| 1. |
- Alaridah, Nader, et al.
(författare)
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Transmission dynamics study of tuberculosis isolates with whole genome sequencing in southern Sweden
- 2019
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Epidemiological contact tracing complemented with genotyping of clinical Mycobacterium tuberculosis isolates is important for understanding disease transmission. In Sweden, tuberculosis (TB) is mostly reported in migrant and homeless where epidemiologic contact tracing could pose a problem. This study compared epidemiologic linking with genotyping in a low burden country. Mycobacterium tuberculosis isolates (n = 93) collected at Scania University Hospital in Southern Sweden were analysed with the standard genotyping method mycobacterial interspersed repetitive units-variable number tandem repeats (MIRU-VNTR) and the results were compared with whole genome sequencing (WGS). Using a maximum of twelve single nucleotide polymorphisms (SNPs) as the upper threshold of genomic relatedness noted among hosts, we identified 18 clusters with WGS comprising 52 patients with overall pairwise genetic maximum distances ranging from zero to nine SNPs. MIRU-VNTR and WGS clustered the same isolates, although the distribution differed depending on MIRU-VNTR limitations. Both genotyping techniques identified clusters where epidemiologic linking was insufficient, although WGS had higher correlation with epidemiologic data. To summarize, WGS provided better resolution of transmission than MIRU-VNTR in a setting with low TB incidence. WGS predicted epidemiologic links better which could consolidate and correct the epidemiologically linked cases, avoiding thus false clustering.
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| 2. |
- Jönsson, Bodil, 1959, et al.
(författare)
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Molecular epidemiology of Mycobacterium abscessus, with focus on cystic fibrosis.
- 2007
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Ingår i: Journal of clinical microbiology. - 0095-1137. ; 45:5, s. 1497-504
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Tidskriftsartikel (refereegranskat)abstract
- Mycobacterium abscessus has been isolated increasingly often from the respiratory tracts of cystic fibrosis (CF) patients. It is not known whether these organisms are transmitted from person to person or acquired from environmental sources. Here, colony morphology and pulsed-field gel electrophoresis (PFGE) pattern were examined for 71 isolates of M. abscessus derived from 14 CF patients, three non-CF patients with chronic respiratory M. abscessus infection or colonization, one patient with mastoiditis, and four patients with infected wounds, as well as for six isolates identified as environmental contaminants in various clinical specimens. Contaminants and wound isolates mainly exhibited smooth colony morphology, while a rough colony phenotype was significantly associated with chronic airway colonization (P=0.014). Rough strains may exhibit increased airway-colonizing capacity, the cause of which remains to be determined. Examination by PFGE of consecutive isolates from the same patient showed that they all represented a single strain, even in cases where both smooth and rough isolates were present. When PFGE patterns were compared, it was shown that 24 patients had unique strains, while four patients harbored strains indistinguishable by PFGE. Two of these were siblings with CF. The other two patients, one of whom had CF, had not had contact with each other or with the siblings. Our results show that most patients colonized by M. abscessus in the airways have unique strains, indicating that these strains derive from the environment and that patient-to-patient transmission rarely occurs.
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| 3. |
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| 4. |
- Brudey, Karine, et al.
(författare)
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Molecular epidemiology of Mycobacterium tuberculosis in western Sweden.
- 2004
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Ingår i: Journal of clinical microbiology. - 0095-1137. ; 42:7, s. 3046-51
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Tidskriftsartikel (refereegranskat)abstract
- The genetic diversity of Mycobacterium tuberculosis isolates among patients from Sweden was determined by a combination of two PCR-based techniques (spoligotyping and variable number of tandem repeats analysis). It resulted in a clustering of 23.6% of the isolates and a rate of recent transmission of 14.1%. The clustered isolates mainly belonged to the Haarlem family (23.2%), followed by the Beijing (9.8%), Latin American and Mediterranean (LAM; 8%), and East African-Indian (EAI; 6.2%) families. A comparison of the spoligotypes with those in the international spoligotyping database showed that 62.5% of the clustered isolates and 36.6% of all isolates typed were grouped into six major shared types. A comparison of the spoligotypes with those in databases for Scandinavian countries showed that 33% of the isolates belonged to an ill-defined T family, followed by the EAI (22%), Haarlem (20%), LAM (11%), Central Asian (5%), X (5%), and Beijing (4%) families. Both the highest number of cases and the proportion of clustered cases were observed in patients ages 15 to 39 years. Nearly 10% of the isolates were resistant to one or more drugs (essentially limited to isoniazid monoresistance). However, none of the strains were multidrug resistant. Data on the geographic origins of the patients showed that more than two-thirds of the clustered patients with tuberculosis were foreign-born individuals or refugees. These results are explained on the basis of both the historical links within specific countries and recently imported cases of tuberculosis into Sweden.
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| 5. |
- Bryant, J. M., et al.
(författare)
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Emergence and spread of a human-transmissible multidrug-resistant nontuberculous mycobacterium
- 2016
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 354:6313, s. 751-757
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Tidskriftsartikel (refereegranskat)abstract
- Lung infections with Mycobacterium abscessus, a species of multidrug-resistant nontuberculous mycobacteria, are emerging as an important global threat to individuals with cystic fibrosis (CF), in whom M. abscessus accelerates inflammatory lung damage, leading to increased morbidity and mortality. Previously, M. abscessus was thought to be independently acquired by susceptible individuals from the environment. However, using whole-genome analysis of a global collection of clinical isolates, we show that the majority of M. abscessus infections are acquired through transmission, potentially via fomites and aerosols, of recently emerged dominant circulating clones that have spread globally. We demonstrate that these clones are associated with worse clinical outcomes, show increased virulence in cell-based and mouse infection models, and thus represent an urgent international infection challenge.
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| 6. |
- Hoffner, S, et al.
(författare)
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Proficiency of drug susceptibility testing of Mycobacterium tuberculosis against pyrazinamide: the Swedish experience
- 2013
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Ingår i: The International Journal of Tuberculosis and Lung Disease. - : International Union Against Tuberculosis and Lung Disease. - 1027-3719 .- 1815-7920. ; 17:11, s. 1486-1490
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Pyrazinamide (PZA) is a key drug in the treatment of tuberculosis (TB), including multidrug-resistant TB. Drug susceptibility testing (DST) of Mycobacterium tuberculosis against PZA is not included in the World Health Organizations yearly proficiency testing. There is an increasing need to establish quality control of PZA DST. less thanbrgreater than less thanbrgreater thanOBJECTIVE: To evaluate the performance of PZA DST and to introduce a quality assurance system for the test in Sweden. less thanbrgreater than less thanbrgreater thanMETHOD: Panels with PZA-susceptible and -resistant isolates were used in three rounds of proficiency testing in all five Swedish clinical TB laboratories and our reference laboratory. All laboratories used the MGIT 960 system. Minimum inhibitory concentrations (MICs) were determined and the pncA gene was sequenced to further characterise the 52 panel strains. less thanbrgreater than less thanbrgreater thanRESULTS: Good agreement was seen between the phenotypic PZA DST and pncA sequence data, and MIC determination confirmed high levels of resistance. However, in contrast to other drugs, for which correct proficiency test results were observed, specificity problems occurred for PZA DST in some laboratories. less thanbrgreater than less thanbrgreater thanCONCLUSIONS: In Sweden, using panel testing, differences were seen in the proficiency of TB laboratories in correctly identifying PZA susceptibility. Improved results were noted in the third round; PZA has therefore been included in yearly proficiency testing.
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| 7. |
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| 8. |
- Jönsson, Bodil, 1959
(författare)
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Epidemiological and immunological studies of environmental mycobacteria - with focus on Mycobacterium abscessus
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Mycobacterium avium, M. abscessus and M. gordonae are three mycobacterial species that are ubiquitous in the environment. M. gordonae is non-pathogenic, while M. avium and M. abscessus can cause skin abscesses and airway disease, the latter mainly in patients with cystic fibrosis. The aim of this thesis was to examine the molecular epidemiology of M. abscessus and interactions of environmental mycobacteria with the human immune system. M. abscessus isolates from the airways of cystic fibrosis patients and from skin infections in patients injured during the tsunami catastrophe in Thailand 2004 were analysed by pulsed-field gel electrophoresis (PFGE). Almost all patients had unique strains, indicating that patient-to-patient transmission was rare. M. abscessus exhibits two colony variants; smooth and rough, the latter thought to be more virulent. Rough isolates dominated in chronic airway infection, while smooth strains caused wound infection or were transient colonizers of the airways, without associated symptoms. Environmental mycobacteria induced a unique cytokine pattern in human peripheral blood mononuclear cells (PBMC) characterized by very high levels of IL-17, high levels of IL-10, moderate levels of IL-23, relatively little IFN-, and no IL-12. The cytokine pattern induced by M. abscessus, M. avium and M. gordonae was identical, despite differences in pathogenic potential. Mycobacterial surface lipids and lipoarabinomannans induced very large amounts of IL-17, but down-regulated production of Th1 cytokines. Morphological analysis of PBMC interacting with M. abscessus showed that smooth isolates were readily phagocytosed, while rough strains formed multibacterial cords that escaped phagocytosis. Instead, monocytes appeared to entrap cord-forming bacteria in meshworks containing dsDNA and histones. These meshworks resembled NETs previously described in neutrophils, but to our knowledge, extracellular traps formed by monocytes have not previously been described. Rough isolates of M. abscessus induced significantly less IL-10 and IL-23, but more IL-1 than smooth isolates. Our results suggest that cord formation increases mycobacterial virulence and that mycobacterial cell wall lipids efficiently modulate innate responses and possess unique IL-17 inducing properties. The cellular basis for this IL-17 production remains to be determined.
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| 9. |
- Jönsson, Bodil, 1959, et al.
(författare)
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Evaluation of the Cobas TaqMan MTB test for detection of Mycobacterium tuberculosis complex.
- 2015
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Ingår i: Infectious diseases (London, England). - : Informa UK Limited. - 2374-4243 .- 2374-4235. ; 47:4, s. 231-6
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Tidskriftsartikel (refereegranskat)abstract
- The Cobas TaqMan MTB assay is used for rapid detection of the Mycobacterium tuberculosis complex (MTC) in clinical samples. It is only validated for respiratory samples, but is often requested by physicians for non-respiratory specimens. The aim of this study was therefore to evaluate the performance of this assay in clinical praxis in a country with low prevalence of tuberculosis (TB).
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| 10. |
- Jönsson, Bodil, 1959, et al.
(författare)
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Non-tuberculous mycobacteria and their surface lipids efficiently induced IL-17 production in human T cells
- 2012
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Ingår i: Microbes and Infection. - : Elsevier BV. - 1286-4579. ; 14:13, s. 1186-1195
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Tidskriftsartikel (refereegranskat)abstract
- Interleukin-17 (IL-17) is produced by a subset of CD4(+) T helper (Th) lymphocytes known as Th17 cells. In humans, IL-1 beta, enhanced by IL-6 and IL-23 is crucial for differentiation of these cells. IL-17 evokes inflammation and is involved in host defence against microorganisms, although little is known about its role in diseases caused by non-tuberculous mycobacteria. The genus Mycobacterium contains both obligate and opportunistic pathogens as well as saprophytes, and the mycobacterial cell envelope is unique in its abundance of lipids. Here we investigated IL-17 and IL-23 production in human PBMC in response to intact UV-inactivated mycobacteria and mycobacterial surface lipids from two opportunistic (Mycobacterium avium and Mycobacterium abscessus) and one generally non-pathogenic (Mycobacterium gordonae) species. Representative Gram-positive (Enterococcus faecalis, Streptococcus mitis) and Gram-negative (Escherichia coli) bacteria were included as controls. Intact mycobacteria induced production of large amounts of IL-17, while IL-17 responses to control bacteria were negligible. Purified CD4(+) T cells, but not CD4-depleted cell fractions, produced this IL-17. Isolated mycobacterial surface lipids induced IL-17, but not IL-23 production. The ability of the non-tuberculous mycobacteria to induce IL-17 production in CD4(+) T cells was the same regardless of the pathogenic potential of the particular mycobacterial species.
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