Boletim epidemiológico: perfil de pacientes com micoses sistêmicas notificados de 2013 a 2018 em hospital de referência do estado de Goiás / Epidemiological bulletin: profile of patients with systemic mycoses notified from 2013 to 2018 in a reference hospital in the state of Goiás

Micoses Sistêmicas são infecções fúngicas causadas por patógenos primários cujo trato respiratório é utilizado como porta de entrada, mas ocasionalmente se disseminam para todo o organismo. As micoses sistêmicas consideradas endêmicas no Brasil são: paracoccidioidomicose, histoplasmose, coccidioidomicose e criptococose. Por se tratarem de doenças fúngicas emergentes constata-se a necessidade de implantação de uma vigilância epidemiológica eficaz, que tenha impacto positivo na saúde pública no que diz respeito à elaboração de diretrizes e execuções de ações para prevenção, tratamento, e controle dessas micoses. Desta forma, este boletim tem como objetivo descrever o perfil de pacientes com micoses sistemas notificados em hospital de referência de Goiás. Trata-se de um estudo transversal descrito, quantitativo, com dados obtidos do Sistema de Informação de Agravos de Notificação (SINAN-NET) de um Núcleo Hospitalar de Vigilância Epidemiológica do estado de Goiás no período de 2013 a 2018

Systemic mycoses are fungal infections caused by primary pathogens whose respiratory tract is used as a gateway, but occasionally disseminate throughout the body. The systemic mycoses considered endemic in Brazil are: paracoccidioidomycosis, histoplasmosis, coccidioidomycosis and cryptococcosis. As they are emerging fungal diseases, there is a need to implement effective epidemiological surveillance, which has a positive impact on public health with regard to the elaboration of guidelines and execution of actions for the prevention, treatment, and control of these mycoses. Thus, this bulletin aims to describe the profile of patients with systemic mycoses reported in a referral hospital in Goiás. This is a descriptive, quantitative, cross-sectional study with data obtained from the Notifiable Diseases Information System (SINAN-NET) of a Hospital Center for Epidemiological Surveillance in the state of Goiás from 2013 to 2018

Imported endemic mycoses in Spain: Evolution of hospitalized cases, clinical characteristics and correlation with migratory movements, 1997-2014.

Endemic mycoses are systemic fungal infections. Histoplasmosis is endemic in all temperate areas of the world; coccidioidomycosis and paracoccidioidomycosis are only present in the American continent. These pathogens are not present in Spain, but in the last years there has been an increase of reported cases due to migration and temporary movements. We obtained from the Spanish hospitals records clinical and demographic data of all hospitalized cases between 1997 and 2014. There were 286 cases of histoplasmosis, 94 of Coccidioidomycosis and 25 of paracoccidioidomycosis. Overall, histoplasmosis was strongly related to HIV infection, as well as with greater morbidity and mortality. For the other mycoses, we did not find any immunosuppressive condition in most of the cases. Although we were not able to obtain data about clinical presentation of all the cases, the most frequently found was pulmonary involvement. We also found a temporal correlation between the Spanish population born in endemic countries and the number of hospitalized cases along this period. This study reflects the importance of imported diseases in non-endemic countries due to migratory movements.

Vertical Transmission of Histoplasmosis Associated With Anti-Tumor Necrosis Factor Therapy.

Therapeutics blocking the activity of tumor necrosis factor (anti-TNF) are a risk factor for invasive fungal infections; however, infectious risks to infants born to mothers receiving anti-TNF therapy are not well defined. We report a case of vertical transmission of disseminated histoplasmosis in a mother-infant pair exposed to anti-TNF therapy.

Systemic fungal infections in patients with human inmunodeficiency virus.

Histoplasmosis is a systemic infection caused by the dimorphic fungus Histoplasma capsulatum. In immunocompromised patients, primary pulmonary infection can spread to the skin and meninges. Clinical manifestations appear in patients with a CD4(+) lymphocyte count of less than 150 cells/µL. Coccidioidomycosis is a systemic mycosis caused by Coccidioides immitis and Coccidioides posadasii. It can present as diffuse pulmonary disease or as a disseminated form primarily affecting the central nervous system, the bones, and the skin. Cryptococcosis is caused by Cryptococcus neoformans (var. neoformans and var. grubii) and Cryptococcus gattii, which are members of the Cryptococcus species complex and have 5 serotypes: A, B, C, D, and AD. It is a common opportunistic infection in patients with human immunodeficiency virus (HIV)/AIDS, even those receiving antiretroviral therapy. Histopathologic examination and culture of samples from any suspicious lesions are essential for the correct diagnosis of systemic fungal infections in patients with HIV/AIDS.

A multinational outbreak of histoplasmosis following a biology field trip in the Ugandan rainforest.

BACKGROUND: Outbreaks of histoplasmosis have been increasingly reported in association with travel to endemic areas. Multiple outbreaks have been reported following travel to the Americas, but reports of pulmonary histoplasmosis in short-term immunocompetent travelers to Africa are rare. METHODS: A biology student was referred to our unit with suspected pulmonary histoplasmosis following her return from a field trip in the Ugandan rainforest. The patient informed us that several of her multinational student colleagues on the same expedition had developed a similar illness. Using an alert in ProMED-mail and a questionnaire forwarded to each of the symptomatic students, we accumulated data on the other cases involved in this apparent outbreak of pulmonary histoplasmosis. RESULTS: Thirteen of 24 students developed respiratory symptoms following the expedition. Chest X-ray appearances were often suggestive of miliary tuberculosis but in most cases a final diagnosis of histoplasmosis was made (confirmed with serology in five cases, clinically diagnosed in six, and retrospectively suspected in two). Detailed questioning indicated that the likely source was a large hollow bat-infested tree within the rainforest. CONCLUSIONS: This is an unusual outbreak of histoplasmosis following short-term travel to Africa. Pulmonary histoplasmosis should always be considered in the differential diagnosis of an acute febrile respiratory illness in travelers returning from endemic areas or reporting activities suggesting exposure.

[Histoplasmosis - an unusual African souvenir]. / Histoplasmose: ein ungewöhnliches Feriensouvenir.

HISTORY AND CLINICAL FINDINGS: A 24-year-old woman (student of biology) was part of a study group in Uganda. She developed fever and headache, which was empirically treated as malaria. After she had returned to Switzerland, a chest x-ray showed bilateral miliary nodular infiltrates. In assumption of an atypical pneumonia, she was treated with levofloxacin, although without success. On admission, she was in a bad general condition and was markedly dyspneic. Rales were heard over both lungs. INVESTIGATIONS AND DIAGNOSIS: CRP, liver enzymes and LDH were elevated. A lung function test revealed a marked impairment of the diffusion capacity. The chest x-ray showed a progression of the lung infiltrates. The informal medical data exchange among the group members by a virtual social network abbreviated our diagnostic workup substantially, since we heard that histoplasmosis had been assumed in another group member. It turned out that the affected persons had visited a colony of bats living in a cave inside the trunk of a tree. Antibodies against Histoplasma capsulatum were positive. TREATMENT AND COURSE: We began a treatment with itraconazole. The condition improved gradually; chest x-ray and lung function normalized after the 8 week treatment. CONCLUSION: Histoplasmosis with such a severe course is rare in immunocompetent humans, which indicates that the inoculum must have been very high. Soil contaminated with bats guano favours the proliferation of Histoplasma capsulatum. Our case is also an illustration of how the widespread use of electronic media can sometimes facilitate our work.

[Progressive malaise and joint pain after travel to Costa Rica]. / Abgeschlagenheit und Gelenkschmerzen nach Costa-Rica-Reise.

HISTORY AND ADMISSION FINDINGS: We report on a 57-year-old patient presenting with progressive malaise, joint pain and skin rashes one month after visiting Costa Rica. After exclusion of common tropical diseases empiric antibiotic therapy was initiated, however, the patient's symptoms did not improve. INVESTIGATIONS: CT scan of the chest demonstrated an intrapulmonary nodular lesion. Bronchoscopy revealed no pathological changes. Microbiologic analysis of the bronchoalveolar lavage fluids identified no pathogen. An abdominal ultrasound examination did not reveal pathological findings. Serological tests were positive for Histoplasma capsulatum. TREATMENT AND COURSE: Treatment with itraconazole resulted in a fast initial clinical improvement, but complete resolution of all symptoms only occurred after completion of a 6-months course of itraconazole. Serial CT scans demonstrated a continuous regression of the pulmonary lesion. CONCLUSION: Histoplasmosis has a low incidence among travelers. However, histoplasmosis should be considered in patients with respiratory symptoms and history of travel to endemic countries, specifically when common traveler diseases have been excluded. Diagnosis is confirmed by serology, imaging and ultimately by biopsy for histological, cultural and molecular identification of the pathogen. Antimycotic drug therapy is the recommended treatment of choice for symptomatic cases.

Outbreak of pulmonary histoplasmosis involving a group of four Polish travellers returning from Ecuador.

Exploring caves is, without doubt, a very exciting adventure; however, it carries some dangers. Three of four travellers were admitted to hospital with lung changes after returning from Ecuador, successively. Epidemiological studies revealed that the travellers visited caves infested by bats, and had contact with bats' guano. They gave a history of fever, fatigue, myalgia, dry cough, and chest pain during the stay or just after returning from Ecuador. In two patients, symptoms persisted in mild nature. Chest X-ray films showed diffuse nodules (coin-like lesions) in the lungs in each case. Histoplasmosis was taken into consideration. Differential diagnosis included paragonimiasis, pulmonary tuberculosis, and pulmonary infection of other causes. Direct examination of sputum was negative. Cultures were negative. Final diagnosis was made on epidemiological histories, as well as typical radiological changes, and was supported by positive tests for antibodies to Histoplasma capsulatum. Immunodiffusion test (ID), complement fixation test (CFTs), and Western blot test were positive. In two cases antifungal treatment was established. Ketoconazole followed by Itraconazole were used. Persons who are going to explore caves should be equipped with anti-dusk masks to prevent pulmonary histoplasmosis. The threat of Histoplasma capsulatum infection in bat-inhabited caves should be emphasized to travellers and also to physicians.

Brote de histoplasmosis en la Escuela de Cadetes de la Base Aérea de Morón, Provincia de Buenos Aires, República Argentina / Histoplasmosis outbreak in Morón, Buenos Aires Province, Argentina

Se describe un brote de histoplasmosis que afectó a 6 cadetes de la Fuerza Aérea Argentina, sin antecedentes patológicos previos. Todos consultaron por problemas respiratorios después de haber limpiado un hangar. En ese recinto se encontraron abundantes deyecciones de animales, presuntamente de palomas y murciélagos. Los pacientes sufrieron fiebre, mialgias, taquipnea y tos no productiva. Las radiografías y tomografías de tórax mostraron imágenes pulmonares micronodulares, engrosamiento de los tabiques interalveolares y adenopatías hiliares. Todos tuvieron una evolución favorable y no requirieron tratamiento antifúngico. Las pruebas de inmunodifusión y contrainmunoelectroforesis con antígenos de Histoplasma capsulatum fueron positivas, al igual que las intradermorreacciones con histoplasmina. Se recogieron 5 muestras de tierra del lugar, las que fueron inoculadas por vía intraperitoneal a 20 hámsteres. De los cultivos de hígado y bazo de dichos animales se consiguió aislar la fase micelial de H. capsulatum. La cepa aislada se comparó con las obtenidas de 12 pacientes argentinos utilizando perfiles genéticos y se observó un clado único con más de 96% de similitud, lo que confirma la homogeneidad de las cepas argentinas. Si bien la histoplasmosis es endémica en la Pampa húmeda, este es el primer brote totalmente documentado al sur del paralelo 34°.

An histoplasmosis outbreak affecting 6 previously healthy Air Force cadets is herein presented. The patients suffered from fever and respiratory symptoms after having cleaned an abandoned hangar soiled with pigeons and bat droppings. They all presented fever, myalgia, tachypnea, and nonproductive cough. Chest X-ray and CT scan studies showed disseminated reticulonodular images affecting both lungs. Hiliar adenomegalies were also observed. All patients achieved a favourable outcome without antifungal treatment. Both serologic tests searching for specificic antibodies (immunodiffusion and counterimmunoelectrophoresis) and histoplasmin skin tests were positive in all cases. Five soil samples mixed with pigeons and bat droppings were collected from the hangar. Suspensions of these samples were inoculated into 20 hamsters by intraperitoneal injection; mycelial phase of H. capsulatum was isolated from liver and spleen cultures. The genetic profile of this strain was compared with 12 isolates obtained from Argentinean patients, and a great degree of homogeneity was observed (> 96% similarity). Although histoplasmosis is endemic in the wet Pampas, this is the first epidemic outbreak reported south of the 34th parallel.

Brotes de histoplasmosis ocupacional en la provincia La Habana / Outbreaks of occupational acquired histoplasmosis in La Habana province

INTRODUCCIÓN: la histoplasmosis, infección causada por el hongo Histoplasma capsulatum, está considerada una de las principales micosis endémicas del continente americano, donde se presenta frecuentemente en forma de brotes epidémicos. En Cuba, la mayoría de ellos han estado relacionados con la realización de actividades de riesgo en lugares que han servido de refugio a los murciélagos. En el presente trabajo se presentan 2 brotes ocupacionales de histoplasmosis ocurridos en la provincia La Habana. MÉTODOS: se estudiaron 116 trabajadores que realizaron actividades generadoras de aerosoles en cuevas. Se efectuaron exámenes micológicos y serológicos a partir de muestras de los pacientes. Se recogieron muestras del suelo de las cuevas para determinar la presencia del agente causal. Se recolectaron datos clínico-epidemiológicos para la caracterización de los brotes. RESULTADOS: las tasas de ataque en ambos brotes fueron de 60 y 78 por ciento. La edad de los pacientes osciló entre 16 y 64 años; las principales manifestaciones clínicas (fiebre, malestar general, tos seca, cefalea, pérdida de peso y dolor torácico) comenzaron a aparecer entre los 10 y 20 d. Se realizó el diagnóstico microbiológico y serológico de histoplasmosis y se confirmó la fuente de infección mediante el aislamiento de H. capsulatum en los sitios donde se habían llevado a cabo intensos trabajos de excavación, con formación de abundantes aerosoles por períodos de hasta 21 d. Los 2 brotes estudiados tuvieron en común la realización de actividades generadoras de aerosoles en lugares de riesgo, sin la utilización de medios de protección. CONCLUSIONES: se hace necesaria la divulgación de las medidas preventivas entre el personal de salud y los grupos de riesgo, así como en la población en general para evitar y controlar futuros brotes de histoplasmosis(AU)

INTRODUCTION: histoplasmosis, an infection caused by Histoplasma capsulatum fungus, is considered as one of the main endemic infections in the American continent where there are frequent epidemic outbreaks. Most of the outbreaks have been associated to risky activities in bat-inhabited places. This paper presented two outbreaks of occupational acquired histoplasmosis occurred in La Habana province. METHODS: one hundred and sixteen workers, who performed aerosol-generating tasks in caves, were studied. Samples from the cave soils were taken to assess the existence of the causal agent. Clinical and epidemiological data were gathered for the outbreak characterization. RESULTS: the rates of infection for both outbreaks were 60 percent and 78 percent respectively. The patients aged 16 to 64 years; additionally, the onset of main clinical manifestations (fever, general malaise, cough, headache, loss of weight, and chest pain) ranged from 10 to 20 days. Histoplasmosis was microbiologically and serologically diagnosed whereas its source of infection was confirmed through H. capsulatum isolation in those places where extensive excavation work had been carried out, resulting in abundant aerosols for up to 21d periods. The similarity between the two outbreaks was the performance of aerosol-generating tasks in risky places without using appropriate safety devices. CONCLUSIONS: It is necessary to disseminate the existing preventive measures among the health care staff and the risky groups as well as the general population in order to prevent and take control of possible histoplasmosis outbreaks in the future(AU)

[Histoplasmosis outbreak in Morón, Buenos Aires Province, Argentina]. / Brote de histoplasmosis en la Escuela de Cadetes de la Base Aérea de Morón, Provincia de Buenos Aires, República Argentina.

A histoplasmosis outbreak affecting 6 previously healthy Air Force cadets is herein presented. The patients suffered from fever and respiratory symptoms after having cleaned an abandoned hangar soiled with pigeons and bat droppings. They all presented fever, myalgia, tachypnea, and nonproductive cough. Chest X-ray and CT scan studies showed disseminated reticulonodular images affecting both lungs. Hiliar adenomegalies were also observed. All patients achieved a favourable outcome without antifungal treatment. Both serologic tests searching for specificic antibodies (immunodiffusion and counterimmunoelectrophoresis) and histoplasmin skin tests were positive in all cases. Five soil samples mixed with pigeons and bat droppings were collected from the hangar. Suspensions of these samples were inoculated into 20 hamsters by intraperitoneal injection; mycelial phase of H. capsulatum was isolated from liver and spleen cultures. The genetic profile of this strain was compared with 12 isolates obtained from Argentinean patients, and a great degree of homogeneity was observed (> 96% similarity). Although histoplasmosis is endemic in the wet Pampas, this is the first epidemic outbreak reported south of the 34th parallel.

Bat-associated histoplasmosis can be transmitted at entrances of bat caves and not only inside the caves.

Our observation of histoplasmosis cases augments the current knowledge on transmission by bats. In the presented cases, the only contact happened in the proximity of a bat cave but not inside the cave. We wish to communicate and stress that even outside of caves, bats may disperse the organism.

[Disseminated histoplasmosis revealed by peripheral blood smear in an African immigrant with AIDS]. / Histoplasmose disséminée révélée par un frottis sanguin chez un immigré africain atteint du sida.

We report a case of disseminated histoplasmosis due to Histoplasma capsulatum var. capsulatum in an African patient with AIDS (born in Ghana) and living in France. This opportunistic fungal infection has never been reported in Ghana, maybe because of limited means of investigation or ignorance. Nevertheless, it was reported in a Ghanaian immigrant living in Italy. In our patient, the first diagnosis was suggested by a peripheral blood smear, which is not a classical biological diagnostic method. The diagnostic interest and the frequency of positive peripheral blood smears in the course of disseminated histoplasmosis are probably under estimated.

Broncholith caused by donor-acquired histoplasmosis in a lung transplant recipient.

A broncholith is a calcified lymph node that erodes into and partially or completely obstructs the bronchial lumen. The natural history of broncholiths is poorly understood. They are frequently encountered in residents of areas that are endemic for Histoplasma capsulatum and Mycobacterium tuberculum. We report the first case of a broncholith in which the fungus Histoplasma capsulatum was transferred from a donor to a lung transplant (LTx) recipient. Our report highlights the time course of broncholith development and its successful management. We suspect that broncholithiasis and transmission of Histoplasma capsulatum from a donor to the recipient are under-reported in the LTx literature. We hypothesize that histoplasmosis can be transmitted from the donor to the recipient and the duration in the formation of calcification of the lymph node or the broncholith can be anywhere from 2 to 10 months.

[Assessment of a quantitative PCR method for clinical diagnosis of imported histoplasmosis]. / Evaluación de una técnica de PCR cuantitativa para el diagnóstico clínico de la histoplasmosis importada.

OBJECTIVE: Evaluation of the usefulness of a quantitative real-time polymerase chain reaction-based (RT-PCR) technique for clinical diagnosis of histoplasmosis. METHODS: Primers and probes were designed on the basis of sequences from the ITS regions of ribosomal DNA of 20 clinical strains of Histoplasma capsulatum. LightCycler procedures (Roche Applied Science) were used with probes marked by fluorescence resonance energy transfer (FRET). Reproducibility, sensitivity, and specificity were analyzed. In addition, an internal control was designed to identify false negative results by PCR inhibition. The RT-PCR assay was tested in 22 clinical samples from 14 patients with proven histoplasmosis. In addition, 30 samples from patients with febrile neutropenia or mycoses other than histoplasmosis, and from healthy volunteers were analyzed as controls. RESULTS: The limit of detection of the assay was 1 fg of genomic DNA per microl of sample. The PCR-based technique was reproducible and highly specific. Positive results were obtained in 11/14 (78.6%) patients and in 17/22 (77.3%) clinical samples. RT-PCR was positive in 100% of respiratory secretions and bone marrow samples, but only 70% of sera (p < 0.01). Mean fungal DNA value was 23.1 fg/microl in serum and 4.85 x 10(3) fg/microl in respiratory and bone marrow samples. RT-PCR results were positive in serum from three HIV patients for which antibody detection by immunodiffusion was negative. Specificity was 100%, since PCR results were negative for all the control samples. CONCLUSION: Thes RT-PCR technique is a sensitive, specific method for early diagnosis of histoplasmosis, particularly when respiratory secretions or bone marrow samples are analyzed. The reliability is lower in serum, but it can be used as an additional, complementary technique to culture and serology in HIV patients.

[First isolation of Histoplasma capsulatum from the urban bat Eumops bonariensis]. / Primer aislamiento de Histoplasma capsulatum de murciélago urbano Eumops bonariensis.

We report the first isolation of Histoplasma capsulatum var. capsulatum from a male bat Eumops bonariensis captured in Buenos Aires city in 2003. The pathogen was recovered from spleen and liver specimens, and was identified by its phenotypic characteristics. PCR with primers 1283, (GTG)5, (GACA)4 and M13 was used to compare both bat isolates with 17 human isolates, 12 from patients residing in Buenos Aires city, and 5 from other countries of the Americas. The profiles obtained with the four primers showed that both bat isolates were identical to each other and closer to Buenos Aires patients than to the other isolates (similarity percentage: 91-100% and 55-97%, respectively). The high genetic relationship between bat isolates and those from patients living in Buenos Aires suggests a common source of infection. This is the first record of E. bonariensis infected with H. capsulatum in the world, and the first isolation of the fungus in the Argentinean Chiroptera population. In the same way as these wild mammals act as reservoir and spread the fungus in the natural environment, infection in urban bats could well be associated with the increase in histoplasmosis clinical cases among immunosuppressed hosts in Buenos Aires city.

Recurrent exposure to Histoplasma capsulatum in modern air-conditioned buildings.

BACKGROUND: Between 1989 and 1996, an epidemic of histoplasmosis occurred on a medical school campus. There had been numerous construction projects on the campus that involved previously wooded land and were adjacent to a large bird sanctuary. METHODS: We investigated the epidemic with active surveillance to detect cases, a histoplasmin skin-test survey, inspection of the air-filtration systems of the involved buildings, and cultures of soil samples. The investigation also included a simulation of entry into air-intakes of the buildings from spore sources by means of a wind-tunnel analysis of a model of the campus that used inert gas. After control procedures were instituted, sentinel population groups had follow-up with yearly serological tests. RESULTS: From 1989 through 1996, there were 29 cases of histoplasmosis that occurred among school employees. All cases with a defined onset began during periods of ongoing campus construction. Positivity rates for histoplasmin skin testing were higher among on-campus personnel (47%) than among off-campus employee control subjects (28%) (P<.001); the rates were highest in employees who worked on the upper floors of 2 research buildings. The air-handling units on the roofs of these buildings were not designed to exclude Histoplasma spores. The wind-tunnel experiment indicated that spores aerosolized in the bird sanctuary were not taken into campus buildings. CONCLUSIONS: The major sources of employee exposure to H. capsulatum spores were the construction sites. Low-level, recurrent exposures occurred over several years inside modern research buildings. This phenomenon, which has not been previously described, may play a role in the epidemiology of spore-transmitted diseases in urban settings.