A Repertoire of the Less Common Clinical Yeasts.

Invasive fungal diseases are a public health problem. They affect a constantly increasing number of at-risk patients, and their incidence has risen in recent years. These opportunistic infections are mainly due to Candida sp. but less common or rare yeast infections should not be underestimated. These so-called "less common" yeasts include Ascomycota of the genera Candida (excluding the five major Candida species), Magnusiomyces/Saprochaete, Malassezia, and Saccharomyces, and Basidiomycota of the genera Cryptococcus (excluding the Cryptococcus neoformans/gattii complex members), Rhodotorula, and Trichosporon. The aim of this review is to (i) inventory the less common yeasts isolated in humans, (ii) provide details regarding the specific anatomical locations where they have been detected and the clinical characteristics of the resulting infections, and (iii) provide an update on yeast taxonomy. Of the total of 239,890 fungal taxa and their associated synonyms sourced from the MycoBank and NCBI Taxonomy databases, we successfully identified 192 yeasts, including 127 Ascomycota and 65 Basidiomycota. This repertoire allows us to highlight rare yeasts and their tropism for certain anatomical sites and will provide an additional tool for diagnostic management.

A Repertoire of Clinical Non-Dermatophytes Moulds.

Humans are constantly exposed to micromycetes, especially filamentous fungi that are ubiquitous in the environment. In the presence of risk factors, mostly related to an alteration of immunity, the non-dermatophyte fungi can then become opportunistic pathogens, causing superficial, deep or disseminated infections. With new molecular tools applied to medical mycology and revisions in taxonomy, the number of fungi described in humans is rising. Some rare species are emerging, and others more frequent are increasing. The aim of this review is to (i) inventory the filamentous fungi found in humans and (ii) provide details on the anatomical sites where they have been identified and the semiology of infections. Among the 239,890 fungi taxa and corresponding synonyms, if any, retrieved from the Mycobank and NCBI Taxonomy databases, we were able to identify 565 moulds in humans. These filamentous fungi were identified in one or more anatomical sites. From a clinical point of view, this review allows us to realize that some uncommon fungi isolated in non-sterile sites may be involved in invasive infections. It may present a first step in the understanding of the pathogenicity of filamentous fungi and the interpretation of the results obtained with the new molecular diagnostic tools.

Fungal exposome, human health, and unmet needs: A 2022 update with special focus on allergy.

Humans inhale, ingest, and touch thousands of fungi each day. The ubiquity and diversity of the fungal kingdom, reflected by its complex taxonomy, are in sharp contrast with our scarce knowledge about its distribution, pathogenic effects, and effective interventions at the environmental and individual levels. Here, we present an overview of salient features of fungi as permanent players of the human exposome and key determinants of human health, through the lens of fungal allergy and other fungal hypersensitivity reactions. Improved understanding of the fungal exposome sheds new light on the epidemiology of fungal-related hypersensitivity diseases, their immunological substratum, the currently available methods, and biomarkers for environmental and medical fungi. Unmet needs are described and potential approaches are highlighted as perspectives.

Pericardial Effusion Due to Trichosporon japonicum: A Case Report and Review of the Literature.

Invasive infections due to Trichosporon spp. are life-threatening opportunistic fungal infections that may affect a wide array of organs. Here, we described a case of pericardial effusion due to Trichosporon japonicum in a 42-year-old female after a heart transplantation. T. japonicum was isolated from the pericardial fluid, pericardial drain hole and the swab of the sternal surgery scar wound. The late mycological diagnosis due to blood culture negative, the ineffective control of pulmonary bacterial infection and the late start antifungal therapy were the contributing factors in the patient's death.

A summary of cryptosporidiosis outbreaks reported in France and overseas departments, 2017-2020.

Cryptosporidium is a known foodborne pathogen, ranked fifth out of 24 among foodborne parasites in terms of importance and a cause of many cryptosporidiosis outbreaks worldwide. In France, very few outbreaks were reported before 2017, and data recently obtained by the Expert Laboratory of the Cryptosporidiosis National Reference Center (CNR-LE-Cryptosporidiosis) have shown that outbreaks are in fact common and frequently underreported. In this work, we aim to report the characteristics of outbreaks detected in France during the period 2017-2020 and present a summary of investigations carried out by the CNR-LE-Cryptosporidiosis. During the study period, there were eleven cryptosporidiosis outbreaks, including three with no identified origin. Among the eight identified outbreaks: six were due to water contamination (five tap water and one recreational water), one was due to direct contact with infected calves, and one was due to consumption of contaminated curd cheese. Among these outbreaks, five of them exceeded one hundred cases. Recent results obtained by the CNR-LE-Cryptosporidiosis revealed the multiannual occurrence of Cryptosporidium outbreaks in France. Waterborne outbreaks were more frequently detected, while foodborne outbreaks which are more difficult to detect were likely underreported.

Cryptosporidiosis outbreak in Amazonia, French Guiana, 2018.

BACKGROUND: Cryptosporidiosis outbreaks in South America are poorly documented. In March 2018, 51 cases of cryptosporidiosis were reported in Maripasoula, a village located in a remote forest area along the border between Surinam and French Guiana. METHOD: To identify the origin of the epidemic, we performed epidemiological, microbiological, and environmental investigations. Only the cases involving diarrhoea and Cryptosporidium-positive stool were considered as bona fide, while cases involving diarrhoea and close contact with a confirmed case were classified as "possible". RESULTS: We identified 16 confirmed cases and 35 possible ones. Confirmed cases comprised nine children (median age of 18 months, range: 6-21), one immunocompromised adult and six soldiers. One child required a hospitalisation for rehydration. All 16 Cryptosporidium stools were PCR positive, and sequencing of the gp60 gene confirmed only one Cryptosporidium hominis subtype IbA10G2. Tap water consumption was the only common risk factor identified. Contamination of the water network with Cryptosporidium parvum subtype IIdA19G2 was found. CONCLUSION: Water quality is a major public health issue in Amazonian French Guiana, especially for population at risk (children, people with comorbidity, travelers). For them, alternative water supply or treatment should be implemented.

Measurement of the IgG Avidity Index in the Diagnosis of Clinical Toxocariasis Patients.

Toxocara spp. are parasitic nematodes responsible for human toxocariasis, a common zoonotic helminth infection. The five main features of human toxocariasis are the classical ocular toxocariasis and visceral larva migrans syndrome, followed by covert toxocariasis, common toxocariasis and neurotoxocariasis. The diagnosis of toxocariasis is feasible by considering clinical symptoms, anamnestic history and serology laboratory results; however, serological criteria cannot be used to distinguish active Toxocara infection from past exposure, which is an area of much discussion in clinical practice. In this context, we developed avidity tests (ELISA and immunoblotting) and evaluated their clinical usefulness in distinguishing past from active toxocariasis. Our study involved 46 patients divided into two groups: "active toxocariasis" (n = 14) and "chronic toxocariasis" (n = 32). According to the avidity indices obtained for both the chronic and active toxocariasis groups, we proposed two thresholds: first, an AI lower than 32% supports an active infection; secondly, a threshold above 42% can exclude an active infection. In order to use this assay in routine clinical practice, however, is still requires standardisation with regards to the method and threshold values, which can be established through studies involving larger populations.

Detection of Pneumocystis jirovecii in Hospitalized Children Less Than 3 Years of Age.

Few data are available in the literature regarding Pneumocystis jirovecii infection in children under 3 years old. This retrospective cohort study aimed to describe medically relevant information among them. All children under 3 years old treated in the same medical units from April 2014 to August 2020 and in whom a P. jirovecii evaluation was undertaken were enrolled in the study. A positive case was defined as a child presenting at least one positive PCR for P. jirovecii in a respiratory sample. Medically relevant information such as demographical characteristics, clinical presentation, microbiological co-infections, and treatments were collected. The objectives were to describe the characteristics of these children with P. jirovecii colonization/infection to determine the key underlying diseases and risk factors, and to identify viral respiratory pathogens associated. The PCR was positive for P. jirovecii in 32 children. Cardiopulmonary pathologies (21.9%) were the most common underlying disease in them, followed by severe combined immunodeficiency (SCID) (18.8%), hyaline membrane disease (15.6%), asthma (9.4%) and acute leukaemia (6.3%). All SCID children were diagnosed with pneumocystis pneumonia. Co-infection with Pj/Rhinovirus (34.4%) was not significant. Overall mortality was 18.8%. Paediatric pneumocystis is not restricted to patients with HIV or SCID and should be considered in pneumonia in children under 3 years old.

Immunoblot for the Diagnosis of Cutaneous Leishmaniasis in French Guiana.

Cutaneous leishmaniasis (CL) is firmly established in South America. We aimed to assess the detection of IgG antibodies against 14 and/or 16 kDa antigens by immunoblot (IB) for CL serological diagnosis in French Guiana, an area where many endemic pathogens could interfere with it. This study was performed retrospectively on sera from 141 patients at the Cayenne tertiary hospital: 30 were patients with confirmed CL, 71 were diagnosed with various other endemic pathogens, 11 were diagnosed with an autoimmune disease, and 29 controls had no history of CL. Antibodies bound to the 14 and/or 16 kDa antigens in 27 of the 30 CL patients' sera and in 39 of the 111 non-CL patients' sera (26 from the infectious diseases group, four from the autoimmune diseases group, and nine from the dermatology department). The method tested showed a high sensitivity (90%) and a low specificity (66%), and a diagnosis odds ratio of 17.5 (95% CI [4.6-78.0]). This IB may be helpful to exclude the diagnosis of CL, prompting physicians to look for another diagnosis in the case of a negative IB.

Evaluation of 11 DNA Automated Extraction Protocols for the Detection of the 5 Mains Candida Species from Artificially Spiked Blood.

The molecular detection of Candida plays an important role in the diagnosis of candidaemia, a major cause of morbidity and mortality. The sensitivity of this diagnosis is partly related to the efficiency of yeast DNA extraction. In this monocentric study, we investigated the suitability of 11 recent automated procedures for the extraction of low and high amounts of Candida DNA from spiked blood. The efficacy of the DNA extraction procedures to detect Candida spp. in blood samples ranged from 31.4% to 80.6%. The NucliSENSTM easyMAGTM procedure was the most efficient, for each species and each inoculum. It significantly outperformed the other procedures at the lower Candida inocula mimicking the clinical setting. This study highlighted a heterogeneity in DNA extraction efficacy between the five main Candida species (Candida albicans, Candida glabrata, Candida parapsilosis, Candida tropicalis and Candida krusei). Up to five automated procedures were appropriate for C. krusei DNA extraction, whereas only one method yielded an appropriate detection of low amount of C. tropicalis. In the era of the syndromic approach to bloodstream infection diagnosis, this evaluation of 11 automated DNA extraction methods for the PCR diagnosis of candidaemia, puts the choice of an appropriate method in routine diagnosis within the reach of laboratories.

Occurrence of Ten Protozoan Enteric Pathogens in Three Non-Human Primate Populations.

Non-human primate populations act as potential reservoirs for human pathogens, including viruses, bacteria and parasites, which can lead to zoonotic infections. Furthermore, intestinal microorganisms may be pathogenic organisms to both non-human primates and humans. It is, therefore, essential to study the prevalence of these infectious agents in captive and wild non-human primates. This study aimed at showing the prevalence of the most frequently encountered human enteric protozoa in non-human primate populations based on qPCR detection. The three populations studied were common chimpanzees (Pan troglodytes) in Senegal and gorillas (Gorilla gorilla) in the Republic of the Congo and in the Beauval Zoo (France). Blastocystis spp. were mainly found, with an occurrence close to 100%, followed by Balantidiumcoli (23.7%), Giardiaintestinalis (7.9%), Encephalitozoonintestinalis (1.3%) and Dientamoebafragilis (0.2%). None of the following protozoa were detected: Entamoebahistolytica, Enterocytozoonbieneusi, Cryptosporidiumparvum, C. hominis, Cyclosporacayetanensis or Cystoisosporabelli. As chimpanzees and gorillas are genetically close to humans, it is important to monitor them frequently against different pathogens to protect these endangered species and to assess potential zoonotic transmissions to humans.

Eukaryotic and Prokaryotic Microbiota Interactions.

The nature of the relationship between the communities of microorganisms making up the microbiota in and on a host body has been increasingly explored in recent years. Microorganisms, including bacteria, archaea, viruses, parasites and fungi, have often long co-evolved with their hosts. In human, the structure and diversity of microbiota vary according to the host's immunity, diet, environment, age, physiological and metabolic status, medical practices (e.g., antibiotic treatment), climate, season and host genetics. The recent advent of next generation sequencing (NGS) technologies enhanced observational capacities and allowed for a better understanding of the relationship between distinct microorganisms within microbiota. The interaction between the host and their microbiota has become a field of research into microorganisms with therapeutic and preventive interest for public health applications. This review aims at assessing the current knowledge on interactions between prokaryotic and eukaryotic communities. After a brief description of the metagenomic methods used in the studies were analysed, we summarise the findings of available publications describing the interaction between the bacterial communities and protozoa, helminths and fungi, either in vitro, in experimental models, or in humans. Overall, we observed the existence of a beneficial effect in situations where some microorganisms can improve the health status of the host, while the presence of other microorganisms has been associated with pathologies, resulting in an adverse effect on human health.

Saprochaete clavata Outbreak Infecting Cancer Center through Dishwasher.

Saprochaete clavata is a pathogenic yeast responsible for rare outbreaks involving immunocompromised patients, especially those with hematologic malignancies. During February 2016-December 2017, we diagnosed S. clavata infections in 9 patients (8 with fungemia), including 3 within 1 month, at a cancer center in Marseille, France. The patients (median age 58 years), 4 of 9 of whom had acute myeloid leukemia, were hospitalized in 3 different wards. Ten environmental samples, including from 2 dishwashers and 4 pitchers, grew S. clavata, but no contaminated food was discovered. The outbreak ended after contaminated utensils and appliances were discarded. Whole-genome sequencing analysis demonstrated that all clinical and environmental isolates belonged to the same phylogenetic clade, which was unrelated to clades from previous S. clavata outbreaks in France. We identified a dishwasher with a deficient heating system as the vector of contamination.

Autochthonous liver cystic hydatid: Past or actual French shepherd's disease?

Autochthonous hydatidosis in France and western Europa are uncommon since the beginning of the 21st century. We report here an authentic indigenous cystic echinococcosis case in a French shepherd. The risk of remerging pathology should not be neglected and measures to interrupt parasite transmission are still relevant.

Evaluation of two DNA extraction methods for the PCR-based detection of eukaryotic enteric pathogens in fecal samples.

OBJECTIVE: Efficient and easy-to-use DNA extraction and purification methods are critical in implementing PCR-based diagnosis of pathogens. In order to optimize the routine clinical laboratory diagnosis of eukaryotic enteric pathogens, we compare, via quantitative PCR cycle threshold (Ct) values, the efficiency of two DNA extraction kits: the semi-automated EZ1® (Qiagen) and the manual QIAamp® DNA Stool Mini Kit (Qiagen), on six protozoa: Blastocystis spp., Cryptosporidium parvum/hominis, Cyclospora cayetanensis, Dientamoeba fragilis, Giardia intestinalis and Cystoisospora belli and one microsporidia: Enterocytozoon bieneusi. RESULTS: Whereas EZ1® (Qiagen) and QIAamp® DNA Stool Mini Kit (Qiagen) yielded similar performances for the detection of Cryptosporidium spp. and D. fragilis, significant lower Ct values (p < 0.002) pointed out a better performance of EZ1® on the five remaining pathogens. DNA extraction using the semi-automated EZ1® procedure was faster and as efficient as the manual procedure in the seven eukaryotic enteric pathogens tested. This procedure is suitable for DNA extraction from stools in both clinical laboratory diagnosis and epidemiological study settings.

First case of B ALL with KMT2A-MAML2 rearrangement: a case report.

BACKGROUND: A large number of chromosomal translocations of the human KMT2A gene, better known as the MLL gene, have so far been characterized. Genetic rearrangements involving KMT2A gene are frequently involved in lymphoid, myeloid and mixed lineage leukemia. One of its rare fusion partners, the mastermind like 2 (MAML2) gene has been reported in four cases of myeloid neoplasms after chemotherapy so far: two acute myeloid leukemias (AML) and two myelodysplasic syndrome (MDS), and two cases of secondary T-cell acute lymphoblastic leukemia (T-ALL). CASE PRESENTATION: Here we report the case of a KMT2A - MAML2 fusion discovered by Next-Generation Sequencing (NGS) analysis in front of an inv11 (q21q23) present in a 47-year-old female previously treated for a sarcoma in 2014, who had a B acute lymphoid leukemia (B ALL). CONCLUSION: It is, to our knowledge, the first case of B acute lymphoblastic leukemia with this fusion gene. At the molecular level, two rearrangements were detected using RNA sequencing juxtaposing exon 7 to exon 2 and exon 9 to intron 1-2 of the KMT2A and MAML2 genes respectively, and one rearrangement using Sanger sequencing juxtaposing exon 8 and exon 2.

Evaluation of empirical treatment for blood culture-negative endocarditis.

OBJECTIVES: Much progress has been made in understanding the main causes of blood culture-negative endocarditis (BCNE). Few studies concerning BCNE treatment (due to previous antibiotics used or fastidious pathogens) are available. We performed this study to evaluate the effectiveness of our therapeutic protocol in BCNE, based on compliance with the protocol, outcome and 1 year mortality. PATIENTS AND METHODS: We collected prospectively and analysed retrospectively cases of BCNE between 2002 and 2014, using a simplified and standardized protocol developed by our multidisciplinary team. We apply two kinds of protocols to treat BCNE, which include only four intravenous antimicrobial agents: amoxicillin, vancomycin, gentamicin and amphotericin B. RESULTS: We had 177 patients with definite BCNE. There were 154 (87.0%) patients treated with both appropriate antimicrobial agents and appropriate duration of treatment. We analysed the causes of inappropriate treatment in 13 (7.3%) cases and inappropriate duration in 10 (5.6%) cases. The treatment changes were justified in all cases except one of discharge against medical advice. The fatality rate was 5.1% (nine cases) and all deaths occurred in the group of patients who were treated with appropriate treatment; however, four deaths were not attributable to empirical treatment failure. Concerning the other deaths, the lack of surgical management, in association with empirical treatment, could explain our protocol's failure, such as poorly tolerated surgery. CONCLUSIONS: Our protocol is efficient and our mortality rate was low, compared with the literature review. This may result from a strategy that uses a sampling procedure and a standardized protocol at the same time.