The Trypanosoma brucei (as well as three other trypanosome species) cause sleeping sickness, known as African trypanosomiasis.
This is in contradistinction to Chagas disease which is known as American trypanosomiasis due to its central and south American distribution.
|T. brucei gambiense||T. brucei rhodesiense||T. brucei brucei|
|Distribution||West Africa||East Africa|
|Vector||Glossina palpalis||G. morsitans, palpides.||G. palpalis, fuscipes, tachinoides|
|Disease||Chronic (mo's-y'rs)||Acute (w'ks-mo's)|
|Host||Human||Humans & Game||Cattle & Game|
The tsetse fly, encompassing all species of the genus Glossina.
Only newly hatched tsetse flies are competent to transmit the disease. Tsetse flies are a poor vector since less than 1% of flies are infected.
TransmissionTrypanosoma brucei species are transmitted by tsetse bites. The tsetse fly contains trypanosomes in its probiscus and salivary glands; thus, T. brucei species are known as saliva-type or salivarian trypanosomes.
|Short-stumpy||Able to infect the tsetse fly vector.|
|Procyclic form||Able to infect a mammalian host.|
|Metacyclic form||Pre-adaption occurs. Mitochondrial genes stop expression by losing cristi.|
|Long-slender||No functioning mitochondria -- glycolytic lifestyle.|
Short-stumpy (Bloodstream trypomastigote)
The non-dividing short-stumpy bloodstream trypomastigote infects the fly upon ingestion of a blood meal. While the meal is retained within the midgut, Trypanasoma brucei differentiates into a procyclic form.
The procyclics divide by binary fission within the insect midgut. After about two weeks, some procyclics migrate from the midgut through the hemocoel to reach the salivary glands. At this point the procyclic form differentiates through an epimastigote stage into a non-dividing metacyclic trypomastigote stage.
Non-Dividing Metacyclic Trypomastigote
The non-dividing metacyclic trypomastigote is infectious for the mammalian host. Metacyclic trypomastigotes are found in the salivary glands ~20 days after the bloodmeal; each bite transfers ~40,000 trypomastigotes; only 400 trypomastigotes are needed to initiate infection.
Dividing Metacyclic Trypomastigote
Metacyclic trypomastigotes replicate at the site of infection. There may be an immune response causing a trypanosomal chancre at the site of the bite. From the bite wound, the trypomastigotes move via the lymphatics to the lymph nodes and then to the bloodstream where they differentiate into the long-slender form.
Long-slender bloodstream trypomastigotes divide by binary fission in the bloodstream. The long-slender trypomastigotes are not infectious for the fly. On occasion, the long-slender protozoa differentiate into the short-stumpy protozoa to continue the cycle in the tsetse fly.
Causes Nagana in animals and African Sleeping Sickness in humans. Symptoms include Winterbottom's sign and swollen lymphnodes on neck.
|Primary stage||Metacyclic trypomastigotes are introduced subcutaneously and multiply. In 2-3 days the bite site is itchy, swollen and red. After 6 days a trypanosomal chancre may develop at the bite site. This is oft dismissed as an innocent boil.|
|Blood stage||Generalized infection manifests as fever, sometimes accompanied by malaise, headache and joint pain. Trypanosomes are found in the bloodstream 5-12 days after infection. Trypanosoma gambiense are scarcer than T. rhodesiense in the bloodstream. Trypanosomes infiltrate the lymphatic system, and the influx of B-cells causes lymphadenopathy. In a Trypanosoma gambiense infection, swollen cervical (neck) lymph nodes are referred to as Winterbottom’s sign. The lysis of trypanosomes releases toxins that TNF-α secretion by macrophages, thus causing cyclic (relapsing) cachexia (fever) with a cycle of 7-10 days.|
|Late Rhodesian||In the Late Stage of Rhodesian Sleeping Sickness, it is just a few weeks before the parasite enters the CNS from the lymphatics. Death is quick upon CNS involvement, if myocarditis was not already fatal.|
|Late Gambian||In the Late Stage of Gambian Sleeping Sickness, the parasite invades the CNS within one or more years and causes personality changes including insomnia and irritability. Inflammatory changes cause a demyelinating meningoencephalitis, causing cerebral edema, hemorrhages, pericarditis, and anemia. The encephalopathy leads to apathy, somnolence and coma. Death is usually due to intercurrent infections such as pneumonia.|
Domestication of cattle occurs only outside the tsetse area.
Losses in meat production, milk yield and tractive power are estimated to cost approximately $500 million annually and, if lost potential in livestock and crop production are also considered, the disease costs Africa an estimated $5 billion per year (1994 prices).
Complete control of tstetse would result in an increase in beef production of 1.5 million tons per annum. However, this would also have a massive impact on the use of land and significantly reduce the possibilities for wild life in Africa. (From http://www.icp.ucl.ac.be/~opperd/parasites/
Trypanosoma brucei gambiense
Sleeping sickness observed.
Human Sleeping Sickness was observed by Arab doctors as early as 1375. In 1702, English naval surgeon John Atkins described sleepy distemper in Africans living along the Guinea Coast. In 1803, physician Thomas Winterbottom worked in the Sierra Leone colony and published an account of African lethargy.
Winterbottom recognized a telltale clinical characteristic: swelling of the cervical lymph nodes.
Human infection identified.
In May 1901, a 42-year-old English laborer on the steamships plying the Gambia River developed a fever. Doctors treated him with quinine to no avail. His blood was examined for malaria parasites but none were found. However, his blood was laced with trypanosomes.
In 1902, this trypanosome of humans was named Trypanosoma gambiense by Joseph Everett Dutton of the Liverpool School of Tropical Medicine.
The vector was identified during an epidemic in Uganda.
In 1901, a severe epidemic of Sleeping Sickness broke out in Uganda. The Royal Society of London sponsored a commission headed by Bruce to investigate its cause. By 1902 the commission had discovered that the distribution of Winterbottom’s Sign corresponded with the distribution of Sleeping Sickness. Further, Dr. Aldo Castellani examined cerebrospinal fluid from a Sleeping Sickness patient and found trypanosomes. Out of 34 Sleeping Sickness patients, 20 had trypanosomes in their cerebrospinal final; none of 12 control cases had trypanosomes.
Bruce suspected that the tse-tse fly transmitted Gambian Sleeping Sickness. When it was found that a tsetse fed on a human patient could transmit the disease to monkeys, it was concluded: Sleeping Sickness is a human tsetse disease.
Trypanosoma brucei rhodesiense
In 1910, J. W. Stephens of the Liverpool School of Tropical Medicine discovered a new species of trypanosomes: it was from a Sleeping Sickness patient who acquird the disease in 1909 in Rhodesia. Trypanosoma gambiense and its vector Glossina palpalis do not exist in Rhodesia.
The Rhodesian Sleeping Sickness was more acute and the parasites had a unique morphology. Stephens called them Trypanosoma rhodesiense.
In 1912, Bruce headed a commission near Lake Nyssa to investigate Rhodesian Sleeping Sickness. Bruce found Trypanosoma rhodesiense in the blood of 1/3 of the 180 game animals examined. Bruce compared the morphology of T. rhodesiense with T. brucei from cases of Nagana and found the parasites to be identical. Bruce concluded that T. rhodesiense and T. brucei are responsible for the same disease.
The tsetse species Glossina morsitans and G. palidipes were found to be the vectors of the East African parasite T. rhodesiense (instead of G. palpalis, G. fuscipes and G. tachinoides for the West African parasite T. brucei brucei).
Trypanosoma brucei brucei
In the early 1890s, British colonial farmers in Zululand saw their European cattle breed (Nebu) decimated by a wasting disease called Nagana, the Zulu word for depression. The native cattle breed (N'Dama) was unaffected by Nagana.
In 1894, Bruce was sent to investigate Nagana. He examined blood from diseased cattle and described a rapidly vibrating protozoan lashing amidst erithrocytes. Bruce successfully used Koch's Postulates to establish this protozoan parasite as the agent of Nagana.
In 1895, Bruce hypothesized and proved about the Nagana parasite that: wild game were the reservoir; the tsetse fly infesting the same land as the wild game was the vector; and that tsetse fly bites were the mode of transmission. The parasite would later be named Trypanosoma brucei brucei.