Trypanosoma lewisi is a globally distributed parasite of Rattus species and other rodents such as mice, and of kangaroo rats in America.

The northern rat flea (Nosopsyllus fasciatus) acts as the vector for the parasite, harboring the epimastigote stage in its midgut.

[8] The parasite can also be grown in mice if the host is supplemented with a controlled diet and intraperitoneal injection of rat serum.

[9] Ablastin, an antibody that arises during an infection in the host's body, prevents the parasite from reproducing although they remain in adult form.

[7] A research paper suggests that the data on the aftermath of introduction of a Trypanosoma lewisi to immunologically naïve murine hosts on Christmas Island around 1900 matches reports of complete extinction within the range of 1–9 years.

In a recent study comparing Brazilian isolates in rats and primates, it was found the DNA sequences were the same when considering Trypanosoma lewisi.

These parasites are usually attacked by ablastin, a trypanocidal IgG antibody produced by their host's immune system beginning 2–4 days postinfection.