Treating progressive disseminated histoplasmosis in people living with HIV

ABSTRACTHistoplasmosis is an important cause of mortality in patients with AIDS, especially in countries with limited access to antiretroviral therapies and diagnostic tests. However, many disseminated infections in Latin America go undiagnosed. A simple, rapid method to detectHistoplasma capsulatuminfection in regions where histoplasmosis is endemic would dramatically decrease the time to diagnosis and treatment, reducing morbidity and mortality. The aim of this study was to validate a commercial monoclonalHistoplasmagalactomannan (HGM) enzyme-linked immunosorbent assay (Immuno-Mycologics [IMMY], Norman, OK, USA) in two cohorts of people living with HIV/AIDS (PLHIV). We analyzed urine samples from 589 people (466 from Guatemala and 123 from Colombia), including 546 from PLHIV and 43 from non-PLHIV controls. Sixty-three of these people (35 from Guatemala and 28 from Colombia) had confirmed histoplasmosis by isolation ofH. capsulatum. Using the standard curve provided by the quantitative commercial test, the sensitivity was 98% (95% confidence interval [CI], 95 to 100%) and the specificity was 97% (95% CI, 96 to 99%) (cutoff = 0.5 ng/ml). Semiquantitative results, using a calibrator of 12.5 ng/ml ofHistoplasmagalactomannan to calculate an enzyme immunoassay index value (EIV) for the samples, showed a sensitivity of 95% (95% CI, 89 to 100%) and a specificity of 98% (95% CI, 96 to 99%) (cutoff ≥ 2.6 EIV). This relatively simple-to-perform commercial antigenuria test showed a high performance with reproducible results in both countries, suggesting that it can be used to detect progressive disseminated histoplasmosis in PLHIV in a wide range of clinical laboratories in countries where histoplasmosis is endemic.

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Diagnostic accuracy of antigen detection in urine and molecular assays testing in different clinical samples for the diagnosis of progressive disseminated histoplasmosis in patients living with HIV/AIDS: A prospective multicenter study in Mexico

PLoS Neglected Tropical Diseases ◽

10.1371/journal.pntd.0009215 ◽

2021 ◽

Vol 15 (3) ◽

pp. e0009215

Author(s):

Areli Martínez-Gamboa ◽

María Dolores Niembro-Ortega ◽

Pedro Torres-González ◽

Janeth Santiago-Cruz ◽

Nancy Guadalupe Velázquez-Zavala ◽

...

Keyword(s):

Bone Marrow ◽

Diagnostic Accuracy ◽

Nested Pcr ◽

Urine Samples ◽

People Living With Hiv ◽

Bone Marrow Tissue ◽

Disseminated Histoplasmosis ◽

Progressive Disseminated Histoplasmosis ◽

Sensitivity Specificity ◽

Living With Hiv

Background The progressive disseminated histoplasmosis (PDH) has been associated with severe disease and high risk of death among people living with HIV (PLWHIV). Therefore, the purpose of this multicenter, prospective, double-blinded study done in ten Mexican hospitals was to determine the diagnostic accuracy of detecting Histoplasma capsulatum antigen in urine using the IMMY ALPHA Histoplasma EIA kit (IAHE), clarus Histoplasma GM Enzyme Immunoassay (cHGEI IMMY) and MiraVista Histoplasma Urine Antigen LFA (MVHUALFA); as well as the Hcp100 and 1281-1283220SCAR nested PCRs in blood, bone-marrow, tissue biopsies and urine. Methodology/Principal findings We included 415 PLWHIV older than 18 years of age with suspicion of PDH. Using as diagnostic standard recovery of H. capsulatum in blood, bone marrow or tissue cultures, or histopathological exam compatible, detected 108 patients (26%, [95%CI, 21.78–30.22]) with proven-PDH. We analyzed 391 urine samples by the IAHE, cHGEI IMMY and MVHUALFA; the sensitivity/specificity values obtained were 67.3% (95% CI, 57.4–76.2) / 96.2% (95% CI, 93.2–98.0) for IAHE, 91.3% (95% CI, 84.2–96.0) / 90.9% (95% CI, 87.0–94.0) for cHGEI IMMY and 90.4% (95% CI, 83.0–95.3) / 92.3% (95% CI, 88.6–95.1) for MVHUALFA. The Hcp100 nested PCR was performed on 393, 343, 75 and 297, blood, bone marrow, tissue and urine samples respectively; the sensitivity/specificity values obtained were 62.9% (95%CI, 53.3–72.5)/ 89.5% (95%CI, 86.0–93.0), 65.9% (95%CI, 56.0–75.8)/ 89.0% (95%CI, 85.2–92.9), 62.1% (95%CI, 44.4–79.7)/ 82.6% (95%CI, 71.7–93.6) and 34.9% (95%CI, 24.8–46.2)/ 67.3% (95%CI, 60.6–73.5) respectively; and 1281-1283220SCAR nested PCR was performed on 392, 344, 75 and 291, respectively; the sensitivity/specificity values obtained were 65.3% (95% CI, 55.9–74.7)/ 58.8% (95%CI, 53.2–64.5), 70.8% (95%CI, 61.3–80.2)/ 52.9% (95%CI, 46.8–59.1), 71.4% (95%CI, 54.7–88.2)/ 40.4% (95%CI, 26.4–54.5) and 18.1% (95%CI, 10.5–28.1)/ 90.4% (95%CI, 85.5–94.0), respectively. Conclusions/Significance The cHGEI IMMY and MVHUALFA tests showed excellent performance for the diagnosis of PDH in PLWHIV. The integration of these tests in clinical laboratories will certainly impact on early diagnosis and treatment.

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Histoplasmosis Diagnosed in Europe and Israel: A Case Report and Systematic Review of the Literature from 2005 to 2020

Journal of Fungi ◽

10.3390/jof7060481 ◽

2021 ◽

Vol 7 (6) ◽

pp. 481

Author(s):

Spinello Antinori ◽

Andrea Giacomelli ◽

Mario Corbellino ◽

Alessandro Torre ◽

Marco Schiuma ◽

...

Keyword(s):

Systematic Review ◽

Hiv Infection ◽

Histoplasma Capsulatum ◽

People Living With Hiv ◽

Immunocompromised Patients ◽

Dimorphic Fungus ◽

Endemic Region ◽

Disseminated Histoplasmosis ◽

Progressive Disseminated Histoplasmosis ◽

Living With Hiv

Human histoplasmosis is a mycosis caused by two distinct varieties of a dimorphic fungus: Histoplasma capsulatum var. capsulatum and H. capsulatum var. duboisii. In Europe, it is usually imported by migrants and travellers, although there have been some autochthonous cases, especially in Italy; however, most European physicians are unfamiliar with its clinical and pathological picture, particularly among immunocompromised patients without HIV infection. This systematic review of all the cases of histoplasmosis reported in Europe and Israel between 2005 and 2020 identified 728 cases diagnosed in 17 European countries and Israel described in 133 articles. The vast majority were imported (mainly from Central and South America), but there were also seven autochthonous cases (six in Europe and one in Israel). The patients were prevalently males (60.4%), and their ages ranged from 2 to 86 years. The time between leaving an endemic region and the diagnosis of histoplasmosis varied from a few weeks to more than 40 years. Progressive disseminated histoplasmosis was the most frequent clinical picture among people living with HIV infection (89.5%) or a different immunocompromising condition (57.1%), but it was also recorded in 6.2% of immunocompetent patients. Twenty-eight cases were caused by Histoplasma duboisii. Immunocompromised patients without HIV infection had the worst outcomes, with a mortality rate of 32%.

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Guidelines for Diagnosing and Managing Disseminated Histoplasmosis among People Living with HIV

10.37774/9789275122488 ◽

2020 ◽

Keyword(s):

Health Care Providers ◽

Guideline Development ◽

Critical Evaluation ◽

World Health ◽

People Living With Hiv ◽

Care Providers ◽

Advisory Boards ◽

Disseminated Histoplasmosis ◽

Persons Living With Hiv ◽

Living With Hiv

Histoplasmosis is a disease caused by the fungus Histoplasma capsulatum. This disease is highly endemic in some regions of North America, Central America, and South America and is also reported in certain countries of Asia and Africa. It often affects people with impaired immunity, including people living with HIV, among whom the most frequent clinical presentation is disseminated histoplasmosis. The symptoms of disseminated histoplasmosis are non-specific and may be indistinguishable from those of other infectious diseases, especially disseminated tuberculosis (TB), thus complicating diagnosis and treatment. Histoplasmosis is one of the most frequent opportunistic infections caused by fungal pathogens among people living with HIV in the Americas and may be responsible for 5–15% of AIDS-related deaths every year in this Region. These guidelines aim to provide recommendations for the diagnosis, treatment, and management of disseminated histoplasmosis in persons living with HIV. Although the burden of disease is concentrated in the Americas, the recommendations presented within these guidelines are applicable globally. These guidelines were produced in accordance with the World Health Organization (WHO) handbook for guideline development. The Guideline Development Group elaborated the final recommendations based on a systematic review of scientific literature and critical evaluation of the evidence available using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. These guidelines are intended for health-care providers, HIV program managers, policy-makers, national treatment advisory boards, researchers, and other professionals involved in caring for people who either have or may be at risk of developing disseminated histoplasmosis.

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COVID-19 associated with AIDS-related disseminated histoplasmosis: a case report

International Journal of STD & AIDS ◽

10.1177/0956462420957518 ◽

2020 ◽

Vol 31 (12) ◽

pp. 1222-1224

Author(s):

Mauro Bertolini ◽

María Felicitas Mutti ◽

José AE Barletta ◽

Adriana Falak ◽

Daniel Cuatz ◽

...

Keyword(s):

Case Report ◽

Male Patient ◽

Respiratory Diseases ◽

Opportunistic Infections ◽

People Living With Hiv ◽

Limited Information ◽

Disseminated Histoplasmosis ◽

Living With Hiv

Limited information is available concerning the coexistence of COVID-19 and opportunistic infections in people living with HIV. The possible association of COVID-19 with AIDS-related respiratory diseases should be considered, particularly in patients with advance immunosuppression. We report the case of a male patient with AIDS-related disseminated histoplasmosis associated with COVID-19.

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Histoplasmosis in Persons Living with HIV

Journal of Fungi ◽

10.3390/jof6010003 ◽

2019 ◽

Vol 6 (1) ◽

pp. 3

Author(s):

Mathieu Nacher

Keyword(s):

Disseminated Histoplasmosis ◽

Number Of Patients ◽

Persons Living With Hiv ◽

Progressive Disseminated Histoplasmosis ◽

Living With Hiv

The increase in the number of immunocompromised persons, following the HIV pandemic, has led to a dramatic amplification of the number of patients with progressive disseminated histoplasmosis [...]

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