Developments in Sleeping Sickness Research

According to the CDC, about 10,000 cases of sleeping sickness are reported in Africa yearly. Sleeping sickness, or human African trypanosomiasis (HAT), is caused by the zooflagellated protozoa, Trypanosoma brucei. Trypanosoma is a single celled parasite that splits its life cycle between a tsetse fly host and a mammalian host. Two subspecies of the parasite are transmitted to humans by the bite of tsetse flies, in the genus Glossina, when the flies take a blood meal. The first subspecies T. b. rhodesiense, is responsible for what is known as East African sleeping sickness, and the second T. b. gambiense is responsible for West African sleeping sickness. The tsetse fly is found only in Africa, and the disease is rarely reported in other countries besides African countries. The few cases in other countries are found in African immigrants or returning travelers from Africa.

Up until recently, doing mechanistic studies of the development of Trypanosoma brucei has been difficult due to the expense and effort of rearing a large enough tsetse fly colony in the lab. After the tsetse fly bites an infected mammal, the trypanosome differentiates from its infective form to a non-infective form inside the midgut of the fly. As the parasite develops, divides, and moves from the fly midgut to its salivary glads, it, once again, becomes infectious to humans. Though this developmental process has been illuminated for a long time, the molecular mechanisms of this development has been difficult to study in the flies themselves.

In December, researchers reported in Science, about a new development in producing the infectious form of the protozoan (metacyclics), in vitro, from the non-infectious form using an overexpression of a single RNA-binding protein, TbRBP6. In the experiment, the metacyclics produced by this method successfully infected lab mice. The trypanosomes that were not induced with RBP6, were not detected in the blood of the mice inoculated with with these (and other) controls. With an effective means of metacyclogenesis, mechanistic research of trypanosome development can progress, hopefully uncovering new ways to control transmission of sleeping sickness.

More recently, in a newly published study, researchers suggest that animal reservoirs of Trypanosoma may be more important than previously thought. This means that even if sleeping sickness is eradicated in the human population, it could resurface again because of its persistence in other animal populations. Researchers say that human treatment programs may not be the reason why trypanosomiasis cases are in decline, but rather, loss of wildlife habitat may be cited as the cause.

Eastern African sleeping sickness has been known to be transmitted from cattle to human hosts. However, this particular form of the disease makes up only about 2% of the total cases of HAT. The other 98% of cases are Western African sleeping sickness, caused by the subspecies, T. b. gambiense. It was previously thought that this form was only found in wild and domestic animals more rarely and that other animals did not transmit the West African form of the disease.

Using blood data from humans, domestic animals, and wild animals over a span of 6 years, scientists built a model revealing that it is likely that more than just humans are playing a role in transmission of the infective parasite. This makes it possible for the disease to be revived, even if eliminated from the human population. Though much ambiguity remains, this knowledge can be useful for future elimination efforts.



Sources:
http://www.sciencemag.org/content/338/6112/1352.full.pdf
http://www.cdc.gov/parasites/sleepingsickness/index.html
http://www.sciencemag.org/content/suppl/2012/12/05/338.6112.1369-b.DC1/SciencePodcast_121207.pdf
http://news.sciencemag.org/sciencenow/2013/01/a-wake-up-call-in-the-fight-agai.html?ref=hp

Photo credits:
http://news.yale.edu/2012/02/09/eye-tsetse-fly
http://www.cdc.gov/parasites/sleepingsickness/biology.html
http://www.phsource.us/PH/HELM/PH_Parasites/Trypanosomiasis_African.htm