Approach Considerations
Prehospital care of African trypanosomiasis (sleeping sickness) centers on management of the acute symptoms of fever and malaise in conjunction with close monitoring of the patient’s neurologic status. In the emergency department, if central nervous system (CNS) symptoms are severe, airway management to prevent aspiration becomes important, along with an immediate blood smear, complete blood count (CBC), and lumbar puncture for trypanosome detection.
If late stage disease is present or CNS disease complications and coma occur, intensive care unit (ICU) staff are needed while treatment is administered (ie, melarsoprol for East African trypanosomiasis or eflornithine for West African trypanosomiasis). Potential adverse effects from such drugs, including hematologic, renal, and hepatic function must be monitored.
Pharmacologic Therapy
The type of drug treatment used depends on the type and stage of African trypanosomiasis. [13]
Table. Medications Recommended for Treatment of African Trypanosomiasis (Open Table in a new window)
Type of Trypanosomiasis |
Medications |
|
Stage 1 (Early or Hemolymphatic Stage) |
Stage 2 (Late or Neurologic Stage) |
|
East African trypanosomiasis (caused by Trypanosoma brucei rhodesiense) |
Suramin 4-5 mg/kg IV test dose, then 20 mg/kg (maximum 1 g/dose) IV on Days 1, 3, 7, 14, 21 |
Melarsoprol 2.2 mg/kg/day (maximum 180-200 mg) IV for 10 days |
West African trypanosomiasis (caused by Trypanosoma brucei gambiense) |
Pentamidine isethionate 4 mg/kg/day IM for 10 days or Suramin 4-5 mg/kg IV test dose, then 20 mg/kg (maximum 1 g/dose) IV on Days 1, 3, 7, 14, 21 or Fexinidazole 20 to < 35 kg: 1200 mg PO qd on Days 1-4, then 600 mg qd on Days 5-10 Fexinidazole 35 kg or greater: 1800 mg PO qd on Days 1-4, then 1200 mg qd on Days 5-10 |
Nifurtimox-Eflornithine Combination Therapy (NECT): Nifurtimox 5 mg/kg PO q8h for 10 days AND Eflornithine 200 mg/kg IV q12h for 7 days or Eflornithine 400 mg/kg/day IV in 2 divided doses for 14 days or Melarsoprol IV for 10 days or Fexinidazole PO for 10 days |
Since 2009, the WHO has adopted the combination of eflornithine and nifurtimox (NECT) as first-line treatment for second-stage gambiense human African trypanosomiasis in all countries with endemic disease. The combination of both drugs reduces the duration of eflornithine monotherapy treatment and is easier to administer, while improving the level of efficacy and safety. The guidelines from WHO were updated in 2019 and reflect simplified and safer treatment options. [14]
In November 2018, the European Medicines Agency (CHMP) adopted a positive opinion for fexinidazole as the first oral-only regimen for the treatment of first–stage (hemolymphatic) and second-stage (meningoencephalitic) human African trypanosomiasis due to T brucei gambiense in adults and children aged 6 years and older and who weigh 20 kg or more. [15]
Fexinidazole was approved by the FDA in July 2021. In a randomized trial including 394 patients with late-stage human African trypanosomiasis due to T brucei gambiense treated with fexinidazole or nifurtimox-eflornithine combination therapy (NECT), success at 18 months was noted in 91% of patients treated with fexinidazole versus 98% of patients treated with NECT. [16] Two single-arm trials in adults and pediatric patients aged 6-15 years demonstrated efficacy of 98.7% and 97.6% respectively at 12 months. [17]
Prevention
No vaccine is available for African trypanosomiasis. Chemoprophylaxis is unavailable.
Avoidance of travel to areas heavily infested with tsetse flies is recommended. Tsetse flies are attracted to moving vehicles and dark contrasting colors. They are not affected by insect repellants and can bite through lightweight clothing. At-risk travelers are advised to wear wrist- and ankle- length clothing that is made of medium-weight fabric in neutral colors.
Treatment of asymptomatic carriers is possible, and infection can be detected by means of the card agglutination test for trypanosomiasis (CATT) or lymph node aspiration and confirmed with smears.
Consultations
An infectious disease specialist should be consulted for evaluation of both early- and late-stage African trypanosomiasis in a symptomatic patient with recent travel or suspicious parasitic exposure.
Because African trypanosomiasis is so rarely encountered in the United States, it may be advisable to contact the Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia, for assistance in the diagnosis and treatment of this disease (Division of Parasitic Diseases, 770-488-7760; Drug Service, 404-639-3670).
Long-Term Monitoring
In both early and late-stage trypanosomiasis, symptoms usually resolve after treatment, and the parasitemia clears on repeat blood smears.
Patients who have recovered from late-stage East African trypanosomiasis should undergo lumbar punctures every 3 months for the first year. Patients who have recovered from West African trypanosomiasis should undergo lumbar punctures every 6 months for 2 years.
If symptoms return, the CSF WBC count is higher than 20/µL, or trypanosomes are still present in blood or CSF, a relapse is suggested. However, a persistently elevated CSF WBC count may also be observed in recovering patients; thus, the change (increase or decrease) in the WBC count is more diagnostically helpful than the count by itself. If a relapse is noted, repeat treatment with melarsoprol or eflornithine may be considered.
-
African trypanosomiasis (sleeping sickness). Human trypanosomes blood smear.
-
Trypanosoma life cycle. Courtesy of the CDC Division of Parasitic Diseases and Malaria (DPDx at https://www.cdc.gov/dpdx/trypanosomiasisafrican/index.html).
-
Trypanosoma brucei in a thin blood smear stained with Giemsa. Courtesy of the CDC Division of Parasitic Diseases and Malaria (DPDx at https://www.cdc.gov/dpdx/trypanosomiasisafrican/index.html).
-
Geographical distribution of human African trypanosomiasis. Courtesy of PLoS Neglected Tropical Diseases [Franco JR, Cecchi G, Paone M, et al. The elimination of human African trypanosomiasis: Achievements in relation to WHO road map targets for 2020. PLoS Negl Trop Dis. 2022 Jan 18;16(1):e0010047. Online at: https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0010047.]
-
The cases of Human African Trypanosomiasis (HAT) have decreased annually from 2000 to 2020. Courtesy of PLoS Neglected Tropical Diseases [Franco JR, Cecchi G, Paone M, et al. The elimination of human African trypanosomiasis: Achievements in relation to WHO road map targets for 2020. PLoS Negl Trop Dis. 2022 Jan 18;16(1):e0010047. Online at: https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0010047.]
Tables
Type of Trypanosomiasis |
Medications |
|
Stage 1 (Early or Hemolymphatic Stage) |
Stage 2 (Late or Neurologic Stage) |
|
East African trypanosomiasis (caused by Trypanosoma brucei rhodesiense) |
Suramin 4-5 mg/kg IV test dose, then 20 mg/kg (maximum 1 g/dose) IV on Days 1, 3, 7, 14, 21 |
Melarsoprol 2.2 mg/kg/day (maximum 180-200 mg) IV for 10 days |
West African trypanosomiasis (caused by Trypanosoma brucei gambiense) |
Pentamidine isethionate 4 mg/kg/day IM for 10 days or Suramin 4-5 mg/kg IV test dose, then 20 mg/kg (maximum 1 g/dose) IV on Days 1, 3, 7, 14, 21 or Fexinidazole 20 to < 35 kg: 1200 mg PO qd on Days 1-4, then 600 mg qd on Days 5-10 Fexinidazole 35 kg or greater: 1800 mg PO qd on Days 1-4, then 1200 mg qd on Days 5-10 |
Nifurtimox-Eflornithine Combination Therapy (NECT): Nifurtimox 5 mg/kg PO q8h for 10 days AND Eflornithine 200 mg/kg IV q12h for 7 days or Eflornithine 400 mg/kg/day IV in 2 divided doses for 14 days or Melarsoprol IV for 10 days or Fexinidazole PO for 10 days |
