Trypanosoma brucei is a parasite that causes the deadly sleeping sickness. Scientists have determined the parasite has its own biological clock that makes it more vulnerable to medications in the afternoon. The finding could lead to improved treatment for sleeping sickness and other parasitic diseases. [UT Southwestern]
Trypanosomiasis, or human Africa sleeping sickness as it is most conventionally called, accounts for a significant amount of morbidity and mortality in sub-Saharan Africa. The parasite is transmitted through the bite of the tsetse fly, and treatment for the disease can be extensive, with therapies often producing a range of harmful side effects. Yet, what if much of the toxic side effects of the drugs used to eradicate the parasite could be mitigated simply by administering them at specific times during the day? Well, that is exactly what a team of researchers from the University of Lisbon and the Peter O'Donnell Jr. Brain Institute at University of Texas Southwestern Medical Center looked to answer.
In a new study, published recently in Nature Microbiology in an article entitled “Trypanosoma brucei Metabolism Is Under Circadian Control,” the investigators found that the sleeping sickness parasite (Trypanosoma brucei) has its own biological clock that makes it more vulnerable to medications during the afternoon. The researchers are hopeful that knowing the optimal time to administer the antiparasitic medications—which can be fatal—they can reduce the duration and dosage of the treatment, ultimately saving more lives.
“This research has opened a door,” explained lead study investigator Filipa Rijo-Ferreira, Ph.D., research fellow at the O'Donnell Brain Institute at UT Southwestern Medical Center. “If the same therapeutic effect can be obtained with a lower dose, then it may be possible to reduce the mortality associated with the treatment.”
Once the trypanosomes have entered the body, the parasite causes such symptoms as inverted sleeping cycles, fever, muscle weakness, and itching. It eventually invades the central nervous system and, depending on its type, can kill its host in anywhere from a few months to several years. Control efforts have significantly reduced the number of cases over the last decade. However, an unknown number of people still die annually from sleeping sickness, as scientists continue seeking a vaccine and alternative treatments to the arsenic-based medications that are occasionally fatal to patients.
In the current study, the authors noted that “T. brucei, the causative agent of human sleeping sickness, has an intrinsic circadian clock that regulates its metabolism in two different stages of the life cycle.” The authors went on to explain that they “found, in vitro, ~10% of genes in T. brucei are expressed with a circadian rhythm. The maximum expression of these genes occurs at two different phases of the day and may depend on a post-transcriptional mechanism. Circadian genes are enriched in cellular metabolic pathways and coincide with two peaks of intracellular adenosine triphosphate concentration.” Additionally, the authors noted that “daily changes in the parasite population lead to differences in suramin sensitivity, a drug commonly used to treat this infection.”
Senior study investigator Joseph Takahashi, Ph.D., professor, and chair of the department of neuroscience at UT Southwestern Medical Center, believes that these recent findings will likely apply to all types of parasites and perhaps lead to improved treatment for their associated conditions.
“There have been many observations of the presence of daily patterns in parasites, but until now we didn't know if this was the result of an intrinsic molecular clock,” Dr. Takahashi noted. “In the future, we may consider biological rhythms when defining therapies to treat sleeping sickness and potentially other infections.”