1. THE BURDEN OF SERIOUS FUNGAL INFECTIONS IN VENEZUELA Maribel Dolande 1, María Mercedes Panizo 1, Giuseppe Ferrara 1, Víctor Alarcón 1, Nataly García 1, Vera Reviakina 1, Ana María Capote 1, Trina Navas 2, Xiomara Moreno 3, Ana Alastruey-Izquierdo 4, David W. Denning 5. 1 Instituto Nacional de Higiene "Rafael Rangel, Caracas, Venezuela. 2 Hospital General del Oeste Dr. José Gregorio Hernández, Caracas, Venezuela. 3 Instituto Médico La Floresta, Caracas, Venezuela. 4 Spanish National Centre for Microbiology, Instituto de Salud Carlos III, Madrid, Spain. 5 The University of Manchester and National Aspergillosis Centre, University Hospital of South Manchester, United Kingdom, in association with the LIFE program at www.LIFE-worldwide.org.www.LIFE-worldwide.org INTRODUCTION: INTRODUCTION: The privileged geographical location of Venezuela at the northern of South America, and its incredible biodiversity and climatic conditions, favour the development of most human pathogenic fungi. Knowledge about fungal diseases affecting Venezuelan population is not known very well, despite the existence of some epidemiological studies. The organization LIFE (Leading International Fungal Infection), has the overall objective to improve the health of people with fungal diseases worldwide, through awareness campaigns and by estimating the risk of acquiring fungal diseases using local data available. OBJECTIVE: OBJECTIVE: The aim of this study was to perform the first estimate of the burden of serious fungal diseases in the Venezuelan population using a mathematical model. METHODS: METHODS: Deterministic scenario modelling was used for risk analysis, using data on incidence and prevalence on both underlying diseases and fungal diseases in specific populations, published by the Mycology Department of the Instituto Nacional de Higiene "Rafael Rangel“ (INHRR) and other groups of Venezuelan researchers, in order to estimate burden. When no published data was available, data of specific populations at risk and frequency of fungal infection in these populations were used [1-9]. Population statistics were obtained from the Instituto Nacional de Estadística [10]. Data on respiratory infections were obtained and inferred from those reported by the World Health Organization for tuberculosis [11,12]. RESULTS Fungal Disease Number of infections per underlying disorder per year Rate /100K Total burden None HIV/AIDS Respiratory Cancer/TxICU Esophageal candidiasis [9] 14,350---48.7514,350 Candidaemia [3] --3,1501,648164,798 Candida spp. peritonitis [4] ---8243 Recurrent vaginal candidiasis (4x/year +) *only womens 474,7203,225*474,720 ABPA [8]-33,440--11433,440 SAFS [8] -44,141 15044,141 Chronic pulmonary aspergillosis [7,8] -1,422--5 Invasive aspergillosis [5,6] --18096341,143 Mucormycosis --59-0.259 Cryptococcosis [2] 693---2 Pneumocystis pneumonia [1] 2,699---9 Disseminated histoplasmosis [2] 1,746---6 Total burden estimated 474,72019,48879,0033,3893,435 580,035 Table 1. Burden of serious fungal infections in Venezuelan specific population Using population data available up to 2011, Venezuela's estimated population was 29,440,000 inhabitants: 71% over 15 years old and about 9% over 60 years [10]. Of the 110,000 HIV-positive patients, an estimated of 59,000 had CD 4 counts below 350 cells/mL and 14,700 were found at high risk of infection [11,12]. In AIDS patients it was estimated that 2,699 could develope Pneumocystis pneumonia, 693 cryptococcosis, 1,746 disseminated histoplasmosis, and 14,350 esophageal candidiasis per year, with 3,800 estimated deaths from AIDS annually. (Table 1, Figure 1) [1,2,9,11]. Candidemia affected 1.72/1,000 hospital admissions (approximately 16/100000 patients), with a total of 4,798 cases nationwide (Table 1, Figure 2) [3]. Eight hundred and twenty four (824) patients were estimated to be at risk of developing intra-abdominal candidiasis in the postoperative period [4]. Approximately 474,720 women (15-50 years old) could suffer from recurrent vulvovaginal candidiasis each year. Regarding invasive aspergillosis, it probably affects 1,143 people every year [5,6], estimating that about 226 patients may develop chronic pulmonary aspergillosis after tuberculosis per year, with a prevalence of 711 cases of an overall of 1,422 patients [7,8]. Assuming allergic bronchopulmonary aspergillosis affects 2.5% of adult asthma patients, a total of 33,440 probable cases and 44,141 cases of severe asthma caused by sensitization to fungi was estimated (Table 1). In this study it was not included information about ringworm, candidiasis, sporotrichosis, chromoblastomycosis, fungal keratitis, coccidioidomycosis, and paracoccidioidomycosis because the data were very limited. Panizo et al. Casuistry of Mycology Department of INHRR (2007-2012) Figure 1. Pneumocystis pneumonia frequency according to patient’s group (2007-2012) 30,8% 31,6% 14% 25,7% CancerAIDSWithout AIDS/Cancer Figure 2. Distribution by gender and species of blood isolated yeasts n=750 (July 2008 – July 2012) Dolande et al. Candidaemia and Antifungal Resistance Surveillance Network. July, 2012 CONCLUSIONS: The model of risk analysis is a powerful tool that allowed us to estimate that 580,035 Venezuelans are at risk of developing serious fungal disease each year, with high mortality rates. These results provided important information about the dynamics of fungal diseases in our country and the populations under study, that will allow estimate the risk of future events, and promote applied research lines contributing to the development of comprehensive strategic plans for its detection, prevention and treatment, in order to generate a positive impact on public health. This establishes the need for a surveillance program of mycoses in Venezuela. More studies based on local casuistry and epidemiology to know the true incidence and prevalence of fungal infections in our country are required. 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