Current Fungal Infection Reports (2019) 13:244–249 https://doi.org/10.1007/s12281-019-00365-3 EPIDEMIOLOGY OF FUNGAL INFECTIONS (T CHILLER AND J BADDLEY, SECTION EDITORS) The Manaus Declaration: Current Situation of Histoplasmosis in the Americas, Report of the II Regional Meeting of the International Histoplasmosis Advocacy Group Diego H. Caceres1 & Antoine Adenis2 & João Vicente Braga de Souza3 & Beatriz L. Gomez4 & Katia Santana Cruz5 & Alessandro C. Pasqualotto6 & Giovanni Ravasi7 & Freddy Perez7 & Tom Chiller1 & Marcus Vinicius Guimarares de Lacerda8,9 & Mathieu Nacher3 & The International Histoplasmosis Advocacy Group (iHAG) Published online: 27 November 2019 # This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2019 Abstract Purpose of Review The aim of this report is to summarize the conclusions of the II Regional Meeting on Histoplasmosis in the Americas held in Manaus, Brazil, on March 22–24, 2019. Recent Findings PersonslivingwithadvancedHIVareathighriskfordeveloping histoplasmosis. Clinical signs and symptoms of this disease are often non-specific, making it difficult to establish a diagnosis. Although with the recent technological advances, in vitro diagnostics and medicines for histoplasmosis are often not available in many regions around the world. In addition, histoplasmosis is often not included in HIV care and treatment programs, resulting in inadequate health system planning and missed opportunities to save lives. Summary The II Regional Meeting on Histoplasmosis in the Americas gathered a multidisciplinary audience. Developed recommendations to be included in the WHO guidelines for diagnosis and treatment of histoplasmosis in advanced HIV were the product of this meeting, and guidelines are aimed to be published in early 2020. Keywords Histoplasma . Histoplasmosis . Diagnosis . Treatment . Guidelines . AIDS Introduction American continent, but it has also been reported in other places around the world. In persons living with HIV Histoplasmosis is a disease caused by the fungus Histoplasma (PLHIV), especially those with advanced disease, progressive capsulatum. This disease is most frequently found in the disseminated histoplasmosis (PDH) is associated with high This article is part of the Topical Collection on Epidemiology of Fungal Infections * Diego H. Caceres 5 Medical Mycology Laboratory, Tropical Medicine Foundation Dr. [email protected]; [email protected] Heitor Vieira Dourado, Manaus, Amazonas AM 69060-001, Brazil 6 Universidade Federal de Ciências da Saúde Porto Alegre, and Santa 1 Centers for Disease Control and Prevention, Mycotic Diseases Casa de misericórdia de Porto Alegre, Porto Alegre, RS, Brazil Branch, Mailstop H24-9, 1600 Clifton Rd, Atlanta, GA 30333, USA 2 ’ Centre d Investigation Clinique Antilles Guyane, Inserm CIC1424, 7 HIV, Hepatitis, Tuberculosis and STI Unit, Pan American Health Centre Hospitalier de Cayenne, Cayenne, French Guiana Organization, D, Washington .C, USA 3 Instituto Nacional de Pesquisas da Amazônia, Coordenação de Sociedade, ambiente e saúde, Laboratório de Micologia, 8 Fundação de Medicina Tropical Dr. Heitor Vieira Dourado Manaus, Amazonas AM 69060-001, Brazil (FMT-HVD), Manaus, Amazonas, Brazil 4 Studies in Translational Microbiology and Emerging Diseases (MICROS) Research Group, School of Medicine and Health 9 Fundação Oswaldo Cruz, Instituto Leônidas e Maria Deane Sciences, Universidad del Rosario, Bogota 11011, Colombia (FIOCRUZ-Amazonas), Manaus, Amazonas, Brazil Curr Fungal Infect Rep (2019) 13:244–249 245 mortality [1]. PDH symptoms are nonspecific, and among diagnosis associated with an increase in the diagnosis of people with advanced HIV disease, these may be similar or histoplasmosis and a decrease in mortality?” indistinguishable to other infectious diseases, especially tuber- & PICO 2: “Among people living with HIV infection with culosis [1]. disseminated histoplasmosis what are the optimal thera- Conventional laboratory methods, specifically culture and peutic alternatives depending on patient severity and histopathology, used for the diagnosis of histoplasmosis have country resource level?” many challenges, including need for high-level laboratory in- & PICO 3: “What modification of the HIV or TB therapy frastructure, need of laboratory personnel trained in medical need to be made for successful outcome of histoplasmosis mycology, long turnaround time for results (median 15 days), on patients co-infected with TB?” and variable test performance. Antibody testing is less sensitive in immunocompromised persons [2]. Molecular assays are The GDG developed recommendations to be included in promising diagnostic tools, but none are available as commer- the final guidelines document, which has a target publication cial kits, making them difficult to implement in clinical labora- date of early 2020. PICO questions and members of GDG are tories [3]. Detection of circulating Histoplasma antigens is the described in Table 1. gold standard for rapid diagnosis of PDH due its high analytical performance and rapid turnaround time [4••]. However, antigen testing is limited outside the United States despite availability of II Regional Meeting on Histoplasmosis commercial kits and recent inclusion of such testing in the in the Americas (iHAG 2019) second World Health Organization (WHO) list of essential in vitro diagnostics [5•, 6••]. Antifungal therapies recommend- The second meeting of the international Histoplasmosis ed for the treatment of histoplasmosis are not widely available Advocacy Group (iHAG 2019) was co-organized by the in endemic countries due to many factors, including complex International Histoplasmosis Advocacy Group (iHAG), national regulations and high costs [7•]. Finally, histoplasmosis, Instituto Nacional de Pesquisas da Amazôna (INPA-Brazil), as with many other fungal diseases, is not included in most Fundação de Medicina Tropical Doutor Heitor Vieira Dourado public health surveillance systems. (FMT-HVD-Brazil), Pan American Health Organization The main objectives of this meeting were to determine the (PAHO)/World Health Organization (WHO), and the Centers availability of in vitro tests for rapid diagnosis and antifungal for Disease Control and Prevention (CDC). The meeting was treatment for histoplasmosis and to discuss strategies for ex- supported by the Fundação de Amparo a Pesquisa do Estado panded access to optimal diagnostics and treatment. At the first do Amazonas (FAPEAM) (Grant No 005/2017 Program to meeting of the International Histoplasmosis Advocacy Group Support the Holding of Scientific and Technological Events in (iHAG), held in Paramaribo, Suriname, during December 4–6, the State of Amazonas—PAREV), Fundação Oswaldo Cruz 2015, participants agreed to launch the “80 by 20” initiative, (Fiocruz), Global Action Fund for Fungal Infections (GAFFI), which aimed to provide rapid diagnostic testing and effective International Society for Human and Animal Mycology treatment access for disseminated histoplasmosis in at least one (ISHAM), Mycoses Study Group Education and Research laboratory per country in 80% of the Americas by 2020 [7•]. Consortium (MSGERC), Centre d'Investigation Clinique Antilles Guyane (Inserm CIC1424) of the Centre Hospitalier de Cayenne, Universidad del Rosario, Universidade Federal de Pre-Meeting: Pan American Health Ciências da Saúde de Porto Alegre (UFCSPA), and Santa Casa Organization/World Health Organization de Misericórdia de Porto Alegre. Histoplasmosis Guidelines Development Dr Marcus Lacerda, João Vicente Souza, and Katia Cruz were the meeting hosts in Manaus, Brazil. The meeting fo- Pan-American Health Organization (PAHO)/World Health cused on the status of epidemiological surveillance, diagnosis, Organization (WHO) facilitated a histoplasmosis Guidelines and treatment throughout the region as well as new develop- Development Group (GDG) pre-meeting to discuss the devel- ments in both laboratory and treatment options. The agenda opment of WHO Guidelines on the Diagnosis and included keynote lectures, scientific presentations, country Management of Progressive Disseminated Histoplasmosis in updates, and policy discussions. More information regarding People living with HIV. On March 22, 2019, before the iHAG the iHAG 2019 meeting is available at: https:// meeting, the GDG determined the following key questions to histoplasmosisadvo.wixsite.com/ihagmeeting2019/ be addressed through systematic reviews using the population, preliminary-agenda. intervention, comparison, outcome (PICO) method (Table 1). Specific objectives of the meeting were the following: & PICO 1: “Among patients with HIV disease, is antigen & Increase awareness and advocacy for histoplasmosis in testing versus standard microbiological techniques of PLHIV in the Americas. 246 Curr Fungal Infect Rep (2019) 13:244–249 Table 1 The PICO questions and members of GDG Population, intervention, comparison, outcome (PICO) questions PICO 1: “Among patients with HIV disease, is antigen testing versus standard microbiological techniques of diagnosis associated with an increase in the diagnosis of histoplasmosis and a decrease in mortality?” Population: Patients with HIV disease Intervention: Antigen testing Comparison: Standard microbiological techniques Outcomes: Proximal: increased accuracy of diagnosis; Distal: decreased mortality PICO 2: “Among people living with HIV infection with disseminated histoplasmosis what are the optimal therapeutic alternatives depending on patient severity