| 1. |
- Deisenhammer, F, et al.
(författare)
-
Prediction of natalizumab anti-drug antibodies persistency
- 2019
-
Ingår i: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1477-0970 .- 1352-4585. ; 25:3, s. 392-398
-
Tidskriftsartikel (refereegranskat)abstract
- Anti-drug antibodies (ADA) against natalizumab develop early during treatment. ADA persistency is defined by two consecutive positive results as performed by the current qualitative ELISA assay (positive/negative). Very little is known about the magnitude of the natalizumab ADA response and persistency. Design/methods: We developed a highly sensitive natalizumab ADA titration assay on the Meso Scale Discovery (MSD) platform and a pharmacokinetic (PK) assay. We included 43 patients with a positive ELISA-ADA result within 6 months of treatment initiation (baseline) of whom a follow-up serum sample was available 12–30 months after treatment start. MSD-ADA titres and drug levels were measured. Results: Median MSD-ADA titre at baseline was 4881 and 303 at follow-up. A titre of >400 at baseline had a 94% sensitivity and 89% specificity to predict ADA persistency. Reversion to ADA negativity occurred in 10 patients with mean drug levels of 10.8 μg/mL. The median trough drug level in ADA-positive samples was 0 µg/mL. PK levels and ADA titres correlated strongly negatively ( r = −0.67). Conclusion: High baseline natalizumab ADA titres accurately predict persistency. Despite continuous treatment, the majority of patients with persistent ADA had no detectable drug levels indicating loss of efficacy in line with phase 3 study results.
|
|
| 2. |
- Brindefalk, B., et al.
(författare)
-
Bacterial composition in Swedish raw drinking water reveals three major interacting ubiquitous metacommunities
- 2022
-
Ingår i: Microbiologyopen. - : Wiley. - 2045-8827. ; 11:5
-
Tidskriftsartikel (refereegranskat)abstract
- Background Surface raw water used as a source for drinking water production is a critical resource, sensitive to contamination. We conducted a study on Swedish raw water sources, aiming to identify mutually co-occurring metacommunities of bacteria, and environmental factors driving such patterns. Methods The water sources were different regarding nutrient composition, water quality, and climate characteristics, and displayed various degrees of anthropogenic impact. Water inlet samples were collected at six drinking water treatment plants over 3 years, totaling 230 samples. The bacterial communities of DNA sequenced samples (n = 175), obtained by 16S metabarcoding, were analyzed using a joint model for taxa abundance. Results Two major groups of well-defined metacommunities of microorganisms were identified, in addition to a third, less distinct, and taxonomically more diverse group. These three metacommunities showed various associations to the measured environmental data. Predictions for the well-defined metacommunities revealed differing sets of favored metabolic pathways and life strategies. In one community, taxa with methanogenic metabolism were common, while a second community was dominated by taxa with carbohydrate and lipid-focused metabolism. Conclusion The identification of ubiquitous persistent co-occurring bacterial metacommunities in freshwater habitats could potentially facilitate microbial source tracking analysis of contamination issues in freshwater sources.
|
|
| 3. |
- Karadenizli, A., et al.
(författare)
-
Genomic analyses of Francisella tularensis strains confirm disease transmission from drinking water sources, Turkey, 2008, 2009 and 2012
- 2015
-
Ingår i: Eurosurveillance. - 1025-496X .- 1560-7917. ; 20:21
-
Tidskriftsartikel (refereegranskat)abstract
- Waterborne epidemics of tularaemia caused by Francisella tularensis are increasingly reported in Turkey. We have used whole genome sequencing to investigate if F. tularensis isolated from patients could be traced back to drinking water sources. Tonsil swabs from 33 patients diagnosed with oropharyngeal tularaemia in three outbreaks and 140 water specimens were analysed. F. tularensis subsp. holarctica was confirmed by microagglutination and PCR in 12 patients and five water specimens. Genomic analysis of three pairs of patient and water isolates from outbreaks in Sivas, Corum, and Kocaeli showed the isolates to belong to two new clusters of the F. tularensis B. 12 genetic clade. The clusters were defined by 19 and 15 single nucleotide polymorphisms (SNPs) in a multiple alignment based on 507 F. tularensis genomes. One synonymous SNP was chosen as a new canonical SNP (canSNP) for each cluster for future use in diagnostic assays. No SNP was identified between the genomes from the patient-water pair of isolates from Kocaeli, one SNP between the pair of isolates from Sivas, whereas the pair from Corum differed at seven SNPs. These results illustrate the power of whole genome sequencing for tracing F. tularensis patient isolates back to their environmental source.
|
|
| 4. |
|
|
| 5. |
- Afset, J. E., et al.
(författare)
-
Phylogeographical pattern of Francisella tularensis in a nationwide outbreak of tularaemia in Norway, 2011
- 2015
-
Ingår i: Eurosurveillance. - 1025-496X .- 1560-7917. ; 20:19, s. 9-14
-
Tidskriftsartikel (refereegranskat)abstract
- In 2011, a nationwide outbreak of tularaemia occurred in Norway with 180 recorded cases. It was associated with the largest peak in lemming density seen in 40 years. Francisella tularensis was isolated from 18 patients. To study the geographical distribution of F. tularensis genotypes in Norway and correlate genotype with epidemiology and clinical presentation, we performed whole genome sequencing of patient isolates. All 18 genomes from the outbreak carried genetic signatures of F. tularensis subsp. holarctica and were assigned to genetic clades using canonical single nucleotide polymorphisms. Ten isolates were assigned to major genetic clade B.6 (subclade B.7), seven to clade B.12, and one to clade B.4. The B.6 subclade B.7 was most common in southern and central Norway, while clade B.12 was evenly distributed between the southern, central and northern parts of the country. There was no association between genotype and clinical presentation of tularaemia, time of year or specimen type. We found extensive sequence similarity with F. tularensis subsp. holarctica genomes from high-endemic tularaemia areas in Sweden. Finding nearly identical genomes across large geographical distances in Norway and Sweden imply a life cycle of the bacterium without replication between the outbreaks and raise new questions about long-range migration mechanisms.
|
|
| 6. |
- Andersson, Agneta, et al.
(författare)
-
Predators and nutrient availability favor protozoa-resisting bacteria in aquatic systems
- 2018
-
Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- The long co-existence of bacteria and protozoa has led to the development of bacterial protozoa resistance strategies, which are suggested to serve as drivers for the evolution of pathogenic bacteria. However, the ecological mechanisms underpinning selection for protozoa-resistance in aquatic bacteria are poorly known. To assess the role of nutrient availability and predation-pressure on selection for protozoa-resisting bacteria (PRB), an enrichment-dilution experiment was designed using laboratory microcosms containing natural lake water. PRB was monitored by screening 16S rRNA amplicon sequence data for reads assigned to bacteria that previously has been shown to resist degradation by amoebae. To estimate the effects of the microbial food web dynamics (microscopy of; heterotrophic bacteria, phytoplankton, protozoa and rotifers) and physicochemical variables on the PRB abundance in the study system, a joint species distribution modelling approach was used. The predation-pressure (ratio between predator and bacterial biomass) had a positive effect on the abundance of the PRB genus Mycobacterium, while perturbation (enrichment and dilution) favored the PRB genus Pseudomonas that dominated the bacterial community in the disturbed systems. Our results show that PRB with different ecological strategies can be expected in water of high and intermediate nutrient levels and after major disturbances of an aquatic system.
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
|
|
