Ecology and impacts of white-nose syndrome on bats.

The recent introduction of Pseudogymnoascus destructans (the fungal pathogen that causes white-nose syndrome in bats) from Eurasia to North America has resulted in the collapse of North American bat populations and restructured species communities. The long evolutionary history between P. destructans and bats in Eurasia makes understanding host life history essential to uncovering the ecology of P. destructans. In this Review, we combine information on pathogen and host biology to understand the patterns of P. destructans spread, seasonal transmission ecology, the pathogenesis of white-nose syndrome and the cross-scale impact from individual hosts to ecosystems. Collectively, this research highlights how early pathogen detection and quantification of host impacts has accelerated the understanding of this newly emerging infectious disease.

Invasive dermatophyte infection: A systematic review.

Dermatophyte infections usually present as various types of superficial cutaneous mycoses; on very rare occasions, dermatophytes enter deep into the dermis and cause invasive infections. In this study, we aimed to perform a systematic review of all reported invasive dermatophytosis cases over the past 20 years. We performed systematic searches in PubMed/Medline, EMBASE and Web of Science and identified 123 papers reporting 160 individual cases of invasive dermatophytosis between 2000 and 2020. Our study included 103 (64.4%) males, and the mean age at diagnosis was 43.0 years (range: 3-87 years). The most common predisposing factor was superficial dermatophytosis (56.9%), followed by solid organ transplantation (26.9%), the use of topical immunosuppressants (15.6%), gene mutations (14.4%), diabetes (14.4%) and trauma (6.9%). Trichophyton (T.) rubrum was the most prevalent pathogen (53.1%) responsible for invasive dermatophytosis, followed by T. mentagrophytes (7.5%), Microsporum canis (6.9%), T. tonsurans (5.6%), T. interdigitale (5.0%) and T. violaceum (3.8%). Patients with CARD9 or STAT3 mutations were prone to have mixed infection of two or more dermatophytes, present with eosinophilia and high IgE, and develop disseminated infections. Overall mortality was 7.9%, and the mortality in patients with and without gene mutations was 17.4% and 5.5%, respectively. Most of the normal host patients responded well to oral antifungal agents, while gene-deficient patients usually required lifelong treatment to stabilise their infection status. Our review indicated the importance of preventive treatment of superficial tinea in patients with immunosuppression and gene deficiencies to avoid the development of invasive dermatophytosis.

Pharmacokinetics of terbinafine in little brown myotis (Myotis lucifugus) infected with Pseudogymnoascus destructans.

OBJECTIVE To determine the pharmacokinetics of terbinafine in little brown myotis (Myotis lucifugus) infected with Pseudogymnoascus destructans. ANIMALS 123 bats from a P destructans-infected hibernation site in Virginia. PROCEDURES 3 bats were euthanized and necropsied to confirm the presence of P destructans within the population. The remaining 120 bats were systematically assigned to 6 groups (20 bats/group). Bats in each of 3 groups received 6, 20, or 60 mg of terbinafine/kg, SC, once daily for 10 days. Bats in another group received 200 mg of terbinafine/kg, SC, once daily for 5 days. Bats in 1 group received the terbinafine vehicle solution (0.1 mL/kg, SC, once daily for 10 days). Bats in the remaining group did not receive any treatment. Following the treatment period (days 1 through 10), bats were housed in a hibernation chamber and monitored daily until euthanasia on day 42, 75, or 109. Tissue specimens were collected from all bats as soon as possible after death or euthanasia to determine terbinafine concentration. Within each group and tissue type, terbinafine concentration data were pooled, and pharmacokinetic parameters were calculated by noncompartmental methods. RESULTS Adverse neurologic effects and a high mortality rate before day 10 were observed in bats that received the highest terbinafine dose (200 mg/kg) but not those that received lower doses. Presumed therapeutic terbinafine concentrations (≥ 2 µg/g) were maintained in skin and wing for at least 30 and 6 days in bats that received the 60 and 20 mg/kg doses, respectively, but were not achieved in most bats that received the 6 mg/kg dose. Tissue terminal half-life ranged from 14 to 22 days. Terbinafine concentration in hair was positively correlated with that in skin and wing. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated terbinafine doses > 6 but < 200 mg/kg should be further evaluated for the treatment of P destructans-infected bats. Collection of serial hair specimens may represent a noninvasive method for monitoring terbinafine concentration in treated bats.

Treatment of urodelans based on temperature dependent infection dynamics of Batrachochytrium salamandrivorans.

The recently emerged chytrid fungus Batrachochytrium salamandrivorans currently causes amphibian population declines. We hypothesized that temperature dictates infection dynamics of B. salamandrivorans, and that therefore heat treatment may be applied to clear animals from infection. We examined the impact of environmental temperature on B. salamandrivorans infection and disease dynamics in fire salamanders (Salamandra salamandra). Colonization of salamanders by B. salamandrivorans occurred at 15°C and 20°C but not at 25°C, with a significantly faster buildup of infection load and associated earlier mortality at 15°C. Exposing B. salamandrivorans infected salamanders to 25°C for 10 days resulted in complete clearance of infection and clinically cured all experimentally infected animals. This treatment protocol was validated in naturally infected wild fire salamanders. In conclusion, we show that B. salamandrivorans infection and disease dynamics are significantly dictated by environmental temperature, and that heat treatment is a viable option for clearing B. salamandrivorans infections.

Opportunistic deep cutaneous mycoses in solid organ transplant recipients.

Invasive fungal infections are a major cause of morbidity and mortality among organ transplant recipients, despite many progresses concerning diagnosis, preventions and treatment. Risk factors for invasive fungal infections in transplanted recipients include type and severity of immunosuppression, especially in life-saving organs as lung or liver, older age at transplantation, and technical complexity of surgery, living in endemic areas or exposure to a contaminated environment. Superficial fungal infections are caused by Candida, Dermatophytes, and Malassezia. In invasive mycoses, skin lesions may occur as a consequence of the systemic dissemination of invasive mycoses, or after direct inoculation in the skin. Aspergillosis, cryptococcosis, Zygomycoses, dark mould infections, fusariosis and infections attributable to Scedosporium and Pseudallescheria species are the most common etiological agents. Cutaneous manifestations of fungal infection are not specific, and a high degree of suspicion is required, and prompt biopsy for histology and culture is needed. Therapy with lyposomal amphotericin B and new triazoles are effective.

Cutaneous histoplasmosis in renal transplant recipients.

Cutaneous histoplasmosis is a rare entity, although it can be seen in a substantial portion of renal transplant recipients with disseminated disease. The prognosis of disseminated disease is worse than isolated cutaneous involvement, and significant delays in diagnosis are reported. We reviewed reports of cutaneous histoplasmosis with and without dissemination in the setting of renal transplantation to examine incidence, timing of diagnosis, clinical features, and prognosis. Remarkable morphologic variability and the non-specific appearance of skin findings suggest that tissue culture is required for definitive diagnosis. Cutaneous lesions represent an easily accessible source for early diagnosis.

Increased incidence of invasive fusariosis with cutaneous portal of entry, Brazil.

Invasive fusariosis (IF) is an infection with Fusarium spp. fungi that primarily affects patients with hematologic malignancies and hematopoietic cell transplant recipients. A cutaneous portal of entry is occasionally reported. We reviewed all cases of IF in Brazil during 2000-2010, divided into 2 periods: 2000-2005 (period 1) and 2006-2010 (period 2). We calculated incidence rates of IF and of superficial infections with Fusarium spp. fungi identified in patients at a dermatology outpatient unit. IF incidence for periods 1 and 2 was 0.86 cases versus 10.23 cases per 1,000 admissions (p<0.001), respectively; superficial fusarial infection incidence was 7.23 versus 16.26 positive cultures per 1,000 superficial cultures (p<0.001), respectively. Of 21 cases of IF, 14 showed a primary cutaneous portal of entry. Further studies are needed to identify reservoirs of these fungi in the community and to implement preventive measures for patients at risk.

Necrotizing cutaneous mucormycosis after a tornado in Joplin, Missouri, in 2011.

BACKGROUND: Mucormycosis is a fungal infection caused by environmentally acquired molds. We investigated a cluster of cases of cutaneous mucormycosis among persons injured during the May 22, 2011, tornado in Joplin, Missouri. METHODS: We defined a case as a soft-tissue infection in a person injured during the tornado, with evidence of a mucormycete on culture or immunohistochemical testing plus DNA sequencing. We conducted a case-control study by reviewing medical records and conducting interviews with case patients and hospitalized controls. DNA sequencing and whole-genome sequencing were performed on clinical specimens to identify species and assess strain-level differences, respectively. RESULTS: A total of 13 case patients were identified, 5 of whom (38%) died. The patients had a median of 5 wounds (range, 1 to 7); 11 patients (85%) had at least one fracture, 9 (69%) had blunt trauma, and 5 (38%) had penetrating trauma. All case patients had been located in the zone that sustained the most severe damage during the tornado. On multivariate analysis, infection was associated with penetrating trauma (adjusted odds ratio for case patients vs. controls, 8.8; 95% confidence interval [CI], 1.1 to 69.2) and an increased number of wounds (adjusted odds ratio, 2.0 for each additional wound; 95% CI, 1.2 to 3.2). Sequencing of the D1-D2 region of the 28S ribosomal DNA yielded Apophysomyces trapeziformis in all 13 case patients. Whole-genome sequencing showed that the apophysomyces isolates were four separate strains. CONCLUSIONS: We report a cluster of cases of cutaneous mucormycosis among Joplin tornado survivors that were associated with substantial morbidity and mortality. Increased awareness of fungi as a cause of necrotizing soft-tissue infections after a natural disaster is warranted.

Differential host susceptibility to Batrachochytrium dendrobatidis, an emerging amphibian pathogen.

The amphibian fungal pathogen Batrachochytrium dendrobatidis (Bd) has received considerable attention due to its role in amphibian population declines worldwide. Although many amphibian species appear to be affected by Bd, there is little information on species-specific differences in susceptibility to this pathogen. We used a comparative experimental approach to examine Bd susceptibility in 6 amphibian species from the United States. We exposed postmetamorphic animals to Bd for 30 days and monitored mortality, feeding rates, and infection levels. In all species tested, Bd-exposed animals had higher rates of mortality than unexposed (control) animals. However, we found differences in mortality rates among species even though the amount of Bd detected on the different species' bodies did not differ. Of the species tested, southern toads (Anaxyrus terrestris) and wood frogs (Lithobates sylvaticus) had the highest rates of Bd-related mortality. Within species, we detected lower levels of Bd on individuals that survived longer and found that the relationship between body size and infection levels differed among species. Our results indicate that, even under identical conditions, amphibian species differ in susceptibility to Bd. This study represents a step toward identifying and understanding species variation in disease susceptibility, which can be used to optimize conservation strategies.

Cutaneous cryptococcosis in solid organ transplant recipients.

Clinical manifestations, treatment, and outcomes of cutaneous cryptococcosis in solid organ transplant (SOT) recipients are not fully defined. In a prospective cohort comprising 146 SOT recipients with cryptococcosis, we describe the presentation, antifungal therapy, and outcome of cutaneous cryptococcal disease. Cutaneous cryptococcosis was documented in 26/146 (17.8%) of the patients and manifested as nodular/mass (34.8%), maculopapule (30.4%), ulcer/pustule/abscess (30.4%), and cellulitis (30.4%) with 65.2% of the skin lesions occurred in the lower extremities. Localized disease developed in 30.8% (8/26), and disseminated disease in 69.2% (18/26) with involvement of the central nervous system (88.9%, 16/18), lung (33.3%, 6/18), or fungemia (55.6%, 10/18). Fluconazole (37.5%) was employed most often for localized and lipid formulations of amphotericin B (61.1%) for disseminated disease. Overall mortality at 90 days was 15.4% (4/26) with 16.7% in disseminated and 12.5% in localized disease (P = 0.78). SOT recipients who died were more likely to have renal failure (75.0% vs. 13.6%, P = 0.028), longer time to onset of disease after transplantation (87.5 vs. 22.6 months, P = 0.023), and abnormal mental status (75% vs. 13.6%, P = 0.028) than those who survived. Cutaneous cryptococcosis represents disseminated disease in most SOT recipients and preferentially involves the extremities. Outcomes with appropriate management were comparable between SOT recipients with localized and disseminated cryptococcosis.

Clinical presentations and outcomes of Penicillium marneffei infections: a series from 1994 to 2004.

OBJECTIVES: To describe the clinical presentation, management, and outcomes of patients with Penicillium marneffei infections in a regional hospital in Hong Kong. DESIGN: Retrospective study. SETTING: A regional and tertiary human immunodeficiency virus-referral hospital in Hong Kong. PATIENTS: Those who had penicilliosis during the inclusive period January 1994 to February 2004. RESULTS: Forty-seven immunocompromised patients (44 being human immunodeficiency virus-positive) with penicilliosis were retrospectively studied. Fever, malaise, and anaemia were the commonest presentations. Most diagnoses were obtained from blood cultures (83%) and lymph node biopsies (34%). Five (11%) died, death being attributable to penicilliosis; four (9%) of them had received no specific antifungal treatment due to late presentation and late diagnosis. The CD4 count of human immunodeficiency virus-infected patients upon diagnosis of penicilliosis was low (median, 20.0 cells/mm3). Most (70%) patients received amphotericin B as an induction treatment, followed by oral itraconazole, although a smaller proportion (21%) received oral itraconazole only. All surviving human immunodeficiency virus-infected patients took highly active antiretroviral treatment and oral itraconazole as secondary prophylaxis after treatment of penicilliosis. The prognosis appeared satisfactory with early diagnosis and administration of appropriate antifungal therapy. Relapse ensued in two (4%) of the patients only. CONCLUSION: Penicillium marneffei infection in immunocompromised patients is a serious disease with significant mortality if not diagnosed early and treated with appropriate antifungal drugs. Simple investigations like blood culture enable the diagnosis in the majority of cases. Immunocompromised patients who have been successfully treated should receive oral itraconazole as a maintenance therapy to prevent relapse.

Emerging disease of amphibians cured by elevated body temperature.

The emerging infectious disease chytridiomycosis is thought to have contributed to many of the recent alarming declines in amphibian populations. Mortalities associated with these declines have often occurred during cooler seasons and at high elevations, suggesting that environmental temperature may be an important factor in disease emergence. We found that thermal environment affects the progress of the disease, and that housing frogs Litoria chloris at an environmental temperature of 37 degrees C for less than 16 h can clear them of the chytrid pathogen Batrachochytrium dendrobatidis. Our experiment demonstrated that elevated body temperatures similar to those experienced in behavioral fever and during normal thermoregulation can clear frogs of chytrid infection; therefore, variation in thermoregulatory opportunities and behaviors are likely to contribute to the differences in disease incidence observed among host species, populations, and regions. Although further refinement of the technique is needed to encompass various host species, appropriately applied thermal manipulations of amphibians and their enclosures may prove to be a safe and effective way of eliminating the fungal pathogen from captive amphibian populations and: preventing accidental spread of the pathogen when animals are translocated or released from captivity.

An overview of fungal infections.

The incidence of fungal infections is increasing at an alarming rate, presenting an enormous challenge to healthcare professionals. This increase is directly related to the growing population of immunocompromised individuals, resulting from changes in medical practice such as the use of intensive chemotherapy and immunosuppressive drugs. HIV and other diseases which cause immunosuppression have also contributed to this problem. Superficial and subcutaneous fungal infections affect the skin, keratinous tissues and mucous membranes. Included in this class are some of the most frequently occurring skin diseases, affecting millions of people worldwide. Although rarely life threatening, they can have debilitating effects on a person's quality of life and may in some circumstances spread to other individuals or become invasive. Most superficial and subcutaneous fungal infections are easily diagnosed and readily amenable to treatment. Systemic fungal infections may be caused by either an opportunistic organism that infects an at-risk host, or may be associated with a more invasive organism that is endemic to a specific geographical area. Systemic infections can be life threatening and are associated with high morbidity and mortality. Because diagnosis is difficult and the causative agent is often confirmed only at autopsy, the exact incidence of systemic infections is difficult to determine. The most frequently encountered pathogens are Candida albicans and Aspergillus spp. but other fungi such as non-albicans Candida spp. are increasingly important.

Experimental exposure of Canadian toads to Basidiobolus ranarum.

Experimental transmission of the fungus Basidiobolus ranarum was induced in two treatment groups of Canadian toads (Bufo hemiophrys) and caused a fatal mycotic dermatitis. Seven of 10 (70%) toads that had their ventral skin mildly abraded and exposed to B. ranarum developed hyperemia, and sloughing of their ventral skin and died. Toads with abraded ventral skin or exposure to infected skin also were affected statistically at a higher rate than those with abraded skin and exposure to pure cultures of B. ranarum inoculated into their water source. Of toads showing clinical disease, B. ranarum was identified by both impression smears and histology in all cases, but not from toads that appeared clinically healthy. The organism was cultured from 5 of 7 (71%) toads with clinical disease but not from any toad that appeared clinically healthy (n = 28). This study documents methods of experimental transmission of B. ranarum, an organism responsible for causing a mycotic dermatitis that is fatal to toads.

Causes of mortality of the Wyoming toad.

Wyoming toads (Bufo baxteri) that died from January 1989 to June 1996 were submitted to the Wyoming State Veterinary Laboratory (Laramie, Wyoming, USA) for postmortem evaluation. These consisted of 108 free-ranging toads and 170 animals from six captive populations. Ninety-seven (90%) of 108 free-ranging toad carcasses were submitted during September and October. From 1989 to 1992, 27 (77%) of 35 mortalities in the captive populations occurred in October, November, and December. From 1993 to 1996, mortality in captive toads occurred without a seasonal pattern and coincided with changes in hibernation protocols that no longer mimicked natural cycles. Cause of mortality was determined in 147 (53%) of the 278 cases. Mycotic dermatitis with secondary bacterial septicemia was the most frequent diagnosis in 104 (71%) of 147 toads. Basidiobolus ranarum was found by microscopic examination of skin sections in 100 (96%) of 104 of these mortalities. This fungus was isolated from 30 (56%) of 54 free-ranging and 24 (48%) of 50 captive toads. This research documents the causes of mortality for both free-ranging and captive endangered Wyoming toads over a 7 yr period.

Mortality of captive Canadian toads from Basidiobolus ranarum mycotic dermatitis.

Twenty-six adult free-ranging Canadian toads (Bufo hemiophrys) were collected from northeastern North Dakota (USA) during the last week of August 1994 and placed in captivity. During late December and January 1995, 21 Canadian toads died. Clinical signs included increased time sitting in water bowls, darkened dorsal skin, constant arching of their backs, and hyperemia and sloughing of ventral epidermis. The condition progressively worsened until death occurred within 5 to 7 days after onset of clinical disease. Mycotic dermatitis due to Basidiobolus ranarum was diagnosed in all toads and the fungus was isolated from 11 (52%) of 21 toads. Histology of the ventral skin and digits revealed numerous fungal spherules and occasional hyphae without significant inflammatory reaction. This condition clinically resembled red leg associated with Aeromonas hydrophila and many other bacterial organisms, and the diseases could be confused without appropriate diagnostic tests. This also is the first report of B. ranarum causing clinical disease in a toad species.

Cutaneous disseminated histoplasmosis in AIDS patients in south Florida.

BACKGROUND: Histoplasma capsulatum is a dimorphic pathogenic fungus endemic to the Mississippi and Ohio river valleys. In the immunocompetent it causes a self-limited disease, but in the immunocompromised may lead to disseminated disease (disseminated histoplasmosis (DH)). It is one of the opportunistic infections which defines the acquired immunodeficiency syndrome (AIDS) and is rarely encountered outside endemic regions. METHODS: Clinical, laboratory, and histologic information concerning seven patients with DH and AIDS in South Florida was recorded. RESULTS: We report seven cases of DH with mucocutaneous lesions in patients infected with the human immunodeficiency virus (HIV). All patients had markedly depressed CD4 counts of less than 40 cells/mm3, and only two had traveled to endemic areas. Two out of the seven patients were diagnosed with HIV/AIDS at the time DH was identified. All of our patients had mucocutaneous lesions at the time of diagnosis, which clinically presented as a generalized papular eruption, ulcers, and erythematous scaly plaques. CONCLUSIONS: Even in non-endemic regions, HIV-positive patients presenting with fever, chills, weight loss, hepatosplenomegaly, anemia, cough, lymphadenopathy, and mucocutaneous lesions should have an early skin biopsy specimen taken for mycologic tissue culture and histopathologic evaluation for disseminated fungal infections.

Cutaneous cryptococcosis in athymic and beige-athymic mice.

The dermotropism of Cryptococcus neoformans SLHA in congenitally athymic (nu/nu) and doubly immunodeficient beige-athymic (bg/bg-nu/nu) mice is described. Both bg/bg-nu/nu and nu/nu mice developed cutaneous cryptococcosis within 7 to 12 days following intravenous challenge with 10(4) encapsulated yeast cells. Macroscopically, cutaneous lesions appeared as small subcutaneous nodules without ulceration. Cryptococcal skin lesions were observed primarily on the flank of nu/nu mice, whereas skin lesions in bg/bg-nu/nu mice were distributed over the trunk, abdomen, and face. While bg/bg-nu/nu mice had four times as many macroscopic skin lesions as nu/nu mice on day 14 after intravenous challenge, the skin lesions in nu/nu mice were larger. Histopathology revealed large foci of encapsulated yeasts extending from the basement membrane of the epidermis through the dermis to the underlying musculature. Yeasts in these lesions evoked a minimal inflammatory response that consisted primarily of macrophages. Interestingly, yeast cells appeared to be degrading collagen bundles located in the dermis. The dermotropic strain used in this study produced gelatinase and other proteases in vitro. These results indicate that C. neoformans can be dermotropic in a T-cell-deficient host and that proteases may be a virulence factor(s).