Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

gambiense human African trypanosomiasis (HAT)

1st line – pentamidine or fexinidazole

Back
ACUTE
|
gambiense human African trypanosomiasis (HAT)
|
first-stage disease
1st line – 

pentamidine or fexinidazole

First-stage disease (also known as early stage or haemolymphatic stage) is defined as ≤5 WBC/microlitre and no trypanosomes in the cerebrospinal fluid (CSF) without clinical features consistent with severe disease.[32][123]​​​

Anti-trypanosomal drugs are highly effective. Treatment options depend on the patient's age and body weight.[32][123]

Patients <6 years of age or body weight <20 kg: pentamidine is the recommended first-line treatment (a lumbar puncture is required).[32][123]

Patients ≥6 years of age and body weight ≥20 kg: fexinidazole is the recommended first-line treatment. Pentamidine is an alternative option if the patient cannot receive fexinidazole (e.g., it is contraindicated or not available), provided there is no suspicion for severe disease (a lumbar puncture is required).[32][123]

Pentamidine is generally well tolerated, but the injection is painful. It has been associated with hypotension, cardiac disorders, nephrotoxicity, leukopenia, thrombocytopenia, anaemia, acute pancreatitis, hypoglycaemia, hyperglycaemia, and diabetes. Treatment should be preceded by the ingestion of sugar to combat the risk of hypoglycaemia. Patients should remain in a supine position for 1-2 hours after administration, while blood pressure and cardiac rhythm are monitored.[32][60]

Fexinidazole has been associated with neuropsychiatric adverse effects, QT prolongation, neutropenia, and gastrointestinal adverse effects. Contraindications include jaundice, bleeding or other clinical signs of hepatic insufficiency, generalised oedema, risk of QT interval prolongation, or Cockayne syndrome. A substantial meal must be consumed prior to dose administration to ensure sufficient absorption to reach therapeutic levels. Direct supervision by trained healthcare staff is necessary to ensure the patient is in a fed condition and for daily compliance. Hospitalisation may be required in certain circumstances. Alcohol should not be consumed during treatment or for 48 hours after the last dose due to a disulfiram-like reaction.[32]

The decision to treat pregnant patients should be determined considering the potential benefits and risks for the mother and fetus.[124]​ Fexinidazole and pentamidine may be given after the first trimester.[32] Consult a specialist for guidance on the management of pregnant women.

Primary options

pentamidine: children <6 years of age or <20 kg body weight: 4 mg/kg intramuscularly/intravenously every 24 hours for 7 days; children ≥6 years of age and ≥20 kg body weight and adults: 4 mg/kg intramuscularly/intravenously every 24 hours for 7 days

OR

fexinidazole: children ≥6 years of age and 20-34 kg body weight: 1200 mg orally once daily for 4 days, followed by 600 mg once daily for 6 days; children ≥6 years of age and ≥35 kg body weight and adults: 1800 mg orally once daily for 4 days, followed by 1200 mg once daily for 6 days

1st line – nifurtimox plus eflornithine (or eflornithine monotherapy) or fexinidazole

Back
ACUTE
|
gambiense human African trypanosomiasis (HAT)
|
second-stage disease: non-severe (<100 WBC/microlitre in CSF)
1st line – 

nifurtimox plus eflornithine (or eflornithine monotherapy) or fexinidazole

Second-stage disease (also known as late stage or meningoencephalitic stage) is defined as >5 WBC/microlitre or trypanosomes in the CSF and with clinical features consistent with severe disease. Non-severe disease is defined as <100 WBC/microlitre in the CSF.[32][123]

Anti-trypanosomal drugs are highly effective. Treatment options depend on the patient's age and body weight.[32][123]

Patients <6 years of age or body weight <20 kg: nifurtimox plus eflornithine is the recommended first-line treatment (a lumbar puncture is required).[32][123]

Patients ≥6 years of age and body weight ≥20 kg: fexinidazole is the recommended first-line treatment. Nifurtimox plus eflornithine is an alternative option (a lumbar puncture is required).[32][123]

Nifurtimox plus eflornithine is the recommended treatment for patients where a lumbar puncture is not done or results are unreliable.[32]

Eflornithine monotherapy is an alternative option to nifurtimox plus eflornithine in areas where nifurtimox is contraindicated or unavailable, or fexinidazole cannot be given. However, the treatment course is longer and requires maintenance of venous access for 14 days. Parasite elimination may not be complete with eflornithine monotherapy in immunocompromised patients.[32]

Nifurtimox is commonly associated with gastrointestinal adverse effects. Eflornithine is a toxic drug with an iatrogenic mortality of 0.7% to 2%.[135]​ It may cause bone marrow suppression, gastrointestinal adverse effects, vertigo, tremor and, more rarely, seizures, and psychotic reactions or hallucinations. Blood cell count monitoring is required during and after treatment.[32]

Fexinidazole has been associated with neuropsychiatric adverse effects, QT prolongation, neutropenia, and gastrointestinal adverse effects. Contraindications include jaundice, bleeding or other clinical signs of hepatic insufficiency, generalised oedema, risk of QT interval prolongation, or Cockayne syndrome. A substantial meal must be consumed prior to dose administration to ensure sufficient absorption to reach therapeutic levels. Direct supervision by trained healthcare staff is necessary to ensure the patient is in a fed condition and for daily compliance. Hospitalisation may be required in certain circumstances. Alcohol should not be consumed during treatment or for 48 hours after the last dose due to a disulfiram-like reaction.[32]

The decision to treat pregnant patients should be determined considering the potential benefits and risks for the mother and fetus.[124]​ Fexinidazole may be given after the first trimester. Nifurtimox and eflornithine are contraindicated in pregnancy, but may be used in certain circumstances depending on the maternal condition. Treatment may be required in order to save the mother's life. Nifurtimox plus eflornithine should be administered only after delivery, if possible.[32] Consult a specialist for guidance on the management of pregnant women.

Primary options

nifurtimox: children <6 years of age or <20 kg body weight: 15 mg/kg/day orally given in 3 divided doses for 10 days; children ≥6 years of age and ≥20 kg body weight and adults: 15 mg/kg/day orally given in 3 divided doses for 10 days

and

eflornithine: children <6 years of age or <20 kg body weight: 200 mg/kg intravenously every 12 hours for 7 days; children ≥6 years of age and ≥20 kg body weight and adults: 200 mg/kg intravenously every 12 hours for 7 days

OR

fexinidazole: children ≥6 years of age and 20-34 kg body weight: 1200 mg orally once daily for 4 days, followed by 600 mg once daily for 6 days; children ≥6 years of age and ≥35 kg body weight and adults: 1800 mg orally once daily for 4 days, followed by 1200 mg once daily for 6 days

Secondary options

eflornithine: children <6 years of age or <20 kg body weight: 100 mg/kg intravenously every 6 hours for 14 days; children ≥6 years of age and ≥20 kg body weight and adults: 100 mg/kg intravenously every 6 hours for 14 days

1st line – nifurtimox plus eflornithine (or eflornithine monotherapy) or fexinidazole

Back
ACUTE
|
gambiense human African trypanosomiasis (HAT)
|
second-stage disease: severe (≥100 WBC/microlitre in CSF)
1st line – 

nifurtimox plus eflornithine (or eflornithine monotherapy) or fexinidazole

Severe second-stage disease is defined as ≥100 WBC/microlitre with or without trypanosomes in the CSF.[32][123]​​

Anti-trypanosomal drugs are highly effective. Nifurtimox plus eflornithine is the recommended first-line treatment, regardless of the patient's age and body weight (a lumbar puncture is required).[32][123]

Fexinidazole is an alternative option in patients ≥6 years of age and body weight ≥20 kg. However, the efficacy of fexinidazole is inferior to nifurtimox plus eflornithine in patients with ≥100 WBC/microlitre in the CSF, and it is therefore only an option for patients who cannot tolerate nifurtimox plus eflornithine, or if nifurtimox or eflornithine are unavailable.[32][123]

Nifurtimox plus eflornithine is the recommended treatment for patients where a lumbar puncture is not done or results are unreliable.[32]

Eflornithine monotherapy is an alternative option to nifurtimox plus eflornithine in areas where nifurtimox is contraindicated or unavailable, or fexinidazole cannot be given. However, the treatment course is longer and requires maintenance of venous access for 14 days. Parasite elimination may not be complete with eflornithine monotherapy in immunocompromised patients.[32]

Nifurtimox is commonly associated with gastrointestinal adverse effects. Eflornithine is a toxic drug with an iatrogenic mortality of 0.7% to 2%.[135]​ It may cause bone marrow suppression, gastrointestinal adverse effects, vertigo, tremor and, more rarely, seizures, and psychotic reactions or hallucinations. Blood cell count monitoring is required during and after treatment.[32]

Fexinidazole has been associated with neuropsychiatric adverse effects, QT prolongation, neutropenia, and gastrointestinal adverse effects. Contraindications include jaundice, bleeding or other clinical signs of hepatic insufficiency, generalised oedema, risk of QT interval prolongation, or Cockayne syndrome. A substantial meal must be consumed prior to dose administration to ensure sufficient absorption to reach therapeutic levels. Direct supervision by trained healthcare staff is necessary to ensure the patient is in a fed condition and for daily compliance. Hospitalisation may be required in certain circumstances. Alcohol should not be consumed during treatment or for 48 hours after the last dose due to a disulfiram-like reaction.[32]

The decision to treat pregnant patients should be determined considering the potential benefits and risks for the mother and fetus.[124]​ Fexinidazole may be given after the first trimester. Nifurtimox and eflornithine are contraindicated in pregnancy, but may be used in certain circumstances depending on the maternal condition. Treatment may be required in order to save the mother's life. Nifurtimox plus eflornithine should be administered only after delivery, if possible.[32] Consult a specialist for guidance on the management of pregnant women.

Primary options

nifurtimox: children <6 years of age or <20 kg body weight: 15 mg/kg/day orally given in 3 divided doses for 10 days; children ≥6 years of age and ≥20 kg body weight and adults: 15 mg/kg/day orally given in 3 divided doses for 10 days

and

eflornithine: children <6 years of age or <20 kg body weight: 200 mg/kg intravenously every 12 hours for 7 days; children ≥6 years of age and ≥20 kg body weight and adults: 200 mg/kg intravenously every 12 hours for 7 days

Secondary options

fexinidazole: children ≥6 years of age and 20-34 kg body weight: 1200 mg orally once daily for 4 days, followed by 600 mg once daily for 6 days; children ≥6 years of age and ≥35 kg body weight and adults: 1800 mg orally once daily for 4 days, followed by 1200 mg once daily for 6 days

OR

eflornithine: children <6 years of age or <20 kg body weight: 100 mg/kg intravenously every 6 hours for 14 days; children ≥6 years of age and ≥20 kg body weight and adults: 100 mg/kg intravenously every 6 hours for 14 days

rhodesiense human African trypanosomiasis (HAT)

1st line – fexinidazole or suramin or pentamidine

Back
ACUTE
|
rhodesiense human African trypanosomiasis (HAT)
|
first-stage disease
1st line – 

fexinidazole or suramin or pentamidine

First-stage disease (also known as early stage or haemolymphatic stage) is defined as ≤5 WBC/microlitre and no trypanosomes in the CSF.[32]

Rhodesiense HAT is the more rapidly progressive form of disease and requires immediate treatment.

Anti-trypanosomal drugs are highly effective. Treatment options depend on the patient's age and body weight.[32]

Patients <6 years of age or body weight <20 kg: suramin is the recommended first-line treatment. Pentamidine is an alternative option. A lumbar puncture is needed for staging.[32]

Patients ≥6 years of age and body weight ≥20 kg: fexinidazole is the recommended first-line treatment. Suramin or pentamidine may be used in patients who cannot receive fexinidazole. However, a lumbar puncture is needed for staging.[32]

Immediate interim treatment with pentamidine may be used if the recommended treatments are not available. However, the patient should be switched to the recommended treatment as soon as it becomes available.[32]

Suramin is associated with hypersensitivity reactions; a test dose is recommended prior to the first full dose. Adverse effects are common, but are usually mild and reversible. Adverse effects include gastrointestinal adverse effects, drug rash, peripheral neuropathy, agranulocytosis, haemolytic anaemia, thrombocytopenia, and nephrotoxicity. Contraindications include severe renal disease. Monitoring of blood parameters and renal function is recommended.[32]

Pentamidine is generally well tolerated, but the injection is painful. It has been associated with hypotension, cardiac disorders, nephrotoxicity, leukopenia, thrombocytopenia, anaemia, acute pancreatitis, hypoglycaemia, hyperglycaemia, and diabetes. Treatment should be preceded by the ingestion of sugar to combat the risk of hypoglycaemia. Patients should remain in a supine position for 1-2 hours after administration, while blood pressure and cardiac rhythm are monitored.[32][60]

Fexinidazole has been associated with neuropsychiatric adverse effects, QT prolongation, neutropenia, and gastrointestinal adverse effects. Contraindications include jaundice, bleeding or other clinical signs of hepatic insufficiency, generalised oedema, risk of QT interval prolongation, or Cockayne syndrome. A substantial meal must be consumed prior to dose administration to ensure sufficient absorption to reach therapeutic levels. Direct supervision by trained healthcare staff is necessary to ensure the patient is in a fed condition and for daily compliance. Hospitalisation may be required in certain circumstances. Alcohol should not be consumed during treatment or for 48 hours after the last dose due to a disulfiram-like reaction.[32] 

The decision to treat pregnant patients should be determined considering the potential benefits and risks for the mother and fetus.[124]​ Fexinidazole and pentamidine may be given after the first trimester. Suramin is contraindicated in pregnancy, but may be used in certain circumstances depending on the maternal condition.[32] Consult a specialist for guidance on the management of pregnant women.

Primary options

suramin: children <6 years of age or <20 kg body weight: 20 mg/kg intravenously once weekly for 5 weeks, maximum 1000 mg/dose; children ≥6 years of age and ≥20 kg body weight and adults: 20 mg/kg intravenously once weekly for 5 weeks, maximum 1000 mg/dose

More

OR

pentamidine: children <6 years of age or <20 kg body weight: 4 mg/kg intramuscularly/intravenously every 24 hours for 7 days; children ≥6 years of age and ≥20 kg body weight and adults: 4 mg/kg intramuscularly/intravenously every 24 hours for 7 days

OR

fexinidazole: children ≥6 years of age and 20-34 kg body weight: 1200 mg orally once daily for 4 days, followed by 600 mg once daily for 6 days; children ≥6 years of age and ≥35 kg body weight and adults: 1800 mg orally once daily for 4 days, followed by 1200 mg once daily for 6 days

1st line – fexinidazole or melarsoprol

Back
ACUTE
|
rhodesiense human African trypanosomiasis (HAT)
|
second-stage disease
1st line – 

fexinidazole or melarsoprol

Second-stage disease (also known as late stage or meningoencephalitic stage) is defined as >5 WBC/microlitre or trypanosomes in the CSF.[32]

Anti-trypanosomal drugs are highly effective. Treatment options depend on the patient's age and body weight.[32]

Patients <6 years of age or body weight <20 kg: melarsoprol is the recommended first-line treatment. Pentamidine is an alternative option. A lumbar puncture is required for staging.[32]

Patients ≥6 years of age and body weight ≥20 kg: fexinidazole is the recommended first-line treatment. Melarsoprol may be used in patients who cannot receive fexinidazole. However, a lumbar puncture is required for staging.[32]

Immediate interim treatment with pentamidine may be used if the recommended treatments are not available. However, the patient should be switched to the recommended treatment as soon as it becomes available.[32]

Fexinidazole has been associated with neuropsychiatric adverse effects, QT prolongation, neutropenia, and gastrointestinal adverse effects. Contraindications include jaundice, bleeding or other clinical signs of hepatic insufficiency, generalised oedema, risk of QT interval prolongation, or Cockayne syndrome. A substantial meal must be consumed prior to dose administration to ensure sufficient absorption to reach therapeutic levels. Direct supervision by trained healthcare staff is necessary to ensure the patient is in a fed condition and for daily compliance. Hospitalisation may be required in certain circumstances. Alcohol should not be consumed during treatment or for 48 hours after the last dose due to a disulfiram-like reaction.[32]

Melarsoprol is a highly toxic drug. It must be administered with prednisolone to help prevent melarsoprol encephalopathy, which occurs in 5% to 18% of cases and is fatal in 10% to 70% of cases. Other adverse effects include skin reactions, exfoliative dermatitis, gastrointestinal adverse effects, myocardial damage, hypertension, cardiac failure, and albuminuria. Close monitoring is required, and treatment stopped immediately in case of significant adverse effects (e.g., encephalopathy, phlebitis, local necrosis). Monitoring of blood parameters and renal and liver function is recommended.[32][137]

The decision to treat pregnant patients should be determined considering the potential benefits and risks for the mother and fetus.[124]​ Fexinidazole and pentamidine may be given after the first trimester. Melarsoprol is contraindicated in pregnancy, but may be used in certain circumstances depending on the maternal condition. Treatment may be required in order to save the mother's life.[32] Consult a specialist for guidance on the management of pregnant women.

Primary options

melarsoprol: children and adults: 2.2 mg/kg intravenously every 24 hours for 10 days, maximum 180-200 mg/day

OR

pentamidine: children <6 years of age or <20 kg body weight: 4 mg/kg intramuscularly/intravenously every 24 hours for 7 days; children ≥6 years of age and ≥20 kg body weight and adults: 4 mg/kg intramuscularly/intravenously every 24 hours for 7 days

OR

fexinidazole: children ≥6 years of age and 20-34 kg body weight: 1200 mg orally once daily for 4 days, followed by 600 mg once daily for 6 days; children ≥6 years of age and ≥35 kg body weight and adults: 1800 mg orally once daily for 4 days, followed by 1200 mg once daily for 6 days

ONGOING

relapse

1st line – repeat anti-trypanosomal treatment

Back
ONGOING
|
relapse
|
gambiense human African trypanosomiasis (HAT)
1st line – 

repeat anti-trypanosomal treatment

Patients must be monitored closely for 24 months after treatment for signs of relapse as there is no test of cure. Relapse may occur more than 1 year after treatment.[32][123]​​

A relapse is defined as the presence of trypanosomes in any body fluid or tissue, or a high WBC in the CSF if trypanosomes are not seen.[32]

The choice of rescue treatment depends on the patient's age and body weight, WBC count in the CSF, and the previous treatments used.[32]

Patients <6 years of age or <20 kg body weight: nifurtimox plus eflornithine is the recommended first-line rescue treatment. The standard course is recommended if ≤5 WBC/microlitre and there are no trypanosomes in the CSF. The longer course (14 days rather than 7 days of eflornithine) is recommended if >5 WBC/microlitre or there are trypanosomes in the CSF. Melarsoprol is an alternative option if >5 WBC/microlitre or there are trypanosomes in the CSF.[32]

Patients ≥6 years of age and ≥20 kg body weight: nifurtimox plus eflornithine (standard or long course) is the recommended rescue treatment if <100 WBC/microlitre in the CSF (non-severe second-stage disease). Nifurtimox plus eflornithine (long course) or melarsoprol are the recommended rescue treatments if ≥100 WBC/microlitre in the CSF (severe second-stage disease) or a failed lumbar puncture.[32]

Consult a specialist for further guidance on treating patients with relapse (including pregnant women).

1st line – repeat anti-trypanosomal treatment

Back
ONGOING
|
relapse
|
rhodesiense human African trypanosomiasis (HAT)
1st line – 

repeat anti-trypanosomal treatment

Patients must be monitored closely for 24 months after treatment for signs of relapse as there is no test of cure. Relapse may occur more than 1 year after treatment.[32][123]​​ Relapses may occur earlier (e.g., weeks or months) compared with gambiense HAT as disease progression is usually more rapid.[32] 

A relapse is defined as the presence of trypanosomes in any body fluid or tissue, or a high WBC in the CSF if trypanosomes are not seen.[32]

The choice of rescue treatment depends on the patient's age and body weight, WBC count in the CSF, and the previous treatments used.[32]

Patients <6 years of age or <20 kg body weight: fexinidazole is the recommended first-line rescue treatment (on a compassionate use basis), regardless of disease stage. Consult a specialist for guidance on a suitable dose in this patient group.[32]

Patients ≥6 years of age and ≥20 kg body weight: suramin is recommended for first-stage disease. Melarsoprol is recommended for second-stage disease. A lumbar puncture is required for staging.[32]

Consult a specialist for further guidance on treating patients with relapse (including pregnant women).

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Choose a patient group to see our recommendations

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

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