eMedicine Specialties > Infectious Diseases > Parasitic Infections
African Trypanosomiasis (Sleeping Sickness): Treatment & Medication
Updated: Feb 16, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
- Prehospital care of African trypanosomiasis (sleeping sickness) centers on management of the acute symptoms of fever and malaise while closely monitoring the patient’s neurologic status.
- In the emergency department, if CNS symptoms are severe, then airway management to prevent aspiration becomes important, along with an immediate blood smear, CBC count, and lumbar puncture for trypanosome detection.
Consultations
- Consult an infectious disease specialist for evaluation of both early- and late-stage African trypanosomiasis in a symptomatic patient with recent travel or suspicious parasitic exposure.
- Contact the Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia, for expertise in the diagnosis and treatment of African trypanosomiasis because it is rarely encountered in the United States (Division of Parasitic Diseases: 770-488-7760 or Drug Service: 404-639-3670).
Medication
The type of drug treatment used depends on the type and stage of African trypanosomiasis (sleeping sickness). The table below outlines management recommendations published in The Medical Letter on Drugs and Therapeutics in March 2000.1
Table 1. Medications Recommended for Treatment of African Trypanosomiasis
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Table
| Type of Trypanosomiasis | Medications Stage 1 (Hemolymphatic Stage) | Medications Stage 2 (Neurologic [CNS] Stage) |
| East African trypanosomiasis (caused by T brucei rhodesiense) | Suramin 100-200 mg IV test dose, then 1 g IV on days 1, 3, 7, 14, 21 | Melarsoprol 2-3.6 mg/kg/d IV for 3 d; after 1 wk, 3.6 mg/kg/d for 3 d; after 10-21 d, repeat the cycle |
| West African trypanosomiasis (caused by T brucei gambiense) | Pentamidine isethionate 4 mg/kg/d IM for 10 d or Suramin 100-200 mg IV test dose, then 1 g IV on days 1, 3, 7, 14, 21 | Melarsoprol 2-3.6 mg/kg/d IV for 3 d; after 1 wk, 3.6 mg/kg/d for 3 days; after 10-21 d, repeat the cycle or Eflornithine 400 mg/kg/d IV in 4 divided doses for 14 d |
| Type of Trypanosomiasis | Medications Stage 1 (Hemolymphatic Stage) | Medications Stage 2 (Neurologic [CNS] Stage) |
| East African trypanosomiasis (caused by T brucei rhodesiense) | Suramin 100-200 mg IV test dose, then 1 g IV on days 1, 3, 7, 14, 21 | Melarsoprol 2-3.6 mg/kg/d IV for 3 d; after 1 wk, 3.6 mg/kg/d for 3 d; after 10-21 d, repeat the cycle |
| West African trypanosomiasis (caused by T brucei gambiense) | Pentamidine isethionate 4 mg/kg/d IM for 10 d or Suramin 100-200 mg IV test dose, then 1 g IV on days 1, 3, 7, 14, 21 | Melarsoprol 2-3.6 mg/kg/d IV for 3 d; after 1 wk, 3.6 mg/kg/d for 3 days; after 10-21 d, repeat the cycle or Eflornithine 400 mg/kg/d IV in 4 divided doses for 14 d |
Combination therapy
Combination therapy may be more effective than monotherapy for the treatment of late-stage T brucei gambiense trypanosomiasis. An open randomized trial involving 278 patients compared melarsoprol monotherapy (two different dosing regimens), nifurtimox monotherapy, and melarsoprol-nifurtimox combination therapy. The 48 relapses reported in the study were limited to patients receiving one of the 3 monotherapy regimens. The trial concluded that a consecutive 10-day low-dose melarsoprol-nifurtimox combination is more effective than the standard melarsoprol regimen.2
A trial that compared the efficacy of eflornithine monotherapy to nifurtimox-eflornithine combination therapy in patients with late-stage T brucei gambiense infection found that cure rates were similar. However, adverse effects were more common in patients who received eflornithine monotherapy (25.5% vs 9.6%). Thus, the nifurtimox-eflornithine combination appears to be a promising regimen for use in late-stage T brucei gambiense trypanosomiasis.3
Anthelmintics
Parasite biochemical pathways are sufficiently different from the human host to allow selective interference by chemotherapeutic agents in relatively small doses.
Suramin (Metaret)
Antiparasitic agent used IV in early-stage African trypanosomiasis and onchocerciasis. Suramin is a polysulfonated naphthylamine derivative of urea. Suramin is trypanocidal and works by inhibiting parasitic enzymes and growth factors. Highly bound to serum proteins and, thus, crosses the blood-brain barrier poorly. Serum levels are approximately 100 mcg/mL. Suramin is more effective and less toxic than pentamidine. Excreted in the urine at a slow rate.
Adult
100-200 mg test dose, then 1 g IV on days 1, 3, 7, 14, 21
Pediatric
1-2 mg test dose, then 20 mg/kg IV on days 1, 3, 7, 14, 21
None reported
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Renal disease and hepatic disease (caused by high levels of unbound suramin); can cause palmar or plantar hyperesthesia, neuritis, pancytopenia, renal and liver failure, and optic atrophy; an immediate hypersensitivity reaction is estimated to occur in 1 per 20,000 patients, so a 200-mg test dose should be given first
Melarsoprol (Melarsen Oxide-BAL, Mel B, RP 3854)
Trivalent arsenical used in the late or CNS stage of African trypanosomiasis. Trypanocidal, inhibiting parasitic glycolysis. Water insoluble and has a half-life of 35 h. Serum levels range from 2-5 mcg/mL, but CSF levels are 50-fold lower. The drug is primarily excreted by the kidneys. Clinical improvement is usually observed within 4 d after starting the drug. Therapy is as high as 90-95% successful in clearing the parasitemia. However, it can be toxic and even fatal in 4-6% of cases.
Studies have now demonstrated the effectiveness of 10-day melarsoprol treatments for late-stage African trypanosomiasis. In addition, melarsoprol resistance has become a concern in the Congo and Uganda; up to 30% of cases do not respond to the drug.
Adult
2-3.6 mg/kg/d IV for 3 d; after 1 wk, 3.6 mg/kg/d IV for 3 d; after 10-21 d, repeat the cycle; always administer each dose slowly on an empty stomach
Pediatric
0.36 mg/kg IV initially; increase gradually to a maximum 3.6 mg/kg at intervals of 1-5 d for a total of 9-10 doses; average dosing is 18-25 mg/kg over 1 mo
None reported
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in renal, cardiac, or hepatic disease; encephalopathy may occur in up to 10% cases 2 d to 2 wk after starting melarsoprol unrelated to dose or dosing frequency; prednisolone can reduce risk of encephalopathy and is administered 1-2 d prior to and during melarsoprol therapy, starting with 1 mg/kg/d, up to 40 mg/d, and tapering quickly after last injection; a Herxheimer reaction with fever and chills may also occur, resulting from trypanosome destruction
Eflornithine (Ornidyl)
Recommended for treatment of patients with West African trypanosomiasis, especially late (or CNS) disease. Selective and irreversible inhibitor of ornithine decarboxylase, which is a critical enzyme for DNA and RNA synthesis. Generally tolerated better and is less toxic than arsenic drugs. Available via World Health Organization. Initial response time is 1-2 wk. Used for patients in whom melarsoprol fails.
Adult
100 mg/kg IV q6h for 14 d
Pediatric
Not established
May reduce effects of immunization with live and rotavirus vaccines
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in coexisting bone marrow suppression or hematologic abnormalities; myelosuppression, pancytopenia, decreased hearing, and seizures may occur
Pentamidine isethionate (Pentam 300, Pentacarinat, NebuPent)
Antiprotozoal agent usually used for early (or stage 1) African trypanosomiasis as well as Pneumocystis carinii pneumonia and leishmaniasis. Works by inhibiting dihydrofolate reductase enzyme, thereby interfering with parasite aerobic glycolysis. Because of poor GI absorption, the drug is administered IV/IM and is strongly bound to tissues, including spleen, liver, and kidney. Clinical improvement usually noted within 24 h of injection. Reported to have a >90% cure rate. Pentamidine does not penetrate the blood-brain barrier effectively and, therefore, does not treat CNS infection.
Adult
4 mg/kg/d IM/IV for 10 d
Pediatric
Administer as in adults
Coadministration with cidofovir may cause nephrotoxicity; hypocalcemia may occur with foscarnet; prolonged QTc observed with grepafloxacin (Withdrawn from US market) and sparfloxacin; pancreatitis reported with zalcitabine
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Can cause leukopenia, anemia, hypotension, arrhythmia, rash, renal failure, and pancreatitis; caution in diabetes mellitus, hypertension or hypotension, hepatic dysfunction, hypoglycemia, leukopenia, and thrombocytopenia
More on African Trypanosomiasis (Sleeping Sickness) |
| Overview: African Trypanosomiasis (Sleeping Sickness) |
| Differential Diagnoses & Workup: African Trypanosomiasis (Sleeping Sickness) |
 Treatment & Medication: African Trypanosomiasis (Sleeping Sickness) |
| Follow-up: African Trypanosomiasis (Sleeping Sickness) |
| Multimedia: African Trypanosomiasis (Sleeping Sickness) |
| References |
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References
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Priotto G, Kasparian S, Ngouama D, Ghorashian S, Arnold U, Ghabri S, et al. Nifurtimox-eflornithine combination therapy for second-stage Trypanosoma brucei gambiense sleeping sickness: a randomized clinical trial in Congo. Clin Infect Dis. Dec 1 2007;45(11):1435-42. [Medline].
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Schmid C, Richer M, Bilenge CM, Josenando T, Chappuis F, Manthelot CR, et al. Effectiveness of a 10-day melarsoprol schedule for the treatment of late-stage human African trypanosomiasis: confirmation from a multinational study (IMPAMEL II). J Infect Dis. Jun 1 2005;191(11):1922-31. [Medline].
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Further Reading
Keywords
sleeping sickness, African trypanosomiasis, human African trypanosomiasis, HAT, Trypanosoma brucei, T brucei, Trypanosoma brucei rhodesiense, Trypanosoma brucei gambiense, tsetse flies, Glossina species, East African trypanosomiasis, Rhodesian African trypanosomiasis, West African trypanosomiasis, Gambian African trypanosomiasis, trypanosomes
