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Like all arenaviruses, Lujo virus has a rodent host as its reservoir. Humans can contract LUHF through contact with an infected rodent. Contact can be direct or through inhalation of aerosolized Lujo virus from the urine or feces of infected rodents.

Person-to-person transmission of Lujo virus was observed in the small, nosocomial cluster of hemorrhagic disease which resulted in the discovery of the Lujo virus.

Transmission of arenaviruses, and Lujo virus in particular, is most likely the result of direct contact with the body fluids of an infected person, in the absence of infection control precautions.

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