Tickborne Relapsing Fever Caused by Borrelia persica, Uzbekistan and Tajikistan

International audienc

First Isolation and Direct Evidence for the Existence of Large Small-Mammal Reservoirs of Leptospira sp. in Madagascar

Background: Leptospirosis has long been a major public health concern in the southwestern Indian Ocean. However, in Madagascar, only a few, old studies have provided indirect serological evidence of the disease in humans or animals. Methodology/Principal Findings: We conducted a large animal study focusing on small-mammal populations. Five field trapping surveys were carried out at five sites, from April 2008 to August 2009. Captures consisted of Rattus norvegicus (35.8%), R. rattus (35.1%), Mus musculus (20.5%) and Suncus murinus (8.6%). We used microbiological culture, serodiagnosis tests (MAT) and real-time PCR to assess Leptospira infection. Leptospira carriage was detected by PCR in 91 (33.9%) of the 268 small mammals, by MAT in 17 of the 151 (11.3%) animals for which serum samples were available and by culture in 9 of the 268 animals (3.3%). Rates of infection based on positive PCR results were significantly higher in Moramanga (54%), Toliara (48%) and Mahajanga (47.4%) than in Antsiranana (8.5%) and Toamasina (14%) (p = 0.001). The prevalence of Leptospira carriage was significantly higher in R. norvegicus (48.9%), S. murinus (43.5%) and R. rattus (30.8%) than in M. musculus (9.1%) (p < 0.001). The MAT detected antibodies against the serogroups Canicola and Icterohaemorrhagiae. Isolates were characterized by serology, secY sequence-based phylogeny, partial sequencing of rrs, multi-locus VNTR analysis and pulsed field gel electrophoresis. The 10 isolates obtained from nine rats were all identified as species L. interrogans serogroup Canicola serovar Kuwait and all had identical partial rrs and secY sequences. Conclusions/Significance: We present here the first direct evidence of widespread leptospiral carriage in small mammals in Madagascar. Our results strongly suggest a high level of environmental contamination, consistent with probable transmission of the infection to humans. This first isolation of pathogenic Leptospira strains in this country may significantly improve the detection of specific antibodies in human cases

Clinical Impact of Antifungal Susceptibility, Biofilm Formation and Mannoside Expression of Candida Yeasts on the Outcome of Invasive Candidiasis in ICU: An Ancillary Study on the Prospective AmarCAND2 Cohort

Background: The link between Candida phenotypical characteristics and invasive candidiasis (IC) prognosis is still partially unknown.Methods:Candida strains isolated during the AmarCAND2 study were centrally analyzed for species identification, antifungal susceptibility, biofilm formation, and expression of surface and glycoconjugate mannosides. Correlation between these phenotypical features and patient outcome was sought using a multivariable Cox survival model.Results:Candida albicans was predominant (65.4%, n = 285), with a mortality rate significantly lower than that in patients with non-albicans strains [HR 0.67 (0.46–1.00), p = 0.048]. The rate of fluconazole-resistant strains was low (C. albicans and Candida glabrata: 3.5 and 6.2%, respectively) as well as caspofungin-resistant ones (1 and 3.1%, respectively). Early biofilm formation was less frequent among C. albicans (45.4%) than among non-albicans (81.2%). While the strains of C. albicans showed variable levels of surface mannosides expression, strains isolated from candidemia exhibited a high expression of β-man, which was correlated with an increased mortality (p = 0.02).Conclusion:Candida albicans IC were associated with lower mortality, and with strains that exhibited less frequently early biofilm formation than non-albicans strains. A high expression of β-man was associated with increased IC mortality. Further studies are warranted to confirm this data and to evaluate other virulence factors in yeasts

The diagnosis of fungal neglected tropical diseases (fungal NTDs) and the role of investigation and laboratory tests: An expert consensus report

The diagnosis of fungal Neglected Tropical Diseases (NTD) is primarily based on initial visual recognition of a suspected case followed by confirmatory laboratory testing, which is often limited to specialized facilities. Although molecular and serodiagnostic tools have advanced, a substantial gap remains between the desirable and the practical in endemic settings. To explore this issue further, we conducted a survey of subject matter experts on the optimal diagnostic methods sufficient to initiate treatment in well-equipped versus basic healthcare settings, as well as optimal sampling methods, for three fungal NTDs: mycetoma, chromoblastomycosis, and sporotrichosis. A survey of 23 centres found consensus on the key role of semi-invasive sampling methods such as biopsy diagnosis as compared with swabs or impression smears, and on the importance of histopathology, direct microscopy, and culture for mycetoma and chromoblastomycosis confirmation in well-equipped laboratories. In basic healthcare settings, direct microscopy combined with clinical signs were reported to be the most useful diagnostic indicators to prompt referral for treatment. The survey identified that the diagnosis of sporotrichosis is the most problematic with poor sensitivity across the most widely available laboratory tests except fungal culture, highlighting the need to improve mycological diagnostic capacity and to develop innovative diagnostic solutions. Fungal microscopy and culture are now recognized as WHO essential diagnostic tests and better training in their application will help improve the situation. For mycetoma and sporotrichosis, in particular, advances in identifying specific marker antigens or genomic sequences may pave the way for new laboratory-based or point-of-care tests, although this is a formidable task given the large number of different organisms that can cause fungal NTDs. © 2019 by the authors

The diagnosis of fungal neglected tropical diseases (fungal NTDs) and the role of investigation and laboratory tests: An expert consensus report

The diagnosis of fungal Neglected Tropical Diseases (NTD) is primarily based on initial visual recognition of a suspected case followed by confirmatory laboratory testing, which is often limited to specialized facilities. Although molecular and serodiagnostic tools have advanced, a substantial gap remains between the desirable and the practical in endemic settings. To explore this issue further, we conducted a survey of subject matter experts on the optimal diagnostic methods sufficient to initiate treatment in well-equipped versus basic healthcare settings, as well as optimal sampling methods, for three fungal NTDs: mycetoma, chromoblastomycosis, and sporotrichosis. A survey of 23 centres found consensus on the key role of semi-invasive sampling methods such as biopsy diagnosis as compared with swabs or impression smears, and on the importance of histopathology, direct microscopy, and culture for mycetoma and chromoblastomycosis confirmation in well-equipped laboratories. In basic healthcare settings, direct microscopy combined with clinical signs were reported to be the most useful diagnostic indicators to prompt referral for treatment. The survey identified that the diagnosis of sporotrichosis is the most problematic with poor sensitivity across the most widely available laboratory tests except fungal culture, highlighting the need to improve mycological diagnostic capacity and to develop innovative diagnostic solutions. Fungal microscopy and culture are now recognized as WHO essential diagnostic tests and better training in their application will help improve the situation. For mycetoma and sporotrichosis, in particular, advances in identifying specific marker antigens or genomic sequences may pave the way for new laboratory-based or point-of-care tests, although this is a formidable task given the large number of different organisms that can cause fungal NTDs

Rôle des gènes RIM et VPS dans la signalisation du pH, la virulence et la résistance aux fongiques chez la levure Candida albicans

Diplôme : Dr. d'UniversiteCandida albicans est le premier pathogène fongique de l'homme. Cette levure, habituellement commensale, peut être à l'origine d'infections profondes mettant en jeu le pronostic vital. L'incidence des candidoses profondes ne cesse d'augmenter parallèlement à l'augmentation du nombre de patients à risque. La virulence de C. albicans s'explique par sa capacité à coloniser puis envahir de nombreux tissus de l'organisme qui constituent autant de microenvironnements différents. Les réponses adaptatives de la cellule aux modifications environnementales sont déterminantes pour sa survie et conditionnent sa virulence. La voie d'endocytose assure la dégradation ou le recyclage des protéines membranaires et joue un rôle important dans la régulation des récepteurs. Elle est également impliquée dans l'activation de la voie de signalisation du pH : la voie Rim. Au début de ce travail, nous avons montré que la voie d'endocytose jouait un rôle majeur dans la réponse au pH, la morphogenèse et la virulence de C. albicans, de façon à la fois dépendante et indépendante de la voie Rim. Nous avons montré que les délétions de deux gènes de la voie d'endocytose, VPS28 et VPS32, produisent non seulement les mêmes effets que les délétions des gènes de la voie Rim, mais les aggravent. Nous avons également mis en évidence le rôle de la voie Rim et des protéines Vps dans la structure de la paroi et la résistance aux antifongiques azolés et aux échinocandines. Là encore, la voie d'endocytose semble impliquée par son action spécifique dans la voie Rim mais aussi par d'autres mécanismes indépendants de la voie Rim. Enfin, nous avons caractérisé les mutants rim9 et rim21 et montré que les protéines Rim9p et Rim21p sont toutes les deux indispensables à l'activation de la voie Rim chez C. albicans. Ce résultat confirme que le mode d'activation de la voie Rim chez C. albicans est proche de celui décrit chez S. cerevisiae et diffère sensiblement de celui d'Aspergillus nidulans ou de Yarrowia lipolytica. Nous avons montré que l'inhibition de la voie d'endocytose induit chez C. albicans une réduction majeure de la virulence associée à une augmentation de la sensibilité aux antifongiques azolés et aux échinocandines. En permettant la potentialisation de l'efficacité des molécules existantes cette voie pourrait constituer une cible intéressante pour le développement de nouveaux traitements antifongiques

Rôle des gènes RIM et VPS dans la signalisation du pH, la virulence et la résistance aux fongiques chez la levure Candida albicans

Diplôme : Dr. d'UniversiteCandida albicans est le premier pathogène fongique de l'homme. Cette levure, habituellement commensale, peut être à l'origine d'infections profondes mettant en jeu le pronostic vital. L'incidence des candidoses profondes ne cesse d'augmenter parallèlement à l'augmentation du nombre de patients à risque. La virulence de C. albicans s'explique par sa capacité à coloniser puis envahir de nombreux tissus de l'organisme qui constituent autant de microenvironnements différents. Les réponses adaptatives de la cellule aux modifications environnementales sont déterminantes pour sa survie et conditionnent sa virulence. La voie d'endocytose assure la dégradation ou le recyclage des protéines membranaires et joue un rôle important dans la régulation des récepteurs. Elle est également impliquée dans l'activation de la voie de signalisation du pH : la voie Rim. Au début de ce travail, nous avons montré que la voie d'endocytose jouait un rôle majeur dans la réponse au pH, la morphogenèse et la virulence de C. albicans, de façon à la fois dépendante et indépendante de la voie Rim. Nous avons montré que les délétions de deux gènes de la voie d'endocytose, VPS28 et VPS32, produisent non seulement les mêmes effets que les délétions des gènes de la voie Rim, mais les aggravent. Nous avons également mis en évidence le rôle de la voie Rim et des protéines Vps dans la structure de la paroi et la résistance aux antifongiques azolés et aux échinocandines. Là encore, la voie d'endocytose semble impliquée par son action spécifique dans la voie Rim mais aussi par d'autres mécanismes indépendants de la voie Rim. Enfin, nous avons caractérisé les mutants rim9 et rim21 et montré que les protéines Rim9p et Rim21p sont toutes les deux indispensables à l'activation de la voie Rim chez C. albicans. Ce résultat confirme que le mode d'activation de la voie Rim chez C. albicans est proche de celui décrit chez S. cerevisiae et diffère sensiblement de celui d'Aspergillus nidulans ou de Yarrowia lipolytica. Nous avons montré que l'inhibition de la voie d'endocytose induit chez C. albicans une réduction majeure de la virulence associée à une augmentation de la sensibilité aux antifongiques azolés et aux échinocandines. En permettant la potentialisation de l'efficacité des molécules existantes cette voie pourrait constituer une cible intéressante pour le développement de nouveaux traitements antifongiques

pH Signalling in Human Fungal Pathogens: a New Target for Antifungal Strategies.

International audience: Fungi are exposed to broadly fluctuating environmental conditions, to which adaptation is crucial for their survival. An ability to respond to a wide pH range, in particular, allows them to cope with rapid changes in their extracellular settings. PacC/Rim signalling elicits the primary pH response in both model and pathogenic fungi and has been studied in multiple fungal species. In the predominant human pathogenic fungi, namely Candida albicans, Aspergillus fumigatus and Cryptococcus neoformans, this pathway is required for many functions associated with pathogenesis and virulence. Aspects of this pathway are fungus-specific and do not exist in mammalian cells. In this review, we highlight recent advances in our understanding of PacC/Rim-mediated functions and discuss the growing interest in this cascade and its factors as potential drug targets for antifungal strategies. We focus on both conserved and distinctive features in model and pathogenic fungi, highlighting the specificities of PacC/Rim signalling in C. albicans, A. fumigatus and C. neoformans. We consider the role of this pathway in fungal virulence, including modulation of the host immune response. Finally, as now recognized for other signalling cascades, we highlight the role of pH in adaptation to antifungal drug pressure. By acting on the PacC/Rim pathway, it may therefore be possible (i) to ensure fungal specificity and to limit the side effects of drugs, (ii) to ensure broad-spectrum efficacy, (iii) to attenuate fungal virulence, (iv) to obtain additive or synergistic effects with existing antifungal drugs through tolerance inhibition and (v) to slow the emergence of resistant mutants