Human African Trypanosomiasis (HAT), commonly known as sleeping sickness, is a parasitic disease caused by two subspecies of the Trypanosoma brucei parasite: Trypanosoma brucei gambiense (T.b. gambiense) and Trypanosoma brucei rhodesiense (T.b. rhodesiense). The disease progresses in two distinct stages. The first stage, or hemolymphatic stage, involves parasites in the blood and lymphatic system, causing non-specific symptoms like fever and headaches. The second stage, or meningoencephalic stage, occurs when the parasites invade the central nervous system (CNS), leading to neurological and sleep-cycle disturbances. Because different drugs are effective against different parasite species and stages, accurate diagnosis is crucial for proper treatment.
The Shift in Treatment Paradigm
Historically, the treatment for advanced sleeping sickness involved highly toxic drugs, most notably melarsoprol, an arsenic derivative. Its severe side effects, including fatal encephalopathic reactions, made treatment hazardous. Over the past few decades, the development of safer and more accessible therapies has revolutionized care. The introduction of Nifurtimox-Eflornithine Combination Therapy (NECT) in 2009 provided a much safer alternative to melarsoprol for second-stage T.b. gambiense. More recently, the development and approval of the all-oral drug fexinidazole have further simplified treatment protocols, especially for non-severe cases, reducing the need for hospitalization and intravenous injections.
Treatment for Trypanosoma brucei gambiense
This form of sleeping sickness is the most common, accounting for over 98% of reported cases, and primarily affects West and Central Africa.
First-stage T.b. gambiense
- Fexinidazole: This oral medication is the preferred treatment for patients aged 6 years and older weighing at least 20 kg. Its ease of administration as a 10-day course of tablets eliminates the need for injections, making it highly suitable for remote, resource-limited settings.
- Pentamidine: An intramuscular or intravenous injection, pentamidine is used for first-stage T.b. gambiense in children under 6 years or weighing less than 20 kg. It is generally well-tolerated but requires medical supervision for administration.
Second-stage T.b. gambiense
- NECT (Nifurtimox-Eflornithine Combination Therapy): This regimen combines oral nifurtimox and intravenous eflornithine over 10 days and is a highly effective treatment for second-stage HAT, including severe cases.
- Fexinidazole: For non-severe second-stage T.b. gambiense in eligible patients (age $\ge$ 6 years and weight $\ge$ 20 kg), fexinidazole offers an oral alternative to NECT. However, NECT is still recommended for more severe cases with higher parasite counts in the cerebrospinal fluid.
Treatment for Trypanosoma brucei rhodesiense
This more acute form of the disease is found in East and Southern Africa.
First-stage T.b. rhodesiense
- Fexinidazole: Based on updated WHO guidelines from June 2024, fexinidazole is the recommended first-line treatment for first-stage T.b. rhodesiense in patients aged 6 years and older weighing at least 20 kg.
- Suramin: Administered intravenously, suramin is used for first-stage T.b. rhodesiense, particularly in young children or those for whom fexinidazole is not suitable.
Second-stage T.b. rhodesiense
- Fexinidazole: The June 2024 WHO update expanded fexinidazole's use to include the second stage of T.b. rhodesiense for eligible patients (age $\ge$ 6 years and weight $\ge$ 20 kg).
- Melarsoprol: Due to its severe toxicity, melarsoprol is reserved for second-stage T.b. rhodesiense in specific cases, primarily for children under 6 years or weighing less than 20 kg where other options are not viable.
Comparison of Sleeping Sickness Drugs
| Drug | Species | Stage(s) | Administration | Key Features/Side Effects |
|---|---|---|---|---|
| Fexinidazole | T.b. gambiense & T.b. rhodesiense | Stage 1, non-severe Stage 2 | Oral (10 days) | First all-oral treatment; simplifies logistics; potential side effects include nausea, headache, and psychiatric reactions. |
| NECT | T.b. gambiense | Stage 2 | Oral (nifurtimox) + IV (eflornithine) | Highly effective for severe cases; administration is complex and resource-intensive. |
| Pentamidine | T.b. gambiense | Stage 1 | IM or IV (7 days) | Less toxic than older drugs; suitable for young children; requires injections. |
| Suramin | T.b. rhodesiense | Stage 1 | IV (series of injections) | Effective for first-stage East African HAT; associated with allergic reactions and nephrotoxicity. |
| Melarsoprol | T.b. rhodesiense | Stage 2 | IV (10 days) | Highly toxic arsenic derivative; reserved for specific, severe cases; high risk of encephalopathy. |
The Impact of Newer Therapies
The advent of oral fexinidazole marks a significant step forward in the management of sleeping sickness. By eliminating the need for complex intravenous infusions or hospitalization for many patients, it makes treatment more accessible and reduces costs for both healthcare systems and patients. This change is particularly impactful in the remote, underserved areas where the disease is most prevalent. It simplifies the logistical burden on clinics and healthcare workers, potentially allowing for earlier intervention and better patient outcomes.
Conclusion
Identifying the correct treatment for sleeping sickness is not a one-size-fits-all approach but a careful process based on the diagnosed parasite subspecies and the disease's progression. The recent expansion of fexinidazole's approval as a first-line treatment for first and second-stage T.b. rhodesiense for eligible patients is a notable development, simplifying the treatment landscape. While older, more toxic drugs like melarsoprol are now largely superseded by safer alternatives, they still play a role in specific clinical scenarios. The ultimate goal is to provide safe, effective, and accessible treatment to all patients, moving closer to the elimination of this neglected tropical disease. For the most current recommendations, healthcare providers should consult authoritative sources like the World Health Organization.
