Aro, Tuomas, decision sum: 40.000 SEK.

Report: With the help of SSAC-grant we have continued the prospective part of our study on multidrug-resistant bacteria among refugees and migrants and it is still ongoing. Additionally, we have conducted a ten-year retrospective study on hospital admissions of refugees, asylum seekers and undocumented migrants. The study has been published in Travel Medicine and Infectious Diseases.

Aro T, Kantele A. Hospital admissions of refugees, asylum seekers and undocumented migrants: Ten-year retrospective study. Travel Med Infect Dis. 2021 Nov-Dec;44:102186. doi: 10.1016/j.tmaid.2021.102186. Epub 2021 Oct 22. PMID: 34688889. https://doi.org/10.1016/j.tmaid.2021.102186

We have also conducted a retrospective study on multidrug-resistant (MDR) bacteria among asylum seekers and refugees treated at Helsinki University Hospital between 2010 and 2017. The study has been published in Eurosurveillance and SSAC has been acknowledged as a financial supporter in the Acknowledgements section:

Aro T, Kantele A. High rates of meticillin-resistant Staphylococcus aureus among asylum seekers and refugees admitted to Helsinki University Hospital, 2010 to 2017. Euro Surveill. 2018 Nov;23(45):1700797. doi: 10.2807/1560-7917.ES.2018.23.45.1700797. PMID: 30424828; PMCID: PMC6234530. https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2018.23.45.1700797

We found that MDR bacterial colonisation is common among asylum seekers and refugees. Of 447 patients 45.0 % were colonized by MDR bacteria. Extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE) was found in 32.9 % and meticillin-resistant Staphylococcus aureus (MRSA) in 21.3% of patients.

 

Bjarnason, Agnar. Decision sum: 100.000 SEK.

Report: Participant recruiting started on the 1st of May 2018 and ended on the 30th of April 2019 for the pneumonia group and the 13th of May 2019 for the control group. In total 1443 episodes

were included, 669 in the control group and 774 in the pneumonia group. Overall, 3234 admissions were screened during this 12-month period, 2158 for participation in the control group and 1076 for the pneumonia group (Figure 1). The total number of participants screened is 1% of the adult population of Iceland (≥18 years of age) [5].
An oropharyngeal sample was collected from all episodes. Sputum and blood were collected from patients in the pneumonia group. The period between 1st of May 2018 and 30th of April 2019 was primarily dedicated to recruiting participants: collecting samples, interviewing, and making follow-up phone calls. From May 2019 - May 2020 medical records, laboratory tests and diagnostic tests for all 1443 participants were examined and the inclusion criteria assessed for all patients. The plan to start PCR and metagenomic analysis in 2020 was delayed because of the current SARS-CoV-2 pandemic. Data analyses are well underway in relation to research papers based on the results of the available epidemiological data which do not require further PCR and metagenomic results.
A paper regarding the effects of aspirin on outcomes in pneumonia has been accepted for publication by the Journal of Internal Medicine. A manuscript comparing the outcomes of patients with symptoms of pneumonia with a confirmed infiltrate by chest x-ray (CAP) and without (SPWI) is ready and has been submitted once and is undergoing re-formatting for the submission to another journal. Preparations for the data and statistical analyses of the third article has started; it will compare the CAP group gathered in 2018-2019 to a previous study done by the study group in 2008-2009 and to the control group included in 2018-2019.

 

Blenstrup Patsche, Cecilie. Decision sum: 50.000 SEK.

Report: The NUTRIATO project began including patients in August 2017. NUTRIATO has been welcomed by both patients and health professionals, and project routines are well-established at the four trial sites. According to sample size calculations, 260 patients should be included. We had to pause inclusions temporarily due to the corona virus outbreak from March 2020 to January 2021. Due to the pause, the study period will be prolonged, but we are hopeful that the study will be concluded in 2022. We are currently at 200 inclusions. Preliminary results of NUTRIATO are not available for statistical reasons.

 

Hughes, Diarmaid. Decision sum: 50.000 SEK.

Report: The funding received from SSAC (SLS-876451, 50 000 SEK) for this project has been acknowledged in four recent publications. Although the grant proposal was on the interplay of selection, mutation and HGT in biofilm environments relative to planktonic environments but the most significant scientific advances were made using planktonic cultures (the publications listed above). In these studies we showed the important of population and transmission bottleneck sizes in the evolution of fluoroquinolone resistance (Garoff et al, 2020), the role played by selection for fitness in the spectrum of mutations found in clinical isolates (Praski Alzrigat et al, 2021), the influence of mutations affecting global transcriptional regulation on antibiotic susceptibility (Brandis et al, 2020/2021), and finally, the influence of antibiotic exposure on the expression of the QepA efflux pump, acquired by E, coli through horizontal gene transfer.

Brandis, G., Gockel, J., Garoff, L., Guy, L. and Hughes, D. (2021) Expression of the qepA1 gene is induced under antibiotic exposure. J. Antimicrob. Chemother. (Accepted, 2021-01-28).

Brandis, G., Granström, S., Leber, A.T., Bartke, K., Garoff, L., Sha, C., Huseby, D.L. and Hughes, D. (2020/2021) Mutant RNA polymerase can reduce susceptibility to antibiotics via ppGpp-independent induction of a stringent-like response. J. Antimicrob. Chemother. DOI:10.1093/jac/dkaa469

Praski Alzrigat, L., Huseby, D.L., Brandis, G. and Hughes. D. (2021) Resistance/fitness trade-off is a barrier to the evolution of MarR inactivation mutants in Escherichia coli. J. Antimicrob. Chemother. 76, 77-83.

Garoff, L., Pietsch, F., Huseby, D.L., Lilja, T., Brandis, G. and Hughes, D. (2020) Population bottlenecks strongly influence the evolutionary trajectory to fluoroquinolone resistance in Escherichia coli. Mol. Biol. Evol. 37, 1637-1646.

I sincerely thank SSAC for their support which has contributed to publications in high profile journals.

 

Lennerstrand, Johan. Decision sum: 40.000 SEK

Report: The grant received helped us to establish in our lab a pipeline for the in silico identification and study of potential inhibitors against Flaviviruses. The in silico methods, comprising molecular docking, molecular dynamics simulations and linear interaction energy methods will be instrumental for the optimization of peptide-hybrids against ZIKV protease as well as for the study and identification of novel compound targeting TBEV and other Flaviviruses. We have also adopted a protease fluorogenic enzymatic assay for testing protease inhibitors against Zika and Tick-borne encephalitis (TBE) viruses NS2B-NS3 recombinant proteases, thus complementing our cell-based assays. Thus, we have applied the in silico and in vitro methods to predict and confirm the activity of known peptide-hybrids against Zika viruses and TBE viruses. These findings represent the first report of inhibitors against TBEV to date. The results and novel methods were reported in one publication (Zika) and one manuscript (TBE) recently submitted and almost accepted with encouraging comments.

Identification of a C2-Symmetric diol based Human immunodeficiency virus protease inhibitor targeting Zika virus NS2B-NS3 protease. Akaberi D, Chinthakindi PK, Båhlström A, Palanisamy N, Sandström A, Lundkvist Å, Lennerstrand J. Journal of Biomolecular Structure and Dynamics, 2019 Dec 27:1-11. Open access publication in link: https://doi.org/10.1080/07391102.2019.1704882

Targeting the NS2B-NS3 protease of tick-borne encephalitis virus with pan-Flaviviral protease inhibitors. Akaberia D, Båhlström A, Chinthakindi PK, Nyman T, Sandström A, Järhult JD, Palanisamy N, Lundkvist Å, Lennerstrand J (Manuscript submitted to Antiviral Research Dec 2020)

 

Matussek, Andreas. Decision sum: 100.000 SEK

Report: The purpose of this study was to identify biomarkers to distinguish between Shiga toxin-producing Escherichia coli (STEC) strains with the potential to cause Hemolytic Uremic Syndrome (HUS) and less virulent strains by comparative genomics and proteomics through a Nordic collaboration. We have collected more than 400 STEC strains from Sweden and Finland, including more than 100 STEC strains from HUS patients. By comparative genomics analysis, a number of virulence genes were found to be statistically associated with severe renal sequele, these genes encoded type II and type III secretion system effectors, chaperones, and other factors. Notably, virulence genes associated with severe clinical outcomes were significantly more prevalent in O157:H7 strains. Besides the Stx, other virulence factors also play important roles in STEC pathogenesis. We analysed two STEC virulence factors intimin (encoded by the eae gene) and enterohemolysin (encoded by ehxA) and their association with disease severity. eae and its subtype γ1 were significantly overrepresented in O157:H7 strains isolated from bloody diarrhea (BD) and HUS patients. The presence of stx2+eae and stx1+stx2+eae was significantly more prevalent in strains from BD and HUS patients, respectively. The presence of ehxA was significantly associated with BD and serotype O157:H7. The ehxA genotypes (subtype B and phylogenetic group Ⅱ) could be used as risk predictors as they were associated with severe clinical symptoms such as BD and HUS. These data suggested that certain genotypes of virulence factors genes can be used as a risk predictor for HUS in STEC infections. This project has generated five manuscripts already now, two have been published in Emerg Microbes Infect and Pediatr Nephrol, the other three are under review.

 

Nilsson, Anna. Decision sum: 50.000 SEK

Report: In an attempt to reduce Staphylococcus aureus (S. aureus) infections in people who inject drugs (PWID), an intervention with repeated chlorhexidine washes was implemented in needle exchange setting. In the longitudinal study semi-quantative S. aureus cultures and interviews and clinical judgement regarding skin or soft tissue infections were performed repeatedly during one year in PWID. Thereafter a one year intervention period with repeated chlorhexidine showers was performed in which the semi quantitative cultures, interviews and clinical judgment regarding skin and soft tissue infections were continued. The results in the initial mapping year were; total number of subjects were 61 (36 men) in whom 49 (80%) S.aureus could be detected in at least of the cultures performed. The number of subjects in whom S. aureus was detected at least once in the nostrils were 35, in the throat 38 and in the perineum 38. Thirty-five subjects experienced a skin or soft tissue infection during the first mapping year and 59 different wound cultures were performed. S. aureus was detected in 24/59 of these cultures and in the rest the cultures were negative. Eight of 59 of the positive culture demonstrated a high grade of S. aureus, 2 an intermediate grade and in 14 S. aureus was detected in a low grade.
During the mapping year 11 subjects were hospitalized due to a suspected injection related infection. In total 3 individuals diseased. In 30 study subjects the chlorhexidine intervention was implemented and of these 4 experienced any type of skin or soft tissue infection. The study results have not yet been fully reviewed. The number of studied subject should be too low to find significant numbers although the preliminary results are promising. Confounding factors to the results are still to be evaluated.

 

Wejse, Christian. Decision sum: 50.000 SEK

Report: 

The trial is still ongoing, so a final report can not be give at this time.
The study was initiated in September 2015.
It is an open label multi-centre stepped wedge cluster-randomized controlled implementation trial of the use of the Bandim TBscore as a clinical tool in TB management. It is running at three Health Centers (HCs) in Bissau and Gondar simultanously. In the beginning all HCs applied usual care and diagnostic standards and then switched to use the TBscore to determine who to send for diagnostic work up at certain timepoints. All three HCs were eventually shifted to the intervention (the latest in November 2017).
Gondar (Ethiopia): The inclusions at the three HCs was stable and considerably higher than in Bissau since there are 4-5 adult consultations/ HC.
By the end of April 2018 there were a total of 1358 presumed TB patients were enrolled in Bissau, and 2896 in Gondar. A total of 233 patients were diagnosed with TB, and follow-up is ongoing, with currently 2089 having been assessed at follow-up, no data on subsequent TB diagnosis is available yet.
Before the switch to intervention (i.e. using the TBscore), only 44% of the patients were sent for sputum smear examination. The number increased considerably after the switch - to 95%. This increased the number of diagnosed smear positive Tuberculosis (TB) patients considerably (data not analyzed yet).
The 2 weeks follow-up rate in Gondar is 90%, ensuring a close follow-up and diagnostic work up.
Before the switch to intervention in March 2017, 40% of all patients were send for sputum
smear examination. Also in Bissau, as in Gondar, this number increased considerably to 99%
after the last center was switched to use the TBscore in November 2017.
The 2 weeks follow-up rate in Bissau is 89%.

The intervention thus seems to be highly effective in terms of increasing use of TB diagnostics, and data on increase of diagnostic yield is pending.