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1.
Microbiol Spectr ; 9(1): e0002621, 2021 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-34346746

RESUMO

Pneumocystis jirovecii is a threat to iatrogenically immunosuppressed individuals, a heterogeneous population at rapid growth. We assessed the ability of an in-house semiquantitative real-time PCR assay to discriminate Pneumocystis pneumonia (PCP) from colonization and identified risk factors for infection in these patients. Retrospectively, 242 PCR-positive patients were compared according to PCP status, including strata by immunosuppressive conditions, human immunodeficiency virus (HIV) infection excluded. Associations between host characteristics and cycle threshold (CT) values, semiquantitative real-time PCR correlates of fungal loads in lower respiratory tract specimens, were investigated. CT values differed significantly according to PCP status. Overall, a CT value of 36 allowed differentiation between PCP and colonization with sensitivity and specificity of 71.3% and 77.1%, respectively. A CT value of less than 31 confirmed PCP, whereas no CT value permitted exclusion. A considerable diversity was uncovered; solid organ transplant (SOT) recipients had significantly higher fungal loads than patients with hematological malignancies. In SOT recipients, a CT cutoff value of 36 resulted in sensitivity and specificity of 95.0% and 83.3%, respectively. In patients with hematological malignancies, a higher CT cutoff value of 37 improved sensitivity to 88.5% but reduced specificity to 66.7%. For other conditions, assay validity appeared inferior. Corticosteroid usage was an independent predictor of PCP in a multivariable analysis and was associated with higher fungal loads at PCP expression. Semiquantitative real-time PCR improves differentiation between PCP and colonization in immunocompromised HIV-negative individuals with acute respiratory syndromes. However, heterogeneity in disease evolution requires separate cutoff values across intrinsic and iatrogenic predisposition for predicting non-HIV PCP. IMPORTANCE Pneumocystis jirovecii is potentially life threatening to an increasing number of individuals with compromised immune systems. This microorganism can cause severe pneumonia in susceptible hosts, including patients with cancer and autoimmune diseases and people undergoing solid organ transplantation. Together, these patients constitute an ever-diverse population. In this paper, we demonstrate that the heterogeneity herein has important implications for how we diagnose and assess the risk of Pneumocystis pneumonia (PCP). Specifically, low loads of microorganisms are sufficient to cause infection in patients with blood cancer compared to those in solid organ recipients. With this new insight into host versus P. jirovecii biology, clinicians can manage patients at risk of PCP more accurately. As a result, we take a significant step toward offering precision medicine to a vulnerable patient population. One the one hand, these patients have propensity for adverse effects from antimicrobial treatment. On the other hand, this population is susceptible to life-threatening infections, including PCP.

2.
BMJ Open ; 11(7): e048370, 2021 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-34272222

RESUMO

OBJECTIVES: There is a lack of data regarding the quality of peripheral intravenous catheter (PIVC)-related care from low-income and middle-income countries, even though the use of PIVCs may lead to local or severe systemic infections. Our main objective was to assess the feasibility and inter-rater agreement on the PIVC-mini Questionnaire (PIVC-miniQ) in a tertiary care hospital in Nepal. DESIGN: We performed an observational cross-sectional quantitative study using the PIVC-miniQ to collect information on PIVC quality. SETTING: Secondary care in a Nepalese hospital. All patients with PIVCs in selected wards were included in the study and PIVCs were assessed independently by two raters. Eight Nepalese nurses, one Nepalese student and three Norwegian students participated as raters. PRIMARY AND SECONDARY OUTCOME MEASURES: The intraclass correlation coefficient (ICC), positive, negative, absolute agreement, Scott's pi and sum score were calculated using PIVC-miniQ. We also aimed to describe PIVC quality of care, as it is important to prevent PIVC-associated complications such as phlebitis or catheter-associated bloodstream infections. RESULTS: A total of 390 patients (409 PIVCs) were included in the study. The ICC between raters was 0.716 for Nepalese raters, 0.644 for Norwegian raters and 0.481 for the pooled data. The most frequently observed problems associated with PIVCs were blood in the intravenous line (51.5%), pain and tenderness on palpation (43.4%), and fixation with opaque tape (38.5%). The average sum score was 3.32 deviations from best practice for PIVCs fixed with non-sterile opaque tape and 2.37 for those fixed with transparent dressing (p<0.001). CONCLUSION: The PIVC-miniQ is a feasible and reliable tool for nurses assessing PIVC quality in hospitalised patients in Nepal. The study revealed gaps in PIVC quality and care that could be improved by providing transparent PIVC dressings for all patients and requiring all PIVC insertions to be documented in patient charts.


Assuntos
Cateterismo Periférico , Cateteres , Estudos Transversais , Estudos de Viabilidade , Humanos , Nepal , Noruega , Inquéritos e Questionários , Centros de Atenção Terciária
3.
BMC Infect Dis ; 21(1): 659, 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34233631

RESUMO

BACKGROUND: Pneumocystis pneumonia (PCP) severely menaces modern chemotherapy and immunosuppression. Detailed description of the epidemiology of Pneumocystis jirovecii today is needed to identify candidates for PCP-prophylaxis. METHODS: We performed a 12-year retrospective study of patients with P. jirovecii detected by polymerase chain reaction in Central Norway. In total, 297 patients were included. Comprehensive biological, clinical and epidemiological data were abstracted from patients' medical records. Regional incidence rates and testing trends were also assessed. RESULTS: From 2007 to 2017 we found a 3.3-fold increase in testing for P. jirovecii accompanied by a 1.8-fold increase in positive results. Simultaneously, regional incidence rates doubled from 5.0 cases per 100,000 person years to 10.8. A majority of the study population had predisposing conditions other than human immunodeficiency virus (HIV). Hematological (36.0%) and solid cancers (25.3%) dominated. Preceding corticosteroids were a common denominator for 72.1%. Most patients (74.4%) presented with at least two cardinal symptoms; cough, dyspnea or fever. Main clinical findings were hypoxia, cytopenias and radiological features consistent with PCP. A total of 88 (29.6%) patients required intensive care and 121 (40.7%) suffered at least one complication. In-hospital mortality was 21.5%. Three patients (1.0%) had received prophylaxis. CONCLUSIONS: P. jirovecii is re-emerging; likely due to increasing immunosuppressants use. This opportunistic pathogen threatens the life of heterogenous non-HIV immunosuppressed populations currently at growth. Corticosteroids seem to be a major risk factor. A strategy to increase prophylaxis is called for.


Assuntos
Hospedeiro Imunocomprometido , Imunossupressores/administração & dosagem , Pneumocystis carinii/isolamento & purificação , Pneumonia por Pneumocystis/diagnóstico , Pneumonia por Pneumocystis/mortalidade , Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Idoso , Feminino , Infecções por HIV/epidemiologia , Neoplasias Hematológicas/epidemiologia , Mortalidade Hospitalar , Humanos , Imunossupressores/uso terapêutico , Incidência , Masculino , Pessoa de Meia-Idade , Noruega/epidemiologia , Pneumocystis carinii/genética , Pneumonia por Pneumocystis/microbiologia , Reação em Cadeia da Polimerase , Estudos Retrospectivos , Fatores de Risco
4.
Viruses ; 12(6)2020 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-32545799

RESUMO

As of June 2020, the number of people infected with severe acute respiratory coronavirus 2 (SARS-CoV-2) continues to skyrocket, with more than 6.7 million cases worldwide. Both the World Health Organization (WHO) and United Nations (UN) has highlighted the need for better control of SARS-CoV-2 infections. However, developing novel virus-specific vaccines, monoclonal antibodies and antiviral drugs against SARS-CoV-2 can be time-consuming and costly. Convalescent sera and safe-in-man broad-spectrum antivirals (BSAAs) are readily available treatment options. Here, we developed a neutralization assay using SARS-CoV-2 strain and Vero-E6 cells. We identified the most potent sera from recovered patients for the treatment of SARS-CoV-2-infected patients. We also screened 136 safe-in-man broad-spectrum antivirals against the SARS-CoV-2 infection in Vero-E6 cells and identified nelfinavir, salinomycin, amodiaquine, obatoclax, emetine and homoharringtonine. We found that a combination of orally available virus-directed nelfinavir and host-directed amodiaquine exhibited the highest synergy. Finally, we developed a website to disseminate the knowledge on available and emerging treatments of COVID-19.


Assuntos
Antivirais/farmacologia , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Testes de Neutralização/métodos , Pneumonia Viral/tratamento farmacológico , Amodiaquina/farmacologia , Animais , COVID-19 , Células CACO-2 , Linhagem Celular Tumoral , Chlorocebus aethiops , Infecções por Coronavirus/terapia , Quimioterapia Combinada , Emetina/farmacologia , Células HEK293 , Células HT29 , Mepesuccinato de Omacetaxina/farmacologia , Humanos , Soros Imunes/imunologia , Imunização Passiva/métodos , Nelfinavir/farmacologia , Pandemias , Piranos/farmacologia , Pirróis/farmacologia , SARS-CoV-2 , Células Vero
5.
BMC Pregnancy Childbirth ; 20(1): 67, 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32005186

RESUMO

BACKGROUND: Guidelines regarding management of prelabor rupture of membranes (PROM) at term vary between immediate induction and expectant management. A long interval between PROM and delivery increases the risk for perinatal infections. Severe perinatal infections are associated with excess risk for cerebral palsy (CP) and perinatal death. We investigated if increasing intervals between PROM and delivery were associated with perinatal death or CP. METHODS: Eligible to participate in this population-based cohort-study were term born singletons without congenital malformations born in Norway during 1999-2009. Data was retrieved from the Medical Birth Registry of Norway (MBRN) and the Cerebral Palsy Register of Norway. In line with the registration in the MBRN, intervals between PROM and delivery of more than 24 h was defined as 'prolonged' and intervals between 12 and 24 h as 'intermediate'. Outcomes were stillbirth, death during delivery, neonatal mortality and CP. Logistic regression was used to calculate odds ratio (OR) with 95% confidence intervals (CI) for adverse outcomes in children born after prolonged and intermediate intervals, compared with a reference group comprising all children born less than 12 h after PROM or without PROM. RESULTS: Among 559,972 births, 34,759 children were born after intermediate and 30,332 were born after prolonged intervals. There was no association between increasing intervals and death during delivery or in the neonatal period, while the prevalence of stillbirths decreased with increasing intervals. Among children born after intermediate intervals 38 (0.11%) had CP, while among those born after prolonged intervals 46 (0.15%) had CP. Compared with the reference group, the OR for CP was 1.16 (CI; 0.83 to 1.61) after intermediate and 1.61 (CI; 1.19 to 2.18) after prolonged intervals. Adjusting for antenatal factors did not affect these associations. Among children with CP the proportion with diffuse cortical injury and basal ganglia pathology on cerebral MRI, consistent with hypoxic-ischemic injuries, increased with increasing intervals. CONCLUSION: Intervals between PROM and delivery of more than 24 h were associated with CP, but not with neonatal mortality or death during delivery. The inverse association with stillbirth is probably due to reverse causality.


Assuntos
Paralisia Cerebral/etiologia , Ruptura Prematura de Membranas Fetais , Adulto , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Mortalidade Infantil , Recém-Nascido , Modelos Logísticos , Masculino , Noruega/epidemiologia , Razão de Chances , Gravidez , Sistema de Registros , Natimorto , Fatores de Tempo , Adulto Jovem
6.
Acta Paediatr ; 108(1): 76-82, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30238492

RESUMO

AIM: Klebsiella spp. have been stated to be the most frequent cause of neonatal intensive care unit (NICU) outbreaks. We report an outbreak of Klebsiella oxytoca in a NICU at a tertiary care hospital in Norway between April 2016 and April 2017. This study describes the outbreak, infection control measures undertaken and the molecular methods developed. METHODS: The outbreak prompted detailed epidemiological and microbial investigations, where whole-genome sequencing (WGS) was particularly useful for both genotyping and development of two new K. oxytoca-specific real-time PCR assays. Routine screening of patients, as well as sampling from numerous environmental sites, was performed during the outbreak. A bundle of infection control measures was instigated to control the outbreak, among them strict cohort isolation. RESULTS: Five neonates had symptomatic infection, and 17 were found to be asymptomatically colonised. Infections varied in severity from conjunctivitis to a fatal case of pneumonia. A source of the outbreak could not be determined. CONCLUSION: This report describes K. oxytoca as a significant pathogen in a NICU outbreak setting and highlights the importance of developing appropriate microbiological screening methods and implementing strict infection control measures to control the outbreak in a setting where the source could not be identified.


Assuntos
Infecção Hospitalar/epidemiologia , Surtos de Doenças/estatística & dados numéricos , Unidades de Terapia Intensiva Neonatal , Infecções por Klebsiella/epidemiologia , Klebsiella oxytoca/patogenicidade , Estudos de Coortes , DNA Bacteriano/análise , Feminino , Mortalidade Hospitalar , Hospitais Universitários , Humanos , Recém-Nascido , Controle de Infecções/organização & administração , Infecções por Klebsiella/diagnóstico , Infecções por Klebsiella/tratamento farmacológico , Masculino , Noruega , Prevalência , Reação em Cadeia da Polimerase em Tempo Real/métodos , Estudos Retrospectivos , Medição de Risco
7.
Infect Dis Obstet Gynecol ; 2018: 4980396, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30224859

RESUMO

Introduction: We have previously determined the prevalence of human papillomavirus (HPV) infection among women in rural Nepal. In the current study, we also wanted to examine the prevalence of and risk factors for other sexually transmitted infections (STIs) in the same population. Methods: Population-based study of nonpregnant women ≥ 15 years who were married or had a history of marriage in the past, residing in five rural villages in Nepal. Data on sociodemographic characteristics, reproductive history, and genitourinary symptoms were collected, and a gynecological examination was conducted. Cervical samples were analyzed by real-time PCR for Neisseria gonorrhoeae, Chlamydia trachomatis, and Trichomonas vaginalis and HPV, and a serum sample was analyzed for syphilis, hepatitis B virus (HBV) and HIV infection by serology. Results: Of 2416 eligible women, 62% participated. Trichomoniasis, Chlamydia trachomatis infection, HPV and HBV infection, and syphilis were detected in 5.4%, 0.8%, 14.3%, 0.3%, and 0.2% of the women. None had gonorrhea or HIV infection. Of those with genitourinary symptoms, 6.3% had a curable STI. Vaginal discharge classified as abnormal by gynecological examination, but not self-reported discharge, was significantly associated with laboratory diagnosis of a curable STI. Risk factors for trichomoniasis were reproductive age and high cast/ethnicity. Due to low prevalence, risk factors for other STIs could not be disclosed. Conclusion: We observed high prevalence of HPV infection followed by trichomoniasis, while other STIs were rare among women in rural Nepal. There was no association between genitourinary symptoms and laboratory-confirmed STIs.


Assuntos
Doenças Sexualmente Transmissíveis/epidemiologia , Adolescente , Adulto , Infecções por Chlamydia/epidemiologia , Feminino , Hepatite B/epidemiologia , Humanos , Modelos Logísticos , Casamento , Pessoa de Meia-Idade , Nepal/epidemiologia , Infecções por Papillomavirus/epidemiologia , Prevalência , Fatores de Risco , População Rural , Sífilis/epidemiologia , Tricomoníase/epidemiologia , Adulto Jovem
8.
Viruses ; 10(8)2018 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-30103549

RESUMO

There are dozens of approved, investigational and experimental antiviral agents. Many of these agents cause serious side effects, which can only be revealed after drug administration. Identification of the side effects prior to drug administration is challenging. Here we describe an ex vivo approach for studying immuno- and neuro-modulatory properties of antiviral agents, which may be associated with potential side effects of these therapeutics. The current approach combines drug toxicity/efficacy tests and transcriptomics, which is followed by mRNA, cytokine and metabolite profiling. We demonstrated the utility of this approach with several examples of antiviral agents. We also showed that the approach can utilize different immune stimuli and cell types. It can also include other omics techniques, such as genomics and epigenomics, to allow identification of individual markers associated with adverse reactions to antivirals with immuno- and neuro-modulatory properties.


Assuntos
Antivirais/efeitos adversos , Sistema Imunitário/efeitos dos fármacos , Sistema Nervoso/efeitos dos fármacos , Biologia de Sistemas/métodos , Citocinas/genética , Citocinas/imunologia , Epigenômica , Perfilação da Expressão Gênica , Genômica , Humanos , Metabolômica , Medicina de Precisão
9.
Intensive Care Med ; 44(8): 1276-1283, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30039264

RESUMO

PURPOSE: As iron is essential for both immune function and microbial growth, alterations in iron status could influence the risk of infections. We assessed the associations of iron status with risk of bloodstream infections (BSIs) and BSI mortality. METHODS: We measured serum iron, transferrin saturation (Tsat) and total iron-binding capacity (TIBC) in 61,852 participants in the population-based HUNT2 study (1995-97). Incident BSIs (1995-2011) were identified through linkage with the Mid-Norway Sepsis Register, which includes prospectively registered information on BSI from local and regional hospitals. We assessed the risk of a first-time BSI and BSI mortality with the iron indices using Cox proportional hazards regression analysis. RESULTS: During a median follow-up of 14.8 years, 1738 individuals experienced at least one episode of BSI, and 370 died within 30 days after a BSI. In age- and sex-adjusted analyses, BSI risk was increased among participants with indices of iron deficiency, serum iron ≤ 2.5th percentile (HR 1.72, 95% CI 1.34-2.21), Tsat ≤ 2.5th percentile (HR 1.48, 95% CI 1.12-1.96) or TIBC ≥ 97.5th percentile (HR 1.46, 95% CI 1.06-2.01). The associations remained similar after adjusting for comorbidities and exclusion of BSI related to cancer, rheumatic illnesses and inflammatory bowel disease. BSI mortality showed similar associations. CONCLUSION: Indices of severe iron deficiency are associated with an increased risk of a future BSI.


Assuntos
Bacteriemia , Ferro , Adulto , Bacteriemia/epidemiologia , Humanos , Ferro/sangue , Ferro/deficiência , Noruega , Estudos Prospectivos , Fatores de Risco , Adulto Jovem
10.
Thorax ; 2018 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-29622693

RESUMO

INTRODUCTION: Targeted testing and treatment of latent TB infection (LTBI) are priorities on the global health agenda, but LTBI management remains challenging. We aimed to evaluate the prognostic value of the QuantiFERON TB-Gold (QFT) test for incident TB, focusing on the interferon (IFN)-γ level, when applied in routine practice in a low TB incidence setting. METHODS: In this large population-based prospective cohort, we linked QFT results in Norway (1 January 2009-30 June 2014) with national registry data (Norwegian Surveillance System for Infectious Diseases, Norwegian Prescription Database, Norwegian Patient Registry and Statistics Norway) to assess the prognostic value of QFT for incident TB. Participants were followed until 30 June 2016. We used restricted cubic splines to model non-linear relationships between IFN-γ levels and TB, and applied these findings to a competing risk model. RESULTS: The prospective analyses included 50 389 QFT results from 44 875 individuals, of whom 257 developed TB. Overall, 22% (n=9878) of QFT results were positive. TB risk increased with the IFN-γ level until a plateau level, above which further increase was not associated with additional prognostic information. The HRs for TB were 8.8 (95% CI 4.7 to 16.5), 19.2 (95% CI 11.6 to 31.6) and 31.3 (95% CI 19.8 to 49.5) times higher with IFN-γ levels of 0.35 to <1.00, 1.00 to <4.00 and >4.00 IU/mL, respectively, compared with negative tests (<0.35 IU/mL). CONCLUSIONS: Consistently, QFT demonstrates increased risk of incident TB with rising IFN-γ concentrations, indicating that IFN-γ levels may be used to guide targeted treatment of LTBI.

11.
J Med Microbiol ; 66(1): 26-33, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28032541

RESUMO

Streptococcus agalactiae (group B streptococci, GBS) are important human and animal pathogens, which can be subdivided based on different capsular polysaccharides and surface-anchored alpha-like proteins (Alps), as well as other proteins. Nearly all GBS strains possess an Alp (Alp GBS), although Alp-negative GBS (non-Alp GBS) do occur. In this study, 10 (1.1 %) of 932 clinical human GBS tested lacked an Alp encoding gene. All 10 strains were from patients with bloodstream infection, confirming that non-Alp GBS can be highly virulent. All non-Alp GBS expressed one or more of the surface-anchored proteins R3, Z1 and Z2, while less than 10 % of unselected clinical strains express any of these proteins. In contrast to Alp GBS, all non-Alp strains tested were PCR negative for the upstream sequence of the insertion site of the Alp encoding gene of Alp GBS. Genome sequencing showed that all but one of the 10 clinical non-Alp strains and the non-Alp reference strain CNCTC 10/84 lacked a region surrounding the Alp gene commonly present in Alp GBS strains. These strains instead harboured an 849 bp region not present in the Cα prototype strain A909. We have shown that non-Alp GBS differ from Alp GBS in the region surrounding the insertion site of Alp genes of Alp GBS as well as in their content of other surface proteins and that PCR for the upstream flanking region of the Alp gene may be useful for differentiation between Alp and non-Alp GBS.


Assuntos
Antígenos de Bactérias/metabolismo , Proteínas de Bactérias/metabolismo , Streptococcus agalactiae/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos de Bactérias/genética , Proteínas de Bactérias/genética , DNA Bacteriano/genética , Feminino , Técnicas de Genotipagem , Humanos , Lactente , Masculino , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Pessoa de Meia-Idade , Mutagênese Insercional , Análise de Sequência de DNA , Sorotipagem , Streptococcus agalactiae/classificação , Streptococcus agalactiae/isolamento & purificação
12.
J Cancer Educ ; 31(3): 547-53, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-26031906

RESUMO

The main purpose of this study was to assess the knowledge of cervical cancer among women in rural Nepal and explore the feasibility and impact of a community-based awareness program on cervical cancer. Community-based educational meetings on cervical cancer and its prevention were conducted among women's groups in rural Nepal. Through a questionnaire, the women's baseline knowledge of risk factors, symptoms, and perceived risk of cervical cancer were identified. The willingness to participate in cervical cancer screening was compared before and after the educational meeting. The meetings were followed by a cervical cancer screening program. Among the 122 participants at the educational meeting, only 6 % had heard of cervical cancer. Their baseline knowledge of risk factors and symptoms was poor. The proportion of women willing to participate in cervical screening increased from 15.6 to 100 % after attending the educational meeting. All the study subjects participated in the screening program. Additionally, the study participants recruited a further 222 of their peers for screening. Poor knowledge of cervical cancer among women in rural Nepal highlights the urgency of public awareness programs for cervical cancer at a national level. A community-based awareness program can change women's attitude to cervical screening, and women's groups can play a major role in promoting participation in cervical cancer screening programs.


Assuntos
Detecção Precoce de Câncer/psicologia , Educação em Saúde , Conhecimentos, Atitudes e Prática em Saúde , Neoplasias do Colo do Útero/diagnóstico , Adulto , Detecção Precoce de Câncer/estatística & dados numéricos , Estudos de Viabilidade , Feminino , Humanos , Pessoa de Meia-Idade , Nepal/epidemiologia , População Rural , Inquéritos e Questionários , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/psicologia , Saúde da Mulher
13.
PLoS One ; 9(10): e111788, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25360710

RESUMO

Shiga toxin-producing Escherichia coli (STEC) cause infections in humans ranging from asymptomatic carriage to bloody diarrhoea and haemolytic uremic syndrome (HUS). Here we present whole genome comparison of Norwegian non-O157 STEC strains with the aim to distinguish between strains with the potential to cause HUS and less virulent strains. Whole genome sequencing and comparisons were performed across 95 non-O157 STEC strains. Twenty-three of these were classified as HUS-associated, including strains from patients with HUS (n = 19) and persons with an epidemiological link to a HUS-case (n = 4). Genomic comparison revealed considerable heterogeneity in gene content across the 95 STEC strains. A clear difference in gene profile was observed between strains with and without the Locus of Enterocyte Effacement (LEE) pathogenicity island. Phylogenetic analysis of the core genome showed high degree of diversity among the STEC strains, but all HUS-associated STEC strains were distributed in two distinct clusters within phylogroup B1. However, non-HUS strains were also found in these clusters. A number of accessory genes were found to be significantly overrepresented among HUS-associated STEC, but none of them were unique to this group of strains, suggesting that different sets of genes may contribute to the pathogenic potential in different phylogenetic STEC lineages. In this study we were not able to clearly distinguish between HUS-associated and non-HUS non-O157 STEC by extensive genome comparisons. Our results indicate that STECs from different phylogenetic backgrounds have independently acquired virulence genes that determine pathogenic potential, and that the content of such genes is overlapping between HUS-associated and non-HUS strains.


Assuntos
Genômica/métodos , Síndrome Hemolítico-Urêmica/microbiologia , Escherichia coli Shiga Toxigênica/genética , Surtos de Doenças/estatística & dados numéricos , Escherichia coli O157/genética , Ontologia Genética , Genes Bacterianos , Síndrome Hemolítico-Urêmica/epidemiologia , Humanos , Noruega/epidemiologia , Filogenia
14.
Vet Microbiol ; 173(3-4): 318-22, 2014 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-25150161

RESUMO

We describe tularaemia in a Norwegian dog caused by Francisella tularensis subspecies holarctica. A Hamilton Hound and his owner developed tulaeremia after hunting an infected mountain hare (Lepus timidus). The dog showed signs of lethargy, anorexia and fever during a period two to four days after hunting and thereafter fully recovered. Its antibody titers increased 32-fold from one to three weeks post exposure. Thereafter, the titer declined and leveled off at moderate positive values up to one year after exposure (end of study). This is believed to be the first case report of clinical F. tularensis subspecies holarctica infection in a European dog. In 2011, enormous numbers of Norway lemmings (Lemmus lemmus) occurred in Finnmark, the northernmost county of Norway and many dogs caught and swallowed lemmings. Some of these dogs developed non-specific signs of disease and the owners consulted a veterinary surgeon, who suspected tularaemia. In order to investigate this hypothesis, serum samples from 33 dogs were examined for antibodies to F. tularensis. The dogs were allocated into three groups: Dogs from Finnmark that became sick (Group 1) or remained healthy following contact with lemmings (Group 2), and healthy control dogs from Oslo without known contact with lemmings (Group 3). All the serum samples were analyzed with a tube agglutination assay. Among dogs exposed to lemmings, 10/11 and 3/12 were antibody positive in Group 1 and Group 2, respectively, whereas none of the control dogs (n=10) were positive for antibodies against F. tularensis. These results strongly indicate that the non-specific disease seen in the dogs in Finnmark was linked to F. tularensis infection acquired through contact with lemmings.


Assuntos
Doenças do Cão/microbiologia , Doenças do Cão/transmissão , Francisella tularensis/imunologia , Lebres/microbiologia , Tularemia/veterinária , Zoonoses/patologia , Testes de Aglutinação , Animais , Anticorpos Antibacterianos/sangue , Arvicolinae/microbiologia , Cães , Humanos , Imuno-Histoquímica/veterinária , Noruega , Projetos Piloto , Tularemia/transmissão
15.
BMC Genomics ; 14: 81, 2013 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-23384204

RESUMO

BACKGROUND: Despite being one of the most intensely studied model organisms, many questions still remain about the evolutionary biology and ecology of Escherichia coli. An important step toward achieving a more complete understanding of E.coli biology entails elucidating relationships between gene content and adaptation to the ecological niche. RESULTS: Here, we present genome comparisons of 16 E.coli strains that represent commensals and pathogens isolated from infants during a specific time period in Trondheim, Norway. Using differential gene content, we characterized enrichment profiles of the collection of strains relating to phylogeny, early vs. late colonization, pathogenicity and growth rate. We found clear gene content distinctions relating to the various grouping criteria. We also found that different categories of strains use different genetic elements for similar biological processes. The sequenced genomes included two pairs of strains where each pair was isolated from the same infant at different time points. One pair, in which the strains were isolated four months apart, showed maintenance of an early colonizer genome profile but also gene content and codon usage changes toward the late colonizer profile. Lastly, we placed our sequenced isolates into a broader genomic context by comparing them with 25 published E.coli genomes that represent a variety of pathotypes and commensal strains. This analysis demonstrated the importance of geography in shaping strain level gene content profiles. CONCLUSIONS: Our results indicate a general pattern where alternative genetic pathways lead toward a consistent ecological role for E.coli as a species. Within this framework however, we saw selection shaping the coding repertoire of E.coli strains toward distinct ecotypes with different phenotypic properties.


Assuntos
Adaptação Fisiológica/genética , Ecossistema , Escherichia coli/genética , Escherichia coli/fisiologia , Genômica , Pré-Escolar , Códon/genética , Escherichia coli/isolamento & purificação , Evolução Molecular , Genótipo , Humanos , Lactente , Recém-Nascido , Intestinos/microbiologia , Fenótipo , Filogenia
16.
BMJ Open ; 2(6)2012.
Artigo em Inglês | MEDLINE | ID: mdl-23135543

RESUMO

OBJECTIVE: Prolonged exposure to adults with pulmonary tuberculosis is a risk factor for infecting children. We have studied to what extent a brief exposure may increase the risk of being infected in children. DESIGN: Observational study of a tuberculosis contact investigation. SETTING: 7 day-care centres and 4 after-school-care centres in Norway. PARTICIPANTS: 606 1-year-old to 9-year-old children who were exposed briefly to a male Norwegian with smear-positive pulmonary tuberculosis. MAIN OUTCOME MEASURES: Number of children with latent and active tuberculosis detected by routine clinical examination, chest x-ray and use of a Mantoux tuberculin skin test (TST) and an interferon-γ release assay (IGRA). RESULTS: The children were exposed to a mean of 6.9 h (range 3-18 h). 2-3 months after the exposure, 11 children (1.8%) had a TST ≥6 mm, 6 (1.0%) had TST 4-5 mm, and 587 (97.2%) had a negative TST result. Two children (0.3%) with negative chest x-rays who were exposed 4.75 and 12 h, respectively, had a positive IGRA test result, and were diagnosed with latent tuberculosis. None developed active tuberculosis. CONCLUSIONS: Children from a high-income country attending day-care and after-school-care centres had low risk of being infected after brief exposure less than 18 h to an adult day-care helper with smear-positive pulmonary tuberculosis.

17.
Vet Microbiol ; 157(3-4): 398-404, 2012 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-22266162

RESUMO

Group B streptococci (GBS) were considered a major cause of mastitis in cattle until preventive measures succeeded in controlling the disease in the 1970s and 1980s. During the last 5-6 years an increasing number of cases have been observed in some Scandinavian countries. A total of 187 GBS isolates from mastitis cases were collected from 119 animals in 34 Norwegian farms in the period from April 2007 to November 2010. 133 (71%) of the isolates were from farms with automated milking systems. The strains underwent typing of capsular polysaccharides (CPS) and surface proteins, and were analyzed by multi-locus variable repeat assay (MLVA) to investigate the epidemiological relationship of strains within and between farms. The GBS strains were differentiated into 12 types by CPS and surface protein analysis, with CPS types V (54%) and IV (34%) predominating. MLVA was superior to CPS and protein typing for strain differentiation, resolving the 187 strains into 37 types. In 29 of 34 farms all GBS strains had identical MLVA profiles specific for each farm. However, in one farm represented with 48 isolates, four MLVA variants with differences in one repeat locus were observed during the almost 3-year long collection period. Similar variations were observed at four other farms. This might reflect the stability of repeat loci under in vivo conditions. Farms with automated milking systems were overrepresented in this material. In conclusion, the five-loci MLVA allowed rapid high-resolution genotyping of the bovine GBS strains within and between farms.


Assuntos
Bovinos/microbiologia , Mastite Bovina/microbiologia , Infecções Estreptocócicas/veterinária , Streptococcus agalactiae/classificação , Animais , Proteínas de Bactérias/genética , Técnicas de Tipagem Bacteriana , Análise por Conglomerados , DNA Bacteriano/genética , Feminino , Genótipo , Mastite Bovina/epidemiologia , Leite/microbiologia , Repetições Minissatélites , Tipagem de Sequências Multilocus , Noruega/epidemiologia , Polissacarídeos Bacterianos/genética , Infecções Estreptocócicas/epidemiologia , Infecções Estreptocócicas/microbiologia , Streptococcus agalactiae/genética , Streptococcus agalactiae/isolamento & purificação
18.
J Clin Microbiol ; 48(7): 2502-8, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20504982

RESUMO

Several methods have been used for typing of Streptococcus agalactiae (group B streptococci [GBS]). Methods currently in use may provide inadequate resolution (e.g., typing of capsular polysaccharides and surface protein) or are labor-intensive and expensive (e.g., multilocus sequence typing [MLST] or pulsed-field gel electrophoresis). This work describes the construction and use of a multiple-locus variant-repeat assay (MLVA) on 126 well-characterized human GBS strains, consisting mostly of invasive Norwegian strains and international reference strains. Based on in silico whole-genomic analysis of the genomes of strains A909, NEM316, and 2603V/R, 18 candidate loci were selected and investigated by PCR. Eleven loci showed diversity, and the five most diverse loci were used for the construction of an MLVA, consisting of a multiplex PCR followed by fragment analysis with capillary electrophoresis. The assay generated clusters which corresponded well with those observed by other methods. However, it provided a considerably higher degree of diversity, with 70 different MLVA types compared to 36 types generated by MLST. Simpson's index of diversity for the 5-locus MLVA was 0.963, compared to 0.899 for the MLST in this strain collection. MLVA results will generally be available within 2 days, which is usually faster than MLST. In our hands, MLVA of GBS represents a rapid, easy, and comparably inexpensive method for high-resolution genotyping of GBS.


Assuntos
Técnicas Bacteriológicas/métodos , Técnicas de Diagnóstico Molecular/métodos , Análise de Sequência de DNA/métodos , Streptococcus agalactiae/genética , Sequências de Repetição em Tandem/genética , Análise por Conglomerados , Genes Bacterianos , Loci Gênicos , Humanos , Reação em Cadeia da Polimerase , Sorotipagem , Infecções Estreptocócicas/microbiologia
19.
Acta Obstet Gynecol Scand ; 89(2): 250-5, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-19916889

RESUMO

OBJECTIVE: To explore risk factors for group B Streptococcus (GBS) colonization during pregnancy and at delivery, estimate the predictive value of early GBS colonization for colonization at delivery and in the newborn, and explore the relationship to adverse perinatal factors. DESIGN AND SETTING: Cohort study of pregnant women from three communities in Zimbabwe. METHODS: Information collected by questionnaire at inclusion and from delivery records. Vaginal and rectal swabs collected for GBS culture at 20 and 26 weeks gestation, at delivery and from the newborn infant. MAIN OUTCOME MEASURES: GBS colonization in pregnancy, colonization of mother and newborn, and perinatal factors. RESULTS: GBS culture results were obtained at one or more occasion for 780 (75.2%) of 1,037 women recruited. Altogether, 470/780 women (60.3%) tested positive for GBS, with colonization rates at 20, 26 weeks and delivery of 47%, 24.2% and 21%, respectively. Positive GBS culture at 20 and 26 weeks gestation had a low positive predictive value on colonization at delivery and in the newborn. Women living in rural areas were significantly more often colonized than those who lived in urban areas (p < 0.001). Other socio-economic, demographic and obstetric factors were not statistically associated with GBS colonization. GBS transmission was not statistically significantly associated with adverse perinatal outcomes. CONCLUSIONS: GBS colonization was common among pregnant women in Zimbabwe. Dwelling in a rural area was significantly associated with GBS colonization while other risk factors were not. Early GBS colonization had a low predictive value for colonization at delivery and colonization was not associated with adverse perinatal outcome.


Assuntos
Complicações Infecciosas na Gravidez/microbiologia , Infecções Estreptocócicas/transmissão , Streptococcus agalactiae , Peso ao Nascer , Estudos de Coortes , Parto Obstétrico , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas , Mecônio , Valor Preditivo dos Testes , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Fatores de Risco , População Rural , Infecções Estreptocócicas/epidemiologia , População Urbana , Zimbábue/epidemiologia
20.
J Clin Microbiol ; 46(7): 2280-90, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18463209

RESUMO

Atypical enteropathogenetic Escherichia coli (EPEC) strains are frequently detected in children with diarrhea but are also a common finding in healthy children. The aim of this study was to compare the phylogenetic ancestry and virulence characteristics of atypical (eae positive, stx and bfpA negative) EPEC strains from Norwegian children with (n = 37) or without (n = 19) diarrhea and to search for an association between phylogenetic ancestry and diarrhea. The strains were classified in phylogenetic groups by phylogenetic marker genes and in sequence types (STs) by multilocus sequence typing. Phylogenetic ancestry was compared to virulence characteristics based on DNA microarray analysis. Serotyping and pulsed-field gel electrophoresis (PFGE) were also performed. All four phylogenetic groups, 26 different STs, and 20 different clonal groups were represented among the 56 atypical EPEC strains. The strains were separated into three clusters by overall virulence gene profile; one large cluster with A, B1, and D strains and two clusters with group B2 strains. There was considerable heterogeneity in the PFGE profiles and serotypes, and almost half of the strains were O nontypeable. The efa1/lifA gene, previously shown to be statistically linked with diarrhea in this strain collection (J. E. Afset et al., J. Clin. Microbiol. 44:3703-3711, 2006), was present in 8 of 26 STs. The two phylogenetic groups B1 and D were weakly associated with diarrhea (P = 0.06 and P = 0.09, respectively). In contrast, group B2 was isolated most frequently from healthy controls (P = 0.05). In conclusion, the atypical EPEC strains were heterogeneous both phylogenetically and by virulence profile. Phylogenetic ancestry was less useful as a predictor of diarrhea than were specific virulence genes.


Assuntos
DNA Bacteriano/genética , Diarreia/microbiologia , Escherichia coli Enteropatogênica/classificação , Escherichia coli Enteropatogênica/genética , Infecções por Escherichia coli/microbiologia , Filogenia , Fatores de Virulência/genética , Adesinas Bacterianas/genética , Toxinas Bacterianas/genética , Estudos de Casos e Controles , Pré-Escolar , Análise por Conglomerados , Eletroforese em Gel de Campo Pulsado , Escherichia coli Enteropatogênica/isolamento & purificação , Proteínas de Escherichia coli/genética , Proteínas de Fímbrias/genética , Genótipo , Humanos , Análise em Microsséries , Noruega , Análise de Sequência de DNA , Sorotipagem , Toxinas Shiga/genética
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