HAT is caused by infection with the T.b. rhodesiense or T.b. gambiense subspecies. Over 20 species and subspecies of tsetse flies transmit these parasites, but only approximately 1 per 1,000 flies has the mature salivary gland infection that is necessary to transmit the parasite to humans. Trypanosomes enter the fly when it takes a meal of parasite-containing blood from an infected human or animal and, over a period of four weeks, undergo morphological and physiological transformations in the alimentary tract and in the salivary glands, where they become infective. During a blood meal on the mammalian host, an infected tsetse fly injects parasites into skin tissue. The parasites pass via the lymphatic system into the bloodstream, which carries them throughout the body. The parasites continue to replicate by binary fission. In late-stage disease the parasites invade the CNS and reside in the cerebrospinal fluid and intercellular spaces. Figure modified with permission from Alexander J. da Silva and Melanie Moser, Centers for Disease Control Public Health Image Library.