Elimination Of Human African Trypanosomiasis Research Articles

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

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. 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. 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.

The internal transcribed spacer 1 sequence polymorphism brings updates to tsetse species distribution in the northern Cameroon: Importance in planning efficient vector control.

Vector control remains one of the best strategies to prevent the transmission of trypanosome infections in humans and livestock and, thus, a good way to achieve the elimination of human African trypanosomiasis and animal African trypanosomiasis. A key prerequisite for the success of any vector control strategy is the accurate identification and correct mapping of tsetse species. In this work, we updated the tsetse fly species identification and distribution in many geographical areas in Cameroon. Tsetse flies were captured from six localities in Cameroon, and their species were morphologically identified. Thereafter, DNA was extracted from legs of each tsetse fly and the length polymorphism of internal transcribed spacer-1 (ITS1) region of each fly was investigated using PCR. ITS1 DNA fragments of each tsetse species were sequenced. The sequences obtained were analysed and compared to those available in GenBank. This enabled to confirm/infirm results of the morphologic identification and then, to establish the phylogenetic relationships between tsetse species. Morphologic features allowed to clearly distinguish all the tsetse species captured in the South Region of Cameroon, that is, Glossina palpalis palpalis, G. pallicera, G. caliginea and G. nigrofusca. In the northern area, G. morsitans submorsitans could also be distinguished from G. palpalis palpalis, G. tachinoides and G. fuscipes, but these three later could not be distinguished with routine morphological characters. The ITS1 length polymorphism was high among most of the studied species and allowed to identify the following similar species with a single PCR, that is, G. palpalis palpalis with 241 or 242 bp and G. tachinoides with 221 or 222 bp, G. fuscipes with 236 or 237 bp. We also updated the old distribution of tsetse species in the areas assessed, highlighting the presence of G. palpalis palpalis instead of G. fuscipes in Mbakaou, or in sympatry with G. morsitans submorsitans in Dodeo (northern Cameroon). This study confirms the presence of G. palpalis palpalis in the Adamawa Region of Cameroon. It highlights the limits of using morphological criteria to differentiate some tsetse species. Molecular tools based on the polymorphism of ITS1 of tsetse flies can differentiate tsetse species through a simple PCR before downstream analyses or vector control planning.

Prevalence of blood and skin trypanosomes in domestic and wild fauna from two sleeping sickness foci in Southern Cameroon.

Although studies on African Trypanosomiases revealed a variety of trypanosome species in the blood of various animal taxa, animal reservoirs of Trypanosoma brucei gambiense and anatomical niches such as skin have been overlooked in most epidemiological settings. This study aims to update epidemiological data on trypanosome infections in animals from human African trypanosomiasis (HAT) foci of Cameroon. Blood and skin snips were collected from 291 domestic and wild animals. DNA was extracted from blood and skin snips and molecular approaches were used to identify different trypanosomes species. Immunohistochemical analyses were used to confirm trypanosome infections in skin snips. PCR revealed 137 animals (47.1%) with at least one trypanosome species in the blood and/or in the skin. Of these 137 animals, 90 (65.7%) and 32 (23.4%) had trypanosome infections respectively in the blood and skin. Fifteen (10.9%) animals had trypanosome infections in both blood and skin snip. Animals from the Campo HAT focus (55.0%) were significantly (X2 = 17.6; P< 0.0001) more infected than those (29.7%) from Bipindi. Trypanosomes of the subgenus Trypanozoon were present in 27.8% of animals while T. vivax, T. congolense forest type and savannah type were detected in 16.5%, 10.3% and 1.4% of animals respectively. Trypanosoma b. gambiense infections were detected in the blood of 7.6% (22/291) of animals. No T. b. gambiense infection was detected in skin. This study highlights the presence of several trypanosome species in the blood and skin of various wild and domestic animals. Skin appeared as an anatomical reservoir for trypanosomes in animals. Despite methodological limitations, pigs, sheep, goats and wild animals were confirmed as potential reservoirs of T. b. gambiense. These animal reservoirs must be considered for the designing of control strategies that will lead to sustainable elimination of HAT.

Towards elimination of human African trypanosomiasis

Human African Trypanosomiasis (HAT) is caused by Trypanosoma brucei which is transmitted by the tsetse fly insect vector (Glossina spp). It is one of the 20 Neglected Tropical Diseases (NTD) listed by the WHO. These diseases affect the poorest and most vulnerable communities, for which the WHO has established a dedicated 2021-2030 roadmap. At the time of Alphonse Laveran, HAT devastated the African continent. In the 1960s, the disease was nearly under control, but it strongly re-emerged in the 1990s. A coordinated effort of all stakeholders, with national control programs as the main actors, a strong contribution of research and important donations by the private sector, allowed to decrease the HAT burden significantly. Since 2018, less than 1000 cases are detected annually. We here review new diagnostics, treatments and vector control tools that have been implemented jointly and successfully in several endemic countries.The next key challenge will be to sustain the gains. Newly emerging research questions include long-term carriage of trypanosomes and adaptation of tools to low prevalence contexts. Challenges out of the research area comprise the continued need of funding, maintenance of dedicated human resources, and the key question of access. Sustainable elimination as "interruption of transmission", which is the 2030 NTD roadmap target, can be reached, if these challenges are solved. We stress the importance of continuing to combine the efforts in the fight against the disease, because sustainable elimination of HAT is the best long-term prevention strategy against re-emergence. As such, HAT elimination can serve as an example for other infectious diseases.

Wing Interferential Patterns (WIPs) and machine learning, a step toward automatized tsetse (Glossina spp.) identification

A simple method for accurately identifying Glossina spp in the field is a challenge to sustain the future elimination of Human African Trypanosomiasis (HAT) as a public health scourge, as well as for the sustainable management of African Animal Trypanosomiasis (AAT). Current methods for Glossina species identification heavily rely on a few well-trained experts. Methodologies that rely on molecular methodologies like DNA barcoding or mass spectrometry protein profiling (MALDI TOFF) haven’t been thoroughly investigated for Glossina sp. Nevertheless, because they are destructive, costly, time-consuming, and expensive in infrastructure and materials, they might not be well adapted for the survey of arthropod vectors involved in the transmission of pathogens responsible for Neglected Tropical Diseases, like HAT. This study demonstrates a new type of methodology to classify Glossina species. In conjunction with a deep learning architecture, a database of Wing Interference Patterns (WIPs) representative of the Glossina species involved in the transmission of HAT and AAT was used. This database has 1766 pictures representing 23 Glossina species. This cost-effective methodology, which requires mounting wings on slides and using a commercially available microscope, demonstrates that WIPs are an excellent medium to automatically recognize Glossina species with very high accuracy.

SHERLOCK4HAT: A CRISPR-based tool kit for diagnosis of Human African Trypanosomiasis.

To achieve elimination of Human African Trypanosomiasis (HAT) caused by Trypanosoma brucei gambiense (gHAT), the development of highly sensitive diagnostics is needed. We have developed a CRISPR based diagnostic for HAT using SHERLOCK (Specific High-sensitivity Enzymatic Reporter unLOCKing) that is readily adaptable to a field-based setting. We adapted SHERLOCK for the detection of T.brucei species. We targeted 7SLRNA, TgSGP and SRA genes and tested SHERLOCK against RNA from blood, buffy coat, dried blood spots (DBS), and clinical samples. The pan-Trypanozoon 7SLRNA and T.b. gambiense-specific TgSGP SHERLOCK assays had a sensitivity of 0.1 parasite/μL and a limit of detection 100 molecules/μL. T.b. rhodesiense-specific SRA had a sensitivity of 0.1 parasite/μL and a limit of detection of 10 molecules/μL. TgSGP SHERLOCK and SRA SHERLOCK detected 100% of the field isolated strains. Using clinical specimens from the WHO HAT cryobank, the 7SLRNA SHERLOCK detected trypanosomes in gHAT samples with 56.1%, 95% CI [46.25-65.53] sensitivity and 98.4%, 95% CI [91.41-99.92] specificity, and rHAT samples with 100%, 95% CI [83.18-100] sensitivity and 94.1%, 95% CI [80.91-98.95] specificity. The species-specific TgSGP and SRA SHERLOCK discriminated between the gambiense/rhodesiense HAT infections with 100% accuracy. The 7SLRNA, TgSGP and SRA SHERLOCK discriminate between gHAT and rHAT infections, and could be used for epidemiological surveillance and diagnosis of HAT in the field after further technical development. Institut Pasteur (PTR-175 SHERLOCK4HAT), French Government's Investissement d'Avenir program Laboratoire d'Excellence Integrative Biology of Emerging Infectious Diseases (LabEx IBEID), and Agence Nationale pour la Recherche (ANR-PRC 2021 SherPa).

Evaluation of antibody responses to tsetse fly saliva in domestic animals in the sleeping sickness endemic foci of Bonon and Sinfra, Côte d'Ivoire.

After intensive control efforts, human African trypanosomiasis (HAT) was declared eliminated in Côte d'Ivoire as a public health problem in December 2020 and the current objective is to achieve the interruption of the transmission (zero cases). Reaching this objective could be hindered by the existence of an animal reservoir of Trypanosoma (T.) brucei (b.) gambiense. In the framework of a study led in 2013 to assess the role of domestic animals in the epidemiology of HAT in the two last active foci from Côte d'Ivoire (Bonon and Sinfra), plasmas were sampled from four species of domestic animals for parasitological (microscopic examination by the buffy coat technique (BCT)), serological (immune trypanolysis (TL)) and molecular (specific PCR: TBR for T. brucei s.l., TCF for T. congolense forest type, TVW for T. vivax and PCR for T. b. gambiense) testing. In order to improve the understanding of the involvement/role of these animals in the transmission of T. b. gambiense, we have quantified in this study the IgG response to whole saliva extracts of Glossina palpalis gambiensis in order to perform an association analysis between anti-saliva responses and the positivity of diagnostic tests. Cattle and pigs had significantly higher rates of anti-tsetse saliva responses compared to goats and sheep (p<0.01). In addition, the anti-tsetse saliva responses were strongly associated with the parasitology (BCT+), serology (TL+) and PCR (TBR+ and TCF+) results (p<0.001). These associations indicate a high level of contacts between the positive/infected animals and tsetse flies. Our findings suggest that protecting cattle and pigs against tsetse bites could have a significant impact in reducing transmission of both animal and human trypanosome species, and advocates for a "One health" approach to better control African trypanosomosis in Côte d'Ivoire.

Review of the Situation of Human African Trypanosomiasis in the Republic of Congo From the 1950s to 2020.

Human African trypanosomiasis (HAT), despite considerable progress in the control, is still occurring in many countries in both west and central African regions. The HAT situation in the Republic of Congo has always been overshadowed by its neighbor the Democratic Republic of Congo where over 60% of all HAT cases occur. In the Republic of Congo, HAT cases have been significantly reduced to about 20 reported cases yearly and the disease is still prevalent in few foci across the country. Although continuous assessment of HAT situation in Congo is been led by the National Control Program for HAT, research on the vector, parasite, and vector control has received little attention. Because there have not been enough reviews summarizing key findings from studies conducted so far, there is still a poor understanding of the global situation of HAT in Congo. In order to achieve sustainable elimination of HAT in Congo a deep appraisal of HAT situation is required. The present study provides a review of studies conducted on HAT in the republic of Congo since the 1950s to date in order to identify gaps in knowledge and help consolidate the gains and progress towards the elimination of sleeping sickness.

The elimination of human African trypanosomiasis: Achievements in relation to WHO road map targets for 2020.

BackgroundIn the 20th century, epidemics of human African trypanosomiasis (HAT) ravaged communities in a number of African countries. The latest surge in disease transmission was recorded in the late 1990s, with more than 35,000 cases reported annually in 1997 and 1998. In 2013, after more than a decade of sustained control efforts and steady progress, the World Health Assembly resolved to target the elimination of HAT as a public health problem by 2020. We report here on recent progress towards this goal.Methodology/principal findingsWith 992 and 663 cases reported in 2019 and 2020 respectively, the first global target was amply achieved (i.e. fewer than 2,000 HAT cases/year). Areas at moderate or higher risk of HAT, where more than 1 case/10,000 people/year are reported, shrunk to 120,000 km2 for the five-year period 2016–2020. This reduction of 83% from the 2000–2004 baseline (i.e. 709,000 km2) is slightly below the target (i.e. 90% reduction). As a result, the second global target for HAT elimination as a public health problem cannot be considered fully achieved yet. The number of health facilities able to diagnose and treat HAT expanded (+9.6% compared to a 2019 survey), thus reinforcing the capacity for passive detection and improving epidemiological knowledge of the disease. Active surveillance for gambiense HAT was sustained. In particular, 2.8 million people were actively screened in 2019 and 1.6 million in 2020, the decrease in 2020 being mainly caused by COVID-19-related restrictions. Togo and Côte d’Ivoire were the first countries to be validated for achieving elimination of HAT as a public health problem at the national level; applications from three additional countries are under review by the World Health Organization (WHO).Conclusions/significanceThe steady progress towards the elimination of HAT is a testament to the power of multi-stakeholder commitment and coordination. At the end of 2020, the World Health Assembly endorsed a new road map for 2021–2030 that set new bold targets for neglected tropical diseases. While rhodesiense HAT remains among the diseases targeted for elimination as a public health problem, gambiense HAT is targeted for elimination of transmission. The goal for gambiense HAT is expected to be particularly arduous, as it might be hindered by cryptic reservoirs and a number of other challenges (e.g. further integration of HAT surveillance and control into national health systems, availability of skilled health care workers, development of more effective and adapted tools, and funding for and coordination of elimination efforts).

Monitoring the elimination of gambiense human African trypanosomiasis in the historical focus of Batié, South-West Burkina Faso.

The World Health Organisation has targeted the elimination of human African trypanosomiasis (HAT) as zero transmission by 2030. Continued surveillance needs to be in place for early detection of re-emergent cases. In this context, the performance of diagnostic tests and testing algorithms for detection of the re-emergence of Trypanosoma brucei gambiense HAT remains to be assessed. We carried out a door-to-door active medical survey for HAT in the historical focus of Batié, South–West Burkina Faso. Screening was done using three rapid diagnostic tests (RDTs). Two laboratory tests (ELISA/T. b. gambiense and immune trypanolysis) and parasitological examination were performed on RDT positives only. In total, 5883 participants were screened, among which 842 (14%) tested positive in at least one RDT. Blood from 519 RDT positives was examined microscopically but no trypanosomes were observed. The HAT Sero-K-Set test showed the lowest specificity of 89%, while the specificities of SD Bioline HAT and rHAT Sero-Strip were 92% and 99%, respectively. The specificity of ELISA/T. b. gambiense and trypanolysis was 99% (98–99%) and 100% (99–100%), respectively. Our results suggest that T. b. gambiense is no longer circulating in the study area and that zero transmission has probably been attained. While a least cost analysis is still required, our study showed that RDT preselection followed by trypanolysis may be a useful strategy for post-elimination surveillance in Burkina Faso.

Feasibility of a dried blood spot strategy for serological screening and surveillance to monitor elimination of Human African Trypanosomiasis in the Democratic Republic of the Congo.

In recent years, the number of reported Human African Trypanosomiasis (HAT) cases caused by Trypanosoma brucei (T.b.) gambiense has been markedly declining, and the goal of ‘elimination as a public health problem’ is within reach. For the next stage, i.e. interruption of HAT transmission by 2030, intensive screening and surveillance will need to be maintained, but with tools and strategies more efficiently tailored to the very low prevalence. We assessed the sequential use of ELISA and Immune Trypanolysis (ITL) on dried blood spot (DBS) samples as an alternative to the traditional HAT field testing and confirmation approach. A cross-sectional study was conducted in HAT endemic and previously endemic zones in Kongo Central province, and a non-endemic zone in Haut Katanga province in the Democratic Republic of the Congo (DRC). Door-to-door visits were performed to collect dried blood spot (DBS) samples on filter paper. ELISA/T.b. gambiense was conducted followed by ITL for those testing positive by ELISA and in a subset of ELISA negatives. In total, 11,642 participants were enrolled. Of these, 11,535 DBS were collected and stored in appropriate condition for ELISA testing. Ninety-seven DBS samples tested positive on ELISA. In the endemic zone, ELISA positivity was 1.34% (95%CI: 1.04–1.64). In the previously endemic zone and non-endemic zone, ELISA positivity was 0.34% (95% CI: 0.13–0.55) and 0.37% (95% CI: 0.15–0.60) respectively. Among the ELISA positives, only two samples had a positive ITL result, both from the endemic zone. One of those was from a former HAT patient treated in 2008 and the other from an individual who unfortunately had deceased prior to the follow-up visit. Our study showed that a surveillance strategy, based on DBS samples and centralized testing with retracing of patients if needed, is feasible in DRC. ELISA seems well suited as initial test with a similar positivity rate as traditional screening tests, but ITL remains complex. Alternatives for the latter, also analyzable on DBS, should be further explored.

Accelerating elimination of sleeping sickness from the Guinean littoral through enhanced screening in the post-Ebola context: A retrospective analysis.

BackgroundActivities to control human African trypanosomiasis (HAT) in Guinea were severely hampered by the Ebola epidemic that hit this country between 2014 and 2016. Active screening was completely interrupted and passive screening could only be maintained in a few health facilities. At the end of the epidemic, medical interventions were progressively intensified to mitigate the risk of HAT resurgence and progress towards disease elimination.Methodology/Principal findingsA retrospective analysis was performed to evaluate the medical activities that were implemented in the three most endemic prefectures of Guinea (Boffa, Dubreka and Forecariah) between January 2016 and December 2018. Passive screening using rapid diagnostic tests (RDTs) was progressively resumed in one hundred and one health facilities, and active screening was intensified by visiting individual households and performing RDTs, and by conducting mass screening in villages by mobile teams using the Card Agglutination Test for Trypanosomiasis. A total of 1885, 4897 and 8023 clinical suspects were tested in passive, while 5743, 14442 and 21093 people were actively screened in 2016, 2017 and 2018, respectively. The number of HAT cases that were diagnosed first went up from 107 in 2016 to 140 in 2017, then subsequently decreased to only 73 in 2018. A progressive decrease in disease prevalence was observed in the populations that were tested in active and in passive between 2016 and 2018.Conclusions/SignificanceIntensified medical interventions in the post-Ebola context first resulted in an increase in the number of HAT cases, confirming the fear that the disease could resurge as a result of impaired control activities during the Ebola epidemic. On the other hand, the decrease in disease prevalence that was observed between 2016 and 2018 is encouraging, as it suggests that the current strategy combining enhanced diagnosis, treatment and vector control is appropriate to progress towards elimination of HAT in Guinea.

Integration of Traditional Healers in Human African Trypanosomiasis Case Finding in Central Africa: A Quasi-Experimental Study.

Background: Based on the premise that Africans in rural areas seek health care from traditional healers, this study investigated a collaborative model between traditional healers and the national Human African Trypanosomiasis (HAT) programs across seven endemic foci in seven central African countries by measuring the model’s contribution to HAT case finding. Method: Traditional healers were recruited and trained by health professionals to identify HAT suspects based on its basics signs and symptoms and to refer them to the National Sleeping Sickness Control Program (NSSCP) for testing and confirmatory diagnosis. Results: 35 traditional healers were recruited and trained, 28 finally participated in this study (80%) and referred 278 HAT suspects, of which 20 (7.19%) were CATT positive for the disease. Most cases originated from Bandundu (45%) in the Democratic Republic of Congo and from Ngabe (35%) in Congo. Twelve (4.32%) patients had confirmatory diagnosis. Although a statistically significant difference was not shown in terms of case finding (p = 0.56), traditional healers were able to refer confirmed HAT cases that were ultimately cared for by NCSSPs. Conclusion: Integrating traditional healers in the control program of HAT will likely enhance the detection of cases, thereby, eventually contributing to the elimination of HAT in the most affected communities.

Analytical sensitivity of loopamp and quantitative real-time PCR on dried blood spots and their potential role in monitoring human African trypanosomiasis elimination

The objective set by WHO to reach elimination of human African trypanosomiasis (HAT) as a public health problem by 2020 is being achieved. The next target is the interruption of gambiense-HAT transmission in humans by 2030. To monitor progress towards this target, in areas where specialized local HAT control capacities will disappear, is a major challenge. Test specimens should be easily collectable and safely transportable such as dried blood spots (DBS). Monitoring tests performed in regional reference centres should be reliable, cheap and allow analysis of large numbers of specimens in a high-throughput format. The aim of this study was to assess the analytical sensitivity of Loopamp, M18S quantitative real-time PCR (M18S qPCR) and TgsGP qPCR as molecular diagnostic tests for the presence of Trypanosoma brucei gambiense in DBS. The sensitivity of the Loopamp test, with a detection limit of 100 trypanosomes/mL, was in the range of parasitaemias commonly observed in HAT patients, while detection limits for M18S and TgsGP qPCR were respectively 1000 and 10,000 trypanosomes/mL. None of the tests was entirely suitable for high-throughput use and further development and implementation of sensitive high-throughput molecular tools for monitoring HAT elimination are needed.

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

BackgroundIn 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 FindingsWith 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/SignificanceThe 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.

An Active Follow-up Strategy for Serological Suspects of Human African Trypanosomiasis with Negative Parasitology Set up by a Health Zone Team in the Democratic Republic of Congo.

Background: The World Health Organization aims for the elimination of Human African Trypanosomiasis (HAT) as a public health problem by 2020 and for full elimination (absence of new cases) by 2030. One of strategies to achieve this is the active follow-up of all HAT serological suspects found during passive screening who have never been re-tested for parasitology. This is important because these cases can maintain HAT transmission and may be responsible for reemergence of the disease. Methods: In order to improve case finding at low cost in the targeted population, a general recall was transmitted to aparasitemic serological suspects about the availability of confirmation services at the general referral hospital. Transport was facilitated for re-testing. The initial examinations were carried out in Health Centers from Bagata Health Zone (HZ) in the Democratic Republic of the Congo between January 2017 and April 2019. This strategy of using a HZ team has not been previously documented. Results: From a total sample of 74 serological suspects listed by the health centers, 36 cases were re-examined at the general reference hospital; 19% (7/36) self-presented and 81% (29/36) were actively followed up by HZ personnel. Of those re-examined at the general reference hospital, 39% (14/36) resulted in a parasitologically confirmed case. Of the 14 people diagnosed with HAT, 14% (2/14) self-presented and the remaining 86% (12/14) were diagnosed in suspects who were actively followed up. This new strategy of facilitating transport from the villages added value by contributing to the detection of 12 HAT cases, compared to the passive approach, waiting for self-reference, which resulted in the detection of 2 new HAT cases. The cost per detected patient was 70 USD from the group of 7 suspects who self-presented for testing at the hospital and 346 USD per detected case for the group of 29 patients who were actively followed up by health zone staff. Conclusion: Targeted active follow-up of aparasitemic serological suspects by HZ teams is a cost-effective and promising approach to identifying additional cases of HAT in areas of very low prevalence, which would contribute to the HAT elimination goal set by the World Health Organization.

Innovative Partnerships for the Elimination of Human African Trypanosomiasis and the Development of Fexinidazole.

Human African Trypanosomiasis (HAT or sleeping sickness) is a life-threatening neglected tropical disease that is endemic in 36 sub-Saharan African countries. Until recently, treatment options were limited and hampered by unsatisfactory efficacy, toxicity, and long and cumbersome administration regimens, compounded by infrastructure inadequacies in the remote rural regions worst affected by the disease. Increased funding and awareness of HAT over the past two decades has led to a steady decline in reported cases (<1000 in 2018). Recent drug development strategies have resulted in development of the first all-oral treatment for HAT, fexinidazole. Fexinidazole received European Medicines Agency positive scientific opinion in 2018 and is now incorporated into the WHO interim guidelines as one of the first-line treatments for HAT, allowing lumbar puncture to become non-systematic. Here, we highlight the role of global collaborations in the effort to control HAT and develop new treatments. The long-standing collaboration between the WHO, Sanofi and the Drugs for Neglected Diseases initiative (Geneva, Switzerland) was instrumental for achieving the control and treatment development goals in HAT, whilst at the same time ensuring that efforts were led by national authorities and control programs to leave a legacy of highly trained healthcare workers and improved research and health infrastructure.

Assessing the impact of aggregating disease stage data in model predictions of human African trypanosomiasis transmission and control activities in Bandundu province (DRC).

Since the turn of the century, the global community has made great progress towards the elimination of gambiense human African trypanosomiasis (HAT). Elimination programs, primarily relying on screening and treatment campaigns, have also created a rich database of HAT epidemiology. Mathematical models calibrated with these data can help to fill remaining gaps in our understanding of HAT transmission dynamics, including key operational research questions such as whether integrating vector control with current intervention strategies is needed to achieve HAT elimination. Here we explore, via an ensemble of models and simulation studies, how including or not disease stage data, or using more updated data sets affect model predictions of future control strategies.

Accelerating towards human African trypanosomiasis elimination: Issues and opportunities.

Human African trypanosomiasis (HAT) has been an alarming global public health issue. The disease affects mainly poor and marginalized people in low-resource settings and is caused by two subspecies of haemoflagellate parasite, Trypanosoma brucei and transmitted by tsetse flies. Progress made in HAT control during the past decade has prompted increasing global dialogue on its elimination and eradication. The disease is targeted by the World Health Organization (WHO) for elimination as a public health problem by 2020 and to terminate its transmission globally by 2030, along-side other Neglected Tropical Diseases (NTD). Several methods have been used to control tsetse flies and the disease transmitted by them. Old and new tools to control the disease are available with constraints. Currently, there are no vaccines available. Efforts towards intervention to control the disease over the past decade have seen considerable progress and remarkable success with incidence dropping progressively, reversing the upward trend of reported cases. This gives credence in a real progress in its elimination. This study reviews various control measures, progress and a highlight of control issues, vector and parasite barriers that may have been hindering progress towards its elimination.

Molecular identification of Trypanosoma brucei gambiense in naturally infected pigs, dogs and small ruminants confirms domestic animals as potential reservoirs for sleeping sickness in Chad.

Human African trypanosomiasis (HAT) has been targeted for zero transmission to humans by 2030. Animal reservoirs of gambiense-HAT could jeopardize these elimination goals. This study was undertaken to identify potential host reservoirs for Trypanosoma brucei gambiense by detecting its natural infections in domestic animals of Chadian HAT foci. Blood samples were collected from 267 goats, 181 sheep, 154 dogs, and 67 pigs. Rapid diagnostic test (RDT) and capillary tube centrifugation (CTC) were performed to search for trypanosomes. DNA was extracted from the buffy coat, and trypanosomes of the subgenus Trypanozoon as well as T. b. gambiense were identified by PCR. Of 669 blood samples, 19.4% were positive by RDT and 9.0% by CTC. PCR revealed 150 animals (22.4%) with trypanosomes belonging to Trypanozoon, including 18 (12%) T. b. gambiense. This trypanosome was found in all investigated animal species and all HAT foci. Between animal species or villages, no significant differences were observed in the number of animals harboring T. b. gambiense DNA. Pigs, dogs, sheep and goats appeared to be potential reservoir hosts for T. b. gambiense in Chad. The identification of T. b. gambiense in all animal species of all HAT foci suggests that these animals should be considered when designing new control strategies for sustainable elimination of HAT. Investigations aiming to decrypt their specific role in each epidemiological setting are important to achieve zero transmission of HAT.