Coccidioidomycosis and other endemic mycoses in Mexico

The endemic mycoses traditionally include coccidioidomycosis, histoplasmosis, blastomycosis and paracoccidioidomycosis. Although sporotrichosis and chromomycosis are technically not included among the endemic mycoses, they are frequently diagnosed in Mexico. Most systemic endemic mycoses are a consequence of inhaling the fungi, while subcutaneous mycoses are acquired through the inoculation of vegetable matter or soil containing the organism. Coccidioidomycosis is caused by Coccidioides spp., a dimorphic pathogenic fungus. Approximately 60% of exposures result in asymptomatic infection; in the rest there are protean manifestations that range from a benign syndrome also known as "Valley Fever" to progressive pulmonary or extrapulmonary disease. Histoplasmosis, caused by the dimorphic fungus Histoplasma capsulatum, is endemic to the Americas. Pulmonary histoplasmosis manifestations are protean, ranging from a brief period of malaise to a severe, prolonged illness. The spectrum of illness in disseminated histoplasmosis ranges from a chronic, intermittent course to an acute and rapidly fatal infection. Paracoccidioidomycosis is a chronic, granulomatous systemic disease caused by Paracoccidioides brasiliensis that characteristically produces a primary pulmonary infection, often asymptomatic, and then disseminates to form ulcerative granulomata of the oral, nasal and occasionally the gastrointestinal mucosa. Sporotrichosis, caused by Sporothrix schenckii, has diverse clinical manifestations; the most frequent is the lymphocutaneous form. Generally, infection results from inoculation of the fungus through thorns, splinters, scratches and small traumas. Chromomycosis (Chromoblastomycosis) is a slowly progressive cutaneous and subcutaneous mycosis attributed to various saprophyte Hypomycetes fungi. The primary lesion is also thought to develop as a result of percutaneous traumatic inoculation.     

Gr-1+ cells play an essential role in an experimental model of disseminated histoplasmosis

Recent studies have shown the participation of Gr-1(+) cells in many types of infections; however, the role played by these cells in the immune response to fungal pathogens is controversial. In this study we determined whether Gr-1(+) cells are involved in the protective immune response in systemic Histoplasma capsulatum infection. Depletion of Gr-1(+) cells using the monoclonal antibody (MAb) RB6-8C5 increased histoplasmosis severity and inhibited the subsequent development of a protective immune response. In addition to the increased fungal burden in lungs and spleens, the Th1 response was found to be unbalanced in these mice and the suppression of the cellular immune response seemed to be associated with increased nitric oxide production. Taken together, these results indicate that Gr-1(+) cell depletion at the beginning of infection allows yeast multiplication and increases mice mortality. This study improves the understanding of the role of Gr-1(+) cells on the protective immunity in histoplasmosis.     

Occurrence of histoplasmosis in Asia

The occurrence of histoplasmosis in Asia has been reviewed. Authentic cases of histoplasmosis in man are known from India, Malaysia, Singapore, Indonesia, Thailand, South Vietnam and Japan, but the autochthonous nature of the cases reported has not been established unequivocally. Of the 30 cases of human histoplasmosis recorded from Asia, 15 were confirmed by positive cultures, and their country-wise distribution is as follows: Malaysia — 4, Indonesia — 3, Singapore — 2, Thailand — 2, South Vietnam — 2 and one each from India and Japan. Authentic cases of histoplasmosis in animals are currently unknown from Asia, and likewise there is no information on the natural habitats of the etiologic agentH. capsulatum in this part of the world except for a solitary isolation from soil in bat-infested cave in Malaysia.The available data on the prevalence of cutaneous hypersensitivity to histoplasmin indicates that histoplasmin sensitivity is absent in Israel, Syria, Saudi Arabia, Lebanon and Qatar; sensitivity is negligible or of a very low order in Iran, Iraq, Pakistan and India, and for these countries it has been even suggested that the positive reactors observed may represent cross-sections with some unknown fungus/fungi which may be antigenically related toH. capsulatum. In Japan the frequency of histoplasmin positive reactors has been negligible except in groups of persons working near a U.S. Army base and in factories which used soil and sand imported from overseas including the U.S.A. In Burma and Taiwan the bulk of positive reactions in which the induration did not exceed 8 mm in diameter has been considered probably non-specific. In Indonesia and South Vietnam, on the other hand, where less than 10 per cent of the reactions tended to concentrate around an induration of 16 mm sensitivity to histoplasmin may represent specificH. capsulatum infection in certain cases. Likewisef the requently large reactions reported from the Philippines have also been interpreted to represent specific histoplasmosis infection.The recovery ofH. capsulatum from soil coupled with the finding of well-documented cases of histoplasmosis in Malaysia suggests that the disease is endemic in that country. It is not unlikely that histoplasmosis is endemic in other parts of Asia although this has not been demonstrated so far. Comprehensive mycological, serological and soil studies are indicated in order to investigate the prevalence and incidence of histoplasmosis and to map out the endemic areas of the disease in Asia.Paper read at the Eighth International Congresses for Tropical Medicine and Malaria, September 1968, Teheran (Iran).     

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.     

A global view on fungal infections in humans and animals: infections caused by dimorphic fungi and dermatophytoses

Fungal infections are still underappreciated and their prevalence is underestimated, which renders them a serious public health problem. Realistic discussions about their distribution, symptoms, and control can improve management and diagnosis and contribute to refinement of preventive actions using currently available tools. This article represents an overview of dermatophytes and endemic fungi that cause infections in humans and animals. In addition, the impact of climate change on the fungal spread is discussed. The endemic fungal infections characterized in this article include coccidioidomycosis, histoplasmosis, blastomycosis, lobomycosis, emergomycosis and sporotrichosis. Moreover the geographic distribution of these fungi, which are known to be climate sensitive and/or limited to endemic tropical and subtropical areas, is highlighted. In turn, dermatophytes cause superficial fungal infections of skin, hairs and nails, which are the most prevalent mycoses worldwide with a high economic burden. Therefore, the possibility of causing zoonoses and reverse zoonoses by dermatophytes is highly important. In conclusion, the article illustrates the current issues of the epidemiology and distribution of fungal diseases, emphasizing the lack of public programmes for prevention and control of these types of infection.     

Histoplasmosis in Montreal During the Fall of 1963, with Observations on Erythema Multiforme

Although Montreal is in an endemic area, significant clinical histoplasmosis with systemic manifestations has been, until recently, infrequently diagnosed. However, since the autumn of 1963, 31 cases of clinically significant histoplasmosis have been seen by the authors. These were divided into two groups: (1) patients in whom the diagnosis was established on the basis of histological and/or cultural demonstration of the fungus; (2) patients in whom the diagnosis was based on a positive histoplasmin skin test, a complement fixation antibody titre of 1:32 or greater and compatible clinical and radiological findings. An additional group of 11 patients who presented with erythema multiforme was investigated and a heretofore unrecognized relationship between histoplasmosis and erythema multiforme was established.     

The protein "mycoarray": a novel serological assay for the laboratory diagnosis of primitive endemic mycoses

A protein microarray containing fungal antigens (the "mycoarray") has been set up to provide rapid and appropriate serodiagnosis of primitive endemic mycoses, an important cause of morbidity and mortality in an increasingly high number of patients. The mycoarray consists of three antigen extracts (histoplasmin, coccidioidin and Coccidioides "TP") and antibody dilution curves were spotted on microarray slides. The arrays were processed with coccidioidomycosis and histoplasmosis patients? sera or with control sera and the occurring immunocomplexes were detected by indirect immunofluorescence. In agreement with clinical and microbiological diagnosis, the results distinguished between histoplasmosis and coccidioidomycosis patients. In addition, the assay could clearly discriminate between IgM and IgG antibody reactivity. No reactivity was ever observed in the arrays processed with negative control sera. Therefore, this pilot study demonstrates that the "mycoarray" is sensitive and specific enough to discriminate between healthy individuals and patients with histoplasmosis or coccidioidomycosis. Because of miniaturization and multiparametricity, the new assay cuts costs and processing time. Thus, once clinically validated and implemented as a large-scale array, the "mycoarray" will be ready to be applied to the daily clinical practice.     

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.     

Explaining observed infection and antibody age-profiles in populations with urogenital schistosomiasis

Urogenital schistosomiasis is a tropical disease infecting more than 100 million people in sub-Saharan Africa. Individuals in endemic areas endure repeated infections with long-lived schistosome worms, and also encounter larval and egg stages of the life cycle. Protective immunity against infection develops slowly with age. Distinctive age-related patterns of infection and specific antibody responses are seen in endemic areas, including an infection 'peak shift' and a switch in the antibody types produced. Deterministic models describing changing levels of infection and antibody with age in homogeneously exposed populations were developed to identify the key mechanisms underlying the antibody switch, and to test two theories for the slow development of protective immunity: that (i) exposure to dying (long-lived) worms, or (ii) experience of a threshold level of antigen, is necessary to stimulate protective antibody. Different model structures were explored, including alternative stages of the life cycle as the main antigenic source and the principal target of protective antibody, different worm survival distributions, antigen thresholds and immune cross-regulation. Models were identified which could reproduce patterns of infection and antibody consistent with field data. Models with dying worms as the main source of protective antigen could reproduce all of these patterns, but so could some models with other continually-encountered life stages acting as the principal antigen source. An antigen threshold enhanced the ability of the model to replicate these patterns, but was not essential for it to do so. Models including either non-exponential worm survival or cross-regulation were more likely to be able to reproduce field patterns, but neither of these was absolutely required. The combination of life cycle stage stimulating, and targeted by, antibody was found to be critical in determining whether models could successfully reproduce patterns in the data, and a number of combinations were excluded as being inconsistent with field data.     

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。     

A case of disseminated histoplasmosis diagnosed after oral presentation in an old HIV‐negative patient in Sweden

Histoplasmosis is an endemic disease in various regions such as North America and South‐East Asia but remains rare in Europe. Disseminated histoplasmosis is unusual in HIV‐negative patients. Here, we describe a case of disseminated histoplasmosis in an HIV‐negative patient diagnosed after oral presentation.     

Acute disseminated histoplasmosis in infancy in Brazil: report of a case and review

Although early age is an important risk factor for the occurrence of acute disseminated histoplasmosis in non immunosuppressed infants, cases of this condition have been rarely reported, even in highly endemic areas. This is a reason to add a new case, the first one diagnosed in the state of Rio Grande do Sul, and, also, to review and comment on the Brazilian literature of histoplasmosis in patients under three years of age.     

Diagnosis and management of histoplasmosis

Histoplasmosis occurs sporadically or during outbreaks in endemic areas. The risk for severe forms of histoplasmosis is substantially higher among the growing population of immunocompromised patients. Recent research efforts have focused on analyzing epidemics, identifying risk factors for the disease, developing improved noninvasive diagnostic assays, and assessing the roles of newer antifungal drugs. Guidelines have been published for the prevention of occupationally acquired histoplasmosis and for reducing the risk of disease in patients with HIV infection. A third-generation Histoplasma antigen assay has been developed, which has superior performance characteristics compared to other noninvasive diagnostic tests. Treatment guidelines for the various clinical forms of histoplasmosis have been formulated and updated. Two newer azoles with activity against Histoplasma capsulatum, voriconazole and posaconazole, have been released; in vitro susceptibility data and animal model results have been reported, and treatment experience with these drugs has accumulated.     

Indigenous Case of Disseminated Histoplasmosis from the <Emphasis Type="Italic">Penicillium marneffei</Emphasis> Endemic Area of China

This is the first indigenous case of disseminated histoplasmosis reported from the Penicillium marneffei endemic area in southern China. It was diagnosed by histopathology of tissue, gross and microscopic morphology of the culture and PCR assay of the isolated fungus. Successful antifungal treatment was with itraconazole 400 mg/day for 5 months. This case suggests that histoplasmosis should be an important differential diagnosis in immunocompromised patients in southern China and South East Asia (the only endemic area for P. marneffei).     

Three cases of imported histoplasmosis in our hospital

Since 1999 we have observed three cases of imported histoplasmosis in our hospital. One was an immunocompetent individual and two further patients were immunosuppressed (renal transplantation and HIV infection C3). Two patients were born in endemic areas (Equatorial Guinea and Ecuador) and a third patient had a history of previous travel to the Peruvian Amazonia. The different clinical presentations and diagnostic tools of histoplasmosis are discussed.     

Heated histoplasmin as a control for non-specificity in the complement fixation test for histoplasmosis

We present data in support of the use of a heated histoplasmin control for the complement fixation (CF) test for histoplasmosis to assist in the detection of the presence of h or m antibody.     

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.     

Current diagnosis of histoplasmosis

Histoplasmosis is a common infection endemic in many regions of America, Asia, India and Africa, with sporadic cases also occurring throughout the world. Although excellent laboratory methods for diagnosis are available, there are deficiencies that must be met by continued research. Clinicians and laboratory directors must be familiar with the uses and limitations of a battery of serologic and mycological tests to accurately diagnose histoplasmosis. Research is needed to reduce false-negative and false-positive results, and to improve the identification of the organism in tissues. Approaches to the diagnosis of histoplasmosis and areas that require further research will be reviewed.     

High prevalence and mortality due to Histoplasma capsulatum in the Brazilian Amazon: An autopsy study

BackgroundHistoplasmosis is acquired by inhalation of spores of the dimorphic fungus Histoplasma spp. Although this pathogen is distributed worldwide, it is more prevalent in the Americas. However, the real burden of histoplasmosis remains undefined in many endemic regions.MethodologyWe conducted a series of 61 autopsies to individuals who died in a hospital in the Brazilian Amazon focused on infectious diseases. We performed a detailed histological and microbiological evaluation with genetic characterization of Histoplasma strains with the aim to evaluate the contribution of histoplasmosis to morbidity and mortality. Additionally, we assessed the clinicopathological correlation.Principal findingsEvidence of Histoplasma infection was detected in 21 patients (34%). Eight cases were disseminated infections, all of them occurred in HIV-positive patients. Six cases were localized histoplasmosis, limited to the lungs. In seven patients Histoplasma DNA was detected by PCR in patients with no histological lesions. Histoplasma infection was detected in 38% of HIV-positive patients and was a major contributor to death in 22% of them. Lungs, liver and spleen were affected in all cases of disseminated histoplasmosis. Phylogenetic analysis of the strains suggested a high diversity of Histoplasma species circulating in the Brazilian Amazon. Histoplasmosis was clinically missed in 75% of the disseminated infections.ConclusionsThe high incidence of histoplasmosis, the low index of clinical suspicion, and the severity of the disseminated disease highlight the need of proactively implementing sensitive routine screening methods for this pathogen in endemic areas. Antifungal prophylaxis against Histoplasma should be encouraged in the severely immunocompromised HIV patients in these areas. In conclusion, substantial mortality is associated with disseminated histoplasmosis among HIV-positive patients in the Brazilian Amazon.     

The ABCs (Antibody, B cells, and Carbohydrate epitopes) of cholera immunity: considerations for an improved vaccine

Cholera, a diarrheal disease, is known for explosive epidemics that can quickly kill thousands. Endemic cholera is a seasonal torment that also has a significant mortality. Not all nations with extensive rural communities can achieve the required infrastructure or behavioral changes to prevent epidemic or endemic cholera. For some communities, a single-dose cholera vaccine that protects those at risk is the most efficacious means to reduce morbidity and mortality. It is clear that our understanding of what a protective cholera immune response is has not progressed at the rate our understanding of the pathogenesis and molecular biology of cholera infection has. This review addresses V. cholerae lipopolysaccharide (LPS)-based immunogens because LPS is the only immunogen proven to induce protective antibody in humans. We discuss the role of anti-LPS antibodies in protection from cholera, the importance and the potential role of B cell subsets in protection that is based on their anatomical location and the intrinsic antigen-receptor specificity of various subsets is introduced.