Azole resistance in Aspergillus flavus and associated fitness cost.

BACKGROUND: The resistance of Aspergillus flavus to the azole antifungal drugs is an emerging problem. Mutations in the molecular targets of the azole antifungals - CYP 51 A, B and C - are possible mechanisms of resistance, but data to confirm this hypothesis are scarce. In addition, the behaviour of resistant strains in vitro and in vivo is not yet understood. OBJECTIVES: This study had 3 objectives. The first was to compare the sequences of CYP51 A, B and C in resistant and susceptible strains of A. flavus. The second was to look for the existence of a fitness cost associated with resistance. The third was to evaluate the activity of voriconazole and posaconazole on resistant strains in the Galleria mellonella model. METHODS: The CYP51 A, B and C sequences of seven resistant strains with those of four susceptible strains are compared. Fitness costs were assessed by growing the strains in RPMI medium and testing their virulence in G. mellonella larvae. In addition, G. mellonella larvae infected with strains of A. flavus were treated with voriconazole and posaconazole. RESULTS: In the CYP51A sequences, we found the A91T, C708T and A1296T nucleotide substitutions only in the resistant strains. The resistant strains showed a fitness cost with reduced in vitro growth and reduced virulence in G. mellonella. In vivo resistance to posaconazole is confirmed in a strain with the highest MIC for this antifungal agent. CONCLUSIONS: These results allow to conclude that some substitutions in CYP51 genes, in particular CYP51A, contribute to resistance to azole drugs in A. flavus. The study of the relationship between drug dosage and treatment duration with resistance and the reduction of fitness costs in resistant strains is a major perspective of this study. This work could help to establish recommendations for the treatment of infections with resistant strains of A. flavus.

A conceptual framework for nomenclatural stability and validity of medically important fungi: a proposed global consensus guideline for fungal name changes supported by ABP, ASM, CLSI, ECMM, ESCMID-EFISG, EUCAST-AFST, FDLC, IDSA, ISHAM, MMSA, and MSGERC.

The rapid pace of name changes of medically important fungi is creating challenges for clinical laboratories and clinicians involved in patient care. We describe two sources of name change which have different drivers, at the species versus the genus level. Some suggestions are made here to reduce the number of name changes. We urge taxonomists to provide diagnostic markers of taxonomic novelties. Given the instability of phylogenetic trees due to variable taxon sampling, we advocate to maintain genera at the largest possible size. Reporting of identified species in complexes or series should where possible comprise both the name of the overarching species and that of the molecular sibling, often cryptic species. Because the use of different names for the same species will be unavoidable for many years to come, an open access online database of the names of all medically important fungi, with proper nomenclatural designation and synonymy, is essential. We further recommend that while taxonomic discovery continues, the adaptation of new name changes by clinical laboratories and clinicians be reviewed routinely by a standing committee for validation and stability over time, with reference to an open access database, wherein reasons for changes are listed in a transparent way.

Penicillium and Talaromyces spp. emerging pathogens in dogs since 1990s.

Penicillium and Talaromyces spp. are environmental saprophytic molds rarely encountered as infectious agents in humans and animals. This article summarizes the clinical features, treatment, and outcomes of proven infections caused by Penicillium or Talaromyces in four dogs in France. Two dogs had disseminated infections, while the other two had a localized form. All dogs had positive histopathological results showing the presence of hyaline septate hyphae and a positive fungal culture with typical Penicillium conidiophores. Talaromyces georgiensis (n = 1), Penicillium labradorum (n = 2), and Penicillium from section Ramosa series Raistrickiorum (n = 1), were identified based on Internal Transcribed Spacer (ITS) Sanger sequencing. The dogs were initially treated with ketoconazole or itraconazole. Second-line treatment was initiated in three dogs, but after several relapses, the prognosis remained poor. Since the 1990s, 18 cases of Penicillium or Talaromyces infections in dogs have been described worldwide. This series of four reports brings new cases to those already reported in the literature, which are probably underestimated in the world.

Penicillium and Talaromyces spp. are molds found in the environment that rarely cause infections in humans and animals. This article summarizes the clinical features and treatment of proven infections caused by Penicillium or Talaromyces species in four dogs in France.

In Vitro Efficacy of Terpenes from Essential Oils against Sarcoptes scabiei.

The mite Sarcoptes scabiei is responsible for the emerging or re-emerging skin disease called scabies in humans and sarcoptic mange in animals. Essential oils represent an appealing alternative strategy for the control of Sarcoptes infections, but the commercial development of essential oils may be hampered by their inconsistency in efficacy due to their varied chemical compositions. In order to address this issue, we assessed the efficacy of six components (carvacrol, eugenol, geraniol, citral, terpinen-4-ol, and linalool) against S. scabiei. At a concentration of 0.5%, carvacrol presented the best miticidal efficacy, with a median lethal time (LT50) value of 6.7 min, followed by eugenol (56.3 min), geraniol (1.8 h), citral (6.1 h), terpinen-4-ol (22.3 h), and linalool (39.9 h). The LC50 values at 30 min for carvacrol, eugenol, and geraniol were 0.24, 0.79, and 0.91%, respectively. In conclusion, carvacrol, eugenol, and geraniol represent potential complementary or alternative agents for S. scabiei infections in humans or animals. Our study provides a scientific basis for the development of scabicidal products based on essential oils.

Aspergillosis in a colony of Humboldt penguins (Spheniscus humboldti) under managed care: a clinical and environmental investigation in a French zoological park.

Aspergillosis is pervasive in bird populations, especially those under human care. Its management can be critically impacted by exposure to high levels of conidia and by resistance to azole drugs. The fungal contamination in the environment of a Humboldt penguin (Spheniscus humboldti) group, housed in a French zoological park next to numerous large crop fields, was assessed through three serial sessions of surface sampling in nests, in 2018-20: all isolates were counted and characterized by sequencing. When identified as Aspergillus fumigatus, they were systematically screened for resistance mutations in the cyp51A gene and tested for minimal inhibitory concentrations (MICs) determination. At the same time, the clinical incidence of aspergillosis was evaluated in the penguin population by the means of systematic necropsy and mycological investigations. A microsatellite-based analysis tracked the circulation of A. fumigatus strains. Environmental investigations highlighted the substantial increase of the fungal load during the summer season (>12-fold vs. the other timepoints) and a large overrepresentation of species belonging to the Aspergillus section Fumigati, ranging from 22.7 to 94.6% relative prevalence. Only one cryptic species was detected (A. nishimurae), and one isolate exhibited G138S resistance mutation with elevated MICs. The overall incidence of aspergillosis was measured at ∼3.4% case-years, and mostly in juveniles. The analysis of microsatellite polymorphism revealed a high level of genetic diversity among A. fumigatus clinical isolates. In contrast, one environmental strain appeared largely overrepresented during the summer sampling session. In all, the rural location of the zoo did not influence the emergence of resistant strains.

In vitro activities of 8 antifungal agents against geophilic dermatophyte isolates.

BACKGROUND: Members of the Nannizzia gypsea complex are globally the most common geophilic dermatophytes which cause infection in animals and human. Although the susceptibility patterns of anthropophilic or zoophilic dermatophyte species to antifungal agents are well documented, the effectiveness of such drugs against geophilic species have rarely been explored. OBJECTIVES: This study was aimed to evaluate the in vitro antifungal activity of common and new antifungals against a set of environmental and clinical geophilic dermatophyte isolates. METHODS: 108 soil and clinical geophilic isolates from two genera Nannizzia (N. fulva n = 59; N. gypsea n = 43) and Arthroderma (A. quadrifidum n = 4; A. gertleri n = 1; A. tuberculatum n = 1) were included in the study. The in vitro antifungal susceptibility patterns of eight common and new antifungals against the isolates were determined according to broth microdilution method and by CLSI M38-A3 (3rd edition) protocol. RESULTS: MIC values across all isolates from five species ranged as: luliconazole: 0.0002-0.002 µg/ml, terbinafine: 0.008-0.125 µg/ml, efinaconazole: 0.008-0.125 µg/ml, ciclopirox olamine: 0.03-0.5 µg/ml, itraconazole: 0.125-1 µg/ml, amorolfine hydrochloride: 0.125-4 µg/ml, griseofulvin: 0.25-2 µg/ml and tavaborole: 1-8 µg/ml, respectively. CONCLUSION: Luliconazole, terbinafine and efinaconazole exhibited the highest in vitro efficacy, regardless of the dermatophyte species. Further surveillance studies are recommended to confirm the implication of such in vitro data for the clinical recovery rate of dermatophytosis with geophilic species following antifungal therapy.

Cellular and molecular insights on the regulation of innate immune responses to experimental aspergillosis in chicken and turkey poults.

Across the world, many commercial poultry flocks and captive birds are threatened by infection with Aspergillus fumigatus. Susceptibility to aspergillosis varies among birds; among galliform birds specifically, morbidity and mortality rates seem to be greater in turkeys than in chickens. Little is known regarding the features of avian immune responses after inhalation of Aspergillus conidia, and to date, scarce information on inflammatory responses during aspergillosis exists. Thus, in the present study, we aimed to improve our understanding of the interactions between A. fumigatus and economically relevant galliform birds in terms of local innate immune responses. Intra-tracheal aerosolization of A. fumigatus conidia in turkey and chicken poults led to more severe clinical signs and lung lesions in turkeys, but leukocyte recovery from lung lavages was higher in chickens at 1dpi only. Interestingly, only chicken CD8+ T lymphocyte proportions increased after infection. Furthermore, the lungs of infected chickens showed an early upregulation of pro-inflammatory cytokines, including IL-1ß, IFN-γ and IL-6, whereas in turkeys, most of these cytokines showed a downregulation or a delayed upregulation. These results confirmed the importance of an early pro-inflammatory response to ensure the development of an appropriate anti-fungal immunity to avoid Aspergillus dissemination in the respiratory tract. In conclusion, we show for the first time that differences in local innate immune responses between chickens and turkeys during aspergillosis may determine the outcome of the disease.

Aspergillus fumigatus infection may cause mortality in poultry, depending on species sensitivity. This study confirms the earlier activation of chickens' pro-inflammatory effectors to control Aspergillus dissemination, whereas turkeys' immune response enables the exacerbation of lung lesions.

In vitro antifungal susceptibility patterns of Trichophyton benhamiae complex isolates from diverse origin.

BACKGROUND: Species from the Trichophyton benhamiae complex are mostly zoophilic dermatophytes which cause inflammatory dermatophytosis in animals and humans worldwide. OBJECTIVES: This study was purposed to (a) to identify 169 reference and clinical dermatophyte strains from the T benhamiae complex species by molecular method and adhering to the newest taxonomy in the complex (b) to evaluate the in vitro antifungal susceptibility profile of these strains against eight common and new antifungal agents that may be used for the treatment of dermatophytosis. METHODS: All isolates, mainly originated from Europe but also from Iran, Japan and USA, were subjected to ITS-rDNA sequencing. The in vitro antifungal susceptibility profiles of eight common and new antifungal drugs against the isolates were determined by CLSI M38-A2 protocol and according to microdilution method. RESULTS: Based on the ITS-rDNA sequencing, T benhamiae was the dominant species (n = 102), followed by T europaeum (n = 29), T erinacei (n = 23), T japonicum (n = 10), Trichophyton sp (n = 4) and T eriotrephon (n = 1). MIC ranges across all isolates were as follows: luliconazole: 0.0002-0.002 µg/ml, terbinafine: 0.008-0.125 µg/ml, efinaconazole: 0.008-0.125 µg/ml, ciclopirox olamine: 0.03-0.5 µg/ml, itraconazole: 0.06-2 µg/ml, griseofulvin: 0.25-4 µg/ml, amorolfine hydrochloride: 0.125-4 µg/ml and tavaborole: 1-16 µg/ml. CONCLUSION: Luliconazole, efinaconazole and terbinafine were the most potent antifungals against T benhamiae complex isolates, regardless of the geographic locations where strains were isolated. These data might help dermatologists to develop effective therapies for successful treatment of infections due to T benhamiae complex species.

In Vitro Activity of Beauvericin against All Developmental Stages of Sarcoptes scabiei.

Scabies is a frequent cutaneous infection caused by the mite Sarcoptes scabiei in a large number of mammals, including humans. As the resistance of S. scabiei against several chemical acaricides has been previously documented, the establishment of alternative and effective control molecules is required. In this study, the potential acaricidal activity of beauvericin was assessed against different life stages of S. scabiei var. suis and in comparison with dimpylate and ivermectin, two commercially available molecules used for the treatment of S. scabiei infection in animals and/or humans. The toxicity of beauvericin against cultured human fibroblast skin cells was evaluated using an MTT proliferation assay. In our in vitro model, developmental stages of S. scabiei were placed in petri dishes filled with Columbia agar supplemented with pig serum and different concentrations of the drugs. Cell sensitivity assays demonstrated low toxicity of beauvericin against primary human fibroblast skin cells. At 0.5 and 5 mM, beauvericin showed higher activity against adults and eggs of S. scabiei compared to dimpylate and ivermectin. These results revealed that the use of beauvericin is promising and might be considered for the treatment of S. scabiei infection.

Comparing acaricidal and ovicidal activity of five terpenes from essential oils against Psoroptes cuniculi.

Essential oils and their components represent an appealing alternative strategy against parasitic mites. The chemical complexity and variability of essential oils limit their use and additional work is required to analyze the efficacy and application rate of essential oils' individual components. In the present study, the activity of five terpenes (terpinen-4-ol, citral, linalool, eugenol, and geraniol) was evaluated against Psoroptes cuniculi motile stages and eggs collected from naturally infected rabbits. Eugenol presented the best acaricidal efficacy with a median lethal concentration (LC50) value of less than 0.1% at 24 h, followed by geraniol (0.33%), linalool (0.38%), citral (0.46%), and terpinen-4-ol (0.66%). Geraniol and eugenol were able to kill all mites within 5 min at 1% concentration. The effective concentration to inhibit 50% (EC50) of egg hatching was 0.65%, 0.66%, 0.85%, 1.47%, and 2.87% for eugenol, geraniol, citral, terpinen-4-ol, and linalool, respectively. In conclusion, eugenol, geraniol, citral, terpinen-4-ol, and linalool should be considered as promising agents for the development of botanical acaricides against Psoroptes cuniculi.

Haemosporidian parasites from captive Strigiformes in France.

Haemosporidia infections may cause major damage to avian populations and represent a concern for veterinarians working in zoological parks or wildlife rescue centres. Following the fatal infection of 9 Great grey owls (Strix nebulosa) at Mulhouse zoological park, between summer 2013 and 2015, a prospective epidemiological investigation was performed in captive strigiform birds in France in 2016. The purpose was to evaluate the prevalence of haemosporidian parasites in captive Strigiformes and to estimate the infection dynamics around the nesting period. Blood samples were taken from 122 strigiform birds representing 14 species from 15 French zoological parks. Parasites were detected by direct examination of blood smears and by PCR targeting the mitochondrial cytochrome b gene. Haemosporidian parasites were detected in 59 birds from 11 zoos. Three distinct Haemoproteus mitochondrial cytochrome b sequences (haplotypes A and C for H. syrnii and haplotype B for Haemoproteus sp.) as well as two species of Plasmodium were detected. The overall prevalence of Haemoproteus infection was 12.8%. The percentage of birds infected by Haemoproteus varied according to the period of sampling. Nesting season seemed to be at greater risk with an average prevalence of 53.9% compared with winter season with an average prevalence of 14.8%, related to the abundance of the vectors. The prevalence of Plasmodium infection in Strigiformes did not exceed 8% throughout the year. This study confirmed how significant Haemosporidia infection could be in Strigiformes from zoological parks in France. The nesting season was identified as a period of higher risk of infection and consequently the appropriate period to apply prophylactic measures.

Biology, diagnosis and treatment of Malassezia dermatitis in dogs and cats Clinical Consensus Guidelines of the World Association for Veterinary Dermatology.

BACKGROUND: The genus Malassezia is comprised of a group of lipophilic yeasts that have evolved as skin commensals and opportunistic cutaneous pathogens of a variety of mammals and birds. OBJECTIVES: The objective of this document is to provide the veterinary community and other interested parties with current information on the ecology, pathophysiology, diagnosis, treatment and prevention of skin diseases associated with Malassezia yeasts in dogs and cats. METHODS AND MATERIAL: The authors served as a Guideline Panel (GP) and reviewed the literature available prior to October 2018. The GP prepared a detailed literature review and made recommendations on selected topics. The World Association of Veterinary Dermatology (WAVD) Clinical Consensus Guideline committee provided guidance and oversight for this process. The document was presented at two international meetings of veterinary dermatology societies and one international mycology workshop; it was made available for comment on the WAVD website for a period of six months. Comments were shared with the GP electronically and responses incorporated into the final document. CONCLUSIONS AND CLINICAL IMPORTANCE: There has been a remarkable expansion of knowledge on Malassezia yeasts and their role in animal disease, particularly since the early 1990's. Malassezia dermatitis in dogs and cats has evolved from a disease of obscurity and controversy on its existence, to now being a routine diagnosis in general veterinary practice. Clinical signs are well recognised and diagnostic approaches are well developed. A range of topical and systemic therapies is known to be effective, especially when predisposing factors are identified and corrected.

Investigation of the Relationships Between Clinical and Environmental Isolates of Aspergillus fumigatus by Multiple-locus Variable Number Tandem Repeat Analysis During Major Demolition Work in a French Hospital.

Background: Genotyping is needed to explore the link between clinical cases from colonization of invasive aspergillosis (IA) and major building construction. Attempts to correlate Aspergillus fumigatus strains from clinical infection or colonization with those found in the environment remain controversial due to the lack of a large prospective study. Our aim in this study was to compare the genetic diversity of clinical and environmental A. fumigatus isolates during a demolition period. Methods: Fungal contamination was monitored daily for 11 months in 2015. Environmental surveillance was undertaken indoors and outdoors at 8 locations with automatic agar samplers. IA infection cases were investigated according to European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group criteria. Isolates were identified by amplification and sequencing of the ß- tubulin gene. They were genotyped by multiple-locus variable number tandem repeat analysis (MLVA). The phylogenetic relationships between isolates were assessed by generating a minimum spanning tree. Results: Based on 3885 samples, 394 A. fumigatus isolates (383 environmental and 11 clinical) were identified and genotyped using MLVA. Clinical isolates were collected from patients diagnosed as having probable IA (n = 2), possible IA (n = 1), or bronchial colonization (n = 6). MLVA generated 234 genotypes. Seven clinical isolates shared genotypes identical to environmental isolates. Conclusions: Among the diversity of genotypes described, similar genotypes were found in clinical and environmental isolates, indicating that A. fumigatus infection and colonization may originate from hospital environments.

Occurrence and species diversity of human-pathogenic Mucorales in commercial food-stuffs purchased in Paris area.

Mucormycoses are life-threatening fungal diseases that affect a variety of patients including those with diabetes mellitus or hematological malignancies. The responsible agents, the Mucorales, are opportunistic pathogens originating from the environment such as soil or decaying organic matter. The aim of the present study was to assess the prevalence and diversity of human-pathogenic species of Mucorales in commercially available foodstuffs in France. All food samples were purchased from January 2014 to May 2015 in France. A total of 159 dried food samples including spices and herbs (n = 68), herbal tea (n = 19), cereals (n = 19), vegetables (n = 14), and other foodstuffs (n = 39) were analyzed. Each strain of Mucorales was identified phenotypically, and molecular identification was performed by ITS sequencing. From the 28 (17.6%) samples that were culture-positive for Mucorales, 30 isolates were recovered. Among the isolates, 13 were identified as Rhizopus arrhizus var. arrhizus, 10 R. arrhizus var. delemar, two Rhizopus microsporus, one Lichtheimia corymbifera, three Lichtheimia ramosa, and one Syncephalastrum racemosum. Culture-positive samples originated from different countries (Europe, Asia) and brands. The samples most frequently contaminated by Mucorales were spices and herbs (19/68, 27.9%), followed by herbal tea (2/19, 10.5%), cereals (2/19, 10.5%), other food products (5/39, 12.8%). The present study showed that human-pathogenic Mucorales were frequently recovered from commercially available foodstuffs in France with a large diversity of species. The potential danger represented by Mucorales present in food for immunocompromised patients should be further analyzed.

In vitro activities of 15 antifungal drugs against a large collection of clinical isolates of Microsporum canis.

BACKGROUND: Microsporum canis is a zoophilic species, found to be the most frequently isolated species in animals. M. canis causes sporadic outbreaks of infections in humans, such as the one that occurred in Canada, where more than 1000 human cases were detected over an 8-year period. Despite the medical importance of M. canis infections, there are limited in vitro data on the antifungal susceptibility to antifungal drugs, including new generation triazoles and imidazoles. OBJECTIVE: The aim of the current study was to comprehensively evaluate the in vitro activity of new azoles and comparator drugs against a large panel of M. canis isolates using a microdilution assay. METHODS: The in vitro susceptibility to novel triazoles and imidazoles was compared to that of other antifungal drugs using a large collection of M. canis clinical isolates (n = 208) obtained from patients and animals with dermatophytosis in Iran, France and Turkey. RESULTS: All isolates exhibited high susceptibility to the majority of the tested antifungal agents. However, luliconazole, lanoconazole and efinaconazole, as well as econazole, demonstrated superior activity against all strains in comparis on with the other drugs. CONCLUSION: FDA-approved antifungal drugs, that is luliconazole, efinaconazole and lanoconazole, showed the highest antifungal activity and should be promising candidates for the treatment of dermatophytosis caused by M canis. However, their therapeutic effectiveness remains to be determined in clinical settings.

Chrysomya bezziana: a case report in a dog from Southern China and review of the Chinese literature.

Chrysomya bezziana is an obligate, myiasis-causing fly in humans and warm-blooded animals throughout the tropical and subtropical Old World. We report a case of cutaneous myiasis due to C. bezziana in a dog from Guangxi province in China. A total of 35 maggots were removed from the lesions. Direct sequencing of the mitochondrial cytochrome b gene showed that the specimen belonged to haplotype CB_bezz02, which was previously reported in Malaysia and the Gulf region. This paper also reviews reported cases of screwworm myiasis from humans and animals in China. Geographical records indicate that the distribution of C. bezziana is expanding, suggesting that an integrated pest management control should be taken into consideration in China.

Comparison of acetate tape impression, deep skin scraping, and microscopic examination of hair for therapeutic monitoring of dogs with juvenile generalized demodicosis: A pilot study.

The standard method for diagnosis and therapeutic monitoring of dogs with demodicosis is microscopic examination of deep skin scrapings. Previous studies have compared deep skin scraping and microscopic hair examination to acetate tape impression with skin squeezing for the diagnosis of demodicosis but the latter has never been evaluated for therapeutic monitoring. The main purpose of this study was to evaluate acetate tape impression with skin squeezing as a therapeutic monitoring tool for dogs with juvenile onset generalized demodicosis. An area of skin with primary lesions for demodicosis was chosen and the 3 techniques were performed. The total number of mites including each of the Demodex canis life stages were recorded. This was done weekly until negative results were obtained. There were no significant differences in the total number of mites in the weekly counts between the deep skin scrapings and the acetate tape impressions with skin squeezing. Acetate tape impression with skin squeezing can be used for therapeutic monitoring of dogs with juvenile onset generalized demodicosis.

Comparaison de l'impression sur ruban acétate, des grattages cutanés profonds et de l'examen microscopique du poil pour la surveillance thérapeutique des chiens atteints de démodicose généralisée juvénile : étude pilote. La méthode standard pour le diagnostic et la surveillance thérapeutique des chiens atteints de démodicose est l'examen microscopique des grattages cutanés profonds. Des études antérieures ont comparé des grattages cutanés profonds et l'examen microscopique du poil à l'impression sur ruban d'acétate avec le pincement de la peau pour le diagnostic de la démodicose, mais cette dernière méthode n'a jamais été évaluée pour la surveillance thérapeutique. Le but principal de cette étude consistait à évaluer l'impression sur ruban d'acétate avec pincement de la peau comme outil de surveillance thérapeutique pour les chiens atteints de démodicose généralisée juvénile. Une région de peau avec des lésions primaires pour la démodicose a été choisie et les trois techniques ont été réalisées. Le nombre total de mites, y compris chaque des stades de vie de Demodex canis, a été consigné. Cette technique a été employée une fois par semaine jusqu'à l'obtention de résultats négatifs. Il n'y avait aucune différence significative dans le nombre total de mites dans les numérations hebdomadaires entre les grattages cutanés profonds et les impressions sur ruban d'acétate avec pincement de la peau. L'impression sur ruban d'acétate avec pincement de la peau peut être utilisée pour la surveillance thérapeutique des chiens atteints de démodicose généralisée juvénile.(Traduit par Isabelle Vallières).

Efficacy and Pharmacokinetics Evaluation of a Single Oral Dose of Afoxolaner against Sarcoptes scabiei in the Porcine Scabies Model for Human Infestation.

Scabies is a major and potentially growing public health problem worldwide with an unmet need for acaricidal agents with greater efficacy and improved pharmacological properties for its treatment. The objective of the present study was to assess the efficacy and describe the pharmacokinetics profile of a novel acaricide, afoxolaner (AFX), in a relevant experimental porcine model. Twelve pigs were experimentally infested and either treated with 2.5 mg/kg single dose oral AFX (n = 4) or 0.2 mg/kg, two doses 8 days apart, oral ivermectin ([IVM] n = 4) or not treated for scabies (n = 4). The response to treatment was assessed by the reduction of mite counts in skin scrapings as well as clinical and pruritus scores over time. Plasma and skin pharmacokinetics profiles for both AFX and IVM were evaluated. AFX efficacy was 100% at days 8 and 14 posttreatment and remained unchanged until the study end (day 45). IVM efficacy was 86% and 97% on days 8 and 14, respectively, with a few mites recovered at the study end. Clinical and pruritus scores decreased in both treated groups and remained constant in the control group. Plasma mean residence times (MRT) were 7.1 ± 2.4 and 1.1 ± 0.2 days for AFX and IVM, respectively. Skin MRT values were 16.2 ± 16.9 and 2.7 ± 0.5 days for AFX and IVM, respectively. Overall, a single oral dose of AFX was efficacious for the treatment of scabies in experimentally infested pigs and showed remarkably long MRTs in plasma and, notably, in the skin.

Fungal infections in animals: a patchwork of different situations.

The importance of fungal infections in both human and animals has increased over the last decades. This article represents an overview of the different categories of fungal infections that can be encountered in animals originating from environmental sources without transmission to humans. In addition, the endemic infections with indirect transmission from the environment, the zoophilic fungal pathogens with near-direct transmission, the zoonotic fungi that can be directly transmitted from animals to humans, mycotoxicoses and antifungal resistance in animals will also be discussed. Opportunistic mycoses are responsible for a wide range of diseases from localized infections to fatal disseminated diseases, such as aspergillosis, mucormycosis, candidiasis, cryptococcosis and infections caused by melanized fungi. The amphibian fungal disease chytridiomycosis and the Bat White-nose syndrome are due to obligatory fungal pathogens. Zoonotic agents are naturally transmitted from vertebrate animals to humans and vice versa. The list of zoonotic fungal agents is limited but some species, like Microsporum canis and Sporothrix brasiliensis from cats, have a strong public health impact. Mycotoxins are defined as the chemicals of fungal origin being toxic for warm-blooded vertebrates. Intoxications by aflatoxins and ochratoxins represent a threat for both human and animal health. Resistance to antifungals can occur in different animal species that receive these drugs, although the true epidemiology of resistance in animals is unknown, and options to treat infections caused by resistant infections are limited.