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So far, research on trypanosomatid infections has been driven by ‘disease by disease’ approaches, leading to different concepts and control strategies. It is, however, increasingly clear that they share common features such as the ability to generate long-lasting asymptomatic infections in their mammalian hosts. Trypanotolerance, long integrated in animal African trypanosomiasis control, historically refers to the ability of cattle breeds to limit Trypanosoma infection and pathology, but has only recently been recognized in humans. Whilst trypanotolerance is absent from the vocabulary on leishmaniasis and Chagas disease, asymptomatic infections also occur. We review the concept of trypanotolerance across the trypanosomatids and discuss the importance of asymptomatic carriage in the current context of elimination. [ABSTRACT FROM AUTHOR]

Abstract: The tsetse fly (Diptera: Glossinidae), the vector of trypanosomes causing human and animal trypanosomiasis, harbors symbiotic microorganisms including the primary symbiont Wigglesworthia glossinidia, involved in the fly’s nutrition and fertility, and the secondary symbiont Sodalis glossinidius, involved in the trypanosome establishment in the fly’s midgut. Both symbionts are maternally transmitted to the intrauterine progeny through the fly’s milk gland secretions. In this study, we investigated the population dynamics of these symbionts during fly development. Wigglesworthia and Sodalis densities were estimated using quantitative PCR performed on Glossina palpalis gambiensis at different developmental stages. The results showed that the density of the primary Wigglesworthia symbiont was higher than that of Sodalis for all host developmental stages. Sodalis densities remained constant in pupae, but increased significantly in adult flies. The opposite situation was observed for Wigglesworthia, whose density increased in pupae and remained constant during the female adult stage. Moreover, Wigglesworthia density increased significantly during the transition from the pupal to the teneral stage, while mating had a contradictory effect depending on the age of the fly. Finally, tsetse fly colonization by both symbionts appears as a continuous and adaptive process throughout the insect’s development. Last, the study demonstrated both symbionts of G. p. gambiensis, the vector of the chronic form of human African trypanosomiasis, to be permanent inhabitants of the colony flies throughout their life span. This was expected for the primary symbiont, Wigglesworthia, but not necessarily for the secondary symbiont, S. glossinidius, whose permanent presence is not required for the fly’s survival. This result is of importance as Sodalis could be involved in the tsetse fly vector competence and may constitute a target in the frame of sleeping sickness fighting strategies. [Copyright &y& Elsevier]

Abstract: 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 &y& Elsevier]

Abstract: In Africa, the protozoan parasite of the genus Trypanosoma causes animal (AAT) and human African trypanosomiasis (HAT). These diseases are responsible for considerable mortality and economic losses, and until now the drugs commonly used have often been very toxic and expensive, with no vaccine available. A range of clinical presentations, from chronic to acute symptoms, is observed in both AAT and HAT. Host, parasite, and environmental factors are likely to be involved in this clinical variability. In AAT, some West African cattle (N’Dama, Bos taurus) have the ability to better control the disease development (and therefore to remain productive) than other taurine breeds (Zebu, Bos indicus). This phenomenon is called trypanotolerance and seems to have major genetic components. In humans, tolerance/resistance to the disease is suspected, however, this needs confirmation. This review focuses on recent advances made in the field of host genetics in African trypanosomiasis in animals (mouse and bovine) and humans. The perspectives for the development of new control strategies and their applications as well as a better understanding of the physiopathology of the disease are discussed. [Copyright &y& Elsevier]

The CRISPR-Cas system, which was originally identified as a prokaryotic defense mechanism, is increasingly being used for the functional study of genes. This technology, which is simple, inexpensive and efficient, has aroused a lot of enthusiasm in the scientific community since its discovery, and every month many publications emanate from very different communities reporting on the use of CRISPR-Cas9. Currently, there are no vaccines to control neglected tropical diseases (NTDs) caused by Trypanosomatidae, particularly Human African Trypanosomiasis (HAT) and Animal African Trypanosomoses (AAT), and treatments are cumbersome and sometimes not effective enough. CRISPR-Cas9 has the potential to functionally analyze new target molecules that could be used for therapeutic and vaccine purposes. In this review, after briefly describing CRIPSR-Cas9 history and how it works, different applications on diseases, especially on parasitic diseases, are reviewed. We then focus the review on the use of CRISPR-Cas9 editing on Trypanosomatidae parasites, the causative agents of NTDs, which are still a terrible burden for human populations in tropical regions, and their vectors. [ABSTRACT FROM AUTHOR]

Trypanosomes are bloodstream protozoan parasites, which are pathogens of veterinary and medical importance. Several mammalian species, including humans, can be infected by different species of the genus Trypanosoma ( T . congolense , T . evansi , T . brucei , T . vivax ) exhibiting more or less virulent and pathogenic phenotypes. A previous screening of the excreted-secreted proteins of T . congolense demonstrated an overexpression of several proteins correlated with the virulence and pathogenicity of the strain. Of these proteins, calreticulin (CRT) has shown differential expression between two T . congolense strains with opposite infectious behavior and has been selected as a target molecule based on its immune potential functions in parasitic diseases. In this study, we set out to determine the role of T . congolense calreticulin as an immune target. Immunization of mice with recombinant T . congolense calreticulin induced antibody production, which was associated with delayed parasitemia and increased survival of the challenged animal. These results strongly suggest that some excreted-secreted proteins of T . congolense are a worthwhile target candidate to interfere with the infectious process. [ABSTRACT FROM AUTHOR]

Abstract: An outbreak of trypanosomosis was observed for the first time in metropolitan France in October 2006, when five camels were proved to be infected by Trypanosoma evansi using parasitological methods. The parasite was isolated and used to produce a soluble antigen for antibody–enzyme linked immunosorbent assay (ELISA) in a protocol derived from a method previously developed for sheep and humans but using protein A conjugate. The animals were treated on three instances, alternatively with melarsomine hydrochloride and quinapyramine and followed up on a monthly basis for 2 years with various diagnostic techniques including parasitological, serological and DNA-based methods. Initially, five animals were detected as being positive using ELISA with 83.3% concordance to parasitological tests. Immediately after the first treatment, parasites and DNA disappeared in all animals; antibody levels decreased regularly until ELISA became negative 3–4 months later. Ten months after the first treatment, parasites and antibodies were detected again in one of the camels previously found to be infected. A retrospective study indicated that the weight of this animal had been underestimated; consequently, it had received underdosages of both trypanocides. However, since hypotheses of re-infection or relapse could not be fully substantiated, it is not known whether the ELISA results for this animal were true- or false-negative over a 7-month period. The study confirmed the value of this ELISA using protein A conjugate to detect antibodies directed against T. evansi in camels and the need to use several diagnostic techniques to optimize detection of infected animals. A warning is raised on surra, a potentially emerging disease in Europe. [Copyright &y& Elsevier]

The purpose of this study was to investigate factors involved in vector competence by analyzing whether the diversity and relative abundance of the different bacterial genera inhabiting the fly's gut could be associated with its trypanosome infection status. This was investigated on 160 randomly selected G. p. palpalis flies - 80 trypanosome-infected, 80 uninfected - collected in 5 villages of the Campo trypanosomiasis focus in South Cameroon. Trypanosome species were identified using specific primers, and the V4 region of the 16S rRNA gene of bacteria was targeted for metabarcoding analysis in order to identify the bacteria and determine microbiome composition. A total of 261 bacterial genera were identified of which only 114 crossed two barriers: a threshold of 0.01% relative abundance and the presence at least in 5 flies. The secondary symbiont Sodalis glossinidius was identified in 50% of the flies but it was not considered since its relative abundance was much lower than the 0.01% relative abundance threshold. The primary symbiont Wigglesworthia displayed 87% relative abundance, the remaining 13% were prominently constituted by the genera Spiroplasma, Tediphilus, Acinetobacter and Pseudomonas. Despite a large diversity in bacterial genera and in their abundance observed in micobiome composition, the statistical analyzes of the 160 tsetse flies showed an association with flies' infection status and the sampling sites. Furthermore, tsetse flies harboring Trypanosoma congolense Savanah type displayed a different composition of bacterial flora compared to uninfected flies. In addition, our study revealed that 36 bacterial genera were present only in uninfected flies, which could therefore suggest a possible involvement in flies' refractoriness; with the exception of Cupriavidus , they were however of low relative abundance. Some genera, including Acinetobacter, Cutibacterium, Pseudomonas and Tepidiphilus, although present both in infected and uninfected flies, were found to be associated with uninfected status of tsetse flies. Hence their effective role deserves to be further evaluated in order to determine whether some of them could become targets for tsetse control of fly vector competence and consequently for the control of the disease. Finally, when comparing the bacterial genera identified in tsetse flies collected during 4 epidemiological surveys, 39 genera were found to be common to flies from at least 2 sampling campaigns. • Association between tsetse fly gut bacteria and fly vector competence was studied. • 114 bacterial genera were identified in 160 tsetse flies sampled in Campo HAT focus. • Differences in microbiota composition are associated with fly infection status. • 36 bacteria genera were associated with the uninfected status of flies. • 39 genera are common to flies caught at least in 2 out of 4 former sampling campaigns. [ABSTRACT FROM AUTHOR]