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Abstract
The endemic mycoses are restricted geographically based on environmental and other factors that favor the growth of these organisms in the soil. Histoplasmosis and blastomycosis mostly afflict patients in the Mississippi and Ohio River Valleys whereas coccidioidomycosis occurs primarily in the dessert south-west United States. Cryptococcosis also may present as pulmonary disease, particularly in persons with cellular immune impairment. These mycoses are increasing in importance as causes for opportunistic disease in immunocompromised patients, especially those with acquired immune deficiency syndrome (AIDS). Aspergillus is a common cause of serious invasive fungal infection in granulocytopenic patients, and may cause lung infection in persons with pre-existing pulmonary diseases or atopy. Infections with less virulent fungi, such as Trichosporon, Fusarium, Alternaria, Pseudallescheria, and dematiaceous fungi, are being recognized more frequently. The lung is the portal of entry for most of these pathogens, and often is prominently involved in the clinical syndrome. This article focuses on the recognition, diagnosis, and management of these important pulmonary mycoses.
... Antigen assay, a non-culture-based method, is widely used in hospitals and mainly includes the galactomannan test (White et al. 2015;Sehgal et al. 2019) and beta-D-glucan test (Badiee et al. 2012;Urabe et al. 2017); however, this technique can underestimate the positive rate and is poor in independent quality control. Pulmonary histopathology is an invasive method often used when other conventional diagnostic methods fail to produce clear results (Wheat et al. 2002). Recently, PCR, including conventional, nested (Hoenigl et al. 2014), and quantitative PCR (Guegan et al. 2018;Springer et al. 2018;Xu et al. 2020), have been used for the detection of pulmonary fungal infection. ...
Pulmonary invasive fungal infection in immunocompromised hosts is difficult to diagnose, and current tools for diagnosis or monitoring of response to antifungal treatments have inherent limitations. Droplet digital PCR (ddPCR) has emerged as a promising tool for pulmonary pathogen detection with high sensitivity. This study presents a novel ddPCR panel for rapid and sensitive identification of pulmonary fungal pathogens. First, a ddPCR method for detecting three fungal genera, including Pneumocystis, Aspergillus, and Cryptococcus, was established and evaluated. Then, the clinical validation performance of ddPCR was compared with that of qPCR using 170 specimens, and the 6 specimens with inconsistent results were further verified by metagenomics next-generation sequencing, which yielded results consistent with the ddPCR findings. Finally, the area under the ROC curve (AUC) was used to evaluate the efficiency of ddPCR. While the qPCR identified 16 (9.41%) cases of Aspergillus and 6 (3.53%) cases of Pneumocystis, ddPCR detected 20 (11.76%) Aspergillus cases and 8 (4.71%) Pneumocystis cases. The AUC for Aspergillus, Cryptococcus, and Pneumocystis was 0.974, 0.998, and 0.975, respectively. These findings demonstrated that the ddPCR assay is a highly sensitive method for identifying pathogens responsible for invasive fungal pulmonary infections, and is a promising tool for early diagnosis.
... Pulmonary histopathology is diagnosed by obtaining pathological specimens through percutaneous lung puncture, bronchoscopy lung biopsy or surgical lung biopsy. Therefore, it is an invasive method and often brings many pains to the patients [5]. Medical imaging techniques are also used for diagnosing pulmonary cryptococcal infection, but the radiographic appearances are often non-specific, which can easily be misdiagnosed as primary lung cancer, metastatic lung cancer, tuberculosis and other diseases [6]. ...
Cryptococcus neoformans (C. neoformans) is a causative agent for acute pulmonary infection, which can further develop to lethal meningoencephalitis if untreated. The meningoencephalitis infections can be prevented, if timely treatment on pulmonary cryptococcal infection can be implemented based on its early diagnosis and accurate assessment. In this study, blood serum surface-enhanced Raman spectroscopy (SERS) method was proposed. The serum SERS measurements were collected from the mice infected with C. neoformans and the healthy mice, in which the infected mice were further divided into four subgroups according to the duration of infection. Based on those SRES measurements, biochemical differences were analyzed among those different groups to investigate the potential biomarkers for identifying and assessing the pulmonary C. neoformans infection. Furthermore, partial least square (PLS) analysis followed by linear discriminant analysis (LDA) model was employed to identify pulmonary cryptococcal infection and to assess the degrees of infection with the accuracies of 96.7% and 85.3%, respectively. Therefore, our study has demonstrated the great clinical potential of using serum SERS technique for an accurate identification and assessment of pulmonary cryptococcal infection.
In recent years, there has been a lot of interest in using nanotechnology in medicine to diagnose and cure various infectious diseases. Although the precise mechanism of action is frequently challenged, many nanosized materials have been extensively explored for this purpose, using their innately unique features. Their functionality has also been enhanced by the addition of various coatings, such as those that increase chemical stability and stealth properties or contain targeting agents that lessen off-target effects while producing effective "smart" nanoplatforms for the early detection, treatment, and possibly resolution of diseases.
This book aims to compile research and review articles that concentrate on the synthesis, characterization, and applications of nanomaterials, such as nanoparticles, with a focus on investigating novel ways to improve their properties and create new efficient diagnostic, therapeutic, or theranostic approaches with a clear understanding of how they work.
Fungal infections have become crucial factors that threaten the prognosis and survival of blood disease patients. Here, we aim to analyze the epidemiological characteristics and early and advanced CT (computed tomography) manifestations of patients with invasive pulmonary fungal infections secondary to blood system diseases. 65 hospitalized patients from October 2018 to October 2020 with invasive pulmonary fungal infections secondary to blood diseases were enrolled. Blood diseases were recorded according to clinical and imaging data, and the serum galactomannan test (GM test) was conducted. Two senior radiologists analyzed the CT data and recorded the distribution of the lesions and CT signs. We analyzed and counted the first chest CT scan images of patients with nodule/mass type secondary to hematological diseases and invasive pulmonary fungal infection. The first CT nodules or mass-type lesions were statistically significant in nodule size, the number of lesions, distribution, and accompanying signs. Pulmonary fungal infection was common in both lungs during 7-day, 14-day, and 30-day follow-up CT. We also found that the nodular mass type was the main manifestation in the positive group of the GM test. Both the positive group and the negative group had the highest incidence of nodules. The incidence of air crescent signs in nodules or mass lesions in the positive group was higher than in the negative group, and the difference was statistically significant. To conclude, follow-up CT signs after antifungal treatment were highly sensitive to the early diagnosis of hematological diseases and secondary invasive pulmonary Eumycetes infection, which could be used for clinical treatment to provide help. GM test results were also related to CT manifestations such as air crescent sign, cavity, and halo sign.
Specific texts on infectious diseases and those in textbooks on pulmonary pathology commonly approach the subject of infection in the lung from an etiological microbiological perspective, listing infectious agents by taxonomy followed by associated pathology. However, in practice one is faced with a specimen in which a reaction pattern is seen (usually of inflammatory nature) which may be indicative of a specific type of infection. In these circumstances an approach leading from reaction pattern to specific microbiological diagnosis is required. This approach will form the basis of this review. General aspects are covered without exhaustive discussion of specific microbiology. For more detailed discussion of specific entities the reader is referred to the excellent textbooks on pulmonary pathology and those on pathology of infectious diseases. The reaction patterns described here are combinations of gross pathology and cellular reactions. The breakdown of these patterns is somewhat arbitrary and artificial. In many cases the pattern will not be absolutely typical and many overlapping features will be present in individual cases.
Lung diseases caused by microbial infections affect hundreds of millions of children and adults throughout the world. In Western populations, the treatment of lung infections is a primary driver of antibiotic resistance. Traditional therapeutic strategies have been based on the premise that the healthy lung is sterile and that infections grow in a pristine environment. As a consequence, rapid advances in our understanding of the composition of the microbiota of the skin and bowel have not yet been matched by studies of the respiratory tree. The recognition that the lungs are as populated with microorganisms as other mucosal surfaces provides the opportunity to reconsider the mechanisms and management of lung infections. Molecular analyses of the lung microbiota are revealing profound adverse responses to widespread antibiotic use, urbanization and globalization. This Opinion article proposes how technologies and concepts flowing from the Human Microbiome Project can transform the diagnosis and treatment of common lung diseases.
Specific texts on infectious diseases and those in textbooks on pulmonary pathology commonly approach the subject of infection in the lung from an etiological microbiological perspective, listing infectious agents by taxonomy followed by associated pathology. However, in practice one is faced with a specimen in which a reaction pattern is seen (usually of inflammatory nature) which may be indicative of a specific type of infection. In these circumstances an approach leading from reaction pattern to specific microbiological diagnosis is required. This approach will form the basis of this review. General aspects are covered without exhaustive discussion of specific microbiology. For more detailed discussion of specific entities the reader is referred to the excellent textbooks on pulmonary pathology and those on pathology of infectious diseases. The reaction patterns described here are combinations of gross pathology and cellular reactions. The breakdown of these patterns is somewhat arbitrary and artificial. In many cases the pattern will not be absolutely typical and many overlapping features will be present in individual cases.
The objective of this study was to clarify the antifungal efficiency of silver nanoparticles (SNPs) against one of pathogenic yeast ,Cryptococcus neoformans that causes pulmonary cryptococcosis .Nostril experimental exposure of male albino rats to a dose of untreated yeast suspension and adose of treated yeast with SNPs , amphoterin B ,and SNPs combined with amphoterine B (gi,gii,giii and giv) respectively .Results show that SNPs have high antifungal activity against Cryptococcus neoformans ,this is indicated by results of histological effects which show that the histological changes that emerged in lung tissues in control group (gi) had eased or disappeared and these tissues began to rectore natural forms when treated with SNPs and antifungal (gi,giii,giv).Also,there are a significant increase in IFN- g levels and (WBC , RBC ,PLT) count in control group (gi) compared with treated groups (gii,giii,giv), This confirms the effectiveness of inhibitory of SNPs. Key words: Cryptococcus , SNPs , pulmonary cryptococcosis , nanoparticles,antifungal effect
The antifungal effects of ambroxol (Amb; the metabolite VIII of bromhexine) against Cryptococcus planktonic cells and mature biofilms were investigated in this study. Amb showed antifungal activity against planktonic cells and mature biofilms. Disk diffusion test similarly showed antifungal profile for planktonic cells. Furthermore, Amb was found to be synergetic with fluconazole against planktonic cells and reduced the adherence of cells to polystyrene. Our results suggest that Amb can inhibit cryptococcal cells and biofilms, indicating its potential role in the prevention and treatment of cryptococcosis.
Infective endocarditis, even if adequately treated, can be associated with significant morbidity and mortality. Clinical outcomes are influenced by multiple factors which include valve characteristics, host factors, causative organisms, development of intracardiac, or systemic complications and the therapeutic options.
This chapter will provide an overview of current treatment regimens for infective endocarditis.
The incidence of severe fungal infections has increased worldwide and represents a serious threat, especially among immunocompromised and critically ill patients. Most common pulmonary fungal infections include aspergillosis, cryptococcosis, and Pneumocystis jiroveci pneumonia. Among nosocomial bloodstream infections, Candida spp. is the most common isolated fungus. Mortality rates up to 60% in critically ill patients with Candida infections and 90% in hematological patients with invasive aspergillosis are reported. Furthermore, fungal infections contribute to high morbidity and prolonged hospitalizations. Since standard cultural methods can show low sensitivity or provide delayed responses, new non-culture-dependent methods such as galactomannan β-D-glucan are now available. Novel antifungal compounds (e.g., amphotericin B lipid formulations, last-generation azoles, and echinocandins) have been introduced in the recent years. Nevertheless, despite new advances the appropriate use of diagnostic assays along with a thorough therapeutic management remain the key to ensure an early appropriate targeted treatment that represents the crucial factor to attain a successful approach to severe fungal infections.
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Pulmonary cryptococcosis is likely to be misdiagnosed due to relatively non-specific clinical and radiological features. It is more frequently associated with immuno-suppressed conditions especially acquired immuno-deficiency syndrome (AIDS) and pulmonary tuberculosis (PTB). Four cases of pulmonary cryptococcosis were diagnosed over a period of eleven years. All patients in this case series were human immune-deficiency virus (HIV)-negative. The predisposing factors in these patients were diabetes mellitus (DM), acute lymphoblastic leukaemia (ALL), post-partum and pregnancy in one each of the patients. Relapse was seen in two cases. All the patients survived due to strict follow-up. Pulmonary cryptococcosis is common in non-AIDS patients and it warrants rapid diagnosis, treatment and follow-up to prevent relapse.
© 2015 Blackwell Verlag GmbH.
Symptomatic pulmonary cryptococcus is rare in healthy patients and uncommon even in immunocompromised patients. We describe a case of pulmonary cryptococcus that caused acute respiratory distress syndrome in a healthy host. Distinctively, this case is a rare description of significant respiratory failure from isolated pulmonary Cryptococcus neoformans with the exclusion of Cryptococcus gattii and review of the literature.
Specific texts on infectious diseases and those in textbooks on pulmonary pathology commonly approach the subject of infection in the lung from an etiological microbiological perspective, listing infectious agents by taxonomy followed by associated pathology. However, in practice one is faced with a specimen in which a reaction pattern is seen (usually of inflammatory nature) which may be indicative of a specific type of infection. In these circumstances an approach leading from reaction pattern to specific microbiological diagnosis is required. This approach will form the basis of this review. General aspects are covered without exhaustive discussion of specific microbiology. For more detailed discussion of specific entities the reader is referred to the excellent textbooks on pulmonary pathology and those on pathology of infectious diseases. The reaction patterns described here are combinations of gross pathology and cellular reactions. The breakdown of these patterns is somewhat arbitrary and artificial. In many cases the pattern will not be absolutely typical and many overlapping features will be present in individual cases.
O presente trabalho relata um caso de criptococose pulmonar isolada em paciente com sintomas respiratórios, sem imunossupressão e sorologia negativa para o vírus da imunodeficiência humana, com massa pulmonar no radiograma de tórax. O diagnóstico foi confirmado pela biópsia transbrônquica e lavado broncoalveolar. A paciente recebeu tratamento ambulatorial com fluconazol, na dose de 300 mg/dia por seis meses, evoluindo com melhora clínica e regressão parcial da imagem radiológica. O presente caso ilustra uma apresentação não freqüente da criptococose pulmonar e faz considerações sobre a abordagem terapêutica com base na literatura.In this study, we report a case of pulmonary cryptococcosis in a patient presenting respiratory symptoms and a lung mass on the chest X-ray. The patient had no concomitant diseases, was seronegative for human immunodeficiency virus and was not receiving immunosuppressive therapy of any kind. The diagnosis was confirmed through transbronchial biopsy and bronchoalveolar lavage. The patient was treated as an outpatient with fluconazole (300 mg/day for six months), evolving to clinical improvement and partial regression of the lung mass, as seen on a second chest X-ray. The current case illustrates an unusual presentation of pulmonary cryptococcosis and raises questions regarding the therapeutic approaches proposed in the literature.
(CHEST 2004; 125:330 –333) A 19-year-old white man was referred to the pulmonary clinic with a 2-month history of refractory cough, low-grade fevers, night sweats, and 30-lb weight loss. He had right-sided pleuritic pain and episodic scant hemoptysis. He denied smoking and using illicit drugs. He was single and had protected sex with two female partners over the past several years. He worked as a pipe fitter and denied any unusual hobbies, hunting, or recent travel. He would frequently go on camping and fishing trips near his hometown lake in southern Indiana. Chest radiographs and CT scans over 2 months showed progressive right upper lobe consolidation. He had negative findings on purified protein derivative and HIV screening. He had undergone bronchoscopy with normal results, and BAL specimens and brushes were culture negative for acid-fact bacilli, fungi, and cytology. He had been treated with multiple antibiotics, including amoxicillin, azithromycin, ciprofloxacin, clindamcyin, and cephalexin.
Most fungi are saprophytic and not pathogenic to plants, animals and humans. However, a relative few fungal species are phytopathogenic, cause disease (e.g., infections, allergies) in man, and produce toxins that affect plants, animals and humans. Among such fungi are members of the Aspergillus and Fusarium genera as well as other genera (e.g., Alternaria, Mucor) comprising the “emerging pathogen” group in humans. These fungi present a common threat to both agricultural production and the health of healthy and immunocompromised individuals. Taken together, these relative few fungi can cause huge economic losses to agriculture, loss of food for consumption, and serious, often fatal diseases in humans and animals. Plants may be a source of antifungal compounds since they have had to develop compounds to resist infections by fungi present in their environment.
IntroductionHIV infection and Mycobacterium tuberculosisHIV infection and non tuberculous mycobacteria (NTM)HIV and Pneumocystis jiroveciiInfections in transplant patients or other immunodeficienciesConcluding remarksKey learning pointsReferences
Some members of the Pseudallescheria (anamorph Scedosporium) have emerged as an important cause of life-threatening infections in humans. These fungi may reach the lungs and bronchial tree causing a wide range of manifestations, from colonization of airways to deep pulmonary infections. Frequently, they may also disseminate to other organs, with a predilection for the brain. In otherwise healthy patients, the infection is characterized by non-invasive type involvement, while invasive and/or disseminated infections were mostly seen in immunocompromised patients.
We reviewed all the available reports on Pseudallescheria/Scedosporium pulmonary infections, focusing on the geographical distribution, immune status of infected individuals, type of infections, clinical manifestations, treatment and outcome.
The main clinical manifestations of the 189 cases of pulmonary pseudallescheriasis reviewed were pneumonia (89), followed by fungus ball (26), and chest abscess (18). Some patients had more than one type of invasive pulmonary manifestations. Among patients with pneumonia, several cases of pneumonia associated with near-drowning (10/89, 11.2%) have also been reported in immunocompetent hosts. Major underlying conditions for non-invasive pulmonary infection were preexisting lung cavities and medical immunosuppression for invasive pulmonary infection. Saprobic airway colonization was mostly seen in patients with mucosal dysfunction, i.e. patients with cystic fibrosis. The mortality rate was closely related to the infection type, being 26.8% in non-invasive type (fungus balls) and 57.2% in invasive type.
To examine risk for mycosis among persons with silicosis, we examined US mortality data for 1979-2004. Persons with silicosis were more likely to die with pulmonary mycosis than were those without pneumoconiosis or those with more common pneumoconioses. Health professionals should consider enhanced risk for mycosis for silica-exposed patients.
The fungicidal properties of purified CAY-1, dissolved silver ion and ethylenediamine tetraacetic acid (EDTA) separately were studied in vitro as were the abilities of silver and EDTA to enhance CAY-1 fungicidal properties. Non-germinated and germinating conidia of Aspergillus flavus, Aspergillus fumigatus, Aspergillus niger, Fusarium verticillioides (Fusarium moniliforme), Fusarium oxysporum and Fusarium solani were incubated separately with CAY-1 (0-24.8 μg ml(-1)), silver (0-111.1 μg ml(-1)), and EDTA (0-2400 μg ml(-1)). Controls consisted of non-germinated or germinated conidia in test medium. To assess combined activity, compounds, based on the sub-lethal doses of each as defined in the initial experiments, were combined and tested in bioassays. Controls for the mixed sets consisted of non-germinated or germinated conidia only or with the sub-lethal CAY-1 test concentrations. The minimum inhibitory concentrations (MICs) for CAY-1 and silver, both separate and combined, were determined. Viability assays showed CAY-1 activity only against the germinating conidia of A. flavus, A. niger and F. solani. Silver was active against the germinating conidia of all fungi and the non-germinated conidia of F. oxysporum and F. solani. Combined silver and CAY-1 produced significant viability loss at concentrations not effective separately. EDTA was not fungicidal separately and did not enhance CAY-1 fungicidal properties. MIC data showed that CAY-1 plus silver had an additive effect. Results indicate that dissolved silver was fungicidal in vitro and enhanced the fungicidal properties of CAY-1 at concentrations ineffective when tested separately.
Candida krusei (Ck) may cause severe infections in immunocompromised hosts and is innately resistant to fluconazole.
During an 18-month period, seven patients with Ck infection were identified at our center. All were treated in the transplant intensive care unit. Candida isolates were grown on Sabouraud agar, and chromosomal DNA was extracted; clonality was investigated using random amplified polymorphic DNA-polymerase chain reaction with primers M13, OPA-18, and OPE-18.
Among the patients with Ck infection, there were three pancreas recipients with intra-abdominal infection, one liver recipient with cholangitis, one lung recipient with pleural empyema, one patient with pleural empyema after esophageal perforation, and one case of pneumonia in a patient with a ventricular assist device. Treatment consisted of caspofungin (n = 3), voriconazole (n = 1), or a combination of the two (n = 2) together with surgery (n = 3) or pigtail catheter drainage (n = 3). One patient underwent drainage without antifungal treatment, and one patient did not have drainage. The infection was controlled in all cases. The patient with the assist device died from multiple organ dysfunction, the lung recipient died after four months from graft failure, and one pancreas graft was lost. Four patients (57%) harbored the same Ck strain.
Solid organ recipients seem to be at particular risk for Ck infections; clonal outbreaks may occur in intensive care units.
To clarify the clinical features and imaging characteristics of non-AIDS patients with pulmonary cryptococcosis.
We retrospectively collected 15 HIV-negative patients with pathology-proved pulmonary cryptococcosis from Sep 1992 to Jan 2008. Their medical records and radiological data were reviewed and analyzed.
Only one patient was asymptomatic.Thirteen patients were immunocompetent and two were immunosuppressed. Three patients had associated cryptococcosis meningitis. The most common radiographic abnormalities were multiple pulmonary nodules or masses, seen in 8 and 5 cases of patients respectively. 14 patients received specific therapy for Cryptococcus neoformans. Two patients died. In the 11 patients with isolated pulmonary cryptococcosis, treatment consisted of fluconazole alone (n=7), in combination with amphotericin B (n=2), and both 5-flucytosine and amphotericin B (n=2). For the other 2 patients with cryptococcosis meningitis, one was treated with amphotericin B alone and the other with fluconazole combined with amphotericin B and 5-flucytosine.
Non-AIDS patients might also susceptible to cryptococcosis infection. Histological examination is the principal method of diagnosis. The most common CT findings are solitary or multiple nodules with or without cavitation in the subpleural areas of the lung.
A fundamental feature of the fungal pathogen Histoplasma capsulatum is its ability to shift from a mycelial phase in the soil to a yeast phase in its human host. Each form plays a critical role in infection and disease, but little is understood about how these two morphologic phases are established and maintained. To identify phase-regulated genes of H. capsulatum, we carried out expression analyses by using a genomic shotgun microarray representing approximately one-third of the genome, and identified 500 clones that were differentially expressed. Genes induced in the mycelial phase included several involved in conidiation, cell polarity, and melanin production in other organisms. Genes induced in the yeast phase included several involved in sulfur metabolism, extending previous observations that sulfur metabolism influences morphology in H. capsulatum. Other genes with increased expression in the yeast phase were implicated in nutrient acquisition and cell cycle regulation. Unexpectedly, differential regulation of the site of transcript initiation was also observed in the two phases. These findings identify genes that may determine some of the major characteristics of the mycelial and yeast phases.
When the essential and distinctive cell walls of either pathogenic or nonpathogenic fungi break, cytoplasmic membranes rupture
and fungi die. This fungicidal activity was discovered previously on nonproliferating Saccharomyces cerevisiae cells treated briefly with the oxidative tool and anticancer drug family of bleomycins. The present studies investigated
effects of bleomycin on growing fungal organisms. These included the medically important Aspergillus fumigatus and Cryptococcus neoformans, as well as the emerging human pathogen and fungal model, S. cerevisiae. Bleomycin had its highest potency against A. fumigatus. Scanning electron microscopy and thin-section transmission electron microscopy were used to study morphological growth characteristics.
Killing and growth inhibition were also measured. Long, thin, and segmented hyphae were observed when A. fumigatus was grown without bleomycin but were never observed when the mold was grown with the drug. Bleomycin arrested conidial germination,
hyphal development, and the progression and completion of cell wall septation. Similarly, the drug inhibited the construction
of yeast cell wall septa, preventing cytokinesis and progression in the cell division cycle of S. cerevisiae. Even when cytoplasms of mother and daughter cells separated, septation and cell division did not necessarily occur. Bizarre
cell configurations, abnormally thickened cell walls at mother-daughter necks, abnormal polarized growth, large undivided
cells, fragmented cells, and empty cell ghosts were also produced. This is the first report of a fungicidal agent that arrests
fungal growth and development, septum formation, and cytokinesis and that also preferentially localizes to cell walls and
alters isolated cell walls as well as intact cell walls on nongrowing cells.
Invasive fungal infections are an important cause of morbidity and mortality in patients with hematological malignancies, and in particular fungal pneumonia is the main clinical manifestation in this category of patients. The fungal agents responsible for this complication are various, but Aspergillus spp. and other molds such as Zygomycetes or Fusarium spp. represent the most frequently isolated micro-organisms. Less commonly, pneumonia could be due to other 'no-molds' fungal agents such as Candida spp, Cryptococcus spp, or Pneumocystis jirovecii . This review mainly focuses on practical aspects relevant to epidemiology, diagnosis and therapeutic management of the rare cases of pneumonia due to no-molds agents in patients affected by hematological malignancies.
Secondary central nervous system (CNS) blastomycosis is an unusual manifestation of blastomycosis. We report a case of recurrent intracerebral blastomycosis that presented histopathologically with giant yeast-like cells and multinucleation that mimicked Coccidioides immitis. The yeast forms of Blastomyces dermatitidis usually range in size from 8 to 20 microm in diameter. Large or giant yeast forms (20-40 microm) are rare. The four cases previously reported in the literature involving giant yeast cell forms of B. dermatitidis are reviewed here. Intracerebral blastomycosis should be suspected in patients with signs and symptoms of CNS lesions and histories of primary blastomycosis, or treatment with corticosteroids, or comprised immune systems. The diagnosis should be confirmed by culture which presents typical biphasic microbiologic features.
We report the first case in Europe of co-infection with disseminated cryptococcosis and histoplasmosis. The diagnosis of invasive histoplasmosis was confirmed by microscopic examination of the anatomic right colon specimen (hemicolectomy). Histoplasma antigen detection is not yet available in France but it could have a key role in the early diagnosis of disseminated histoplasmosis co-existing with a cryptococcal infection, especially in HIV-infected African people. © 2005 The British Infection Society. Published by Elsevier Ltd. All rights reserved.
The objective of this study was to clarify clinical and high-resolution computed tomography (HRCT) characteristics in non-AIDS patients with pulmonary cryptococcosis. We analyzed the medical records and HRCT scans in 22 patients with pulmonary cryptococcosis from 1988 to 2003. Thirteen patients (59%) were immunocompetent and nine (41%) were immunosuppressed, seven of whom had diabetes mellitus. No patients exhibited extrapulmonary involvement. Nineteen patients (86%) were asymptomatic. Radiography revealed incidental chest abnormality in all but two patients. The typical HRCT findings were solitary or multiple nodules in the subpleural area. Cavitation was present in 30% of the patients who had nodules. The most frequently applied and reliable diagnostic procedure was video-assisted thoracoscopic surgery (VATS). Treatment included antifungal therapy alone in 11 patients, surgery alone in eight including four treated by VATS, surgery plus antifungal therapy in two and none in one. Patients who underwent surgery alone did not develop any relapse. The majority of non-AIDS patients with pulmonary cryptococcosis present with incidental chest radiographic abnormalities. The most common HRCT findings are solitary or multiple nodules with or without cavitation in the subpleural areas of the lung. VATS is a useful tool for both diagnosis and treatment of isolated pulmonary cryptococcosis.
Patients with compromised immune systems often complain of chronic cough. While these patients are susceptible to opportunistic infections that should be considered in the evaluation, common causes should also be investigated.
MEDLINE search using the terms "cough," "immunocompromise," "HIV," "AIDS," "neutropenia," and "corticosteroids," from 1966 through the end of 2003.
Patients with compromised immune systems and chronic cough usually have the same disorders causing cough as in the general population. However, depending on the nature and severity of the immune defect, they may also have a variety of infections not usually encountered in immunocompetent hosts.
In immunocompromised patients presenting with cough, the initial diagnostic evaluation should be the same as that for healthy hosts. However, when these diagnoses have been excluded, opportunistic infections should be considered.
The fungus, Histoplasma capsulatum, produces a persistent infection. Reactivation histoplasmosis is largely a result of impaired immunity, but the perturbations associated with escape of the fungus from host defenses remain ill-defined. We analyzed a murine model of reactivation to elucidate the host defects that permit reactivation. C57BL/6 mice were infected intranasally and, 42 days later, they were depleted of CD4(+) and CD8(+) cells. Elimination of these cells, but not either alone, produced a persistent infection over several weeks. Neutralization of IFN-gamma, TNF-alpha, or both did not induce reactivation. Endogenous IL-10 exacerbated reactivation. Depletion of T cells in B cell(-/-) mice induced a markedly higher burden in organs when compared with wild type. However, the infection remained persistent. Elimination of CD4(+) cells alone or neutralization of cytokines increased the fungal load. The persistent infection was not dependent on gammadelta T cells or NK cells. Elimination of Thy-1.2(+) cells in mice given mAb to CD4 and CD8 transformed reactivation into a progressive, lethal infection in B cell(-/-) and wild-type mice, but the tempo of progression was accelerated in the former. The data reveal the complex control by the host to prevent reactivation of this fungus.
Composite tissue allograft recipients require intensive immunosuppression and are therefore at risk of infections. Filamentous fungal infections are among the complications most difficult to manage in organ transplant recipients.
Case report and literature review.
Two years after bilateral forearm transplantation, a 35-year-old patient presented with a tumor-like lesion on his thigh after a penetrating injury caused by a sliver acquired during hiking. The lesion was excised completely, and microscopic examination revealed a filamentous fungal infection. Alternaria alternata was identified as the causative agent. Induction therapy with liposomal amphotericin B for one week followed by oral itraconazole maintenance therapy for eight weeks was successful, with no signs of recurrence or side effects at 18 months' follow-up.
This is the first reported case of invasive A. alternata infection in a composite tissue allograft recipient. The infection was managed successfully with local excision and systemic antifungal treatment.
Infections caused by yeasts and molds continue to be associated with high rates of morbidity and mortality in both immunocompromised and immunocompetent patients. Many antifungal drugs have been developed over the past 15 years to aid in the management of these infections. However, treatment is still not optimal, as the epidemiology of the fungal infections continues to change and the available antifungal agents have varying toxicities and drug-interaction potential. Several investigational antifungal drugs, as well as nonantifungal drugs, show promise for the management of these infections.