Relations hôtes – parasites zoonotiques : diversité, aspects évolutifs et implications épidémiologiques. Le cas de la leptospirose dans les îles du sud-ouest de l’océan Indien

Leptospirosis is considered as the most widespread zoonosis worldwide but the incidence levels are higher in tropical regions and particularly on islands. The South-Western Indian Ocean islands are no exception and the disease is of major medical concern in several islands notably in Seychelles, displaying some of the highest human incidence ever reported. Based on available data, the human epidemiology appears contrasted in the region: on Mayotte, human cases result from the infection with four distinct Leptospira species whereas on Reunion Island or Seychelles, a single species causes the majority of clinical cases. The main objective of this thesis is to identify some of the drivers of this singular epidemiology. We first completed the information available on this human disease in the region by investigating the leptospirosis situation in the Union of the Comoros, a country where no autochthonous transmission has been reported so far. Our results indicate that Comorian populations are exposed to Leptospira, which are antigenically comparable to those detected in the neighbouring island of Mayotte. This finding suggests that the apparent absence of leptospirosis in some islands rather reflects a lack of surveillance. We then investigated the genetic diversity of Leptospira on distinct islands home to distinct endemic animal species that may shed distinct Leptospira lineages and thus at least in part explain the contrasted epidemiology of leptospirosis in the region. Specifically, we describe a high diversity of pathogenic Leptospira within Malagasy bats (Chiroptera) and further show that Leptospira diversity is not structured by geography. Instead, we show that these Leptospira display a strong specificity towards their hosts, which may result from different evolutionary processes including co-speciation and host switching. Using this tight host specificity, we investigated the leptospirosis epidemiology on Mayotte, where we show that the important bacterial diversity reported in clinical cases is due of the presence of several distinct animal species acting as reservoirs, some of which introduced from the neighbouring Madagascar. Altogether, results presented herein combined to data produced by our lab suggest that the epidemiology of leptospirosis in the SWOI results from distinct assemblages of cosmopolitan and autochthonous/endemic Leptospira. Keywords : Leptospirosis, Leptospira, Chiroptera, small mammals, hosts-parasites associations, MAT, MLST, co-phylogeny, Madagascar, Mayotte, Union of Comoros, South-Western Indian Ocean.La leptospirose est considérée comme la zoonose la plus répandue au monde mais les incidences sont les plus élevées dans les régions tropicales et en particulier sur les îles. Les îles du Sud-Ouest de l'Océan Indien ne dérogent pas à la règle puisque la maladie y représente un problème de santé humaine majeur sur plusieurs îles, notamment aux Seychelles qui enregistrent un des plus fort taux d'incidence humaine au monde. Sur la base des données disponibles, l'épidémiologie humaine apparait contrastée à l'échelle de la région : les cas cliniques sur Mayotte résultent d'infections par quatre espèces de leptospires distinctes alors qu'à La Réunion ou aux Seychelles, une seule espèce est à l'origine de la grande majorité des cas cliniques. L'objectif général de cette thèse est d'identifier certains des déterminants de cette épidémiologie singulière. Nous avons dans un premier temps complété les informations humaines en investiguant la leptospirose en Union des Comores, pays n'ayant jamais rapporté de transmission autochtone. Nos résultats indiquent que les populations humaines y sont exposées à des antigènes de leptospires comparables à ceux retrouvés sur l'île voisine de Mayotte. Ce résultat suggére que l'absence de leptospirose sur certaines îles est le résultat d'un déficit de surveillance. Nous avons ensuite caractérisé la diversité génétique des leptospires au sein de la faune de certaines îles, caractérisées par des niveaux d'endémisme élevés à même d'être en partie à l'origine de cette épidémiologie contrastée. Nous décrivons d'une part une importante diversité des leptospires pathogènes chez les chauves-souris (Chiroptères) malgaches. Nous montrons d'autre part que cette diversité de leptospires n'est pas structurée géographiquement mais présente au contraire une importante spécificité d'hôte, résultant de différents processus évolutifs incluant co-spéciation et host-switch. Nous avons exploité cette spécificité d'hôte pour éclairer l'épidémiologie de la leptospirose à Mayotte, où nous montrons que l'importante diversité bactérienne impliquée dans les cas cliniques résulte de la présence de nombreux réservoirs, dont certains originaires de Madagascar. Ainsi, il apparaît que l'épidémiologie humaine de la leptospirose dans le SOOI est le reflet d'assemblages distincts de leptospires cosmopolites et autochtones/endémiques maintenus et excrétés par des réservoirs animaux particuliers

Human leptospirosis on Reunion Island, Indian Ocean: are rodents the (only) ones to blame?

Background: Although leptospirosis is a zoonosis of major concern on tropical islands, the molecular epidemiology of the disease aiming at linking human cases to specific animal reservoirs has been rarely explored within these peculiar ecosystems. Methodology/Principal Findings: Five species of wild small mammals (n = 995) as well as domestic animals (n = 101) were screened for Leptospira infection on Reunion Island; positive samples were subsequently genotyped and compared to Leptospira from clinical cases diagnosed in 2012–2013 (n = 66), using MLST analysis. We identified two pathogenic species in human cases, namely Leptospira interrogans and Leptospira borgpetersenii. Leptospira interrogans was by far dominant both in clinical samples (96.6%) and in infected animal samples (95.8%), with Rattus spp and dogs being its exclusive carriers. The genetic diversity within L. interrogans was apparently limited to two sequence types (STs): ST02, identified among most clinical samples and in all rats with complete MLST, and ST34, identified in six humans, but not in rats. Noteworthy, L. interrogans detected in two stray dogs partially matched with ST02 and ST34. Leptospira borgpetersenii was identified in two clinical samples only (3.4%), as well as in cows and mice; four haplotypes were identified, of which two seemingly identical in clinical and animal samples. Leptospira borgpetersenii haplotypes detected in human cases were clearly distinct from the lineage detected so far in the endemic bat species Mormopterus francoismoutoui, thus excluding a role for this volant mammal in the local human epidemiology of the disease. Conclusions/Significance: Our data confirm rats as a major reservoir of Leptospira on Reunion Island, but also pinpoint a possible role of dogs, cows and mice in the local epidemiology of human leptospirosis. This study shows that a comprehensive molecular characterization of pathogenic Leptospira in both clinical and animal samples helps to gaining insight into leptospirosis epidemiology within a specific environmental setting

Malagasy bats shelter a considerable genetic diversity of pathogenic Leptospira suggesting notable host-specificity patterns

Pathogenic Leptospira are the causative agents of leptospirosis, a disease of global concern with major impact in tropical regions. Despite the importance of this zoonosis for human health, the evolutionary and ecological drivers shaping bacterial communities in host reservoirs remain poorly investigated. Here, we describe Leptospira communities hosted by Malagasy bats, composed of mostly endemic species, in order to characterize host-pathogen associations and investigate their evolutionary histories. We screened 947 individual bats (representing 31 species, 18 genera and seven families) for Leptospira infection and subsequently genotyped positive samples using three different bacterial loci. Molecular identification showed that these Leptospira are notably diverse and include several distinct lineages mostly belonging to Leptospira borgpetersenii and L. kirschneri. The exploration of the most probable host-pathogen evolutionary scenarios suggests that bacterial genetic diversity results from a combination of events related to the ecology and the evolutionary history of their hosts. Importantly, based on the data set presented herein, the notable host-specificity we have uncovered, together with a lack of geographical structuration of bacterial genetic diversity, indicates that the Leptospira community at a given site depends on the co-occurring bat species assemblage. The implications of such tight host-specificity on the epidemiology of leptospirosis are discussed.http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1574-69412017-06-30hb2016Microbiology and Plant Patholog

Identification of Tenrec ecaudatus, a wild mammal Introduced to Mayotte Island, as a reservoir of the newly identified human pathogenic Leptospira mayottensis

Leptospirosis is a bacterial zoonosis of major concern on tropical islands. Human populations on western Indian Ocean islands are strongly affected by the disease although each archipelago shows contrasting epidemiology. For instance, Mayotte, part of the Comoros Archipelago, differs from the other neighbouring islands by a high diversity of Leptospira species infecting humans that includes Leptospira mayottensis, a species thought to be unique to this island. Using bacterial culture, molecular detection and typing, the present study explored the wild and domestic local mammalian fauna for renal carriage of leptospires and addressed the genetic relationships of the infecting strains with local isolates obtained from acute human cases and with Leptospira strains hosted by mammal species endemic to nearby Madagascar. Tenrec (Tenrec ecaudatus, Family Tenrecidae), a terrestrial mammal introduced from Madagascar, is identified as a reservoir of L. mayottensis. All isolated L. mayottensis sequence types form a monophyletic clade that includes Leptospira strains infecting humans and tenrecs on Mayotte, as well as two other Malagasy endemic tenrecid species of the genus Microgale. The lower diversity of L. mayottensis in tenrecs from Mayotte, compared to that occurring in Madagascar, suggests that L. mayottensis has indeed a Malagasy origin. This study also showed that introduced rats (Rattus rattus) and dogs are probably the main reservoirs of Leptospira borgpetersenii and Leptospira kirschneri, both bacteria being prevalent in local clinical cases. Data emphasize the epidemiological link between the two neighbouring islands and the role of introduced small mammals in shaping the local epidemiology of leptospirosis.S1 Fig. Distribution of small mammals sampling sites on Mayotte. Numbers correspond to the 18 sampling sites where Rattus rattus and Tenrec ecaudatus (white) and bats (orange) were trapped. Map was created with QGIS 2.8.1 (QGIS Development Team, 2016, QGIS Geographic Information System, Open Source Geospatial Foundation Project). Photography of Mayotte: BD Topo IGN, 2008.S2 Fig. The figures A and B display Bayesian phylogenetic trees of pathogenic Leptospira from Mayotte (blue) and Madagascar (green) based on 452 bp (57 taxa, HKY+I+G) (A) and 245 bp (64 taxa, K80+I) (B) of the rrs2 gene. At the nodes, the black numbers indicate posterior probabilities. The sequences highlighted in grey (A) and red (B) represent PCR positive samples for which only the rrs2 gene was obtained. Strain numbers of cultures produced herein are indicated in parentheses, “K” and “U” designating sequences obtained from kidney or urine, respectively. Specimen system: MDI and MAY = CRVOI specimen catalogue during field trips to Mayotte; all Canis lupus familiaris were sampled during field trips to Mayotte; FMNH = Field Museum of Natural History, Chicago; UADBA = Université d’Antananarivo, Département de Biologie Animale, Madagascar; for the other bacterial sequences from Homo sapiens and Microgale spp. see Bourhy et al. 2012 [15]and Dietrich et al. 2014 [4]. Museum numbers for Microgale spp.: 575 = UADBA 30869; 588 = UADBA 30289; 590 = UADBA 30291; 1335 = UADBA 32122; 1453 = UADBA 32125; 1467 = UADBA 32101.ERDF-POCT Réunion, LeptOI (#32913), ParamyxOI (#33857); Centre National de la Recherche Scientifique - Institut Ecologie et Environnement (ECOSAN BatMan) and Agence Régionale de la Santé Ocean Indien.http://www.plosntds.orgam2016Medical Virolog

Biogeography of Leptospira in wild animal communities inhabiting the insular ecosystem of the western Indian Ocean islands and neighboring Africa

Understanding the processes driving parasite assemblages is particularly important in the context of zoonotic infectious diseases. Leptospirosis is a widespread zoonotic bacterial infection caused by pathogenic species of the genus Leptospira. Despite a wide range of animal hosts, information is still lacking on the factors shaping Leptospira diversity in wild animal communities, especially in regions, such as tropical insular ecosystems, with high host species richness and complex biogeographical patterns. Using a large dataset (34 mammal species) and a multilocus approach at a regional scale, we analyzed the role of both host species diversity and geography in Leptospira genetic diversity in terrestrial small mammals (rodents, tenrecs, and shrews) and bats from 10 different islands/countries in the western Indian Ocean (WIO) and neighboring Africa. At least four Leptospira spp. (L. interrogans, L. borgpetersenii, L. kirschneri, and L. mayottensis) and several yet-unidentified genetic clades contributed to a remarkable regional Leptospira diversity, which was generally related to the local occurrence of the host species rather than the geography. In addition, the genetic structure patterns varied between Leptospira spp., suggesting different evolutionary histories in the region, which might reflect both in situ diversification of native mammals (for L. borgpetersenii) and the more recent introduction of non-native host species (for L. interrogans). Our data also suggested that host shifts occurred between bats and rodents, but further investigations are needed to determine how host ecology may influence these events

Zika vector competence data reveals risks of outbreaks: the contribution of the European ZIKAlliance project

First identified in 1947, Zika virus took roughly 70 years to cause a pandemic unusually associated with virus-induced brain damage in newborns. Zika virus is transmitted by mosquitoes, mainly Aedes aegypti, and secondarily, Aedes albopictus, both colonizing a large strip encompassing tropical and temperate regions. As part of the international project ZIKAlliance initiated in 2016, 50 mosquito populations from six species collected in 12 countries were experimentally infected with different Zika viruses. Here, we show that Ae. aegypti is mainly responsible for Zika virus transmission having the highest susceptibility to viral infections. Other species play a secondary role in transmission while Culex mosquitoes are largely non-susceptible. Zika strain is expected to significantly modulate transmission efficiency with African strains being more likely to cause an outbreak. As the distribution of Ae. aegypti will doubtless expand with climate change and without new marketed vaccines, all the ingredients are in place to relive a new pandemic of Zika

Zika vector competence data reveals risks of outbreaks: the contribution of the European ZIKAlliance project

First identified in 1947, Zika virus took roughly 70 years to cause a pandemic unusually associated with virus-induced brain damage in newborns. Zika virus is transmitted by mosquitoes, mainly Aedes aegypti, and secondarily, Aedes albopictus, both colonizing a large strip encompassing tropical and temperate regions. As part of the international project ZIKAlliance initiated in 2016, 50 mosquito populations from six species collected in 12 countries were experimentally infected with different Zika viruses. Here, we show that Ae. aegypti is mainly responsible for Zika virus transmission having the highest susceptibility to viral infections. Other species play a secondary role in transmission while Culex mosquitoes are largely non-susceptible. Zika strain is expected to significantly modulate transmission efficiency with African strains being more likely to cause an outbreak. As the distribution of Ae. aegypti will doubtless expand with climate change and without new marketed vaccines, all the ingredients are in place to relive a new pandemic of Zika.info:eu-repo/semantics/publishedVersio

No English title available

La leptospirose est considérée comme la zoonose la plus répandue au monde mais les incidences sont les plus élevées dans les régions tropicales et en particulier sur les îles. Les îles du Sud-Ouest de l'Océan Indien ne dérogent pas à la règle puisque la maladie y représente un problème de santé humaine majeur sur plusieurs îles, notamment aux Seychelles qui enregistrent un des plus fort taux d'incidence humaine au monde. Sur la base des données disponibles, l'épidémiologie humaine apparait contrastée à l'échelle de la région : les cas cliniques sur Mayotte résultent d'infections par quatre espèces de leptospires distinctes alors qu'à La Réunion ou aux Seychelles, une seule espèce est à l'origine de la grande majorité des cas cliniques. L'objectif général de cette thèse est d'identifier certains des déterminants de cette épidémiologie singulière. Nous avons dans un premier temps complété les informations humaines en investiguant la leptospirose en Union des Comores, pays n'ayant jamais rapporté de transmission autochtone. Nos résultats indiquent que les populations humaines y sont exposées à des antigènes de leptospires comparables à ceux retrouvés sur l'île voisine de Mayotte. Ce résultat suggére que l'absence de leptospirose sur certaines îles est le résultat d'un déficit de surveillance. Nous avons ensuite caractérisé la diversité génétique des leptospires au sein de la faune de certaines îles, caractérisées par des niveaux d'endémisme élevés à même d'être en partie à l'origine de cette épidémiologie contrastée. Nous décrivons d'une part une importante diversité des leptospires pathogènes chez les chauves-souris (Chiroptères) malgaches. Nous montrons d'autre part que cette diversité de leptospires n'est pas structurée géographiquement mais présente au contraire une importante spécificité d'hôte, résultant de différents processus évolutifs incluant co-spéciation et host-switch. Nous avons exploité cette spécificité d'hôte pour éclairer l'épidémiologie de la leptospirose à Mayotte, où nous montrons que l'importante diversité bactérienne impliquée dans les cas cliniques résulte de la présence de nombreux réservoirs, dont certains originaires de Madagascar. Ainsi, il apparaît que l'épidémiologie humaine de la leptospirose dans le SOOI est le reflet d'assemblages distincts de leptospires cosmopolites et autochtones/endémiques maintenus et excrétés par des réservoirs animaux particuliers.Leptospirosis is considered as the most widespread zoonosis worldwide but the incidence levels are higher in tropical regions and particularly on islands. The South-Western Indian Ocean islands are no exception and the disease is of major medical concern in several islands notably in Seychelles, displaying some of the highest human incidence ever reported. Based on available data, the human epidemiology appears contrasted in the region: on Mayotte, human cases result from the infection with four distinct Leptospira species whereas on Reunion Island or Seychelles, a single species causes the majority of clinical cases. The main objective of this thesis is to identify some of the drivers of this singular epidemiology. We first completed the information available on this human disease in the region by investigating the leptospirosis situation in the Union of the Comoros, a country where no autochthonous transmission has been reported so far. Our results indicate that Comorian populations are exposed to Leptospira, which are antigenically comparable to those detected in the neighbouring island of Mayotte. This finding suggests that the apparent absence of leptospirosis in some islands rather reflects a lack of surveillance. We then investigated the genetic diversity of Leptospira on distinct islands home to distinct endemic animal species that may shed distinct Leptospira lineages and thus at least in part explain the contrasted epidemiology of leptospirosis in the region. Specifically, we describe a high diversity of pathogenic Leptospira within Malagasy bats (Chiroptera) and further show that Leptospira diversity is not structured by geography. Instead, we show that these Leptospira display a strong specificity towards their hosts, which may result from different evolutionary processes including co-speciation and host switching. Using this tight host specificity, we investigated the leptospirosis epidemiology on Mayotte, where we show that the important bacterial diversity reported in clinical cases is due of the presence of several distinct animal species acting as reservoirs, some of which introduced from the neighbouring Madagascar. Altogether, results presented herein combined to data produced by our lab suggest that the epidemiology of leptospirosis in the SWOI results from distinct assemblages of cosmopolitan and autochthonous/endemic Leptospira. Keywords : Leptospirosis, Leptospira, Chiroptera, small mammals, hosts-parasites associations, MAT, MLST, co-phylogeny, Madagascar, Mayotte, Union of Comoros, South-Western Indian Ocean