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OBJECTIVES: The aim of the present study was to evaluate minimally invasive diagnostic techniques, such as the semi-quantitative indirect IgG antibody enzyme immunoassay (EIA) using blood serum and the urinary lateral flow assay (LFA), for the detection of Histoplasma capsulatum in cats with histoplasmosis. METHODS: Eight client-owned domestic cats diagnosed with histoplasmosis were selected based on cytological, histopathological, mycological, molecular or antigenic techniques. The blood serum of these animals was tested in a semi-quantitative indirect IgG antibody EIA for the detection of H capsulatum. Urine samples were tested for H capsulatum antigen using LFA. RESULTS: Five cats were seropositive on IgG EIA (5/8, with diagnostic sensitivity equal to 62.5%; 95% confidence interval [CI] 24.5-91.5) and five cats were positive on H capsulatum antigen LFA (5/7, with diagnostic sensitivity equal to 71.4%; 95% CI 29.0-96.3). The combined diagnostic sensitivity when interpreted in parallel was 87.5% (7/8, 95% CI 47.3-99.7). The specificity for the anti-Histoplasma IgG EIA was 100% (95% CI 71.5-100) and for the H capsulatum antigen LFA it was also 100% (95% CI 71.5-100). CONCLUSIONS AND RELEVANCE: The semi-quantitative indirect IgG antibody EIA for the detection of H capsulatum in blood serum and the urinary LFA for the detection of the same agent emerge as new minimally invasive diagnostic techniques that can assist in the approach to disseminated and pulmonary feline histoplasmosis, especially when both techniques are considered together.

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The mycosis histoplasmosis is also considered a zoonosis that affects humans and other mammalian species worldwide. Among the wild mammals predisposed to be infected with the etiologic agent of histoplasmosis, bats are relevant because they are reservoir of Histoplasma species, and they play a fundamental role in maintaining and spreading fungal propagules in the environments since the infective mycelial phase of Histoplasma grows in their accumulated guano. In this study, we detected the fungal presence in organ samples of bats randomly captured in urban areas of Araraquara City, São Paulo, Brazil. Fungal detection was performed using a nested polymerase chain reaction to amplify a molecular marker (Hcp100) unique to H. capsulatum, which revealed the pathogen presence in organ samples from 15 out of 37 captured bats, indicating 40.5% of infection. Out of 22 Hcp100-amplicons generated, 41% corresponded to lung and trachea samples and 59% to spleen, liver, and kidney samples. Data from these last three organs suggest that bats develop disseminated infections. Considering that infected bats create environments with a high risk of infection, it is important to register the percentage of infected bats living in urban areas to avoid risks of infection to humans, domestic animals, and wildlife.

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Definitive diagnosis of histoplasmosis relies on culture and/or cytology/histopathology; however, these procedures have limited sensitivity and cultures are time-consuming. Antibodies detection by immunodiffusion has low sensitivity in immunocompromised individuals and uses histoplasmin (HMN), a crude antigenic extract, as reagent. Novel protein antigen candidates have been recently identified and produced by DNA-recombinant techniques to obtain standardized and specific reagents for diagnosing histoplasmosis. To compare the analytical performance of novel enzyme-linked immunosorbent assays (ELISAs) for antibodies testing for diagnosing histoplasmosis using different Histoplasma capsulatum antigens as reagents. The H. capsulatum 100 kDa protein (Hcp100), the M antigen and its immunoreactive fragment F1 were produced by DNA-recombinant techniques. Galactomannan was purified from both the yeast and mycelial cell walls (yGM and mGM, respectively). The analytical performance of the ELISA tests for the serological detection of antibodies against these antigens was evaluated and compared with those obtained using HMN as reagent. Antibodies detection by the Hcp100 ELISA demonstrated 90.0% sensitivity and 92.0% specificity, versus 43.3% sensitivity and 95.0% specificity of the M ELISA, 33.3% sensitivity and 84.0% specificity of the F1 ELISA, 96.7% sensitivity and 94.0% specificity of the yGM ELISA, 83.3% sensitivity and 88.0% specificity of the mGM ELISA, and 70.0% sensitivity and 86.0% specificity for the HMN ELISA. In summary, Hcp100 is proposed as the most promising candidate for the serodiagnosis of histoplasmosis. The primary immunoreactive element in HMN proved to be GM rather than the M antigen. Nevertheless, a higher incidence of cross-reactions was noted with GM compared to M.

Hcp100 is a promising serodiagnostic candidate for histoplasmosis, boasting high sensitivity and specificity. Notably, GM, rather than M antigen, emerged as the primary immunoreactive element in HMN, despite a higher incidence of cross-reactions with GM compared to M.

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Patients with severe COVID-19 are at increased risk for invasive fungal infections, which are underestimated. Histoplasmosis reactivation in endemic areas should not be overlooked in this population. In a previous study, seroconversion to anti-histoplasmin antibodies by ELISA was detected in 6/39 (15.4%) patients with severe COVID-19. In this work, samples were further investigated to detect seroconversion to antibodies against the Histoplasma capsulatum 100-kDa antigen (Hcp100) by ELISA. Seroconversion to anti-Hcp100 antibodies was detected in 7/39 patients, of whom 6 also seroconverted anti-histoplasmin antibodies. These results reinforce previous findings that show histoplasmosis as an underdiagnosed fungal entity complicating COVID-19.

This study verifies that patients with severe COVID-19 at intensive care units are at risk for histoplasmosis reactivation in endemic areas. Accurate diagnosis of this deadly fungal disease among critically ill patients with COVID-19 living in endemic areas for histoplasmosis is needed.

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In this retrospective study, the clinical and anatomopathological findings of fungal diseases in dogs and cats in Northeastern Brazil are described. During the study period, 6,827 histopathological examinations (4,090 necropsies and 2,737 biopsies) of companion animals were reviewed, and fungal infections were diagnosed in 54 cases. Of these, 32 cases were diagnosed in cats and 22 in dogs. Sporotrichosis was the most prevalent mycosis (19/54), followed by dermatophytosis (9/54), cryptococcosis (8/54), candidiasis (7/54), and phaeohyphomycosis (4/54). Other diseases had two cases each, including aspergillosis, mucormycosis, and histoplasmosis, whereas coccidioidomycosis occurred once. Mycoses were diagnosed through microscopic lesions associated with the histomorphological characteristics of the agent, as evidenced by routine and special histochemical stains. They were occasionally confirmed by immunohistochemistry and microbiological cultivation. This retrospective study showed that despite being uncommon, fungal diseases are important causes of death in dogs and cats in the region, with cats being the most affected species and sporotrichosis being the most prevalent mycosis. Clinical signs were correlated with the portal of entry of the infection associated with localized or disseminated superficial and deep skin lesions or affecting parenchymal organs, especially in systemic infections. Microscopic lesions were mainly characterized by pyogranulomatous inflammation associated with fungal structures. In dogs, mycoses occurred mainly owing to an immunological impairment secondary to canine distemper virus co-infection.

Neste estudo retrospectivo, são descritos os achados clínicos e anatomopatológicos das doenças fúngicas em cães e gatos no Nordeste do Brasil. Durante o período de estudo, foram revisados 6.827 exames histopatológicos (4.090 necropsias e 2.737 biópsias) de animais de companhia e diagnosticados 54 casos de infecções fúngicas. Destes, 32 casos foram diagnosticados em gatos e 22 em cães. A esporotricose foi a micose mais prevalente (19/54), seguida pela dermatofitose (9/54), criptococose (8/54), candidíase (7/54) e feo-hifomicose (4/54). Outras doenças tiveram dois casos cada, incluindo aspergilose, mucormicose e histoplasmose, enquanto a coccidioidomicose ocorreu uma vez. As micoses foram diagnosticadas por meio das lesões microscópicas associadas às características histomorfológicas do agente, evidenciadas pelas colorações de rotina e histoquímicas especiais, e ocasionalmente confirmadas pela imuno-histoquímica e cultivo microbiológico. Esse estudo retrospectivo demonstrou que apesar de incomuns, as doenças fúngicas são importantes causas de morte em cães e gatos da região, sendo os gatos a espécie mais afetada e a esporotricose, a micose mais prevalente. Os sinais clínicos estavam correlacionados com a porta de entrada da infecção, associados a lesões cutâneas localizadas ou disseminadas superficiais e profundas ou afetando órgãos parenquimatosos, especialmente em infecções sistêmicas. As lesões microscópicas eram caracterizadas principalmente por inflamação piogranulomatosa associada a estruturas fúngicas. Nos cães, as micoses ocorreram principalmente devido ao comprometimento imunológico secundária a coinfecção pelo vírus da cinomose canina.

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A histoplasmose é uma doença zoonótica, causada por um fungo oportunista, chamado Histoplasma capsulatum. O fungo é endêmico de regiões subtropicais e temperadas, sendo sua presença relatada principalmente nas Américas, na Índia e no Sudoeste Asiático.Acredita-se que os casos de histoplasmose em gatos ainda sejam subestimados. No Brasil, a maioria dos casos relatados foram provenientes do estado do Ceará. A histoplasmose é considerada a segunda causa mais comum de afecção micótica sistêmica em gatos. Desta forma, o objetivo do presente trabalho foi relatar a ocorrência de um caso com resolução satisfatória em Fortaleza/Ceará. O animal apresentou histórico de espirros crônicos, secreção nasal e um aumento de volume na região nasal, além de um nódulo ulcerado no flanco direito. Foram solicitadas citologia e cultura da lesão, onde foram evidenciadas leveduras sugestivas de Histoplasma capsulatum. O tratamento escolhido foi itraconazol na dose de 100mg/gato, sendo administrada por via oral uma cápsula ao dia. Após 30 dias, o animal retornou ao consultório, apresentando uma melhora considerável, sem aumento de plano nasal, processo obstrutivo nasal e lesões de pele.

Histoplasmosis is a zoonotic disease caused by an opportunistic fungus called Histoplasma capsulatum. The fungus is endemic to subtropical and temperate regions, with its presence being reported mainly in the Americas, India, and Southeast Asia. It is believed that the cases of histoplasmosis in cats are still underestimated. In Brazil, most reported cases were from the state of Ceará. Histoplasmosis is considered the second most common cause of systemic mycotic disease in cats. Thus, the present study aimed to report the occurrence of a case with satisfactory resolution in Fortaleza/Ceará. The animal showed a history of chronic sneezing, nasal secretion, and an increase in volume in the nasal region, in addition to an ulcerated nodule on the right flank. Cytology and culture of the lesion were requested, where yeasts suggestive of Histoplasma capsulatum were evidenced. The chosen treatment was itraconazole at a dose of 100mg/cat, being administered orally one capsule a day. After 30 days, the animal returned to the clinic showing considerable improvement, without an increase in the nasal plane, nasal obstructive process, and skin lesions.

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Histoplasmosis is a mycotic infection principally affecting pulmonary tissue; sometimes, histoplasmosis can progress into a systemic disease. This infection involves immunocompetent and immunosuppressed human and other mammalian hosts, depending on particular circumstances. Histoplasmosis infection has been documented worldwide. The infection is acquired by inhaling infective mycelial propagules of the dimorphic fungus Histoplasma capsulatum. New reports of clinical cases of histoplasmosis in extreme latitudes could be related to human social adaptations and climate changes in the world, which are creating new favorable environments for this fungus and for bats, its major natural reservoirs and dispersers. Histoplasma has been isolated from most continents, and it is considered a complex of cryptic species, consisting of various groups of isolates that differ genetically and correlate with a particular geographic distribution. Based on updated studies, Histoplasma taxonomy is adjusting to new genetic data. Here, we have suggested that Histoplasma has at least 14 phylogenetic species distributed worldwide and new genotypes that could be under deliberation. Histoplasma's geographic radiation began in South America millions of years ago when the continents were joined and the climate was favorable. For fungal spreading, the role of bats and some birds is crucial, although other natural factors could also participate.

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Histoplasma capsulatum é o agente causador da histoplasmose, uma das principais doenças que acomete o sistema respiratório inferior de cães e gatos. Este patógeno é frequentemente isolado de fezes de aves e morcegos. A infecção ocorre por inalação dos esporos fúngicos em solos contaminados com as fezes. As manifestações clínicas da doença são divididas em infecção pulmonar, gastrointestinal, subclínica e disseminada. Esta revisão descreve como a doença ocorre em cães e felinos domésticos, seus achados clínicos, diagnóstico, tratamento e prevenção, evidenciando sua importância na clínica médica de pequenos animais.(AU)

Histoplasma capsulatum is the causative agent of histoplasmosis, one of the main diseases that affects the lower respiratory system of dogs and cats. This pathogen is often isolated from bird and bat droppings. Infection occurs by inhaling fungal spores in soil contaminated with faeces. The clinical manifestations of the disease are divided into pulmonary, gastrointestinal, subclinical and disseminated infection. This review describes how the disease occurs in dogs and domestic cats, their clinical findings, diagnosis, treatment and prevention, highlighting its importance in the medical clinic of small animals.(AU)

Histoplasma capsulatum es el agente causante de la histoplasmosis, una de las principales enfermedades que afecta al sistema respiratorio inferior de perros y gatos. Este patógeno a menudo se aísla de los excrementos de pájaros y murciélagos. La infección se produce al inhalar esporas de hongos en suelo contaminado con heces. Las manifestaciones clínicas de la enfermedad se dividen en infección pulmonar, gastrointestinal, subclínica y diseminada. Esta revisión describe cómo se presenta la enfermedad en perros y gatos domésticos, sus hallazgos clínicos, diagnóstico, tratamiento y prevención, destacando su importancia en la clínica médica de pequeños animales.(AU)

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Histoplasma capsulatum é o agente causador da histoplasmose, uma das principais doenças que acomete o sistema respiratório inferior de cães e gatos. Este patógeno é frequentemente isolado de fezes de aves e morcegos. A infecção ocorre por inalação dos esporos fúngicos em solos contaminados com as fezes. As manifestações clínicas da doença são divididas em infecção pulmonar, gastrointestinal, subclínica e disseminada. Esta revisão descreve como a doença ocorre em cães e felinos domésticos, seus achados clínicos, diagnóstico, tratamento e prevenção, evidenciando sua importância na clínica médica de pequenos animais.

Histoplasma capsulatum is the causative agent of histoplasmosis, one of the main diseases that affects the lower respiratory system of dogs and cats. This pathogen is often isolated from bird and bat droppings. Infection occurs by inhaling fungal spores in soil contaminated with faeces. The clinical manifestations of the disease are divided into pulmonary, gastrointestinal, subclinical and disseminated infection. This review describes how the disease occurs in dogs and domestic cats, their clinical findings, diagnosis, treatment and prevention, highlighting its importance in the medical clinic of small animals.

Histoplasma capsulatum es el agente causante de la histoplasmosis, una de las principales enfermedades que afecta al sistema respiratorio inferior de perros y gatos. Este patógeno a menudo se aísla de los excrementos de pájaros y murciélagos. La infección se produce al inhalar esporas de hongos en suelo contaminado con heces. Las manifestaciones clínicas de la enfermedad se dividen en infección pulmonar, gastrointestinal, subclínica y diseminada. Esta revisión describe cómo se presenta la enfermedad en perros y gatos domésticos, sus hallazgos clínicos, diagnóstico, tratamiento y prevención, destacando su importancia en la clínica médica de pequeños animales.

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Histoplasma capsulatum, the fungus causing histoplasmosis, has a strong impact on public health. Histoplasmosis is one of the most prevalent systemic mycoses in the Americas and occurs in several mammalian species. Bats are important in the epidemiological cycle of histoplasmosis because they disseminate the fungus throughout the environment. The aim of the present study was to investigate natural H. capsulatum infection in bats located in forested areas, which have undergone anthropogenic perturbations, as well as in the urban areas of the state of Pará. Twenty-two species of bats were captured in 18 municipalities of Pará; the samples obtained from these animals were subjected to nested PCR for amplification of H. capsulatum DNA. The HCI/HCII and HCIII/HCIV primers were used, and the final 210-pb fragment was amplified. Of the 100 bats analysed, two were confirmed to be positive for H. capsulatum. Samples amplified by nested PCR were sequenced and found to share identity and have 100% match with H. capsulatum DNA. H. capsulatum was detected in the area of study: the state of Pará has a wide diversity of bat species, and the region under investigation is situated in the north of the state, which suffers the most severe environmental and climatic changes. Therefore, it is essential to elucidate the distribution of H. capsulatum hosts in this region to facilitate the implementation of effective disease surveillance.

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