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Overview and Recommendations
Background
- •Human African trypanosomiasis (HAT), or sleeping sickness, is a parasitic disease caused by the protozoan and transmitted by the in sub-Saharan Africa. Two subspecies cause human disease: T. b. gambiense (chronic form, >95% of cases, West and Central Africa) and T. b. rhodesiense (acute form, East and Southern Africa). Untreated, HAT is uniformly fatal, with death occurring within months (rhodesiense) to years (gambiense).
- •The disease disproportionately affects rural agricultural populations, with occupational exposure (farming, fishing, hunting) increasing risk. Incidence has fallen dramatically from an estimated 50,000-70,000 cases in 2009 to fewer than 3000 reported cases per year, driven by sustained control efforts. The WHO has targeted elimination of transmission of gambiense HAT by 2030.
- •The central pathogenic mechanism is antigenic variation of the (VSG) coat, which allows the parasite to continuously evade the host antibody response. To survive in humans, T. b. rhodesiense expresses the serum resistance-associated (SRA) protein, while T. b. gambiense uses the TgsGP glycoprotein, both neutralizing the host trypanolytic factor . Genetic variants in APOL1 (G1 and G2) that protect against rhodesiense infection paradoxically accelerate gambiense disease progression.
- •HAT progresses through two stages: the hemolymphatic stage (stage 1), with parasites in blood and lymph, and the meningoencephalitic stage (stage 2), defined by invasion of the central nervous system (CSF white cell count >5/μL or trypanosomes in CSF). Stage 2 disease requires drugs that cross the blood-brain barrier. Recent evidence also identifies a dermal reservoir of extravascular trypanosomes that may maintain transmission even when blood parasitemia is undetectable.
Evaluation
- •Suspect HAT in any patient with fever, headache, arthralgias, and progressive neurologic symptoms who has lived in or traveled to rural sub-Saharan Africa, even if the exposure was remote. The incubation period ranges from 1-3 weeks (rhodesiense) to months or years (gambiense).
- •Ask about exposure to tsetse flies, occupational activities (farming, hunting, fishing), and duration of symptoms. In gambiense HAT, symptoms evolve slowly over months; in rhodesiense HAT, onset is acute with high fever and rapid progression.
- •Examine for the classic painless chancre at the tsetse fly bite site (appears 5-15 days after bite), posterior cervical lymphadenopathy ( ), and hepatosplenomegaly. Later findings include sleep-wake cycle inversion (daytime somnolence, nighttime insomnia), personality changes, ataxia, tremor, seizures, and coma.
- •Order parasitological confirmation: examine thick and thin blood smears, lymph node aspirate, or CSF for motile trypanosomes. In gambiense HAT, parasitemia may be low; concentration techniques (e.g., mini anion-exchange centrifugation) increase sensitivity. Serological screening with the (card agglutination test for trypanosomiasis) is used in endemic areas but requires parasitological confirmation.
- •Perform lumbar puncture for CSF analysis to determine disease stage. Stage 2 is defined by CSF white cell count >5/μL or the presence of trypanosomes in CSF. However, according to WHO 2024 guidelines, lumbar puncture may be omitted if fexinidazole is intended and there is no clinical suspicion of severe stage 2 (CSF WBC ≥100/μL).
- •Assess severity using performance status ( score) and neurological assessment ( for rhodesiense HAT). CSF biomarkers such as IL-10 ≥37 pg/mL and WBC ≥102/μL predict treatment failure.
- •Also consider alternative diagnoses: malaria, tuberculosis, HIV, neurosyphilis, viral encephalitis, and other causes of lymphadenopathy and fever. In travelers, acute febrile illness with neurologic features should prompt consideration of HAT.
Management
- •Initiate as first-line therapy for all patients aged ≥6 years and weighing ≥20 kg with either gambiense or rhodesiense HAT, regardless of disease stage (WHO 2024 strong recommendation). Dose: for patients ≥35 kg, give 1800 mg (three 600 mg tablets) orally once daily with food for 4 days (loading), then 1200 mg once daily for 6 days (maintenance). For patients 20-34 kg, give 1200 mg once daily for 4 days, then 600 mg once daily for 6 days. Total treatment duration is 10 days.
- •For patients with contraindications to fexinidazole (hypersensitivity to nitroimidazoles, severe hepatic impairment, congenital QT prolongation, history of cardiac arrhythmia) or those with CSF WBC ≥100/μL (severe stage 2), use (nifurtimox-eflornithine combination therapy): eflornithine 400 mg/kg/day intravenously in two 2-hour infusions for 7 days, plus nifurtimox 15 mg/kg/day orally in three divided doses for 10 days.
- •For stage 1 gambiense HAT in children <6 years or weighing <20 kg, use 4 mg/kg/day intramuscularly for 7 days. Avoid intravenous administration due to risk of severe hypotension.
- •For rhodesiense HAT when fexinidazole is unavailable: use for stage 1 (test dose 100 mg IV, then 20 mg/kg IV on days 1, 3, 7, 14, 21) or for stage 2 (2.2 mg/kg/day IV for 10 days, with corticosteroids to prevent encephalopathy). Melarsoprol is highly toxic and should be avoided if alternatives exist.
- •Monitor for adverse events during fexinidazole therapy: vomiting (occurs in 24-69%; repeat dose if within 30 minutes), QT prolongation (mean QTcF increase ~10 ms; obtain baseline ECG and monitor), neuropsychiatric reactions (insomnia, anxiety, rarely suicidal ideation), and mild neutropenia/thrombocytopenia. Hospitalize for the first 10 days of treatment; selected outpatients with caregiver support may complete therapy at home.
- •Assess treatment response at follow-up visits at 3, 6, 12, and 18 months post-treatment. At each visit, perform clinical examination, parasitological tests (blood and CSF), and CSF cell count. A CSF WBC ≤5 cells/μL at 6 months indicates cure (negative predictive value >0.93). A CSF WBC ≥8 cells/μL combined with LATEX/IgM titer ≥1:4 at 12 months predicts treatment failure with 97% specificity.
- •If treatment failure is confirmed (trypanosomes detected or CSF criteria not met), switch to an alternative regimen: for gambiense HAT, change from fexinidazole to NECT; for rhodesiense HAT, change from fexinidazole to melarsoprol (or suramin if stage 1).
- •Do not use melarsoprol for gambiense HAT when fexinidazole or NECT is available. Do not use non-dihydropyridine calcium channel blockers (diltiazem, verapamil) as they may exacerbate heart failure if present. Do not administer pentamidine intravenously.
- •Refer patients with suspected HAT to an infectious disease specialist or tropical medicine center. Hospitalization is recommended for initiation of therapy and management of adverse events. Discharge criteria include completion of the 10-day course, stable vital signs, and no severe adverse events requiring inpatient care.
- •For pregnant women after the first trimester and breastfeeding women, fexinidazole is considered safe based on limited data; administer in hospital. For children <6 years or <20 kg, use NECT or pentamidine as appropriate.
Board Review — High Yield
- •Winterbottom's sign, Painless posterior cervical lymphadenopathy in gambiense HAT.
- •VSG coat, Variant surface glycoprotein enables antigenic variation and immune evasion.
- •APOL1, Human trypanolytic factor; G1/G2 variants protect against rhodesiense but accelerate gambiense.
- •CSF WBC >5/μL, Defines stage 2 (meningoencephalitic) disease.
- •Fexinidazole, Oral nitroimidazole, first-line for both subspecies, effective across all stages.
- •NECT, Nifurtimox-eflornithine combination therapy for severe stage 2 gambiense HAT.
- •Melarsoprol, Arsenical drug, highly toxic (encephalopathy), now replaced by fexinidazole.
- •Tsetse fly, Glossina spp., vector for both T. b. gambiense and T. b. rhodesiense.
- •Elimination target, WHO aims for elimination of transmission of gambiense HAT by 2030.
- •Dermal reservoir, Extravascular trypanosomes in skin may maintain transmission even when blood parasitemia is undetectable.
Deep Dive — Evidence Details
Definition, Classification and Causative Organisms
- ▸Two human-pathogenic subspecies: *T. b. gambiense* (chronic, >95% cases) and *T. b. rhodesiense* (acute) [9][12].
- ▸Disease staging (CSF WBC ≤20 vs >20/μL) determines need for CNS-penetrating drugs [2][3].
Human African trypanosomiasis (HAT) is caused by Trypanosoma brucei subspecies: T. b. gambiense (chronic, West/Central Africa) and T. b. rhodesiense (acute, East/Southern Africa) [9]C4[12]D5. T. b. brucei causes animal disease only [13]D5. Disease stages guide treatment: Stage 1 (hemolymphatic) with CSF WBC ≤20/μL; Stage 2 (meningoencephalitic) with CSF WBC >20/μL or parasites in CSF [2]D5[3]C4. Stage 2 requires drugs crossing the blood-brain barrier (melarsoprol, eflornithine, fexinidazole) [2]D5[3]C4. Fexinidazole is approved only for gambiense HAT; rhodesiense HAT still requires suramin or melarsoprol depending on stage.
Pearl: The distinction between T. b. gambiense and T. b. rhodesiense is critical because treatment regimens differ: fexinidazole is approved only for gambiense HAT, while rhodesiense HAT still requires suramin or melarsoprol depending on stage.
Microbiology and Pathogenesis
- ▸VSG antigenic switching is key to immune evasion [23][30].
- ▸APOL1 G1/G2 variants have opposing effects on subspecies [35].
Pathogenesis hinges on antigenic variation of the variant surface glycoprotein (VSG) coat, enabling immune evasion [23]D5[30]D5. T. b. rhodesiense expresses SRA protein to neutralize APOL1; T. b. gambiense uses TgsGP [23]D5[25]D5[27]D5[30]D5. Additional evasion: polyclonal B cell activation, memory B cell destruction, regulatory T cell induction [23]D5[30]D5. Infection begins with tsetse bite, local chancre, then dissemination [23]D5[29]D5. Stage 1 involves M1 macrophage activation, anemia via galectin-3 and MIF [23]D5[30]D5[33]D5. Stage 2: trypanosomes cross blood-brain barrier, causing neuroinflammation and sleep-wake disruption [23]D5[26]D5[32]D5. APOL1 G1/G2 variants protect against T. b. rhodesiense but paradoxically accelerate T. b. gambiense [35]B3b.
Pearl: The two human-infective subspecies use entirely different molecular mechanisms (SRA in T. b. rhodesiense, TgsGP in T. b. gambiense) to neutralize the same host trypanolytic factor APOL1, and the APOL1 G1/G2 variants that protect against T. b. rhodesiense paradoxically accelerate T. b. gambiense disease progression [35]B3b.
Epidemiology, Transmission and Risk Factors
- ▸Incidence <3000/year; elimination target 2030 [46][47].
- ▸Dermal reservoir may sustain transmission [39][51].
Incidence <3000 reported cases/year; elimination of gambiense transmission targeted for 2030 [46]D5[47]D5[50]D5. Almost all cases are T. b. gambiense in West/Central Africa; T. b. rhodesiense in East/Southern Africa [50]D5. Risk factors: residence in endemic rural areas, occupational exposure (farming, fishing, hunting), travel to endemic regions [47]D5[50]D5[53]C4[54]C4[55]C4. Iatrogenic transmission historically via reused needles [42]B3b. Dermal reservoir: extravascular trypanosomes in skin of seropositive individuals (up to 71% of confirmed cases) may maintain transmission even with undetectable blood parasitemia [39]C4[51]B2b. Imported cases occur in travelers; consider HAT in febrile neurologic illness with exposure history [47]D5[53]C4[54]C4[55]C4.
Pearl: In any febrile patient with progressive neurologic symptoms who has lived in or travelled to sub-Saharan Africa, even if incidence is low, consider HAT and obtain a careful exposure history, including remote visits to rural areas, because imported cases continue to occur and the disease is fatal if untreated [47]D5[53]C4[54]C4[55]C4.
Severity Assessment and Risk Stratification
- ▸CSF WBC >5/μL defines stage 2; fexinidazole may eliminate need for LP [68][70].
- ▸Geographic focus affects progression rate [69].
Staging based on CSF WBC count: WHO defines late-stage as trypanosomes in CSF or CSF WBC >5 cells/μL [69]B3b. A threshold of 5 cells/μL is safer than 10 cells/μL for defining stage 2, especially when eflornithine is available [70]C4. Further subdivision: early stage 2 (CSF WBC 6-20/μL) and late stage 2 (>20/μL) [68]C4. Fexinidazole is effective across all stages, so lumbar puncture may be unnecessary unless severe stage 2 (CSF WBC ≥100/μL) is suspected [68]C4[89]D5. Clinical severity: Karnofsky score >50 and ability to eat for fexinidazole trials [68]C4; Glasgow Coma Score ≤8 in rhodesiense HAT associated with fatal outcome [69]B3b. Geographic focus affects progression: Soroti focus (Uganda) progresses in <2 months; Nkhotakota (Malawi) chronic [69]B3b. Higher plasma IFN-γ associated with rapid CNS invasion [81]D5.
Pearl: A CSF WBC threshold of 5 cells/μL is safer than 10 cells/μL for defining stage 2 gambiense HAT, but the advent of fexinidazole, effective across all stages, may soon make lumbar puncture unnecessary for treatment decisions in most patients [68]C4[70]C4.
| Stage | CSF WBC count (cells/μL) | Trypanosomes in CSF | Typical treatment |
|---|---|---|---|
| Stage 1 (hemolymphatic) | ≤5 | Absent | Pentamidine or fexinidazole [68]C4 |
| Early stage 2 (meningoencephalitic) | 6-20 | May be present | Fexinidazole or NECT [68]C4 |
| Late stage 2 (meningoencephalitic) | >20 | May be present | NECT or fexinidazole [68]C4 |
Empiric Management, Acute Care and Source Control
- ▸Fexinidazole first-line for both subspecies, all stages, ≥6 yr, ≥20 kg [86][89].
- ▸NECT for severe stage 2 (CSF WBC ≥100/μL) or contraindications [92].
WHO 2024 guidelines: fexinidazole is first-line for most patients with gambiense or rhodesiense HAT (≥6 years, ≥20 kg), regardless of stage [86]B2a[89]D5[92]D5. Lumbar puncture not required unless CSF WBC ≥100/μL suspected (then use NECT) [89]D5. Fexinidazole dosing: loading 1800 mg (≥35 kg) or 1200 mg (20-34 kg) once daily for 4 days, then maintenance 1200 mg or 600 mg once daily for 6 days [92]D5. Total 10 days. Must be taken with food. Monitor for vomiting, QT prolongation, neuropsychiatric reactions, neutropenia [90]A1b[92]D5. Alternative regimens: NECT (eflornithine 400 mg/kg/day IV + nifurtimox 15 mg/kg/day PO for 10 days) for severe stage 2 or contraindications [92]D5; pentamidine 4 mg/kg/day IM for 7 days for stage 1 in children <6 years or <20 kg [92]D5; suramin for stage 1 rhodesiense if fexinidazole unavailable [86]B2a. Treatment failure: switch to NECT (gambiense) or melarsoprol (rhodesiense) [92]D5. Follow-up at 3,6,12,18 months; CSF WBC ≤5/μL at 6 months indicates cure [67]A1b.
| Option | Indication / Line | Dose or Specifics | Key Trial | Outcome | Evidence Level |
|---|---|---|---|---|---|
| Fexinidazole | First-line for gambiense and rhodesiense HAT (≥6 yr, ≥20 kg) | Oral: 1800/1200 mg (≥35 kg) or 1200/600 mg (20-34 kg) daily ×10 days [92]D5 | FEX004 (N=394) [43]B2b; FEX006 (N=125) [90]A1b; rhodesiense study (N=45) [94]B2b | 91% success at 18 mo (gambiense) [43]B2b; 0% fatality (rhodesiense stage 2) [94]B2b | 1b (gambiense), 2b (rhodesiense) |
| NECT | First-line for gambiense HAT with CSF WBC ≥100/μL; second-line for fexinidazole failure | Eflornithine 400 mg/kg/day IV ×7 d + nifurtimox 15 mg/kg/day PO ×10 d [92]D5 | NECT pivotal trial (N=286) [41]A1b | 96.5% cure (ITT) [41]A1b | 1b |
| Pentamidine | First-line for stage 1 gambiense HAT in children <6 yr or <20 kg | 4 mg/kg/day IM ×7 d [92]D5 | Historical controls | ~92% cure (meta-analysis) [90]A1b | 4 |
| Acoziborole | Investigational; single-dose for gambiense HAT (≥15 yr) | Single oral 960 mg dose [87]B2b | Phase 2/3 (N=208) [87]B2b | 95.2% success at 18 mo (late-stage) [87]B2b | 2b |
| Drug | Starting dose | Target / max dose | Renal adjustment | Hepatic adjustment | Key monitoring |
|---|---|---|---|---|---|
| Fexinidazole (≥35 kg) | 1800 mg PO once daily days 1-4 | 1200 mg PO once daily days 5-10 | No data | Contraindicated in severe impairment | ECG (QTc), LFT, FBC, neuropsychiatric |
| Fexinidazole (20-34 kg) | 1200 mg PO once daily days 1-4 | 600 mg PO once daily days 5-10 | No data | Contraindicated in severe impairment | Same as above |
| Eflornithine (NECT) | 400 mg/kg/day IV in 2 divided 2-h infusions | Same for 7 days | No data | No data | FBC, electrolytes, renal function |
| Nifurtimox (NECT) | 15 mg/kg/day PO in 3 divided doses | Same for 10 days | No data | No data | FBC, LFT, GI tolerance |
| Pentamidine | 4 mg/kg/day IM | Same for 7 days | No data | No data | Blood glucose, BP, ECG, renal function |
| Acoziborole | 960 mg PO single dose | Single dose | No data | No data | FBC, LFT |
Pearl: Initiate fexinidazole as first-line empiric therapy for all patients aged ≥6 years and weighing ≥20 kg with either gambiense or rhodesiense HAT, regardless of stage; avoid lumbar puncture unless clinical suspicion of CSF leucocyte count ≥100/μL, in which case use NECT instead (WHO 2024) [86]B2a[89]D5.
| Bodyweight | Loading dose (days 1-4) | Maintenance dose (days 5-10) |
|---|---|---|
| ≥35 kg | 1800 mg (3 tablets) once daily | 1200 mg (2 tablets) once daily |
| 20-34 kg | 1200 mg (2 tablets) once daily | 600 mg (1 tablet) once daily |
| Option | Indication / Line | Dose or Specifics | Key Trial | Outcome | Evidence Level |
|---|---|---|---|---|---|
| Fexinidazole | First-line for gambiense and rhodesiense HAT (≥6 yr, ≥20 kg) | Oral: 1800/1200 mg (≥35 kg) or 1200/600 mg (20-34 kg) daily ×10 days [92]D5 | FEX004 (N=394) [43]B2b; rhodesiense study (N=45) [94]B2b | 91% success at 18 mo (gambiense) [43]B2b; 0% fatality (rhodesiense stage 2) [94]B2b | 1b (gambiense), 2b (rhodesiense) |
| NECT | First-line for gambiense HAT with CSF WBC ≥100/μL; second-line for fexinidazole failure | Eflornithine 400 mg/kg/day IV ×7 d + nifurtimox 15 mg/kg/day PO ×10 d [92]D5 | NECT pivotal trial (N=286) [41]A1b | 96.5% cure (ITT) [41]A1b | 1b |
| Pentamidine | First-line for stage 1 gambiense HAT in children <6 yr or <20 kg | 4 mg/kg/day IM ×7 d [92]D5 | Historical controls | ~92% cure (meta-analysis) [90]A1b | 4 |
| Acoziborole | Investigational; single-dose for gambiense HAT (≥15 yr) | Single oral 960 mg dose [87]B2b | Phase 2/3 (N=208) [87]B2b | 95.2% success at 18 mo (late-stage) [87]B2b | 2b |
Antimicrobial Resistance and Stewardship
- ▸Cross-resistance between fexinidazole and nifurtimox; pentamidine and melarsoprol [111][65].
- ▸SHERLOCK assays can detect resistance markers [65].
Resistance threatens elimination targets [92]D5[116]B2a. Fexinidazole resistance via TbNTR1 loss; cross-resistance with nifurtimox [111]D5. Pentamidine/melarsoprol resistance via TbAQP2 deletion/chimerization (AQP2/3(814) chimera detected in 31.7% of melarsoprol-resistant infections) [65]D5[92]D5[116]B2a. Eflornithine resistance via AAT6 loss [113]D5[116]B2a. Acoziborole resistance via CPSF3 N232H mutation [65]D5[118]D5. SHERLOCK assays detect resistance markers [65]D5. Stewardship: use combination therapy (NECT, fexinidazole), ensure adherence, monitor for relapse up to 24 months [92]D5[116]B2a[120]D5. WHO 2024 recommendation to replace melarsoprol with fexinidazole for rhodesiense stage 2 is a key stewardship measure [92]D5.
| Drug | Resistance Mechanism | Genetic Basis | Cross-Resistance |
|---|---|---|---|
| Fexinidazole | Reduced activation | TbNTR1 loss/mutation | Nifurtimox [111]D5 |
| Nifurtimox | Reduced activation | TbNTR1 loss/mutation | Fexinidazole [111]D5 |
| Pentamidine | Impaired uptake | TbAQP2 deletion/chimerization; TbAT1 loss | Melarsoprol [65]D5[92]D5 |
| Melarsoprol | Impaired uptake | TbAQP2 deletion/chimerization; TbAT1 loss | Pentamidine [65]D5 |
| Eflornithine | Impaired uptake | AAT6 loss | None reported |
| Acoziborole | Target alteration | CPSF3 N232H mutation | None reported [65]D5 |
Pearl: The greatest stewardship intervention is the 2024 WHO recommendation to use fexinidazole as first-line for both gambiense and rhodesiense HAT, as oral therapy with a high barrier to resistance reduces the selection pressure that drove melarsoprol failure rates exceeding 50% in some foci [65]D5[92]D5.
Complications
- ▸Vomiting and seizures are common but manageable [40][41][68].
- ▸QT prolongation and neutropenia require monitoring [92].
Drug-related adverse events are common. NECT: 14% grade 3-4 reactions; 86% at least one AE (vomiting, dizziness, headache, convulsions) [40]C4[41]A1b. Fexinidazole: 93% AEs (nausea, vomiting, headache, asthenia, dizziness, insomnia, tremor) [68]C4; vomiting in 69% of children [127]B2b. Pentamidine: hypotension ~10% IM, up to 75% IV; also azotemia, thrombocytopenia, QT prolongation, anaphylaxis [92]D5. Melarsoprol: life-threatening encephalopathy [86]B2a. Cardiovascular: ECG changes common but benign; drug-induced QT prolongation with fexinidazole/pentamidine [88]D5[92]D5. Neurological: seizures (4-6% with NECT/fexinidazole), neuropsychiatric reactions [41]A1b[92]D5. Gastrointestinal: fexinidazole causes more GI AEs than pentamidine/NECT (63% vs 19%) [105]B3b. Hematologic: neutropenia, thrombocytopenia with pentamidine/NECT [92]D5. In-hospital mortality: NECT-FIELD [129]B2b; fexinidazole trials low [68]C4[87]B2b.
| Complication | Frequency | Prevention | Management |
|---|---|---|---|
| Hypotension (pentamidine) | ~10% IM, up to 75% IV [92]D5 | Use IM route; patient lies down 1 h post-injection; monitor vital signs [92]D5 | IV fluids, vasopressors if severe; discontinue if refractory |
| Seizures (NECT/fexinidazole) | ~4-6% [41]A1b | Screen for risk factors; ensure anticonvulsant availability | Benzodiazepines; evaluate for other causes |
| Vomiting (fexinidazole) | 63-69% [105]B3b[127]B2b | Administer with food; antiemetic prophylaxis | Antiemetics; re-dose if vomiting within 30 min [92]D5 |
| Neutropenia (fexinidazole) | ~3% [68]C4 | Monitor CBC during treatment | Hold drug if severe; supportive care |
| QT prolongation (fexinidazole/pentamidine) | Rare [92]D5 | ECG before and during therapy; correct electrolytes | Discontinue drug; cardiology consult |
Pearl: The most common complications of HAT therapy are gastrointestinal and neurological; vomiting and seizures are manageable with antiemetics and anticonvulsants, but QT prolongation and neutropenia require active monitoring.
Prognosis and Natural History
- ▸NECT cure rate 94.1% at 24 months; fexinidazole 91% at 18 months [103][43].
- ▸CSF WBC ≤5/μL at 6 months indicates cure [67].
Untreated HAT is uniformly fatal [48]B3b. Treated outcomes: NECT cure rate 94.1% at 24 months [103]B2b; fexinidazole 91% success at 18 months (non-inferior to NECT) [43]B2b; real-world fexinidazole 93% effectiveness [90]A1b; pentamidine >92% for stage 1 [90]A1b. Predictors of treatment failure: pretreatment CSF WBC ≥102/μL, CSF IL-10 ≥37 pg/mL, LATEX/IgM ≥1:32 [67]A1b. Post-treatment: CSF WBC ≤5/μL at 6 months indicates cure (NPV >0.93); at 12 months, CSF WBC ≥8/μL + LATEX/IgM ≥1:4 predicts failure (97% specificity) [67]A1b. SL-RNA detection in blood/CSF shows ≥98.9% specificity for outcome assessment [62]B2b.
Pearl: A CSF WBC count ≤5 cells/μL at 6 months post-treatment reliably indicates cure; values ≥8 cells/μL with elevated LATEX/IgM at 12 months predict relapse with 97% specificity, these thresholds guide decisions on rescue therapy.
| Regimen | Population | Follow-up | Success Rate | Relapse Rate | Mortality |
|---|---|---|---|---|---|
| NECT [103]B2b | Stage 2, field setting (n=629) | 24 months | 94.1% | 1.3% | 4.3% (mostly unrelated) |
| Fexinidazole [43]B2b | Stage 2, pivotal trial (n=264) | 18 months | 91% | Not reported separately | 3% (9/264) |
| Fexinidazole [90]A1b | All stages, wider population (n=174) | 18 months | 93% | 5% (9/174) | 0.6% (1/174, unrelated) |
| Pentamidine [90]A1b | Stage 1 (historical meta-analysis) | Variable | ~92% | Not reported | Not reported |
Prevention and Infection Control
- ▸No vaccine or RCT for prevention [136][140].
- ▸Vector avoidance and surveillance are key [136][143].
No vaccine available; no RCT for any prevention strategy [136]A1a[140]D5. Vector control: long-sleeved neutral clothing, insecticide-treated nets, permethrin on clothing; community-level bush clearing and traps [136]A1a. Surveillance: active and passive screening; optimized placement of diagnostic facilities can maintain coverage [143]D5. Iatrogenic transmission prevention: single-use needles, standard precautions [137]D5. Travelers: avoid tsetse bites; seek evaluation for fever or chancre after exposure [142]D5. Patient education: early presentation for screening in endemic areas.
Pearl: No RCT has ever evaluated a prevention strategy for human African trypanosomiasis [136]A1a; vector avoidance, optimized passive surveillance, and injection safety remain the only evidence-informed interventions, and the projected rise in disease burden [138]B3b underscores the urgency of filling this evidence gap.
Special Hosts and Populations
- ▸Fexinidazole first-line for children ≥6 yr, ≥20 kg; success 97.6% [127].
- ▸Pregnant women after first trimester can receive fexinidazole [90].
Children ≥6 yr and ≥20 kg: fexinidazole first-line; success 97.6% at 12 months [127]B2b. Dosing weight-based: 20-34 kg: 1200 mg loading, 600 mg maintenance; ≥35 kg: adult regimen [127]B2b. Common AEs: vomiting (69%), headache (33%) [127]B2b. Children <6 yr or <20 kg: NECT preferred [89]D5. Pregnant women: fexinidazole after first trimester considered safe; NECT also used [90]A1b[103]B2b[129]B2b. Breastfeeding: fexinidazole safe [90]A1b. Immunocompromised: limited data; use standard stage-based treatment with close monitoring [59]D5. Elderly/organ dysfunction: caution with fexinidazole in severe hepatic/renal impairment; NECT for Karnofsky ≤40 or very advanced disease [3]C4[89]D5[90]A1b.
Pearl: Fexinidazole is now first-line for most patients aged ≥6 years and weighing ≥20 kg, including pregnant women after the first trimester and breastfeeding women, but NECT remains the preferred regimen for those with CSF white blood cell count ≥100/μL or severe clinical disease.
| Bodyweight | Loading dose (days 1-4) | Maintenance dose (days 5-10) |
|---|---|---|
| 20 kg to <35 kg | 1200 mg (2 × 600 mg) once daily | 600 mg (1 × 600 mg) once daily |
| ≥35 kg | 1800 mg (3 × 600 mg) once daily | 1200 mg (2 × 600 mg) once daily |
References
- [1]
Yansouni CP, Bottieau E, Lutumba P et al.. “Rapid diagnostic tests for neurological infections in central Africa.” The Lancet. Infectious diseases (2013). PMID: 23623369 ↗
L5NARRATIVE_REVIEWCited in: Definition, Classification and Causative Organisms, Microbiology and Pathogenesis, Clinical Presentation, Diagnosis and Workup, Empiric Management, Acute Care and Source Control, Complications, Special Hosts and Populations - [2]
Yang G, Zhu W, Kim K et al.. “In Vitro and In Vivo Investigation of the Inhibition of Trypanosoma brucei Cell Growth by Lipophilic Bisphosphonates.” Antimicrobial agents and chemotherapy (2015). PMID: 26392508 ↗
L5NARRATIVE_REVIEWCited in: Definition, Classification and Causative Organisms, Epidemiology, Transmission and Risk Factors, Prognosis and Natural History - [3]
Watson JA, Strub-Wourgraft N, Tarral A et al.. “Pharmacokinetic-Pharmacodynamic Assessment of the Hepatic and Bone Marrow Toxicities of the New Trypanoside Fexinidazole.” Antimicrobial agents and chemotherapy (2019). PMID: 30670439 ↗
L4PHASE_1_TRIALCited in: Definition, Classification and Causative Organisms, Empiric Management, Acute Care and Source Control, Definitive Therapy: Dosing, PK/PD, Duration and De-escalation, Special Hosts and Populations - [4]
Cammerer SB, Jimenez C, Jones S et al.. “Quinuclidine derivatives as potential antiparasitics.” Antimicrobial agents and chemotherapy (2007). PMID: 17709461 ↗
L5OTHERCited in: Definition, Classification and Causative Organisms - [5]
Bot C, Hall BS, Alvarez G et al.. “Evaluating 5-nitrofurans as trypanocidal agents.” Antimicrobial agents and chemotherapy (2013). PMID: 23335745 ↗
L5OTHERCited in: Definition, Classification and Causative Organisms, Antimicrobial Resistance and Stewardship - [6]
Efstathiou A, Gaboriaud-Kolar N, Myrianthopoulos V et al.. “Indirubin Analogues Inhibit Trypanosoma brucei Glycogen Synthase Kinase 3 Short and T. brucei Growth.” Antimicrobial agents and chemotherapy (2019). PMID: 30910902 ↗
L5OTHERCited in: Definition, Classification and Causative Organisms, Prognosis and Natural History - [7]
Jones AJ, Kaiser M, Avery VM. “Identification and Characterization of FTY720 for the Treatment of Human African Trypanosomiasis.” Antimicrobial agents and chemotherapy (2015). PMID: 26666915 ↗
L5OTHERCited in: Definition, Classification and Causative Organisms - [8]
Sevidzem SL, Koumba AA, Mavoungou JF et al.. “Spatial meta-analysis of the occurrence and distribution of tsetse-transmitted animal trypanosomiasis in Cameroon over the last 30 years.” Epidemiology and infection (2022). PMID: 35473820 ↗
L2SR_COHORTCited in: Definition, Classification and Causative Organisms - [9]
Nambala P, Mulindwa J, Noyes H et al.. “Differences in gene expression profiles in early and late stage rhodesiense HAT individuals in Malawi.” PLoS neglected tropical diseases (2023). PMID: 38055777 ↗
L4CASE_CONTROLCited in: Definition, Classification and Causative Organisms - [10]
Henriquez-Figuereo A, Morán-Serradilla C, Angulo-Elizari E et al.. “Small molecules containing chalcogen elements (S, Se, Te) as new warhead to fight neglected tropical diseases.” European journal of medicinal chemistry (2022). PMID: 36493616 ↗
L5NARRATIVE_REVIEWCited in: Definition, Classification and Causative Organisms - [11]
De Rycker M, Wyllie S, Horn D et al.. “Anti-trypanosomatid drug discovery: progress and challenges.” Nature reviews. Microbiology (2022). PMID: 35995950 ↗
L5NARRATIVE_REVIEWCited in: Definition, Classification and Causative Organisms - [12]
Hasker E, Hope A, Bottieau E. “Gambiense human African trypanosomiasis: the bumpy road to elimination.” Current opinion in infectious diseases (2022). PMID: 35942856 ↗
L5NARRATIVE_REVIEWCited in: Definition, Classification and Causative Organisms - [13]
Lukeš J, Kachale A, Votýpka J et al.. “African trypanosome strategies for conquering new hosts and territories: the end of monophyly?” Trends in parasitology (2022). PMID: 35680542 ↗
L5NARRATIVE_REVIEWCited in: Definition, Classification and Causative Organisms - [14]
de Castro Neto AL, da Silveira JF, Mortara RA. “Role of Virulence Factors of Trypanosomatids in the Insect Vector and Putative Genetic Events Involved in Surface Protein Diversity.” Frontiers in cellular and infection microbiology (2022). PMID: 35573777 ↗
L5NARRATIVE_REVIEWCited in: Definition, Classification and Causative Organisms - [15]
Steketee PC, Giordani F, Vincent IM et al.. “Transcriptional differentiation of Trypanosoma brucei during in vitro acquisition of resistance to acoziborole.” PLoS neglected tropical diseases (2021). PMID: 34752454 ↗
L5NARRATIVE_REVIEWCited in: Definition, Classification and Causative Organisms - [16]
Tamgue O, Mezajou CF, Ngongang NN et al.. “Non-Coding RNAs in the Etiology and Control of Major and Neglected Human Tropical Diseases.” Frontiers in immunology (2021). PMID: 34737736 ↗
L5NARRATIVE_REVIEWCited in: Definition, Classification and Causative Organisms - [17]
de Castro Neto AL, da Silveira JF, Mortara RA. “Comparative Analysis of Virulence Mechanisms of Trypanosomatids Pathogenic to Humans.” Frontiers in cellular and infection microbiology (2021). PMID: 33937106 ↗
L5NARRATIVE_REVIEWCited in: Definition, Classification and Causative Organisms, Microbiology and Pathogenesis - [18]
Kaufer A, Stark D, Ellis J. “A review of the systematics, species identification and diagnostics of the Trypanosomatidae using the maxicircle kinetoplast DNA: from past to present.” International journal for parasitology (2020). PMID: 32333942 ↗
L5NARRATIVE_REVIEWCited in: Definition, Classification and Causative Organisms - [19]
Matos ÂP, Saldanha-Corrêa FMP, Gomes RDS et al.. “Exploring microalgal and cyanobacterial metabolites with antiprotozoal activity against Leishmania and Trypanosoma parasites.” Acta tropica (2023). PMID: 38159713 ↗
L5NARRATIVE_REVIEWCited in: Definition, Classification and Causative Organisms - [20]
Dofuor AK, Ademolue TS, Kuampah KNA et al.. “In Vitro Mechanism of Action of Acanthospermum hispidum in Trypanosoma brucei.” Advances in pharmacological and pharmaceutical sciences (2022). PMID: 36304140 ↗
L5NARRATIVE_REVIEWCited in: Definition, Classification and Causative Organisms - [21]
Rodenko B, Wanner MJ, Alkhaldi AA et al.. “Targeting the parasite's DNA with methyltriazenyl purine analogs is a safe, selective, and efficacious antitrypanosomal strategy.” Antimicrobial agents and chemotherapy (2015). PMID: 26282430 ↗
L5OTHERCited in: Microbiology and Pathogenesis - [22]
Lucinda PPD, Sinton MC, Quintana JF et al.. “Dual faces of γδ T cells in trypanosomatid infections.” Trends in parasitology (2026). PMID: 41833460 ↗
L5NARRATIVE_REVIEWCited in: Microbiology and Pathogenesis - [23]
Morrison LJ, Steketee PC, Tettey MD et al.. “Pathogenicity and virulence of African trypanosomes: From laboratory models to clinically relevant hosts.” Virulence (2023). PMID: 36419235 ↗
L5NARRATIVE_REVIEWCited in: Microbiology and Pathogenesis - [24]
Álvarez-Rodríguez A, Jin BK, Radwanska M et al.. “Recent progress in diagnosis and treatment of Human African Trypanosomiasis has made the elimination of this disease a realistic target by 2030.” Frontiers in medicine (2022). PMID: 36405602 ↗
L5NARRATIVE_REVIEWCited in: Microbiology and Pathogenesis - [25]
Pays E, Radwanska M, Magez S. “The Pathogenesis of African Trypanosomiasis.” Annual review of pathology (2022). PMID: 36055769 ↗
L5NARRATIVE_REVIEWCited in: Microbiology and Pathogenesis, Antimicrobial Resistance and Stewardship, Prevention and Infection Control - [26]
Ngarka L, Siewe Fodjo JN, Aly E et al.. “The Interplay Between Neuroinfections, the Immune System and Neurological Disorders: A Focus on Africa.” Frontiers in immunology (2022). PMID: 35095888 ↗
L5NARRATIVE_REVIEWCited in: Microbiology and Pathogenesis - [27]
Pays E, Nolan DP. “Genetic and immunological basis of human African trypanosomiasis.” Current opinion in immunology (2021). PMID: 33721725 ↗
L5NARRATIVE_REVIEWCited in: Microbiology and Pathogenesis - [28]
Parab AR, McCall LI. “Tryp-ing Up Metabolism: Role of Metabolic Adaptations in Kinetoplastid Disease Pathogenesis.” Infection and immunity (2021). PMID: 33526564 ↗
L5NARRATIVE_REVIEWCited in: Microbiology and Pathogenesis - [29]
Alfituri OA, Quintana JF, MacLeod A et al.. “To the Skin and Beyond: The Immune Response to African Trypanosomes as They Enter and Exit the Vertebrate Host.” Frontiers in immunology (2020). PMID: 32595652 ↗
L5NARRATIVE_REVIEWCited in: Microbiology and Pathogenesis - [30]
Onyilagha C, Uzonna JE. “Host Immune Responses and Immune Evasion Strategies in African Trypanosomiasis.” Frontiers in immunology (2019). PMID: 31824512 ↗
L5NARRATIVE_REVIEWCited in: Microbiology and Pathogenesis, Prevention and Infection Control - [31]
Moreno CJG, Temporão A, Torres T et al.. “Trypanosoma brucei Interaction with Host: Mechanism of VSG Release as Target for Drug Discovery for African Trypanosomiasis.” International journal of molecular sciences (2019). PMID: 30934540 ↗
L5NARRATIVE_REVIEWCited in: Microbiology and Pathogenesis - [32]
Kennedy PGE, Rodgers J. “Clinical and Neuropathogenetic Aspects of Human African Trypanosomiasis.” Frontiers in immunology (2019). PMID: 30740102 ↗
L5NARRATIVE_REVIEWCited in: Microbiology and Pathogenesis, Severity Assessment and Risk Stratification - [33]
Stijlemans B, De Baetselier P, Magez S et al.. “African Trypanosomiasis-Associated Anemia: The Contribution of the Interplay between Parasites and the Mononuclear Phagocyte System.” Frontiers in immunology (2018). PMID: 29497418 ↗
L5NARRATIVE_REVIEWCited in: Microbiology and Pathogenesis - [34]
Kruzel-Davila E, Skorecki K. “The double-edged sword of evolution.” eLife (2017). PMID: 28671870 ↗
L5NARRATIVE_REVIEWCited in: Microbiology and Pathogenesis - [35]
Cooper A, Ilboudo H, Alibu VP et al.. “APOL1 renal risk variants have contrasting resistance and susceptibility associations with African trypanosomiasis.” eLife (2017). PMID: 28537557 ↗
L3CASE_CONTROLCited in: Microbiology and Pathogenesis - [36]
Nunes MC, Guimarães Júnior MH, Diamantino AC et al.. “Cardiac manifestations of parasitic diseases.” Heart (British Cardiac Society) (2017). PMID: 28285268 ↗
L5NARRATIVE_REVIEWCited in: Microbiology and Pathogenesis - [37]
Casas-Sánchez A, Acosta-Serrano Á. “Skin deep.” eLife (2016). PMID: 27740910 ↗
L5NARRATIVE_REVIEWCited in: Microbiology and Pathogenesis - [38]
Morrison LJ, Vezza L, Rowan T et al.. “Animal African Trypanosomiasis: Time to Increase Focus on Clinically Relevant Parasite and Host Species.” Trends in parasitology (2016). PMID: 27167665 ↗
L5NARRATIVE_REVIEWCited in: Microbiology and Pathogenesis - [39]
Camara M, Soumah AM, Ilboudo H et al.. “Extravascular Dermal Trypanosomes in Suspected and Confirmed Cases of gambiense Human African Trypanosomiasis.” Clinical infectious diseases : an official publication of the Infectious Diseases Society of America (2021). PMID: 32638003 ↗
L4PROSPECTIVE_COHORTCited in: Epidemiology, Transmission and Risk Factors, Clinical Presentation, Diagnosis and Workup - [40]
Alirol E, Schrumpf D, Amici Heradi J et al.. “Nifurtimox-eflornithine combination therapy for second-stage gambiense human African trypanosomiasis: Médecins Sans Frontières experience in the Democratic Republic of the Congo.” Clinical infectious diseases : an official publication of the Infectious Diseases Society of America (2012). PMID: 23074318 ↗
L4COHORTCited in: Epidemiology, Transmission and Risk Factors, Empiric Management, Acute Care and Source Control, Definitive Therapy: Dosing, PK/PD, Duration and De-escalation, Complications, Special Hosts and Populations - [41]
Priotto G, Kasparian S, Mutombo W et al.. “Nifurtimox-eflornithine combination therapy for second-stage African Trypanosoma brucei gambiense trypanosomiasis: a multicentre, randomised, phase III, non-inferiority trial.” Lancet (London, England) (2009). PMID: 19559476 ↗
L1RCTCited in: Epidemiology, Transmission and Risk Factors, Clinical Presentation, Diagnosis and Workup, Empiric Management, Acute Care and Source Control, Definitive Therapy: Dosing, PK/PD, Duration and De-escalation, History and Evolution of Treatment, Complications - [42]
Pépin J, Labbé AC, Mamadou-Yaya F et al.. “Iatrogenic transmission of human T cell lymphotropic virus type 1 and hepatitis C virus through parenteral treatment and chemoprophylaxis of sleeping sickness in colonial Equatorial Africa.” Clinical infectious diseases : an official publication of the Infectious Diseases Society of America (2010). PMID: 20735238 ↗
L3CROSS_SECTIONALCited in: Epidemiology, Transmission and Risk Factors, Empiric Management, Acute Care and Source Control, Definitive Therapy: Dosing, PK/PD, Duration and De-escalation, History and Evolution of Treatment, Prognosis and Natural History, Special Hosts and Populations - [43]
Mesu VKBK, Kalonji WM, Bardonneau C et al.. “Oral fexinidazole for late-stage African Trypanosoma brucei gambiense trypanosomiasis: a pivotal multicentre, randomised, non-inferiority trial.” Lancet (London, England) (2017). PMID: 29113731 ↗
L2RCT_PHASE2Cited in: Epidemiology, Transmission and Risk Factors, Clinical Presentation, Diagnosis and Workup, Empiric Management, Acute Care and Source Control, Definitive Therapy: Dosing, PK/PD, Duration and De-escalation, History and Evolution of Treatment, Complications, Prognosis and Natural History - [44]
Geerts M, Van Reet N, Leyten S et al.. “Trypanosoma brucei gambiense-iELISA: A Promising New Test for the Post-Elimination Monitoring of Human African Trypanosomiasis.” Clinical infectious diseases : an official publication of the Infectious Diseases Society of America (2021). PMID: 32856049 ↗
L5OTHERCited in: Epidemiology, Transmission and Risk Factors, Clinical Presentation, Diagnosis and Workup - [45]
Minter A, Medley GF, Hollingsworth TD. “Using Passive Surveillance to Maintain Elimination as a Public Health Problem for Neglected Tropical Diseases: A Model-Based Exploration.” Clinical infectious diseases : an official publication of the Infectious Diseases Society of America (2024). PMID: 38662695 ↗
L5OTHERCited in: Epidemiology, Transmission and Risk Factors, Empiric Management, Acute Care and Source Control - [46]
Lejon V, Lindner AK, Franco JR. “Human African trypanosomiasis.” Lancet (London, England) (2025). PMID: 40089378 ↗
L5NARRATIVE_REVIEWCited in: Epidemiology, Transmission and Risk Factors, Clinical Presentation, Diagnosis and Workup, Definitive Therapy: Dosing, PK/PD, Duration and De-escalation - [47]
Büscher P, Cecchi G, Jamonneau V et al.. “Human African trypanosomiasis.” Lancet (London, England) (2017). PMID: 28673422 ↗
L5NARRATIVE_REVIEWCited in: Epidemiology, Transmission and Risk Factors, Clinical Presentation, Diagnosis and Workup, Severity Assessment and Risk Stratification, Definitive Therapy: Dosing, PK/PD, Duration and De-escalation - [48]
Lozano R, Naghavi M, Foreman K et al.. “Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010.” Lancet (London, England) (2012). PMID: 23245604 ↗
L3CROSS_SECTIONALCited in: Epidemiology, Transmission and Risk Factors, History and Evolution of Treatment, Prognosis and Natural History, Special Hosts and Populations - [49]
Lutumba P, Makieya E, Shaw A et al.. “Human African trypanosomiasis in a rural community, Democratic Republic of Congo.” Emerging infectious diseases (2007). PMID: 17479887 ↗
L3CROSS_SECTIONALCited in: Epidemiology, Transmission and Risk Factors, Special Hosts and Populations - [50]
Brun R, Blum J, Chappuis F et al.. “Human African trypanosomiasis.” Lancet (London, England) (2009). PMID: 19833383 ↗
L5OTHERCited in: Epidemiology, Transmission and Risk Factors, Clinical Presentation, Diagnosis and Workup, Complications - [51]
Soumah AM, Camara M, Kaboré JW et al.. “Prevalence of dermal trypanosomes in suspected and confirmed cases of gambiense human African trypanosomiasis in Guinea.” PLoS neglected tropical diseases (2024). PMID: 39159265 ↗
L2PROSPECTIVE_COHORTCited in: Epidemiology, Transmission and Risk Factors, Clinical Presentation, Diagnosis and Workup, Special Hosts and Populations - [52]
Vander Kelen C, Mpanya A, Nzuzi R et al.. “Towards elimination: Challenges in community participation to a gHAT 'screen and treat' strategy using the new oral drug acoziborole in the Democratic Republic of the Congo.” PLoS neglected tropical diseases (2025). PMID: 40540511 ↗
L2NON_RANDOMIZED_TRIALCited in: Epidemiology, Transmission and Risk Factors, Clinical Presentation, Diagnosis and Workup, Definitive Therapy: Dosing, PK/PD, Duration and De-escalation - [53]
Yagnik KJ, Pezo-Salazar A, Rosenbaum D et al.. “A Wandering Missionary's Burden: Persistent Fever and Progressive Somnolence in a Returning Traveler.” Open forum infectious diseases (2021). PMID: 34381849 ↗
L4CASE_SERIESCited in: Epidemiology, Transmission and Risk Factors - [54]
Wang X, Ruan Q, Xu B et al.. “Human African Trypanosomiasis in Emigrant Returning to China from Gabon, 2017.” Emerging infectious diseases (2018). PMID: 29350158 ↗
L4CASE_SERIESCited in: Epidemiology, Transmission and Risk Factors - [55]
Luintel A, Lowe P, Cooper A et al.. “Case of Nigeria-Acquired Human African Trypanosomiasis in United Kingdom, 2016.” Emerging infectious diseases (2017). PMID: 28628444 ↗
L4CASE_SERIESCited in: Epidemiology, Transmission and Risk Factors, Clinical Presentation, Diagnosis and Workup, History and Evolution of Treatment - [56]
Barker RH, Liu H, Hirth B et al.. “Novel S-adenosylmethionine decarboxylase inhibitors for the treatment of human African trypanosomiasis.” Antimicrobial agents and chemotherapy (2009). PMID: 19289530 ↗
L5OTHERCited in: Epidemiology, Transmission and Risk Factors, Prognosis and Natural History - [57]
Graça NA, Gaspar L, Costa DM et al.. “Activity of Bisnaphthalimidopropyl Derivatives against Trypanosoma brucei.” Antimicrobial agents and chemotherapy (2016). PMID: 26787703 ↗
L5OTHERCited in: Epidemiology, Transmission and Risk Factors, Antimicrobial Resistance and Stewardship, Prognosis and Natural History - [58]
Rosenblatt JE. “Laboratory diagnosis of infections due to blood and tissue parasites.” Clinical infectious diseases : an official publication of the Infectious Diseases Society of America (2009). PMID: 19691431 ↗
L5NARRATIVE_REVIEWCited in: Clinical Presentation, Diagnosis and Workup - [59]
Walker M, Kublin JG, Zunt JR. “Parasitic central nervous system infections in immunocompromised hosts: malaria, microsporidiosis, leishmaniasis, and African trypanosomiasis.” Clinical infectious diseases : an official publication of the Infectious Diseases Society of America (2005). PMID: 16323101 ↗
L5NARRATIVE_REVIEWCited in: Clinical Presentation, Empiric Management, Acute Care and Source Control, Special Hosts and Populations - [60]
Deborggraeve S, Büscher P. “Molecular diagnostics for sleeping sickness: what is the benefit for the patient?” The Lancet. Infectious diseases (2010). PMID: 20510283 ↗
L5OTHERCited in: Clinical Presentation, Diagnosis and Workup - [61]
Camara O, Camara M, Falzon LC et al.. “Performance of clinical signs and symptoms, rapid and reference laboratory diagnostic tests for diagnosis of human African trypanosomiasis by passive screening in Guinea: a prospective diagnostic accuracy study.” Infectious diseases of poverty (2023). PMID: 36941656 ↗
L2NON_RANDOMIZED_TRIALCited in: Clinical Presentation, Diagnosis and Workup - [62]
Ngay Lukusa I, Van Reet N, Mumba Ngoyi D et al.. “Trypanosome spliced leader RNA for diagnosis of acoziborole treatment outcome in gambiense human African trypanosomiasis: A longitudinal follow-up study.” EBioMedicine (2022). PMID: 36436279 ↗
L2NON_RANDOMIZED_TRIALCited in: Clinical Presentation, Diagnosis and Workup, Prognosis and Natural History - [63]
Bottieau E, Van Duffel L, El Safi S et al.. “Etiological spectrum of persistent fever in the tropics and predictors of ubiquitous infections: a prospective four-country study with pooled analysis.” BMC medicine (2022). PMID: 35491421 ↗
L2NON_RANDOMIZED_TRIALCited in: Clinical Presentation, Diagnosis and Workup, Special Hosts and Populations - [64]
Cottle LE, Peters JR, Hall A et al.. “Multiorgan dysfunction caused by travel-associated African trypanosomiasis.” Emerging infectious diseases (2012). PMID: 22305185 ↗
L4CASE_SERIESCited in: Clinical Presentation, Diagnosis and Workup - [65]
Pérez Antón E, Dujeancourt-Henry A, Rotureau B et al.. “A CRISPR-based diagnostic tool to survey drug resistance in human African trypanosomiasis.” Antimicrobial agents and chemotherapy (2025). PMID: 41251373 ↗
L5OTHERCited in: Clinical Presentation, Diagnosis and Workup, Antimicrobial Resistance and Stewardship - [66]
Giordani F, Munde M, Wilson WD et al.. “Green fluorescent diamidines as diagnostic probes for trypanosomes.” Antimicrobial agents and chemotherapy (2013). PMID: 24366732 ↗
L5OTHERCited in: Clinical Presentation, Diagnosis and Workup - [67]
Lejon V, Roger I, Mumba Ngoyi D et al.. “Novel markers for treatment outcome in late-stage Trypanosoma brucei gambiense trypanosomiasis.” Clinical infectious diseases : an official publication of the Infectious Diseases Society of America (2008). PMID: 18494605 ↗
L1RCTCited in: Diagnosis and Workup, Empiric Management, Acute Care and Source Control, Definitive Therapy: Dosing, PK/PD, Duration and De-escalation, History and Evolution of Treatment, Prognosis and Natural History - [68]
Kande Betu Ku Mesu V, Mutombo Kalonji W, Bardonneau C et al.. “Oral fexinidazole for stage 1 or early stage 2 African Trypanosoma brucei gambiense trypanosomiasis: a prospective, multicentre, open-label, cohort study.” The Lancet. Global health (2021). PMID: 34143998 ↗
L4PROSPECTIVE_COHORTCited in: Severity Assessment and Risk Stratification, History and Evolution of Treatment, Complications - [69]
MacLean LM, Odiit M, Chisi JE et al.. “Focus-specific clinical profiles in human African Trypanosomiasis caused by Trypanosoma brucei rhodesiense.” PLoS neglected tropical diseases (2010). PMID: 21151878 ↗
L3RETROSPECTIVE_COHORTCited in: Severity Assessment and Risk Stratification - [70]
Balasegaram M, Harris S, Checchi F et al.. “Treatment outcomes and risk factors for relapse in patients with early-stage human African trypanosomiasis (HAT) in the Republic of the Congo.” Bulletin of the World Health Organization (2006). PMID: 17128357 ↗
L4COHORTCited in: Severity Assessment and Risk Stratification - [71]
Franco JR, Cecchi G, Priotto G et al.. “Human African trypanosomiasis cases diagnosed in non-endemic countries (2011-2020).” PLoS neglected tropical diseases (2022). PMID: 36342910 ↗
L4CASE_SERIESCited in: Severity Assessment and Risk Stratification - [72]
Nsubuga J, Kato CD, Nanteza A et al.. “Plasma cytokine profiles associated with rhodesiense sleeping sickness and falciparum malaria co-infection in North Eastern Uganda.” Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology (2019). PMID: 31687034 ↗
L3CASE_CONTROLCited in: Severity Assessment and Risk Stratification - [73]
Eperon G, Balasegaram M, Potet J et al.. “Treatment options for second-stage gambiense human African trypanosomiasis.” Expert review of anti-infective therapy (2014). PMID: 25204360 ↗
L5NARRATIVE_REVIEWCited in: Severity Assessment and Risk Stratification - [74]
Simarro PP, Cecchi G, Franco JR et al.. “Estimating and mapping the population at risk of sleeping sickness.” PLoS neglected tropical diseases (2012). PMID: 23145192 ↗
L5OTHERCited in: Severity Assessment and Risk Stratification - [75]
Simarro PP, Cecchi G, Franco JR et al.. “Monitoring the Progress towards the Elimination of Gambiense Human African Trypanosomiasis.” PLoS neglected tropical diseases (2015). PMID: 26056823 ↗
L5OTHERCited in: Severity Assessment and Risk Stratification - [76]
Lumbala C, Simarro PP, Cecchi G et al.. “Human African trypanosomiasis in the Democratic Republic of the Congo: disease distribution and risk.” International journal of health geographics (2015). PMID: 26047813 ↗
L5OTHERCited in: Severity Assessment and Risk Stratification - [77]
Courtioux B, Boda C, Vatunga G et al.. “A link between chemokine levels and disease severity in human African trypanosomiasis.” International journal for parasitology (2006). PMID: 16765963 ↗
L5OTHERCited in: Severity Assessment and Risk Stratification - [78]
Limou S, Nelson GW, Lecordier L et al.. “Sequencing rare and common APOL1 coding variants to determine kidney disease risk.” Kidney international (2015). PMID: 25993319 ↗
L5OTHERCited in: Severity Assessment and Risk Stratification - [79]
Grab DJ, Nikolskaia OV, Courtioux B et al.. “Using detergent-enhanced LAMP for African trypanosome detection in human cerebrospinal fluid and implications for disease staging.” PLoS neglected tropical diseases (2019). PMID: 31425540 ↗
L5OTHERCited in: Severity Assessment and Risk Stratification - [80]
Gautret P, Clerinx J, Caumes E et al.. “Imported human African trypanosomiasis in Europe, 2005-2009.” Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin (2009). PMID: 19758542 ↗
L5OTHERCited in: Severity Assessment and Risk Stratification - [81]
Maclean L, Odiit M, Macleod A et al.. “Spatially and genetically distinct African Trypanosome virulence variants defined by host interferon-gamma response.” The Journal of infectious diseases (2007). PMID: 18008245 ↗
L5OTHERCited in: Severity Assessment and Risk Stratification - [82]
Wardrop NA, Fèvre EM, Atkinson PM et al.. “An exploratory GIS-based method to identify and characterise landscapes with an elevated epidemiological risk of Rhodesian human African trypanosomiasis.” BMC infectious diseases (2012). PMID: 23171150 ↗
L5OTHERCited in: Severity Assessment and Risk Stratification - [83]
Koko J, Ategbo SJ, Gahouma D et al.. “[Human African trypanosomiasis: report of three cases].” Archives de pediatrie : organe officiel de la Societe francaise de pediatrie (2013). PMID: 23827376 ↗
L4CASE_SERIESCited in: Severity Assessment and Risk Stratification - [84]
Kasozi KI, MacLeod ET, Welburn SC. “African animal trypanocide resistance: A systematic review and meta-analysis.” Frontiers in veterinary science (2023). PMID: 36686196 ↗
L2SR_COHORTCited in: Severity Assessment and Risk Stratification - [85]
Priotto G, Kasparian S, Ngouama D et al.. “Nifurtimox-eflornithine combination therapy for second-stage Trypanosoma brucei gambiense sleeping sickness: a randomized clinical trial in Congo.” Clinical infectious diseases : an official publication of the Infectious Diseases Society of America (2007). PMID: 17990225 ↗
L1RCTCited in: Empiric Management, Acute Care and Source Control, Definitive Therapy: Dosing, PK/PD, Duration and De-escalation, History and Evolution of Treatment, Complications - [86]
Lindner AK, Lejon V, Barrett MP et al.. “New WHO guidelines for treating rhodesiense human African trypanosomiasis: expanded indications for fexinidazole and pentamidine.” The Lancet. Infectious diseases (2024). PMID: 39389073 ↗
L2SR_COHORTCited in: Empiric Management, Acute Care and Source Control, Definitive Therapy: Dosing, PK/PD, Duration and De-escalation, Complications, Special Hosts and Populations - [87]
Betu Kumeso VK, Kalonji WM, Rembry S et al.. “Efficacy and safety of acoziborole in patients with human African trypanosomiasis caused by Trypanosoma brucei gambiense: a multicentre, open-label, single-arm, phase 2/3 trial.” The Lancet. Infectious diseases (2022). PMID: 36460027 ↗
L2NON_RANDOMIZED_TRIALCited in: Empiric Management, Acute Care and Source Control, Definitive Therapy: Dosing, PK/PD, Duration and De-escalation, History and Evolution of Treatment, Complications - [88]
Blum JA, Zellweger MJ, Burri C et al.. “Cardiac involvement in African and American trypanosomiasis.” The Lancet. Infectious diseases (2008). PMID: 18922485 ↗
L5NARRATIVE_REVIEWCited in: Empiric Management, Acute Care and Source Control, Complications - [89]
Lindner AK, Lejon V, Chappuis F et al.. “New WHO guidelines for treatment of gambiense human African trypanosomiasis including fexinidazole: substantial changes for clinical practice.” The Lancet. Infectious diseases (2019). PMID: 31879061 ↗
L5OTHERCited in: Empiric Management, Acute Care and Source Control, Definitive Therapy: Dosing, PK/PD, Duration and De-escalation, Special Hosts and Populations - [90]
Kumeso VKB, Perdrieu C, Menétrey C et al.. “Effectiveness and safety of fexinidazole for gambiense human African trypanosomiasis and exploration of adherence in outpatients: a phase 3b, prospective, open-label, non-randomised, cohort study.” The Lancet. Global health (2025). PMID: 40288399 ↗
L1RCTCited in: Empiric Management, Acute Care and Source Control, Definitive Therapy: Dosing, PK/PD, Duration and De-escalation, Prognosis and Natural History, Special Hosts and Populations - [91]
Gillon J-Y, Simon F, Sidhu S et al.. “Mass balance, pharmacokinetics, metabolism, and excretion of radiolabeled acoziborole, a potential novel treatment for human African trypanosomiasis, following single microtracer oral dose to humans.” Antimicrobial agents and chemotherapy (2025). PMID: 40980908 ↗
L4PHASE_1_TRIALCited in: Empiric Management, Acute Care and Source Control, Definitive Therapy: Dosing, PK/PD, Duration and De-escalation - [92]
Barrett MP. “Transforming the chemotherapy of human African trypanosomiasis.” Clinical microbiology reviews (2025). PMID: 39772631 ↗
L5NARRATIVE_REVIEWCited in: Empiric Management, Acute Care and Source Control, Definitive Therapy: Dosing, PK/PD, Duration and De-escalation, Antimicrobial Resistance and Stewardship, Complications - [93]
Hidron A, Vogenthaler N, Santos-Preciado JI et al.. “Cardiac involvement with parasitic infections.” Clinical microbiology reviews (2010). PMID: 20375355 ↗
L5NARRATIVE_REVIEWCited in: Empiric Management, Acute Care and Source Control - [94]
Matovu E, Nyirenda W, Eriatu A et al.. “Fexinidazole as a new oral treatment for human African trypanosomiasis due to Trypanosoma brucei rhodesiense: a prospective, open-label, single-arm, phase 2-3, non-randomised study.” The Lancet. Global health (2025). PMID: 40288400 ↗
L2RCT_PHASE2Cited in: Empiric Management, Acute Care and Source Control, Definitive Therapy: Dosing, PK/PD, Duration and De-escalation, Special Hosts and Populations - [95]
Ahmed QU, Mat Nasir NA, Begum T et al.. “Harnessing nature: a systematic exploration of in vitro antileishmanial and antihuman African trypanosomal properties in traditional medicinal plants and their active principles.” Pharmaceutical biology (2026). PMID: 41777027 ↗
L2SR_COHORTCited in: Empiric Management, Acute Care and Source Control, Definitive Therapy: Dosing, PK/PD, Duration and De-escalation, Antimicrobial Resistance and Stewardship - [96]
Serem EK, Mburu DM, Abdullahi OA et al.. “A scoping review on tsetse fly blood meal sources and its assay methods since 1956 to 2022.” Parasites & vectors (2024). PMID: 38308365 ↗
L2SR_COHORTCited in: Definitive Therapy: Dosing, PK/PD, Duration and De-escalation - [97]
Xu Y, Ding K, Peng Z et al.. “Evaluating for Correlations between Specific Metabolites in Patients Receiving First-Line or Second-Line Immunotherapy for Metastatic or Recurrent NSCLC: An Exploratory Study Based on Two Cohorts.” Molecular cancer therapeutics (2024). PMID: 38346938 ↗
L2PROSPECTIVE_COHORTCited in: Definitive Therapy: Dosing, PK/PD, Duration and De-escalation, Prognosis and Natural History - [98]
Schmid C, Nkunku S, Merolle A et al.. “Efficacy of 10-day melarsoprol schedule 2 years after treatment for late-stage gambiense sleeping sickness.” Lancet (London, England) (Unknown). PMID: 15337407 ↗
L1RCTCited in: History and Evolution of Treatment - [99]
Burri C, Nkunku S, Merolle A et al.. “Efficacy of new, concise schedule for melarsoprol in treatment of sleeping sickness caused by Trypanosoma brucei gambiense: a randomised trial.” Lancet (London, England) (2000). PMID: 10791526 ↗
L1RCTCited in: History and Evolution of Treatment - [100]
Jansson-Löfmark R, Na-Bangchang K, Björkman S et al.. “Enantiospecific reassessment of the pharmacokinetics and pharmacodynamics of oral eflornithine against late-stage Trypanosoma brucei gambiense sleeping sickness.” Antimicrobial agents and chemotherapy (2014). PMID: 25512417 ↗
L1RCTCited in: History and Evolution of Treatment - [101]
Cox FE. “History of human parasitology.” Clinical microbiology reviews (2002). PMID: 12364371 ↗
L5NARRATIVE_REVIEWCited in: History and Evolution of Treatment - [102]
Chen J, Wu H, Zhang W et al.. “Ribose-5-phosphate isomerases: characteristics, structural features, and applications.” Applied microbiology and biotechnology (2020). PMID: 32533303 ↗
L2SR_COHORTCited in: History and Evolution of Treatment - [103]
Kuemmerle A, Schmid C, Bernhard S et al.. “Effectiveness of Nifurtimox Eflornithine Combination Therapy (NECT) in T. b. gambiense second stage sleeping sickness patients in the Democratic Republic of Congo: Report from a field study.” PLoS neglected tropical diseases (2021). PMID: 34748572 ↗
L2NON_RANDOMIZED_TRIALCited in: History and Evolution of Treatment, Complications, Prognosis and Natural History, Special Hosts and Populations - [104]
Pécoul B, Chirac P, Trouiller P et al.. “Access to essential drugs in poor countries: a lost battle?” JAMA (1999). PMID: 9929090 ↗
L5OTHERCited in: History and Evolution of Treatment - [105]
Mariotti F, Paggi R, Basilico M et al.. “Use of fexinidazole in gambiense human African trypanosomiasis: a retrospective analysis of cases treated in Lui Hospital, South Sudan (2018-2024).” Infection (2025). PMID: 40906063 ↗
L3RETROSPECTIVE_COHORTCited in: History and Evolution of Treatment, Complications, Prognosis and Natural History - [106]
Hietanen H, Pfavayi LT, Mutapi F. “Unlocking the blueprint to eliminating neglected tropical diseases: A review of efforts in 50 countries that have eliminated at least 1 NTD.” PLoS neglected tropical diseases (2025). PMID: 40906712 ↗
L5NARRATIVE_REVIEWCited in: History and Evolution of Treatment - [107]
Ouma JO, Kayembe S, Bessell PR et al.. “Bold strides towards the elimination of gambiense human African trypanosomiasis (gHAT) as a public health problem-A case study of Angola.” PLoS neglected tropical diseases (2025). PMID: 39937734 ↗
L5NARRATIVE_REVIEWCited in: History and Evolution of Treatment - [108]
Crump RE, Aliee M, Sutherland SA et al.. “Modelling timelines to elimination of sleeping sickness in the Democratic Republic of Congo, accounting for possible cryptic human and animal transmission.” Parasites & vectors (2024). PMID: 39123265 ↗
L5NARRATIVE_REVIEWCited in: History and Evolution of Treatment - [109]
Escrig JI, Miyamoto Y, Aznar AD et al.. “Antigiardial and antiamebic activities of fexinidazole and its metabolites: new drug leads for giardiasis and amebiasis.” Antimicrobial agents and chemotherapy (2023). PMID: 38063401 ↗
L5OTHERCited in: Antimicrobial Resistance and Stewardship - [110]
Bakshi RP, Sang D, Morrell A et al.. “Activity of indenoisoquinolines against African trypanosomes.” Antimicrobial agents and chemotherapy (2008). PMID: 18824603 ↗
L5OTHERCited in: Antimicrobial Resistance and Stewardship, Prognosis and Natural History - [111]
Sokolova AY, Wyllie S, Patterson S et al.. “Cross-resistance to nitro drugs and implications for treatment of human African trypanosomiasis.” Antimicrobial agents and chemotherapy (2010). PMID: 20439607 ↗
L5OTHERCited in: Antimicrobial Resistance and Stewardship - [112]
Kwofie KD, Tung NH, Suzuki-Ohashi M et al.. “Antitrypanosomal Activities and Mechanisms of Action of Novel Tetracyclic Iridoids from Morinda lucida Benth.” Antimicrobial agents and chemotherapy (2016). PMID: 26953191 ↗
L5OTHERCited in: Antimicrobial Resistance and Stewardship - [113]
Ranade RM, Gillespie JR, Shibata S et al.. “Induced resistance to methionyl-tRNA synthetase inhibitors in Trypanosoma brucei is due to overexpression of the target.” Antimicrobial agents and chemotherapy (2013). PMID: 23587950 ↗
L5OTHERCited in: Antimicrobial Resistance and Stewardship - [114]
Ward CP, Wong PE, Burchmore RJ et al.. “Trypanocidal furamidine analogues: influence of pyridine nitrogens on trypanocidal activity, transport kinetics, and resistance patterns.” Antimicrobial agents and chemotherapy (2011). PMID: 21402852 ↗
L5OTHERCited in: Antimicrobial Resistance and Stewardship - [115]
Berg M, Kohl L, Van der Veken P et al.. “Evaluation of nucleoside hydrolase inhibitors for treatment of African trypanosomiasis.” Antimicrobial agents and chemotherapy (2010). PMID: 20194690 ↗
L5OTHERCited in: Antimicrobial Resistance and Stewardship - [116]
Kasozi KI, MacLeod ET, Welburn SC. “Systematic Review and Meta-Analysis on Human African Trypanocide Resistance.” Pathogens (Basel, Switzerland) (2022). PMID: 36297157 ↗
L2SR_COHORTCited in: Antimicrobial Resistance and Stewardship - [117]
Kasozi KI, MacLeod ET, Waiswa C et al.. “Systematic Review and Meta-Analysis on Knowledge Attitude and Practices on African Animal Trypanocide Resistance.” Tropical medicine and infectious disease (2022). PMID: 36136616 ↗
L2SR_COHORTCited in: Antimicrobial Resistance and Stewardship - [118]
Zoltner M, Horn D, Field MC. “Pass the boron: benzoxaboroles as antiparasite drugs.” Trends in parasitology (2024). PMID: 39107181 ↗
L5NARRATIVE_REVIEWCited in: Antimicrobial Resistance and Stewardship - [119]
Abbasi Shiran J, Kaboudin B, Panahi N et al.. “Privileged small molecules against neglected tropical diseases: A perspective from structure activity relationships.” European journal of medicinal chemistry (2024). PMID: 38643671 ↗
L5NARRATIVE_REVIEWCited in: Antimicrobial Resistance and Stewardship - [120]
Jamabo M, Mahlalela M, Edkins AL et al.. “Tackling Sleeping Sickness: Current and Promising Therapeutics and Treatment Strategies.” International journal of molecular sciences (2023). PMID: 37569903 ↗
L5NARRATIVE_REVIEWCited in: Antimicrobial Resistance and Stewardship - [121]
Ungogo MA, Aldfer MM, Natto MJ et al.. “Cloning and Characterization of Trypanosoma congolense and T. vivax Nucleoside Transporters Reveal the Potential of P1-Type Carriers for the Discovery of Broad-Spectrum Nucleoside-Based Therapeutics against Animal African Trypanosomiasis.” International journal of molecular sciences (2023). PMID: 36834557 ↗
L5NARRATIVE_REVIEWCited in: Antimicrobial Resistance and Stewardship - [122]
Christopher R. “Antitrypanosomal secondary metabolites from medicinal plants: a review.” Naunyn-Schmiedeberg's archives of pharmacology (2025). PMID: 40410549 ↗
L5NARRATIVE_REVIEWCited in: Antimicrobial Resistance and Stewardship - [123]
Gineau L, Courtin D, Camara M et al.. “Human Leukocyte Antigen-G: A Promising Prognostic Marker of Disease Progression to Improve the Control of Human African Trypanosomiasis.” Clinical infectious diseases : an official publication of the Infectious Diseases Society of America (2016). PMID: 27470243 ↗
L5OTHERCited in: Complications - [124]
Pohlig G, Bernhard SC, Blum J et al.. “Efficacy and Safety of Pafuramidine versus Pentamidine Maleate for Treatment of First Stage Sleeping Sickness in a Randomized, Comparator-Controlled, International Phase 3 Clinical Trial.” PLoS neglected tropical diseases (2016). PMID: 26882015 ↗
L1RCTCited in: Complications, Special Hosts and Populations - [125]
Tarral A, Blesson S, Mordt OV et al.. “Determination of an optimal dosing regimen for fexinidazole, a novel oral drug for the treatment of human African trypanosomiasis: first-in-human studies.” Clinical pharmacokinetics (2014). PMID: 24535888 ↗
L1RCTCited in: Complications - [126]
Burri C, Yeramian PD, Allen JL et al.. “Efficacy, Safety, and Dose of Pafuramidine, a New Oral Drug for Treatment of First Stage Sleeping Sickness, in a Phase 2a Clinical Study and Phase 2b Randomized Clinical Studies.” PLoS neglected tropical diseases (2016). PMID: 26881924 ↗
L2RCT_PHASE2Cited in: Complications - [127]
Kande Betu Kumesu V, Mutombo Kalonji W, Bardonneau C et al.. “Safety and efficacy of oral fexinidazole in children with gambiense human African trypanosomiasis: a multicentre, single-arm, open-label, phase 2-3 trial.” The Lancet. Global health (2022). PMID: 36179736 ↗
L2NON_RANDOMIZED_TRIALCited in: Complications, Special Hosts and Populations - [128]
Kuemmerle A, Schmid C, Kande V et al.. “Prescription of concomitant medications in patients treated with Nifurtimox Eflornithine Combination Therapy (NECT) for T.b. gambiense second stage sleeping sickness in the Democratic Republic of the Congo.” PLoS neglected tropical diseases (2020). PMID: 31986140 ↗
L2NON_RANDOMIZED_TRIALCited in: Complications - [129]
Schmid C, Kuemmerle A, Blum J et al.. “In-hospital safety in field conditions of nifurtimox eflornithine combination therapy (NECT) for T. b. gambiense sleeping sickness.” PLoS neglected tropical diseases (2012). PMID: 23209861 ↗
L2NON_RANDOMIZED_TRIALCited in: Complications, Special Hosts and Populations - [130]
Hiltensperger G, Hecht N, Kaiser M et al.. “Quinolone Amides as Antitrypanosomal Lead Compounds with In Vivo Activity.” Antimicrobial agents and chemotherapy (2016). PMID: 27139467 ↗
L5OTHERCited in: Prognosis and Natural History - [131]
Tang SC, Shapiro TA. “Newly identified antibacterial compounds are topoisomerase poisons in African trypanosomes.” Antimicrobial agents and chemotherapy (2009). PMID: 20008775 ↗
L5OTHERCited in: Prognosis and Natural History - [132]
Behera R, Thomas SM, Mensa-Wilmot K. “New chemical scaffolds for human african trypanosomiasis lead discovery from a screen of tyrosine kinase inhibitor drugs.” Antimicrobial agents and chemotherapy (2014). PMID: 24468788 ↗
L5OTHERCited in: Prognosis and Natural History - [133]
Shibata S, Gillespie JR, Kelley AM et al.. “Selective inhibitors of methionyl-tRNA synthetase have potent activity against Trypanosoma brucei Infection in Mice.” Antimicrobial agents and chemotherapy (2011). PMID: 21282428 ↗
L5OTHERCited in: Prognosis and Natural History - [134]
Ojo KK, Gillespie JR, Riechers AJ et al.. “Glycogen synthase kinase 3 is a potential drug target for African trypanosomiasis therapy.” Antimicrobial agents and chemotherapy (2008). PMID: 18644955 ↗
L5OTHERCited in: Prognosis and Natural History - [135]
Chin A, Bieberich CJ, Stewart TM et al.. “Polyamine Depletion Strategies in Cancer: Remodeling the Tumor Immune Microenvironment to Enhance Anti-Tumor Responses.” Medical sciences (Basel, Switzerland) (2022). PMID: 35736351 ↗
L5NARRATIVE_REVIEWCited in: Prognosis and Natural History - [136]
Kappagoda S, Ioannidis JP. “Prevention and control of neglected tropical diseases: overview of randomized trials, systematic reviews and meta-analyses.” Bulletin of the World Health Organization (2014). PMID: 24839325 ↗
L1SR_MA_RCTCited in: Prevention and Infection Control - [137]
Gürtler LG, Eberle J. “Aspects on the history of transmission and favor of distribution of viruses by iatrogenic action: perhaps an example of a paradigm of the worldwide spread of HIV.” Medical microbiology and immunology (2017). PMID: 28434128 ↗
L5NARRATIVE_REVIEWCited in: Prevention and Infection Control - [138]
Li M, Yang Y, Xue C et al.. “Global, regional, and national disease burden of arthropod-borne diseases: Projections to 2030 based on the global burden of disease study 2021.” PLoS neglected tropical diseases (2026). PMID: 42085455 ↗
L3CROSS_SECTIONALCited in: Prevention and Infection Control - [139]
Buguet A, Gati Ouonkoye R, Bogui P et al.. “Geoclimatology and sleep in Africa: A mini-review.” Revue neurologique (2019). PMID: 31253360 ↗
L5NARRATIVE_REVIEWCited in: Prevention and Infection Control - [140]
Magez S, Caljon G, Tran T et al.. “Current status of vaccination against African trypanosomiasis.” Parasitology (2010). PMID: 20441680 ↗
L5NARRATIVE_REVIEWCited in: Prevention and Infection Control - [141]
Romero-Ramirez A, Casas-Sánchez A, Autheman D et al.. “Vivaxin genes encode highly immunogenic, non-variant antigens on the Trypanosoma vivax cell-surface.” PLoS neglected tropical diseases (2022). PMID: 36129968 ↗
L5OTHERCited in: Prevention and Infection Control - [142]
Leder K, Torresi J, Libman MD et al.. “GeoSentinel surveillance of illness in returned travelers, 2007-2011.” Annals of internal medicine (2013). PMID: 23552375 ↗
L5OTHERCited in: Prevention and Infection Control - [143]
Longbottom J, Wamboga C, Bessell PR et al.. “Optimising passive surveillance of a neglected tropical disease in the era of elimination: A modelling study.” PLoS neglected tropical diseases (2021). PMID: 33651803 ↗
L5OTHERCited in: Prevention and Infection Control - [144]
Sayeed SA, Kushwaha PP, Afrin M et al.. “Trypanosoma brucei TEL2 inhibits VSG switching and protects PIKKs from the 26S proteasome-mediated degradation.” Microbiology spectrum (2026). PMID: 42214372 ↗
L5OTHERCited in: Prevention and Infection Control - [145]
Magez S, Radwanska M. “African trypanosomiasis and antibodies: implications for vaccination, therapy and diagnosis.” Future microbiology (2009). PMID: 19824795 ↗
L5NARRATIVE_REVIEWCited in: Prevention and Infection Control - [146]
Houweling TA, Karim-Kos HE, Kulik MC et al.. “Socioeconomic Inequalities in Neglected Tropical Diseases: A Systematic Review.” PLoS neglected tropical diseases (2016). PMID: 27171166 ↗
L2SR_COHORTCited in: Special Hosts and Populations - [147]
Boelaert M, Mukendi D, Bottieau E et al.. “A Phase III Diagnostic Accuracy Study of a Rapid Diagnostic Test for Diagnosis of Second-Stage Human African Trypanosomiasis in the Democratic Republic of the Congo.” EBioMedicine (2017). PMID: 29246478 ↗
L2NON_RANDOMIZED_TRIALCited in: Special Hosts and Populations - [148]
Alirol E, Horie NS, Barbé B et al.. “Diagnosis of Persistent Fever in the Tropics: Set of Standard Operating Procedures Used in the NIDIAG Febrile Syndrome Study.” PLoS neglected tropical diseases (2016). PMID: 27812090 ↗
L2NON_RANDOMIZED_TRIALCited in: Special Hosts and Populations