PARASITES, CLOCKS, AND IMMUNITY: A Within-Host Mathematical Model of Human African Trypanosomiasis

Abstract

Human African Trypanosomiasis, or Sleeping Sickness, is a neglected tropical disease that threatens thousands of people living in Sub-Saharan Africa. This chronic infection is caused by the single-celled Trypanosoma brucei when transmitted by the Tsetse fly. There is limited treatment that keeps the disease from being fatal, so priority has been placed on developing efficient medicine and reducing transmission. One approach is to take a small-scale ecological perspective on infection to investigate how the host and parasite are interacting to shape the dynamics of the disease, with consideration of multiple environmental factors, such as biological rhythms. Here, we construct a mathematical model that incorporates host rhythms in temperature and immunity with parasite replication, differentiation, and immune evasion. We also conduct an in vitro temperature experiment to parameterize trypanosome growth for the model. Three groups of T. brucei cells were grown for 5 days: in constant 34°C, in constant 37°C, and alternating between the two temperatures. We find a growth rate that changes significantly within the 3°C. Our current model predicts that biological rhythms (in temperature and immunity) play an important role in shaping the parasite dynamics in their mammalian host. It also predicts an additive circadian response directly drives the dynamics of the infection. Further biological data on the within-host interactions of HAT infections with explicit consideration for circadian rhythms could expand the model framework and allow more accurate simulation and expose the potential vulnerabilities of the parasite.