Seoul Orthohantavirus in Wild Black Rats, Senegal, 2012-2013.

Hantaviruses cause hemorrhagic fever in humans worldwide. However, few hantavirus surveillance campaigns occur in Africa. We detected Seoul orthohantavirus in black rats in Senegal, although we did not find serologic evidence of this disease in humans. These findings highlight the need for increased surveillance of hantaviruses in this region.

Host resistance, population structure and the long-term persistence of bubonic plague: contributions of a modelling approach in the Malagasy focus.

Although bubonic plague is an endemic zoonosis in many countries around the world, the factors responsible for the persistence of this highly virulent disease remain poorly known. Classically, the endemic persistence of plague is suspected to be due to the coexistence of plague resistant and plague susceptible rodents in natural foci, and/or to a metapopulation structure of reservoirs. Here, we test separately the effect of each of these factors on the long-term persistence of plague. We analyse the dynamics and equilibria of a model of plague propagation, consistent with plague ecology in Madagascar, a major focus where this disease is endemic since the 1920s in central highlands. By combining deterministic and stochastic analyses of this model, and including sensitivity analyses, we show that (i) endemicity is favoured by intermediate host population sizes, (ii) in large host populations, the presence of resistant rats is sufficient to explain long-term persistence of plague, and (iii) the metapopulation structure of susceptible host populations alone can also account for plague endemicity, thanks to both subdivision and the subsequent reduction in the size of subpopulations, and extinction-recolonization dynamics of the disease. In the light of these results, we suggest scenarios to explain the localized presence of plague in Madagascar.

Invasion genetics of the introduced black rat (Rattus rattus) in Senegal, West Africa.

An understanding of the evolutionary history and dynamics of invasive species is required for the construction of predictive models of future spread and the design of biological management measures. The black rat (Rattus rattus) is a major vertebrate invader with a worldwide distribution. Despite the severe ecological, economic and health impacts of this species, its evolutionary history has been little studied. We carried out extensive specimen sampling in Senegal, West Africa, and used microsatellite markers to describe the pattern and processes of invasion in this large continental area. The genetic data obtained were combined with historical knowledge concerning the presence of this species in Senegal. Data were analysed by a combination of Bayesian clustering and approximate Bayesian computation methods. The invasion pathways closely paralleled the history of human trade routes in Senegal. In several places, we detected the occurrence of multiple introductions from genetically different sources. Long-distance migration between towns and villages was also observed. Our findings suggest that genetic bottlenecks and admixture have played a major role in shaping the genetics of invasive black rats. These two processes may generate genetic novelty and favour rapid evolution along the invasion pathways.

Sharing space between native and invasive small mammals: Study of commensal communities in Senegal.

Urbanization processes are taking place at a very high rate, especially in Africa. At the same time, a number of small mammal species, be they native or invasive, take advantage of human-induced habitat modifications. They represent commensal communities of organisms that cause a number of inconveniences to humans, including potential reservoirs of zoonotic diseases. We studied via live trapping and habitat characterization such commensal small mammal communities in small villages to large cities of Senegal, to try to understand how the species share this particular space. Seven major species were recorded, with exotic invasive house mice (Mus musculus) and black rats (Rattus rattus) dominating in numbers. The shrew Crocidura olivieri appeared as the main and more widespread native species, while native rodent species (Mastomys natalensis, M. erythroleucus, Arvicanthis niloticus and Praomys daltoni) were less abundant and/or more localized. Habitat preferences, compared between species in terms of room types and characteristics, showed differences among house mice, black rats and M. natalensis especially. Niche (habitat component) breadth and overlap were measured. Among invasive species, the house mouse showed a larger niche breadth than the black rat, and overall, all species displayed high overlap values. Co-occurrence patterns were studied at the global and local scales. The latter show cases of aggregation (between the black rat and native species, for instance) and of segregation (as between the house mouse and the black rat in Tambacounda, or between the black rat and M. natalensis in Kédougou). While updating information on commensal small mammal distribution in Senegal, a country submitted to a dynamic process of invasion by the black rat and the house mouse, we bring original information on how species occupy and share the commensal space, and make predictions on the evolution of these communities in a period of ever-accelerating global changes.

Commensal small mammal trapping data in Southern Senegal, 2012-2015: where invasive species meet native ones.

Describing patterns and testing hypotheses on processes driving biological invasions represent major issues in ecology. Addressing these questions requires building adequate data sets, i.e., covering areas and spanning periods adapted to the invasion processes studied. Rodents include major invasive species, among which the black rat Rattus rattus and the domestic mouse Mus musculus have nearly colonized the entire world, from their native Asian range. To do so, they have benefitted from their ability to cope with human-modified environments and to live in the immediate vicinity of Man, who served as a vector of their dispersal between regions and continents. In Senegal, both R. rattus and M. musculus, initially introduced by early West European colonizers some centuries ago, are currently expanding thanks to road traffic and infrastructure development and rampant urbanization that concerns even remote regions of the country. As part of projects aimed at studying (1) the role of invasive black rat populations in the emergence of zoonotic diseases in southeastern Senegal, and (2) the evolutionary consequences of parasites in R. rattus and M. musculus invasions in Senegal, we conducted a series of field campaigns throughout the southern half of the country, between May 2012 and September 2015. The objectives were to catch commensal small mammals using standard trapping procedures, identify them using morphological or molecular tools, and take samples from them upon autopsy, to look for zoonotic parasites and pathogens. Along with data on individual specimens, information on microhabitats was gathered at each trap position. This resulted in the constitution of a data set of more than 13,000 trapnights, which allowed the capture of more than 3,100 small mammals, all characterized by a series of associated biological, geographical, and environmental data. The small mammals concerned are mainly rodents (10 species), shrews, and hedgehogs. The two invasive rodent species were the most numerous, exceeding in numbers all the other species pooled. This data set makes it possible to study coarse to fine-scaled distribution of species of this commensal community in southern Senegal, as well as the possible determinants of this distribution in terms of habitat preferences and/or interspecific interactions. This data set can be freely used for non-commercial purposes and is licensed under a Creative Commons Attribution 4.0 International License.

Phylogeography of a Sahelian rodent species Mastomys huberti: a Plio-Pleistocene story of emergence and colonization of humid habitats.

The multimammate rat Mastomys huberti is a Sahelian species restricted to West Africa. Throughout its distribution area, the species is associated with humid habitats, flood plains and ponds, which make its current distribution highly fragmented. Knowing that humid and dry climatic phases regularly alternated along the Quaternary in West Africa, it can be postulated that the evolutionary history of the species and its genetic variation largely reflect these climatic oscillations. We used mitochondrial cytochrome b sequences to investigate the phylogenetic relationships of M. huberti populations across the totality of the species' geographical range (Mali, Senegal, Guinea and Mauritania). We found that cytochrome b sequence variation is partitioned into four divergent clades (mean Kimura 2-parameter genetic distances varying from 0.57 to 3.08%) corresponding to distinct geographical regions. We dated the separation events of these clades between 0.93 and 0.17 million years ago, suggesting that M. huberti history was strongly influenced by the Quaternary climatic variations and related hydrographic network changes. Relationships between lineages and the partitioning of genetic diversity suggest the occurrence of two refuges along the Atlantic coast during arid periods. Moreover, the species' current range results from a stepwise colonization from west to east. M. huberti colonized recently the Inner Delta of Niger River in Mali, probably during a humid episode some 0.6 million years ago. Demographically stable and highly diversified populations were found in South Senegal and Guinea while populations in North Senegal and in Mali experienced low numbers followed by a demographic expansion during the African Humid Period (c. 14 800-5500 bp). During the last arid period (c. 23 000-18 000 years ago), Malian populations found refuge in the northern parts of the Inner Delta of the Niger River, then expended to the southern parts of the delta and along the course of the Niger River downstream Tombouctou. More recently, M. huberti would have rapidly expanded into irrigated areas along the Senegal River and along the Canal du Sahel, Mali, reflecting the invasive and the pest character of this species.

The Asian house shrew Suncus murinus as a reservoir and source of human outbreaks of plague in Madagascar.

Identifying key reservoirs for zoonoses is crucial for understanding variation in incidence. Plague re-emerged in Mahajanga, Madagascar in the 1990s but there has been no confirmed case since 1999. Here we combine ecological and genetic data, from during and after the epidemics, with experimental infections to examine the role of the shrew Suncus murinus in the plague epidemiological cycle. The predominance of S. murinus captures during the epidemics, their carriage of the flea vector and their infection with Yersinia pestis suggest they played an important role in the maintenance and transmission of plague. S. murinus exhibit a high but variable resistance to experimental Y. pestis infections, providing evidence of its ability to act as a maintenance host. Genetic analyses of the strains isolated from various hosts were consistent with two partially-linked transmission cycles, with plague persisting within the S. murinus population, occasionally spilling over into the rat and human populations. The recent isolation from a rat in Mahajanga of a Y. pestis strain genetically close to shrew strains obtained during the epidemics reinforces this hypothesis and suggests circulation of plague continues. The observed decline in S. murinus and Xenopsylla cheopis since the epidemics appears to have decreased the frequency of spillover events to the more susceptible rats, which act as a source of infection for humans. Although this may explain the lack of confirmed human cases in recent years, the current circulation of plague within the city highlights the continuing health threat.

From Human Geography to Biological Invasions: The Black Rat Distribution in the Changing Southeastern of Senegal.

In the contemporary context of zoonosis emergence and spread, invasive species are a major issue since they represent potential pathogen hosts. Even though many progresses have been done to understand and predict spatial patterns of invasive species, the challenge to identify the underlying determinants of their distribution remains a central question in invasion biology. This is particularly exacerbated in the case of commensal species that strictly depend on humankind for dispersal and perennial establishment of new populations. The distribution of these species is predicted to be influenced by dispersal opportunities and conditions acting on establishment and proliferation, such as environmental characteristics, including spatio-temporal components of the human societies. We propose to contribute to the understanding of the recent spread of a major invasive rodent species, the black rat (Rattus rattus), in the changing southeastern of Senegal. We address the factors that promote the dispersal and distribution of this invasive rodent from the perspective of human geography. We first describe characteristics of human settlements in terms of social and spatial organization of human societies (i.e. economic activities, commercial and agricultural networks, roads connectivity). We then explore the relationship between these characteristics and the distribution of this invasive rodent. Finally we propose that historical and contemporary dynamics of human societies have contributed to the risk of invasion of the black rat. We argue that the diffusion processes of invasive species cannot be considered as a result of the spatial structure only (i.e. connectivity and distance), but as a part of the human territory that includes the social and spatial organization. Results suggest that the distribution of invasive rodents partly results from the contemporary and inherited human socio-spatial systems, beyond the existence of suitable ecological conditions that are classically investigated by biologists.

Borrelia infection in small mammals in West Africa and its relationship with tick occurrence inside burrows.

Tick-borne relapsing fever (TBRF) is a zoonotic disease caused by several Borrelia species transmitted to humans by Ornithodoros tick vectors. In West Africa, Borrelia crocidurae is a common cause of disease in many rural populations. Small mammals act as reservoirs of infection. We report here the results of surveys that investigated the occurrence of B. crocidurae infection in rodents and insectivores from eight countries of West and Central Africa. Animals were identified at the species level and tested for Borrelia either by examination of thick blood film, intra-peritoneal inoculation of blood or brain tissues into laboratory mice, or by molecular techniques. A total of 4358 small mammals belonging to 38 species and 7 families were collected, including 3225 specimens collected in areas where the occurrence of Ornithodoros sonrai tick in rodent burrows was documented, and 1133 in areas where this tick was absent. In areas with O. sonrai, Borrelia infection was demonstrated in 287 of 3109 (9.2%) small mammals tested, and none was documented in 1004 animals tested from other areas. There was no relationship between the occurrence of Rhipicephalus, Hyaloma and Argas ticks in burrows and the distribution of Borrelia infection in small mammals. The 287 specimens infected by Borrelia belonged to 15 rodent and shrew species, including three Saharo-Sahelian species - Gerbillus gerbillus, Gerbillus occiduus and Gerbillus tarabuli - identified as reservoirs for TBRF with a distribution restricted to this area. In Sudan and Sudano-Sahelian areas, Arvicanthis niloticus, Mastomys erythroleucus and Mastomys huberti were the main reservoir of infection. Although most small mammals species collected had a large distribution in West and Central Africa, the fact that only animals collected in areas with O. sonrai were found infected suggest that this tick is the only vector of TBRF in rodents and insectivores in this part of Africa.

Understanding the persistence of plague foci in Madagascar.

Plague, a zoonosis caused by Yersinia pestis, is still found in Africa, Asia, and the Americas. Madagascar reports almost one third of the cases worldwide. Y. pestis can be encountered in three very different types of foci: urban, rural, and sylvatic. Flea vector and wild rodent host population dynamics are tightly correlated with modulation of climatic conditions, an association that could be crucial for both the maintenance of foci and human plague epidemics. The black rat Rattus rattus, the main host of Y. pestis in Madagascar, is found to exhibit high resistance to plague in endemic areas, opposing the concept of high mortality rates among rats exposed to the infection. Also, endemic fleas could play an essential role in maintenance of the foci. This review discusses recent advances in the understanding of the role of these factors as well as human behavior in the persistence of plague in Madagascar.

Mitochondrial and nuclear genes-based phylogeography of Arvicanthis niloticus (Murinae) and sub-Saharan open habitats pleistocene history.

A phylogeographic study was conducted on the Nile grass rat, Arvicanthis niloticus, a rodent species that is tightly associated with open grasslands from the Sudano-Sahelian regions. Using one mitochondrial (cytochrome b) and one nuclear (intron 7 of Beta Fibrinogen) gene, robust patterns were retrieved that clearly show that (i) the species originated in East Africa concomitantly with expanding grasslands some 2 Ma, and (ii) four parapatric and genetically well-defined lineages differentiated essentially from East to West following Pleistocene bioclimatic cycles. This strongly points towards allopatric genetic divergence within savannah refuges during humid episodes, then dispersal during arid ones; secondary contact zones would have then stabilized around geographic barriers, namely, Niger River and Lake Chad basins. Our results pertinently add to those obtained for several other African rodent as well as non-rodent species that inhabit forests, humid zones, savannahs and deserts, all studies that now allow one to depict a more comprehensive picture of the Pleistocene history of the continent south of the Sahara. In particular, although their precise location remains to be determined, at least three Pleistocene refuges are identified within the West and Central African savannah biome.

Plague circulation and population genetics of the reservoir Rattus rattus: the influence of topographic relief on the distribution of the disease within the Madagascan focus.

BACKGROUND: Landscape may affect the distribution of infectious diseases by influencing the population density and dispersal of hosts and vectors. Plague (Yersinia pestis infection) is a highly virulent, re-emerging disease, the ecology of which has been scarcely studied in Africa. Human seroprevalence data for the major plague focus of Madagascar suggest that plague spreads heterogeneously across the landscape as a function of the relief. Plague is primarily a disease of rodents. We therefore investigated the relationship between disease distribution and the population genetic structure of the black rat, Rattus rattus, the main reservoir of plague in Madagascar. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a comparative study of plague seroprevalence and genetic structure (15 microsatellite markers) in rat populations from four geographic areas differing in topology, each covering about 150-200 km(2) within the Madagascan plague focus. The seroprevalence levels in the rat populations mimicked those previously reported for humans. As expected, rat populations clearly displayed a more marked genetic structure with increasing relief. However, the relationship between seroprevalence data and genetic structure differs between areas, suggesting that plague distribution is not related everywhere to the effective dispersal of rats. CONCLUSIONS/SIGNIFICANCE: Genetic diversity estimates suggested that plague epizootics had only a weak impact on rat population sizes. In the highlands of Madagascar, plague dissemination cannot be accounted for solely by the effective dispersal of the reservoir. Human social activities may also be involved in spreading the disease in rat and human populations.

The epidemiology and geographic distribution of relapsing fever borreliosis in West and North Africa, with a review of the Ornithodoros erraticus complex (Acari: Ixodida).

BACKGROUND: Relapsing fever is the most frequent bacterial disease in Africa. Four main vector / pathogen complexes are classically recognized, with the louse Pediculus humanus acting as vector for B. recurrentis and the soft ticks Ornithodoros sonrai, O. erraticus and O. moubata acting as vectors for Borrelia crocidurae, B. hispanica and B. duttonii, respectively. Our aim was to investigate the epidemiology of the disease in West, North and Central Africa. METHODS AND FINDINGS: From 2002 to 2012, we conducted field surveys in 17 African countries and in Spain. We investigated the occurrence of Ornithodoros ticks in rodent burrows in 282 study sites. We collected 1,629 small mammals that may act as reservoir for Borrelia infections. Using molecular methods we studied genetic diversity among Ornithodoros ticks and Borrelia infections in ticks and small mammals. Of 9,870 burrows investigated, 1,196 (12.1%) were inhabited by Ornithodoros ticks. In West Africa, the southern and eastern limits of the vectors and Borrelia infections in ticks and small mammals were 13°N and 01°E, respectively. Molecular studies revealed the occurrence of nine different Ornithodoros species, including five species new for science, with six of them harboring Borrelia infections. Only B. crocidurae was found in West Africa and three Borrelia species were identified in North Africa: B. crocidurae, B. hispanica, and B. merionesi. CONCLUSIONS: Borrelia Spirochetes responsible for relapsing fever in humans are highly prevalent both in Ornithodoros ticks and small mammals in North and West Africa but Ornithodoros ticks seem absent south of 13°N and small mammals are not infected in these regions. The number of Ornithodoros species acting as vector of relapsing fever is much higher than previously known.

Contrasted patterns of selection on MHC-linked microsatellites in natural populations of the Malagasy plague reservoir.

Plague (Yersinia pestis infection) is a highly virulent rodent disease that persists in many natural ecosystems. The black rat (Rattus rattus) is the main host involved in the plague focus of the central highlands of Madagascar. Black rat populations from this area are highly resistant to plague, whereas those from areas in which the disease is absent (low altitude zones of Madagascar) are susceptible. Various lines of evidence suggest a role for the Major Histocompatibility Complex (MHC) in plague resistance. We therefore used the MHC region as a candidate for detecting signatures of plague-mediated selection in Malagasy black rats, by comparing population genetic structures for five MHC-linked microsatellites and neutral markers in two sampling designs. We first compared four pairs of populations, each pair including one population from the plague focus and one from the disease-free zone. Plague-mediated selection was expected to result in greater genetic differentiation between the two zones than expected under neutrality and this was observed for one MHC-class I-linked locus (D20Img2). For this marker as well as for four other MHC-linked loci, a geographic pattern of genetic structure was found at local scale within the plague focus. This pattern would be expected if plague selection pressures were spatially variable. Finally, another MHC-class I-linked locus (D20Rat21) showed evidences of balancing selection, but it seems more likely that this selection would be related to unknown pathogens more widely distributed in Madagascar than plague.

Rodent host cell/Lassa virus interactions: evolution and expression of α-Dystroglycan, LARGE-1 and LARGE-2 genes, with special emphasis on the Mastomys genus.

Arenaviruses are usually rodent-borne viruses that constitute a major threat for human health. Among them, Lassa Fever Virus (LFV) occurs in Western Africa where it infects hundreds of thousands of people annually. According to the most recent surveys, LFV is hosted by one of the multimammate rats, Mastomys natalensis, but has never been detected in its sibling and sometimes sympatric species Mastomys erythroleucus. This pattern suggests that intrinsic, i.e. genetic properties underlie such a drastic epidemiological difference (M. natalensis as a reservoir vs. M. erythroleucus as a non-reservoir species). Here we investigate genomic differences between these two closely related rodent species by focusing on three genes that have recently been described as pivotal for LFV/human cell interactions: Dystroglycan (the LFV cellular receptor), LARGE-1 and LARGE-2 (two enzymes that are essential to Dystroglycan functioning). For all three genes, sequence analyses showed that amino-acid chains undergo extremely strong purifying selective pressures, and indicated that no nucleotide (therefore no tertiary structure) change can be advocated to explain species-specific differences in LFV-cellular mediation. Nevertheless, preliminary studies of kidney-specific expression profiles suggested that important species-specific differences exist between Mastomys species. Taking into account current knowledge about LFV-human cell interactions, our results may point towards a possible role for LARGE-1 and LARGE-2 enzymes at the intracellular replication level of the virus, rather than at the LFV-host cell receptor binding step.

Study on the movement of Rattus rattus and evaluation of the plague dispersion in Madagascar.

Plague affects mainly the rural areas in the central highlands of Madagascar. Rattus rattus is the main rodent host of Yersinia pestis in these localities. Since the introduction of plague, endemic foci have continued to expand, and spatiotemporal variability in the distribution of human plague has been observed. To assess the movements of R. rattus and evaluate the risk of dispersion of the disease, a field study at the scale of the habitats (houses, hedges of sisals, and rice fields) in the plague villages was carried out during high and low seasons of plague transmission to humans. The systemic oral marker Rhodamine B was used to follow rats' movements. Baits were placed in different habitats, and trapping success was carried out once a month for 3 months after the bait distribution. Plague indicators (reservoirs' abundance, flea index, Y. pestis prevalence in fleas, and Y. pestis antibody prevalence in rats) were determined. The highest abundance of rats and marking efficiency were observed in the sisal hedges and the rice fields. Marked rats were captured most commonly near the points where baits were initially placed. The main movements of rats were observed between the houses and sisal hedges. Major differences were observed between the seasons of high and low plague transmission. During the season of low plague transmission, rats were more abundant in the sisal hedges and rice fields, with rats moving from the houses to the rice fields. During the high plague transmission season, rats moved from the hedges of sisal to the rice fields. Important indicators of vector abundance and plague transmission were higher during the high plague transmission season. The three study habitats were the risk areas for plague transmission, but the risk appeared highest in the houses and sisals. Rats' movements according to the season were likely directed by the availability of food.

First isolation and direct evidence for the existence of large small-mammal reservoirs of Leptospira sp. in Madagascar.

BACKGROUND: Leptospirosis has long been a major public health concern in the southwestern Indian Ocean. However, in Madagascar, only a few, old studies have provided indirect serological evidence of the disease in humans or animals. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a large animal study focusing on small-mammal populations. Five field trapping surveys were carried out at five sites, from April 2008 to August 2009. Captures consisted of Rattus norvegicus (35.8%), R. rattus (35.1%), Mus musculus (20.5%) and Suncus murinus (8.6%). We used microbiological culture, serodiagnosis tests (MAT) and real-time PCR to assess Leptospira infection. Leptospira carriage was detected by PCR in 91 (33.9%) of the 268 small mammals, by MAT in 17 of the 151 (11.3%) animals for which serum samples were available and by culture in 9 of the 268 animals (3.3%). Rates of infection based on positive PCR results were significantly higher in Moramanga (54%), Toliara (48%) and Mahajanga (47.4%) than in Antsiranana (8.5%) and Toamasina (14%) (p = 0.001). The prevalence of Leptospira carriage was significantly higher in R. norvegicus (48.9%), S. murinus (43.5%) and R. rattus (30.8%) than in M. musculus (9.1%) (p<0.001). The MAT detected antibodies against the serogroups Canicola and Icterohaemorrhagiae. Isolates were characterized by serology, secY sequence-based phylogeny, partial sequencing of rrs, multi-locus VNTR analysis and pulsed field gel electrophoresis. The 10 isolates obtained from nine rats were all identified as species L. interrogans serogroup Canicola serovar Kuwait and all had identical partial rrs and secY sequences. CONCLUSIONS/SIGNIFICANCE: We present here the first direct evidence of widespread leptospiral carriage in small mammals in Madagascar. Our results strongly suggest a high level of environmental contamination, consistent with probable transmission of the infection to humans. This first isolation of pathogenic Leptospira strains in this country may significantly improve the detection of specific antibodies in human cases.

Host habitat patchiness and the distance decay of similarity among gastro-intestinal nematode communities in two species of Mastomys (southeastern Senegal).

Beta-diversity, or how species composition changes with geographical distance, has seldom been studied for different habitats. We present here quantitative estimates of the relationship between geographic distance and similarity of parasitic nematode communities in two closely related rodent host species that live in habitats with very different spatial configurations. In southeastern Senegal Mastomys natalensis lives exclusively inside human villages whereas M. erythroleucus is continuously distributed outside villages. Both host species and their gastro-intestinal nematodes were sampled on the same spatial scale. Beta-diversity was found to be higher in parasite communities of M. erythroleucus than in those of M. natalensis, and significantly related to geographic distance in this first species. Even on the local spatial scale studied, host dispersal limitation, and stochastic events, may affect species turnover in nematode communities of M. erythroleucus. In M. natalensis, no relationship was found between geographic distance and nematode community similarity, however, suggesting low host dispersal rates between habitat patches. Together with previous population genetic results, this study illustrates the need for different approaches with regard to dispersal in natural populations and its effect on biodiversity.

From the recent lessons of the Malagasy foci towards a global understanding of the factors involved in plague reemergence.

Re-emergence of human cases of plague after decades of silence does not necessarily mean that plague foci are re-emerging. Most often, Yersinia pestis bacteria have been maintained and circulating at low levels in the rodent populations. It seems therefore more appropriate to speak in terms of expansion or regression phases for sylvatic rodent plague foci and to reserve the term re-emergence for human cases. From the analysis of well-documented human plague cases in Madagascar, we underline the causes of re-emergence that can be generalized to most world foci, and can help define environments at risk where the threat of new emergence lurks. In all recent plague outbreaks, usually more than one risk factor was at the origin of the re-emergence. The reduction or discontinuance of surveillance and control, as well as poverty and insalubrity are the main factors in the re-emergence of human cases, allowing increased contacts with infected rodents and fleas. Environment changes (i.e. climatic changes, deforestation, urbanization) induce changes in flea and rodent populations by (i) extension of rodent habitats (for example by replacing forests by steppes or farmlands); (ii) modifications in population dynamics (possible outbreaks due to an increase of available food resources); but also, (iii) emergence of new vectors, reservoirs and new Y. pestis genotypes. Numerous and spontaneous genomic rearrangements occur at high frequencies in Y. pestis, which may confer selective advantages, enhancing the ability of Y. pestis to survive, to be transmitted to new hosts, and to colonize new environments. Therefore, any environmental change should be taken as a warning signal and active surveillance programs should be initiated.