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Histoplasma and Histoplasmosis
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Histoplasma and Histoplasmosis

A special issue of Journal of Fungi (ISSN 2309-608X).

Deadline for manuscript submissions: closed (30 April 2019) | Viewed by 34475

Special Issue Editor

Prof. Dr. Mathieu Nacher

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Guest Editor
Medicine Department, Ecosystemes Amazoniens et Pathologie Tropicale, EA 3593, Labex CEBA, University of French Guiana, Cayenne, France
Interests: HIV infectious diseases; malaria; AIDS; Plasmodium; Falciparum malaria; Vivax malaria
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Histoplasmosis should be on the list of neglected diseases, but, regrettably, it is not. Throughout Latin America and beyond, it is indeed a neglected disease that still causes a great burden of mortality among those with advanced HIV infection because it is often misdiagnosed as tuberculosis. The main reason for this is the lack of awareness of the need of rapid diagnostic tools. In Latin America, there is a limited number of centers that have reached, for different historical reasons, histoplasmosis awareness. In 2015, researchers from 13 countries set an ambitious goal of having all major hospitals equipped with simple rapid diagnostic tests and antifungals to better diagnose and treat disseminated histoplasmosis by 2020. Have we gotten any closer to this goal? What new developments will help us reach this goal? Are there any obstacles that should be addressed?

In this Special Issue of the Journal of Fungi, a variety of authors will chart our progress towards the goal of alleviating the burden of disseminated histoplasmosis.

Sincerely,

Dr. Mathieu Nacher
Guest Editor

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Keywords

  • Histoplasma and Histoplasmosis
  • Fungal burden
  • Fungal infections in HIV

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Related Special Issues

Published Papers (7 papers)

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Editorial

Jump to: Research, Review, Other

2 pages, 172 KiB  
Editorial
Histoplasmosis in Persons Living with HIV
by Mathieu Nacher
J. Fungi 2020, 6(1), 3; https://doi.org/10.3390/jof6010003 - 18 Dec 2019
Cited by 3 | Viewed by 2211
Abstract
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 [...] Full article
(This article belongs to the Special Issue Histoplasma and Histoplasmosis)

Research

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7 pages, 240 KiB  
Communication
Getting Histoplasmosis on the Map of International Recommendations for Patients with Advanced HIV Disease
by Felix Bongomin, Richard Kwizera and David W. Denning
J. Fungi 2019, 5(3), 80; https://doi.org/10.3390/jof5030080 - 2 Sep 2019
Cited by 29 | Viewed by 4638
Abstract
Progressive disseminated histoplasmosis, caused by H. capsulatum, is a life-threatening illness and is an AIDS-defining opportunistic infection. It is neglected, worryingly under-diagnosed, and often misdiagnosed as cancer or tuberculosis with fatal consequences. Globally, over 100,000 cases of disseminated histoplasmosis have been estimated. [...] Read more.
Progressive disseminated histoplasmosis, caused by H. capsulatum, is a life-threatening illness and is an AIDS-defining opportunistic infection. It is neglected, worryingly under-diagnosed, and often misdiagnosed as cancer or tuberculosis with fatal consequences. Globally, over 100,000 cases of disseminated histoplasmosis have been estimated. In 2017, the World Health Organization (WHO) noted that disseminated histoplasmosis is a significant cause of mortality in AIDS patients. Through the rigorous efforts of the Global Action Fund for Fungal Infections (GAFFI) and partners, in 2019, the Histoplasma antigen test was included on the 2nd Edition of the WHO List of Essential Diagnostics. The drugs used in the treatment of histoplasmosis (amphotericin B and itraconazole) are on the WHO Essential Medicine List. The Manaus Declaration on histoplasmosis in the Americas and the Caribbean, where histoplasmosis kills more people with HIV than tuberculosis, advocates for universal access to rapid testing for histoplasmosis and availability of essential drugs for the treatment of histoplasmosis in every country by 2025. Hyperendemic areas are present in the Americas, Caribbean, Southeast Asia, and Latin America. In conclusion, histoplasmosis remains an important clinical and public health problem. To reduce HIV-associated mortality, disseminated histoplasmosis must be addressed through advocacy, increased awareness, and universal access to essential diagnostics and antifungal agents. Full article
(This article belongs to the Special Issue Histoplasma and Histoplasmosis)
8 pages, 248 KiB  
Article
Accuracy of Buffy Coat in the Diagnosis of Disseminated Histoplasmosis in AIDS-Patients in an Endemic Area of Brazil
by Terezinha M. J. Silva Leitão, Antonio M. P. Oliveira Filho, José Evaldo P. Sousa Filho, Bruno M. Tavares, Jacó R. L. Mesquita, Luís Arthur B. G. Farias, Rosa S. Mota, Mathieu Nacher and Lisandra S. Damasceno
J. Fungi 2019, 5(2), 47; https://doi.org/10.3390/jof5020047 - 9 Jun 2019
Cited by 8 | Viewed by 3533
Abstract
The buffy coat is obtained routinely for disseminated histoplamosis (DH) diagnosis in Ceará, Brazil. The aim of this study is to describe the accuracy of staining smears for Histoplasma in the buffy coat of AIDS-patients with DH. From 2012–2013, all results of stained [...] Read more.
The buffy coat is obtained routinely for disseminated histoplamosis (DH) diagnosis in Ceará, Brazil. The aim of this study is to describe the accuracy of staining smears for Histoplasma in the buffy coat of AIDS-patients with DH. From 2012–2013, all results of stained buffy coat smears and culture for fungi performed at São José Hospital were recorded. In total, 489 buffy coats of 361 patients were studied; 19/361 (5.3%; 95%CI = 2.9–7.6%) had positive direct examination stained smears for Histoplasma and 61/361 (16.9%; 95%CI = 13.0–20.8%) had growth in culture. For those with positive Histoplasma cultures, the CD4 count was significantly lower (139.3 vs. 191.7cells/µL; p = 0.014) than others, and death was 18%. The sensitivity and specificity of stained smears was 25.9% and 100%, respectively. A second test, performed up to 36 days from the first one, increased the sensitivity of stained smears to 32.2%. Stained smears of buffy coat have low accuracy; nonetheless, they are easy to perform and can give a quick diagnosis in low-resource endemic areas. Despite the decrease in mortality, it is not yet to the low levels observed in areas that have better and more efficient methods. Full article
(This article belongs to the Special Issue Histoplasma and Histoplasmosis)

Review

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12 pages, 725 KiB  
Review
The Broad Clinical Spectrum of Disseminated Histoplasmosis in HIV-Infected Patients: A 30 Years’ Experience in French Guiana
by Pierre Couppié, Katarina Herceg, Morgane Bourne-Watrin, Vincent Thomas, Denis Blanchet, Kinan Drak Alsibai, Dominique Louvel, Felix Djossou, Magalie Demar, Romain Blaizot and Antoine Adenis
J. Fungi 2019, 5(4), 115; https://doi.org/10.3390/jof5040115 - 13 Dec 2019
Cited by 18 | Viewed by 7068
Abstract
Histoplasmosis is a common but neglected AIDS-defining condition in endemic areas for Histoplasma capsulatum. At the advanced stage of HIV infection, the broad spectrum of clinical features may mimic other frequent opportunistic infections such as tuberculosis and makes it difficult for clinicians [...] Read more.
Histoplasmosis is a common but neglected AIDS-defining condition in endemic areas for Histoplasma capsulatum. At the advanced stage of HIV infection, the broad spectrum of clinical features may mimic other frequent opportunistic infections such as tuberculosis and makes it difficult for clinicians to diagnose histoplasmosis in a timely manner. Diagnosis of histoplasmosis is difficult and relies on a high index of clinical suspicion along with access to medical mycology facilities with the capacity to implement conventional diagnostic methods (direct examination and culture) in a biosafety level 3 laboratory as well as indirect diagnostic methods (molecular biology, antibody, and antigen detection tools in tissue and body fluids). Time to initiation of effective antifungals has an impact on the patient’s prognosis. The initiation of empirical antifungal treatment should be considered in endemic areas for Histoplasma capsulatum and HIV. Here, we report on 30 years of experience in managing HIV-associated histoplasmosis based on a synthesis of clinical findings in French Guiana with considerations regarding the difficulties in determining its differential diagnosis with other opportunistic infections. Full article
(This article belongs to the Special Issue Histoplasma and Histoplasmosis)
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10 pages, 630 KiB  
Review
Histoplasmosis and Tuberculosis Co-Occurrence in People with Advanced HIV
by Diego H. Caceres and Audrey Valdes
J. Fungi 2019, 5(3), 73; https://doi.org/10.3390/jof5030073 - 9 Aug 2019
Cited by 36 | Viewed by 6079
Abstract
Distinguishing between histoplasmosis, tuberculosis (TB), and co-occurrence of disease is a frequent dilemma for clinical staff treating people with advanced Human Immunodeficiency Virus (HIV) infection. This problem is most frequently observed in clinical settings in countries where both diseases are endemic. It is [...] Read more.
Distinguishing between histoplasmosis, tuberculosis (TB), and co-occurrence of disease is a frequent dilemma for clinical staff treating people with advanced Human Immunodeficiency Virus (HIV) infection. This problem is most frequently observed in clinical settings in countries where both diseases are endemic. It is also a challenge outside these endemic countries in HIV clinics that take care of patients coming from countries with endemic histoplasmosis and TB. The gold standard for diagnosis of both of these diseases is based on conventional laboratory tests (culture, histopathology and special stains). These tests have several limitations, such as lack of laboratory infrastructure for handling isolates (biosafety level 3), shortage of laboratory staff who have appropriate training and experience, variable analytical performance of tests and long turn-around time. Recently, novel rapid assays for the diagnosis of histoplasmosis and TB became available. However, this technology is not yet widely used. Mortality in immunocompromised patients, such as people with advanced HIV, is directly linked with the ability to rapidly diagnose opportunistic diseases. The aim of this review is to synthesize the main aspects of epidemiology, clinical characteristics, diagnosis and treatment of histoplasmosis/TB co-occurrence in people with advanced HIV. Full article
(This article belongs to the Special Issue Histoplasma and Histoplasmosis)
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11 pages, 877 KiB  
Review
Histoplasma Responses to Nutritional Immunity Imposed by Macrophage Activation
by Peter J. Brechting and Chad A. Rappleye
J. Fungi 2019, 5(2), 45; https://doi.org/10.3390/jof5020045 - 5 Jun 2019
Cited by 14 | Viewed by 5721
Abstract
The fungal pathogen Histoplasma capsulatum resides within the phagosome of host phagocytic cells. Within this intracellular compartment, Histoplasma yeast replication requires the acquisition of several essential nutrients, including metal ions. Recent work has shown that while iron, zinc, and copper are sufficiently abundant [...] Read more.
The fungal pathogen Histoplasma capsulatum resides within the phagosome of host phagocytic cells. Within this intracellular compartment, Histoplasma yeast replication requires the acquisition of several essential nutrients, including metal ions. Recent work has shown that while iron, zinc, and copper are sufficiently abundant in resting macrophages, cytokine activation of these host cells causes restriction of these metals from intracellular yeasts as a form of nutritional immunity. Faced with limited iron availability in the phagosome following macrophage activation by IFN-γ, Histoplasma yeasts secrete iron-scavenging siderophores and employ multiple strategies for reduction of ferric iron to the more physiologically useful ferrous form. IFN-γ activation of macrophages also limits availability of copper in the phagosome, forcing Histoplasma reliance on the high affinity Ctr3 copper importer for copper acquisition. GM-CSF activation stimulates macrophage production of zinc-chelating metallothioneins and zinc transporters to sequester zinc from Histoplasma yeasts. In response, Histoplasma yeasts express the Zrt2 zinc importer. These findings highlight the dynamics of phagosomal metal ion concentrations in host-pathogen interactions and explain one mechanism by which macrophages become a less permissive environment for Histoplasma replication with the onset of adaptive immunity. Full article
(This article belongs to the Special Issue Histoplasma and Histoplasmosis)
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Other

6 pages, 662 KiB  
Commentary
The Fight against HIV-Associated Disseminated Histoplasmosis in the Americas: Unfolding the Different Stories of Four Centers
by Mathieu Nacher, Terezinha Silva Leitao, Beatriz L. Gómez, Pierre Couppié, Antoine Adenis, Lisandra Damasceno, Magalie Demar, Blanca Samayoa, Diego H. Cáceres, Roger Pradinaud, Anastacio de Queiroz Sousa, Eduardo Arathoon and Angela Restrepo
J. Fungi 2019, 5(2), 51; https://doi.org/10.3390/jof5020051 - 17 Jun 2019
Cited by 25 | Viewed by 4004
Abstract
Disseminated histoplasmosis is a major opportunistic infection of HIV-infected patients, killing thousands in Latin America each year. Yet, it remains a neglected disease that is often confused with tuberculosis, for lack of simple, affordable, and rapid diagnostic tools. There is great heterogeneity in [...] Read more.
Disseminated histoplasmosis is a major opportunistic infection of HIV-infected patients, killing thousands in Latin America each year. Yet, it remains a neglected disease that is often confused with tuberculosis, for lack of simple, affordable, and rapid diagnostic tools. There is great heterogeneity in the level of histoplasmosis awareness. The purpose of this report was to describe how the historical “awakening” to the threat of histoplasmosis came to be in four different centers that have actively described this disease: In Brazil, the Sao José hospital in Fortaleza; in Colombia, the Corporación para Investigaciones Biológicas in Medellin; in French Guiana, Cayenne Hospital; and in Guatemala, the Association de Salud Integral in Guatemala city. In Brazil and French Guiana, the search for leishmaniasis on the buffy coat or skin smears, respectively, led to the rapid realization that HIV patients were suffering from disseminated histoplasmosis. With time and progress in fungal culture, the magnitude of this problem turned it into a local priority. In Colombia and Guatemala, the story is different because for these mycology centers, it was no surprise to find histoplasmosis in HIV patients. In addition, collaborations with the CDC to evaluate antigen-detection tests resulted in researchers and clinicians developing the capacity to rapidly screen most patients and to demonstrate the very high burden of disease in these countries. While the lack of awareness is still a major problem, it is instructive to review the ways through which different centers became histoplasmosis-aware. Nevertheless, as new rapid diagnostic tools are becoming available, their implementation throughout Latin America should rapidly raise the level of awareness in order to reduce the burden of histoplasmosis deaths. Full article
(This article belongs to the Special Issue Histoplasma and Histoplasmosis)
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