- Pentamidine
Pentamidine (Lomidine) is used only for the early phase of the disease, since it does not cross the blood-brain barrier. It is active against T. gambiense, but it should not be used against T. rhodesiense, since primary resistance to it has been found in some areas. It should also not be used in areas where pentamidine has been widely employed for chemoprophylaxis, such as in the former Belgian Congo. As chemoprophylaxis pentamidine as an intramuscular injection of 4 mg/kg has been assumed to protect for several months. This is not recommended anymore since the dose is subcurative and may mask an underlying infection. Moreover, the prophylactic use of pentamidine has has provoked resitance in several areas. The recommended dose for treatment is 4 mg of pentamidine base per kg of body weight given intramuscularly in a total of 7 injections daily or on alternating days. - Suramin
Suramin has been developed in 1916 as a spin off of the german dye industry. It is a highly charged compound and so it is believed not to cross the blood-brain barrier. Therefore, monotherapy should only be used in the early stage of the disease. It is the preferred drug for use in the infection in East Africa. The drug is administered intravenously at a dosage of 20 mg/kg. It circulates in the blood in tight association with serum albumin and low density lipoproteins and is taken up slowly by both host and parasite, probably by receptor mediated endocytosis. Suramin is deposited in the renal tubes. Therefore it should not be administered at patients with renal disease. Urine should be checked before and during treatment for proteinuria. Suramin is also used for the treatment of onchocerciasis or river blindness in West Africa and therefore it is preferred not to be used for the treetment of sleeping sickness in this region.
- Melarsoprol, Arsobal, Mel
B
This drug is in use for trypanosomiasis since 1947. It is very effective in the treatment of both the early and the late stage of sleeping sickness, however, due to the risks associated with its use (see below) the drug is used only for the treatment of the late stage of the disease, both in West and in East Africa. The maximum dose for each injection is 3.6 mg/kg. The usual treatment comprises several series of injections, each separated by at least one week. Treatment may be associated with an acute reactive encephalopathy in 5 - 10 % of the cases, which may result in paralysis, brain damage or even death.
Official figures from the World Health Organization state between 10 and 20 000 cases of sleeping sickness per year. However, the deteriorating situation in Central Africa has led to major outbreaks of the disease, with recently hundres of thousands of estimated cases in Zaire / Congo alone. As a result annually only 20 000 dosages of Arsobal are produced in two batches per year. Last year (1996) due to production problems a complete batch of Arsobal had to be destroyed, resulting in a total lack of drug in Africa for several months. The number of people that died from this shortage of drug can only be estimated.
- Eflornitine
Difluoromethyl ornithine (DFMO) or Eflornithine is a newly developed drug that is effective in the treatment of both the early and the late stage of West African sleeping sickness. It is not effective in the treatment of T. rhodesiense infections in east Africa. It is an ornithine analogue that inhibits the enzyme ornithine decarboxylase, the first enzyme in the synthesis of polyamines, essential in cell division and in the protection against oxidant stress in the trypanosome.(see elsewhere). However, due to rapid excretion of the drug, the compound has to be given in very large quantities. A full treatment takes 400 grams of Eflornithine over a total period of two weeks, first as an infusion, followed by oral adminsitration in fruit juice. This drug is also called the "resurrection" drug, since comatous patients treated with Eflornithine may wake up rapidly and resume their activities.
There are drugs that are widely used for the treatment of nagana or cattle trypanosomiasis such as ethidium, isomethamidium (Samorin), or berenil. These drugs are effective, both for treatment and for prophylaxis, but are known to intercalate into the DNA and, therefore, are suspected of being mutagenic and tumorigenic and thus cannot be used for the treatment of humans. Cattle treated with these drugs may only be slaughtered and used for consumption, several months after treatment, when there is no residual drug left in the animal.