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How serious?
Risk of death
No
Vaccine available?
Time to symptoms
Countries affected
Active outbreaks
Very rare in travelers — fewer than 1 case per year among tourists. Transmitted by tsetse flies in rural Sub-Saharan Africa. Wear neutral-colored clothing (tsetse attracted to blue/black), use insect repellent, and avoid bushland. Seek care for persistent fever with chancre after safari travel.
Parasitic disease ("sleeping sickness") transmitted by tsetse fly bites in Sub-Saharan Africa. Two forms: gambiense (chronic, West/Central Africa) and rhodesiense (acute, East/Southern Africa). Fatal without treatment. Nearing elimination as a public health problem.
Symptoms | Frequency | Severity | Onset |
|---|---|---|---|
| Fever | 85% | Mild | Early |
| Headache | 70% | Mild | Early |
| Swollen lymph nodes | 80% | Mild | Early |
| Arthralgia | 40% | Mild | Early |
| Hepatomegaly | 35% | Mild | Early |
| Itching | 25% | Mild | Early |
| Malaise | 65% | Mild | Early |
| Myalgia | 35% | Mild | Early |
| Night sweats | 30% | Mild | Early |
| Skin ulcer | 7% | Mild | Early |
| Splenomegaly | 40% | Mild | Early |
| Sleep disturbance | 65% | Moderate | Peak |
| Confusion | 50% | Severe | Peak |
| Personality changes | 35% | Moderate | Peak |
| Tremor | 30% | Moderate | Peak |
| Weight loss | 60% | Moderate | Peak |
| Irritability | 25% | Mild | Peak |
| Altered consciousness | 15% | Critical | Late |
| Ataxia | 25% | Moderate | Late |
| Seizures | 10% | Severe | Late |
| Fatigue | 75% | Moderate | Any phase |
| Edema | 30% | Mild | Any phase |
| Tachycardia | 25% | Mild | Any phase |
Human African trypanosomiasis (HAT), commonly known as sleeping sickness, is a vector-borne parasitic disease caused by protozoa of the species Trypanosoma brucei, transmitted by the bite of infected tsetse flies (genus Glossina). Two subspecies cause disease in humans: T. b. gambiense (responsible for ~97% of reported cases) and T. b. rhodesiense (~3% of cases), which differ markedly in their epidemiology, clinical course, and geographic distribution.
The disease is endemic in sub-Saharan Africa, occurring in 36 countries where tsetse fly habitats overlap with human populations. Historically, HAT devastated African populations in epidemic waves — the epidemic of the early 20th century killed an estimated 300,000–500,000 people in the Congo Basin alone. Through sustained control efforts, the number of new cases has declined dramatically from ~300,000 estimated cases in 1998 to fewer than 1,000 reported cases per year since 2018, bringing the disease to the verge of elimination.
Without treatment, HAT is virtually 100% fatal. The disease progresses through two stages: an initial hemolymphatic stage followed by a meningoencephalitic (neurological) stage in which the parasite crosses the blood-brain barrier, causing the characteristic sleep disturbances that give the disease its common name. The WHO has targeted the elimination of gambiense HAT as a public health problem by 2030 and interruption of transmission (zero cases) by 2040.
Human African trypanosomiasis is a neglected tropical disease with a complex biology involving trypanosome parasites, tsetse fly vectors, and both human and animal reservoir hosts.
Key facts:
Causative agents:
Vector: Tsetse flies (genus Glossina, ~30 species), large blood-feeding flies found in woodland, savanna, and riverine habitats
Incubation period: T. b. gambiense: weeks to months (may be years before symptoms are recognized); T. b. rhodesiense: 1–3 weeks
Global burden (2024): <1,000 new cases reported/year; 55 million at risk; 36 endemic countries
Case fatality: Nearly 100% if untreated for both forms
Two-stage disease progression:
Distinction between forms:
Feature T. b. gambiense T. b. rhodesiense Geography West/Central Africa East/Southern Africa Course Chronic (months–years) Acute (weeks–months) Reservoir Humans (anthroponotic) Animals (zoonotic) Proportion ~97% of cases ~3% of casesSeek immediate medical attention if you develop any of the following symptoms during or after travel to tsetse-endemic areas in sub-Saharan Africa:
Urgent indicators of HAT:
Painful bite-site nodule (chancre) developing within 1–2 weeks of a tsetse fly bite — particularly important for travelers, as this is often the first recognizable sign
Unexplained intermittent fever persisting for more than 1 week after return from sub-Saharan Africa, especially East Africa (where T. b. rhodesiense progresses rapidly)
Posterior cervical lymphadenopathy (Winterbottom sign) — non-tender, rubbery nodes in the neck
Severe persistent headache unresponsive to standard analgesics
Emergency signs indicating stage 2 (CNS) disease:
Excessive daytime sleepiness or inability to maintain a normal sleep-wake cycle
Confusion, disorientation, or behavioral changes — may be mistaken for psychiatric illness
Seizures — indicate advanced CNS involvement
Motor difficulties — tremor, difficulty walking, slurred speech
Decreasing level of consciousness progressing toward coma
Critical considerations:
T. b. rhodesiense HAT can progress from initial symptoms to death within weeks if untreated — this is a true medical emergency, especially for travelers to East Africa (Tanzania, Uganda, Malawi, Zambia)
HAT is virtually 100% fatal without treatment, but highly curable when diagnosed early (stage 1 cure rates >95%)
Always inform your physician of travel to tsetse-endemic areas — HAT is rare in non-endemic countries, and clinicians may not consider the diagnosis without a clear travel history
Stage 2 disease requires treatment with drugs that cross the blood-brain barrier — delayed diagnosis significantly worsens outcomes
Most common signs and symptoms
The clinical presentation of HAT follows a biphasic pattern, with the two subspecies producing different timelines of disease progression.
Tsetse bite reaction:
Stage 1 — Hemolymphatic phase:
Intermittent fever — irregular bouts of high fever lasting days, separated by afebrile intervals; characteristic "undulant" pattern due to antigenic variation of the parasite
Lymphadenopathy — Winterbottom sign: painless, non-tender enlargement of posterior cervical lymph nodes; pathognomonic for T. b. gambiense HAT
Headache — persistent, often severe
Pruritus — generalized itching, sometimes with a transient erythematous rash (trypanids)
Hepatosplenomegaly — moderate enlargement
Edema — facial puffiness, peripheral edema
Arthralgia and myalgia
Stage 2 — Meningoencephalitic phase:
Sleep disturbance — the hallmark symptom; initially manifests as daytime somnolence and nighttime insomnia (disruption of the circadian rhythm); progresses to uncontrollable daytime sleeping episodes
Neuropsychiatric symptoms — personality changes, irritability, psychosis, depression, indifference
Motor dysfunction — tremor, fasciculations, ataxia, abnormal gait, speech disturbances (dysarthria)
Sensory disturbances — deep hyperesthesia (Kerandel sign — delayed severe pain after compression of soft tissues), generalized pruritus
Endocrine dysfunction — amenorrhea, impotence, adrenal insufficiency
Progressive deterioration — seizures, progressive obtundation, coma, and death
Timeline differences:
T. b. gambiense: Stage 1 may last months to years before CNS involvement becomes apparent; often diagnosed in stage 2
T. b. rhodesiense: Rapid progression; stage 2 can develop within weeks to a few months; often fatal within 6 months if untreated
Knowing the symptoms is the first step to a quick response.
The natural history of HAT follows a predictable two-stage progression, with the timeline differing dramatically between the two subspecies.
Tsetse bite and establishment (days 1–14):
Tsetse fly injects metacyclic trypomastigotes during a blood meal
Parasites multiply locally in the subcutaneous tissue
A trypanosomal chancre may develop at the bite site (more common with T. b. rhodesiense and in non-immune travelers)
Local lymph node invasion occurs within days
Stage 1 — Hemolymphatic phase:
Parasites enter the bloodstream and lymphatic system
Antigenic variation — T. brucei undergoes sequential changes in its variant surface glycoprotein (VSG), producing waves of parasitemia; each wave corresponds to a new antigenic variant escaping antibody response
This produces the characteristic intermittent fever pattern
Parasites disseminate to lymph nodes, liver, spleen, heart, and endocrine organs
T. b. gambiense: This stage may persist for months to years with relatively mild symptoms
T. b. rhodesiense: This stage lasts only weeks to a few months before CNS invasion; myocarditis is a frequent cause of early death
Stage 2 — Meningoencephalitic phase:
Parasites cross the blood-brain barrier and invade the CNS
Neuroinflammation: Perivascular infiltration by lymphocytes, plasma cells, and morula cells (modified plasma cells) in the brain parenchyma
Progressive disruption of circadian rhythms — mediated by parasite effects on the suprachiasmatic nucleus and melatonin/cortisol secretion
T. b. gambiense: CNS symptoms develop gradually over months to years — personality changes, sleep disturbances, cognitive decline
T. b. rhodesiense: Rapid CNS deterioration over weeks — encephalitis, coma, death
Terminal phase (untreated):
Severe somnolence (the patient becomes unarousable)
Cachexia, seizures, systemic organ failure
Death — from secondary infections, cardiac failure, or CNS deterioration
T. b. gambiense: typically within 1–3 years of symptom onset
T. b. rhodesiense: typically within 3–6 months
How this disease is identified
Diagnosis of HAT involves screening, parasitological confirmation, and staging — a three-step process critical for appropriate treatment.
Step 1 — Screening:
Card agglutination test for trypanosomiasis (CATT): Rapid serological test for T. b. gambiense; used for mass screening in endemic populations; sensitivity ~87–98%, specificity ~93–95%; not valid for T. b. rhodesiense
Rapid diagnostic tests (RDTs): Newer lateral flow tests targeting T. b. gambiense-specific antigens; increasingly replacing CATT for field use
Clinical suspicion in travelers: Any febrile illness with lymphadenopathy after travel to tsetse-endemic Africa should raise suspicion
Step 2 — Parasitological confirmation:
Blood examination:
Lymph node aspirate: Fine-needle aspiration of enlarged lymph nodes (particularly posterior cervical); Giemsa-stained smear examined for trypanosomes; useful for T. b. gambiense
Chancre aspirate: If a trypanosomal chancre is present, aspirate and examine for parasites
Note: T. b. rhodesiense typically produces higher parasitemia and is easier to detect in blood than T. b. gambiense
Step 3 — Staging (lumbar puncture):
Mandatory before treatment to determine the disease stage
Stage 2 criteria: Trypanosomes present in CSF, OR WBC >5 cells/µL, OR elevated total protein
CSF examination includes: cell count, total protein, parasite search (direct examination + centrifugation), and intrathecal IgM
Additional diagnostic methods:
PCR: Highly sensitive and specific; can detect subspecies; not widely available in endemic settings but valuable for travelers in reference laboratories
Loop-mediated isothermal amplification (LAMP): Simpler molecular test; suitable for field use
Xenodiagnosis: Feeding laboratory-reared tsetse flies on the patient — historical method, rarely used now
Available treatment methods
Treatment of HAT is stage-dependent and subspecies-specific. Accurate staging through lumbar puncture is essential to guide drug selection.
T. b. gambiense (West/Central Africa):
Stage 1 (hemolymphatic):
Stage 2 (meningoencephalitic):
Fexinidazole (oral) — WHO-recommended first-line since 2019; 1,800 mg/day for 4 days, then 1,200 mg/day for 6 days (taken with food); the first all-oral treatment for both stages; cure rate ~91% in stage 2 (with WBC <100/µL in CSF)
NECT (nifurtimox-eflornithine combination therapy) — second-line for severe stage 2 or fexinidazole failure; eflornithine 400 mg/kg/day IV in 2 infusions for 7 days + nifurtimox 15 mg/kg/day orally in 3 doses for 10 days; cure rate >96%
Eflornithine monotherapy — 400 mg/kg/day IV in 4 infusions for 14 days; effective but cumbersome (56 IV infusions)
Acoziborole — investigational single-dose oral drug; Phase III results highly promising; potential game-changer for elimination
T. b. rhodesiense (East/Southern Africa):
Stage 1:
Stage 2:
Melarsoprol — the only drug effective against stage 2 T. b. rhodesiense; 2.2 mg/kg/day IV for 10 days; cure rate ~95% BUT carries a 5% risk of fatal reactive encephalopathy (arsenical encephalopathy)
Fexinidazole and eflornithine are NOT effective against T. b. rhodesiense
Staging (lumbar puncture):
Stage 2 is defined by: trypanosomes in CSF, or WBC >5 cells/µL in CSF, or elevated CSF protein
Staging determines treatment — accurate staging is critical because stage 2 drugs have greater toxicity
Most cases are effectively treated with early diagnosis.
How to protect yourself
There is no vaccine for HAT, and no chemoprophylaxis is available. Prevention relies on tsetse fly avoidance and vector control.
Personal protective measures (essential for travelers to tsetse areas):
Wear medium-weight, neutral-colored clothing — tsetse flies are attracted to dark colors (especially blue and black) and very bright colors; khaki, olive, and tan are least attractive
Wear long sleeves and long trousers — tsetse flies can bite through thin fabric, so medium-weight material is recommended
Avoid brushy habitats near rivers and lakes during peak tsetse activity (daytime, especially early morning and late afternoon)
Inspect vehicles — tsetse flies are attracted to moving vehicles and often enter through open windows; keep windows closed when driving through tsetse habitat
DEET-based repellents — provide some protection but are less effective against tsetse than against mosquitoes and sandflies
Permethrin-treated clothing — provides additional protection
Avoid wearing dark blue or black clothing — these colors are specifically attractive to tsetse species
Vector control (public health level):
Tsetse traps and targets — blue-and-black cloth panels impregnated with insecticide; highly effective and cost-efficient for reducing tsetse populations
Sequential Aerosol Technique (SAT) — ultra-low-volume aerial spraying over tsetse habitats
Sterile Insect Technique (SIT) — release of irradiation-sterilized male tsetse flies; used successfully in Zanzibar to eliminate G. austeni
Community-based surveillance: Active case detection and treatment reduces the human reservoir for T. b. gambiense
Elimination progress:
The number of reported HAT cases has declined from ~300,000 estimated (1998) to <1,000/year (2018–present)
T. b. gambiense elimination as a public health problem achieved in several countries
The WHO roadmap targets zero transmission by 2040
Preparation is the best protection.
Risk assessment for travelers: The risk of HAT for travelers is very low overall, but cases in tourists and short-term visitors do occur, particularly in East African safari destinations where T. b. rhodesiense is transmitted. An estimated 20–40 cases are reported in travelers each decade.
Highest-risk destinations for travelers:
T. b. rhodesiense (acute form, greater concern for travelers):
T. b. gambiense (chronic form, mainly affects local populations):
High-risk activities:
Game drives and safari activities — tsetse flies inhabit woodland and savanna frequented by wildlife; they are attracted to moving vehicles
Walking safaris and bush camping — close contact with tsetse habitat
River activities — fishing, canoeing, and river crossings in tsetse-endemic areas
Practical advice:
No vaccine or chemoprophylaxis exists
Wear medium-weight, neutral-colored clothing (avoid blue and black)
Keep vehicle windows closed when driving through bush
Use DEET repellent and permethrin-treated clothing
Be aware that tsetse bites are painful (unlike mosquito bites) — this may help identify exposure
Post-travel:
A painful nodule at a bite site within 1–2 weeks of exposure should prompt urgent evaluation
Febrile illness within 3 weeks of safari travel in East Africa warrants consideration of T. b. rhodesiense — this is a medical urgency
Inform your physician of specific travel locations — HAT is often not considered in differential diagnoses outside Africa
Statistics and geographic data
Human African trypanosomiasis is endemic in sub-Saharan Africa, with a geographic distribution determined by the tsetse fly vector habitat.
Current burden (WHO, 2024):
<1,000 new cases reported annually (663 cases reported in 2022)
~55 million people at risk in 36 endemic countries
Approximately 97% of cases are caused by T. b. gambiense and 3% by T. b. rhodesiense
Historic decline: from an estimated 300,000 cases in 1998 to <1,000 in 2018–present
T. b. gambiense distribution (West and Central Africa):
Democratic Republic of Congo — reports >70% of all gambiense cases globally; provinces of Haut-Uélé, Bas-Uélé, Ituri, and Équateur are most affected
Central African Republic — second highest burden
South Sudan, Angola, Chad, Cameroon, Republic of Congo, Guinea, Côte d'Ivoire — active foci
Countries approaching elimination: Equatorial Guinea, Gabon, Ghana, Nigeria, Uganda (gambiense areas)
T. b. rhodesiense distribution (East and Southern Africa):
Uganda — the only country with both gambiense (northwest) and rhodesiense (southeast) foci
Tanzania — Serengeti ecosystem and western regions
Malawi, Zambia, Zimbabwe, Mozambique — sporadic cases
Zoonotic nature makes elimination more challenging (wildlife reservoir)
Historical epidemics:
Three major epidemics in the 20th century: 1896–1906, 1920s, and 1970s–1990s
The early 20th-century epidemic killed an estimated 300,000–500,000 in the Congo Basin alone
Colonial-era sleeping sickness campaigns were among the first large-scale public health interventions in Africa
Elimination progress:
Sustained decline due to: active surveillance, treatment, vector control (traps/targets), and political commitment
WHO has validated elimination as a public health problem (<1 case per 10,000 per year at health district level) in Togo (2020), Equatorial Guinea (2022), and other countries
2030 target: Elimination as a public health problem in all endemic countries
2040 target: Interruption of transmission (zero cases)
Challenges to elimination:
Remote and conflict-affected endemic areas with poor healthcare access
Asymptomatic carriers of T. b. gambiense may sustain transmission
Animal reservoir for T. b. rhodesiense makes elimination by treatment alone impossible
Climate change may alter tsetse fly distribution
Who is most at risk
The risk of acquiring HAT is determined primarily by exposure to tsetse flies in endemic habitats.
Geographic and environmental risk factors:
Residence in or travel to tsetse-endemic areas — 36 countries in sub-Saharan Africa; the tsetse belt extends from roughly 14°N to 29°S latitude
Proximity to tsetse habitats — riverine woodland, savanna woodland, lakeshores, and gallery forests; tsetse species have specific habitat preferences (G. palpalis group: riverine; G. morsitans group: savanna; G. fusca group: forest)
Occupational exposure — farmers, fishermen, hunters, cattle herders, and forestry workers in endemic areas have the highest exposure
Game parks and wildlife reserves — tsetse populations are maintained by wild animal blood meals; safari tourists are exposed in these settings
Behavioral risk factors:
Daytime outdoor activities in tsetse habitat — tsetse flies are diurnal feeders (unlike mosquitoes)
Wearing dark-colored clothing — tsetse flies are visually attracted to dark colors, especially blue and black
Walking through dense bush or along waterways in endemic areas
Driving through bush with windows open — tsetse are attracted to moving vehicles
Host factors:
Immune status — non-immune individuals (travelers, migrants from non-endemic areas) may develop more severe initial reactions (chancre) and faster disease progression
No acquired immunity — unlike many infections, previous HAT infection does not confer protective immunity; reinfection occurs
Age and sex — in endemic areas, peak incidence is in adults 20–40 years (reflecting occupational exposure patterns); males are more commonly affected due to greater occupational risk
Factors affecting disease severity:
Infecting subspecies — T. b. rhodesiense causes more acute and rapidly fatal disease
Delay in diagnosis — the most critical factor determining outcome; stage 2 disease has worse prognosis and requires more toxic treatment
Co-infections — HIV co-infection may alter clinical presentation and treatment outcomes
Potential complications
HAT produces complications primarily through CNS invasion and the adverse effects of treatment.
Neurological complications (Stage 2):
Progressive encephalitis — diffuse brain inflammation with perivascular cuffing by lymphocytes, plasma cells, and morula cells; leads to progressive cognitive decline, personality changes, and motor impairment
Severe sleep-wake cycle disruption — disruption of circadian rhythms leading to polyphasic sleep-wake patterns (sleeping in short bursts throughout 24 hours); results in severe daytime somnolence that progresses to stupor and coma
Seizures — generalized tonic-clonic seizures occur in advanced stage 2; may be the presenting feature
Movement disorders — cerebellar ataxia, tremor (particularly of the tongue and fingers), chorea, and dysarthria
Psychiatric manifestations — depression, psychosis, aggressive behavior; patients are sometimes misdiagnosed with psychiatric illness before HAT is considered
Endocrine dysfunction — hypothalamic-pituitary axis involvement causing amenorrhea, impotence, thyroid dysfunction, and adrenal insufficiency
Cardiac complications (especially T. b. rhodesiense):
Myocarditis — pericardial effusion and myocardial inflammation; a significant cause of early death in T. b. rhodesiense infection
Cardiac arrhythmias and conduction defects
Treatment-related complications:
Melarsoprol reactive encephalopathy — the most feared complication of HAT treatment; occurs in ~5–10% of melarsoprol-treated patients and is fatal in approximately 50% of those affected (overall treatment mortality ~5%); manifests as acute onset of coma, seizures, and cerebral edema during or shortly after treatment; prednisolone co-administration reduces but does not eliminate the risk
Eflornithine complications — bone marrow suppression (reversible), seizures, gastrointestinal toxicity
Suramin complications — nephrotoxicity, hypersensitivity reactions (urticaria, anaphylaxis), peripheral neuropathy
Post-treatment sequelae:
Residual neuropsychiatric symptoms may persist for months after successful treatment of stage 2 disease
Cognitive impairment and sleep disturbances may not fully resolve
Patients require 24 months of follow-up including lumbar punctures to detect relapse
Expected outcomes and recovery
The prognosis of HAT is primarily determined by the stage at diagnosis and the infecting subspecies.
Without treatment:
Virtually 100% fatal for both T. b. gambiense and T. b. rhodesiense
T. b. rhodesiense: Death typically within 6 months of symptom onset
T. b. gambiense: Death within 1–3 years, though some untreated patients have survived up to 6–7 years
With treatment — Stage 1:
Cure rate >95% for both forms (pentamidine for gambiense, suramin for rhodesiense)
Minimal long-term sequelae when treated in stage 1
Relapse rate <5% with adequate treatment and follow-up
With treatment — Stage 2:
T. b. gambiense with fexinidazole: ~91% cure rate (higher in patients with lower CSF WBC counts)
T. b. gambiense with NECT: >96% cure rate
T. b. rhodesiense with melarsoprol: ~95% cure rate, but 5% risk of reactive encephalopathy (often fatal; overall treatment mortality ~5%)
Neurological sequelae may persist even after successful treatment in advanced stage 2 — residual sleep disturbances, cognitive impairment, and motor deficits have been reported
Follow-up:
All treated patients require 24 months of follow-up with periodic lumbar punctures (at 6, 12, and 24 months) to detect relapse
A patient is considered cured after 24 months with no parasites and normal CSF parameters
Prognostic factors:
Stage at diagnosis — the single most important determinant; early detection dramatically improves outcomes
Infecting subspecies — T. b. rhodesiense is more rapidly fatal and treatment carries higher risk
CSF parameters — higher WBC counts and presence of trypanosomes in CSF indicate advanced stage 2 and predict lower cure rates with fexinidazole
Age and nutritional status — malnourished patients and very young or elderly patients have worse outcomes
The content on this page is for informational and educational purposes only. It does not constitute medical advice, diagnosis, or treatment recommendations. If you have health concerns, consult a qualified healthcare professional. Medova is not a medical service provider.
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