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Summary: Background: Crimean-Congo hemorrhagic fever (CCHF) is a virulent tick-borne disease reported in more than 30 countries across Europe, Africa, and Asia. The disease is considered endemic in several Central Asian countries, including Tajikistan; however reports of human cases from these regions rarely reach the West. Methods: We analyzed all historical confirmed cases of CCHF in Tajikistan, mapping these reports against geographic data to assess risk areas. In addition, comprehensive analysis was undertaken on the 2010 human CCHF cohort to demonstrate effective methodologies for diagnosing this disease in-country. Results: These data show that CCHF is endemic in Tajikistan, and several large clusters have been recorded. Endemic foci of disease are localized to the southern region, with geographical factors such as altitude, monthly mean temperature, and monthly mean precipitation levels limiting establishment of tick vectors in other areas. Genomic analysis of viral RNA from a 2010 human case revealed high nucleotide homology (99%) to a strain isolated in Tajikistan in 1990. Conclusions: CCHF is an important vector-borne and nosocomial pathogen in Tajikistan. The ability to rapidly detect cases using real-time RT-PCR shortly after admission in the hospital setting allows prompt implementation of barrier nursing techniques, therefore reducing onward transmission of the virus. [Copyright &y& Elsevier]