Éditeur(s) : HAL CCSD
Résumé : International audience
Background Mycobacterium ulcerans infection is the third most common mycobacterial disease in the world after tuberculosis and leprosy. To date, transmission pathways from its environmental reservoir to humans are still unknown. In South America, French Guiana has the highest reported number of M ulcerans infections across the continent. This empirical study aimed to characterise the epidemiology of M ulcerans infection in French Guiana between 1969 and 2013.MethodsData were collected prospectively mainly by two dermatologists at Cayenne Hospital’s dermatologydepartment between Jan 1, 1969, and Dec 31, 2013, for age, date of diagnosis, sex, residence, location of the lesion,type of lesion, associated symptoms, and diagnostic method (smear, culture, PCR, or histology) for all confirmed andsuspected cases of M ulcerans. We obtained population data from censuses. We calculated mean M ulcerans infectionincidences, presented as the number of cases per 100 000 person-years.Findings 245 patients with M ulcerans infections were reported at Cayenne Hospital’s dermatology department duringthe study period. M ulcerans infection incidence decreased over time, from 6·07 infections per 100 000 person-years(95% CI 4·46–7·67) in 1969–83 to 4·77 infections per 100 000 person-years (3·75–5·79) in 1984–98 and to3·49 infections per 100 000 person-years (2·83–4·16) in 1999–2013. The proportion of children with infections alsodeclined with time, from 42 (76%) of 55 patients in 1969–83 to 26 (31%) of 84 in 1984–98 and to 22 (21%) of 106 in1999–2013. Most cases occurred in coastal areas surrounded by marshy savannah (incidence of 21·08 per100 000 person-years in Sinnamary and 21·18 per 100 000 person-years in Mana). Lesions mainly affected limbs (lowerlimbs 161 [66%] patients; upper limbs 60 [24%] patients). We diagnosed no bone infections.Interpretation The decrease of M ulcerans infection incidence and the proportion of children with infections over a45 year period in this ultra-peripheral French territory might have been mostly driven by improving living conditions,prophylactic recommendations, and access to health care.
The Lancet Planetary Health

inserm-01545603
http://www.hal.inserm.fr/inserm-01545603
http://www.hal.inserm.fr/inserm-01545603/document
http://www.hal.inserm.fr/inserm-01545603/file/2017%2C%20Douine%20-%20Mycobacterium%20ulcerans%20infection%20%28Buruli%20ulcer%29.pdf
http://www.hal.inserm.fr/inserm-01545603/file/Comments.pdf

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
The CoPanFlu-France cohort of households was set up in 2009 to study the risk factors for infection by the pandemic influenza virus (H1N1pdm) in the French general population. The authors developed an integrative data-driven approach to identify individual, collective and environmental factors associated with the post-seasonal serological H1N1pdm geometric mean titer, and derived a nested case-control analysis to identify risk factors for infection during the first season. This analysis included 1377 subjects (601 households). The GMT for the general population was 47.1 (95% confidence interval (CI): 45.1, 49.2). According to a multivariable analysis, pandemic vaccination, seasonal vaccination in 2009, recent history of influenza-like illness, asthma, chronic obstructive pulmonary disease, social contacts at school and use of public transports by the local population were associated with a higher GMT, whereas history of smoking was associated with a lower GMT. Additionally, young age at inclusion and risk perception of exposure to the virus at work were identified as possible risk factors, whereas presence of an air humidifier in the living room was a possible protective factor. These findings will be interpreted in light of the longitudinal analyses of this ongoing cohort.
ISSN: 1932-6203

Droits : http://creativecommons.org/licenses/by-sa/
hal-01122215
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01122215
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01122215/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01122215/file/journal.pone.0060127.pdf
PUBMED : 23613718

Éditeur(s) : HAL CCSD Ferrata Storti Foundation
Résumé : International audience
BACKGROUND: Abnormal interactions between red blood cells, leukocytes and endothelial cells play a critical role in the occurrence of the painful vaso-occlusive crises associated with sickle cell disease. We investigated the interaction between circulating leukocytes and red blood cells which could lead to aggregate formation, enhancing the incidence of vaso-occlusive crises. DESIGN AND METHODS: Blood samples from patients with sickle cell disease (n=25) and healthy subjects (n=5) were analyzed by imaging and classical flow cytometry after density gradient separation. The identity of the cells in the peripheral blood mononuclear cell layer was determined using antibodies directed specifically against white (anti-CD45) or red (anti-glycophorin A) blood cells. RESULTS: Aggregates between red blood cells and peripheral blood mononuclear cells were visualized in whole blood from patients with sickle cell disease. The aggregation rate was 10-fold higher in these patients than in control subjects. Both mature red blood cells and reticulocytes were involved in these aggregates through their interaction with mononuclear cells, mainly with monocytes. The size of the aggregates was variable, with one mononuclear cell binding to one, two or several red blood cells. Erythroid Lu/basal cell adhesion molecule and α(4)β(1) integrin were involved in aggregate formation. The aggregation rate was lower in patients treated with hydroxycarbamide than in untreated patients. CONCLUSIONS: Our study gives visual evidence of the existence of circulating red blood cell-peripheral blood mononuclear cell aggregates in patients with sickle cell disease and shows that these aggregates are decreased during hydroxycarbamide treatment. Our results strongly suggest that erythroid Lu/basal cell adhesion molecule proteins are implicated in these aggregates through their interaction with α(4)β(1) integrin on peripheral blood mononuclear cells.
ISSN: 0390-6078

inserm-00821120
http://www.hal.inserm.fr/inserm-00821120
http://www.hal.inserm.fr/inserm-00821120/document
http://www.hal.inserm.fr/inserm-00821120/file/1841.full.pdf
DOI : 10.3324/haematol.2010.026294

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
AIM: To describe the main characteristics and the treatment of cryptococcosis in patients with sarcoidosis. DESIGN: Multicenter study including all patients notified at the French National Reference Center for Invasive Mycoses and Antifungals. METHODS: Retrospective chart review. Each case was compared with two controls without opportunistic infections. RESULTS: Eighteen cases of cryptococcosis complicating sarcoidosis were analyzed (13 men and 5 women). With 2749 cases of cryptococcosis registered in France during the inclusion period of this study, sarcoidosis accounted for 0.6% of all the cryptococcosis patients and for 2.9% of the cryptococcosis HIV-seronegative patients. Cryptococcosis and sarcoidosis were diagnosed concomitantly in four cases; while sarcoidosis was previously known in 14/18 patients, including 12 patients (67%) treated with steroids. The median rate of CD4 T cells was 145 per mm(3) (range: 55-1300) and not related to steroid treatment. Thirteen patients had cryptococcal meningitis (72%), three osteoarticular (17%) and four disseminated infections (22%). Sixteen patients (89%) presented a complete response to antifungal therapy. After a mean follow-up of 6 years, no death was attributable to cryptococcosis. Extra-thoracic sarcoidosis and steroids were independent risk factors of cryptococcosis in a logistic regression model adjusted with the sex of the patients. CONCLUSIONS: Cryptococcosis is a significant opportunistic infection during extra-thoracic sarcoidosis, which occurs in one-third of the cases in patients without any treatment; it is not associated to severe CD4 lymphocytopenia and has a good prognosis.
ISSN: 1460-2725

hal-00873410
https://hal.archives-ouvertes.fr/hal-00873410
DOI : 10.1093/qjmed/hct052
PUBMED : 23515400

Éditeur(s) : HAL CCSD
Résumé : International audience
Up-to-date estimates of the health outcomes of preterm children are needed for assessing perinatal care, informing parents, making decisions about care, and providing evidence for clinical guidelines. To determine survival and neonatal morbidity of infants born from 22 through 34 completed weeks' gestation in France in 2011 and compare these outcomes with a comparable cohort in 1997. The EPIPAGE-2 study is a national, prospective, population-based cohort study conducted in all maternity and neonatal units in France in 2011. A total of 2205 births (stillbirths and live births) and terminations of pregnancy at 22 through 26 weeks' gestation, 3257 at 27 through 31 weeks, and 1234 at 32 through 34 weeks were studied. Cohort data were collected from January 1 through December 31, 1997, and from March 28 through December 31, 2011. Analyses for 1997 were run for the entire year and then separately for April to December; the rates for survival and morbidities did not differ. Data are therefore presented for the whole year in 1997 and the 8-month and 6-month periods in 2011. Survival to discharge and survival without any of the following adverse outcomes: grade III or IV intraventricular hemorrhage, cystic periventricular leukomalacia, severe bronchopulmonary dysplasia, retinopathy of prematurity (stage 3 or higher), or necrotizing enterocolitis (stages 2-3). A total of 0.7% of infants born before 24 weeks' gestation survived to discharge: 31.2% of those born at 24 weeks, 59.1% at 25 weeks, and 75.3% at 26 weeks. Survival rates were 93.6% at 27 through 31 weeks and 98.9% at 32 through 34 weeks. Infants discharged home without severe neonatal morbidity represented 0% at 23 weeks, 11.6% at 24 weeks, 30.0% at 25 weeks, 47.5% at 26 weeks, 81.3% at 27 through 31 weeks, and 96.8% at 32 through 34 weeks. Compared with 1997, the proportion of infants surviving without severe morbidity in 2011 increased by 14.4% (P < .001) at 25 through 29 weeks and 6% (P < .001) at 30 through 31 weeks but did not change appreciably for those born at less than 25 weeks. The rates of antenatal corticosteroid use, induced preterm deliveries, cesarean deliveries, and surfactant use increased significantly in all gestational-age groups, except at 22 through 23 weeks. The substantial improvement in survival in France for newborns born at 25 through 31 weeks' gestation was accompanied by an important reduction in severe morbidity, but survival remained rare before 25 weeks. Although improvement in survival at extremely low gestational age may be possible, its effect on long-term outcomes requires further studies. The long-term results of the EPIPAGE-2 study will be informative in this regard.
ISSN: 2168-6211

hal-01258705
http://hal.univ-brest.fr/hal-01258705
PUBMED : 25621457
DOI : 10.1001/jamapediatrics.2014.3351

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
In 2008 a fatal case of primary amoebic meningoencephalitis, due to the amoeboflagellate Naegleria fowleri, occurred in Guadeloupe, French West Indies, after a child swam in a bath fed with geothermal water. In order to improve the knowledge on free-living amoebae in this tropical part of France, we investigated on a monthly basis, the presence of Naegleria spp. in the recreational baths, and stream waters which feed them. A total of 73 water samples, 48 sediments and 54 swabs samples were collected from 6 sampling points between June 2011 and July 2012. The water samples were filtered and the filters transferred to non-nutrient agar plates seeded with a heat-killed suspension of Escherichia coli while sediment and swab samples were placed directly on these plates. The plates were incubated at 44°C for the selective isolation of thermophilic Naegleria. To identify the Naegleria isolates the internal transcribed spacers, including the 5.8S rDNA, were amplified by polymerase chain reaction and the sequence of the PCR products was determined. Thermophilic amoebae were present at nearly all collection sites. The pathogenic N. fowleri was the most frequently encountered thermophilic species followed by N. lovaniensis. The concentration of N. fowleri was rather low in most water samples, ranging from 0 to 22 per liter. Sequencing revealed that all N. fowleri isolates belonged to a common Euro-American genotype, the same as detected in the human case in Guadeloupe. These investigations need to be continued in order to counsel the health authorities about prevention measures, because these recreational thermal baths are used daily by local people and tourists.
ISSN: 1932-6203

pasteur-00782031
https://hal-riip.archives-ouvertes.fr/pasteur-00782031
https://hal-riip.archives-ouvertes.fr/pasteur-00782031/document
https://hal-riip.archives-ouvertes.fr/pasteur-00782031/file/article_naegleria_plos_one.pdf
DOI : 10.1371/journal.pone.0054414

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
BackgroundMalaria is endemic in French Guiana, an overseas territory of France on the Guiana Shield. Since 2005, notified malaria cases are decreasing. However, new data show that malaria affects many Brazilian gold miners working illegally in French Guiana, the majority of whom are not counted in official data. In addition, one major concern is the usual practice of improper self-treatment in this mining population, raising fear of the development of antimalarial resistance. This prospective study, conducted in 2015, aimed to estimate the prevalence of Plasmodium spp. in illegal gold miners working in French Guiana. MethodsThe recruitment of gold miners was carried out in resting sites along the French Guiana-Suriname border, where they go for supplies, medical care or leisure. After recording agreement, three malaria diagnostic methods were performed: rapid diagnostic test, microscopy and PCR,ResultsAmong 421 persons recruited in the study, malaria prevalence, detected by nested-PCR, was 22.3% (CI=[18.3-26.3], n=94/421) of which 84% were asymptomatic. ConclusionThis significant malaria reservoir in a mobile and illegal population with difficult access to a health care system raises the threat of artemisinin resistance and puts the population of the Guiana Shield at risk of new transmission foci while countries of the region aim at malaria elimination. Even though French legislation may hamper dealing with this population, France must face the reality of malaria in illegal gold miners in order to meet its commitment to malaria elimination.
ISSN: 1475-2875

hal-01346800
https://hal.archives-ouvertes.fr/hal-01346800
https://hal.archives-ouvertes.fr/hal-01346800/document
https://hal.archives-ouvertes.fr/hal-01346800/file/2016%2C%20Douine%20-%20Prevalence%20of%20Plasmodium%20spp.%20in%20illegal%20gold%20miners%20in%20French%20Guiana%20in%202015.pdf
DOI : 10.1186/s12936-016-1367-6

Éditeur(s) : HAL CCSD Centers for Disease Control and Prevention
Résumé : International audience
To assess the prevalence of malaria among illegal gold miners in the French Guiana rainforest, we screened 205 miners during May-June 2014. Malaria prevalence was 48.3%; 48.5% of cases were asymptomatic. Patients reported self-medication with artemisinin-based combination therapy. Risk for emergence and spread of artemisinin resistance among gold miners in the rainforest is high.
ISSN: 1080-6040

Droits : http://creativecommons.org/licenses/by/
pasteur-01305106
https://hal-pasteur.archives-ouvertes.fr/pasteur-01305106
https://hal-pasteur.archives-ouvertes.fr/pasteur-01305106/document
https://hal-pasteur.archives-ouvertes.fr/pasteur-01305106/file/15-1957.pdf
DOI : 10.3201/eid2205.151957.

Éditeur(s) : HAL CCSD Lippincott, Williams & Wilkins
Résumé : International audience
The aim of the study was to investigate the impact of first-line combined antiretroviral therapy (cART) regimen on the course of CD8 + T-cell counts in human immunodeficiency virus (HIV)-infected patients. A retrospective observational study conducted on the French DAT'AIDS Cohort of HIV-infected patients. We selected 605 patients initiating a first-line cART between 2002 and 2009, and which achieved a sustained undetectable HIV plasma viral load (pVL) for at least 12 months without cART modification. The evolution of CD8 + T-cell counts according to cART regimen was assessed. CD8 + T-cell counts were assessed in 572 patients treated with 2NRTIs+1PI/r (n= 297), 2NRTIs+1NNRTI (n= 207) and 3NRTIs (n= 68). In multivariate analysis, after 12 months of follow-up, the 3NRTIs regimen was associated with a significantly smaller decrease of CD8 + T-cell count compared with NNRTI-containing regimens (–10.2 cells/mL in 3NRTIs vs –105.1 cells/mL; P=0.02) but not compared with PI-containing regimens (10.2 vs –60.9 cells/mL; P=0.21). After 24 months, the 3NRTIs regimen was associated with a smaller decrease of CD8 + T-cell count and % compared with PI/r-and NNRTI-containing regimens (0.2 in 3NRTIs vs –9.9 with PI/r-regimens, P=0.001, and vs –11.1 with NNRTI-regimens, p < 0.0001). A focus analysis on 11 patients treated with an INSTI-containing cART regimen during the study period showed after 12 months of follow-up, a median decrease of CD8 + T-cell count of –155 [inter quartile range: –302; –22] cells/mL. Our data highlight the fact that cART regimens have differential effects on CD8 pool down regulation. Abbreviations: cART = combined antiretroviral therapy, HIV = human immunodeficiency virus, INSTI = integrase strand transfer inhibitor, NNRTI = non-nucleotide reverse transcriptase inhibitor, NRTI = nucleotide reverse transcriptase inhibitor, PI/r = Ritonavir-boosted protease inhibitor, pVL = plasma viral load.
ISSN: 0025-7974

inserm-01408002
http://www.hal.inserm.fr/inserm-01408002
http://www.hal.inserm.fr/inserm-01408002/document
http://www.hal.inserm.fr/inserm-01408002/file/2016%2C%20Poizot-Martin%20-%20First-line%20cART%20regimen%20impacts%20the%20course%20of%20CD8%2B%20T-cell%20counts%20in%20HIV-infected%20patients.pdf
DOI : 10.1097/MD.0000000000005087

Éditeur(s) : HAL CCSD Taylor & Francis
Résumé : International audience
To analyze the characteristics and outcome of infective endocarditis (IE) according to the time interval between IE first symptoms and diagnosis.
Among the IE cases of a French population-based epidemiological survey, patients having early-diagnosed IE (diagnosis of IE within 1 month of first symptoms) were compared with those having late-diagnosed IE (diagnosis of IE more than 1 month after first symptoms).
Among the 486 definite-IE, 124 (25%) had late-diagnosed IE whereas others had early-diagnosed IE. Early-diagnosed IE were independently associated with female gender (OR = 1.8; 95% CI [1.0-3.0]), prosthetic valve (OR= 2.6; 95% CI [1.4-5.0]) and staphylococci as causative pathogen (OR = 3.7; 95% CI [2.2-6.2]). Cardiac surgery theoretical indication rates were not different between early and late-diagnosed IE (56.3% vs 58.9%), whereas valve surgery performance was lower in early-diagnosed IE (41% vs 53%; p = .03). In-hospital mortality rates were higher in early-diagnosed IE than in late-diagnosed IE (25.1% vs 16.1%; p < .001).
The time interval between IE first symptoms and diagnosis is closely related to the IE clinical presentation, patient characteristics and causative microorganism. Better prognosis reported in late-diagnosed IE may be related to a higher rate of valvular surgery. KEY MESSAGES Infective endocarditis, which time interval between first symptoms and diagnosis was less than one month, were mainly due to Staphylococcus aureus in France. Staphylococcus aureus infective endocarditis were associated with septic shock, transient ischemic attack or stroke and higher mortality rates than infective endocarditis due to other bacteria or infective endocarditis, which time interval between first symptoms and diagnosis was more than one month. Infective endocarditis, which time interval between first symptoms and diagnosis was more than one month, were accounting for one quarter of all infective endocarditis in our study and were associated with vertebral osteomyelitis and a higher rate of cardiac surgery performed for hemodynamic indication than other infective endocarditis.
ISSN: 0785-3890

hal-01509563
https://hal.archives-ouvertes.fr/hal-01509563
PUBMED : 27607562

Éditeur(s) : HAL CCSD Saint-Maurice (Val de Marne) : Institut de veille sanitaire
Résumé : International audience
ISSN: 0245-7466

Droits : info:eu-repo/semantics/OpenAccess
hal-01675363
https://hal.archives-ouvertes.fr/hal-01675363
https://hal.archives-ouvertes.fr/hal-01675363/document
https://hal.archives-ouvertes.fr/hal-01675363/file/BEH_lepto.pdf

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
Our knowledge and understanding of the 3-D lithospheric structure of the Himalayas and the Tibetan Plateau is still challenging although numerous geophysical studies have been performed in the region. The GOCE satellite mission has the ambitious goal of mapping Earth's gravity field with unprecedented precision (i.e. an accuracy of 1-2 mGal for a spatial resolution of 100 km) to observe the lithosphere and upper-mantle structure. Consequently, it gives new insights in the lithospheric structure beneath the Himalayas and the Tibetan Plateau. Indeed, the GOCE gravity data now allow us to develop a new strategy for joint gravimetry-seismology inversion. Combined with teleseismic data over a large region in a joint inversion scheme, they will lead to lithospheric velocity-density models constrained in two complementary ways. We apply this joint inversion scheme to the Hi-CLIMB (Himalayan-Tibetan Continental Lithosphere during Mountain Building) seismological network which was deployed in South Tibet and the Himalayas for a 3-yr period. The large size of the network, the high quality of the seismological data and the new GOCE gravity data set allow us to image the entire lithosphere of this active area in an innovative way. We image 3-D low velocity and density structures in the middle crust that fit the location of discontinuous low S-velocity zones revealed by receiver functions in previous geophysical studies. In the deeper parts of our velocity model we image a positive anomaly interpreted to be the heterogenous Indian lithosphere vertically descending beneath the centre of the Tibetan Plateau.
ISSN: 0956-540X

hal-00858024
https://hal.archives-ouvertes.fr/hal-00858024
DOI : 10.1093/gji/ggs110

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
Two genome-wide association studies (GWASs) recently highlighted the HLA-DRA and HLA-DRB5 genes as associated with Parkinson disease (PD). However, because HLA-DRA displays a low level of polymorphisms and HLA-DRB5 is only present in approximately 20% of the population, these findings are difficult to interpret. Our aims were: (1) to replicate and investigate in greater detail the association between PD and the HLA-DR region; (2) to identify PD-associated HLA alleles; and (3) to perform a meta-analysis of our top finding. As part of 2 French population-based case-control studies of PD including highly ethnically homogeneous participants, we investigated the association between PD and 51 Single-nucleotide polymorphisms (SNPs) in the HLA-DR region. HLA-DRB1 alleles were imputed using the HLA(*) IMP software. HLA typing was performed in a subsample of the participants. We performed a meta-analysis of our top finding based on 4 GWAS data sets. Among 499 cases and 1123 controls, after correction for multiple testing, we found an association with rs660895 (OR/minor allele, 0.70; 95% CI, 0.57-0.87) within the HLA-DRB1 gene, which encodes the most polymorphic HLA-DR chain (DRβ). A meta-analysis (7996 cases, 36455 controls) confirmed this association (OR, 0.86; 95% CI, 0.82-0.91; P < .0001). SNP-based imputation of HLA alleles showed an inverse association between PD and the HLA-DRB1(*) 04 allele. We replicated an association between PD and the HLA-DR region and provided further insight into the loci and alleles involved. The highly polymorphic HLA-DRB1 locus contains rs660895, which represents a more legitimate candidate than previous ones. Our finding is in agreement with the hypothesis of an immune component in PD pathophysiology. © 2012 Movement Disorder Society.
ISSN: 0885-3185

inserm-00721562
http://www.hal.inserm.fr/inserm-00721562
http://www.hal.inserm.fr/inserm-00721562/document
http://www.hal.inserm.fr/inserm-00721562/file/Table1.pdf
http://www.hal.inserm.fr/inserm-00721562/file/Table2.pdf

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
Plasmodium vivax malaria is an important public health issue in the Amazon region, and it accounts for approximately 84 % of cases of the disease. Migration across the border between Brazil and French Guiana contributes to the maintenance of the disease. The aim of this study was to evaluate the therapeutic and parasitological responses of patients with P. vivax malaria treated with chloroquine and primaquine in the socio-environmental context of cross-border interactions between Brazil and French Guiana. The factors controlled were diagnostic agreement, adherence, adjustment of primaquine doses for patient weight, and quality of the drugs used. A prospective study was conducted in 2011 with 103 individuals aged 10-60 years with a positive diagnosis of P. vivax treated with chloroquine (10 mg base/kg on the first day, followed by 7.5 mg/kg on the second and third days) and primaquine for 7 days, who were followed for 28 days. The primaquine doses were adjusted for the patients' weight. A number of factors were determined: epidemiological characteristics, origin of patients, signs and symptoms, initial parasitaemia and parasitaemia clearance time, blood concentrations of chloroquine and primaquine, quality of anti-malarial drugs and diagnostic agreement. Ninety-five patients were followed for 28 days. There was a 100 % agreement in microscopic diagnosis between field laboratory and reference centre. The adhesion to the treatment was 100 %. Of these patients, 32.6 % received a weight-adjusted dose of primaquine. The chloroquine and primaquine tablets were consistent with the optimal quality limits for human consumption. The investigated patients achieved optimal blood exposure to anti-malarial drugs. The parasitological and therapeutic response was adequate in 99.0 % of cases. In the municipality of Oiapoque, the therapeutic regime used for the treatment of P. vivax malaria using chloroquine combined with primaquine remains effective, when external factors are controlled, such as the quality of anti-malarial drugs, the adhesion to the treatment prescribed, the correct diagnostic and the adjustment of primaquine dose for patient body weight.
ISSN: 1475-2875

Droits : http://creativecommons.org/licenses/by/
pasteur-01229355
https://hal-pasteur.archives-ouvertes.fr/pasteur-01229355
https://hal-pasteur.archives-ouvertes.fr/pasteur-01229355/document
https://hal-pasteur.archives-ouvertes.fr/pasteur-01229355/file/s12936-015-0925-7.pdf
PUBMEDCENTRAL : PMC4600333

Éditeur(s) : HAL CCSD American Association for Cancer Research
Résumé : International audience
The aim of this study was to test in vitro the efficacy of TAC, an original G-quadruplex ligand, as a potential radiosensitizing agent for glioblastoma multiforme (GBM). Two human radioresistant telomerase-positive GBM cell lines (SF763 and SF767) were analyzed, with and without TAC treatment, for telomere length, cell proliferation, apoptosis, cell-cycle distribution, gene expression, cytogenetic aberrations, clonogenic survival assay, 53BP1 immunofluorescence staining, and γH2AX phosphorylation. We found that low concentrations of TAC (0.5 and 1 μmol/L) inhibited the proliferation of GBM cells in a concentration-dependent manner after only 1 week of treatment, with minimal effects on cell cycle and apoptosis. TAC treatment had no visible effect on average telomere length but modified expression levels of telomere-related genes (hTERT, TRF1, and TRF2) and induced concentration-dependent DNA damage response and dicentric chromosomes. Survival curves analysis showed that exposure to nontoxic, subapoptotic concentrations of TAC enhanced radiation-induced killing of GBM cells. Analysis of DNA repair after irradiation revealed delayed repair kinetics in GBM cells treated with TAC. Furthermore, the combined treatment (TAC and radiation) significantly increased the frequency of chromosomal aberrations as compared with radiation alone. These findings provide the first evidence that exposure to a G4 ligand radiosensitizes human glioblastoma cells and suggest the prospect of future therapeutic applications.
ISSN: 1535-7163

hal-00851184
https://hal.archives-ouvertes.fr/hal-00851184
DOI : 10.1158/1535-7163.MCT-10-0664
PUBMED : 21987532

Éditeur(s) : HAL CCSD Elsevier Masson
Résumé : National audience
Introduction Les péritonites secondaires à levures représentent une part importante des candidoses profondes et de leur traitement. Peu d’outils sont disponibles afin de prédire au mieux les patients susceptible d’avoir une culture du liquide péritonéal positive. L’étude AMARCAND II (10/202–09/2013) a analysé les patients de réanimation recevant un traitement antifongique pour un candidose invasive prouvée ou suspectée. L’analyse des patients ayant un traitement probabiliste pour péritonite à levure suspectée est présentée ici. Patients et méthodes Cent soixante-douze patients parmi les 835 inclus ont été analysés. Les patients ayant une documentation mycologique (groupe D) ont été comparés à ceux ayant une culture à levure négative (groupe ND). La performance du Candida score [1] et du Peritonitis score [2] ont été évalués dans cette population de candidose profonde suspectée. Résultats Parmi les 172 patients, 51 ont eu une péritonite documentée à levure et 121 un culture à levure négative. Les caractéristiques des groupes sont présentées dans le Tableau 1. L’AUC du Peritonitis score était de 0,63 [0,54–0,72] contre 0,40 [0,31–0,49] pour le Candida score, p = 0,005. Pour un Peritonitis score ≥ 3, la sensibilité était de 39,2 %, la spécificité de 81,8 %, la VPP de 47,6 % et la VPN de 76,2 %. Le Candida score ne permettait pas de classer les patients atteints de péritonite à levure. Discussion Peu d’éléments permettent de différencier les patients qui vont avoir une infection documentée des autres. La localisation sus-mésocolique de l’infection et l’antibiothérapie de plus de 48 heures sont les éléments les plus fiables retrouvés. Le Peritonitis score reste intéressant dans ce contexte mais le Candida score n’a aucune utilité
ISSN: 2352-5800

hal-01244999
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01244999
DOI : 10.1016/j.anrea.2015.07.329

Éditeur(s) : HAL CCSD Lippincott, Williams & Wilkins
Résumé : International audience
o abstract
ISSN: 0269-9370

hal-01560146
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01560146
DOI : 10.1097/QAD.0000000000001474
PUBMED : 28492398

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Ethnopharmacological relevancePsidium acutangulum Mart. ex DC is a small tree used by the Wayana Amerindians from the Upper-Maroni in French Guiana for the treatment of malaria.Aim of the studyIn a previous study, we highlighted the in vitro antiplasmodial, antioxidant and anti-inflammatory potential of the traditional decoction of P. acutangulum aerial parts. Our goal was then to investigate on the origin of the biological activity of the traditional remedy, and eventually characterize active constituents.Materials and methodsLiquid-liquid extractions were performed on the decoction, and the antiplasmodial activity evaluated against chloroquine-resistant FcB1 ([3H]-hypoxanthine bioassay) and 7G8 (pLDH bioassay) P. falciparum strains, and on a chloroquine sensitive NF54 ([3H]-hypoxanthine bioassay) P. falciparum strain. The ethyl acetate fraction (D) was active and underwent bioguided fractionation. All the isolated compounds were tested on P. falciparum FcB1 strain. In vitro anti-inflammatory activity (IL-1β, IL-6, IL-8, TNFα) of the ethyl acetate fraction and of an anti-Plasmodium active compound, was concurrently assessed on LPS-stimulated human PBMC and NO secretion inhibition was measured on LPS stimulated RAW murine macrophages. Cytotoxicity of the fractions and pure compounds was measured on VERO cells, L6 mammalian cells, PBMCs, and RAW cells.ResultsFractionation of the ethyl acetate soluble fraction (IC50 ranging from 3.4 to <1 µg/mL depending on the parasite strain) led to the isolation of six pure compounds: catechin and five glycosylated quercetin derivatives. These compounds have never been isolated from this plant species. Two of these compounds (wayanin and guaijaverin) were found to be moderately active against P. falciparum FcB1 in vitro (IC50 5.5 and 6.9 µM respectively). We proposed the name wayanin during public meetings organized in June 2015 in the Upper-Maroni villages, in homage to the medicinal knowledge of the Wayana population. At 50 µg/mL, the ethyl acetate fraction (D) significantly inhibited IL-1β secretion (−46%) and NO production (−21%), as previously observed for the decoction. The effects of D and guiajaverin (4) on the secretion of other cytokines or NO production were not significant.ConclusionsThe confirmed antiplasmodial activity of the ethyl acetate soluble fraction of the decoction and of the isolated compounds support the previous results obtained on the P. acutangulum decoction. The antiplasmodial activity might be due to a mixture of moderately active non-toxic flavonoids. The anti-inflammatory activities were less marked for ethyl acetate fraction (D) than for the decoction.
ISSN: 0378-8741

hal-01313006
http://hal.upmc.fr/hal-01313006
http://hal.upmc.fr/hal-01313006/document
http://hal.upmc.fr/hal-01313006/file/Houel_Wayanin_and.pdf
DOI : 10.1016/j.jep.2016.04.053

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
OBJECTIVES: To compare virological effectiveness in patients who continued on a virologically successful first-line boosted protease inhibitor (PI)-containing combination antiretroviral therapy (cART) regimen or who switched to a PI-free cART including efavirenz, nevirapine or abacavir. METHODS: From the French Hospital Database on HIV, we selected 439 patients with undetectable viral load (VL) on a first-line boosted PI-containing cART regimen who switched to a PI-free combination including efavirenz, nevirapine or abacavir. Each of these patients was matched with three patients who continued to take their first-line cART regimen, on the basis of gender, age, CD4 cell count, VL, date of cART initiation and the duration of VL undetectability. Time to virological failure (VF) was analysed with Kaplan-Meier curves and Cox models. RESULTS: The 12 month probabilities of VF were 3.7% and 5.7% in non-switch and switch patients, respectively, and 3.9%, 7.2% and 9.0% in patients switching to efavirenz-, nevirapine- and abacavir-containing cART, respectively. After adjustment, only patients switching to abacavir-containing cART had a higher risk of VF than non-switch patients (adjusted hazard ratio, 1.99; 95% confidence interval, 1.05-3.79). CONCLUSIONS: Switching from a virologically successful first-line boosted PI-containing cART regimen to a non-nucleoside reverse transcriptase inhibitor-containing cART regimen containing either efavirenz or nevirapine is virologically safe, while switching to abacavir-containing cART should be avoided.
ISSN: 0305-7453

hal-00875284
https://hal.archives-ouvertes.fr/hal-00875284
DOI : 10.1093/jac/dkr208
PUBMED : 21636583

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
French Guiana is a South American French territory, where HIV prevalence consistently exceeds 1% in the adult population. In the only correctional facility, HIV prevalence fluctuates at around 4%.
After describing the population of HIV-positive inmates, we aimed to evaluate mortality after release from the correctional facility, and to identify its predictive factors.
Outside North American settings, data on treatment outcome and vital status of HIV-positive former inmates are scarce. There were no data in French Guiana. Filling this gap represents a basis for potential improvements.
All HIV-infected adults released from an incarceration of 30 days or more, between 2007 and 2013, were enrolled in a retrospective cohort study. Mortality was described over time, one to seven years following release, using Kaplan-Meier estimates. Factors associated with mortality were identified through a non-parametric survival regression model.
147 former inmates were included. The male to female ratio was 4.4. The median age was 37.3 years. The majority were migrants, 25.8% were homeless, 70.1% suffered from substance abuse, with 34.0% of crack-cocaine users. On admission, 78.1% had an early HIV-stage infection (CDC-stage A), with a median CD4 count of 397.5/mm3, 34.0% had one comorbidity, mainly hypertension. Upon release, 50.3% were on ART. Reasons for not being treated were not fulfilling the criteria for 74.6%, and refusing for 15.1%. Before release, 84.5% of the patients on ART had a viral load≤200cp/ml. After release, 8.2% of the cohort had died, with a crude incidence of 33.8/1000 person-years. All recorded deaths were males, with an incidence of 42.2/1000 person-years. Comparing with the age-specific mortality rates for males in French Guiana, the standardized mortality ratio was 14.8. In multivariate analysis, factors associated with death were age and CD4 count before release.
Despite access to ART while incarcerated, with good virological outcome, the post-release mortality was very high for males, almost 15 times what is observed in the general male population living in French Guiana, after age standardization. Access to ART in correctional facilities may be a necessary, but not sufficient condition to protect male inmates from death after release.
ISSN: 1932-6203

inserm-01519987
http://www.hal.inserm.fr/inserm-01519987
http://www.hal.inserm.fr/inserm-01519987/document
http://www.hal.inserm.fr/inserm-01519987/file/2017%2C%20Huber%20-%20Mortality%20HIV%20prisoners%20after%20release.pdf
DOI : 10.1371/journal.pone.0175740.t002