African trypanosomiasis is an insect-borne parasitic infection of humans and other animals caused by the protozoan species Trypanosoma brucei, which is transmitted by the bite of an infected tsetse fly. Human African trypanosomiasis (HAT) is also known as sleeping sickness. Humans are infected by two subspecies of T. brucei: T. brucei gambiense is primarily transmitted between humans and causes over 92% of cases, while T. brucei rhodesiense is zoonotic, with animals such as cattle serving as reservoirs. During the first stage of the disease, T. brucei parasites replicate in the blood and lymph, causing fever, headache, itchiness, and joint pains about one to three weeks after the bite. Weeks to months later, the parasite crosses the blood–brain barrier and the second stage begins with neurological symptoms including confusion, poor coordination, numbness, and trouble sleeping. Without treatment, African trypanosomiasis almost always results in death. Diagnosis involves detecting the parasite in a blood smear or lymph node fluid. A lumbar puncture is often needed to tell the difference between first- and second-stage disease. T. brucei gambiense causes chronic infection that can take months to years to develop symptoms, while T. brucei rhodesiense infection causes symptoms within weeks to months. Prevention involves avoiding tsetse fly bites, for example by the use of insect repellents and protective clothing. Vector control measures, such as spraying insecticides and releasing sterilized tsetse flies in endemic areas, have significantly reduced the incidence of disease. Screening the at-risk population with blood tests for T. brucei gambiense can prevent the development of severe disease. Treatment is easier when the disease is detected early and before neurological symptoms begin. The use of pentamidine or suramin treats the first stage of T. brucei infection, but if the disease progresses to the neurological stage, dosages of eflornithine or a combination of nifurtimox and eflornithine are the preferred treatment. Fexinidazole is a more recent treatment that can be taken by mouth for either stage of T. brucei gambiense. While melarsoprol works for both types of sleeping sickness, it is typically used only for T. brucei rhodesiense, due to its serious side effects. The disease occurs regularly in some regions of sub-Saharan Africa with the population at risk being about 70 million in 36 countries. An estimated 11,000 people are currently infected with 2,800 new infections in 2015. In 2024, there were 583 confirmed cases recorded. In 2015, it caused around 3,500 deaths, down from 34,000 in 1990. More than 80% of these cases are in the Democratic Republic of the Congo. Three major outbreaks have occurred in recent history: one from 1896 to 1906 primarily in Uganda and the Congo Basin, and two in 1920 and 1970, in several African countries. It is classified as a neglected tropical disease. Other animals, such as cows, may carry the disease and become infected in which case it is known as nagana or animal trypanosomiasis.
Risk factors Risk factors include living in or traveling to rural areas of sub-Saharan Africa where tsetse flies are present. Occupations such as farming, fishing, and hunting increase exposure risk.
Signs and symptoms African trypanosomiasis symptoms occur in two stages: 1) the hemolymphatic stage and 2) the neurological or meningoencephalitic stage. The hemolymphatic stage is to the period when parasites are present in the blood and lymphatic system, prior to central nervous system involvement. The neurological stage, also called the meningoencephalitic stage, begins when Trypanosoma parasites cross the blood–brain barrier and invade the central nervous system. In addition to the hemolymphatic stage neurological symptoms can still present themselves, resulting in a difficulty in distinguishing the two stages based on clinical features alone. The disease has been reported to present with atypical symptoms in infected individuals who originate from non-endemic areas (e.g., travelers). In such persons, the infection is said to present mainly as fever with gastrointestinal symptoms (e.g., diarrhea and jaundice) and with lymphadenopathy rarely developing. An earlier study noted a greater dominance of the neurological symptoms, and also reported the presence of jaundice. The reasons for this are unclear and may be genetic or linked to a lack of previous exposure to forms of trypanosomes not pathogenic to humans. The low number of such cases may also have skewed findings. These symptomatological differences have resulted in delayed or missed diagnosis.
Trypanosomal ulcer Systemic disease is sometimes presaged by a trypanosomal ulcer developing at the site of the infectious fly bite within 2 days of infection. The ulcer is most commonly observed in T. b. rhodesiense infection and rarely in T. b. gambiense infection, where ulcers are more common in persons from non-endemic areas.
Hemolymphatic stage The incubation period is 1–3 weeks for T. b. rhodesiense, and longer (but less precisely characterised) in T. b. gambiense infection. The first/initial stage, known as the hemolymphatic stage, is characterized by non-specific, generalised symptoms like: fever (intermittent), headaches (severe), joint pains, itching, weakness, malaise, fatigue, weight loss, lymphadenopathy, and hepatosplenomegaly. Diagnosis may be delayed due to the vagueness of initial symptoms. The disease may also be mistaken for malaria (which may occur as a co-infection).
Intermittent fever Fever is intermittent, with attacks lasting from a day to a week, separated by intervals of a few days to a month or longer. Episodes of fever become less frequent throughout the disease.
Lymphadenopathy Invasion of the circulatory and lymphatic systems by the parasite is associated with severe swelling of lymph nodes, often to tremendous sizes. Posterior cervical lymph nodes are most commonly affected; however, axillary, inguinal, and epitrochlear lymph node involvement may also occur. Winterbottom's sign is a clinical finding involving swollen lymph nodes at the base of the skull or along the back of the neck, particularly characteristic of T. b. gambiense infections.
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