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African Trypanosomosis is cyclically transmitted by tsetse flies, although other haematophagus insects are capable of transmitting mechanically the parasite, mainly T. vivax. The word tsetse originates from the Tswana (Botswana) language and means "fly which kills livestock". Tsetse flies are now restricted to tropical Africa but fossil specimens dating back to the Miocene have been found in Colorado. When a tsetse feeds on the blood of a parasitized host it also ingests blood-stream forms of the trypanosome. Within the tsetse, now the vector of the parasite, a series of changes take place in the trypanosome before transformation to the infecting metatrypanosome occurs. In the course of the next blood meal, the infective metatrypanosomes (metacyclic forms) will be transmitted to another host.

In the fly, the period from ingesting infected blood to the appearance of the infective forms varies from one to three weeks. Once infective metatrypanosomes are present the fly remains infective for the remainder of its life.

Carnivores may be infected with T. evansi and T. brucei by ingesting meat or organs from infected animals. In this case, infection occurs probably through the mucosa of the mouth in which bone splinters make wounds through which the parasites penetrate.

The iatrogenic transmission can occur when a (veterinary) operator uses the same needle or surgical instrument on more than one animal, at sufficient short intervals that blood on the needle or instrument does not dry. It is not an uncommon occurrence when animals are vaccinated or treated by injection, or when blood is collected from several animals in a row, without changing or disinfecting needles or pins.

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