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1.
Nat Commun ; 13(1): 2476, 2022 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-35513437

RESUMO

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.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19/prevenção & controle , Humanos , SARS-CoV-2 , Vacinas Sintéticas
2.
Front Immunol ; 13: 869990, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35529867

RESUMO

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.


Assuntos
COVID-19 , SARS-CoV-2 , Anticorpos Antivirais , Vacinas contra COVID-19 , Humanos , Leucócitos Mononucleares , RNA Mensageiro/genética , Glicoproteína da Espícula de Coronavírus , Linfócitos T
3.
Travel Med Infect Dis ; 48: 102331, 2022 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-35447322

RESUMO

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.

4.
J Travel Med ; 2022 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-35234907

RESUMO

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, while 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.

5.
Microbiol Spectr ; 10(2): e0225221, 2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35262410

RESUMO

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.


Assuntos
COVID-19 , SARS-CoV-2 , Anticorpos Neutralizantes , Anticorpos Antivirais , Formação de Anticorpos , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Humanos , RNA Mensageiro , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus , Vacinação , Vacinas Sintéticas
6.
Vaccine ; 40(9): 1299-1305, 2022 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-35101266

RESUMO

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.


Assuntos
Vírus da Encefalite Transmitidos por Carrapatos , Encefalite Transmitida por Carrapatos , Vacinas Virais , Adulto , Anticorpos Antivirais , Encefalite Transmitida por Carrapatos/prevenção & controle , Humanos , Esquemas de Imunização , Pessoa de Meia-Idade
7.
J Travel Med ; 29(1)2022 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-33834207

RESUMO

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.


Assuntos
Infecções por Escherichia coli , Escherichia coli , Antibacterianos/uso terapêutico , Azitromicina , Diarreia/tratamento farmacológico , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/epidemiologia , Infecções por Escherichia coli/microbiologia , Fezes/microbiologia , Humanos , Estudos Prospectivos , beta-Lactamases
8.
Clin Microbiol Infect ; 28(1): 107-113, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34949510

RESUMO

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.


Assuntos
COVID-19 , /estatística & dados numéricos , COVID-19/epidemiologia , COVID-19/etnologia , Estudos de Coortes , Cuidados Críticos , Finlândia/epidemiologia , Hospitalização , Humanos , Unidades de Terapia Intensiva , Idioma , Estudos Retrospectivos
9.
Acta Neuropathol Commun ; 9(1): 199, 2021 12 23.
Artigo em Inglês | MEDLINE | ID: mdl-34949230

RESUMO

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.


Assuntos
Apolipoproteína E4/genética , COVID-19/complicações , COVID-19/genética , Hemorragia Cerebral/genética , Fadiga Mental/genética , Gravidade do Paciente , Adulto , Idoso , Autopsia , Bancos de Espécimes Biológicos , COVID-19/diagnóstico , COVID-19/epidemiologia , Hemorragia Cerebral/diagnóstico , Hemorragia Cerebral/epidemiologia , Estudos de Coortes , Feminino , Finlândia/epidemiologia , Estudos de Associação Genética/métodos , Heterozigoto , Humanos , Masculino , Fadiga Mental/diagnóstico , Fadiga Mental/epidemiologia , Microvasos/patologia , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Adulto Jovem
10.
Viruses ; 13(12)2021 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-34960758

RESUMO

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.


Assuntos
Antivirais/farmacologia , Interferon-alfa/farmacologia , SARS-CoV-2/efeitos dos fármacos , Linhagem Celular , Sinergismo Farmacológico , Humanos , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/virologia , Metaboloma/efeitos dos fármacos , Organoides , RNA Viral/biossíntese , RNA Viral/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Transcriptoma/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos , Vírus/classificação , Vírus/efeitos dos fármacos
11.
Thromb Res ; 208: 129-137, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34768097

RESUMO

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.


Assuntos
Vacinas contra Adenovirus , COVID-19 , Adenoviridae , Plaquetas , Vacinas contra COVID-19 , Humanos , Imunoglobulina G , Fator Plaquetário 4 , SARS-CoV-2
12.
Microbiol Spectr ; 9(3): e0113121, 2021 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-34787485

RESUMO

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.


Assuntos
Anticorpos Antivirais/imunologia , Teste Sorológico para COVID-19/métodos , Imunofluorescência/métodos , Imunoglobulina A/imunologia , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Proteínas do Nucleocapsídeo/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Anticorpos Neutralizantes/imunologia , COVID-19/diagnóstico , Proteínas do Nucleocapsídeo de Coronavírus/imunologia , Humanos , Nucleoproteínas , Fosfoproteínas/imunologia , SARS-CoV-2 , Sensibilidade e Especificidade
13.
Travel Med Infect Dis ; 44: 102186, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34688889

RESUMO

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.


Assuntos
Refugiados , Migrantes , Adulto , Feminino , Hospitalização , Hospitais Universitários , Humanos , Gravidez , Estudos Retrospectivos
14.
Euro Surveill ; 26(39)2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34596014

RESUMO

BackgroundWhile 20-80% of regular visitors to (sub)tropical regions become colonised by extended-spectrum ß-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.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana Múltipla , Enterobacteriaceae , Finlândia/epidemiologia , Hospitais Universitários , Humanos , Staphylococcus aureus Resistente à Meticilina/genética , beta-Lactamases/genética
15.
PLoS Negl Trop Dis ; 15(9): e0009709, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34587158

RESUMO

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.


Assuntos
Bactérias/isolamento & purificação , Infecções Bacterianas/microbiologia , Diarreia/microbiologia , Diarreia/virologia , Viroses/virologia , Vírus/isolamento & purificação , Bactérias/classificação , Bactérias/genética , Infecções Bacterianas/epidemiologia , Pré-Escolar , Diarreia/epidemiologia , Fezes/microbiologia , Fezes/virologia , Feminino , Guiné-Bissau/epidemiologia , Humanos , Lactente , Masculino , Viroses/epidemiologia , Vírus/classificação , Vírus/genética
16.
PLoS Pathog ; 17(7): e1009721, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34228753

RESUMO

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.


Assuntos
COVID-19/imunologia , Granulócitos/classificação , Doença Aguda , Adulto , Idoso , COVID-19/sangue , Estudos de Casos e Controles , Estudos de Coortes , Convalescença , Progressão da Doença , Feminino , Seguimentos , Granulócitos/citologia , Humanos , Tolerância Imunológica/imunologia , Masculino , Pessoa de Meia-Idade , Receptores Depuradores Classe E/análise , Índice de Gravidade de Doença
17.
Viruses ; 13(6)2021 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-34073577

RESUMO

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.


Assuntos
Anticorpos Neutralizantes/imunologia , COVID-19/imunologia , SARS-CoV-2/imunologia , Animais , Anticorpos Antivirais/imunologia , COVID-19/diagnóstico , COVID-19/virologia , Chlorocebus aethiops , Proteínas do Nucleocapsídeo de Coronavírus/imunologia , Humanos , Imunoglobulina G/imunologia , Cinética , Testes de Neutralização , Fosfoproteínas/imunologia , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença , Glicoproteína da Espícula de Coronavírus/imunologia , Células Vero
18.
Nat Commun ; 12(1): 3991, 2021 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-34183681

RESUMO

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.


Assuntos
Anticorpos Amplamente Neutralizantes/sangue , Vacinas contra COVID-19/imunologia , COVID-19/prevenção & controle , Imunogenicidade da Vacina , SARS-CoV-2/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Anticorpos Amplamente Neutralizantes/imunologia , COVID-19/sangue , COVID-19/epidemiologia , COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Proteção Cruzada/imunologia , Feminino , Finlândia/epidemiologia , Humanos , Imunização Secundária/métodos , Imunização Secundária/estatística & dados numéricos , Masculino , Vacinação em Massa/métodos , Vacinação em Massa/estatística & dados numéricos , Pessoa de Meia-Idade , Testes de Neutralização/estatística & dados numéricos , Reinfecção/imunologia , Reinfecção/prevenção & controle , Reinfecção/virologia , SARS-CoV-2/genética , Adulto Jovem
19.
Lancet Microbe ; 2(4): e151-e158, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33821248

RESUMO

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 ß-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.


Assuntos
Antibacterianos , Farmacorresistência Bacteriana Múltipla , Antibacterianos/farmacologia , Bactérias , Farmacorresistência Bacteriana Múltipla/genética , Humanos , Estudos Prospectivos , Amostragem
20.
Viruses ; 13(2)2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33498157

RESUMO

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.


Assuntos
Teste Sorológico para COVID-19/métodos , COVID-19/diagnóstico , Imunoensaio/métodos , SARS-CoV-2/isolamento & purificação , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , COVID-19/sangue , Proteínas do Nucleocapsídeo de Coronavírus/imunologia , Humanos , Fosfoproteínas/imunologia , SARS-CoV-2/imunologia , Sensibilidade e Especificidade , Glicoproteína da Espícula de Coronavírus/imunologia
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