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About

• Human African trypanosomiasis, also known as sleeping sickness, is a vector-borne parasitic disease
• Caused by infection with protozoan parasites belonging to the genus Trypanosoma.

Aetiology

• They are transmitted to humans by tsetse fly (Glossina genus) bites which have acquired their infection from human beings or from animals harbouring human pathogenic parasites.
• Tsetse flies are found just in sub-Saharan Africa though only certain species transmit the disease. For reasons that are so far unexplained, in many regions where tsetse flies are found, sleeping sickness is not.
• Rural populations living in regions where transmission occurs and which depend on agriculture, fishing, animal husbandry or hunting are the most exposed to the tsetse fly and therefore to the disease.
• The disease develops in areas ranging from a single village to an entire region. Within an infected area, the intensity of the disease can vary from one village to the next.

Different forms: Human African trypanosomiasis takes 2 forms, depending on the parasite involved:

• Trypanosoma brucei gambiense is found in West and Central Africa and currently accounts for 97% of reported cases of sleeping sickness and causes a chronic infection. A person can be infected for months or even years without major signs or symptoms of the disease. In advanced disease the CNS is affected.
• Trypanosoma brucei rhodesiense is found in eastern and southern Africa. Nowadays, this form represents under 3% of reported cases and causes an acute infection. The disease develops after a few months or weeks after infection and rapidly invades the CNS. Only Uganda presents both forms of the disease, but in separate zones.
• Another form of trypanosomiasis occurs mainly in Latin America. It is known as American trypanosomiasis or Chagas disease. The causal organism belongs to a different Trypanosoma subgenus and is transmitted by a different vector.

Clinical

• First stage: In the first stage, the trypanosomes multiply in subcutaneous tissues, blood and lymph. This is also called the haemo-lymphatic stage, which entails bouts of fever, headaches, joint pains and itching. Look for swollen rubbery painless cervical lymph nodes. Winterbottom's sign is enlarged posterior cervical nodes.
• Second stage: the parasites cross the blood-brain barrier to the CNS. This is known as the neurological or meningo-encephalic stage. There is a change of behaviour, confusion, sensory disturbances and poor coordination with disturbance of the sleep cycle, which gives the disease its name, is an important feature. Some develop movement disorders such as choreiform, tremor, fasciculations and ataxia. Without treatment, sleeping sickness is considered fatal although cases of healthy carriers have been reported.

Investigations

• Serological screening (only available for T.b.gambiense)
• Diagnosing by establishing whether the parasite is present in body fluids.
• LP and CSF examination may show raised protein and raised pressure and raised mononuclear cells

Management

• Depends on the disease stage. First stage drugs are safer and easier to administer than those for the second stage. The earlier the disease is identified, the better the prospect of a cure. Needs follow up of the patient up to 24 months and entails laboratory exams of body fluids including CSF as parasites may remain viable for long periods and reproduce the disease months after treatment.
• Treatment success in the second stage depends on drugs that cross the blood-brain barrier to reach the parasite. Such drugs are toxic and complicated to administer.
• In total five different drugs are used for the treatment of sleeping sickness. These drugs are donated to WHO by manufacturers and distributed free of charge to disease-endemic countries.
• Drugs used in first stage treatment: Pentamidine: used for the treatment of the first stage of T.b. gambiense sleeping sickness. Generally well tolerated by patients. Suramin: discovered in 1920, used for the treatment of the first stage of T.b. rhodesiense. It provokes certain undesirable effects, including urinary tract and allergic reactions.
• Drugs used in second stage treatment: Melarsoprol: discovered in 1949, it is used for the treatment of both gambiense and rhodesiense infections. It is derived from arsenic and has many undesirable side effects, the most dramatic of which is reactive encephalopathy (encephalopathic syndrome) which can be fatal (3% to 10%). An increase in resistance to the drug has been observed in several foci, particularly in central Africa. It is currently recommended as a first-line treatment for the rhodesiense form, and as second-line for the gambiense form. Eflornithine: this molecule, less toxic than melarsoprol, was registered in 1990. It is only effective against T.b. gambiense. The regimen is complex and difficult to apply. Nifurtimox: A combination treatment of nifurtimox and eflornithine was introduced in 2009. It simplifies the use of eflornithine by reducing the duration of treatment and the number of IV perfusions, but unfortunately, it has not been studied for T.b. rhodesiense. Nifurtimox is registered for the treatment of American trypanosomiasis but not for human African trypanosomiasis. Nevertheless, after safety and efficacy data provided by clinical trials, its use in combination with eflornithine has been included in the "WHO List of Essential Medicines" and is currently recommended as a first-line treatment for the gambiense form. Both drugs are provided free of charge by WHO to endemic countries with a kit containing all the material needed for its administration.

References

• WHO information

Revisions