Dermatophytoses include a wide variety of diseases involving glabrous skin, nails and hair. These superficial infections are a common cause of consultation in dermatology. In many cases, their ...diagnosis is not clinically obvious, and mycological analysis therefore is required. Direct microscopic examination of the samples using clearing agents provides a quick response to the clinician and is usually combined with cultures on specific media, which must be used to overcome the growth of contaminating moulds that may hamper the recovery of dermatophytes. Accurate identification of the causative agent (i.e. at the species level), currently based on morphological criteria, is necessary not only to initiate an appropriate treatment but also for setting prophylactic measures. However, conventional methods often lack sensitivity and species identification may require up to 4 weeks if subcultures are needed. Histological analysis, which is considered the “gold standard” for the diagnosis of onychomycoses, is seldom performed, and as direct examination, it does not allow precise identification of the pathogen. Nevertheless, a particular attention to the quality of clinical specimens is warranted. Moreover, the sensitivity of direct examination may be greatly enhanced by the use of fluorochromes such as calcofluor white. Likewise, sensitivity of the cultures could be enhanced by the use of culture media containing antifungal deactivators. With the generalization of molecular identification by gene sequencing or MALDI-TOF mass spectrometry, the contribution of historical biochemical or physiological tests to species identification of atypical isolates is now limited. Nevertheless, despite the recent availability of several PCR-based kits and an extensive literature on molecular methods allowing the detection of fungal DNA or both detection and direct identification of the main dermatophyte species, the biological diagnosis of dermatophytosis in 2016 still relies on both direct examination and cultures of appropriate clinical specimens.
Pneumocystis jirovecii (P. jirovecii) is an opportunistic fungus responsible for Pneumocystis pneumonia (PCP) in deeply immunocompromised patients and for pulmonary colonization in individuals with ...mild immunosuppression or impaired respiratory function. PCP and Cytomegalovirus (CMV) co-infections have been widely described whereas those involving other Herpesviruses (HVs) such as Epstein-Barr virus (EBV), Herpes simplex virus type 1 and type 2 (HSV-1 and -2), and Varicella zoster virus (VZV) remain scarce. To date, no data are available concerning HVs co-infections in P. jirovecii colonization.
Our main objective was to evaluate the frequency of HVs in bronchoalveolar lavage fluid (BALF) samples from patients with PCP or with pulmonary colonization. The secondary objective was to assess the relationship between HVs and the mortality rate in PCP patients. A retrospective single-center study over a seven-year period was conducted. All patients with P. jirovecii detected using PCR in a BALF sample and for whom a PCR assay for HVs detection was performed were included in the study.
One hundred and twenty-five patients were included, corresponding to 77 patients with PCP and 48 colonized patients. At least one HV was detected in 54/77 (70.1%) PCP patients and in 28/48 (58.3%) colonized patients. EBV was the most frequent in both groups. Furthermore, the 30-day survival rate in PCP patients was significantly lower with EBV + CMV co-infection than that with EBV co-infection, EBV + HSV-1 co-infection and without HV co-infection.
Our results show that the frequency of HV, alone or in combination is similar in PCP and colonization. They also suggest that EBV + CMV detection in BALF samples from PCP patients is associated with an increased mortality rate, underlying the significance to detect HVs in the course of PCP.
Historically, rabies is the most popular viral brain infection and caused by various Lyssavirus species that are transmitted by dog bites in approximately 99% of human cases 12. ...JC virus (JCV), a ...polyomavirus that commonly establishes asymptomatic infection in the general population, is responsible for progressive multifocal leukoencephalopathy (PML), a fatal demyelinating disease of the CNS, in patients with severe immune deficiency. Fungal infections Unlike bacteria, fungi are eukaryotic (mostly saprophytic) organisms with membrane-bound nuclei that obtain nutrients from organic matter. Aspergillosis and mucormycosis are relatively rare but devastating in immunosuppressed patients, while cerebral phaeohyphomycoses mainly occur in immunocompetent individuals 16. Besides immunological disorders, some environmental, iatrogenic, and host-related factors may predispose an individual to the fungal CNS infection.
Despite considerable efforts, malaria remains one of the most devastating infectious disease worldwide. In the absence of an effective vaccine, the prophylaxis and management of Plasmodium infections ...still rely on the therapeutic use of antimalarial agents. However, the emergence of resistant parasites has jeopardized the efficiency of virtually all antimalarial drugs, including artemisinin combination therapies (ACTs). Thus, there is an urgent need for innovative treatments with novel targets to avoid or overcome drug resistance. In this context, Huang & colleagues prioritized compounds that can block the activity of epigenetic enzymes, and described the discovery of a selective P. falciparum histone deacetylase (HDAC) inhibitor with high activity against various stages of the parasite. These findings may pave the way toward developing new lead compounds with broad‐spectrum activity, thus facilitating malaria treatment and elimination.
Pick & mix: Malaria is one of the most devastating infectious diseases worldwide. There is an urgent need for innovative treatments with novel targets. Huang & colleagues prioritized compounds that can block the activity of epigenetic enzymes, and described the discovery of a selective P. falciparum histone deacetylase (HDAC) inhibitor with high activity against various stages of the parasite. These findings may pave the way toward developing new lead compounds with broad‐spectrum activity, thus facilitating malaria treatment and elimination.
Abstract
Species of Scedosporium and Lomentospora are considered as emerging opportunists, affecting immunosuppressed and otherwise debilitated patients, although classically they are known from ...causing trauma-associated infections in healthy individuals. Clinical manifestations range from local infection to pulmonary colonization and severe invasive disease, in which mortality rates may be over 80%. These unacceptably high rates are due to the clinical status of patients, diagnostic difficulties, and to intrinsic antifungal resistance of these fungi. In consequence, several consortia have been founded to increase research efforts on these orphan fungi. The current review presents recent findings and summarizes the most relevant points, including the Scedosporium/Lomentospora taxonomy, environmental distribution, epidemiology, pathology, virulence factors, immunology, diagnostic methods, and therapeutic strategies.
Schistosomiasis is frequently detected in persons entering Europe. In 2017, we detected a Schistosoma mansoni-Schistosoma haematobium hybrid parasite infection in a migrant boy from Côte d'Ivoire ...entering France. Because such parasites might be established in Europe, as illustrated by an outbreak on Corsica Island, vectors of these parasites should be investigated.
Cystic fibrosis (CF) is a genetic inherited disease due to mutations in the gene cystic fibrosis transmembrane conductance regulator (
CFTR
). Because of the huge diversity of
CFTR
mutations, the CF ...phenotypes are highly heterogeneous, varying from typical to mild form of CF, also called atypical CF. These atypical features are more frequently diagnosed at adolescence or adulthood, and among clinical signs and symptoms leading to suspect a mild form of CF, colonization or infection of the respiratory tract due to well-known CF pathogens should be a warning signal.
Exophiala dermatitidis
is a melanized dimorphic fungus commonly detected in respiratory specimens from CF patients, but only very rarely from respiratory specimens from non-CF patients. We described here two cases of chronic colonization of the airways by
E. dermatitidis
, with recurrent pneumonia and hemoptysis in one patient, which led clinicians to diagnose mild forms of CF in these elderly patients who were 68- and 87-year-old. These cases of late CF diagnosis suggest that airway colonization or respiratory infections due to
E. dermatitidis
in patients with bronchiectasis should led to search for a mild form of CF, regardless of the age and associated symptoms. On a broader level, in patients with chronic respiratory disease and recurrent pulmonary infections, an allergic bronchopulmonary mycosis or an airway colonization by CF-related fungi like
E. dermatitidis
or some
Aspergillus
,
Scedosporium
or
Rasamsonia
species, should be considered as potential markers of atypical CF and should led clinicians to conduct investigations for CF diagnosis.
Commercial multiplex PCR assay panels were developed to overcome the limitations of microscopic examination for parasitological diagnosis on stool samples. However, given the increased supply of this ...diagnostic approach, these assays must be evaluated to position them in a diagnostic algorithm. Analytical performances of the multiplex PCR assay G-DiaParaTrio, Allplex
GI parasite and RIDA
GENE parasitic stool panel for detecting Blastocystis sp., Entamoeba histolytica, Giardia duodenalis, Cryptosporidium spp., Dientamoeba fragilis, and Cyclospora cayetanensis, were assessed through a retrospective comparative study on 184 stool samples initially sent for parasitological investigation. The composite reference method for parasitological diagnosis was microscopic observation and Entamoeba histolytica-specific adhesion detection when necessary. Multiplex PCR assays were performed on extracted DNA from each stool, following the manufacturer's recommendations. Discrepant results with the composite reference method were investigated with species-specific PCR to approach a final parasitological diagnosis. Overall sensitivity/specificity for the multiplex PCR assays was 93.2%/100% for G-DiaParaTrio, 96.5%/98.3% for Allplex
GI parasite and 89.6%/98.3% for RIDA
GENE, whereas the composite reference method presented an overall sensitivity/specificity of 59.6%/99.8%. These results confirmed the added diagnostic value of the multiplex PCR approach for gastrointestinal protists. Nevertheless, the PCR procedure and the analytical performance for each protist of interest, variable depending on the multiplex PCR assay, must be considered when implementing a PCR-based diagnostic approach.
Background:
Serum (1,3)-β-D-glucan (BG) testing is increasingly being used in the diagnostic armamentarium for invasive fungal diseases. Given its high sensitivity, some studies suggest that a ...negative BG result contributes to rule out a diagnosis of
Pneumocystis
pneumonia (PCP). However, recent reports described a suboptimal sensitivity in HIV-negative immunocompromised patients. In this study, we evaluated the performance of BG assay for PCP diagnosis in HIV-negative patients with diverse PCP risk factors. We also assessed the correlation between
Pneumocystis jirovecii
load in pulmonary samples and serum BG levels.
Methods:
We retrospectively included HIV-negative patients with microscopically proven PCP and for whom a BG result was available. We also enrolled patients colonized by
Pneumocystis
as control group. Colonized patients were matched with PCP patients based on their underlying condition that exposed to PCP. Pulmonary fungal loads were determined by an in-house real-time PCR, and BG levels were measured by using the Fungitell® kit (Associates of Cape Cod, Inc.).
Results:
Thirty-nine patients were included in each of the two groups. Thirty-four of 39 PCP patients and one of 39 colonized patient had a positive BG test, resulting in a sensitivity of 0.87 (95% CI: 0.73–0.94), a specificity of 0.97 (95% CI: 0.87–0.99), a positive predictive value of 0.97 (95% CI: 0.85–0.99), and a negative predictive value of 0.88 (95% CI: 0.75–0.95) for BG assay. Nonetheless, median BG level differed according to the underlying condition. Among the PCP group, the lowest median level of 211 pg/ml was observed in patients with hematological malignancy (HM) and differed significantly from that observed either in solid organ transplants (3,473 pg/ml) or in patients with autoimmune or inflammatory disorder (3,480 pg/ml). Indeed, the sensitivity of BG assay was estimated at 0.64 (95% CI: 0.35–0.85) in HM patients and was lower than the one observed in the whole PCP group. Furthermore, BG level and fungal burden correlated poorly among all PCP patients.
Conclusion:
BG is not a reliable biomarker for ruling out PCP in HIV-negative patients with HM. Interpretation of a negative BG result should take into account, but not be limited to, the underlying condition predisposing to PCP.
Scedosporium
species are opportunistic fungi which preferentially affect patients with underlying conditions such as immunosuppression or cystic fibrosis (CF). While being the second most common ...molds capable to chronically colonize the CF lungs, the natural history of infection remains unclear. In filamentous fungi, a broad range of important secondary metabolites that are recognized as virulence factors are produced by multidomain non-ribosomal peptide synthetases (NRPSs). The aim of this study was to provide a global
in silico
analysis of NRPS-encoding genes based on the recently sequenced
Scedosporium apiospermum
genome. We uncovered a total of nine NRPS genes, of which six exhibited sufficient similarity scores with other fungal NRPSs to predict the class of the generated peptide: siderophores (
n
= 2), epidithiodioxopiperazines (
n
= 2), and cyclopeptides (
n
= 2). Phylogenetic trees based on the multiple alignments of adenylation (A) domain sequences corroborated these findings. Nevertheless, substrate prediction methods for NRPS A-domains tended to fail, thus questioning about the exact nature of the peptide produced. Further studies should be undertaken since NRPSs, which are not synthesized by human cells, could represent attractive therapeutic targets.
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