Dimorphic Fungus Histoplasma Capsulatum Research Articles

Factors influencing histoplasmosis incidence in multidrug-resistant pulmonary tuberculosis patients: A cross-sectional study in Indonesia.

Histoplasmosis is an infectious disease caused by the dimorphic fungus Histoplasma capsulatum, which in chronic conditions, is generally difficult to distinguish from pulmonary tuberculosis (TB) based on its clinical appearance; therefore, diagnostic errors could occur. Meanwhile, the prevalence of multidrug-resistant pulmonary TB (MDR-TB) in Indonesia remains high. Study determining the incidence of histoplasmosis in MDR-TB is unavailable worldwide. The aim of this study was to determine the risk factors of histoplasmosis incidence in MDR-TB patients in Indonesia. A cross-sectional was conducted at H. Adam Malik General Hospital, Medan, Indonesia and the ELISA platform (semi-quantitative) was used to detect histoplasma antibodies. Factors associated with histoplasmosis incidence among MDR-TB were determined using a Chi-squared test. A total of 50 MDR-TB patients were included this study of which 14 of them (28%) had histoplasmosis. The majority of histoplasmosis occurred in males, in MDR-TB patients with a history of TB treatment and among who had chest x-rays with far-advanced lesions. However, statistical analyses indicated none of those factors (sex, TB treatment history, status of the lung) as well as age group, acid-fast bacillus result, Mycobacterium tuberculosis culture result, having pet, living in damp house, working in the field or plantation, having HIV infection and smoking status were associated with histoplasmosis incidence. This study highlights that the incidence of histoplasmosis is relatively high and therefore further studies are important to be conducted in Indonesia that has a high MDR-TB cases.

Identification and production of novel potential pathogen-specific biomarkers for diagnosis of histoplasmosis.

Immunological assays based on the detection of circulating fungal biomarkers are helpful in clinical practice for diagnosing invasive fungal infections. Some of these targeting antigenic components are common to several different fungi. Histoplasmosis is a mycosis caused by the dimorphic fungus Histoplasma capsulatum, which in recent years has gained significant relevance due to the increase in the population susceptible to developing severe clinical forms, including those living with HIV/AIDS. Immunological tests that detect cell wall polysaccharide antigens are among the most used laboratory techniques for diagnosing this mycosis. However, none have shown adequate performance, and cross-reactivity with other fungal pathogens may be observed. Considering that there is a real need to improve the sensitivity and specificity of current diagnostic methods, we explored a novel strategy for the identification of H. capsulatum-specific antigens (Hc_Ags) that could be detected in clinical samples during infection based on a computational analysis model that included the application of bioinformatics tools and the analysis of experimental data from transcriptomics and proteomics. The Hc_Ags identified were expressed and purified by eukaryotic and prokaryotic systems. First, the Hc_Ags were used in an in-house immunization model in mice (BALB/c) to obtain Hc_Ag-specific polyclonal antibodies (Hc_Ag_PAb). Then, the presence of these antigens in H. capsulatum-yeast culture extracts and the specificity of Hc_Ag_PAb against culture extracts of Candida albicans, Aspergillus fumigatus, Cryptococcus neoformans, Fusarium spp., and Paracoccidioides brasiliensis were confirmed. Finally, we demonstrated the immunoreactivity of these Hc_Ag-specific polyclonal antibodies with urine samples from patients previously diagnosed with histoplasmosis.IMPORTANCEHistoplasmosis is considered one of the most important mycoses due to the increasing number of individuals susceptible to develop severe clinical forms, particularly those with HIV/AIDS or receiving immunosuppressive biological therapies, the high mortality rates reported when antifungal treatment is not initiated in a timely manner, and the limitations of conventional diagnostic methods. In this context, there is a clear need to improve the capacity of diagnostic tools to specifically detect the fungal pathogen, regardless of the patient's clinical condition or the presence of other co-infections. The proposed novel pathogen-specific biomarkers have the potential to be used in immunodiagnostic platforms and antifungal treatment monitoring in histoplasmosis. In addition, the bioinformatics strategy used in this study could be applied to identify potential diagnostic biomarkers in other models of fungal infection of public health importance.

Closing the Gap in Proteomic Identification of Histoplasma capsulatum: A Case Report and Review of Literature.

Histoplasmosis is a globally distributed systemic infection caused by the dimorphic fungus Histoplasma capsulatum (H. capsulatum). This fungus can cause a wide spectrum of clinical manifestations, and the diagnosis of progressive disseminated histoplasmosis is often a challenge for clinicians. Although microscopy and culture remain the gold standard diagnostic tests for Histoplasma identification, matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS) has emerged as a method of microbial identification suitable for the confirmation of dimorphic fungi. However, to our knowledge, there are no entries for H. capsulatum spectra in most commercial databases. In this review, we describe the case of disseminated histoplasmosis in a patient living with HIV admitted to our university hospital that we failed to identify by the MALDI-TOF method due to the limited reference spectrum of the instrument database. Furthermore, we highlight the utility of molecular approaches, such as conventional polymerase chain reaction (PCR) and DNA sequencing, as alternative confirmatory tests to MALDI-TOF technology for identifying H. capsulatum from positive cultures. An overview of current evidence and limitations of MALDI-TOF-based characterization of H. capsulatum is also presented.

Application of Real-Time PCR Assays for the Diagnosis of Histoplasmosis in Human FFPE Tissues Using Three Molecular Targets.

Histoplasmosis is a fungal infection caused by the thermally dimorphic fungus Histoplasma capsulatum. This infection causes significant morbidity and mortality in people living with HIV/AIDS, especially in countries with limited resources. Currently used diagnostic tests rely on culture and serology but with some limitations. No molecular assays are commercially available and the results from different reports have been variable. We aimed to evaluate quantitative real-time PCR (qPCR) targeting three protein-coding genes of Histoplasma capsulatum (100-kDa, H and M antigens) for detection of this fungus in formalin-fixed paraffin-embedded (FFPE) samples from patients with proven histoplasmosis. The sensitivity of 100-kDa, H and M qPCR assays were 93.9%, 91% and 57%, respectively. The specificity of 100-kDa qPCR was 93% when compared against samples from patients with other mycoses and other infections, and 100% when samples from patients with non-infectious diseases were used as controls. Our findings demonstrate that real-time PCR assays targeting 100-kDa and H antigen showed the most reliable results and can be successfully used for diagnosing this mycosis when testing FFPE samples.

Atypical Presentations of Progressive Disseminated Histoplasmosis in an Immunocompetent Adult: Ectopic Calcification (Aneurysm of Sinus of Valsalva) and Large Vessel (Left Subclavian Artery) Stenosis in the Background of Adrenal Insufficiency

Histoplasmosis is a systemic fungal disease caused by the dimorphic fungus Histoplasma capsulatum and is more common in immunocompromised patients. Histoplasmosis can present with a wide range of clinical manifestations from asymptomatic illness to severe organ dysfunctions and may need hospitalization. Histoplasmosis is a major opportunistic infection in North and Central America. Disseminated histoplasmosis is a progressive extrapulmonary infection, caused by hematogenous spread, mostly found in immunosuppressed patients.
 Reports of histoplasmosis in nonendemic regions are very rare. Due to the varied and nonspecific clinical manifestations of histoplasmosis, most of the infections are misdiagnosed or underreported.
 Here, we report a case of disseminated histoplasmosis in an immunocompetent individual from a non-endemic zone in eastern India, presented with long term fever along with ectopic calcification (Aneurysm of Sinus of Valsalva) and large vessel (left subclavian artery) stenosis in the background of adrenal insufficiency.

Disseminated histoplasmosis: A threatening emergent disease in Tunisia

Introduction: Histoplasmosis is an infection due to a dimorphic fungus Histoplasma capsulatum. In Tunisia, there is no cases described among native Tunisians, but it is emerging as an exotic imported infection from Sub-Saharan Africa.

Antifungal Susceptibility Testing and Drug Discovery in the Dimorphic Fungus Histoplasma Capsulatum.

The thermal dimorphism of the fungal pathogen Histoplasma is linked to its virulence in mammalian hosts. Mammalian body temperature triggers differentiation of the fungus into virulent yeasts which successfully infect host phagocytes. Accurate determination of antifungal susceptibility with relevance to infection requires that the tests be performed specifically using the yeast form, not the filamentous environmental form. However, traditional CLSI methodology for antifungal susceptibility testing of yeasts with Histoplasma is in adequate. We present optimized methodology for performing antifungal susceptibility assays on Histoplasma yeasts with an emphasis on quantitative yeast growth determination. Colorimetric and fluorometric assays for Histoplasma growth overcome challenges associated with quantifying some Histoplasma strains which grow as aggregates of yeasts. We also describe antifungal susceptibility testing of Histoplasma yeasts within macrophages to provide improved accuracy and better physiological relevance of antifungal susceptibility profiles.

Pathogenicity & Virulence of Histoplasma capsulatum - a multifaceted organism adapted to intracellular environments

Histoplasmosis is a systemic mycosis caused by the thermally dimorphic fungus Histoplasma capsulatum. Although healthy individuals can develop histoplasmosis, the disease is particularly life-threatening in immunocompromised patients, with a wide range of clinical manifestations depending on the inoculum and virulence of the infecting strain. In this review, we discuss the established virulence factors and pathogenesis traits that make H. capsulatum highly adapted to a wide variety of hosts, including mammals. Understanding and integrating these mechanisms is a key step towards devising new preventative and therapeutic interventions.

Histoplasmosis of Adrenal Gland: A 5 Years' Review from a Multispecialty Diagnostic Centre.

Objective Histoplasmosis is an infectious disease caused by the dimorphic fungus Histoplasma capsulatum . Histoplasmosis is considered to be endemic to India, especially the Gangetic belt. Disseminated histoplasmosis may affect almost all systems. Disseminated histoplasmosis with asymptomatic adrenal involvement has been described in immunocompromised patients, whereas isolated adrenal involvement as the presenting manifestation in immunocompetent is uncommon. We aimed to determine the clinicopathological and radiological findings of adrenal histoplasmosis in immunocompetent patients attending a multispecialty diagnostic center referred from different clinics and hospitals. Materials and Methods All tissue samples were initially examined microscopically by performing potassium hydroxide (KOH) wet mounts, followed by culture on two tubes of Sabouraud dextrose agar and phase conversion. Histopathological correlation was done using tissue stains, hematoxylin and eosin, periodic acid-Schiff, and Gomori methenamine silver. Results We evaluated 84 clinically suspected cases radiologically for adrenal mass. The pathological and microbiological work-up was done from these suspected cases. A total of 19 cases were evident from the tissue stain and fungal culture methods. The affected population were mostly above 45 years and male. Seven patients had bilateral adrenal involvement. All these patients received amphotericin B and/or itraconazole treatment, which led to symptomatic improvement in most cases. Conclusion Diagnosis of invasive fungal infection requires a high index of suspicion, especially in immunocompetent patients presenting with nonspecific symptoms, clinical signs, and laboratory and radiological features that often resemble adrenal neoplasms. Clinical specimens, together with fungal culture, must be sent for cytopathology/histopathology for a definite diagnosis and appropriate management.

Current perspective of adrenal histoplasmosis in India: A prospective study in a tertiary care hospital, Eastern India

PurposeAdrenal histoplasmosis (AH) is an uncommon form of disseminated histoplasmosis caused by the dimorphic fungus Histoplasma capsulatum. Though, India is considered to be a non-endemic area for histoplasmosis, a high rise of AH cases is reported currently from various parts of India. Our study aimed to evaluate the current perspective of adrenal histoplasmosis in India by reviewing its clinical course, differential diagnosis, treatment, and mortality of our eleven confirmed cases of AH along with the review of authentic reported AH cases from India. Material &methodClinical materials were taken from radiologically suspected all 15 cases either with unilateral or bilateral adrenal enlargement, referred between 2018 and 2020 for microbiological investigations. Fungal stain and fungal culture along with other tests for possible differential diagnosis with AH were conducted. ResultOut of fifteen incidentaloma detected by radio-imaging, eleven cases of AH had been diagnosed in our hospital with yield of Rhodotorula spp. in one mimicking case. Nine of them were male (82%) and all were HIV nonreactive, which corroborates with the literature review. All of them had nonspecific clinical presentation of chronic abdominal pain, fever, weight loss, and anorexia. Four developed primary adrenal insufficiency, which are similar to the literature review (41%). On treatment with itraconazole and/or amphotericin B, all patients survived except one lost in follow-up. ConclusionMale preponderance and non-compromised immune status are two special characteristics of most AH though reasons are ill understood. So, mycological investigations are to be done for every such case.

P251 Disseminated Histoplasmosis in a Ghanaian HIV Patient: Role of Urine Histoplasma Antigen Testing in Rapid Diagnosis

Poster session 2, September 22, 2022, 12:30 PM - 1:30 PMBackgroundThe inhalation of the thermally dimorphic fungus Histoplasma capsulatum, may result in a wide spectrum of clinical manifestations, ranging from asymptomatic to acute or chronic pulmonary infection to disseminated infection. Symptomatic infections usually occur with high-level exposures or in immunocompromised patients mainly people with HIV. Despite the improved access to antiretroviral therapy, HIV-associated histoplasmosis remains a significant opportunistic infection in endemic regions including Africa. Unfortunately, histoplasmosis is rarely on the diagnostic radar of clinicians in several African countries such as Ghana due to insufficient awareness, inadequate epidemiological data, and poor fungal diagnostic capacity. Herein, we present a case of disseminated histoplasmosis in an HIV/AIDS patient in a tertiary hospital in Ghana.Case PresentationClinical history: A 43-year-old female was referred to the Dermatology Clinic of the Komfo Anokye Teaching Hospital (KATH) with symptoms of fever, cough, and anorexia. She had a history of a skin rash six weeks prior, which initially began on her face and later spread to the trunk and extremities. She was a known HIV/AIDS patient on anti-retroviral drugs (EFV, TFV, 3TC) with no other chronic conditions. She was anemic with a previous hemoglobin level of 7.6 g/dl. Initial diagnostic workup for cutaneous bacterial or viral infection detected no abnormality.ExaminationShe was semi-conscious, and her nostrils were clogged with crust. The patient appeared pale, warm, and anicteric. The face, trunk, and extremities (including palms) were covered with mucocutaneous erosions, ulcers, multiple papule plaques, and nodules. Examination of the cervix revealed the presence of lymph nodes.InvestigationsA fungal diagnostic work-up was done to rule out cutaneous or disseminated mycosis particularly cryptococcosis which was previously captured as a differential diagnosis. Serum cryptococcal antigen lateral flow assay (LFA) (CrAg LFA, IMMY) and Aspergillus galactomannan (GM) (sona Aspergillus GM LFA, IMMY) tests were both negative, but urine Histoplasma GM enzyme immunoassay (EIA) (clarus Histoplasma GM EIA, IMMY) test was positive with a very high optical density indicating high fungal burden was reported. A skin biopsy was also sent for histopathology and fungal culture. Histopathology analysis revealed the presence of yeast cells with round central nuclei and cytoplasmic clearing. Special staining with Periodic acid–Schiff (PAS) confirmed the presence of yeast cells, suggestive of histoplasmosis. Fungal culture was however negative after 8 weeks of incubation. A diagnosis of disseminated histoplasmosis was made.Treatment and outcomeThe patient was administered 200 mg bid of itraconazole. Few weeks after treatment, most of her skin lesions and ulcers were healed. The patient was discharged on itraconazole after the disappearance of some of her lesions. Few weeks later, the patient was admitted but died due to complications of anemia.ConclusionDisseminated histoplasmosis in HIV may be a relatively common but largely unrecognized condition in Ghana. This case report highlights the need to improve awareness of histoplasmosis among clinicians in Ghana and enhance laboratory capacity to provide timely simple contemporary fungal tests for rapid diagnosis and prompt initiation of effective antifungal agents.

A molecular beacon assay for monitoring RNA splicing.

Small molecule targeting of self-splicing RNAs like group I and II introns has been limited in part by the lack of a universal high-throughput screening platform for studies of splicing inhibition and kinetics. Here, we present the development of a molecular beacon assay for monitoring the accumulation of spliced exons during RNA splicing reactions. In this case, we applied it to the autocatalyzed reaction of the H.c.LSU group II intron found in the mitochondria of the pathogenic dimorphic fungus Histoplasma capsulatum. We find that a molecular beacon with the loop length of 18 nucleotides selectively recognizes ligated exons formed during self-splicing and exhibits high fluorescent signal upon binding of its target. We demonstrate that the fluorescent assay using molecular beacons can be successfully applied to kinetic characterization of the splicing reaction and determination of inhibition constants for small molecules. The results presented herein offer support for a molecular beacon approach to identifying small molecule inhibitors of intron splicing.

Properties and Effect of Fresh Concentrated Extract of Garlic on Different Bacteria and Fungi

Aims: Study some characteristics of fresh concentrated extract of garlic (FCEG) and analyze its effect on the growth of different bacteria and fungi.
 Place and Duration of Study: Sample: Faculty of Chemical Sciences. Autonomous University of San Luís Potosí, S.L.P., between march and November 2020.
 Methodology: To obtain the FCEG, 15 heads of raw garlic, previously peeled, were ground in a mortar and the suspension obtained was filtered through gauze, pressing to obtain a greater amount of filtrate, and kept covered at 4oC. For the study of some of their characteristics, the yeast Candida albicans was used. Petri dishes containing Sabouraud dextrose agar were inoculated with 1 x 106 yeasts/mL and 50 µL of FCEG, and were incubated at 28oC for 5 days, comparing growth with respect to a control without FCEG (all inhibition experiments described below were performed with the same protocol), while for the study of antifungal properties analyzed the effect of the extract on different strains of bacteria, yeasts, and fungi.
 Results: Some of the factors that modify antifungal activity of FCEG are dilution, incubation temperature, protein concentration, half-life, capping and uncapping of tubes, and treatment with activated carbon. Regarding the growth inhibition analyses, it was found that all the species analyzed were susceptible to FCEG, among which the following stand out: the the dimorphic fungus Histoplasma capsulatum, causing systemic mycoses, the yeasts Cryptococcus neoformans and C. albicans, as well as different species of Dermatophytes, Aspergillus, and bacteria.
 Conclusion: FCEG shows a good antimicrobial effect against a wide variety of bacteria, yeast, and fungal species, which makes its application in medical therapy and agriculture, as well as being cheap, easy to obtain and does not cause side effects, although more studies are required for its therapeutic application.

Considerations about the Geographic Distribution of Histoplasma Species.

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.

Histoplasmosis in Africa: Current perspectives, knowledge gaps, and research priorities.

BackgroundHistoplasmosis is a chronic granulomatous disease caused by the thermally dimorphic fungus Histoplasma capsulatum. The 2 variants Histoplasma capsulatum var. capsulatum (Hcc) and Histoplasma capsulatum var. duboisii (Hcd) causes infection in humans and commonly termed classical or American histoplasmosis and African histoplasmosis, respectively. Histoplasma capsulatum var. farciminosum (Hcf) affects equines. In recent times, there have been heightened sensitization on fungal infections such as histoplasmosis in Africa, aimed at improving awareness among relevant stakeholders, particularly healthcare workers. This effort is expected to be paralleled with increased detection of both classical and African histoplasmosis, which has remained underdiagnosed over the years. In this narrative review, we describe the current perspectives of histoplasmosis in Africa, identify knowledge gaps, and suggest research priorities.MethodsA PubMed, Google Scholar, and Africa Journal Online (AJOL) literature search was conducted for studies on histoplasmosis in Africa between 2000 and 2020. Histoplasmosis essays in medical mycology textbooks were also consulted. This narrative review was prepared from the data gathered.FindingsIn the past 2 decades, histoplasmosis in general has seen a relative increase in case detection in some Africa countries, probably attributable to the gradually increasing medical mycology advocacy efforts in Africa. Histoplasmosis cases are dominated by African histoplasmosis mostly in Western and Central Africa, while classical histoplasmosis is more common in Southern and Northern Africa. Although both classical and African histoplasmosis are common in Africa, the latter is more restricted to Africa, and cases outside the continent usually have a travel history to the continent. Despite the clinical and laboratory difference between African histoplasmosis and classical histoplasmosis, it is not straightforward to distinguish them. The typical manifestation of African histoplasmosis is the appearance of lesions affecting the skin, bones, and lymph nodes and unusually linked to human immunodeficiency virus (HIV)/AIDS. By contrast, classical histoplasmosis mostly affects the lungs and is often associated with immunosuppression, mainly HIV/AIDS. The present perspectives of histoplasmosis in Africa highlight unclear details on the true burden, strain diversity, infection route and genetic basis of African histoplasmosis, availability of specie-specific diagnostic tools, and compliance with recommended antifungal therapy. These knowledge gaps represent research questions that require scientific exploration.ConclusionsDespite a subtle increase in identifying histoplasmosis cases in Africa, it remains underdiagnosed and neglected in some parts of the continent. Increasing awareness and training among healthcare workers, bridging diagnostic and therapeutic gaps, and encouraging more research in Africa are crucial to improve the current perspectives of histoplasmosis in Africa.

Pulmonary histoplasmosis: A case report

Histoplasmosis is a systemic fungal infection caused by dimorphic fungus Histoplasma capsulatum. It is widely distributed throughout the world. In present study, the case of a 50-year-old male patient diagnosed as pulmonary histoplasmosis. Initially, the patient was suspected as a case of alcoholic hepatitis but subsequently the diagnosis of pulmonary histoplasmosis was confirmed by lung biopsy. The symptoms were dissuaded following amphotericin B and itraconazole treatment.

DISSEMINATED HISTOPLASMOSIS IN A PATIENT WITH NEWLY DIAGNOSED AIDS

TOPIC: Chest Infections TYPE: Medical Student/Resident Case Reports INTRODUCTION: Disseminated Histoplasmosis (DH) is an AIDS-defining illness caused by the dimorphic fungus Histoplasma capsulatum. Outbreaks have been associated with exposure to bird or bat droppings and amongst construction workers. It remains unclear whether DH represents an acute infection or a reactivation of latent infection. We present a case of DH in a newly diagnosed AIDS patient. CASE PRESENTATION: A 50 year old male Hispanic construction worker presented with a month history of persisting fever, chills, diaphoresis, progressive shortness of breath on exertion, non-bloody diarrhea and 15lbs weight loss. HIV screen was positive (new diagnosis) and his CD4+ cell count was 3 per cubic millimeter with a viral load of over 1 million copies/ml. CXR showed diffuse interstitial infiltrates in both lung fields and CT chest showed numerous punctate miliary pattern pulmonary nodules in the lungs with necrotic appearing lymph nodes in the proximal jejunal mesentery. SARS-CoV2 PCR was negative. BAL culture grew Histoplasma capsulatum, Lung biopsy pathology showed broad based budding yeast and urine histoplasma antigen was positive at greater than 23 ng/ml. He was treated with highly active antiretroviral therapy (HAART), IV liposomal amphotericin, and steroid. Empiric anti-TB therapy was stopped with negative quantiferon TB gold, BAL AFB smear and BAL MTB complex PCR. Silver stain for PCP, serum cryptococcal antigen, serum galactomammanan and fungitell assays were all negative. Hospital course was complicated by pneumothorax, septic shock, line related bloodstream infections that resolved with line removal and antimicrobials. Despite appropriate antifungal therapy for 40 days with decrease in his urine histoplasma antigen to 11 ng/ml, and HIV viral load decreasing to 330 copies/ml after 3 weeks of HAART, he remained ventilator dependent, on chest tubes and could not be weaned off sedation. His family made him comfort care only on hospital day 43 and he died peacefully after. DISCUSSION: Histoplasmosis has been recognized as an opportunistic infection in patients with AIDS and typically presents as disseminated disease. DH in conjunction with HIV infection is particularly common among Hispanic persons in the United states. In AIDS patients, DH is associated with a nonspecific clinical presentation—usually unexplained fever and weight loss. Histoplasmosis causes significant morbidity and mortality. Fungal infections deaths in AIDS were estimated at more than 700, 000 deaths (47%) annually. The frequent occurence of histoplasmosis with other opportunistic infections especially tuberculosis requires that tuberculosis be ruled out even if histoplasmosis is diagnosed. CONCLUSIONS: This case highlights the fact that although miliary pattern on CT Chest typically signifies tuberculosis, it can also be seen in histoplasmosis. Also associated morbidity and mortality of DH remains high in AIDS patients not on HAART. REFERENCE #1: Rana A. Hajjeh. Disseminated Histoplasmosis in Persons Infected with Human Immunodeficiency Virus. Clinical Infectious Diseases 1995; 21(Suppl 1):S108 -10. REFERENCE #2: Stuart M. Levitz, and Eugene J. Mark. Case 38-1998 — A 19-Year-Old Man with the Acquired Immunodeficiency Syndrome and Persistent Fever. N Engl J Med 1998; 339:1835-1843. REFERENCE #3: David W. Denning. Minimizing fungal disease deaths will allow the UNAIDS target of reducing annual AIDS deaths below 500 000 by 2020 to be realized. Philos Trans R Soc Lond B Biol Sci. 2016 Dec 5;371(1709). DISCLOSURES: No relevant relationships by Oluwadamilola Adeyemi, source=Web Response No relevant relationships by Ingrid Gils, source=Web Response No relevant relationships by Drew Ludwig, source=Web Response No relevant relationships by Biana Modilevsky, source=Web Response

Disseminated Histoplasmosis in a Retropositive Young Male: A Case Report

Disseminated histoplasmosis is caused by the dimorphic fungus Histoplasma capsulatum. This fungal infection is commonly seen in immunocompromised patients, especially in AIDS patients, children and elderly population. Here we present a case report of a 24-year-old male who was admitted with generalised fatigue and generalised lymphadenopathy. He was found to be retropositive on evaluation and FNAC of the node surprisingly revealed Histoplasmosis. Presence of these organisms were also seen on the peripheral smear which could be picked up only on reviewing the smear again. With this case report we wish to emphasize the need for careful and diligent search of these organisms in the peripheral smear.

Histoplasmosis: diagnostic and therapeutic aspect

Histoplasmosis has been reported since 1932 in various regions in Indonesia. This disease is caused by thermally dimorphic fungus Histoplasma capsulatum var. capsulatum which is experiencing an increasing incidence worldwide. Human infection occurs when spores in soil contaminated with bird and bat droppings are inhaled and change to form yeast in the lungs. The majority of these forms of infection are mild and can heal on their own, but if large numbers of spores/ inoculum are inhaled, or the host is immunosuppressed, serious lung disease and even dissemination may occur with a high mortality rate. The diagnosis can be made by combining clinical symptoms with laboratory test results. Conventional laboratory methods such as direct examination or histopathology and culture are the gold standards for histoplasmosis diagnosis. The weakness of culture is the nature of H. capsulatum as a slow grower fungus that takes 4-6 weeks to grow. In addition, laboratory tests can be carried out with antibody detection or antigen detection. Antigen detection is more benefi cial for hosts with immunosuppression or acute form, while antibody detection is more important in the chronic form of the diseases. Molecular-based assays have high specifi city but are not yet available commercially and are more widely used for culture identifi cation to confi rm the species of H. capsulatum. Histoplasmosis therapy usually begins with the administration of amphotericin B for around two weeks, followed by maintenance with itraconazole for 6 - 9 months duration. A careful history of possible exposure and the appropriate laboratory diagnostic approach is essential to provide appropriate therapy.

Diagnosis of histoplasmosis: current status and perspectives.

Histoplasmosis is a worldwide-distributed systemic mycosis caused by the dimorphic fungus Histoplasma capsulatum. Its clinical manifestations range from subclinical or mild respiratory illness to progressive disseminated histoplasmosis (PDH), a life-threatening disease, whose accurate diagnosis is still challenging and limited in many countries, where this disease is highly endemic. In this regard, Histoplasma antigen testing is now included in the WHO Essential Diagnostics List. The final diagnosis of histoplasmosis is established by culture and/or visualization of the yeast cells by cytology or histopathology using specific stains. However, both procedures have limited sensitivity to detect the disease and cultures are time-consuming. Antibody detection assays are effective for the subacute and chronic clinical forms of histoplasmosis. However, their sensitivity is low in the immunocompromised host. Several molecular "in-house" tests were also developed and showed promising results, but none of these tests are commercially available and their standardization and validation are still pending. Antigen detection assays have high sensitivity in PDH cases and are of great value for the follow-up of patients with histoplasmosis; however, cross-reactivity with other related fungi are common. In addition, this assay is expensive and only performed in few laboratories. Novel protein antigen candidates have been recently identified and produced by DNA-recombinant techniques in order to obtain standardized and specific reagents for the diagnosis of histoplasmosis, as opposed to the unspecific antigens or crude extracts currently used. This review describes the currently available assays, highlighting their strengths and limitations and reports the latest approaches to achieve reliable and rapid diagnostic tests for histoplasmosis. KEY POINTS: • PDH causes thousands of deaths per year globally. • Rapid accurate diagnosis of PDH is unfeasible in many regions. • Fast, accurate, and low-cost diagnostic alternatives are currently under development.