Acute Pulmonary Histoplasmosis Research Articles

Insights on Covid-19 with superimposed pulmonary histoplasmosis: The possible nexus.

A novel coronavirus (CoV) known as severe acute respiratory syndrome CoV type 2 is the causative agent for the development of CoV disease 2019 (Covid-19). Covid-19 may increase the risk of developing pulmonary histoplasmosis due to immune dysregulation. In addition, Covid-19 may enhance the propagation of acute pulmonary histoplasmosis due to lung injury and inflammation, and using corticosteroids in severely affected Covid-19 patients may reactivate latent pulmonary histoplasmosis. Likewise, activation of inflammatory signaling pathways during H. capsulatum infection may increase the severity of Covid-19 and vice versa. Furthermore, lymphopenia in Covid-19 may increase the risk for the progress of pulmonary histoplasmosis besides activation of inflammatory signaling pathways during H. capsulatum infection may increase the severity of Covid-19 and vice versa. Therefore, this critical review aimed to find the potential link between Covid-19 pneumonia and pulmonary histoplasmosis concerning the immunological response.

Histoplasmosis in Sri Lanka – barely recognized, yet present

Histoplasmosis has been reported in Sri Lanka for decades; however, clinical recognition and diagnosis of the disease are rare. We conducted a comprehensive search of English-language medical literature from 1969 to February 2022. Our analysis found one population survey of histoplasmin skin sensitivity testing in 1969 (5.7% positive incidence) and ten cases of histoplasmosis across Sri Lanka. The highest number of cases were reported from the Central province, where the positive histoplasmin tests were observed previously. None of the patients were positive for HIV, and both diabetes and betel chewing seem linked with oral histoplasmosis. Out of the reported cases, 50% were diagnosed with disseminated histoplasmosis; asymptomatic, acute pulmonary, and chronic pulmonary histoplasmosis were not observed. The clinical presentation varied from oral lesions (the most common presentation), skin lesions, and fever of unknown origin to adrenal crisis. Fungal culture and histopathology were used for diagnosis, with no use of antigen and antibody testing. Amphotericin B and itraconazole were used as treatment options. The rising at-risk population mandates enhancing laboratory diagnostic facilities and increasing the awareness of medical professionals in Sri Lanka on histoplasmosis.

Acute pulmonary histoplasmosis of immunocompetent subjects from Martinique, Guadeloupe and French Guiana: a case series

IntroductionHistoplasmosis is a fungal disease caused by Histoplasma capsulatum. Histoplasma capsulatum var capsulatum is found in Martinique.Cluster cases following working in deserted house, have been described in Martinique. Cases of acute pulmonary histoplasmosis have been described in immunosuppressed individuals, or in case of substantial exposure to reservoirs of Histoplasma capsulatum; however, cases of acute histoplasmosis are rare in immunocompetent individuals.Cases seriesWe report a series of 4 cases of sporadic acute pulmonary histoplasmosis in immunocompetent subjects. Investigation revealed definite exposure in one patient and 3 cases with potential exposure. The diagnosis was microbiological and histological in 3 patients and histological in one patient. All subjects had positive serology to histoplasmosis. Pulmonary involvement was in the form of nodules and micronodules in 3 cases and ground glass lesions in one case. Patients were treated with itraconazole for 3 months and all had a favourable outcome.ConclusionWe report a series of 4 cases of acute pulmonary histoplasmosis in immunocompetent individuals, occurring in a context where exposure was uncertain. This raises the problem of occult exposure in the Caribbean. Interventions to raise awareness and encourage caution are warranted targeting the population of the French West Indies and French Guiana.

Pulmonary Histoplasmosis: A Clinical Update.

Histoplasma capsulatum, the etiological agent for histoplasmosis, is a dimorphic fungus that grows as a mold in the environment and as a yeast in human tissues. The areas of highest endemicity lie within the Mississippi and Ohio River Valleys of North America and parts of Central and South America. The most common clinical presentations include pulmonary histoplasmosis, which can resemble community-acquired pneumonia, tuberculosis, sarcoidosis, or malignancy; however, certain patients can develop mediastinal involvement or progression to disseminated disease. Understanding the epidemiology, pathology, clinical presentation, and diagnostic testing performance is pivotal for a successful diagnosis. While most immunocompetent patients with mild acute or subacute pulmonary histoplasmosis should receive therapy, all immunocompromised patients and those with chronic pulmonary disease or progressive disseminated disease should also receive therapy. Liposomal amphotericin B is the agent of choice for severe or disseminated disease, and itraconazole is recommended in milder cases or as "step-down" therapy after initial improvement with amphotericin B. In this review, we discuss the current epidemiology, pathology, diagnosis, clinical presentations, and management of pulmonary histoplasmosis.

A RARE CASE OF ACUTE PULMONARY HISTOPLASMOSIS FOLLOWING COVID-19 INFECTION

SESSION TITLE: COVID-19 Case Report Posters 3SESSION TYPE: Case Report PostersPRESENTED ON: 10/19/2022 12:45 pm - 01:45 pmINTRODUCTION: The most reported fungal infections in patients with COVID-19 include aspergillosis, invasive candidiasis, and mucormycosis. We hereby present a case of a male who developed acute pulmonary histoplasmosis (APH) after COVID-19 infection.CASE PRESENTATION: 51-year-old male with PMHx of COVID-19 infection 3 weeks ago presenting with worsening shortness of breath. Patient had a complicated hospital course with COVID-19 treated with high doses of methylprednisolone. Patient was local to Arizona and lived on a ranch with livestock. CT chest suggestive of multilobar pneumonia and bilateral pleural effusions (Image 1). Coccidiomycosis serology came back negative. Urinary Histoplasma galactomannan antigen came back positive. The diagnosis of APH after COVID-19 infection was established. Patient was started on voriconazole. His symptoms significantly improved. Patient was discharged to skilled nursing facility with outpatient infectious disease follow-up.DISCUSSION: The current literature on APH in the setting of COVID-19 infection is limited. The few proposed mechanisms are: 1. Liberal use of high dose steroids in COVID-19 leading to reactivation of latent H. Capsulatum. 2. Systemic inflammation in COVID-19 causes interstitial lung damage permitting conidia to proliferate leading to acute infection. The Histoplasma urine antigen test is highly sensitive in the diagnosis of APH, especially in immunocompromised patients like our patient. With this case we would like to increase awareness of the possibility of rare fungal infections like APH in patients with COVID-19, as timely diagnosis and appropriate management can lead to improved outcomes.CONCLUSIONS: Rare fungal infections following COVID-19 have been documented and timely diagnosis and management are imperative to improve patient outcomes.Reference #1: Macedo, Priscila M, et al. APH following COVID-19. Case Report J.Fungi 2021DISCLOSURES: No relevant relationships by Ali Rajano disclosure on file for Yamin Saddouk;No relevant relationships by Parita SoniNo relevant relationships by Lyndie Wilkins Parker SESSION TITLE: COVID-19 Case Report Posters 3 SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: The most reported fungal infections in patients with COVID-19 include aspergillosis, invasive candidiasis, and mucormycosis. We hereby present a case of a male who developed acute pulmonary histoplasmosis (APH) after COVID-19 infection. CASE PRESENTATION: 51-year-old male with PMHx of COVID-19 infection 3 weeks ago presenting with worsening shortness of breath. Patient had a complicated hospital course with COVID-19 treated with high doses of methylprednisolone. Patient was local to Arizona and lived on a ranch with livestock. CT chest suggestive of multilobar pneumonia and bilateral pleural effusions (Image 1). Coccidiomycosis serology came back negative. Urinary Histoplasma galactomannan antigen came back positive. The diagnosis of APH after COVID-19 infection was established. Patient was started on voriconazole. His symptoms significantly improved. Patient was discharged to skilled nursing facility with outpatient infectious disease follow-up. DISCUSSION: The current literature on APH in the setting of COVID-19 infection is limited. The few proposed mechanisms are: 1. Liberal use of high dose steroids in COVID-19 leading to reactivation of latent H. Capsulatum. 2. Systemic inflammation in COVID-19 causes interstitial lung damage permitting conidia to proliferate leading to acute infection. The Histoplasma urine antigen test is highly sensitive in the diagnosis of APH, especially in immunocompromised patients like our patient. With this case we would like to increase awareness of the possibility of rare fungal infections like APH in patients with COVID-19, as timely diagnosis and appropriate management can lead to improved outcomes. CONCLUSIONS: Rare fungal infections following COVID-19 have been documented and timely diagnosis and management are imperative to improve patient outcomes. Reference #1: Macedo, Priscila M, et al. APH following COVID-19. Case Report J.Fungi 2021 DISCLOSURES: No relevant relationships by Ali Raja no disclosure on file for Yamin Saddouk; No relevant relationships by Parita Soni No relevant relationships by Lyndie Wilkins Parker

CYCLIC FEVERS AND PLEURAL EFFUSIONS IN SUSPECTED PULMONARY HISTOPLASMOSIS

CYCLIC FEVERS AND PLEURAL EFFUSIONS IN SUSPECTED PULMONARY HISTOPLASMOSIS

P286 Histoplasmosis in Sri Lanka

Poster session 2, September 22, 2022, 12:30 PM - 1:30 PMBackgroundHistoplasmosis is a systemic mycosis caused by Histoplasma capsulatum, a dimorphic fungus. More severe disease has been observed in immunocompromised individuals. Most cases occur in certain endemic regions of the world however it seems to have a much wider global distribution. Histoplasmosis is infrequently recognized in Sri Lanka and the dispersion of information on cases is fragmented.MethodThe comprehensive search of medical literature in the English language through databases from any time to February 2022. Either, culture-proven or histopathologically proven cases were selected as diagnostically confirmed histoplasmosis. Duplicate reports were excluded. All available data on demography, clinical presentation, diagnostic method, management, and clinical outcome were appraised for the reported cases.ResultOne survey of histoplasmin skin sensitivity testing and ten cases of histoplasmosis across Sri Lanka were observed during the above period. A total of 5.7% of histoplasmin positivity had been observed in the survey of histoplasmin sensitivity among 1366 Sri Lankan volunteers of the Western and the Central Provinces in 1969. Most of the patients were reported from the Central province which had the positive histoplasmin test previously. In addition, cases were observed in Southern Province, the Sabragamuwa Province, and the Eastern Province. The majority of affected individuals were adult males (90%) and pediatric patients were not observed. The clinical presentation stretched from oral lesions (the most common presentation), skin lesions, and fever of unknown origin, to adrenal crisis. Disseminated histoplasmosis was diagnosed in 50% of the patients however asymptomatic, acute pulmonary, and chronic pulmonary histoplasmosis was not observed. Both diabetes and betel chewing are likely to be linked with oral histoplasmosis and none of the patients were positive for HIV. Both histopathology and fungal culture methods were used for the diagnosis while the use of antigen and antibody testing were not popular. Both itraconazole and amphotericin B were used for the treatment of the patients with variable outcomes.ConclusionHistoplasmosis exists in Sri Lanka. The number of cases could be expected to be much higher than reported along with the increase in at-risk populations. These mandates enhance laboratory diagnostic facilities and increase the awareness of medical professionals in Sri Lanka.

WEAR A MASK NOT ONLY FOR COVID-19: TWO IMMUNOCOMPETENT COWORKERS WITH PULMONARY HISTOPLASMOSIS

TOPIC: Chest Infections TYPE: Medical Student/Resident Case Reports INTRODUCTION: Acute Pulmonary Histoplasmosis (APH) can present in a broad variety of signs and symptoms in immunocompetent individuals but is generally a benign disease that may not require treatment. If symptoms are more severe or longer-lasting, treatment is indicated. CASE PRESENTATION: Two healthy 32- and 36-year-old males (Patient A and B respectively) presented with 1 week of high-grade fever, headache, shortness of breath, productive cough, pleuritic chest pain, and diarrhea. 2 weeks prior, they deep-cleaned a chimney filled with bat guano without wearing their respirators. Upon presentation, both patients had fever, tachycardia, tachypnea with normal resting pulse oximetry despite air hunger. Physical exam revealed diffuse crackle in both lung fields but was otherwise unremarkable. The initial lab only showed elevated procalcitonin and CRP. Viral panels were negative for COVID-19 and other viral infections. Chest CT for both cases showed extensive centrilobular and perilymphatic nodules with associated mediastinal and hilar adenopathy. Based on history and imaging, APH was suspected. Urine Histoplasma antigen was sent which later resulted in positive (3.9 and 7.3 ng/ml respectively). BAL sample was only obtained from patient B due to similarities in the two cases and a possible common pathogen. BAL fluid was grayish in color with 523 nucleated cells and monocytic predominance. Fungitell, aspergillus, fungal culture, and acid-fast stain were all negative. Meanwhile, due to the severity of our patients' presentation and extensive lung involvements, both patients were treated with daily infusion of Amphotericin B for a week and showed significant symptomatic improvement within 2 days. They were switched to oral itraconazole and were eventually discharged from the hospital. Intraconazole was continued for 12 weeks thereafter. DISCUSSION: Histoplasmosis is acquired by inhalation of Histoplasma capsulatum var. capsulatum. Clinical manifestations depend on the intensity of exposure and the patient's immunological status. It has 3 main forms which are acute pulmonary, chronic cavitary pulmonary, and disseminated histoplasmosis. it is generally a self-limited disease. Treatment may be indicated if patient becomes hypoxemic or symptoms persist over 1 month. Guidelines suggest itraconazole as treatment if symptoms persist for more than 1 month and liposomal amphotericin B followed by itraconazole in moderately severe to severe APH. However, in our two cases, patients had moderate symptoms but considering the high intensity of exposure, they were treated with a lower dose of liposomal amphotericin B followed by itraconazole and showed significant improvement. CONCLUSIONS: A detailed history of occupational exposures can help reach a prompt diagnosis and treatment of APH. Patients with moderate symptoms may be considered for treatment with lower doses of amphotericin B followed by itraconazole. REFERENCE #1: 1. Staffolani S, Buonfrate D, Angheben A, et al. Acute histoplasmosis in immunocompetent travelers: a systematic review of literature. BMC Infect Dis. 2018;18(1):673. Published 2018 Dec 18. doi:10.1186/s12879-018-3476-z REFERENCE #2: 2. Sobel JD. Practice guidelines for the treatment of fungal infections. For the Mycoses Study Group. Infectious Diseases Society of America. Clin Infect Dis. 2000 Apr;30(4):652. doi: 10.1086/313746. Epub 2000 Apr 20. PMID: 10770725. REFERENCE #3: 3. L. Joseph Wheat, Alison G. Freifeld, Martin B. Kleiman, John W. Baddley, David S. McKinsey, James E. Loyd, Carol A. Kauffman, Clinical Practice Guidelines for the Management of Patients with Histoplasmosis: 2007 Update by the Infectious Diseases Society of America, Clinical Infectious Diseases, Volume 45, Issue 7, 1 October 2007, Pages 807–825. doi.org/10.1086/521259 DISCLOSURES: no disclosure on file for Ashlee Russo;No relevant relationships by Abolfazl Sodagar, source=Web Response No relevant relationships by Jeannie Ur, source=Web Response

ACUTE PULMONARY HISTOPLASMOSIS: A DIAGNOSTIC DILEMMA DURING COVID-19 PANDEMIC

TOPIC: Chest Infections TYPE: Medical Student/Resident Case Reports INTRODUCTION: Acute histoplasmosis is usually a concern in immunocompromised individuals. In immunocompetent patients, histoplasmosis is generally mild or asymptomatic unless there is inhalation of a large inoculum. Below, we present a case of severe acute pulmonary histoplasmosis in an otherwise healthy, immunocompetent person and discuss the diagnostic challenges it presented during the COVID-19 pandemic. CASE PRESENTATION: A 30-year-old non-smoking Caucasian man with hypertension presented to our hospital with 1 week duration of headache, dyspnea, productive cough and high fever. He was admitted with a provisional diagnosis of COVID-19 pneumonia and started on dexamethasone and empiric antibiotics. He had elevated inflammatory markers. Chest x-ray showed diffuse bilateral interstitial and alveolar opacities. CT chest demonstrated numerous clustered ground glass nodular opacities bilaterally with mediastinal and hilar adenopathy. Subsequently, RT-PCR for SARS-CoV2 returned negative. The patient continued to deteriorate clinically over the next few days. Repeat imaging showed diffuse micronodules with mediastinal adenopathy. Upon further questioning, the patient recalled demolishing a chimney at his parents' house in Michigan 2 weeks prior to admission. The differential diagnosis was broadened to include acute hypersensitivity pneumonitis and fungal infection. BAL, transbronchial biopsies and EBUS-TBNA was performed while escalating steroids. The lung biopsy confirmed Histoplasma. Urine Histoplasma antigen returned positive. The patient was treated with itraconazole with an overlap of steroids for 2 weeks upon discharge. He was readmitted within a week with worsening hypoxia and worsening infiltrates on lung imaging. He was then treated with liposomal amphotericin with gradual clinical improvement. Follow-up 1 month post discharge revealed complete clinical and radiologic resolution. DISCUSSION: Viral pneumonia and acute pulmonary histoplasmosis have overlapping clinical and radiologic features which can make diagnosis challenging. COVID-19 pneumonia typically presents with peripheral ground glass opacities with or without superimposed consolidations. Invasive fungal pneumonia can have a similar appearance on CT usually with additional findings of hilar and mediastinal adenopathy. CONCLUSIONS: This case highlights the challenges involved in diagnosing acute pulmonary histoplasmosis in an immunocompetent individual in the midst of the pandemic. Clinicians should always maintain a wide differential diagnosis to avoid diagnostic delay. REFERENCE #1: Staffolani, S., Buonfrate, D., Angheben, A., Gobbi, F., Giorli, G., Guerriero, M., Barchiesi, F. (2018). Acute histoplasmosis in immunocompetent travelers: A systematic review of literature. BMC Infectious Diseases, 18(1). doi:10.1186/s12879-018-3476-z REFERENCE #2: Duzgun, S. A., Durhan, G., Demirkazik, F. B., Akpinar, M. G., & Ariyurek, O. M. (2020). COVID-19 pneumonia: the great radiological mimicker. Insights into imaging, 11(1), 118. https://doi.org/10.1186/s13244-020-00933-z REFERENCE #3: Klein, M., Khan, M., Salinas, J. L., & Sanchez, R. (2019). Disseminated pulmonary histoplasmosis in immunocompetent patients: A common epidemiological exposure. BMJ Case Reports, 12(3). doi:10.1136/bcr-2018-227994 DISCLOSURES: No relevant relationships by Joseph Arguinchona, source=Web Response No relevant relationships by Michael Kaster, source=Web Response No relevant relationships by Muazzam Mirza, source=Web Response No relevant relationships by Anusha Pinjala, source=Web Response no disclosure on file for Venketraman Sahasranaman;

Biodiverse Histoplasma Species Elicit Distinct Patterns of Pulmonary Inflammation following Sublethal Infection.

Histoplasma is an endemic dimorphic fungus that can cause disease in healthy and immunocompromised individuals after the transition of inhaled spores into the facultative intracellular yeast form. There is substantial diversity among Histoplasma species, but it is not clear how this heterogeneity impacts the progression of pathology and cellular immune responses during acute respiratory infection, which represents the vast majority of histoplasmosis disease burden. After inoculating mice intranasally with a sublethal inoculum, we characterized the immune response to Histoplasma capsulatum (strain G186A) and Histoplasma ohiense (strain G217B) using comprehensive flow cytometric and single-cell analyses. Within 8 days after inoculation, H. ohiense induced a significantly higher infiltration of neutrophils and inflammatory monocytes into the lung compared to H. capsulatum Microscopic analysis of infected lung tissue revealed that although the total number of fungi was similar within inflamed lung lesions, we observed different species-dependent intracellular yeast distribution patterns. Inoculation with gfp-expressing strains indicated that H. ohiense, but not H. capsulatum, was associated primarily with alveolar macrophages early after infection. Interestingly, we observed a significant reduction in the total number of alveolar macrophages 12 to 16 days after H. ohiense, but not H. capsulatum infection, despite similar intracellular growth dynamics within AMJ2-C11 alveolar macrophages in vitro Together, our data suggest that H. ohiense, but not H. capsulatum, preferentially interacts with alveolar macrophages early after infection, which may lead to a different course of inflammation and resolution despite similar rates of fungal clearance.IMPORTANCE Acute pulmonary histoplasmosis in healthy individuals comprises most of the disease burden caused by the fungal pathogen Histoplasma Fungal pneumonia is frequently delayed in diagnosis and treatment due to a prolonged period of quiescence early during infection. In this study, we used a murine respiratory model of histoplasmosis to investigate how different Histoplasma species modulate lung inflammation throughout the complete course of infection. We propose that a relatively low, sublethal inoculum is ideal to model acute pulmonary histoplasmosis in humans, primarily due to the quiescent stage of fungal growth that occurs in the lungs of mice prior to the initiation of inflammation. Our results reveal the unique course of lung immunity associated with divergent species of Histoplasma and imply that the progression of clinical disease is considerably more heterogeneous than previously recognized.

Histoplasmose pulmonaire chez un patient immunocompétent avec nodules pulmonaires multiples évoluant vers la nécrose

Acute pulmonary histoplasmosis (APH) is rare in an immunocompetent patient. We report a case of APH diagnosed by culture of broncho-alveolar lavage (BAL) in a patient presenting a pseudo-tumoral form with nodules progressing to cavitation. A 41 year-old male smoker was hospitalized with a persistent fever, dry cough and dyspnoea on exertion. The first CT scan showed a reticulo-nodular interstitial infiltrate with lymphadenopathy that progressed rapidly to multiple pulmonary nodules with central cavitation. Bronchial endoscopy, with BAL culture, provided the diagnosis of Histoplasma capsulatum, variety capsulatum. The infection may have occurred during work in a hangar in Guadeloupe that was scattered with bats' guano. After two months of treatment by itraconazole, the patient's condition improved clinically and radiologically with reduction of the nodules and their cavitation. This case presents an immunocompetent patient with pulmonary histoplasmosis and multiple, radiologically atypical, nodules. The diagnosis was established by BAL culture.

Survey of Histoplasma capsulatum in bat guano and status of histoplasmosis in Slovenia, Central Europe

There have been increasing reports on the presence of Histoplasma capsulatum in some European countries. The study investigated the presence of Histoplasma in bat guanos, speleologists with records of visiting Histoplasma-endemic regions and patients with histoplasmosis. A commercial ALPHA Histoplasma Antigen enzyme immunoassay was tested as an alternative methodology to detect Histoplasma in environment and compared with polymerase chain reaction (PCR) assays. The presence of Histoplasma antigen in bat guanos was not confirmed by PCR. Among 14 healthy speleologists, two were indicated as having the Histoplasma antigen in urine, but expressed negative PCR-specific results for the Histoplasma antigen. Five unequivocal cases of imported acute pulmonary histoplasmosis in Slovenia between years 2005 and 2016 were confirmed in patients returning from North and South America after visiting hazardous localities e.g., caves with guano, and places with dust. Currently there is no evidence of autochthonous histoplasmosis in Slovenia, or that bat guano is a source of H. capsulatum. Involvement of histoplasmosis in travellers’ and cavers’ morbidity might be underestimated in non-endemic areas. It is crucial to ensure the use of appropriate protective equipment in Histoplasma hazardous localities, to spread information about this hazardous microbe to vulnerable populations and to monitor the health of the environment. A differential diagnosis for a febrile respiratory disease outbreak in patients returning from endemic regions should trigger routine consideration of possible histoplasmosis.

275. Delayed Diagnosis of Histoplasmosis in Pediatric Patients due to Atypical Clinical Presentations

BackgroundHistoplasmosis is a systemic mycosis with a wide range of clinical manifestations which represents a diagnostic challenge. It affects immunocompromised patients but also, previously healthy individuals that are exposed to a large inoculum of Histoplasma. The aim of our study was to describe the clinical presentation, epidemiologic features, laboratory/imaging findings and outcome of pediatric patients with histoplasmosis.Methodsa retrospective study including patients diagnosed as Histoplasmosis according to ICD-10 at a tertiary care center in Mexico City during 2009 to 2019. Clinical, epidemiological and laboratory/imaging data were gathered from each patient’s clinical file.Results5 patients with diagnosis of histoplasmosis were included; 2 patients were classified as proven with histopathologic confirmation, 2 patients as probable and 1 patient as possible according to the EORTC/MSG. The mean age of presentation was 7 years, 3/5 patients were male and 3/5 reported exposure to bats. Diagnosis was delayed by an average time of 6 months due to the variability of clinical presentations (progressive disseminated histoplasmosis, spinal histoplasmosis, cerebral histoplasmosis, intestinal histoplasmosis and mild acute pulmonary histoplasmosis). For the diagnosis, 1/5 had positive ELISA, 1/5 positive immunodiffusion (M band), 1/5 positive EIA in cerebrospinal fluid and 2/5 with histopathology findings that matched histoplasmosis. Pulmonary imaging with interstitial infiltrates in 4/5 and evidence of cavitation in one patient. Hemophagocytic syndrome was a complication in 1/5 and medullary syndrome was developed in the patient with spinal histoplasmosis which resolved with treatment. Liposomal amphotericin B was the treatment in 4/5, followed by itraconazole as the maintenance therapy.ConclusionThis study shows variable clinical presentations of Histoplasmosis which resulted in an important delay in diagnosis. This study highlights the importance of diagnostic suspicion in both healthy children and immunocompromised patients, always taking into account epidemiological risks such as exposure to bats.Disclosures All authors: No reported disclosures.

A RARE CASE OF HISTOPLASMOSIS PRESENTING WITH PLEURAL EFFUSION IN A NORMAL HOST

SESSION TITLE: Monday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM INTRODUCTION: Histoplasmosis is an endemic mycosis that is usually asymptomatic in healthy hosts. We present a rare case of pulmonary histoplasmosis presenting with pleural effusion in an immunocompetent patient. CASE PRESENTATION: A 44 year old male smoker presented to the emergency department with progressive left-sided pleuritic pain, cough, night sweats, and weight loss. Chest x-ray was unremarkable and he was released to follow-up with primary care. His symptoms persisted and chest CT obtained three weeks later revealed a 2.5 cm left lower lobe pleural-based nodule, left hilar lymphadenopathy, and a small left-sided pleural effusion. Thoracentesis yielded 520 ml of exudative pleural fluid with 43% lymphocytes and 16% eosinophils. Testing for histoplasmosis including urine and serum antigens as well as serology were negative. However, pleural fungal culture grew Histoplasma capsulatum. Fluid reaccumulated within a week and repeat thoracentesis again grew H. capsulatum. In the interim, the patient was initiated on itraconazole and pleural effusion resolved. DISCUSSION: Histoplasmosis is a mycosis caused by H. capsulatum which is transmitted via inhalation of microconidia and associated with environments containing bird or bat guano. Infection is generally asymptomatic in healthy hosts and resolves through cell-mediated immunity. However, with large inoculum pulmonary histoplasmosis can manifest in an acute, subacute, or chronic illness. Acute pulmonary histoplasmosis is characterized by fever, dyspnea, and cough with chest imaging showing bilateral patchy opacities, nodules, and lymphadenopathy. In contrast, subacute pulmonary histoplasmosis progresses over several months and imaging reveals more focal opacities. Chronic histoplasmosis is characterized by exacerbations of cough, dyspnea, fever, chest pain, night sweats, and weight loss with radiographic features of cavitation, fibrosis, pleural thickening, and calcified lymph nodes. Pleural effusion secondary to any form of histoplasmosis is exceedingly rare. Diagnosis of histoplasmosis is made via identification of ovoid yeast cells in tissue or body fluid, cultures of blood, sputum, or bronchoscopy specimens, serum and urine antigen, or antibody testing. Antigen testing provides highest yield in acute pulmonary and disseminated histoplasmosis. Combined serum and urine antigen is reportedly 81% sensitive and 99% specific, and therefore negative antigen does not rule out infection as was the case with our patient who had positive pleural culture despite negative antigen testing. CONCLUSIONS: Pulmonary histoplasmosis can present with a variety of clinical and radiographic findings depending upon size of inoculum and immune status of the host. Diagnosis can be challenging and relies on a combination of culture, pathology, antigen, and serologic testing. Our patient is a very rare case of histoplasmosis presenting with culture positive pleural effusion. Reference #1: Wheat, L.J.; Azar, M.M.; Bahr, N.C.; Spec, A.; Relich, R.F.; Hage, C. Histoplasmosis. Infect Dis Clin N Am 30. 2016; 207-227. https://doi.org/10.1016/j..idc.2015.10.009. Reference #2: Di Mango, A.L.; Zanetti, G.; Penha, D.; Mebba Barreto, M.; Marchiori, E. Endemic pulmonary fungal diseases in immunocompetent patients: an emphasis on thoracic imaging. Exper Rev Respir Med. 2019; 13(3): 263-277. https://doi.org/10.1080/17476348.2019.1571914. Reference #3: Patterson, J.; Graham, D.; George, A.; Will, M.; Sutter, D. Right Middle Lobe Collapse and Pleural Effusion in an 18-Year-Old-Man. Chest. 2017; 152(2):e33-e38. DISCLOSURES: No relevant relationships by Brian Boer, source=Web Response No relevant relationships by Amber Johnson, source=Web Response

Histoplasmosis: Epidemiology, Diagnosis, and Clinical Manifestations

This review highlights the epidemiology, diagnosis, and clinical manifestations of histoplasmosis. There is an increasing awareness of histoplasmosis in Central and South America in patients with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), and deaths from histoplasmosis in this region may outnumber deaths from tuberculosis. Diagnosis in this region is hampered by lack of rapid diagnostic tests. Growth of H. capsulatum in culture is definitive, but takes weeks. In areas in which antigen testing is available, this has become an important rapid diagnostic tool, and methods combining antigen and antibody testing appear to improve diagnostic accuracy for acute pulmonary and central nervous system histoplasmosis. Pulmonary histoplasmosis, although usually self-limited, rarely can lead to life-threatening complications. Uncommon, but serious and sometimes fatal complications of disseminated histoplasmosis include Addison’s disease, meningitis, culture-negative endocarditis, and hemophagocytic lymphohistiocytosis. The use of antigen testing has improved our ability to diagnose histoplasmosis, but these tests are not universally available. Complications of both pulmonary and disseminated histoplasmosis remain challenging.

DISSEMINATED PULMONARY HISTOPLASMOSIS IN IMMUNOCOMPETENT PATIENTS: A COMMON EPIDEMIOLOGICAL EXPOSURE IN CONSTRUCTION WORKERS

SESSION TITLE: Chest Infections 4 SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/09/2018 01:15 PM - 02:15 PM INTRODUCTION: Most histoplasmosis infections in immunocompetent patients are asymptomatic and self-limited. The following are four immunocompetent patients with a common epidemiologic exposure--construction work---that presented with disseminated pulmonary histoplasmosis and acute respiratory failure. CASE PRESENTATION: The first three cases involved 19, 44 and 70-year-old males presenting with fevers, severe dyspnea and productive cough over 2 weeks after remodeling a same old apartment building. Diffuse crackles were heard on lung auscultation. Chest X-rays and CT chests showed bilateral diffuse lung nodules and alveolar opacities. Patients failed antibiotic therapy and was transferred from a local hospital due to worsening respiratory status. The 19-year-old patient was the first admitted to the ICU. Initially, patient was diagnosed with severe community acquired pneumonia and treated with vancomycin and piperacillin-tazobactam. However, given worsening conditions and history of recent construction work, acute pulmonary histoplasmosis was suspected. Patient was started on empiric amphotericin B and systemic corticosteroid. The 44 and 70-year-old patients were later transferred and started on same antifungal therapy given same exposure. Later, histoplasmosis was confirmed with positive bronchoalveolar lavage (BAL) cultures and urine/serum/BAL Histoplasma antigen. The last case was a 48-year-old male presenting with similar symptoms, physical exam, and chest x-ray and CT chest findings as above. Given his recent work remodeling an old building, patient was empirically started on itraconazole and systemic prednisone. Histoplasmosis was later confirmed with positive BAL/sputum cultures and urine/serum Histoplasma antigen. All four patients recovered with 12 weeks of antifungal therapy. DISCUSSION: Patients most likely developed disseminated pulmonary histoplasmosis due to high level of fungal inoculum from construction work in old buildings. Diagnosis of histoplasmosis is often challenging because (1) clinical presentation resembles bacterial or mycobacterial infections, or inflammatory conditions, (2) diagnosis is confirmed through isolation of the fungus in cultures which take several weeks or histopathology that is invasive. Detection of Histoplasma antigen or Histoplasma antibodies aids in diagnosis but also limited by long turnaround time, low sensitivity and cross reactivity with other mycosis. Misdiagnosis often leads to inappropriate therapy with unnecessary antibiotics or immunosuppressive agents and delay in appropriate antifungal therapy. CONCLUSIONS: It is important to recognize any epidemiologic exposure (construction work, traveling, hiking, farming) for histoplasmosis, promptly start a diagnostic work-up and have a low threshold to start empiric antifungal therapy. Also, workers with potential exposure to bat/bird droppings should be educated on use of N95 respirator as recommended by NIOSH. Reference #1: Benedict K, Mody RK. Epidemiology of Histoplasmosis Outbreaks, United States, 1938-2013. Emerg Infect Dis. 2016;22(3):370-8. Reference #2: Azar MM, Zhang X, Assi R, Hage C, Wheat LJ, Malinis MF. Clinical and epidemiological characterization of histoplasmosis cases in a nonendemic area, Connecticut, United States. Med Mycol. 2017. Reference #3: Wheat LJ, Azar MM, Bahr NC, Spec A, Relich RF, Hage C. Histoplasmosis. Infect Dis Clin North Am. 2016;30(1):207-27. DISCLOSURES: No relevant relationships by Swan Lee, source=Web Response No relevant relationships by Rolando Sanchez, source=Web Response

Histoplasmose pulmonar grave em um gato doméstico: tratamento com Anfotericina B e Itraconazol

Background: Histoplasmosis is a systemic mycosis whose etiologic agent is the fungus Histoplasma capsulatum. This fungal infection, which is the second most frequent systemic mycotic fungal disease in felines in the United States, has rarely been found in cats in Brazil. This paper reports on a case of acute pulmonary histoplasmosis in a domestic cat treated with oral itraconazole associated with amphotericin B administered subcutaneously. This treatment resulted in clinical remission of the patient’s symptoms, as evidenced by radiographic follow-ups.Case: A domestic cat suffering from acute dyspnea was taken to a veterinary clinic. The animal was subjected to emergency oxygen therapy, and kept at rest through sedation with midazolam. A physical examination revealed normally colored mucosa, 8% dehydration, bristly fur, body condition score 2/9, tachypnea with respiratory rate of 100 breaths per minute and expiratory dyspnea. The radiographic examination showed marked opacification of all the pulmonary fields, with a mixed pattern (interstitial and alveolar) of heterogeneous appearance and diffuse distribution, which are changes consistent with an inflammatory infectious process (pneumonia). A cytological analysis of the pleural fluid revealed round to oval-shaped intracytoplasmic structures, varying in size from 2 to 4 μm, inside foamy macrophages, consistent with Histoplasma capsulatum. Based on the diagnosis of pulmonary histoplasmosis, and in view of the patient’s acute respiratory distress, it was decided to treat the cat using itraconazole associated with amphotericin B. Itraconazole was administered orally at a dose of 100 mg/cat every 24 h, while amphotericin B was administered subcutaneously at a dose of 0.5 mg/kg, combined with 100 mL of sodium chloride 0.9% and 100 mL of 5% glycated serum, with monitoring of serum concentrations of symmetric dimethylarginine (SDMA). Amphotericin B was administered every 48 h up to the 7th dose, followed by three times a week up to the 11th dose, and then twice a week up to the 16th dose. The animal was released from the veterinary hospital 10 days after its admission, showing a considerably improved respiratory condition and a respiratory rate of 40 breaths per minute. Continuation of the antifungal treatment with itraconazole was prescribed, maintaining the same dose and frequency of administration until a new recommendation would be made, as well as frequent return visits for the administration of amphotericin B and reassessment of the animal. The administration of amphotericin B was discontinued when the animal’s respiratory condition stabilized; hence, the feline received a total of 16 doses of the drug. The animal showed remission of clinical respiratory symptoms, confirmed by follow-up chest X-rays, which revealed significantly less radiodense pulmonary parenchyma in response to treatment with itraconazole and amphotericin B. Five months after beginning its treatment, the cat is being treated orally with itraconazole (100 mg/cat, every 24 h), without recrudescence of the clinical symptoms.Discussion: To date, six cases of feline histoplasmosis have been reported in Brazil, only one of which had pulmonary involvement and was treated successfully. The use of oral itraconazole associated with subcutaneous amphotericin B has proved to be effective for the treatment of acute pulmonary histoplasmosis in domestic cats. Note that a rapid diagnosis of pulmonary disease is essential in order to immediately implement a combined drug therapy linked with monitoring to ensure the protocol is safe for the patient

Gastrointestinal Histoplasmosis: A Case Series.

Histoplasmosis is an invasive mycosis caused by inhalation of the spores of dimorphic fungi Histoplasma capsulatum. The disease manifests in the lung as acute or chronic pulmonary histoplasmosis and in severe cases gets disseminated in multiple organs like skin, adrenal gland, central nervous system, lymph node, liver, spleen, bone marrow, and gastrointestinal tract. It occurs most commonly in immunodeficient patients like HIV-positive patients and transplant recipients, while immunocompetent hosts are affected rarely. In cases of gastrointestinal histoplasmosis, the samples are collected for culture and biopsy should be sent for histopathological examination for definitive diagnosis. We conducted a retrospective study of colonic biopsies performed in the department of gastroenterology in a tertiary care hospital of north India from January 2014 to December 2015. Five cases of colonic histoplasmosis were diagnosed on histopathology out of which 4 patients were from north India while 1 patient was from Myanmar. The patients presented with various complaints, including loose stools, diarrhea, altered bowel habits, and gastrointestinal bleeding. The prognosis is very good after early and aggressive treatment while the disease is fatal if it remains untreated. In our study, 2 patients died within few days of diagnosis due to delay in the diagnosis, dissemination, and associated complications. Other patients were started on amphotericin B deoxycholate and are under follow-up. An early diagnosis of gastrointestinal histoplasmosis is important as appropriate treatment leads to long-term survival while untreated cases are almost fatal.

IgG and IgM Antibody Testing Assists in Diagnosis of Acute Pulmonary Histoplasmosis

Acute pulmonary histoplasmosis (APH) can be difficult to identify due to limited sensitivity of diagnostic tests. Urine or serum antigen tests may be falsely negative in 38% of cases, and complement fixation (CF) and immunodiffusion (ID) antibody tests may also be insensitive. MiraVista Diagnostics has developed a new enzyme-linked immunoassay (EIA) …

Improved Diagnosis of Acute Pulmonary Histoplasmosis by Combining Antigen and Antibody Detection.

Acute pulmonary histoplasmosis can be severe, especially following heavy inoculum exposure. Rapid diagnosis is critical and often possible by detection of antigen, but this test may be falsely negative in 17% of such cases. Antibody detection by enzyme immunoassay (EIA) may increase sensitivity and permit the measurement of immunoglobulin M (IgM) and immunoglobulin G (IgG) classes of antibodies separately. Microplates coated with Histoplasma antigen were used for testing of serum from patients with acute pulmonary histoplasmosis and controls in the MVista Histoplasma antibody EIA. Results for IgG and IgM were reported independently. IgG antibodies were detected in 87.5%, IgM antibodies in 67.5%, and IgG and/or IgM antibodies in 88.8% of patients with acute pulmonary histoplasmosis in this assay, while immunodiffusion, complement fixation, and antigen testing showed sensitivities of 55.0%, 73.1%, and 67.5%, respectively (n = 80). Combining antigen and antibody detection increased the sensitivity to 96.3%. The MVista Histoplasma antibody EIA offers increased sensitivity over current antibody tests while also allowing separate detection of IgG and IgM antibodies and complementing antigen detection. Combining antigen and EIA antibody testing provides an optimal method for diagnosis of acute pulmonary histoplasmosis.