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Human African trypanosomiasis (HAT), or African sleeping sickness, is a fatal disease found throughout sub-Saharan Africa. The disease is close to elimination in many areas, although it was similarly close to elimination once before and subsequently reemerged, despite seemingly low rates of transmission. Determining how these foci persisted and overcame an apparent transmission paradox is key to finally eliminating HAT. By assessing clinical, laboratory, and mathematical data, we propose that asymptomatic infections contribute to transmission through the presence of an overlooked reservoir of skin-dwelling parasites. Our assessment suggests that a combination of asymptomatic and parasitaemic cases is sufficient to maintain transmission at foci without animal reservoirs, and we argue that the current policy not to treat asymptomatic HAT should be reconsidered., African sleeping sickness is an important disease of sub-Saharan Africa that is approaching elimination, but this Essay maintains that an overlooked anatomical reservoir — human skin — may impact control efforts.

Background Human African trypanosomiasis (HAT) is a neglected tropical disease caused by Trypanosoma brucei gambiense transmitted by tsetse flies in sub-Saharan West Africa. In southern Chad the most active and persistent focus is the Mandoul focus, with 98% of the reported human cases, and where African animal trypanosomosis (AAT) is also present. Recently, a control project to eliminate tsetse flies (Glossina fuscipes fuscipes) in this focus using the sterile insect technique (SIT) was initiated. However, the release of large numbers of sterile males of G. f. fuscipes might result in a potential temporary increase in transmission of trypanosomes since male tsetse flies are also able to transmit the parasite. The objective of this work was therefore to experimentally assess the vector competence of sterile males treated with isometamidium for Trypanosoma brucei brucei. Methods An experimental infection was set up in the laboratory, mimicking field conditions: the same tsetse species that is present in Mandoul was used. A T. b. brucei strain close to T. b. gambiense was used, and the ability of the sterile male tsetse flies fed on blood with and without a trypanocide to acquire and transmit trypanosomes was measured. Results Only 2% of the experimentally infected flies developed an immature infection (midgut) while none of the flies developed a metacyclic infection of T. b. brucei in the salivary glands. We did not observe any effect of the trypanocide used (isometamidium chloride at 100 mg/l) on the development of infection in the flies. Conclusions Our results indicate that sterile males of the tested strain of G. f. fuscipes were unable to cyclically transmit T. b. brucei and might even be refractory to the infection. The data of the research indicate that the risk of cyclical transmission of T. brucei by sterile male G. f. fuscipes of the strain colonized at IAEA for almost 40 years appears to be small. Graphical Abstract

International audience; Tsetse flies (Glossina spp.) are major vectors of African trypanosomes, causing either Human or Animal African Trypanosomiasis (HAT or AAT). Several approaches have been developed to control the disease, among which is the anti-vector Sterile Insect Technique. Another approach to anti-vector strategies could consist of controlling the fly's vector competence through hitherto unidentified regulatory factors (genes, proteins, biological pathways, etc.). The present work aims to evaluate the protein abundance in the midgut of wild tsetse flies (Glossina palpalis palpalis) naturally infected by Trypanosoma congolense s.l. Infected and non-infected flies were sampled in two HAT/AAT foci in Southern Cameroon. After dissection, the proteomes from the guts of parasite-infected flies were compared to that of uninfected flies to identify quantitative and/or qualitative changes associated with infection. Among the proteins with increased abundance were fructose-1,6-biphosphatase, membrane trafficking proteins, death proteins (or apoptosis proteins) and SERPINs (inhibitor of serine proteases, enzymes considered as trypanosome virulence factors) that displayed the highest increased abundance. The present study, together with previous proteomic and transcriptomic studies on the secretome of trypanosomes from tsetse fly gut extracts, provides data to be explored in further investigations on, for example, mammal host immunisation or on fly vector competence modification via para-transgenic approaches.

International audience; Serological methods should meet the needs of leishmaniasis diagnosis due to their high sensitivity and specificity, economical and adaptable rapid diagnostic test format, and ease of use. Currently, the performances of serological diagnostic tests, despite improvements with recombinant proteins, vary greatly depending on the clinical form of leishmaniasis and the endemic area. Peptide-based serological tests are promising as they could compensate for antigenic variability and improve performance, independently of Leishmania species and subspecies circulating in the endemic areas. The objective of this systematic review was to inventory all studies published from 2002 to 2022 that evaluate synthetic peptides for serological diagnosis of human leishmaniases and also to highlight the performance (e.g., sensitivity and specificity) of each peptide reported in these studies. All clinical forms of leishmaniasis, visceral and tegumentary, and all Leishmania species responsible for these diseases were considered. Following PRISMA statement recommendations, 1,405 studies were identified but only 22 articles met the selection criteria and were included in this systematic review. These original research articles described 77 different peptides, of which several have promising performance for visceral or tegumentary leishmaniasis diagnosis. This review highlights the importance of and growing interest in synthetic peptides used for serological diagnosis of leishmaniases, and their performances compared to some widely used tests with recombinant proteins.; Serological methods should meet the needs of leishmaniasis diagnosis due to their high sensitivity and specificity, economical and adaptable rapid diagnostic test format, and ease of use. Currently, the performances of serological diagnostic tests, despite improvements with recombinant proteins, vary greatly depending on the clinical form of leishmaniasis and the endemic area. Peptide-based serological tests are promising as they could compensate for antigenic variability and improve performance, independently of Leishmania species and subspecies circulating in the endemic areas. The objective of this systematic review was to inventory all studies published from 2002 to 2022 that evaluate synthetic peptides for serological diagnosis of human leishmaniases and also to highlight the performance (e.g., sensitivity and specificity) of each peptide reported in these studies. All clinical forms of leishmaniasis, visceral and tegumentary, and all Leishmania species responsible for these diseases were considered. Following PRISMA statement recommendations, 1,405 studies were identified but only 22 articles met the selection criteria and were included in this systematic review. These original research articles described 77 different peptides, of which several have promising performance for visceral or tegumentary leishmaniasis diagnosis. This review highlights the importance of and growing interest in synthetic peptides used for serological diagnosis of leishmaniases, and their performances compared to some widely used tests with recombinant proteins. Re ´sume ´-Revue systématique des tests sérologiques à base de peptides pour le diagnostic de la leishmaniose. D'une sensibilité et d'une spécificité élevées, faciles à réaliser, économiques et adaptables à un format de test de diagnostic rapide, les méthodes sérologiques devraient répondre aux besoins du diagnostic de la leishmaniose. Actuellement, les performances des tests de diagnostic sérologique, malgré des améliorations avec les protéines recombinantes, varient fortement selon la forme clinique de la leishmaniose et les zones d'endémie. Les tests sérologiques à base de peptides sont prometteurs car ils pourraient compenser la variabilité antigénique et améliorer les performances, indépendamment des espèces et sous-espèces de Leishmania circulant dans les zones endémiques. L'objectif de cette revue systématique était d'inventorier toutes les études publiées de 2002 à 2022 qui évaluent les peptides synthétiques pour le diagnostic sérologique des leishmanioses humaines et également de mettre en évidence les performances (dont la sensibilité et la spécificité) de chaque peptide rapporté dans ces études. Toutes les formes cliniques de leishmanioses, viscérales et tégumentaires, et toutes les espèces de Leishmania responsables de ces maladies ont été considérées. Suite aux recommandations de la déclaration PRISMA, 1405 études ont été identifiées mais seuls 22 articles répondaient aux critères de sélection et ont été inclus dans cette revue systématique. Ces articles de recherche originaux décrivent 77 peptides différents, dont plusieurs sont prometteurs pour le diagnostic de la leishmaniose viscérale ou tégumentaire. Cette revue met en évidence l'importance et l'intérêt croissant accordés aux peptides synthétiques utilisés pour le diagnostic sérologique des leishmanioses, et leurs performances par rapport à certains tests largement utilisés avec des protéines recombinantes.

Animal African trypanosomosis, caused by blood protozoan parasites transmitted mainly by tsetse flies, represents a major constraint for millions of cattle in sub-Saharan Africa. Exposed cattle include trypanosusceptible indicine breeds, severely affected by the disease, and West African taurine breeds called trypanotolerant owing to their ability to control parasite development, survive and grow in enzootic areas. Until now the genetic basis of trypanotolerance remains unclear. Here, to improve knowledge of the biological processes involved in trypanotolerance versus trypanosusceptibility, we identified bovine genes differentially expressed in five West African cattle breeds during an experimental infection byTrypanosoma congolenseand their biological functions. To this end, whole blood genome-wide transcriptome of three trypanotolerant taurine breeds (N’Dama, Lagune and Baoulé), one susceptible zebu (Zebu Fulani) and one African taurine x zebu admixed breed (Borgou) were profiled by RNA sequencing at four time points, one before and three during infection. As expected, infection had a major impact on cattle blood transcriptome regardless of the breed. The functional analysis of differentially expressed genes over time in each breed confirmed an early activation of the innate immune response, followed by an activation of the humoral response and an inhibition of T cell functions at the chronic stage of infection. More importantly, we highlighted overlooked features, such as a strong disturbance in host metabolism and cellular energy production that differentiates trypanotolerant and trypanosusceptible breeds. N’Dama breed showed the earliest regulation of immune response, associated with a strong activation of cellular energy production, also observed in Lagune, and to a lesser extent in Baoulé. Susceptible Zebu Fulani breed differed from other breeds by the strongest modification in lipid metabolism regulation. Overall, this study provides a better understanding of the biological mechanisms at work during infection, especially concerning the interplay between immunity and metabolism that seems differentially regulated depending on the cattle breeds.

Funding Information: This study was supported by FCT (Project TickGenoMi, reference PTDC/SAU-PAR/28947/2017). Funding Information: The digitalization of Acarologia papers prior to 2000 was supported by Agropolis Fondation under the reference ID 1500-024 through the « Investissements d’avenir » programme (Labex Agro: ANR-10-LABX-0001-01) Publisher Copyright: © 2023, Les Amis d'Acarologia. All rights reserved. Ixodes ricinus is an important vector of several human and veterinary infectious agents. Its wide geographical distribution and permissive feeding behaviour have prompted earlier studies on its population genetics. Results were, nevertheless, not conclusive. Furthermore, no research has fully focused on the south-western distribution range of I. ricinus, where exchanges between European and North African populations are more likely to occur. The presence of an additional species, Ixodes inopinatus, in the area further confuses the topic, as the two species are hard to differentiate morphologically. The present work describes the testing of microsatellite markers previously described for I. ricinus using Portuguese and Tunisian tick populations of both species. In addition, new microsatellite loci were developed to complement the available marker toolbox. Loci showed different amplification successes across subpopulations, with Tunisian DNA less readily amplified. Altogether, 15 loci were considered suitable for genetic analyses of Portuguese subpopulations, 10 for Tunisian samples, and seven, common to both populations, were considered to be informative at the inter-continental level. A preliminary analysis of both datasets revealed two isolated populations, which can correspond to two different species. Furthermore, Tunisian specimens identified by sequencing of 16S rDNA as having I. ricinus or I. inopinatus sequence profiles all clustered together in one single population using the proposed microsatellites. This confirms that taxonomic decisions based only on 16S rRNA gene sequencing can be misleading. The application of the proposed set of microsatellite markers to a larger sample, representative of the south-western Ixodes’ distribution range, will be crucial to clarify the distribution of both species. publishersversion published

International audience; SARS-CoV-2, the virus responsible for COVID-19 in humans, can efficiently infect a large number of animal species. Like any virus, and particularly RNA viruses, SARS-CoV-2 undergoes mutations during its life cycle some of which bring a selective advantage, leading to the selection of a given lineage. Minks are very susceptible to SARS-CoV-2 and owing to their presence in mass rearing, they make a good model for studying the relative importance of mutations in viral adaptation to host species. Variants, such as the mink-selected SARS-CoV-2 Y453F and D614G or H69del/V70del, Y453F, I692V and M1229I were identified in humans after spreading through densely caged minks. However, not all mink-specific mutations are conserved when the virus infects human populations back. Many questions remain regarding the interspecies evolution of SARS-CoV-2 and the dynamics of transmission leading to the emergence of new variant strains. We compared the human and mink ACE2 receptor structures and their interactions with SARS-CVoV-2 variants. In minks, ACE2 presents a Y34 amino acid instead of the H34 amino acid found in the human ACE2. H34 is essential for the interaction with the Y453 residue of the SARS-CoV-2 Spike protein. The Y453F mink mutation abolishes this conflict. A series of 18 mutations not involved in the direct ACE2 interaction was observed in addition to the Y453F and D614G in 16 different SARS-CoV-2 strains following bidirectional infections between humans and minks. These mutations were not random and were distributed into five different functional groups having an effect on the kinetics of ACE2-RD interaction. The interspecies transmission of SARS-CoV-2 from humans to minks and back to humans, generated specific mutations in each species which improved the affinity for the ACE2 receptor either by direct mutation of the core 453 residue or by associated compensatory mutations.

The first release of the SILVI script generated during the current study, including the source code and all data files, are publicly available in the GitHub repository (https://github.com/JoanaPissarra/SILVI2020) and the Zenodo repository (https://doi.org/10.5281/zenodo.6865909).; International audience; High-throughput screening of available genomic data and identification of potential antigenic candidates have promoted the development of epitope-based vaccines and therapeutics. Several immunoinformatic tools are available to predict potential epitopes and other immunogenicity-related features, yet it is still challenging and time-consuming to compare and integrate results from different algorithms. We developed the R script SILVI (short for: from in silico to in vivo ), to assist in the selection of the potentially most immunogenic T-cell epitopes from Human Leukocyte Antigen (HLA)-binding prediction data. SILVI merges and compares data from available HLA-binding prediction servers, and integrates additional relevant information of predicted epitopes, namely BLASTp alignments with host proteins and physical-chemical properties. The two default criteria applied by SILVI and additional filtering allow the fast selection of the most conserved, promiscuous, strong binding T-cell epitopes. Users may adapt the script at their discretion as it is written in open-source R language. To demonstrate the workflow and present selection options, SILVI was used to integrate HLA-binding prediction results of three example proteins, from viral, bacterial and parasitic microorganisms, containing validated epitopes included in the Immune Epitope Database (IEDB), plus the Human Papillomavirus (HPV) proteome. Applying different filters on predicted IC50, hydrophobicity and mismatches with host proteins allows to significantly reduce the epitope lists with favourable sensitivity and specificity to select immunogenic epitopes. We contemplate SILVI will assist T-cell epitope selections and can be continuously refined in a community-driven manner, helping the improvement and design of peptide-based vaccines or immunotherapies. SILVI development version is available at: https://github.com/JoanaPissarra/SILVI2020 and https://doi.org/10.5281/zenodo.6865909 .

Reliable diagnostic tools are needed to choose the appropriate treatment and proper control measures for animal trypanosomoses, some of which are pathogenic.Trypanosoma cruzi, for example, is responsible for Chagas disease in Latin America. Similarly, pathogenic animal trypanosomoses of African origin (ATAO), including a variety ofTrypanosomaspecies and subspecies, are currently found in Africa, Latin America and Asia. ATAO limit global livestock productivity and impact food security and the welfare of domestic animals. This review focusses on implementing previously reviewed diagnostic methods, in a complex epizootiological scenario, by critically assessing diagnostic results at the individual or herd level. In most cases, a single diagnostic method applied at a given time does not unequivocally identify the various parasitological and disease statuses of a host. These include “non-infected”, “asymptomatic carrier”, “sick infected”, “cured/not cured” and/or “multi-infected”. The diversity of hosts affected by these animal trypanosomoses and their vectors (or other routes of transmission) is such that integrative, diachronic approaches are needed that combine: (i) parasite detection, (ii) DNA, RNA or antigen detection and (iii) antibody detection, along with epizootiological information. The specificity of antibody detection tests is restricted to the genus or subgenus due to cross-reactivity with otherTrypanosomaspp. and Trypanosomatidae, but sensitivity is high. The DNA-based methods implemented over the last three decades have yielded higher specificity and sensitivity for active infection detection in hosts and vectors. However, no single diagnostic method can detect all active infections and/or trypanosome species or subspecies. The proposed integrative approach will improve the prevention, surveillance and monitoring of animal trypanosomoses with the available diagnostic tools. However, further developments are required to address specific gaps in diagnostic methods and the sustainable control or elimination of these diseases.Graphical Abstract

International audience; Most neglected tropical diseases (NTDs) are intrinsically embedded within the One Health approach: NTD researchers have already been dealing with multidisciplinary and intersectoral work for decades simply because it is essential for understanding and controlling the usually complex transmission of the pathogens causing NTDs.This long experience has already enrooted the idea of the horizontal integration of research, control, elimination and eradication strategies. The ongoing epidemiological transitions of most NTDs urges pursuing and amplifying the development of co-constructed multidisciplinary and intersectoral research initiatives for improving control/elimination/eradication processes. Lessons from NTDs may also be useful for other diseases targeted by ongoing One Health initiatives.

International audience

Persistent pathogens have evolved to avoid elimination by the mammalian immune system including mechanisms to evade complement. Infections with African trypanosomes can persist for years and cause human and animal disease throughout sub-Saharan Africa. It is not known how trypanosomes limit the action of the alternative complement pathway. Here we identify an African trypanosome receptor for mammalian factor H, a negative regulator of the alternative pathway. Structural studies show how the receptor binds ligand, leaving inhibitory domains of factor H free to inactivate complement C3b deposited on the trypanosome surface. Receptor expression is highest in developmental stages transmitted to the tsetse fly vector and those exposed to blood meals in the tsetse gut. Receptor gene deletion reduced tsetse infection, identifying this receptor as a virulence factor for transmission. This demonstrates how a pathogen evolved a molecular mechanism to increase transmission to an insect vector by exploitation of a mammalian complement regulator., African trypanosome infections can persist for years, but immune evasion mechanisms are not fully understood. Here, Macleod et al. identify a trypanosome receptor for mammalian factor H, a negative regulator of the alternative complement pathway, that increases parasite transmission to tsetse flies.

International audience

International audience; Different groups of parasites (Helminths, Protozoa, Acarians and Insects) and the associated pathologies remain a main constraint on ruminant breeding. For decades, the control of these parasitic infections has mainly relied on synthetic antiparasitic drugs, developed and provided regularly by the pharmaceutical industry. However, this monolithic approach to control parasitism based on a quasi-exclusive reliance on chemical drugs is nowadays facing several limits. On the one hand, there is an increasing public demand to promote a more sustainable, agroecological agriculture aiming at lower chemical inputs. On the other hand, the phenomenon of resistance to antiparasitic drugs is an overall and constant process identified in the different groups of parasites. In this context, the new paradigm to control parasitic infections and their consequences in ruminants is based on the concept of integrated management combining different alternative solutions in addition to synthetic treatments. The aim of this review was to illustrate different alternative options, corresponding to different principles, based on 2 main parasitic models: gastro intestinal nematodes and insects affecting either small ruminants and/or cattle.; Les parasites (Helminthes, Protozoaires, Acariens, Insectes) restent responsables de pathologie majeures impactant l’élevage des ruminants. Pendant des décennies, la maitrise de ces divers groupes de parasites a reposé pour l’essentiel sur des molécules de synthèse développées par l’industrie pharmaceutique. Cependant, cette gestion quasi exclusive par des traitements chimiques se trouve désormais confrontée à plusieurs limites : d’une part, une demande sociétale croissante pour réduire les intrants chimiques en élevage dans le cadre d’une agriculture évoluant vers des critères agroécologiques ; d’autre part, le phénomène général de résistances aux antiparasitaires dans les différents groupes mentionnés. Dans ce contexte, le concept de gestion intégrée du parasitisme fondée sur une combinaison de solutions alternatives aux molécules de synthèse devient le nouveau paradigme de lutte applicable aux divers groupes de pathogènes. L’objectif de cette revue est de présenter quelques exemples de solutions complémentaires aux substances de synthèse en se fondant sur deux modèles principaux : les nématodes gastro intestinaux et les insectes chez des petits ruminants ou les bovins.

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.Suivi de l’élimination de la Trypanosomiase Humaine Africaine dans le foyer historique de Batié au sud-ouest du Burkina Faso.L’Organisation mondiale de la santé a ciblé l’élimination de la trypanosomiase humaine africaine (THA) comme transmission zéro d’ici 2030. Une surveillance continue doit être mise en place pour la détection précoce des cas réémergents. Dans ce contexte, la performance des tests de diagnostic et des algorithmes de test pour la détection de la réémergence de la THA de Trypanosoma brucei gambiense reste à évaluer. Nous avons réalisé une enquête médicale en porte-à-porte pour la THA dans le foyer historique de Batié, au sud-ouest du Burkina Faso. Le dépistage a été effectué à l’aide de trois tests de diagnostic rapide (TDR). Deux tests de laboratoire (ELISA/T. b. gambiense et trypanolyse immunitaire) et un examen parasitologique ont été effectués uniquement sur les TDR positifs. Au total, 5883 participants ont été dépistés, parmi lesquels 842 (14 %) ont été testés positifs dans au moins un TDR. Le sang de 519 TDR positifs a été examiné au microscope mais aucun trypanosome n’a été observé. Le test HAT Sero-K-Set a montré la spécificité la plus faible de 89 %, tandis que les spécificités de SD Bioline HAT et rHAT Sero-Strip étaient de 92 % et 99 %, respectivement. La spécificité d’ELISA/T. b. gambiense et de la trypanolyse étaient respectivement de 99 % (98–99 %) et 100 % (99–100 %). Nos résultats suggèrent que T. b. gambiense ne circule plus dans la zone d’étude et que la transmission zéro a probablement été atteinte. Bien qu’une analyse de moindre coût soit toujours nécessaire, notre étude a montré qu’une présélection par TDR suivie d’une trypanolyse peut être une stratégie utile pour la surveillance post-élimination au Burkina Faso.

International audience; Next generation sequencing technologies enabled high-density genotyping for large numbers of samples. Nowadays SNP calling pipelines produce up to millions of such markers, but which need to be filtered in various ways according to the type of analyses. One of the main challenges still lies in the management of an increasing volume of genotyping files that are difficult to handle for many applications. Here, we provide a practical guide for efficiently managing large genomic variation data using Gigwa, a user-friendly, scalable and versatile application that may be deployed either remotely on web servers or on a local machine.

International audience; Scenario simulations are the main tool for studying the impact of a nuclear reactor fleet on the related fuel cycle facilities. This equilibrium preliminary study aims to present the functionalities of a new tool and to show the wide variety of reactors/cycles/strategies that can be studied in steady state conditions and validated with more details thanks to dynamic code. Different types of scenario simulation tools have been developed at CEA over the years, this study focuses on dynamic and equilibrium codes. Dynamic fuel cycle simulation code models the ingoing and outgoing material flow in all the facilities of a nuclear reactor fleet and their evolutions through the different nuclear processes over a given period of time. Equilibrium fuel cycle simulation code models advanced nuclear fuel cycles in equilibrium conditions, i.e. in conditions which stabilize selected nuclear inventories such as spent nuclear fuel constituents, plutonium or some minor actinides. The principle of this work is to analyze different nuclear reactors (PWR, AMR) and several fuel types (UOX, MOX, ERU, MIX) to simulate advanced nuclear fleet with partial and fully plutonium and uranium multi-recycling strategies at equilibrium. At this first stage, selected results are compared with COSI6 simulations in order to evaluate the precision of this new tool, showing a significant general agreement.

Primer sequences and raw data are available in the supplementary file S1 at: https://doi.org/10.5281/zenodo.6460010. Samples and associated data were deposited in the Small Mammal Collection at the IRD/CBGP (https://doi.org/10.15454/WWNUPO) as well as at URIB/LARBA/EPAC and Kasetsart University (Thailand). They are available upon request.Preprint version 3 of this article has been peer-reviewed and recommended by Peer Community InInfections.; Trypanosoma lewisi belongs to the so-called atypical trypanosomes that occasionally affect humans. It shares the same hosts and flea vector of other medically relevant pathogenic agents as Yersinia pestis, the agent of plague. Increasing knowledge on the population structure (reproductive mode, population size, dispersal) of this parasite thus represents a challenging but important issue. The use of polymorphic genetic markers, together with suitable population genetics tools, is a convenient way to achieve such objectives. To date, the population biology of T. lewisi is poorly known and, to our knowledge, no population genetics studies have ever been conducted. Here, we present the development of nine microsatellite markers of this species. We investigated their polymorphism in different countries from Africa and South-East Asia from DNAs extracted from the spleen of their rodent reservoirs (essentially rat species). Several amplification problems arose, especially with South-East Asian individuals. This led to retain only those individuals with complete genotypes (most of them originating from West Africa, notably Cotonou, Benin) to ensure an optimal estimate of heterozygosity. Our results pointed towards a mainly (at least 95-99%) clonal mode of propagation, a strong subdivision at the smallest scale available (i.e., urban neighborhoods, i.e. 0.250 km²), and a generation time most probably shorter than 4 months. In future studies, more extensive sampling at smaller geographic scales (i.e., households), within a one- or two-months window and with improved amplification conditions, should lead to a more precise picture of the fine population structure of this parasite.

International audience; Leishmaniasis is one of the most impactful parasitic diseases worldwide, endangering the lives of 1 billion people every year. There are 20 different species of Leishmania able to infect humans, causing cutaneous (CL), visceral (VL), and/or mucocutaneous leishmaniasis (MCL). Leishmania parasites are known to secrete a plethora of proteins to establish infection and modulate the host's immune system. In this study, we analyzed using tandem mass spectrometry the total protein content of the secretomes produced by promastigote forms from seven Leishmania species grown in serum-free in vitro cultures. The core secretome shared by all seven Leishmania species corresponds to up to one-third of total secreted proteins, suggesting conserved mechanisms of adaptation to the vertebrate host. The relative abundance confirms the importance of known virulence factors and some proteins uniquely present in CL- or VL-causing species and may provide further insight regarding their pathogenesis. Bioinformatic analysis showed that most proteins were secreted via unconventional mechanisms, with an important role for vesicle-based secretion for all species. Gene Ontology annotation and enrichment analyses showed a high level of functional conservation among species. This study contributes to the current knowledge on the biological significance of differently secreted proteins and provides new information on the correlation of Leishmania secretome to clinical outcomes and species-specific pathogenesis.

In the context of the human African trypanosomiasis elimination process, reliable and accurate diagnostic tools are crucial for exploring the role of a potential animal reservoir of Trypanosoma brucei gambiense. The immune trypanolysis test (TL) using the variant antigen types (VAT) LiTat 1.3 and LiTat 1.5, described as a specific serological method to detect people infected by T. b. gambiense, seems to be a promising tool. However, its specificity was recently questioned during field animal surveys. The present study evaluates the performance of TL during experimental T. b. brucei infection in pigs. Eight infected pigs and four uninfected pigs were followed up with blood and plasma collection. Blood was used for parasitological investigation. TL was performed on the plasma with the LiTat 1.3, LiTat 1.5 and LiTat 1.6 VATs. All control pigs remained negative to parasitological investigation and TL. Trypanosomes were detected in all the infected pigs and the first detection was between 10 and 14 days post infection (dpi). TL results showed that infected pigs developed antibodies against the three VATs. The first antibody detections by TL occurred between 14 and 21 dpi for antibodies directed against LiTat 1.6, 21 and 168 dpi for antibodies directed against LiTat 1.5 and 70, and 182 dpi for antibodies directed against LiTat 1.3. This study highlights for the first time that TL using LiTat 1.3 and LiTat 1.5 VATs is not specific to T. b. gambiense. Development of specific diagnostic tools for the detection of T. b. gambiense infections in animals, especially in pigs, is still needed.Évidence expérimentale que la trypanolyse basée sur les types d’antigène variable LiTat 1.3 et LiTat 1.5 n’est pas spécifique de Trypanosoma brucei gambiense.Dans le contexte d’élimination de la trypanosomiase humaine Africaine, des outils de diagnostic fiables et précis sont essentiels afin d’explorer le rôle d’un potentiel réservoir animal de Trypanosoma brucei gambiense. La trypanolyse (TL) qui utilise les types d’antigène variable (TAV) LiTat 1.3 et LiTat 1.5, et qui est décrite comme une méthode sérologique spécifique pour détecter les personnes infectées par T. b. gambiense, semble être un outil prometteur. Cependant, sa spécificité a été récemment remise en question lors d’enquêtes sur les animaux. La présente étude évalue la performance de ce test lors d’une infection expérimentale à T. b. brucei chez le porc. Huit porcs infectés et quatre porcs témoins non infectés ont été suivis avec des prélèvements de sang et de plasma. Le sang a été utilisé pour l’examen parasitologique. La TL a été réalisée sur les échantillons de plasma avec les TAV LiTat 1.3, LiTat 1.5 et LiTat 1.6. Tous les porcs témoins ont été négatifs en parasitologie et à la TL. Les trypanosomes ont été détectés sur tous les porcs infectés avec les premières détections entre 10 et 14 jours post-infection (jpi). Les résultats de la TL ont montré que les porcs infectés ont développé des anticorps contre les trois TAV. Les premiers anticorps détectés par la TL étaient dirigés contre le LiTat 1.6 entre 14 et 21 jpi, puis le LiTat 1.5 entre 21 et 168 jpi et enfin le LiTat 1.3 entre 70 et 182 jpi. Cette étude démontre pour la première fois que la TL basée sur les TAV LiTat 1.3 et LiTat 1.5 n’est pas spécifique de T. b. gambiense. Il est donc toujours nécessaire et urgent de développer un outil de diagnostic spécifique pour la détection des infections à T. b. gambiense chez les animaux, notamment chez les porcs.

Background African animal trypanosomosis (AAT), transmitted by tsetse flies, is arguably the main disease constraint to integrated crop-livestock agriculture in sub-Saharan Africa, and African heads of state and governments adopted a resolution to rid the continent of this scourge. In order to sustainably reduce or eliminate the burden of AAT, a progressive and evidence-based approach is needed, which must hinge on harmonized, spatially explicit information on the occurrence of AAT and its vectors. Methods A digital repository was assembled, containing tsetse and AAT data collected in Burkina Faso between 1990 and 2019. Data were collected either in the framework of control activities or for research purposes. Data were systematically verified, harmonized, georeferenced and integrated into a database (PostgreSQL). Entomological data on tsetse were mapped at the level of individual monitoring traps. When this was not possible, mapping was done at the level of site or location. Epidemiological data on AAT were mapped at the level of location or village. Results Entomological data showed the presence of four tsetse species in Burkina Faso. Glossina tachinoides, present from the eastern to the western part of the country, was the most widespread and abundant species (56.35% of the catches). Glossina palpalis gambiensis was the second most abundant species (35.56%), and it was mainly found in the west. Glossina morsitans submorsitans was found at lower densities (6.51%), with a patchy distribution in the southern parts of the country. A single cluster of G. medicorum was detected (less than 0.25%), located in the south-west. Unidentified tsetse flies accounted for 1.33%. For the AAT component, data for 54,948 animal blood samples were assembled from 218 geographic locations. The samples were tested with a variety of diagnostic methods. AAT was found in all surveyed departments, including the tsetse-free areas in the north. Trypanosoma vivax and T. congolense infections were the dominant ones, with a prevalence of 5.19 ± 18.97% and 6.11 ± 21.56%, respectively. Trypanosoma brucei infections were detected at a much lower rate (0.00 ± 0.10%). Conclusions The atlas provides a synoptic view of the available information on tsetse and AAT distribution in Burkina Faso. Data are very scanty for most of the tsetse-free areas in the northern part of the country. Despite this limitation, this study generated a robust tool for targeting future surveillance and control activities. The development of the atlas also strengthened the collaboration between the different institutions involved in tsetse and AAT research and control in Burkina Faso, which will be crucial for future updates and the sustainability of the initiative. Graphical Abstract

Trypanosoma brucei causes human African trypanosomiasis (HAT). Three subspecies were described: T. b. gambiense (Tbg) and T. b. rhodesiense (Tbr) in humans, and T. b. brucei (Tbb) in animals. Molecular markers subdivided Tbg into two groups: Tbg1 and Tbg2, of which the latter is different from Tbg1 and Tbr (absence of the SRA gene), but indistinguishable from Tbb. Tbg2 is considered to be a zoonotic form of HAT in West Africa. Tbg2 was found mainly in Côte d'Ivoire between 1978 and 1992, but the latest description was made in Ghana in 2013. New molecular tools would be welcome to characterize such infections and determine their origins (resistance to human serum or patient immunodeficiency) in the current context of HAT elimination.

Bartonella spp. are Gram-negative zoonotic bacteria transmitted to humans via various blood-sucking arthropods. Rodents have been identified as reservoir hosts of several zoonotic pathogens, including Bartonella spp. In Thailand, studies of Bartonella spp. in rodents from urban areas are limited; thus, a study in this area is necessary. The objectives of this study were to detect Bartonella spp. in rodents in Thailand and to compare the species’ distribution across different areas. In total, 70 blood samples from rodents in urban and suburban areas were tested for Bartonella spp. using a conventional polymerase chain reaction that targeted the citrate synthase (gltA) gene. All Bartonella-positive sequences were analyzed using polymorphism in order to build a phylogenetic tree. Approximately 38% of the rodents studied contained Bartonella DNA. Both Rattus exulans (Pacific rat) and R. tanezumi (Asian house rat) contained Bartonella spp. Four species of Bartonella were detected in blood samples: B. tribocorum, B. phoceensis, B. grahamii, and B. rattimassiliensis. In addition, eight Pacific rats contained the B. kosoyi–B. tribocorum complex. Bartonella phoceensis and B. tribocorum–B. kosoyi complexes were found in a specific habitat (p < 0.05). Interestingly, only seven haplotypes were identified in the sequences analyzed, and only haplotype A was found in both rodent species. Finally, a monitoring program for zoonotic Bartonella infection, especially the B. kosoyi–B. tribocorum complex, B. phoceensis, B. grahamii, and B. rattimassiliensis should be established, especially in high-risk areas.

Background Leishmaniases are neglected tropical diseases of public health concern in Algeria. The immunocompromised patients with HIV, autoimmune diseases, or chronic alcohol abuse are at a higher risk of leishmaniasis. Herein, we present the case of an immunocompetent diabetic patient infected by Leishmania major, leading to life-threatening consequences. Case presentation An Algerian diabetic patient developed a cutaneous lesion with large polymorphous inflamed granuloma and pyoderma gangrenosum in the left foot, following L. major infection. A delayed follow-up led to a treatment failure, resulting in the amputation. Conclusions This report highlights the absence of timely treatment of Leishmania infection as a life-threatening point among high-risk diabetic patients. Clinicians should be aware of this parasitosis leading to severe complications in diabetic patients.

International audience; Since the beginning of the COVID-19 pandemic in 2020 caused by SARS-CoV-2, the question of the origin of this virus has been a highly debated issue. Debates have been, and are still, very disputed and often violent between the two main hypotheses: a natural origin through the “spillover” model or a laboratory-leak origin. Tenants of these two options are building arguments often based on the discrepancies of the other theory. The main problem is that it is the initial question of the origin itself which is biased. Charles Darwin demonstrated in 1859 that all species are appearing through a process of evolution, adaptation and selection. There is no determined origin to any animal or plant species, simply an evolutionary and selective process in which chance and environment play a key role. The very same is true for viruses. There is no determined origin to viruses, simply also an evolutionary and selective process in which chance and environment play a key role. However, in the case of viruses the process is slightly more complex because the “environment” is another living organism. Pandemic viruses already circulate in humans prior to the emergence of a disease. They are simply not capable of triggering an epidemic yet. They must evolve in-host, i.e. in-humans, for that. The evolutionary process which gave rise to SARS-CoV-2 is still ongoing with regular emergence of novel variants more adapted than the previous ones. The real relevant question is how these viruses can emerge as pandemic viruses and what the society can do to prevent the future emergence of pandemic viruses.

International audience; The rapid spread of SARS-CoV-2 variants has quickly spanned doubts and the fear about their ability escape vaccine protection. Some of these variants initially identified in caged were also found in humans. The claim that these variants exhibited lower susceptibility to antibody neutralization led to the slaughter of 17 million minks in Denmark. SARS-CoV-2 prevalence tests led to the discovery of infected farmed minks worldwide. In this study, we revisit the issue of the circulation of SARS-CoV-2 variants in minks as a model of sarbecovirus interspecies evolution by: (1) comparing human and mink angiotensin I converting enzyme 2 (ACE2) and neuropilin 1 (NRP-1) receptors; (2) comparing SARS-CoV-2 sequences from humans and minks; (3) analyzing the impact of mutations on the 3D structure of the spike protein; and (4) predicting linear epitope targets for immune response. Mink-selected SARS-CoV-2 variants carrying the Y453F/D614G mutations display an increased affinity for human ACE2 and can escape neutralization by one monoclonal antibody. However, they are unlikely to lose most of the major epitopes predicted to be targets for neutralizing antibodies. We discuss the consequences of these results for the rational use of SARS-CoV-2 vaccines.

International audience; Biting midges of the genus Culicoides (Diptera: Ceratopogonidae) are the biological vectors of arboviruses of global importance in animal health. We characterized the physicochemical parameters that determine the density and composition of the main Culicoides species of veterinary interest in larval habitats of the Niayes region of Senegal. For this purpose, we combined larval and substrate sampling in the field in different habitat types with adult emergence and physicochemical analyses in the laboratory. Three major habitat types were identified, conditioning the predominant species of Culicoides and pH and the amount of organic matter were positively correlated with the abundance of larvae and emerging Culicoides, as opposed to salinity. The diversity of emerging Culicoides was positively correlated with pH while it was negatively correlated with salinity. Culicoides distinctipennis was the predominant species in the larval habitat group of freshwater lake edges. In the larval habitat group of pond and puddle edges, C. oxystoma and C. nivosus were predominant; both species were again most abundant in the larval habitat group of saltwater lake edges. These variabilities in physicochemical parameters support the distribution of different Culicoides species in different habitat groups. These results make it possible to implement effective, selective and environmental-friendly control measures but also to improve current models for estimating the abundance of adult vector populations at a local scale.

International audience; MacLean and colleagues recently published a very elegant analysis demonstrating that SARS-CoV-2 carries signs of positive selection and that it was already adapted to humans prior to the emergence of COVID-19. Using the Spillover theory as a reference model for zoonotic emergence, they conclude that SARS-CoV-2 must have acquired this human adaptation in bats. We reinterpreted the data from MacLean et al. using a different model of zoonotic emergence as reference, the Circulation model. The use of the Circulation model provides a more parsimonious interpretation showing that this adaptation to humans occurs in the human population after primo infection.

Background The diagnosis of gambiense human African trypanosomiasis (gHAT) typically involves 2 steps: a serological screen, followed by the detection of living trypanosome parasites in the blood or lymph node aspirate. Live parasites can, however, remain undetected in some seropositive individuals, who, we hypothesize, are infected with Trypanosoma brucei gambiense parasites in their extravascular dermis. Methods To test this hypothesis, we conducted a prospective observational cohort study in the gHAT focus of Forecariah, Republic of Guinea. Of the 5417 subjects serologically screened for gHAT, 66 were enrolled into our study and underwent a dermatological examination. At enrollment, 11 seronegative, 8 unconfirmed seropositive, and 18 confirmed seropositive individuals had blood samples and skin biopsies taken and examined for trypanosomes by molecular and immunohistological methods. Results In seropositive individuals, dermatological symptoms were significantly more frequent, relative to seronegative controls. T.b. gambiense parasites were present in the blood of all confirmed cases (n = 18) but not in unconfirmed seropositive individuals (n = 8). However, T. brucei parasites were detected in the extravascular dermis of all unconfirmed seropositive individuals and all confirmed cases. Skin biopsies of all treated cases and most seropositive untreated individuals progressively became negative for trypanosomes 6 and 20 months later. Conclusions Our results highlight the skin as a potential reservoir for African trypanosomes, with implications for our understanding of this disease’s epidemiology in the context of its planned elimination and underlining the skin as a novel target for gHAT diagnostics., Live trypanosomes can remain undetected in the blood of individuals seropositive for sleeping sickness. Here, we show that they could be infected with parasites in their extravascular dermis, highlighting the skin as a potential reservoir for trypanosomes.

International audience; Tsetse flies are vectors of parasites that cause diseases responsible for significant economic losses and health issues in sub-Saharan Africa, including sleeping sickness in humans and nagana in domestic animals. Efficient vector-control campaigns require good knowledge of the demographic parameters of the targeted populations. In the last decade, population genetics emerged as a convenient way to measure population densities and dispersal in tsetse flies. Here, by revealing a strong negative density-dependent dispersal in two dimensions, we suggest that control campaigns might unleash dispersal from untreated areas. If confirmed by direct measurement of dispersal before and after control campaigns, area-wide and/or sequential treatments of neighboring sites will be necessary to prevent this issue.

Algeria ranks second after Afghanistan for the incidence of cutaneous leishmaniasis (CL) worldwide. Here, we report a 34-years retrospective analysis of CL in Algeria and focused on the most affected region, the M’Sila province. All 66 cutaneous isolates corresponded to Leishmania (L.) major. Our study of the sandfly and rodent fauna further highlighted the high density of Phlebotomus papatasi and additional phlebotomine species of medical importance, not previously identified in M’Sila. Wild rodents belonging to nine species were trapped in M’Sila, and Psammomys obesus and Meriones shawi were found infected by L. major. In addition, Leishmania infantum was isolated from two visceral leishmaniasis cases, one dog and its proven vectors (P. perniciosus, P. longicuspis, and P. perfiliewi) inventoried during the survey. The high incidence of CL in the M’Sila province is likely a consequence of the increase in minimum temperatures recorded that constitutes suitable conditions for establishing a high endemicity and leads to an explosive rise in leishmaniases cases in this region. A thorough investigation of the underlying risk factors is urgently needed to detect new cases earlier. All these would improve the preparedness to fight the disease.

This assessment was conducted by the ad hoc working group ‘ASF vectors’ of the French Agency for Food, Environmental and Occupational Health & Safety (Anses).; International audience; African swine fever (ASF) represents a global threat with huge economic consequences for the swine industry. Even though direct contact is likely to be the main transmission route from infected to susceptible hosts, recent epidemiological investigations have raised questions regarding the role of haematophagous arthropods, in particular the stable fly (Stomoxys calcitrans). In this study, we developed a mechanistic vector-borne transmission model for ASF virus (ASFV) within an outdoor domestic pig farm in order to assess the relative contribution of stable flies to the spread of the virus. The model was fitted to the ecology of the vector, its blood-feeding behaviour and pig-to-pig transmission dynamic. Model outputs suggested that in a context of low abundance (

Background Glossina austeni and Glossina brevipalpis (Diptera: Glossinidae) are the sole cyclical vectors of African trypanosomes in South Africa, Eswatini and southern Mozambique. These populations represent the southernmost distribution of tsetse flies on the African continent. Accurate knowledge of infested areas is a prerequisite to develop and implement efficient and cost-effective control strategies, and distribution models may reduce large-scale, extensive entomological surveys that are time consuming and expensive. The objective was to develop a MaxEnt species distribution model and habitat suitability maps for the southern tsetse belt of South Africa, Eswatini and southern Mozambique. Methodology/Principal findings The present study used existing entomological survey data of G. austeni and G. brevipalpis to develop a MaxEnt species distribution model and habitat suitability maps. Distribution models and a checkerboard analysis indicated an overlapping presence of the two species and the most suitable habitat for both species were protected areas and the coastal strip in KwaZulu-Natal Province, South Africa and Maputo Province, Mozambique. The predicted presence extents, to a small degree, into communal farming areas adjacent to the protected areas and coastline, especially in the Matutuíne District of Mozambique. The quality of the MaxEnt model was assessed using an independent data set and indicated good performance with high predictive power (AUC > 0.80 for both species). Conclusions/Significance The models indicated that cattle density, land surface temperature and protected areas, in relation with vegetation are the main factors contributing to the distribution of the two tsetse species in the area. Changes in the climate, agricultural practices and land-use have had a significant and rapid impact on tsetse abundance in the area. The model predicted low habitat suitability in the Gaza and Inhambane Provinces of Mozambique, i.e., the area north of the Matutuíne District. This might indicate that the southern tsetse population is isolated from the main tsetse belt in the north of Mozambique. The updated distribution models will be useful for planning tsetse and trypanosomosis interventions in the area., Author summary The two tsetse species transmitting nagana in South Africa, Eswatini and southern Mozambique represent the southernmost distribution of this genus on the African continent. Distribution models were developed to support tsetse control. These models indicated that the main factors contributing to tsetse distribution in the area are the presence of host animals, variation in climate and vegetation mostly observed in protected areas, agricultural practises and land-use also had a significant and rapid impact on tsetse abundance in the area. Application of the model to areas north of the southern distribution predict a low presence of suitable habitats in the Gaza and Inhambane Provinces of Mozambique, thereby indicating that this southern population is geographically isolated from the main tsetse belt starting in the north of Mozambique.

International audience; The current Coronavirus Disease 2019 (COVID-19) pandemic, with more than 111 million reported cases and 2,500,000 deaths worldwide (mortality rate currently estimated at 2.2%), is a stark reminder that coronaviruses (CoV)-induced diseases remain a major threat to humanity. COVID-19 is only the latest case of betacoronavirus (β-CoV) epidemics/pandemics. In the last 20 years, two deadly CoV epidemics, Severe Acute Respiratory Syndrome (SARS; fatality rate 9.6%) and Middle East Respiratory Syndrome (MERS; fatality rate 34.7%), plus the emergence of HCoV-HKU1 which causes the winter common cold (fatality rate 0.5%), were already a source of public health concern. Betacoronaviruses can also be a threat for livestock, as evidenced by the Swine Acute Diarrhea Syndrome (SADS) epizootic in pigs. These repeated outbreaks of β-CoV-induced diseases raise the question of the dynamic of propagation of this group of viruses in wildlife and human ecosystems. SARS-CoV, SARS-CoV-2, and HCoV-HKU1 emerged in Asia, strongly suggesting the existence of a regional hot spot for emergence. However, there might be other regional hot spots, as seen with MERS-CoV, which emerged in the Arabian Peninsula. β-CoVs responsible for human respiratory infections are closely related to bat-borne viruses. Bats are present worldwide and their level of infection with CoVs is very high on all continents. However, there is as yet no evidence of direct bat-to-human coronavirus infection. Transmission of β-CoV to humans is considered to occur accidentally through contact with susceptible intermediate animal species. This zoonotic emergence is a complex process involving not only bats, wildlife and natural ecosystems, but also many anthropogenic and societal aspects. Here, we try to understand why only few hot spots of β-CoV emergence have been identified despite worldwide bats and bat-borne β-CoV distribution. In this work, we analyze and compare the natural and anthropogenic environments associated with the emergence of β-CoV and outline conserved features likely to create favorable conditions for a new epidemic. We suggest monitoring South and East Africa as well as South America as these regions bring together many of the conditions that could make them future hot spots.

International audience; Our understanding of the viral communities associated to animals has not yet reached the level attained on the bacteriome. This situation is due to, among others, technical challenges in adapting metagenomics using high-throughput sequencing to the study of RNA viromes in animals. Although important developments have been achieved in most steps of viral metagenomics, there is yet a key step that has received little attention: the library preparation. This situation differs from bacteriome studies in which developments in library preparation have largely contributed to the democratisation of metagenomics. Here, we present a library preparation optimized for metagenomics of RNA viruses from insect vectors of viral diseases. The library design allows a simple PCR-based preparation, such as those routinely used in bacterial metabarcoding, that is adapted to shotgun sequencing as required in viral metagenomics. We first optimized our library preparation using mock viral communities and then validated a full metagenomic approach incorporating our preparation in two pilot studies with field-caught insect vectors; one including a comparison with a published metagenomic protocol. Our approach provided a fold increase in virus-like sequences compared to other studies, and nearly-full genomes from new virus species. Moreover, our results suggested conserved trends in virome composition within a population of a mosquito species. Finally, the sensitivity of our approach was compared to a commercial diagnostic PCR for the detection of an arbovirus in field-caught insect vectors. Our approach could facilitate studies on viral communities from animals and the democratization of metagenomics in community ecology of viruses.

One health (OH) approaches have increasingly been used in the last decade in the fight against zoonotic neglected tropical diseases (NTDs). However, descriptions of such collaborations between the human, animal and environmental health sectors are still limited for French-speaking tropical countries. The objective of the current survey was to explore the diversity of OH experiences applied to research, surveillance and control of NTDs by scientists from French-speaking countries, and discuss their constraints and benefits. Six zoonotic NTDs were targeted: echinococcoses, trypanosomiases, leishmaniases, rabies, Taenia solium cysticercosis and leptospiroses. Invitations to fill in an online questionnaire were sent to members of francophone networks on NTDs and other tropical diseases. Results from the questionnaire were discussed during an international workshop in October 2019. The vast majority (98%) of the 171 respondents considered OH approaches relevant although only 64% had implemented them. Among respondents with OH experience, 58% had encountered difficulties mainly related to a lack of knowledge, interest and support for OH approaches by funding agencies, policy-makers, communities and researchers. Silos between disciplines and health sectors were still strong at both scientific and operational levels. Benefits were reported by 94% of respondents with OH experience, including increased intellectual stimulation, stronger collaborations, higher impact and cost-efficiency of interventions. Recommendations for OH uptake included advocacy, capacity-building, dedicated funding, and higher communities’ involvement. Improved research coordination by NTD networks, production of combined human-animal health NTD impact indicators, and transversal research projects on diagnostic and reservoirs were also considered essential., Author summary The fight against zoonotic diseases, including NTDs, has greatly benefited from One Health approaches over the last 20 years. The results of this survey show the large attraction these approaches have for scientists working on NTD research, surveillance and control activities in French-speaking tropical countries. However, implementing them is still challenging due to inconsistent political will, insufficient dedicated funding and difficulties in building bridges across multiple sectors and disciplines that each have their own vocabulary, priorities, and ways of conducting research and development projects. There is a significant margin of improvement for One Health uptake, which will be favored by studies on prevalence and economic data integrating impacts at the human, animal and environmental levels, and by studies demonstrating the added value of One Health approaches when they are relevant. Scientific NTD networks have a great role to play in terms of breaking down barriers among sectors and disciplines, promoting exchanges of experiences, and coordinating research to avoid duplication and reinforce synergies. In a world where the poorest populations are also the most heavily affected by climatic disasters, social or political crises, and armed conflicts, NTD scientists from all backgrounds need to better team up to develop and implement more effective and impactful research and interventions.

While the COVID-19 pandemic continues to spread with currently more than 117 million cumulated cases and 2.6 million deaths worldwide as per March 2021, its origin is still debated. Although several hypotheses have been proposed, there is still no clear explanation about how its causative agent, SARS-CoV-2, emerged in human populations. Today, scientifically-valid facts that deserve to be debated still coexist with unverified statements blurring thus the knowledge on the origin of COVID-19. Our retrospective analysis of scientific data supports the hypothesis that SARS-CoV-2 is indeed a naturally occurring virus. However, the spillover model considered today as the main explanation to zoonotic emergence does not match the virus dynamics and somehow misguided the way researches were conducted. We conclude this review by proposing a change of paradigm and model and introduce the circulation model for explaining the various aspects of the dynamic of SARS-CoV-2 emergence in humans., Graphical abstract Unlabelled Image

International audience; arasitic protozoan trypanosomes of the genus Trypanosoma cause infections in both man and livestock in Africa. Understanding the current spatial distribution of trypanosomes, herd-level factors associated with Trypanosoma brucei infection as well as local knowledge of African trypanosomosis is key to its prevention and control. A cross-sectional study was performed that sampled 53 livestock farmers and 444 cattle throughout Malawi. Cattle were screened for trypanosomes using serology and molecular techniques. Questionnaires were administered to livestock herders and incidence of hospital diagnosed human trypanosome infections was estimated from reports submitted to the Department of Health Unit. The apparent prevalence of trypanosome species based on molecular detection was low for Trypanosoma brucei (2%; 95 % CI: 1–4 %) and Trypanosoma congolense (3%; 95 % CI: 2–5 %) but higher for Trypanosoma theileri (26 %; 95 % CI: 22–30 %). The central region of the country was identified as being at a higher risk of T.brucei infection. One of the sampled cattle was confirmed as being infected with Trypanosoma brucei rhodesiense. Human trypanosome cases were more frequently reported in the northern region with an estimated incidence of 5.9 cases per 100,000 people in Rumphi District. The control of zoonotic diseases that impact poor livestock herders requires a One Health approach due to the close contact between humans and their animals and the reliance on animal production for a sustainable livelihood.

International audience; Spatio-temporally heterogeneous environments may lead to unexpected population dynamics. Knowledge is needed on local properties favouring population resilience at large scale. For pathogen vectors, such as tsetse flies transmitting human and animal African trypanosomosis, this is crucial to target management strategies. We developed a mechanistic spatio-temporal model of the age-structured population dynamics of tsetse flies, parametrized with field and laboratory data. It accounts for density- and temperature-dependence. The studied environment is heterogeneous, fragmented and dispersal is suitability-driven. We confirmed that temperature and adult mortality have a strong impact on tsetse populations. When homogeneously increasing adult mortality, control was less effective and induced faster population recovery in the coldest and temperature-stable locations, creating refuges. To optimally select locations to control, we assessed the potential impact of treating them and their contribution to the whole population. This heterogeneous control induced a similar population decrease, with more dispersed individuals. Control efficacy was no longer related to temperature. Dispersal was responsible for refuges at the interface between controlled and uncontrolled zones, where resurgence after control was very high. The early identification of refuges, which could jeopardize control efforts, is crucial. We recommend baseline data collection to characterize the ecosystem before implementing any measures.; hôtes-vecteurs-parasites-environnement dans les maladies tropicales négligées dues aux trypanosomatides', Cirad

International audience; Background: Efficiently managing large, heterogeneous data in a structured yet flexible way is a challenge to research laboratories working with genomic data. Specifically regarding both shotgun- and metabarcoding-based metagenomics, while online reference databases and user-friendly tools exist for running various types of analyses (e.g., Qiime, Mothur, Megan, IMG/VR, Anvi'o, Qiita, MetaVir), scientists lack comprehensive software for easily building scalable, searchable, online data repositories on which they can rely during their ongoing research. Results: metaXplor is a scalable, distributable, fully web-interfaced application for managing, sharing, and exploring metagenomic data. Being based on a flexible NoSQL data model, it has few constraints regarding dataset contents and thus proves useful for handling outputs from both shotgun and metabarcoding techniques. By supporting incremental data feeding and providing means to combine filters on all imported fields, it allows for exhaustive content browsing, as well as rapid narrowing to find specific records. The application also features various interactive data visualization tools, ways to query contents by BLASTing external sequences, and an integrated pipeline to enrich assignments with phylogenetic placements. The project home page provides the URL of a live instance allowing users to test the system on public data. Conclusion: metaXplor allows efficient management and exploration of metagenomic data. Its availability as a set of Docker containers, making it easy to deploy on academic servers, on the cloud, or even on personal computers, will facilitate its adoption.

International audience; In 2005, the Government of Senegal initiated a project entitled "Projet de lutte contre les glossines dans les Niayes" (Tsetse control project in the Niayes) with the aim of creating a zone free of Glossina palpalis gambiensis in that area. The project received technical and financial support from the International Atomic Energy Agency (IAEA), the Food and Agriculture Organization of the United Nations (FAO), the Centre de Cooperation Internationale en Recherche Agronomique pour le Developpement (CIRAD) and the US Department of State through the Peaceful Uses Initiative (PUI). It was implemented in the context of the Pan African Tsetse and Trypanosomosis Eradication Campaign (PATTEC) following a phased conditional approach (PCA) that entails implementation in distinct phases, in which support to the next phase is conditional upon completion of all (or at least the majority of) activities in the previous phase. In the case of the tsetse project in Senegal, the PCA consisted of 4 phases: (1) commitment of all stakeholders and training, (2) baseline data collection, feasibility studies and strategy development, (3) preparatory pre-operational activities and (4) operational activities. This paper provides an overview of the main activities that were carried out within each phase, with emphasis on the operational research carried out in phases 2 and 3, that was instrumental in guiding the project's decision-making. Activities of phase 2 focused on the collection of entomological, veterinary, socio-economic and environmental baseline data, and a population genetics study that proved the isolated character of the G. p. gambiensis population of the Niayes. These data enabled the tsetse-infested area to be delimited to 1000 km(2), the impact of animal trypanosomosis on the farmers' welfare to be quantified (annual benefits of 2 million Euro in the tsetse-infested zone), and the formulation of an area-wide integrated pest management (AW-IPM) strategy that included a sterile insect (SIT) component to eradicate the isolated tsetse populations from the Niayes. In view of the extreme fragmentation of the remaining favourable habitat of the Niayes and the high human population density (peri-urban area), which excluded the possibility of using the Sequential Aerosol Technique, the IPM strategy that was selected comprised the suppression of the tsetse population with insecticide-impregnated traps/targets and the use of "pour-on" for cattle, followed by the release of sterile males to eliminate the remaining relic pockets. During phase 3, the pre-operational phase, a series of activities were carried out that were needed to implement the operational phase. These included the establishment of a colony of tsetse originating from the target area in Senegal, competitiveness studies between the sterile flies and those from the target area, development of transport methods for long-distance shipments of sterile male pupae, competitiveness of the sterile male flies after release in the target area, development of aerial release methods (including a new chilled adult release system) and development of a Maxent-based distribution model to guide the suppression, sterile male releases and monitoring of the eradication campaign. To be able to properly manage the eradication campaign in different phases, the entire target area was divided into 3 operational blocks. This paper demonstrates how, during the operational phase, scientific principles continued to guide the implementation process. The results to date are encouraging, i.e. the deployment of 269 insecticide-impregnated Vavoua traps in favourable habitat of Block 1 reduced the apparent density of the G. p. gambiensis population significantly (from 0.42 (SD 0.39) to 0.04 (SD 0.11) flies/trap/day). This was followed by the aerial release of sterile males that reduced the apparent density to zero after six months of releases. The last wild fly was trapped on August 9, 2012 in Block 1. In Block 2, during the suppression, the apparent fly density dropped from 1.24 (SD 1.23) to 0.005 (SD 0.017) flies/trap/day. Sterile male releases were initiated in February 2014 and expanded to cover the entire Block 2 in January 2015. The apparent fly density has so far been reduced to < 0.001 fly per trap per day until the end of 2018 and releases are still ongoing. The results of the campaign are discussed with respect to the "adaptive management approach" used, which was deemed critical for the success of the campaign.

International audience; 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.

La compréhension de l'épidémiologie d'une maladie infectieuse ou parasitaire passe par la connaissance du fonctionnement des populations vivantes concernées. L'utilisation de marqueurs génétiques et des outils de la génétique des populations permet d'avoir accès, à travers des méthodes indirectes, à des informations clés sur les agents pathogènes et leurs vecteurs : biologie, mode de reproduction, écologie, déplacements, taille des populations... De telles informations peuvent ainsi permettre d'évaluer les risques d'invasions ou d'épidémies, de préciser le potentiel de diffusion de gènes de résistance et d'anticiper les stratégies de lutte.Ce manuel didactique présente les principales méthodes de la génétique empirique des populations et les modèles de base utilisés, avec l'application à des cas concrets analysés pas à pas. Pour cette 2e édition, revue et augmentée, certaines approches ont été améliorées et un "guide de survie" a été ajouté en fin de volume. Ce manuel sera un auxiliaire précieux pour les étudiants, enseignants-chercheurs et personnels de santé qui veulent maîtriser les bases de la génétique des populations et l'utiliser comme outil d'analyse.

La trypanosomiase humaine africaine ou maladie du sommeil est causée par plusieurs sous-espèces membres de l'espèce Trypanosoma brucei : Trypanosoma brucei rhodesiense (Tbr) et Trypanosoma brucei gambiense groupe 1 (Tbg1). Leur biologie a été étudiée en détail, en particulier en ce qui concerne les protéines impliquées dans les mécanismes de résistance au sérum humain (SH). Il existe un autre groupe également capable d'infecter l'homme nommé Trypanosoma brucei gambiense groupe 2 (Tbg2). Celui-ci se résume à une trentaine de souches répertoriées dans la littérature, ne pose pas de problème de santé publique et par conséquent a été très peu étudié, pour ne pas dire oublié. Après un rappel des mécanismes qui permettent à Tbr et Tbg1 de résister à l'action lytique du SH, nous résumerons les connaissances acquises sur Tbg2. Les phénotypes de résistance au sérum humain sont très variables et seulement une de ces souches a fait l'objet de quelques recherches. La résistance de cette dernière est conditionnelle et implique des mécanismes ayant une action directe sur ApoL-1. Cette revue sera donc l'occasion non seulement de rappeler l'état des connaissances concernant la « course à l'armement » menée entre les trypanosomes et l'homme au cours de l'évolution, mais nous permettra également d'entamer une réflexion sur ce groupe particulier et hétérogène qu'est Tbg2, un trypanosome pathogène pour l'homme mais dont le caractère zoonotique doit être pris en compte dans la perspective du contexte de post-élimination de la maladie du sommeil.

Accurate and reliable diagnostic tools are an essential requirement for neglected tropical diseases (NTDs) programmes. However, the NTD community has historically underinvested in the development and improvement of diagnostic tools, potentially undermining the successes achieved over the last 2 decades. Recognizing this, the WHO, in its newly released draft roadmap for NTD 2021–2030, has identified diagnostics as one of four priority areas requiring concerted action to reach the 2030 targets. As a result, WHO established a Diagnostics Technical Advisory Group (DTAG) to serve as the collaborative mechanism to drive progress in this area. Here, the purpose and role of the DTAG are described in the context of the challenges facing NTD programmes.

Efforts to eliminate tropical diseases always led to failures, undoubtedly due to a lack of innovation and a drastic reduction of political support, including human and financial resources. Elimination of diseases cannot be achieved without implementation of adequate tools and strategies to ensure sustainability. Human African trypanosomiasis, on the way to elimination, could be one of the first or maybe even the first to do so.

The animal trypanosomiases of African origin are a rather typical example of a neglected tropical disease. They are caused by blood parasites of the Trypanosoma genus transmitted by haematophagous insects, cyclically by tsetse flies for Trypanosoma congolense, T. vivax and T. brucei brucei, which cause nagana, mechanically by T. evansi, the agent of surra, and finally by T. equiperdum, adapted to sexual transmission, which causes dourine. Nagana affects 38 African countries in the sub-Saharan region with 55 million cattle at risk, not counting small ruminants. These diseases deteriorate the animal’s physical condition, leading to a sharp drop in productivity; in the most severe cases, and in the absence of treatment, the animal dies within a few weeks. The socio-economic impact is estimated at US$ 4.75 billion in annual losses, making these diseases one of the major obstacles to livestock development in Africa. The control of these diseases is hampered by the lack of vaccines, a handful of molecules for treatment against which parasites are increasingly developing resistance, and finally, molecular or serological diagnostics whose robustness needs to be greatly improved. Clinical signs are not specific, parasitological diagnosis is often not very sensitive, and molecular methods are not applicable in the field. Immunodiagnostic methods in the form of rapid diagnostic tests are the only ones suitable for the field, but the few existing tests are poorly available and lack specificity and/or sensitivity. Here we address the advantages and limitations of current diagnostic methods and propose new ways of improving them for better disease control., Les trypanosomiases animales d’origine africaine représentent typiquement une maladie tropicale négligée. Elles sont causées par des parasites sanguicoles du genre Trypanosoma transmis par des insectes hématophages, de manière cyclique par les mouches tsé-tsé pour Trypanosoma congolense, T. vivax et T. brucei brucei, qui causent la nagana, de manière mécanique pour T. evansi, agent de la surra, et enfin par transmission sexuelle pour T. equiperdum, qui cause la dourine. La nagana est présente dans 38 pays d’Afrique subsaharienne où elle peut affecter de nombreuses espèces animales, sauvages et domestiques. Près de 55 millions de bovins vivent sous risque trypanosomien, sans compter les petits ruminants. Ces maladies détériorent la condition physique de l’animal, induisant une forte baisse de productivité. Dans les cas les plus sévères, et en l’absence de traitement, la mort survient en quelques semaines. L’impact socio-économique est estimé à 4,75 milliards de dollars de pertes annuelles, ce qui fait de ces maladies l’un des obstacles majeurs au développement de l’élevage en Afrique. Le contrôle de ces maladies se heurte à l’absence de vaccin, à des traitements dont les molécules sont peu nombreuses et contre lesquelles se développent de plus en plus de résistances de la part des parasites, et enfin à un diagnostic, moléculaire ou sérologique, dont la robustesse demande à être grandement améliorée. Les signes cliniques ne sont pas spécifiques, le diagnostic parasitologique est souvent peu sensible, et les méthodes moléculaires ne sont pas applicables sur le terrain. Les méthodes d’immunodiagnostic sous forme de tests de diagnostic rapide sont les seules adaptées au terrain, mais les rares tests existants sont très peu accessibles (disponibilité, prix), et manquent de spécificité et/ou de sensibilité. Ici, nous traiterons des limites et des avantages comparatifs des méthodes actuelles de diagnostic et proposerons de nouvelles pistes d’amélioration de ces dernières pour un meilleur contrôle de la maladie.

La trypanosomiase humaine africaine (THA) est l'une des maladies tropicales les plus négligées en Afrique subsaharienne. Avec moins de 1 000 cas déclarés en 2018 et 2019, elle a été ciblée comme maladie pouvant être éliminée d'ici 2030. Des réservoirs cryptiques de Trypanosoma brucei gambiense, tels que les animaux domestiques ou sauvages, apparaissent comme des déterminants pouvant compromettre cet objectif. Mieux comprendre l'impact d'un tel réservoir sur le maintien de la transmission de T. b gambiense nous permettra d'affiner les stratégies de lutte contre la THA. Dans cette revue, nous discutons des différents obstacles (techniques, biologiques, épidémiologiques) auxquels ont été confrontés les chercheurs qui se sont penchés sur cette problématique. Ces obstacles, qui perdurent aujourd'hui, expliquent en partie pourquoi, près d'un siècle après les premières études, l'impact du réservoir animal est toujours un sujet controversé.

International audience; Fighting trypanosomiasis with an anti-trypanosome vaccine is ineffective, the parasite being protected by a Variable Surface Glycoprotein (VSG) whose structure is modified at each peak of parasitaemia, which allows it to escape the host's immune defenses. However, the host immunization against an essential factor for the survival of the parasite or the expression of its pathogenicity could achieve the same objective. Here we present the results of mouse immunization against the Translationally Controlled Tumor Protein (TCTP), a protein present in the Trypanosoma brucei gambiense (Tbg) secretome, the parasite responsible for human trypanosomiasis. Mice immunization was followed by infection with Tbg parasites. The production of IgG, IgG1 and IgG2a begun after the second TCTP injection and was dose-dependant, the maximum level of anti-TCTP antibodies remained stable up to 4 days post-infection and then decreased. Regarding cytokines (IL-2, 4, 6, 10, INFγ, TNFα), the most striking result was their total suppression after immunization with the highest TCTP dose. Compared to the control group, the immunized mice displayed a reduced first peak of parasitaemia, a 100% increase in the time to onset of the second peak, and an increased time of mice survival. The effect of immunization was only transient but demonstrated the likely important role that TCTP plays in host-parasite interactions and that some key parasite proteins could reduce infection impact.