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.

International audienceBACKGROUND: 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. METHODOLOGYPRINCIPAL 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. CONCLUSIONSSIGNIFICANCE: 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

Rodent control to fight plague : field assessment of methods based on rat density reduction

Research funding: Directorate General for International Relations and Strategy. Grant Number: 2018‐SB‐024‐18SSEOC049‐PMG7‐SSA5‐IPMMADAGASCAR ACKNOWLEDGMENTS: We are especially grateful to the health authorities and the population in Miantso and Ankazobe for allowing us to do this work and being so helpful. We thank the staff of the Plague Unit, Institut Pasteur de Madagascar, for helping with the field and laboratory work, especially Alain Berthin Rakotoarisoa and Andrianiaina Parfait Rakotonindrainy. This work was supported by a Directorate General for International Relations and Strategy grant (2018‐SB‐024‐18SSEOC049‐PMG7‐SSA5‐IPMMADAGASCAR) covering the project “Développement de contre‐mesures médicales à la peste à Madagascar” with scientific support of IRBA (French Armed Forces Biomedical Research Institute), within the framework of French MoD's involvement in G7 Global partnership. The French Agency for International Technical Expertise (AFETI) ensures the proper financial execution of the project and contributes to the implementation of cooperation actions under the control of the Directorate General for International Relations and Strategy. This research was also funded in part by the Wellcome Trust [095171/Z/10/Z] and the Institut Pasteur de Madagascar. For the purpose of Open Access, the authors have applied a CC BY public copyright license to any Author Accepted Manuscript version arising from this submission. K.S. was supported by the Biotechnology and Biological Sciences Research Council (BBSRC) under the EastBio DTP (grant number BB/M010996/1).Peer reviewedPublisher PD

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

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.

International audienceBACKGROUND: 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. METHODOLOGYPRINCIPAL 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. CONCLUSIONSSIGNIFICANCE: 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

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

Microsatellite data (17 loci) for 38 population samples of Malagasy Rattus rattus

L1: title; L2-18: locus names; individual genotypes in a "Genepop" format. Population samples are separated by "pop" and labelled according the 4 first letters of the individual code

High Prevalence of Leptospira spp. in Rodents in an Urban Setting in Madagascar

International audienceLeptospirosis is a neglected zoonotic bacterial disease caused by pathogenic Leptospira spp. Only limited studies have been conducted on the presence of Leptospira spp. in rats in Antananarivo, the capital city of Madagascar. We assessed Leptospira prevalence in small mammals in urban areas of Antananarivo where sanitation is inadequate and there is risk of flooding during the rainy season. We captured rodents and shrews at two sites and examined kidney samples from 114 animals using culture and a real-time polymerase chain reaction (PCR) assay specific to pathogenic Leptospira spp. We identified 23 positive samples containing Leptospira interrogans and Leptospira borgpetersenii, with a high prevalence in Rattus norvegicus (44.9%). Our results indicate that small mammals, in particular R. norvegicus, present a major public health risk for acquiring leptospirosis in Antananarivo

Mixed Leptospira Infections in a Diverse Reservoir Host Community, Madagascar, 2013–2015

We identified mixed infections of pathogenic Leptospira in small mammals across a landscape-scale study area in Madagascar by using primers targeting different Leptospira spp. Using targeted primers increased prevalence estimates and evidence for transmission between endemic and invasive hosts. Future studies should assess rodentborne transmission of Leptospira to humans

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

International audiencePlague 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