122 results on '"Minoarisoa Rajerison"'
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2. Multiple Introductions of Yersinia pestis during Urban Pneumonic Plague Epidemic, Madagascar, 2017
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Voahangy Andrianaivoarimanana, Cyril Savin, Dawn N. Birdsell, Amy J. Vogler, Anne-Sophie Le Guern, Soloandry Rahajandraibe, Sylvie Brémont, Soanandrasana Rahelinirina, Jason W. Sahl, Beza Ramasindrazana, Rado Jean Luc Rakotonanahary, Fanjasoa Rakotomanana, Rindra Randremanana, Viviane Maheriniaina, Vaoary Razafimbia, Aurelia Kwasiborski, Charlotte Balière, Maherisoa Ratsitorahina, Laurence Baril, Paul Keim, Valérie Caro, Voahangy Rasolofo, André Spiegel, Javier Pizarro-Cerda, David M. Wagner, and Minoarisoa Rajerison
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pneumonic plague ,Yersinia pestis ,bacteria ,respiratory infections ,Madagascar ,Medicine ,Infectious and parasitic diseases ,RC109-216 - Abstract
Pneumonic plague (PP) is characterized by high infection rate, person-to-person transmission, and rapid progression to severe disease. In 2017, a PP epidemic occurred in 2 Madagascar urban areas, Antananarivo and Toamasina. We used epidemiologic data and Yersinia pestis genomic characterization to determine the sources of this epidemic. Human plague emerged independently from environmental reservoirs in rural endemic foci >20 times during August–November 2017. Confirmed cases from 5 emergences, including 4 PP cases, were documented in urban areas. Epidemiologic and genetic analyses of cases associated with the first emergence event to reach urban areas confirmed that transmission started in August; spread to Antananarivo, Toamasina, and other locations; and persisted in Antananarivo until at least mid-November. Two other Y. pestis lineages may have caused persistent PP transmission chains in Antananarivo. Multiple Y. pestis lineages were independently introduced to urban areas from several rural foci via travel of infected persons during the epidemic.
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- 2024
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3. Review of genotyping methods for Yersinia pestis in Madagascar.
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Lovasoa Nomena Randriantseheno, Voahangy Andrianaivoarimanana, Javier Pizarro-Cerdá, David M Wagner, and Minoarisoa Rajerison
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Arctic medicine. Tropical medicine ,RC955-962 ,Public aspects of medicine ,RA1-1270 - Abstract
BackgroundPlague, a zoonotic disease caused by Yersinia pestis, was responsible for 3 historical human pandemics that killed millions of people. It remains endemic in rodent populations in Africa, Asia, North America, and South America but human plague is rare in most of these locations. However, human plague is still highly prevalent in Madagascar, which typically records a significant part of all annual global cases. This has afforded an opportunity to study contemporary human plague in detail using various typing methods for Y. pestis.AimThis review aims to summarize the methods that have been used to type Y. pestis in Madagascar along with the major discoveries that have been made using these approaches.MethodsPubmed and Google Scholar were used to search for the keywords: "typing Yersinia pestis Madagascar," "evolution Yersinia pestis Madagascar," and "diversity Yersinia pestis Madagascar." Eleven publications were relevant to our topic and further information was retrieved from references cited in those publications.ResultsThe history of Y. pestis typing in Madagascar can be divided in 2 periods: the pre-genomics and genomics eras. During the pre-genomics era, ribotyping, direct observation of plasmid content and plasmid restriction fragment length polymorphisms (RFLP) were employed but only revealed a limited amount of diversity among Malagasy Y. pestis strains. Extensive diversity only started to be revealed in the genomics era with the use of clustered regularly interspaced palindromic repeats (CRISPR), multiple-locus variable number tandem repeats (VNTR) analysis (MLVA), and single-nucleotide polymorphisms (SNPs) discovered from whole genome sequences. These higher-resolution genotyping methods have made it possible to highlight the distribution and persistence of genotypes in the different plague foci of Madagascar (Mahajanga and the Central and Northern Highlands) by genotyping strains from the same locations across years, to detect transfers between foci, to date the emergence of genotypes, and even to document the transmission of antimicrobial resistant (AMR) strains during a pneumonic plague outbreak. Despite these discoveries, there still remain topics that deserve to be explored, such as the contribution of horizontal gene transfer to the evolution of Malagasy Y. pestis strains and the evolutionary history of Y. pestis in Madagascar.ConclusionsGenotyping of Y. pestis has yielded important insights on plague in Madagascar, particularly since the advent of whole-genome sequencing (WGS). These include a better understanding of plague persistence in the environment, antimicrobial AMR and multi-drug resistance in Y. pestis, and the person-to-person spread of pneumonic plague. Considering that human plague is still a significant public health threat in Madagascar, these insights can be useful for controlling and preventing human plague in Madagascar and elsewhere, and also are relevant for understanding the historical pandemics and the possible use of Y. pestis as a biological weapon.
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- 2024
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4. A self-amplifying RNA vaccine provides protection in a murine model of bubonic plague
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Robin John Shattock, Voahangy Andrianaivoarimanana, Paul F. McKay, Lovasoa Nomena Randriantseheno, Valarmathy Murugaiah, K. Samnuan, Paul Rogers, John S. Tregoning, Minoarisoa Rajerison, Kristoffer M. Moore, Thomas Robert Laws, and E. Diane Williamson
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saRNA ,mRNA ,vaccine ,plague ,efficacy ,mouse ,Microbiology ,QR1-502 - Abstract
Mice were immunized with a combination of self-amplifying (sa) RNA constructs for the F1 and V antigens of Yersinia pestis at a dose level of 1 μg or 5 μg or with the respective protein sub-units as a reference vaccine. The immunization of outbred OF1 mice on day 0 and day 28 with the lowest dose used (1 μg) of each of the saRNA constructs in lipid nanoparticles protected 5/7 mice against subsequent sub-cutaneous challenge on day 56 with 180 cfu (2.8 MLD) of a 2021 clinical isolate of Y. pestis termed 10-21/S whilst 5/7 mice were protected against 1800cfu (28MLD) of the same bacteria on day 56. By comparison, only 1/8 or 1/7 negative control mice immunized with 10 μg of irrelevant haemagglutin RNA in lipid nanoparticles (LNP) survived the challenge with 2.8 MLD or 28 MLD Y. pestis 10-21/S, respectively. BALB/c mice were also immunized with the same saRNA constructs and responded with the secretion of specific IgG to F1 and V, neutralizing antibodies for the V antigen and developed a recall response to both F1 and V. These data represent the first report of an RNA vaccine approach using self-amplifying technology and encoding both of the essential virulence antigens, providing efficacy against Y. pestis. This saRNA vaccine for plague has the potential for further development, particularly since its amplifying nature can induce immunity with less boosting. It is also amenable to rapid manufacture with simpler downstream processing than protein sub-units, enabling rapid deployment and surge manufacture during disease outbreaks.
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- 2023
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5. The surveillance of plague among rodents and dogs in Western Iran.
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Saber Esmaeili, Ahmad Mahmoudi, Parisa Esmaeili, Zohreh Yousefi Ghalejoogh, Alireza Mordadi, Ahmad Ghasemi, Ali Mohammadi, Amin Bagheri, Aria Sohrabi, Mina Latifian, Minoarisoa Rajerison, Javier Pizarro-Cerda, and Ehsan Mostafavi
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Arctic medicine. Tropical medicine ,RC955-962 ,Public aspects of medicine ,RA1-1270 - Abstract
BackgroundThe causative agent of plague, Yersinia pestis, is maintained in nature via a flea-rodent cycle. Western Iran is an old focus for plague, and recent data indicate that rodents and dogs in this region have serological evidence of Y. pestis infection. The purpose of this study was to conduct a large-scale investigation of Y. pestis infection in shepherd dogs, rodents, and their fleas in old foci for plague in Western Iran.Materials and methodsThis study was conducted in Hamadan province from 2014 to 2020. Rodents and fleas were collected from various locations throughout this region. Y. pestis was investigated in rodent spleen samples and fleas using culture, serology, and real-time PCR methods. Additionally, sera samples were collected from carnivores and hares in this region, and the IgG antibody against the Y. pestis F1 antigen was assessed using an ELISA.ResultsIn this study, 927 rodents were captured, with Meriones spp. (91.8%) and Microtus qazvinensis (2.6%) being the most prevalent. A total of 6051 fleas were collected from rodents and carnivores, most of which were isolated from Meriones persicus. None of the rodents or fleas examined tested positive for Y. pestis using real-time PCR and culture methods. Meanwhile, IgG antibodies were detected in 0.32% of rodents. All serologically positive rodents belonged to M. persicus. Furthermore, none of the sera from the 138 carnivores (129 sheepdogs, five Vulpes vulpes, four Canis aureus), and nine hares tested positive in the ELISA test.ConclusionThis primary survey of rodent reservoirs shows serological evidence of Y. pestis infection. Western Iran is an endemic plague focus, and as such, it requires ongoing surveillance.
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- 2023
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6. Living with rodent pests: Unifying stakeholder interests to prioritise pest management in rural Madagascar
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Kathryn Scobie, Xavier Lambin, Sandra Telfer, Mendrika Fenohasina Rasahivelo, Rova Nandrianina Raheliarison, Minoarisoa Rajerison, and Juliette Young
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stakeholder engagement ,community‐based intervention ,Madagascar ,agriculture ,rodent control ,public health ,Human ecology. Anthropogeography ,GF1-900 ,Ecology ,QH540-549.5 - Abstract
Abstract Rodent pests can have major social, economic, and environmental impacts. Their management, therefore, represents a complex socio‐ecological problem involving a network of stakeholders from across different sectors, with diverging and sometimes competing interests. Failure to incorporate stakeholder interests can result in ineffective or unsustainable management programmes, with unintended negative consequences for people and nature. Participatory approaches to decision‐making have been proposed as suitable strategies to tackle complex problems, yet, these processes are often considered too difficult, costly, or time‐consuming to implement. To facilitate a participatory approach to rodent control in Madagascar, we identified and mapped key stakeholders and developed a multisector framework for guiding rodent management programmes based on current literature and expert recommendations. We then carried out interviews and focus groups with stakeholders and end‐users to validate the final framework. The final framework unifies stakeholder interests around the dimensions of People, Resources, Knowledge and Power. Combined application of the stakeholder map and framework provides decision‐makers with the tools to identify stakeholder interests; to explore areas of conflict, as well as areas of agreement; and to ensure that these are addressed within the design of control programmes. As an assessment tool, the framework can also be used to evaluate the responsiveness of programmes to the needs of different stakeholders and assess whether objectives are being reached. We recommend the application of the stakeholder map and framework to encourage and strengthen participatory approaches aimed at rodent pest control. Due to the inclusive and interdisciplinary nature of the framework, it can be applied to address numerous complex social, environmental, and economic issues across scales, sectors, and systems. Read the free Plain Language Summary for this article on the Journal blog.
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- 2023
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7. Knockdown resistance mutations are common and widely distributed in Xenopsylla cheopis fleas that transmit plague in Madagascar.
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Shelby M Hutton, Adelaide Miarinjara, Nathan E Stone, Fara N Raharimalala, Annick O Raveloson, Ravo Rakotobe Harimanana, Mireille Harimalala, Soanandrasana Rahelinirina, Ryelan F McDonough, Abbe D Ames, Crystal Hepp, Minoarisoa Rajerison, Joseph D Busch, David M Wagner, and Romain Girod
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Arctic medicine. Tropical medicine ,RC955-962 ,Public aspects of medicine ,RA1-1270 - Abstract
BackgroundPlague, caused by the bacterium Yersinia pestis, remains an important disease in Madagascar, where the oriental rat flea, Xenopsylla cheopis, is a primary vector. To control fleas, synthetic pyrethroids (SPs) have been used for >20 years, resulting in resistance in many X. cheopis populations. The most common mechanisms of SP resistance are target site mutations in the voltage-gated sodium channel (VGSC) gene.Methodology/principal findingsWe obtained 25 collections of X. cheopis from 22 locations across Madagascar and performed phenotypic tests to determine resistance to deltamethrin, permethrin, and/or dichlorodiphenyltrichloroethane (DDT). Most populations were resistant to all these insecticides. We sequenced a 535 bp segment of the VGSC gene and identified two different mutations encoding distinct substitutions at amino acid position 1014, which is associated with knockdown resistance (kdr) to SPs in insects. Kdr mutation L1014F occurred in all 25 collections; a rarer mutation, L1014H, was found in 12 collections. There was a significant positive relationship between the frequency of kdr alleles and the proportion of individuals surviving exposure to deltamethrin. Phylogenetic comparisons of 12 VGSC alleles in Madagascar suggested resistant alleles arose from susceptible lineages at least three times. Because genotype can reasonably predict resistance phenotype, we developed a TaqMan PCR assay for the rapid detection of kdr resistance alleles.Conclusions/significanceOur study provides new insights into VGSC mutations in Malagasy populations of X. cheopis and is the first to report a positive correlation between VGSC genotypes and SP resistance phenotypes in fleas. Widespread occurrence of these two SP resistance mutations in X. cheopis populations in Madagascar reduces the viability of these insecticides for flea control. However, the TaqMan assay described here facilitates rapid detection of kdr mutations to inform when use of these insecticides is still warranted to reduce transmission of plague.
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- 2023
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8. Characterization of Klebsiella pneumoniae isolated from patients suspected of pulmonary or bubonic plague during the Madagascar epidemic in 2017
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Andriniaina Rakotondrasoa, Lova Maminirina Andrianonimiadana, Soloandry Rahajandraibe, Solohery Razafimahatratra, Voahangy Andrianaivoarimanana, Soanandrasana Rahelinirina, Tania Crucitti, Sylvain Brisse, Victor Jeannoda, Minoarisoa Rajerison, and Jean-Marc Collard
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Medicine ,Science - Abstract
Abstract Klebsiella pneumoniae can lead to a wide range of diseases including pneumonia, bloodstream and urinary tract infections. During a short period of a pulmonary plague epidemic in October 2017 in Madagascar, 12 K. pneumoniae isolates were identified in ten sputum and two buboes aspirate samples. These isolates were from 12 patients suspected of plague, without epidemiological relationships, but were negative for Yersinia pestis in culture. Data were collected from the plague national surveillance system. The isolates were characterized by antimicrobial susceptibility testing and whole-genome sequencing. Real-time PCR was performed to confirm the presence of K. pneumoniae DNA in buboes. All isolates were identified as K. pneumoniae sensu stricto. Five isolates were extended-spectrum β-lactamases producers; eleven different sequence types were identified. Five isolates belonged to known hypervirulent sequence types. Our results demonstrate community-acquired pneumonia caused by K. pneumoniae isolates in patients suspected of plague stressing the importance of bed-side differential diagnosis.
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- 2022
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9. Assessing the effectiveness of intervention to prevent plague through community and animal-based survey
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Soanandrasana Rahelinirina, Soloandry Rahajandraibe, Sitraka Rakotosamimanana, and Minoarisoa Rajerison
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Public aspects of medicine ,RA1-1270 - Published
- 2023
10. Analytical framework to evaluate and optimize the use of imperfect diagnostics to inform outbreak response: Application to the 2017 plague epidemic in Madagascar.
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Quirine Ten Bosch, Voahangy Andrianaivoarimanana, Beza Ramasindrazana, Guillain Mikaty, Rado J L Rakotonanahary, Birgit Nikolay, Soloandry Rahajandraibe, Maxence Feher, Quentin Grassin, Juliette Paireau, Soanandrasana Rahelinirina, Rindra Randremanana, Feno Rakotoarimanana, Marie Melocco, Voahangy Rasolofo, Javier Pizarro-Cerdá, Anne-Sophie Le Guern, Eric Bertherat, Maherisoa Ratsitorahina, André Spiegel, Laurence Baril, Minoarisoa Rajerison, and Simon Cauchemez
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Biology (General) ,QH301-705.5 - Abstract
During outbreaks, the lack of diagnostic "gold standard" can mask the true burden of infection in the population and hamper the allocation of resources required for control. Here, we present an analytical framework to evaluate and optimize the use of diagnostics when multiple yet imperfect diagnostic tests are available. We apply it to laboratory results of 2,136 samples, analyzed with 3 diagnostic tests (based on up to 7 diagnostic outcomes), collected during the 2017 pneumonic (PP) and bubonic plague (BP) outbreak in Madagascar, which was unprecedented both in the number of notified cases, clinical presentation, and spatial distribution. The extent of these outbreaks has however remained unclear due to nonoptimal assays. Using latent class methods, we estimate that 7% to 15% of notified cases were Yersinia pestis-infected. Overreporting was highest during the peak of the outbreak and lowest in the rural settings endemic to Y. pestis. Molecular biology methods offered the best compromise between sensitivity and specificity. The specificity of the rapid diagnostic test was relatively low (PP: 82%, BP: 85%), particularly for use in contexts with large quantities of misclassified cases. Comparison with data from a subsequent seasonal Y. pestis outbreak in 2018 reveal better test performance (BP: specificity 99%, sensitivity: 91%), indicating that factors related to the response to a large, explosive outbreak may well have affected test performance. We used our framework to optimize the case classification and derive consolidated epidemic trends. Our approach may help reduce uncertainties in other outbreaks where diagnostics are imperfect.
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- 2022
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11. Influence of Sociospatial determinants on knowledge, attitudes and practices related to the plague in a population living in endemic areas in the central highlands, Madagascar
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Sitraka Rakotosamimanana, Feno Jacob Rakotoarimanana, Vaomalala Raharimanga, François Taglioni, Josélyne Ramamonjisoa, Rindra Vatosoa Randremanana, Minoarisoa Rajerison, and Fanjasoa Rakotomanana
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Plague ,Madagascar ,Central highlands ,KAP scores ,Sociospatial determinants ,Public aspects of medicine ,RA1-1270 - Abstract
Abstract Background Plague is endemic to the central highlands of Madagascar. Sporadic human cases or outbreaks can occur annually in these areas. In Madagascar, the associations between endemicity and the knowledge, attitudes and practices (KAP) of the population with regard to this disease remain poorly documented. The aim of this study was to assess KAP related to plague among the population living in the central highlands. Methods A cross-sectional survey was conducted in the general population from June to August 2017. Based on the reported cases of plague between 2006 and 2015 in two central highland districts, a KAP questionnaire was administered in the population. Based on the proportion of correct answers provided by respondents, KAP scores were classified into three KAP categories: low (< Mean - SD), medium (Mean ± SD) and good (> Mean + SD). Multivariate analyses were performed to determine the associations between population KAP scores related to plague and sociodemographic and epidemiological factors. In addition, individual interviews and focus groups with health professionals were conducted to assess plague perception. Results A total of 597 individuals participated in the survey; 20% (n = 119) had a good KAP score, 62% (n = 370) a medium KAP score and 18% (n = 108) a low KAP score. Among the 119 respondents with good KAP scores, 80% (n = 95) resided in Ambositra district, and 20% (n = 24) resided in Tsiroanomandidy district. According to the health professionals in the two districts, populations in endemic areas are well aware of the plague. There were significant associations (p
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- 2021
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12. A decade of plague in Madagascar: a description of two hotspot districts
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Sitraka Rakotosamimanana, Daouda Kassie, François Taglioni, Josélyne Ramamonjisoa, Fanjasoa Rakotomanana, and Minoarisoa Rajerison
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Plague ,Madagascar ,Central highlands ,Epidemiology ,Deviation from the decadal mean of the incidence (DDMI) ,Public aspects of medicine ,RA1-1270 - Abstract
Abstract Background Human plague cases, mainly in the bubonic form, occur annually in endemic regions of the central highlands of Madagascar. The aim of this study was to compare the dynamics of the epidemiological features of the human plague in two districts of the central highlands region. Methods In Madagascar, all clinically suspected plague cases that meet clinical and epidemiological criteria specified in the World Health Organization (WHO) standard case definition are reported to the national surveillance system. Data on plague cases reported between 2006 and 2015 in the districts of Ambositra and Tsiroanomandidy were analysed. Statistical comparisons between the epidemiological characteristics of the two districts were conducted. Results A total of 840 cases of plague were reported over the studied period, including 563 (67%) probable and confirmed cases (P + C). Out of these P + C cases, nearly 86% (488/563) were cases of bubonic plague. Reported clinical forms of plague were significantly different between the districts from 2006 to 2015 (p = 0.001). Plague cases occurred annually in a period of 10 years in the Tsiroanomandidy district. During the same period, the Ambositra district was characterized by a one-year absence of cases. Conclusion The differences in the epidemiological situation with respect to the plague from 2006 to 2015 in the two central highlands districts may suggest that several factors other than biogeographical factors determine the representation of the plague and its dynamics in this region. Considering the epidemiological situations according to the specific contexts of the districts could improve the results in the fight against the plague in Madagascar.
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- 2021
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13. Short- and long-term humoral immune response against Yersinia pestis in plague patients, Madagascar
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Voahangy Andrianaivoarimanana, Alice Lantoniaina Iharisoa, Lila Rahalison, Marie Laurette Ralimanantsoa, Maherisoa Ratsitorahina, Rado J. L. Rakotonanahary, Elisabeth Carniel, Christian Demeure, and Minoarisoa Rajerison
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Yersinia pestis ,Immune response ,Plague ,Human ,Madagascar ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background Plague, a fatal disease caused by the bacillus, Yersinia pestis, still affects resources-limited countries. Information on antibody response to plague infection in human is scarce. Anti-F1 Ig G are among the known protective antibodies against Y. pestis infection. As a vaccine preventable disease, knowledge on antibody response is valuable for the development of an effective vaccine to reduce infection rate among exposed population in plague-endemic regions. In this study, we aim to describe short and long-term humoral immune responses against Y. pestis in plague-confirmed patients from Madagascar, the most affected country in the world. Methods Bubonic (BP) and pneumonic plague (PP) patients were recruited from plague- endemic foci in the central highlands of Madagascar between 2005 and 2017. For short-term follow-up, 6 suspected patients were enrolled and prospectively investigated for kinetics of the anti-F1 IgG response, whereas the persistence of antibodies was retrospectively studied in 71 confirmed convalescent patients, using an ELISA which was validated for the detection of plague in human blood samples in Madagascar. Results Similarly to previous findings, anti-F1 IgG rose quickly during the first week after disease onset and increased up to day 30. In the long-term study, 56% of confirmed cases remained seropositive, amongst which 60 and 40% could be considered as high- and low-antibody responders, respectively. Antibodies persisted for several years and up to 14.8 years for one individual. Antibody titers decreased over time but there was no correlation between titer and time elapsed between the disease onset and serum sampling. In addition, the seroprevalence rate was not significantly different between gender (P = 0.65) nor age (P = 0.096). Conclusion Our study highlighted that the circulating antibody response to F1 antigen, which is specific to Y. pestis, may be attributable to individual immune responsiveness. The finding that a circulating anti-F1 antibody titer could persist for more than a decade in both BP and PP recovered patients, suggests its probable involvement in patients’ protection. However, complementary studies including analyses of the cellular immune response to Y. pestis are required for the better understanding of long-lasting protection and development of a potential vaccine against plague.
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- 2020
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14. Proteomic Signatures of Antimicrobial Resistance in Yersinia pestis and Francisella tularensis
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Brooke L. Deatherage Kaiser, Dawn N. Birdsell, Janine R. Hutchison, Johanna Thelaus, Sarah C. Jenson, Voahangy Andrianaivoarimanana, Mona Byström, Kerstin Myrtennäs, Ryelan F. McDonough, Roxanne D. Nottingham, Jason W. Sahl, Herbert P. Schweizer, Minoarisoa Rajerison, Mats Forsman, David S. Wunschel, and David M. Wagner
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proteomics ,antimicrobial resistance (AMR) ,Yersinia pestis ,Francisella tularensis ,fatty acid biosynthesis ,Medicine (General) ,R5-920 - Abstract
Antimicrobial resistance (AMR) is a well-recognized, widespread, and growing issue of concern. With increasing incidence of AMR, the ability to respond quickly to infection with or exposure to an AMR pathogen is critical. Approaches that could accurately and more quickly identify whether a pathogen is AMR also are needed to more rapidly respond to existing and emerging biological threats. We examined proteins associated with paired AMR and antimicrobial susceptible (AMS) strains of Yersinia pestis and Francisella tularensis, causative agents of the diseases plague and tularemia, respectively, to identify whether potential existed to use proteins as signatures of AMR. We found that protein expression was significantly impacted by AMR status. Antimicrobial resistance-conferring proteins were expressed even in the absence of antibiotics in growth media, and the abundance of 10–20% of cellular proteins beyond those that directly confer AMR also were significantly changed in both Y. pestis and F. tularensis. Most strikingly, the abundance of proteins involved in specific metabolic pathways and biological functions was altered in all AMR strains examined, independent of species, resistance mechanism, and affected cellular antimicrobial target. We have identified features that distinguish between AMR and AMS strains, including a subset of features shared across species with different resistance mechanisms, which suggest shared biological signatures of resistance. These features could form the basis of novel approaches to identify AMR phenotypes in unknown strains.
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- 2022
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15. An open-label, randomized, non-inferiority trial of the efficacy and safety of ciprofloxacin versus streptomycin + ciprofloxacin in the treatment of bubonic plague (IMASOY): study protocol for a randomized control trial
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Rindra Vatosoa Randremanana, Mihaja Raberahona, Mamy Jean de Dieu Randria, Minoarisoa Rajerison, Voahangy Andrianaivoarimanana, Agathe Legrand, Tsinjo Fehizoro Rasoanaivo, Ravaka Randriamparany, Théodora Mayouya-Gamana, Reziky Mangahasimbola, Josie Bourner, Alex Salam, Annelies Gillesen, Tansy Edwards, Matthieu Schoenhals, Laurence Baril, Peter Horby, and Piero Olliaro
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Plague ,Bubonic plague ,Pneumonic plague ,Streptomycin ,Ciprofloxacin ,Medicine (General) ,R5-920 - Abstract
Abstract Background Bubonic plague is the primary manifestation of infection with Yersinia pestis, accounting for 90% of all plague cases and with 75% of global cases reported in Madagascar. All drugs in use for treating plague are registered based on experimental data and anecdotal evidence, and no regimen currently recommended is supported by a randomized clinical trial. The IMASOY trial intends to fill this knowledge gap by comparing two 10-day regimens included in the national guidelines in Madagascar. The primary objective of the trial is to test the hypothesis that ciprofloxacin monotherapy is non-inferior to streptomycin followed by ciprofloxacin for the treatment of bubonic plague, thus avoiding the need for injectable, potentially toxic, aminoglycosides. Methods A two-arm parallel-group randomized control trial will be conducted across peripheral health centres in Madagascar in five districts. Males and non-pregnant females of all ages with suspected bubonic or pneumonic plague will be recruited over the course of three plague ‘seasons’. The primary endpoint of the trial is to assess the proportion of patients with bubonic plague who have a therapeutic response to treatment (defined as alive, resolution of fever, 25% reduction in the size of measurable buboes, has not received an alternative treatment and no clinical decision to continue antibiotics) as assessed on day 11. Discussion If successful, the trial has the potential to inform the standard of care guidelines not just in Madagascar but in other countries afflicted by plague. The trial is currently ongoing and expected to complete recruitment in 2022. Trial registration ClinicalTrials.gov NCT04110340 . Registered on 1 October 2019
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- 2020
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16. Human Exposure to Hantaviruses Associated with Rodents of the Murinae Subfamily, Madagascar
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Harinirina Aina Rabemananjara, Vololoniaina Raharinosy, Ravo Michèle Razafimahefa, Jean Pierre Ravalohery, Jean Théophile Rafisandratantsoa, Soa Fy Andriamandimby, Minoarisoa Rajerison, Soanandrasana Rahelinirina, Aina Harimanana, Judickaelle Irinantenaina, Marie-Marie Olive, Christophe Rogier, Noël Tordo, Rainer G. Ulrich, Jean-Marc Reynes, Stéphane Petres, Jean-Michel Heraud, Sandra Telfer, and Claudia Filippone
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hantavirus ,Madagascar ,seroprevalence ,human population ,rodents ,viruses ,Medicine ,Infectious and parasitic diseases ,RC109-216 - Abstract
We conducted a national human serologic study of a hantavirus detected in Madagascar rodents using a commercial kit and a new ELISA targeting the virus. Our results suggest a conservative estimate of 2.7% (46/1,680) IgG seroprevalence. A second single-district study using the new ELISA revealed a higher prevalence (7.2%; 10/139).
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- 2020
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17. Performance of plague rapid diagnostic test compared to bacteriology: a retrospective analysis of the data collected in Madagascar
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Minoarisoa Rajerison, Marie Melocco, Voahangy Andrianaivoarimanana, Soloandry Rahajandraibe, Feno Rakotoarimanana, André Spiegel, Maherisoa Ratsitorahina, and Laurence Baril
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Plague ,Yersinia pestis ,Bacteriological culture, rapid diagnostic test, test performance ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background Plague is a highly fatal disease caused by Yersinia pestis. Late diagnosis hampers disease outcome and effectiveness of control measures, induces death and disease spread. Advance on its diagnosis was the use of lateral flow rapid diagnostic test (RDT). Methods We assessed the performance of the plague RDT based on Y. pestis F1 antigen detection more than 15 years after its deployment in Madagascar. We compared the RDT with bacteriological culture results, using data from plague notified cases collected during the periods for which both tests were performed independently and systematically. Results Used with bubonic plague (BP) patient samples, RDTs had a sensitivity of 100% (95% CI: 99.7–100%), a specificity of 67% (95% CI: 64–70%) with a good agreement between bacteriology and RDT results (86%; κ = 0.70, 95% CI 0.67–0.73). For pneumonic plague (PP), RDT had a sensitivity of 100% (95% CI: 91–100%) and a specificity of 59% (95% CI: 49–68%) and concordance between the bacteriological and plague RDT results was moderate (70%; κ = 0.43, 95% CI 0.32–0.55). Analysis focusing on the 2017–2018 plague season including the unprecedented epidemic of PP showed that RDT used on BP samples still had a sensitivity of 100% (95% CI: 85–100%) and a specificity of 82% (95% CI: 48–98%) with a very good agreement with bacteriology 94% (κ = 0.86, 95% CI 0.67–1); for PP samples, concordance between the bacteriological and plague RDT results was poor (61%; κ = − 0.03, 95% CI -0.17 – 0.10). Conclusions RDT performance appeared to be similar for the diagnosis of BP and PP except during the 2017 PP epidemic where RDT performance was low. This RDT, with its good sensitivity on both plague clinical forms during a normal plague season, remained a potential test for alert. Particularly for BP, it may be of great value in the decision process for the initiation of therapy. However, for PP, RDT may deliver false negative results due to inconsistent sample quality. Plague diagnosis could be improved through the development of next generation of RDTs.
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- 2020
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18. The impact of COVID-19 on clinical research for Neglected Tropical Diseases (NTDs): A case study of bubonic plague.
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Tsinjo Fehizoro Rasoanaivo, Josephine Bourner, Ravaka Niaina Randriamparany, Théodora Mayouya Gamana, Voahangy Andrianaivoarimanana, Mily Harijaona Raherivelo, Harivelo Randriamampionona, Minoarisoa Rajerison, Mihaja Raberahona, Alex Paddy Salam, Tansy Edwards, Piero L Olliaro, and Rindra Vatosoa Randremanana
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Arctic medicine. Tropical medicine ,RC955-962 ,Public aspects of medicine ,RA1-1270 - Abstract
BackgroundAmong the many collaterals of the COVID-19 pandemic is the disruption of health services and vital clinical research. COVID-19 has magnified the challenges faced in research and threatens to slow research for urgently needed therapeutics for Neglected Tropical Diseases (NTDs) and diseases affecting the most vulnerable populations. Here we explore the impact of the pandemic on a clinical trial for plague therapeutics and strategies that have been considered to ensure research efforts continue.MethodsTo understand the impact of the COVID-19 pandemic on the trial accrual rate, we documented changes in patterns of all-cause consultations that took place before and during the pandemic at health centres in two districts of the Amoron'I Mania region of Madagascar where the trial is underway. We also considered trends in plague reporting and other external factors that may have contributed to slow recruitment.ResultsDuring the pandemic, we found a 27% decrease in consultations at the referral hospital, compared to an 11% increase at peripheral health centres, as well as an overall drop during the months of lockdown. We also found a nation-wide trend towards reduced number of reported plague cases.DiscussionCOVID-19 outbreaks are unlikely to dissipate in the near future. Declining NTD case numbers recorded during the pandemic period should not be viewed in isolation or taken as a marker of things to come. It is vitally important that researchers are prepared for a rebound in cases and, most importantly, that research continues to avoid NTDs becoming even more neglected.
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- 2021
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19. Trends of Human Plague, Madagascar, 1998–2016
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Voahangy Andrianaivoarimanana, Patrice Piola, David M. Wagner, Fanjasoa Rakotomanana, Viviane Maheriniaina, Samuel Andrianalimanana, Suzanne Chanteau, Lila Rahalison, Maherisoa Ratsitorahina, and Minoarisoa Rajerison
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Yersinia pestis ,bacteria ,plague ,human plague ,bubonic plague ,trends ,Medicine ,Infectious and parasitic diseases ,RC109-216 - Abstract
Madagascar is more seriously affected by plague, a zoonosis caused by Yersinia pestis, than any other country. The Plague National Control Program was established in 1993 and includes human surveillance. During 1998–2016, a total of 13,234 suspected cases were recorded, mainly from the central highlands; 27% were confirmed cases, and 17% were presumptive cases. Patients with bubonic plague (median age 13 years) represented 93% of confirmed and presumptive cases, and patients with pneumonic plague (median age 29 years) represented 7%. Deaths were associated with delay of consultation, pneumonic form, contact with other cases, occurrence after 2009, and not reporting dead rats. A seasonal pattern was observed with recrudescence during September–March. Annual cases peaked in 2004 and decreased to the lowest incidence in 2016. This overall reduction occurred primarily for suspected cases and might be caused by improved adherence to case criteria during widespread implementation of the F1 rapid diagnostic test in 2002.
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- 2019
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20. Exposure to Yersinia pestis increases resistance to plague in black rats and modulates transmission in Madagascar
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Voahangy Andrianaivoarimanana, Minoarisoa Rajerison, and Ronan Jambou
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Plague ,Rattus rattus ,F1 antigen ,Madagascar ,Outbreak ,Medicine ,Biology (General) ,QH301-705.5 ,Science (General) ,Q1-390 - Abstract
Abstract Objectives In Madagascar, plague (Yersinia pestis infection) is endemic in the central highlands, maintained by the couple Rattus rattus/flea. The rat is assumed to die shortly after infection inducing migration of the fleas. However we previously reported that black rats from endemic areas can survive the infection whereas those from non-endemic areas remained susceptible. We investigate the hypothesis that lineages of rats can acquire resistance to plague and that previous contacts with the bacteria will affect their survival, allowing maintenance of infected fleas. For this purpose, laboratory-born rats were obtained from wild black rats originating either from plague-endemic or plague-free zones, and were challenged with Y. pestis. Survival rate and antibody immune responses were analyzed. Results Inoculation of low doses of Y. pestis greatly increase survival of rats to subsequent challenge with a lethal dose. During challenge, cytokine profiles support activation of specific immune response associated with the bacteria control. In addition, F1 rats from endemic areas exhibited higher survival rates than those from non-endemic ones, suggesting a selection of a resistant lineage. In Madagascar, these results support the role of black rat as long term reservoir of infected fleas supporting maintenance of plague transmission.
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- 2018
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21. Human plague: An old scourge that needs new answers.
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Xavier Vallès, Nils Chr Stenseth, Christian Demeure, Peter Horby, Paul S Mead, Oswaldo Cabanillas, Mahery Ratsitorahina, Minoarisoa Rajerison, Voahangy Andrianaivoarimanana, Beza Ramasindrazana, Javier Pizarro-Cerda, Holger C Scholz, Romain Girod, B Joseph Hinnebusch, Ines Vigan-Womas, Arnaud Fontanet, David M Wagner, Sandra Telfer, Yazdan Yazdanpanah, Pablo Tortosa, Guia Carrara, Jane Deuve, Steven R Belmain, Eric D'Ortenzio, and Laurence Baril
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Arctic medicine. Tropical medicine ,RC955-962 ,Public aspects of medicine ,RA1-1270 - Abstract
Yersinia pestis, the bacterial causative agent of plague, remains an important threat to human health. Plague is a rodent-borne disease that has historically shown an outstanding ability to colonize and persist across different species, habitats, and environments while provoking sporadic cases, outbreaks, and deadly global epidemics among humans. Between September and November 2017, an outbreak of urban pneumonic plague was declared in Madagascar, which refocused the attention of the scientific community on this ancient human scourge. Given recent trends and plague's resilience to control in the wild, its high fatality rate in humans without early treatment, and its capacity to disrupt social and healthcare systems, human plague should be considered as a neglected threat. A workshop was held in Paris in July 2018 to review current knowledge about plague and to identify the scientific research priorities to eradicate plague as a human threat. It was concluded that an urgent commitment is needed to develop and fund a strong research agenda aiming to fill the current knowledge gaps structured around 4 main axes: (i) an improved understanding of the ecological interactions among the reservoir, vector, pathogen, and environment; (ii) human and societal responses; (iii) improved diagnostic tools and case management; and (iv) vaccine development. These axes should be cross-cutting, translational, and focused on delivering context-specific strategies. Results of this research should feed a global control and prevention strategy within a "One Health" approach.
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- 2020
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22. Development and evaluation of loop-mediated isothermal amplification for detection of Yersinia pestis in plague biological samples.
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Lovasoa N Randriantseheno, Anjanirina Rahantamalala, Ando L Randrianierenana, Minoarisoa Rajerison, and Voahangy Andrianaivoarimanana
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Medicine ,Science - Abstract
BACKGROUND:Several tests are available for plague confirmation but bacteriological culture with Yersinia pestis strain isolation remains the gold standard according to the World Health Organization. However, this is a time consuming procedure; requiring specific devices and well-qualified staff. In addition, strain isolation is challenging if antibiotics have been administered prior to sampling. Here, we developed a loop-mediated isothermal amplification (LAMP) technique, a rapid, simple, sensitive and specific technique that would be able to detect Y. pestis in human biological samples. METHODS:LAMP primers were designed to target the caf1 gene which is specific to Y. pestis. The detection limit was determined by testing 10-fold serial dilution of Y. pestis DNA. Cross-reactivity was tested using DNA extracts from 14 pathogens and 47 residual samples from patients suffering from non-plague diseases. Specificity and sensitivity of the LAMP caf1 were assessed on DNA extracts of 160 human biological samples. Then, the performance of the LAMP caf1 assay was compared to conventional PCR and bacteriological culture. RESULTS:The detection limit of the developed Y. pestis LAMP assay was 3.79 pg/μl, similar to conventional PCR. The result could be read out within 45 min and as early as 35 minutes in presence of loop primer, using a simple water bath at 63°C. This is superior to culture with respect to time (requires up to 10 days) and simplicity of equipment compared to PCR. Furthermore, no cross-reactivity was found when tested on DNA extracts from other pathogens and human biological samples from patients with non-plague diseases. Compared to the gold standard, LAMP sensitivity and specificity were 97.9% (95% CI: 89.1%-99.9%) and 94.6% (95% CI: 88.6%-97.9%), respectively. CONCLUSION:LAMP detected Y. pestis effectively with high sensitivity and specificity in human plague biological samples. It can potentially be used in the field during outbreaks in resource limited countries such as Madagascar.
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- 2020
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23. Can we make human plague history? A call to action
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Nils Christian Stenseth, Minoarisoa Rajerison, Maherisoa Ratsitorahina, Javier Pizarro-Cerdá, Christian Demeure, Steve Belmain, Holger Scholz, Romain Girod, Joseph Hinnebusch, Ines Vigan-Womas, Eric Bertherat, Yazdan Yazadanpanah, Guia Carrara, Jane Deuve, Eric D'ortenzio, and Jose Oswaldo Cabanillas Angulo
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Medicine (General) ,R5-920 ,Infectious and parasitic diseases ,RC109-216 - Published
- 2019
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24. Mixed pneumonic plague and nosocomial MDR-bacterial infection of lung: a rare case report
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Voahangy Andrianaivoarimanana, Eric Bertherat, Rojo Rajaonarison, Tiana Rakotondramaro, Christophe Rogier, and Minoarisoa Rajerison
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Yersinia pestis ,Stenotrophomonas maltophilia ,Pneumonia ,Madagascar ,Diseases of the respiratory system ,RC705-779 - Abstract
Abstract Background Plague is a life-threatening disease caused by the bacterium, Yersinia pestis. Madagascar is the leading country for human plague cases worldwide. Human plague is a serious disease, particularly in its septicaemic and pneumonic forms. We report a case of pneumonic plague co-infected by a MDR-Stenotrophomonas maltophilia. Case presentation A 24 year-old man originated from Soavinandriana, a plague focus, felt uneasy and developed high fever with chills. He started treatment by himself, by private medical care and by a traditional healer for nine days moving several times from place to place. His condition had deteriorated when he presented to a district hospital with a syndrome of dyspnea, bronchial rale and altered state of consciousness. Two days later, plague diagnosis, performed as a last resort, revealed a positive F1 antigen on rapid diagnostic test. Additional tests (pla PCR and plague serology) evidenced a Y. pestis infection. However, streptomycin treatment did not achieve a complete recovery as the course of disease was complicated by the presence of MDR-S. maltophilia in his lung. This opportunistic infection could have been favored by an immunosuppression due to Y. pestis pulmonary infection and probably been acquired during his stay at a District Hospital. He was treated with a combination of ciprofloxacin and gentamycin and recovered fully. Conclusions Pneumonic plague infection may promote another virulent or avirulent bacterial infection particularly when it is not initially suspected. However, coinfection is rarely described and its occurrence frequency is unknown. In middle or low resources areas, which is the case of most plague endemic countries, control and prevention of infections in health facilities is not optimal. Co-infection with an opportunistic pathogen agent, such as S. maltophilia, is a risk which must not be disregarded as demonstrated by this case report. When deciding of a national control strategy, it should be taken into account in the choice of the first line treatment.
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- 2018
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25. Plague risk in vulnerable community: assessment of Xenopsylla cheopis susceptibility to insecticides in Malagasy prisons
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Adélaïde Miarinjara, Jean Vergain, Jean Marcel Kavaruganda, Minoarisoa Rajerison, and Sébastien Boyer
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Plague ,Prison ,Flea ,Insecticide ,Madagascar ,Infectious and parasitic diseases ,RC109-216 ,Public aspects of medicine ,RA1-1270 - Abstract
Abstract Background Prisons in Madagascar are at high risk of plague outbreak. Occurrence of plague epidemic in prisons can cause significant episode of urban plague through the movement of potentially infected humans, rodents and fleas. Rodent and flea controls are essential in plague prevention, by reducing human contact with plague reservoirs and vectors. Insecticide treatment is the key step available for the control of rat fleas which transmit the disease from infected rodents to human. The implementation of an adapted flea control strategy should rely on the insecticide susceptibility status of the targeted population. For the purpose of plague prevention campaign in prisons, we conducted insecticide resistance survey on Xenopsylla cheopis, the rat flea. Methods Fleas were collected on rats caught in six prisons of Madagascar. They were exposed to insecticide treated filter papers and mortality was recorded following World Health Organization protocol. Results The fleas collected in the prisons had different resistance patterns, while a high level of resistance to insecticides tested was described in the Antanimora prison, located in the heart of Antananarivo, the capital of Madagascar. Conclusions This finding is alarming in the context of public health, knowing that the effectiveness of flea control could be jeopardized by insecticide resistance. In order to establish more accurate rat fleas control in prisons, the main recommendations are based on continuous monitoring insecticide susceptibility of flea, insecticide rotation, and the development of a new method for flea control.
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- 2017
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26. Genetic structure and gene flow of the flea Xenopsylla cheopis in Madagascar and Mayotte
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Mireille Harimalala, Sandra Telfer, Hélène Delatte, Phillip C. Watts, Adélaïde Miarinjara, Tojo Rindra Ramihangihajason, Soanandrasana Rahelinirina, Minoarisoa Rajerison, and Sébastien Boyer
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Madagascar ,Mayotte ,Xenopsylla cheopis ,Microsatellites ,Genetic structure ,Gene flow ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background The flea Xenopsylla cheopis (Siphonaptera: Pulicidae) is a vector of plague. Despite this insect’s medical importance, especially in Madagascar where plague is endemic, little is known about the organization of its natural populations. We undertook population genetic analyses (i) to determine the spatial genetic structure of X. cheopis in Madagascar and (ii) to determine the potential risk of plague introduction in the neighboring island of Mayotte. Results We genotyped 205 fleas from 12 sites using nine microsatellite markers. Madagascan populations of X. cheopis differed, with the mean number of alleles per locus per population ranging from 1.78 to 4.44 and with moderate to high levels of genetic differentiation between populations. Three distinct genetic clusters were identified, with different geographical distributions but with some apparent gene flow between both islands and within Malagasy regions. The approximate Bayesian computation (ABC) used to test the predominant direction of flea dispersal implied a recent population introduction from Mayotte to Madagascar, which was estimated to have occurred between 1993 and 2012. The impact of this flea introduction in terms of plague transmission in Madagascar is unclear, but the low level of flea exchange between the two islands seems to keep Mayotte free of plague for now. Conclusion This study highlights the occurrence of genetic structure among populations of the flea vector of plague, X. cheopis, in Madagascar and suggests that a flea population from Mayotte has been introduced to Madagascar recently. As plague has not been reported in Mayotte, this introduction is unlikely to present a major concern for plague transmission. Nonetheless, evidence of connectivity among flea populations in the two islands indicates a possibility for dispersal by fleas in the opposite direction and thus a risk of plague introduction to Mayotte.
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- 2017
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27. Pneumonic Plague Transmission, Moramanga, Madagascar, 2015
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Beza Ramasindrazana, Voahangy Andrianaivoarimanana, Jean Marius Rakotondramanga, Dawn N. Birdsell, Maherisoa Ratsitorahina, and Minoarisoa Rajerison
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Yersinia pestis ,pneumonic plague ,transmission ,Madagascar ,outbreak ,bubonic plague ,Medicine ,Infectious and parasitic diseases ,RC109-216 - Abstract
During a pneumonic plague outbreak in Moramanga, Madagascar, we identified 4 confirmed, 1 presumptive, and 9 suspected plague case-patients. Human-to-human transmission among close contacts was high (reproductive number 1.44) and the case fatality rate was 71%. Phylogenetic analysis showed that the Yersinia pestis isolates belonged to group q3, different from the previous outbreak.
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- 2017
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28. Mixed Leptospira Infections in a Diverse Reservoir Host Community, Madagascar, 2013–2015
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Mark Moseley, Soanandrasana Rahelinirina, Minoarisoa Rajerison, Benoit Garin, Stuart Piertney, and Sandra Telfer
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co-infections ,zoonoses ,neglected tropical diseases ,reservoir hosts ,maintenance hosts ,introduced species ,Medicine ,Infectious and parasitic diseases ,RC109-216 - Abstract
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.
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- 2018
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29. Field assessment of insecticide dusting and bait station treatment impact against rodent flea and house flea species in the Madagascar plague context.
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Adélaïde Miarinjara, Soanandrasana Rahelinirina, Nadia Lova Razafimahatratra, Romain Girod, Minoarisoa Rajerison, and Sebastien Boyer
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Arctic medicine. Tropical medicine ,RC955-962 ,Public aspects of medicine ,RA1-1270 - Abstract
Bubonic is the most prevalent plague form in Madagascar. Indoor ground application of insecticide dust is the conventional method used to control potentially infected rodent fleas that transmit the plague bacterium from rodents to humans. The use of bait stations is an alternative approach for vector control during plague epidemics, as well as a preventive control method during non-epidemic seasons. Bait stations have many advantages, principally by reducing the amount of insecticide used, lowering the cost of the treatment and minimizing insecticide exposure in the environment. A previous study reported promising results on controlling simultaneously the reservoir and vectors, when slow-acting rodenticide was incorporated in bait stations called "Boîtes de Kartman". However, little evidence of an effective control of the fleas prior to the elimination of rodents was found. In this study, we evaluated bait stations containing insecticide powder and non-toxic attractive rodent bait for their potential to control rat fleas. Its efficacy was compared to the standard method. The impact of both methods on indoor and outdoor rodent fleas, as well as the human household flea Pulex irritans were analyzed at different time points after treatments. Bait stations did not cause any significant immediate or delayed reduction of rat fleas and increasing the number of operational bait stations per household did not significantly improve their efficacy. Insecticide ground dusting appeared to be the most efficient method to control indoor rat fleas. Both methods appeared to have little impact on the density of outdoor rat fleas and human fleas. These results demonstrate limited effectiveness for bait stations and encourage the maintenance of insecticide dusting as a first-line control strategy in case of epidemic emergence of plague, when immediate effect on rodent fleas is needed. Recommendations are given to improve the efficacy of the bait station method.
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- 2019
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30. Low cost, low tech SNP genotyping tools for resource-limited areas: Plague in Madagascar as a model.
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Cedar L Mitchell, Voahangy Andrianaivoarimanana, Rebecca E Colman, Joseph Busch, Heidie Hornstra-O'Neill, Paul S Keim, David M Wagner, Minoarisoa Rajerison, and Dawn N Birdsell
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Arctic medicine. Tropical medicine ,RC955-962 ,Public aspects of medicine ,RA1-1270 - Abstract
Genetic analysis of pathogenic organisms is a useful tool for linking human cases together and/or to potential environmental sources. The resulting data can also provide information on evolutionary patterns within a targeted species and phenotypic traits. However, the instruments often used to generate genotyping data, such as single nucleotide polymorphisms (SNPs), can be expensive and sometimes require advanced technologies to implement. This places many genotyping tools out of reach for laboratories that do not specialize in genetic studies and/or lack the requisite financial and technological resources. To address this issue, we developed a low cost and low tech genotyping system, termed agarose-MAMA, which combines traditional PCR and agarose gel electrophoresis to target phylogenetically informative SNPs.To demonstrate the utility of this approach for generating genotype data in a resource-constrained area (Madagascar), we designed an agarose-MAMA system targeting previously characterized SNPs within Yersinia pestis, the causative agent of plague. We then used this system to genetically type pathogenic strains of Y. pestis in a Malagasy laboratory not specialized in genetic studies, the Institut Pasteur de Madagascar (IPM). We conducted rigorous assay performance validations to assess potential variation introduced by differing research facilities, reagents, and personnel and found no difference in SNP genotyping results. These agarose-MAMA PCR assays are currently employed as an investigative tool at IPM, providing Malagasy researchers a means to improve the value of their plague epidemiological investigations by linking outbreaks to potential sources through genetic characterization of isolates and to improve understanding of disease ecology that may contribute to a long-term control effort.The success of our study demonstrates that the SNP-based genotyping capacity of laboratories in developing countries can be expanded with manageable financial cost for resource constraint laboratories. This is a practical formula that reduces resource-driven limitations to genetic research and promises to advance global collective knowledge of infectious diseases emanating from resource limited regions of the world.
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- 2017
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31. The Asian house shrew Suncus murinus as a reservoir and source of human outbreaks of plague in Madagascar.
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Soanandrasana Rahelinirina, Minoarisoa Rajerison, Sandra Telfer, Cyril Savin, Elisabeth Carniel, and Jean-Marc Duplantier
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Arctic medicine. Tropical medicine ,RC955-962 ,Public aspects of medicine ,RA1-1270 - Abstract
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.
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- 2017
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32. Pneumonic Plague Outbreak, Northern Madagascar, 2011
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Vincent Richard, Julia M. Riehm, Perlinot Herindrainy, Rahelinirina Soanandrasana, Maherisoa Ratsitoharina, Fanjasoa Rakotomanana, Samuel Andrianalimanana, Holger C. Scholz, and Minoarisoa Rajerison
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pneumonic plague ,outbreak ,Yersinia pestis ,bacteria ,drug resistance ,pathogenicity ,Medicine ,Infectious and parasitic diseases ,RC109-216 - Abstract
Yersinia pestis, the causative agent of plague, is endemic to Madagascar, particularly to the central highlands. Although plague has not been previously reported in northern Madagascar, an outbreak of pneumonic plague occurred in this remote area in 2011. Over a 27-day period, 17 suspected, 2 presumptive, and 3 confirmed human cases were identified, and all 15 untreated 20 patients died. Molecular typing of Y. pestis isolated from 2 survivors and 5 Rattus rattus rat samples identified the Madagascar-specific 1.ORI3-k single-nucleotide polymorphism genotype and 4 clustered regularly interspaced short palindromic repeat patterns. This outbreak had a case-fatality rate of 100% for nontreated patients. The Y. pestis 1.ORI3-k single-nucleotide polymorphism genotype might cause larger epidemics. Multidrug-resistant strains and persistence of the pathogen in natural foci near human settlements pose severe risks to populations in plague-endemic regions and require outbreak response strategies.
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- 2015
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33. Temporal phylogeography of Yersinia pestis in Madagascar: Insights into the long-term maintenance of plague.
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Amy J Vogler, Voahangy Andrianaivoarimanana, Sandra Telfer, Carina M Hall, Jason W Sahl, Crystal M Hepp, Heather Centner, Genevieve Andersen, Dawn N Birdsell, Lila Rahalison, Roxanne Nottingham, Paul Keim, David M Wagner, and Minoarisoa Rajerison
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Arctic medicine. Tropical medicine ,RC955-962 ,Public aspects of medicine ,RA1-1270 - Abstract
Yersinia pestis appears to be maintained in multiple, geographically separate, and phylogenetically distinct subpopulations within the highlands of Madagascar. However, the dynamics of these locally differentiated subpopulations through time are mostly unknown. To address that gap and further inform our understanding of plague epidemiology, we investigated the phylogeography of Y. pestis in Madagascar over an 18 year period.We generated whole genome sequences for 31 strains and discovered new SNPs that we used in conjunction with previously identified SNPs and variable-number tandem repeats (VNTRs) to genotype 773 Malagasy Y. pestis samples from 1995 to 2012. We mapped the locations where samples were obtained on a fine geographic scale to examine phylogeographic patterns through time. We identified 18 geographically separate and phylogenetically distinct subpopulations that display spatial and temporal stability, persisting in the same locations over a period of almost two decades. We found that geographic areas with higher levels of topographical relief are associated with greater levels of phylogenetic diversity and that sampling frequency can vary considerably among subpopulations and from year to year. We also found evidence of various Y. pestis dispersal events, including over long distances, but no evidence that any dispersal events resulted in successful establishment of a transferred genotype in a new location during the examined time period.Our analysis suggests that persistent endemic cycles of Y. pestis transmission within local areas are responsible for the long term maintenance of plague in Madagascar, rather than repeated episodes of wide scale epidemic spread. Landscape likely plays a role in maintaining Y. pestis subpopulations in Madagascar, with increased topographical relief associated with increased levels of localized differentiation. Local ecological factors likely affect the dynamics of individual subpopulations and the associated likelihood of observing human plague cases in a given year in a particular location.
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- 2017
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34. Plague Outbreak in Libya, 2009, Unrelated to Plague in Algeria
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Nicolas Cabanel, Alexandre Leclercq, Viviane Chenal-Francisque, Badereddin Annajar, Minoarisoa Rajerison, Souad Bekkhoucha, Eric Bertherat, and Elisabeth Carniel
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plague ,outbreak ,reemergence ,Yersinia pestis ,bacteria ,Tobruk ,Medicine ,Infectious and parasitic diseases ,RC109-216 - Abstract
After 25 years of no cases of plague, this disease recurred near Tobruk, Libya, in 2009. An epidemiologic investigation identified 5 confirmed cases. We determined ribotypes, Not1 restriction profiles, and IS100 and IS1541 hybridization patterns of strains isolated during this outbreak. We also analyzed strains isolated during the 2003 plague epidemic in Algeria to determine whether there were epidemiologic links between the 2 events. Our results demonstrate unambiguously that neighboring but independent plague foci coexist in Algeria and Libya. They also indicate that these outbreaks were most likely caused by reactivation of organisms in local or regional foci believed to be dormant (Libya) or extinct (Algeria) for decades, rather than by recent importation of Yersinia pestis from distant foci. Environmental factors favorable for plague reemergence might exist in this area and lead to reactivation of organisms in other ancient foci.
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- 2013
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35. Has Madagascar lost its exceptional leptospirosis free-like status?
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Maherisoa Ratsitorahina, Soanandrasana Rahelinirina, Alain Michault, Minoarisoa Rajerison, Soatiana Rajatonirina, Vincent Richard, and Surveillance Workshop group
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Medicine ,Science - Abstract
BACKGROUND:Leptospirosis is a widespread but underreported cause of morbidity and mortality. It has rarely been reported in either humans or animals in Madagascar. METHODS:We conducted a cross-sectional survey of the inhabitants in Moramanga, Madagascar, in June 2011, to estimate the prevalence of human infection using the microscopic agglutination test (MAT). This activity was carried out as part of a workshop implemented by the Pasteur Institute of Madagascar, focusing on surveillance with a one week field study and targeting the health staff of the district level. RESULTS:In total, we sampled 678 inhabitants from 263 households. The sex ratio (M/F) was 0.65 and the mean age 26.7 years. We obtained a value of 2.9% for the first recorded seroprevalence of this disease in the human community of Moramanga. Questionnaire responses revealed frequent contacts between humans and rodents in Moramanga. However, activities involving cattle were identified as a risk factor significantly associated with seropositivity (OR=3). CONCLUSION:Leptospirosis remains a neglected disease in Madagascar. This study highlights the need to quantify the public health impact of this neglected disease in a more large scale, in all the country and to establish point-of-care laboratories in remote areas.
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- 2015
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36. Serologic Survey of Plague in Animals, Western Iran
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Saber Esamaeili, Kayhan Azadmanesh, Saied Reza Naddaf, Minoarisoa Rajerison, Elisabeth Carniel, and Ehsan Mostafavi
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Yersinia pestis ,plague ,rodents ,dogs ,seroepidemiology ,bacteria ,Medicine ,Infectious and parasitic diseases ,RC109-216 - Published
- 2013
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37. Understanding the persistence of plague foci in Madagascar.
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Voahangy Andrianaivoarimanana, Katharina Kreppel, Nohal Elissa, Jean-Marc Duplantier, Elisabeth Carniel, Minoarisoa Rajerison, and Ronan Jambou
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Arctic medicine. Tropical medicine ,RC955-962 ,Public aspects of medicine ,RA1-1270 - Abstract
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.
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- 2013
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38. Immune responses to plague infection in wild Rattus rattus, in Madagascar: a role in foci persistence?
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Voahangy Andrianaivoarimanana, Sandra Telfer, Minoarisoa Rajerison, Michel A Ranjalahy, Fehivola Andriamiarimanana, Corinne Rahaingosoamamitiana, Lila Rahalison, and Ronan Jambou
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Medicine ,Science - Abstract
Plague is endemic within the central highlands of Madagascar, where its main reservoir is the black rat, Rattus rattus. Typically this species is considered susceptible to plague, rapidly dying after infection inducing the spread of infected fleas and, therefore, dissemination of the disease to humans. However, persistence of transmission foci in the same area from year to year, supposes mechanisms of maintenance among which rat immune responses could play a major role. Immunity against plague and subsequent rat survival could play an important role in the stabilization of the foci. In this study, we aimed to investigate serological responses to plague in wild black rats from endemic areas of Madagascar. In addition, we evaluate the use of a recently developed rapid serological diagnostic test to investigate the immune response of potential reservoir hosts in plague foci.We experimentally infected wild rats with Yersinia pestis to investigate short and long-term antibody responses. Anti-F1 IgM and IgG were detected to evaluate this antibody response. High levels of anti-F1 IgM and IgG were found in rats one and three weeks respectively after challenge, with responses greatly differing between villages. Plateau in anti-F1 IgM and IgG responses were reached for as few as 500 and 1500 colony forming units (cfu) inoculated respectively. More than 10% of rats were able to maintain anti-F1 responses for more than one year. This anti-F1 response was conveniently followed using dipsticks.Inoculation of very few bacteria is sufficient to induce high immune response in wild rats, allowing their survival after infection. A great heterogeneity of rat immune responses was found within and between villages which could heavily impact on plague epidemiology. In addition, results indicate that, in the field, anti-F1 dipsticks are efficient to investigate plague outbreaks several months after transmission.
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- 2012
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39. Yersinia pestis in Pulex irritans Fleas during Plague Outbreak, Madagascar
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Jocelyn Ratovonjato, Minoarisoa Rajerison, Soanandrasana Rahelinirina, and Sébastien Boyer
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fleas ,Pulex irritans ,Yersinia pestis ,plague ,Madagascar ,bacteria ,Medicine ,Infectious and parasitic diseases ,RC109-216 - Published
- 2014
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40. Distinct clones of Yersinia pestis caused the black death.
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Stephanie Haensch, Raffaella Bianucci, Michel Signoli, Minoarisoa Rajerison, Michael Schultz, Sacha Kacki, Marco Vermunt, Darlene A Weston, Derek Hurst, Mark Achtman, Elisabeth Carniel, and Barbara Bramanti
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Immunologic diseases. Allergy ,RC581-607 ,Biology (General) ,QH301-705.5 - Abstract
From AD 1347 to AD 1353, the Black Death killed tens of millions of people in Europe, leaving misery and devastation in its wake, with successive epidemics ravaging the continent until the 18(th) century. The etiology of this disease has remained highly controversial, ranging from claims based on genetics and the historical descriptions of symptoms that it was caused by Yersinia pestis to conclusions that it must have been caused by other pathogens. It has also been disputed whether plague had the same etiology in northern and southern Europe. Here we identified DNA and protein signatures specific for Y. pestis in human skeletons from mass graves in northern, central and southern Europe that were associated archaeologically with the Black Death and subsequent resurgences. We confirm that Y. pestis caused the Black Death and later epidemics on the entire European continent over the course of four centuries. Furthermore, on the basis of 17 single nucleotide polymorphisms plus the absence of a deletion in glpD gene, our aDNA results identified two previously unknown but related clades of Y. pestis associated with distinct medieval mass graves. These findings suggest that plague was imported to Europe on two or more occasions, each following a distinct route. These two clades are ancestral to modern isolates of Y. pestis biovars Orientalis and Medievalis. Our results clarify the etiology of the Black Death and provide a paradigm for a detailed historical reconstruction of the infection routes followed by this disease.
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- 2010
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41. Development and evaluation of two simple, rapid immunochromatographic tests for the detection of Yersinia pestis antibodies in humans and reservoirs.
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Minoarisoa Rajerison, Sylvie Dartevelle, Lalao A Ralafiarisoa, Idir Bitam, Thi Ngoc Tuyet Dinh, Voahangy Andrianaivoarimanana, Faridabano Nato, and Lila Rahalison
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Arctic medicine. Tropical medicine ,RC955-962 ,Public aspects of medicine ,RA1-1270 - Abstract
BACKGROUND: Tools for plague diagnosis and surveillance are not always available and affordable in most of the countries affected by the disease. Yersinia pestis isolation for confirmation is time-consuming and difficult to perform under field conditions. Serologic tests like ELISA require specific equipments not always available in developing countries. In addition to the existing rapid test for antigen detection, a rapid serodiagnostic assay may be useful for plague control. METHODS/PRINCIPAL FINDINGS: We developed two rapid immunochromatography-based tests for the detection of antibodies directed against F1 antigen of Y. pestis. The first test, SIgT, which detects total Ig (IgT) anti-F1 in several species (S) (human and reservoirs), was developed in order to have for the field use an alternative method to ELISA. The performance of the SIgT test was evaluated with samples from humans and animals for which ELISA was used to determine the presumptive diagnosis of plague. SIgT test detected anti-F1 Ig antibodies in humans with a sensitivity of 84.6% (95% CI: 0.76-0.94) and a specificity of 98% (95% CI: 0.96-1). In evaluation of samples from rodents and other small mammals, the SlgT test had a sensitivity of 87.8% (95% CI: 0.80-0.94) and a specificity of 90.3% (95% CI: 0.86-0.93). Improved performance was obtained with samples from dogs, a sentinel animal, with a sensitivity of 93% (95% CI: 0.82-1) and a specificity of 98% (95% CI: 0.95-1.01). The second test, HIgM, which detects human (H) IgM anti-F1, was developed in order to have another method for plague diagnosis. Its sensitivity was 83% (95% CI: 0.75-0.90) and its specificity about 100%. CONCLUSION/SIGNIFICANCE: The SIgT test is of importance for surveillance because it can detect Ig antibodies in a range of reservoir species. The HIgM test could facilitate the diagnosis of plague during outbreaks, particularly when only a single serum sample is available.
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- 2009
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42. Tracking of Mammals and Their Fleas for Plague Surveillance in Madagascar, 2018–2019
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Soanandrasana, Rahelinirina, Mireille, Harimalala, Jerry, Rakotoniaina, Mamy Gabriel, Randriamanantsoa, Catherine, Dentinger, Sarah, Zohdy, Romain, Girod, and Minoarisoa, Rajerison
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Infectious Diseases ,animal diseases ,Virology ,Parasitology - Abstract
Plague, a zoonotic disease caused by the bacterium Yersinia pestis, remains a major public health threat in Madagascar. To better understand the risk of transmission to humans and to guide targeted plague prevention and control measures, a survey of Y. pestis infection and exposure in mammals and their fleas was implemented. Small mammals were captured in five districts of Madagascar ranging in levels of plague endemicity, as measured by notified cases, from none to active foci. Blood and spleen samples and fleas were collected from small mammals for the detection of anti–Y. pestis F1 antibodies by ELISA, F1 antigens by rapid diagnostic tests, and pla, caf1, and inv genes by polymerase chain reaction. Some rodent fleas were kept alive and reared in the insectary to assess susceptibility to insecticides. Blood was also collected from 15 dogs and tested for anti-F1 antibodies. A total of 557 spleens, 484 sera, and 1,539 fleas were collected from 557 rodents and shrews. Nineteen (3.4%) spleens were positive for F1 antigen, most from Toamasina (N = 13), a historical plague focus. One dog was also found seropositive in Toamasina. Twenty-two (4.5%) serologic specimens from small mammals were positive for anti-F1 antibodies. The flea index was highest in the city of Antananarivo (8.8). No flea was positive for Y. pestis DNA. Flea populations exhibited resistance to various insecticides weakening the efficacy of vector control. This study highlights the potential use of animal-based surveillance to identify the risk of plague transmission in endemic and nonendemic foci for targeted prevention and control.
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- 2022
43. High Rickettsial Diversity in Rodents and Their Ectoparasites From the Central Highlands of Madagascar
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Fanohinjanaharinirina Rasoamalala, Mamionah N J Parany, Soloandry Rahajandraibe, Malala N Rakotomanga, Tojo Ramihangihajason, Voahangy Soarimalala, Sébastien Boyer, Minoarisoa Rajerison, and Beza Ramasindrazana
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Mammals ,Ixodes ,General Veterinary ,Communicable Diseases, Emerging ,Rats ,Muridae ,Rodent Diseases ,Infectious Diseases ,Insect Science ,Madagascar ,Animals ,Siphonaptera ,Parasitology ,Rickettsia - Abstract
Rickettsioses are among emerging infectious diseases around the world. In Madagascar, little information is available regarding Rickettsia (Rickettsiales: Rickettsiaceae) diversity and their potential impacts on public health. In fact, molecular screening of ectoparasites of mammals reported the presence of three species, Rickettsia africae, Rickettsia typhi, and Rickettsia felis. The present study aims to investigate the diversity of Rickettsia in small mammals and associated ectoparasites (fleas and ticks) using a molecular approach. In September and December 2016, fieldworks were undertaken in two districts of Madagascar to capture small mammals using standard traps (Tomahawk and Sherman traps) and collect associated ectoparasites. In total, 12 taxa of ectoparasites (5 flea and 7 tick species) were collected from 89 individuals of four species of terrestrial small mammals. Rickettsia spp. were molecularly identified in one specimen of Rattus rattus (Rodentia: Muridae), one specimen of Pulex irritans (Siphonaptera: Pulicidae) as well as four specimens of Ixodes cf. colasbelcouri (Ixodida: Ixodidae). This study showed the presence of three phylogenetically distinct taxa of Rickettsia in small mammals and their ectoparasites. The current study broadens our knowledge on the diversity of Rickettsia in the Central Highlands of Madagascar and highlights for the first time the presence of Ri. felis in R. rattus and in tick, I. cf. colasbelcouri in Madagascar. Additional studies are needed to have exhaustive information on Rickettsia in small mammals and their ectoparasites, to determine their pathogenicity as well as their potential effects on public health in order to update the national policy for the control of emerging infectious diseases in Madagascar.
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- 2021
44. Phylogenetic analysis of the origin and spread of plague in Madagascar
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Luis R. Esquivel Gomez, Cyril Savin, Voahangy Andrianaivoarimanana, Soloandry Rahajandraibe, Lovasoa Nomena Randriantseheno, Zhemin Zhou, Arthur Kocher, Minoarisoa Rajerison, Xavier Didelot, Denise Kühnert, and Samy, A.
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Infectious Diseases ,Public Health, Environmental and Occupational Health - Abstract
BackgroundPlague is a zoonotic disease caused by the bacterium Yersinia pestis, highly prevalent in the Central Highlands, a mountainous region in the center of Madagascar. After a plague-free period of over 60 years in the northwestern coast city of Mahajanga, the disease reappeared in 1991 and caused several outbreaks until 1999. Previous research indicates that the disease was reintroduced to the city of Mahajanga from the Central Highlands instead of reemerging from a local reservoir. However, it is not clear how many reintroductions occurred and when they took place.Methodology/Principal findingsIn this study we applied a Bayesian phylogeographic model to detect and date migrations of Y. pestis between the two locations that could be linked to the re-emergence of plague in Mahajanga. Genome sequences of 300 Y. pestis strains sampled between 1964 and 2012 were analyzed. Four migrations from the Central Highlands to Mahajanga were detected. Two resulted in persistent transmission in humans, one was responsible for most of the human cases recorded between 1995 and 1999, while the other produced plague cases in 1991 and 1992. We dated the emergence of the Y. pestis sub-branch 1.ORI3, which is only present in Madagascar and Turkey, to the beginning of the 20th century, using a Bayesian molecular dating analysis. The split between 1.ORI3 and its ancestor lineage 1.ORI2 was dated to the second half of the 19th century.Conclusions/SignificanceOur results indicate that two independent migrations from the Central Highlands caused the plague outbreaks in Mahajanga during the 1990s, with both introductions occurring during the early 1980s. They happened over a decade before the detection of human cases, thus the pathogen likely survived in wild reservoirs until the spillover to humans was possible. This study demonstrates the value of Bayesian phylogenetics in elucidating the re-emergence of infectious diseases.Author summaryIn 1991 human cases of plague were reported in the city of Mahajanga, located in the west coast of Madagascar, after 60 years without human cases. Existing evidence suggests that Yersinia pestis, the causal agent of the disease, was reintroduced to the city from a mountainous region known as the Central Highlands. We performed a phylogeographic analysis on 300 Y. pestis genome sequences to determine how many migrations of the pathogen between the two locations were related to the reappearance of the disease in Mahajanga. The results revealed that two migrations from the Central Highlands were the cause of the outbreaks of plague in the west coast of the country during the 1990s. We also aimed to date the emergence of the Y.pestis variant that circulates in Madagascar and is also present in Turkey. To do this, we conducted a molecular dating analysis using an extended data set of 445 sequences, which contained sequences from Turkey and India (the country from which the pathogen was exported to Madagascar for the first time). The analysis indicated that this particular variant emerged in the first decade of the 20th century.
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- 2023
45. Field assessment of dog as sentinel animal for plague in endemic foci of Madagascar
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Maherisoa Ratsitorahina, Lila Rahalison, Sandra Telfer, Voahangy Andrianaivoarimanana, Minoarisoa Rajerison, Soanandrasana Rahelinirina, and Suzanne Chanteau
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0106 biological sciences ,medicine.medical_specialty ,Bacterial Zoonoses ,Endemic Diseases ,Prevalence ,Zoology ,Plague (disease) ,010603 evolutionary biology ,01 natural sciences ,Disease Outbreaks ,Serology ,Dogs ,Epidemiology ,Madagascar ,medicine ,Animals ,Humans ,0501 psychology and cognitive sciences ,Dog Diseases ,050102 behavioral science & comparative psychology ,Seroconversion ,Plague ,biology ,05 social sciences ,Outbreak ,biology.organism_classification ,Antibodies, Bacterial ,Canis ,Yersinia pestis ,Sentinel Species ,Animal Science and Zoology ,Sentinel Surveillance - Abstract
The epidemiology of Yersinia pestis, the causative agent of plague, involves vectors and reservoirs in its transmission cycle. The passive plague surveillance in Madagascar targets mainly rodent and fleas. However, carnivores are routinely surveyed as sentinels of local plague activity in some countries. The aim of this study is to assess the use of domestic dog (Canis familiaris) as sentinel animal for field surveillance of plague in a highly endemic area in Madagascar. Cross-sectional surveys of plague antibody prevalence in C. familiaris were conducted in endemic areas with contrasting histories of plague cases in humans, as well as a plague free area. Rodent capture was done in parallel to evaluate evidence for Y. pestis circulation in the primary reservoirs. In 2 sites, dogs were later re-sampled to examine evidence of seroconversion and antibody persistence. Biological samplings were performed between March 2008 and February 2009. Plague antibody detection was assessed using anti-F1 ELISA. Our study showed a significant difference in dog prevalence rates between plague-endemic and plague-free areas, with no seropositive dogs detected in the plague free area. No correlation was found between rodents and dog prevalence rates, with an absence of seropositive rodents in some area where plague circulation was indicated by seropositive dogs. This is consistent with high mortality rates in rodents following infection. Re-sampling dogs identified individuals seropositive on both occasions, indicating high rates of re-exposure and/or persistence of plague antibodies for at least 9 months. Seroconversion or seropositive juvenile dogs indicated recent local plague circulation. In Madagascar, dog surveillance for plague antibody could be useful to identify plague circulation in new areas or quiescent areas within endemic zones. Within active endemic areas, monitoring of dog populations for seroconversion (negative to positive) or seropositive juvenile dogs could be useful for identifying areas at greatest risk of human outbreaks.
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- 2021
46. Rodent control to fight plague: field assessment of methods based on rat density reduction
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Soanandrasana Rahelinirina, Xavier Lambin, Voahangy Andrianaivoarimanana, Fanohinjanaharinirina Rasoamalala, Lovasoa Nomena Randriantseheno, Minoarisoa Rajerison, Olivier Gorgé, Kathryn Scobie, Eric Valade, Beza Ramasindrazana, Sandra Telfer, and Jerry Sylvio Rakotoniaina
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0106 biological sciences ,Flea ,Bacterial Zoonoses ,Rodent ,Density reduction ,Zoology ,Plague (disease) ,010603 evolutionary biology ,01 natural sciences ,law.invention ,Abundance (ecology) ,law ,biology.animal ,Madagascar ,Animals ,0501 psychology and cognitive sciences ,050102 behavioral science & comparative psychology ,Population Density ,Plague ,biology ,05 social sciences ,Field assessment ,Insect Vectors ,Rats ,Transmission (mechanics) ,Vector (epidemiology) ,Rodent Control ,Siphonaptera ,Animal Science and Zoology - Abstract
Rodents represent a serious threat to food security and public health. The extent to which rodent control can mitigate the risk from rodent-borne disease depends on both the effectiveness of control in reducing rodent abundance and the impact on disease epidemiology. Focusing on a plague-endemic region of Madagascar, this study compared the effectiveness of 3 methods: live-traps, snap-traps, and rodenticides. Control interventions were implemented inside houses between May and October 2019. Tracking tiles monitored rodent abundance. Rodent fleas, the vector involved in plague transmission, were collected. Rodent populations consisted of Rattus rattus and Mus musculus. In terms of trap success, we found that our live-trap regime was more effective than snap-traps. While all 3 control strategies appeared to reduce in-house rodent activity in the short term, we found no evidence of a longer-term effect, with in-house rodent abundance in treated sites comparable to non-treatment sites by the following month. Endemic flea, Synopsyllus fonquerniei, is a key plague vector usually found on rats living outdoors. Although we found no evidence that its abundance inside houses increased following control, this may have been due to a lack of power caused by significant variation in S. fonquerniei abundance. The presence of S. fonquerniei in houses was more likely when S. fonquerniei abundance on outdoor rats was higher, which in turn correlated with high rat abundance. Our results emphasize that control strategies need to consider this connectivity between in-house rat-flea populations and the outdoor populations, and any potential consequences for plague transmission.
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- 2021
47. Plague in Tanzania: first report of sylvatic plague in Morogoro region, persistence in Mbulu focus, and ongoing quiescence in Lushoto and Iringa foci
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Lavinia Haikukutu, Japhet R. Lyaku, Charles Lyimo, Christopher J. Kasanga, Sengiyumva E. Kandusi, Soanandrasana Rahelinirina, Fanohinjanaharinirina Rasoamalala, Minoarisoa Rajerison, and Rhodes Makundi
- Abstract
Plague has been a threat to human health in Tanzania since 1886. This zoonotic disease has established several endemic foci in the country, posing a risk of outbreaks. This study was conducted to investigate the presence ofBlood from 645 captured small mammals was screened for antibodies against the fraction 1 (F1) antigen ofSpecific antibodies againstThese results provide evidence of the circulation of
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- 2022
48. Transmission of Antimicrobial Resistant Yersinia pestis during a Pneumonic Plague Outbreak
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Jason W. Sahl, Minoarisoa Rajerison, Nawarat Somprasong, Birgit Nikolay, Carina M. Hall, Harimahefa Razafimandimby, Christophe Rogier, Voahangy Andrianaivoarimanana, David M. Wagner, Amy J. Vogler, Lovasoa Nomena Randriantseheno, Herbert P. Schweizer, Simon Cauchemez, Faniry Rakotoarimanana, Dawn N. Birdsell, Institut Pasteur de Madagascar, Réseau International des Instituts Pasteur (RIIP), Northern Arizona University [Flagstaff], Modélisation mathématique des maladies infectieuses - Mathematical modelling of Infectious Diseases, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), University of Florida [Gainesville] (UF), Ministère de la Santé Publique - Ministry of Public Health [Antananarivo, Madagascar], and This work was supported by the Institut Pasteur de Madagascar
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Microbiology (medical) ,Pneumonic plague ,Yersinia pestis ,[SDV]Life Sciences [q-bio] ,Virulence ,Bubonic plague ,Disease Outbreaks ,Antibiotic resistance ,medicine ,Animals ,antimicrobial resistance ,Retrospective Studies ,Plague ,biology ,outbreak ,Transmission (medicine) ,business.industry ,Outbreak ,biology.organism_classification ,medicine.disease ,Virology ,Anti-Bacterial Agents ,Infectious Diseases ,Streptomycin ,pneumonic plague ,business ,medicine.drug - Abstract
Background Pneumonic plague (PP), caused by Yersinia pestis, is the most feared clinical form of plague due to its rapid lethality and potential to cause outbreaks. PP outbreaks are now rare due to antimicrobial therapy. Methods A PP outbreak in Madagascar involving transmission of a Y. pestis strain resistant to streptomycin, the current recommended first-line treatment in Madagascar, was retrospectively characterized using epidemiology, clinical diagnostics, molecular characterization, and animal studies. Results The outbreak occurred in February 2013 in the Faratsiho district of Madagascar and involved 22 cases, including 3 untreated fatalities. The 19 other cases participated in funeral practices for the fatal cases and fully recovered after combination antimicrobial therapy: intramuscular streptomycin followed by oral co-trimoxazole. The Y. pestis strain that circulated during this outbreak is resistant to streptomycin resulting from a spontaneous point mutation in the 30S ribosomal protein S12 (rpsL) gene. This same mutation causes streptomycin resistance in 2 unrelated Y. pestis strains, one isolated from a fatal PP case in a different region of Madagascar in 1987 and another isolated from a fatal PP case in China in 1996, documenting this mutation has occurred independently at least 3 times in Y. pestis. Laboratory experiments revealed this mutation has no detectable impact on fitness or virulence, and revertants to wild-type are rare in other species containing it, suggesting Y. pestis strains containing it could persist in the environment. Conclusions Unique antimicrobial resistant (AMR) strains of Y. pestis continue to arise in Madagascar and can be transmitted during PP outbreaks.
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- 2022
49. An open-label, randomized, non-inferiority trial of the efficacy and safety of ciprofloxacin versus streptomycin + ciprofloxacin in the treatment of bubonic plague (IMASOY): study protocol for a randomized control trial
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Piero Olliaro, Josie Bourner, Ravaka Randriamparany, Tsinjo Fehizoro Rasoanaivo, Mihaja Raberahona, Minoarisoa Rajerison, Théodora Mayouya-Gamana, Matthieu Schoenhals, Annelies Gillesen, Tansy Edwards, Reziky Tiandraza Mangahasimbola, Agathe Legrand, Alex P. Salam, Mamy Jean de Dieu Randria, Laurence Baril, Voahangy Andrianaivoarimanana, Rindra Randremanana, and Peter Horby
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Male ,Pneumonic plague ,medicine.medical_specialty ,Yersinia pestis ,Medicine (miscellaneous) ,Equivalence Trials as Topic ,Bubonic plague ,law.invention ,Study Protocol ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,law ,Ciprofloxacin ,Internal medicine ,Madagascar ,Clinical endpoint ,Humans ,Medicine ,Pharmacology (medical) ,030212 general & internal medicine ,Plague ,lcsh:R5-920 ,biology ,business.industry ,biology.organism_classification ,medicine.disease ,3. Good health ,Regimen ,Streptomycin ,Female ,business ,lcsh:Medicine (General) ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Background Bubonic plague is the primary manifestation of infection with Yersinia pestis, accounting for 90% of all plague cases and with 75% of global cases reported in Madagascar. All drugs in use for treating plague are registered based on experimental data and anecdotal evidence, and no regimen currently recommended is supported by a randomized clinical trial. The IMASOY trial intends to fill this knowledge gap by comparing two 10-day regimens included in the national guidelines in Madagascar. The primary objective of the trial is to test the hypothesis that ciprofloxacin monotherapy is non-inferior to streptomycin followed by ciprofloxacin for the treatment of bubonic plague, thus avoiding the need for injectable, potentially toxic, aminoglycosides. Methods A two-arm parallel-group randomized control trial will be conducted across peripheral health centres in Madagascar in five districts. Males and non-pregnant females of all ages with suspected bubonic or pneumonic plague will be recruited over the course of three plague ‘seasons’. The primary endpoint of the trial is to assess the proportion of patients with bubonic plague who have a therapeutic response to treatment (defined as alive, resolution of fever, 25% reduction in the size of measurable buboes, has not received an alternative treatment and no clinical decision to continue antibiotics) as assessed on day 11. Discussion If successful, the trial has the potential to inform the standard of care guidelines not just in Madagascar but in other countries afflicted by plague. The trial is currently ongoing and expected to complete recruitment in 2022. Trial registration ClinicalTrials.gov NCT04110340. Registered on 1 October 2019
- Published
- 2020
50. Factors Influencing Atypical Clinical Presentations during the 2017 Madagascar Pneumonic Plague Outbreak: A Prospective Cohort Study
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Rindra Randremanana, Reziky Tiandraza Mangahasimbola, Rodrigue N. E. Hasiniatsy, Dominique Razafimandimby, Tiana Razafinambinintsoa, Anna L. Funk, Laurence Baril, Andrew M. Lovering, Randrianirina Frédérique, Minoarisoa Rajerison, Alex P. Salam, Arnaud Fontanet, Mihaja Raberahona, Faraniaina Andrianarintsiferantsoa, Mamy Jean de Dieu Randria, Norosoa Harline Razanajatovo, Voahangy Andrianaivoarimanana, Peter Horby, Eric Bertherat, Prisca Andriantsalama, Rado Rakotomalala, Jean-Michel Heraud, Lyndsey Castle, Bertrand Renaud, Liam Read, University of Oxford, UK Public Health Rapid Support Team [London] (UK-PHRST), London School of Hygiene and Tropical Medicine (LSHTM)-Public Health England [London], Hôpital Joseph Raseta Befelatanana, CHU d’Antananarivo, Institut Pasteur de Madagascar, Réseau International des Instituts Pasteur (RIIP), North Bristol NHS Trust [Bristol, UK], Centre Hospitalier Anti-pesteux d'Ambohimiandra [Antananarivo, Madagascar] (CHAPA), Centre Hospitalier de Soavinandriana (CENHOSOA), Institut Pasteur [Paris] (IP), Université Paris Descartes - Paris 5 (UPD5), World Health Organisation (WHO), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), This study was funded by the United Kingdom Public Health Rapid Support Team., University of Oxford [Oxford], and Institut Pasteur [Paris]
- Subjects
Male ,Pediatrics ,Cohort Studies ,MESH: Madagascar ,0302 clinical medicine ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,MESH: Child ,Prospective Studies ,Overdiagnosis ,Child ,Prospective cohort study ,MESH: Cohort Studies ,MESH: Aged ,[SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases ,MESH: Middle Aged ,Articles ,Middle Aged ,MESH: Infant ,3. Good health ,Infectious Diseases ,Child, Preschool ,[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,Cohort ,Female ,medicine.symptom ,Cohort study ,Adult ,Pneumonic plague ,medicine.medical_specialty ,Adolescent ,030231 tropical medicine ,MESH: Plague ,Bubonic plague ,03 medical and health sciences ,Virology ,Madagascar ,medicine ,Humans ,Aged ,MESH: Adolescent ,Plague ,MESH: Humans ,business.industry ,MESH: Child, Preschool ,Infant ,Outbreak ,MESH: Adult ,[SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology ,medicine.disease ,MESH: Male ,MESH: Prospective Studies ,Sputum ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,Parasitology ,business ,MESH: Female - Abstract
International audience; In late 2017, Madagascar experienced a large urban outbreak of pneumonic plague, the largest outbreak to date this century. During the outbreak, there were widespread reports of plague patients presenting with atypical symptoms, such as prolonged duration of illness and upper respiratory tract symptoms. Reported mortality among plague cases was also substantially lower than that reported in the literature (25% versus 50% in treated patients). A prospective multicenter observational study was carried out to investigate potential reasons for these atypical presentations. Few subjects among our cohort had confirmed or probable plague, suggesting that, in part, there was overdiagnosis of plague cases by clinicians. However, 35% subjects reported using an antibiotic with anti-plague activity before hospital admission, whereas 55% had antibiotics with anti-plague activity detected in their serum at admission. Although there may have been overdiagnosis of plague by clinicians during the outbreak, the high frequency of community antibiotic may partly explain the relatively few culture-positive sputum samples during the outbreak. Community antibiotic use may have also altered the clinical presentation of plague patients. These issues make accurate detection of patients and the development of clinical case definitions and triage algorithms in urban pneumonic plague outbreaks difficult.
- Published
- 2020
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