播散型组织胞浆菌病研究进展

组织胞浆菌病是由组织胞浆菌引起的深部真菌疾病。播散型组织胞浆菌病为所有临床分型中最为凶险的类型,其特点为起病急、发展快、死亡率高,诊断及治疗也颇为棘手。该病既往被认为是一种地方流行性疾病,多见于美国中西部等西半球地区,我国少见且多为输入性病例。但现阶段我国本土病例也屡有报道,故本文在复习相关文献基础上总结了播散型组织胞浆菌病的流行病学现状、易感人群、临床表现、诊断方法及治疗进展,以飨读者。     

Unusual Orofacial Manifestations of Histoplasmosis in Renal Transplanted Patient

Histoplasmosis is a fungal infection caused by the Histoplasma capsulatum. Mucosal manifestations are uncommon, but, when present, they are usually associated with pulmonary or chronic disseminated infection. The course of the disease is often related to the host immune response. The purpose of this article is to describe the clinical and microscopic findings of unusual involvement of nasal cartilage and septal destruction, and oral lesions of histoplasmosis in an immunosuppressed patient who presented an unusual form of the disease.     

宏基因组学诊断播散型组织胞浆菌病1例

播散型组织胞浆菌病是一种进行性肺外疾病好发于免疫缺陷者。该病诊断的应结合组织胞浆菌病的高危因素(免疫抑制剂、高龄、高风险的暴露等)与临床表现。本文报道一例播散型组织胞浆菌病但免疫功能健全的病例,其表现为亚急性起病,后期病程进展迅速,骨髓涂片及宏基因测序诊断为播散型组织胞浆菌病。予以两性霉素B去氧胆酸盐及伊曲康唑治疗后病情明显好转。     

Chronic Cavitary Histoplasmosis of the Lung

Four main clinical types of disease result from infection by the fungus Histoplasma capsulatum: (1) the primary complex; (2) acute pulmonary histoplasmosis; (3) chronic cavitary pulmonary histoplasmosis; (4) disseminated systemic histoplasmosis.Chronic cavitary histoplasmosis of the lung is indistinguishable clinically and radiographically from pulmonary tuberculosis. In this disease, however, the histoplasmin skin test and the histoplasmin complement fixation test are positive in more than 80% of cases and sputum cultures are usually positive for Histoplasma capsulatum. The mortality rate of the chronic cavitary type is greater than 30%. The antibiotic, amphotericin B, is the most effective drug in treatment. If surgical resection of the cavitary lesion is feasible, under amphotericin coverage, this is the treatment of choice.During the past year, two patients with chronic cavitary histoplasmosis illustrating the aforementioned features were diagnosed at the Toronto Hospital for Tuberculosis.     

Immunologic,genetic and social human risk factors associated to histoplasmosis: Studies in the State of Guerrero,Mexico

Immunologic and occupational aspects of the susceptible population exposed to Histoplasma capsulatum, the causative agent of histoplasmosis were analyzed in the Mexican State of Guerrero. Three areas were studied, Juxtlahuaca, Olinala, and Coyuca; in the first two, their populations refer contact with bat guano and/or avian excreta, which contain nutrients for fungal growth, while the Coyuca population referred no contact with the above mentioned excreta. Previous infection with H. capsulatum was determined by histoplasmin-skin test, and the response was higher in men than in women (93.87, 85.71, and 6.6% for men, and 78.94, 66.6, and 0% for women) in Juxtlahuaca, Olinala, and Coyuca, respectively. Labor activities related to a persistent contact with the fungus were considered as an occupational risk factor, histoplasmin-skin test reached 88.57 and 36.36% of positive response in individuals with high and low risk activities. A high percentage of histoplasmin responses was observed in subjects with constant contact with H. capsulatum, such as, cave-tourist guides, peasants, and game-cock handlers, and generally they developed the largest diameter of skin reactions. Genetic risk factor was determined by studying the gene frequency of the Major Histocompatibility Complex antigens in a sample of individuals and their first degree relatives in Juxtlahuaca, Olinala, and Coyuca. Significant differences were found for HLA-B22 and B17 antigens in Juxtlahuaca, and for HLA-B22 in Olinala, in comparison to the usual gene frequency observed in the normal Mexican population. HLA results were important, considering that HLA-B22 was previously found to be possibly related to pulmonary histoplasmosis in Guerrero. This revised version was published online in June 2006 with corrections to the Cover Date.     

Identification of the infectious source of an unusual outbreak of histoplasmosis, in a hotel in Acapulco, state of Guerrero, Mexico

Three isolates of Histoplasma capsulatum were identified from mice lung, liver, and spleen inoculated with soil samples of the X hotel's ornamental potted plants that had been fertilized with organic material known as compost. The presence of H. capsulatum in the original compost was detected using the dot-enzyme-linked immunosorbent assay. Nested-PCR, using a specific protein Hcp100 coding gene sequence, confirmed the fungal identification associated with an unusual histoplasmosis outbreak in Acapulco. Although, diversity between the H. capsulatum isolate from the hotel and some clinical isolates from Guerrero (positive controls) was observed using random amplification of polymorphic DNA based-PCR, sequence analyses of H-anti and ole fragment genes revealed a high homology (92-99%) between them.     

Detection of constitutive molecules on Histoplasma capsulatum yeasts through single chain variable antibody fragments displayed in M13 phages

A nonimmune library, containing single chain variable fragments (scFv) of immunoglobulin human genes displayed on the surface of M13 filamentous phages, was used to recognize molecules exposed on Histoplasma capsulatum yeasts' surface, during their growth in synthetic medium. The scFv clones were checked in their consistency by Dot-ELISA using HRP/anti-M13 conjugate, and they were tested to recognize molecules on H. Capsulatum yeasts' surface by ELISA in plates. Three out of 80 scFv cones (C2, C6, and C52) reacted consistently with H. capsulatum molecules, and they recognized molecules from both H. capsulatum morphologic phases. However, C6 and C52 clones reacted better with molecules on the surface of whole yeasts, with molecules from the yeasts' cell-wall extract, and with molecules released to the supernatant of the yeast culture. Mycelial supernatants from other fungi, as well as from a Mycobacterium filtrate, were not recognized by scFv phage monoclones. Monoclones C2, C6, and C52 recognized yeast molecules irrespective of the H. capsulatum strains used; the C6 clone revealed a specific immunohistochemistry reaction when tested against homologous and heterologous fungal infected tissues. The scFv clones isolated will be a useful toll to define the role of their target molecules in the host-parasite relationship of histoplasmosis.     

Diagnostic usefulness of the intradermal test with histoplamin in non-endemic areas of histoplasmosis

The histoplasmosis in Spain is an imported disease presenting in most of case diagnostic difficulties. In this paper, the intradermal skin test with Histoplasma capsulatum antigen as diagnostic method in immunocompetent patients with clinical and radiological signs compatible with histoplasmosis after being visited Central and South American endemic counties, in which this mycosis is endemic. Nine Spanish patients coming from different countries of Latin America with fever and acute respiratory symptoms compatible with histoplasmosis were studied. Other nine accompanying subjects and five controls were also evaluated. Patients underwent mycological cultures and and serological tests for H. capsulatum. Intradermal test with 1% histoplasmine were done in all patients. Serology and skin tests tests were also performed in accompanying people. Intradermal were done in healthy controls. Skin test with histoplasmine were positive in seven of the nine patients. Six of these showed precipitating antibodies against the same antigen. H. capsulatum was only isolated from bone marrow biopsy samples in one patient. The seven patients were given itraconazole by oral route and all symptoms improved after 2 and 4 weeks. In five accompanying subjects the skin test were also positive so that a subclinical histoplasmosis was diagnosed. In the remaining patients and healthy accompanying subjects histoplasmosis infection was excluded. In non endemic geographical areas of histoplasmosis intradermal skin test with histoplasmin when used in immunocompetent individuals is an easy and reliable method for the diagnosis of this mycosis as well as for epidemiological studies.     

Disseminated histoplasmosis with hemophagocytic syndrome in a patient with AIDS: description of one case and review of the Spanish literature

We report a case of disseminated histoplasmosis in a 33-year old Ecuadorian patient with AIDS and a CD4 lymphocyte count of 39 cells/microl. He presented with prolonged fever and cough, was diagnosed with hemophagocytic syndrome and multiple organ failure and died 18 days after admission. Histoplasma capsulatum was isolated post-mortem from bone marrow biopsy and blood culture. In a literature review we found 22 published cases of disseminated histoplasmosis in patients with AIDS in Spain since 1988. All but two were men under 50 years old. Nineteen had been born or had lived in endemic areas. The diagnosis of histoplasmosis was established by culture of bone marrow biopsy in 10 cases. Itraconazole was introduced as a second drug after amphotericin B in ten of the thirteen patients who survived.     

Feline Histoplasmosis in Brazil: Clinical and Laboratory Aspects and a Comparative Approach of Published Reports

The present study described clinical and epidemiological aspects of three cases of feline histoplasmosis and compared them to previously described cases. A detailed mycological identification and antifungal susceptibility profile of each isolate are presented. Secondarily, a serological survey for anti-Histoplasma antibodies was performed with domestic and wild cats. Diseased animals presented nodular to ulcerated skin lesions and respiratory disorders as main clinical signs. H. capsulatum var. capsulatum was isolated and the strains showed to be susceptible to antifungal drugs. Considering that feline histoplasmosis is uncommonly observed in veterinary clinics, diagnosis, and clinical management in endemic areas should be improved.     

Histoplasmosis en un varón inmunocompetente manifestada 45 años después de la infección

We report a case of a lung reactivation of a latent histoplasmosis in a 68 year-old patient without immunologic dysfunction living in Barcelona (Spain).The Histoplasma capsulatum var. capsulatum infection was probably acquired in a previous stay in Equatorial Guinea 48 years before.Diagnosis of mild chronic pulmonary histoplasmosis was performed by histopathology of lung biopsy plus antibodies detection against H. capsulatum. Treatment with oral itraconazol during three months leaded to a complete clinical cure, and antibodies disappeared after four years of follow up.     

Histoplasmosis in a Brazilian center: clinical forms and laboratory tests

Histoplasmosis, caused by the dimorphic fungus Histoplasma capsulatum, is endemic in many regions of the Americas, Asia and Africa. It has a wide spectrum of clinical manifestations, from asymptomatic infection to severe disseminated disease. A retrospective study was carried out to describe the clinical forms and assess the clinical significance of the laboratory diagnostic tests of patients with histoplasmosis during the period of July 1987 to December 2003 at Instituto de Pesquisa Clínica Evandro Chagas/ FIOCRUZ, RJ, Brazil. Seventy-four patients were included. Forty-nine percent of the cases (n = 36) occurred in HIV positive patients who presented with disseminated disease. The remaining 38 cases were classified in different clinical forms. Histoplasma capsulatum was isolated from 69.5% of the clinical specimens sent to culture. Immunodiffusion and immunoblot were positive in 72.6% and 100% of the performed tests, respectively. Histopathologic findings suggestive of H. capsulatum were found in 63.2% of the performed exams. Serology had a lower proportion of positivity amongst AIDS patients, when compared with HIV negative patients (X2 = 6.65; p lower than 0.008). Statistical differences between AIDS and non-AIDS patients were not observed with culture and histopathology. The specific role of each test varies according to the clinical form. Physicians need to know the value and limitations of the available diagnostic tests, but before that, they have to think about histoplasmosis and consider this clinical entity in their differential diagnosis.     

Evaluation of a Microtiter Latex Agglutination Test for Histoplasmosis

Experiments were designed to evaluate a Microtiter latex agglutination (Micro-LA) test, as a serological aid in the diagnosis of histoplasmosis, and to compare this test with the conventional microtiter-complement fixation (CF) test for histoplasmosis. Sera tested were from cases of acute and chronic pulmonary and disseminated histoplasmosis, as well as from individuals not having histoplasmosis. Ninety-seven percent of the cases of acute pulmonary histoplasmosis had positive Micro-LA tests, whereas 91% had positive CF tests. Ninety-six percent of the patients having chronic pulmonary histoplasmosis showed positive Micro-LA tests and 91% had positive CF tests. In contrast, 64% of the cases of disseminated histoplasmosis had positive Micro-LA tests, whereas 82% had positive CF tests. None of these differences was statistically significant. Although there were no significant differences in complement fixing and agglutinating antibody cross-reactivity with Blastomyces antigens, more patients demonstrated CF titers than Micro-LA titers. Sera from patients with acute and chronic histoplasmosis showed higher Micro-LA titers than CF titers, whereas sera from cases of disseminated histoplasmosis showed higher CF titers. Histoplasmin skin testing has less of a boosting effect on agglutinating antibodies than on CF antibodies to histoplasmin. Anticomplementary sera can be used in the Micro-LA test. This test is simple to perform, and results can be obtained in 2 to 4 hr.     

Histoplasmosis and Thrombocytopenic Purpura: Transmission by Renal Homotransplantation

Two patients with disseminated histoplasmosis are reported. One patient presented with severe thrombocytopenic purpura and splenomegaly. Histoplasmin skin test, blood and bone marrow cultures and smears, sputum cultures, and chest radiographs were negative for Histoplasma capsulatum. She died on the sixth hospital day from a massive intracerebral hemorrhage. Cardiorespiratory function was maintained until one kidney was removed for homotransplantation. The second patient, with chronic glomerulonephritis and uremia, received the renal homograft from the first patient. Initial signs of homograft rejection developed five days postoperatively. Diffuse thrombocytopenic purpura occurred shortly thereafter. Spores of Histoplasma capsulatum were observed in blood smears, in leukocyte concentrates, and in five-day leukocyte cultures from the blood obtained prior to death. Disseminated histoplasmosis was found in both patients at autopsy. The severe platelet deficit in both cases suggests that systemic histoplasmosis should be considered as a cause of thrombocytopenic purpura.To our knowledge, this is the first reported instance of direct transmission of Histoplasma capsulatum, and must be considered a hazard in homotransplantation.In vitro leukocyte cultures as a method for early diagnosis of certain disseminated fungous infections needs further investigation.     

Imported and autochthonous histoplasmosis in Italy: new cases and old problems

In the past the Italian soil was considered as a low-endemic pabulum for H. capsulatum var. capsulatum and only few autochthonous cases of histoplasmosis were reported in Italy, especially in the Po valley. The aim of the paper was to evaluate this possibility by reviewing the literature and providing our own personal data. Four additional cases of histoplasmosis were observed during 1999-2003 in AIDS immigrant or in Italian citizens, and in travellers to endemic areas. One of the AIDS patients was an autochthonous case of histoplasmosis. The Italian literature was reviewed. Recent cases and literature data confirm the possible autochthonous presence of histoplasmosis in Italy, especially in the Northern regions.     

Histoplasmosis: cytodiagnosis and review of literature with special emphasis on differential diagnosis on cytomorphology

N. Gupta, S. K. Arora, A. Rajwanshi, R. Nijhawan and R. Srinivasan
Histoplasmosis: cytodiagnosis and review of literature with special emphasis on differential diagnosis on cytomorphology Background: Human infection with Histoplasma capsulatum runs the gamut from asymptomatic to disseminated disease. In immunocompromised patients, a tiny inoculum can lead to widespread disseminated infection. Early diagnosis and initiation of treatment is therefore important. Objective: To review the cases of histoplasmosis diagnosed on fine needle aspiration cytology (FNAC) and to discuss the clinical presentation, associated inflammatory response, load of organisms and differential diagnosis on cytomorphology in these cases. Methods: Retrospective review of seven cases of histoplasmosis at a tertiary‐care centre during the period from 1998 to 2009 was performed. Clinical presentation along with cytomorphological features were studied and discussed in detail. Results: The mean age of patients was 48.6 years and six out of seven were male. History of immunodeficiency (HIV) was available in five cases. Six patients presented with peripheral and/or abdominal lymphadenopathy. One patient had nodular shadows in both lungs and two also had skin lesions. On cytological smears, a variable load of uniform round to oval, about 2–4 μm in diameter, budding yeasts were seen intracellularly (within histiocytes) as well as extracellularly. In one case (HIV positive), these organisms were also seen within neutrophil polymorphonuclear leucocytes. In two cases, an inflammatory response in the form of epithelioid cell granulomas along with multinucleated giant cells was seen. Conclusions: FNAC is a reliable tool to recognize infection with H. capsulatum in tissues. This infection can cause a variable inflammatory response, which should be considered while reporting on such cases.     

Histoplasma capsulatum in the environment of sporadic histoplasmosis cases

Conclusions 1. Acute pulmonary histoplasmosis in adults is demonstrated to be associated with exogenous sources of infection in one-half of a series of cases. 2. No exogenous sources of infection were found in chronic pulmonary histoplasmosis in adults by methods comparable to those used in acute pulmonary histoplasmosis. 3. The significance of these findings for the pathogenesis of the three clinical forms of histoplasmosis is discussed. 4. In acute pulmonary histoplasmosis in adults, the isolation ofH. capsulatum from the environment at sites of exposure aided in specific diagnosis.Two acute pulmonary histoplasmosis cases were reported previously (2–3).     

Histoplasmosis as cause of penile ulcer in acquired immune deficiency syndrome (AIDS): three case reports

Background Histoplasma capsulatum is the causative agent of American histoplasmosis. The relationship between disseminated histoplasmosis and AIDS has been well established. Widespread hematogenous dissemination of Histoplasma capsulatum in HIV positive patients can cause a plethora of clinical manifestations; virtually any organic system can be affected. However, genital ulceration by H. capsulatum in patients with AIDS is a real challenge during investigation of the infection due to the great variety of differential diagnoses that are involved. Method The diagnosis was performed by histopathologic study; H. capsulatum was detected by silver staining (Grocott staining) and confirmed by immunocytochemistry. Results We report three cases of histoplasmosis in patients with AIDS, in which we observed genital ulcers, an unusual form of presentation of this disease. In one of these cases, the treatment resulted in total cure. Conclusion The cases reported herein are to illustrate the plurality of pathologies and clinical manifestations, which may affect immunocompromised patients. The correct diagnosis of fungal diseases in these patients following well established treatment will improve the prognosis.     

Histoplasmosis in individuals with acquired immunodeficiency syndrome (AIDS): Report of six cases with cutaneous-mucosal involvement

The authors report the first six cases of disseminated histoplasmosis and acquired immunodeficiency syndrome (AIDS) seen at the University Hospital, Faculty of Medicine of Ribeirão Preto, University of São Paulo, from 1987 to 1989, with emphasis on dermatological clinical manifestations, nasal mucosa lesions and treatment. The mycosis was the first manifestation of AIDS in four patients. It is concluded that biopsies of the lesions for histopathologic study and fungal culture are important for diagnosis.