Treatment

A recent agreement and ongoing discussions between WHO and the pharmaceutical industry give patients hope for survival.The treatment of sleeping sickness depends on five key drugs needed for the different forms and stages of the disease.

Suramin
Pentamidine
Melarsoprol
Eflornithine
Nifurtimox

Three of these drugs—pentamidine, melarsoprol and eflornithine—are now being donated to WHO, for exclusive use in the treatment of sleeping sickness, in a quantity adequate to meet global needs for the next five years.

Pentamidine is used for the initial phase of the T.b. gambiense form of sleeping sickness.

Melarsoprol is used for the second phase of the T.b. gambiense form, while eflornithine isused for the advanced neurological phase of this condition.

Suramin used to treat the initial phase of the T.b. rhodesiense form of the disease; free supply of the drig is under discussion.

Nifurtimox is currently registered for the treatment of Chagas disease but not for sleeping sickness. WHO is considering to undertake certain development work to support a so-called "label extension" of nifurtimox for sleeping sickness.
If, based on such possible development work, a label extension can be obtained, WHO shall undertake further discussions to also obtain free supplies of nifurtimox for sleeping sickness.

Initial Phase treatment - Phase 1

If detected and treated early chances for a cure are good. The early drugs suramine and pentamidine affected only one subtype and had moderate to severe side effects. They are used in the initial stage of the disease

SURAMIN

Suramin was discovered in 1921 is used exclusively for the treatment of the initial phase of T.b. rhodesiense infection. Vials contain 1 g of active compound in the form of powder that is disolved in distilled water as a 10% solution immediately prior to injection. renal complications.

Dosage
The recommended dosage is 20 mg/kg/day with a maximum dose of 1 g per injection.The drug is administered intravenously at the rate of one injection per week.The treatment course is 5 weeks for a total of five injections.

Adverse reactions
Due to the risk of a severe anaphylactic reaction, it is recommended that a test injection of 0.2 ml be administered intravenously to verify the drug tolerance of the patient.

Pentamidine

Pentamidine is used for the treatment of T.b. gambiense infection in its early stages. Pentamidine is available in two forms:
• vials containing 300 mg of pentamidine isethionate (Pentacarinat®) for conditions other than sleeping sickness;
• vials containing 200 mg of pentamidine isethionate, specifically formulated for WHO and provided free of charge for the treatment of sleeping sickness for many years. WHO will continue to distribute this formulation for sleeping sickness.

Dosage
Dosage is 4 mg/kg/day given by intramuscular injection for seven consecutive days.

Adverse reactions
Side-effects are rare and generally reversible on interruption of treatment.A rest period of one to two hours immediately following the injection of the drug is needed to minimize the risk of arterial
hypotension.

Pentamidine is also a treatment in HIV/AIDS for PCP pneumoni

Late stage Treatment - Phase 2

There are only two effective drugs for the late, neurological stages of African trypansomiasis Melarsoprol and Suramin

Melarsoprol

Discovered in 1949 was until recently the only drug that could cross the blood brain barrier to reach the parasite in the later stages of the disease, no matter which parasite was the cause. It is the last arsenic derivative in existence.

Melarsoprol is strictly used for the second (neurological) phase of T.b. gambiense disease. Each 5 ml melarsoprol ampoule contains 180 mg of active compound.

Dosage
The most frequently used dosage is: three series of injections administered with a rest period of 8 to 10 days between each series. A series consists of one injection of 3.6 mg/kg/day for 3 consecutive days.

Injections are intravenous and must be given slowly due to the risk of thrombo-phlebitis and necrosis at the injection site if the liquid is injected into the tissues surrounding the vein. Such a reaction generally precludes the use of this site for another injection for an extended period.

NOTE: An open ampoule must be used the same day. The injection must take place immediately upon preparation.

Adverse reactions
Melarsoprol is a very dangerous drug. Melarsoprol treatment frequently has severe adverse effects. The most serious complication of melarsoprol treatment is reactive encephalopathies. They occur at varying frequencies in 5–10% of treated cases. The reaction is fatal for about 10–70% of the patients afflicted. There is also significant drug resistance rising to 30% in some areas of central Africa. (WHO,2000, 2002)

Convulsions, coma or unexpected neurological alterations call for an immediate interruption of treatment until all signs have disappeared.

Eflornithine

Eflornithine (difluoromethylornithine or DMFO) was first registered for in sleeping sickness in 1990's decade and was the first new drug to be approved for use in African trypanosomiasis for over 40 years.  It was hailed as a ‘miracle drug’ because of it’s ability to resurrect comatose patients. However, the drug has number of drawbacks: it is only effective in cases of T b. gambiense infection; it is expensive, 14 vials are required to treat each patient at a cost that varies from US$884 to US$392. (Khonde & Mpia, 1998) Furthermore, because it is given intravenously, it can only be administered in a hospital setting to the patient.

Eflornithine is reserved for the treatment of the advanced neurological stage of T.b. gambiense disease. Bottles of 100 ml of eflornithine contain 200 mg/ml, or 20 g of active compound.

Dosage:
• adult dosage is 400 mg/kg/day administered in four daily slow infusions
(lasting approximately 2 hours). Infusions are given every 6 hours, which represents a dose of 100 mg/kg per infusion;

• the recommended dosage for children is 150 mg/kg per infusion, following the same protocol as for adults.

Each dose should be diluted in 250 cc isotonic saline solution. Particular indications: when used following melarsoprol treatment failure, the treatment schedule with eflornithine is 7 days. As a first-line treatment, the schedule is 14 days.

Adverse reactions
Adverse reactions are numerous and patients must remain under close medical supervision. Anaemia, diarrhoea, convulsions and vomiting are the most frequent adverse reactions.This drug can be deadly.

Nifurtimox

Nifurtimox has been registered for the treatment of American trypanosomiasis (Chagas disease); it is currently not registered for sleeping sickness. The drug is effective at both stages of T.b. gambiense infection. At this time, the curative effect of nifurtimox against infections due to T.b. rhodesiense is not documented. Several trials have taken place using different dosages for the treatment of sleeping sickness, and nifurtimox is currently used by certain programmes as compassionate treatment when other registered drugs have failed.

Tablets contain 120 mg of the active ingredient.

Dosage:
- adults: 5 mg/kg/day orally, 3 times a day; - children: 7 mg/kg/day orally, 3 times a day. The treatment schedule is 14 to 21 days.The 21- day schedule as well as dosage must not be exceeded owing to the risk of complications. Clinical trials are to be implemented in order for the drug to be registered for sleeping sickness and to determine the optimal dosage.

Adverse reactions
Mainly anorexia and neurological alterations (psychiatric and somatic).

NOTE
The drug is not registered for sleeping sickness, but for Chagas disease. Further nformation: janninj@who.int

Recommendations for auxiliary treatment

As in the case of any other disease treatment, the medical officer is responsible for treating other infections the patient may have which quite often coexist within the patient. The aim is to improve the patient’s general health and thus ensure that the patient receives treatment for sleeping sickness under the best possible conditions. However, it is also essential not to delay the specific treatment for sleeping sickness.

The following conditions must be treated: parasitic infections such as malaria, > nutritional deficiencies and severe anaemia, acute bacterial and viral infections. Symptomatic treatment can be given for other conditions. In general, other conditions can be treated after administration of the specific treatment for sleeping sickness.

Auxiliary drugs are not provided by WHO. They must be procured by the patient or local health authorities in accordance with national policyi.

FAQS

DRUGS & TREATMENT

African Sleeping Sickness

Programme Against African Trypanosomiasis