbreaks in WA. Complete penicillin resistance (MIC ≥2µg/ml was found in 1.6% of serotype 19A (5.2%, 19F (4.9% and 16F (3.2% isolates and reduced penicillin susceptibility (MIC ≥0.125µg/ml in 24.9% of isolates, particularly 19F (92.7%, 19A (41.3%, 16F (29.0%. Multi-resistance to cotrimoxazole, tetracycline and erythromycin was found in 83.0% of 23F isolates. Among non-serotypeable isolates 76.0% had reduced susceptibility and 4.0% showed complete resistance to penicillin. CONCLUSIONS: Ten years after introduction of 7vPCV for Aboriginal Australian children, 7vPCV serotypes account for a small proportion of carried
Full Text Available Molecular identification of Streptococcus pneumoniae serotype 19F is routinely performed by PCR targeting the wzy gene of the capsular biosynthetic locus. However, 19F isolates with genetic similarity to 19A have been reported in the United States and Brazil. We screened 78 pneumococcal carriage isolates and found six 19F wzy variants that originated from children in Papua New Guinea and Fiji. Isolates were characterized using multilocus sequence typing and opsonophagocytic assays. The 19F wzy variants displayed similar susceptibility to anti-19F IgG antibodies compared to standard 19F isolates. Our findings indicate that these 19F variants may be more common than previously believed.
Kietzman, Colin C; Gao, Geli; Mann, Beth; Myers, Lance; Tuomanen, Elaine I
Bacterial pathogens produce complex carbohydrate capsules to protect against bactericidal immune molecules. Paradoxically, the pneumococcal capsule sensitizes the bacterium to antimicrobial peptides found on epithelial surfaces. Here we show that upon interaction with antimicrobial peptides, encapsulated pneumococci survive by removing capsule from the cell surface within minutes in a process dependent on the suicidal amidase autolysin LytA. In contrast to classical bacterial autolysis, during capsule shedding, LytA promotes bacterial survival and is dispersed circumferentially around the cell. However, both autolysis and capsule shedding depend on the cell wall hydrolytic activity of LytA. Capsule shedding drastically increases invasion of epithelial cells and is the main pathway by which pneumococci reduce surface bound capsule during early acute lung infection of mice. The previously unrecognized role of LytA in removing capsule to combat antimicrobial peptides may explain why nearly all clinical isolates of pneumococci conserve this enzyme despite the lethal selective pressure of antibiotics. PMID:26924467
Full Text Available Objective. To investigate the impact of seven-valent pneumococcal conjugate vaccine on tube insertions in a partial immunized pediatric population. Study Design. Retrospective ecological study. Methods. This study used Taiwan National Health Insurance Research Database for the period 2000–2009. Every child under 17 years old who received tubes during this 10-year period was identified and analyzed. The tube insertion rates in different age groups and the risk to receive tubes in different birth cohorts before and after the release of the vaccine in 2005 were compared. Results. The tube insertion rates for children under 17 years of age ranged from 21.6 to 31.9 for 100,000 persons/year. The tube insertion rate of children under 2 years old decreased significantly after 2005 in period effect analysis (β = −0.074, P < 0.05, and the negative β value means a downward trend and increased in children 2 to 9 years old throughout the study period (positive β values which mean upward trends, P < 0.05. The rate of tube insertion was lower in 2004-2005 and 2006-2007 birth cohorts than that of 2002-2003 birth cohort (RR = 0.90 and 0.21, 95% CI 0.83–0.97 and 0.19–0.23, resp.. Conclusion. The seven-valent pneumococcal conjugate vaccine may reduce the risk of tube insertion for children of later birth cohorts. The vaccine may have the protective effect on tube insertions in a partial immunized pediatric population.
Yildirim, Inci; Hanage, William P.; Lipsitch, Marc; Shea, Kimberly M.; Stevenson, Abbie; Finkelstein, Jonathan; Huang, Susan S.; Lee, Grace M.; Kleinman, Ken; Pelton, SI
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
Kantsø, Bjørn; Halkjær, Sofie Ingdam; Thomsen, Ole Østergaard;
with and without immunosuppressive treatment four weeks post vaccination. METHODS: In a randomized trial of the 23-valent pneumococcal polysaccharide vaccine (PPV23) and the 13-valent pneumococcal conjugated vaccine (PCV13), a group of CD patients treated with immunosuppressive drugs (IS) alone or in...... between treatment groups showed that immunosuppressive treatment impaired the antibody response to both vaccines and that TNF-a treatment further conveyed additional impairment of the response. CONCLUSION: PCV13 induces higher antibody response for some serotypes compared to PPV23. In addition, CD...... patients treated with immunosuppressive drugs alone or in combination with TNF-α antagonists had an impaired antibody response to both PPV23 and PCV13 compared to patients not receiving any of these treatments. The study has been registered in the European Clinical Trials Database (EudraCT, record no 2012...
Harris, Aaron M; Aol, George; Ouma, Dominic; Bigogo, Godfrey; Montgomery, Joel M; Whitney, Cynthia G; Breiman, Robert F; Kim, Lindsay
With the accelerated introduction of new vaccines in low-income settings, understanding immunization program performance is critical. We sought to improve immunization history acquisition from Ministry of Health vaccination cards during a vaccine impact study of 10-valent pneumococcal conjugate vaccine on pneumococcal carriage among young children in Kenya in 2012 and 2013. We captured immunization history in a low proportion of study participants in 2012 using vaccination cards. To overcome this challenge, we implemented a household-based reminder system in 2013 using community health workers (CHWs), and increased the retrieval of vaccine cards from 62% in 2012 to 89% in 2013 (P history data quality in a resource-poor setting. PMID:27139446
Abdullahi, O; A. Karani; Tigoi, CC; Mugo, D; Kungu, S; Wanjiru, E; Jomo, J; Musyimi, R; Lipsitch, M.; Scott, JAG
BACKGROUND Pneumococcal conjugate vaccines (PCV) reduce nasopharyngeal carriage of vaccine-serotype pneumococci but increase in the carriage of non-vaccine serotypes. We studied the epidemiology of carriage among children 3-59 months old before vaccine introduction in Kilifi, Kenya. METHODS In a rolling cross-sectional study from October 2006 to December 2008 we approached 3570 healthy children selected at random from the population register of the Kilifi Health and Demographic Surveilla...
Anjana; Jagadeesh; Ravi Kumar; Rashmi,; Ashwini; Shwethalatha
ABSTRACT: CONTEXT : Streptococcus pneumoniae (S. pneumoniae) infections are an important cause of mortality in young children. There are a n umber of problems associated with establishing the microbial etiology by conventional methods, thus highlighting the need for a rapid, improved and accurate test method. A rapid imm unochromatographic assay has been developed for detecting a pneumococcal cell wall anti gen common to all 92 serotypes. AIM: The aim of...
Suresh, Madathilparambil V.; Singh, Sanjay K.; Ferguson, Donald A.; Agrawal, Alok
Human C-reactive protein (CRP) protects mice from lethality after infection with virulent Streptococcus pneumoniae type 3. For CRP-mediated protection, the complement system is required; however, the role of complement activation by CRP in the protection is not defined. Based on the in vitro properties of CRP, it has been assumed that protection of mice begins with the binding of CRP to pneumococcal C-polysaccharide on S. pneumoniae and subsequent activation of the mouse complement system. In...
Too, Lay Khoon; Mitchell, Andrew J; McGregor, Iain S; Hunt, Nicholas H
During pneumococcal meningitis, clearance of bacteria by recruited neutrophils is crucial for host protection. However, these innate immune mechanisms are often insufficient and treatment with antibiotics is necessary to prevent death. Despite this antibiotic treatment, approximately half of all survivors suffer lifelong neurological problems. There is growing evidence indicating the harmful effects of neutrophils on CNS integrity. Therefore, the present study investigated the roles of neutrophils in the acute inflammatory response and the resulting long-term neuropsychological effects in murine pneumococcal meningitis. Long-term behavioural and cognitive functions in mice were measured using an automated IntelliCage system. Neutrophil depletion with antibody 1A8 as adjunctive therapy was shown to remarkably impair survival in meningitic C57BL/6J mice despite antibiotic (ceftriaxone) treatment. This was accompanied by increased bacterial load in the cerebrospinal fluid (CSF) and an increase in IL-1β, but decrease in TNF, within the CSF at 20h after bacterial inoculation. In the longer term, the surviving neutrophil-depleted post-meningitic (PM) mice displayed reduced diurnal hypolocomotion compared to PM mice treated with an isotype antibody. However, they showed nocturnal hyperactivity, and greater learning impairment in a patrolling task that is believed to depend upon an intact hippocampus. The data thus demonstrate two important mechanisms: 1. Neutrophil extravasation into the CNS during pneumococcal meningitis influences the pro-inflammatory response and is central to control of the bacterial load, an increase in which may lead to death. 2. Neutrophil-mediated changes in the acute inflammatory response modulate the neuropsychological sequelae in mice that survive pneumococcal meningitis. PMID:26965652
Griffioen, A W; Rijkers, G T; Janssens-Korpela, P; Zegers, B J
The immunoregulatory function of the complement system has been the focus of many investigations. In particular, fragments of complement factor C3 have been shown to play a role in B-lymphocyte activation and proliferation, lymphokine production, and the generation of in vitro antibody production. Purified pneumococcal polysaccharides (PS) can induce direct activation of C3 via the alternative pathway. Using sera of C1q-deficient patients and healthy subjects, we demonstrated that C3d, a spli...
Tijmen J Hommes
Full Text Available Streptococcus (S. pneumoniae is the most common causative pathogen in community-acquired pneumonia. Nucleotide-binding oligomerization domain-containing (NOD 2 is a pattern recognition receptor located in the cytosol of myeloid cells that is able to detect peptidoglycan fragments of S. pneumoniae. We here aimed to investigate the role of NOD2 in the host response during pneumococcal pneumonia. Phagocytosis of S. pneumoniae was studied in NOD2 deficient (Nod2-/- and wild-type (Wt alveolar macrophages and neutrophils in vitro. In subsequent in vivo experiments Nod2-/- and Wt mice were inoculated with serotype 2 S. pneumoniae (D39, an isogenic capsule locus deletion mutant (D39Δcps or serotype 3 S. pneumoniae (6303 via the airways, and bacterial growth and dissemination and the lung inflammatory response were evaluated. Nod2-/- alveolar macrophages and blood neutrophils displayed a reduced capacity to internalize pneumococci in vitro. During pneumonia caused by S. pneumoniae D39 Nod2-/- mice were indistinguishable from Wt mice with regard to bacterial loads in lungs and distant organs, lung pathology and neutrophil recruitment. While Nod2-/- and Wt mice also had similar bacterial loads after infection with the more virulent S. pneumoniae 6303 strain, Nod2-/- mice displayed a reduced bacterial clearance of the normally avirulent unencapsulated D39Δcps strain. These results suggest that NOD2 does not contribute to host defense during pneumococcal pneumonia and that the pneumococcal capsule impairs recognition of S. pneumoniae by NOD2.
David N Durrheim
Full Text Available The aim of this work was to determine the feasibility of improving Aboriginal and Torres Strait Islander status recording for notifiable diseases using all Invasive Pneumococcal Disease (IPD notifications in a regional area of New South Wales, Australia.In Australia people with IPD are nearly always admitted to hospital and their Aboriginal and Torres Strait Islander status is recorded. Aboriginal and Torres Strait Islander status was determined for IPD notifications by referring to the routine hospital admission data, in a regional area of New South Wales, Australia.There were 234 notifications in the regional area of Hunter New England during the period 2007–2009. Initially, 168 (72% notifications had Aboriginal and Torres Strait Islander status recorded. After referring to the routine hospital admission data the recorded status increased to 232 (99%. Updating the surveillance data required less than five minutes per notification.Referring to routine hospital admission data proved a useful and time-efficient surveillance strategy to increase the proportion of notifications with Aboriginal and Torres Strait Islander status. These data can then be used to better understand the current epidemiology of IPD. Aboriginal and Torres Strait Islander children aged 0–4 years have a two- to threefold higher rate of invasive pneumococcal disease than non-Aboriginal children, thus high levels of timely pneumococcal immunization coverage remain important for young Aboriginal and Torres Strait Islander children.
Full Text Available BACKGROUND: Specific antibodies mediate humoral and cellular protection against invading pathogens such as Streptococcus pneumoniae by activating complement mediated immunity, promoting phagocytosis and stimulating bacterial clearance. The emergence of pneumococcal strains with high levels of antibiotic resistance is of great concern worldwide and a serious threat for public health. METHODOLOGY/PRINCIPAL FINDINGS: Flow cytometry was used to determine whether complement-mediated immunity against three antibiotic-resistant S. pneumoniae clinical isolates is enhanced in the presence of sub-inhibitory concentrations of cefditoren and ceftriaxone. The binding of acute phase proteins such as C-reactive protein and serum amyloid P component, and of complement component C1q, to pneumococci was enhanced in the presence of serum plus either of these antibiotics. Both antibiotics therefore trigger the activation of the classical complement pathway against S. pneumoniae. C3b deposition was also increased in the presence of specific anti-pneumococcal antibodies and sub-inhibitory concentrations of cefditoren and ceftriaxone confirming that the presence of these antibiotics enhances complement-mediated immunity to S. pneumoniae. CONCLUSIONS/SIGNIFICANCE: Using cefditoren and ceftriaxone to promote the binding of acute phase proteins and C1q to pneumococci, and to increase C3b deposition, when anti-pneumococcal antibodies are present, might help reduce the impact of antibiotic resistance in S. pneumoniae infections.
Silvio D Brugger
Full Text Available BACKGROUND: Simultaneous carriage of more than one strain of Streptococcus pneumoniae promotes horizontal gene transfer events and may lead to capsule switch and acquisition of antibiotic resistance. We studied the epidemiology of cocolonization with S. pneumoniae before and after introduction of the seven-valent conjugated pneumococcal vaccine (PCV7. METHODOLOGY: Nasopharyngeal swabs (n 1120 were collected from outpatients between 2004 and 2009 within an ongoing nationwide surveillance program. Cocolonization was detected directly from swabs by restriction fragment length polymorphism (RFLP analysis. Serotypes were identified by agglutination, multiplex PCR and microarray. PRINCIPAL FINDINGS: Rate of multiple colonization remained stable up to three years after PCV7 introduction. Cocolonization was associated with serotypes of low carriage prevalence in the prevaccine era. Pneumococcal colonization density was higher in cocolonized samples and cocolonizing strains were present in a balanced ratio (median 1.38. Other characteristics of cocolonization were a higher frequency at young age, but no association with recurrent acute otitis media, recent antibiotic exposure, day care usage and PCV7 vaccination status. CONCLUSIONS: Pneumococcal cocolonization is dominated by serotypes of low carriage prevalence in the prevaccine era, which coexist in the nasopharynx. Emergence of such previously rare serotypes under vaccine selection pressure may promote cocolonization in the future.
[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].
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
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
Vintiñi Elisa O
Full Text Available Abstract Background At present, available pneumococcal vaccines have failed to eradicate infections caused by S. pneumoniae. Search for effective vaccine continues and some serotype independent pneumococcal proteins are considered as candidates for the design of new vaccines, especially a mucosal vaccine, since pneumococci enter the body through mucosal surfaces. Selection of the appropriate adjuvant is important for mucosal vaccines, and lactic acid bacteria (LAB with immunostimulant properties are promissory candidates. In this work, we assessed the adjuvant effect of a probiotic strain, Lactobacillus casei (L. casei, when nasally administered with a pneumococcal antigen (pneumococcal protective protein A: PppA for the prevention of pneumococcal infection. Adjuvanticity of both live (LcV and heat-killed (LcM was evaluated and humoral and cellular antigen-specific immune response was assessed in mucosal and systemic compartments. The potential mechanisms induced by nasal immunization were discussed. Results Nasal immunization of young mice with PppA+LcV and PppA+LcM induced anti-PppA IgA and IgG antibodies in mucosal and systemic compartments and levels of these specific antibodies remained high even at day 45 after the 3rd Immunization (3rd I. These results were correlated with IL-4 induction by the mixture of antigen plus LcV and LcM. Also, PppA+Lc (V and M induced stimulation of Th1 and Th17 cells involved in the defence against pneumococci. The protection against pneumococcal respiratory challenge at day 30 after the 3rd I showed that PppA+LcV and PppA+LcM immunizations significantly reduced pathogen counts in nasal lavages while prventing their passage into lung and blood. Survival of mice immunized with the co-application of PppA plus LcV and LcM was significantly higher than in mice immunized with PppA alone and control mice when intraperitoneal challenge was performed. No significant differences between the treatments involving LcV and
Jenny A Herbert
Full Text Available The pneumococcal serine threonine protein kinase (StkP acts as a global regulator in the pneumococcus. Bacterial mutants deficient in StkP are less virulent in animal models of infection. The gene for this regulator is located adjacent to the gene for its cognate phosphatase in the pneumococcal genome. The phosphatase dephosphorylates proteins phosphorylated by StkP and has been shown to regulate a number of key pneumococcal virulence factors and to modulate adherence to eukaryotic cells. The role of StkP in adherence of pneumococci to human cells has not previously been reported. In this study we show StkP represses the pneumococcal pilus, a virulence factor known to be important for bacterial adhesion. In a serotype 4 strain regulation of the pilus by StkP modulates adherence to human brain microvascular endothelial cells (HBMEC and human lung epithelial cells. This suggests that the pneumococcal pilus may play a role in adherence during infections such as meningitis and pneumonia. We show that regulation of the pilus occurs at the population level as StkP alters the number of pili-positive cells within a single culture. As far as we are aware this is the first gene identified outside of the pilus islet that regulates the biphasic expression of the pilus. These findings suggest StkPs role in cell division may be linked to regulation of expression of a cell surface adhesin.
Bruce Y Lee
Full Text Available Although the substantial burdens of rotavirus and pneumococcal disease have motivated many countries to consider introducing the rotavirus vaccine (RV and heptavalent pneumococcal conjugate vaccine (PCV-7 to their National Immunization Programs (EPIs, these new vaccines could affect the countries' vaccine supply chains (i.e., the series of steps required to get a vaccine from their manufacturers to patients. We developed detailed computational models of the Trang Province, Thailand, vaccine supply chain to simulate introducing various RV and PCV-7 vaccine presentations and their combinations. Our results showed that the volumes of these new vaccines in addition to current routine vaccines could meet and even exceed (1 the refrigerator space at the provincial district and sub-district levels and (2 the transport cold space at district and sub-district levels preventing other vaccines from being available to patients who arrive to be immunized. Besides the smallest RV presentation (17.1 cm³/dose, all other vaccine introduction scenarios required added storage capacity at the provincial level (range: 20 L-1151 L per month for the three largest formulations, and district level (range: 1 L-124 L per month across all introduction scenarios. Similarly, with the exception of the two smallest RV presentation (17.1 cm³/dose, added transport capacity was required at both district and sub-district levels. Added transport capacity required across introduction scenarios from the provincial to district levels ranged from 1 L-187 L, and district to sub-district levels ranged from 1 L-13 L per shipment. Finally, only the smallest RV vaccine presentation (17.1 cm³/dose had no appreciable effect on vaccine availability at sub-districts. All other RV and PCV-7 vaccines were too large for the current supply chain to handle without modifications such as increasing storage or transport capacity. Introducing these new vaccines to Thailand could have dynamic effects
Kohler, Thomas P; Scholz, Annemarie; Kiachludis, Delia; Hammerschmidt, Sven
Streptococcus pneumoniae is a widespread colonizer of the mucosal epithelia of the upper respiratory tract of human. However, pneumococci are also responsible for numerous local as well as severe systemic infections, especially in children under the age of five and the elderly. Under certain conditions, pneumococci are able to conquer the epithelial barrier, which can lead to a dissemination of the bacteria into underlying tissues and the bloodstream. Here, specialized macrophages represent an essential part of the innate immune system against bacterial intruders. Recognition of the bacteria through different receptors on the surface of macrophages leads thereby to an uptake and elimination of bacteria. Accompanied cytokine release triggers the migration of leukocytes from peripheral blood to the site of infection, where monocytes differentiate into mature macrophages. The rearrangement of the actin cytoskeleton during phagocytosis, resulting in the engulfment of bacteria, is thereby tightly regulated by receptor-mediated phosphorylation cascades of different protein kinases. The molecular cellular processes including the modulation of central protein kinases are only partially solved. In this study, the human monocytic THP-1 cell line was used as a model system to examine the activation of Fcγ and complement receptor-independent signal cascades during infection with S. pneumoniae. Pneumococci cultured either in chemically defined or complex medium showed no significant differences in pneumococcal phagocytosis by phorbol 12-myristate 13-acetate (PMA) differentiated THP-1 cells. Double immuno-fluorescence microscopy and antibiotic protection assays demonstrated a time-dependent uptake and killing of S. pneumoniae 35A inside of macrophages. Infections of THP-1 cells in the presence of specific pharmacological inhibitors revealed a crucial role of actin polymerization and importance of the phosphoinositide 3-kinase (PI3K) and Protein kinase B (Akt) as well during
Thomas Peter Kohler
Full Text Available Streptococcus pneumoniae is a widespread colonizer of the mucosal epithelia of the upper respiratory tract of human. However, pneumococci are also responsible for numerous local as well as severe systemic infections, especially in children under the age of five and the elderly. Under certain conditions, pneumococci are able to conquer the epithelial barrier, which can lead to a dissemination of the bacteria into underlying tissues and the bloodstream. Here, specialized macrophages represent an essential part of the innate immune system against bacterial intruders. Recognition of the bacteria through different receptors on the surface of macrophages leads thereby to an uptake and elimination of bacteria. Accompanied cytokine release triggers the migration of leukocytes from peripheral blood to the site of infection, where monocytes differentiate into mature macrophages. The rearrangement of the actin cytoskeleton during phagocytosis, resulting in the engulfment of bacteria, is thereby tightly regulated by receptor-mediated phosphorylation cascades of different protein kinases. The molecular cellular processes including the modulation of central protein kinases are only partially solved. In this study, the human monocytic THP-1 cell line was used as a model system to examine the activation of Fcγ and complement receptor-independent signal cascades during infection with S. pneumoniae. Pneumococci cultured either in chemically defined or complex medium showed no significant differences in pneumococcal phagocytosis by phorbol 12-myristate 13-acetate (PMA differentiated THP-1 cells. Double immuno-fluorescence microscopy and antibiotic protection assays demonstrated a time-dependent uptake and killing of S. pneumoniae 35A inside of macrophages. Infections of THP-1 cells in the presence of specific pharmacological inhibitors revealed a crucial role of actin polymerization and importance of the phosphoinositide 3-kinase (PI3K and Protein kinase B (Akt
Full Text Available Abstract Background Pili were recently recognized in Streptococcus pneumoniae and implicated in the virulence of this bacterium, which led to the proposal of using these antigens in a future pneumococcal vaccine. However, pili were found to be encoded by the rlrA islet that was not universally distributed in the species. We examined the distribution of the pilus islet, using the presence of the rlrA gene as a marker for the locus, among a collection of invasive isolates recovered in Portugal and analyzed its association with capsular serotypes, clusters defined by the pulsed-field gel electrophoretic profiles (PFGE and multilocus sequence types. Results Only a minority of the isolates were positive for the presence of the rlrA gene (27%. There was a high correspondence between the serotype and the presence or absence of rlrA (Wallace coefficient, W = 0.778. In particular, there was an association between the presence of rlrA and the vaccine serotypes 4, 6B, 9V and 14 whereas the gene was significantly absent from other serotypes, namely 1, 7F, 8, 12B and 23F, a group that included a vaccine serotype (23F and serotype 1 associated with enhanced invasiveness. Even within serotypes, there was variation in the presence of the pilus islet between PFGE clones and a higher Wallace coefficient (W = 0.939 indicates that carriage of the islet is a clonal property of pneumococci. Analysis of rlrA negative isolates revealed heterogeneity in the genomic region downstream of the rfl gene, the region where the islet is found in other isolates, compatible with recent loss of the islet in some lineages. Conclusion The pilus islet is present in a minority of pneumococcal isolates recovered from human invasive infections and is therefore not an essential virulence factor in these infections. Carriage of the pilus islet is a clonal property of pneumococci that may vary between isolates expressing the same serotype and loss and acquisition of the islet may be
Horácio, Andreia N.; Silva-Costa, Catarina; Diamantino-Miranda, Jorge; Lopes, Joana P.; Ramirez, Mario; Melo-Cristino, José
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
Tóthpál, A; Laub, K; Kardos, S; Tirczka, T; Kocsis, A; VAN DER Linden, M; Dobay, O
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
Pholwat, Suporn; Sakai, Fuminori; Turner, Paul; Vidal, Jorge E; Houpt, Eric R
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
Suarez, Victor; Michel, Fabiana; Toscano, Cristiana M; Bierrenbach, Ana Luiza; Gonzales, Marco; Alencar, Airlane Pereira; Ruiz Matus, Cuauhtemoc; Andrus, Jon K; de Oliveira, Lucia H
Streptococcus pneumoniae is the leading cause of bacterial pneumonia, meningitis and sepsis in children worldwide. Despite available evidence on pneumococcal conjugate vaccine (PCV) impact on pneumonia hospitalizations in children, studies demonstrating PCV impact in morbidity and mortality in middle-income countries are still scarce. Given the disease burden, PCV7 was introduced in Peru in 2009, and then switched to PCV10 in late 2011. National public healthcare system provides care for 60% of the population, and national hospitalization, outpatient and mortality data are available. We thus aimed to assess the effects of routine PCV vaccination on pneumonia hospitalization and mortality, and acute otitis media (AOM) and all cause pneumonia outpatient visits in children under one year of age in Peru. We conducted a segmented time-series analysis using outcome-specific regression models. Study period was from January 2006 to December 2012. Data sources included the National information systems for hospitalization, mortality, outpatient visits, and RENACE, the national database of aggregated weekly notifications of pneumonia and other acute respiratory diseases (both hospitalized and non-hospitalized). Study outcomes included community acquired pneumonia outpatient visits, hospitalizations and deaths (ICD10 codes J12-J18); and AOM outpatient visits (H65-H67). Monthly age- and sex-specific admission, outpatient visit, and mortality rates per 100,000 children aged Peru. PMID:27521230
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
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
Nicola Maria Vitola
Full Text Available BACKGROUND A crude rate of mortality of 5% has been quoted for anorexia nervosa in recent studies. Nowadays the mechanism of death is unclear and various authors recommend that any anorexia nervosa death be reported and that, where possible, an autopsy be performed. METHODS In this work we present a case of sudden death in anorexia nervosa with unexpected autopsy findings. A 21-years-old woman with long-standing anorexia nervosa, severely underweight with a body mass index of 14.47 kg/m2, has been taken to the Emergency Department in very critical conditions. Despite the attempts of resuscitation, she died shortly afterwards. Therefore an autopsy has been requested in order to clarify the causes of death. RESULTS The clinical picture, laboratory parameters, histology and microbiological investigations were consistent with pneumococcal sepsis associated adrenal apoplexy. CONCLUSIONS The cause of death in anorexia nervosa cannot reliably be established from antemortem clinical features. All anorexia nervosa deaths should be reported together with description of necropsy. This may lead to advances in the knowledge and treatment practices.
Full Text Available Abstract Background Intranasal inoculation of Streptococcus pneumoniae D39 serotype 2 causes fatal pneumonia in mice. The cytotoxic and inflammatory properties of pneumolysin (PLY have been implicated in the pathogenesis of pneumococcal pneumonia. Methods To examine the role of PLY in this experimental model we performed ELISA assays for PLY quantification. The distribution patterns of PLY and apoptosis were established by immunohistochemical detection of PLY, caspase-9 activity and TUNEL assay on tissue sections from mice lungs at various times, and the results were quantified with image analysis. Inflammatory and apoptotic cells were also quantified on lung tissue sections from antibody treated mice. Results In bronchoalveolar lavages (BAL, total PLY was found at sublytic concentrations which were located in alveolar macrophages and leukocytes. The bronchoalveolar epithelium was PLY-positive, while the vascular endothelium was not PLY reactive. The pattern and extension of cellular apoptosis was similar. Anti-PLY antibody treatment decreased the lung damage and the number of apoptotic and inflammatory cells in lung tissues. Conclusion The data strongly suggest that in vivo lung injury could be due to the pro-apoptotic and pro-inflammatory activity of PLY, rather than its cytotoxic activity. PLY at sublytic concentrations induces lethal inflammation in lung tissues and is involved in host cell apoptosis, whose effects are important to pathogen survival.
Layla K Mahdi
Full Text Available Streptococcus pneumoniae (the pneumococcus continues to account for significant morbidity and mortality worldwide, causing life-threatening diseases such as pneumonia, bacteremia and meningitis, as well as less serious infections such as sinusitis, conjunctivitis and otitis media. Current polysaccharide vaccines are strictly serotype-specific and also drive the emergence of non-vaccine serotype strains. In this study, we used microarray analysis to compare gene expression patterns of either serotype 4 or serotype 6A pneumococci in the nasopharynx and blood of mice, as a model to identify genes involved in invasion of blood in the context of occult bacteremia in humans. In this manner, we identified 26 genes that were significantly up-regulated in the nasopharynx and 36 genes that were significantly up-regulated in the blood that were common to both strains. Gene Ontology classification revealed that transporter and DNA binding (transcription factor activities constitute the significantly different molecular functional categories for genes up-regulated in the nasopharynx and blood. Targeted mutagenesis of selected genes from both niches and subsequent virulence and pathogenesis studies identified the manganese-dependent superoxide dismutase (SodA as most likely to be essential for colonization, and the cell wall-associated serine protease (PrtA as important for invasion of blood. This work extends our previous analyses and suggests that both PrtA and SodA warrant examination in future studies aimed at prevention and/or control of pneumococcal disease.
Li, Guiling; Liang, Zhuowen; Wang, Xiatai; Yang, Yonghong; Shao, Zhujun; Li, Machao; Ma, Yueyun; Qu, Fen; Morrison, Donald A; Zhang, Jing-Ren
Natural genetic transformation of Streptococcus pneumoniae, an important human pathogen, mediates horizontal gene transfer for the development of drug resistance, modulation of carriage and virulence traits, and evasion of host immunity. Transformation frequency differs greatly among pneumococcal clinical isolates, but the molecular basis and biological importance of this interstrain variability remain unclear. In this study, we characterized the transformation frequency and other associated phenotypes of 208 S. pneumoniae clinical isolates representing at least 30 serotypes. While the vast majority of these isolates (94.7%) were transformable, the transformation frequency differed by up to 5 orders of magnitude between the least and most transformable isolates. The strain-to-strain differences in transformation frequency were observed among many isolates producing the same capsule types, indicating no general association between transformation frequency and serotype. However, a statistically significant association was observed between the levels of transformation and colonization fitness/virulence in the hypertransformable isolates. Although nontransformable mutants of all the selected hypertransformable isolates were significantly attenuated in colonization fitness and virulence in mouse infection models, such mutants of the strains with relatively low transformability had no or marginal fitness phenotypes under the same experimental settings. This finding strongly suggests that the pneumococci with high transformation capability are "addicted" to a "hypertransformable" state for optimal fitness in the human host. This work has thus provided an intriguing hint for further investigation into how the competence system impacts the fitness, virulence, and other transformation-associated traits of this important human pathogen. PMID:27068094
Nicholas J Loman
Full Text Available Streptococcus pneumoniae causes invasive infections, primarily at the extremes of life. A seven-valent conjugate vaccine (PCV7 is used to protect against invasive pneumococcal disease in children. Within three years of PCV7 introduction, we observed a fourfold increase in serotype 6C carriage, predominantly due to a single clone. We determined the whole-genome sequences of nineteen S. pneumoniae serotype 6C isolates, from both carriage (n = 15 and disease (n = 4 states, to investigate the emergence of serotype 6C in our population, focusing on a single multi-locus sequence type (MLST clonal complex 395 (CC395. A phylogenetic network was constructed to identify different lineages, followed by analysis of variability in gene sets and sequences. Serotype 6C isolates from this single geographical site fell into four broad phylogenetically distinct lineages. Variation was seen in the 6C capsular locus and in sequences of genes encoding surface proteins. The largest clonal complex was characterised by the presence of lantibiotic synthesis locus. In our population, the 6C capsular locus has been introduced into multiple lineages by independent capsular switching events. However, rapid clonal expansion has occurred within a single MLST clonal complex. Worryingly, plasticity exists within current and potential vaccine-associated loci, a consideration for future vaccine use, target selection and design.
Center, Kimberly J; Strauss, Ann
Documentation of the safety of any vaccine is of paramount importance given the nature and scale of vaccination as a public health intervention. Prevenar was first approved for use in 2000, and includes seven pneumococcal serotypes conjugated to CRM(197), a carrier protein that has been used safely in multiple conjugate vaccines for more than 20 years. The safety profile of Prevenar was established prior to licensure in 5 clinical trials involving more than 18,000 infants and children. The largest postmarketing study of the safety of Prevenar given concomitantly with other recommended vaccines was conducted in the United States, and included more than 162,000 subjects. This analysis did not suggest any new safety consideration that would alter the risk-benefit balance of the vaccine, and demonstrated the favorable safety profile of Prevenar. To date, global surveillance of spontaneously reported adverse events to the manufacturer after more than 198 million doses distributed has confirmed these findings. The WHO has recommended the priority inclusion of this vaccine in national childhood immunization programs based on both its documented efficacy and safety. We will discuss the importance of monitoring vaccine safety and the methodologies by which this may be done, using Prevenar as an illustrative example. PMID:19200818
... Conditions Frequently Asked Questions Español Condiciones Chinese Conditions Adult Strabismus En Español Read in Chinese Can anything be done for adults with strabismus (misaligned eyes)? Yes. Adults can benefit ...
Vestrheim, Didrik F; Steinbakk, Martin; Aaberge, Ingeborg S; Caugant, Dominique A
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
Duitman, JanWillem; Schouten, Marcel; Groot, Angelique P.; Borensztajn, Keren S.; Daalhuisen, Joost B.; Florquin, Sandrine; van der Poll, Tom; Spek, C Arnold
CCAAT/enhancer-binding protein δ (C/EBPδ) recently emerged as an essential player in the inflammatory response to bacterial infections. C/EBPδ levels increase rapidly after a proinflammatory stimulus, and increasing C/EBPδ levels seem to be indispensable for amplification of the inflammatory response. Here we aimed to elucidate the role of C/EBPδ in host defense in community-acquired pneumococcal pneumonia. We show that C/EBPδ−/− mice are relatively resistant to pneumococcal pneumonia, as ind...
Youssif M Ali
Full Text Available The complement system plays a key role in host defense against pneumococcal infection. Three different pathways, the classical, alternative and lectin pathways, mediate complement activation. While there is limited information available on the roles of the classical and the alternative activation pathways of complement in fighting streptococcal infection, little is known about the role of the lectin pathway, mainly due to the lack of appropriate experimental models of lectin pathway deficiency. We have recently established a mouse strain deficient of the lectin pathway effector enzyme mannan-binding lectin associated serine protease-2 (MASP-2 and shown that this mouse strain is unable to form the lectin pathway specific C3 and C5 convertases. Here we report that MASP-2 deficient mice (which can still activate complement via the classical pathway and the alternative pathway are highly susceptible to pneumococcal infection and fail to opsonize Streptococcus pneumoniae in the none-immune host. This defect in complement opsonisation severely compromises pathogen clearance in the lectin pathway deficient host. Using sera from mice and humans with defined complement deficiencies, we demonstrate that mouse ficolin A, human L-ficolin, and collectin 11 in both species, but not mannan-binding lectin (MBL, are the pattern recognition molecules that drive lectin pathway activation on the surface of S. pneumoniae. We further show that pneumococcal opsonisation via the lectin pathway can proceed in the absence of C4. This study corroborates the essential function of MASP-2 in the lectin pathway and highlights the importance of MBL-independent lectin pathway activation in the host defense against pneumococci.
Jackelline Rodrigues Alvares
Full Text Available OBJECTIVES: To determine the prevalence of pneumococcal serotypes and antimicrobial susceptibility in patients with meningitis, and to evaluate the implications for vaccine coverage. METHODS: Pneumococcal strains obtained from normally sterile fluids from patients admitted with meningitis were isolated at the Hospital de Clínicas of the Universidade Federal de Uberlândia, Minas Gerais State, and sent to the Instituto Adolfo Lutz, city of São Paulo, São Paulo State, for further identification, serotyping, and antimicrobial susceptibility determination. RESULTS: From April 1999 to April 2009, 338 pneumococcal strains were isolated, and 72 obtained from patients with meningitis, were analyzed. Patients' ages varied from one month to 82.2 years (mean of 18.4 ± 22.9 years; median of 5.2 years and 46 (63.9% patients were male. Strains were isolated from cerebrospinal fluid [66 occasions (91.7%] and blood [6 occasions (8.3%]. The most commonly identified serotypes were 14, 19F, 3, 7F, 6A, 6B, 10A, 18C, 23F, 5, and 34. Of the 20 [27.8%] oxacillin-resistant strains, 17 [23.6%] were resistant to penicillin and nine [12.5%] to ceftriaxone, both resistance patterns being more common in children aged two years or less and during the 2005-2009 period. CONCLUSIONS: Resistance to penicillin and ceftriaxone was detected in 23.6% and 12.5% of the strains, respectively, and predominated in children aged two years or less and during the 2005-2009 period. There were 24 different serotypes of pneumococcus and 79.8% of the serotypes were represented in the 7-valent conjugated vaccine [PVC7].
William S Pomat
Full Text Available BACKGROUND: Approximately 826,000 children, mostly young infants, die annually from invasive pneumococcal disease. A 6-10-14-week schedule of pneumococcal conjugate vaccine (PCV is efficacious but neonatal PCV may provide earlier protection and better coverage. We conducted an open randomized controlled trial in Papua New Guinea to compare safety, immunogenicity and priming for memory of 7-valent PCV (PCV7 given in a 0-1-2-month (neonatal schedule with that of the routine 1-2-3-month (infant schedule. METHODS: We randomized 318 infants at birth to receive PCV7 in the neonatal or infant schedule or no PCV7. All infants received 23-valent pneumococcal polysaccharide vaccine (PPV at age 9 months. Serotype-specific serum IgG for PCV7 (VT serotypes and non-VT serotypes 2, 5 and 7F were measured at birth and 2, 3, 4, 9, 10 and 18 months of age. Primary outcomes were geometric mean concentrations (GMCs and proportions with concentration ≥ 0.35 µg/ml of VT serotype-specific pneumococcal IgG at age 2 months and one month post-PPV. RESULTS: We enrolled 101, 105 and 106 infants, respectively, into neonatal, infant and control groups. Despite high background levels of maternally derived antibody, both PCV7 groups had higher GMCs than controls at age 2 months for serotypes 4 (p<0.001 and 9V (p<0.05 and at age 3 months for all VTs except 6B. GMCs for serotypes 4, 9V, 18C and 19F were significantly higher (p<0.001 at age 2 months in the neonatal (one month post-dose2 PCV7 than in the infant group (one month post-dose1 PCV7. PPV induced significantly higher VT antibody responses in PCV7-primed than unprimed infants, with neonatal and infant groups equivalent. High VT and non-VT antibody concentrations generally persisted to age 18 months. CONCLUSIONS: PCV7 is well-tolerated and immunogenic in PNG neonates and young infants and induces immunologic memory to PPV booster at age 9 months with antibody levels maintained to age 18 months. TRIAL REGISTRATION
Rødgaard-Hansen, Sidsel; Rafique, Aisha; Weis, Nina;
Background: The soluble mannose receptor (sMR) is a new serum marker of macrophage activation. The aim of the present study was to investigate sMR as a prognostic marker in patients with invasive pneumococcal disease (IPD), and compareit to other inflammatory biomarkers. Methods: Samples from 128...... patients 75 years or older the AUC was lower for all three markers (sMR = 0.56, sCD163 = 0.38, CRP = 0.66).Conclusions: The results of this study designate sMR as a potential new biomarker in infectious disease. Additionally, it emphasizes the importance of research into macrophage malfunction in elderly...
Full Text Available INTRODUCTION In Serbia, there is a significant number of persons suffering of pneumococcal pneumonia. Persons aged 65 years or older, immunocompromised patients, patients with co-morbidities, such as chronic obstructive lung disease and congestive heart failure, are at the highest risk for developing pneumococcal pneumonia. Most of the patients are treated empirically, although it is often overlooked that Streptococcus pneumoniae can be resistant to the used antibiotics. The treatment costs of such inpatients and outpatients are very high. In Serbia, immunization of persons at risk to develop the diseases caused by Streptococcus pneumoniae is carried out using pneumococcus polysaccharide vaccine according to clinical indications. The exact number of immunized persons and the total number of registered patients are still unknown, but it is certain of being unjustifiably low. OBJECTIVE The goal of the study was to investigate, during a one-year period, the number and basic characteristics of persons hospitably treated for pneumonia, the type of cause of the infection, applied antibiotic medications, duration and costs of hospital treatment at the Institute for Lung Diseases and Tuberculosis of the Clinical Centre of Serbia in Belgrade. METHOD We retrospectively analyzed the medical records of patients with pneumonia treated at the Institute for Lung Diseases and Tuberculosis of the Clinical Centre of Serbia in Belgrade during 2006. RESULTS During the observed one-year period, 290 patients underwent hospital treatment, of whom the cause of the infection was confirmed in 116 (40%. The average duration of hospitalization was 12 days, with treatment cost of 32,031.74 RSD (402.42 EUR per patient. The treatment cost per patient including general and intensive care was 18,290.01 RSD (229.78 EUR. The distribution cost of Pneumo 23 vaccine in Serbia, without purchase tax, was 746.90 RSD (9.38 EUR. CONCLUSION Pneumococcal pneumonia is a significant medical
Guevara, Marcela; Barricarte, Aurelio; Torroba, Luis; Herranz, Mercedes; Gil-Setas, Alberto; Gil, Francisco; Bernaola, Enrique; Ezpeleta, Carmen; Castilla, Jesús
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
McCombs, Janet E; Kohler, Jennifer J
Neuraminidases (sialidases) are enzymes that hydrolytically remove sialic acid from sialylated proteins and lipids. Neuraminidases are encoded by a range of human pathogens, including bacteria, viruses, fungi, and protozoa. Many pathogen neuraminidases are virulence factors, indicating that desialylation of host glycoconjugates can be a critical step in infection. Specifically, desialylation of host cell surface glycoproteins can enable these molecules to function as pathogen receptors or can alter signaling through the plasma membrane. Despite these critical effects, no unbiased approaches exist to identify glycoprotein substrates of neuraminidases. Here, we combine previously reported glycoproteomics methods with quantitative proteomics analysis to identify glycoproteins whose sialylation changes in response to neuraminidase treatment. The two glycoproteomics methods-periodate oxidation and aniline-catalyzed oxime ligation (PAL) and galactose oxidase and aniline-catalyzed oxime ligation (GAL)-rely on chemoselective labeling of sialylated and nonsialylated glycoproteins, respectively. We demonstrated the utility of the combined approaches by identifying substrates of two pneumococcal neuraminidases in a human cell line that models the blood-brain barrier. The methods deliver complementary lists of neuraminidase substrates, with GAL identifying a larger number of substrates than PAL (77 versus 17). Putative neuraminidase substrates were confirmed by other methods, establishing the validity of the approach. Among the identified substrates were host glycoproteins known to function in bacteria adherence and infection. Functional assays suggest that multiple desialylated cell surface glycoproteins may act together as pneumococcus receptors. Overall, this method will provide a powerful approach to identify glycoproteins that are desialylated by both purified neuraminidases and intact pathogens. PMID:26954852
Askenase, Phillip W; Bryniarski, Krzysztof; Paliwal, Vipin; Redegeld, Frank; Groot Kormelink, Thomas; Kerfoot, Steven; Hutchinson, Andrew T; van Loveren, Henk; Campos, Regis; Itakura, Atsuko; Majewska-Szczepanik, Monika; Yamamoto, Natsuo; Nazimek, Katarzyn; Szczepanik, Marian; Ptak, Wold
We propose that there is a special B-1a B cell subset ("sB-1a" cells) that mediates linked processes very early after immunization to initiate cutaneous contact sensitivity (CS), delayed-type hypersensitivity (DTH), and immune resistance to pneumococcal pneumonia. Our published data indicate that in CS and DTH, these initiating processes are required for elicitation of the delayed onset and late-occurring classical T cell-mediated responses. sB-1a cells resemble memory B2 cells, as they are stimulated within 1 h of immunization and depend on T helper cytokines-uniquely IL-4 from hepatic iNKT cells--for activation and rapid migration from the peritoneal cavity to the spleen to secrete IgM antibody (Ab) and Ab-derived free light chains (FLCs) by only 1 day after immunization. Unlike conventional B-1a (cB-1a) cell-produced IgM natural Ab, IgM Ab produced by sB-1a cells has high Ag affinity owing to immunoglobulin V-region mutations induced by activation-induced cytidine deaminase (AID). The dominant cB-1a cells are increased in immunized AID-deficient mice but do not mediate initiation, CS, or pneumonia resistance because natural Ab has relatively low Ag affinity because of unmutated germ-line V regions. In CS and DTH, sB-1a IgM Ag affinity is sufficiently high to mediate complement activation for generation of C5a that, together with vasoactive mediators such as TNF-α released by FLC-sensitized mast cells, activate local endothelium for extravascular recruitment of effector T cells. We conclude by discussing the possibility of functional sB-1 cells in humans. PMID:26662721
Gilley, Ryan P; González-Juarbe, Norberto; Shenoy, Anukul T; Reyes, Luis F; Dube, Peter H; Restrepo, Marcos I; Orihuela, Carlos J
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
Hartmann, Carolin; Behrendt, Ann-Kathrin; Henken, Stefanie; Wölbeling, Florian; Maus, Ulrich A; Hansen, Gesine
Colonization with Streptococcus pneumoniae (S. pneumoniae) is associated with an increased risk for recurrent wheeze and asthma. Killed S. pneumoniae showed some potential as an effective immunomodulatory therapy in a murine model of asthma. Murine studies demonstrated protection against allergic asthma by symbiotic bacteria via triggering regulatory T cell response: treatment with killed S. pneumoniae resulted in suppressed levels of allergen-specific Th2 cytokines, while early immunization generated a protective Th1 response. We investigated the impact of lung infection with live S. pneumoniae on both the development and maintenance of allergic airway inflammation and respiratory tolerance in mice. BALB/c mice were infected intratracheally with S. pneumoniae either prior to or after tolerance or allergy were induced, using ovalbumin (OVA) as model allergen. Infection of mice with S. pneumoniae prior to sensitization or after manifestation of allergic airway inflammation suppressed the development of an allergic phenotype as judged by reduced eosinophil counts in bronchoalveolar lavage fluid, decreased IgE serum levels and Th2 cytokines, relative to non-infected allergic control mice. In contrast, infection of mice with S. pneumoniae after manifestation of allergic airway inflammation combined with late mucosal re-challenge did not affect the allergic response. Moreover, induction and maintenance of respiratory tolerance to OVA challenge were not altered in S. pneumoniae-infected mice, demonstrating that mice remained tolerant to the model allergen and were protected from the development of allergic airway inflammation regardless of the time point of infection. Our results suggest that a bacterial infection may decrease the manifestation of an allergic phenotype not only prior to sensitization but also after manifestation of allergic airway inflammation in mice, whereas both, induction and maintenance of respiratory tolerance are not affected by pneumococcal
Full Text Available Abstract Background Vaccination programs often organize subsidies and public relations in order to obtain high uptake rates and coverage. However, effects of subsidies and public relations have not been studied well in the literature. In this study, the demand function of pneumococcal vaccination among the elderly in Japan is estimated, incorporating effects of public relations and subsidy. Methods Using a data from a questionnaire survey sent to municipalities, the varying and constant elasticity models were applied to estimate the demand function. The response variable is the uptake rate. Explanatory variables are: subsidy supported shot price, operating years of the program, target population size for vaccination, shot location intensity, income and various public relations tools. The best model is selected by c-AIC, and varying and constant price elasticities are calculated from estimation results. Results The vaccine uptake rate and the shot price have a negative relation. From the results of varying price elasticity, the demand for vaccination is elastic at municipalities with a shot price higher than 3,708 JPY (35.7 USD. Effects of public relations on the uptake rate are not found. Conclusions It can be suggested that municipalities with a shot price higher than 3,708 JPY (35.7 USD could subsidize more and reduce price to increase the demand for vaccination. Effects of public relations are not confirmed in this study, probably due to measurement errors of variables used for public relations, and studies at micro level exploring individual’s response to public relations would be required.
Full Text Available Abstract Background Influenza is characterized by seasonal outbreaks, often with a high rate of morbidity and mortality. It is also known to be a cause of significant amount secondary bacterial infections. Streptococcus pneumoniae is the main pathogen causing secondary bacterial pneumonia after influenza and subsequently, influenza could participate in acquiring Invasive Pneumococcal Disease (IPD. Methods In this study, we aim to investigate the relation between influenza and IPD by estimating the yearly excess of IPD cases due to influenza. For this purpose, we use influenza periods as an indicator for influenza activity as a risk factor in subsequent analysis. The statistical modeling has been made in two modes. First, we constructed two negative binomial regression models. For each model, we estimated the contribution of influenza in the models, and calculated number of excess number of IPD cases. Also, for each model, we investigated several lag time periods between influenza and IPD. Secondly, we constructed an "influenza free" baseline, and calculated differences in IPD data (observed cases and baseline (expected cases, in order to estimate a yearly additional number of IPD cases due to influenza. Both modes were calculated using zero to four weeks lag time. Results The analysis shows a yearly increase of 72–118 IPD cases due to influenza, which corresponds to 6–10% per year or 12–20% per influenza season. Also, a lag time of one to three weeks appears to be of significant importance in the relation between IPD and influenza. Conclusion This epidemiological study confirms the association between influenza and IPD. Furthermore, negative binomial regression models can be used to calculate number of excess cases of IPD, related to influenza.
Stolberg, Valerie R; McCubbrey, Alexandra L; Freeman, Christine M; Brown, Jeanette P; Crudgington, Sean W; Taitano, Sophina H; Saxton, Bridget L; Mancuso, Peter; Curtis, Jeffrey L
Inhaled corticosteroids (ICS) increase community-acquired pneumonia (CAP) incidence in patients with chronic obstructive pulmonary disease (COPD) by unknown mechanisms. Apoptosis is increased in the lungs of COPD patients. Uptake of apoptotic cells (ACs) ("efferocytosis") by alveolar macrophages (AMøs) reduces their ability to combat microbes, including Streptococcus pneumoniae, the most common cause of CAP in COPD patients. Having shown that ICS significantly increase AMø efferocytosis, we hypothesized that this process, termed glucocorticoid-augmented efferocytosis, might explain the association of CAP with ICS therapy in COPD. To test this hypothesis, we studied the effects of fluticasone, AC, or both on AMøs of C57BL/6 mice in vitro and in an established model of pneumococcal pneumonia. Fluticasone plus AC significantly reduced TLR4-stimulated AMø IL-12 production, relative to either treatment alone, and decreased TNF-α, CCL3, CCL5, and keratinocyte-derived chemoattractant/CXCL1, relative to AC. Mice treated with fluticasone plus AC before infection with viable pneumococci developed significantly more lung CFUs at 48 h. However, none of the pretreatments altered inflammatory cell recruitment to the lungs at 48 h postinfection, and fluticasone plus AC less markedly reduced in vitro mediator production to heat-killed pneumococci. Fluticasone plus AC significantly reduced in vitro AMø killing of pneumococci, relative to other conditions, in part by delaying phagolysosome acidification without affecting production of reactive oxygen or nitrogen species. These results support glucocorticoid-augmented efferocytosis as a potential explanation for the epidemiological association of ICS therapy of COPD patients with increased risk for CAP, and establish murine experimental models to dissect underlying molecular mechanisms. PMID:25987742
Full Text Available Traditional genetic association studies are very difficult in bacteria, as the generally limited recombination leads to large linked haplotype blocks, confounding the identification of causative variants. Beta-lactam antibiotic resistance in Streptococcus pneumoniae arises readily as the bacteria can quickly incorporate DNA fragments encompassing variants that make the transformed strains resistant. However, the causative mutations themselves are embedded within larger recombined blocks, and previous studies have only analysed a limited number of isolates, leading to the description of "mosaic genes" as being responsible for resistance. By comparing a large number of genomes of beta-lactam susceptible and non-susceptible strains, the high frequency of recombination should break up these haplotype blocks and allow the use of genetic association approaches to identify individual causative variants. Here, we performed a genome-wide association study to identify single nucleotide polymorphisms (SNPs and indels that could confer beta-lactam non-susceptibility using 3,085 Thai and 616 USA pneumococcal isolates as independent datasets for the variant discovery. The large sample sizes allowed us to narrow the source of beta-lactam non-susceptibility from long recombinant fragments down to much smaller loci comprised of discrete or linked SNPs. While some loci appear to be universal resistance determinants, contributing equally to non-susceptibility for at least two classes of beta-lactam antibiotics, some play a larger role in resistance to particular antibiotics. All of the identified loci have a highly non-uniform distribution in the populations. They are enriched not only in vaccine-targeted, but also non-vaccine-targeted lineages, which may raise clinical concerns. Identification of single nucleotide polymorphisms underlying resistance will be essential for future use of genome sequencing to predict antibiotic sensitivity in clinical microbiology.
Zitta B Harboe
Full Text Available A seven-valent pneumococcal conjugate vaccine (PCV7 was introduced in the Danish childhood immunization program (2+1 schedule in October 2007, followed by PCV13 starting from April 2010. The nationwide incidence of IPD among children younger than 5 years nearly halved after the introduction of PCV7 in the program, mainly due to a decline in IPD caused by PCV7-serotypes. We report the results from a nationwide population-based cohort study of laboratory confirmed IPD cases in children younger than 5 years during October 1, 2007 to December 31, 2010 and describe the characteristics of children suspected to present with a vaccine failure. The period between April 19 and December 31, 2010 was considered a PCV7/PCV13 transitional period, where both vaccines were offered. We identified 45 episodes of IPD caused by a PCV7 serotype (23% of the total number and 105 (55% caused by one of the 6 additional serotypes in PCV13. Ten children had received at least one PCV7 dose before the onset of IPD caused by a PCV7 serotype. Seven children were considered to be incompletely vaccinated before IPD, but only three cases fulfilled the criteria of vaccine failure (caused by serotypes 14, 19F and 23F. One case of vaccine failure was observed in a severely immunosuppressed child following three PCV7 doses, and two cases were observed in immunocompetent children following two infant doses before they were eligible for their booster. None of the IPD cases caused by the additional PCV13 serotypes had been vaccinated by PCV13 and there were therefore no PCV13-vaccine failures in the first 8-months after PCV13 introduction in Denmark.
The complete pneumococcal autolysin LytC has been crystallized by the hanging-drop vapor-diffusion method. A SAD data set has been collected in-house from a Gd derivative up to 2.6 Å resolution. LytC, one of the major autolysins from the human pathogen Streptococcus pneumoniae, has been crystallized as needles by the hanging-drop technique using 10%(w/v) PEG 3350 as precipitant and 10 mM HEPES pH 7.5. LytC crystals were quickly soaked in mother liquor containing 2 mM of the complex Gd-HPDO3A to produce derivatized crystals (LytCGd-HPDO3A). Both native LytC and isomorphous LytCGd-HPDO3A crystals were flash-cooled in a nitrogen flow at 120 K prior to X-ray data collection using an in-house Enraf–Nonius rotating-anode generator (λ = 1.5418 Å) and a MAR345 imaging-plate detector. In both cases, good-quality diffraction patterns were obtained at high resolution. LytCGd-HPDO3A crystals allowed the collection of a SAD X-ray data set to 2.6 Å resolution indexed in terms of a P21 monoclinic unit cell with parameters a = 59.37, b = 67.16, c = 78.85 Å, β = 105.69°. The anomalous Patterson map allowed the identification of one heavy-atom binding site, which was sufficient for the calculation of an interpretable anomalous map at 2.6 Å resolution
Silfverdal, Sven Arne; Høgh, Birthe; Bergsaker, Marianne Riise;
BACKGROUND: The immunogenicity of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV) was determined following a simplified 2-dose priming and the more commonly employed 3-dose priming both followed by a booster dose. METHODS: A total of 351 healthy...
Leonard, Ethan G.; Canaday, David H.; Harding, Clifford V.; Schreiber, John R.
The pneumococcal (Pn) conjugate vaccine includes seven different polysaccharides (PS) conjugated to CRM197. Utilizing antigen-processing cells and a CRM197-specific mouse T-cell hybridoma, we found that the serotype of conjugated PnPS dramatically affected antigen processing of CRM197. Unconjugated CRM197 and serotype conjugates 14 and 18C were processed more efficiently.
Alsuwaidi, Ahmed R; Albawardi, Alia; Khan, Navidul Haq; Souid, Abdul-Kader
Introduction Adjuvants (for example, aluminum salts) are frequently incorporated in licensed vaccines to enhance the host immune response. Such vaccines include the pneumococcal conjugate, combinations of diphtheria–tetanus/acellular pertussis, tetanus– diphtheria/acellular pertussis, hepatitis B, some Haemophilus influenzae type b, hepatitis A, and human papillomavirus. These preparations have been associated with complicated local adverse events, especially if administered subcutaneously or...
Bae, Il Kwon; Park, Dongchul; Kim, Na Young; Song, Sae Am; Urm, Sang-Hwa; Shin, Jeong Hwan
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
Bjornson, AB; Falletta, JM; Verter, JI; Buchanan, GR; Miller, ST; Pegelow, CH; Iyer, RV; Johnstone, HS; DeBaun, MR; Wethers, DL; Woods, GM; Holbrook, CT; Becton, DL; Kinney, TR; Reaman, GH; Kalinyak, K; Grossman, NJ; Vichinsky, E; Reid, CD
Objectives: (1) To determine serotype-specific IgG antibody responses to reimmunization with pneumococcal polysaccharide vaccine at age 5 years ski children with sickle cell anemia and (2) to determine whether continued penicillin prophylaxis had any adverse effects on these responses. Study design:
Kort beskrivelse Bogen, 'Adult Education og Adult Learning', giver et fyldestgørende overblik over forståelsen af voksenuddannelse og læring. Abstract I "Adult Education and Adult Learning' ser Knud Illeris på voksenuddannelse fra to perspektiver. På den ene side beskrives de aktuelle udfordringer...
Dörr, Arndt; Kress, Eugenia; Podschun, Rainer; Pufe, Thomas; Tauber, Simone C; Brandenburg, Lars-Ove
Antimicrobial peptides (AP) are important components of the innate immune system. Our previous work revealed a higher mortality rate and up-regulation of proinflammatory gene expression as well as glial cell activation in cathelicidin-related antimicrobial peptide (CRAMP)-deficient mice after bacterial meningitis. However, the influence of CRAMP application on the progression of inflammation and its impact on mortality after bacterial meningitis remains unknown. To assess the effects of continuous CRAMP exposure in the brain, C57BL/6 wildtype mice were given intracerebroventricular infusion of CRAMP to investigate the effects on mortality, glial cell activation and inflammation in a mouse model of pneumococcal meningitis using immunohistochemistry and realtime RT-PCR. Our results revealed a decrease of mortality after CRAMP infusion. The intrathecal CRAMP infusion after pneumococcal meningitis resulted in a decreased mRNA expression of pro-inflammatory cytokines, whereas the immune responses including the expression of pattern recognition receptors and chemokines were increased in bacterial meningitis. Taken together, the results support the important role of CRAMP as part of the innate immune response against pathogens in bacterial CNS infections. The APs may be a promising approach for the development of an adjuvant therapy for bacterial meningitis. PMID:25896094
van der Maten, Erika; van Selm, Saskia; Langereis, Jeroen D; Bootsma, Hester J; van Opzeeland, Fred J H; de Groot, Ronald; de Jonge, Marien I; van der Flier, Michiel
Streptococcus pneumoniae is a common cause of sepsis. Effective complement activation is an important component of host defence against invading pathogens, whilst excessive complement activation has been associated with endothelial dysfunction and organ damage. The alternative pathway amplification loop is important for the enhancement of complement activation. Factor H is a key negative regulator of the alternative pathway amplification loop and contributes to tight control of complement activation. We assessed the effect of inhibition of the alternative pathway on sepsis associated inflammation and disease severity using human factor H treatment in a clinically relevant mice model of pneumococcal sepsis. Mice were infected intravenously with live Streptococcus pneumoniae. At the first clinical signs of infection, 17 hours post-infection, mice were treated with ceftriaxone antibiotic. At the same time purified human factor H or in controls PBS was administered. Treatment with human factor H did not attenuate disease scores, serum pro-inflammatory cytokines, or vascular permeability and did not significantly affect C3 and C3a production at 26 h post-infection. Therefore, we conclude that inhibition of the alternative complement pathway by exogenous human factor H fails to attenuate inflammation and vascular leakage at a clinically relevant intervention time point in pneumococcal sepsis in mice. PMID:26872035
Rautanen, Anna; Pirinen, Matti; Mills, Tara C; Rockett, Kirk A; Strange, Amy; Ndungu, Anne W; Naranbhai, Vivek; Gilchrist, James J; Bellenguez, Céline; Freeman, Colin; Band, Gavin; Bumpstead, Suzannah J; Edkins, Sarah; Giannoulatou, Eleni; Gray, Emma; Dronov, Serge; Hunt, Sarah E; Langford, Cordelia; Pearson, Richard D; Su, Zhan; Vukcevic, Damjan; Macharia, Alex W; Uyoga, Sophie; Ndila, Carolyne; Mturi, Neema; Njuguna, Patricia; Mohammed, Shebe; Berkley, James A; Mwangi, Isaiah; Mwarumba, Salim; Kitsao, Barnes S; Lowe, Brett S; Morpeth, Susan C; Khandwalla, Iqbal; Blackwell, Jenefer M; Bramon, Elvira; Brown, Matthew A; Casas, Juan P; Corvin, Aiden; Duncanson, Audrey; Jankowski, Janusz; Markus, Hugh S; Mathew, Christopher G; Palmer, Colin N A; Plomin, Robert; Sawcer, Stephen J; Trembath, Richard C; Viswanathan, Ananth C; Wood, Nicholas W; Deloukas, Panos; Peltonen, Leena; Williams, Thomas N; Scott, J Anthony G; Chapman, Stephen J; Donnelly, Peter; Hill, Adrian V S; Spencer, Chris C A
Bacteremia (bacterial bloodstream infection) is a major cause of illness and death in sub-Saharan Africa but little is known about the role of human genetics in susceptibility. We conducted a genome-wide association study of bacteremia susceptibility in more than 5,000 Kenyan children as part of the Wellcome Trust Case Control Consortium 2 (WTCCC2). Both the blood-culture-proven bacteremia case subjects and healthy infants as controls were recruited from Kilifi, on the east coast of Kenya. Streptococcus pneumoniae is the most common cause of bacteremia in Kilifi and was thus the focus of this study. We identified an association between polymorphisms in a long intergenic non-coding RNA (lincRNA) gene (AC011288.2) and pneumococcal bacteremia and replicated the results in the same population (p combined = 1.69 × 10(-9); OR = 2.47, 95% CI = 1.84-3.31). The susceptibility allele is African specific, derived rather than ancestral, and occurs at low frequency (2.7% in control subjects and 6.4% in case subjects). Our further studies showed AC011288.2 expression only in neutrophils, a cell type that is known to play a major role in pneumococcal clearance. Identification of this novel association will further focus research on the role of lincRNAs in human infectious disease. PMID:27236921
M Mohammad - Zadeh
Full Text Available Introduction: Streptococcus pneumoniae is one of the most important causes of pneumonia, meningitis and septicemia. Decades after successful treatment of this infection with penicillin, frequency of penicillin resistance is reportedly on the rise throughout the world. This cross sectional study was designed in Yazd to determine the prevalence of pneumococcal pharyngeal carriers and its succeptibility pattern in children of day care centers. Method & materials : Two hundred children were selected randomly from 10 day care centers and pharyngeal swabs were collected and cultured in February, 2002. Results :51% of our study sample were boys and 49% were girls. Their age range was between 7 and 65 months. Prevalence of pharyngeal carriers was 37.5%. The rate of resistance detected was as follows: 50% to penicillin, 62.5% to erythromycin and TMP,SMX, 30.6% to tetracycline, 15.3 % to cephalothin, 5.6% to ceftizoxime and 4.2% to ciprofloxacin. Conclusion: We conclude that penicillin is not the drug of choice in invasive pneumococcal infections in Yazd and a third gereration cephalosporin should be used instead as the first line of treatment while awaiting the culture and sensitivity results.
Angela B Brueggemann
Full Text Available The 10-valent pneumococcal conjugate vaccine (PCV10 was introduced in Kenya in 2011. Introduction of any PCV will perturb the existing pneumococcal population structure, thus the aim was to genotype pneumococci collected in Kilifi before PCV10.Using multilocus sequence typing (MLST, we genotyped >1100 invasive and carriage pneumococci from children, the largest collection genotyped from a single resource-poor country and reported to date. Serotype 1 was the most common serotype causing invasive disease and was rarely detected in carriage; all serotype 1 isolates were members of clonal complex (CC 217. There were temporal fluctuations in the major circulating sequence types (STs; and although 1-3 major serotype 1, 14 or 23F STs co-circulated annually, the two major serotype 5 STs mainly circulated independently. Major STs/CCs also included isolates of serotypes 3, 12F, 18C and 19A and each shared ≤ 2 MLST alleles with STs that circulate widely elsewhere. Major CCs associated with non-PCV10 serotypes were predominantly represented by carriage isolates, although serotype 19A and 12F CCs were largely invasive and a serotype 10A CC was equally represented by invasive and carriage isolates.Understanding the pre-PCV10 population genetic structure in Kilifi will allow for the detection of changes in prevalence of the circulating genotypes and evidence for capsular switching post-vaccine implementation.
Karlsson, Johanna; Roalfe, Lucy; Hogevik, Harriet; Zancolli, Marta; Andréasson, Björn; Goldblatt, David; Wennerås, Christine
Patients with multiple myeloma and other B cell disorders respond poorly to pneumococcal vaccination. Vaccine responsiveness is commonly determined by measuring pneumococcal serotype-specific antibodies by enzyme-linked immunosorbent assay (ELISA), by a functional opsonophagocytosis assay (OPA), or by both assays. We compared the two methods in vaccinated elderly patients with multiple myeloma, Waldenstrom's macroglobulinemia, and monoclonal gammopathy of undetermined significance (MGUS). Postvaccination sera from 45 patients (n= 15 from each patient group) and 15 control subjects were analyzed by multiplexed OPA for pneumococcal serotypes 4, 6B, 14, and 23F, and the results were compared to IgG and IgM antibody titers measured by ELISA. While there were significant correlations between pneumococcal OPA and IgG titers for all serotypes among the control subjects (correlation coefficients [r] between 0.51 and 0.85), no significant correlations were seen for any of the investigated serotypes in the myeloma group (r= -0.18 to 0.21) or in the group with Waldenstrom's macroglobulinemia (borderline significant correlations for 2 of 4 serotypes). The MGUS group resembled the control group by having good agreement between the two test methods for 3 of 4 serotypes (r= 0.53 to 0.80). Pneumococcal postvaccination IgM titers were very low in the myeloma patients compared to the other groups and did not correlate with the OPA results. To summarize, our data indicate that ELISA measurements may overestimate antipneumococcal immunity in elderly subjects with B cell malignancies and that a functional antibody test should be used specifically for myeloma and Waldenstrom's macroglobulinemia patients. PMID:26912783
Background A recently developed 10-valent pneumococcal non-typeable H influenzae protein D-conjugate vaccine (PHiD-CV) is expected to afford protection against more than two thirds of isolates causing IPD in children in Latin America, and also against acute otitis media caused by both Spn and NTHi. The objective of this study is to assess the cost-effectiveness of PHiD-CV in comparison to non-vaccination in children under 10 years of age in Argentina, Brazil, Chile, Colombia, Mexico and Peru. Methods We used a static, deterministic, compartmental simulation model. The dosing regimen considered included three vaccine doses (at 2 months, 4 months and 6 months) and a booster dose (at 13 months) (3 + 1 schedule). Model outcomes included number of cases prevented, deaths averted, quality-adjusted life-years (QALYs) gained and costs. Discount for costs and benefits of long term sequelae was done at 3.5%, and currency reported in 2008-2009 U$S varying between countries. Results The largest effect in case prevention was observed in pneumococcal meningitis (from 27% in Peru to 47% in Colombia), neurologic sequelae after meningitis (from 38% in Peru to 65% in Brazil) and bacteremia (from 42% in Argentina to 49% in Colombia). The proportion of predicted deaths averted annually ranged from 18% in Peru to 33% in Brazil. Overall, the health benefits achieved with PHiD-CV vaccination resulted in a lower QALY loss (from 15% lower in Peru to 26% in Brazil). At a cost of USD 20 per vaccine dose, vaccination was cost-effective in all countries, from being cost saving in Chile to a maximum Incremental Cost-effectiveness Ratio of 7,088 US$ Dollars per QALY gained. Results were robust in the sensitivity analysis, and scenarios with indirect costs affected results more than those with herd immunity. Conclusions The incorporation of the 10-valent pneumococcal conjugate vaccine into routine infant immunization programs in Latin American countries could be a cost-effective strategy
Full Text Available Abstract Background Aboriginal children in remote Australia have high rates of complicated middle ear disease associated with Streptococcus pneumoniae and other pathogens. We assessed the effectiveness of pneumococcal vaccination for prevention of otitis media in this setting. Methods We compared two birth cohorts, one enrolled before (1996–2001, and the second enrolled after introduction of 7-valent pneumococcal conjugate and booster 23-valent polysaccharide vaccine (2001–2004. Source populations were the same for both cohorts. Detailed examinations including tympanometry, video-recorded pneumatic otoscopy and collection of discharge from tympanic membrane perforations, were performed as soon as possible after birth and then at regular intervals until 24 months of life. Analyses (survival, point prevalence and incidence were adjusted for confounding factors and repeated measures with sensitivity analyses of differential follow-up. Results Ninety-seven vaccinees and 51 comparison participants were enrolled. By age 6 months, 96% (81/84 of vaccinees and 100% (41/41 of comparison subjects experienced otitis media with effusion (OME, and by 12 months 89% and 88% experienced acute otitis media (AOM, 34% and 35% experienced tympanic membrane perforation (TMP and 14% and 23% experienced chronic suppurative otitis media (CSOM. Age at the first episode of OME, AOM, TMP and CSOM was not significantly different between the two groups. Adjusted incidence of AOM (incidence rate ratio: 0.88 [95% confidence interval (CI: 0.69–1.13] and TMP (incidence rate ratio: 0.63 [0.36–1.11] was not significantly reduced in vaccinees. Vaccinees experienced less recurrent TMP, 9% (8/95 versus 22% (11/51, (odds ratio: 0.33 [0.11–1.00]. Conclusion Results of this study should be interpreted with caution due to potential bias and confounding. It appears that introduction of pneumococcal vaccination among Aboriginal infants was not associated with significant changes
Ali, Youssif M; Lynch, Nicholas J; Haleem, Kashif S;
pathways of complement in fighting streptococcal infection, little is known about the role of the lectin pathway, mainly due to the lack of appropriate experimental models of lectin pathway deficiency. We have recently established a mouse strain deficient of the lectin pathway effector enzyme mannan......The complement system plays a key role in host defense against pneumococcal infection. Three different pathways, the classical, alternative and lectin pathways, mediate complement activation. While there is limited information available on the roles of the classical and the alternative activation......-binding lectin associated serine protease-2 (MASP-2) and shown that this mouse strain is unable to form the lectin pathway specific C3 and C5 convertases. Here we report that MASP-2 deficient mice (which can still activate complement via the classical pathway and the alternative pathway) are highly susceptible...
Hinge, Maja; Ingels, Helene A S; Slotved, Hans-Christian;
Patients with multiple myeloma are known to have an increased risk of infections with Streptococcus pneumoniae and vaccination is recommended. We retrospectively investigated the response of a 23-valent polysaccharide-based pneumococcal vaccine in 60 patients with multiple myeloma administered...... prior to autologous stem cell transplantation (ASCT). Specific antibody titers were measured before and after vaccination. Disease stage was evaluated and associated to the response. We found that 33% of the patients responded to the vaccine. There was a statistic significant association between...... response to the vaccine and disease stage (p = 0.01). We conclude that vaccination against S. pneumoniae prior to ASCT is reasonable at least in patients responding well to induction therapy, but still it is important to be aware that the response is frequently poor and the duration of it is unknown....
The authors have studied the chemical basis of the antigen-antibody reaction between Klebsiella K2 LPS and specific antiserum, and cross-reactivity with pneumococcal group 19 PSs. K2 LPS was isolated and purified from Klebsiella K2 strain by the methods of hot phenol-water extraction, ultracentrifugation, treatment with enzymes and gel filtration. K2 LPS was hydrolyzed with 1% acetic acid to produce 2 fractions, separated by Sephadex G-50 column. Fraction G-I was passed through Sepharose 4B column to separate into 3 peaks (4B-I, -II, and -III). Peak 4B-II showed a molecular size of Kd, 0.35 and 4B-III had Kd, 0.79. When K2 LPS was injected to mice, IgM and IgG antibody responses were induced, as determined by ELISA. In contrast, with the 19F and 19A PSs, the K2 LPS induced antibody was mostly IgM. They have studied the ability of PS fractions (4B-II, 4B-III and G-I) to inhibit the binding of K2 LPS to specific IgM and IgG antibodies. Among these fractions, 4B-II PS showed a highest inhibition to the binding activity; approximately 1000-fold greater inhibiting ability than 4B-III and G-I PS. These results indicate that 4B-II PS may serve as an immunologic determinant of K2 LPS. Pneumococcal 19F and 19A PSs induced low inhibition of the binding activity between K2 LPS and specific IgM antibody. The fraction 4B-II as immunologic determinant of K2 LPS was further characterized by 125I-K2 LPS anti-serum and Western blotting electrophoresis
Nina Katharina Stock
Full Text Available Invasive pneumococcal disease (IPD is caused by Streptococcus pneumoniae and mostly presents as pneumonia, sepsis or meningitis. A notable portion of IPD cases is vaccine preventable and the pneumococcal conjugate vaccine (PCV was introduced into the routine childhood immunization programs in many countries during the last decades.Before PCV introduction in the Czech Republic in 2010, a national surveillance system for IPD was implemented in 2008 and further improved in 2011. In this study, we describe the new surveillance system for the first time and measure its sensitivity between 2010 and 2013 using the capture-recapture method. Furthermore, we describe the recent epidemiological trend of IPD, taking sensitivity estimates into account.Between 2010 and 2013 the estimated sensitivity of the overall IPD surveillance increased from 81% to 99%. The sensitivity of individual reporting sources increased from 72% to 87% for the laboratory system and from 31% to 89% for the epidemiological notification system. Crucial for this improvement was the introduction of quarterly report reminders in 2011. Due to positive source dependency, the presented sensitivity estimates are most probably overestimated and reflect the upper limit of reporting completeness. Stratification showed variation in sensitivity of reporting particularly according to region. An effect of the PVC vaccination in the Czech Republic is visible in the incidence of IPD in target age groups (<5 y. This influence was not evident in the total IPD incidence and may interfere with increasing sensitivity of reporting. In 2013, an increase in the IPD incidence was observed. This finding requires further observation and a detailed vaccine impact analysis is needed to assess the current immunization strategy.
Gyhrs, A; Pedersen, B K; Bygbjerg, I;
diphosphate (1,000 mg/week), or 4) proguanil hydrochloride (200 mg/day) for six weeks. Skin testing was performed on days 0 and 28. Vaccinations with diphtheria, tetanus, polio, and pneumococcal polysaccharide antigen vaccines were performed on day 28, and the presence of specific antibodies was determined on...... days 0, 28, and 42. The skin tests induced a significant increase in skin reactive areas from day 0 to day 28 in all groups. Furthermore, the skin test induced an increase in the level of specific IgG for diphtheria and tetanus, but had no effect on antibodies to antigens not included in the skin test...... chemoprophylactic dosages, does not induce any detectable suppression of delayed-type hypersensitivity or vaccination responses to diphtheria, tetanus, polio, or pneumococcal polysaccharide antigens....
Objective To investigate the treatment of pneumococcal pneumonia.Methods28 cases of pneumococcal pneumonia patients in May 2012 to September admitted to data analysis. Results28 patients were cured and discharged without complications.Conclusion The diagnosis should be used immediately after symptomatic patients for drugs to stop the disease continues to spread.%目的：探讨肺炎球菌肺炎的治疗体会。方法对2012年5～9月收治的28例肺炎球菌肺炎患者资料进行分析。结果28例患者均治愈出院，无并发症发生。结论确诊后应立即使用对症、适合的药品制止患者病情的发展。
Full Text Available Abstract Background The introduction of pneumococcal conjugate vaccine (PCV to the U.S. recommended childhood immunization schedule in the year 2000 added three injections to the number of vaccinations a child is expected to receive during the first year of life. Surveys have suggested that the addition of PCV has led some immunization providers to move other routine childhood vaccinations to later ages, which could increase the possibility of missing these vaccines. The purpose of this study was to evaluate whether introduction of PCV affected immunization coverage for recommended childhood vaccinations among 13-month olds in four large provider groups. Methods In this retrospective cohort study, we analyzed computerized data on vaccinations for 33,319 children in four large provider groups before and after the introduction of PCV. The primary outcome was whether the child was up to date for all non-PCV recommended vaccinations at 13 months of age. Logistic regression was used to evaluate the association between PCV introduction and the primary outcome. The secondary outcome was the number of days spent underimmunized by 13 months. The association between PCV introduction and the secondary outcome was evaluated using a two-part modelling approach using logistic and negative binomial regression. Results Overall, 93% of children were up-to-date at 13 months, and 70% received all non-PCV vaccinations without any delay. Among the entire study population, immunization coverage was maintained or slightly increased from the pre-PCV to post-PCV periods. After multivariate adjustment, children born after PCV entered routine use were less likely to be up-to-date at 13 months in one provider group (Group C: OR = 0.5; 95% CI: 0.3 – 0.8 and were less likely to have received all vaccine doses without any delay in two Groups (Group B: OR = 0.4, 95% CI: 0.3 – 0.6; Group C: OR = 0.5, 95% CI: 0.4 – 0.7. This represented 3% fewer children in Group C who
Full Text Available BACKGROUND: Pharyngeal bacteria are exposed to different sugar conditions depending on the diet of the child. We hypothesized that dietary factors such as daily intake of carbohydrates could be associated with pneumococcal carriage and the occurrence of otitis media in children. METHODS: Our study design was a cross-sectional study among 1006 children attending child day care centers. Parents filled in a food frequency questionnaire. Oropharyngeal swabs were collected from each child. The primary outcome was the occurrence of pneumococcal carriage and the secondary outcome the number of acute otitis media episodes during life. Principal component analysis was used to group dietary intake into nine factors. The models were adjusted for age, gender of the child and educational level of the mother. RESULTS: The dietary factor which included high consumption of sweet pastries and jam was associated with an increased risk of pneumococcal carriage (OR 1.17, 95% CI 1.01 to 1.36, P-value 0.04. The factor including frequent consumption of fruit and berries was associated with a decreased risk of acute otitis (regression coefficient -0.51, 95% CI -0.98 to -0.03, P=0.04. A high intake of consumption of sweets and snacks (OR 1.36, 95% CI 1.03 to 1.80, P=0.03 was associated with an increased risk of caries. CONCLUSIONS: Diet was associated with a risk of pneumococcal carriage and the occurrence of otitis media. Diet may thus be a modifiable risk factor for the occurrence of acute otitis media.
肺炎链球菌是肺炎、脑膜炎、败血症、中耳炎和鼻窦炎的主要致病菌.目前针对肺炎链球菌疾病的预防主要是以多糖为基础的23价多糖疫苗和7价多糖蛋白结合疫苗,但因其有血清型的限制,应用有很大的局限性.因此以肺炎链球菌表面毒力因子或蛋白为基础的、无血清型限制的肺炎链球菌蛋白疫苗将成为新型肺炎链球菌疫苗发展的方向,此文综述了肺炎链球菌蛋白疫苗的研究进展.%Streptococcus prteumoniae is a major pathogen for community-acquired pneumonia,meningitis,septicemia,otitis media,and sinusitis.The licensed polysaceharide-based 23-valent pneumococcal polysaccharide vaccine and 7-valent pneumococcal polysaccharide-protein conjugate vaccine (PCV7) only elicit protective antibodies against the infection caused by serotypes that are included in the vaccines.To broaden the protection,the use of pneumococcal serotype-indepondent protein vaccines based on surface protein components will be a feasible and preferable alternative.In this review,advances in the research of pneumococcal protein vaccines are discussed.
Zhang, Q; Bernatoniene, J.; Bagrade, L.; Paton, J C; Mitchell, T J; Hammerschmidt, S.; Nunez, D A; Finn, A
Nasopharyngeal tonsils (adenoids) are part of human nasopharynx-associated lymphoid tissue, which may play an important role in local defense against pneumococci. Recent studies with animals have suggested that several pneumococcal proteins, including CbpA and pneumolysin (Ply), may be vaccine candidates. Our recent data obtained with children suggest that antibodies to these proteins may protect against carriage. This study was performed to investigate the regulation of the T-cell-dependent ...
Suresh, Madathilparambil V.; Singh, Sanjay K.; Ferguson, Donald A.; Agrawal, Alok
C-reactive protein (CRP) is not an acute-phase protein in mice, and therefore, mice are widely used to investigate the functions of human CRP. It has been shown that CRP protects mice from pneumococcal infection, and an active complement system is required for full protection. In this study, we assessed the contribution of CRP's ability of activating the classical pathway of complement in the protection of mice from lethal infection with virulent Streptococcus pneumoniae type 3. We used two C...
Restori, Katherine H.; Kennett, Mary J.; Ross, A. Catharine
Vaccination reduces morbidity and mortality from pneumonia, but its effect on the tissue-level response to infection is still poorly understood. We evaluated pneumonia disease progression, acute-phase response, and lung gene expression profiles in mice inoculated intranasally with virulent Gram-positive Streptococcus pneumoniae serotype 3 (ST 3) with and without prior immunization with pneumococcal polysaccharide ST 3 (PPS3) or after coimmunization with PPS3 and a low dose of lipopolysacchari...
Arrecubieta, C; López, Rubens; García, Ernesto
The cap3B gene, which is involved in the formation of the capsule of Streptococcus pneumoniae type 3, encodes a 49-kD protein that has been identified as a polysaccharide synthase. Escherichia coli cells harboring the recombinant plasmid pTBP3 (cap3B) produced pneumococcal type 3 polysaccharide, as demonstrated by immunological tests. Biochemical and cell fractionation analyses revealed that this polysaccharide had a high molecular mass and was localized in substantial amounts in the periplas...
Bai, Li; Deng, Shenglou; Reboulet, Rachel; Mathew, Rebecca; Teyton, Luc; Savage, Paul B.; Bendelac, Albert
Antibodies directed against microbial polysaccharides are a critical component of protective immune responses and vaccines. We used nanoparticles coexpressing pneumococcal capsular polysaccharides and a cell wall lipid antigen analog to model NKT–B-cell interactions. Our study demonstrated CD1d-restricted cognate interactions, isotype switch, affinity maturation, and long-term memory, despite the apparent failure of NKT cells to differentiate into follicular helper cells. The findings demonst...
Bhim Gopal Dhoubhadel; Michio Yasunami; Hien Anh Thi Nguyen; Motoi Suzuki; Thu Huong Vu; Ai Thi Thuy Nguyen; Duc Anh Dang; Lay-Myint Yoshida; Koya Ariyoshi
BACKGROUND: Among pneumococcal serotypes, some serotypes are more prevalent in the nasopharynx than others; determining factors for higher prevalence remain to be fully explored. As non-vaccine serotypes have emerged after the introduction of 7-valent conjugate vaccines, study of serotype specific epidemiology is in need. When two or more serotypes co-colonize, they evolve rapidly to defend host's immune responses; however, a clear association of co-colonization with a clinical outcome is lac...
Fatma Filiz Coskun-Ari
Full Text Available The life-threatening illnesses caused by Streptococcus pneumoniae have been declined significantly after the use of pneumococcal conjugate vaccines. Continuous monitoring of the vaccine serogroups/types is necessary to follow the changing epidemiology of invasive pneumococcal diseases. Recently, the sequential multiplex PCR approach, which uses several different sets of reactions, has been commonly adopted for determining capsular serogroups/types of S. pneumoniae isolates. In our study, we focused on development of a one-step multiplex PCR assay detecting all 1, 3, 4, 5, 6A/B, 7F, 9V, 14, 18C, 19A, 19F and 23F serogroups/types targeted by PCV13. The content of multiplex PCR mix and the cycling conditions were optimized in a manner that allowed rapid and accurate serotyping of a pneumococcal isolate by performing only a single amplification reaction. In our study of 182 clinical isolates, the one-step multiplex PCR assay exhibited 100% sensitivity and specificity, suggesting that its utilization can significantly reduce the use of traditional antiserum method requiring expensive reagents.
Golden, Alyssa R; Adam, Heather J; Zhanel, George G
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
Schulte, Tim; Mikaelsson, Cecilia; Beaussart, Audrey; Kikhney, Alexey; Deshmukh, Maya; Wolniak, Sebastian; Pathak, Anuj; Ebel, Christine; Löfling, Jonas; Fogolari, Federico; Henriques-Normark, Birgitta; Dufrêne, Yves F.; Svergun, Dmitri; Nygren, Per-Åke; Achour, Adnane
The major human pathogen Streptococcus pneumoniae is a leading cause of disease and death worldwide. Pneumococcal biofilm formation within the nasopharynx leads to long-term colonization and persistence within the host. We have previously demonstrated that the capsular surface-associated pneumococcal serine rich repeat protein (PsrP), key factor for biofilm formation, binds to keratin-10 (KRT10) through its microbial surface component recognizing adhesive matrix molecule (MSCRAMM)-related globular binding region domain (BR187–385). Here, we show that BR187–385 also binds to DNA, as demonstrated by electrophoretic mobility shift assays and size exclusion chromatography. Further, heterologous expression of BR187–378 or the longer BR120–378 construct on the surface of a Gram-positive model host bacterium resulted in the formation of cellular aggregates that was significantly enhanced in the presence of DNA. Crystal structure analyses revealed the formation of BR187–385 homo-dimers via an intermolecular β-sheet, resulting in a positively charged concave surface, shaped to accommodate the acidic helical DNA structure. Furthermore, small angle X-ray scattering and circular dichroism studies indicate that the aggregate-enhancing N-terminal region of BR120–166 adopts an extended, non-globular structure. Altogether, our results suggest that PsrP adheres to extracellular DNA in the biofilm matrix and thus promotes pneumococcal biofilm formation. PMID:27582320
Pobereskin, L; Treip, C
Twelve cases of adult onset medulloblastoma are presented. Clinical features, treatment and outcome are discussed. It was found that the survival rates for adults are no better than for children. There were no clinical or histological features that distinguished these tumours from those occurring in childhood, except for a higher incidence of hemisphere lesions.