[Towards elimination of human African trypanosomiasis]. / Vers l'élimination de la maladie du sommeil.

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

Seroprevalence of brucellosis, Q fever and Rift Valley fever in domestic ruminants in Guinea in 2017-2019.

BACKGROUND: Brucellosis, Q fever and Rift Valley fever are considered as Neglected Zoonotic Diseases (NZDs) leading to socioeconomic losses in livestock globally, and particularly in developing countries of Africa where they are under-reported. In this study, we evaluated the seroprevalence of these 3 zoonotic diseases in domestic ruminants in Guinea from 2017 to 2019. A total of 1357 sera, sampled from 463 cattle, 408 goats and 486 sheep, were collected in 17 Guinean prefectures and analyzed by enzyme-linked immunosorbent assay (ELISA). RESULTS: Cattle was the species with highest seroprevalence (5 to 20-fold higher than in small ruminants) for the three diseases. The seroprevalence of brucellosis, mostly focused in Western Guinea, was 11.0% (51 of 463) in cattle, 0.4% (2 in 486) in sheep while no specific antibodies were found in goats. Q fever, widespread across the country, was the most frequently detected zoonosis with a mean seroprevalence of 20.5% (95 in 463), 4.4% (18 in 408) and 2.3% (11 in 486) in cattle, goats and sheep, respectively. The mean seroprevalence of RVF was 16.4% (76 in 463) in cattle, 1.0% (4 in 408) in goats and 1.0% (5 in 486) in sheep. Among the samples 19.3% were seropositive for at least one of the three NZDs, 2.5% showed specific antibodies against at least two pathogens and 4 cattle (0.8%) were seropositive for all three pathogens. In cattle, adults over 3-years old and females presented a higher antibody seroprevalence for the three diseases, in congruence with putative exposure risk. CONCLUSIONS: This study confirms the circulation of these three zoonotic pathogens in Guinea and highlights the need for implementing a syndromic surveillance of ruminant abortions by the Guinean veterinary authorities as well as for the screening of the human population at risk (veterinarians, breeders, slaughterers) in a One Health perspective.

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

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

Developing and quality testing of microsatellite loci for four species of Glossina.

Microsatellite loci still represent valuable resources for the study of the population biology of non-model organisms. Discovering or adapting new suitable microsatellite markers in species of interest still represents a useful task, especially so for non-model organisms as tsetse flies (genus Glossina), which remain a serious threat to the health of humans and animals in sub-Saharan Africa. In this paper, we present the development of new microsatellite loci for four species of Glossina: two from the Morsitans group, G. morsitans morsitans (Gmm) from Zimbabwe, G. pallidipes (Gpalli) from Tanzania; and the other two from the Palpalis group, G. fuscipes fuscipes (Gff) from Chad, and G. palpalis gambiensis (Gpg) from Guinea. We found frequent short allele dominance and null alleles. Stuttering could also be found and amended when possible. Cryptic species seemed to occur frequently in all taxa but Gff. This explains why it may be difficult finding ecumenical primers, which thus need adaptation according to each taxonomic and geographic context. Amplification problems occurred more often in published old markers, and Gmm and Gpg were the most affected (stronger heterozygote deficits). Trinucleotide markers displayed selection signature in some instances (Gmm). Combining old and new loci, for Gmm, eight loci can be safely used (with correction for null alleles); and five seem particularly promising; for Gpalli, only five to three loci worked well, depending on the clade, which means that the use of loci from other species (four morsitans loci seemed to work well), or other new primers will need to be used; for Gff, 14 loci behaved well, but with null alleles, seven of which worked very well; and for G. palpalis sl, only four loci, needing null allele and stuttering corrections seem to work well, and other loci from the literature are thus needed, including X-linked markers, five of which seem to work rather well (in females only), but new markers will probably be needed. Finally, the high proportion of X-linked markers (around 30%) was explained by the non-Y DNA quantity and chromosome structure of tsetse flies studied so far.

Sleeping sickness in the historical focus of forested Guinea: update using a geographically based method.

In 2017, 1447 new cases of Human African Trypanosomiasis (HAT) were reported, which reflects considerable progress towards the World Health Organisation's target of eliminating HAT as a public health problem by 2020. However, current epidemiological data are still lacking for a number of areas, including historical HAT foci. In order to update the HAT situation in the historical focus of forested Guinea, we implemented a geographically based methodology: Identification of Villages at Risk (IVR). The methodology is based on three sequential steps: Desk-based IVR (IVR-D), which selects villages at risk of HAT on the basis of HAT archives and geographical items; Field-based IVR (IVR-F), which consists in collecting additional epidemiological and geographical information in the field in villages at risk; and to be Medically surveyed IVR (IVR-M), a field data analysis through a Geographic Information System (GIS), to compile a list of the villages most at risk of HAT, suitable to guide active screening and passive surveillance. In an area of 2385 km2 with 1420,530 inhabitants distributed in 1884 settlements, 14 villages with a population of 11,236 inhabitants were identified as most at risk of HAT and selected for active screening. Although no HAT cases could be confirmed, subjects that had come into contact with Trypanosoma brucei gambiense were identified and two sentinel sites were chosen to implement passive surveillance. IVR, which could be applied to any gambiense areas where the situation needs to be clarified, could help to reach the objective of HAT elimination.

TITLE: Maladie du sommeil dans le foyer historique de Guinée forestière : actualisation grâce à une méthode géographique. ABSTRACT: En 2017, 1447 nouveaux cas de Trypanosomiase Humaine Africaine (THA) ont été rapportés, ce qui constitue une avancée importante pour atteindre l'objectif affiché par l'OMS d'éliminer la THA comme problème de santé publique d'ici 2020. Cependant, il existe toujours un manque d'informations épidémiologiques dans certaines zones, incluant des foyers historiques de THA. Afin d'actualiser la situation de la THA dans le foyer historique de Guinée forestière, nous avons appliqué une méthode géographique : l'Identification des Villages à Risque (IVR). La méthode s'effectue en 3 étapes successives : l'identification des villages à risque au bureau (IVR-D), qui sélectionne des villages à risque de THA sur la base d'archives de la THA et d'éléments géographiques ; l'identification des villages à risque sur le terrain (IVR-F), qui consiste à collecter des données épidémiologiques et géographiques des villages à risque sur le terrain ; l'identification des villages à risque à prospecter (IVR-M), une analyse des données de terrain, à travers un système d'information géographique, visant à dresser une liste de villages les plus à risque de THA, qui permettront d'orienter le dépistage actif et la surveillance passive. Dans une aire de 2385 km2, avec 1 420 530 habitants distribués dans 1884 peuplements, 14 villages d'une population de 11 236 habitants ont été identifiés comme les plus à risque de THA et sélectionnés pour un dépistage actif. Bien qu'aucun cas de THA n'ait été confirmé, des individus qui sont entrés en contact avec Trypanosoma brucei gambiense ont été identifiés et 2 sites sentinelles ont été retenus pour la surveillance passive. IVR, qui pourrait être appliquée dans n'importe quelle zone à gambiense où la situation nécessite d'être clarifiée, pourrait aider à atteindre l'objectif d'élimination de la THA.

Reducing Human-Tsetse Contact Significantly Enhances the Efficacy of Sleeping Sickness Active Screening Campaigns: A Promising Result in the Context of Elimination.

BACKGROUND: Control of gambiense sleeping sickness, a neglected tropical disease targeted for elimination by 2020, relies mainly on mass screening of populations at risk and treatment of cases. This strategy is however challenged by the existence of undetected reservoirs of parasites that contribute to the maintenance of transmission. In this study, performed in the Boffa disease focus of Guinea, we evaluated the value of adding vector control to medical surveys and measured its impact on disease burden. METHODS: The focus was divided into two parts (screen and treat in the western part; screen and treat plus vector control in the eastern part) separated by the Rio Pongo river. Population census and baseline entomological data were collected from the entire focus at the beginning of the study and insecticide impregnated targets were deployed on the eastern bank only. Medical surveys were performed in both areas in 2012 and 2013. FINDINGS: In the vector control area, there was an 80% decrease in tsetse density, resulting in a significant decrease of human tsetse contacts, and a decrease of disease prevalence (from 0.3% to 0.1%; p=0.01), and an almost nil incidence of new infections (<0.1%). In contrast, incidence was 10 times higher in the area without vector control (>1%, p<0.0001) with a disease prevalence increasing slightly (from 0.5 to 0.7%, p=0.34). INTERPRETATION: Combining medical and vector control was decisive in reducing T. b. gambiense transmission and in speeding up progress towards elimination. Similar strategies could be applied in other foci.

Baited-boats: an innovative way to control riverine tsetse, vectors of sleeping sickness in West Africa.

BACKGROUND: Human African Trypanosomiasis (HAT) is an important neglected tropical disease caused by Trypanosoma spp. parasites transmitted by species of tsetse fly (Glossina spp). The most important vectors of HAT are riverine tsetse and these can be controlled by attracting them to stationary baits such as insecticide-impregnated traps or targets deployed along the banks of rivers. However, the geographical nature of some riverine habitats, particularly mangroves but also extensive lake and river networks, makes deployment of baits difficult and limits their efficacy. It is known that tsetse are attracted by the movement of their hosts. Our hypothesis was that mounting a target on canoes typically used in Africa ('pirogues') would produce an effective means of attracting-and-killing riverine tsetse in extensive wetland habitats. METHODS: In Folonzo, southern Burkina Faso, studies were made of the numbers of tsetse attracted to a target (75 × 50 cm) of blue cloth and netting mounted on a pirogue moving along a river, versus the same target placed on the riverbank. The targets were covered with a sticky film which caught tsetse as they contacted the target. RESULTS: The pirogue-mounted target caught twice as many G. tachinoides and G. p. gambiensis, and 8 times more G. morsitans submorsitans than the stationary one (P < 0.001). CONCLUSION: Pirogues are common vehicle for navigating the rivers, lakes and swamps of West Africa. The demonstration that tsetse can be attracted to targets mounted on such boats suggests that pirogues might provide a cost-effective and convenient platform for deploying targets to control tsetse in the mangrove systems of West Africa where HAT persists. Further studies to assess the impact of pirogue-mounted targets on tsetse populations in HAT foci and the protective value of targets for pirogue passengers are recommended.

Epidemiology of sleeping sickness in Boffa (Guinea): where are the trypanosomes?

Human African Trypanosomiasis (HAT) in West Africa is a lethal, neglected disease caused by Trypanosoma brucei gambiense transmitted by the tsetse Glossina palpalis gambiensis. Although the littoral part of Guinea with its typical mangrove habitat is the most prevalent area in West Africa, very few data are available on the epidemiology of the disease in such biotopes. As part of a HAT elimination project in Guinea, we carried a cross-sectional study of the distribution and abundance of people, livestock, tsetse and trypanosomes in the focus of Boffa. An exhaustive census of the human population was done, together with spatial mapping of the area. Entomological data were collected, a human medical survey was organized together with a survey in domestic animals. In total, 45 HAT cases were detected out of 14445 people who attended the survey, these latter representing 50.9% of the total population. Potential additional carriers of T. b. gambiense were also identified by the trypanolysis test (14 human subjects and two domestic animals). No trypanosome pathogenic to animals were found, neither in the 874 tsetse dissected nor in the 300 domestic animals sampled. High densities of tsetse were found in places frequented by humans, such as pirogue jetties, narrow mangrove channels and watering points. The prevalence of T. b. gambiense in humans, combined to low attendance of the population at risk to medical surveys, and to an additional proportion of human and animal carriers of T. b. gambiense who are not treated, highlights the limits of strategies targeting HAT patients only. In order to stop T. b. gambiense transmission, vector control should be added to the current strategy of case detection and treatment. Such an integrated strategy will combine medical surveillance to find and treat cases, and vector control activities to protect people from the infective bites of tsetse.

Progress towards the eradication of Tsetse from the Loos islands, Guinea.

BACKGROUND: The tsetse fly Glossina palpalis gambiensis is the main vector of sleeping sickness (Human African Trypanosomiasis - HAT) in West Africa, in particular in littoral Guinea where this disease is currently very active. The Loos islands constitute a small archipelago some 5 km from mainland Guinea, where G. p. gambiensis is well known as a nuisance and potential disease vector by inhabitants of the three main islands, Fotoba, Room, and Kassa. The National Control Program against HAT of Guinea has decided to eradicate tsetse in Loos islands in order to sustainably protect humans and economic activities. After baseline data collection, tsetse control began on the islands in 2006. On each of the three islands a specific combination of control methods was implemented according to the entomological situation found. RESULTS: Starting densities before control operations were 10, 3 and 1 tsetse/trap/day in Kassa, Room and Fotoba respectively, but by July 2010, tsetse were no longer caught in any of the sentinel traps used for monitoring. The reduction rate was faster where several control methods were implemented as a combination (impregnated traps and targets ITT, selective groundspraying, epicutaneous insecticide treatment of pigs, and impregnated fences around pig pens), whereas it was slower when ITT were used as the only control method. CONCLUSIONS: This 100% suppression is a promising step in the eradication process, but G. p. gambiensis may still occur at very low, undetectable, densities on the archipelago. Next step will consist in assessing a 0.05 probability of tsetse absence to ascertain a provisional eradication status. Throughout these operations, a key factor has been the involvement of local teams and local communities without whom such results would be impossible to obtain. Work will continue thanks to the partners involved until total eradication of the tsetse on Loos islands can be declared.

The population structure of Glossina palpalis gambiensis from island and continental locations in Coastal Guinea.

BACKGROUND: We undertook a population genetics analysis of the tsetse fly Glossina palpalis gambiensis, a major vector of sleeping sickness in West Africa, using microsatellite and mitochondrial DNA markers. Our aims were to estimate effective population size and the degree of isolation between coastal sites on the mainland of Guinea and Loos Islands. The sampling locations encompassed Dubréka, the area with the highest Human African Trypanosomosis (HAT) prevalence in West Africa, mangrove and savannah sites on the mainland, and two islands, Fotoba and Kassa, within the Loos archipelago. These data are discussed with respect to the feasibility and sustainability of control strategies in those sites currently experiencing, or at risk of, sleeping sickness. PRINCIPAL FINDINGS: We found very low migration rates between sites except between those sampled around the Dubréka area that seems to contain a widely dispersed and panmictic population. In the Kassa island samples, various effective population size estimates all converged on surprisingly small values (10

Genetic and morphometric evidence for population isolation of Glossina palpalis gambiensis (Diptera: Glossinidae) on the Loos islands, Guinea.

Allele frequencies at four microsatellite loci, and morphometric features based on 11 wing landmarks, were compared among three populations of Glossina palpalis gambiensis (Diptera: Glossinidae) in Guinea. One population originated from the Loos islands separated from the capital Conakry by 5 km of sea, and the two others originated from the continental mangrove area close to Dubreka, these two groups being separated by approximately 30 km. Microsatellites and wing geometry data both converged to the idea of a separation of the Loos island population from those of the mangrove area. Although occasional contacts cannot be excluded, our results support the hypothesis of the Loos population of tsetse flies being a completely isolated population. This situation will favor a sequenced intervention against human African trypanosomosis and the possibility of an elimination of tsetse from this island.