| 1. |
- By, Asa, et al.
(författare)
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Comparing Health Outcomes and Costs of General Vaccination with Pneumococcal Conjugate Vaccines in Sweden: A Markov Model
- 2012
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Ingår i: Clinical Therapeutics. - : Elsevier BV. - 0149-2918 .- 1879-114X. ; 34:1, s. 177-189
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Tidskriftsartikel (refereegranskat)abstract
- Background: Two new pneumococcal conjugate vaccines were licensed to immunize infants and young children against pneumococcal disease. Objectives: The objective of this study was to estimate the expected health benefits, costs, and incremental cost-effectiveness of routine vaccination with the 10-valent pneumococcal nontypeable hemophilus influenza protein-D conjugate vaccine (PHiD-CV) compared with the 13-valent pneumococcal conjugate vaccine (PCV13) in Sweden. Methods: A Markov cohort model was used to estimate the effect of vaccination at vaccine steady state, taking a societal perspective and using a 2+1 vaccination schedule. Price parity was assumed between the vaccines. Outcomes were measured by reduction in disease burden, costs, quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio. Results: The results predicted that PCV13 would prevent 3 additional cases of invasive pneumococcal disease and 34 additional cases of pneumonia, whereas PHiD-CV would avoid 3 additional cases of mastoiditis, 1010 tube insertions, and 10,420 cases of ambulatory acute otitis media compared with PCV13. By combining morbidity and mortality benefits of all clinical outcomes, PHiD-CV would generate 45.3 additional QALYs compared with PCV13 and generate savings of an estimated 62 million Swedish kronors. Conclusion: The present study predicted lower costs and better health outcome (QALYs) gained by introducing PHiD-CV compared with PCV13 in routine vaccination. Our results indicated that PHiD-CV is cost-effective compared with PCV13 in Sweden. (Clin Ther. 2012;34:177-189) (C) 2012 Elsevier HS Journals, Inc. All rights reserved.
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| 2. |
- Ahl, Jonas, et al.
(författare)
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High incidence of septic shock caused by Streptococcus pneumoniae serotype 3-a retrospective epidemiological study
- 2013
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Ingår i: BMC Infectious Diseases. - : Springer Science and Business Media LLC. - 1471-2334. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Background: More than 90 immunologically distinct serotypes of Streptococcus pneumoniae exist, and it is not fully elucidated whether the serotype is a risk factor for severity of invasive pneumococcal disease (IPD). Our hypothesis is that serotypes differ in their capacity to cause septic shock. Methods: We performed a retrospective study in Southern Sweden based upon 513 patients with IPD in the pre-vaccine era 2006-2008. The serotype, co-morbidity, and sepsis severity were determined. Serotypes were compared to serotype 14 as a reference and grouped according to their invasive potential, that is, high (serogroups 1, 5 and 7), intermediate (serogroups 4, 9, 14 and 18) and, finally, low invasive potential (serogroups 3, 6, 8, 15, 19, 23 and 33). Results: Patients with S. pneumoniae serotype 3 had significantly more often septic shock (25%, odds ratio (OR) 6.33 [95% confidence interval (CI) 1.59-25.29]), higher mortality (30%, OR 2.86 [CI 1.02-8.00]), and more often co-morbidities (83%, OR 3.82 [CI 1.39-10.54]) when compared to serotype 14. A significant difference in age and co-morbidities (p= 0.001) was found when patient data were pooled according to the invasive potential of the infecting pneumococci. The median age and percentage of patients with underlying co-morbidities were 72 years and 79%, respectively, for serogroups associated with low invasiveness, 68 years and 61%, respectively, for serogroups with intermediate invasiveness, and, finally, 62 years and 48%, respectively, for serogroups with high invasiveness. No difference in sepsis severity was found between the three groups. Conclusions: S. pneumoniae serotype 3 more often caused septic shock compared to serotype 14. Our results support the hypothesis that serotypes with high invasiveness mainly cause IPD in younger patients with less co-morbidities. In contrast, serogroups with low and intermediate invasive potential mostly cause IPD in the elderly with defined co-morbidities, and thus can be considered as opportunistic.
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| 3. |
- Ahrén, Irini Lazou, et al.
(författare)
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The importance of a β-glucan receptor in the nonopsonic entry of nontypeable Haemophilus influenzae into human monocytic and epithelial cells
- 2001
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Ingår i: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 0022-1899 .- 1537-6613. ; 184:2, s. 150-158
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Tidskriftsartikel (refereegranskat)abstract
- Previous reports showed that nontypeable Haemophilus influenzae (NTHi) reside in macrophage-like cells in human adenoid tissue. This study investigated the ability of nonopsonized NTHi and encapsulated H. influenzae type b (Hib) to enter human monocytic and epithelial cells. The number of intracellular bacteria was determined by a viability assay and flow cytometry. To characterize the mechanisms responsible for the internalization of NTHi, different inhibitors of surface molecules, receptor turnover, and the cytoskeleton were used. Hib were found in monocytic cells at very low numbers (<100 bacteria/2 × 105 cells). In contrast, a great variation in intracellular numbers was detected between the different NTHi isolates (range, 0.0007%-0.28% of the inoculum for monocytes and 0.053%-3.5% for epithelial cells). NTHi entered human monocytic and epithelial cells via a receptor-mediated endocytosis involving mainly a β-glucan receptor that could be blocked by laminarin.
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| 4. |
- Akkoyunlu, Mustafa, et al.
(författare)
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Biological activity of serum antibodies to a nonacylated form of lipoprotein D of Haemophilus influenzae
- 1996
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Ingår i: Infection and Immunity. - 1098-5522. ; 64:11, s. 4586-4592
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Tidskriftsartikel (refereegranskat)abstract
- Protein D, a surface-exposed 42-kDa membrane lipoprotein, is well conserved among both type b and nontypeable Haemophilus influenzae strains, and it is considered a vaccine against H. influenzae infections. Here, we report the large-scale purification of a nonacylated form of protein D (PDm) from the periplasmic space of Escherichia coli overexpressing PDm. Screening of human sera for levels of antibodies to PDm demonstrated that the immunoglobulin G (IgG) antibody level is above background levels in infants less than 6 months of age. Following a drop to background values in the age group 6 months to 1 year, IgG antibody levels start to increase, together with IgA antibody levels, after 1 year of age. The first appearance of serum IgM antibodies is in 6-month- to 1-year-old infants whose IgG antibody levels have dropped to the postnatal background level. Affinity-purified antibodies from humans and from PDm-immunized rats detected epitopes of protein D which are normally exposed on the bacterial surface. Affinity-isolated human anti-PDm antibodies eluted in acidic buffer were not bactericidal against H. influenzae. Loss of bactericidal activity may occur in this buffer, as was demonstrated in pooled human sera with high bactericidal activity after incubation in the same buffer. Hyperimmunization of rats with PDm induced high levels of serum IgG and IgA antibodies against PDm and significant bactericidal activity against homologous and heterologous H. influenzae strains.
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| 5. |
- Akkoyunlu, Mustafa, et al.
(författare)
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The acylated form of protein D of Haemophilus influenzae is more immunogenic than the nonacylated form and elicits an adjuvant effect when it is used as a carrier conjugated to polyribosyl ribitol phosphate
- 1997
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Ingår i: Infection and Immunity. - 0019-9567 .- 1098-5522. ; 65:12, s. 5010-5016
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Tidskriftsartikel (refereegranskat)abstract
- The nonacylated form of protein D (PDm) of Haemophilus influenzae has been shown to induce the production of antibodies that are bactericidal to homologous and heterologous nontypeable H. influenzae (NTHi) strains. In this study, immunization of rats with lipoprotein D (LPD) induced higher levels of anti-protein D immunoglobulin G and A serum antibodies than immunization with PDm, and the bactericidal activities of sera from LPD-immunized rats were greater than those of sera from PDm-immunized rats. Immunization with LPD or PDm did not prevent the development of acute otitis media (AOM) when rats were challenged with 10(4) CFU of an NTHi strain. However, on the eighth day of bacterial challenge, 50% (5 of 10) of LPD-immunized rats had recovered from otitis media and 30% (3 of 10) had negative middle ear cultures, whereas only 30% (3 of 10) of PDm-immunized rats had recovered, though none was culture positive. Immunization with an inactivated homologous bacterial strain elicited 70% protection (i.e., 7 of 10 rats) in the rat otitis media model. LPD and PDm were also conjugated to the H. influenzae type b (Hib) capsular polysaccharide, polyribosyl ribitol phosphate (PRP), to test protein D-conjugated PRP vaccine's potential for protection against Hib infection. When two LPD-conjugated and two PDm-conjugated PRP vaccines, each containing a different protein concentration, and a tetanus toxoid-conjugated vaccine (ACT-HIB) were tested in the experimental model of rat otitis induced with a Hib strain (Minn A), both of the LPD-conjugated and one of the PDm-conjugated vaccines induced significant protection from AOM, the level of protection being highest in animals given the vaccine with the highest LPD content. Sera from these rats also manifested the highest anti-PRP and anti-LPD antibody levels and the highest bactericidal activities against a Hib strain and an NTHi strain.
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| 6. |
- Bredberg, Anders, et al.
(författare)
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4-quinolone antibiotics : Positive genotoxic screening tests despite an apparent lack of mutation induction
- 1989
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Ingår i: Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis. - : Elsevier BV. - 1879-2871 .- 0027-5107. ; 211:1, s. 171-180
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Tidskriftsartikel (refereegranskat)abstract
- The effects of different 4-quinolone antibiotic derivatives (4-Qs) in a number of short-term tests commonly employed for the evaluation of genetic toxicity were studied. Incorporation of [3H]thymidine into mitogen-stimulated peripheral blood lymphocytes was strongly enhanced at a low concentration (1.56 μg/ml) for most of the tested 4-Qs, whereas DNA strand breakage in lymphoblastoid cells was evident only for ciprofloxacin (10 μg/ml and upwards), ofloxacin (80 μg/ml) and norfloxacin (160 μg/ml). Ciphrofloxacin induced a significant amount of unscheduled DNA synthesis, but was found to be negative in a shuttle vector plasmid mutation test. Ciprofloxacin (80 μg/ml) did not inhibit enzymes involved in the early steps of pyrimidine biosynthesis. Cell growth was slightly depressed at a concentration of 20 μg/ml, becoming marked at 80 μg/ml. In conculsion, this study seeks to contribute to an improved evaluation of genotoxic screening test data, by focuding attention on the conflicting effects imposed by the 4-Qs on a battery of such tests.
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| 7. |
- Bråbäck, Martin, et al.
(författare)
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Susceptibilities of Mycobacterium marinum to Gatifloxacin, Gemifloxacin, Levofloxacin, Linezolid, Moxifloxacin, Telithromycin, and Quinupristin-Dalfopristin (Synercid) Compared to Its Susceptibilities to Reference Macrolides and Quinolones.
- 2002
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Ingår i: Antimicrobial Agents and Chemotherapy. - 1098-6596. ; 46:4, s. 1114-1116
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Tidskriftsartikel (refereegranskat)abstract
- The susceptibility pattern of Mycobacterium marinum was determined. Quinupristin-dalfopristin and telithromycin were less active than clarithromycin. Linezolid showed good antimicrobial activity at clinically achievable concentrations. Gatifloxacin, levofloxacin, and moxifloxacin displayed activities similar to those of ciprofloxacin. Gemifloxacin was less active. The Etest method showed variable agreement with the reference method.
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