| 1. |
- Beser, Jessica, et al.
(författare)
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Seroprevalence of SARS-CoV-2 in Sweden, April 26 to May 9, 2021
- 2022
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- A national point seroprevalence study of SARS-CoV-2 was conducted in Sweden in April–May 2021. In total, 2860 individuals 3 to 90 years old from a probability-based web panel were included. Results showed that an estimated 32.6% of the population in Sweden had detectable levels of antibodies, and among non-vaccinated 20.1% had detectable levels of antibodies. We tested for differences in seroprevalence between age groups and by sex and estimated seroprevalence among previously infected participants by time since reporting.
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| 2. |
- Davies Forsman, Lina, et al.
(författare)
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Minimum Inhibitory Concentrations of Fluoroquinolones and Pyrazinamide Susceptibility Correlate to Clinical Improvement in Multidrug-resistant Tuberculosis Patients: A Nationwide Swedish Cohort Study Over 2 Decades
- 2019
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Ingår i: Clinical Infectious Diseases. - : OXFORD UNIV PRESS INC. - 1058-4838 .- 1537-6591. ; 69:8, s. 1394-1402
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Tidskriftsartikel (refereegranskat)abstract
- Background. Minimum inhibitory concentration (MIC) testing, unlike routine drug susceptibility testing (DST) at a single critical concentration, quantifies drug resistance. The association of MICs and treatment outcome in multidrug-resistant (MDR)-tuberculosis patients is unclear. Therefore, we correlated MICs of first- and second-line tuberculosis drugs with time to sputum culture conversion (tSCC) and treatment outcome in MDR-tuberculosis patients. Methods. Clinical and demographic data of MDR-tuberculosis patients in Sweden, including DST results, were retrieved from medical records from 1992 to 2014. MIC determinations were performed retrospectively for the stored individual Mycobacterium tuberculosis (Mtb) isolates using broth microdilution in Middlebrook 7H9. We fitted Cox proportional hazard models correlating MICs, DST results, and clinical variables to tSCC and treatment outcome. Results. Successful treatment outcome was observed in 83.5% (132/158) of MDR-tuberculosis patients. Increasing MICs of fluoroquinolones, diabetes, and age amp;gt;40 years were significantly associated with unsuccessful treatment outcome. Patients treated with pyrazinamide (PZA) had a significantly shorter tSCC compared to patients who were not (median difference, 27 days). Conclusions. Increasing MICs of fluoroquinolones were correlated with unsuccessful treatment outcome in MDR-tuberculosis patients. Further studies, including MIC testing and clinical outcome data to define clinical Mtb breakpoints, are warranted. PZA treatment was associated with shorter tSCC, highlighting the importance of PZA DST.
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| 3. |
- Groenheit, Ramona, et al.
(författare)
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High Prevalence of SARS-CoV-2 Omicron Infection Despite High Seroprevalence, Sweden, 2022
- 2023
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Ingår i: Emerging Infectious Diseases. - : CENTERS DISEASE CONTROL & PREVENTION. - 1080-6040 .- 1080-6059. ; 29:6
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Tidskriftsartikel (refereegranskat)abstract
- We performed 2 surveys during 2022 to estimate point prevalences of SARS-CoV-2 infection compared with overall viral seroprevalence in Sweden. Point prevalence was 1.4% in March and 1.5% in September. Estimated seroprevalence was >80%, including among unvaccinated children. Continued SARS-CoV-2 surveillance is necessary for detecting emerging, possibly more pathogenic variants.
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| 4. |
- Groenheit, Ramona
(författare)
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Molecular epidemiology of tuberculosis
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Tuberculosis is a global epidemic, with one third of the world’s population estimated to be infected, around 9 million new active cases per year and close to 2 million deaths per year. Without adequate chemotherapy tuberculosis may be a mortal disease. A century ago, the estimated tuberculosis incidence in Sweden was higher than in most high incidence countries of today’s sub-Saharan Africa. Today however, the majority of patients with tuberculosis in Sweden are immigrants from countries with a high incidence of tuberculosis. The incidence among the Swedish-born population has continued to decrease while it has increased among the foreign-born. In the West African country Guinea-Bissau, tuberculosis is a common disease and the incidence is believed to be further increased by the epidemic of the human immunodeficiency virus. In countries like Sweden the mortality was dramatically reduced about half a century ago when living conditions improved, public health measures were taken and treatments were made available. These gains are however seriously jeopardized by the now emerging multidrug resistant and extensively drug-resistant tuberculosis. Different genotypes of Mycobacterium tuberculosis complex predominate in different geographical regions of the world and strain-to-strain variations may have important consequences for instance when it comes to transmissibility. Future diagnostics, drugs and vaccines are affected by these strain variations and it is therefore of great importance to establish the whole spectrum of strains of the M. tuberculosis complex worldwide. Despite the high prevalence of tuberculosis in Africa, relatively little is known about the M. tuberculosis complex genetic diversity in this continent. The studies included in this thesis phylogenetically and epidemiologically characterized M. tuberculosis complex isolates obtained from tuberculosis patients in Sweden and Guinea-Bissau using molecular techniques such as Restriction Fragment Length Polymorphism, spacer oligonucleotide typing and 24-loci Mycobacterial Interspersed Repetitive Units-Variable Numbers of Tandem Repeats. The work was performed with the view to understand species and strain diversity as well as transmission patterns. It was illustrated that the great majority of tuberculosis patients with drug resistant isolates in Sweden were foreign-born and that their strain lineages to a large extent reflected genotypes common in their country of origin. One large outbreak of isoniazid resistant tuberculosis was identified, up to date (October 2011) involving 117 patients, mainly from the Horn of Africa. This outbreak represents one of the largest outbreaks of tuberculosis ever reported in a low incidence country and was an important warning signal to the Swedish authorities. By whole genome sequencing this outbreak strain showed to be exceptionally stable genetically. It was obvious that molecular epidemiological typing is a powerful tool to monitor and identify chains of transmission which could indicate deficiencies in national tuberculosis control programs. It was also discovered that Beijing lineage strains, which elsewhere in the world have caused large outbreaks, have not been able to spread within Sweden in spite of the proximity to high prevalence countries such as Russia and the Baltic countries. When isolates from patients born in Sweden before 1945 were studied, a highly homogenous bacterial population with a domination of the T, Haarlem and Latin-American-Mediterranean lineages was found. It was concluded that evolutionary recent (PGG2/3) strains restricted to Sweden and its immediate neighbours appeared to have caused the epidemic during the first half of the 20th century, while ancestral (PGG1) strains were usually linked to immigrant populations in today ́s Sweden. Guinea-Bissau was revisited and it was established that the country has the highest prevalence of M. africanum recorded in the African continent and that the Guinea-Bissau family of strains demonstrated high phylogeographical specificity for Western Africa.
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| 5. |
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| 6. |
- Kuhlin, Johanna, et al.
(författare)
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Genotypic resistance of pyrazinamide but not MIC is associated with longer time to sputum culture conversion in patients with multidrug-resistant tuberculosis
- 2021
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Ingår i: Clinical Infectious Diseases. - : Oxford University Press. - 1058-4838 .- 1537-6591. ; 73:9, s. E3511-E3517
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: PZA resistance in multidrug-resistant tuberculosis (MDR-TB) is common and it is not clear how it affects interim and treatment outcomes. Although rarely performed, phenotypic drug susceptibility testing (pDST) is used to define PZA resistance but genotypic DST (gDST) and minimum inhibitory concentration (MIC) could be beneficial. We aimed to assess the impact of PZA gDST and MIC on time to sputum culture conversion (SCC) and treatment outcome in patients with MDR-TB.METHODS: Clinical, microbiological and treatment data was collected in this cohort study for all patients diagnosed with MDR-TB in Sweden 1992-2014. MIC, pDST and whole genome sequencing of the pncA, rpsA and panD genes were used to define PZA resistance. A Cox regression model was used for statistical analyses.RESULTS: Of 157 patients with MDR-TB, 56.1% (n=88) had PZA resistant strains and 49.7% (n=78) were treated with PZA. In crude and adjusted analyses, PZA gDST resistance was associated with a 29-day longer time to SCC (hazard ratio [HR] 0.57, 95% confidence interval [CI] 0.36-0.89, p=0.013 and HR 0.49, 95% CI 0.29-0.82, p=0.007, respectively). A two-fold decrease in dilutions of PZA MIC for PZA susceptible strains showed no association with SCC in crude or adjusted analyses (HR 0.98, 95% CI 0.73-1.31, p=0.89). Genotypic DST and MIC for PZA were not associated with treatment outcome.CONCLUSION: In patients with MDR-TB, gDST PZA resistance was associated with a longer time to SCC. Rapid PZA gDST is important to identify patients who may benefit from PZA treatment.
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| 7. |
- Muvva, Jagadeeswara Rao, et al.
(författare)
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Immunomodulatory Agents Combat Multidrug-Resistant Tuberculosis by Improving Antimicrobial Immunity
- 2021
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Ingår i: Journal of Infectious Diseases. - : Oxford University Press. - 0022-1899 .- 1537-6613. ; 224:2, s. 332-344
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Tidskriftsartikel (refereegranskat)abstract
- Background. Multidrug-resistant (MDR) tuberculosis has low treatment success rates, and new treatment strategies are needed. We explored whether treatment with active vitamin D-3 (vitD) and phenylbutyrate (PBA) could improve conventional chemotherapy by enhancing immune-mediated eradication of Mycobacterium tuberculosis. Methods. A clinically relevant model was used consisting of human macrophages infected with M. tuberculosis isolates (n = 15) with different antibiotic resistance profiles. The antimicrobial effect of vitD+PBA, was tested together with rifampicin or isoniazid. Methods included colony-forming units (intracellular bacterial growth), messenger RNA expression analyses (LL-37, beta-defensin, nitric oxide synthase, and dual oxidase 2), RNA interference (LL-37-silencing in primary macrophages), and Western blot analysis and confocal microscopy (LL-37 and LC3 protein expression). Results. VitD+PBA inhibited growth of clinical MDR tuberculosis strains in human macrophages and strengthened intracellular growth inhibition of rifampicin and isoniazid via induction of the antimicrobial peptide LL-37 and I,C3-dependent autophagy. Gene silencing of LL-37 expression enhanced MDR tuberculosis growth in vitD+PBA-treated macrophages. Me combination of vitD+PBA and isoniazid were as effective in reducing intracellular MDR tuberculosis growth as a >125-fold higher dose of isoniazid alone, suggesting potent additive effects of vitD+PBA with isoniazid. Conclusions. Immunomodulatory agents that trigger multiple immune pathways can strengthen standard MDR tuberculosis treatment and contribute to next-generation individualized treatment options for patients with difficult-to-treat pulmonary tuberculosis.
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| 8. |
- Pandey, Sushil, et al.
(författare)
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Loss-of-function mutations in ndh do not confer delamanid, ethionamide, isoniazid, or pretomanid resistance in Mycobacterium tuberculosis
- 2024
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Ingår i: Antimicrobial Agents and Chemotherapy. - : AMER SOC MICROBIOLOGY. - 0066-4804 .- 1098-6596. ; 68:1
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Tidskriftsartikel (refereegranskat)abstract
- Results from clinical strains and knockouts of the H37Rv and CDC1551 laboratory strains demonstrated that ndh (Rv1854c) is not a resistance-conferring gene for isoniazid, ethionamide, delamanid, or pretomanid in Mycobacterium tuberculosis. This difference in the susceptibility to NAD-adduct-forming drugs compared with other mycobacteria may be driven by differences in the absolute intrabacterial NADH concentration.
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| 9. |
- Sandegren, Linus, et al.
(författare)
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Genomic Stability over 9 Years of an Isoniazid Resistant Mycobacterium tuberculosis Outbreak Strain in Sweden
- 2011
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:1, s. e16647-
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Tidskriftsartikel (refereegranskat)abstract
- In molecular epidemiological studies of drug resistant Mycobacterium tuberculosis (TB) in Sweden a large outbreak of an isoniazid resistant strain was identified, involving 115 patients, mainly from the Horn of Africa. During the outbreak period, the genomic pattern of the outbreak strain has stayed virtually unchanged with regard to drug resistance, IS6110 restriction fragment length polymorphism and spoligotyping patterns. Here we present the complete genome sequence analyses of the index isolate and two isolates sampled nine years after the index case as well as experimental data on the virulence of this outbreak strain. Even though the strain has been present in the community for nine years and passaged between patients at least five times in-between the isolates, we only found four single nucleotide polymorphisms in one of the later isolates and a small (4 amino acids) deletion in the other compared to the index isolate. In contrast to many other evolutionarily successful outbreak lineages (e. g. the Beijing lineage) this outbreak strain appears to be genetically very stable yet evolutionarily successful in a low endemic country such as Sweden. These findings further illustrate that the rate of genomic variation in TB can be highly strain dependent, something that can have important implications for epidemiological studies as well as development of resistance.
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