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      HIV-Associated Histoplasmosis Early Mortality and Incidence Trends: From Neglect to Priority

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          Abstract

          Background

          Histoplasmosis is an endemic fungal infection in French Guiana. It is the most common AIDS-defining illness and the leading cause of AIDS-related deaths. Diagnosis is difficult, but in the past 2 decades, it has improved in this French overseas territory which offers an interesting model of Amazonian pathogen ecology. The objectives of the present study were to describe the temporal trends of incidence and mortality indicators for HIV-associated histoplasmosis in French Guiana.

          Methods

          A retrospective study was conducted to describe early mortality rates observed in persons diagnosed with incident cases of HIV-associated Histoplasma capsulatum var. capsulatum histoplasmosis admitted in one of the three main hospitals in French Guiana between 1992 and 2011. Early mortality was defined by death occurring within 30 days after antifungal treatment initiation. Data were collected on standardized case report forms and analysed using standard statistical methods.

          Results

          There were 124 deaths (45.3%) and 46 early deaths (16.8%) among 274 patients. Three time periods of particular interest were identified: 1992–1997, 1998–2004 and 2005–2011. The two main temporal trends were: the proportion of early deaths among annual incident histoplasmosis cases significantly declined four fold (χ2, p<0.0001) and the number of annual incident histoplasmosis cases increased three fold between 1992–1997 and 1998–2004, and subsequently stabilized.

          Conclusion

          From an occasional exotic diagnosis, AIDS-related histoplasmosis became the top AIDS-defining event in French Guiana. This was accompanied by a spectacular decrease of early mortality related to histoplasmosis, consistent with North American reference center mortality rates. The present example testifies that rapid progress could be at reach if awareness increases and leads to clinical and laboratory capacity building in order to diagnose and treat this curable disease.

          Author Summary

          Histoplasmosis is an endemic fungal infection in French Guiana. It is the most common AIDS-defining illness and the leading cause of AIDS-related deaths. Diagnosis is difficult, but in the past 2 decades, it has improved. The objectives of the present study were to describe the temporal trends of incidence and mortality indicators for HIV-associated histoplasmosis in French Guiana. A retrospective study was conducted to describe early mortality rates observed in persons diagnosed with incident cases of HIV-associated histoplasmosis admitted in one of the three main hospitals of French Guiana between 1992 and 2011. Early mortality was defined by death occurring within 30 days after antifungal treatment initiation. Data were collected on standardized case report forms and analysed using standard statistical methods. Among 274 patients there were 46 early deaths (16.8%). The two main temporal trends were: the proportion of early deaths significantly divided four fold and the number of annual incident histoplasmosis cases increased three fold. The present example testifies that rapid progress could be at reach if awareness increases and leads to clinical and laboratory capacity building in order to diagnose and treat this curable disease.

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          Most cited references14

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          Epidemiology of endemic systemic fungal infections in Latin America.

          Although endemic mycoses are a frequent health problem in Latin American countries, clinical and epidemiological data remain scarce and fragmentary. These mycoses have a significant impact on public health, and early diagnosis and appropriate treatment remain important. The target population for endemic disease in Latin America is mostly represented by low-income rural workers with limited access to a public or private health system. Unfortunately, diagnostic tools are not widely available in medical centers in Latin America; consequently, by the time patients are diagnosed with fungal infection, many are already severely ill. Among immunocompromised patients, endemic mycoses usually behave as opportunistic infections causing disseminated rather than localized disease. This paper reviews the epidemiology of the most clinically significant endemic mycoses in Latin America: paracoccidioidomycosis, histoplasmosis, and coccidioidomycosis. The burdens of disease, typically affected populations, and clinical outcomes also are discussed.
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            Disseminated histoplasmosis in the acquired immune deficiency syndrome: clinical findings, diagnosis and treatment, and review of the literature.

            Histoplasmosis is a serious opportunistic infection in patients with AIDS, often representing the first manifestation of the syndrome. Most infections occurring within the endemic region are caused by exogenous exposure, while those occurring in nonendemic areas may represent endogenous reactivation of latent foci of infection or exogenous exposure to microfoci located within those nonendemic regions. However, prospective investigations are needed to prove the mode of acquisition. The infection usually begins in the lungs even though the chest roentgenogram may be normal. Clinical findings are nonspecific; most patients present with symptoms of fever and weight loss of at least 1 month's duration. When untreated, many cases eventually develop severe clinical manifestations resembling septicemia. Chest roentgenograms, when abnormal, show interstitial or reticulonodular infiltrates. Many cases have been initially misdiagnosed as disseminated mycobacterial infection or Pneumocystis carinii pneumonia. Patients are often concurrently infected with other opportunistic pathogens, supporting the need for a careful search for co-infections. Useful diagnostic tests include serologic tests for anti-H. capsulatum antibodies and HPA, silver stains of tissue sections or body fluids, and cultures using fungal media from blood, bone marrow, bronchoalveolar lavage fluid, and other tissues or body fluids suspected to be infected on clinical grounds. Treatment with amphotericin B is highly effective, reversing the clinical manifestations of infection in at least 80% of cases. However, nearly all patients relapse within 1 year after completing courses of amphotericin B of 35 mg/kg or more, supporting the use of maintenance treatment to prevent recurrence. Relapse rates are lower (9 to 19%) in patients receiving maintenance therapy with amphotericin B given at doses of about 50 mg weekly or biweekly than with ketoconazole (50-60%), but controlled trials comparing different maintenance regimens have not been conducted. Until results of such trials become available, our current approach is to administer an induction phase of 15 mg/kg of amphotericin B given over 4 to 6 weeks, followed by maintenance therapy with 50 to 100 mg of amphotericin B given once or twice weekly, or biweekly. If results of a prospective National Institutes of Allergy and Infectious Disease study of itraconazole maintenance therapy document its effectiveness, alternatives to amphotericin B may be reasonable.
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              Histoplasmosis.

              Histoplasmosis is the most common endemic mycosis causing human infection. Large outbreaks have been ascribed to histoplasmosis, but most infections are sporadic. Similar to the other fungi in this category, initial exposure to Histoplasma capsulatum is by way of the respiratory tract, but once inhaled into the alveoli, the organism readily spreads in macrophages throughout the reticuloendothelial system. Compared with a decade ago, improvements in diagnostic tests have made it feasible to more quickly establish a diagnosis of histoplasmosis, thus allowing appropriate antifungal therapy to be started promptly. Treatment guidelines have been updated recently and are reviewed for the various forms of histoplasmosis.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS Negl Trop Dis
                PLoS Negl Trop Dis
                plos
                plosntds
                PLoS Neglected Tropical Diseases
                Public Library of Science (San Francisco, USA )
                1935-2727
                1935-2735
                August 2014
                21 August 2014
                : 8
                : 8
                : e3100
                Affiliations
                [1 ]Inserm CIC 1424, Centre d'Investigation Clinique Antilles Guyane, Centre Hospitalier de Cayenne, Cayenne, France
                [2 ]Equipe EA3593, Epidémiologie des Parasitoses et des Mycoses Tropicales, Université des Antilles et de la Guyane, Cayenne, France
                [3 ]Service de Médecine Interne, Centre Hospitalier de l'Ouest Guyanais, Saint Laurent du Maroni, France
                [4 ]Laboratoire de Biologie Médicale, Centre Hospitalier de l'Ouest Guyanais, Saint Laurent du Maroni, France
                [5 ]Laboratoire Hospitalo-Universitaire de Parasitologie-Mycologie, Centre Hospitalier de Cayenne, Cayenne, France
                [6 ]Unité des Maladies Infectieuses et Tropicales, Centre Hospitalier de Cayenne, Cayenne, France
                [7 ]Service de Dermatologie Vénérologie, Centre Hospitalier de Cayenne, Cayenne, France
                Baylor College of Medicine, United States of America
                Author notes

                The authors have declared that no competing interests exist.

                Conceived and designed the experiments: AA MN PC. Performed the experiments: AA MN MH VV RB DB MD CA BC PC. Analyzed the data: AA MN MH PC. Contributed reagents/materials/analysis tools: RB DB MD CA BC. Wrote the paper: AA MN MH VV RB DB MD CA BC PC.

                Article
                PNTD-D-13-01600
                10.1371/journal.pntd.0003100
                4140672
                25144374
                a812bdda-47aa-45c8-9c6f-867ab85e6585
                Copyright @ 2014

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 18 September 2013
                : 7 July 2014
                Page count
                Pages: 5
                Funding
                This work has benefited from an “Investissement d'Avenir” grant managed by Agence Nationale de la Recherche (CEBA, ref. ANR-10-LABX-0025). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine and Health Sciences
                Infectious Diseases
                Fungal Diseases
                Histoplasmosis
                Viral Diseases
                AIDS
                Infectious Disease Control
                Sexually Transmitted Diseases
                Tropical Diseases
                Neglected Tropical Diseases

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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