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Human African Trypanosomiasis

    Overview

    Sleeping sickness threatens millions of people in 36 countries in sub-Saharan Africa. Many of the affected populations live in remote rural areas with limited access to adequate health services, which complicates the surveillance and therefore the diagnosis and treatment of cases. In addition, displacement of populations, war and poverty are important factors that facilitate transmission.

    • By the mid-1960s HAT was under control with below 5000 annual cases continent-wide. As surveillance relaxed, a resurgence ensued, reaching epidemic proportions in several regions by 1970. In 1998 almost 40 000 cases were reported, amidst an estimated 300 000 undetected and untreated cases. The prevalence reached 50% in several villages in Angola, the Democratic Republic of the Congo (DRC), and South Sudan. HAT was the first or second greatest cause of mortality in those communities.
    • The efforts of WHO, national control programmes, bilateral cooperation, and nongovernmental organizations during the 1990s and early 2000s reversed the curve, and the WHO Neglected Tropical Diseases Roadmap targeted for 2020 its elimination as a public health problem, and for 2030 the interruption of transmission (zero case).
       

    Symptoms, signs and diagnosis

    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 2024, WHO issued the guidelines for the treatment of human African trypanosomiasis.

    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. The recommended treatment is fexinidazole in first stage and second-stage. As second line and children below 6 years or less than 200 kg of body weight intravenous suramin is recommended in first stage, and intravenous melarsoprol in second stage.

    Strategies and Prevention

    In the absence of a vaccine or chemoprophylaxis, human African trypanosomiasis is controlled through case detection and treatment, and, to a lesser extent, vector control.

    For T brucei gambiense human African trypanosomiasis, the most effective control strategy is case finding and treatment, which reduces the human reservoir and thus decreases parasite transmission. 

    Cases of T brucei gambiense disease are detected through active screening campaigns by mobile teams, consisting of up to eight people travelling in four-wheel drive vehicles or boats, and through passive screening in fixed health structures.

    This labour-intensive strategy is no longer cost-effective in the numerous low-prevalence settings. In low-prevalence settings, targeted door to-door surveys focused on the immediate vicinities of former patients with human African trypanosomiasis may provide an alternative to mass screening and complement passive case detection.

    Active screening can also be performed by so-called light mobile teams, consisting of one or two people travelling on motorbikes, who can reach villages or camps that are inaccessible to four-wheel drive vehicles. In the current elimination context, it is also crucial to reinforce passive surveillance, integrating it into the general health-care system and focusing on self-presenting patients.

    Because passive surveillance relies on clinical suspicion followed by serological tests, it mostly detects patients with second-stage disease, who are likely to have fed the transmission cycle for years before detection. It is therefore necessary to carry out reactive screening campaigns in the probable areas of infection of these patients.

    Factsheet

    Key Facts

    • Human African trypanosomiasis (HAT) called Sleeping sickness is caused by protozoan parasites transmitted by infected tsetse flies. It is endemic in 36 sub-Saharan Africa countries. Without treatment, HAT is generally fatal.
    • Most exposed people live in rural areas and depend on agriculture, fishing, animal husbandry or hunting.
    • HAT takes 2 forms, depending on the subspecies of the infecting parasite: Trypanosoma brucei gambiense (92% of reported cases) and Trypanosoma brucei rhodesiense (8%).
    • Sustained control efforts have reduced the number of new cases by 97% in the last 20 years.
    • Diagnosis and treatment are complex and require specific skills.
    Role Of WHO And Partners

    WHO plays a major role in defining strategies, supporting countries in their implementation, and advocating resource mobilization with partners and endemic countries alike.

    Advocacy for the production and donation of trypanocides by pharmaceutical companies.

    Facilitate collaboration and coordination between partners in the scientific sector (academics; researchers; producers, etc.)  NGOs and implementing agencies.

    In terms of interventions, between 2021-2023, countries were supported by WHO and partners to :

    • Introduce new treatment guidelines with fexinidazole for gHAT and conduct training in 11 countries . 
    • Ensure that treatment is available for all detected cases 
    • Implement active pharmacovigilance of fexinidazole in those 11 countries 
    • Coordinate different stakeholders and co-organize with HQ the stakeholders’ meetings 

    (5th WHO stakeholders meeting on HAT elimination 7-9 June 2023)

    • Supported sentinel surveillance of HAT ongoing in 19 countries  
    • Maintained HAT specimen bank and provided samples for different research institutions
    • Support surveillance of rHAT in six endemic countries 
    • Facilitated staff training on HAT elimination strategies in Malawi and Uganda

    In 2023 and 2024 we have continued to organize annual stakeholder meetings as well as the coordination of endemic countries and the various partners.

    [1] Angola, Cameroon, Chad, Central African Republic, Congo, Democratic Republic of the Congo, Equatorial Guinea, Gabon, Guinea, South Sudan and Uganda

    [2] Angola, Benin, Burkina Faso, Cameroon, Central African Republic, Chad, Congo, Côte d’Ivoire, Democratic Republic of the Congo, Equatorial Guinea, Gabon, Ghana, Guinea, Liberia, Mali, Senegal, South Sudan, Togo and Uganda
    [3] Malawi, Rwanda, Uganda, United Republic of Tanzania, Zambia and Zimbabwe

    Definition of the disease

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

    Transmission and incubation period

    Human African trypanosomiasis (HAT), or sleeping sickness, is caused by trypanosome parasites that are transmitted by tsetse flies. HAT transmission requires the interaction of humans, tsetse flies and parasite reservoirs (humans, and domestic and wild animals).

    For gambiense HAT, the main reservoir is other human beings. Rhodesiense HAT, however, is a zoonosis, a “disease or infection naturally transmitted between vertebrate animals and humans”. After infection, trypanosomes multiply in the blood and lymph (first stage, haemolymphatic) and, following a variable incubation period (from days to months), 

    Clinical characteristics of cases

    Causative organism

    Human African trypanosomiasis is caused by 2 types of parasites:

    • Trypanosoma brucei gambiense in 24 countries in west and central Africa.
    • Trypanosoma brucei rhodesiense in 13 countries in eastern and southern Africa.
       
    The elimination of human African trypanosomiasis: monitoring progress towards the 2021–2030 WHO road map targets

    In 2012, WHO targeted the elimination of the disease as a public health problem by 2020. This goal has been reached and a new ambitious target was stated in the WHO road map for NTDs 2021–2030 and endorsed by the 73rd World Health Assembly: the elimination of gambiense HAT transmission (i.e., reducing the number of reported cases to zero). The interruption of transmission was not considered as an achievable goal for rhodesiense HAT, as it would require vast veterinary interventions rather than actions at the public health level
     

    Progress in the Africa Region 2000 - 2023

    Significant progress has been made in the g-HAT elimination effort in the WHO Region for Africa. The annual number of cases reported in the region has dropped by over 97% from 25,841 cases in 2000, to 675 cases in 2023. 

    Verification of interruption of transmission

    According to our target in 2021 -2030 Roadmap; 15 gambiense HAT countries must work for verification of interruption of transmission 


     

    Best Practices and Lessons Learned
    • Lessons learnt from countries who were validated for HAT elimination, indicate that strong political will, sustainable funding for health, community engagement and health promotion, improved surveillance systems and multi-sectoral collaboration were key determinants in the elimination of HAT
    • The adaptation of active HAT screening according to the epidemiological context and geographical accessibility by using mini-mobile units and door-to-door screening has made it possible to cover populations in hard-to-reach areas
       
    Key challenges

    In addition to the usual challenge of insufficient financial resources, some new challenges are:

    • Maintaining the commitment of states and partners in the context where elimination is validated, and surveillance must continue
       
    Strategic direction and priority activities

    To detect and treat HAT seropositive people if possible

    Research priorities

    The TDR Diseases reference Group identified the following top research priorities for human African trypanosomiasis:

    • Research on new diagnostics for case detection and characterization, including drug resistance and tests of cure.
    • Research on new therapeutics to avoid drug resistance, including exploring combinations of approved anti-kinetoplastid drugs, repurposing of existing approved drugs, and developing new drugs.
    • Research on new vector control technologies, including markers of successful vector control. 
    • Research on vector population characteristics, including insecticide resistance. 
    • Operational research on integrated disease and vector control.
    • Research to assess the importance of asymptomatic infection.
       
    Databases and tools

    With the list of new cases per village that endemic countries send to the WHO, a database called HAT ATLAS  is managed in collaboration with the FAO.

    Technical work

    Control of Neglected Tropical Diseases

    We are working to help achieve the targets of the Neglected Tropical Diseases Roadmap 2021 -2030; specifically for the elimination of HAT.
     

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