| 1. |
- Munk, P., et al.
(författare)
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Genomic analysis of sewage from 101 countries reveals global landscape of antimicrobial resistance
- 2022
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Antimicrobial resistance (AMR) is a major threat to global health. Understanding the emergence, evolution, and transmission of individual antibiotic resistance genes (ARGs) is essential to develop sustainable strategies combatting this threat. Here, we use metagenomic sequencing to analyse ARGs in 757 sewage samples from 243 cities in 101 countries, collected from 2016 to 2019. We find regional patterns in resistomes, and these differ between subsets corresponding to drug classes and are partly driven by taxonomic variation. The genetic environments of 49 common ARGs are highly diverse, with most common ARGs carried by multiple distinct genomic contexts globally and sometimes on plasmids. Analysis of flanking sequence revealed ARG-specific patterns of dispersal limitation and global transmission. Our data furthermore suggest certain geographies are more prone to transmission events and should receive additional attention.
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| 2. |
- Boswell, M. T., et al.
(författare)
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Intrahost evolution of the HIV-2 capsid correlates with progression to AIDS
- 2022
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Ingår i: Virus Evolution. - : Oxford University Press (OUP). - 2057-1577. ; 8:2
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Tidskriftsartikel (refereegranskat)abstract
- HIV-2 infection will progress to AIDS in most patients without treatment, albeit at approximately half the rate of HIV-1 infection. HIV-2 capsid (p26) amino acid polymorphisms are associated with lower viral loads and enhanced processing of T cell epitopes, which may lead to protective Gag-specific T cell responses common in slower progressors. Lower virus evolutionary rates, and positive selection on conserved residues in HIV-2 env have been associated with slower progression to AIDS. In this study we analysed 369 heterochronous HIV-2 p26 sequences from 12 participants with a median age of 30 years at enrolment. CD4% change over time was used to stratify participants into relative faster and slower progressor groups. We analysed p26 sequence diversity evolution, measured site-specific selection pressures and evolutionary rates, and determined if these evolutionary parameters were associated with progression status. Faster progressors had lower CD4% and faster CD4% decline rates. Median pairwise sequence diversity was higher in faster progressors (5.7x10-3 versus 1.4x10-3 base substitutions per site, P<0.001). p26 evolved under negative selection in both groups (dN/dS=0.12). Median virus evolutionary rates were higher in faster than slower progressors – synonymous rates: 4.6x10-3 vs. 2.3x10-3; and nonsynonymous rates: 6.9x10-4 vs. 2.7x10-4 substitutions/site/year, respectively. Virus evolutionary rates correlated negatively with CD4% change rates (ρ = -0.8, P=0.02), but not CD4% level. The signature amino acid at p26 positions 6, 12 and 119 differed between faster (6A, 12I, 119A) and slower (6G, 12V, 119P) progressors. These amino acid positions clustered near to the TRIM5α/p26 hexamer interface surface. p26 evolutionary rates were associated with progression to AIDS and were mostly driven by synonymous substitutions. Nonsynonymous evolutionary rates were an order of magnitude lower than synonymous rates, with limited amino acid sequence evolution over time within hosts. These results indicate HIV-2 p26 may be an attractive therapeutic target.
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| 3. |
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| 4. |
- Ahmed, R K S, et al.
(författare)
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Antigen-specific beta-chemokine production and CD8(+) T-cell noncytotoxic antiviral activity in HIV-2-infected individuals
- 2005
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Ingår i: Scandinavian Journal of Immunology. - : Wiley. - 1365-3083 .- 0300-9475. ; 61:1, s. 63-71
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Tidskriftsartikel (refereegranskat)abstract
- Human immunodeficiency virus-2 (HIV-2) is less pathogenic than HIV-1, and the disease progression in HIV-2-infected individuals seems to be similar to that seen in HIV-1-infected long-term nonprogressors. Cell-mediated immune responses and the production of noncytotoxic CD8(+) T-cell antiviral factors (CAF) and beta-chemokines have been correlated to protection against HIV-1 and associated with asymptomatic infection and slower disease progression. We investigated the antigen-induced beta-chemokine production in HIV-2-infected patients living in Sweden and in Guinea-Bissau. We also compared in vitro CD8(+) T-cell-mediated noncytotoxic antiviral activity against beta-chemokine-sensitive R5 virus (HIV-1(Bal)) and beta-chemokine-insensitive X4 virus (HIV-1(IIIB)) in HIV-2-infected patients with that in HIV-1-infected patients. HIV-2-specific beta-chemokine production was demonstrated in a majority of the HIV-2-infected subjects. CD8(+) T cells of both HIV-1 and HIV-2-infected individuals suppressed R5 virus replication in vitro in a similar manner, while the inhibition of X4 virus replication seemed to be more frequent and of a higher magnitude among HIV-2-infected patients compared to HIV-1-infected subjects. Taken together, our results indicate that the production of CD8(+) T-cell noncytotoxic antiviral factors may contribute to the low transmission of the virus and slower disease progression in HIV-2-infected patients.
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| 5. |
- Almquist, H, et al.
(författare)
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Performance of simultaneous emission-transmission systems for attenuation-corrected SPEct: a method for validation applied to two camera systems
- 2001
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Ingår i: Nuclear Medicine Communications. - 1473-5628. ; 22:7, s. 759-766
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Tidskriftsartikel (refereegranskat)abstract
- Several commercially available systems for attenuation correction in single photon emission computed tomography (SPECT) based on a transmission scan have been introduced that vary in performance. A test procedure for attenuation correction in SPECT is described and applied to two principally different gamma camera systems (the Siemens Multispect 3 triple-headed system [3HS] and the ADAC Genesys Vertex double-headed system [2HS]). The test procedure was based on geometrically well-defined phantoms. A torso phantom was used to illustrate the attenuation correction methods. The test procedure can be used without detailed knowledge of or access to the algorithms used for attenuation correction. The influence on the transmission measurement of radioactivity in a phantom was higher for the 2HS than for the 3HS. The 3HS produced satisfactory attenuation maps and corrected emission count rates to a constant value independent of phantom density and size. With the 2HS, there was a progressive decrease in the correction of emission count rates with increasing phantom density, and about 30% lower corrected count rates in the large compared with the small phantom. A decrease in measured attenuation coefficients in the vicinity of an emission source was demonstrated in large but not small phantoms. A likely explanation is erroneous correction of downscatter into the transmission energy window. This study demonstrates the need for independent evaluation of systems for attenuation correction in SPECT.
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| 9. |
- Bächle, Susanna M., et al.
(författare)
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Elevated levels of iNKT cell and NK cell activation correlate with disease progression in HIV-1 and HIV-2 infections
- 2016
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Ingår i: AIDS. - 0269-9370. ; 30:11, s. 1713-1722
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE:: In this study we aimed to investigate the frequency and activation of invariant natural killer T (iNKT) cells and natural killer (NK) cells among HIV-1, HIV-2, or dually HIV-1/HIV-2 (HIV-D)-infected individuals, in relation to markers of disease progression. DESIGN:: Whole blood samples were collected from treatment-naïve HIV-1 (n?=?23), HIV-2 (n?=?34) and HIV-D (n?=?11) infected individuals, as well as HIV-seronegative controls (n?=?25), belonging to an occupational cohort in Guinea-Bissau. METHODS:: Frequencies and activation levels of iNKT and NK cell subsets were analysed using multi-colour flow cytometry and results were related to HIV-status, CD4+ T cell levels, viral load, and T cell activation. RESULTS:: HIV-1, HIV-D, and viremic HIV-2 individuals had lower numbers of CD4+ iNKT cells in circulation compared to seronegative controls. Numbers of CD56 NK cells were also reduced in HIV-infected individuals as compared to control subjects. Notably, iNKT cell and NK cell activation levels, assessed by CD38 expression, were increased in HIV-1 and HIV-2 single, as well as dual, infections. HIV-2 viremia was associated with elevated activation levels in CD4+ iNKT cells, CD56 and CD56 NK cells, as compared to aviremic HIV-2 infection. Additionally, disease markers such as CD4+ T cell percentages, viral load, and CD4+ T cell activation were associated with CD38 expression levels of both iNKT and NK cells, which activation levels also correlated with each other. CONCLUSIONS:: Our data indicate that elevated levels of iNKT cell and NK cell activation are associated with viremia and disease progression markers in both HIV-1 and HIV-2 infections.
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| 10. |
- Hendriksen, Rene S., et al.
(författare)
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Global monitoring of antimicrobial resistance based on metagenomics analyses of urban sewage
- 2019
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- © 2019, The Author(s). Antimicrobial resistance (AMR) is a serious threat to global public health, but obtaining representative data on AMR for healthy human populations is difficult. Here, we use metagenomic analysis of untreated sewage to characterize the bacterial resistome from 79 sites in 60 countries. We find systematic differences in abundance and diversity of AMR genes between Europe/North-America/Oceania and Africa/Asia/South-America. Antimicrobial use data and bacterial taxonomy only explains a minor part of the AMR variation that we observe. We find no evidence for cross-selection between antimicrobial classes, or for effect of air travel between sites. However, AMR gene abundance strongly correlates with socio-economic, health and environmental factors, which we use to predict AMR gene abundances in all countries in the world. Our findings suggest that global AMR gene diversity and abundance vary by region, and that improving sanitation and health could potentially limit the global burden of AMR. We propose metagenomic analysis of sewage as an ethically acceptable and economically feasible approach for continuous global surveillance and prediction of AMR.
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