143 results on '"Kantele, Anu"'
Search Results
2. Carbapenemase-producing Enterobacterales emerging in Finland's capital region over 2010-2023: increasing proportion of CPE cases first detected in clinical samples.
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Kajova M, Khawaja T, Kainulainen K, and Kantele A
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- 2024
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3. The assembly of neutrophil inflammasomes during COVID-19 is mediated by type I interferons.
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Cabrera LE, Jokiranta ST, Mäki S, Miettinen S, Kant R, Kareinen L, Sironen T, Pietilä JP, Kantele A, Kekäläinen E, Lindgren H, Mattila P, Kipar A, Vapalahti O, and Strandin T
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- Humans, Animals, Mice, Male, Female, Middle Aged, Immunity, Innate, Adult, Mice, Inbred C57BL, COVID-19 immunology, Neutrophils immunology, Neutrophils metabolism, Interferon Type I metabolism, Interferon Type I immunology, Inflammasomes immunology, Inflammasomes metabolism, SARS-CoV-2 immunology
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The severity of COVID-19 is linked to excessive inflammation. Neutrophils represent a critical arm of the innate immune response and are major mediators of inflammation, but their role in COVID-19 pathophysiology remains poorly understood. We conducted transcriptomic profiling of neutrophils obtained from patients with mild and severe COVID-19, as well as from SARS-CoV-2 infected mice, in comparison to non-infected healthy controls. In addition, we investigated the inflammasome formation potential in neutrophils from patients and mice upon SARS-CoV-2 infection. Transcriptomic analysis of polymorphonuclear cells (PMNs), consisting mainly of mature neutrophils, revealed a striking type I interferon (IFN-I) gene signature in severe COVID-19 patients, contrasting with mild COVID-19 and healthy controls. Notably, low-density granulocytes (LDGs) from severe COVID-19 patients exhibited an immature neutrophil phenotype and lacked this IFN-I signature. Moreover, PMNs from severe COVID-19 patients showed heightened nigericin-induced caspase1 activation, but reduced responsiveness to exogenous inflammasome priming. Furthermore, IFN-I emerged as a priming stimulus for neutrophil inflammasomes. These findings suggest a potential role for neutrophil inflammasomes in driving inflammation during severe COVID-19. Altogether, these findings open promising avenues for targeted therapeutic interventions to mitigate the pathological processes associated with the disease., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Cabrera et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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- 2024
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4. Infective SARS-CoV-2 in Skull Sawdust at Autopsy, Finland.
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Kantonen JN, Kuivanen S, Smura T, Puttonen H, Kekäläinen E, Sajantila A, Myllykangas L, Kantele A, Vapalahti O, Mäyränpää MI, and Carpén O
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- Humans, Finland epidemiology, Male, Female, Occupational Exposure, Middle Aged, Aged, Adult, Personal Protective Equipment, Aged, 80 and over, COVID-19 epidemiology, COVID-19 virology, COVID-19 pathology, SARS-CoV-2 genetics, SARS-CoV-2 isolation & purification, Autopsy, Skull pathology, Skull virology
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We assessed the distribution of SARS-CoV-2 at autopsy in 22 deceased persons with confirmed COVID-19. SARS-CoV-2 was found by PCR (2/22, 9.1%) and by culture (1/22, 4.5%) in skull sawdust, suggesting that live virus is present in tissues postmortem, including bone. Occupational exposure risk is low with appropriate personal protective equipment.
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- 2024
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5. Deep sequencing of Escherichia coli exposes colonisation diversity and impact of antibiotics in Punjab, Pakistan.
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Khawaja T, Mäklin T, Kallonen T, Gladstone RA, Pöntinen AK, Mero S, Thorpe HA, Samuelsen Ø, Parkhill J, Izhar M, Akhtar MW, Corander J, and Kantele A
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- Pakistan epidemiology, Humans, Feces microbiology, Female, Male, Genome, Bacterial genetics, Adult, Genetic Variation, Middle Aged, Young Adult, Phylogeny, Adolescent, Child, Escherichia coli genetics, Escherichia coli drug effects, Escherichia coli isolation & purification, Anti-Bacterial Agents pharmacology, Escherichia coli Infections epidemiology, Escherichia coli Infections microbiology, Escherichia coli Infections drug therapy, Drug Resistance, Multiple, Bacterial genetics, High-Throughput Nucleotide Sequencing
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Multi-drug resistant (MDR) E. coli constitute a major public health burden globally, reaching the highest prevalence in the global south yet frequently flowing with travellers to other regions. However, our comprehension of the entire genetic diversity of E. coli colonising local populations remains limited. We quantified this diversity, its associated antimicrobial resistance (AMR), and assessed the impact of antibiotic use by recruiting 494 outpatients and 423 community dwellers in the Punjab province, Pakistan. Rectal swab and stool samples were cultured on CLED agar and DNA extracted from plate sweeps was sequenced en masse to capture both the genetic and AMR diversity of E. coli. We assembled 5,247 E. coli genomes from 1,411 samples, displaying marked genetic diversity in gut colonisation. Compared with high income countries, the Punjabi population generally showed a markedly different distribution of genetic lineages and AMR determinants, while use of antibiotics elevated the prevalence of well-known globally circulating MDR clinical strains. These findings implicate that longitudinal multi-regional genomics-based surveillance of both colonisation and infections is a prerequisite for developing mechanistic understanding of the interplay between ecology and evolution in the maintenance and dissemination of (MDR) E. coli., (© 2024. The Author(s).)
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- 2024
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6. Veterinarians and zoonotic pathogens, infections and diseases - questionnaire study and case series, Finland.
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Jokelainen P, Virtala AK, Raulo S, Kantele A, Vapalahti O, and Kinnunen PM
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- Dogs, Animals, Humans, Horses, Cattle, Finland epidemiology, Zoonoses epidemiology, Surveys and Questionnaires, Veterinarians, Bites and Stings, Gastroenteritis epidemiology, Tinea
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Background: Veterinarians are at risk for numerous zoonotic infections. In this paper, we summarise descriptions of zoonotic infections from a questionnaire study and a series of work-related zoonotic cases, aiming to add to the knowledge on occupational zoonotic risks of veterinarians., Methods: We collected data on zoonotic infections contracted by veterinarians in Finland in two studies:1) using a questionnaire in 2009, and 2) inviting veterinarians who had encountered an occupational zoonosis to report it in structured interviews in 2019., Results and Conclusions: In the questionnaire study in 2009, of 306 veterinarians several reported zoonotic bacterial skin infections (12%), dermatophytosis (ringworm; 4.2%), virus infections (3.9%), bacterial gastroenteritis (3.3%), other bacterial zoonoses (2.3%), and parasitic infections/infestations (2.3%). In the 2019 interviews, 16 occupational zoonosis cases were reported. Of them, seven were selected to the case series. The selected cases included Capnocytophaga canimorsus sepsis following a dog bite, cryptosporidiosis after a contact with calves, cutaneous listeriosis following calving assistance, Salmonella gastroenteritis contracted at laboratory, Trichophyton dermatophytosis after equine contact, Bacillus anthracis exposure at necropsy, and exposure to rabies through a horse bite. In four of the seven cases, the veterinarian disagreed or strongly disagreed with having had good knowledge of the zoonosis before the incident. The results from the questionnaire study and the case series illustrate the variety of zoonotic pathogens that veterinarians may encounter. There is a need to improve the occupational health of veterinarians and to increase awareness in the occupational health sector. We encourage addressing this need using a One Health approach.
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- 2024
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7. Whole Blood as a Sample Matrix in Homogeneous Time-Resolved Assay-Förster Resonance Energy Transfer-Based Antibody Detection.
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Lintala A, Vapalahti O, Nousiainen A, Kantele A, and Hepojoki J
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The protein-L-utilizing Förster resonance energy transfer (LFRET) assay enables mix-and-read antibody detection, as demonstrated for sera from patients with, e.g., severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Zika virus, and orthohantavirus infections. In this study, we compared paired serum and whole blood (WB) samples of COVID-19 patients and SARS-CoV-2 vaccine recipients. We found that LFRET also detects specific antibodies in WB samples. In 44 serum-WB pairs from patients with laboratory-confirmed COVID-19, LFRET showed a strong correlation between the sample materials. By analyzing 89 additional WB samples, totaling 133 WB samples, we found that LFRET results were moderately correlated with enzyme-linked immunosorbent assay results for samples collected 2 to 14 months after receiving COVID-19 diagnosis. However, the correlation decreased for samples >14 months after receiving a diagnosis. When comparing the WB LFRET results to neutralizing antibody titers, a strong correlation emerged for samples collected 1 to 14 months after receiving a diagnosis. This study also highlights the versatility of LFRET in detecting antibodies directly from WB samples and suggests that it could be employed for rapidly assessing antibody responses to infectious agents or vaccines.
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- 2024
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8. Mucosal-Associated Invariant T Cells are not susceptible in vitro to SARS-CoV-2 infection but accumulate into the lungs of COVID-19 patients.
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Huang X, Kantonen J, Nowlan K, Nguyen NA, Jokiranta ST, Kuivanen S, Heikkilä N, Mahzabin S, Kantele A, Vapalahti O, Myllykangas L, Heinonen S, Mäyränpää MI, Strandin T, and Kekäläinen E
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- Humans, Angiotensin-Converting Enzyme 2, Leukocytes, Mononuclear, SARS-CoV-2, Lung, Mucosal-Associated Invariant T Cells, COVID-19, Lymphopenia
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Prolonged T cell lymphopenia is common in COVID-19, caused by SARS-CoV-2. While the mechanisms of lymphopenia during COVID-19 remain elusive, it is especially pronounced in a specialized innate-like T cell population called Mucosal Associated Invariant T cells (MAITs). MAITs has been suggested to express Angiotensin-Converting Enzyme 2 (ACE2), which is the well-known cellular receptor for SARS-CoV-2. However, it is still unclear if SARS-CoV-2 can infect or affect MAIT cells directly. In this study, we performed multicolor flow cytometry on peripheral blood mononuclear cells obtained from COVID-19 patients to assess the frequencies of CD8
+ Vα7.2+ CD161+ MAIT subsets at acute and convalescent disease phases. The susceptibility of MAITs and T cells to direct exposure by SARS-CoV-2 was analysed using cells isolated from healthy donor buffy coats by viability assays, virus-specific RT-PCR, and flow cytometry. In situ lung immunofluorescence was used to evaluate retention of T cells, especially MAIT cells, in lung tissues during acute COVID-19. Our study confirms previous reports indicating that circulating MAITs are activated, and their frequency is declined in patients with acute SARS-CoV-2 infection, whereas an accumulation of MAITs and T cells was seen in the lung tissue of individuals with fatal COVID-19. However, despite a fraction of MAITs found to express ACE2, no evidence for the susceptibility of MAITs for direct infection or activation by SARS-CoV-2 particles was observed. Thus, their activation and decline in the circulation is most likely explained by indirect mechanisms involving other immune cells and cytokine-induced pro-inflammatory environment but not by direct exposure to viral particles at the infection site., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)- Published
- 2024
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9. Neutralizing antibodies after the third COVID-19 vaccination in healthcare workers with or without breakthrough infection.
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Reinholm A, Maljanen S, Jalkanen P, Altan E, Tauriainen S, Belik M, Skön M, Haveri A, Österlund P, Iakubovskaia A, Pasternack A, Naves RA, Ritvos O, Miettinen S, K Häkkinen H, Ivaska L, Tähtinen PA, Lempainen J, Kantele A, Kakkola L, Julkunen I, and Kolehmainen P
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Background: Vaccinations against the SARS-CoV-2 are still crucial in combating the ongoing pandemic that has caused more than 700 million infections and claimed almost 7 million lives in the past four years. Omicron (B.1.1.529) variants have incurred mutations that challenge the protection against infection and severe disease by the current vaccines, potentially compromising vaccination efforts., Methods: We analyzed serum samples taken up to 9 months post third dose from 432 healthcare workers. Enzyme-linked immunosorbent assays (ELISA) and microneutralization tests (MNT) were used to assess the prevalence of vaccine-induced neutralizing antibodies against various SARS-CoV-2 Omicron variants., Results: In this serological analysis we show that SARS-CoV-2 vaccine combinations of BNT162b2, mRNA-1273, and ChAdOx1 mount SARS-CoV-2 binding and neutralizing antibodies with similar kinetics, but with differing neutralization capabilities. The most recent Omicron variants, BQ.1.1 and XBB.1.5, show a significant increase in the ability to escape vaccine and infection-induced antibody responses. Breakthrough infections in thrice vaccinated adults were seen in over 50% of the vaccinees, resulting in a stronger antibody response than without infection., Conclusions: Different three-dose vaccine combinations seem to induce considerable levels of neutralizing antibodies against most SARS-CoV-2 variants. However, the ability of the newer variants BQ1.1 and XBB 1.5 to escape vaccine-induced neutralizing antibody responses underlines the importance of updating vaccines as new variants emerge., (© 2024. The Author(s).)
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- 2024
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10. Stable Levels of Antibodies Against Unrelated Toxoid Vaccines After COVID-19: COVID-19 Infection Does Not Affect Toxoid Vaccine Antibody Levels.
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Jokiranta ST, Miettinen S, Salonen S, Kareinen L, Uusitalo R, Korhonen EM, Virtanen J, Kivistö I, Aaltonen K, Mosselhy DA, Lääveri T, Kantele A, Arstila TP, Jarva H, Vapalahti O, Heinonen S, and Kekäläinen E
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Background: Lymphopenia is common in COVID-19. This has raised concerns that COVID-19 could affect the immune system akin to measles infection, which causes immune amnesia and a reduction in protective antibodies., Methods: We recruited COVID-19 patients (n = 59) in Helsinki, Finland, and collected plasma samples on 2 to 3 occasions during and after infection. We measured IgG antibodies to diphtheria toxin, tetanus toxoid, and pertussis toxin, along with total IgG, SARS-CoV-2 spike protein IgG, and neutralizing antibodies. We also surveyed the participants for up to 17 months for long-term impaired olfaction as a proxy for prolonged post-acute COVID-19 symptoms., Results: No significant differences were found in the unrelated vaccine responses while the serological response against COVID-19 was appropriate. During the acute phase of the disease, the SARSCoV-2 IgG levels were lower in outpatients when compared to inpatients. SARS-CoV-2 serology kinetics matched expectations. In the acute phase, anti-tetanus and anti-diphtheria IgG levels were lower in patients with prolonged impaired olfaction during follow up than in those without., Conclusions: We could not detect significant decline in overall humoral immunity during or after COVID-19 infection. In severe COVID-19, there appears to be a temporary decline in total IgG levels., Competing Interests: All authors declare that they have no conflicts of interest., (Copyright © 2024 Pathogens and Immunity.)
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- 2024
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11. International travel increases risk of urinary tract infection caused by extended-spectrum beta-lactamase-producing Enterobacterales-three-arm case-control study.
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Patjas A, Martelius A, Ollgren J, and Kantele A
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- Female, Humans, Male, Anti-Bacterial Agents therapeutic use, beta-Lactamases, Case-Control Studies, Escherichia coli, Risk Factors, Escherichia coli Infections drug therapy, Urinary Tract Infections drug therapy, Urinary Tract Infections epidemiology
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Background: Extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-PE) have worldwide become increasingly prevalent as pathogens causing urinary tract infections (UTIs), posing challenges in their treatment. Of particular concern are travellers to low- and middle-income countries (LMICs), a substantial proportion of whom become colonized by ESBL-PE, with UTIs as the most common clinical manifestation. Seeking tools for preventing ESBL-PE UTI, we explored factors associated with (i) any UTI (versus control), (ii) ESBL-PE UTI (versus control) and (iii) ESBL-PE versus non-ESBL-PE UTI., Methods: During 2015-20, we recruited patients with recent ESBL-PE or non-ESBL-PE UTIs, and controls with no UTI to fill in questionnaires covering potential (ESBL-PE-)UTI risk factors., Results: Of our 430 participants, 130 had ESBL-PE UTI and 187 non-ESBL-PE UTI; 113 were controls. Our three comparisons showed several risk factors as exemplified for any UTI versus controls by female sex, lower education, age, diabetes, antibiotic use, diarrhoea; for ESBL-PE UTI versus controls by travel to LMICs, antibiotic use, swimming; and ESBL-PE versus non-ESBL-PE UTI by male sex, higher education, LMIC travel (participant/household member), pets and antibiotic use. Weekly fish meals appeared protective against both UTI and ESBL-PE UTI., Conclusions: Of the numerous factors predisposing to UTI and/or ESBL-PE UTI, our study highlights antibiotic use and LMIC travel. Household members' LMIC travel appears to pose a risk of ESBL-PE UTI, pointing to household transmission of travel-acquired uropathogens. As predisposing factors to multidrug-resistant UTI, international travel and antibiotic use constitute practical targets for prevention efforts., (© International Society of Travel Medicine 2023. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)
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- 2024
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12. Phenotypic Detection of Carbapenemase and AmpC-β-Lactamase Production among Extended Spectrum β-Lactamase (ESBL)-Producing Escherichia coli and Klebsiella spp. Isolated from Clinical Specimens.
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Garba Z, Kaboré B, Bonkoungou IJO, Natama MH, Rouamba T, Haukka K, Kirveskari JP, Tinto H, Sangaré L, Barro N, and Kantele A
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Introduction : Data on antimicrobial resistance (AMR) are sparse across numerous African countries, as microbiological analyses are not routinely conducted and surveillance data are not collected. Accordingly, clinical samples are not routinely tested for carbapenem-resistant bacteria and, therefore, the general understanding of their prevalence in the region remains limited. Methods : Between January 2020 and June 2022, we collected extended spectrum β-lactamase (ESBL)-producing Enterobacterales (ESBL-PE) isolates from five hospitals in Burkina Faso. After an initial culture on ESBL-selective media, the species were identified using API20E and isolates were tested against 13 antimicrobial agents using the disc diffusion method on Mueller-Hinton (MH) agar. ESBL production was confirmed via a double-disc synergy test. Production of carbapenemases and AmpC-β-lactamases and phenotypic co-resistance were determined. Results : Among the 473 ESBL-PE, 356 were ESBL- E. coli (ESBL-Ec) and 117 were Klebsiella spp. (ESBL-K). Of these isolates, 5.3% were carbapenemase and 5.3% were AmpC-β-lactamase-positive. Three types of carbapenemases were identified: 19 NDM, 3 OXA-48-like and 1 VIM. Two isolates produced both NDM and OXA-48-like carbapenemases. Carbapenemase producers were detected at all levels of healthcare. Co-resistance rates were up to 85% for aminoglycosides, 90% for sulfonamides, 95% for fluoroquinolones and 25% for chloramphenicol. Fosfomycin resistance was 6% for ESBL-Ec and 49% for ESBL-K (49%). Conclusions : Some of the ESBL-Ec and ESBL-K co-produced carbapenemases and/or AmpC-β-lactamases at all healthcare levels and in various sample types with high co-resistance rates to non-betalactams. Carbapenem resistance is no longer rare, calling for testing in routine diagnostics, a comprehensive resistance surveillance system and infection control within healthcare.
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- 2023
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13. Long COVID-associated symptoms prevalent in both SARS-CoV-2 positive and negative individuals: A prospective follow-up study.
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Kantele A, Paajanen J, Pietilä JP, Vapalahti O, Pakkanen SH, and Lääveri T
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Background: Research into persistent symptoms among SARS-CoV-2-positive i.e. CoV(+) patients mostly focuses on hospitalized individuals. Our prospective follow-up study compares long COVID-associated symptoms among laboratory-confirmed CoV(+) and SARS-CoV-2 negative [CoV(-)] individuals., Methods: SARS-CoV-2 RT-PCR-tested volunteers were recruited into four cohorts: 1) CoV(+) outpatients, 2) CoV(-) outpatients, 3) CoV(+) intensive care unit (ICU) inpatients, and 4) CoV(+) non-ICU inpatients. Neutralizing antibodies were assessed and questionnaires filled in at enrolment and days 90-120, 121-180, 181-270, 271-365, and 365-533., Results: Of the 1326 participants, 1191 were CoV(+): 46 ICU, 123 non-ICU, and 1022 outpatients; 135 were CoV(-) outpatient controls. Both CoV(+) outpatients and CoV(-) controls showed high overall symptom rates at all time points. More prevalent among CoV(+) than CoV(-) outpatients were only impaired olfaction and taste; many others proved more frequent for CoV(-) participants. At ≥181 days, fatigue, dyspnoea, various neuropsychological symptoms and several others were recorded more often for CoV(+) inpatients than outpatients., Conclusions: Long COVID-associated symptoms were more frequent among hospitalized than non-hospitalized CoV(+) participants. As for outpatients, only impaired olfaction and taste showed higher rates in the CoV(+) group; some symptoms proved even more common among those CoV(-). Besides suggesting low long COVID prevalences for outpatients, our results highlight the weight of negative controls., Competing Interests: Tinja Lääveri: Honoraria (Pfizer) unrelated to this article. Anu Kantele: Research grants (Valneva, Pfizer) unrelated to this article. None of the authors declare any competing interests that could have influenced the work reported in this paper. Other authors declare no conflict of interests., (© 2023 The Authors. Published by Elsevier Ltd.)
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- 2023
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14. Coadministered pneumococcal conjugate vaccine decreases immune response to hepatitis A vaccine: a randomized controlled trial.
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Riekkinen M, Pakkanen SH, Hutse V, Roukaerts I, Ollgren J, Käyhty H, Herzog C, Rombo L, and Kantele A
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- Humans, Adolescent, Adult, Hepatitis A Vaccines adverse effects, Vaccines, Conjugate, Hepatitis A Antibodies, Antibodies, Bacterial, Pneumococcal Vaccines, Streptococcus pneumoniae, Immunity, Immunoglobulin G, Double-Blind Method, Hepatitis A prevention & control, Pneumococcal Infections prevention & control
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Objectives: We explored the influence of coadministration on safety and immunogenicity of the most common travellers' vaccine hepatitis A (HepA) and the pneumococcal conjugate vaccine (PCV) increasingly used both at home and before travel., Methods: Volunteers aged ≥18 years (n = 305) were randomly assigned 1:1:1 into three groups receiving: 13-valent PCV (PCV13) + HepA, PCV13, or HepA. Anti-pneumococcal IgG concentrations, opsonophagocytic activity (OPA) titres, and total hepatitis A antibody (anti-HAV) concentrations were measured before and 28 ± 3 days after vaccination. Adverse events (AEs) were recorded over 4 weeks., Results: After vaccination, the anti-HAV geometric mean concentration was significantly lower in the PCV13+HepA than the HepA group: 34.47 mIU/mL (95% CI: 26.42-44.97 mIU/mL) versus 72.94 mIU/mL (95% CI: 55.01-96.72 mIU/mL), p < 0.001. Anti-HAV ≥10 mIU/mL considered protective was reached by 71 of 85 (83.5%) in the PCV13+HepA group versus 76 of 79 (96.2%) in the HepA group, p 0.008. The increases in anti-pneumococcal IgG and OPA levels were comparable in the PCV13+HepA and PCV13 groups, apart from a bigger rise in the PCV13+HepA group for serotype 3 (one-way ANOVA: serotype 3 IgG p 0.010, OPA p 0.002). AEs proved more frequent among those receiving PCV13 than HepA, but simultaneous administration did not increase the rates: ≥one AE was reported by 45 of 56 (80.4%) PCV13, 43 of 54 (79.6%) PCV13+HepA, and 25 of 53 (47.2%) HepA recipients providing structured AE data., Discussion: Coadministration of HepA and PCV13 did not cause safety concerns, nor did it impact the patients' response to PCV13, apart from serotype 3. However, coadministered PCV13 significantly impaired antibody responses to HepA., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
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- 2023
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15. Safety and immunogenicity of ETVAX®, an oral inactivated vaccine against enterotoxigenic Escherichia coli diarrhoea: a double-blinded, randomized, placebo-controlled trial amongst Finnish travellers to Benin, West Africa.
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Kantele A, Riekkinen M, Jokiranta TS, Pakkanen SH, Pietilä JP, Patjas A, Eriksson M, Khawaja T, Klemets P, Marttinen K, Siikamäki H, Lundgren A, Holmgren J, Lissmats A, Carlin N, and Svennerholm AM
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- Child, Humans, Benin, Vaccines, Inactivated, Finland, Lipopolysaccharides, Africa, Western, Diarrhea prevention & control, Immunoglobulin A, Enterotoxigenic Escherichia coli
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Background: No licensed human vaccines are available against enterotoxigenic Escherichia coli (ETEC), a major diarrhoeal pathogen affecting children in low- and middle-income countries and foreign travellers alike. ETVAX®, a multivalent oral whole-cell vaccine containing four inactivated ETEC strains and the heat-labile enterotoxin B subunit (LTB), has proved promising in Phase 1 and Phase 1/ 2 studies., Methods: We conducted a Phase 2b double-blinded, randomized, placebo-controlled trial amongst Finnish travellers to Benin, West Africa. This report presents study design and safety and immunogenicity data. Volunteers aged 18-65 years were randomized 1:1 to receive ETVAX® or placebo. They visited Benin for 12 days, provided stool and blood samples and completed adverse event (AE) forms. IgA and IgG antibodies to LTB and O78 lipopolysaccharide (LPS) were measured by electrochemiluminescence., Results: The AEs did not differ significantly between vaccine (n = 374) and placebo (n = 375) recipients. Of the solicited AEs, loose stools/diarrhoea (26.7/25.9%) and stomach ache (23.0/20.0%) were reported most commonly. Of all possibly/probably vaccine-related AEs, the most frequent were gastrointestinal symptoms (54.0/48.8%) and nervous system disorders (20.3/25.1%). Serious AEs were recorded for 4.3/5.6%, all unlikely to be vaccine related. Amongst the ETVAX® recipients, LTB-specific IgA antibodies increased 22-fold. For the 370/372 vaccine/placebo recipients, the frequency of ≥2-fold increases against LTB was 81/2.4%, and against O78 LPS 69/2.7%. The majority of ETVAX® recipients (93%) responded to either LTB or O78., Conclusions: This Phase 2b trial is the largest on ETVAX® undertaken amongst travellers to date. ETVAX® showed an excellent safety profile and proved strongly immunogenic, which encourages the further development of this vaccine., (© International Society of Travel Medicine 2023. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)
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- 2023
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16. Treatment of Dientamoeba fragilis : A retrospective Finnish analysis of faecal clearance and clinical cure comparing four antiprotozoal drugs.
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Pietilä JP, Häkkinen TA, Pakarinen L, Ollgren J, and Kantele A
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Background: Dientamoeba fragilis ( DF ), the most common intestinal protozoal pathogen in affluent countries, causes asymptomatic or symptomatic infections with severity ranging from mild to disabling. Currently, many studies of treatment options only have small sample sizes and report results that are partly contradictory., Methods: Investigating data retrieved from Helsinki University Hospital and Helsinki City patient records, we searched for the most effective antiprotozoal in treating DF infections. To study microbiological clearance of DF , we collected laboratory results of control samples from patients given one of four commonly used antiprotozoals: doxycycline, metronidazole, paromomycin, or secnidazole. For patients symptomatic prior to antiprotozoal treatment, we also retrieved data on clinical outcomes. Furthermore, we explored factors associated with faecal clearance and clinical cure., Results: A total of 369 patients (median age 38) and 492 treatment episodes were included. Paromomycin (n = 297) proved effective (clearance rate 83%), showing strong association with faecal clearance (aOR 18.08 [7.24-45.16], p < 0.001). For metronidazole the rate was 42% (n = 84), for secnidazole 37% (n = 79), and doxycycline 22% (n = 32). In pairwise comparisons, paromomycin outdid the three other regimens (p < 0.001, χ
2 test). Faecal clearance was associated with clinical cure (aOR 5.85 [3.02-11.32], p < 0.001)., Conclusions: Faecal clearance, strongly associated with clinical cure, is most effectively achieved with a course of paromomycin, followed by metronidazole, secnidazole and doxycycline. Our findings will be useful in devising treatment guidelines for adults with symptomatic D. fragilis infection., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)- Published
- 2023
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17. Image-based and machine learning-guided multiplexed serology test for SARS-CoV-2.
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Pietiäinen V, Polso M, Migh E, Guckelsberger C, Harmati M, Diosdi A, Turunen L, Hassinen A, Potdar S, Koponen A, Sebestyen EG, Kovacs F, Kriston A, Hollandi R, Burian K, Terhes G, Visnyovszki A, Fodor E, Lacza Z, Kantele A, Kolehmainen P, Kakkola L, Strandin T, Levanov L, Kallioniemi O, Kemeny L, Julkunen I, Vapalahti O, Buzas K, Paavolainen L, Horvath P, and Hepojoki J
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- Humans, COVID-19 Testing, Acclimatization, Machine Learning, SARS-CoV-2, COVID-19
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We present a miniaturized immunofluorescence assay (mini-IFA) for measuring antibody response in patient blood samples. The method utilizes machine learning-guided image analysis and enables simultaneous measurement of immunoglobulin M (IgM), IgA, and IgG responses against different viral antigens in an automated and high-throughput manner. The assay relies on antigens expressed through transfection, enabling use at a low biosafety level and fast adaptation to emerging pathogens. Using severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as the model pathogen, we demonstrate that this method allows differentiation between vaccine-induced and infection-induced antibody responses. Additionally, we established a dedicated web page for quantitative visualization of sample-specific results and their distribution, comparing them with controls and other samples. Our results provide a proof of concept for the approach, demonstrating fast and accurate measurement of antibody responses in a research setup with prospects for clinical diagnostics., Competing Interests: P.H. is the founder and shareholder and A. Kriston and F.K. are employees of Single-Cell Technologies Ltd. This study has been protected with invention disclosures (ID965/2020 and ID115/2021 University of Helsinki, Finland), and the patent application has been filed (Hungary, no. P2100295)., (© 2023 The Authors.)
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- 2023
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18. Isolation and characterization of three novel Acinetobacter baumannii phages from Beninese hospital wastewater.
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Kolsi A, Haukka K, Dougnon V, Agbankpè AJ, Fabiyi K, Virta M, Skurnik M, Kantele A, and Kiljunen S
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- Humans, Wastewater, Phylogeny, Host Specificity, Anti-Bacterial Agents, Bacteriophages genetics, Acinetobacter baumannii
- Abstract
Acinetobacter baumannii is an opportunistic pathogen that is mostly associated with hospital-acquired infections. The rapid emergence of multi- and pan-drug-resistant Acinetobacter strains poses an increasing challenge in hospitals. Phage therapy offers one treatment option for infections caused by A. baumannii. We isolated three phages from Beninese hospital wastewater - fBenAci001, fBenAci002, and fBenAci003 - that infected clinical A. baumannii strains from Finnish patients. Phylogenetic analysis showed that these phages resemble phages of the genus Friunavirus, family Autographiviridae. The isolated phages meet the requirements set for phages used for phage therapy. However, they were found to have a narrow host range, which may limit their therapeutic use., (© 2023. The Author(s).)
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- 2023
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19. Safety and Immunogenicity of an Investigational Respiratory Syncytial Virus Vaccine (RSVPreF3) in Mothers and Their Infants: A Phase 2 Randomized Trial.
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Bebia Z, Reyes O, Jeanfreau R, Kantele A, De Leon RG, Sánchez MG, Banooni P, Gardener GJ, Rasero JLB, Pardilla MBE, Langley JM, Di Leo CM, Botelho-Nevers E, Buttery J, Laurichesse H, Madhi SA, García AM, Stanley T, Barjat T, Griffith R, Castrejón-Alba MM, de Heusch M, Dieussaert I, Hercor M, Lese P, Qian H, Tullio AN, and Henry O
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- Pregnancy, Humans, Female, Infant, Infant, Newborn, Adolescent, Young Adult, Adult, Antibodies, Viral, Antibodies, Neutralizing, Mothers, Viral Fusion Proteins, Placenta, Immunogenicity, Vaccine, Respiratory Syncytial Virus Vaccines, Respiratory Syncytial Virus Infections prevention & control, Respiratory Syncytial Virus, Human
- Abstract
Background: In a phase 1/2 study, a maternal respiratory syncytial virus vaccine candidate (RSVPreF3) demonstrated an acceptable safety profile and efficiently increased RSV-specific humoral immune responses in non-pregnant women., Methods: In this phase 2 observer-blind, placebo-controlled, randomized clinical trial (NCT04126213), the safety of RSVPreF3 (60 or 120 µg), administered during late second or third trimester, was evaluated in 213 18- to 40-year-old healthy pregnant women through 6 months postdelivery and their offspring through infancy; immunogenicity was evaluated through day 43 postdelivery and day 181 postbirth, respectively., Results: RSVPreF3 was well tolerated. No pregnancy-related or neonatal adverse events of special interest were considered vaccine/placebo related. In the 60 and 120 µg RSVPreF3 groups: (1) neutralizing antibody (nAb) titers in mothers increased 12.7- and 14.9-fold against RSV-A and 10.6- and 13.2-fold against RSV-B, respectively, 1 month postvaccination and remained 8.9-10.0-fold over prevaccination at day 43 postdelivery; (2) nAb titers were consistently higher compared to placebo recipients; (3) placental transfer ratios for anti-RSVPreF3 antibodies at birth were 1.62 and 1.90, respectively, and (4) nAb levels in infants were highest at birth and declined through day 181 postbirth., Conclusions: RSVPreF3 maternal vaccination had an acceptable safety risk profile and induced robust RSV-specific immune responses with successful antibody transfer to their newborns., Clinical Trials Registration: NCT04126213., Competing Interests: Potential conflicts of interest. A. N. T., H. Q., I. D., M. H., M. d. H., O. H., P. L., M. M. C., and Z. B. are or were employees of the GSK group of companies at the time of the study. A. N. T., I. D., M. d. H., M. M. C., and O. H. report holding shares of the GSK group of companies. P. L. reports personal fees from GSK. O. R. declares personal fees from CEVAXIN during the conduct of the study and outside the submitted work. A. K. declares institutional financial support from GSK for conducting this study; investigator-initiated grants from Valneva and Pfizer, the latter two outside this study; and declares no personal fees from any vaccine companies. M. G. S. declares personal fees and institutional financial support from GSK during the conduct of the study. J. M. L. declares holding the Canadian Institutes of Health Research-GSK Chair in Pediatric Vaccinology at Dalhousie University; institutional financial support from GSK during the conduct of the study; other compensation from Immunovaccine; and grants from Novavax, Janssen, and Regeneron, outside the submitted work; in all cases these are paid to Dalhousie University. J. B. declares institutional financial support from GSK, Pfizer, and MedImmune during the conduct of the study and outside the submitted work. S. A. M. has received institution grants and personal fees from BMGF and GSK; and institution grants from Pfizer, Novavax, AstraZeneca, and Minervax during the conduct of the study. R. G. declares personal fees from Optimal Clinical Trials during the conduct of the study. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)
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- 2023
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20. Superspreading of SARS-CoV-2 Omicron BA.2.23 among vaccinated Finnish adults: symptomatic COVID-19 only contracted by those without recent infection.
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Riekkinen M, Kajova M, Eriksson M, Luukkainen A, Holmberg V, Aro T, Pakkanen SH, Miettinen S, Montonen R, Smura T, Lääveri T, and Kantele A
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- Humans, SARS-CoV-2 genetics, Finland epidemiology, Disease Outbreaks, Fever, COVID-19 prevention & control
- Abstract
An outbreak of SARS-CoV-2 was confirmed after an academic party in Helsinki, Finland, in 2022. All 70 guests were requested to fill in follow-up questionnaires; serologic analyses and whole-genome sequencing (WGS) were conducted when possible.Of those participating - all but one with ≥3 vaccine doses - 21/53 (40%) had test-confirmed symptomatic COVID-19: 7% of those with earlier episodes and 76% of those without. Half (11/21) were febrile, but none needed hospitalisation. WGS revealed subvariant BA.2.23.Compared to vaccination alone, our data suggest remarkable protection by hybrid immunity against symptomatic infection, particularly in instances of recent infections with homologous variants.
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- 2023
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21. The highly diverse plasmid population found in Escherichia coli colonizing travellers to Laos and its role in antimicrobial resistance gene carriage.
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Snaith AE, Dunn SJ, Moran RA, Newton PN, Dance DAB, Davong V, Kuenzli E, Kantele A, Corander J, and McNally A
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- Humans, Anti-Bacterial Agents pharmacology, Laos, beta-Lactamases genetics, Drug Resistance, Bacterial genetics, Plasmids genetics, Escherichia coli, Escherichia coli Infections epidemiology
- Abstract
Increased colonization by antimicrobial-resistant organisms is closely associated with international travel. This study investigated the diversity of mobile genetic elements involved with antimicrobial resistance (AMR) gene carriage in extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli that colonized travellers to Laos. Long-read sequencing was used to reconstruct complete plasmid sequences from 48 isolates obtained from the daily stool samples of 23 travellers over a 3 week period. This method revealed a collection of 105 distinct plasmids, 38.1 % ( n =40) of which carried AMR genes. The plasmids in this population were diverse, mostly unreported and included 38 replicon types, with F-type plasmids ( n =23) the most prevalent amongst those carrying AMR genes. Fine-scale analysis of all plasmids identified numerous AMR gene contexts and emphasized the importance of IS elements, specifically members of the IS 6/ IS 26 family, in the evolution of complex multidrug resistance regions. We found a concerning convergence of ESBL and colistin resistance determinants, with three plasmids from two different F-type lineages carrying bla
CTX-M and mcr genes. The extensive diversity seen here highlights the worrying probability that stable new vehicles for AMR will evolve in E. coli populations that can disseminate internationally through travel networks.- Published
- 2023
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22. Bivalent Prefusion F Vaccine in Pregnancy to Prevent RSV Illness in Infants.
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Kampmann B, Madhi SA, Munjal I, Simões EAF, Pahud BA, Llapur C, Baker J, Pérez Marc G, Radley D, Shittu E, Glanternik J, Snaggs H, Baber J, Zachariah P, Barnabas SL, Fausett M, Adam T, Perreras N, Van Houten MA, Kantele A, Huang LM, Bont LJ, Otsuki T, Vargas SL, Gullam J, Tapiero B, Stein RT, Polack FP, Zar HJ, Staerke NB, Duron Padilla M, Richmond PC, Koury K, Schneider K, Kalinina EV, Cooper D, Jansen KU, Anderson AS, Swanson KA, Gruber WC, and Gurtman A
- Subjects
- Female, Humans, Infant, Infant, Newborn, Pregnancy, Antibodies, Viral, Communicable Diseases therapy, Double-Blind Method, Injections, Intramuscular, Respiratory Syncytial Viruses, Treatment Outcome, Vaccination adverse effects, Vaccination methods, Vaccine Efficacy, Vaccines, Combined administration & dosage, Vaccines, Combined adverse effects, Vaccines, Combined therapeutic use, Respiratory Syncytial Virus Infections epidemiology, Respiratory Syncytial Virus Infections prevention & control, Respiratory Syncytial Virus Vaccines administration & dosage, Respiratory Syncytial Virus Vaccines adverse effects, Respiratory Syncytial Virus Vaccines therapeutic use, Respiratory Tract Infections epidemiology, Respiratory Tract Infections prevention & control
- Abstract
Background: Whether vaccination during pregnancy could reduce the burden of respiratory syncytial virus (RSV)-associated lower respiratory tract illness in newborns and infants is uncertain., Methods: In this phase 3, double-blind trial conducted in 18 countries, we randomly assigned, in a 1:1 ratio, pregnant women at 24 through 36 weeks' gestation to receive a single intramuscular injection of 120 μg of a bivalent RSV prefusion F protein-based (RSVpreF) vaccine or placebo. The two primary efficacy end points were medically attended severe RSV-associated lower respiratory tract illness and medically attended RSV-associated lower respiratory tract illness in infants within 90, 120, 150, and 180 days after birth. A lower boundary of the confidence interval for vaccine efficacy (99.5% confidence interval [CI] at 90 days; 97.58% CI at later intervals) greater than 20% was considered to meet the success criterion for vaccine efficacy with respect to the primary end points., Results: At this prespecified interim analysis, the success criterion for vaccine efficacy was met with respect to one primary end point. Overall, 3682 maternal participants received vaccine and 3676 received placebo; 3570 and 3558 infants, respectively, were evaluated. Medically attended severe lower respiratory tract illness occurred within 90 days after birth in 6 infants of women in the vaccine group and 33 infants of women in the placebo group (vaccine efficacy, 81.8%; 99.5% CI, 40.6 to 96.3); 19 cases and 62 cases, respectively, occurred within 180 days after birth (vaccine efficacy, 69.4%; 97.58% CI, 44.3 to 84.1). Medically attended RSV-associated lower respiratory tract illness occurred within 90 days after birth in 24 infants of women in the vaccine group and 56 infants of women in the placebo group (vaccine efficacy, 57.1%; 99.5% CI, 14.7 to 79.8); these results did not meet the statistical success criterion. No safety signals were detected in maternal participants or in infants and toddlers up to 24 months of age. The incidences of adverse events reported within 1 month after injection or within 1 month after birth were similar in the vaccine group (13.8% of women and 37.1% of infants) and the placebo group (13.1% and 34.5%, respectively)., Conclusions: RSVpreF vaccine administered during pregnancy was effective against medically attended severe RSV-associated lower respiratory tract illness in infants, and no safety concerns were identified. (Funded by Pfizer; MATISSE ClinicalTrials.gov number, NCT04424316.)., (Copyright © 2023 Massachusetts Medical Society.)
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- 2023
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23. A comprehensive assessment of four whole blood stabilizers for flow-cytometric analysis of leukocyte populations.
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Nguyen NA, Huang X, Cabrera LE, Pekkarinen PT, Nowlan K, Strandin T, Kantele A, Vapalahti O, Heinonen S, and Kekäläinen E
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- Humans, Flow Cytometry, Leukocytes, Granulocytes, Proteomics, COVID-19
- Abstract
Though cryopreservation of cell fractions is widely used in flow cytometry studies, whole blood cryopreservation is more challenging due to the presence of erythrocytes and effects of fixatives commonly used for preservation. Here, we evaluated and compared head-to-head the performance of four commercial whole blood cryopreservation kits; (1) Cytodelics, (2) Stable-Lyse V2 and Stable-Store V2 (SLSS-V2), (3) Proteomic stabilizer (PROT-1), and (4) Transfix. We found that PROT-1, Transfix, and Cytodelics maintained the distribution of major leukocyte subsets-granulocytes, T cells, natural killer cells, and B cells, on a comparable level to unpreserved samples, despite the attenuation of fluorescence intensities in flow cytometric assays. Moreover, these three stabilizers also maintained the activated phenotypes of neutrophils upon stimulation with N-formylmethionyl-leucyl-phenylalanine and lipopolysaccharides. The upregulation of adhesion molecules (CD11b), Fc receptors (CD16), and granule proteins (CD66b), as well as the shedding of surface L-selectin (CD62L), was conserved most efficiently in PROT-1 and Cytodelics when compared to samples only treated with erythrocyte lysing. However, none of the stabilizers provided a reliable detection of CCR7 for accurate quantification of T cell maturation stages. We also evaluated the performance of Cytodelics in longitudinal clinical samples obtained from acute COVID-19 patients, where it allowed reliable detection of lymphopenia and granulocyte expansion. These results support the feasibility of whole blood cryopreservation for immunophenotyping by flow cytometry, particularly in longitudinal studies. In conclusion, the performance of different stabilizers is variable and therefore the choice of stabilizers should depend on cell type of interest, as well as antibody clones and experimental design of each study., (© 2022 The Authors. Cytometry Part A published by Wiley Periodicals LLC on behalf of International Society for Advancement of Cytometry.)
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- 2023
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24. Seasonal variation of diarrhoeal pathogens among Guinea-Bissauan children under five years of age.
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Mero S, Lääveri T, Ursing J, Rombo L, Kofoed PE, and Kantele A
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- Infant, Humans, Child, Child, Preschool, Seasons, Prospective Studies, Guinea, Diarrhea microbiology, Cryptosporidiosis complications, Cryptosporidium genetics, Bacteriophages
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Background: Diarrhoea remains a major cause of childhood morbidity and mortality in low-income countries (LICs). The frequency of diarrhoeal episodes may vary by season, yet few prospective cohort studies have examined seasonal variation among various diarrhoeal pathogens using multiplex qPCR to analyse bacterial, viral and parasitic pathogens., Methods: We combined our recent qPCR data of diarrhoeal pathogens (nine bacterial, five viral and four parasitic) among Guinea-Bissauan children under five years old with individual background data, dividing by season. The associations of season (dry winter and rainy summer) and the various pathogens were explored among infants (0-11 months) and young children (12-59 months) and those with and without diarrhoea., Results: Many bacterial pathogens, especially EAEC, ETEC and Campylobacter, and parasitic Cryptosporidium, prevailed in the rainy season, whereas many viruses, particularly the adenovirus, astrovirus and rotavirus proved common in the dry season. Noroviruses were found constantly throughout the year. Seasonal variation was observed in both age groups., Conclusion: In childhood diarrhoea in a West African LIC, seasonal variation appears to favour EAEC, ETEC, and Cryptosporidium in the rainy and viral pathogens in the dry season., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: TL received honoraria from Pfizer unrelated to this article. AK received research grants from Valneva and Pfizer unrelated to this article. Other authors have declared that no competing interests., (Copyright: © 2023 Mero et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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- 2023
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25. Metagenomic Analysis of the Abundance and Composition of Antibiotic Resistance Genes in Hospital Wastewater in Benin, Burkina Faso, and Finland.
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Markkanen MA, Haukka K, Pärnänen KMM, Dougnon VT, Bonkoungou IJO, Garba Z, Tinto H, Sarekoski A, Karkman A, Kantele A, and Virta MPJ
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- Humans, Burkina Faso, Benin, Finland, Drug Resistance, Microbial genetics, Hospitals, Anti-Bacterial Agents pharmacology, Wastewater
- Abstract
Antibiotic resistance is a global threat to human health, with the most severe effect in low- and middle-income countries. We explored the presence of antibiotic resistance genes (ARGs) in the hospital wastewater (HWW) of nine hospitals in Benin and Burkina Faso, two low-income countries in West Africa, with shotgun metagenomic sequencing. For comparison, we also studied six hospitals in Finland. The highest sum of the relative abundance of ARGs in the 68 HWW samples was detected in Benin and the lowest in Finland. HWW resistomes and mobilomes in Benin and Burkina Faso resembled each other more than those in Finland. Many carbapenemase genes were detected at various abundances, especially in HWW from Burkina Faso and Finland. The bla
GES genes, the most widespread carbapenemase gene in the Beninese HWW, were also found in water intended for hand washing and in a puddle at a hospital yard in Benin. mcr genes were detected in the HWW of all three countries, with mcr-5 being the most common mcr gene. These and other mcr genes were observed in very high relative abundances, even in treated wastewater in Burkina Faso and a street gutter in Benin. The results highlight the importance of wastewater treatment, with particular attention to HWW. IMPORTANCE The global emergence and increased spread of antibiotic resistance threaten the effectiveness of antibiotics and, thus, the health of the entire population. Therefore, understanding the resistomes in different geographical locations is crucial in the global fight against the antibiotic resistance crisis. However, this information is scarce in many low- and middle-income countries (LMICs), such as those in West Africa. In this study, we describe the resistomes of hospital wastewater in Benin and Burkina Faso and, as a comparison, Finland. Our results help to understand the hitherto unrevealed resistance in Beninese and Burkinabe hospitals. Furthermore, the results emphasize the importance of wastewater management infrastructure design to minimize exposure events between humans, HWW, and the environment, preventing the circulation of resistant bacteria and ARGs between humans (hospitals and community) and the environment.- Published
- 2023
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26. Doxycycline as an antimalarial: Impact on travellers' diarrhoea and doxycycline resistance among various stool bacteria - Prospective study and literature review.
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Kantele A, Mero S, and Lääveri T
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- Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents therapeutic use, Bacteria, Diarrhea drug therapy, Diarrhea microbiology, Doxycycline pharmacology, Doxycycline therapeutic use, Enterobacteriaceae, Humans, Prospective Studies, Travel, Travel-Related Illness, beta-Lactamases, Antimalarials pharmacology, Antimalarials therapeutic use, Enterobacteriaceae Infections microbiology
- Abstract
Background: Antibiotics predispose travellers to acquire multidrug-resistant bacteria, such as extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-PE). Although widely used in antimalarial prophylaxis, doxycycline has scarcely been studied in this respect., Methods: We explored the impact of doxycycline on rates of traveller's diarrhoea (TD), ESBL-PE acquisition and, particularly, doxycycline co-resistance among travel-acquired ESBL-PE in a sample of 412 visitors to low- and middle-income countries. We reviewed the literature on traveller studies of doxycycline/tetracycline resistance among stool pathogens and the impact of doxycycline on TD rates, ESBL-PE acquisition, and doxycycline/tetracycline resistance., Results: The TD rates were similar for doxycycline users (32/46; 69.6%) and non-users (256/366; 69.9%). Of the 90 travel-acquired ESBL-PE isolates, 84.4% were co-resistant to doxycycline: 100% (11/11) among users and 82.3% (65/79) among non-users. The literature on doxycycline's effect on TD was not conclusive nor did it support a recent decline in doxycycline resistance. Although doxycycline did not increase ESBL-PE acquisition, doxycycline-resistance among stool pathogens proved more frequent for users than non-users., Conclusions: Our prospective data and the literature review together suggest the following: 1) doxycycline does not prevent TD; 2) doxycycline use favours acquisition of doxy/tetracycline-co-resistant intestinal bacteria; 3) although doxycycline does not predispose to travel-related ESBL-PE acquisition per se, it selects ESBL-PE strains co-resistant to doxycycline; 4) doxycycline resistance rates are high among stool bacteria in general with no evidence of any tendency to decrease., Competing Interests: Declaration of competing interest AK has received investigator-initiated grants from Valneva and Pfizer, neither of which are relevant for the current manuscript. SM and TL declare no conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)
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- 2022
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27. A Two-Week Vacation in the Tropics and Psychological Well-Being-An Observational Follow-Up Study.
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Laukkala T, Rosenström T, and Kantele A
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- Adult, Diarrhea, Female, Follow-Up Studies, Humans, Male, Surveys and Questionnaires, Dysentery, Travel
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Despite the vast annual number of international visitors to the tropics, surprisingly little data are available on the psychological well-being associated with the travels or with travelers’ diarrhoea (TD). We herein recruited participants of a vaccination trial, OEV-123, before their 12-day holiday in Benin, West Africa. We assessed the travelers’ psychological distress with a general health questionnaire (GHQ-12) and retrieved data on TD from the trial database. The GHQ-12 was completed before (wave 0), at return (wave 1), and 1-month after (wave 2) the trip. Of the 174 participants, 73% were women, with a mean age 40 years. Moreover, 24% reported psychological distress before traveling, 10% immediately after, and 16% 1-month after the trip (GHQ-12, 3 or more; 0−12 scoring). The findings showed that psychological well-being increased after the tropical holiday. The GHQ-12 middle wave sum score differed from the wave 0 (p < 0.001) and wave 2 (p = 0.008) sum scores, with travelers reporting highest levels of well-being on their return, with evidence of a lasting improvement. TD was experienced by 71%, and it had a negative impact on psychological well-being only if experienced after travel.
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- 2022
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28. European hospitals as source of multidrug-resistant bacteria: analysis of travellers screened in Finland after hospitalization abroad.
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Kajova M, Khawaja T, and Kantele A
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- Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents therapeutic use, Bacteria, Drug Resistance, Multiple, Bacterial, Escherichia coli, Finland epidemiology, Hospitalization, Hospitals, Humans, Prevalence, Methicillin-Resistant Staphylococcus aureus, Vancomycin-Resistant Enterococci
- Abstract
Background: As hospitals have a high prevalence of multidrug-resistant organisms (MDRO), hospitalization abroad indicates for travellers an increased risk of acquiring MDRO-and carrying the strains home. Antimicrobial resistance (AMR) rates are highest in the (sub)tropics, whereas Europe is considered a lower risk region. Since AMR prevalences vary within Europe, we aimed to gather country-specific data on the risks for hospitalized travellers., Methods: At hospitals of the Helsinki and Uusimaa district in Finland, patients hospitalized abroad over the past 12 months are systematically screened for methicillin-resistant Staphylococcus aureus (MRSA), extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales (ESBL-PE), carbapenemase-producing bacteria and vancomycin-resistant Enterococcus spp. (VRE). Among patients screened 2010-19, we selected those hospitalized in Europe, recorded their MDRO findings, infections and mortality, and analysed MDRO-associated risk factors., Results: Of the 1772 patients treated in 41 European countries, 16.6% (295) carried MDRO, 12.5% (221) ESBL-PE, 7.8% (138) solely ESBL-E. coli, 2.6% (46) MRSA, 2.2% (30) of those screened VRE and 2.2% (39) carbapenem-resistant Gram-negatives. Among those colonized, 9.8% (29) had symptomatic MDRO infections and 0.3% (one) died. Colonization was most frequently recorded for those treated in eastern and southern Europe, with Bulgaria, Cyprus and the Russian Federation scoring highest. MDRO colonization was associated with antibiotic treatment and showed a negative correlation with time from discharge to screening., Conclusions: After hospitalization in European countries, ESBL-PE carriage was relatively common (12.5%), while other MDROs proved less frequent (<5%). Antibiotic treatment and short time since hospitalization abroad increased the risk of MDRO colonization. Clear differences between countries and regions were revealed, with highest rates in the east and the south., (© International Society of Travel Medicine 2022. Published by Oxford University Press.)
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- 2022
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29. International travel and travelers' diarrhea - Increased risk of urinary tract infection.
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Patjas A and Kantele A
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- Diarrhea prevention & control, Female, Humans, Male, Prospective Studies, Risk Factors, Travel, Urinary Tract Infections epidemiology
- Abstract
Background: Urinary tract infections (UTIs) rank among the most common infections encountered in health care, with an annual incidence of 12% for women. Despite the vast numbers of international travels (over 1.5 billion annually), no prospective studies have had primary focus on UTIs during travel., Methods: We recruited in 2008-17 international travelers who all filled out pre- and post-travel questionnaires. Incidence rates of UTI were calculated separately for both sexes. Multivariable analyses were conducted to identify risk factors for UTI during travel., Results: In total 15/517 (2,9%) travelers acquired UTI during travel, yielding an annual incidence of 62% for female and 18% for male travelers. Travelers' diarrhea (TD) was identified as a factor predisposing to UTI (OR 9.2, 95% CI 1.5-+∞, p = 0.011); all UTI cases were recorded by travelers with TD., Conclusions: To our knowledge, this is the first prospective study with a primary focus on UTI during travel. Our data reveal that among travelers the incidence of UTI far exceeds that reported for the general population. TD was identified as a major risk factor for the infection. Our results suggest TD prevention as a means of also preventing UTI during travel., (Copyright © 2022. Published by Elsevier Ltd.)
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- 2022
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30. Comparative analysis of COVID-19 vaccine responses and third booster dose-induced neutralizing antibodies against Delta and Omicron variants.
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Belik M, Jalkanen P, Lundberg R, Reinholm A, Laine L, Väisänen E, Skön M, Tähtinen PA, Ivaska L, Pakkanen SH, Häkkinen HK, Ortamo E, Pasternack A, Ritvos MA, Naves RA, Miettinen S, Sironen T, Vapalahti O, Ritvos O, Österlund P, Kantele A, Lempainen J, Kakkola L, Kolehmainen P, and Julkunen I
- Subjects
- 2019-nCoV Vaccine mRNA-1273, Antibodies, Neutralizing, Antibodies, Viral, BNT162 Vaccine, Humans, SARS-CoV-2, Vaccines, Synthetic, mRNA Vaccines, COVID-19 prevention & control, COVID-19 Vaccines
- Abstract
Two COVID-19 mRNA (of BNT162b2, mRNA-1273) and two adenovirus vector vaccines (ChAdOx1 and Janssen) are licensed in Europe, but optimization of regime and dosing is still ongoing. Here we show in health care workers (n = 328) that two doses of BNT162b2, mRNA-1273, or a combination of ChAdOx1 adenovirus vector and mRNA vaccines administrated with a long 12-week dose interval induce equally high levels of anti-SARS-CoV-2 spike antibodies and neutralizing antibodies against D614 and Delta variant. By contrast, two doses of BNT162b2 with a short 3-week interval induce 2-3-fold lower titers of neutralizing antibodies than those from the 12-week interval, yet a third BNT162b2 or mRNA-1273 booster dose increases the antibody levels 4-fold compared to the levels after the second dose, as well as induces neutralizing antibody against Omicron BA.1 variant. Our data thus indicates that a third COVID-19 mRNA vaccine may induce cross-protective neutralizing antibodies against multiple variants., (© 2022. The Author(s).)
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- 2022
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31. Scent dogs in detection of COVID-19: triple-blinded randomised trial and operational real-life screening in airport setting.
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Kantele A, Paajanen J, Turunen S, Pakkanen SH, Patjas A, Itkonen L, Heiskanen E, Lappalainen M, Desquilbet L, Vapalahti O, and Hielm-Björkman A
- Subjects
- Airports, Animals, Dogs, Humans, Odorants, COVID-19 diagnosis, SARS-CoV-2
- Abstract
Objective: To estimate scent dogs' diagnostic accuracy in identification of people infected with SARS-CoV-2 in comparison with reverse transcriptase polymerase chain reaction (RT-PCR). We conducted a randomised triple-blinded validation trial, and a real-life study at the Helsinki-Vantaa International Airport, Finland., Methods: Four dogs were trained to detect COVID-19 using skin swabs from individuals tested for SARS-CoV-2 by RT-PCR. Our controlled triple-blinded validation study comprised four identical sets of 420 parallel samples (from 114 individuals tested positive and 306 negative by RT-PCR), randomly presented to each dog over seven trial sessions. In a real-life setting the dogs screened skin swabs from 303 incoming passengers all concomitantly examined by nasal swab SARS-CoV-2 RT-PCR. Our main outcomes were variables of diagnostic accuracy (sensitivity, specificity, positive predictive value, negative predictive value) for scent dog identification in comparison with RT-PCR., Results: Our validation experiments had an overall accuracy of 92% (95% CI 90% to 93%), a sensitivity of 92% (95% CI 89% to 94%) and a specificity of 91% (95% CI 89% to 93%) compared with RT-PCR. For our dogs, trained using the wild-type virus, performance was less accurate for the alpha variant (89% for confirmed wild-type vs 36% for alpha variant, OR 14.0, 95% CI 4.5 to 43.4). In the real-life setting, scent detection and RT-PCR matched 98.7% of the negative swabs. Scant airport prevalence (0.47%) did not allow sensitivity testing; our only SARS-CoV-2 positive swab was not identified (alpha variant). However, ad hoc analysis including predefined positive spike samples showed a total accuracy of 98% (95% CI 97% to 99%)., Conclusions: This large randomised controlled triple-blinded validation study with a precalculated sample size conducted at an international airport showed that trained scent dogs screen airport passenger samples with high accuracy. One of our findings highlights the importance of continuous retraining as new variants emerge. Using scent dogs may present a valuable approach for high-throughput, rapid screening of large numbers of people., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at http://www.icmje.org/disclosure-of-interest/ and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous 3 years; no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2022
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32. Vaccine-Induced Antibody Responses against SARS-CoV-2 Variants-Of-Concern Six Months after the BNT162b2 COVID-19 mRNA Vaccination.
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Jalkanen P, Kolehmainen P, Haveri A, Huttunen M, Laine L, Österlund P, Tähtinen PA, Ivaska L, Maljanen S, Reinholm A, Belik M, Smura T, Häkkinen HK, Ortamo E, Kantele A, Julkunen I, Lempainen J, and Kakkola L
- Subjects
- Antibodies, Neutralizing, Antibodies, Viral, Antibody Formation, BNT162 Vaccine, COVID-19 Vaccines, Humans, RNA, Messenger, Spike Glycoprotein, Coronavirus, Vaccination, Vaccines, Synthetic, mRNA Vaccines, COVID-19 prevention & control, SARS-CoV-2 genetics
- Abstract
The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has raised concern about increased transmissibility, infectivity, and immune evasion from a vaccine and infection-induced immune responses. Although COVID-19 mRNA vaccines have proven to be highly effective against severe COVID-19 disease, the decrease in vaccine efficacy against emerged Beta and Delta variants emphasizes the need for constant monitoring of new virus lineages and studies on the persistence of vaccine-induced neutralizing antibodies. To analyze the dynamics of COVID-19 mRNA vaccine-induced antibody responses, we followed 52 health care workers in Finland for 6 months after receiving two doses of BNT162b2 vaccine with a 3-week interval. We demonstrate that, although anti-S1 antibody levels decrease 2.3-fold compared to peak antibody levels, anti-SARS-CoV-2 antibodies persist for months after BNT162b2 vaccination. Variants D614G, Alpha, and Eta are neutralized by sera of 100% of vaccinees, whereas neutralization of Delta is 3.8-fold reduced and neutralization of Beta is 5.8-fold reduced compared to D614G. Despite this reduction, 85% of sera collected 6 months postvaccination neutralizes Delta variant. IMPORTANCE A decrease in vaccine efficacy against emerging SARS-CoV-2 variants has increased the importance of assessing the persistence of SARS-CoV-2 spike protein-specific antibodies and neutralizing antibodies. Our data show that after 6 months post two doses of BNT162b2 vaccine, antibody levels decrease yet remain detectable and capable of neutralizing emerging variants. By monitoring the vaccine-induced antibody responses, vaccination strategies and administration of booster doses can be optimized.
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- 2022
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33. Long-Lasting T Cell Responses in BNT162b2 COVID-19 mRNA Vaccinees and COVID-19 Convalescent Patients.
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Hurme A, Jalkanen P, Heroum J, Liedes O, Vara S, Melin M, Teräsjärvi J, He Q, Pöysti S, Hänninen A, Oksi J, Vuorinen T, Kantele A, Tähtinen PA, Ivaska L, Kakkola L, Lempainen J, and Julkunen I
- Subjects
- Antibodies, Viral, BNT162 Vaccine, COVID-19 Vaccines, Humans, Leukocytes, Mononuclear, RNA, Messenger genetics, Spike Glycoprotein, Coronavirus, T-Lymphocytes, COVID-19, SARS-CoV-2
- Abstract
The emergence of novel variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made it more difficult to prevent the virus from spreading despite available vaccines. Reports of breakthrough infections and decreased capacity of antibodies to neutralize variants raise the question whether current vaccines can still protect against COVID-19 disease. We studied the dynamics and persistence of T cell responses using activation induced marker (AIM) assay and Th1 type cytokine production in peripheral blood mononuclear cells obtained from BNT162b2 COVID-19 mRNA vaccinated health care workers and COVID-19 patients. We demonstrate that equally high T cell responses following vaccination and infection persist at least for 6 months against Alpha, Beta, Gamma, and Delta variants despite the decline in antibody levels., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hurme, Jalkanen, Heroum, Liedes, Vara, Melin, Teräsjärvi, He, Pöysti, Hänninen, Oksi, Vuorinen, Kantele, Tähtinen, Ivaska, Kakkola, Lempainen and Julkunen.)
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- 2022
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34. Three-dose versus four-dose primary schedules for tick-borne encephalitis (TBE) vaccine FSME-immun for those aged 50 years or older: A single-centre, open-label, randomized controlled trial.
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Kantele A, Rombo L, Vene S, Kundi M, Lindquist L, and Erra EO
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- Adult, Antibodies, Viral, Humans, Immunization Schedule, Middle Aged, Encephalitis Viruses, Tick-Borne, Encephalitis, Tick-Borne prevention & control, Viral Vaccines
- Abstract
Background: TBE vaccination failures among those past middle age have raised concern about immune response declining with age. We investigated immunogenicity of the TBE-vaccine FSME-Immun among those aged 50+ years using the standard three-dose primary series and alternative four-dose schedules., Methods: In this single-centre, open-label, randomized controlled trial, 200 TBE-naive Swedish adults were given primary TBE vaccination with FSME-Immun. Those aged 50+ years (n = 150) were randomized to receive the standard three-dose (days 0-30-360) or one of two four-dose series (0-7-21-360; 0-30-90-360). For participants < 50 years (n = 50) the standard three-dose schedule was used. Titres of neutralizing antibodies were determined on days 0, 60, 120, 360, and 400. The main outcome was the log titre of TBE virus-specific neutralizing antibodies on day 400., Results: The three-dose schedule yielded lower antibody titres among those aged 50+ years than the younger participants on day 400 (geometric mean titre 41 versus 74, p < 0.05). The older group showed higher titres for the four-dose 0-7-21-360 than the standard three-dose schedule both on day 400 (103 versus 41, p < 0.01; primary end point) and at the other testing points (days 60, 120, 360). Using the other four-dose schedule (0-30-90-360), no such difference was observed on day 400 (63 versus 41, NS)., Conclusion: Immune response to the TBE vaccine declined with age. A four-dose schedule (0-7-21-360) may benefit those aged 50 years or older. This study is registered at ClinicalTrials.gov, NCT01361776., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)
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- 2022
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35. Extended-spectrum beta-lactamase-producing strains among diarrhoeagenic Escherichia coli-prospective traveller study with literature review.
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Kantele A and Lääveri T
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- Anti-Bacterial Agents therapeutic use, Azithromycin, Diarrhea drug therapy, Feces microbiology, Humans, Prospective Studies, beta-Lactamases, Escherichia coli, Escherichia coli Infections drug therapy, Escherichia coli Infections epidemiology, Escherichia coli Infections microbiology
- Abstract
Background: Antibiotics are no longer the primary approach for treating all travellers' diarrhoea (TD): most cases resolve without antibiotics and using them predisposes to colonization by multidrug-resistant bacteria. Data are accumulating on increasing resistance among TD pathogens, yet research into the most common agents, diarrhoeagenic Escherichia coli (DEC), remains limited., Methods: A total of 413 travellers to the (sub)tropics were analyzed for travel-acquired diarrhoeal pathogens and ESBL-PE. To identify ESBL-producing DEC, ESBL-producing E. coli (ESBL-EC) isolates were subjected to multiplex qPCR for various DEC pathotypes: enteroaggregative (EAEC), enteropathogenic (EPEC), enterotoxigenic (ETEC), enteroinvasive (EIEC) and enterohaemorrhagic (EHEC) E. coli.For a literature review, we screened studies among travellers and locals in low- and middle-income countries (LMICs) on the frequency of ESBL-producing DEC, and among travellers, also DEC with resistance to ciprofloxacin, azithromycin, and rifamycin derivatives., Results: Our rate of ESBL-EC among all DEC findings was 2.7% (13/475); among EAEC 5.7% (10/175), EPEC 1.1% (2/180), ETEC 1.3% (1/80) and EHEC (0/35) or EIEC 0% (0/5). The literature search yielded three studies reporting ESBL-EC frequency and thirteen exploring resistance to TD antibiotics among travel-acquired DEC. For EAEC and ETEC, the ESBL-EC rates were 10-13% and 14-15%, resistance to fluoroquinolones 0-42% and 0-40%, azithromycin 0-29% and 0-61%, and rifaximin 0% and 0-20%. The highest rates were from the most recent collections. Proportions of ESBL-producing DEC also appear to be increasing among locals in LMICs and even carbapenemase-producing DEC were reported., Conclusion: ESBL producers are no longer rare among DEC, and the overall resistance to various antibiotics is increasing. The data predict decreasing efficacy of antibiotic treatment, threatening its benefits, for disadvantages still prevail when efficacy is lost., (© The Author(s) 2021. Published by Oxford University Press on behalf of International Society of Travel Medicine.)
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- 2022
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36. Association between first language and SARS-CoV-2 infection rates, hospitalization, intensive care admissions and death in Finland: a population-based observational cohort study.
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Holmberg V, Salmi H, Kattainen S, Ollgren J, Kantele A, Pynnönen J, Järvinen A, Forsblom E, Silén S, Kivivuori SM, Meretoja A, and Hästbacka J
- Subjects
- Cohort Studies, Critical Care, Finland epidemiology, Hospitalization, Humans, Intensive Care Units, Language, Retrospective Studies, COVID-19 epidemiology, COVID-19 ethnology, Ethnic and Racial Minorities statistics & numerical data
- Abstract
Objectives: Motivated by reports of increased risk of coronavirus disease 2019 (COVID-19) in ethnic minorities of high-income countries, we explored whether patients with a foreign first language are at an increased risk of COVID-19 infections, more serious presentations, or worse outcomes., Methods: In a retrospective observational population-based quality registry study covering a population of 1.7 million, we studied the incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), admissions to specialist healthcare and the intensive care unit (ICU), and all-cause case fatality in different language groups between 27th February and 3rd August 2020 in Southern Finland. A first language other than Finnish, Swedish or Sámi served as a surrogate marker for a foreign ethnic background., Results: In total, 124 240 individuals were tested, and among the 118 300 (95%) whose first language could be determined, 4005 (3.4%) were COVID-19-positive, 623 (0.5%) were admitted to specialized hospitals, and 147 (0.1%) were admitted to the ICU; 254 (0.2%) died. Those with a foreign first language had lower testing rates (348, 95%CI 340-355 versus 758, 95%CI 753-762 per 10 000, p < 0.0001), higher incidence (36, 95%CI 33-38 versus 22, 95%CI 21-23 per 10 000, p < 0.0001), and higher positivity rates (103, 95%CI 96-109 versus 29, 95%CI 28-30 per 1000, p < 0.0001). There was no significant difference in ICU admissions, disease severity at ICU admission, or ICU outcomes. Case fatality by 90 days was 7.7% in domestic cases and 1.2% in those with a foreign first language, explained by demographics (age- and sex-adjusted HR 0.49, 95%CI 0.21-1.15)., Conclusions: The population with a foreign first language was at an increased risk for testing positive for SARS-CoV-2, but when hospitalized they had outcomes similar to those in the native, domestic language population. This suggests that special attention should be paid to the prevention and control of infectious diseases among language minorities., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)
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- 2022
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37. APOE ε4 associates with increased risk of severe COVID-19, cerebral microhaemorrhages and post-COVID mental fatigue: a Finnish biobank, autopsy and clinical study.
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Kurki SN, Kantonen J, Kaivola K, Hokkanen L, Mäyränpää MI, Puttonen H, Martola J, Pöyhönen M, Kero M, Tuimala J, Carpén O, Kantele A, Vapalahti O, Tiainen M, Tienari PJ, Kaila K, Hästbacka J, and Myllykangas L
- Subjects
- Adult, Aged, Autopsy, Biological Specimen Banks, COVID-19 diagnosis, COVID-19 epidemiology, Cerebral Hemorrhage diagnosis, Cerebral Hemorrhage epidemiology, Cohort Studies, Female, Finland epidemiology, Genetic Association Studies methods, Heterozygote, Humans, Male, Mental Fatigue diagnosis, Mental Fatigue epidemiology, Microvessels pathology, Middle Aged, Prospective Studies, Risk Factors, Young Adult, Post-Acute COVID-19 Syndrome, Apolipoprotein E4 genetics, COVID-19 complications, COVID-19 genetics, Cerebral Hemorrhage genetics, Mental Fatigue genetics, Patient Acuity
- Abstract
Apolipoprotein E ε4 allele (APOE4) has been shown to associate with increased susceptibility to SARS-CoV-2 infection and COVID-19 mortality in some previous genetic studies, but information on the role of APOE4 on the underlying pathology and parallel clinical manifestations is scarce. Here we studied the genetic association between APOE and COVID-19 in Finnish biobank, autopsy and prospective clinical cohort datasets. In line with previous work, our data on 2611 cases showed that APOE4 carriership associates with severe COVID-19 in intensive care patients compared with non-infected population controls after matching for age, sex and cardiovascular disease status. Histopathological examination of brain autopsy material of 21 COVID-19 cases provided evidence that perivascular microhaemorrhages are more prevalent in APOE4 carriers. Finally, our analysis of post-COVID fatigue in a prospective clinical cohort of 156 subjects revealed that APOE4 carriership independently associates with higher mental fatigue compared to non-carriers at six months after initial illness. In conclusion, the present data on Finns suggests that APOE4 is a risk factor for severe COVID-19 and post-COVID mental fatigue and provides the first indication that some of this effect could be mediated via increased cerebrovascular damage. Further studies in larger cohorts and animal models are warranted., (© 2021. The Author(s).)
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- 2021
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38. A Highly Sensitive and Specific SARS-CoV-2 Spike- and Nucleoprotein-Based Fluorescent Multiplex Immunoassay (FMIA) to Measure IgG, IgA, and IgM Class Antibodies.
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Solastie A, Virta C, Haveri A, Ekström N, Kantele A, Miettinen S, Lempainen J, Jalkanen P, Kakkola L, Dub T, Julkunen I, and Melin M
- Subjects
- Antibodies, Neutralizing immunology, COVID-19 diagnosis, Coronavirus Nucleocapsid Proteins immunology, Humans, Nucleoproteins, Phosphoproteins immunology, SARS-CoV-2, Sensitivity and Specificity, Antibodies, Viral immunology, COVID-19 Serological Testing methods, Fluorescent Antibody Technique methods, Immunoglobulin A immunology, Immunoglobulin G immunology, Immunoglobulin M immunology, Nucleocapsid Proteins immunology, Spike Glycoprotein, Coronavirus immunology
- Abstract
Validation and standardization of accurate serological assays are crucial for the surveillance of the coronavirus disease 2019 (COVID-19) pandemic and population immunity. We describe the analytical and clinical performance of an in-house fluorescent multiplex immunoassay (FMIA) for simultaneous quantification of antibodies against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleoprotein and spike glycoprotein. Furthermore, we calibrated IgG-FMIA against World Health Organization (WHO) International Standard and compared FMIA results to an in-house enzyme immunoassay (EIA) and a microneutralization test (MNT). We also compared the MNT results of two laboratories. IgG-FMIA displayed 100% specificity and sensitivity for samples collected 13 to 150 days post-onset of symptoms (DPO). For IgA- and IgM-FMIA, 100% specificity and sensitivity were obtained for a shorter time window (13 to 36 and 13 to 28 DPO for IgA- and IgM-FMIA, respectively). FMIA and EIA results displayed moderate to strong correlation, but FMIA was overall more specific and sensitive. IgG-FMIA identified 100% of samples with neutralizing antibodies (NAbs). Anti-spike IgG concentrations correlated strongly (ρ = 0.77 to 0.84, P < 2.2 × 10
-16 ) with NAb titers, and the two laboratories' NAb titers displayed a very strong correlation (ρ = 0.95, P < 2.2 × 10-16 ). Our results indicate good correlation and concordance of antibody concentrations measured with different types of in-house SARS-CoV-2 antibody assays. Calibration against the WHO international standard did not, however, improve the comparability of FMIA and EIA results. IMPORTANCE SARS-CoV-2 serological assays with excellent clinical performance are essential for reliable estimation of the persistence of immunity after infection or vaccination. In this paper we present a thoroughly validated SARS-CoV-2 serological assay with excellent clinical performance and good comparability to neutralizing antibody titers. Neutralization tests are still considered the gold standard for SARS-CoV-2 serological assays, but our assay can identify samples with neutralizing antibodies with 100% sensitivity and 96% specificity without the need for laborious and slow biosafety level 3 (BSL-3) facility-requiring analyses.- Published
- 2021
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39. Synergistic Interferon-Alpha-Based Combinations for Treatment of SARS-CoV-2 and Other Viral Infections.
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Ianevski A, Yao R, Zusinaite E, Lello LS, Wang S, Jo E, Yang J, Ravlo E, Wang W, Lysvand H, Løseth K, Oksenych V, Tenson T, Windisch MP, Poranen MM, Nieminen AI, Nordbø SA, Fenstad MH, Grødeland G, Aukrust P, Trøseid M, Kantele A, Lastauskienė E, Vitkauskienė A, Legrand N, Merits A, Bjørås M, and Kainov DE
- Subjects
- Cell Line, Drug Synergism, Humans, Lung drug effects, Lung metabolism, Lung virology, Metabolome drug effects, Organoids, RNA, Viral biosynthesis, RNA, Viral drug effects, Signal Transduction drug effects, Transcriptome drug effects, Virus Replication drug effects, Viruses classification, Viruses drug effects, Antiviral Agents pharmacology, Interferon-alpha pharmacology, SARS-CoV-2 drug effects
- Abstract
Background: There is an urgent need for new antivirals with powerful therapeutic potential and tolerable side effects., Methods: Here, we tested the antiviral properties of interferons (IFNs), alone and with other drugs in vitro., Results: While IFNs alone were insufficient to completely abolish replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), IFNα, in combination with remdesivir, EIDD-2801, camostat, cycloheximide, or convalescent serum, proved to be more effective. Transcriptome and metabolomic analyses revealed that the IFNα-remdesivir combination suppressed SARS-CoV-2-mediated changes in Calu-3 cells and lung organoids, although it altered the homeostasis of uninfected cells and organoids. We also demonstrated that IFNα combinations with sofosbuvir, telaprevir, NITD008, ribavirin, pimodivir, or lamivudine were effective against HCV, HEV, FLuAV, or HIV at lower concentrations, compared to monotherapies., Conclusions: Altogether, our results indicated that IFNα can be combined with drugs that affect viral RNA transcription, protein synthesis, and processing to make synergistic combinations that can be attractive targets for further pre-clinical and clinical development against emerging and re-emerging viral infections.
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- 2021
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40. COVID-19 adenovirus vaccine triggers antibodies against PF4 complexes to activate complement and platelets.
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Pitkänen HH, Jouppila A, Helin T, Dulipati V, Kotimaa J, Meri S, Kantele A, Jalkanen P, Julkunen I, and Lassila R
- Subjects
- Adenoviridae, Blood Platelets, COVID-19 Vaccines, Humans, Immunoglobulin G, Platelet Factor 4, SARS-CoV-2, Adenovirus Vaccines, COVID-19
- Abstract
Background: Vaccine-induced thrombotic thrombocytopenia (VITT) is a rare coagulation disorder reported after administration of COVID-19 adenovirus-vectored vaccines. VITT is mediated by anti-platelet factor 4 (PF4) antibodies activating platelets through the Fcγ-receptor II (FcγRII), and it is associated with strong fibrin turnover. The complement system is involved in several other immunothrombotic entities, but its impact on VITT is not established., Objective: To assess antibodies in interaction with the activation of platelets and complement triggered by VITT., Methods: Antibodies against adenovirus type 2 hexon protein, ChAdOx1 adenoviral vector-specific IgG and PF4 were analyzed by enzyme immunoassays from VITT patients (n = 5). The EDTA plasma samples of the patients and controls were used to measure both terminal complement complexes (TCC) by ELISA and aggregation of healthy donor platelets. We studied the effects of human immunoglobulin (IVIG) and glycoprotein IIb/IIIa inhibitor (GPIIb/IIIa) on spontaneous and collagen-induced platelet aggregation supplemented with VITT plasma., Results: None of the patients had experienced a COVID-19 infection. Antibody analyses confirmed the immunogenicity of the adenovirus-vectored ChAdOx1 vaccine. Moreover, VITT plasma had anti-PF4 antibodies and elevated TCC levels as a sign of complement activation. In isolated healthy donor platelets, VITT patient plasma caused marked, spontaneous aggregation of platelets, which was abolished by eptifibatide and high-dose therapeutic IVIG., Conclusions: Our findings suggest that VITT is triggered by antibodies against adenovirus vector and PF4-polyanion complexes which strongly co-activate complement and platelets. The spontaneous platelet aggregation was suppressed by IVIG or eptifibatide, indicating that besides FcγRII, also GPIIb/IIIa receptor exerts platelet procoagulant role in VITT., (Copyright © 2021 Elsevier Ltd. All rights reserved.)
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- 2021
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41. Hospital admissions of refugees, asylum seekers and undocumented migrants: Ten-year retrospective study.
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Aro T and Kantele A
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- Adult, Female, Hospitalization, Hospitals, University, Humans, Pregnancy, Retrospective Studies, Refugees, Transients and Migrants
- Abstract
Introduction: The worldwide population of forcibly displaced people has increased over the past decade, approaching 80 million and encompassing more than 30 million refugees and asylum seekers. Research into refugee and migrant health has remained scarce, however., Methods: To investigate the reasons for hospital admissions of refugees, asylum seekers and undocumented migrants, we collected medical data from Helsinki University Hospital (HUH) records 2010-20., Results: The study population consisted of 647 patients originally from 54 different countries, mainly Iraq, Syria, and Afghanistan. Among adults, 40.9% of the admissions were related to pregnancy. For minors, the group comprising congenital malformations, deformations, and chromosomal abnormalities accounted for most hospitalizations, followed by diseases of the digestive or nervous system. Every fifth patient (19.3%) was admitted because of an infection: adults mostly for urinary tract infection (16.3%), pneumonia (14.1%), and tuberculosis (9.8%), and minors for acute gastroenteritis (15.2%). Infectious reason was more frequent within two months after immigration than later., Conclusions: Our data reveal a unique admission profile for forced migrants: in addition to infectious diseases, a particularly high rate of obstetric diagnoses was recorded, the two ranking as the most common reasons for hospitalization., (Copyright © 2021. Published by Elsevier Ltd.)
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- 2021
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42. Prevalence of diarrhoeal pathogens among children under five years of age with and without diarrhoea in Guinea-Bissau.
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Mero S, Timonen S, Lääveri T, Løfberg S, Kirveskari J, Ursing J, Rombo L, Kofoed PE, and Kantele A
- Subjects
- Bacteria classification, Bacteria genetics, Bacterial Infections epidemiology, Child, Preschool, Diarrhea epidemiology, Feces microbiology, Feces virology, Female, Guinea-Bissau epidemiology, Humans, Infant, Male, Virus Diseases epidemiology, Viruses classification, Viruses genetics, Bacteria isolation & purification, Bacterial Infections microbiology, Diarrhea microbiology, Diarrhea virology, Virus Diseases virology, Viruses isolation & purification
- Abstract
Background: Childhood diarrhoea, a major cause of morbidity and mortality in low-income regions, remains scarcely studied in many countries, such as Guinea-Bissau. Stool sample drying enables later qPCR analyses of pathogens without concern about electricity shortages., Methods: Dried stool samples of children under five years treated at the Bandim Health Centre in Bissau, Guinea-Bissau were screened by qPCR for nine enteric bacteria, five viruses, and four parasites. The findings of children having and not having diarrhoea were compared in age groups 0-11 and 12-59 months., Results: Of the 429 children- 228 with and 201 without diarrhoea- 96.9% and 93.5% had bacterial, 62.7% and 44.3% viral, and 52.6% and 48.3% parasitic pathogen findings, respectively. Enteroaggregarive Escherichia coli (EAEC; 60.5% versus 66.7%), enteropathogenic E. coli (EPEC; 61.4% versus 62.7%), Campylobacter (53.2% versus 51.8%), and enterotoxigenic E. coli (ETEC; 54.4% versus 44.3%) were the most common bacterial pathogens. Diarrhoea was associated with enteroinvasive E. coli (EIEC)/Shigella (63.3%), ETEC (54.4%), astrovirus (75.0%), norovirus GII (72.6%) and Cryptosporidium (71.2%). The only pathogen associated with severe diarrhoea was EIEC/Shigella (p<0.001). EAEC was found more frequent among the infants, and EIEC/Shigella, Giardia duodenalis and Dientamoeba fragilis among the older children., Conclusions: Stool pathogens proved common among all the children regardless of them having diarrhoea or not., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: JK is an employee of Mobidiag; the company did not sponsor the study nor did it have a role in study design, data collection and analyses, decision to publish, or preparation of the manuscript. All other authors declare no conflicts of interest.
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- 2021
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43. Import of multidrug-resistant bacteria from abroad through interhospital transfers, Finland, 2010-2019.
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Kajova M, Khawaja T, Kangas J, Mäkinen H, and Kantele A
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- Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents therapeutic use, Drug Resistance, Multiple, Bacterial, Enterobacteriaceae, Finland epidemiology, Hospitals, University, Humans, beta-Lactamases genetics, Methicillin-Resistant Staphylococcus aureus genetics
- Abstract
BackgroundWhile 20-80% of regular visitors to (sub)tropical regions become colonised by extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-PE), those hospitalised abroad often also carry other multidrug-resistant (MDR) bacteria on return; the rates are presumed to be highest for interhospital transfers.AimThis observational study assessed MDR bacterial colonisation among patients transferred directly from hospitals abroad to Helsinki University Hospital. We investigated predisposing factors, clinical infections and associated fatalities.MethodsData were derived from screening and from diagnostic samples collected between 2010 and 2019. Risk factors of colonisation were identified by multivariable analysis. Microbiologically verified symptomatic infections and infection-related mortality were recorded during post-transfer hospitalisation.ResultsColonisation rates proved highest for transfers from Asia (69/96; 71.9%) and lowest for those within Europe (99/524; 18.9%). Of all 698 patients, 208 (29.8%) were colonised; among those, 163 (78.4%) carried ESBL-PE, 28 (13.5%) MDR Acinetobacter species, 25 (12.0%) meticillin-resistant Staphylococcus aureus , 25 (12.0%) vancomycin-resistant Enterococcus , 14 (6.7%) carbapenemase-producing Enterobacteriaceae , and 12 (5.8%) MDR Pseudomonas aeruginosa ; 46 strains tested carbapenemase gene-positive. In multivariable analysis, geographical region, intensive care unit (ICU) treatment and antibiotic use abroad proved to be risk factors for colonisation. Clinical MDR infections, two of them fatal (1.0%), were recorded for 22 of 208 (10.6%) MDR carriers.ConclusionsColonisation by MDR bacteria was common among patients transferred from foreign hospitals. Region of hospitalisation, ICU treatment and antibiotic use were identified as predisposing factors. Within 30 days after transfer, MDR colonisation manifested as clinical infection in more than 10% of the carriers.
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- 2021
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44. Characterization of low-density granulocytes in COVID-19.
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Cabrera LE, Pekkarinen PT, Alander M, Nowlan KHA, Nguyen NA, Jokiranta S, Kuivanen S, Patjas A, Mero S, Pakkanen SH, Heinonen S, Kantele A, Vapalahti O, Kekäläinen E, and Strandin T
- Subjects
- Acute Disease, Adult, Aged, COVID-19 blood, Case-Control Studies, Cohort Studies, Convalescence, Disease Progression, Female, Follow-Up Studies, Granulocytes cytology, Humans, Immune Tolerance immunology, Male, Middle Aged, Scavenger Receptors, Class E analysis, Severity of Illness Index, COVID-19 immunology, Granulocytes classification
- Abstract
Severe COVID-19 is characterized by extensive pulmonary complications, to which host immune responses are believed to play a role. As the major arm of innate immunity, neutrophils are one of the first cells recruited to the site of infection where their excessive activation can contribute to lung pathology. Low-density granulocytes (LDGs) are circulating neutrophils, whose numbers increase in some autoimmune diseases and cancer, but are poorly characterized in acute viral infections. Using flow cytometry, we detected a significant increase of LDGs in the blood of acute COVID-19 patients, compared to healthy controls. Based on their surface marker expression, COVID-19-related LDGs exhibit four different populations, which display distinctive stages of granulocytic development and most likely reflect emergency myelopoiesis. Moreover, COVID-19 LDGs show a link with an elevated recruitment and activation of neutrophils. Functional assays demonstrated the immunosuppressive capacities of these cells, which might contribute to impaired lymphocyte responses during acute disease. Taken together, our data confirms a significant granulocyte activation during COVID-19 and suggests that granulocytes of lower density play a role in disease progression., Competing Interests: The authors have declared that no competing interests exist.
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- 2021
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45. COVID-19 mRNA vaccine induced antibody responses against three SARS-CoV-2 variants.
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Jalkanen P, Kolehmainen P, Häkkinen HK, Huttunen M, Tähtinen PA, Lundberg R, Maljanen S, Reinholm A, Tauriainen S, Pakkanen SH, Levonen I, Nousiainen A, Miller T, Välimaa H, Ivaska L, Pasternack A, Naves R, Ritvos O, Österlund P, Kuivanen S, Smura T, Hepojoki J, Vapalahti O, Lempainen J, Kakkola L, Kantele A, and Julkunen I
- Subjects
- Adult, Aged, Aged, 80 and over, Antibodies, Viral blood, Antibodies, Viral immunology, BNT162 Vaccine, Broadly Neutralizing Antibodies immunology, COVID-19 blood, COVID-19 epidemiology, COVID-19 immunology, COVID-19 Vaccines administration & dosage, Cross Protection immunology, Female, Finland epidemiology, Humans, Immunization, Secondary methods, Immunization, Secondary statistics & numerical data, Male, Mass Vaccination methods, Mass Vaccination statistics & numerical data, Middle Aged, Neutralization Tests statistics & numerical data, Reinfection immunology, Reinfection prevention & control, Reinfection virology, SARS-CoV-2 genetics, Young Adult, Broadly Neutralizing Antibodies blood, COVID-19 prevention & control, COVID-19 Vaccines immunology, Immunogenicity, Vaccine, SARS-CoV-2 immunology
- Abstract
As SARS-CoV-2 has been circulating for over a year, dozens of vaccine candidates are under development or in clinical use. The BNT162b2 mRNA COVID-19 vaccine induces spike protein-specific neutralizing antibodies associated with protective immunity. The emergence of the B.1.1.7 and B.1.351 variants has raised concerns of reduced vaccine efficacy and increased re-infection rates. Here we show, that after the second dose, the sera of BNT162b2-vaccinated health care workers (n = 180) effectively neutralize the SARS-CoV-2 variant with the D614G substitution and the B.1.1.7 variant, whereas the neutralization of the B.1.351 variant is five-fold reduced. Despite the reduction, 92% of the seronegative vaccinees have a neutralization titre of >20 for the B.1.351 variant indicating some protection. The vaccinees' neutralization titres exceeded those of recovered non-hospitalized COVID-19 patients. Our work provides evidence that the second dose of the BNT162b2 vaccine induces cross-neutralization of at least some of the circulating SARS-CoV-2 variants.
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- 2021
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46. Kinetics of Neutralizing Antibodies of COVID-19 Patients Tested Using Clinical D614G, B.1.1.7, and B 1.351 Isolates in Microneutralization Assays.
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Virtanen J, Uusitalo R, Korhonen EM, Aaltonen K, Smura T, Kuivanen S, Pakkanen SH, Mero S, Patjas A, Riekkinen M, Kantele A, Nurmi V, Hedman K, Hepojoki J, Sironen T, Huhtamo E, and Vapalahti O
- Subjects
- Animals, Antibodies, Viral immunology, COVID-19 diagnosis, COVID-19 virology, Chlorocebus aethiops, Coronavirus Nucleocapsid Proteins immunology, Humans, Immunoglobulin G immunology, Kinetics, Neutralization Tests, Phosphoproteins immunology, SARS-CoV-2 genetics, SARS-CoV-2 isolation & purification, Severity of Illness Index, Spike Glycoprotein, Coronavirus immunology, Vero Cells, Antibodies, Neutralizing immunology, COVID-19 immunology, SARS-CoV-2 immunology
- Abstract
Increasing evidence suggests that some newly emerged SARS-CoV-2 variants of concern (VoCs) resist neutralization by antibodies elicited by the early-pandemic wild-type virus. We applied neutralization tests to paired recoveree sera ( n = 38) using clinical isolates representing the first wave (D614G), VoC1, and VoC2 lineages (B.1.1.7 and B 1.351). Neutralizing antibodies inhibited contemporary and VoC1 lineages, whereas inhibition of VoC2 was reduced 8-fold, with 50% of sera failing to show neutralization. These results provide evidence for the increased potential of VoC2 to reinfect previously SARS-CoV-infected individuals. The kinetics of NAbs in different patients showed similar decline against all variants, with generally low initial anti-B.1.351 responses becoming undetectable, but with anti-B.1.1.7 NAbs remaining detectable (>20) for months after acute infection.
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- 2021
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47. Dynamics of intestinal multidrug-resistant bacteria colonisation contracted by visitors to a high-endemic setting: a prospective, daily, real-time sampling study.
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Kantele A, Kuenzli E, Dunn SJ, Dance DAB, Newton PN, Davong V, Mero S, Pakkanen SH, Neumayr A, Hatz C, Snaith A, Kallonen T, Corander J, and McNally A
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- Bacteria, Humans, Prospective Studies, Sampling Studies, Anti-Bacterial Agents pharmacology, Drug Resistance, Multiple, Bacterial genetics
- Abstract
Background: Antimicrobial resistance is highly prevalent in low-income and middle-income countries. International travel contributes substantially to the global spread of intestinal multidrug-resistant Gram-negative bacteria. Hundreds of millions of annual visitors to low-income and middle-income countries are all exposed to intestinal multidrug-resistant Gram-negative bacteria resulting in 30-70% of them being colonised at their return. The colonisation process in high-exposure environments is poorly documented because data have only been derived from before travel and after travel sampling. We characterised colonisation dynamics by exploring daily stool samples while visiting a low-income and middle-income countries., Methods: In this prospective, daily, real-time sampling study 20 European visitors to Laos volunteered to provide daily stool samples and completed daily questionnaires for 22 days. Samples were initially assessed at Mahosot Hospital, Vientiane, Laos, for acquisition of extended-spectrum β-lactamase-producing (ESBL) Gram-negative bacteria followed by whole-genome sequencing of isolates at MicrobesNG, University of Birmingham, Birmingham, UK. The primary outcome of the study was to obtain data on the dynamics of intestinal multidrug-resistant bacteria acquisition., Findings: Between Sept 18 and Sept 20, 2015, 23 volunteers were recruited, of whom 20 (87%) European volunteers were included in the final study population. Although colonisation rates were 70% at the end of the study, daily sampling revealed that all participants had acquired ESBL-producing Gram-negative bacteria at some point during the study period; the colonisation status varied day by day. Whole-genome sequencing analysis ascribed the transient pattern of colonisation to sequential acquisition of new strains, resulting in a loss of detectable colonisation by the initial multidrug-resistant Gram-negative strains. 19 (95%) participants acquired two to seven strains. Of the 83 unique strains identified (53 Escherichia coli , 10 Klebsiella spp, and 20 other ESBL-producing Gram-negative bacteria), some were shared by as many as four (20%) participants., Interpretation: To our knowledge, this is the first study to characterise in real-time the dynamics of acquiring multidrug-resistant Gram-negative bacterial colonisation during travel. Our data show multiple transient colonisation events indicative of constant microbial competition and suggest that travellers are exposed to a greater burden of multidrug-resistant bacteria than previously thought. The data emphasise the need for preventing travellers' diarrhoea and limiting antibiotic use, addressing the two major factors predisposing colonisation., Funding: The Finnish Governmental Subsidy for Health Science Research, The Scandinavian Society for Antimicrobial Chemotherapy, the Sigrid Jusélius Foundation, Biotechnology and Biological Sciences Research Council; Wellcome Trust, Medical Research Council; The Royal Society; Joint Programming Initiative on Antimicrobial Resistance, and European Research Council., (© 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license.)
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- 2021
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48. Bacterial, viral and parasitic pathogens analysed by qPCR: Findings from a prospective study of travellers' diarrhoea.
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Lääveri T, Antikainen J, Mero S, Pakkanen SH, Kirveskari J, Roivainen M, and Kantele A
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- Animals, Diarrhea, Escherichia coli, Feces, Humans, Prospective Studies, Cryptosporidiosis, Cryptosporidium, Parasites
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Background: The diagnostics of travellers' diarrhoea (TD) has been revolutionised by multiplex qPCR assays. While mostly of bacterial aetiology, viruses and parasites account for the disease among 10-20% of travellers. Despite this, prospective studies applying qPCR assays remain scarce that cover not only bacteria, such as the various diarrhoeagenic Escherichia coli (DEC), but also viral and parasitic pathogens., Method: We analysed by qPCR pre- and post-travel stool samples of 146 Finnish travellers for bacterial, viral and parasitic pathogens: enteropathogenic (EPEC), enteroaggregative (EAEC), enterotoxigenic (ETEC), enterohaemorrhagic (EHEC), and enteroinvasive (EIEC) E. coli; Shigella, Campylobacter, Salmonella, Yersinia and Vibrio cholerae; norovirus G1 and G2, rotavirus, enteroviruses, and sapovirus; and Giardia lamblia, Entamoeba histolytica, and Cryptosporidium. Symptoms and medication data during travel were collected by questionnaires., Results: We detected bacterial pathogens in 102/146 samples (69.9%; EAEC, EPEC, ETEC most common), viral ones in 13 (8.9%; norovirus most common), and parasitic ones in one (0.7%; Giardia). Noroviruses were associated with severe symptoms (23.5% versus non-severe 4.9%). In the TD group, 41.7% (5/12) of those with viral pathogens (vs. 13.3%; 11/83 without) took antibiotics., Conclusion: Viral pathogens, particularly noroviruses, prevail in severe TD. The symptoms of viral disease are often severe and lead to unwarranted use of antibiotics., (Copyright © 2020. Published by Elsevier Ltd.)
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- 2021
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49. Effects of Environmental Factors on Severity and Mortality of COVID-19.
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Kifer D, Bugada D, Villar-Garcia J, Gudelj I, Menni C, Sudre C, Vučković F, Ugrina I, Lorini LF, Posso M, Bettinelli S, Ughi N, Maloberti A, Epis O, Giannattasio C, Rossetti C, Kalogjera L, Peršec J, Ollivere L, Ollivere BJ, Yan H, Cai T, Aithal GP, Steves CJ, Kantele A, Kajova M, Vapalahti O, Sajantila A, Wojtowicz R, Wierzba W, Krol Z, Zaczynski A, Zycinska K, Postula M, Lukšić I, Čivljak R, Markotić A, Brachmann J, Markl A, Mahnkopf C, Murray B, Ourselin S, Valdes AM, Horcajada JP, Castells X, Pascual J, Allegri M, Primorac D, Spector TD, Barrios C, and Lauc G
- Abstract
Background: Most respiratory viruses show pronounced seasonality, but for SARS-CoV-2, this still needs to be documented. Methods: We examined the disease progression of COVID-19 in 6,914 patients admitted to hospitals in Europe and China. In addition, we evaluated progress of disease symptoms in 37,187 individuals reporting symptoms into the COVID Symptom Study application. Findings: Meta-analysis of the mortality risk in seven European hospitals estimated odds ratios per 1-day increase in the admission date to be 0.981 (0.973-0.988, p < 0.001) and per increase in ambient temperature of 1°C to be 0.854 (0.773-0.944, p = 0.007). Statistically significant decreases of comparable magnitude in median hospital stay, probability of transfer to the intensive care unit, and need for mechanical ventilation were also observed in most, but not all hospitals. The analysis of individually reported symptoms of 37,187 individuals in the UK also showed the decrease in symptom duration and disease severity with time. Interpretation: Severity of COVID-19 in Europe decreased significantly between March and May and the seasonality of COVID-19 is the most likely explanation., Competing Interests: The authors declare that this study received funding from Zoe Global Ltd. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication., (Copyright © 2021 Kifer, Bugada, Villar-Garcia, Gudelj, Menni, Sudre, Vučković, Ugrina, Lorini, Posso, Bettinelli, Ughi, Maloberti, Epis, Giannattasio, Rossetti, Kalogjera, Peršec, Ollivere, Ollivere, Yan, Cai, Aithal, Steves, Kantele, Kajova, Vapalahti, Sajantila, Wojtowicz, Wierzba, Krol, Zaczynski, Zycinska, Postula, Lukšić, Čivljak, Markotić, Brachmann, Markl, Mahnkopf, Murray, Ourselin, Valdes, Horcajada, Castells, Pascual, Allegri, Primorac, Spector, Barrios and Lauc.)
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- 2021
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50. A 10-Minute "Mix and Read" Antibody Assay for SARS-CoV-2.
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Rusanen J, Kareinen L, Levanov L, Mero S, Pakkanen SH, Kantele A, Amanat F, Krammer F, Hedman K, Vapalahti O, and Hepojoki J
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- Antibodies, Neutralizing blood, Antibodies, Viral blood, COVID-19 blood, Coronavirus Nucleocapsid Proteins immunology, Humans, Phosphoproteins immunology, SARS-CoV-2 immunology, Sensitivity and Specificity, Spike Glycoprotein, Coronavirus immunology, COVID-19 diagnosis, COVID-19 Serological Testing methods, Immunoassay methods, SARS-CoV-2 isolation & purification
- Abstract
Accurate and rapid diagnostic tools are needed for management of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Antibody tests enable detection of individuals past the initial phase of infection and help examine vaccine responses. The major targets of human antibody response in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are the spike glycoprotein (SP) and nucleocapsid protein (NP). We have developed a rapid homogenous approach for antibody detection termed LFRET (protein L-based time-resolved Förster resonance energy transfer immunoassay). In LFRET, fluorophore-labeled protein L and antigen are brought to close proximity by antigen-specific patient immunoglobulins of any isotype, resulting in TR-FRET signal. We set up LFRET assays for antibodies against SP and NP and evaluated their diagnostic performance using a panel of 77 serum/plasma samples from 44 individuals with COVID-19 and 52 negative controls. Moreover, using a previously described SP and a novel NP construct, we set up enzyme linked immunosorbent assays (ELISAs) for antibodies against SARS-CoV-2 SP and NP. We then compared the LFRET assays with these ELISAs and with a SARS-CoV-2 microneutralization test (MNT). We found the LFRET assays to parallel ELISAs in sensitivity (90-95% vs. 90-100%) and specificity (100% vs. 94-100%). In identifying individuals with or without a detectable neutralizing antibody response, LFRET outperformed ELISA in specificity (91-96% vs. 82-87%), while demonstrating an equal sensitivity (98%). In conclusion, this study demonstrates the applicability of LFRET, a 10-min "mix and read" assay, to detection of SARS-CoV-2 antibodies.
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- 2021
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