Project Summary/Abstract Acute febrile illness (AFI) is an important cause of morbidity and productivity loss in Latin America. Despite efforts for surveillance and advancements in diagnostic capacity, the etiology of AFI is still unknown in over 50% of cases. Our Project of Febrile Illness Surveillance in the Andean and Amazon Countries (?PISAAC?) proposes to study AFI etiology and epidemiology, to strengthen the core public health systems that prevent and mount prompt containing responses in front of outbreaks. PISAAC, led by Dr. Eduardo Gotuzzo at Universidad Cayetano Heredia, is a multi institutional initiative developed in close collaboration with key actors and institutions at the Peruvian Ministry of Health (MoH), including the Peruvian National Health Institute (INS). This initiative will be carried out in partnership with the National Institute of Health Leopoldo Izquieta Perez (INSPI) and Escuela Superior Politécnica del Litoral (ESPOL), in Ecuador, aiming to develop a coordinated effort to establish a systematic surveillance system within the Coastal, Andean and Amazon regions of South America. Additional key partners include U.S. Naval Medical Research Unit Nº6, and the University of Texas Medical Branch in Galveston. Our specific aims are to determine the etiology and epidemiology of acute undifferentiated febrile illness in strategically selected regions of Peru and Ecuador, improve laboratory capacity for the diagnosis of illness, produce timely and accurate surveillance data, and develop a workforce that can continue with these measures. Additionally, we aim to determine the prevalence of antimicrobial resistance, and the etiology and antimicrobial resistance of acute diarrheal disease. The study will start in two regions in Peru during the first year. Subsequently, during the second year, two regions in Ecuador will be added, and 1 to 2 new regions per country will be added per year. The initial stage is a prospective study of sentinel surveillance that will enroll subjects that present to healthcare centers of primary and secondary care level with AFIs. Blood and serum samples will be taken at acute presentation for PCR based tests and serology. Additionally, urine and nasal samples will be collected and stored along with serum alliquotes in a biorepository for future studies. Convalescent sera will be collected for paired serology testing in those patients that resulted negative for initial testing with molecular methods. During the second year, components of antimicrobial resistance (AMR) surveillance and diarrheal disease surveillance will be implemented, as these two health problems are considered public health priorities for Peru. PISAAC is in a unique position to strengthen the national surveillance and emergency response systems as it builds upon the pre-existing infrastructure and public health delivery platforms, provides strategic complementary partnerships across lab diagnosis to disease control and addresses the core technical areas demanded by the Global Health Security Agenda.