Sleeping Sickness

Disease management is made in 3 steps:

Screening for potential infection. This involves using serological tests (only available for T. b.gambiense) and checking for clinical signs - especially swollen cervical lymph nodes.

Diagnosing by establishing whether the parasite is present in body fluids.

Staging to determine the state of disease progression. This entails clinical examination and in some cases analysis of the cerebrospinal fluid obtained by lumbar puncture.

Diagnosis must be made as early as possible to avoid progressing to the neurological stage in order to elude complicated and risky treatment procedures

The long, relatively asymptomatic first stage of T. b. gambiense sleeping sickness is one of the reasons why an exhaustive, active screening of the population at risk is recommended, to identify patients at an early stage and reduce transmission by removing their status of reservoir. Exhaustive screening requires a major investment in human and material resources. In Africa such resources are often scarce, particularly in remote areas where the disease is mostly found. As a result, some infected individuals may die before they can ever be diagnosed and treated.

The type of treatment depends on the form of the disease and the disease stage. The earlier the disease is identified, the better the prospect of a cure. The assessment of treatment outcome requires follow up of the patient up to 24 months and entails clinical assessment and laboratory exams of body fluids including in some cases, cerebrospinal fluid obtained by lumbar puncture, 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.

New treatment guidelines for gambiense human African trypanosmiasis were issued by WHO in 2019. In total six 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 the treatment of first stage:

Pentamidine: discovered in 1940, used for the treatment of the first stage of T. b. gambiense sleeping sickness. Despite non-negligible undesirable effects, it is in general 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 nephrotoxicity and allergic reactions.

Drugs used in the treatment of second stage:

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%). It is currently recommended as first-line treatment for the rhodesiense form, but rarely used in the gambiense form.

Eflornithine: much less toxic than melarsoprol, registered in 1990 is only effective against T.b. gambiense. It is generally used in combination with nifurtimox (as part of the Nifurtimox-eflornithine combination therapy, NECT) but can be used also as monotherapy. The regimen is complex and cumbersome to apply.

Nifurtimox: The Nifurtimox-eflornithine combination therapy, NECT, 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. Both drugs are provided free of charge by WHO to endemic countries with a kit containing all the material needed for its administration.

Drugs used in the treatment of both stages:

Fexinidazole is an oral treatment for gambiense human African trypanosomiasis It was included in 2019 in the WHO Essential medicines list and WHO human African Trypanosomiasis treatment guidelines. This molecule is indicated as first line for first stage and non-severe second stage. It should be administered for 10 days within 30 minutes after a solid meal and under supervision of trained medical staff. Currently a clinical trial for its use in rhodesiense HAT is ongoing.