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      Point of care tests for invasive fungal infections: a blueprint for increasing availability in Africa

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          Abstract

          Invasive fungal infections (IFIs) such as cryptococcosis, disseminated histoplasmosis, and chronic pulmonary aspergillosis are significant causes of morbidity and mortality in Africa. Lack of laboratory infrastructure and laboratory personnel trained in diagnostic mycology hamper prompt detection and management of IFIs on the continent. Point-of-care tests (POCT) obviate the need for complex infrastructure, skilled technicians, and stable electricity and have had major impacts on the diagnosis of bacterial, viral, and parasitic infections in low- and middle-income countries. Over the last 10 years, POCTs for IFIs have become increasingly available and they have the potential to revolutionize the management of these infections if scaled up in Africa. At the beginning of 2021, the World Health Organization (WHO) Essential Diagnostic List (EDL) included a cryptococcal antigen test for the diagnosis of cryptococcosis, Histoplasma antigen test for the diagnosis of disseminated histoplasmosis, and Aspergillus-specific test for the diagnosis of chronic pulmonary aspergillosis. All of these are available in formats that may be used as POCTs and it is hoped that this will improve the diagnosis of these life-threatening IFIs, especially in low- and middle-income countries. This perspective review discusses commercially available POCTs and outlines strategies of a blueprint to achieve their roll-out in Africa. The strategies include raising awareness, conducting research that uncovers the exact burden of IFIs, increasing advocacy, integrating diagnosis of IFIs into existing public health programs, adoption of the WHO EDL at country levels, and improving logistics and supply chains.

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          Most cited references80

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          Global and Multi-National Prevalence of Fungal Diseases—Estimate Precision

          Fungal diseases kill more than 1.5 million and affect over a billion people. However, they are still a neglected topic by public health authorities even though most deaths from fungal diseases are avoidable. Serious fungal infections occur as a consequence of other health problems including asthma, AIDS, cancer, organ transplantation and corticosteroid therapies. Early accurate diagnosis allows prompt antifungal therapy; however this is often delayed or unavailable leading to death, serious chronic illness or blindness. Recent global estimates have found 3,000,000 cases of chronic pulmonary aspergillosis, ~223,100 cases of cryptococcal meningitis complicating HIV/AIDS, ~700,000 cases of invasive candidiasis, ~500,000 cases of Pneumocystis jirovecii pneumonia, ~250,000 cases of invasive aspergillosis, ~100,000 cases of disseminated histoplasmosis, over 10,000,000 cases of fungal asthma and ~1,000,000 cases of fungal keratitis occur annually. Since 2013, the Leading International Fungal Education (LIFE) portal has facilitated the estimation of the burden of serious fungal infections country by country for over 5.7 billion people (>80% of the world’s population). These studies have shown differences in the global burden between countries, within regions of the same country and between at risk populations. Here we interrogate the accuracy of these fungal infection burden estimates in the 43 published papers within the LIFE initiative.
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            Global burden of disease of HIV-associated cryptococcal meningitis: an updated analysis.

            Cryptococcus is the most common cause of meningitis in adults living with HIV in sub-Saharan Africa. Global burden estimates are crucial to guide prevention strategies and to determine treatment needs, and we aimed to provide an updated estimate of global incidence of HIV-associated cryptococcal disease.
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              Histoplasmosis: a Clinical and Laboratory Update

              Infection with Histoplasma capsulatum occurs commonly in areas in the Midwestern United States and Central America, but symptomatic disease requiring medical care is manifest in very few patients. The extent of disease depends on the number of conidia inhaled and the function of the host's cellular immune system. Pulmonary infection is the primary manifestation of histoplasmosis, varying from mild pneumonitis to severe acute respiratory distress syndrome. In those with emphysema, a chronic progressive form of histoplasmosis can ensue. Dissemination of H. capsulatum within macrophages is common and becomes symptomatic primarily in patients with defects in cellular immunity. The spectrum of disseminated infection includes acute, severe, life-threatening sepsis and chronic, slowly progressive infection. Diagnostic accuracy has improved greatly with the use of an assay for Histoplasma antigen in the urine; serology remains useful for certain forms of histoplasmosis, and culture is the ultimate confirming diagnostic test. Classically, histoplasmosis has been treated with long courses of amphotericin B. Today, amphotericin B is rarely used except for severe infection and then only for a few weeks, followed by azole therapy. Itraconazole is the azole of choice following initial amphotericin B treatment and for primary treatment of mild to moderate histoplasmosis.

                Author and article information

                Contributors
                Journal
                Ther Adv Infect Dis
                Ther Adv Infect Dis
                TAI
                sptai
                Therapeutic Advances in Infectious Disease
                SAGE Publications (Sage UK: London, England )
                2049-9361
                2049-937X
                16 August 2021
                Jan-Dec 2021
                : 8
                : 20499361211034266
                Affiliations
                [1-20499361211034266]Department of Medical Microbiology, School of Medicine, College of Medical Sciences, University of Benin, Benin City, Nigeria, Department of Medical Microbiology, University of Benin Teaching Hospital, Benin City, Nigeria
                [2-20499361211034266]Department of Medical Microbiology and Immunology, Faculty of Medicine, Gulu University, Gulu, Uganda
                Author notes
                Author information
                https://orcid.org/0000-0001-8111-0743
                https://orcid.org/0000-0003-4515-8517
                Article
                10.1177_20499361211034266
                10.1177/20499361211034266
                8371725
                34422265
                2acac5e6-c0ae-4058-bf90-e656030815c3
                © The Author(s), 2021

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                : 25 February 2021
                : 5 July 2021
                Categories
                Fungal Diseases in Africa: Epidemiologic, Diagnostic and Therapeutic Advances
                Review
                Custom metadata
                January-December 2021
                ts1

                africa,aspergillosis,cryptococcosis,histoplasmosis,invasive fungal infections,point-of-care tests

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