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Strategies to detect Human African Trypanosomiasis (HAT) cases rely on serological screening of populations exposed to trypanosomes. In Guinea, mass medical screening surveys performed with the Card Agglutination Test for Trypanosomiasis have been progressively replaced by door-to-door approaches using Rapid Diagnostic Tests (RDTs) since 2016. However, RDTs availability represents a major concern and medical teams must often adapt, even in the absence of prior RDT performance evaluation. For the last 5 years, the Guinean HAT National Control Program had to combine three different RDTs according to their availability and price: the SD Bioline HAT (not available anymore), the HAT Sero-K-SeT (most expensive), and recently the Abbott Bioline HAT 2.0 (limited field evaluation). Here, we assess the performance of these RDTs, alone or in different combinations, through the analysis of both prospective and retrospective data. A parallel assessment showed a higher positivity rate of Abbott Bioline HAT 2.0 (6.0%, n = 2,250) as compared to HAT Sero-K-SeT (1.9%), with a combined positive predictive value (PPV) of 20.0%. However, an evaluation of Abbott Bioline HAT 2.0 alone revealed a low PPV of 3.9% (n = 6,930) which was surpassed when using Abbott Bioline HAT 2.0 in first line and HAT Sero-K-SeT as a secondary test before confirmation, with a combined PPV reaching 44.4%. A retrospective evaluation of all 3 RDTs was then conducted on 189 plasma samples from the HAT-NCP biobank, confirming the higher sensitivity (94.0% [85.6-97.7%]) and lower specificity (83.6% [76.0-89.1%]) of Abbott Bioline HAT 2.0 as compared to SD Bioline HAT (Se 64.2% [52.2-74.6%]-Sp 98.4% [94.2-99.5%]) and HAT Sero-K-SeT (Se 88.1% [78.2-93.8%]-Sp 98.4% [94.2-99.5%]). A comparison of Abbott Bioline HAT 2.0 and malaria-RDT positivity rates on 479 subjects living in HAT-free malaria-endemic areas further revealed that a significantly higher proportion of subjects positive in Abbott Bioline HAT 2.0 were also positive in malaria-RDT, suggesting a possible cross-reaction of Abbott Bioline HAT 2.0 with malaria-related biological factors in about 10% of malaria cases. This would explain, at least in part, the limited specificity of Abbott Bioline HAT 2.0. Overall, Abbott Bioline HAT 2.0 seems suitable as first line RDT in combination with a second HAT RDT to prevent confirmatory lab overload and loss of suspects during referral for confirmation. A state-of-the-art prospective comparative study is further required for comparing all current and future HAT RDTs to propose an optimal combination of RDTs for door-to-door active screening., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Camara et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Tsetse flies (genus Glossina) transmit deadly trypanosomes to human populations and domestic animals in sub-Saharan Africa. Some foci of Human African Trypanosomiasis due to Trypanosoma brucei gambiense (g-HAT) persist in southern Chad, where a program of tsetse control was implemented against the local vector Glossina fuscipes fuscipes in 2018 in Maro. We analyzed the population genetics of G. f. fuscipes from the Maro focus before control (T0), one year (T1), and 18 months (T2) after the beginning of control efforts. Most flies captured displayed a local genetic profile (local survivors), but a few flies displayed outlier genotypes. Moreover, disturbance of isolation by distance signature (increase of genetic distance with geographic distance) and effective population size estimates, absence of any genetic signature of a bottleneck, and an increase of genetic diversity between T0 and T2 strongly suggest gene flows from various origins, and a limited impact of the vector control efforts on this tsetse population. Continuous control and surveillance of g-HAT transmission is thus recommended in Maro. Particular attention will need to be paid to the border with the Central African Republic, a country where the entomological and epidemiological status of g-HAT is unknown., (© S. Ravel et al., published by EDP Sciences, 2024.)

African animal trypanosomoses are vector-borne diseases that cause enormous livestock losses in sub-Saharan Africa, with drastic socio-economic impacts. Vector control in the context of an area-wide integrated pest management program with a sterile insect technique component requires the production of high-quality sterile male tsetse flies. In our study, we evaluated the effect of irradiation on the fecundity of Glossina palpalis gambiensis to identify the optimal dose that will induce maximum sterility while maintaining biological performance as much as possible. In addition, male mating performance was evaluated in semi-field cages. The irradiation doses used were 90, 100, 110, 120, 130, 140, and 150 Gy, and untreated males were used as the control. The results showed that pupal production and emergence rates were higher in batches of females that had mated with fertile males than in those that had mated with irradiated males with any experimental dose. A dose of 120 Gy administered to male flies induced 97-99% sterility after mating with virgin females. For the semi-field cage experiments, males irradiated with 120 Gy showed good sexual competitiveness as compared to fertile males and those irradiated with 140 Gy, considering the level of filling of spermatheca and the number of pairs formed. The optimal radiation dose of 120 Gy found in this study is slightly different from the traditional dose of 110 Gy that has been used in several eradication programmes in the past. The potential reasons for this difference are discussed, and an argument is made for the inclusion of reliable dosimetry systems in these types of studies., (© S. Pagabeleguem et al., published by EDP Sciences, 2023.)

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., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Purpose: The boom in Burkina Faso's artisanal gold mining since 2007 has attracted populations from Côte d'Ivoire and Guinea, which are the West African countries most affected by human African trypanosomiasis (HAT) and therefore increases its risk of re-emergence. Our aim was to update the HAT data in Burkina Faso in the risk of the re-emergence context with the advent of artisanal gold mining., Methods: The study was carried out in the southwestern Burkina Faso where entomological surveys were conducted using biconical traps in March 2017. Follow by an active medical survey in April 2017, which was targeted the gold panners in 7 villages closer to artisanal gold sites, using CATT, mini-anion exchange centrifugation technique, trypanolysis test (TL) and ELISA test to measure human/tsetse contacts. The buffy coat technique and the TL were also applied in pigs to check their reservoir role of human trypanosomes., Results: Our results have shown no case of HAT among 958 individuals tested and all the 50 pigs were also negative, but the level of antibodies against tsetse saliva evidenced by ELISA revealed low human/tsetse contact. Moreover, gold panners practise agriculture and breeding in an infected tsetse area, which are increased the risk., Conclusion: Our results illustrate that the risk of re-emergence is low. The passive surveillance system implemented in 2015 in southwestern Burkina Faso is needed to increase the sentinel sites to better cover this area by taking into account the gold mining. Finally, awareness-raising activities are needed among populations about HAT., (© 2022. The Author(s) under exclusive licence to Witold Stefański Institute of Parasitology, Polish Academy of Sciences.)

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., (© C.F.A. Compaoré et al., published by EDP Sciences, 2022.)

Background: Diminazene diaceturate (DA) and isometamidium chloride hydrochloride (ISM) are with homidium bromide, the main molecules used to treat African Animal Trypanosomosis (AAT). These drugs can be purchased from official suppliers but also from unofficial sources like local food markets or street vendors. The sub-standard quality of some of these trypanocides is jeopardizing the efficacy of treatment of sick livestock, leading thus to economic losses for the low-resource farmers and is contributing to the emergence and spread of drug resistance. The objective of this study was to assess the quality of trypanocidal drugs sold in French speaking countries of West Africa. In total, 308 drug samples including 282 of DA and 26 of ISM were purchased from official and unofficial sources in Benin, Burkina Faso, Côte d'Ivoire, Mali, Niger and Togo. All samples were analysed at LACOMEV (Dakar, Senegal), a reference laboratory of the World Organisation for Animal Health, by galenic inspection and high performance liquid chromatography., Results: The results showed that 51.90% of the samples were non-compliant compared to the standards and were containing lower quantity of the active ingredient compared to the indications on the packaging. The non-compliances ranged from 63.27% in Togo to 32.65% in Burkina Faso (61.82% in Benin, 53.84% in Mali, 50% in Côte d'Ivoire, 47.36% in Niger). The rates of non-compliance were not statistically different (P = 0.572) from official or unofficial suppliers and ranged from 30 to 75% and from 0 to 65% respectively. However, the non-compliance was significantly higher for ISM compared to DA (P = 0.028)., Conclusions: The high non-compliance revealed in this study compromises the efficacy of therapeutic strategies against AAT, and is likely to exacerbate chemoresistance in West Africa. Corrective actions against sub-standard trypanocides urgently need to be taken by policy makers and control authorities.

Trypanosoma brucei gambiense (T. b. gambiense) is the major causative agent of human African trypanosomiasis (HAT). A great variety of clinical outcomes have been observed in West African foci, probably due to complex host-parasite interactions. In order to separate the roles of parasite genetic diversity and host variability, we have chosen to precisely characterize the pathogenicity and virulence of T. b. gambiense field isolates in a mouse model. Thirteen T. b. gambiense strains were studied in experimental infections, with 20 Balb/C infected mice per isolate. Mice were monitored for 30 days, in which mortality, parasitemia, anemia, and weight were recorded. Mortality rate, prepatent period, and maximum parasitemia were estimated, and a survival analysis was performed to compare strain pathogenicity. Mixed models were used to assess parasitemia dynamics, weight, and changes in Packed Cell Volume (PCV). Finally, a multivariate analysis was performed to infer relationships between all variables. A large phenotypic diversity was observed. Pathogenicity was highly variable, ranging from strains that kill their host within 9 days to a non-pathogenic strain (no deaths during the experiment). Virulence was also variable, with maximum parasitemia values ranging from 42 million to 1 billion trypanosomes/ml. Reduced PCV and weight occurred in the first two weeks of the infection, with the exception of two strains. Finally, the global analysis highlighted three groups of strains: a first group with highly pathogenic strains showing an early mortality associated with a short prepatent period; a second group of highly virulent strains with intermediate pathogenicity; and a third group of isolates characterized by low pathogenicity and virulence patterns. Such biological differences could be related to the observed clinical diversity in HAT. A better understanding of the biological pathways underlying the observed phenotypic diversity could thus help to clarify the complex nature of the host-parasite interactions that determine the resistance/susceptibility status to T. brucei gambiense., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Human African trypanosomiasis (HAT), a lethal disease induced by Trypanosoma brucei gambiense, has a range of clinical outcomes in its human host in West Africa: an acute form progressing rapidly to second stage, spontaneous self-cure and individuals able to regulate parasitaemia at very low levels, have all been reported from endemic foci. In order to test if this clinical diversity is influenced by host genetic determinants, the association between candidate gene polymorphisms and HAT outcome was investigated in populations from HAT active foci in Guinea., Methodology and Results: Samples were collected from 425 individuals; comprising of 232 HAT cases, 79 subjects with long lasting positive and specific serology but negative parasitology and 114 endemic controls. Genotypes of 28 SNPs in eight genes passed quality control and were used for an association analysis. IL6 rs1818879 allele A (p = 0.0001, OR = 0.39, CI95 = [0.24-0.63], BONF = 0.0034) was associated with a lower risk of progressing from latent infection to active disease. MIF rs36086171 allele G seemed to be associated with an increased risk (p = 0.0239, OR = 1.65, CI95 = [1.07-2.53], BONF = 0.6697) but did not remain significant after Bonferroni correction. Similarly MIF rs12483859 C allele seems be associated with latent infections (p = 0.0077, OR = 1.86, CI95 = [1.18-2.95], BONF = 0.2157). We confirmed earlier observations that APOL1 G2 allele (DEL) (p = 0.0011, OR = 2.70, CI95 = [1.49-4.91], BONF = 0.0301) is associated with a higher risk and APOL1 G1 polymorphism (p = 0.0005, OR = 0.45, CI95 = [0.29-0.70], BONF = 0.0129) with a lower risk of developing HAT. No associations were found with other candidate genes., Conclusion: Our data show that host genes are involved in modulating Trypanosoma brucei gambiense infection outcome in infected individuals from Guinea with IL6 rs1818879 being associated with a lower risk of progressing to active HAT. These results enhance our understanding of host-parasite interactions and, ultimately, may lead to the development of new control tools.

Human African trypanosomiasis (HAT) in the Democratic Republic of the Congo (DRC) is caused by the protozoan Trypanosoma brucei gambiense. Until recently, all patients in the second or neurological stage of the disease were treated with melarsoprol. At the end of the past and the beginning of the present century, alarmingly high relapse rates in patients treated with melarsoprol were reported in isolated HAT foci. In the Mbuji-Mayi focus of DRC, a particular mutation that confers cross resistance for pentamidine and melarsoprol was recently found for all strains studied. Nevertheless, treatment successfully cured a significant proportion of patients. To check for the existence of other possible genetic factors of the parasites, we genotyped trypanosomes isolated from patients before and after treatment (relapsing patients) with eight microsatellite markers. We found no evidence of any genetic correlation between parasite genotype and treatment outcome and we concluded that relapse or cure probably depend more on patients' factors such as disease progression, nutritional or immunological status or co-infections with other pathogens. The existence of a melarsoprol and pentamidine resistance associated mutation at such high rates highlights an increasing problem, even for other drugs, especially those using the same transporters as melarsoprol and pentamidine., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Most African trypanosome species are sensitive to trypanolytic factors (TLFs) present in human serum. Trypanosome lysis was demonstrated to be associated with apolipoprotein L-I (APOL1). Trypanosoma brucei (T. b.) gambiense and Trypanosoma brucei rhodesiense, the two human infective trypanosome species, have both developed distinct resistance mechanisms to APOL1 mediated lysis. Whereas T. b. rhodesiense resistance is linked with the expression of the serum resistance associated (SRA) protein that interacts with APOL1 inside the parasite lysosome, inhibiting its lytic action; T. b. gambiense resistance is rather controlled by a reduced expression of the parasite HpHb receptor, limiting APOL1 absorption by trypanosomes. Based on this last observation we hypothesised that variation in the host APOL1 environment could significantly alter T. b. gambiense growth and thus resistance/susceptibility to sleeping sickness. To test this hypothesis, we have measured blood APOL1 relative expression in HAT patients, uninfected endemic controls and serologically positive subjects (SERO TL(+)) that are suspected to control infection to parasitological levels that are undetectable by the available test used in the field. All RNA samples were obtained from medical surveys led in the HAT mangrove foci of Coastal Guinea. Results indicate that APOL1 expression is a complex trait dependant on a variety of factors that need to be taken into account in the analysis. Nevertheless, multivariate analysis showed that APOL1 expression levels were significantly higher in both HAT and SERO TL(+) subject as compared to endemic controls (p=0.006). This result suggests that APOL1 expression is likely induced by T. b. gambiense, but is not related to resistance/susceptibility in its human host., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Thanks to its sensitivity and its ease of use in the field, the card agglutination test for trypanosomiasis (CATT) is widely used for serological screening of Trypanosoma brucei gambiense human African trypanosomiasis (HAT). Positive subjects are then examined by microscopy to confirm the disease. However, the CATT exhibits false-positive results raising the question of whether CATT-positive subjects who are not confirmed by microscopic detection of trypanosomes (SERO) are truly exposed to T.b. gambiense infection. For this purpose, we applied microsatellite genotyping on DNA extracted from blood of both HAT confirmed patients and SERO subjects in Guinea and Côte d'Ivoire since microsatellite genotyping has proved useful for the study of T.b. gambiense genetic diversity. Problems of amplification failures raise the question of the sensitivity of microsatellite markers when applied on biological samples especially from SERO subjects for who low blood parasitaemia are suspected. Nevertheless, we have shown that the trypanosomes from SERO individuals that have been genotyped belong to T.b. gambiense group 1 and were identical to those found in HAT patients. These results constitute the first evidences that at least some SERO are indeed infected by T.b. gambiense group 1 and that they may constitute a human reservoir of parasite in HAT foci. Whether these individuals should undergo treatment remains an open question as long as their role in HAT transmission is unknown. Our results strongly recommend the follow-up of such subjects to improve control strategies., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Human African trypanosomiasis (HAT) or sleeping sickness is a major public health problem in sub-Saharan Africa and is due to the kinetoplastid parasite Trypanosoma brucei gambiense in West and Central Africa. The exact role of multiple infections, the basis of clinical diversity observed in patients and the determinism that leads trypanosomes into different body fluids of the host remain opened questions to date. In this paper we investigate, in three Guinean foci, whether strains found in blood, lymph or cerebrospinal fluid (CSF) or in patients at different phase of HAT (phase 1, early phase 2 and late phase 2) are representative of the focus they belong to. Amplifications of parasites directly from body fluids led to substantial amounts of allelic drop outs, especially so for blood and CSF samples, which required data recoding of all homozygous sites into missing data. While controlling for geography, date of sampling and patient's phase of the disease, we found no effect of body fluids in the genetic structure of T. b. gambiense despite the presence of mixed infections. On the contrary, we found that the strains found in patients in different phase of the disease differed genetically, with early phase patients being more likely to be infected with more recent strains than patients at a more advanced phase of the disease. Thus, the combination of date of sampling and patient's status represents a parameter to be controlled for in population genetic structure analyses. Additional studies will also be required to explore further the phenomenon of mixed infections and its consequences., (Copyright © 2011 Elsevier B.V. All rights reserved.)