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| ID | Type | Description | Link |
|---|---|---|---|
| 2011_33 | Other Grant/Funding Number | French Ministry of Health PHRC national 2011 | |
| 2012-A00485-38 | Other Identifier | ID-RCB number, ANSM |
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| Name | Class |
|---|---|
| Ministry of Health, France | OTHER_GOV |
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It is proposed to carry out the study in three medical or surgical intensive care units (ICU) in the CHRU, Lille, and the CHU, Besançon. In all patients admitted to these ICU (see Figure 2), a corrected index of colonisation (CIC) will be determined and blood samples will be taken for genotyping of the lectins MBL, Dectin-1 and Galectin-3 and for serology. Over the duration of hospitalisation (on average 28 days) and weekly, fungal colonisation will be assessed in all patients (according to the CIC), and antibodies to yeast glycans will be determined by a simultaneous multiparametric analysis involving several families of natural or synthetic antigens, and the detection of circulating antigens (mannan and β-1,3 glucan).
Determination of the CIC:
The CIC will be determined on admission and then once a week during hospitalisation. This will be carried out on a fixed day for all patients; we will avoid determining the CIC any closer than 2 days apart. It is not planned in this study to modify the therapeutic strategy of the ICU services. The strains isolated will be stored in glycerol solution at -80°C. The specimens for genetic and serological analysis will be stored centrally in a local mycology laboratory.
Genotyping of lectin genes and TLRs:
Two tubes containing 6 ml of blood in EDTA will be taken from each patient for extraction of DNA
Serological study, detection of antibodies to yeast glycans:
10 ml of whole blood will be taken from each patient on the day of inclusion and over the duration of hospitalisation (maximum total quantity of 40 ml). This will be done on a fixed day for all patients; we will avoid sampling any closer than 2 days apart.
Functional tests on peripheral blood mononuclear cells (PBMCs) Taking into account the fact that the results of genotyping will not be available in real time and the need to work with freshly collected cells, a group size of 50 patients in group 2 (negative CIC over the duration of hospitalisation) and 50 patients in group 3 (negative CIC at admission but positive at hospital discharge) will be analysed.
Stimulation tests will be carried out in the presence of whole yeasts or yeast extracts on sub-populations of cells isolated from 20 ml of peripheral blood in EDTA.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group 1 | Patients with candidemia | ||
| Group 2 | Patients without colonization during follow up | ||
| Group 3 | Patients without colonization at admission, with subsequent colonization during hospitalization | ||
| Group | Patients colonized at admission, and during the whole hospitalization | ||
| Group 5 | Patients who develop colonization during hospitalization and become negative at discharge |
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| Measure | Description | Time Frame |
|---|---|---|
| Frequency of polymorphisms | the frequency is measured for the association between the presence of a polymorphism and colonization by Candida sp. frequency of polymorphisms at least one lectin gene or TLRs between some colonized patients (G5) and the non-colonized patients (G2). | From date of inclusion until the last day hospital stay (at once a week) |
| Measure | Description | Time Frame |
|---|---|---|
| Genotyping of lectin genes and toll-like-receptors (TLRs) | The analysis relates to genetic factors already described for lectins and will also include variants of genes involved in innate immunity host-microorganism interactions such as TLRs | From date of inclusion until the last day hospital stay (at once a week) |
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Inclusion Criteria:
Exclusion Criteria:
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Critically ill patients
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| Name | Affiliation | Role |
|---|---|---|
| Daniel Mathieu, Prof | CHRU de Lille | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CHRU de Lille | Lille | Nord | 59037 | France | ||
| Centre hospitalier |
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| ID | Term |
|---|---|
| D016638 | Critical Illness |
| D020022 | Genetic Predisposition to Disease |
| D002177 | Candidiasis |
| ID | Term |
|---|---|
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D004198 | Disease Susceptibility |
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whole blood, serum, yeast strains, PBMCs
| Colonization index |
This index is calculated for each patient at the entrance of the service and then once a week until discharge (at least two weeks after admission). This index is the ratio between the number of body sites colonized heavily on the number of body sites explored when at least one colony of Candida spp. was observed. The determination of Candida colonization index requires the implementation of several samples from different body sites. The sampled anatomical sites concern
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| at admission and weekly for at least two weeks after. |
| Functional tests on peripheral blood mononuclear cells (PBMC) | Functional tests on peripheral blood mononuclear cells (PBMC) obtained from mutated patients for given Innate-immunity genes will be carried out through stimulation tests in the presence of whole yeast or derived-molecules on isolated cell subpopulations. | at admission and weekly for at least two weeks after. |
| Arras |
| France |
| Centre hosptialier | Boulogne-sur-Mer | France |
| CH Schaffner | Lens | France |
| Hôpital Saint-Philibert | Lomme | France |
| CH Victor Provo | Roubaix | France |
| D009181 | Mycoses |
| D001423 | Bacterial Infections and Mycoses |
| D007239 | Infections |