C. Mahoudeau/MSF
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                                Human African trypanosomiasis (sleeping sickness)

                                  Overview

                                  Human African trypanosomiasis (HAT), or sleeping sickness, is caused by trypanosome parasites that are transmitted by tsetse flies. HAT is found only in sub-Saharan Africa. Two subspecies of Trypanosoma brucei cause disease: T. b. gambiense in West and Central Africa, and T. b. rhodesiense in East Africa.

                                  This life-threatening disease mostly affects poor rural populations, causing significant harm. Travellers to endemic regions may also be at risk of infection.

                                  HAT transmission requires the interaction of humans, tsetse flies and parasite reservoirs (humans, and domestic and wild animals). The animal reservoir is very important in T. b. rhodesiense and less so in T. b. gambiense, although it could explain the long-term endemicity in some foci despite control interventions.

                                  Transmission can be interrupted by depleting the parasite reservoirs through detection and treatment of infected people and/or domestic animals and by reducing the tsetse fly population and human–tsetse contact.

                                  In 1995, about 25 000 cases were detected, 300 000 undetected cases were estimated and 60 million people were estimated to be at risk of HAT infection. In 2001, WHO launched an initiative to reinforce control and surveillance, and HAT decreased markedly in the ensuing years. In 2019, fewer than 1000 cases were found. This reduction does not reflect a lack of control efforts as in general active and passive screening has been maintained at similar levels (around 2.5 million people screened per year).

                                  Symptoms

                                  After infection, trypanosomes multiply in the blood and lymph (first-stage, haemolymphatic) and, following a variable incubation period (from days to months), unspecific symptoms and signs such as headache, fever, weakness, joint pain, and lymphadenopathy appear. Over time, the parasites cross the blood–brain barrier to invade the central nervous system (second-stage, meningoencephalitic), causing various neurological disturbances including sleep disorders (excessive daytime sleepiness, nocturnal insomnia), deep sensory disturbances, abnormal movements, tremor, ataxia, walking difficulties, speech difficulties, psychiatric disorders, seizures, coma and ultimately death. Most signs and symptoms are common to both stages, and sleep disorders in particular can appear already during the first stage.

                                  Rhodesiense HAT is typically acute, progressing to second-stage within a few weeks, and to death within 6 months. Gambiense HAT progresses slowly over around 3 years (highly variable).

                                  An inoculation chancre (dermal reaction of 3–4 cm at the tsetse bite site) may appear 2–3 days after infection with rhodesiense HAT in up to 25% of local patients, but more frequently in patients from non-endemic regions. It is rare with gambiense HAT.

                                  Sleeping sickness is diagnosed in several steps: after a clinical suspicion, serological tests (card agglutination trypanosomiasis test or HAT rapid diagnostic tests) can reinforce the suspicion, which should be confirmed by parasitological findings (in chancre exudate, lymphatic juice, blood and cerebrospinal fluid). Unfortunately, the usual serological tests are only applicable to T. b. gambiense. Stage is determined by the number of white blood cells and the presence of trypanosomes in cerebrospinal fluid examination.

                                  Treatment

                                  All confirmed HAT cases require treatment. Available treatment can cure most patients, completely eliminating trypanosomes from the body. Treatment of cases suspected by serology depends on specific conditions set by national protocols, which usually set specific conditions defining a higher suspicion index.

                                  The current treatment options include six medicines, all of which are donated by the manufacturers; WHO ensures their worldwide distribution free of charge.

                                  Treatment choices are based on the causative trypanosome and the disease stage. The medicines for treatment of second-stage must cross the blood–brain barrier and tend to be more toxic and complex to administer than first-stage medicines.

                                  In 2019, WHO issued interim guidelines for treatment of gambiense HAT. For treatment of rhodesiense HAT, the former guidelines remain valid.

                                  Gambiense HAT can be treated with oral fexinidazole in first-stage and also non-severe second-stage, with some limitations of age and body weight and following some important specific rules to ensure efficacy. In first-stage, intramuscular pentamidine can be also used, and in second stage nifurtimox–eflornithine combination therapy (NECT).

                                  Rhodesiense HAT must be treated without delay, because it can provoke multi-organ failure and progress to second stage within a few weeks. In first-stage, the treatment is intravenous suramin, with pentamidine as an alternative. In second-stage, the only treatment is intravenous melarsoprol.

                                   

                                  Publications

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                                  Target product profile for a test for rhodesiense human African trypanosomiasis diagnosis usable in peripheral health facilities
                                  The development of this target product profile (TPP) was led by the WHO Department of Control of Neglected Tropical Diseases (NTD) following standard WHO...
                                  Elimination of Human African Trypanosomiasis as public health problem

                                  First countries to eliminate Human African Trypanosomiasis as public health problem: Togo and Cote d’Ivoire.Human African trypanosomiasis (HAT),...

                                  Report of the third WHO stakeholders meeting on rhodesiense human African trypanosomiasis

                                  2020 is the year set in the roadmap on neglected tropical diseases (NTDs), published by the World Health Organization (WHO) in 2012, as the target...