Pulmonary aspergillosis due toAspergillus terreus combined with staphylococcal pneumonia and hepatic candidiasis

A female patient with systemic lupus erythematosus (SLE) developed pulmonary aspergillosis with staphylococcal pneumonia and hepatic candidiasis.Aspergillus terreus, which is a rare causative organism of pulmonary aspergilosis, was identified from a pulmonary lesion by culture. The aleurioconidium production, a characeristic of the genusAspergillus sect.terrei, was demonstrated on short and irregular hyphal features in tissue sections. This report is the first of a combined case of pulmonary aspergillosis due toA. terreus with infections caused by other microorganisms.     

Systemic dissemination of chronic necrotizing pulmonary aspergillosis in an elderly woman without comorbidity: a case report

ABSTRACT: INTRODUCTION: Chronic necrotizing pulmonary aspergillosis usually occurs in mildly immune-compromised hosts or those with underlying pulmonary disease. The radiographic pattern of chronic necrotizing pulmonary aspergillosis is typically a progressive upper lobe cavitary infiltrate with pleural thickening. We report here an atypical case of chronic necrotizing pulmonary aspergillosis mimicking lung cancer, which developed into a disseminated fatal disease in an older woman with no comorbidity. CASE PRESENTATION: An 80-year-old Japanese woman was referred to our hospital for a chest roentgenogram abnormality. Repeated fiber-optic bronchoscopy could not confirm any definite diagnosis, and she refused further examinations. Considering the roentgenogram findings and her age, she was followed-up as a suspected case of lung cancer without any treatment. Then, 10 months later, she complained of visual disturbance and was admitted to our department of ophthalmology. She was diagnosed as having endophthalmitis. After treatment with corticosteroids for 20 days, she developed acute encephalitis and died four weeks later. Autopsy revealed dissemination of Aspergillus hyphae throughout her body, including her brain. CONCLUSIONS: In older patients, even if they do not have any comorbidity, chronic necrotizing pulmonary aspergillosis should be added to the differential diagnosis of solitary pulmonary lesions in a chest roentgenogram.     

Proven Invasive Pulmonary Aspergillosis in Stem Cell Transplant Recipient Due to <Emphasis Type="Italic">Aspergillus sublatus</Emphasis>, a Cryptic Species of <Emphasis Type="Italic">A. nidulans</Emphasis>

Invasive fungal disease represents one of the severe complications in haematopoietic stem cell transplant recipients. We describe a case of a patient treated for relapse of chronic lymphoblastic leukaemia 6 years after HSCT. The patient was treated for invasive pulmonary aspergillosis but died 3 months later from multiple organ failures consisting of haemorrhagic necrotizing fungal pneumonia, refractory chronic hepatic graft versus host disease and cytomegalovirus hepatitis. Autopsy samples revealed histopathological evidence of fungal hyphae and an unusual Aspergillus nidulans-like species was isolated in pure culture. More precise identification was achieved by using scanning electron microscopy of ascospores and sequencing of calmodulin gene, and the isolate was subsequently re-identified as A. sublatus (section Nidulantes) and showed good in vitro susceptibility against all classes of antifungals. Commonly used ITS rDNA region and β-tubulin gene fail to discriminate A. sublatus from related pathogenic species, especially A. quadrilineatus and A. nidulans. Although this is the first case of proven IPA attributed to A. sublatus, we demonstrated that at least some previously reported infections due to A. quadrilineatus were probably caused by this cryptic species.     

Estudio comparativo de las reacciones serologicas cuantitativas con un antigeno metabolico de Aspergillus fumigatus

Summary The following quantitative serologic reactions: agar-gel immunodiffusion, complement-fixation, opposite electrophoresis and latex particle agglutination tests have been performed in 38 sera from mycologically proved pulmonary aspergillosis cases. A metabolic antigen from a strain ofAspergillus fumigatus according toAjello et al technic modified by us, has been employed. Sera from 120 subjects suffering from non-mycotic lung conditions, as well as 10 sera from histoplasmosis cases, 10 sera from S. A. blastomycosis and 2 sera from patients with lung aspergillosis produced byA. niger, gave negative results with the above mentioned seroligic reactions.One hundred per cent of positive results were obtained with the complement-fixation test (titre ranging from 1/20 to 1/1280), agar-gel immunodiffusion test (titre up to 1/64) and the opposite immunoelectrophoresis (titre ranging from 1/2 to 1/256). Twenty five per cent negative and 4 non-specific results were registered with the latex particle agglutination test.A correlation of the number of serum precipition bands obtained by the electrophoresis technic with the titre of the quantitative serologic reactions, as well as a correlation of the titre of the circulating antibodies with the severity of the clinical form of aspergillosis seems to be present.Electrophoretic motility of the specific antibody performed in 10 sera showed results like the IgM in 1 instance and an intermediate position between IgA and IgG in 9 samples.     

Challenges in Diagnosing Invasive Pulmonary Aspergillosis in Patients With COPD and Other Chronic Lung Disorders

Invasive pulmonary aspergillosis (IPA) is a necrotizing pneumonia caused by airborne opportunistic fungi of Aspergillus species. Patients with chronic obstructive pulmonary disease (COPD) or other chronic lung disorders (CLD) have emerged to be at risk for IPA, with a related mortality rate greater than 70%. Host factors playing a role in the occurrence of IPA in CLD patients differ from those in patients with hematologic disorders and may be largely responsible for a distinct pattern of the disease. Furthermore, these host factors affect the results of standard diagnostic procedures recommended for IPA. Therefore, the diagnosis of IPA in patients with COPD and other CLD remains challenging for physicians. This review puts into perspective the host factors contributing to the pathogenesis of IPA in CLD patients and discusses the use and interpretation of the main diagnostic tools currently available.     

Multiple Bilateral Pulmonary “Fungus Balls” in an Immunocompetent Patient Unsuitable for Surgical Treatment: Efficacy of Azoles Treatment

Data guiding management of pulmonary mycetomas are based on uncontrolled trials and case reports. Surgical resection represents a definitive treatment associated with high mortality and sometimes not feasible due to clinical conditions. We report a case of an immunocompetent patient with multiple pulmonary mycetomas, suggestive for probable chronic aspergillosis, in which surgery was contraindicated. The patient experienced a good response to long-term oral voriconazole therapy with remarkable clinical and radiological improvement at three-month follow-up. In cases of probable chronic aspergillomas, when surgery is contraindicated, long-term antifungal therapy with voriconazole seems to be a valid alternative option.     

Aspergillus fumigatus MedA governs adherence,host cell interactions and virulence

In medically important fungi, regulatory elements that control development and asexual reproduction often govern the expression of virulence traits. We therefore cloned the Aspergillus fumigatus developmental modifier MedA and characterized its role in conidiation, host cell interactions and virulence. As in the model organism Aspergillus nidulans, disruption of medA in A. fumigatus dramatically reduced conidiation. However, the conidiophore morphology was markedly different between the two species. Further, gene expression analysis suggested that MedA governs conidiation through different pathways in A. fumigatus compared with A. nidulans. The A. fumigatusΔmedA strain was impaired in biofilm production and adherence to plastic, as well as adherence to pulmonary epithelial cells, endothelial cells and fibronectin in vitro. The ΔmedA strain also had reduced capacity to damage pulmonary epithelial cells, and stimulate pro‐inflammatory cytokine mRNA and protein expression. Consistent with these results, the A. fumigatusΔmedA strain also exhibited reduced virulence in both an invertebrate and a mammalian model of invasive aspergillosis. Collectively, these results suggest that the downstream targets of A. fumigatus MedA mediate virulence, and may provide novel therapeutic targets for invasive aspergillosis.     

The innate immune response to Aspergillus fumigatus

Despite the development of new treatments, the mortality due to invasive pulmonary aspergillosis remains above 50%, reaching 95% in certain situations. The battle against Aspergillus fumigatus involves several components of the pulmonary innate immune system: cells, mediators, and natural antifungal molecules involved in the recognition and elimination of the fungus, thereby preventing colonization of the respiratory system.With the 10,000–15,000 l of air we inhale each day, the lungs are constantly exposed to a wide range of microorganisms, such as A. fumigatus. This fungus is ubiquitous in the environment and can release large numbers of spores able, due to their small size, to penetrate the respiratory tract. The spores of A. fumigatus, like any other pathogen, are then confronted with the innate immune system, a constitutive defense system that is permanently active and tightly regulated. The various elements of the pulmonary innate immune system—physical and cellular barriers and soluble mediators—are involved in the recognition and elimination of pathogens, thereby preventing colonization of the respiratory system. Consequently, the presence of spores in immunocompetent hosts is completely innocuous, because these spores are normally eliminated. However, changes in one of the components of the defense system may lead to the development of pulmonary infections. Thus, in immunocompromised individuals, the spores are able to develop and cause pulmonary mycoses. These mycoses, known as aspergillosis, are highly variable, with the range of presentations extending from an allergy-type illness, allergic bronchopulmonary aspergilloses, to a very serious generalized and frequently fatal infection: invasive pulmonary aspergillosis (IPA).     

Deep mycoses in India

Available published reports on deep mycoses in India have been critically and exhaustively reviewed. So far there seem to be only 9 cases of actinomycosis reported, mostly of thoracic type and diagnosed on the basis of the presence of sulphur granules in the lesions. Nocardiosis and its chief causal agentNocardia asteroides have received particular attention in recent studies. To-date there are 18 authentic cases reported from India and significantly 12 of these have been diagnosed by applying the paraffin bait technique to the isolation ofN. asteroides from sputa and other clinical specimens. In most of these 12 cases timely diagnosis allowed for the successful treatment of the disease with heavy doses of sulphadiazine. Case reports on cryptococcosis which include 26 adequately documented cases, have been published from various parts of the country. Occurrence ofCryptococcus neoformans in soil and its association with old pigeon excreta have also been confirmed by studies done in some northern and western regions of this country. The status of histoplasmosis in India still remains a debatable subject although there is a suggestive evidence that the disease may be endemic in the northeastern parts. There are 9 case reports in which diagnosis has been supported by histopathologic findings and in 3 cultures have also been positive. However, attempts to isolateHistoplasma capsulatum from soil or any other extra-human source have remained futile and the limited surveys have revealed only low skin sensitivity to histoplasmin and none to blastomycin and coccidioidin. As yet there is no authentic case of blastomycosis, coccidioidomycosis or paracoccidioidomycosis reported from India. Two cases of invasive aspergillosis and 6 of bronchopulmonary aspergillomas have been published. In the latterAspergillus fumigatus, A. niger andA. flavus have been found to be the aetiologic agents. In addition, a recent report on a series of 8 patients recognises for the first time the occurrence of allergic aspergillosis in this country. Two cases of phycomycoses, involving the lungs in one and brain in the other case have been described. Diagnosis of bronchopulmonary candidiasis has been claimed in as many as 16 patients by several authors but in none the evidence is unequivocal. The isolation ofCandida viswanathii from the cerebrospinal fluid of two fatal cases is suggestive of the possible aetiologic role of this new yeast in human meningitis. Besides, there are 3 cases of brain mycoses described in Indian literature, two due toCladosporium trichoides while in the third caseUstilago maydis, the causal agent of maize smut, has been implicated.     

The role of muscle flaps in pulmonary aspergillosis

Pulmonary invades the lung parenchyma and vessels, causing necrotizing pneumonia and massive hemoptysis in immunocompromised patients. Medical treatment alone often fails to clear the organism. Early surgical intervention is advocated in localized disease to remove infection near pulmonary vessels. The resection is limited in an attempt to preserve as much lung function as possible. However, preexisting cavitations and lung disease predispose to postoperative space problems, including prolonged air leak, bronchopleural fistula, and empyema. Muscle flaps provide a solution to these problems by obliterating residual space and providing protective coverage to the bronchial stump. The authors present four cases of pulmonary aspergillosis treated by multimodality therapy and extrathoracic muscle flap transposition. Factors that may contribute to successful treatment include underlying condition of the host and history of cancer, radiation therapy, and great vessel involvement. Despite aggressive medical and surgical therapy, pulmonary aspergillosis has a poor prognosis.     

The effect of fungal ribosome inactivating proteins upon feeding choice in C. freemani,and indications of a mutualistic relationship with A. restrictus. Environmental Mycology

Carpophilus freemani beetles' feeding on the fungusAspergillus nidulans was substantially inhibited when A. nidulans was transformed and induced to secrete the ribosome inactivating protein, restrictocin (genetic source: Aspergillus restrictus). No inhibition of feeding was observed when A. nidulans was transformed and induced to produce an inactive form of restrictocin with a single amino-acid substitution in the active site. Similarly, there was no inhibition of feeding upon transgenic strains when the production of restrictocin was not induced. Feeding inhibition of C. freemani by restrictocin requires that the ribonuclease be active and is not due to other characteristics of the protein or the transgenic host fungus.This revised version was published online in October 2005 with corrections to the Cover Date.     

慢性坏死性肺曲霉病18例临床分析

目的 探讨慢性坏死性肺曲霉病（CNPA）的临床特征、诊断与治疗,以提高对该病的认识。方法 对2003年1月-2006年3月广州呼吸疾病研究所经病理证实的18例慢性坏死性肺曲霉病住院病例进行回顾性研究,结合文献分析其临床表现、影像学、诊断和治疗方法。结果CNPA症状无特异性,主要表现为咳嗽、咳痰18例（100.0％）,咯血9例（50.0％）,咳血痰1例（5．6％）,发热7例（38．9％）,气促5例（27．8％）,盗汗3例（16．7％）,胸痛3例（16.7％）,消瘦3例（16．7％）,疲乏无力2例（11.1％）。右肺病变5例（27．8％）,左肺病变11例（61．1％）,双肺受累2例（11.1％）。病灶位于下肺6例（33．3％）,上中肺9例（50.0％）,双肺弥漫病变1例（5．6％）,双肺多发空洞1例（5．6％）,左侧毁损肺1例（5．6％）,不常见的胸膜（腔）受累共4例。“空气新月征”有提示诊断意义,在本组中发现8例（44.4％）。全部病例均经病理确诊,其中经支气管肺组织活检确诊7例。结论CNPA临床表现无特异性,影像学检查在诊断中起重要作用,而诊断需要病理依据。存在肺部基础疾病,出现发热、血痰及空气新月征三联征时,应高度警惕CNPA。系统抗真菌治疗无效、合并大咯血或肺部阴影与肿瘤不能鉴别时,可考虑手术切除。     

An animal model of Curvularia geniculata and its relationship with human disease

The conidiospore of Curvularia geniculata was observed in the bronchial washings of a patient who subsequently developed pulmonary aspergillosis. Curvularia geniculata was grown in culture and used in experiments in mice to explore its possible role as a disease causing agent. The fungus, after intraperitoneal injection, produced granulomas in the liver and spleen. Studies on the pathogenicity of this fungus in mice produced similar lesions to those observed in the human case. A comparison of the lesions in the patient's lung and in the animal experimental model is presented.     

ThehapC gene ofAspergillus nidulans is involved in the expression of CCAAT-containing promoters

The 5 regulatory region of theamdS gene ofAspergillus nidulans, which encodes an acetamidase required for growth on acetamide as a carbon and nitrogen source, contains a CCAAT sequence which is required for setting the basal level ofamdS expression. Mobility shift studies have identified a factor inA. nidulans nuclear extracts which binds to this CCAAT sequence. InSaccharomyces cerevisiae theHAP3 gene encodes one component of a multisubunit complex that binds CCAAT sequences. A search of the EMBL and SwissProt databases has revealed anA. nidulans sequence with significant homology to theHAP3 gene adjacent to the previously cloned regulatory geneamdR. Sequencing of the remainder of this region has confirmed the presence of a gene, designatedhapC, with extensive homology toHAP3. The predicted amino acid sequence of HapC shows extensive identity to HAP3 in the central conserved domain, but shows little conservation in the flanking sequences. A haploid carrying ahapC deletion has been created and is viable, but grows poorly on all media tested. This null mutant grows especially slowly on acetamide as a sole carbon and nitrogen source, indicating thathapC plays a role inamdS expression. In agreement with this notion, it has been shown that thehapC deletion results in reduced levels of expression of anamdS::lacZ reporter gene and this effect is particularly evident under conditions of carbon limitation. Nuclear extracts prepared from thehapC deletion mutant show no CCAAT binding activity to theamdS orgatA promoters, indicating thathapC may encode a component of the complex binding at this sequence.     

Prevalence of pulmonary mycoses in smear-negative patients with suspected tuberculosis in the Brazilian Amazon

BackgroundPulmonary mycoses resemble clinically and radiologically chronic pulmonary tuberculosis. Studies describing the prevalence, etiology and clinical features of pulmonary mycosis are of crucial importance in the Brazilian Amazon.AimsTo estimate the frequency of pulmonary mycoses in smear-negative tuberculosis patients; to describe their demographic, epidemiological, and clinical characteristics; and to evaluate diagnostic methods.MethodsA cross-sectional study was conducted at two tuberculosis reference institutions in Amazonas, Brazil. We included 213 patients and collected clinical data, blood and induced sputum to perform serological, direct microscopy, microbiologic culture and PCR-based assays to identify infections caused by Aspergillus fumigatus, Paracoccidioides brasiliensis, Histoplasma capsulatum, Cryptococcus, and HIV. Chest computed tomography was also performed.ResultsPulmonary mycoses were diagnosed in 7% (15/213) of the cases, comprising ten aspergillosis cases, three cases of paracoccidioidomycosis and one case each of histoplasmosis and cryptococcosis. Among the patients with pulmonary mycoses, 86.7% were former tuberculosis patients. The most significant clinical characteristics associated with pulmonary mycoses were cavity-shaped lung injuries, prolonged chronic cough and hemoptysis.ConclusionsOur study confirmed the high prevalence of pulmonary mycoses in smear-negative tuberculosis patients in the Brazilian Amazon.     

Pulmonary Toxocariasis Mimicking Invasive Aspergillosis in a Patient with Ulcerative Colitis

A 45-year-old-male who had underlying ulcerative colitis and presented with fever and dry cough. Initially, the patient was considered to have invasive aspergillosis due to a positive galactomannan assay. He was treated with amphotericin B followed by voriconazole. Nevertheless, the patient deteriorated clinically and radiographically. The lung biopsy revealed eosinophilic pneumonia, and ELISA for Toxocara antigen was positive, leading to a diagnosis of pulmonary toxocariasis. After a 10-day treatment course with albendazole and adjunctive steroids, the patient recovered completely without any sequelae. Pulmonary toxocariasis may be considered in patients with subacute or chronic pneumonia unresponsive to antibiotic agents, particularly in cases with eosinophilia.     

Tolerance to higher temperature byAspergillus nidulans and its possible implication in biological control of wilt disease of pigeon-pea

Summary During the course of studies on the ecology ofFusarium udum Butler, the incitant of wilt disease of pigeon-pea (Cajanus cajan (L.) Millsp.),Aspergillus nidulans was found to tolerate higher temperatures of summer, and other species includingF. udum were suppressed in field soil. The population ofA. nidulans increased in the soil incubated at 40±2°C at pH6 and 7 while the population ofF. udum was highly suppressed. The wilt disease of pigeon-pea was significantly suppressed at 38±2°C in the soil having a mixture of the inocula ofF. udum andA. nidulans whereas at lower temperature (25±2°C) no significant impact ofA. nidulans on the disease was found. On the basis of this study an integrated use of higher temperature, alkaline pH andA. nidulans has been suggested for biological control of wilt disease of pigeon-pea.     

Curvularia lunata peritonitis complicating peritoneal dialysis

A case of peritonitis due toCurvularia lunata during continuous ambulatory peritoneal dialysis is reported. Diagnosis was established by culture of dialysis effluent and peritoneal exudate, and was also confirmed through histological examination.     

Fungi in healthy and diseased sea fans (<Emphasis Type="Italic">Gorgonia ventalina)</Emphasis>: is <Emphasis Type="Italic">Aspergillus sydowii</Emphasis> always the pathogen?

Caribbean corals, including sea fans (Gorgonia spp.), are being affected by severe and apparently new diseases. In the case of sea fans, the pathogen is reported to be the fungus Aspergillus sydowii, and the disease is named aspergillosis. In order to understand coral diseases and pathogens, knowledge of the microbes associated with healthy corals is also necessary. In this study the fungal community of healthy Gorgonia ventalina colonies was contrasted with that of diseased colonies. In addition, the fungal community of healthy and diseased tissue within colonies with aspergillosis was contrasted. Fungi were isolated from healthy and diseased fans from 15 reefs around Puerto Rico, and identified by sequencing the nuclear ribosomal ITS region and by morphology. Thirty fungal species belonging to 15 genera were isolated from 203 G. ventalina colonies. Penicillum and Aspergillus were the most common genera isolated from both healthy and diseased fans. However, the fungal community of healthy fans was distinct and more diverse than that of diseased ones. Within diseased fans, fungal communities from diseased tissues were distinct and more diverse than from healthy tissue. The reduction of fungi in diseased colonies may occur prior to infection due to environmental changes affecting the host, or after infection due to increase in dominance of the pathogen, or because of host responses to infection. Data also indicate that the fungal community of an entire sea fan colony is affected even when only a small portion of the colony suffers from aspergillosis. An unexpected result was that A. sydowii was found in healthy sea fans but never in diseased ones. This result suggests that A. sydowii is not the pathogen causing aspergillosis in the studied colonies, and suggests several fungi common to healthy and diseased colonies as opportunistic pathogens. Given that it is not clear that Aspergillus is the sole pathogen, calling this disease aspergillosis is an oversimplification at best. Communicated by Biology Editor Dr Michael Lesser     

慢性阻塞性肺疾病合并肺曲菌病一例及文献复习

目的:提高对慢性阻塞性肺疾病合并侵袭性肺曲菌病(COPD合并IPA)临床特点、诊断及治疗的认识.方法:回顾性分析2011年4月收治的一例COPD合并IPA患者的临床资料及诊治经过,并复习相关文献.结果:男患,“咳嗽、咳痰30余年,气短3年,加重1月余”入院,肺部CT示双肺多发结节影、空洞影,经抗炎、抗念珠菌治疗无效,CT下肺结节病灶活检病理示肺曲菌.抗曲菌治疗后症状好转、肺部影像明显吸收.结论:COPD合并IPA正逐渐引起重视,临床特征无明显特异性,肺部影像以结节影、空洞影多见,早期常规治疗无效时应积极抗曲菌治疗,可明显改善症状,降低死亡率,病理活检是确诊的依据.