African Trypanosomiasis (Sleeping Sickness) Medication
- Author: Randy O Odero; Chief Editor: Burke A Cunha, MD more...
Medication Summary
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.[4]
Table 1. Medications Recommended for Treatment of African Trypanosomiasis (Open Table in a new window)
| 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.[5]
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.[6]
Anthelmintics
Class Summary
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.
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.
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.
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.
Truc P, Lando A, Penchenier L, Vatunga G, Josenando T. Human African trypanosomiasis in Angola: clinical observations, treatment, and use of PCR for stage determination of early stage of the disease. Trans R Soc Trop Med Hyg. Jan 2012;106(1):10-4. [Medline].
Simarro PP, Cecchi G, Franco JR, Paone M, Fèvre EM, Diarra A, et al. Risk for human african trypanosomiasis, central Africa, 2000-2009. Emerg Infect Dis. Dec 2011;17(12):2322-4. [Medline].
Kohagne TL, M'eyi MP, Kamkuimo RG, Kaba D, Louis JF, Mimpfoundi R. Transmission of human African trypanosomiasis in the Komo-Mondah focus, Gabon. Pan Afr Med J. 2011;8:36. [Medline]. [Full Text].
Abramowicz M. Drugs For Parasitic Infections. In: Abramowicz M, ed. The Medical Letter on Drugs and Therapeutics. New Rochelle, NY: The Medical Letter, Inc; 2000:1-12.
[Best Evidence] Bisser S, N'Siesi FX, Lejon V, Preux PM, Van Nieuwenhove S, Miaka Mia Bilenge C, et al. Equivalence trial of melarsoprol and nifurtimox monotherapy and combination therapy for the treatment of second-stage Trypanosoma brucei gambiense sleeping sickness. J Infect Dis. Feb 1 2007;195(3):322-9. [Medline].
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].
Barrett MP. The fall and rise of sleeping sickness. Lancet. Apr 3 1999;353(9159):1113-4. [Medline].
Brun R, Balmer O. New developments in human African trypanosomiasis. Curr Opin Infect Dis. Oct 2006;19(5):415-20. [Medline].
Centers for Disease Control and Prevention. Trypanosomiasis Fact Sheet. CDC. May, 2000;[Full Text].
Chappuis F, Loutan L, Simarro P, Lejon V, Büscher P. Options for field diagnosis of human african trypanosomiasis. Clin Microbiol Rev. Jan 2005;18(1):133-46. [Medline].
Drugs for Parasitic Infections. Medical Lett Drugs Ther. August/2004.
Hide G. History of sleeping sickness in East Africa. Clin Microbiol Rev. Jan 1999;12(1):112-25. [Medline].
Kozarsky PE, Arguin PM, Navin AW. African Trypanosomiasis (African Sleeping Sickness). Travelers' Health: Yellow Book. Health Information for International Travel, 20. 2005-2006;[Full Text].
Legros D, Evans S, Maiso F, Enyaru JC, Mbulamberi D. Risk factors for treatment failure after melarsoprol for Trypanosoma brucei gambiense trypanosomiasis in Uganda. Trans R Soc Trop Med Hyg. Jul-Aug 1999;93(4):439-42. [Medline].
Lejon V, Büscher P. Review Article: cerebrospinal fluid in human African trypanosomiasis: a key to diagnosis, therapeutic decision and post-treatment follow-up. Trop Med Int Health. May 2005;10(5):395-403. [Medline].
Micromedex. Antiparasitic drug information. Micromedex electronic database. May, 2000.
Pepin J. African Trypanosomiasis. In: Strickland GT, ed. Hunter's Tropical Medicine. 7th ed. Philadelphia, Pa: WB Saunders; 1998:643-53.
Pepin J, Milord F, Guern C. Trial of prednisolone for prevention of melarsoprol-induced encephalopathy in gambiense sleeping sickness. Lancet. Jun 3 1989;1(8649):1246-50. [Medline].
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].
Sinha A, Grace C, Alston WK. African trypanosomiasis in two travelers from the United States. Clin Infect Dis. Oct 1999;29(4):840-4. [Medline].
Smith DH, Pepin J, Stich AH. Human African trypanosomiasis: an emerging public health crisis. Br Med Bull. 1998;54(2):341-55. [Medline].
Turner CM. Antigenic variation in Trypanosoma brucei infections: an holistic view. J Cell Sci. Oct 1999;112 (Pt 19):3187-92. [Medline].
World Health Organization. Control and surveillance of African trypanosomiasis. Report of a WHO Expert Committee. World Health Organ Tech Rep Ser. 1998;881:I-VI, 1-114. [Medline].
World Health Organization. WHO fact sheet on African Trypanosomiasis. WHO fact sheets. Revised August 2006;Fact sheet 259:[Full Text].
| 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 |
Print
