Prevalence of fungal infections detected from biopsies and autopsies in the past 11 years at the University Hospital Joan XXIII in Tarragona, Spain

Infectious diseases caused by fungal pathogens have increased in the past 10 years. More than 300 pathogenic fungal species have been incriminated as the etiologic agents. We carried out a retrospective study (1994-2004) to evaluate the prevalence of mycoses at the University Hospital Joan XXIII (330 beds). This report found 0.24% of the studied cases (78,310 biopsies and 753 autopsies) were diagnosed as fungal infections (0.21% of the total studied biopsy and 4.25% of the whole autopsies). Skin and mucose were involved in 66% of cases, followed by other less affected anatomical areas. 61% of studied cases were caused by Candida spp (the most frequent in our environment), followed by Aspergillus spp (10%) and the Zygomycetes (5%). The most important underlying illness was obstructive chronic pulmonary disease followed by diabetes and AIDS. The incidence of mycoses increased with the patient's age, especially those patients in their 80s. Antifungal management improved the clinical outcome of the patient but predisposing factors are crucial for diagnosis. Systemic mycoses have poor prognosis with 91% of fatal outcome. Thus, it is important to perform a rapid diagnosis of the fungal infections a diagnostic area in which pathology could play a major role.     

Aspectos actuales de las enfermedades invasivas por hongos filamentosos

Invasive fungal infections have become a major cause of morbimortality in intensive care patients, persons suffering from cancer or immune deficiencies, and other diseases with impaired immunity. Candida albicans remains the most frequent fungal pathogen, but advances in the diagnosis, prevention and treatment of invasive candidiasis are leading to important etiological changes. Among the emerging invasive mycoses, are those caused by filamentous fungi, such as Aspergillus, Lomentospora/Scedosporium, Fusarium or the Mucorales. Invasive aspergillosis is difficult to diagnose, and although there are diagnostic tools available, their use is not widespread, and their effectiveness vary depending on the group of patients. Clinical suspicion in high-risk patients, radiological diagnosis and the use of biomarkers, such as 1,3-β-D-glucan and galactomannan, can be of great help. However, diagnostic resources are limited in other mycoses, but radiology, pathological studies and the microbiological diagnosis can be useful. The high mortality of these mycoses requires early empirical antifungal treatment in many cases. Voriconazole is the first choice for treatment of the majority of aspergillosis, scedosporiasis, fusariosis and other hyalohyphomycoses. The treatment of mucormycoses, Lomentospora prolificans infections or mycoses by dematiaceous fungi are more complicated. Amphotericin B is active against many mucoralean fungi, but the combination of two or more antifungal agents could be a therapeutic alternative in many amphotericin B-refractory mycoses. Current clinical challenges include improving the diagnosis and the treatment of these mycoses, along with improving the adequate prevention in patients at high risk of suffering from them.     

病理确诊深部真菌病45例分析

目的 探讨深部真菌病病理诊断的价值。方法 回顾性分析我院1995年1月-2004年12月期间,经病理确诊为深部真菌病45例患者的临床及病理资料,其中副鼻窦真菌感染14例;肺部真菌病19例;胃肠道真菌病4例;口腔真菌病2例,脑部真菌病2例,其他真菌病4例。结果 我院近5年来真菌病的确诊病例明显增多,且内脏及器官真菌病患者多合并基础性疾病,如血液病、肿瘤等。部分病例的致病菌根据病理确定有曲霉、念珠菌及隐球菌等。临床上主要采用手术结合氟康唑静滴的治疗方法。结论 我院经病理确诊的真菌病例呈上升趋势,病理组织学特点结合特殊染色可将大部分致病菌鉴定至属,治疗前最好进行培养鉴定至种。     

Serodiagnosis of Mycoses Using Recombinant Antigens

The early diagnosis of mycoses is important for the institution of an effective antifungal therapy. Detection of antibodies against crude antigenic extracts is one of the standard techniques for the diagnosis of most mycoses. However, while these crude antigenic extracts are relatively easy to obtain, they usually show low reproducibility and are not very specific, since antibodies from patients with different mycoses may show cross-reactivity. The application of molecular biology techniques to the study of fungal antigens has allowed the production of recombinant antigens that may help to solve these problems. The purpose of this review is to discuss the use of recombinant fungal antigens in the diagnosis of mycoses.     

Morphology of severe mycoses. Role of the pathologist in the diagnosis

Mycoses are diseases caused by fungi. To be regarded as pathogenic, a fungus has to be able to complete a number of steps in order to initiate infection. Although culture remains the gold standard to diagnose the causative agent, presumptive identification of these fungi in histologic slides is of great value because invasion is only demonstrated in tissue sections. When culture is not available, histopathologic examination may be the sole source of information about the nature of the infection. To make a diagnosis, the pathologist needs to be familiar with the morphologic appearance of the different types of fungi, and has also to be aware of the limitations in their identification. The purpose of this work is to review the current problems on this subject, specially referring to the most frequent severe mycoses of our environment.     

Aiming for a bull’s-eye: Targeting antifungals to fungi with dectin-decorated liposomes

Globally, there are several million individuals with life-threatening invasive fungal diseases such as candidiasis, aspergillosis, cryptococcosis, Pneumocystis pneumonia (PCP), and mucormycosis. The mortality rate for these diseases generally exceeds 40%. Annual medical costs to treat these invasive fungal diseases in the United States exceed several billion dollars. In addition to AIDS patients, the risks of invasive mycoses are increasingly found in immune-impaired individuals or in immunosuppressed patients following stem cell or organ transplant or implantation of medical devices. Current antifungal drug therapies are not meeting the challenge, because (1) at safe doses, they do not provide sufficient fungal clearance to prevent reemergence of infection; (2) most become toxic with extended use; (3) drug-resistant fungal isolates are emerging; and (4) only one new class of antifungal drugs has been approved for clinical use in the last 2 decades. DectiSomes represent a novel design of drug delivery to drastically increase drug efficacy. Antifungals packaged in liposomes are targeted specifically to where the pathogen is, through binding to the fungal cell walls or exopolysaccharide matrices using the carbohydrate recognition domains of pathogen receptors. Relative to untargeted liposomal drug, DectiSomes show order of magnitude increases in the binding to and killing of Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus in vitro and similarly improved efficacy in mouse models of pulmonary aspergillosis. DectiSomes have the potential to usher in a new antifungal drug treatment paradigm.     

Advances in combating fungal diseases: vaccines on the threshold

The dramatic increase in fungal diseases in recent years can be attributed to the increased aggressiveness of medical therapy and other human activities. Immunosuppressed patients are at risk of contracting fungal diseases in healthcare settings and from natural environments. Increased prescribing of antifungals has led to the emergence of resistant fungi, resulting in treatment challenges. These concerns, together with the elucidation of the mechanisms of protective immunity against fungal diseases, have renewed interest in the development of vaccines against the mycoses. Most research has used murine models of human disease and, as we review in this article, the knowledge gained from these studies has advanced to the point where the development of vaccines targeting human fungal pathogens is now a realistic and achievable goal.     

Identification of Fungal Pathogens by Visible Microarray System in Combination with Isothermal Gene Amplification

The increasing incidence of infectious diseases caused by fungi in immunocompromised patients has encouraged researchers to develop rapid and accurate diagnosis methods. Identification of the causative fungal species is critical in deciding the appropriate treatment, but it is not easy to get satisfactory results due to the difficulty of fungal cultivation and morphological identification from clinical samples. In this study, we established a microarray system that can identify 42 species from 24 genera of clinically important fungal pathogens by using a chemical color reaction in the detection process. The array uses the internal transcribed spacer region of the rRNA gene for identification of fungal DNA at the species level. The specificity of this array was tested against a total of 355 target and nontarget fungal species. The fungal detection was succeeded directly from 10³ CFU/ml for whole blood samples, and 50 fg DNA per 1 ml of serum samples indicating that the array system we established is sensitive to identify infecting fungi from clinical sample. Furthermore, we conducted isothermal amplification in place of PCR amplification and labeling. The successful identification with PCR-amplified as well as isothermally amplified target genes demonstrated that our microarray system is an efficient and robust method for identifying a variety of fungal species in a sample.     

New antifungal agents for the systemic mycoses

The azoles are the prominent broad spectrum oral antifungal agents in use or under clinical investigation for the systemic mycoses. This class of antifungal agents is represented by the marketed drug ketoconazole (Nizoral) and the experimental triazoles furthest along in clinical trials in the United States, itraconazole and fluconazole. Ketoconazole use is limited by its side effect profile and activity spectrum. Itraconazole appears to be better tolerated and less toxic to liver function, does not cause adrenal suppression and is more active against Aspergillus and Sporothrix schenckii. Fluconazole appears to be a highly promising agent due its highly favorable pharmacokinetic profile; it is water soluble, is well tolerated, is not metabolized to inactive constituents, it has a long half-life and, unlike the other azoles, high cerebrospinal fluid levels are readily attained for consideration in meningeal mycoses. It remains to be determined what place these new triazoles have in managing immunosuppressed patients including those with acquired immune deficiency syndrome known as AIDS. Other experimental antifungal agents, including ambruticin, amphotericin B methyl ester and saramycetin are also described. Sales figures are presented of drugs marketed in the United States for the systemic mycoses and reflect the growing problem of fungal diseases in the population.Presented as part of the Everett S. Beneke Symposium in Mycology, May 27, 1988.     

重要深部真菌病研究进展

近20年来,由于接受肿瘤化学治疗、细胞毒药物治疗的患者不断增多,器官移植和骨髓移植术广泛开展,深部真菌病的发病率和病死率急剧上升.而生物技术的进步和人们对真菌研究的深入,为临床提供了早期、特异的诊断方法和新型抗真菌药物.本文归纳了深部真菌病流行病学调查、真菌与宿主相互作用、深部真菌病诊断和治疗等方面的最新内容,这些研究...     

Immunology of fungal infections: lessons learned from animal models

The continuing AIDS epidemic coupled with increased usage of immunosuppressive drugs to prevent organ rejection or treat autoimmune diseases has resulted in an increase in individuals at risk for acquiring fungal diseases. These concerns highlight the need to elucidate mechanisms of inducing protective immune responses against fungal pathogens. Consequently, several experimental models of human mycoses have been developed to study these diseases. The availability of transgenic animal models allows for in-depth analysis of specific components, receptors, and signaling pathways that elicit protection against fungal diseases. This review focuses on recent advances in our understanding of immune responses to fungal infections gained using animal models.     

The pathology clinic – pathologists should see patients

S. Manek The pathology clinic – pathologists should see patients This invited review describes why and how a pathologist should talk to patients in order to enhance the patient care pathway. The pathologist–patient interaction should become a natural extension to multidisciplinary team decision making, and also become the forum in which patients are helped to understand important aspects of their conditions and the pathological basis for their treatment plans. There is a vast amount of information available through the internet and to digest this can be a difficult process for a patient who is already having to cope with a medical condition. The pathologist is often best placed to sieve through this information and offer the patient the relevant detail necessary to understand the condition and the management pathway. Pathologists can provide up‐to‐date, simple information about malignant and even certain significant benign conditions, and they can do this with the help of several pictorial tools. In this way, the pathologist becomes an even more active member of a clinical team and helps both clinicians and patients to deal with illnesses in a novel way hitherto not considered.     

The fungal cell wall as a target for the development of new antifungal therapies

In the past three decades invasive mycoses have globally emerged as a persistent source of healthcare-associated infections. The cell wall surrounding the fungal cell opposes the turgor pressure that otherwise could produce cell lysis. Thus, the cell wall is essential for maintaining fungal cell shape and integrity. Given that this structure is absent in host mammalian cells, it stands as an important target when developing selective compounds for the treatment of fungal infections. Consequently, treatment with echinocandins, a family of antifungal agents that specifically inhibits the biosynthesis of cell wall (1-3)β-D-glucan, has been established as an alternative and effective antifungal therapy. However, the existence of many pathogenic fungi resistant to single or multiple antifungal families, together with the limited arsenal of available antifungal compounds, critically affects the effectiveness of treatments against these life-threatening infections. Thus, new antifungal therapies are required. Here we review the fungal cell wall and its relevance in biotechnology as a target for the development of new antifungal compounds, disclosing the most promising cell wall inhibitors that are currently in experimental or clinical development for the treatment of some invasive mycoses.     

侵袭性真菌病的诊断：现状与展望

近二十年来,医学科学很多领域都取得重大进步。但全球范围内,侵袭性真菌病的发病率及死亡率却仍明显上升,严重威胁人类健康。侵袭性真菌病发病隐匿、临床表现不典型、治疗手段有限、病死率与致残率高,早期、特异的诊断对于改善预后意义重大。目前,以培养、病理为代表的形态学诊断方法虽有局限,但仍是侵袭性真菌病诊断的金标准;以G试验、GM试验、高分辨率CT为代表的新兴血清学及影像学诊断方法值得在临床大力推广;而以PCR技术为基础的核酸诊断技术方法前景光明,但其临床应用之路却仍任重而道远。联合使用并不断改良现有培养、病理等形态学诊断方法、血清学方法及先进影像学技术是提高侵袭性真菌病诊断水平的现实最佳途径。     

Present and future in the immunodiagnosis of the animal mycoses

The problems that exist in the clinical, microbiological, and histopathological diagnosis of animal mycoses establish the necessity to investigate immunological methodologies in the diagnosis of these diseases. In this way, it may be possible to develop easy and fast techniques, allowing early detection of the disease, and efficient therapy. In our laboratory we have developed an indirect ELISA methodology to the diagnosis of aspergillosis in dog, cat, cow, sheep and birds, and dermatophytoses in dog and cat. Our results suggest this kind of technique may be useful not only in the diagnosis of animal mycosis, but in important fields as the elucidation of the fungal pathogenicity or the elaboration of effective vaccines, and with the possible application in human medicine.     

Rôle du pathologiste dans la prise en charge et le diagnostic d’une infection osseuse

The diagnosis of a bone infection is sometimes made difficult when clinical signs and imaging are not typical. In these cases, the role of a pathologist is important since he makes the diagnosis and improves the management of the infection. The main histopathological features of a bone infection and its complications, as well as the involvement of a pathologist in this pathology, are described in this article.     

Environmental Isolates of Fungi from Aquarium Pools Housing Killer Whales (Orcinus orca)

Systemic mycoses in killer whales (Orcinus orca) are rare diseases, but have been reported. Two killer whales died by fungal infections at the Port of Nagoya Public Aquarium in Japan. In this study, the fungal flora of the pool environment at the aquarium was characterized. Alternaria spp., Aspergillus spp. (A. fumigatus, A. niger, A. versicolor), Fusarium spp. and Penicillium spp. were isolated from the air and the pool surroundings. The other isolates were identified as fungal species non-pathogenic for mammals. However, the species of fungi isolated from the environmental samples in this study were not the same as those isolated from the cases of disease in killer whales previously reported.     

A global view on fungal infections in humans and animals: opportunistic infections and microsporidioses

After cardiovascular diseases, infectious diseases are the second most common cause of death worldwide. Although these infections are caused mainly by viruses or bacteria, a systematically growing prevalence of human and animal opportunistic fungal infections is noticeable worldwide. More attention is being paid to this problem, especially due to the growing frequency of recalcitrant and recurrent mycoses. The latter are classically divided into superficial, which are the most common type, subcutaneous, and systemic. This work discusses opportunistic fungal pathogens without proven horizontal transmission between different animal species including humans and microsporidia as spore-forming unicellular parasites related to fungi; however, with a yet undetermined taxonomic position. The review also mentions aetiological agents, risk factors, epidemiology, geographical distribution, and finally symptoms characteristic for individual disease entities. This paper provides insight into fungal infections from a global perspective and simultaneously draws attention to emerging pathogens, whose prevalence is continuously increasing. Finally, this work also takes into consideration the correct nomenclature of fungal disease entities and the importance of secondary metabolites in the pathogenesis of fungal infections.     

Las micosis en Venezuela: casuística de los Grupos de Trabajo en Micología (1984-2010)

BackgroundIn 1984 the Venezuelan Work Groups in Mycology (VWGM) were created introducing an innovative approach to the study of the mycoses in Venezuela.AimTo study the occurrence of the mycoses in Venezuela.MethodsReview the reported cases of mycoses by the newsletter Boletín Informativo Las Micosis en Venezuela (VWGM) from 1984 to 2010.ResultsThe data collected showed 36,968 reported cases of superficial mycoses, 1,989 of deep systemic cases, and 822 of localized mycoses. Pityriasis dermatophytosis was the most common superficial infection, and paracoccidioidomycosis and histoplasmosis the most frequent deep systemic infection. Chromoblastomycosis was the most frequently diagnosed subcutaneous infection. The data provided showed the distribution by geographical area for each of the fungal infections studied, which may help to establish the endemic areas.DiscussionSuperficial mycosis is a public health problem due to its high morbidity and is probably responsible for some of the outbreaks in high-risk groups. Paracoccidioidomycosis and histoplasmosis were reported more often, which agrees with earlier reports prior to the formation of the VWGM. Cases of sporotrichosis and chromoblastomycosis in Venezuela can be considered unique due to the high number of cases. This study highlights the contribution of the VWGM to the behavior of the mycoses in Venezuela, its incidence, prevalence, and the recognition of these infections as a problem of public health importance. The VWGM should keep working in this endeavor, not only reporting new cases, but also unifying the clinical and epidemiological criteria, in order to properly monitor the evolving epidemiological changes reported in these types of infections.