Trypanosoma brucei gambiense

Vincendeau, P. et al., Nitric oxide-mediated cytostatic activity on Trypanosoma brucei gambiense and Trypanosoma brucei brucei, Exp. Parasitol., 75, 353, 1992. 

S.2.3.3 Treatment of Trypanosomiasis The difluoromethylornithine (DFMO), eflomithine is a mechanism-based inhibitor of ornithine decarboxylase— a pyridoxal-dependent key enzyme of the polyamine s biosynthesis from ornithine. Fluorine atoms are essential for the inhibition process (cf. Chapter 7). Eflornithine was first clinically developed for cancer, but its development has been abandoned for this indication. The activity of eflornithine on trypanosomes was then discovered. Now, despite its very low bioavailability, eflornithine is the best therapy for sleeeping sickness (trypanosomiasis)—in particular, at the cerebral stage—due to Trypanosoma brucei gambiense parasite. Eflornithine is registered with orphan drug status and is distributed by the WHO. 

Bisser S 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 2007 195 322. [PMID 17205469]... 

Priotto G et al Nifurtimox-eflornithine combination therapy for second-stage Trypanosoma brucei gambiense sleeping sickness A randomized clinical trial in Congo. Clin Infect Dis 2007 45 1435. [PMID 17990225]... 

Burri C, Nkunku S, Merolle A et al (2000) Efficacy of new, concise schedule for melarsoprol in treatment of sleeping sickness caused by Trypanosoma brucei gambiense a randomised trial. Lancet 355 1419-1425... 

Pepin J, Mpia B (2006) Randomized controlled trial of three regimens of melarsoprol in the treatment of Trypanosoma brucei gambiense trypanosomiasis. Trans R Soc Trop Med Hyg 100 437 141... 

In 42 patients with late-stage Trypanosoma brucei gambiense trypanosomiasis, who relapsed after initial treatment with melarsoprol, a sequential combination of intravenous efiornithine (100 mg/kg every 6 hours for 4 days) followed by three daily injections of melarsoprol (3.6 mg/kg, up to 180 mg) was used (8). They were followed for 24 months. In one case, the administration of efiornithine had to be interrupted for 48 hours because of convulsions, but treatment was then resumed without recurrence. Other adverse effects during treatment were abdominal pain or vomiting (n = A each), diarrhea (n = 1), and loss of hearing (n = 1). Two patients died during treatment ... 

In a randomized trial in 500 patients infected with Trypanosoma brucei gambiense treated with 10 daily consecutive doses of melarsoprol 2.2 mg/kg, the adverse effects were encephalopathic syndrome 5.6%, death from encephalopathy 2.4%, polyneuropathy less than 1%, severe bullous dermatitis 1.2%, severe maculopapu-lar rash 3.2%, severe pruritus 3.2% (5). Milder reactions were fever, headache, and diarrhea. 

Pepin J, Milord F, Meurice F, Ethier L, Loko L, Mpia B. High-dose nifurtimox for arseno-resistant Trypanosoma brucei gambiense sleeping sickness an open trial in central Zaire. Trans R Soc Trop Med Hyg 1992 86(3) 254-6. 

Stimulate appetite in AIDS Lambert-Eaton myasthenic syndrome and Charcot-Marie tooth disease Trypanosoma brucei gambiense (sleeping sickness) Pneumocystis carinii pneumonia in AIDS organ transplant recipients Corneal epithelial regeneration and healing Anemia associated with end-stage renal disease Anemia associated with end-stage renal disease Primary pulmonary hypertension Acute lymphocytic leukemia... 

Tschudi, C., Richards, F. F. and Ullu, E. (1986) The U2 RNA analogue of Trypanosoma brucei gambiense implications for splicing mechanisms in trypanosomes. Nucleic Acids Res. 14 8893 8903. 

Darling, T. N., Balber, A. E. and Blum, J. J. (1988) A comparative study of D-lactate and L-lactate formation by four species of Leishmania and of Trypanosoma lewisi and Trypanosoma brucei gambiense. Mol. Biochem. Parasitol. 30 253-258. 

Fish, W. R., Marr, J. J. and Berens, R. L. (1982) Purine metabolism in Trypanosoma brucei gambiense. Biochim. Biophys. Acta 714 422-428. 

Suramin is the drug of choice for the early hemolymphatic stage of both Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense infections before nervous system invasion occurs [17 ]. The dose is 15-20 mg/kg/week, given intravenously, up to a maximum single dose of 1 g. Suramin, which is excreted by the kidneys, binds to plasma proteins and can persist in the circulation in low concentrations for as long as 3 months. A single course for an adult is usually 5 g, never to exceed 7 g. The primary adverse reactions are fever, rash, conjunctivitis, renal insufficiency, abdominal pain, paresthesia, and muscle pain. 

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