Epidemiology of visceral mycoses in patients with acute leukemia and myelodysplastic syndrome: Analyzing the national autopsy database in Japan.

Visceral mycoses (VM) are a deadly common infection in patients with acute leukemia and myelodysplastic syndrome (MDS). We retrospectively analyzed the data from the centralized "Annual Report of Autopsy Cases in Japan" that archives the national autopsy cases since 1989. Among the total of 175,615 archived autopsy cases, 7183 cases (4.1%) were acute leukemia and MDS patients. While VM was only found in 7756 cases (4.4% in total cases), we found VM had a disproportionally high prevalence among acute leukemia and MDS patients: 1562 VM cases (21.7%) and nearly sixfold higher in prevalence. Aspergillus spp. was the most predominant causative agent (45.0%), and Candida spp. was the second (22.7%) among confirmed single pathogen involved cases. The prevalence of Candida spp. infection decreased about 50% due to the widely use of fluconazole prophylaxis, which may skew toward doubling of the Mucormycetes incidence compared to 30 years ago. Complicated fungal infection (> one pathogen) was 11.0% in acute leukemia and MDS in 2015. It was 14.7 times higher than in other populations. Among 937 patients who received allogeneic hematopoietic cell transplantation (HCT), the prevalence of VM was 28.3% and 23.3% with GVHD. Aspergillus spp. was less prevalent, but Candida spp. was more associated with GVHD. Its prevalence remains stable. Although Aspergillus spp. was the primary causative agent, non-albicans Candida spp. was increasing as a breakthrough infection especially in GVHD cases. Complicated pathogen cases were more common in acute leukemia and MDS.

Gastrointestinal manifestations of Talaromyces marneffei infection in an HIV-infected patient rapidly verified by metagenomic next-generation sequencing: a case report.

BACKGROUND: The manifestation of Talaromyces marneffei infection in some HIV-infected patients may be atypical. Cases with gastrointestinal involvement have rarely been reported. It is hard to make a diagnosis when patients are lacking the characteristic rash and positive blood culture. CASE PRESENTATION: Here, we described a patient living with HIV who complained of fever and abdominal pain, and was rapidly diagnosed with Talaromyces marneffei infection by metagenomic next-generation sequencing (mNGS) using formalin-fixation and paraffin-embedded (FFPE) samples of omentum majus tissue. We also reviewed reported related cases. CONCLUSIONS: Talaromyces marneffei is an unusual cause of clinical presentations involving obvious abdominal pain and lower gastrointestinal bleeding, but can be included in the differential diagnosis. As an important diagnostic tool, the significance of mNGS using FFPE samples of lesions provides a more targeted diagnosis.

Testing the febrile response of snakes inoculated with Ophidiomyces ophidiicola, the causative agent of snake fungal disease.

Snake Fungal Disease (SFD) negatively impacts wild snake populations in the eastern United States and Europe. Ophidiomyces ophidiicola causes SFD and manifests clinically by the formation of heterophilic granulomas around the mouth and eyes, weight loss, impaired vision, and sometimes death. Field observations have documented early seasonal basking behaviors in severely infected snakes, potentially suggesting induction of a behavioral febrile response to combat the mycosis. This study tested the hypothesis that snakes inoculated with Ophidiomyces ophidiicola would seek elevated basking temperatures to control body temperature and behaviorally induce a febrile response. Eastern ribbon snakes (Thamnophis saurita, n = 29) were experimentally or sham inoculated with O. ophidiicola. Seven days after inoculation, snakes were tested on a thermal gradient and the internal body temperature and substrate temperature of each snake was recorded over time. Quantitative PCR was used when snakes arrived, during pre-inoculation, and post-inoculation to test snakes for the presence of O. ophidiicola. Some snakes arrived with O. ophidiicola and were subsequently inoculated, allowing for an assessment of secondary exposure effects. Snake thermoregulatory behavior was compared between 1) O. ophidiicola inoculated vs. sham inoculated treatments, 2) infected vs. disease negative groups, and 3) disease naïve vs. pre-exposed immune response categories. Neither internal nor substrate temperatures differed among initially prescribed, and qPCR recovered disease states, although infected snakes tended to reach a preferred body temperature faster than disease negative snakes. Snakes experiencing their first exposure (disease naïve) sought higher substrate temperatures than snakes experiencing their second exposure (pre-exposed). Here, we recover no evidence for behaviorally induced fever in snakes with SFD but do elucidate a febrile immune response associated with secondary exposure.

Clinical pattern of fungal balls in the paranasal sinuses: our experience with 70 patients.

PURPOSE: Many physicians recommend endoscopic sinus surgery (ESS) even when an asymptomatic paranasal sinus (PNS) fungal ball is detected incidentally. The aim of this study was to investigate the natural behavior of PNS fungal balls via sinus imaging techniques. METHODS: A follow-up study of 74 pathologically confirmed fungus balls was conducted in 70 patients who underwent multiple head and neck computed tomography (CT) scans or magnetic resonance imaging (MRI). We investigated the changes in symptoms and lesion size, as well as any new occurrences. RESULTS: Of the 74 fungus balls detected in 70 patients, we observed the renewed formation of a fungal ball in 21 patients, which was not present on initial imaging conducted over a period of 2-162 months. The fungal ball was already present in 53 patients on the initial screening, and the longest follow-up was 197 months (range 1-197 months). Of these 53 lesions, 29 lesions showed an increase in size (29/53, 54.7%), whereas 12 lesions were not associated with any clinical symptoms (12/53, 22.6%). In the 21 newly formed fungal balls, further development was observed in 10 lesions, with 4 lesions showing an increase in size. Thus, size increment occurred in 33 of the 57 fungus balls. CONCLUSIONS: The fungal balls can exist without local tissue invasion for up to 17 years and new formation of the fungal balls was observed even within 2 months, especially when accompanied by initial clinical symptoms of sinusitis.

Mechanisms and disease relevance of neutrophil extracellular trap formation.

While the microscopic appearance of neutrophil extracellular traps (NETs) has fascinated basic researchers since its discovery, the (patho)physiological mechanisms triggering NET release, the disease relevance and clinical translatability of this unconventional cellular mechanism remained poorly understood. Here, we summarize and discuss current concepts of the mechanisms and disease relevance of NET formation.

A pathogenic skin fungus and sloughing exacerbate cutaneous water loss in amphibians.

Batrachochytrium dendrobatidis (Bd) is a pathogenic fungus that causes the cutaneous, infectious disease chytridiomycosis and has been implicated in population declines of numerous anuran species worldwide. Proximate cause of death by chytridiomycosis is asystolic cardiac arrest as a consequence of severe disruption to electrolyte balance. Animals heavily infected with Bd also experience a disruption to their skin sloughing regime, indicating that core functions of the skin, such as water retention, may be severely impacted. This study examined how skin sloughing, body size and Bd infection interact to influence water loss rates in five Australian frog species: Litoria caerulea, Limnodynastes peronii, Lechriodus fletcheri, Limnodynastes tasmaniensis and Platyplectrum ornatum Rates of water loss more than doubled during sloughing in L.caerulea During active periods across all species, water loss rates were on average 232% higher in Bd infected frogs than in uninfected frogs. This indicates that dehydration stress may be a significant factor contributing to the morbidity of severely Bd infected anurans, a symptom that is then exacerbated by an increased rate of sloughing. When taking size into account, smaller and/or juvenile anurans may be more at risk from dehydration due to Bd infection, as they lose a greater amount of water and slough more frequently than adults. This may in part explain the higher mortality rates typical for small and juvenile frogs infected with Bd Understanding how Bd affects the core functions of the skin, including rates of water loss, can improve our predictions of disease outcome in amphibians.

Necrotizing Microascus tracheobronchitis in a bilateral lung transplant recipient.

Invasive fungal infections are a major cause of mortality among solid organ transplant recipients. Scopulariopsis species and their teleomorph Microascus are molds found in soil and decaying organic matter. We report here the case of a woman who underwent bilateral lung transplantation for severe emphysema. On day 25 after transplantation, endobronchial green-black lesions were detected during routine endoscopy. Endobronchial swabs, biopsies, and bronchoalveolar lavage samples were positive for Microascus cirrosus. This fungal infection developed despite voriconazole given for previous persistent invasive aspergillosis. Treatment consisted of a combination of antifungal medication (voriconazole, terbinafine, amphotericin B, and caspofungin) and endoscopic resection of necrosed bronchial mucosa. A favorable clinical outcome was achieved after 7 weeks of treatment. Seven cases of Scopulariopsis/Microascus infection have been previously described in solid organ transplant recipients. Only two survived after treatment with an antifungal combination therapy including echinocandins, posaconazole, and terbinafine. In immunocompromised patients, infection by Microascus species is a rare but life-threatening event because of innate resistance to most common antifungal drugs. Our patient was successfully cured by combined therapy including intravenous voriconazole and caspofungin, oral terbinafine, and inhaled voriconazole and amphotericin B administered for 7 weeks in association with iterative endoscopic debridement to reduce fungal inoculum.

Swim bladder mycosis in pretty tetra (Hemigrammus pulcher) caused by Exophiala pisciphila and Phaeophleospora hymenocallidicola, and experimental verification of pathogenicity.

Spontaneous invasive and chronic disseminated mycosis affected Hemigrammus pulcher kept in a public aquarium, and infection was manifested by inappetence, exophthalmia, erratic swimming, eroded scales, anaemia of the gills and abdominal distension. Internally, there was a grossly swollen swim bladder with a thickened wall filled with a dark mass. The body cavities contained a clear, light amber fluid and a swollen intestine which was full of a watery fluid containing small gas bubbles. Histopathology revealed a granulomatous inflammatory response with fungal hyphae in the lumen and wall of the swim bladder, hepatopancreas, spleen and kidneys with signs of nephrohydrosis. Exophiala pisciphila and Phaeophleospora hymenocallidicola were isolated from the swim bladder, abdominal cavity and gastrointestinal tract. The exogenous source of infection was probably the ample wooden decoration and plants inside the aquarium. Koch's postulates were fulfilled by re-isolation of both fungal species from fish artificially infected under laboratory conditions. As P. hymenocallidicola is less capable of defence against phagocytosis, E. pisciphila probably played a major role. Severe clinical manifestations with 100% mortality developed in two fish species infected by E. pisciphila. A significant increase in the plasma levels of amino acids was observed as a result of the activation of proteolysis.

[The role of microbiota in chronic pharyngitis]. / Rol' mikobioty pri khronicheskim faringite.

This article describes the modern approaches to the diagnostics and treatment of fungoid conditions of the pharynx with special reference to the main methods for the detection of pharyngomycosis and its clinical manifestations based on the results of analysis of the investigations carried out during the period from 2012 till 2016. Among the 3,465 patients presenting with chronic inflammatory pathology of the pharynx who sought medical advice and treatment at the clinical departments of the Institute, 861 ones (25%) were found to have mycotic lesions of the pharynx. Erythematous (atrophic) chronic pharyngitis was the predominant form of the disease documented in 2,059 patients whereas the remaining 1, 406 ones presented with the hypertrophic forms. The fungal infection was diagnosed in 403 (19,5%) patients with erythematous atrophic chronic pharyngitis in comparison with 458 (32,5%) patients suffering from the hypertrophic forms of this pathology including pseudomembranous, hyperplastic (granulomatous), and erosive-ulcerative ones. The principal pathogenic agents responsible for the development of fungal pharyngitis in our patients were fungi of the genus Candida that accounted for 97 - 99% of all the cases of this disease. The currently available modalities for the treatment of pharyngomycosis are described.

[The treatment of laryngomycosis]. / Lechenie laringomikoza.

The objective of the present study was to elaborate the therapeutic algorithm for the treatment of laryngomycosis. We have examined a total of 430 patients suffering from chronic laryngitis including 100 ones (23.2%) having the fungal flora. Mycosis was diagnosed by the microscopic study of the stained preparations with the application of various techniques; moreover, cultivation in elective nutrient media was used. The yeast-like fungi of the genus Candida were identified in 98 (98%) and mold fungi of the genus Aspergillus in the remaining 2 (2%) patients. All these 100 patients were given the antifungal treatment. 98 of them presenting with candidal laryngitis were allocated to three groups. Group A was comprised of 33 patients who received the local treatment alone, group B contained 31 patients given only systemic therapy, and group C included 34 patients undergoing the combined treatment with the use of the medications possessed of both the local and systemic actions. The best clinical results were obtained in the patients of the latter group in which the therapeutic efficiency proved to be as high as 79.4%. It is concluded that all the patients suffering from laryngomycosis are in need of the combined treatment designed to eradicate the causative agent, restore the vocal function, and achieve the stable remission of the chronic inflammatory process in the larynx. The combined treatment with the antimycotic medications exhibiting both the general systemic and local activities during 3 weeks appears to be the optimal therapeutic modality for the management of laryngomycosis. Of special importance is the dynamic follow-up of the treated patients including the control examinations in the course of the treatment (days 7, 14, and 21) to be followed by the mycological study after the termination of therapy and its repetition every 3 months during the subsequent period.

Biofilm Exopolysaccharides of Pathogenic Fungi: Lessons from Bacteria.

Exopolysaccharides play an important structural and functional role in the development and maintenance of microbial biofilms. Although the majority of research to date has focused on the exopolysaccharide systems of biofilm-forming bacteria, recent studies have demonstrated that medically relevant fungi such as Candida albicans and Aspergillus fumigatus also form biofilms during infection. These fungal biofilms share many similarities with those of bacteria, including the presence of secreted exopolysaccharides as core components of the extracellular matrix. This review will highlight our current understanding of fungal biofilm exopolysaccharides, as well as the parallels that can be drawn with those of their bacterial counterparts.

Surgical and pathogenetic considerations of frontal sinus fungus ball.

Fungus ball (FB) is an non-invasive form of mycosis, that generally affects immunocompetent and non-atopic subjects. Involvement of the frontal sinus is extremely rare. We report two cases with frontal sinus fungus ball that underwent endoscopic endonasal frontal Draf type IIb or III sinusotomy with complete removal of the cheesy clay-like material. There were no intra-operative or postoperative complications, and no recurrence of disease was evident during the follow-up of 51 and 26 months, respectively. The Draf type IIb or type III frontal sinusotomy seems to be highly effective for the treatment of frontal sinus FB and can represent a valid alternative to the traditional external approaches.

Isolated sphenoid sinus fungus ball: a retrospective study conducted at a tertiary care referral center in Korea.

Fungus ball (FB) is the most common form of extramucosal fungal rhinosinusitis involving one or more paranasal sinuses. The sphenoid sinus is an uncommon site of this disease. Here, we present our 20-year experience of managing isolated sphenoid sinus FB (SSFB). We retrospectively reviewed a series of 47 cases of isolated SSFB encountered between 1996 and 2015 with reference to the chronological incidence, demographics, clinical features, radiological findings, treatment modalities, and outcome. Recently, the number of patients with isolated SSFB has increased markedly. The mean age of the patients in this study was 63.1 years (range 26-84 years), and there was significant female predominance. The most common symptom was headache (72.3%), which was localised in various regions. On the other hand, nasal symptoms presented at a relatively low rate. On computed tomography, the most common findings were total opacification, calcification, and sclerosis of the bony walls. There was no significant difference in the presence of SSFB between the ipsilateral and contralateral sides of the nasal septal deviation and concha bullosa. Magnetic resonance imaging demonstrated an isointensity on T1-weighted images and marked hypointensity on T2-weighted images. Treatment consisted of endonasal endoscopic sphenoidotomy with complete removal of the FB. The prognosis was good, with no recurrence after a mean follow-up of 13.2 months. Isolated SSFB is a rare disease, but its prevalence is increasing. Although the clinical presentation is usually vague and nonspecific, SSFB should be considered in patients with unexplained headache, especially in elderly women. Endoscopic sphenoidotomy is a reliable treatment with low morbidity and recurrence rates.

[The prevalence of the fungal flora in association with chronic inflammatory pathology of the larynx]. / Rasprostranennost' gribkovoi flory pri khronicheskoi vospalitel'noi patologii gortani.

The present article was designed to analyze the prevalence and clinical features of laryngomycosis associated with chronic inflammatory diseases of the larynx. We examined 430 patients suffering from chronic pharyngitis and found the fungal flora in 100 (23.2%) of them. Diagnostics of the fungal infection was performed by the microscopic study of the stained preparations (including the Gram method, Romanovskiy-Giemsa and fluorescent microscopy). The sowing on elective nutrient media was used. The study revealed the presence of yeast fungi (Candida) in 98 patients (98%) and mold fungi (Aspergillus) in the remaining two (2%). The hyperplastic form of fungal pharyngitis was diagnosed in 55% of the patients. We have identified the following predisposing factors for fungal laryngitis: the gastroesophageal reflux disease in 56% of the patients, smoking in 50%, the long-term use of the removable dentures with the inadequate care for them in 30%, and the consistent use of inhaled corticosteroids in 27%. Hyperglycemia was documented in 6% and the history of long-term treatment with antibiotics in in 10% of the patients. The scheme for the combined antifungal therapy has been developed. Its practical application allowed to achieve the eradication of the fungal flora and to improve the clinical course of chronic laryngitis in 75% of the patients.

Enhanced call effort in Japanese tree frogs infected by amphibian chytrid fungus.

Some amphibians have evolved resistance to the devastating disease chytridiomycosis, associated with global population declines, but immune defences can be costly. We recorded advertisement calls of male Japanese tree frogs (Hyla japonica) in the field. We then assessed whether individuals were infected by Batrachochytrium dendrobatidis (Bd), the causal agent of the disease. This allowed us to analyse call properties of males as a function of their infection status. Infected males called more rapidly and produced longer calls than uninfected males. This enhanced call effort may reflect pathogen manipulation of host behaviour to foster disease transmission. Alternatively, increased calling may have resulted from selection on infected males to reproduce earlier because of their shortened expected lifespan. Our results raise the possibility that sublethal effects of Bd alter amphibian life histories, which contributes to long-term population declines.

A cross sectional analysis of a case-control study about quality of life in CRS in the UK; a comparison between CRS subtypes.

BACKGROUND: The Sinonasal Outcome Test (SNOT-22) has been used as a patient reported outcome measure to grade symptom severity before and after treatment for chronic rhinosinusitis (CRS). METHODOLOGY: This analysis uses data from the CRS Epidemiology Study (CRES). The overarching aim of CRES was to determine factors that influence the onset and severity of CRS. A study-specific questionnaire including SNOT-22 was distributed to patients with CRS attending ENT clinics across 30 centres in the United Kingdom. The aim of this analysis was to compare SNOT-22 scores between those with different types of CRS to determine any differences present in the total score or the subdomains and to assess whether any differences varied according to gender. RESULTS: There were a total of 1249 CRS participants in the following subgroups: CRS without nasal polyps (CRSsNPs) (n=553), CRS with nasal polyps (CRSwNPs) (n=651), allergic fungal rhinosinusitis (AFRS) (n=45). Since there were differing gender ratios in each subgroup, males and females were analysed separately. The mean and standard deviation for SNOT-22 was: males CRSsNP 41.1 (21.0), CRSwNP 41.7 (20.5); females CRSsNP 49.6 (19.7), CRSwNP 49.5 (22.9). In the nasal domain, those with CRSwNP scored more highly than those with CRSsNP; for males 18.1 (8.1) vs. 15.9 (7.9); for females 19.6 (8.0) vs 16.7 (7.5). CONCLUSIONS: Patients with CRSwNPs report higher symptom scores in the nasal domain of SNOT-22 than those with CRSsNPs with women in both subgroups reporting higher total scores than men.

An unusual pathogen in ambulatory care: two cases of Scedosporium soft tissue infections presenting as "unresponsive cellulitis".

Soft tissue infections with Scedosporium spp. are an uncommon but serious and emerging cause of infection in immunocompromised patients. Acute Medical Units (AMUs) in the UK are increasingly managing patients with cellulitis in an outpatient setting, therefore acute physicians should be aware of some of the more uncommon causes of soft tissue infection, particularly in patients not responding to initial antibiotic therapy. We present two cases of Scedosporium presenting to the AMU as cellulitis not responding to initial antibiotic therapy and outline the assessment and management of this important condition.

Temperature variability and moisture synergistically interact to exacerbate an epizootic disease.

Climate change is altering global patterns of precipitation and temperature variability, with implications for parasitic diseases of humans and wildlife. A recent study confirmed predictions that increased temperature variability could exacerbate disease, because of lags in host acclimation following temperature shifts. However, the generality of these host acclimation effects and the potential for them to interact with other factors have yet to be tested. Here, we report similar effects of host thermal acclimation (constant versus shifted temperatures) on chytridiomycosis in red-spotted newts (Notophthalmus viridescens). Batrachochytrium dendrobatidis (Bd) growth on newts was greater following a shift to a new temperature, relative to newts already acclimated to this temperature (15°C versus 25°C). However, these acclimation effects depended on soil moisture (10, 16 and 21% water) and were only observed at the highest moisture level, which induced greatly increased Bd growth and infection-induced mortality. Acclimation effects were also greater following a decrease rather than an increase in temperature. The results are consistent with previous findings that chytridiomycosis is associated with precipitation, lower temperatures and increased temperature variability. This study highlights host acclimation as a potentially general mediator of climate-disease interactions, and the need to account for context-dependencies when testing for acclimation effects on disease.

Interruption to cutaneous gas exchange is not a likely mechanism of WNS-associated death in bats.

Pseudogymnoascus destructans is the causative fungal agent of white-nose syndrome (WNS), an emerging fungal-borne epizootic. WNS is responsible for a catastrophic decline of hibernating bats in North America, yet we have limited understanding of the physiological interactions between pathogen and host. Pseudogymnoascus destructans severely damages wings and tail membranes, by causing dryness that leads to whole sections crumbling off. Four possible mechanisms have been proposed by which infection could lead to dehydration; in this study, we tested one: P. destructans infection could cause disruption to passive gas-exchange pathways across the wing membranes, thereby causing a compensatory increase in water-intensive pulmonary respiration. We hypothesized that total evaporative water loss would be greater when passive gas exchange was inhibited. We found that bats did not lose more water when passive pathways were blocked. This study provides evidence against the proposed proximal mechanism that disruption to passive gas exchange causes dehydration and death to WNS-infected bats.