Reemergence of Human African Trypanosomiasis Caused by Trypanosoma brucei rhodesiense, Ethiopia.

We report 4 cases of human African trypanosomiasis that occurred in Ethiopia in 2022, thirty years after the last previously reported case in the country. Two of 4 patients died before medicine became available. We identified the infecting parasite as Trypanosoma brucei rhodesiense. Those cases imply human African trypanosomiasis has reemerged.

Target product profile: Trypanosoma brucei gambiense test to verify elimination.

Human African trypanosomiasis is a life-threatening parasitic infection transmitted by the tsetse fly in sub-Saharan Africa. The most common form is caused by Trypanosoma brucei gambiense, with humans as the main reservoir. Diagnosis in the field requires microscopic examination performed by specifically trained personnel. After over two decades of sustained efforts, the incidence of the disease is strongly declining, and some historically endemic countries are no longer detecting cases. The World Health Organization (WHO) has targeted the elimination of transmission of gambiense human African trypanosomiasis by 2030, defined as zero autochthonous cases for at least five consecutive years. Endemic countries reaching this goal must maintain dedicated surveillance to detect re-emergence or re-introduction. With this new agenda, new tools are needed for verification of the absence of transmission. WHO has therefore developed a target product profile calling for development of a method for population-level cross-cutting surveillance of T. b. gambiense transmission. The method needs to be performed in national or sub-national reference laboratories, and to test in parallel numerous samples shipped from remote rural areas. Among other characteristics the product profile specifies: (i) a simple specimen collection procedure; (ii) no cold-chain requirement to transfer specimens to reference laboratories; (iii) high sensitivity and specificity; (iv) high-throughput, substantially automatized; (v) low cost per specimen, when analysed in large batches; and (vi) applicable also in animals.

La trypanosomiase humaine africaine est une infection parasitaire potentiellement mortelle transmise par la mouche tsé-tsé en Afrique subsaharienne. La forme la plus répandue est causée par Trypanosoma brucei gambiense, les humains constituant son principal réservoir. Établir un diagnostic sur le terrain nécessite un examen microscopique réalisé par du personnel formé à cet effet. Après plus de deux décennies d'efforts soutenus, l'incidence de la maladie diminue fortement et quelques pays historiquement endémiques ne découvrent plus aucun cas. L'objectif de l'Organisation mondiale de la Santé (OMS) est d'éliminer la transmission de la trypanosomiase humaine africaine à T. b. gambiense d'ici 2030, ce qui correspond à zéro cas autochtone pendant au moins cinq années consécutives. Les pays endémiques qui atteignent cet objectif doivent maintenir une surveillance spécifique afin de détecter toute réémergence ou réintroduction. Ce nouveau programme doit s'accompagner de nouveaux outils servant à vérifier l'absence de transmission. L'OMS a donc élaboré un profil de produit cible pour le développement d'un procédé de surveillance transversale de la transmission de T. b. gambiense à l'échelle de la population. Ce procédé doit être effectué dans des laboratoires de référence nationaux ou infranationaux et tester simultanément de nombreux échantillons envoyés depuis des régions rurales isolées. Ce profil de produit comporte notamment les caractéristiques suivantes: (i) une procédure simple de collecte d'échantillons; (ii) aucune exigence concernant le respect de la chaîne du froid lors du transfert des échantillons vers les laboratoires de référence; (iii) un niveau élevé de sensibilité et de spécificité; (iv) un haut débit, en grande partie automatisé; (v) de faibles coûts par échantillon lors d'analyses en masse; et enfin, (vi) applicable aux animaux également.

La tripanosomiasis humana africana es una infección parasitaria potencialmente mortal transmitida por la mosca tsetsé en el África Subsahariana. El principal reservorio es el ser humano, y la forma más común está causada por Trypanosoma brucei gambiense. El diagnóstico práctico requiere un examen microscópico a cargo de personal con formación específica. Tras más de dos décadas de esfuerzos sostenidos, la incidencia de la enfermedad está disminuyendo considerablemente, y en algunos países históricamente endémicos ya no se detectan casos. La Organización Mundial de la Salud (OMS) se ha fijado como objetivo la eliminación de la transmisión de la tripanosomiasis africana humana gambiense para 2030, es decir, cero casos autóctonos durante al menos cinco años consecutivos. Los países endémicos que alcancen este objetivo deben mantener una vigilancia permanente para detectar la reaparición o reintroducción de la enfermedad. Con esta agenda nueva, se necesitan herramientas nuevas para verificar la ausencia de transmisión. Por consiguiente, la OMS ha elaborado un perfil de producto objetivo en el que se pide el desarrollo de un método para la vigilancia transversal a nivel de población sobre la transmisión de T. b. gambiense. El método debe realizarse en laboratorios de referencia nacionales o subnacionales y analizar en paralelo numerosas muestras enviadas desde regiones rurales remotas. Entre otras características, el perfil del producto detalla: (i) un procedimiento sencillo de recogida de muestras; (ii) ningún requisito de cadena de frío para transferir las muestras a los laboratorios de referencia; (iii) alta sensibilidad y especificidad; (iv) alto rendimiento, sustancialmente automatizado; (v) bajo coste por muestra, cuando se analizan en grandes lotes; y (vi) aplicable también en animales.

Target product profile: diagnostic test for Trypanosoma brucei rhodesiense.

Rhodesiense human African trypanosomiasis is a lethal parasitic infection caused by Trypanosoma brucei rhodesiense and transmitted by tsetse flies in eastern and southern Africa. It accounts for around 5% of all cases of human African trypanosomiasis. Currently, there is no simple serological test for rhodesiense human African trypanosomiasis and diagnosis relies on microscopic confirmation of trypanosomes in samples of blood or other tissues. The availability of a simple and accurate diagnostic test would aid the control, surveillance and treatment of the disease. A subcommittee of the World Health Organization's Neglected Tropical Diseases Diagnostics Technical Advisory Group has developed a target product profile for a diagnostic tool to identify T. b. rhodesiense infection. The optimum tool would have a sensitivity and specificity above 99% for detecting T. b. rhodesiense, but be simple enough for use by minimally trained health-care workers in unsophisticated peripheral health facilities or mobile teams in villages. The test should yield a qualitative result that can be easily observed and can be used to determine treatment. An antigen test would be preferable, with blood collected by finger-prick. Ideally, there should be no need for a cold chain, instrumentation or precision liquid handling. The test should be usable between 10 °C and 40 °C and between 10% and 88% relative humidity. Basic training should take under 2 hours and the test should involve fewer than five steps. The unit cost should be less than 1 United States dollar.

La trypanosomiase humaine africaine à T. b. rhodesiense est une infection parasitaire mortelle causée par Trypanosoma brucei rhodesiense et transmise par les mouches tsé-tsé en Afrique orientale et australe. Elle représente environ 5% de l'ensemble des cas de trypanosomiase humaine africaine. À l'heure actuelle, il n'existe aucun test sérologique simple pour l'infection à T. b. rhodesiense et le diagnostic repose sur la confirmation microscopique de la présence de trypanosomes dans des échantillons de sang ou d'autres tissus. Fournir un test de diagnostic simple et précis favoriserait la lutte, la surveillance et la prise en charge de la maladie. Un sous-comité du Groupe consultatif technique sur les produits de diagnostic des maladies tropicales négligées de l'Organisation mondiale de la Santé a donc élaboré un profil de produit cible pour un outil visant à détecter une infection par T. b. rhodesiense. L'outil le plus adapté présenterait un niveau de sensibilité et de spécificité supérieur à 99% pour la détection de T. b. rhodesiense, tout en étant à la portée de professionnels de la santé ayant reçu une formation sommaire, tant dans des structures de santé périphériques basiques qu'au sein d'équipes mobiles dans les villages. Cet outil doit fournir un résultat fiable, facile à interpréter, qui peut servir à établir un traitement. Un test antigénique serait préférable, avec prélèvement de l'échantillon sanguin par le biais d'une piqûre au bout du doigt. Idéalement, l'outil ne doit pas être thermosensible, ni nécessiter un équipement spécifique ou une manipulation de liquides délicate. Le test doit pouvoir être utilisé à une température comprise entre 10 °C et 40 °C, ainsi que dans une humidité relative de 10% à 88%. La formation requise pour son utilisation doit durer moins de deux heures et le test doit être effectué en moins de cinq étapes, Enfin, son coût unitaire doit être inférieur à un dollar américain.

La tripanosomiasis humana africana rhodesiense es una infección letal parasitaria causada por el Trypanosoma brucei rhodesiense, y es transmitida por la mosca tse-tsé en África oriental y meridional. Representa aproximadamente el 5% de todos los casos de tripanosomiasis humana africana. Actualmente, no existe ninguna prueba serológica simple para la tripanosomiasis humana africana rhodesiense, y el diagnóstico se basa en la confirmación microscópica de tripanosomas existentes en muestras de sangre u otros tejidos. Una prueba diagnóstica sencilla y precisa ayudaría a controlar, vigilar y tratar la enfermedad. Un subcomité del Grupo Asesor Técnico de Diagnóstico de Enfermedades Tropicales Desatendidas de la Organización Mundial de la Salud ha creado un perfil de producto objetivo para una herramienta de diagnóstico que permita identificar la infección T. b. rhodesiense. La herramienta óptima tendría una sensibilidad y una especificidad superiores al 99% para detectar la T. b. rhodesiense y, al ser lo suficientemente sencilla, podrían utilizarla trabajadores sanitarios mínimamente formados, en centros sanitarios periféricos no sofisticados, o bien equipos móviles. La prueba debe arrojar un resultado cualitativo de fácil lectura y que pueda utilizarse para determinar el tratamiento. Sería preferible una prueba de antígenos, con sangre extraída mediante punción digital. Idealmente, no debería ser necesaria la cadena de frío, la instrumentación ni la manipulación de líquidos de precisión. La prueba debe poder utilizarse entre 10 °C y 40 °C, con una humedad relativa de entre el 10% y el 88%. La instrucción básica debe llevar menos de 2 horas y la prueba debe incluir menos de cinco pasos. El coste de la unidad debe ser inferior a 1 dólar estadounidense.

Target product profile: Trypanosoma brucei gambiense test for low-prevalence settings.

Having caused devastating epidemics during the 20th century, the incidence of life-threatening human African trypanosomiasis has fallen to historically low levels as a result of sustained and coordinated efforts over the past 20 years. Humans are the main reservoir of one of the two pathogenic trypanosome subspecies, Trypanosoma brucei gambiense, found in western and central Africa. The expected advent of a safe and easy-to-use treatment to be given to seropositive but microscopically unconfirmed individuals would lead to further depletion; in the meantime, the presence of T. b. gambiense infection in the community must be monitored to allow the control strategy to be adapted and the elimination status to be assessed. The World Health Organization has therefore developed a target product profile that describes the optimal and minimal characteristics of an individual laboratory-based test to assess T. b. gambiense infection in low-prevalence settings. Development of the target product profile involved the formation of a Neglected Tropical Diseases Diagnostics Technical Advisory Group and a subgroup on human African trypanosomiasis diagnostic innovation needs, and an analysis of the available products and development pipeline. According to the product profile, the test should ideally: (i) require a minimally invasive or non-invasive specimen, collectable at peripheral facilities by minimally trained health workers; (ii) demonstrate good sensitivity and high specificity; (iii) have a stability of samples allowing transfer to reference laboratories preferably without cold chain; (iv) be stable over a wide range of environmental conditions for more than 2 years; and (v) after marketing, be available at low cost for at least 7 years.

Après avoir causé des épidémies dévastatrices au cours du 20e siècle, la trypanosomiase humaine africaine, potentiellement mortelle, a vu son incidence chuter à un niveau historiquement bas grâce aux efforts conjoints et soutenus déployés ces deux dernières décennies. Les humains constituent le principal réservoir de l'une des deux sous-espèces pathogéniques de trypanosome, Trypanosoma brucei gambiense, que l'on retrouve en Afrique occidentale et centrale. L'arrivée d'un traitement sûr et simple d'utilisation, qui serait administré aux individus séropositifs mais sans confirmation microscopique, devrait entraîner une nouvelle diminution; dans l'intervalle, la présence d'une infection à T. b. gambiense au sein de la communauté doit être surveillée afin de pouvoir adapter la stratégie de lutte et évaluer le statut d'élimination. Par conséquent, l'Organisation mondiale de la Santé a élaboré un profil de produit cible qui détaille les caractéristiques minimales et optimales d'un test individuel en laboratoire visant à confirmer l'infection à T. b. gambiense dans les régions à faible prévalence. La mise au point de ce profil a entraîné la formation d'un Groupe consultatif technique sur le diagnostic des maladies tropicales négligées et d'un sous-groupe consacré aux besoins en matière d'innovation diagnostique pour la trypanosomiase humaine africaine, qui a conduit une analyse des produits existants et des projets de développement. Selon le profil de produit, le test devrait idéalement: (i) nécessiter un prélèvement d'échantillon peu ou non invasif, pouvant être effectué dans des structures périphériques par des professionnels de la santé ayant reçu une formation sommaire; (ii) faire preuve d'un bon niveau de sensibilité et d'un niveau élevé de spécificité; (iii) avoir une stabilité des échantillons permettant le transfert vers des laboratoires de référence, de préférence sans chaîne de froid; (iv) rester stable dans un large éventail de conditions environnementales pendant plus de deux ans; et enfin, (v) après commercialisation, être disponible à bas coût pendant au moins sept ans.

Tras haber causado epidemias devastadoras durante el siglo XX, la incidencia de la tripanosomiasis humana africana potencialmente mortal ha descendido a niveles históricamente bajos gracias a los esfuerzos sostenidos y coordinados de los últimos 20 años. El ser humano es el principal reservorio de una de las dos subespecies patógenas del tripanosoma, Trypanosoma brucei gambiense, presente en África Occidental y Central. La prevista disponibilidad de un tratamiento seguro y fácil de administrar a personas seropositivas, pero no confirmadas al microscopio, permitiría una mayor eliminación; mientras tanto, se debe vigilar la presencia de la infección por T. b. gambiense en la comunidad para poder adaptar la estrategia de control y evaluar el estado de eliminación. Por consiguiente, la Organización Mundial de la Salud ha elaborado un perfil de producto objetivo que describe las características óptimas y mínimas de una prueba de laboratorio individual para evaluar la infección por T. b. gambiense en regiones de baja prevalencia. El desarrollo del perfil de producto objetivo implicó la formación de un Grupo de Asesoramiento Técnico sobre Diagnóstico de Enfermedades Tropicales Desatendidas y un subgrupo sobre las necesidades de innovación en el diagnóstico de la tripanosomiasis humana africana, así como un análisis de los productos disponibles y en desarrollo. Según el perfil objetivo, lo ideal sería que la prueba: (i) requiriera una muestra mínimamente invasiva o no invasiva, que pudiera ser recogida en centros periféricos por personal sanitario con una capacitación mínima; (ii) demostrara una buena sensibilidad y alta especificidad; (iii) tuviera una estabilidad de las muestras que permita su transferencia a laboratorios de referencia, preferiblemente sin cadena de frío; (iv) fuera estable en un amplio rango de condiciones ambientales durante más de 2 años; y (v) tras su comercialización, estuviera disponible a bajo coste durante al menos 7 años.

Target product profile: diagnostic test for Trypanosoma brucei gambiense.

Human African trypanosomiasis is a life-threatening parasitic infection endemic to sub-Saharan Africa. Around 95% of cases are due to Trypanosoma brucei gambiense, found in western and central Africa. Clinical signs and symptoms are nonspecific, current diagnostic tests are not sufficiently accurate, and parasitological confirmation of infection requires microscopic examination of body fluids and specialized techniques for concentrating parasites. Moreover, current treatment is not recommended on the basis of suspicion alone because it is not sufficiently safe. The availability of a simple and accurate diagnostic test to identify individuals harbouring parasites would widen treatment and help decrease disease prevalence. A subcommittee of the World Health Organization's Neglected Tropical Diseases Diagnostics Technical Advisory Group has developed a target product profile for a diagnostic tool to identify T. b. gambiense infection. This tool should have a high sensitivity for detecting T. b. gambiense but be simple enough to use in rural Africa. Ideally, the tool could be applied by any minimally trained individual in an unsophisticated peripheral health facility, or a mobile team in a village with little infrastructure. The test should be able to function under hot and humid conditions. Basic training should take under 2 hours and the test should involve fewer than five steps. There should be no need for instrumentation or precision liquid handling. The test should yield a qualitative result in under 20 minutes that can be easily observed, and one test should be sufficient for determining treatment. A unit cost below 1 United States dollar (US$) would enable mass screening.

La trypanosomiase humaine africaine est une infection parasitaire potentiellement mortelle endémique en Afrique subsaharienne. Dans près de 95% des cas, elle est causée par Trypanosoma brucei gambiense, que l'on trouve en Afrique occidentale et centrale. Les symptômes et signes cliniques sont aspécifiques, les tests de diagnostic existants ne sont pas assez précis et la confirmation parasitologique de l'infection nécessite un examen microscopique des liquides corporels ainsi que des techniques spécialisées pour concentrer les parasites. En outre, il n'est pas recommandé d'entamer le traitement actuel sur la base d'une simple suspicion car celui-ci n'est pas suffisamment sûr. Fournir un test de diagnostic simple et précis permettant d'identifier les individus porteurs de parasites contribuerait à élargir le traitement et à une diminution de la prévalence de la maladie. Un sous-comité du Groupe consultatif technique sur les produits de diagnostic des maladies tropicales négligées de l'Organisation mondiale de la Santé a élaboré un profil de produit cible pour un outil visant à détecter une infection par T. b. gambiense. Cet outil doit être suffisamment sensible pour déceler la présence de T. b. gambiense mais suffisamment simple pour être utilisé dans les régions rurales du continent. Idéalement, il doit pouvoir être employé par toute personne ayant reçu une formation sommaire, tant dans des structures de santé périphériques basiques qu'au sein d'une équipe mobile dans un village doté d'infrastructures restreintes. Par ailleurs, il doit fonctionner dans une atmosphère chaude et humide. La formation requise pour son utilisation doit durer moins de deux heures et le test doit être effectué en moins de cinq étapes, sans exiger d'équipement spécifique ni de manipulation délicate. Cet outil doit fournir un résultat fiable en moins de 20 minutes, facile à interpréter, et un seul test doit suffire à établir un traitement. Enfin, afin d'organiser un dépistage de masse, son coût unitaire ne doit pas dépasser un dollar américain.

La tripanosomiasis humana africana es una infección parasitaria potencialmente mortal endémica del África Subsahariana. Alrededor del 95% de los casos se deben al Trypanosoma brucei gambiense, presente en África Occidental y Central. Los signos y síntomas clínicos no son específicos, las pruebas diagnósticas actuales no son suficientemente precisas y la confirmación parasitológica de la infección requiere el examen microscópico de los fluidos corporales y técnicas especializadas de concentración de parásitos. Además, el tratamiento actual no se recomienda a partir de la sola sospecha porque no es suficientemente seguro. La disponibilidad de una prueba diagnóstica sencilla y precisa para identificar a las personas con parásitos ampliaría el tratamiento y ayudaría a disminuir la prevalencia de la enfermedad. Un subcomité del Grupo de Asesoramiento Técnico sobre Diagnóstico de Enfermedades Tropicales Desatendidas de la Organización Mundial de la Salud ha desarrollado un perfil de producto objetivo para una herramienta de diagnóstico destinada a identificar la infección por T. b. gambiense. Esta herramienta debe tener una alta sensibilidad para detectar T. b. gambiense, pero ser lo suficientemente sencilla para su uso en las regiones rurales de África. Lo ideal sería que la herramienta pudiera ser aplicada por cualquier persona mínimamente capacitada en un centro sanitario periférico poco sofisticado o por un equipo móvil en un pueblo con poca infraestructura. La prueba debería funcionar en condiciones de calor y humedad. La formación básica debe durar menos de 2 horas y la prueba debe constar de menos de cinco pasos. No debe necesitarse instrumentación ni manipulación precisa de líquidos. La prueba debe dar un resultado cualitativo en menos de 20 minutos que pueda observarse fácilmente y debe bastar una prueba para determinar el tratamiento. Su coste unitario, inferior a un dólar estadounidense, permitiría un cribado masivo.

Human African trypanosomiasis.

Human African trypanosomiasis (sleeping sickness) is a parasitic infection that almost invariably progresses to death unless treated. Human African trypanosomiasis caused devastating epidemics during the 20th century. Thanks to sustained and coordinated efforts over the past 15 years, the number of reported cases has fallen to an historically low level. Fewer than 3000 cases were reported in 2015, and the disease is targeted for elimination by WHO. Despite these recent successes, the disease is still endemic in parts of sub-Saharan Africa, where it is a considerable burden on rural communities, most notably in central Africa. Since patients are also reported from non-endemic countries, human African trypanosomiasis should be considered in differential diagnosis for travellers, tourists, migrants, and expatriates who have visited or lived in endemic areas. In the absence of a vaccine, disease control relies on case detection and treatment, and vector control. Available drugs are suboptimal, but ongoing clinical trials provide hope for safer and simpler treatments.

Human African trypanosomiasis in the Democratic Republic of the Congo: disease distribution and risk.

BACKGROUND: For the past three decades, the Democratic Republic of the Congo (DRC) has been the country reporting the highest number of cases of human African trypanosomiasis (HAT). In 2012, DRC continued to bear the heaviest burden of gambiense HAT, accounting for 84 % of all cases reported at the continental level (i.e., 5,968/7,106). This paper reviews the status of sleeping sickness in DRC between 2000 and 2012, with a focus on spatio-temporal patterns. Epidemiological trends at the national and provincial level are presented. RESULTS: The number of HAT cases reported yearly from DRC decreased by 65 % from 2000 to 2012, i.e., from 16,951 to 5,968. At the provincial level a more complex picture emerges. Whilst HAT control in the Equateur province has had a spectacular impact on the number of cases (97 % reduction), the disease has proved more difficult to tackle in other provinces, most notably in Bandundu and Kasai, where, despite substantial progress, HAT remains entrenched. HAT prevalence presents its highest values in the northern part of the Province Orientale, where a number of constraints hinder surveillance and control. Significant coordinated efforts by the National Sleeping Sickness Control Programme and the World Health Organization in data collection, reporting, management and mapping, culminating in the Atlas of HAT, have enabled HAT distribution and risk in DRC to be known with more accuracy than ever before. Over 18,000 locations of epidemiological interest have been geo-referenced (average accuracy ≈ 1.7 km), corresponding to 93.6 % of reported cases (period 2000-2012). The population at risk of contracting sleeping sickness has been calculated for two five-year periods (2003-2007 and 2008-2012), resulting in estimates of 33 and 37 million people respectively. CONCLUSIONS: The progressive decrease in HAT cases reported since 2000 in DRC is likely to reflect a real decline in disease incidence. If this result is to be sustained, and if further progress is to be made towards the goal of HAT elimination, the ongoing integration of HAT control and surveillance into the health system is to be closely monitored and evaluated, and active case-finding activities are to be maintained, especially in those areas where the risk of infection remains high and where resurgence could occur.

The elimination of human African trypanosomiasis: Monitoring progress towards the 2021-2030 WHO road map targets.

BACKGROUND: Human African trypanosomiasis (HAT) is a neglected tropical disease that usually occurs in rural areas in sub-Saharan Africa. It caused devastating epidemics during the 20th century. Sustained, coordinated efforts by different stakeholders working with national sleeping sickness control programmes (NSSCPs) succeeded in controlling the disease and reducing the number of cases to historically low levels. 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. METHODOLOGY/PRINCIPAL FINDINGS: Data reported to WHO by NSSCPs were harmonized, verified, georeferenced and included in the atlas of HAT. A total of 802 cases were reported in 2021 and 837 in 2022. This is below the target for elimination as a public health problem at the global level (< 2000 HAT cases/year); 94% of the cases were caused by infection with T. b. gambiense. The areas reporting ≥ 1 HAT case/10 000 inhabitants/year in 2018-2022 cover a surface of 73 134 km2, with only 3013 km2 at very high or high risk. This represents a reduction of 90% from the baseline figure for 2000-2004, the target set for the elimination of HAT as a public health problem. For the surveillance of the disease, 4.5 million people were screened for gambiense HAT with serological tests in 2021-2022, 3.6 million through active screening and 0.9 million by passive screening. In 2021 and 2022 the elimination of HAT as a public health problem was validated in Benin, Uganda, Equatorial Guinea and Ghana for gambiense HAT and in Rwanda for rhodesiense HAT. To reach the next goal of elimination of transmission of gambiense HAT, countries have to report zero cases of human infection with T. b. gambiense for a period of at least 5 consecutive years. The criteria and procedures to verify elimination of transmission have been recently published by WHO. CONCLUSIONS/SIGNIFICANCE: HAT elimination as a public health problem has been reached at global level, with seven countries already validated as having reached this goal. This achievement was made possible by the work of NSSCPs, supported by different public and private partners, and coordinated by WHO. The new challenging goal now is to reach zero cases by 2030. To reach this goal is crucial to maintain the engagement and support of donors and stakeholders and to keep the involvement and coordination of all partners. Along with the focus on elimination of transmission of gambiense HAT, it is important not to neglect rhodesiense HAT, which is targeted for elimination as a public health problem in the WHO road map for NTDs 2021-2030.

New WHO guidelines for treating rhodesiense human African trypanosomiasis: expanded indications for fexinidazole and pentamidine.

Human African trypanosomiasis is a neglected tropical disease that is usually fatal without treatment. WHO has revised its rhodesiense human African trypanosomiasis treatment guidelines on the basis of an independent systematic literature review and following the GRADE methodology. This Review reports on the decision-making process and summarises the new recommendations and their potential implications for health-care professionals and policy makers. Due to data scarcity, all recommendations are conditional and based on very low certainty of evidence. Fexinidazole replaces suramin and melarsoprol as the first-line therapy in individuals aged 6 years and older with a bodyweight of 20 kg or more. As fexinidazole is effective in both stages of rhodesiense human African trypanosomiasis, a lumbar puncture for staging is no longer required. In settings in which first-choice drugs are not readily available, immediate interim treatment with pentamidine is suggested. The introduction of oral fexinidazole represents an advancement in the management of rhodesiense human African trypanosomiasis considering the life-threatening adverse reactions individuals can have to melarsoprol. However, children below the age or weight limits remain ineligible for treatment with fexinidazole.

Human African trypanosomiasis cases diagnosed in non-endemic countries (2011-2020).

BACKGROUND: Sleeping sickness, or human African trypanosomiasis (HAT), is transmitted by tsetse flies in endemic foci in sub-Saharan Africa. Because of international travel and population movements, cases are also occasionally diagnosed in non-endemic countries. METHODOLOGY/PRINCIPAL FINDINGS: Antitrypanosomal medicines to treat the disease are available gratis through the World Health Organization (WHO) thanks to a public-private partnership, and exclusive distribution of the majority of them enables WHO to gather information on all exported cases. Data collected by WHO are complemented by case reports and scientific publications. During 2011-2020, 49 cases of HAT were diagnosed in 16 non-endemic countries across five continents: 35 cases were caused by Trypanosoma brucei rhodesiense, mainly in tourists visiting wildlife areas in eastern and southern Africa, and 14 cases were due to T. b. gambiense, mainly in African migrants originating from or visiting endemic areas in western and central Africa. CONCLUSIONS/SIGNIFICANCE: HAT diagnosis in non-endemic countries is rare and can be challenging, but alertness and surveillance must be maintained to contribute to WHO's elimination goals. Early detection is particularly important as it considerably improves the prognosis.

Nifurtimox-eflornithine combination therapy for second-stage African Trypanosoma brucei gambiense trypanosomiasis: a multicentre, randomised, phase III, non-inferiority trial.

BACKGROUND: Human African trypanosomiasis (HAT; sleeping sickness) caused by Trypanosoma brucei gambiense is a fatal disease. Current treatment options for patients with second-stage disease are toxic, ineffective, or impractical. We assessed the efficacy and safety of nifurtimox-eflornithine combination therapy (NECT) for second-stage disease compared with the standard eflornithine regimen. METHODS: A multicentre, randomised, open-label, active control, phase III, non-inferiority trial was done at four HAT treatment centres in the Republic of the Congo and the Democratic Republic of the Congo. Patients aged 15 years or older with confirmed second-stage T b gambiense infection were randomly assigned by computer-generated randomisation sequence to receive intravenous eflornithine (400 mg/kg per day, every 6 h; n=144) for 14 days or intravenous eflornithine (400 mg/kg per day, every 12 h) for 7 days with oral nifurtimox (15 mg/kg per day, every 8 h) for 10 days (NECT; n=143). The primary endpoint was cure (defined as absence of trypanosomes in body fluids and a leucocyte count

Monitoring the elimination of human African trypanosomiasis at continental and country level: Update to 2018.

BACKGROUND: In 2012 human African trypanosomiasis (HAT), also known as sleeping sickness, was targeted for elimination as a public health problem, set to be achieved by 2020. The World Health Organization (WHO) provides here the 2018 update on the progress made toward that objective. Global indicators are reviewed, in particular the number of reported cases and the areas at risk. Recently developed indicators for the validation of HAT elimination at the national level are also presented. METHODOLOGY/PRINCIPAL FINDINGS: With 977 cases reported in 2018, down from 2,164 in 2016, the main global indicator of elimination is already well within the 2020 target (i.e. 2,000 cases). Areas at moderate or higher risk (i.e. ≥ 1 case/10,000 people/year) are also steadily shrinking (less than 200,000 km2 in the period 2014-2018), thus nearing the 2020 target [i.e. 90% reduction (638,000 km2) from the 2000-2004 baseline (709,000 km2)]. Health facilities providing diagnosis and treatment of gambiense HAT continued to increase (+7% since the previous survey), with a better coverage of at-risk populations. By contrast, rhodesiense HAT health facilities decreased in number (-10.5%) and coverage. At the national level, eight countries meet the requirements to request validation of gambiense HAT elimination as a public health problem (i.e. Benin, Burkina Faso, Cameroon, Côte d'Ivoire, Ghana, Mali, Rwanda, and Togo), while for other endemic countries more efforts are needed in surveillance, control, or both. CONCLUSIONS/SIGNIFICANCE: The 2020 goal of HAT elimination as a public health problem is within grasp, and eligible countries are encouraged to request validation of their elimination status. Beyond 2020, the HAT community must gear up for the elimination of gambiense HAT transmission (2030 goal), by preparing for both the expected challenges (e.g. funding, coordination, integration of HAT control into regular health systems, development of more adapted tools, cryptic trypanosome reservoirs, etc.) and the unexpected ones.

New WHO guidelines for treatment of gambiense human African trypanosomiasis including fexinidazole: substantial changes for clinical practice.

Human African trypanosomiasis caused by Trypanosoma brucei gambiense is a parasitic infection that usually progresses to coma and death unless treated. WHO has updated its guidelines for the treatment of this infection on the basis of independent literature reviews and using the Grading of Recommendations Assessment, Development and Evaluation methodology. The first-line treatment options, pentamidine and nifurtimox-eflornithine combination therapy, have been expanded to include fexinidazole, an oral monotherapy given a positive opinion from the European Medicines Agency. Fexinidazole is recommended for individuals who are aged 6 years and older with a bodyweight of 20 kg or more, who have first-stage or second-stage gambiense human African trypanosomiasis and a cerebrospinal fluid leucocyte count less than 100 per µL. Nifurtimox-eflornithine combination therapy remains recommended for patients with 100 leucocytes per µL or more. Without clinical suspicion of severe second-stage disease, lumbar puncture can be avoided and fexinidazole can be given. Fexinidazole should only be administered under supervision of trained health staff. Because these recommendations are expected to change clinical practice considerably, health professionals should consult the detailed WHO guidelines. These guidelines will be updated as evidence accrues.

Monitoring the elimination of human African trypanosomiasis: Update to 2016.

BACKGROUND: Human African trypanosomiasis (HAT) is a neglected tropical disease targeted for elimination 'as a public health problem' by 2020. The indicators to monitor progress towards the target are based on the number of reported cases, the related areas and populations exposed at various levels of risk, and the coverage of surveillance activities. Based on data provided by the National Sleeping Sickness Control Programmes (NSSCP), Non-Governmental Organizations (NGOs) and research institutions-and assembled in the Atlas of HAT-the World Health Organization (WHO) provides here an update to 2016 for these indicators, as well as an analysis of the epidemiological situation. RESULTS: Trends for the two primary indicators of elimination are on track for the 2020 goal: 2,164 cases of HAT were reported in 2016 (as compared to the milestone of 4,000 cases), and for the period 2012-2016 280,000 km2 are estimated to be at moderate risk or higher (i.e. ≥ 1 case/10,000 people/year), as compared to the milestone of 230,000 km2. These figures correspond to reductions of 92% and 61% as compared to the respective baselines (i.e. 26,550 HAT cases in the year 2000, and 709,000 km2 exposed at various levels of risk for the period 2000-2004). Among the secondary indicators, an overall improvement in the coverage of at risk populations by surveillance activities was observed. Regarding passive surveillance, the number of fixed health facilities providing gambiense HAT diagnosis or treatment expanded, with 1,338 enumerated in endemic countries in 2017 (+52% as compared to the survey completed only sixteen months earlier). Concerning rhodesiense HAT, 124 health facilities currently provide diagnosis or treatment. The broadening of passive surveillance is occurring in a context of fairly stable intensity of active case finding, with between 1.8 million and 2.4 million people screened per year over the period 2012-2016. DISCUSSION: Elimination of HAT as a public health problem by 2020 seems within reach, as the epidemiological trends observed in previous years are confirmed in this latest 2016 monitoring update. However, looking beyond 2020, and in particular to the 2030 goal of elimination of transmission as zero cases for the gambiense form of the disease only, there is no room for complacency. Challenges still abound, including ensuring the effective integration of HAT control activities in the health system, sustaining the commitment of donors and HAT endemic countries, and clarifying the extent of the threat posed by cryptic reservoirs (e.g. human asymptomatic carriers and the possible animal reservoirs in gambiense HAT epidemiology). WHO provides through the network for HAT elimination the essential coordination of the wide range of stakeholders to ensure synergy of efforts.

Nifurtimox-eflornithine combination therapy for second-stage Trypanosoma brucei gambiense sleeping sickness: a randomized clinical trial in Congo.

BACKGROUND: Human African trypanosomiasis caused by Trypanosoma brucei gambiense is a fatal disease. Current treatment options for patients with second-stage disease are either highly toxic or impracticable in field conditions. We compared the efficacy and safety of the nifurtimox-eflornithine drug combination with the standard eflornithine regimen for the treatment of second-stage disease. METHODS: A randomized, open-label, active-control, phase III clinical trial comparing 2 arms was conducted at the Sleeping Sickness Treatment Center, which was run by Medecins Sans Frontieres, in Nkayi, Bouenza Province, Republic of Congo. Patients were screened for inclusion and randomly assigned to receive eflornithine alone (400 mg/kg per day given intravenously every 6 h for 14 days) or eflornithine (400 mg/kg per day given intravenously every 12 h for 7 days) plus nifurtimox (15 mg/kg per day given orally every 8 h for 10 days). Patients were observed for 18 months. The study's outcomes were cure and adverse events attributable to treatment. RESULTS: A total of 103 patients with second-stage disease were enrolled. Cure rates were 94.1% for the eflornithine group and 96.2% for the nifurtimox-eflornithine group. Drug reactions were frequent in both arms, and severe reactions affected 25.5% of patients in the eflornithine group and 9.6% of those in the nifurtimox-eflornithine group, resulting in 2 and 1 treatment suspensions, respectively. There was 1 death in the eflornithine arm and no deaths in the nifurtimox-eflornithine arm. CONCLUSIONS: The nifurtimox-eflornithine combination appears to be a promising first-line therapy for second-stage sleeping sickness. If our findings are corroborated by ongoing findings from additional sites (a multicenter extension of this study), the new nifurtimox-eflornithine combination therapy will mark a major and multifaceted advance over current therapies.

Monitoring the elimination of human African trypanosomiasis: Update to 2014.

BACKGROUND: The World Health Organization (WHO) has targeted the elimination of Human African trypanosomiasis (HAT) 'as a public health problem' by 2020. The selected indicators of elimination should be monitored every two years, and we provide here a comprehensive update to 2014. The monitoring system is underpinned by the Atlas of HAT. RESULTS: With 3,797 reported cases in 2014, the corresponding milestone (5,000 cases) was surpassed, and the 2020 global target of 'fewer than 2,000 reported cases per year' seems within reach. The areas where HAT is still a public health problem (i.e. > 1 HAT reported case per 10,000 people per year) have halved in less than a decade, and in 2014 they corresponded to 350 thousand km2. The number and potential coverage of fixed health facilities offering diagnosis and treatment for HAT has expanded, and approximately 1,000 are now operating in 23 endemic countries. The observed trends are supported by sustained surveillance and improved reporting. DISCUSSION: HAT elimination appears to be on track. For gambiense HAT, still accounting for the vast majority of reported cases, progress continues unabated in a context of sustained intensity of screening activities. For rhodesiense HAT, a slow-down was observed in the last few years. Looking beyond the 2020 target, innovative tools and approaches will be increasingly needed. Coordination, through the WHO network for HAT elimination, will remain crucial to overcome the foreseeable and unforeseeable challenges that an elimination process will inevitably pose.

Monitoring the Progress towards the Elimination of Gambiense Human African Trypanosomiasis.

BACKGROUND: Over the last few years, momentum has gathered around the feasibility and opportunity of eliminating gambiense human African trypanosomiasis (g-HAT). Under the leadership of the World Health Organization (WHO), a large coalition of stakeholders is now committed to achieving this goal. A roadmap has been laid out, and indicators and milestones have been defined to monitor the progress of the elimination of g-HAT as a public health problem by 2020. Subsequently, a more ambitious objective was set for 2030: to stop disease transmission. This paper provides a situational update to 2012 for a number of indicators of elimination: number of cases annually reported, geographic distribution of the disease and areas and populations at different levels of risk. RESULTS: Comparing the 5-year periods 2003-2007 and 2008-2012, the area at high or very high risk of g-HAT shrank by 60%, while the area at moderate risk decreased by 22%. These are the areas where g-HAT is still to be considered a public health problem (i.e. > 1 HAT reported case per 10,000 people per annum). This contraction of at-risk areas corresponds to a reduction of 57% for the population at high or very high risk (from 4.1 to 1.8 million), and 20% for moderate risk (from 14.0 to 11.3 million). DISCUSSION: Improved data completeness and accuracy of the Atlas of HAT enhanced our capacity to monitor the progress towards the elimination of g-HAT. The trends in the selected indicators suggest that, in recent years, progress has been steady and in line with the elimination goal laid out in the WHO roadmap on neglected tropical diseases.