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1.
Infect Dis (Lond) ; 51(6): 425-434, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31010380

RESUMO

BACKGROUND: In Norway, the epidemiological situation of candidemia is followed closely. We have previously demonstrated the highest incidence of candidemia in elderly >65 years of age. However, knowledge of other aspects of this infection is lacking. OBJECTIVE: The aim of this nationwide, retrospective study was to examine risk factors, therapeutic practice and outcome in adult candidemia patients according to age. METHODS: We retrieved data from medical records from patients who developed candidemia in Norway between 1 January 2008 and 31 December 2012. Data were analyzed according to age, younger patients being between 18 and 65 years, elderly being ≥65 years of age. RESULTS: From 771 eligible patients, 738 patients (95.7%) were included (58% men, mean age 65.2 years, 58.1% being ≥65 years). Exposure to health-care related risk factors for candidemia were significantly more common in the younger patients (neutropenia, central venous catheter, mechanical ventilation and chemotherapy) who received empirical treatment more often than the elderly (29.8% vs. 21.7%, p = .01). More elderly did not received any antifungal therapy (27.3% vs 16.8%, p < 0001) and had higher mortality compared to younger patients (45.5% vs 23.9%, p < .0001). In the study population, mortality was higher with age (per 10-years increase, OR 1.43;1.28-1.59, p < 0.0001), in patients not receiving targeted therapy (OR 2.5; CI 1.82-3.36, p < .0001) or any therapy at all (OR 4.64; 3.23-6.68, p < .0001). CONCLUSIONS: Risk factors for candidemia, treatment and outcome differed significantly according to age. Given the increasing numbers of elderly, scrutiny on our clinical practice is warranted.

5.
J Fungi (Basel) ; 4(1)2018 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-29466284

RESUMO

The aim of this study was to examine the burden of fungal disease in Norway, contributing to a worldwide effort to improve awareness of the needs for better diagnosis and treatment of such infections. We used national registers and actual data from the Departments of Microbiology from 2015 and estimated the incidence and/or prevalence of superficial, allergic and invasive fungal disease using published reports on specific populations at risk. One in 6 Norwegians suffered from fungal disease: Superficial skin infections (14.3%: 745,600) and recurrent vulvovaginal candidiasis in fertile women (6%: 43,123) were estimated to be the most frequent infections. Allergic fungal lung disease was estimated in 17,755 patients (341/100,000). Pneumocystis jirovecii was diagnosed in 262 patients (5/100,000), invasive candidiasis in 400 patients (7.7/100,000), invasive aspergillosis in 278 patients (5.3/100,000) and mucormycosis in 7 patients (0.1/100,000). Particular fungal infections from certain geographic areas were not observed. Overall, 1.79% of the population was estimated to be affected by serious fungal infections in Norway in 2015. Even though estimates for invasive infections are small, the gravity of such infections combined with expected demographic changes in the future emphasizes the need for better epidemiological data.

6.
Blood ; 129(14): 1927-1939, 2017 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-28209719

RESUMO

Heterozygous GATA2 mutation is associated with immunodeficiency, lymphedema, and myelodysplastic syndrome. Disease presentation is variable, often coinciding with loss of circulating dendritic cells, monocytes, B cells, and natural killer (NK) cells. Nonetheless, in a proportion of patients carrying GATA2 mutation, NK cells persist. We found that peripheral blood NK cells in symptomatic patients uniformly lacked expression of the transcription factor promyelocytic leukemia zinc finger (PLZF), as well as expression of intracellular signaling proteins FcεRγ, spleen tyrosine kinase (SYK), and EWS/FLI1-Activated Transcript 2 (EAT-2) in a variegated manner. Moreover, consistent with an adaptive identity, NK cells from patients with GATA2 mutation displayed altered expression of cytotoxic granule constituents and produced interferon-γ upon Fc-receptor engagement but not following combined interleukin-12 (IL-12) and IL-18 stimulation. Canonical, PLZF-expressing NK cells were retained in asymptomatic carriers of GATA2 mutation. Developmentally, GATA-binding protein-2 (GATA-2) was expressed in hematopoietic stem cells, but not in NK-cell progenitors, CD3-CD56bright, canonical, or adaptive CD3-CD56dim NK cells. Peripheral blood NK cells from individuals with GATA2 mutation proliferated normally in vitro, whereas lineage-negative progenitors displayed impaired NK-cell differentiation. In summary, adaptive NK cells can persist in patients with GATA2 mutation, even after NK-cell progenitors expire. Moreover, our data suggest that adaptive NK cells are more long-lived than canonical, immunoregulatory NK cells.


Assuntos
Proliferação de Células , Fator de Transcrição GATA2 , Células-Tronco Hematopoéticas/imunologia , Células Matadoras Naturais/imunologia , Mutação , Adolescente , Adulto , Proteínas de Ligação a Calmodulina/genética , Proteínas de Ligação a Calmodulina/imunologia , Criança , Feminino , Fator de Transcrição GATA2/genética , Fator de Transcrição GATA2/imunologia , Humanos , Interleucina-12/genética , Interleucina-12/imunologia , Interleucina-18/genética , Interleucina-18/imunologia , Masculino , Pessoa de Meia-Idade , Proteína EWS de Ligação a RNA , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/imunologia , Receptores de IgE/genética , Receptores de IgE/imunologia , Quinase Syk/genética , Quinase Syk/imunologia , Fatores de Transcrição/genética , Fatores de Transcrição/imunologia
7.
Mycoses ; 60(1): 11-19, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27464892

RESUMO

National data from Denmark, Finland, Norway and Sweden demonstrate remarkable differences in candidaemia epidemiology. Only Denmark has reported a high incidence of 10 per 100 000 inhabitants and a species shift towards increased C. glabrata candidaemias. The reasons for this development remain unclear. The aim of this study was to explore possible contributing factors for the differences in Candida epidemiology in the Nordic countries. We used public data from 2011 from Denmark, Finland, Norway and Sweden on epidemiology, demographics, health facilities, predisposing risk factors, consumption of antimicrobial drugs and fungicides in agricultural industry. Only the prevalence of haematological malignancies (P < 0.001) was significantly higher in Denmark compared to the other Nordic countries. The antibacterial drug use of metronidazole, piperacillin-tazobactam, ciprofloxacin, colistin and carbapenems, and antifungal use of fluconazole in humans (P < 0.001), were significantly higher in Denmark compared to the other Nordic countries (all P < 0.001). Our findings suggest haematological malignancy, the use of certain antibacterial drugs and azoles in humans as possible contributing factors for the differences in Candida epidemiology. However, our results should be interpreted with caution due to the lack of long-term, case-specific data. Further studies are needed.


Assuntos
Antifúngicos/efeitos adversos , Candida glabrata/isolamento & purificação , Candidemia/epidemiologia , Infecção Hospitalar/epidemiologia , Padrões de Prática Médica/estatística & dados numéricos , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Antibacterianos/uso terapêutico , Antifúngicos/administração & dosagem , Antifúngicos/uso terapêutico , Candida glabrata/efeitos dos fármacos , Candidemia/tratamento farmacológico , Candidemia/microbiologia , Causalidade , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/microbiologia , Demografia , Farmacorresistência Fúngica , Feminino , Humanos , Incidência , Masculino , Saúde da População , Fatores de Risco , Países Escandinavos e Nórdicos/epidemiologia , Estatística como Assunto
8.
J Allergy Clin Immunol ; 139(1): 232-245, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27577878

RESUMO

BACKGROUND: Primary immunodeficiency diseases (PIDDs) are clinically and genetically heterogeneous disorders thus far associated with mutations in more than 300 genes. The clinical phenotypes derived from distinct genotypes can overlap. Genetic etiology can be a prognostic indicator of disease severity and can influence treatment decisions. OBJECTIVE: We sought to investigate the ability of whole-exome screening methods to detect disease-causing variants in patients with PIDDs. METHODS: Patients with PIDDs from 278 families from 22 countries were investigated by using whole-exome sequencing. Computational copy number variant (CNV) prediction pipelines and an exome-tiling chromosomal microarray were also applied to identify intragenic CNVs. Analytic approaches initially focused on 475 known or candidate PIDD genes but were nonexclusive and further tailored based on clinical data, family history, and immunophenotyping. RESULTS: A likely molecular diagnosis was achieved in 110 (40%) unrelated probands. Clinical diagnosis was revised in about half (60/110) and management was directly altered in nearly a quarter (26/110) of families based on molecular findings. Twelve PIDD-causing CNVs were detected, including 7 smaller than 30 Kb that would not have been detected with conventional diagnostic CNV arrays. CONCLUSION: This high-throughput genomic approach enabled detection of disease-related variants in unexpected genes; permitted detection of low-grade constitutional, somatic, and revertant mosaicism; and provided evidence of a mutational burden in mixed PIDD immunophenotypes.


Assuntos
Síndromes de Imunodeficiência/genética , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Variações do Número de Cópias de DNA , Feminino , Genômica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Adulto Jovem
10.
Case Rep Infect Dis ; 2017: 4173246, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29435377

RESUMO

A 24-year-old woman with coeliac disease and transient neutropenia developed mucormycosis with extensive involvement of the liver and small intestine. She was successfully treated with aggressive surgical debridements and long-term antifungal therapy with liposomal amphotericin B and posaconazole.

11.
Lepr Rev ; 86(4): 403-6, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26964439

RESUMO

A patient from Southeast Asia was diagnosed with systemic lupus erythematosus. One year later, she experienced exacerbation of skin lesions and was diagnosed with erythema nodosum leprosum. Upon treatment, the patient developed hemophagocytic lymphohistiocytosis with multi-organ failure and died from invasive fungal infection. Hemophagocytic lymphohistiocytosis has to our knowledge, not previously been reported in leprosy.


Assuntos
Hanseníase/complicações , Linfo-Histiocitose Hemofagocítica/etiologia , Adulto , Feminino , Humanos
15.
J Infect ; 61(6): 465-70, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20813130

RESUMO

OBJECTIVES: Listeria monocytogenes is a foodborne pathogen with a high mortality rate. We report a large, nosocomial outbreak of Listeria monocytogenes infection. METHODS: Patients with L. monocytogenes isolated from a sterile site, or from faeces when diarrhoea and fever were present, were included. Clinical data were collected from the patient records. The incubation period was calculated as the time between exposure and start of symptoms. RESULTS: Seventeen patients (11 women, median age 64 years) were infected of whom 15 patients were at increased risk for listeriosis. Eleven patients received empiric antibiotic treatment, eight of them with cephalosporins. Three patients died with a resulting mortality rate of 18%. The source of the outbreak was a Camembert cheese made from pasteurised milk containing up to 360 million colony forming units per portion. The median incubation period was 3-4 days. CONCLUSIONS: The incubation period in this outbreak was significantly shorter than previously reported, a fact that may be due to the high number of ingested bacteria. Furthermore, food restrictions in hospitals seem warranted, as do treatment with antibiotics effective against L. monocytogenes in at-risk populations.


Assuntos
Infecção Hospitalar/epidemiologia , Surtos de Doenças , Período de Incubação de Doenças Infecciosas , Listeria monocytogenes/isolamento & purificação , Listeriose/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Queijo/microbiologia , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/microbiologia , Infecção Hospitalar/mortalidade , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Ribossômico/química , DNA Ribossômico/genética , Feminino , Doenças Transmitidas por Alimentos/tratamento farmacológico , Doenças Transmitidas por Alimentos/epidemiologia , Doenças Transmitidas por Alimentos/microbiologia , Doenças Transmitidas por Alimentos/mortalidade , Hospitais , Humanos , Listeriose/tratamento farmacológico , Listeriose/microbiologia , Listeriose/mortalidade , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Resultado do Tratamento
16.
Tidsskr Nor Laegeforen ; 128(22): 2607-11, 2008 Nov 20.
Artigo em Norueguês | MEDLINE | ID: mdl-19023376

RESUMO

BACKGROUND: The incidence of invasive fungal infections is increasing in parallel with an increase of patients with immunodeficiencies. Resistance to these drugs is becoming a problem in spite of increased and improved treatment options. MATERIAL AND METHODS: Literature retrieved from Medline and personal findings and experience form the basis for this article. RESULTS: Candida albicans is still the most common species causing invasive fungal infections, but Candida non-albicans species are increasing in number. Invasive Aspergillus infections and infection with other moulds than Aspergillus spp. do occur, but do not constitute a large proportion of these infections. As of today we have four classes of antifungal agents and seven drugs with different mechanisms of action are registered in Norway. Primary resistance to several of these drugs has been observed in a number of Candida and Aspergillus species and this is the dominating form of resistance we observe today. Secondary resistance due to treatment is still an uncommon finding. Clinical resistance, which, in spite of in vitro susceptibility does not lead to eradication of the fungus, is also commonly observed. INTERPRETATION: The incidence of natural resistant fungi is increasing. Our main current challenge is therefore to rapidly and precisely identify the fungi so the proper drug is used to quickly initiate treatment on the correct indication.


Assuntos
Farmacorresistência Fúngica , Micoses/tratamento farmacológico , Antifúngicos/efeitos adversos , Antifúngicos/uso terapêutico , Aspergilose/tratamento farmacológico , Candidíase/tratamento farmacológico , Farmacorresistência Fúngica/genética , Humanos , Hospedeiro Imunocomprometido , Fungos Mitospóricos/efeitos dos fármacos , Fungos Mitospóricos/genética , Micoses/imunologia , Micoses/microbiologia
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