Drugs available for the treatment of
sleeping sickness and Nagana
Treatment of the early phase of the disease is with either
pentamidine in West Africa or suramin in East Africa and for the late
stage of the disease with organic arsenicals (Arsobal, Melarsoprol,
Mel B). The latter treatment is not without danger and may lead in
5-10% of cases to a fatal encephalopathy. There are several problems
related to some if not all of these drugs.
- Drugs for use in humans
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 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
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.
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
- Drugs for veterinary use.
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.
Continue with Chags' Disease
Last updated: 3 November 1997.
created by :Fred