trypanosoma brucei trypanosoma brucei trypanosoma brucei is a species of parasitic kinetoplastid belonging to the genus trypanosoma that is present in sub-saharan africa. unlike other protozoan parasites that normally infect blood and tissue cells, it is exclusively extracellular and inhabits the blood plasma and body fluids. it causes deadly vector-borne diseases: african trypanosomiasis or sleeping sickness in humans, and animal trypanosomiasis or nagana in cattle and horses. it is a species complex grouped into three subspecies: t. b. brucei, t. b. gambiense and t. b. rhodesiense. the first is a parasite of non-human mammals and causes nagana, while the latter two are zoonotic infecting both humans and animals and cause african trypanosomiasis. trypanosoma brucei t. b. brucei treu667 (bloodstream form, phase-contrast picture. black bar indicates 10 µm.) scientific classification domain: eukaryota phylum: euglenozoa class: kinetoplastea order: trypanosomatida family: trypanosomatidae genus: trypanosoma species: t. brucei binomial name trypanosoma bruceiplimmer & bradford, 1899 subspecies trypanosoma brucei brucei trypanosoma brucei gambiense trypanosoma brucei rhodesiense t. brucei is transmitted between mammal hosts by an insect vector belonging to different species of tsetse fly (glossina). transmission occurs by biting during the insect's blood meal. the parasites undergo complex morphological changes as they move between insect and mammal over the course of their life cycle. the mammalian bloodstream forms are notable for their cell surface proteins, variant surface glycoproteins, which undergo remarkable antigenic variation, enabling persistent evasion of host adaptive immunity leading to chronic infection. t. brucei is one of only a few pathogens known to cross the blood brain barrier. there is an urgent need for the development of new drug therapies, as current treatments can have severe side effects and can prove fatal to the patient. whilst not historically regarded as t. brucei subspecies due to their different means of transmission, clinical presentation, and loss of kinetoplast dna, genetic analyses reveal that t. equiperdum and t. evansi are evolved from parasites very similar to t. b. brucei, and are thought to be members of the brucei clade. the parasite was discovered in 1894 by sir david bruce, after whom the scientific name was given in 1899. history and discovery early records sleeping sickness in animals were described in ancient egyptian writings. during the middle ages, arabian traders noted the prevalence of sleeping sickness among africans and their dogs. it was a major infectious diseases in southern and eastern africa in the 19th century. the zulu kingdom (now part of south africa) was severely struck by the disease, which became known to the british as nagana, a zulu word for to be low or depressed in spirit. in other parts of africa, europeans called it the "fly disease." a man having sleeping sickness at buruma island, uganda. john aktins, an english naval surgeon, gave first medical description of human sleeping sickness in 1734. he attributed deaths which he called "sleepy distemper" in guinea to the infection. another english physician thomas masterman winterbottom gave clearer description of the symptoms from sierra leone in 1803. winterbottom described a key feature of the disease as swollen posterior cervical lymph nodes and slaves who developed such swellings were ruled unfit for trade. the symptom is eponymously known as "winterbottom's sign." discovery of the parasite the royal army medical corps appointed david bruce, who at the time was assistant professor of pathology at the army medical school in netley with a rank of captain in the army, in 1894 to investigate a disease known as nagana in south africa. the disease caused severe problems among the local cattle and british army horses. on 27 october 1894, bruce and his microbiologist-wife mary elizabeth bruce (née steele) moved to ubombo hill, where the disease was most prevalent. on the sixth day of investigation, bruce identified parasites from the blood of diseased cows. he initially noted them as a kind of filaria (tiny roundworms), but by the end of the year established that the parasites were "haematozoa" (protozoan) and were the cause of nagana . it was the discovery of trypanosoma brucei. the scientific name was created by british zoologists henry george plimmer and john rose bradford in 1899 as trypanosoma brucii due to printer's error. the genus trypanosoma was already introduced by hungarian physician david gruby in his description of t. sanguinis, a species he discovered in frogs in 1843. outbreaks in uganda, the first case of human infection was reported in 1898. it was followed by an outbreak in 1900. by 1901, it became severe with death toll estimated to about 20,000. more than 250,000 people died in the epidemic that lasted for two decades. the disease commonly popularised as "negro lethargy." it was not known whether the human sleeping sickness and nagana were similar or the two disease were caused by similar parasites. even the observations of forde and dutton did not indicate that the trypanosome was related to sleeping sickness. sleeping sickness commission main article: sleeping sickness commission the royal society constituted a three-member sleeping sickness commission on 10 may 1902 to investigate the epidemic in uganda. the commission comprised george carmichael low from the london school of hygiene and tropical medicine as the leader, his colleague aldo castellani and cuthbert christy, a medical officer on duty in bombay, india. at the time, a debate remained on the etiology, some favoured bacterial infection while some believed as helminth infection. the first investigation focussed on filaria perstans (later renamed mansonella perstans), a small roundworm transmitted by flies, and bacteria as possible causes, only to discover that the epidemic was not related to these pathogens. the team was described as an "ill-assorted group" and a "queer lot", and the expedition "a failure." low, whose conduct was described as "truculent and prone to take offence," left the commission and africa after three months. in february 1902, the british war office, following a request from the royal society, appointed david bruce to lead the second sleeping sickness commission. with david nunes nabarro (from the university college hospital), bruce and his wife joined castellani and christy on 16 march. in november 1902, castellani had found the trypanosomes in the cerebrospinal fluid of an infected person. he was convinced that the trypanosome was the causative parasite of sleeping sickness. like low, his conduct has been criticised and the royal society refused to publish his report. he was further infuriated when bruce advised him not to make rash conclusion without further evidences, as there were many other parasites to consider. castellani left africa in april and published his report as "on the discovery of a species of trypanosoma in the cerebrospinal fluid of cases of sleeping sickness" in the lancet. by then the royal society had already published the report. by august 1903, bruce and his team established that the disease was transmitted by the tsetse fly, glossina palpalis. however, bruce did not understand the trypanosoma life cycle and believed that the parasites were simply transmitted from one person to another. around the same time, germany sent an expeditionary team led by robert koch to investigate the epidemic in togo and east africa. in 1909, one of the team members, friedrich karl kleine discovered that the parasite had developmental stages in the tsetse flies. bruce, in the third sleeping sickness commission (1908–1912) that included albert ernest hamerton, h.r. bateman and frederick percival mackie, established the basic developmental cycle through which the trypanosome in tsetse fly must pass. an open question, noted by bruce at this stage, was how the trypanosome finds its way to the salivary glands. muriel robertson, in experiments carried out between 1911 and 1912, established how ingested trypanosomes finally reach the salivary glands of the fly. discovery of human trypanosomes british colonial surgeon robert michael forde was the first to find the parasite in human. he found it from an english steamboat captain who was admitted to a hospital at bathurst, gambia, in 1901. his report in 1902 indicates that he believed it to be a kind of filarial worm. from the same person, forde's colleague joseph everett dutton identified it as a protozoan belonging to the genus trypanosoma. knowing the distinct features, dutton proposed a new species name in 1902: at present then it is impossible to decide definitely as to the species, but if on further study it should be found to differ from other disease-producing trypanosomes i would suggest that it be called trypanosoma gambiense. another human trypanosome (now called t. brucei rhodesiense) was discovered by british parasitologists john william watson stephens and harold benjamin fantham. in 1910, stephens noted in his experimental infection in rats that the trypanosome, obtained from an individual from northern rhodesia (later zambia), was not the same as t. gambiense. the source of the parasite, an englishman travelling in rhodesia was found with the blood parasites in 1909, and was transported to and admitted at the royal southern hospital in liverpool under the care of ronald ross. fantham described the parasite's morphology and found that it was a different trypanosome. species t. brucei is a species complex that includes: t. brucei gambiense which causes slow onset chronic trypanosomiasis in humans. it is most common in central and western africa, where humans are thought to be the primary reservoir. in 1973, david hurst molyneux was the first to find infection of this strain in wildlife and domestic animals. since 2002, there are several reports showing that animals, including cattle, are also infected. it is responsible for 98% of all human african trypanosomiasis, and is roughly 100% fatal. t. brucei rhodesiense which causes fast onset acute trypanosomiasis in humans. a highly zoonotic parasite, it is prevalent in southern and eastern africa, where game animals and livestock are thought to be the primary reservoir. t. brucei brucei which causes animal trypanosomiasis, along with several other species of trypanosoma. t. b. brucei is not infective to humans due to its susceptibility to lysis by trypanosome lytic factor-1 (tlf-1). however, it is closely related to, and shares fundamental features with the human-infective subspecies. only rarely can the t. b. brucei infect a human. the subspecies cannot be distinguished from their structure as they are all identical under microscopes. geographical location is the main distinction. molecular markers have been developed for individual identification. serum resistance-associated (sra) gene is used to differentiate t. b. rhodesiense from other subspecies. tgsgp gene, found only in type 1 t. b. gambiense is also a specific distinction between t. b. gambiense strains. the subspecies lack many of the features commonly considered necessary to constitute monophyly. as such lukeš et al., 2022 proposes a new polyphyly by ecotype. etymology the genus name is derived from two greek words: τρυπανον (trypanon or trupanon), which means "borer" or "auger", referring to the corkscrew-like movement; and σῶμα (sôma), meaning "body." the specific name is after david bruce, who discovered the parasites in 1894. the subspecies, the human strains, are named after the regions in africa where they were first identified: t. brucei gambiense was described from an englishman in gambia in 1901; t. brucei rhodesiense was found from another englishman in northern rhodesia in 1909. structure sem false colour micrograph of the procyclic form as found in the tsetse fly midgut. the cell body is shown in orange and the flagellum is in red. 84 pixels/μm.t. brucei is a typical unicellular eukaryotic cell, and measures 8 to 50 μm in length. it has an elongated body having a streamlined and tapered shape. its cell membrane (called pellicle) encloses the cell organelles, including the nucleus, mitochondria, endoplasmic reticulum, golgi apparatus, and ribosomes. in addition, there is an unusual organelle called the kinetoplast, which is a complex of thousands of mitochondria. the kinetoplast lies near the basal body with which it is indistinguishable under microscope. from the basal body arises a single flagellum that run towards the anterior end. along the body surface, the flagellum is attached to the cell membrane forming an undulating membrane. only the tip of the flagellum is free at the anterior end. the cell surface of the bloodstream form features a dense coat of variant surface glycoproteins (vsgs) which is replaced by an equally dense coat of procyclins when the parasite differentiates into the procyclic phase in the tsetse fly midgut. the six main morphologies of trypanosomatids. the different life cycle stages of t brucei