Éditeur(s) : HAL CCSD
Résumé : International audience
This article describes a previously unreported mutation at position 210 (C210T) of the mitochondrial large subunit ribosomal RNA (mtLSUrRNA) gene of Pneumocystis jirovecii, which led to a false-negative result of a real-time polymerase chain reaction (PCR) assay. Since the aforementioned real-time PCR assay is widely used in France, a French multicenter study was conducted to estimate the mutation frequency and its potential impact on the routine diagnosis of Pneumocystis pneumonia (PCP). Through analysis of data obtained from eight centers, the mutation frequency was estimated at 0.28%. This low frequency should not call into question the routine use of this PCR assay. Nonetheless, the occurrence of the false-negative PCR result provides arguments for maintaining microscopic techniques combined to PCR assays to achieve PCP diagnosis.
Medical Mycology

hal-01477200
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01477200
DOI : 10.1093/mmy/myw051
PUBMED : 27489302

Éditeur(s) : HAL CCSD Springer Verlag
Résumé : International audience
The purpose of this investigation was to characterize the management and prognosis of severe Pneumocystis jirovecii pneumonia (PJP) in human immunodeficiency virus (HIV)-negative patients. An observational cohort study of HIV-negative adults with PJP documented by bronchoalveolar lavage (BAL) through Gomori-Grocott staining or immunofluorescence, admitted to one intensive care unit (ICU) for acute respiratory failure, was undertaken. From 1990 to 2010, 70 patients (24 females, 46 males) were included, with a mean age of 58.6 ± 18.3 years. The mean Simplified Acute Physiology Score (SAPS)-II was 36.9 ± 20.4. Underlying conditions included hematologic malignancies (n = 21), vasculitis (n = 13), and solid tumors (n = 13). Most patients were receiving systemic corticosteroids (n = 63) and cytotoxic drugs (n = 51). Not a single patient received trimethoprim-sulfamethoxazole as PJP prophylaxis. Endotracheal intubation (ETI) was required in 42 patients (60.0 %), including 38 with acute respiratory distress syndrome (ARDS). In-ICU mortality was 52.9 % overall, reaching 80.9 % and 86.8 %, respectively, for patients who required ETI and for patients with ARDS. In the univariate analysis, in-ICU mortality was associated with SAPS-II (p = 0.0131), ARDS (p < 0.0001), shock (p < 0.0001), and herpes simplex virus (HSV) or cytomegalovirus (CMV) on BAL (p = 0.0031). In the multivariate analysis, only ARDS was associated with in-ICU mortality (odds ratio [OR] 23.4 [4.5-121.9], p < 0.0001). PJP in non-HIV patients remains a serious disease with high in-hospital mortality. Pulmonary co-infection with HSV or CMV may contribute to fatal outcome.
ISSN: 0934-9723

inserm-00872789
http://www.hal.inserm.fr/inserm-00872789
DOI : 10.1007/s10096-012-1730-7
PUBMED : 22930407

Éditeur(s) : HAL CCSD Elsevier Masson
Résumé : National audience
La détection d’Aspergillus dans le liquide bronchiolo-alvéolaire (LBA) est un des critères du diagnostic probable ou prouvé de l’aspergillose invasive (AI). Parallèlement à l’examen mycologique (ED et/ou culture) et à la détection de l’antigène galactomannane (GM) identifiés comme critères EORTC/MSG du diagnostic d’AI probable (de Pauw 2008), la PCR sur prélèvements pulmonaires est devenue un argument majeur du diagnostic de routine. Plusieurs méthodes d’amplification ont été publiées et l’objectif de ce travail était d’évaluer les performances de 2 cibles d’amplification : le gène mitochondrial d’A. fumigatus (AFmito) et l’ARN ribosomal 28S. Entre 01/2012 et 10/2015, 324 LBA ont été prospectivement collectés et analysés sur le plan mycologique (ED et culture) et ont bénéficié d’une détermination du GM (EIA Platelia assay Biorad, seuil à 1,0 si mesure isolée dans le LBA, ou 0,8 si associée à une mesure dans le sérum > 0,5) et d’une PCR AFmito. Puis rétrospectivement, un test PCR 28S a été effectué sur les ADN extraits disponibles (312/324). Selon les critères EORTC/MSG modifiés de 2008, les patients testés étaient classés comme suit : 1 AI prouvée, 47 AI probables et 11 AI possibles. Les autres patients étaient considérés comme 11 colonisés, et 256 non infectés. Les sensibilités du GM dans le LBA, de la PCR 28S et de la PCR AFmito étaient de 58 %, 61 % et 50 %, respectivement. La sensibilité de l’examen mycologique (ED ± culture) était de 33 %. La spécificité du GM dans le LBA, des PCR 28S et AFmito PCR et de la culture étaient de 94 %, 97 %, 97 % et 98 %, respectivement. Les valeurs prédictives négatives étaient de 93 %, 95 %, 92 % et 89 %, respectivement. La concordance entre les 2 PCR était de 97 % (cœfficient kappa 0,84), alors qu’elle était de 88 % (kappa 0,40) entre la PCR 28S et le GM dans le LBA, et de 88 % (kappa 0,43) entre la PCR AFmito PCR et le GM dans le LBA. En conclusion, la PCR 28S a présenté la meilleure performance pour la détection moléculaire d’Aspergillus dans le LBA comparativement à la PCR AFmito. La combinaison de la PCR 28S et de la détection du GM dans le LBA permet d’atteindre une sensibilité de 80 % tout en conservant une excellente spécificité (91 %)
ISSN: 1156-5233

hal-01334068
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01334068
DOI : 10.1016/j.mycmed.2016.04.048

Éditeur(s) : HAL CCSD
Résumé : International audience
Early antifungal therapeutic strategies are proposed during invasive fungal infection (IFI), but antifungal stewardship programs should institute a systematic reevaluation of prescriptions, particularly in the context of empirical treatment. Here, we aimed to evaluate the performances and particularly the negative predictive value (NPV) of diagnostic strategies, including a whole blood panfungal quantitative PCR assay (PF-qPCR) in a high risk population for IFI. The first step was to standardize and optimize a new PF- rtPCR targeting ITS2 region. Then, this method was evaluated in a multicenter prospective study including 313 patients with suspected IFI for whom an early antifungal treatment was prescribed. All patients enrolled at day 0 of their treatment benefited from serum Aspergillus galactomannan (GM) antigen detection twice a week, weekly PF-qPCR assay, and when indicated and feasible, CT-scan and mycological sampling. In total, 125 of 313 patients were diagnosed with IFI: 68 invasive aspergillosis (eight proven, 48 probable and 12 possible), one fusariosis, 47 candidemia, three disseminated candidiasis and six cryptococcosis. Globally, the sensitivity of the PF-qPCR assay was only 40%, but the specificity, PPV and NPV were 96%, 88% and 69%, respectively. In the population of patients at high risk for invasive aspergillosis who also benefited from Aspergillus GM detection, the sensitivity and the NPV of the combined detection reached to 78% and 84%, respectively. Even higher NPV were obtained when combining negative PF-qPCR and CT scan (95%) as well as negative GM and CT scan (93%), thus allowing to rationalize and re-evaluate the prescription of empirical treatment in such highly selected population.
The Journal of Infection

hal-01146845
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01146845
DOI : 10.1016/j.jinf.2015.04.005
PUBMED : 25896093

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
BACKGROUND: Early in life, cystic fibrosis (CF) patients are infected with microorganisms. The role of macrophages has largely been underestimated in literature, whereas the focus being mostly on neutrophils and epithelial cells. Macrophages may however play a significant role in the initiating stages of this disease, via an inability to act as a suppressor cell. Yet macrophage dysfunction may be the first step in cascade of events leading to chronic inflammation/infection in CF. Moreover, reports have suggested that CFTR contribute to altered inflammatory response in CF by modification of normal macrophage functions. OBJECTIVES: In order to highlight possible intrinsic macrophage defects due to impaired CFTR, we have studied inflammatory cytokines secretions, recognition of pathogens and phagocytosis in peripheral blood monocyte-derived macrophages from stable adult CF patients and healthy subjects (non-CF). RESULTS: In CF macrophage supernatants, concentrations of sCD14, IL-1β, IL-6, TNF-α and IL-10 were strongly raised. Furthermore expression of CD11b and TLR-5 were sorely decreased on CF macrophages. Beside, no difference was observed for mCD14, CD16, CD64, TLR-4 and TLR1/TLR-2 expressions. Moreover, a strong inhibition of phagocytosis was observed for CF macrophages. Elsewhere CFTR inhibition in non-CF macrophages also led to alterations of phagocytosis function as well as CD11b expression. CONCLUSIONS: Altogether, these findings demonstrate excessive inflammation in CF macrophages, characterized by overproduction of sCD14 and inflammatory cytokines, with decreased expression of CD11b and TLR-5, and impaired phagocytosis. This leads to altered clearance of pathogens and non-resolution of infection by CF macrophages, thereby inducing an exaggerated pro-inflammatory response.
ISSN: 1932-6203

inserm-00872278
http://www.hal.inserm.fr/inserm-00872278
http://www.hal.inserm.fr/inserm-00872278/document
http://www.hal.inserm.fr/inserm-00872278/file/Impaired_Functions.accepted.pdf
DOI : 10.1371/journal.pone.0075667

Éditeur(s) : HAL CCSD Elsevier [Commercial Publisher]
Résumé : International audience
BACKGROUND: Pneumocystis jiroveci pneumonia in HIV-negative immunocompromised patients is associated with high mortality rates. Although trimethoprim-sulfamethoxazole (TMP-SMX) provides a very effective prophylaxis, pneumocystosis still occurs and may even be emerging, due to sub-optimal characterization of patients most at risk, hence precluding targeted prophylaxis. METHODS: We retrospectively analyzed all cases of documented pneumocystosis in HIV-negative patients admitted in our institution, a referral center in the area, from January 1990 to June 2010, and extracted data on their underlying condition(s). To estimate incidence rates within each condition, we estimated the number of patients followed-up in our area for each condition, by measuring the number of patients admitted with the corresponding international classification diagnostic code, through the national hospital discharge database (PMSI). RESULTS: From 1990 to 2010, 293 cases of pneumocystosis were documented, of whom 154 (52.6%) tested negative for HIV. The main underlying conditions were hematological malignancies (32.5%), solid tumors (18.2%), inflammatory diseases (14.9%), solid organ transplant (12.3%), and vasculitis (9.7%). Estimated incidence rates could be ranked in three categories: i) high risk (incidence rates extgreater 45 cases per 100,000 patient-year): polyarteritis nodosa, granulomatosis with polyangiitis, polymyositis/dermatopolymyositis, acute leukemia, chronic lymphocytic leukemia, and non-Hodgkin lymphoma; ii) intermediate risk (25-45 cases per 100,000 patient-year): Waldenström macroglobulinemia, multiple myeloma, and central nervous system cancer; and iii) low risk ( extless 25 cases per 100,000 patient-year): other solid tumors, inflammatory diseases, and Hodgkin lymphoma. CONCLUSIONS: These estimates may be used as a guide to better target pneumocystosis prophylaxis in the groups most at risk.
ISSN: 0002-9343

hal-01063911
https://hal.archives-ouvertes.fr/hal-01063911
https://hal.archives-ouvertes.fr/hal-01063911/document
https://hal.archives-ouvertes.fr/hal-01063911/file/1-s2.0-S0002934314005907-main.pdf
DOI : 10.1016/j.amjmed.2014.07.010

Éditeur(s) : HAL CCSD
Résumé : International audience
Two fluorescent galactofuranosides were synthesized and their biological activities evaluated on non-infected and Leishmania infected macrophages. Both tagged scaffolds were able to penetrate macrophages. Compared to the activity of the parent octyl galactofuranoside used as a reference, the fluorescein-conjugate showed altered biological properties while the rhodamine 6G one synergistically acted with the lipid chain to significantly increase antiparasitic activity.
Bioorganic & Medicinal Chemistry Letters

hal-01446721
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01446721
PUBMED : 27956346
DOI : 10.1016/j.bmcl.2016.11.090

Éditeur(s) : HAL CCSD American Society for Microbiology
Résumé : International audience
This study aimed to evaluate the repeated sequence REP-529 compared to the B1 gene for the molecular diagnosis of toxoplasmosis by quantitative PCR (qPCR) in routine diagnosis.Over a ten-year period (2003-2013), all patients prospectively diagnosed with a positive REP-529 qPCR result for toxoplasmosis were included. All DNA samples (76 samples from 56 patients) were simultaneously tested using the two qPCR methods (REP-529 and B1).The mean Ct obtained with the B1 qPCR was significantly higher (+4.71 cycles) than that obtained with REP-529 qPCR (p<0.0001). Thirty-one out of 69 extracts (45.6%) positive with REP-529 qPCR were not amplified with the B1 qPCR (relative sensitivity 54.4%, compared to REP-529), yielding false negative results on 15/28 placentas, 5 cord blood, 2 amniotic fluids, 4 cerebrospinal fluids, 1 aqueous humor, 2 lymph node punctures and 1 abortion product. This defect in sensitivity would have left 20/56 patients undiagnosed, distributed as follows: 12/40 congenital toxoplasmosis, 4/5 cerebral toxoplasmosis, 2/8 patients with retinochoroiditis, and both patients with chronic lymphadenopathy. This poor performance of B1 qPCR could be related to low parasite loads, since the mean Toxoplasma quantification in extracts with B1 false negative results was 0.4 parasite/reaction.These results clearly show the superiority of the REP-529 sequence in the diagnosis of toxoplasmosis by PCR suggest that this target should be adopted as part of standardization of the PCR assay.
ISSN: 0095-1137

hal-01118293
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01118293
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01118293/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01118293/file/A%2010-Year%20Retrospective%20Comparison%20of%20Two%20Target%20Sequences-belaz2015.pdf
PUBMEDCENTRAL : PMC4365238

Éditeur(s) : HAL CCSD
Résumé : National audience
Pneumocystis jirovecii (P. jirovecii) est un champignon atypique et transmissible à fort tropisme pulmonaire. La prévalence de P. jirovecii chez les patients atteints de mucoviscidose a été évaluée en Allemagne à 7,4 %, en Espagne à 21,6 % et au Brésil à 38,2 %. En revanche, les données concernant la prévalence de P. jirovecii chez les patients atteints de mucoviscidose en France restent parcellaires en particulier en Bretagne, région où la prévalence de la mucoviscidose est élevée. L’objectif de ce travail a été de déterminer la prévalence de la colonisation de P. jirovecii en Bretagne chez les patients mucoviscidosiques suivis dans les CRCM de Rennes et de Brest-Roscoff. Les expectorations de 86 patients (178 prélèvements) suivis à Rennes et 76 patients (146 prélèvements) suivis à Brest-Roscoff ont été analysées rétrospectivement. La détection de P. jirovecii a été réalisée à l’aide d’une PCR en temps réel ciblant le gène codant pour l’ARN de la grande sous-unité du ribosome de la mitochondrie. P. jirovecii a été détecté chez 3/86 patients (3,5 %) suivis à Rennes et 1/76 patients (1,3 %) suivis à Brest-Roscoff, soit une prévalence globale de 2,5 %. Ces résultats portant sur 2 centres bretons montrent que la prévalence de P. jirovecii chez les patients atteints de mucoviscidose en Bretagne est faible en comparaison de celle observée en Allemagne, en Espagne et au Brésil. Cette étude constitue l’étape préalable indispensable pour déterminer les facteurs de risque d’acquisition du champignon chez les patients mucoviscidosiques et expliquer ces différences de prévalence
Congrès de la SFMM
Talence-Bordeaux, France

hal-01198633
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01198633
DOI : 10.1016/j.mycmed.2015.06.035

Éditeur(s) : HAL CCSD
Résumé : International audience
Leishmania parasites induce an immunomodulation by subverting the host immune response towards a CD4(+) Th2 lymphocytic cell response that favors parasite persistence. Here, we report that after successful treatment of visceral leishmaniasis due to Leishmania infantum, an immune reconstitution syndrome revealing hip septic arthritis was associated with a switch from Th2 towards a Th1 cytokine profile, and a decrease in the level of immunomodulating factors, such as soluble HLA-G and indoleamine 2,3-dioxygenase (IDO) activity. We then measured IDO activity in a cohort of 39 patients and uninfected control subjects. Results showed significantly enhanced IDO activity in patients with visceral Leishmania infection, compared with uninfected control subjects (P < 0.001), but also compared with treated patients (P < 0.05). A decrease in IDO activity could constitute a relevant biomarker for the restoration of the immune response during visceral leishmaniasis.
Innate Immunity

inserm-00818884
http://www.hal.inserm.fr/inserm-00818884
DOI : 10.1177/1753425912473170
PUBMED : 23413147

Éditeur(s) : HAL CCSD Publisher : Paris : Baillière [1980-. Latest Publisher : Paris : Elsevier
Résumé : National audience
Pneumocystis jiroveci (anciennement P. carinii) est un champignon opportuniste responsable de pneumopathies chez les patients immunodéprimés. Les pneumocystoses des patients non infectés par le VIH se distinguent des pneumocystoses du sida par des difficultés diagnostiques accrues, et un pronostic plus sombre. Il est donc indispensable de cibler les immunodépressions les plus à risque, qui bénéficieront d’un traitement par triméthoprime-sulfaméthoxazole à faible dose au long cours, très efficace en prophylaxie des pneumocystoses : ainsi, les vascularites des moyens et petits vaisseaux, les hémopathies lymphoïdes B (leucémie lymphoïde chronique ou aiguë, lymphome malin non hodgkinien) et les cancers solides sous corticothérapie prolongée doivent faire envisager cette prophylaxie. À l’inverse, la généralisation de la prophylaxie à l’ensemble des patients porteurs de pathologies inflammatoires sous corticothérapie n’est pas justifiée. La prise en charge des pneumocystoses des patients non infectés par le VIH suit les principes établis pour les pneumocystoses du sida. Le diagnostic de certitude repose sur la mise en évidence de kystes de P. jiroveci sur des prélèvements respiratoires, tandis que la PCR ne permet pas formellement, en 2015, de différencier colonisation et infection. Le traitement repose sur le triméthoprime-sulfaméthoxazole à fortes doses. Par contre, l’intérêt de la corticothérapie adjuvante pour les patients hypoxémiques, parfaitement documenté au cours du sida, est discuté pour les autres immunodépressions, d’autant que les patients sont en général déjà sous corticoïdes au moment du diagnostic de pneumocystose. Celle-ci est cependant préconisée par plusieurs experts et sociétés savantes, compte tenu du bénéfice démontré sur la morbi-mortalité au cours du sida. Abstract Pneumocystis jiroveci (formerly P. carinii) is an opportunistic fungus responsible for pneumonia in immunocompromised patients. Pneumocystosis in non-HIV-infected patients differs from AIDS-associated pneumocystosis in mostly two aspects: diagnosis is more difficult, and prognosis is worse. Hence, efforts should be made to target immunocompromised patients at higher risk of pneumocystosis, so that they are prescribed long-term, low-dose, trimethoprime-sulfamethoxazole, highly effective for pneumocystosis prophylaxis. Patients at highest risk include those with medium and small vessels vasculitis, lymphoproliferative B disorders (chronic or acute lymphocytic leukaemia, non-Hodgkin lymphoma), and solid cancer on long-term corticosteroids. Conversely, widespread use of prophylaxis in all patients carrier of inflammatory diseases on long-term corticosteroids is not warranted. The management of pneumocystosis in non-AIDS immunocompromised patients follows the rules established for AIDS patients. The diagnosis relies on the detection of P. jiroveci cyst on respiratory samples, while PCR does not reliably discriminate infection from colonization, in 2015. High-doses trimethoprim-sulfamethoxazole is, by far, the treatment of choice. The benefit of adjuvant corticosteroid therapy for hypoxic patients, well documented in AIDS patients, has a much lower level of evidence in non-HIV-infected patients, most of them being already on corticosteroid by the time of pneumocystosis diagnosis anyway. However, based on its striking impact on morbi-mortality in AIDS patients, adjuvant corticosteroid is recommended in hypoxic, non-HIV-infected patients with pneumocystosis by many experts and scientific societies
ISSN: 0248-8663

hal-01237080
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01237080
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01237080/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01237080/file/Pneumocystose%20chez%20les%20patients%20immunod%C3%A9prim%C3%A9s%20non%20infect%C3%A9s%20par%20le%20VIH.pdf
DOI : 10.1016/j.revmed.2015.10.002

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
BACKGROUND: In the context of recent guidelines on invasive candidiasis (IC), how French intensive care units (ICUs) are managing IC? METHODS: This is a prospective observational multicenter cohort study. During 1 year (2012-2013), 87 French ICUs enrolled consecutive patients with suspected or proven IC (SIC or PIC) and receiving systemic antifungal therapy (SAT). Data were collected up to 28 days after inclusion. RESULTS: We studied 835 patients, 291 with PIC and 544 with SIC. At SAT initiation, patients with SIC were significantly more severe (SAPS II 50.1 ± 18.7 vs. 46.2 ± 18.0). Severe sepsis or septic shock prompted to initiate empiric SAT in 70 % of SIC. Within 4 days in median, the initial SAT was modified in 49 % of patients with PIC vs. 33 % patients with SIC. Modifications were most often motivated by mycological results, and de-escalation was the most frequent change. Regarding compliance to IC management guidelines, echinocandin was used for 182 (62.5 %) patients with PIC, and 287 (52.7 %) of those with SIC; central venous catheter was removed in 87 (54.3 %) of patients with candidaemia, and 43 of the remaining patients received echinocandin; and de-escalation was undertaken after 5 days of SAT in 142 patients, after 10 days in 13 patients. As 20.6 % of SIC were secondarily documented, 403/835 (48 %) patients had finally a proven IC. Candida albicans was the main pathogen (65.3 %), then Candida glabrata (15.9 %). The 28-day mortality rates were 40.0 % in candidaemia, 25.4 % in cIAI, and 26.7 % in deep-seated candidiasis. In the overall population of patients with proven IC, four independent prognostic factors were identified: immunosuppression (Odds Ratio (OR) = 1.977: 1.03-3.794 95 % confidence interval (CI), p = 0.04), age (OR = 1.035; 1.017-1.053 95 % CI; p  extless 0.001), SAPS extgreater46 on ICU admission (OR = 2.894; 1.81-4.626 95 % CI; p  extless 0.001), and surgery just before or during ICU stay (OR = 0.473; 0.29-0.77 95 % CI; p  extless 0.001). CONCLUSION: When SAT is initiated in French ICUs, the IC is ultimately proven for 48 % of patients. Empiric SAT is initiated in severely ill ICU patients. The initial SAT is often adapted, with de-escalation to fluconazole when possible. Mortality rate remains high
ISSN: 2110-5820

hal-01259216
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01259216
DOI : 10.1186/s13613-015-0103-7
PUBMED : 26743881

Éditeur(s) : HAL CCSD American Medical Association (AMA)
Résumé : International audience
IMPORTANCE Although frequently used in treating intensive care unit (ICU) patients with sepsis, empirical antifungal therapy, initiated for suspected fungal infection, has not been shown to improve outcome. OBJECTIVE To determine whether empirical micafungin reduces invasive fungal infection (IFI)-free survival at day 28. DESIGN, SETTING, AND PARTICIPANTS Multicenter double-blind placebo-controlled study of 260 nonneutropenic, nontransplanted, critically ill patients with ICU-acquired sepsis, multiple Candida colonization, multiple organ failure, exposed to broad-spectrum antibacterial agents, and enrolled between July 2012 and February 2015 in 19 French ICUs. INTERVENTIONS Empirical treatment with micafungin (100mg, once daily, for 14 days) (n = 131) vs placebo (n = 129). MAIN OUTCOMES AND MEASURES The primary end pointwas survival without proven IFI 28 days after randomization. Key secondary end points included new proven fungal infections, survival at day 28 and day 90, organ failure, serum (1-3)-beta-D-glucan level evolution, and incidence of ventilator-associated bacterial pneumonia. RESULTS Among 260 patients (mean age 63 years; 91 [35%] women), 251 (128, micafungin group; 123, placebo group) were included in the modified intent-to-treat analysis. Median values were 8 for Sequential Organ Failure Assessment (SOFA) score, 3 for number of Candida-colonized sites, and 99 pg/mL for level of (1-3)-beta-D-glucan. On day 28, there were 82 (68%) patients in the micafungin group vs 79 (60.2%) in the placebo group who were alive and IFI free (hazard ratio [HR], 1.35 [95% CI, 0.87-2.08]). Results were similar among patients with a (1-3)-beta-D-glucan level of greater than 80 pg/mL (n = 175; HR, 1.41 [95% CI, 0.85-2.33]). Day-28 IFI-free survival in patients with a high SOFA score (> 8) was not significantly different when compared between the micafungin vs placebo groups (HR, 1.69 [95% CI, 0.96-2.94]). Use of empirical micafungin decreased the rate of new invasive fungal infection in 4 of 128 patients (3%) in the micafungin group vs placebo (15/123 patients [12%]) (P =.008). CONCLUSIONS AND RELEVANCE Among nonneutropenic critically ill patients with ICU-acquired sepsis, Candida species colonization at multiple sites, and multiple organ failure, empirical treatment with micafungin, compared with placebo, did not increase fungal infection-free survival at day 28.
ISSN: 0098-7484

hal-01405822
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01405822
DOI : 10.1001/jama.2016.14655
PUBMED : 27706483

Éditeur(s) : HAL CCSD Royal Society of Chemistry
Résumé : International audience
Although leishmaniasis has been studied for over a century, the fight against cutaneous, mucocutaneous and visceral forms of the disease remains a hot topic. This review refers to the parasitic cell wall and more particularly to the constitutive glycoconjugates. The structures of the main glycolipids and glycoproteins, which are species-dependent, are described. The focus is on the disturbance of the lipid membrane by existing drugs and possible new ones, in order to develop future therapeutic agents
ISSN: 1477-0520

hal-01174899
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01174899
DOI : 10.1039/c5ob00563a
PUBMED : 26130402

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
The development of inflammatory granulomas around infected Kupffer cells is necessary for hepatic parasite clearance during visceral leishmaniasis. Invariant NKT (iNKT) cells are predominant T cells in the mouse liver and can synthesize large quantities of IL-4 and IFN-γ, two cytokines involved in granuloma formation. This study analyzed the role of iNKT cells in the hepatic immune response during Leishmania donovani infection, using a murine model of wild-type (WT) and iNKT cell-deficient (Jα18⁻/⁻) C57BL/6 mice sacrificed 15, 30 or 60 days post-infection. We recorded hepatic parasite loads, cytokine expression, and analyzed granulomatous response by immunohistochemistry and hepatic immune cell infiltration by flow cytometry. Whereas WT animals rapidly controlled the infection and developed an inflammatory response associated with a massive influx of iNKT cells observed by flow cytometry, Jα18⁻/⁻ mice had significantly higher parasitic loads on all time points. This lack of control of parasite burden was associated with a delay in granuloma maturation (28.1% of large granulomas at day 60 versus 50.7% in WT). Cytokine transcriptome analysis showed that mRNA of 90/101 genes encoding chemokines, cytokines and their receptors, was underexpressed in Jα18⁻/⁻ mice. Detection of IL-4 and TNF-α by ELISA in liver extracts was also significantly lower in Jα18⁻/⁻ mice. Consistent with flow cytometry analysis, cytokinome profile in WT mice showed a bias of expression towards T cell-chemoattractant chemokines on D15, and displayed a switch towards expression of granulocytes and/or monocytes -chemoattractant chemokines on D60. In Jα18⁻/⁻ mice, the significantly lower expression of CXCL5, MIP-2 and CCL2 mRNA was correlated with a defect in myeloperoxidase positive-cell attraction observed by immunohistochemistry and with a lower granulocyte and monocyte infiltration in the liver, as shown by flow cytometry. These data indicate that iNKT cells play a role in early and sustained pro-inflammatory cytokine response warranting efficient organization of hepatic granulomas and parasite clearance.
ISSN: 1932-6203

hal-00696897
https://hal.archives-ouvertes.fr/hal-00696897
https://hal.archives-ouvertes.fr/hal-00696897/document
https://hal.archives-ouvertes.fr/hal-00696897/file/Invariant_NKT_Cells_Drive-accepted.pdf
DOI : 10.1371/journal.pone.0033413

Éditeur(s) : HAL CCSD European Centre for Disease Prevention and Control
Résumé : International audience
Leishmaniasis is endemic in southern Europe, and in other European countries cases are diagnosed in travellers who have visited affected areas both within the continent and beyond. Prompt and accurate diagnosis poses a challenge in clinical practice in Europe. Different methods exist for identification of the infecting Leishmania species. Sixteen clinical laboratories in 10 European countries, plus Israel and Turkey, conducted a study to assess their genotyping performance. DNA from 21 promastigote cultures of 13 species was analysed blindly by the routinely used typing method. Five different molecular targets were used, which were analysed with PCR-based methods. Different levels of identification were achieved, and either the Leishmania subgenus, species complex, or actual species were reported. The overall error rate of strains placed in the wrong complex or species was 8.5%. Various reasons for incorrect typing were identified. The study shows there is considerable room for improvement and standardisation of Leishmania typing. The use of well validated standard operating procedures is recommended, covering testing, interpretation, and reporting guidelines. Application of the internal transcribed spacer 1 of the rDNA array should be restricted to Old World samples, while the heat-shock protein 70 gene and the mini-exon can be applied globally.
ISSN: 1560-7917

hal-01460743
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01460743
DOI : 10.2807/1560-7917.ES.2016.21.49.30418
PUBMED : 27983510

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
ISSN: 1773-035X

hal-01118465
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01118465
DOI : 10.1016/S1773-035X(13)72269-X

Éditeur(s) : HAL CCSD Wiley-Blackwell
Résumé : International audience
Seven patients from a group of 16 travelers were diagnosed at our institution with one or more sand fleas on their toes, 1 day to 3 weeks after returning from Madagascar. A questionnaire was sent to the whole group to collect clinical and epidemiological information, which showed that 9 of 13 (69%) had received pre-travel medical advice, but none were aware of sand flea; thus prevention measures were rarely applied. Five of seven (71%) patients wore open sandals throughout the trip. Overall, 10 sand fleas were extracted
ISSN: 1195-1982

hal-01162380
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01162380
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01162380/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01162380/file/Tungiasis%20outbreak%20in%20Madagascar-1.pdf
DOI : 10.1111/jtm.12217

Éditeur(s) : HAL CCSD Elsevier
Résumé : National audience
Résumé Les leishmanioses résultent de l’infection par un parasite protozoaire responsable d’un large panel de présentations cliniques, depuis la leishmaniose cutanée jusqu’à la leishmaniose viscérale. Elles sont présentes sur l’ensemble du globe à l’exception de l’Océanie, et les cliniciens et biologistes doivent savoir que la leishmaniose viscérale et la leishmaniose cutanée sont également autochtones sur le pourtour méditerranéen et en Guyane Française. Les modalités diagnostiques reposent sur la mise en évidence du parasite par examen direct, culture ou PCR. Les outils sérologiques peuvent venir compléter le faisceau d’arguments. Sur le plan thérapeutique, de nouvelles modalités sont actuellement proposées, notamment utilisation de l’amphotéricine B liposomale à forte dose.
ISSN: 1773-035X

hal-01243039
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01243039
DOI : 10.1016/S1773-035X(15)30317-8

Éditeur(s) : HAL CCSD
18th European Congress of Clinical Microbiology an Infectious Diseases (ECCMID)
Barcelone, Spain

hal-00676899
https://hal.archives-ouvertes.fr/hal-00676899