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Background: Carrion's disease affects small Andean communities in Peru, Colombia and Ecuador and is characterized by two distinct disease manifestations: an abrupt acute bacteraemic illness (Oroya fever) and an indolent cutaneous eruptive condition (verruga Peruana). Case fatality rates of untreated acute disease can exceed 80% during outbreaks. Despite being an ancient disease that has affected populations since pre-Inca times, research in this area has been limited and diagnostic and treatment guidelines are based on very low evidence reports. The apparently limited geographical distribution and ecology of Bartonella bacilliformis may present an opportunity for disease elimination if a clear understanding of the epidemiology and optimal case and outbreak management can be gained. Methods: All available databases were searched for English and Spanish language articles on Carrion's disease. In addition, experts in the field were consulted for recent un-published work and conference papers. The highest level evidence studies in the fields of diagnostics, treatment, vector control and epidemiology were critically reviewed and allocated a level of evidence, using the Oxford Centre for Evidence-Based Medicine (CEBM) guidelines. Results: A total of 44 studies were considered to be of sufficient quality to be included in the analysis. The majority of these were level 4 or 5 (low quality) evidence and based on small sample sizes. Few studies had been carried out in endemic areas. Conclusions: Current approaches to the diagnosis and management of Carrion's disease are based on small retrospective or observational studies and expert opinion. Few studies take a public health perspective or examine vector control and prevention. High quality studies performed in endemic areas are required to define optimal diagnostic and treatment strategies. Author Summary: Carrion's disease is one of the truly neglected tropical diseases. It affects children predominantly in small Andean communities in Peru, Colombia and Ecuador. Case fatality rates of untreated acute disease can exceed 80% during outbreaks. Diagnostic and treatment guidelines are based on very low evidence reports and public health and prevention programs have been limited. This paper presents the first systematic review of Carrion's disease in Peru and encompasses a detailed analysis of all the highest level evidence regarding not only diagnosis and management but also vector control and prevention. In the review, the authors highlight the considerable knowledge gaps in this field and suggest a strategy for a renewed effort in its investigation. The authors hope that through this work we will be able to develop a better understanding of the epidemiology, natural history and optimal approaches to case and outbreak [ABSTRACT FROM AUTHOR]