Fate of antimony contamination generated by road traffic - A focus on Sb geochemistry and speciation in stormwater ponds.

Although antimony (Sb) contamination has been documented in urban areas, knowledge gaps remain concerning the contributions of the different sources to the Sb urban biogeochemical cycle, including non-exhaust road traffic emissions, urban materials leaching/erosion and waste incineration. Additionally, details are lacking about Sb chemical forms involved in urban soils, sediments and water bodies. Here, with the aim to document the fate of metallic contaminants emitted through non-exhaust traffic emissions in urban aquatic systems, we studied trace element contamination, with a particular focus on Sb geochemistry, in three highway stormwater pond systems, standing as models of surface environments receiving road-water runoff. In all systems, differentiated on the basis of lead isotopic signatures, Sb shows the higher enrichment factor with respect to the geochemical background, up to 130, compared to other traffic-related inorganic contaminants (Co, Cr, Ni, Cu, Zn, Cd, Pb). Measurements of Sb isotopic composition (δ123Sb) performed on solid samples, including air-exposed dusts and underwater sediments, show an average signature of 0.07 ±â€¯0.05‰ (n = 25, all sites), close to the δ123Sb value measured previously in certified reference material of road dust (BCR 723, δ123Sb = 0.03 ±â€¯0.05‰). Moreover, a fractionation of Sb isotopes is observed between solid and dissolved phases in one sample, which might result from Sb (bio)reduction and/or adsorption processes. SEM-EDXS investigations show the presence of discrete submicrometric particles concentrating Sb in all the systems, interpreted as friction residues of Sb-containing brake pads. Sb solid speciation determined by linear combination fitting of X-Ray Absorption Near Edge Structure (XANES) spectra at the Sb K-edge shows an important spatial variability in the ponds, with Sb chemical forms likely driven by local redox conditions: "dry" samples exposed to air exhibited contributions from Sb(V)-O (52% to 100%) and Sb(III)-O (<10% to 48%) species whereas only underwater samples, representative of suboxic/anoxic conditions, showed an additional contribution from Sb(III)-S (41% to 80%) species. Altogether, these results confirm the traffic emission as a specific source of Sb emission in surface environments. The spatial variations of Sb speciation observed along the road-to-pond continuum likely reflect a high geochemical reactivity, which could have important implications on Sb transfer properties in (sub)surface hydrosystems.

Precipitation of greigite and pyrite induced by Thermococcales: an advantage to live in Fe- and S-rich environments?

Thermococcales, a major order of archaea inhabiting the iron- and sulfur-rich anaerobic parts of hydrothermal deep-sea vents, have been shown to rapidly produce abundant quantities of pyrite FeS2 in iron-sulfur-rich fluids at 85°C, suggesting that they may contribute to the formation of 'low temperature' FeS2 in their ecosystem. We show that this process operates in Thermococcus kodakarensis only when zero-valent sulfur is directly available as intracellular sulfur vesicles. Whether in the presence or absence of zero-valent sulfur, significant amounts of Fe3 S4 greigite nanocrystals are formed extracellularly. We also show that mineralization of iron sulfides induces massive cell mortality but that concomitantly with the formation of greigite and/or pyrite, a new generation of cells can grow. This phenomenon is observed for Fe concentrations of 5 mM but not higher suggesting that above a threshold in the iron pulse all cells are lysed. We hypothesize that iron sulfides precipitation on former cell materials might induce the release of nutrients in the mineralization medium further used by a fraction of surviving non-mineralized cells allowing production of new alive cells. This suggests that biologically induced mineralization of iron-sulfides could be part of a survival strategy employed by Thermococcales to cope with mineralizing high-temperature hydrothermal environments.

Ibrutinib, a Bruton's tyrosine kinase inhibitor, a new risk factor for cryptococcosis.

PURPOSE: Invasive fungal diseases and especially Cryptococcus neoformans infections are increasingly reported in patients with hematological malignancies receiving ibrutinib, a Bruton's tyrosine kinase inhibitor. PATIENTS AND METHOD: We reported three additional cases and reviewed 16 previous published cases together with cases from the international pharmacovigilance database. RESULTS: Patients were mainly treated for chronic lymphocytic leukemia. Cryptococcosis mostly occurred during the first six months (66%) and especially the first two months (44%) of treatment. Clinical presentation is often pulmonary (68%) and the outcome is usually favorable despite ibrutinib continuation. CONCLUSION: Clinicians must be aware of this infection in patients with hematological malignancies on ibrutinib.

Determination of antifungal caspofungin in RPMI-1640 cell culture medium by column-switching HPLC-FLD.

The actual scenario in the fight against fungal infections forces researchers to carry through with resistance studies to improve the therapies. These studies, which are performed in cell culture media, need accurate and sensitive analytical methodologies. That is why, in this work, an analytical method for caspofungin (CSF) concentration determination in RPMI-1640 cell culture medium with on-line sample treatment was developed and validated. CSF concentration was determined by HPLC-FLD using a column-switching procedure. The chromatographic analysis was carried out in less than 10 min using a C8 column (4 × 4 mm, 5 µm) as extraction stationary phase and a HSS T3 column (4.6 × 100 mm, 5 µm) as the analytical column. The used mobile phases were mixtures of phase A: pH 2 (adjusted with TFA) aqueous phase and phase B: ACN. For the extraction, the composition was (95:5, A:B v/v) and for the analysis (60:40, A:B v/v), both done in isocratic elution mode. These chromatographic conditions allowed reaching a limit of quantification of 10 µg/L, using 100 µL of sample with an injected volume of 40 µL. The proposed method was successfully validated in terms of selectivity, carryover, linear concentration range, accuracy and precision according to the criteria established by the Food and Drug Administration. Available amount of CSF in RPMI-1640 solution was found critical. CSF concentrations remained stable up to 2 h at room temperature. The developed method was applied for the direct analysis of CSF concentrations from in vitro experiments in presence of C. glabrata (CAGL18). The results highlight the decrease of cell proliferation even if the CSF amount decreases too, which asks question about the real value of the efficient concentration for CSF antifungal activity.

Species Distribution and Comparison between EUCAST and Gradient Concentration Strips Methods for Antifungal Susceptibility Testing of 112 Aspergillus Section Nigri Isolates.

Aspergillus niger, the third species responsible for invasive aspergillosis, has been considered as a homogeneous species until DNA-based identification uncovered many cryptic species. These species have been recently reclassified into the Aspergillus section Nigri However, little is yet known among the section Nigri about the species distribution and the antifungal susceptibility pattern of each cryptic species. A total of 112 clinical isolates collected from 5 teaching hospitals in France and phenotypically identified as A. niger were analyzed. Identification to the species level was carried out by nucleotide sequence analysis. The MICs of itraconazole, voriconazole, posaconazole, isavuconazole, and amphotericin B were determined by both the EUCAST and gradient concentration strip methods. Aspergillus tubingensis (n = 51, 45.5%) and Aspergillus welwitschiae (n = 50, 44.6%) were the most common species while A. niger accounted for only 6.3% (n = 7). The MICs of azole drugs were higher for A. tubingensis than for A. welwitschiae The MIC of amphotericin B was 2 mg/liter or less for all isolates. Importantly, MICs determined by EUCAST showed no correlation with those determined by the gradient concentration strip method, with the latter being lower than the former (Spearman's rank correlation tests ranging from 0.01 to 0.25 depending on the antifungal agent; P > 0.4). In conclusion, A. niger should be considered as a minority species in the section Nigri The differences in MICs between species for different azoles underline the importance of accurate identification. Significant divergences in the determination of MIC between EUCAST and the gradient concentration strip methods require further investigation.

Cryptosporidiosis and microsporidiosis as causes of diarrhea in kidney and/or pancreas transplant recipients.

INTRODUCTION: Gastrointestinal disorders in solid organ recipients may have various origins including cryptosporidiosis and microsporidiosis. The prevalence of these infections is poorly known in solid organ transplant (SOT) patients in industrialized countries. METHODS: We prospectively assessed the infectious causes of diarrhea in SOT patients. Secondary objectives were to gain further insight into the main characteristics of cryptosporidiosis, and to assess risk factors for this infection. All adult kidney and/or pancreas recipients presenting with diarrhea and admitted to our facility between May 1, 2014 and June 30, 2015 were enrolled. A stool sample was analyzed using a standardized protocol including bacteriological, virological, and parasitological investigations. Data related to clinical symptoms, immunosuppression, and environmental potential risk factors were collected through a self-administered questionnaire and computerized medical records. RESULTS: Out of 73 enrolled patients, 36 had infectious diarrhea (49.3%). Viruses ranked first (17/36), followed by parasites and fungi (11/17). Cryptosporidiosis was the most common parasitic disease (n=6 patients). We observed four microsporidiosis cases. The estimated prevalence of cryptosporidiosis and microsporidiosis in this cohort was 3.7 and 2.40/00, respectively. No significant risk factor for cryptosporidiosis or microsporidiosis, neither environmental nor immunological, could be evidenced. CONCLUSION: Both cryptosporidiosis and microsporidiosis represent a significant cause of diarrhea in kidney transplant recipients.

One year prospective survey of azole resistance in Aspergillus fumigatus at a French cystic fibrosis reference centre: prevalence and mechanisms of resistance.

BACKGROUND: Studies on Aspergillus fumigatus azole resistance in cystic fibrosis patients are scarce despite the fact that it is the most frequently isolated fungus from respiratory samples from these individuals. OBJECTIVES: To evaluate resistance prevalence, investigate mechanisms of resistance and explore the relationship between resistant isolates by genotyping. METHODS: We conducted a prospective 1 year study (from 1 January to 31 December 2015), based on the investigation of up to five colonies per sample from cystic fibrosis patients. RESULTS: Twenty-three (6.5%) isolates among the 355 tested were resistant to at least one triazole drug, using the EUCAST reference method, leading to a prevalence of 6.8% (6/88 patients). Analysis of resistance mechanisms highlighted TR34/L98H (n = 10), TR46/Y121F/T289A (n = 1), WT cyp51A (n = 11) and F46Y/M172V/N248T/D255E/E427K (n = 1). No genotype was shared between patients. CONCLUSIONS: This study showed a relatively stable resistance prevalence in comparison with the previous study conducted in 2010-11 (8%), although resistance mechanisms varied between the two studies.

Evaluation of a new multiplex PCR assay (ParaGENIE G-Amoeba Real-Time PCR kit) targeting Giardia intestinalis, Entamoeba histolytica and Entamoeba dispar/Entamoeba moshkovskii from stool specimens: evidence for the limited performances of microscopy-based approach for amoeba species identification.

OBJECTIVES: Besides the potential to identify a wide variety of gastrointestinal parasites, microscopy remains the reference standard in clinical microbiology for amoeba species identification and, especially when coupled with adhesin detection, to discriminate the pathogenic Entamoeba histolytica from its sister but non-pathogenic species Entamoeba dispar/Entamoeba moshkovskii. However, this approach is time-consuming, requires a high-level of expertise that can be jeopardized considering the low prevalence of gastrointestinal parasites in non-endemic countries. Here, we evaluated the CE-IVD-marked multiplex PCR (ParaGENIE G-Amoeba, Ademtech) targeting E. histolytica and E. dispar/E. moshkovskii and Giardia intestinalis. METHODS: This evaluation was performed blindly on a reference panel of 172 clinical stool samples collected prospectively from 12 laboratories and analysed using a standardized protocol relying on microscopy (and adhesin detection by ELISA for the detection of E. histolytica) including G. intestinalis (n = 37), various amoeba species (n = 55) including E. dispar (n = 15), E. histolytica (n = 5), as well as 17 other gastrointestinal parasites (n = 80), and negative samples (n = 37). RESULTS: This new multiplex PCR assay offers fast and reliable results with appropriate sensitivity and specificity for the detection of G. intestinalis and E. dispar/E. moshkovskii from stools (89.7%/96.9% and 95%/100%, respectively). Detection rate and specificity were greatly improved by the PCR assay, highlighting several samples misidentified by microscopy, including false-negative and false-positive results for both E. dispar/E. moshkovskii and E. histolytica. CONCLUSION: Given the clinical relevance of amoeba species identification, microbiologists should be aware of the limitations of using an algorithm relying on microscopy coupled with adhesin detection by ELISA.

Emergence of Aspergillus fumigatus azole resistance in azole-naïve patients with chronic obstructive pulmonary disease and their homes.

Azole-resistant Aspergillus fumigatus (ARAF) has been reported in patients with chronic obstructive pulmonary disease (COPD) but has not been specifically assessed so far. Here, we evaluated ARAF prevalence in azole-naïve COPD patients and their homes, and assessed whether CYP51A mutations were similar in clinical and environmental reservoirs. Sixty respiratory samples from 41 COPD patients with acute exacerbation and environmental samples from 36 of these patient's homes were prospectively collected. A. fumigatus was detected in respiratory samples from 11 of 41 patients (27%) and in 15 of 36 domiciles (42%). Cyp51A sequencing and selection on itraconazole medium of clinical (n = 68) and environmental (n = 48) isolates yielded ARAF detection in 1 of 11 A. fumigatus colonized patients with COPD (9%) and 2 of 15 A. fumigatus-positive patient's homes (13%). The clinical isolate had no CYP51A mutation. Two environmental isolates from two patients harbored TR34 /L98H mutation, and one had an H285Y mutation. Coexistence of different cyp51A genotypes and/or azole resistance profiles was detected in 3 of 8 respiratory and 2 of 10 environmental samples with more than one isolate, confirming the need for a systematic screening of all clinically relevant isolates. The high prevalence of ARAF in patients with COPD and their homes supports the need for further studies to assess the prevalence of azole resistance in patients with Aspergillus diseases in Northern France.

Azole Resistance in Aspergillus fumigatus in Patients with Cystic Fibrosis: A Matter of Concern?

Aspergillus fumigatus is the most frequent filamentous fungus isolated from respiratory specimens from patients with cystic fibrosis (CF). Triazoles are the most widely used antifungals in the treatment of allergic bronchopulmonary aspergillosis (ABPA) and invasive aspergillosis (IA) in CF patients. Treatment success could be severely compromised by the occurrence of azole-resistant A. fumigatus (ARAf), which is increasingly reported worldwide from both clinical samples and the environment. In previous studies, ARAf has been detected in up to 8% of CF patients. Isolates from CF patients requiring antifungal treatment should therefore be routinely subjected to antifungal susceptibility testing. The optimal treatment of ABPA or IA in CF patients with azole-resistant isolates has not been established; treatment options include liposomal amphotericin B i.v. and/or echinocandins i.v.

Biological attenuation of arsenic and iron in a continuous flow bioreactor treating acid mine drainage (AMD).

Passive water treatments based on biological attenuation can be effective for arsenic-rich acid mine drainage (AMD). However, the key factors driving the biological processes involved in this attenuation are not well-known. Here, the efficiency of arsenic (As) removal was investigated in a bench-scale continuous flow channel bioreactor treating As-rich AMD (∼30-40 mg L-1). In this bioreactor, As removal proceeds via the formation of biogenic precipitates consisting of iron- and arsenic-rich mineral phases encrusting a microbial biofilm. Ferrous iron (Fe(II)) oxidation and iron (Fe) and arsenic removal rates were monitored at two different water heights (4 and 25 mm) and with/without forced aeration. A maximum of 80% As removal was achieved within 500 min at the lowest water height. This operating condition promoted intense Fe(II) microbial oxidation and subsequent precipitation of As-bearing schwertmannite and amorphous ferric arsenate. Higher water height slowed down Fe(II) oxidation, Fe precipitation and As removal, in relation with limited oxygen transfer through the water column. The lower oxygen transfer at higher water height could be partly counteracted by aeration. The presence of an iridescent floating film that developed at the water surface was found to limit oxygen transfer to the water column and delayed Fe(II) oxidation, but did not affect As removal. The bacterial community structure in the biogenic precipitates in the bottom of the bioreactor differed from that of the inlet water and was influenced to some extent by water height and aeration. Although potential for microbial mediated As oxidation was revealed by the detection of aioA genes, removal of Fe and As was mainly attributable to microbial Fe oxidation activity. Increasing the proportion of dissolved As(V) in the inlet water improved As removal and favoured the formation of amorphous ferric arsenate over As-sorbed schwertmannite. This study proved the ability of this bioreactor-system to treat extreme As concentrations and may serve in the design of future in-situ bioremediation system able to treat As-rich AMD.

Multicenter Comparison of the Etest and EUCAST Methods for Antifungal Susceptibility Testing of Candida Isolates to Micafungin.

In vitro susceptibility of 933 Candida isolates, from 16 French hospitals, to micafungin was determined using the Etest in each center. All isolates were then sent to a single center for determination of MICs by the EUCAST reference method. Overall essential agreement between the two tests was 98.5% at ±2 log2 dilutions and 90.2% at ±1 log2 dilutions. Categorical agreement was 98.2%. The Etest is a valuable alternative to EUCAST for the routine determination of micafungin MICs in medical mycology laboratories.

Is real-time PCR-based diagnosis similar in performance to routine parasitological examination for the identification of Giardia intestinalis, Cryptosporidium parvum/Cryptosporidium hominis and Entamoeba histolytica from stool samples? Evaluation of a new commercial multiplex PCR assay and literature review.

Microscopy is the reference standard for routine laboratory diagnosis in faecal parasitology but there is growing interest in alternative methods to overcome the limitations of microscopic examination, which is time-consuming and highly dependent on an operator's skills and expertise. Compared with microscopy, DNA detection by PCR is simple and can offer a better turnaround time. However, PCR performances remain difficult to assess as most studies have been conducted on a limited number of positive clinical samples and used in-house PCR methods. Our aim was to evaluate a new multiplex PCR assay (G-DiaParaTrio; Diagenode Diagnostics), targeting Giardia intestinalis, Cryptosporidium parvum/Cryptosporidium hominis and Entamoeba histolytica. To minimize the turnaround time, PCR was coupled with automated DNA extraction (QiaSymphony; Qiagen). The PCR assay was evaluated using a reference panel of 185 samples established by routine microscopic examination using a standardized protocol including Ziehl-Neelsen staining and adhesin detection by ELISA (E. histolytica II; TechLab). This panel, collected from 12 French parasitology laboratories, included 135 positive samples for G. intestinalis (n = 38), C. parvum/C. hominis (n = 26), E. histolytica (n = 5), 21 other gastrointestinal parasites, together with 50 negative samples. In all, the G-DiaParaTrio multiplex PCR assay identified 38 G. intestinalis, 25 C. parvum/C. hominis and five E. histolytica leading to sensitivity/specificity of 92%/100%, 96%/100% and 100%/100% for G. intestinalis, C. parvum/C. hominis and E. histolytica, respectively. This new multiplex PCR assay offers fast and reliable results, similar to microscopy-driven diagnosis for the detection of these gastrointestinal protozoa, allowing its implementation in routine clinical practice.

Multifocal phaeohyphomycosis caused by Exophiala xenobiotica in a kidney transplant recipient.

In recent years, black fungi have been increasingly reported as causing opportunistic infections after solid organ transplantation. Here, we report a case of insidious, relentless, and multifocal Exophiala xenobiotica infection in a kidney transplant recipient that eventually required multiple surgical excisions along with oral and intravenous antifungal combination therapy using liposomal amphotericin B and posaconazole. We compare the present case with all previously reported cases of Exophiala infection after kidney transplantation.

Remanence of lead pollution in an urban river system: a multi-scale temporal and spatial study in the Seine River basin, France.

Total lead (Pb) concentration and Pb isotopic ratio ((206)Pb/(20)7Pb) were determined in 140 samples from the Seine River basin (France), covering a period of time from 1945 to 2011 and including bed sediments (bulk and size fractionated samples), suspended particulate matter (SPM), sediment cores, and combined sewer overflow (CSO) particulate matter to constrain the spatial and temporal variability of the lead sources at the scale of the contaminated Seine River basin. A focus on the Orge River subcatchment, which exhibits a contrasted land-use pattern, allows documenting the relation between hydrodynamics, urbanization, and contamination sources. The study reveals that the Pb contamination due to leaded gasoline that peaked in the 1980s has a very limited impact in the river nowadays. In the upstream Seine River, the isotopic ratio analysis suggests a pervasive contamination which origin (coal combustion and/or gasoline lead) should be clarified. The current SPM contamination trend follows the urbanization/industrialization spatial trend. Downstream of Paris, the lead from historical use originating from the Rio Tinto mine, Spain ((206)Pb/(207)Pb=1.1634 ± 0.0001) is the major Pb source. The analysis of the bed sediments (bulk and grain size fractionated) highlights the diversity of the anthropogenic lead sources in relation with the diversity of the human activities that occurred in this basin over the years. The "urban" source, defined by waste waters including the CSO samples ((206)Pb/(207)Pb=1.157 ± 0.003), results of a thorough mixing of leaded gasoline with "historical" lead over the years. Finally, a contamination mixing scheme related to hydrodynamics is proposed.

[Identification of three Candida africana strains in Senegal]. / Identification de trois souches de Candida africana au Sénégal.

JUSTIFICATION: The frequency of candidiasis has increased dramatically in recent years. Candida albicans is the most common species. However, other species which are pathogenic and resistant to usual antifungal agents beginning to emerge. These include Candida dubliniensis and Candida africana, which share morphological similarities with Candida albicans. Thus, it is of interest to correctly identify the fungal isolates. OBJECTIVE: To seek these new species among Candida strains isolated in Dakar. MATERIAL AND METHODS: Oropharyngeal and vaginal swabs were performed at Fann Universitary Hospital in Dakar. The strains were identified by the germ tube test, the chlamydospore production test and an auxanogram. Then identification by PCR targeting the hyphal wall protein 1(hwp1) gene, was performed for the discrimination between Candida albicans, Candida dubliniensis and Candida africana. RESULTS: In total, 243 yeasts were isolated from samples including 231 in vaginal swab and 12 in oropharyngeal swab. Species identified by phenotypic methods are Candida albicans, which is the most frequent, Candida tropicalis, Candida glabrata, Candida dubliniensis, Candida kefyr and Candida lusitaniae. PCR performed on the 150 strains germ tube test positive identifies three Candida africana, 109 Candida albicans and no strain of Candida dubliniensis. CONCLUSION: This study isolates Candida africana for the first time in Senegal. Further studies on a larger sample will better know the actual proportion of these three species among the isolated yeasts.

[Prevalence of Candida parapsilosis, C. orthopsilosis and C. metapsilosis in candidemia over a 5-year period at Nantes hospital and in vitro susceptibility to three echinocandins by E-test®]. / Prévalence de Candida parapsilosis, C. orthopsilosis et de C. metapsilosis au sein des candidémies au CHU de Nantes et profil de sensibilité aux échinocandines par la méthode E-test®: étude rétrospective de cinq ans (2004-2009).

AIM OF THE STUDY: To determine the prevalence of C. parapsilosis sensu stricto, C. orthopsilosis and C. metapsilosis among candidemia at Nantes University Hospital and to evaluate the in vitro susceptibility of the isolates against three echinocandin drugs (caspofungin, micafungin and anidulafungin). MATERIAL AND METHODS: Retrospective study (march 2004 to july 2009) of 178 cases of candidemia corresponding to 183 Candida spp. strains identified by means of routine phenotypical methods. Re-identification of C. parapsilosis sensu lato isolates was performed by ITS rDNA sequencing analysis. Minimal inhibitory concentrations (MIC) were determined by E-test(®). All echinocandin non-susceptible isolates (MIC>2 µg/mL) were analyzed for the presence/absence of FKS1 mutations associated with resistance. RESULTS: During this period, C. parapsilosis sensu lato was responsible for 27 candidemia, ranging at the second most common Candida species after C. albicans (n=99, 54.1%). Neither isolates belong to C. orthopsilosis nor C. metapsilosis. According to the literature, all the isolates displayed high MICs against the three echinocandin drugs. All the isolates displayed both susceptibility (MIC ≤ 2 µg/mL) and a good agreement between MICs read at 24h and 48 h for caspofungin and micafungin (MIC(50)=0.75 µg/mL, MIC(90)=1.5 µg/mL). Surprisingly, whereas most of the strains were susceptible to anidulafungin at 24h (MIC(50)=1 µg/mL, MIC(90)=1.5 µg/mL), 14 (52 %) displayed non-susceptibility, despite the lack of mutation associated with resistance on FKS1, when reading was performed at 48 h (MIC(50)=3 µg/mL, MIC(90)=12 µg/mL). CONCLUSION: Prevalence of C. orthopsilosis and C. metapsilosis in patients with candidemia is low at Nantes University Hospital. The difficulty encountered with MIC reading by E-test(®) are discussed.

[Contribution of molecular biology and Aspergillus galactomannan antigen assay for the diagnosis of histoplasmosis]. / Contribution de la biologie moléculaire et de l'antigénémie galactomannane aspergillaire au diagnostic de l'histoplasmose.

We report a case of a pulmonary histoplasmosis in an HIV-positive patient usually living in Cambodia, with a positive Aspergillus galactomannan antigenemia resulting from a cross-reaction, that decreased after antifungal therapy. We discuss the potential interest of the detection of fungal DNA by PCR and Aspergillus galactomannan antigenemia for the diagnosis of histoplasmosis, especially in countries where Histoplasma capsulatum antigen testing is not available.

A 3D-QSAR CoMSIA study on 3-azolylmethylindoles as anti-leishmanial agents.

A three-dimensional quantitative structure-activity relationship (3D-QSAR) study using Comparative Molecular Similarity Indices Analysis (CoMSIA) was conducted on a series of 3-azolylmethylindoles as anti-leishmanial agents. Evaluation of 24 compounds synthesized in our laboratory served to establish the model. A random search was performed on the library of compounds, and molecules of the training set were aligned on common elements of template molecule 13, one of the most active compounds. The best predictions were obtained from multifit procedure with a CoMSIA model combining steric, electrostatic, hydrophobic and hydrogen bond acceptor fields (q2 = 0.594, r2 = 0.897). The model was validated using an external test set of 7 compounds giving a satisfactory predictive r2 value of 0.649. Information obtained from CoMSIA contour maps could be used for further design of more promising inhibitors.