Human African Sleeping Sickness: Biology of Trypanosoma brucei
The protozoan parasite Trypanosoma brucei is the causative agent of African trypanosomiasis, otherwise known as human African sleeping sickness. The disease has two forms, depending on the subspecies of Trypanosoma involved; Trypanosoma brucei gambiense (West African sleeping sickness) accounts for around 97% of cases, whereas Trypanosoma brucei rhodesiense (East African sleeping sickness) is responsible for less than 3% of reported cases. Other species of Trypanosoma can be pathogenic to wild animals such as T. vivax, which causes nagana in antelope and other ungulate mammals. The lifecycle of T. brucei is complex and involves an insect vector in the form of the tsetse fly (Glossina spp.). The definitive hosts of T. brucei includes ungulate mammals and humans, and between 300,000 and 500,000 cases of human African sleeping sickness are reported per year, with the majority of cases being fatal if left untreated.
Biology of Trypanosoma brucei
Trypanosoma is a kinetoplastid haemoflagellate, closely related to Leishmania, another parasitic protozoan whose vector is the sand fly. Kinetoplastids are so named after the kinetoplast, an organelle found only in this group of flagellates which consists of a mass of mitochondrial DNA which codes for mitochondrial proteins. However not all kinetoplastids are parasitic; indeed the group also includes the mixotrophic free-living flagellate Euglena. Trypanosomes have several distinct morphological forms depending on the stage of development.
Two subspecies of T. brucei, T. b. rhodesiense and T. b. gambiense, are the causative agents of East African and West African sleeping sickness (respectively) in humans, which can be lethal if left untreated, whilst other subspecies such as Trypanosoma brucei brucei are only pathogenic in wild animals such as mice. Infection can lead to muscle aches, headaches, fever and swollen lymph glands, and as the parasites reach the central nervous system confusion, slurred speech and alterations to sleeping patterns are noticed as the parasites affect the circadian rhythm of the host.
Lifecycle and Transmission
The lifecycle of Trypanosoma brucei is indirect and involves two hosts – the tsetse fly (genus Glossina) which acts as the vector, and large mammals including humans. In T. b. gambiense and T. b. rhodesiense, humans are the definitive host for the parasite, with mammals such as game animals and cattle acting as reservoir hosts.
When an infected tsetse fly takes a blood meal from a mammal, metacyclic trypomastigotes residing in the salivary glands of the fly are injected into the bloodstream of the mammal, where they develop into bloodstream trypomastigotes, and spread through the hosts lymphatic and circulatory systems, dividing by binary fission. The bloodstream trypomastigotes are then taken up a feeding tsetse fly. Upon uptake, the bloodstream trypomastigotes develop into procyclic trypomastigotes in the midgut of the fly, and replicate further by binary fission. After replication, the procyclic trypomastigotes then leave the midgut and develop into epimastigotes, which multiply within the salivary glands by binary fission. The epimastigotes then develop into metacyclic trypomastigotes which will be injected into the bloodstream of a mammal when the fly takes its next meal.
Epidemiology of Human African Trypanosomiasis (HAT)
Human African trypanosomiasis is restricted to sub-Saharan Africa with a risk population of approximately 65 million people in 36 countries. East African and West African trypanosomiasis are geographically isolated from each other by the African Rift Valley, and Uganda is the only country which has cases of both T. b. rhodesiense and T. b. gambiense. West African trypanosomiasis, caused by T. b. gambiense, is prevalent in West and Central African nations, such as the Democratic Republic of Congo and Angola, and is responsible for the majority of cases of HAT. East African trypanosomiasis, caused by T. b. rhodesiense, is much rarer and found in East and Southern Africa, in countries such as Uganda, and is responsible for less than 3% of HAT cases.
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