Journal articles: 'Yersinia pestis – Madagascar'

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Vogler, Amy J., Fabien Chan, David M. Wagner, Philippe Roumagnac, Judy Lee, Roxanne Nera, Mark Eppinger, et al. "Phylogeography and Molecular Epidemiology of Yersinia pestis in Madagascar." PLoS Neglected Tropical Diseases 5, no. 9 (September 13, 2011): e1319. http://dx.doi.org/10.1371/journal.pntd.0001319.

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Titball, Richard W. "Plague: A natural history of Yersinia pestis." Biochemist 26, no. 2 (April 1, 2004): 11–14. http://dx.doi.org/10.1042/bio02602011.

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Yersinia pestis is the aetiological agent of plague, a disease that has a place in history as one the major causes of death from the 14th to the 17th Centuries1. It is estimated that, during the Black Death pandemic, approximately 30% of the population of Europe died of plague, and so great in number were the corpses that, in many parts of Europe, the dead were placed in burial pits rather than receiving individual burials. Y. pestis has also been responsible for two other pandemics of disease. The first of these, the Justinian plague, occurred during the 1st Century. The third pandemic occurred during the latter part of the 19th Century and was confined mainly to South-East Asia1. Even today, several thousand cases of plague are reported to the World Health Organization each year, mainly from South-East Asia, the southwestern parts of the USA, Madagascar and Africa.

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Guiyoule, A., B. Rasoamanana, C. Buchrieser, P. Michel, S. Chanteau, and E. Carniel. "Recent emergence of new variants of Yersinia pestis in Madagascar." Journal of clinical microbiology 35, no. 11 (1997): 2826–33. http://dx.doi.org/10.1128/jcm.35.11.2826-2833.1997.

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Riehm, Julia M., Michaela Projahn, Amy J. Vogler, Minoaerisoa Rajerison, Genevieve Andersen, Carina M. Hall, Thomas Zimmermann, et al. "Diverse Genotypes of Yersinia pestis Caused Plague in Madagascar in 2007." PLOS Neglected Tropical Diseases 9, no. 6 (June 12, 2015): e0003844. http://dx.doi.org/10.1371/journal.pntd.0003844.

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Alderson, Jennifer, Max Quastel, Emily Wilson, and Duncan Bellamy. "Factors influencing the re-emergence of plague in Madagascar." Emerging Topics in Life Sciences 4, no. 4 (December 1, 2020): 423–33. http://dx.doi.org/10.1042/etls20200334.

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Plague is an infectious disease found worldwide and has been responsible for pandemics throughout history. Yersinia pestis, the causative bacterium, survives in rodent hosts with flea vectors that also transmit it to humans. It has been endemic in Madagascar for a century but the 1990s saw major outbreaks and in 2006 the WHO described the plague as re-emerging in Madagascar and the world. This review highlights the variety of factors leading to plague re-emergence in Madagascar, including climate events, insecticide resistance, and host and human behaviour. It also addresses areas of concern for future epidemics and ways to mitigate these. Pinpointing and addressing current and future drivers of plague re-emergence in Madagascar will be essential to controlling future outbreaks both in Madagascar and worldwide.

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Rahalison, L., E. Vololonirina, M. Ratsitorahina, and S. Chanteau. "Diagnosis of Bubonic Plague by PCR in Madagascar under Field Conditions." Journal of Clinical Microbiology 38, no. 1 (January 2000): 260–63. http://dx.doi.org/10.1128/jcm.38.1.260-263.2000.

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ABSTRACT The diagnostic value of a PCR assay that amplifies a 501-bp fragment of the Yersinia pestis caf1 gene has been determined in a reference laboratory with 218 bubo aspirates collected from patients with clinically suspected plague managed in a regional hospital in Madagascar. The culture of Y. pestis and the detection of the F1 antigen (Ag) by enzyme-linked immunosorbent assay (ELISA) were used as reference diagnostic methods. The sensitivity of PCR was 89% (57 of 64) for the Y. pestis -positive patients, and 80.7% (63 of 78) for the F1 Ag-positive patients. The specificity of PCR for the culture-, F1 Ag-, and antibody-negative patients ( n = 105) was 100%. Because in Madagascar most patients with plague are managed and their clinical samples are collected in remote villages, the usefulness of PCR was evaluated for routine diagnostic use in the operational conditions of the control program. The sensitivity of PCR was 50% (25 of 50) relative to the results of culture and 35.2% (19 of 54) relative to the results of the F1 Ag immunocapture ELISA. The specificity of PCR under these conditions was 96%. In conclusion, the PCR method was found to be very specific but not as sensitive as culture or the F1 Ag detection method. The limitation in sensitivity may have been due to suboptimal field conditions and the small volumes of samples used for DNA extraction. This technique is not recommended as a routine diagnostic test for plague in Madagascar.

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Harimalala, Mireille, Soanandrasana Rahelinirina, and Romain Girod. "Presence of the Oriental Rat Flea (Siphonaptera: Pulicidae) Infesting an Endemic Mammal and Confirmed Plague Circulation in a Forest Area of Madagascar." Journal of Medical Entomology 57, no. 4 (February 26, 2020): 1318–23. http://dx.doi.org/10.1093/jme/tjaa026.

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Abstract The Oriental rat flea, Xenopsylla cheopis (Rothschild 1903), is a cosmopolitan flea usually found infesting domestic rats. This flea is a well-known major human plague vector in Madagascar. As part of field sampling, fleas and small mammals were collected in the village of South Andranofeno and the natural reserve of Sohisika, two sites of the district of Ankazobe, located in the Central Highlands of Madagascar. Rats inside houses and forest small mammals were trapped using Besancon Technical Services and pitfall traps, respectively. Their fleas were collected and preserved for laboratory works. Collected fleas from the village and forest belonged to five species, which were X. cheopis, Synopsyllus fonquerniei (Wagner and Roubaud 1932) (Siphonaptera: Pulicidae), Echidnophaga gallinacea (Westwood 1875) (Siphonaptera: Pulicidae), Ctenocephalides felisstrongylus (Jordan 1925) (Siphonaptera: Pulicidae), Pulex irritans (Linnaeus 1758) (Siphonaptera: Pulicidae). After sampling in the forest zone, one specimen of X. cheopis was unexpectedly collected while infesting an endemic tenrec Setifer setosus (Schreber 1777) (Afrosoricida: Tenrecidae). Polymerase chain reaction (PCR) diagnosis on all collected fleas allowed detecting plague bacterium Yersinia pestis (Lehmann and Neumann 1896) (Enterobacterales: Yersiniaceae) on nine specimens of the endemic flea S. fonquerniei collected inside forest. The presence of the oriental rat flea in forest highlights the connection between human and wild environments due to animal movements and the fact that the rat flea can infest various hosts. As only one specimen of X. cheopis was collected on S. setosus, we hypothesize that flea was carried from the village to forest. Yersinia pestis infection of forest fleas outlines plague circulation in this sylvatic area.

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Vogler, Amy J., Voahangy Andrianaivoarimanana, Sandra Telfer, Carina M. Hall, Jason W. Sahl, Crystal M. Hepp, Heather Centner, et al. "Temporal phylogeography of Yersinia pestis in Madagascar: Insights into the long-term maintenance of plague." PLOS Neglected Tropical Diseases 11, no. 9 (September 5, 2017): e0005887. http://dx.doi.org/10.1371/journal.pntd.0005887.

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Tollenaere, C., L. Rahalison, M. Ranjalahy, J. M. Duplantier, S. Rahelinirina, S. Telfer, and C. Brouat. "Susceptibility to Yersinia pestis Experimental Infection in Wild Rattus rattus, Reservoir of Plague in Madagascar." EcoHealth 7, no. 2 (May 5, 2010): 242–47. http://dx.doi.org/10.1007/s10393-010-0312-3.

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Urich, Sandra K., Linda Chalcraft, Martin E. Schriefer, Brook M. Yockey, and Jeannine M. Petersen. "Lack of Antimicrobial Resistance in Yersinia pestis Isolates from 17 Countries in the Americas, Africa, and Asia." Antimicrobial Agents and Chemotherapy 56, no. 1 (October 24, 2011): 555–58. http://dx.doi.org/10.1128/aac.05043-11.

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ABSTRACTYersinia pestisis the causative agent of plague, a fulminant disease that is often fatal without antimicrobial treatment. Plasmid (IncA/C)-mediated multidrug resistance inY. pestiswas reported in 1995 in Madagascar and has generated considerable public health concern, most recently because of the identification of IncA/C multidrug-resistant plasmids in other zoonotic pathogens. Here, we demonstrate no resistance in 392Y. pestisisolates from 17 countries to eight antimicrobials used for treatment or prophylaxis of plague.

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Pan, Jing-Cao, Rong Ye, Hao-Qiu Wang, Hai-Qing Xiang, Wei Zhang, Xin-Fen Yu, Dong-Mei Meng, and Zhe-Sheng He. "Vibrio cholerae O139 Multiple-Drug Resistance Mediated by Yersinia pestis pIP1202-Like Conjugative Plasmids." Antimicrobial Agents and Chemotherapy 52, no. 11 (August 18, 2008): 3829–36. http://dx.doi.org/10.1128/aac.00375-08.

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ABSTRACT A conjugative plasmid, pMRV150, which mediated multiple-drug resistance (MDR) to at least six antibiotics, including ampicillin, streptomycin, gentamicin, tetracycline, chloramphenicol, and trimethoprim-sulfamethoxazole, was identified in a Vibrio cholerae O139 isolate from Hangzhou, eastern China, in 2004. According to partial pMRV150 DNA sequences covering 15 backbone regions, the plasmid is most similar to pIP1202, an IncA/C plasmid in an MDR Yersinia pestis isolate from a Madagascar bubonic plague patient, at an identity of 99.99% (22,180/22,183 nucleotides). pMRV150-like plasmids were found in only 7.69% (1/13) of the O139 isolates tested during the early period of the O139 epidemic in Hangzhou (1994, 1996, and 1997); then the frequency increased gradually from 60.00% (3/5) during 1998 and 1999 to 92.16% (47/51) during 2000 to 2006. Most (42/51) of the O139 isolates bearing pMRV150-like plasmids were resistant to five to six antibiotics, whereas the plasmid-negative isolates were resistant only to one to three antibiotics. In 12 plasmid-bearing O139 isolates tested, the pMRV150-like plasmids ranged from approximately 140 kb to 170 kb and remained at approximately 1 or 2 copies per cell. High (4.50 × 10−2 and 3.08 × 10−2) and low (0.88 × 10−8 to 3.29 × 10−5) plasmid transfer frequencies, as well as no plasmid transfer (under the detection limit), from these O139 isolates to the Escherichia coli recipient were observed. The emergence of pMRV150-like or pIP1202-like plasmids in many bacterial pathogens and nonpathogens occupying diverse niches with global geographical distribution indicates an increasing risk to public health worldwide. Careful tracking of these plasmids in the microbial ecosystem is warranted.

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Malloy, Giovanni S. P., Margaret L. Brandeau, and Jeremy D. Goldhaber-Fiebert. "Modeling the Cost-Effectiveness of Interventions to Prevent Plague in Madagascar." Tropical Medicine and Infectious Disease 6, no. 2 (June 11, 2021): 101. http://dx.doi.org/10.3390/tropicalmed6020101.

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Plague (Yersinia pestis) remains endemic in certain parts of the world. We assessed the cost-effectiveness of plague control interventions recommended by the World Health Organization with particular consideration to intervention coverage and timing. We developed a dynamic model of the spread of plague between interacting populations of humans, rats, and fleas and performed a cost-effectiveness analysis calibrated to a 2017 Madagascar outbreak. We assessed three interventions alone and in combination: expanded access to antibiotic treatment with doxycycline, mass distribution of doxycycline prophylaxis, and mass distribution of malathion. We varied intervention timing and coverage levels. We calculated costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios from a healthcare perspective. The preferred intervention, using a cost-effectiveness threshold of $1350/QALY (GDP per capita in Madagascar), was expanded access to antibiotic treatment with doxycycline with 100% coverage starting immediately after the first reported case, gaining 543 QALYs at an incremental cost of $1023/QALY gained. Sensitivity analyses support expanded access to antibiotic treatment and leave open the possibility that mass distribution of doxycycline prophylaxis or mass distribution of malathion could be cost-effective. Our analysis highlights the potential for rapid expansion of access to doxycycline upon recognition of plague outbreaks to cost-effectively prevent future large-scale plague outbreaks and highlights the importance of intervention timing.

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Nelson, Christina, Shannon Fleck-Derderian, Katharine Cooley, Heidi Becksted, Dana Meaney-Delman, and Paul Mead. "1636. Antibiotic Treatment of Human Plague: A Systematic Literature Review of Worldwide Cases, 1937–2016." Open Forum Infectious Diseases 6, Supplement_2 (October 2019): S596—S597. http://dx.doi.org/10.1093/ofid/ofz360.1500.

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Abstract Background Yersinia pestis remains endemic in countries throughout Africa, Asia, and the Americas and is a tier 1 bioterrorism agent. Antibiotic treatment with aminoglycosides such as streptomycin or gentamicin is effective when initiated early in the course of illness but can have serious side effects. Alternatives such as fluoroquinolones, tetracyclines, and sulfonamides are potentially safer but currently lack robust human data on their efficacy. Methods We searched PubMed Central, Medline, Embase, CINAHL, and other databases for articles in any language with terms related to plague, Yersinia pestis, and antibiotics. Articles that contained case-level information on antibiotic treatment and patient outcome were included. We abstracted information related to patient demographics, clinical features of plague, treatment, and survival using a standardized form. Results Among 4,874 articles identified and screened, we found 723 published cases of treated plague reported between 1937 and 2016. Fifty-two percent of patients were male; median age was 22 years (range: 8 days-80 years). Cases were most commonly reported from the United States (21%), India (13%), China (11%), Vietnam (10%), and Madagascar (10%). Overall, the case fatality rate was 21%. The majority of patients had primary bubonic (64%), pneumonic (21%), or septicemic (4%) plague, of which survival was 83%, 71%, and 55%, respectively. Among those treated with an aminoglycoside (n = 386, 53%), survival was 86%. Among those treated with a tetracycline (n = 145, 20%), fluoroquinolone (n = 45, 6%), or sulfonamide (n = 311, 43%), survival was 90%, 84%, and 77%, respectively. Survival rates did not substantially differ between patients treated with one vs. two classes of antibiotics (table). Conclusion Published cases of treated plague offer an opportunity to evaluate the treatment efficacy of different antibiotic classes. In addition to aminoglycosides, tetracyclines, fluoroquinolones, and sulfonamides appear to be effective for plague treatment, although publication bias and low numbers in certain treatment groups may limit interpretation. Disclosures All authors: No reported disclosures.

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Ehlers, Julian, Andreas Krüger, Solofomalala Jacques Rakotondranary, Rakotomalala Yedidya Ratovonamana, Sven Poppert, Jörg Ulrich Ganzhorn, and Dennis Tappe. "Molecular detection of Rickettsia spp., Borrelia spp., Bartonella spp. and Yersinia pestis in ectoparasites of endemic and domestic animals in southwest Madagascar." Acta Tropica 205 (May 2020): 105339. http://dx.doi.org/10.1016/j.actatropica.2020.105339.

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Rivo Lova Herilanto, Rakotomalala, Randriamanga Lovasoa, Karol Mihary Soa, Aurélien Mioramalala Sedera, and Robinson Annick Lalaina. "Clinical picture of pulmonary plague observed in the paediatric wards of antananarivo." Journal of Advanced Pediatrics and Child Health 4, no. 1 (May 13, 2021): 046–49. http://dx.doi.org/10.29328/journal.japch.1001031.

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Introduction: In Madagascar, plague is a highly contagious acute endemic infectious disease. The diagnosis of the most severe form of pneumonic plague remains difficult in children, hence the objectives of the present study; which is to identify the clinical signs of this clinical form in children and to describe its epidemiological and evolutionary profile. Methods: A retrospective case-control study was conducted in four pediatric wards in Antananarivo during the urban pneumonic plague outbreak from September 2017 to January 2018. Those cases were defined as children aged 0-15 years old suspected of having plague with positive RDT and PCR, and they were defined as children aged 0-15 years old with negative RDT and PCR. Results: Fifty-two cases of pneumonic plague were identified, half of which (50%) were under 24 months of age. A male predominance was noted with a sex ratio of 1.23 and 86.54% of the patients were from urban areas. Several clinical signs were found but none was specific for pneumonic plague: cough (59.62% p: 0.5), dyspnea (3.85% p: 0.16), chest pain (3.85% p: 0.26%), hemoptysis (7.69% p: 0.17), vomiting (9.62% p: 0.14), diarrhea (11.54% p: 0.45), altered general condition (38.46% p: 0.24%). Two deaths were noted (3.8%). Conclusion: No specific clinical warning signs have been identified in childhood pneumonic plague. In the event of an epidemic of urban pneumonic plague, any bacterial pneumonia should at least initially include active treatment against Yersinia pestis.

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Fricke, W. Florian, Timothy J. Welch, Patrick F. McDermott, Mark K. Mammel, J. Eugene LeClerc, David G. White, Thomas A. Cebula, and Jacques Ravel. "Comparative Genomics of the IncA/C Multidrug Resistance Plasmid Family." Journal of Bacteriology 191, no. 15 (May 29, 2009): 4750–57. http://dx.doi.org/10.1128/jb.00189-09.

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ABSTRACT Multidrug resistance (MDR) plasmids belonging to the IncA/C plasmid family are widely distributed among Salmonella and other enterobacterial isolates from agricultural sources and have, at least once, also been identified in a drug-resistant Yersinia pestis isolate (IP275) from Madagascar. Here, we present the complete plasmid sequences of the IncA/C reference plasmid pRA1 (143,963 bp), isolated in 1971 from the fish pathogen Aeromonas hydrophila, and of the cryptic IncA/C plasmid pRAx (49,763 bp), isolated from Escherichia coli transconjugant D7-3, which was obtained through pRA1 transfer in 1980. Using comparative sequence analysis of pRA1 and pRAx with recent members of the IncA/C plasmid family, we show that both plasmids provide novel insights into the evolution of the IncA/C MDR plasmid family and the minimal machinery necessary for stable IncA/C plasmid maintenance. Our results indicate that recent members of the IncA/C plasmid family evolved from a common ancestor, similar in composition to pRA1, through stepwise integration of horizontally acquired resistance gene arrays into a conserved plasmid backbone. Phylogenetic comparisons predict type IV secretion-like conjugative transfer operons encoded on the shared plasmid backbones to be closely related to a group of integrating conjugative elements, which use conjugative transfer for horizontal propagation but stably integrate into the host chromosome during vegetative growth. A hipAB toxin-antitoxin gene cluster found on pRA1, which in Escherichia coli is involved in the formation of persister cell subpopulations, suggests persistence as an early broad-spectrum antimicrobial resistance mechanism in the evolution of IncA/C resistance plasmids.

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Andrianaivoarimanana, Voahangy, David M. Wagner, Dawn N. Birdsell, Birgit Nikolay, Faniry Rakotoarimanana, Lovasoa N. Randriantseheno, Amy J. Vogler, et al. "Transmission of Antimicrobial Resistant Yersinia pestis During a Pneumonic Plague Outbreak." Clinical Infectious Diseases, July 9, 2021. http://dx.doi.org/10.1093/cid/ciab606.

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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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Andrianaivoarimanana, Voahangy, Alice Lantoniaina Iharisoa, Lila Rahalison, Marie Laurette Ralimanantsoa, Maherisoa Ratsitorahina, Rado J. L. Rakotonanahary, Elisabeth Carniel, Christian Demeure, and Minoarisoa Rajerison. "Short- and long-term humoral immune response against Yersinia pestis in plague patients, Madagascar." BMC Infectious Diseases 20, no. 1 (November 10, 2020). http://dx.doi.org/10.1186/s12879-020-05565-8.

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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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Ramasindrazana, Beza, Mamionah N. J. Parany, Fanohinjanaharinirina Rasoamalala, Mercia Rasoanoro, Soloandry Rahajandraibe, Amy J. Vogler, Jason W. Sahl, Voahangy Andrianaivoarimanana, Minoarisoa Rajerison, and David M. Wagner. "Local‐scale diversity of Yersinia pestis : A case study from Ambohitromby, Ankazobe District, Madagascar." Zoonoses and Public Health, September 3, 2021. http://dx.doi.org/10.1111/zph.12892.

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Aftalion, Moshe, Ronit Aloni-Grinstein, Voahangy Andrianaivoarimanana, Alice Lantoniaina Iharisoa, Shlomo Shmaya, David Gur, Orly Laskar, Minoarisoa Rajerison, and Emanuelle Mamroud. "Improved Selective BIN Agar for a Better Rate of Yersinia pestis Isolation from Primary Clinical Specimens in Suspected Madagascar Plague Cases." Journal of Clinical Microbiology 59, no. 8 (July 19, 2021). http://dx.doi.org/10.1128/jcm.00564-21.

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According to the WHO, 75% of the world’s plague cases are found in Madagascar, with an average of 200 to 700 cases suspected annually (mainly bubonic plague). In 2017, a pneumonic plague epidemic of unusual proportions occurred, which raised several challenges for laboratory confirmation of cases, pointing to the need for the development of Yersinia pestis isolation procedures, especially those that can be performed in remote areas. As the WHO gold standard for plague diagnosis is bacterial culture, we sought to develop a simple method to prepare a highly selective medium, fit for use in remote areas where plague is endemic. The performance of the new medium, named improved BIN, was examined in terms of growth support and selectivity with spiked samples as well in isolating Y. pestis from clinical specimens, and it was compared to the results obtained with commercially available selective media.

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Andrianaivoarimanana, Voahangy, Minoarisoa Rajerison, and Ronan Jambou. "Exposure to Yersinia pestis increases resistance to plague in black rats and modulates transmission in Madagascar." BMC Research Notes 11, no. 1 (December 2018). http://dx.doi.org/10.1186/s13104-018-3984-3.

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Krasil'nikova, E., A. Trunyakova, A. Vagaiskaya, T. Svetoch, R. Shaikhutdinova, and S. Dentovskaya. "A SEARCH FOR NEW MOLECULAR TARGETS FOR OPTIMIZING PLAGUE PREVENTIVE VACCINATION AND THERAPY." Russian Journal of Infection and Immunity, June 26, 2019. http://dx.doi.org/10.15789/2220-7619-snm-1254.

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The causative agent of plague, Yersinia pestis, is a highly virulent bacterial pathogen and a potential bioweapon. Depending on the route of infection, two prevalent forms of the disease – bubonic and pneumonic, are known. The latter is featured by a high fatality rate. Mortality in untreated bubonic plague patients reaches up to 40-60%, whereas untreated pneumonic plague is always lethal. The development of the infectious process in susceptible host is accounted for by a whole set of pathogenicity factors in plaque pathogen displaying various functional modalities being expressed depending on stage of infectious process, providing their coordinated expression. Knocking out any of such factors, in turn, may not either affect microbe virulence or lead to its attenuation. A search for new Yersinia pestis pathogenicity factors and subsequent development of highly effective subunit and live attenuated plague vaccines inducing development of pronounced cellular and humoral immune reactions, and/or assessment of their potential use as molecular targets for plague therapy still remain a pressing issue, as both currently licensed plague vaccines do not meet the WHO requirements, whereas strains of plague microbe isolated in Madagascar are resistant to all drugs recommended for plague antibacterial therapy. Here we summarize an impact of described and newly discovered pathogenicity factors into the virulence of Y. pestis strains and their protective anti-plague activity. An effect of loss of genes encoding regulatory proteins as well as mutations in the genes for various transport systems of Y. pestis on attenuation of virulent strains is described as well. Perspectives for introducing characterized antigens into prototype subunit vaccine as well as some other obtained mutants into prototypes of living attenuating vaccines were assessed. The use of antibiotics for plague treatment has been embraced by the World Health Organization Expert Committee on Plague as the ‘gold standard’ treatment. However, concerns regarding development of antibiotic-resistant Y. pestis strains accounted for further exploring alternatives to plaque therapy. Several research groups continue working on seeking for other alternative approaches, e.g. treatment with inhibitors of pathogenicity factors. Preliminary data attempting to treat plague patients with pathogenicity factor inhibitors are summarized. Аnti-virulence drugs targeting key microbial factors represent new promising therapeutic options in fight against antibiotic-resistant bacteria.

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Journal articles on the topic 'Yersinia pestis – Madagascar'

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