Trypanosoma brucei is a single-celled parasite responsible for Human African Trypanosomiasis (HAT), also known as African sleeping sickness. This disease is transmitted to humans through the bite of an infected tsetse fly, a species found in rural sub-Saharan Africa. Once inside a human host, the parasite begins a complex life cycle that leads to a progressive and often fatal illness if not treated.
The Parasite’s Life Cycle
The life cycle of Trypanosoma brucei uses a two-host system, alternating between a mammalian host and the tsetse fly vector. The cycle begins when an infected tsetse fly takes a blood meal, injecting metacyclic trypomastigotes into the skin. The parasites move into the lymphatic system and bloodstream, where they transform into bloodstream trypomastigotes and multiply rapidly by binary fission.
As the parasite population grows, some transition from a slender, dividing form to a short, stumpy, non-dividing form. This stumpy stage is adapted for transmission back to the insect. When a tsetse fly bites an infected mammal, it ingests these bloodstream trypomastigotes.
Inside the fly’s midgut, the parasites transform into procyclic trypomastigotes and multiply before migrating to the fly’s salivary glands. During this migration, they change into epimastigotes, which attach to the salivary gland and continue to multiply.
The final stage within the fly is the transformation into infective metacyclic trypomastigotes. This developmental process takes approximately three weeks. The fly is then capable of transmitting the parasite to a new mammalian host, completing the cycle.
Human African Trypanosomiasis
Human African Trypanosomiasis (HAT) progresses in two stages. The first, or hemolymphatic stage, begins after the parasite enters the body. During this period, trypanosomes multiply in the subcutaneous tissues, blood, and lymph system. Symptoms are often general and can include intermittent fever, headaches, joint pains, intense itching, and swollen lymph nodes, particularly in the neck.
This first stage can last from weeks to months, and its non-specific symptoms can be mistaken for other illnesses. If the disease is not diagnosed and treated during this phase, the parasites will eventually cross the blood-brain barrier and invade the central nervous system.
The second, or meningoencephalitic stage, marks a severe escalation of the disease. The resulting neurological damage leads to more obvious symptoms, including confusion, poor coordination, and behavioral changes. A defining characteristic of this stage is the disruption of the sleep-wake cycle, which gives the disease its name, “sleeping sickness.” Patients experience fragmented sleep at night and overwhelming sleepiness during the day. Without treatment, the neurological deterioration is progressive, leading to coma and death.
Subspecies and Geographic Impact
The disease manifests differently depending on the subspecies of Trypanosoma brucei. Trypanosoma brucei gambiense is the dominant form, causing over 92% of reported cases. It is endemic to 24 countries in West and Central Africa, and humans are its main reservoir.
Infection with T. b. gambiense results in a chronic form of HAT. The first stage can progress slowly over months or even years with mild symptoms. Consequently, diagnosis often occurs only after the disease has advanced to the more severe second stage.
In contrast, Trypanosoma brucei rhodesiense causes a more acute and rapidly progressing illness. Found in 13 countries in Eastern and Southern Africa, it is primarily a zoonotic disease, circulating in animals like cattle, with humans as accidental hosts.
Following infection with T. b. rhodesiense, symptoms appear within weeks. The disease develops quickly and can lead to death within months, often before the neurological symptoms of the second stage fully manifest. The geographical ranges of the two subspecies are historically separated by the Great Rift Valley, with some overlap in Uganda.
Detection and Treatment Approaches
Diagnosing African sleeping sickness begins with identifying the parasite in a patient’s body fluids. For T. b. gambiense, screening often involves serological tests for antibodies, while confirmation requires microscopic examination of fluid from a lymph node or blood. For T. b. rhodesiense, blood smears are the preferred source for diagnosis.
Once the parasite is confirmed, determining the disease stage is the next step. This requires a lumbar puncture to collect cerebrospinal fluid (CSF). The CSF is analyzed for trypanosomes or an elevated white blood cell count, which indicates the infection has reached the second stage. Staging is necessary as the choice of treatment depends on whether the central nervous system is involved.
Treatment for first-stage HAT is simpler and uses drugs with lower toxicity. For T. b. gambiense, options include pentamidine or the oral drug fexinidazole. First-stage T. b. rhodesiense is treated with suramin. These medications are effective as long as the parasite has not invaded the central nervous system.
Treating the second, neurological stage is more complex because the drugs must cross the blood-brain barrier. Historically, treatment for late-stage disease involved melarsoprol, a toxic arsenic-based drug. Safer options are now available for late-stage gambiense disease, including a combination of nifurtimox and eflornithine (NECT) or fexinidazole for non-severe cases. Treatment requires follow-up for up to two years to ensure the parasite is cleared.