RESUMO
The molecular detection of Toxoplasma gondii DNA is a key tool for the diagnosis of disseminated and congenital toxoplasmosis. This multicentric study from the Molecular Biology Pole of the French National Reference Center for toxoplasmosis aimed to evaluate Toxoplasma gondii Real-TM PCR kit (Sacace). The study compared the analytical and clinical performances of this PCR assay with the reference PCRs used in proficient laboratories. PCR efficiencies varied from 90% to 112%; linearity zone extended over four log units (R2 > 0.99) and limit of detection varied from 0.01 to ≤1 Tg/mL depending on the center. Determined on 173 cryopreserved DNAs from a large range of clinical specimens, clinical sensitivity was 100% [106/106; 95 confidence interval (CI): 96.5%-100%] and specificity was 100% (67/67; 95 CI: 94.6%-100%). The study revealed two potential limitations of the Sacace PCR assay: the first was the inconsistency of the internal control (IC) when added to the PCR mixture. This point was not found under routine conditions when the IC was added during the extraction step. The second is a lack of practicality, as the mixture is distributed over several vials, requiring numerous pipetting operations. Overall, this study provides useful information for the molecular diagnosis of toxoplasmosis; the analytical and clinical performances of the Sacace PCR kit were satisfactory, the kit having sensitivity and specificity similar to those of expert center methods and being able to detect low parasite loads, at levels where multiplicative analysis gives inconsistently positive results. Finally, the study recommends multiplicative analysis in particular for amniotic fluids, aqueous humor, and other single specimens.
Assuntos
Toxoplasma , Toxoplasmose Congênita , Toxoplasmose , Humanos , Toxoplasma/genética , Toxoplasmose/diagnóstico , Toxoplasmose/parasitologia , Toxoplasmose Congênita/diagnóstico , Toxoplasmose Congênita/parasitologia , DNA , Kit de Reagentes para Diagnóstico , Sensibilidade e Especificidade , DNA de Protozoário/genética , DNA de Protozoário/análiseRESUMO
OBJECTIVES: We aimed to describe features and outcomes of cryptococcosis among HIV-seronegative individuals in a large surveillance network for cryptococcosis in France. METHODS: We included incident cases of cryptococcosis in HIV-seronegative individuals from 2005 to 2020. We compared patient characteristics, disease presentations, cryptococcal antigen results, and induction antifungal treatments according to underlying disease. We examined factors associated with 90-day mortality. Among patients with disseminated infections, we investigated whether receipt of flucytosine and polyene combination was associated with lower mortality. RESULTS: Among 652 individuals, 209 (32.1%) had malignancy, 130 (19.9%) were solid-organ transplant recipients, 204 (31.3%) had other immunocompromising conditions, and 109 (16.7%) had no reported underlying factor. The commonest presentations were disseminated infections (63.3%, 413/652) and isolated pulmonary infections (25.3%, 165/652). Solid-organ transplant patients were most likely to have disseminated infections and a positive serum cryptococcal antigen result. Patients with malignancy were older and less likely to receive a flucytosine-containing regimen for disseminated infections than others (58.7%, 78/133 vs. 73.2%, 194/265; p 0.029). The crude 90-day case-fatality ratio was 27.2% (95% CI, 23.5%-31.1%). Age ≥60 years (aOR: 2.75 [1.78-4.26]; p < 0.001), meningitis/fungaemia (aOR: 4.79 [1.80-12.7]; p 0.002), and malignancy (aOR: 2.4 [1.14-5.07]; p 0.02) were associated with higher 90-day mortality. Receipt of flucytosine and polyene combination was associated with lower 90-day mortality (aOR: 0.40 [0.23-0.71]; p 0.002) in multivariable analysis and inverse probability of treatment weighted analysis (aOR: 0.45 [0.25-0.80]; p 0.006). DISCUSSION: HIV-seronegative individuals with cryptococcosis comprise a wide range of underlying conditions with different presentations and outcomes, requiring a tailored approach to diagnosis and management.
Assuntos
Antifúngicos , Criptococose , Humanos , França/epidemiologia , Feminino , Masculino , Criptococose/epidemiologia , Criptococose/mortalidade , Pessoa de Meia-Idade , Adulto , Estudos Transversais , Antifúngicos/uso terapêutico , Idoso , Flucitosina/uso terapêutico , Soronegatividade para HIV , Polienos/uso terapêutico , Adulto Jovem , Hospedeiro ImunocomprometidoRESUMO
Among 1107 cryptococcosis cases from the French surveillance network (2005-2020), the proportion of HIV-seronegative individuals has recently surpassed that of HIV-seropositive individuals. We observed marked differences in patient characteristics, disease presentations, cryptococcal antigen results, infecting species, and mortality according to HIV serostatus.
RESUMO
Aspergillus series Versicolores are molds distributed among 17 species, commonly found in our environment, and responsible for infections. Since 2022, a new taxonomy has grouped them into 4 major lineages: A. versicolor, A. subversicolor, A. sydowii, and A. creber. Matrix-Assisted Laser Desorption/Ionization Time-Of-Flight Mass Spectrometry (MALDI-TOF MS) could be a faster and more cost-effective alternative to molecular techniques for identifying them by developing a local database. To evaluate this technique, 30 isolates from Aspergillus series Versicolores were used. A total of 59 main spectra profiles (MSPs) were created in the local database. This protocol enabled accurate identification of 100% of the extracted isolates, of which 97% (29/30) were correctly identified with a log score ≥ 2.00. Some MSPs recorded as Aspergillus versicolor in the supplier's database could lead to false identifications as they did not match with the correct lineages. Although the local database is still limited in the number and diversity of species of Aspergillus series Versicolores, it is sufficiently effective for correct lineage identification according to the latest taxonomic revision, and better than the MALDI-TOF MS supplier's database. This technology could improve the speed and accuracy of routine fungal identification for these species.
RESUMO
Intestinal microsporidiosis is most often caused by Enterocytozoon bieneusi, and to a lesser extent by species of the genus Encephalitozoon. Until now, Encephalitozoon hellem was not clearly known to induce disease restricted to the intestine, or rarely in HIV subjects or in tropical countries. We report here 11 cases of delineated intestinal microsporidioses due to E. hellem diagnosed in France in non-HIV patients. Briefly, all patients were immunocompromised. They all suffered from diarrhoea, associated in nearly 50% of cases with weight loss. Concerning treatment, 5/11 patients had a discontinuation or a decrease of their immunosuppressive therapy, and 4/11 received albendazole. All patients recovered. Five different genotypes were identified based on the rRNA ITS sequence.
Assuntos
Encephalitozoon , Enterocytozoon , Microsporidiose , Humanos , Encephalitozoon/genética , Enterocytozoon/genética , Intestinos , FezesRESUMO
OBJECTIVES: We aimed to describe patients with autoimmune diseases (AID) developing invasive fungal disease (IFD) and identify factors associated with short-term mortality. METHODS: We analysed cases of IFD associated with AID from the surveillance network of invasive fungal diseases (Réseau de surveillance des infections fongiques invasives, RESSIF) registry of the French national reference centre for invasive mycoses. We studied association of AID-specific treatments with 30-day mortality. We analysed total lymphocyte and CD4-T cell counts in patients with Pneumocystis jirovecii pneumonia (PCP). RESULTS: From 2012 to 2018, 549 individuals with IFD and AID were included, mainly with PCP (n=227, 41.3%), fungemia (n=167, 30.4%) and invasive aspergillosis (n=84, 15.5%). Rheumatoid arthritis (RA) and anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitides (AAV) were the most frequent AID in PCP (n=55 and 25, respectively) and invasive aspergillosis (n=15 and 10, respectively), inflammatory bowel diseases (IBDs) were predominant in fungemia (n=36). At IFD diagnosis, 365 (66.5%) patients received glucocorticoids (GCs), 285 (51.9%) immunosuppressants, 42 (7.7%) tumor necrosis factor (TNF)-α blockers, 75 (13.7%) other biologics. Mortality at 30 days was 28.1% (143/508). Fungemia and high-dose GCs were independently associated with higher 30-day mortality. In PCP patients, lymphopenia <1500/mm3 was frequent (132/179, 73.7%) even if CD4+T cell count exceeded 200/mm3 in 56/78 patients (71.8%) (median 472.5/mm3, IQR 160-858). CONCLUSION: IFD associated with AID occurs primarily in RA, AAV and IBD, especially when treated with GCs and immunosuppressants. Mortality is high, especially for patients on high-dose GCs. Lymphopenia may help identify risk of PCP, but normal CD4+T cell count does not rule out the risk. Further studies are needed to assess the individual risk factors for IFD.
Assuntos
Doenças Autoimunes , Infecções Fúngicas Invasivas , Doenças Autoimunes/complicações , Doenças Autoimunes/terapia , Infecções Fúngicas Invasivas/complicações , Infecções Fúngicas Invasivas/epidemiologia , Infecções Fúngicas Invasivas/etiologia , Infecções Fúngicas Invasivas/mortalidade , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Glucocorticoides/efeitos adversos , Glucocorticoides/uso terapêutico , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Fatores de Risco , França , PrevalênciaRESUMO
Little is known about localized osteoarticular Scedosporiosis (LOS). Most data come from case reports and small case series. Here we present an ancillary study of the nationwide French Scedosporiosis Observational Study (SOS), describing 15 consecutive cases of LOS diagnosed between January 2005 and March 2017. Adult patients diagnosed with LOS defined by osteoarticular involvement without distant foci reported in SOS were included. Fifteen LOS were analyzed. Seven patients had underlying disease. Fourteen patients had prior trauma as potential inoculation. Clinical presentation was arthritis (n = 8), osteitis (n = 5), and thoracic wall infection (n = 2). The most common clinical manifestation was pain (n = 9), followed by localized swelling (n = 7), cutaneous fistulization (n = 7), and fever (n = 5). The species involved were Scedosporium apiospermum (n = 8), S. boydii (n = 3), S. dehoogii (n = 1), and Lomentospora prolificans (n = 3). The species distribution was unremarkable except for S. boydii, which was associated with healthcare-related inoculations. Management was based on medical and surgical treatment for 13 patients. Fourteen patients received antifungal treatment for a median duration of 7 months. No patients died during follow-up. LOS exclusively occurred in the context of inoculation or systemic predisposing factors. It has a non-specific clinical presentation and is associated with an overall good clinical outcome, provided there is a prolonged course of antifungal therapy and adequate surgical management.
Localized osteoarticular scedosporiosis mostly occurs following direct inoculation. Management was most often based on voriconazole therapy and concomitant surgery. Unlike other invasive scedosporiosis, no patient died during follow-up.
Assuntos
Infecções Fúngicas Invasivas , Scedosporium , Antifúngicos/uso terapêutico , Infecções Fúngicas Invasivas/tratamento farmacológico , Infecções Fúngicas Invasivas/veterinária , HumanosRESUMO
The moulds of the genus Aspergillus section Nidulantes series Versicolores are ubiquitous and particularly recurrent in indoor air. They are considered present in 70% of the bioaerosols to which we are exposed most of our time spent indoors. With the taxonomic revision proposed in 2012 and the discovery of four new species, the series Versicolores currently includes 18 species. These moulds, although considered as cryptic (except Aspergillus sydowii), are opportunistic pathogens that can exhibit increased minimal inhibitory concentrations to conventional antifungal agents. In this review, we discuss the ecology and clinical implications of each species belonging to the series Versicolores. This survey also highlights the lack of consideration for taxonomic revisions in clinical practice and in scientific studies which greatly limits the acquisition of specific knowledge on species belonging to the series Versicolores.
Assuntos
Aspergillus , Fungos , Aspergillus/genética , Fungos/genética , Antifúngicos/farmacologia , Testes de Sensibilidade MicrobianaRESUMO
OBJECTIVES: To determine the epidemiological cut-off values (ECVs) of ten antifungal agents in a wide range of yeasts and Aspergillus spp. using gradient concentration strips. METHODS: The minimum inhibitory concentrations for amphotericin B, anidulafungin, caspofungin, micafungin, flucytosine, fluconazole, itraconazole, isavuconazole, posaconazole, and voriconazole, determined with gradient concentration strips at 35 French microbiology laboratories between 2002 and 2020, were retrospectively collected. Then, the ECVs were calculated using the iterative method and a cut-off value of 97.5%. RESULTS: Minimum inhibitory concentrations were available for 17 653 clinical isolates. In total, 48 ECVs (including 32 new ECVs) were determined: 29 ECVs for frequent yeast species (e.g. Candida albicans and itraconazole/flucytosine, and Candida glabrata species complex [SC] and flucytosine) and rare yeast species (e.g. Candida dubliniensis, Candida inconspicua, Saccharomyces cerevisiae, and Cryptococcus neoformans) and 19 ECVs for Aspergillusflavus SC, Aspergillusfumigatus SC, Aspergillusnidulans SC, Aspergillusniger SC, and Aspergillusterreus SC. CONCLUSIONS: These ECVs can be added to the already available gradient concentration strip-specific ECVs to facilitate minimum inhibitory concentration interpretation and streamline the identification of nonwild type isolates.
Assuntos
Antifúngicos , Itraconazol , Humanos , Antifúngicos/farmacologia , Itraconazol/farmacologia , Flucitosina , Saccharomyces cerevisiae , Estudos Retrospectivos , Filogenia , Fluconazol/farmacologia , Aspergillus , Testes de Sensibilidade Microbiana , Farmacorresistência FúngicaRESUMO
Cases of intestinal microsporidiosis infection are underestimated and affect both immunocompromized and immunocompetent patients. Real-time PCR is superseding microscopic examination for its diagnosis in medical analysis laboratories. However, few manufacturers include microsporidia in their PCR panel for the diagnosis of infectious gastroenteritis. Here, we evaluated the performances of the real-time PCR assays microsporidia generic and microsporidia typing (Bio-Evolution, France) on the Rotor-Gene Q real-time PCR cycler (Qiagen, France). We included 45 negative and 44 positive stool samples for Enterocytozoon bieneusi (n = 34, with various genotypes), Encephalitozoon intestinalis (n = 4), Encephalitozoon hellem (n = 4), and Encephalitozoon cuniculi (n = 2). We also studied a four-year survey of an inter-laboratory quality control program including 9 centers that used this commercial assay. Sensitivity and specificity of the microsporidia generic assay were 86.4% and 93.3%, respectively. Encephalitozoon hellem and Encephalitozoon cuniculi were detected by the microsporidia generic PCR assay but not by the microsporidia typing PCR assay. These results were consistent with the results of the inter-laboratory quality control program. In conclusion, Bio-Evolution Real-time PCR assays are useful tools for intestinal microsporidiosis, but negative results for microsporidia typing assays require supplementary analyses to confirm E. hellem or E. cuniculi infections.
Title: Évaluation des tests de PCR en temps réel Bio-Evolution Microsporidia generic et typing pour le diagnostic de la microsporidiose intestinale. Abstract: Les microsporidioses intestinales sont des infections sous-estimées affectant à la fois les patients immunodéprimés et immunocompétents. Le diagnostic microscopique en laboratoire médical est aujourd'hui supplanté par la PCR en temps réel. Cependant, peu de fabricants incluent les microsporidies dans leurs panels PCR pour le diagnostic des gastro-entérites infectieuses. Ici, nous avons évalué les performances des tests PCR en temps réel microsporidia generic et microsporidia typing (Bio-Evolution, France) sur le thermocycleur PCR en temps réel Rotor-Gene Q (Qiagen, France). Nous avons inclus 45 échantillons de selles négatifs et 44 échantillons positifs pour Enterocytozoon bieneusi (n = 34, avec divers génotypes), Encephalitozoon intestinalis (n = 4), Encephalitozoon hellem (n = 4) et Encephalitozoon cuniculi (n = 2). Nous avons également analysé les résultats sur 4 ans d'un programme de contrôle qualité inter-laboratoires dont 9 centres ont utilisé ces kits commerciaux. La sensibilité et la spécificité du kit microsporidia generic étaient respectivement de 86,4 % et 93,3 %. Encephalitozoon hellem et E. cuniculi ont été détectés par le kit microsporidia generic mais pas par le kit microsporidia typing. Ces résultats étaient cohérents avec ceux du programme de contrôle de qualité inter-laboratoires. En conclusion, les tests de PCR en temps réel Bio-Evolution sont des outils intéressants pour la microsporidiose intestinale, mais un résultat négatif pour le test de typage microsporidia nécessite une analyse supplémentaire pour confirmer les infections à E. hellem ou E. cuniculi.
Assuntos
Enterocytozoon , Microsporídios , Microsporidiose , Humanos , Microsporídios/genética , Reação em Cadeia da Polimerase em Tempo Real , Microsporidiose/diagnóstico , Enterocytozoon/genéticaRESUMO
BACKGROUND: Cases of Toxoplasma reactivation or more severe primary infection have been reported in patients receiving immunosuppressive (IS) treatment for autoimmune diseases (AID). The purpose of this study was to describe features of toxoplasmosis occurring in patients with AID treated by IS therapy, excluded HIV-positive and transplant patients. METHODS: A multicenter descriptive study was conducted using data from the French National Reference Center for Toxoplasmosis (NRCT) that received DNA extracts or strains isolated from patients, associated with clinical data. Other cases were retrieved through a questionnaire sent to all French parasitology and internal medicine departments. Furthermore, a systematic literature review was conducted. RESULTS: 61 cases were collected: 25 retrieved by the NRCT and by a call for observations and 36 from a literature review. Half of the cases were attributed to reactivation (50.9%), and most of cases (49.2%) were cerebral toxoplasmosis. The most common associated AID were rheumatoid arthritis (28%) and most frequent treatments were antimetabolites (44.3%). Corticosteroids were involved in 60.7% of cases. Patients had a favorable outcome (50.8%) but nine did not survive. For 12 cases, a successful Toxoplasma strain characterization suggested the possible role of this parasitic factor in ocular cases. CONCLUSION: Although this remains a rare condition, clinicians should be aware for the management of patients and for the choice of IS treatment.
Assuntos
Doenças Autoimunes , Toxoplasma , Toxoplasmose Cerebral , Corticosteroides , Doenças Autoimunes/complicações , Doenças Autoimunes/tratamento farmacológico , Humanos , Imunossupressores/efeitos adversos , Estudos Multicêntricos como Assunto , Toxoplasma/genéticaRESUMO
Cryptococcosis is the third most common cause of invasive fungal infection in solid organ transplant recipients and cryptococcal meningitis (CM) its main clinical presentation. CM outcomes, as well as its clinical features and radiological characteristics, have not yet been considered on a large scale in the context of kidney transplantation (KT). We performed a nationwide retrospective study of adult patients diagnosed with cryptococcosis after KT between 2002 and 2020 across 30 clinical centers in France. We sought to describe overall and graft survival based on whether KT patients with cryptococcosis developed CM or not. Clinical indicators of CNS involvement and brain radiological characteristics were assessed. Eighty-eight cases of cryptococcosis were diagnosed during the study period, with 61 (69.3%) cases of CM. Mortality was high (32.8%) at 12 months (M12) but not significantly different whether or not patients presented with CM. Baseline hyponatremia and at least one neurological symptom were independently associated with CM (p < 0.001). Positive serum cryptococcal antigen at diagnosis was also significantly associated with CM (p < 0.001). On magnetic resonance imaging (MRI), three patterns of brain injury were identified: parenchymal, meningeal, and vascular lesions. Although CM does not affect graft function directly, it entails a grim prognosis.
RESUMO
The French National Reference Center for Invasive Mycoses and Antifungals leads an active and sustained nationwide surveillance program on probable and proven invasive fungal diseases (IFDs) to determine their epidemiology in France. Between 2012 and 2018, a total of 10,886 IFDs were recorded. The incidence increased slightly over time (2.16 to 2.36/10,000 hospitalization days, P = 0.0562) in relation with an increase of fungemia incidence (1.03 to 1.19/10,000, P = 0.0023), while that of other IFDs remained stable. The proportion of ≥65-year-old patients increased from 38.4% to 45.3% (P < 0.0001). Yeast fungemia (n = 5,444) was due mainly to Candida albicans (55.6%) with stable proportions of species over time. Echinocandins became the main drug prescribed (46.7% to 61.8%), but global mortality rate remained unchanged (36.3% at 1 month). Pneumocystis jirovecii pneumonia (n = 2,106) was diagnosed mostly in HIV-negative patients (80.7%) with a significantly higher mortality than in HIV-positive patients (21.9% versus 5.4% at 1 month, P < 0.0001). Invasive aspergillosis (n = 1,661) and mucormycosis (n = 314) were diagnosed mostly in hematology (>60% of the cases) with a global mortality rate of 42.5% and 59.3%, respectively, at 3 months and significant changes in diagnosis procedure over time. More concurrent infections were also diagnosed over time (from 5.4% to 9.4% for mold IFDs, P = 0.0115). In conclusion, we observed an aging of patients with IFD with a significant increase in incidence only for yeast fungemia, a trend toward more concurrent infections, which raises diagnostic and therapeutic issues. Overall, global survival associated with IFDs has not improved despite updated guidelines and new diagnostic tools. IMPORTANCE The epidemiology of invasive fungal diseases (IFDs) is hard to delineate given the difficulties in ascertaining the diagnosis that is often based on the confrontation of clinical and microbiological criteria. The present report underlines the interest of active surveillance involving mycologists and clinicians to describe the global incidence and that of the main IFDs. Globally, although the incidence of Pneumocystis pneumonia, invasive aspergillosis, and mucormycosis remained stable over the study period (2012 to 2018), that of yeast fungemia increased slightly. We also show here that IFDs seem to affect older people more frequently. The most worrisome observation is the lack of improvement in the global survival rate associated with IFDs despite the increasing use of more sensitive diagnostic tools, the availability of new antifungal drugs very active in clinical trials, and a still low/marginal rate of acquired in vitro resistance in France. Therefore, other tracks of improvement should be investigated actively.
Assuntos
Aspergilose , Fungemia , Infecções Fúngicas Invasivas , Mucormicose , Pneumonia por Pneumocystis , Idoso , Antifúngicos/uso terapêutico , Aspergilose/tratamento farmacológico , Aspergilose/epidemiologia , Fungemia/tratamento farmacológico , Humanos , Infecções Fúngicas Invasivas/epidemiologia , Mucormicose/tratamento farmacológico , Conduta ExpectanteRESUMO
OBJECTIVES: The objective of this study was to evaluate the association between ESCMID adherence and 30-day mortality in candidemia. METHODS: We performed a retrospective cohort study in two French tertiary-care hospitals. All patients with at least one positive blood culture (BC) for Candida spp. between January 2013 and December 2019 were included. An adherent case was defined as a candidemia case for which the treatment fulfilled a bundle of defined criteria based on the latest ESCMID recommendations. We explored factors associated with adherence to ESCMID recommendations in an unadjusted model, and we used a propensity score method to address potential channeling biases with regard to 30-day mortality. RESULTS: During the study period, 165 cases of candidemia were included. Among the ESCMID criteria, funduscopic examination was not performed in 45% and neither was echocardiography in 31%, while the ESCMID criteria were fully implemented in 44 cases (27%). In the propensity score analysis, the all-cause 30-day mortality rate was significantly lower among adherent cases (3.4/36.6, 9%) than among nonadherent cases (42.4/119.5, 36%) (OR = 5.3 95% CI [1.6-17.1]). CONCLUSIONS: In our study, adherence to the bundle of criteria for candidemia management was associated with increased survival, supporting additional efforts to implement these recommendations.
RESUMO
The Aspergilli of the section Nidulantes series Versicolores are among the most recurrent molds in indoor environments. These species cause damage to the quality of air. Indeed, they are responsible for allergies, aggravation of asthma and can even cause infections in immunocompromised patients. Molds belonging to the Versicolores series also produce sterigmatocystin, a mycotoxin classified as potential human carcinogen by the International Agency for Research on Cancer (group 2B). Here, we provide for the first time the genome of three species of the series Versicolores: Aspergillus creber, Aspergillus jensenii and Aspergillus protuberus which are the most abundant species of this series in bioaerosols. The genomes of these three species could be assembled with a percentage of completeness of 97.02%, 96.21% and 95.35% for Aspergillus creber, A. jensenii and A. protuberus respectively. These data will allow to study the genes and gene clusters responsible for the expression of virulence factors, the biosynthesis of mycotoxins and the proliferation of these ubiquitous and recurrent molds.
RESUMO
Molds are ubiquitous biological pollutants in bioaerosols. Among these molds, the genus Aspergillus is found in the majority of indoor air samples, and includes several species with pathogenic and toxigenic properties. Aspergillus species in the series Versicolores remain little known despite recurrence in bioaerosols. In order to investigate their toxicity, we studied 22 isolates of clinical and environmental origin, corresponding to seven different species of the series Versicolores. Spore suspensions and ethyl acetate extracts prepared from fungal isolates were subjected to oxidative potential measurement using the dithiothreitol (DTT) test and cell survival measurement. The DTT tests showed that all species of the series Versicolores had an oxidative potential, either by their spores (especially for Aspergillus jensenii) or by the extracts (especially from Aspergillus amoenus). Measurements of cell survival of A549 and HaCaT cell lines showed that only the spore suspension containing 105 spores/mL of Aspergillus jensenii caused a significant decrease in survival after 72 h of exposure. The same tests performed with mixtures of 105 spores/mL showed a potentiation of the cytotoxic effect, with a significant decrease in cell survival for mixtures containing spores of two species (on A549 cells, p = 0.05 and HaCaT cells, p = 0.001) or three different species (on HaCaT cells, p = 0.05). Cell survival assays after 72 h of exposure to the fungal extracts showed that Aspergillus puulaauensis extract was the most cytotoxic (IC50 < 25 µg/mL), while Aspergillus fructus caused no significant decrease in cell survival.
RESUMO
Air quality can be altered by fungal contaminants suspended in the air, forming bioaerosols. Aspergilli section Nidulantes series Versicolores are recurrent in bioaerosols and are mainly responsible for allergies and asthma aggravation. Phylogenetic studies recently identified 12 new species within this series. This study is the first to identify species of Aspergillus series Versicolores in French bioaerosols and to characterize them macroscopically, microscopically and molecularly. Bioaerosols were collected in a cancer treatment center, in contaminated homes and in agricultural environments. A total of 93 isolates were cultured on selective media, observed by optical microscopy and identified by benA amplification before sequencing. The field data (temperature and relative humidity) were statistically tested to explore the ecology of these species. Eight species were identified from bioaerosols: Aspergillus creber and A. jensenii, which represent more than 80% of the isolates, and A. protuberus, A. puulaauensis, A. sydowii, A. tabacinus, A. amoenus and A. fructus. Aspergilli series Versicolores are distributed differently depending on the sampling site and climatic determinants. Aspergillus protuberus was found in bioaerosols collected under significantly lower relative humidity (p = 3.899 × 10-4). Characterization and repartition of these isolates belonging to the Versicolores series constitute an important step to better assess exposure to fungal bioaerosols.
RESUMO
We report a case of a severe visceral leishmaniasis revealing an HIV-1 infection presenting as an acute primary infection. A young French man living in Paris with history of unprotected sex with a recent male partner and recent travel in Greece was admitted in our Infectious Diseases Department, presenting with acute febrile psychotic disorder, and positive HIV-1 serology with high viral load, very low CD4+ T-cells count and a western blot pattern suggesting an acute infection. The psychotic disorder was finally related to hemophagocytic lymphohistiocytosis diagnosed on bone marrow aspiration, supposedly secondary to HIV acute primary infection. The progressive worsening of pancytopenia despite antiretroviral treatment and the persistence of fever, chills and sweat led to the diagnosis of visceral leishmaniasis through bone marrow biopsy and leishmanial serology. He was treated with intravenous liposomal amphotericin B with quick improvement. We discuss the way HIV infection and visceral leishmaniasis may have interact to lead to the clinical presentation of our patient.
Assuntos
Coinfecção , Infecções por HIV/diagnóstico , Teste de HIV , HIV-1/patogenicidade , Leishmaniose Visceral/diagnóstico , Linfo-Histiocitose Hemofagocítica/diagnóstico , Adulto , Fármacos Anti-HIV/uso terapêutico , Antiprotozoários/uso terapêutico , Exame de Medula Óssea , Contagem de Linfócito CD4 , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Humanos , Leishmaniose Visceral/tratamento farmacológico , Leishmaniose Visceral/parasitologia , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Linfo-Histiocitose Hemofagocítica/parasitologia , Masculino , Valor Preditivo dos Testes , Testes Sorológicos , Índice de Gravidade de Doença , Resultado do Tratamento , Carga ViralRESUMO
In the non-AIDS group, several underlying conditions and immune defects could lead to different PCP presentations. This study compared PCP presentation and outcome according to the underlying disease. A secondary analysis of a previously published prospective observational study including 544 PCP patients was done. Only non-AIDS patients were included. Underlying disease was defined as chronic lymphocytic leukemia (CLL), organ transplantation, solid cancer, allogeneic hematopoietic stem cell transplant (AHSCT), other hematological diseases, and immunosuppressive treatment. Clinical characteristics and outcomes were compared between groups. Multiple correspondent analyses compared clinical characteristics at diagnosis. Day 30 mortality was analyzed. Three hundred and twenty-one patients were included in the study. The underlying diseases were hematological malignancy (n = 75), AHSCT (n = 14), CLL (n = 19), solid organ transplant (n = 94), solid tumor (n = 39), and immunosuppressive treatment (n = 57). Compared with other underlying diseases, PCP related to CLL was closer to PCP related to AIDS presentation (long duration of symptoms before diagnosis, high level of dyspnea, and low oxygen saturation at diagnosis). Day 30 mortality was associated with underlying disease, oxygen flow, and shock at ICU admission. PCP presentations may vary according to the underlying reason for immunosuppression. Response to treatment and adjuvant steroid therapy should be analyzed regarding this result.