| 1. |
- Agarwal, Vaibhav, et al.
(författare)
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An Alternative Role of C1q in Bacterial Infections: Facilitating Streptococcus pneumoniae Adherence and Invasion of Host Cells.
- 2013
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Ingår i: Journal of Immunology. - : The American Association of Immunologists. - 1550-6606 .- 0022-1767. ; 191:8, s. 4235-4245
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Tidskriftsartikel (refereegranskat)abstract
- Streptococcus pneumoniae (pneumococcus) is a major human pathogen, which evolved numerous successful strategies to colonize the host. In this study, we report a novel mechanism of pneumococcal-host interaction, whereby pneumococci use a host complement protein C1q, primarily involved in the host-defense mechanism, for colonization and subsequent dissemination. Using cell-culture infection assays and confocal microscopy, we observed that pneumococcal surface-bound C1q significantly enhanced pneumococcal adherence to and invasion of host epithelial and endothelial cells. Flow cytometry demonstrated a direct, Ab-independent binding of purified C1q to various clinical isolates of pneumococci. This interaction was seemingly capsule serotype independent and mediated by the bacterial surface-exposed proteins, as pretreatment of pneumococci with pronase E but not sodium periodate significantly reduced C1q binding. Moreover, similar binding was observed using C1 complex as the source of C1q. Furthermore, our data show that C1q bound to the pneumococcal surface through the globular heads and with the host cell-surface receptor(s)/glycosaminoglycans via its N-terminal collagen-like stalk, as the presence of C1q N-terminal fragment and low m.w. heparin but not the C-terminal globular heads blocked C1q-mediated pneumococcal adherence to host cells. Taken together, we demonstrate for the first time, to our knowledge, a unique function of complement protein C1q, as a molecular bridge between pneumococci and the host, which promotes bacterial cellular adherence and invasion. Nevertheless, in some conditions, this mechanism could be also beneficial for the host as it may result in uptake and clearance of the bacteria.
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| 2. |
- Ahl, Jonas, et al.
(författare)
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Bacterial aetiology in ventilator-associated pneumonia at a Swedish university hospital
- 2010
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Ingår i: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 1651-1980 .- 0036-5548. ; 42:6-7, s. 469-474
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Tidskriftsartikel (refereegranskat)abstract
- Ventilator-associated pneumonia (VAP) is a common complication of respiratory support and is associated with increased mortality, morbidity and costs, and a prolonged stay in the intensive care unit. Scandinavian data on the aetiology in VAP are lacking. We hereby present a retrospective study on the aetiology of VAP diagnosed by protective specimen brush culture at Malmo University Hospital in relation to early-and late-onset VAP, antibiotic treatment and the incidence of drug-resistant bacteria. Patients registered with a diagnosis of VAP between January 2004 and September 2007 were included in the study. Sixty-five of 109 patients diagnosed with VAP met the inclusion criteria, and 103 bacterial isolates were cultured from these patients. The most common findings among the 65 VAP episodes were Enterobacteriaceae (28), Pseudomonas aeruginosa (13), Haemophilus influenzae (12) and Staphylococcus aureus (8). Patients with no antibiotic treatment at the onset of VAP had significantly more H. influenzae (p = 0.035) and Gram-positive pathogenic bacteria (p = 0.019). There was no difference in incidence of P. aeruginosa between early-and late-onset VAP. Resistant bacteria were found in 18% of the patients.
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| 3. |
- 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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| 4. |
- Ahl, Jonas, et al.
(författare)
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Prevalence of penicillin-non-susceptible Streptococcus pneumoniae in children in day-care centres subjected to an intervention to prevent dispersion.
- 2015
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Ingår i: Infectious Diseases. - : Informa UK Limited. - 2374-4243 .- 2374-4235. ; 47:5, s. 338-344
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Tidskriftsartikel (refereegranskat)abstract
- Background: The aim of this study was to evaluate the day-care interventions implemented in southern Sweden to restrict the dispersion of penicillin-non-susceptible pneumococci with a minimum inhibitory concentration of penicillin G of at least 0.5 mg/l (PNSP0.5). Methods: A retrospective epidemiological study was performed and data from 109 day-care centre interventions from 2000 to 2010 were analysed, including screening results from 7157 individuals. Results: It was found that 42% of the children were carriers of pneumococci and 5% of the screened children were PNSP0.5 carriers. Very few personnel were PNSP0.5 carriers and they were carriers for only a short time. Significantly more contact cases with the same serogroup as the index case were found in the first screening and in the same department as the index case, but a substantial number of contact cases were found in adjacent departments. Conclusions: Screening of personnel is not worth the effort. Based on our results, procedures to restrict dispersion of PNSP0.5 in day-care centres could be improved. To find the majority of contact cases with PNSP0.5 an early screening including adjacent departments seems to be the best approach.
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| 5. |
- Ahl, Jonas
(författare)
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Respiratory Tract Infections: Aspects of Aetiology, Virulence, and Communicable Disease Control
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The paediatric nasopharyngeal flora is regarded as the largest reservoir for Streptococcus pneumoniae, and the carrier state is always antecedent to infection and a prerequisite for dispersion of these bacteria. Pneumococci are the predominant aetiology of bacterial respiratory tract infections and a major cause of morbidity and mortality, in the most severe cases due to invasive pneumococcal disease (IPD; mainly sepsis and meningitis).The development and spread of resistant pneumococci are facilitated in day care centres (DCCs), which constitute an optimal environment for these processes. In Sweden, penicillin non-susceptible pneumococci (PNSP) have remained relatively uncommon,an important aspect considering that penicillin is the drug of choice for respiratory tract infections. When a tendency towards increasing PNSP was noted in Skåne County in southern Sweden, a DCC intervention program including screening started when an attending child has been found to be PNSP carrier. To restrict dispersion, all carriers were suspended from DCCs until they were declared free from PNSP. Today, there is no scientific proof that such DCC interventions can effectively restrict PNSP dispersion on a community level. Our retrospective study of the DCC interventions showed that 5% of the children were PNSP carriers during an outbreak. Personnel were rarely carriers (0.4%) and, if so, for only a very short time. PNSP was found a long time after the intervention started in a few children cultured late due to absence from the DCC for other reasons, indicating a long-lasting risk for dispersion. Furthermore, PNSP carriage was observed in a substantial number of children at DCC departments other than the department attended by the index case, indicating that the index case is not always at the centre of an outbreak. There was also significant seasonal variation seen as lower carrier rates after major holidays, indicating that these rates decline when children are not at DCCs. Day care group size and young age proved to be risk factors for pneumococcal carriage. Our findings can support development of future guidelines for managing PNSP outbreaks in DCCs. Eradication therapy of children with prolonged PNSP carriage was effective, but none of the treated children harboured any highly resistant or multidrug-resistant strains. Our retrospective study of IPD demonstrated that pneumococcal serotypes differ regarding their capacity to cause septic shock and, together with age and co-morbidities, have an important impact on outcome. The primary endpoint in our investigation was septic shock, a state produced by the immune system and triggered by the invading microorganism. This parameter was chosen instead of the case fatality rate (CFR),which is usually studied as outcome but is biased because serotypes with a low CFR infect healthier and younger individuals and vice versa. Septic shock was significantly more common among patients infected with serotype 3 compared to those with serotype 14, a worrisome finding since the effect of the conjugate vaccine on this serotype seems to be uncertain. Ventilator-associated pneumonia (VAP) is a common infection and complication in intensive care units. We found that the bacterial aetiology in VAP differed depending on whether the patients were receiving antibiotics at the time of the VAP diagnosis. Pseudomonas aeruginosa was a surprisingly widespread cause of early-onset VAP, but most of the patients had been treated with antibiotics. There was a trend towards more resistant bacteria in late-onset VAP.
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| 6. |
- Ahl, Jonas, et al.
(författare)
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Risk Factors for Pneumococcal Carriage in Day Care Centers: A Retrospective Study During a 10-year Period.
- 2014
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Ingår i: Pediatric Infectious Disease Journal. - 1532-0987. ; 33:5, s. 536-538
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Tidskriftsartikel (refereegranskat)abstract
- In this retrospective epidemiologic study, we present pneumococcal carriage data from 109 Swedish day care centers over a period of 10 years. Aspects of season, age, personnel and group size were studied. We found a significant seasonal variation in pneumococcal carriage. Group size was a significant risk factor for pneumococcal carriage. Pneumococcal carriage was 4.5 % in personnel.
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| 7. |
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| 8. |
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| 9. |
- Hansen, Karin, et al.
(författare)
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Exploring the microbial landscape uncovering the pathogens associated with community-acquired pneumonia in hospitalized patients
- 2023
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Ingår i: Frontiers in Public Health. - 2296-2565. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: This study aimed to investigate the etiology, clinical features, and outcomes of community-acquired pneumonia (CAP) in adults. Understanding the causative pathogens is essential for effective treatment and prevention.DESIGN: Between 2016-2018, 518 hospitalized adults with CAP and 241 controls without symptoms were prospectively enrolled. Urine samples were collected for pneumococcal urinary antigen tests and nasopharyngeal swabs for viral and bacterial analysis, combined with routine diagnostic care.RESULTS: Among the included CAP patients, Streptococcus pneumoniae was the most common pathogen, detected in 28% of patients, followed by Haemophilus influenzae in 16%. Viruses were identified in 28%, and concurrent viruses and bacteria were detected in 15%. There was no difference in mortality, length of stay, or symptoms at hospitalization when comparing patients with bacterial, viral, or mixed etiologies. Among the control subjects without respiratory symptoms, S. pneumoniae, H. influenzae, or Moraxella catarrhalis were detected in 5-7%, and viruses in 7%. CONCLUSION: Streptococcus pneumoniae emerged as the predominant cause of CAP, followed closely by viruses and H. influenzae. Intriguingly, symptoms and outcome were similar regardless of etiology. These findings highlight the complexity of this respiratory infection and emphasize the importance of comprehensive diagnostic and treatment strategies. Clinical Trial Registration: ClinicalTrials.gov, identifier [NCT03606135].
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| 10. |
- Hansen, Karin, et al.
(författare)
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Radiographically confirmed community-acquired pneumonia in hospitalized adults due to pneumococcal vaccine serotypes in Sweden, 2016–2018—The ECAPS study
- 2023
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Ingår i: Frontiers in Public Health. - : Frontiers Media SA. - 2296-2565. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: In Sweden, pneumococcal serotype distribution in adults with community-acquired pneumonia (CAP) and potential coverage of currently licensed pneumococcal conjugate vaccines (PCVs) is unknown. Methods: During 2016–2018, patients aged ≥18 years hospitalized with radiologically confirmed (RAD+) CAP were enrolled at Skåne University Hospital in a study on the etiology of CAP in Sweden (ECAPS). Urine samples and blood cultures were collected per-protocol. Streptococcus pneumoniae (Spn) culture isolates were serotyped and urine samples tested for the pan-pneumococcal urinary antigen (PUAT) and multiplex urine antigen detection (UAD) assay, detecting 24 serotypes. Results: Analyses included 518 participants with RAD+CAP; 67.4% were ≥65 years of age, 73.4% were either immunocompromised or had an underlying chronic medical condition. The proportion of CAP due to Spn identified by any method was 24.3% of which 9.3% was detected by UAD alone. The most frequently identified serotypes were 3 (26 cases, 5.0% of all CAP), and 8, 11A and 19A (10 cases each, 1.9%). In individuals aged 18–64 and ≥65 years, respectively, PCV20 serotypes contributed to 35 of 169 (20.7%) and 53 of 349 cases of all CAP (15.2%), and PCV13 serotypes caused 21 of 169 (12.4%) and 35 of 349 (10.0%) cases. PCV15 coverage was 23 of 169 (13.6%) and 42 of 349 (12.0%) in individuals aged 18–64 and ≥65 years, respectively. Overall, PCV20 increases the coverage of all CAP from 10.8% (PCV13) to 17.0%. Conclusion: Compared to earlier pneumococcal vaccines, PCV20 expands the coverage of all-cause CAP. Routine diagnostic tests underestimate the proportion of CAP caused by Spn.
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