Materiały źródłowe

• #1 Laboratory Diagnostics for Histoplasmosis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5442517/

  The diagnosis of histoplasmosis is based on a multifaceted approach that includes clinical, radiographic, and laboratory evidence of disease. […] The gold standards for laboratory diagnosis include demonstration of yeast on pathological examination of tissue and isolation of the mold in the culture of clinical specimens; however, antigen detection has provided a rapid, noninvasive, and highly sensitive method for diagnosis and is a useful marker of treatment response. […] Demonstration of the yeast on pathological stains and isolation of the mold in culture of clinical specimens constitute the gold standard tests for the diagnosis of histoplasmosis. […] Serologic testing for histoplasmosis is another widely employed method for diagnosis and is particularly useful for chronic disease manifestations in which the sensitivity of antigen detection is suboptimal.

• #1 Testing Algorithm for Histoplasmosis | Histoplasmosis | CDC

  https://www.cdc.gov/histoplasmosis/hcp/algorithm/index.html

  Histoplasmosis is an invasive fungal disease that often presents as community-acquired pneumonia in primary and urgent care settings. […] Histoplasmosis cannot be reliably distinguished from other causes of respiratory illness by signs or symptoms alone. […] Clinicians in urgent care and outpatient settings can use this algorithm to help make determinations about clinical testing. […] Consider testing patients with community-acquired pneumonia who: Live in or recently traveled to an endemic area and have not improved with at least one course of empiric antibiotics. […] If a patient lives in or has traveled to a histoplasmosis-endemic area and has: CAP of unknown etiology not responding to a course of empiric antibiotics or Initial CAP visit if: Notable exposure to bird or bat droppings (cave or demolition/remodeling exposure; note that many patients do not recall a specific exposure) OR Chest X-ray showing new nodules or lymphadenopathy OR Link to known histoplasmosis outbreak.

• #1 Laboratory Diagnostics for Histoplasmosis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5442517/

  The sensitivity of cultures for detection of H. capsulatum depends on the clinical manifestation (pulmonary versus disseminated), the net state of immunity of the host, and the burden of disease. […] Patients with disseminated histoplasmosis have a higher rate of positive cultures (74%) than patients with acute pulmonary histoplasmosis (42%). […] Demonstrating the presence of yeast cells consistent with H. capsulatum in tissue supports the diagnosis of histoplasmosis (although not necessarily active infection). […] The presence of H. capsulatum yeast in certain tissues or sterile body fluid (such as skin lesions) and in the appropriate clinical context (such as acute pneumonia) is indicative of active infection. […] Antigen testing has become a leading modality to diagnose histoplasmosis.

• #1 Diagnosis of Progressive Disseminated Histoplasmosis in Advanced HIV: A Meta-Analysis of Assay Analytical Performance

  https://www.mdpi.com/2309-608X/5/3/76

  Histoplasmosis is an important cause of mortality in people with advanced HIV, especially in countries with limited access to diagnostic assays. Histoplasmosis can be diagnosed using culture, histopathology, and antibody, antigen, and molecular assays. Several factors may affect the analytical performance of these laboratory assays, including sample type, clinical stage of the disease, and previous use of antifungal treatment, among others. […] The gold standard for diagnosis of histoplasmosis is based on conventional laboratory assays using culture and histopathology (including special stains). These assays have several limitations, including the need for high-level laboratory infrastructure for culture handling (biosecurity level 3) the need for highly trained laboratory staff, variable assay analytical performance, and a long turn-around time for results. Other alternatives for histoplasmosis diagnosis include assays for the detection of specific host antibodies against Histoplasma antigens; detection of circulating Histoplasma antigens in urine, serum, and bronchoalveolar lavage (BAL); and detection of fungal DNA.

• #1 Clinical Overview of Histoplasmosis | Histoplasmosis | CDC

  https://www.cdc.gov/histoplasmosis/hcp/clinical-overview/index.html

  Histoplasma antigen detection in urine or serum is the most widely used and most sensitive method. […] Other methods include antibody tests, culture, and microscopy. The most appropriate diagnostic test may depend on clinical manifestation and severity. […] Enzyme immunoassay (EIA) typically performed on urine or serum but can also be used on cerebrospinal fluid or bronchoalveolar lavage fluid. Urine antigen testing may have the highest sensitivity of non-invasive diagnostic tests and the quickest turnaround. […] Development of antibodies to Histoplasma can take 2 to 6 weeks. Antibody tests are not as useful as antigen detection tests for diagnosing acute histoplasmosis. This is especially true in immunosuppressed persons, who may not mount a strong immune response. However, antibody tests can be used in combination with antigen tests to increase sensitivity.

• #1 Histoplasmosis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK448185/

  Histoplasmosis is the most common endemic mycosis in the United States. […] The workup includes serological tests such as complement fixation, immunodiffusion and enzyme immunoassays. […] Antibody tests are useful for diagnosis and management of histoplasmosis but not in all cases. […] The two standard assays are complement fixation and immunodiffusion assay. […] Detection of antigen may be more effective and useful in acute disease as well as in patients who are immunocompromised and do not have good antibody response. […] Urinary antigen detection is more sensitive than serum antigen detection (95% versus 86% in one study).

• #1 Diagnosing Histplasmosis by Antigen Detection Serum and Urine

  https://miravistalabs.com/diagnosing-histoplasmosis-by-antigen-detection/

  FEATURE: Diagnosing Histoplasmosis by Antigen Detection […] Most physicians are familiar with the useful role of antigen detection for diagnosis of disseminated histoplasmosis but are not aware that both the urine and serum must be tested for optimal sensitivity. […] In acute pulmonary histoplasmosis, the sensitivity for antigen detection was 83%, but 38% were positive only in the serum and would have been missed by testing only the urine. […] While many physicians are aware of testing urinary antigen to diagnose histoplasmosis, the practice of testing serum antigen for diagnosis is not as well-known. […] Testing both urine AND serum consistently provides the highest sensitivity for Histoplasma antigen. […] 38% of acute pulmonary histoplasmosis cases may not be properly diagnosed if only urine is tested. […] 5-10% of progressive disseminated histoplasmosis cases may not be properly diagnosed if only urine is tested.

• #1 The Current and Future States of Diagnostic Tests for Histoplasmosis with a Focus on People with HIV and Disseminated Histoplasmosis

  https://www.mdpi.com/2309-608X/9/8/793

  Antigen testing performs well for disseminated disease and acute pulmonary disease, particularly in the context of advanced HIV. […] Antigen testing is less sensitive in chronic pulmonary histoplasmosis due to the lower availability of peripheral antigen to be detected. […] A variety of antibody tests are available for histoplasmosis, including immunodiffusion, complement fixation, and enzyme immunoassays. […] Antibody testing offers higher sensitivity for subacute pulmonary histoplasmosis and chronic pulmonary histoplasmosis but is less reliable in testing for acute pulmonary histoplasmosis and early disseminated disease as it may take weeks for sufficient numbers of antibodies to develop. […] PCR has great potential, but implementation has been inconsistent. […] Antigen testing is the most sensitive modality for diagnosing disseminated histoplasmosis.

• #1 The Current and Future States of Diagnostic Tests for Histoplasmosis with a Focus on People with HIV and Disseminated Histoplasmosis

  https://www.mdpi.com/2309-608X/9/8/793

  The development of lateral flow assays has the potential to make for true rapid point-of-care assays for histoplasmosis, but in order to meet that promise, the tests must be widely available and affordable. […] Diagnostic certainty is of particular importance in disseminated histoplasmosis, which is uniformly fatal if not treated. […] Traditional diagnostic techniques are slow (culture) and/or of variable sensitivity (direct visualization). […] Antigen detection tests are fairly rapid and sensitive, but they have not generally been widely available outside of the United States. […] In this review, we will discuss the current state of diagnostic testing for histoplasmosis. […] We will further discuss diagnostic test performance differences between people with and without HIV. […] We will also discuss newer tests that are expected to be commercially available in the near future, are currently being tested, or are expected to begin testing in the coming months to years.

• #1 Laboratory Diagnostics for Histoplasmosis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5442517/

  Although a definitive diagnosis of histoplasmosis necessitates culture or histopathologic confirmation, a probable diagnosis can still be made when a host factor (immunocompromising condition), compatible clinical picture, and mycological evidence (such as antigen positivity) are present. […] Antibody testing is most useful for subacute and chronic forms of histoplasmosis (including mediastinal histoplasmosis), in which circulating antibodies are present and the sensitivity of antigen detection is suboptimal. […] Isolation of H. capsulatum on culture or identification of yeast on histopathology are the gold standards for diagnosis. […] Antigen testing and serology are also available, with antigen testing being both highly sensitive and easily interpretable, making it widely accessible to clinicians. […] Molecular methods may be the next frontier in Histoplasma diagnostics, but current assays have not been FDA approved for routine clinical use.

• #1 Clinical Overview of Histoplasmosis | Histoplasmosis | CDC

  https://www.cdc.gov/histoplasmosis/hcp/clinical-overview/index.html

  Tests for the presence of H (indicates chronic or severe acute infection) and M (develops within weeks of acute infection). These persist for months to years after the infection has resolved; precipitin bands; ~80% sensitivity. […] Complement-fixing antibodies may take up to 6 weeks to appear after infection. CF is more sensitive but less specific than immunodiffusion. […] Can be performed on tissue, blood, and other body fluids, but may take up to 6 weeks to become positive; most useful in the diagnosis of the severe forms of histoplasmosis. A commercially available DNA probe (AccuProbe, GenProbe Inc.) can be used to confirm. […] For detection of budding yeast in tissue or body fluids. It has low sensitivity but can provide a quick proven diagnosis if positive. […] PCR for detection of Histoplasma directly from clinical specimens is not widely available; however, it can be performed on serum, tissue, or BAL fluid and is promising.

• #1 Histoplasmosis: Causes, Symptoms, Diagnosis & Treatment

  https://my.clevelandclinic.org/health/diseases/24811-histoplasmosis

  A healthcare provider might test your blood, pee (urine), mucus from your lungs (sputum), bone marrow or a sample of affected tissue to diagnose histoplasmosis. They can use these samples to: […] Theyll also use imaging like chest X-rays or CT scans to look for changes or damage caused by H. capsulatum. The specific types of test they use depends on what kind of histoplasmosis they think you have and how severe your symptoms are. […] In addition to imaging (like chest X-rays or CT scans), your provider may collect samples of fluids or tissues to look for signs of H. capsulatum or try to grow it over time. They can collect these fluids using: […] Histoplasmosis is treated with antifungal medications if necessary. If you have mild symptoms that havent gone on for a long time and youre not at high risk for serious infection, your provider may not treat you right away.

• #1 Histoplasmosis – Infectious Diseases – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/infectious-diseases/fungi/histoplasmosis

  Diagnosis is by identification of the organism in sputum or tissue or use of specific serum and urine antigen tests. […] The index of suspicion for histoplasmosis must be high because symptoms are nonspecific. […] Histopathology and cultures […] Serologic testing […] Antigen testing […] Chest x-rays should be done and may show the following: In acute infection: Normal or a diffuse nodular or miliary pattern […] In chronic pulmonary histoplasmosis: Cavitary lesions in most patients […] In progressive disease: Hilar adenopathy with diffuse nodular infiltrates in approximately 50% of patients […] Bronchoalveolar lavage or tissue biopsy may be necessary to obtain histology specimens; serologic testing and culture of urine, blood, and sputum specimens are also done. […] Microscopic histopathology can strongly suggest the diagnosis, particularly in patients with AIDS and extensive infections; in such patients, intracellular yeasts may be seen in Wright- or Giemsa-stained peripheral blood or buffy coat specimens.

• #1 SciELO Brazil – Diagnosis of histoplasmosis Diagnosis of histoplasmosis

  https://www.scielo.br/j/bjm/a/wKzLsWjbhHkhbk4rvNL8b3q/?lang=en

  Recently, some molecular biology techniques have been developed that may further improve the diagnosis of histoplasmosis, particularly for the detection of disease in an early stage and to improve the specificity of the diagnosis. […] Definitive diagnosis is still based on the isolation and identification of H. capsulatum from clinical and biological specimens. […] Non-culture methods have been developed to improve the rate and speed of diagnosis. […] Antigen detection tests may be more effective than antibody testing for diagnosing of histoplasmosis. […] Antigen detection can be particularly useful in acute disease, especially in individuals also infected with HIV, who frequently have the disseminated form of histoplasmosis without detectable antibodies to the fungus. […] Overall, this test detected antigen in 71.4% of the histoplasmosis serum samples tested.

• #1

  https://link.springer.com/article/10.1007/s12281-019-00341-x

  This review highlights the epidemiology, diagnosis, and clinical manifestations of histoplasmosis. […] 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. […] The use of antigen testing has improved our ability to diagnose histoplasmosis, but these tests are not universally available. […] This paper points out the enormity of the problem of diagnosis of histoplasmosis in Latin America, emphasizing issues related to persons living with HIV infection. […] This paper gives results of testing residual stored samples of CSF from patients diagnosed with Histoplasma meningitis. The authors show that sensitivity for establishing a diagnosis of Histoplasma meningitis is increased greatly when both Histoplasma antigen and antibodies against Histoplasma are sought.

• #1 The Current and Future States of Diagnostic Tests for Histoplasmosis with a Focus on People with HIV and Disseminated Histoplasmosis

  https://www.mdpi.com/2309-608X/9/8/793

  Histoplasma antigen detection has revolutionized the diagnosis of disseminated histoplasmosis, given its excellent performance and the ability to test non-invasive samples such as urine. […] Histoplasma antigen is now seen as the standard of care for AIDS patients suspected of having disseminated histoplasmosis. […] The diagnosis of histoplasmosis remains complicated, influenced by clinical syndromes and host immune status. […] Antigen testing is now accepted as the preferred diagnostic technique for disseminated histoplasmosis and is particularly effective in those with HIV and high fungal burdens. […] The availability of widespread, affordable, and accurate LFAs would drastically improve our understanding of the true burden of disease and would likely improve outcomes as well.

• #1 Histoplasmosis: Adult and Adolescent OIs | NIH

  https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/histoplasmosis

  In 85% of people with HIV and disseminated histoplasmosis, H. capsulatum can be cultured from blood (using the lysis-centrifugation technique), bone marrow, respiratory secretions, or samples from other involved sites; however, the organism requires several weeks to grow before final results can be interpreted. […] The diagnosis of Histoplasma meningitis is often difficult. […] Histoplasma antigen can be detected in CSF in a far greater number of cases, and antibodies against H. capsulatum are seen in at least one-half of cases. […] A positive antigen or antibody test result from CSF is diagnostic for histoplasmosis.

• #1

  https://www.aao.org/eye-health/diseases/what-is-histoplasmosis

  Your ophthalmologist looks for two main things to find histoplasmosis: histo spots and swelling of the retina, which signals the growth of new blood vessels that are not normal. […] Your doctor may have you use an Amsler grid to check for symptoms such as wavy, blurry or dark areas in your vision. […] Your ophthalmologist will dilate (widen) your pupils with eye drops, look at your retina and other areas in the back of the eye, and look for fluid or blood vessels that are not normal. […] If you have these signs, your ophthalmologist will take special photographs of your eye. They use optical coherence tomography (OCT), OCT angiography, or fluorescein angiography to take these photographs. […] OCT uses light waves to make detailed pictures of the area beneath the retina. OCT images show how thick the retina is. They can help your ophthalmologist find swelling and blood vessels that are not normal.

• #1 SciELO Brazil – Diagnosis of histoplasmosis Diagnosis of histoplasmosis

  https://www.scielo.br/j/bjm/a/wKzLsWjbhHkhbk4rvNL8b3q/?lang=en

  The complement fixation (CF) test, a methodology extensively used on the past, is less specific (60 to 90%). […] Detecting fungal antigens by immunoassays is valuable in immunocompromised individuals where such assays achieve positive predictive values of 96-98%. […] Most current tests in diagnostic laboratories still utilize unpurified antigenic complexes from either whole fungal cells or their culture filtrates. […] In this paper, we review the current conventional diagnostic tools, such as complement fixation and immunodiffusion, outline the development of novel diagnostic reagents and methods, and discuss their relative merits and disadvantages to the immunodiagnostic of this mycosis. […] Although the clinical manifestations of histoplasmosis are well described, the diagnosis of histoplasmosis cannot be achieved on the basis of clinical information alone, since there is significant overlap of histoplasmosis with other diseases.

• #1 Histoplasmosis – Infectious Diseases – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/infectious-diseases/fungi/histoplasmosis

  Fungal culture confirms the diagnosis of histoplasmosis. […] A test for H. capsulatum antigen is sensitive and specific, particularly when simultaneous serum and urine specimens are tested; Histoplasma antigen is present in the serum in 80% of patients with disseminated histoplasmosis and is present in the urine in 90% of these patients. […] However, cross-reactivity with other fungi (Coccidioides immitis, Blastomyces dermatitidis, Paracoccidioides brasiliensis, and Penicillium marneffei) has been noted.

• #1 Testing Algorithm for Histoplasmosis | Histoplasmosis | CDC

  https://www.cdc.gov/histoplasmosis/hcp/algorithm/index.html

  Consider enzyme immunoassay (EIA) urine antigen and immunodiffusion (ID) or complement fixation (CF) serum antibody testing. […] Note: in the first two weeks of infection, false-negative tests may occur with antigen testing. […] We recommend ordering enzyme immunoassay (EIA) urine antigen tests. […] If a high degree of suspicion remains despite negative initial testing, a clinician may consider ordering (or repeating) antibody testing since tests may be negative early in illness. […] Consultation with specialists in infectious diseases or pulmonology may be considered when a high degree of suspicion remains as well. […] Histoplasma antigen and antibody tests have extensive cross-reactivity with Blastomyces. […] Clinicians should refer to the Infectious Diseases Society of America’s histoplasmosis treatment guidelines or an infectious disease physician when determining therapy after a positive result.

• #1 Laboratory Diagnosis of Histoplasmosis: An Update | IntechOpen

  https://www.intechopen.com/chapters/72935

  Early diagnosis of histoplasmosis is essential to establish a suitable antifungal therapy, which results in the reduction of mortality rates. […] While culture and histopathological examination are considered the gold standards methods for histoplasmosis diagnosis, these techniques show moderate sensitivity. […] New approaches as MALDI-ToF MS technology allow for a rapid identification, but studies are still scarce. […] Despite limitations concerning sensitivity in certain populations and specificity have been widely reported, H. capsulatum antigen detection has been recently included in the second edition of the list of essential in vitro diagnostics. […] In summary, the aim of this chapter was to summarize the diagnostic pipeline currently available for the diagnosis of histoplasmosis in microbiological laboratories.

• #2 HISTOPLASMOSIS: DIAGNOSTIC CHALLENGES

  https://www.redalyc.org/journal/5609/560962360001/html/

  Histoplasmosis is an infection usually caused by a fungal pathogen that, in most cases, occurs in the respiratory tract, which explains the high frequency of clinical manifestations in the lungs. […] In Europe, cases are on the rise because of the speculation of a global distribution of histoplasmosis, and emphasis has been on improving methods for its diagnosis. […] The symptoms of progressive histoplasmosis are nonspecific, so its differentiation with other infections, especially tuberculosis, is a challenge, even to determine the presence of coinfections that occur frequently in patients with HIV/AIDS. […] The laboratory tests available for the conventional diagnosis of this fungal infection have several limitations: Collecting blood, respiratory tract or tissue samples for cultures is the golden standard, but sensitivity is variable based on the immunity of the patient, so the culture sometimes yields false-negative results.

• #2 Diagnosis and treatment of pulmonary histoplasmosis – UpToDate

  https://www.uptodate.com/contents/diagnosis-and-treatment-of-pulmonary-histoplasmosis

  Diagnosis and treatment of pulmonary histoplasmosis […] The diagnosis and treatment of the various histoplasmosis pulmonary syndromes will be reviewed here. […] Pulmonary histoplasmosis should be considered in patients with the following clinical presentations, particularly in the appropriate epidemiologic setting: Pneumonia with mediastinal or hilar lymphadenopathy […] Community-acquired pneumonia of unknown etiology that has not responded to a course of empiric antibiotics.

• #2 Histoplasmosis in Animals – Infectious Diseases – Merck Veterinary Manual

  https://www.merckvetmanual.com/infectious-diseases/fungal-infections/histoplasmosis-in-animals

  Histoplasmosis should be considered when the clinical signs include the following: weight loss, chronic diarrhea, respiratory distress, enlarged bronchial lymph nodes, pulmonary nodules. […] Diagnosis is usually made from cytology with or without antigen testing; standard treatment is long-term azoles. […] Demonstration of yeasts in blood or tissue. […] Antigen assays, particularly on urine. […] Cytology of bone marrow may be diagnostic in cats. […] Antigen testing using a quantitative antigen ELISA can be performed on urine, serum, and CSF, though urine is the most sensitive substrate.

• #2 Clinical Overview of Histoplasmosis | Histoplasmosis | CDC

  https://www.cdc.gov/histoplasmosis/hcp/clinical-overview/index.html

  Histoplasma antigen detection in urine or serum is the most widely used and most sensitive method. […] Other methods include antibody tests, culture, and microscopy. The most appropriate diagnostic test may depend on clinical manifestation and severity. […] Enzyme immunoassay (EIA) typically performed on urine or serum but can also be used on cerebrospinal fluid or bronchoalveolar lavage fluid. Urine antigen testing may have the highest sensitivity of non-invasive diagnostic tests and the quickest turnaround. […] Development of antibodies to Histoplasma can take 2 to 6 weeks. Antibody tests are not as useful as antigen detection tests for diagnosing acute histoplasmosis. This is especially true in immunosuppressed persons, who may not mount a strong immune response. However, antibody tests can be used in combination with antigen tests to increase sensitivity.

• #2 Diagnosis of Progressive Disseminated Histoplasmosis in Advanced HIV: A Meta-Analysis of Assay Analytical Performance

  https://www.mdpi.com/2309-608X/5/3/76

  Histoplasmosis is an important cause of mortality in people with advanced HIV, especially in countries with limited access to diagnostic assays. Histoplasmosis can be diagnosed using culture, histopathology, and antibody, antigen, and molecular assays. Several factors may affect the analytical performance of these laboratory assays, including sample type, clinical stage of the disease, and previous use of antifungal treatment, among others. […] The gold standard for diagnosis of histoplasmosis is based on conventional laboratory assays using culture and histopathology (including special stains). These assays have several limitations, including the need for high-level laboratory infrastructure for culture handling (biosecurity level 3) the need for highly trained laboratory staff, variable assay analytical performance, and a long turn-around time for results. Other alternatives for histoplasmosis diagnosis include assays for the detection of specific host antibodies against Histoplasma antigens; detection of circulating Histoplasma antigens in urine, serum, and bronchoalveolar lavage (BAL); and detection of fungal DNA.

• #2 Overview of Histoplasmosis | AAFP

  https://www.aafp.org/pubs/afp/issues/2002/1215/p2247.html

  Histoplasmosis can be diagnosed by culture, fungal stains, serologic tests for antibodies, and antigen detection. […] Culture is the gold standard for diagnosing histoplasmosis but is limited by a two- to four-week incubation period and decreased sensitivity to self-limited disease. […] Fungal staining of tissue and blood is rapid but has a significantly lower sensitivity than culture or antigen detection. […] Serologic tests that detect antibodies to H. capsulatum are rapid and relatively sensitive but have some limitations. […] Antigen detection is a rapid means of diagnosis in patients with disseminated disease. Sensitivity is greater with urine (92 percent) than other fluids; however, optimal diagnostic yield is the result of testing both urine and serum.

• #2 The Current and Future States of Diagnostic Tests for Histoplasmosis with a Focus on People with HIV and Disseminated Histoplasmosis

  https://www.mdpi.com/2309-608X/9/8/793

  The development of lateral flow assays has the potential to make for true rapid point-of-care assays for histoplasmosis, but in order to meet that promise, the tests must be widely available and affordable. […] Diagnostic certainty is of particular importance in disseminated histoplasmosis, which is uniformly fatal if not treated. […] Traditional diagnostic techniques are slow (culture) and/or of variable sensitivity (direct visualization). […] Antigen detection tests are fairly rapid and sensitive, but they have not generally been widely available outside of the United States. […] In this review, we will discuss the current state of diagnostic testing for histoplasmosis. […] We will further discuss diagnostic test performance differences between people with and without HIV. […] We will also discuss newer tests that are expected to be commercially available in the near future, are currently being tested, or are expected to begin testing in the coming months to years.

• #2 Histoplasmosis: Adult and Adolescent OIs | NIH

  https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/histoplasmosis

  In 85% of people with HIV and disseminated histoplasmosis, H. capsulatum can be cultured from blood (using the lysis-centrifugation technique), bone marrow, respiratory secretions, or samples from other involved sites; however, the organism requires several weeks to grow before final results can be interpreted. […] The diagnosis of Histoplasma meningitis is often difficult. […] Histoplasma antigen can be detected in CSF in a far greater number of cases, and antibodies against H. capsulatum are seen in at least one-half of cases. […] A positive antigen or antibody test result from CSF is diagnostic for histoplasmosis.

• #2 Laboratory Diagnostics for Histoplasmosis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5442517/

  The sensitivity of cultures for detection of H. capsulatum depends on the clinical manifestation (pulmonary versus disseminated), the net state of immunity of the host, and the burden of disease. […] Patients with disseminated histoplasmosis have a higher rate of positive cultures (74%) than patients with acute pulmonary histoplasmosis (42%). […] Demonstrating the presence of yeast cells consistent with H. capsulatum in tissue supports the diagnosis of histoplasmosis (although not necessarily active infection). […] The presence of H. capsulatum yeast in certain tissues or sterile body fluid (such as skin lesions) and in the appropriate clinical context (such as acute pneumonia) is indicative of active infection. […] Antigen testing has become a leading modality to diagnose histoplasmosis.

• #2 Histoplasmosis: Adult and Adolescent OIs | NIH

  https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/histoplasmosis

  Histoplasmosis is a fungal infection caused by the dimorphic fungus Histoplasma capsulatum (H. capsulatum). […] The detection of Histoplasma antigen in blood or urine (the detection method preferred by the World Health Organization) is a sensitive method for the rapid diagnosis of disseminated histoplasmosis in people with HIV. […] In a study using a certain quantitative enzyme immunoassay (EIA), Histoplasma antigen was detected in 100% of urine samples and 92% of serum samples from people with AIDS and disseminated histoplasmosis. […] A lateral flow assay for the detection of Histoplasma antigen in urine was reported to have a sensitivity of 96% and specificity of 96%. […] In people with severe disseminated histoplasmosis, peripheral blood smears might occasionally show the organisms engulfed by white blood cells if observed with careful attention.

• #2 SciELO Brazil – Diagnosis of histoplasmosis Diagnosis of histoplasmosis

  https://www.scielo.br/j/bjm/a/wKzLsWjbhHkhbk4rvNL8b3q/?lang=en

  Recently, some molecular biology techniques have been developed that may further improve the diagnosis of histoplasmosis, particularly for the detection of disease in an early stage and to improve the specificity of the diagnosis. […] Definitive diagnosis is still based on the isolation and identification of H. capsulatum from clinical and biological specimens. […] Non-culture methods have been developed to improve the rate and speed of diagnosis. […] Antigen detection tests may be more effective than antibody testing for diagnosing of histoplasmosis. […] Antigen detection can be particularly useful in acute disease, especially in individuals also infected with HIV, who frequently have the disseminated form of histoplasmosis without detectable antibodies to the fungus. […] Overall, this test detected antigen in 71.4% of the histoplasmosis serum samples tested.

• #2 15 Minute Histoplasmosis Diagnostic Test – Optimum Imaging Diagnostics (OIDx)

  http://optimumidx.com/services/rapid-testing/

  Histoplasma Rapid Test. The OIDx Histoplasma capsulatum rapid urinary assay delivers accurate results in only 15 minutes. With the rapid Histoplasma capsulatum quicker and easier histoplasmosis diagnosis is possible, reducing the time to treatment. […] This is the only test in the world that allows for easy, fast patient screening in only 15 minutes. With the OIDx Rapid Histoplasmosis Diagnostic Test, a better understanding of the true global threat of histoplasmosis can be developed and faster access to treatment can be had to help improve patient outcomes. […] This test represents a serious revolution in histoplasmosis diagnostics and can be used to aid in screening HIV patients in these newly understood endemic regions to ensure treatment can begin sooner than ever before.

• #2 Histoplasmosis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK448185/

  Histoplasmosis is the most common endemic mycosis in the United States. […] The workup includes serological tests such as complement fixation, immunodiffusion and enzyme immunoassays. […] Antibody tests are useful for diagnosis and management of histoplasmosis but not in all cases. […] The two standard assays are complement fixation and immunodiffusion assay. […] Detection of antigen may be more effective and useful in acute disease as well as in patients who are immunocompromised and do not have good antibody response. […] Urinary antigen detection is more sensitive than serum antigen detection (95% versus 86% in one study).

• #2 SciELO Brazil – Diagnosis of histoplasmosis Diagnosis of histoplasmosis

  https://www.scielo.br/j/bjm/a/wKzLsWjbhHkhbk4rvNL8b3q/?lang=en

  The complement fixation (CF) test, a methodology extensively used on the past, is less specific (60 to 90%). […] Detecting fungal antigens by immunoassays is valuable in immunocompromised individuals where such assays achieve positive predictive values of 96-98%. […] Most current tests in diagnostic laboratories still utilize unpurified antigenic complexes from either whole fungal cells or their culture filtrates. […] In this paper, we review the current conventional diagnostic tools, such as complement fixation and immunodiffusion, outline the development of novel diagnostic reagents and methods, and discuss their relative merits and disadvantages to the immunodiagnostic of this mycosis. […] Although the clinical manifestations of histoplasmosis are well described, the diagnosis of histoplasmosis cannot be achieved on the basis of clinical information alone, since there is significant overlap of histoplasmosis with other diseases.

• #2 Testing Algorithm for Histoplasmosis | Histoplasmosis | CDC

  https://www.cdc.gov/histoplasmosis/hcp/algorithm/index.html

  Consider enzyme immunoassay (EIA) urine antigen and immunodiffusion (ID) or complement fixation (CF) serum antibody testing. […] Note: in the first two weeks of infection, false-negative tests may occur with antigen testing. […] We recommend ordering enzyme immunoassay (EIA) urine antigen tests. […] If a high degree of suspicion remains despite negative initial testing, a clinician may consider ordering (or repeating) antibody testing since tests may be negative early in illness. […] Consultation with specialists in infectious diseases or pulmonology may be considered when a high degree of suspicion remains as well. […] Histoplasma antigen and antibody tests have extensive cross-reactivity with Blastomyces. […] Clinicians should refer to the Infectious Diseases Society of America’s histoplasmosis treatment guidelines or an infectious disease physician when determining therapy after a positive result.

• #2 Histoplasmosis Symptoms and Diagnosis | American Lung Association

  https://www.lung.org/lung-health-diseases/lung-disease-lookup/histoplasmosis/symptoms-diagnosis

  Your healthcare provider will want a detailed medical history, including any potential exposure and travel history. They will then complete a physical exam, analyze your symptoms and order blood or urine tests which are the most common way to test for histoplasmosis. Imaging tests such as a chest X-ray or CT scan may be needed to get a better picture of your lungs. […] When your healthcare provider suspects the infections has spread from your lungs to other parts of the body (disseminated histoplasmosis), a culture or a lung biopsy are the most effective and widely used methods to secure an accurate and timely diagnosis.

• #2 What tests can diagnose histoplasmosis?

  https://www.medicalnewstoday.com/articles/histoplasmosis-tests

  Histoplasmosis is a respiratory infection caused by the Histoplasma capsulatum fungus. After assessing medical and travel history and symptoms, then performing a physical examination, a doctor can order laboratory tests to help confirm a diagnosis. […] To get an accurate diagnosis of histoplasmosis, the doctor may order multiple tests, including a lung biopsy, chest X-ray, CT scan, blood test, and urine test. […] A blood test, urine test, skin test, biopsy, and chest X-ray can help a doctor diagnose histoplasmosis.

• #2 Clinical Overview of Histoplasmosis | Histoplasmosis | CDC

  https://www.cdc.gov/histoplasmosis/hcp/clinical-overview/index.html

  Tests for the presence of H (indicates chronic or severe acute infection) and M (develops within weeks of acute infection). These persist for months to years after the infection has resolved; precipitin bands; ~80% sensitivity. […] Complement-fixing antibodies may take up to 6 weeks to appear after infection. CF is more sensitive but less specific than immunodiffusion. […] Can be performed on tissue, blood, and other body fluids, but may take up to 6 weeks to become positive; most useful in the diagnosis of the severe forms of histoplasmosis. A commercially available DNA probe (AccuProbe, GenProbe Inc.) can be used to confirm. […] For detection of budding yeast in tissue or body fluids. It has low sensitivity but can provide a quick proven diagnosis if positive. […] PCR for detection of Histoplasma directly from clinical specimens is not widely available; however, it can be performed on serum, tissue, or BAL fluid and is promising.

• #2

  https://link.springer.com/article/10.1007/s12281-019-00341-x

  This review highlights the epidemiology, diagnosis, and clinical manifestations of histoplasmosis. […] 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. […] The use of antigen testing has improved our ability to diagnose histoplasmosis, but these tests are not universally available. […] This paper points out the enormity of the problem of diagnosis of histoplasmosis in Latin America, emphasizing issues related to persons living with HIV infection. […] This paper gives results of testing residual stored samples of CSF from patients diagnosed with Histoplasma meningitis. The authors show that sensitivity for establishing a diagnosis of Histoplasma meningitis is increased greatly when both Histoplasma antigen and antibodies against Histoplasma are sought.

• #2 The Current and Future States of Diagnostic Tests for Histoplasmosis with a Focus on People with HIV and Disseminated Histoplasmosis

  https://www.mdpi.com/2309-608X/9/8/793

  Antigen testing performs well for disseminated disease and acute pulmonary disease, particularly in the context of advanced HIV. […] Antigen testing is less sensitive in chronic pulmonary histoplasmosis due to the lower availability of peripheral antigen to be detected. […] A variety of antibody tests are available for histoplasmosis, including immunodiffusion, complement fixation, and enzyme immunoassays. […] Antibody testing offers higher sensitivity for subacute pulmonary histoplasmosis and chronic pulmonary histoplasmosis but is less reliable in testing for acute pulmonary histoplasmosis and early disseminated disease as it may take weeks for sufficient numbers of antibodies to develop. […] PCR has great potential, but implementation has been inconsistent. […] Antigen testing is the most sensitive modality for diagnosing disseminated histoplasmosis.

• #2 Diagnosis of Progressive Disseminated Histoplasmosis in Advanced HIV: A Meta-Analysis of Assay Analytical Performance

  https://www.mdpi.com/2309-608X/5/3/76

  Diagnostic assays are crucial to improving the care of patients with advanced HIV disease who are most at risk of developing progressive disseminated histoplasmosis (PDH). Results from this meta-analysis demonstrated that antigen and molecular diagnostic assays had greater sensitivity and specificity in identifying PDH in PLHIV compared with culture and antibody assays.

• #2 Presumed Ocular Histoplasmosis (POHS): Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/5635-histoplasmosis

  Histoplasmosis is caused by a fungus that can make you sick if you inhale it. […] POHS is an eye condition thats a complication of histoplasmosis. It happens when the disease travels through the bloodstream to the back of the eyes. […] The first step is an evaluation from an eye doctor (ophthalmologist). They examine the back of the eye for: Scar tissue. Swelling. […] You will need a dilated eye exam to assess histoplasmosis symptoms in greater detail. The ophthalmologist uses eye drops to expand (dilate) your pupils, the black center of the eye. Dilation makes it possible to perform a more thorough evaluation and check for: Abnormal blood vessels. Fluid. Inflammation. Small white spots. […] Your care may also include a fluorescein angiography. The procedure starts by injecting a special dye into a vein. The dye travels through the bloodstream to reach the blood vessels in your eye. A special camera takes pictures, making it possible to detect choroidal neovascularization.

• #2 Presumed Ocular Histoplasmosis Syndrome – EyeWiki

  https://eyewiki.org/Presumed_Ocular_Histoplasmosis_Syndrome

  The diagnosis of POHS is based upon fundoscopic exam for the four cardinal features and fluorescein angiography for characterization of CNV. […] Slit lamp examination and dilated fundoscopic exam are necessary for diagnosis. […] Three characteristic findings of POHS are typically found on fundoscopic exam: multiple white atrophic chorioretinal scars or histoplasmosis spots, PPA, and the absence of vitritis. […] Fluorescein angiography (FA) can assist in the diagnosis of POHS. […] The histoplasmin skin antigen test can help to identify if a patient has been exposed to H. capsulatum. However, based upon the study from the Netherlands cohort as previously discussed, exposure to H. capsulatum is not necessary for the clinical findings of POHS. […] If the retinal findings are classic, histoplasmin testing is not performed routinely.

• #2 Histoplasmosis : Health Care Provider Information : Programs : Programs & Services : Two Rivers Public Health Department

  https://www.trphd.ne.gov/programs-services/programs/health-care-provider-information/histoplasmosis.html

  The CDC recommends antigen testing via urine or serum screening although other methods are available. Antigen detection can be done on urine or serum samples and provides rapid detection of the microbe which is particularly helpful in those patients with severe illness. […] Antibody testing is available but the testing takes several weeks and may delay treatment. PCR testing has not been proven as a preferred method of diagnostic evaluation; however, recent studies do indicate that this method is showing clinical value. […] Cultures take weeks for results and are most useful for patients suspected of having chronic pulmonary histoplasmosis.

• #2 HISTOPLASMA ANTIBODY IMMUNODIFFUSION TEST

  https://miravistalabs.com/medical-fungal-infection-testing/antibody-detection/histoplasma-antibody-immunodiffusion/

  The histoplasma antibody immunodiffusion test is used for the in vitro determination of precipitating antibodies to Histoplasma sp. It is also used as an aid in the diagnosis of Histoplasmosis. […] This test detects the presence of two significant precipitin bands. Presence of both the H and the M band indicates active histoplasmosis. The presence of the M band alone indicates early or chronic disease. The M band may also be present following a recent histoplasmin skin test. […] The result is not intended to be used as the sole means for clinical diagnosis or patient management decisions. […] Negative serologic tests may be observed among culturally demonstrable cases, which limits the predictive value of a negative test. […] Negative serologic results obtained during the first month may warrant repeat testing. […] Falsely negative results may be obtained when testing immunocompromised patients. […] Test results cannot be used solely, to distinguish between active infection and prior exposure.

• #2 Histoplasmosis – Symptoms, diagnosis and treatment | BMJ Best Practice

  https://bestpractice.bmj.com/topics/en-gb/918

  Other diagnostic factors include abdominal pain, fatigue, malaise, arthralgias, weight loss, hepatosplenomegaly, scattered crackles on chest auscultation, bronchial breathing on chest auscultation, distant breath sounds on chest auscultation, haemoptysis, meningitis-like symptoms, skin lesions, gastrointestinal symptoms, and sepsis-like syndrome. […] 1st investigations to order include chest x-ray, culture, antigen testing, serology (immunodiffusion precipitin test), serology (complement fixation assay), serology (enzyme immunoassay), CT scan of chest, FBC, and LFTs. […] Investigations to consider include tissue biopsy.

• #2 Laboratory Diagnosis of Histoplasmosis: An Update | IntechOpen

  https://www.intechopen.com/chapters/72935

  Early diagnosis of histoplasmosis is essential to establish a suitable antifungal therapy, which results in the reduction of mortality rates. […] While culture and histopathological examination are considered the gold standards methods for histoplasmosis diagnosis, these techniques show moderate sensitivity. […] New approaches as MALDI-ToF MS technology allow for a rapid identification, but studies are still scarce. […] Despite limitations concerning sensitivity in certain populations and specificity have been widely reported, H. capsulatum antigen detection has been recently included in the second edition of the list of essential in vitro diagnostics. […] In summary, the aim of this chapter was to summarize the diagnostic pipeline currently available for the diagnosis of histoplasmosis in microbiological laboratories.

• #2 HISTOPLASMOSIS: DIAGNOSTIC CHALLENGES

  https://www.redalyc.org/journal/5609/560962360001/html/

  Immunological tests can detect antigens or antibodies in serum and other biological fluids, but the detection of antibodies can give false-negative results due to its low sensitivity in immunosuppressed patients (particularly patients with AIDS, in whom the production of antibodies decreases); however, antigen detection in these individuals is more sensitive. […] All these limitations cause a delay in the diagnosis and subsequent mismanagement of patients. […] It is important that, in the presence of clinical suspicion, physicians have knowledge of the set of tests that can be used, as well as of their limitations, in order to confirm the diagnosis, provide the most appropriate therapeutic management for each patient, and influence the reduction of the mortality rate.

• #2 Improving disseminated histoplasmosis diagnosis in HIV/AIDS patients in Suriname: The role of a urine lateral flow assay | PLOS Neglected Tropical Diseases

  https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0012272

  An alternative to the above-described diagnostic methods is a Histoplasma antigen test. […] Recent studies evaluating the use of a MiraVista Histoplasma capsulatum antigen lateral flow assay (LFA) for the diagnosis of disseminated histoplasmosis in PLWHA have shown a sensitivity between 79-96% and a specificity between 90-99%. […] Our data show that clinical criteria alone are insufficient in determining whether a patient with late-stage HIV infection is likely to have DH in our setting and if treatment should be started. […] This study highlights the utility of the Histoplasma urine antigen LFA in diagnosing disseminated histoplasmosis in HIV patients in Suriname. […] It shows that neither the Histoplasma LFA nor the clinical picture alone are sensitive enough to determine which patients should be treated for disseminated histoplasmosis. Combining clinical signs with LFA results enhances diagnostic accuracy and is cost effective, leading to better treatment decisions. […] The Histoplasma urine antigen LFA is a valuable addition to histoplasmosis diagnostics, aiding in accurate and timely diagnosis.

• #3 The Current and Future States of Diagnostic Tests for Histoplasmosis with a Focus on People with HIV and Disseminated Histoplasmosis

  https://www.mdpi.com/2309-608X/9/8/793

  Histoplasmosis is caused by Histoplasma capsulatum and, although endemic in large parts of the world, is often underrecognized in many locations. […] In addition to underrecognition, inadequate availability of diagnostic tests is a major contributor to poor outcomes in disseminated disease in people with HIV. […] For those with advanced HIV and disseminated disease, antibody testing is less useful. […] Culture and histopathology can be useful in this situation, but each has limitations, including variable sensitivity by site and, in the case of culture, the need for a biosafety level three laboratory and a long period of growth. […] Antigen testing has proven useful for disseminated histoplasmosis due to the excellent sensitivity of urine. […] Yet, turnaround is slower than ideal due to use in a limited number of centers.

• #3 Diagnosis and treatment of disseminated histoplasmosis in patients without HIV – UpToDate

  https://www.uptodate.com/contents/diagnosis-and-treatment-of-disseminated-histoplasmosis-in-patients-without-hiv

  Diagnosis of disseminated histoplasmosis requires a high index of suspicion, recognition of the common modes of presentation, and familiarity with the appropriate diagnostic tests. […] The diagnosis of disseminated histoplasmosis should be suspected in patients with risk factors for disease (eg, immunosuppression or extremes of age and risk factors for exposure) in combination with clinical manifestations that are consistent with disseminated histoplasmosis. […] The most common symptoms of disseminated histoplasmosis are fever, fatigue, and weight loss. Other clinical symptoms depend on the organ system involved.

• #3 Histoplasmosis – Symptoms, diagnosis and treatment | BMJ Best Practice

  https://bestpractice.bmj.com/topics/en-gb/918

  Histoplasmosis infection is usually asymptomatic or minimally symptomatic; however, infection with a large number of organisms or in people with immunodeficiency can result in severe, symptomatic pulmonary infection, which requires treatment. […] Risk factors for more severe respiratory disease include inhalation of a large inoculum, impaired cellular immunity (e.g., AIDS/HIV infection, chronic immunosuppressive therapy), age 2 years, and chronic lung disease. […] Histoplasmosis is an infectious disease caused by the fungus Histoplasma capsulatum. It is not communicable from person to person but is acquired from inhalational exposure to infectious spores found in soil contaminated with bird or bat droppings. […] Key diagnostic factors include presence of risk factors, fever, headache, dyspnoea, dry or non-productive cough, pleuritic chest pain, anorexia, and productive cough.

• #3 Histoplasma capsulatum and Histoplasmosis: Current Concept for the Diagnosis | IntechOpen

  https://www.intechopen.com/chapters/72531

  Since 1978, the introduction of the Histoplasma antigen assay significantly improved the diagnosis by allowing a rapid, noninvasive, and sensitive method. […] This review describes the current diagnostics for the laboratory identification of H. capsulatum, with focus on their performance and context-based value. […] The gold standard for histoplasma diagnosis remains culture. Its a time-consuming process and has limitations in sensitivity. […] Nonculture methods have been developed to improve and accelerate diagnosis of histoplasmosis, such as histoplasma antigen detection, antibody detection, and molecular biology.

• #3 Laboratory Diagnosis of Histoplasmosis: An Update | IntechOpen

  https://www.intechopen.com/chapters/72935

  Early diagnosis of histoplasmosis is essential to establish a suitable antifungal therapy and reduce morbidity and mortality rates. […] However, laboratory diagnosis remains challenging due to the low availability of proper methods and the lack of clinical suspicion. […] Conventional diagnosis is still largely used even though limitations are well known. […] New approaches based on the detection of antibodies and antigens have been developed and commercialized last years. […] Although sensitivity and specificity of these methods is variable, antigen detection has been recently listed as an essential diagnostic test for AIDS patients due to its excellent performance. […] The detection of H. capsulatum antigens in clinical samples represented a breakthrough in the early diagnosis of histoplasmosis and has been included in the EORTC/MSG criteria for diagnosis of IFIs for almost 20 years.

• #3 Diagnosing Histplasmosis by Antigen Detection Serum and Urine

  https://miravistalabs.com/diagnosing-histoplasmosis-by-antigen-detection/

  FEATURE: Diagnosing Histoplasmosis by Antigen Detection […] Most physicians are familiar with the useful role of antigen detection for diagnosis of disseminated histoplasmosis but are not aware that both the urine and serum must be tested for optimal sensitivity. […] In acute pulmonary histoplasmosis, the sensitivity for antigen detection was 83%, but 38% were positive only in the serum and would have been missed by testing only the urine. […] While many physicians are aware of testing urinary antigen to diagnose histoplasmosis, the practice of testing serum antigen for diagnosis is not as well-known. […] Testing both urine AND serum consistently provides the highest sensitivity for Histoplasma antigen. […] 38% of acute pulmonary histoplasmosis cases may not be properly diagnosed if only urine is tested. […] 5-10% of progressive disseminated histoplasmosis cases may not be properly diagnosed if only urine is tested.

• #3 Improving disseminated histoplasmosis diagnosis in HIV/AIDS patients in Suriname: The role of a urine lateral flow assay | PLOS Neglected Tropical Diseases

  https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0012272

  An alternative to the above-described diagnostic methods is a Histoplasma antigen test. […] Recent studies evaluating the use of a MiraVista Histoplasma capsulatum antigen lateral flow assay (LFA) for the diagnosis of disseminated histoplasmosis in PLWHA have shown a sensitivity between 79-96% and a specificity between 90-99%. […] Our data show that clinical criteria alone are insufficient in determining whether a patient with late-stage HIV infection is likely to have DH in our setting and if treatment should be started. […] This study highlights the utility of the Histoplasma urine antigen LFA in diagnosing disseminated histoplasmosis in HIV patients in Suriname. […] It shows that neither the Histoplasma LFA nor the clinical picture alone are sensitive enough to determine which patients should be treated for disseminated histoplasmosis. Combining clinical signs with LFA results enhances diagnostic accuracy and is cost effective, leading to better treatment decisions. […] The Histoplasma urine antigen LFA is a valuable addition to histoplasmosis diagnostics, aiding in accurate and timely diagnosis.

• #3 Diagnosis of Progressive Disseminated Histoplasmosis in Advanced HIV: A Meta-Analysis of Assay Analytical Performance

  https://www.mdpi.com/2309-608X/5/3/76

  The analytical performance of the assays for the diagnosis of histoplasmosis varies according to disease stage and clinical form. For that reason, the aim of our study was to perform a systematic review of the literature and a meta-analysis to evaluate the analytical performance of laboratory assays for the diagnosis of PDH in PLHIV. […] The results of the meta-analysis showed that laboratory assays based on the detection of circulating Histoplasma antigen demonstrated the best analytical performance. […] Results from this meta-analysis demonstrated that antibody detection assays have high specificity, but the sensitivity of this type of diagnostic assay in PLHIV with advanced diseases was poor. These findings can be explained by the highly immunosuppressed state of this patient population. However, the detection of specific anti-Histoplasma antibodies in patient’s sera or cerebrospinal fluid could be a complementary diagnostic tool, particularly in PLHIV with subacute and chronic forms of PDH where patients have a progressive long-term infection characterized by a lower fungal burden.

• #3 Laboratory Diagnosis of Histoplasmosis: An Update | IntechOpen

  https://www.intechopen.com/chapters/72935

  The H. capsulatum polysaccharide antigen can be detected in both serum and urine samples with similar diagnostic value and has been recently listed as an essential diagnostic test for advanced AIDS patients. […] Antibody detection tests are still considered as valuable diagnostic tools and have been demonstrated to improve diagnostic yield when combined with other diagnostic methods. […] PCR methods based on the detection of fungal DNA directly from clinical samples are currently implemented in the routine of several laboratories for the diagnosis of main fungal infections, but there are considerably fewer PCR tests for the diagnosis of histoplasmosis. […] The majority of PCR tests for the diagnosis of histoplasmosis have been developed in house and none of them has been commercialized.

• #3 Histoplasmosis: Adult and Adolescent OIs | NIH

  https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/histoplasmosis

  Histoplasmosis is a fungal infection caused by the dimorphic fungus Histoplasma capsulatum (H. capsulatum). […] The detection of Histoplasma antigen in blood or urine (the detection method preferred by the World Health Organization) is a sensitive method for the rapid diagnosis of disseminated histoplasmosis in people with HIV. […] In a study using a certain quantitative enzyme immunoassay (EIA), Histoplasma antigen was detected in 100% of urine samples and 92% of serum samples from people with AIDS and disseminated histoplasmosis. […] A lateral flow assay for the detection of Histoplasma antigen in urine was reported to have a sensitivity of 96% and specificity of 96%. […] In people with severe disseminated histoplasmosis, peripheral blood smears might occasionally show the organisms engulfed by white blood cells if observed with careful attention.

• #3 Testing Algorithm for Histoplasmosis | Histoplasmosis | CDC

  https://www.cdc.gov/histoplasmosis/hcp/algorithm/index.html

  Consider enzyme immunoassay (EIA) urine antigen and immunodiffusion (ID) or complement fixation (CF) serum antibody testing. […] Note: in the first two weeks of infection, false-negative tests may occur with antigen testing. […] We recommend ordering enzyme immunoassay (EIA) urine antigen tests. […] If a high degree of suspicion remains despite negative initial testing, a clinician may consider ordering (or repeating) antibody testing since tests may be negative early in illness. […] Consultation with specialists in infectious diseases or pulmonology may be considered when a high degree of suspicion remains as well. […] Histoplasma antigen and antibody tests have extensive cross-reactivity with Blastomyces. […] Clinicians should refer to the Infectious Diseases Society of America’s histoplasmosis treatment guidelines or an infectious disease physician when determining therapy after a positive result.

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