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- Athlin, Simon, 1971-, et al.
(author)
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Association between serotype-specific antibody response and serotype characteristics in patients with pneumococcal pneumonia, with special reference to degree of encapsulation and invasive potential
- 2014
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In: Clinical and Vaccine Immunology. - : American Society for Microbiology. - 1556-6811 .- 1556-679X. ; 21:11, s. 1541-1549
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Journal article (peer-reviewed)abstract
- We studied the immunoglobulin (Ig) response to causative serotype-specific capsular polysaccharides in adult pneumococcal pneumonia patients. The serotypes were grouped according to their degree of encapsulation and invasive potential. Seventy patients with pneumococcal pneumonia, 20 of whom were bacteremic, were prospectively studied. All pneumococcal isolates from the patients were serotyped, and the Ig titers to the homologous serotype were determined in acute- and convalescent-phase sera using a serotype-specific enzyme-linked immunosorbent assay. The Ig titers were lower in bacteremic cases than in nonbacteremic cases (P < 0.042). The Ig titer ratio (convalescent/acute titer) was ≥2 in 33 patients, 1 to 1.99 in 20 patients, and <1 in 17 patients. Patients ≥65 years old had a lower median Ig titer ratio than did younger patients (P < 0.031). The patients with serotypes with a thin capsule (1, 4, 7F, 9N, 9V, and 14) and medium/high invasive potential (1, 4, 7F, 9N, 9V, 14, and 18C) had higher Ig titer ratios than did patients with serotypes with a thick capsule (3, 6B, 11A, 18C, 19A, 19F, and 23F) and low invasive potential (3, 6B, 19A, 19F, and 23F) (P < 0.05 for both comparisons after adjustment for age). Ig titer ratios of <1 were predominantly noted in patients with serotypes with a thick capsule. In 8 patients with pneumococcal DNA detected in plasma, the three patients with the highest DNA load had the lowest Ig titer ratios. In conclusion, a high antibody response was associated with serotypes with a thin capsule and medium/high invasive potential, although a low antibody response was associated with serotypes with a thick capsule and a high pneumococcal plasma load.
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| 2. |
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| 3. |
- Alpkvist, Helena, et al.
(author)
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Clinical and Microbiological Factors Associated with High Nasopharyngeal Pneumococcal Density in Patients with Pneumococcal Pneumonia
- 2015
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In: PLOS ONE. - : Public Library Science. - 1932-6203. ; 10:10
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Journal article (peer-reviewed)abstract
- Background: We aimed to study if certain clinical and/or microbiological factors are associated with a high nasopharyngeal (NP) density of Streptococcus pneumoniae in pneumococcal pneumonia. In addition, we aimed to study if a high NP pneumococcal density could be useful to detect severe pneumococcal pneumonia.Methods: Adult patients hospitalized for radiologically confirmed community-acquired pneumonia were included in a prospective study. NP aspirates were collected at admission and were subjected to quantitative PCR for pneumococcal DNA (Spn9802 DNA). Patients were considered to have pneumococcal etiology if S. pneumoniae was detected in blood culture and/ or culture of respiratory secretions and/or urinary antigen test.Results: Of 166 included patients, 68 patients had pneumococcal DNA detected in NP aspirate. Pneumococcal etiology was noted in 57 patients (84%) with positive and 8 patients (8.2%) with negative test for pneumococcal DNA (p<0.0001). The median NP pneumococcal density of DNA positive patients with pneumococcal etiology was 6.83 log(10) DNA copies/mL (range 1.79-9.50). In a multivariate analysis of patients with pneumococcal etiology, a high pneumococcal density was independently associated with severe pneumonia (Pneumonia Severity Index risk class IV-V), symptom duration >= 2 days prior to admission, and a medium/high serum immunoglobulin titer against the patient's own pneumococcal serotype. NP pneumococcal density was not associated with sex, age, smoking, co-morbidity, viral co-infection, pneumococcal serotype, or bacteremia. Severe pneumococcal pneumonia was noted in 28 study patients. When we studied the performance of PCR with different DNA cut-off levels for detection of severe pneumococcal pneumonia, we found sensitivities of 54-82% and positive predictive values of 37-56%, indicating suboptimal performance.Conclusions: Pneumonia severity, symptom duration similar to 2 days, and a medium/high serum immunoglobulin titer against the patient's own serotype were independently associated with a high NP pneumococcal density. NP pneumococcal density has limited value for detection of severe pneumococcal pneumonia.
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| 5. |
- Littorin, Nils, et al.
(author)
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Serotypes With Low Invasive Potential Are Associated With an Impaired Antibody Response in Invasive Pneumococcal Disease
- 2018
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In: Frontiers in Microbiology. - : Frontiers Media S.A.. - 1664-302X. ; 9
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Journal article (peer-reviewed)abstract
- Pneumococcal polysaccharide vaccines may elicit a hyporesponse under certain conditions. There is limited knowledge, however, on the type of specific antibody response in individuals with invasive pneumococcal disease (IPD). The aim of this study was to investigate the functional antibody response in patients with IPD caused by different serotypes. Pre-immune and convalescent sera from 40 patients (age 14-91 years) with IPD caused by serotypes with low (serotype 3, 19F, and 23F) and high (1, 4, 7F, and 14) invasive potential were investigated. For each patient, the homologous serotype-specific antibody concentration was determined. The functionality of induced antibodies post-IPD was evaluated in an opsonophagocytic assay (OPA). Undetectable or decreased pneumococcal killing in OPA following IPD, i.e., a nonfunctional antibody response, was observed in 24 of 40 patients (60%). Patients with nonfunctional antibody responses had lower serotype specific IgG antibody ratios post-IPD than patients with increased OPA titres. A nonfunctional antibody response was associated with low invasive serotypes (3, 19F, and 23F, p = 0.015). In conclusion, a nonfunctional antibody response may follow IPD, and was in our cohort associated to serotypes with low invasive potential. These findings need to be confirmed in a larger material.
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| 6. |
- Uddén, Fabian, et al.
(author)
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Characterization of Streptococcus pneumoniae detected in clinical respiratory tract samples in southern Sweden 2 to 4 years after introduction of PCV13
- 2021
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In: Journal of Infection. - : Elsevier BV. - 0163-4453. ; 83:2, s. 190-196
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Journal article (peer-reviewed)abstract
- Objective: To determine the serotype distribution and antimicrobial resistance of Streptococcus pneumoniae associated with mucosal infections in patients of all ages, 2 to 4 years after the transition from a 10-valent pneumococcal conjugate vaccine (PCV10) to PCV13 in the childhood immunization programme. Methods: Background information and antimicrobial susceptibility data regarding all respiratory tract, middle ear, and conjunctival samples positive for growth of S. pneumoniae (n = 2,131) were collected during 18 months in 2016–2018. Available corresponding bacterial isolates were serotyped by PCR and/or antisera (n = 1,858). Results: In total, 17% of isolates were covered by PCV13, predominantly represented by serotypes 3 (9%) and 19A (5%). The most common nonvaccine serotypes were 11A (10%), 23B (10%), 15A (6%) and 35F (5%). Isolates exhibiting serotype 15A or 23B were often multidrug-resistant (21%) or penicillin nonsusceptible (38%), respectively. Conclusions: The overall proportion of serotype 19A was halved compared to a previous observation period when PCV10 was used (years 2011–2013), suggesting herd protection related to PCV13. The proportion of serotype 3 was, however, unchanged. Despite most nonvaccine serotypes causing mucosal infections have a low invasive potential, certain antibiotic resistant serotypes may pose a clinical problem.
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| 7. |
- Uddén, Fabian, et al.
(author)
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Pneumococcal carriage among children aged 4 – 12 years in Angola 4 years after the introduction of a pneumococcal conjugate vaccine
- 2020
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In: Vaccine. - : Elsevier BV. - 0264-410X. ; 38:50, s. 7928-7937
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Journal article (peer-reviewed)abstract
- Children in Angola are affected by a high burden of disease caused by pneumococcal infections. The 13-valent pneumococcal conjugate vaccine (PCV13) was introduced in the childhood immunization programme in 2013 but the serotype distribution of Streptococcus pneumoniae and antimicrobial susceptibility patterns are unknown. We did a cross-sectional nasopharyngeal carriage study in Luanda and Saurimo, Angola (PCV13 3rd dose coverage 67% and 84%, respectively) during November to December 2017 comprising 940 children aged 4–12 years. The main objective was to assess vaccine serotype coverage and antimicrobial susceptibility rates for S. pneumoniae. Our secondary aim was to characterize colonizinig strains of Haemophilus influenzae and Moraxella catarrhalis. Pneumococcal colonization was found in 35% (95% CI 32–39%) of children (n = 332), with 41% of serotypes covered by PCV13. The most common serotypes were 3 (8%), 18C (6%), 23F (6%), 11A (6%), 34 (6%), 19F (5%) and 16 (5%). Carriage of H. influenzae and M. catarrhalis was detected in 13% (95% CI 11–15%) and 15% (95% CI 13–17%) of children, respectively. Non-susceptibility to penicillin was common among pneumococci (40%), particularly among PCV13-included serotypes (50% vs. 33%; p = 0.003), although the median minimal inhibitory concentration was low (0.19 µg/mL, IQR 0.13–0.25 µg/mL). Most pneumococci and H. influenzae were susceptible to amoxicillin (99% and 88%, respectively). Furthermore, resistance to trimethoprim-sulfamethoxazole was>70% among all three species. Multidrug-resistant pneumococci (non-susceptible to ≥ 3 antibiotics; 7% [n = 24]) were further studied with whole genome sequencing to investigate clonality as an underlying cause for this phenotype. No clearly dominating clone(s) were, however, detected. The results indicate that continued use of PCV13 may have positive direct and herd effects on pneumococcal infections in Angola as carriage of vaccine serotypes was common in the non-vaccinated age group. Finally, amoxicillin is assessed to be a feasible empirical treatment of respiratory tract infections in Angola.
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| 8. |
- Yamba Yamba, Linda, et al.
(author)
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Extensive/Multidrug-Resistant Pneumococci Detected in Clinical Respiratory Tract Samples in Southern Sweden Are Closely Related to International Multidrug-Resistant Lineages
- 2022
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In: Frontiers in cellular and infection microbiology. - : Frontiers Media SA. - 2235-2988. ; 12, s. 1-11
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Journal article (peer-reviewed)abstract
- Background/Objective: The frequencies of non-susceptibility against common antibiotics among pneumococci vary greatly across the globe. When compared to other European countries antibiotic resistance against penicillin and macrolides has been uncommon in Sweden in recent years. Multidrug resistance (MDR) is, however, of high importance since relevant treatment options are scarce. The purpose of this study was to characterize the molecular epidemiology, presence of resistance genes and selected virulence genes of extensively drug-resistant (XDR) (n=15) and MDR (n=10) Streptococcus pneumoniae detected in clinical respiratory tract samples isolated from patients in a southern Swedish county 2016-2018. With the aim of relating them to global MDR pneumococci.Methods: Whole genome sequencing (WGS) was performed to determine molecular epidemiology, resistance genes and presence of selected virulence factors. Antimicrobial susceptibility profiles were determined using broth microdilution testing. Further analyses were performed on isolates from the study and from the European nucleotide archive belonging to global pneumococcal sequence cluster (GPSC) 1 (n=86), GPSC9 (n=55) and GPSC10 (n=57). Bacteria were analyzed regarding selected virulence determinants (pilus islet 1, pilus islet 2 and Zinc metalloproteinase C) and resistance genes.Results: Nineteen of 25 isolates were related to dominant global MDR lineages. Seventeen belonged to GPSC1, GPSC9 or GPSC10 with MDR non-PCV serotypes in GPSC9 (serotype 15A and 15C) as well as GPSC10 (serotype 7B, 15B and serogroup 24). Pilus islet-1 and pilus islet-2 were present in most sequence types belonging to GPSC1 and in two isolates within GPSC9 but were not detected in isolates belonging to GPSC10. Zinc metalloproteinase C was well conserved within all analyzed isolates belonging to GPSC9 but were not found in isolates from GPSC1 or GPSC10.Conclusions: Although MDR S. pneumoniae is relatively uncommon in Sweden compared to other countries, virulent non-PCV serotypes that are MDR may become an increasing problem, particularly from clusters GPSC9 and GPSC10. Since the incidence of certain serotypes (3, 15A, and 19A) found among our MDR Swedish study isolates are persistent or increasing in invasive pneumococcal disease further surveillance is warranted.
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