{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T15:01:26Z","timestamp":1793718086180,"version":"4.6.1"},"reference-count":120,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,4,25]],"date-time":"2024-04-25T00:00:00Z","timestamp":1714003200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>Leptospirosis, one of the most common global zoonotic infections, significantly impacts global human health, infecting more than a million people and causing approximately 60,000 deaths annually. This mini-review explores effective treatment strategies for leptospirosis, considering its epidemiology, clinical manifestations, and current therapeutic approaches. Emphasis is placed on antibiotic therapy, including recommendations for mild and severe cases, as well as the role of probiotics in modulating the gut microbiota. Furthermore, novel treatment options, such as bacteriophages and newly synthesized\/natural compounds, are discussed, and the findings are expected to provide insights into promising approaches for combating leptospirosis.<\/jats:p>","DOI":"10.3389\/fmicb.2024.1403765","type":"journal-article","created":{"date-parts":[[2024,4,25]],"date-time":"2024-04-25T00:52:00Z","timestamp":1714006320000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":54,"title":["Current treatment options for leptospirosis: a mini-review"],"prefix":"10.3389","volume":"15","author":[{"given":"Pavlo","family":"Petakh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Payam","family":"Behzadi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentyn","family":"Oksenych","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oleksandr","family":"Kamyshnyi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,4,25]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1016\/0378-1135(86)90087-8","article-title":"Development of an improved selective medium for isolation of leptospires from clinical material","volume":"12","author":"Adler","year":"1986","journal-title":"Vet. Microbiol."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1080043","DOI":"10.3389\/fimmu.2023.1080043","article-title":"Gut and airway microbiota dysbiosis and their role in COVID-19 and long-COVID","volume":"14","author":"Ancona","year":"2023","journal-title":"Front. Immunol."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"15","DOI":"10.4103\/ijmr.IJMR_1022_16","article-title":"Advances & challenges in leptospiral vaccine development","volume":"147","author":"Bashiru","year":"2018","journal-title":"Indian J. Med. Res."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/j.cell.2014.03.011","article-title":"Role of the microbiota in immunity and inflammation","volume":"157","author":"Belkaid","year":"2014","journal-title":"J Cell Metab."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"1353","DOI":"10.1093\/trstmh\/trab036","article-title":"Prevention, control and management of leptospirosis in India: an evidence gap map","volume":"115","author":"Beri","year":"2021","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1038\/s41579-019-0278-2","article-title":"The pan-immune system of bacteria: antiviral defence as a community resource","volume":"18","author":"Bernheim","year":"2020","journal-title":"Nat. Rev. Microbiol."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2017\/5035371","article-title":"Desired turbulence? Gut-lung axis, immunity, and lung cancer","volume":"2017","author":"Bingula","year":"2017","journal-title":"J. Oncol."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"1167","DOI":"10.3390\/pathogens12091167","article-title":"Leptospirosis and the environment: A review and future directions","volume":"12","author":"Bradley","year":"2023","journal-title":"Pathogens."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"995","DOI":"10.1093\/infdis\/jir875","article-title":"Leptospiral immunoglobulin-like proteins interact with human complement regulators factor H, FHL-1, FHR-1, and C4BP","volume":"205","author":"Castiblanco-Valencia","year":"2012","journal-title":"J Infect Dis"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"100741","DOI":"10.1016\/j.cegh.2021.100741","article-title":"A short review on leptospirosis: clinical manifestations, diagnosis and treatment","volume":"11","author":"Chacko","year":"2021","journal-title":"Clin Epidemiol Global Health."},{"key":"ref11","first-page":"501","article-title":"Antibiotics for the treatment of leptospirosis: systematic review and meta-analysis of controlled trials","volume":"4","author":"Charan","year":"2013","journal-title":"Int. J. Prev. Med."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"2441","DOI":"10.1128\/IAI.01635-06","article-title":"Physiological osmotic induction of Leptospira interrogans adhesion: LigA and LigB bind extracellular matrix proteins and fibrinogen","volume":"75","author":"Choy","year":"2007","journal-title":"Infect. Immun."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"191","DOI":"10.3390\/ani11010191","article-title":"Insight into the epidemiology of leptospirosis: A review of Leptospira isolations from \u201cunconventional\u201d hosts","volume":"11","author":"Cilia","year":"2021","journal-title":"Animals"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"e0003898","DOI":"10.1371\/journal.pntd.0003898","article-title":"Global morbidity and mortality of leptospirosis: a systematic review","volume":"9","author":"Costa","year":"2015","journal-title":"PLoS Negl. Trop. Dis."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1179\/000349809X12554106963717","article-title":"Hypomagnesaemia in the first 10 days of severe leptospirosis","volume":"103","author":"Craig","year":"2009","journal-title":"Ann. Trop. Med. Parasitol."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"1844","DOI":"10.1016\/j.vaccine.2019.02.010","article-title":"Evaluation of different strategies to promote a protective immune response against leptospirosis using a recombinant LigA and LigB chimera","volume":"37","author":"da Cunha","year":"2019","journal-title":"Vaccine"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"1195094","DOI":"10.3389\/frwa.2023.1195094","article-title":"Leptospirosis: toward a better understanding of the environmental lifestyle of Leptospira","volume":"5","author":"Davignon","year":"2023","journal-title":"Front Water."},{"key":"ref18","volume-title":"Jarisch Herxheimer reaction","author":"Dhakal","year":"2022"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1590\/S1413-86702007000100029","article-title":"Pathology and pathophysiology of pulmonary manifestations in leptospirosis","volume":"11","author":"Dolhnikoff","year":"2007","journal-title":"Braz. J. Infect. Dis."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"4120","DOI":"10.1126\/science.aar4120","article-title":"Systematic discovery of antiphage defense systems in the microbial pangenome","volume":"359","author":"Doron","year":"2018","journal-title":"Science"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"50","DOI":"10.3390\/v9030050","article-title":"A review of phage therapy against bacterial pathogens of aquatic and terrestrial organisms","volume":"9","author":"Doss","year":"2017","journal-title":"Viruses"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"1427","DOI":"10.1080\/10408398.2020.1843396","article-title":"Antibiotic-induced gut dysbiosis and barrier disruption and the potential protective strategies","volume":"62","author":"Duan","year":"2022","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref23","first-page":"567","article-title":"Pharmacological treatments for acute respiratory distress syndrome: systematic review","volume":"81","author":"Duggal","year":"2015","journal-title":"Minerva Anestesiol."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1186\/s12916-023-02961-0","article-title":"Probiotic supplementation during antibiotic treatment is unjustified in maintaining the gut microbiome diversity: a systematic review and meta-analysis","volume":"21","author":"\u00c9li\u00e1s","year":"2023","journal-title":"BMC Med."},{"key":"ref25","volume-title":"Leptospira and leptospirosis","author":"Faine","year":"1999"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"1849","DOI":"10.1016\/B978-0-12-818619-0.00159-3","article-title":"Leptospira and leptospirosis","volume-title":"Molecular medical microbiology","author":"Fraga","year":"2024"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1093\/clinids\/13.2.207","article-title":"The Jarisch-Herxheimer reaction in leptospirosis: possible pathogenesis and review","volume":"13","author":"Friedland","year":"1991","journal-title":"Rev. Infect. Dis."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"1187","DOI":"10.1038\/nm.4176","article-title":"Neonatal gut microbiota associates with childhood multisensitized atopy and T cell differentiation","volume":"22","author":"Fujimura","year":"2016","journal-title":"J. Nat. Med."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1016\/j.femsle.2005.02.004","article-title":"Whole-genome analysis of Leptospira interrogans to identify potential vaccine candidates against leptospirosis","volume":"244","author":"Gamberini","year":"2005","journal-title":"FEMS Microbiol. Lett."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"1131","DOI":"10.1016\/0923-2508(90)90086-6","article-title":"First isolation of bacteriophages for a spirochaete: potential genetic tools for Leptospira","volume":"141","author":"Girons","year":"1990","journal-title":"Res. Microbiol."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"44","DOI":"10.11604\/pamj.2023.44.121.34244","article-title":"Incidence and distribution of human leptospirosis in the Western Cape Province, South Africa (2010-2019): a retrospective study","volume":"44","author":"Gizamba","year":"2023","journal-title":"Pan Afr. Med. J."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1590\/S0036-46651998000100012","article-title":"Use of doxycycline for leptospirosis after high-risk exposure in S\u00e3o Paulo, Brazil","volume":"40","author":"Gonsalez","year":"1998","journal-title":"Rev. Inst. Med. Trop. S\u00e3o Paulo"},{"key":"ref33","first-page":"61","article-title":"Modified EMJH medium for cultivation of Leptospira interrogans serogroup ballum","volume":"38","author":"Gonz\u00e1lez","year":"2006","journal-title":"Rev. Argent. Microbiol."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.bjbas.2016.12.007","article-title":"Microwave-assisted synthesis, structural activity relationship and biological activity of some new quinoxaline Schiff base derivatives as highly potent spirochete bactericidal agents","volume":"6","author":"Gopi","year":"2017","journal-title":"Beni-Suef Univ J Basic Appl Sci"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"1018","DOI":"10.1007\/s42399-021-00833-3","article-title":"Recent progress in the treatment of leptospirosis","volume":"3","author":"Gopi","year":"2021","journal-title":"SN Comprehens Clin Med."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"463","DOI":"10.3389\/fimmu.2017.00463","article-title":"Discovery of novel leptospirosis vaccine candidates using reverse and structural vaccinology","volume":"8","author":"Grassmann","year":"","journal-title":"Front. Immunol."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"256","DOI":"10.3389\/fimmu.2017.00256","article-title":"A universal vaccine against leptospirosis: are we going in the right direction?","volume":"8","author":"Grassmann","year":"","journal-title":"Front. Immunol."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1097\/QCO.0b013e3280106818","article-title":"Antimicrobial therapy of leptospirosis","volume":"19","author":"Griffith","year":"2006","journal-title":"Curr. Opin. Infect. Dis."},{"key":"ref39","doi-asserted-by":"publisher","first-page":"347","DOI":"10.4103\/0970-2113.102822","article-title":"Pulmonary manifestations of leptospirosis","volume":"29","author":"Gulati","year":"2012","journal-title":"Lung India"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"1125","DOI":"10.3390\/pathogens10091125","article-title":"Current evidence on the antimicrobial treatment and chemoprophylaxis of human leptospirosis: a meta-analysis","volume":"10","author":"Guzm\u00e1n P\u00e9rez","year":"2021","journal-title":"Pathogens."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1007\/978-3-662-45059-8_5","article-title":"Leptospirosis in humans","volume":"387","author":"Haake","year":"2015","journal-title":"Leptospira Leptospir"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"e1010694","DOI":"10.1371\/journal.pgen.1010694","article-title":"The defense island repertoire of the Escherichia coli pan-genome","volume":"19","author":"Hochhauser","year":"2023","journal-title":"PLoS Genet."},{"key":"ref43","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1038\/nature18848","article-title":"The microbiota in adaptive immune homeostasis and disease","volume":"535","author":"Honda","year":"2016","journal-title":"Nature"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"2646","DOI":"10.1128\/AAC.47.8.2646-2648.2003","article-title":"In vitro susceptibilities of seven Leptospira species to traditional and newer antibiotics","volume":"47","author":"Hospenthal","year":"2003","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref45","doi-asserted-by":"publisher","first-page":"5787","DOI":"10.1016\/j.vaccine.2006.05.008","article-title":"The antipoverty vaccines","volume":"24","author":"Hotez","year":"2006","journal-title":"Vaccine"},{"key":"ref46","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1016\/S0065-2164(10)70007-1","article-title":"Bacteriophage host range and bacterial resistance","volume":"70","author":"Hyman","year":"2010","journal-title":"Adv. Appl. Microbiol."},{"key":"ref47","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.ejmech.2016.09.020","article-title":"Discovery of 6,7-dihydro-3H-pyrano[4,3-c]isoxazol-3-ones as a new class of pathogen specific anti-leptospiral agents","volume":"125","author":"Ilangovan","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"ref48","doi-asserted-by":"publisher","DOI":"10.21161\/mjm.180213","article-title":"In-vitro antileptospiral activity of Canarium odontophyllum Miq. (Dabai) leaves extract","author":"Ishak","year":"2019","journal-title":"Malays J Microbiol"},{"key":"ref49","doi-asserted-by":"publisher","first-page":"219","DOI":"10.15406\/jmen.2018.06.00218","article-title":"Leptospirosis: A disease with global prevalence","volume":"6","author":"Jamal Khan","year":"2018","journal-title":"J Microbiol Exp."},{"key":"ref50","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1590\/0074-02760170130","article-title":"Whole-genome sequencing of Leptospira interrogans from southern Brazil: genetic features of a highly virulent strain","volume":"113","author":"Jorge","year":"2018","journal-title":"Mem. Inst. Oswaldo Cruz"},{"key":"ref51","doi-asserted-by":"publisher","first-page":"835","DOI":"10.1007\/s10096-019-03797-4","article-title":"Leptospirosis: a neglected tropical zoonotic infection of public health importance\u2014an updated review","volume":"39","author":"Karpagam","year":"2020","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref52","doi-asserted-by":"publisher","first-page":"204993612311544","DOI":"10.1177\/20499361231154443","article-title":"Current understanding of antibiotic-associated dysbiosis and approaches for its management","volume":"10","author":"Kesavelu","year":"2023","journal-title":"Therapeut Adv Infect Dis."},{"key":"ref53","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.vetimm.2013.08.002","article-title":"A new tetravalent canine leptospirosis vaccine provides at least 12 months immunity against infection","volume":"158","author":"Klaasen","year":"2014","journal-title":"Vet. Immunol. Immunopathol."},{"key":"ref54","first-page":"210","article-title":"Leptospirosis vaccines: past, present, and future","volume":"51","author":"Koizumi","year":"2005","journal-title":"J. Postgrad. Med."},{"key":"ref55","doi-asserted-by":"publisher","first-page":"2775","DOI":"10.1111\/j.1462-2920.2009.01970.x","article-title":"Position paper: the creation of a rational scheme for the nomenclature of viruses of Bacteria and Archaea","volume":"11","author":"Kropinski","year":"2009","journal-title":"Environ. Microbiol."},{"key":"ref56","article-title":"Indian guidelines for the diagnosis and management of human leptospirosis","volume-title":"Medicine Update","author":"Kumar","year":"2013"},{"key":"ref57","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1111\/j.1469-0691.2007.01662.x","article-title":"Safety and immunogenicity of subcutaneous or intramuscular administration of a monovalent inactivated vaccine against Leptospira interrogans serogroup Icterohaemorrhagiae in healthy volunteers","volume":"13","author":"Laurichesse","year":"2007","journal-title":"Clin. Microbiol. Infect."},{"key":"ref58","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1016\/j.ejphar.2018.05.003","article-title":"Pro-and anti-inflammatory effects of short chain fatty acids on immune and endothelial cells","volume":"831","author":"Li","year":"2018","journal-title":"Eur J Pharmacol."},{"key":"ref59","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1016\/j.ijantimicag.2017.12.024","article-title":"Antibiotic susceptibilities of livestock isolates of leptospira","volume":"51","author":"Liegeon","year":"2018","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref60","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1590\/S1678-91992011000400006","article-title":"Ovine leptospirosis in Brazil","volume":"17","author":"Lucheis","year":"2011","journal-title":"J Venom Anim Toxins incl. Trop Dis."},{"key":"ref61","doi-asserted-by":"publisher","first-page":"4360","DOI":"10.1093\/nar\/gkt157","article-title":"Comparative genomics of defense systems in archaea and bacteria","volume":"41","author":"Makarova","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref62","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1590\/s1020-49892004000400005","article-title":"Efficacy and safety of a vaccine against human leptospirosis in Cuba","volume":"15","author":"Mart\u00ednez","year":"2004","journal-title":"Pan Am. J. Public Health"},{"key":"ref63","doi-asserted-by":"publisher","first-page":"696","DOI":"10.7326\/0003-4819-100-5-696","article-title":"Doxycycline therapy for leptospirosis","volume":"100","author":"McClain","year":"1984","journal-title":"Ann. Intern. Med."},{"key":"ref64","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1111\/j.1365-2672.2009.04220.x","article-title":"Leptospirosis: risks during recreational activities","volume":"107","author":"Monahan","year":"2009","journal-title":"J. Appl. Microbiol."},{"key":"ref65","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1093\/jac\/dkl453","article-title":"Effect of timing and duration of azithromycin therapy of leptospirosis in a hamster model","volume":"59","author":"Moon","year":"2007","journal-title":"J. Antimicrob. Chemother."},{"key":"ref66","doi-asserted-by":"publisher","first-page":"229","DOI":"10.5694\/j.1326-5377.2004.tb06248.x","article-title":"Fatal leptospirosis presenting as musculoskeletal pain","volume":"181","author":"Morgan","year":"2004","journal-title":"Med. J. Aust."},{"key":"ref67","doi-asserted-by":"publisher","DOI":"10.13140\/2.1.1209.1527","article-title":"In vitro anti leptospiral activity of chloroform extract of Piper betle L. world","author":"Nagarajan","year":"2014","journal-title":"J. Pharm. Sci."},{"key":"ref68","doi-asserted-by":"publisher","first-page":"24","DOI":"10.22192\/ijcrbm.2017.02.02.004","article-title":"In vitro anti leptospiral activity of ethanolic extract of the leaf of Andrographis paniculata Nees (Acanthaceae)","volume":"2","author":"Natarajaseenivasan","year":"2017","journal-title":"Int J Curr Res Biol Med."},{"key":"ref69","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1093\/femsre\/fuy018","article-title":"Antibiotics in early life: dysbiosis and the damage done","volume":"42","author":"Neuman","year":"2018","journal-title":"FEMS Microbiol. Rev."},{"key":"ref70","doi-asserted-by":"publisher","first-page":"403","DOI":"10.3103\/S1068367415050134","article-title":"Bactericidal action of the Bacillus subtilis bacterial strains on the agents of leptospirosis","volume":"41","author":"Neustroev","year":"2015","journal-title":"Russ. Agric. Sci."},{"key":"ref71","doi-asserted-by":"publisher","first-page":"1073","DOI":"10.3390\/nu11051073","article-title":"Impact of gut microbiota composition on onset and progression of chronic non-communicable diseases","volume":"11","author":"Noce","year":"2019","journal-title":"J. Nutr."},{"key":"ref72","doi-asserted-by":"publisher","first-page":"1507","DOI":"10.1086\/375226","article-title":"Ceftriaxone compared with sodium penicillin G for treatment of severe leptospirosis","volume":"36","author":"Panaphut","year":"2003","journal-title":"Clin. Infect. Dis."},{"key":"ref73","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1016\/j.ijantimicag.2006.08.021","article-title":"Optimal treatment of leptospirosis: queries and projections","volume":"28","author":"Pappas","year":"2006","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref74","doi-asserted-by":"publisher","first-page":"e0011454","DOI":"10.1371\/journal.pntd.0011454","article-title":"Demographic and clinical risk factors associated with severity of lab-confirmed human leptospirosis in Colombia, 2015\u20132020","volume":"17","author":"Parra Barrera","year":"2023","journal-title":"PLoS Negl. Trop. Dis."},{"key":"ref75","doi-asserted-by":"publisher","first-page":"5607","DOI":"10.1099\/ijsem.0.004332","article-title":"List of prokaryotic names with standing in nomenclature (LPSN) moves to the DSMZ","volume":"70","author":"Parte","year":"2020","journal-title":"Int. J. Syst. Evol. Microbiol."},{"key":"ref76","doi-asserted-by":"publisher","first-page":"1830","DOI":"10.3390\/biom12121830","article-title":"Weil's disease-Immunopathogenesis, multiple organ failure, and potential role of gut microbiota","volume":"12","author":"Petakh","year":"","journal-title":"Biomol. Ther."},{"key":"ref77","doi-asserted-by":"publisher","first-page":"584","DOI":"10.1089\/vbz.2022.0063","article-title":"Leptospirosis: prognostic model for patient mortality in the Transcarpathian region, Ukraine","volume":"22","author":"Petakh","year":"","journal-title":"Vector Borne Zoonotic Dis."},{"key":"ref78","doi-asserted-by":"publisher","first-page":"272","DOI":"10.53854\/liim-3002-13","article-title":"Predictors of lethality in severe leptospirosis in Transcarpathian region of Ukraine","volume":"30","author":"Petakh","year":"2022","journal-title":"Infez. Med."},{"key":"ref79","doi-asserted-by":"publisher","first-page":"1345684","DOI":"10.3389\/fmicb.2024.1345684","article-title":"Exploring the complex interplay: gut microbiome, stress, and leptospirosis","volume":"15","author":"Petakh","year":"","journal-title":"Front. Microbiol."},{"key":"ref80","doi-asserted-by":"publisher","first-page":"546","DOI":"10.3390\/microorganisms12030546","article-title":"Exploring Leptospira interrogans FDAARGOS_203: insights into AMR and anti-phage","volume":"12","author":"Petakh","year":"","journal-title":"Defense"},{"key":"ref81","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1177\/00494755231187673","article-title":"Identifying risk factors and disease severity in leptospirosis: A meta-analysis of clinical predictors","volume":"53","author":"Petakh","year":"2023","journal-title":"Trop. Doct."},{"key":"ref82","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1186\/s40101-023-00347-y","article-title":"Leptospirosis in Malaysia: current status, insights, and future prospects","volume":"42","author":"Philip","year":"2023","journal-title":"J. Physiol. Anthropol."},{"key":"ref83","doi-asserted-by":"publisher","first-page":"e0005870","DOI":"10.1371\/journal.pntd.0005870","article-title":"Pre-treatment with Lactobacillus plantarum prevents severe pathogenesis in mice infected with Leptospira interrogans and may be associated with recruitment of myeloid cells","volume":"11","author":"Potula","year":"2017","journal-title":"PLoS Negl. Trop. Dis."},{"key":"ref84","doi-asserted-by":"publisher","first-page":"788","DOI":"10.4103\/0250-474X.49124","article-title":"In vitro evaluation of Eclipta alba against serogroups of Leptospira interrogans","volume":"70","author":"Prabhu","year":"2008","journal-title":"Indian J. Pharm. Sci."},{"key":"ref85","first-page":"1000","article-title":"Synthesis, characterisation and pharmacological evaluation of novel 4-aryl-3-chloro-N-pyridine-2-yl-2-azetidinone","volume":"1","author":"Puratchikody","year":"2009","journal-title":"Int. J. ChemTech Res."},{"key":"ref86","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3109\/1040841X.2013.787387","article-title":"Pathogenic, diagnostic and vaccine potential of leptospiral outer membrane proteins (OMPs)","volume":"41","author":"Raja","year":"2015","journal-title":"Crit. Rev. Microbiol."},{"key":"ref87","doi-asserted-by":"publisher","first-page":"14","DOI":"10.7861\/clinmed.2021-0784","article-title":"Leptospirosis: clinical aspects","volume":"22","author":"Rajapakse","year":"2022","journal-title":"Clin. Med."},{"key":"ref88","doi-asserted-by":"publisher","first-page":"572912","DOI":"10.3389\/fcimb.2020.572912","article-title":"Antibiotics as major disruptors of gut microbiota","volume":"10","author":"Ramirez","year":"2020","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref89","doi-asserted-by":"publisher","first-page":"e228","DOI":"10.1371\/journal.pntd.0000228","article-title":"Impact of environment and social gradient on Leptospira infection in urban slums","volume":"2","author":"Reis","year":"2008","journal-title":"PLoS Negl. Trop. Dis."},{"key":"ref90","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1093\/trstmh\/tru148","article-title":"High dose corticosteroids in severe leptospirosis: a systematic review","volume":"108","author":"Rodrigo","year":"2014","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"ref91","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1016\/j.medmal.2004.02.006","article-title":"Efficacy of Spirolept vaccine against human leptospirosis as estimated by passive protection of laboratory rodents","volume":"34","author":"Rodriguez-Gonzalez","year":"2004","journal-title":"Med. Mal. Infect."},{"key":"ref92","first-page":"37","article-title":"Reactogenecity and immunogenecity of Cuban trivalent inactivated vaccine against human leptospirosis in different vaccination schedules","volume":"54","author":"S\u00e1nchez","year":"2002","journal-title":"Rev. Cubana Med. Trop."},{"key":"ref93","doi-asserted-by":"publisher","first-page":"11781","DOI":"10.1038\/s41598-018-29983-6","article-title":"Characterization of LE3 and LE4, the only lytic phages known to infect the spirochete Leptospira","volume":"8","author":"Schiettekatte","year":"2018","journal-title":"Sci. Rep."},{"key":"ref94","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1016\/S0174-3031(81)80096-0","article-title":"Studies on the effect of antibiotic substances on leptospires and their cultivation from material with a high bacterial count. Zentralblatt fur Bakteriologie 1 Abt Originale A: Medizinische Mikrobiologie","volume":"249","author":"Sch\u00f6nberg","year":"1981","journal-title":"Infektionskrankheiten und Parasitologie."},{"key":"ref95","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1016\/S0924-8579(99)00134-X","article-title":"Randomized controlled trial of doxycycline prophylaxis against leptospirosis in an endemic area","volume":"13","author":"Sehgal","year":"2000","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref96","first-page":"775","article-title":"Biological evaluation of some novel quinoxaline bearing azetidinones including leptospirocidal study","volume-title":"J. Pharm. Res.","author":"Selvaraj","year":"2013"},{"key":"ref97","doi-asserted-by":"publisher","first-page":"2521","DOI":"10.1186\/s12889-023-17391-z","article-title":"Spatio-temporal modeling of human leptospirosis prevalence using the maximum entropy model","volume":"23","author":"Shirzad","year":"2023","journal-title":"BMC Public Health"},{"key":"ref98","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1099\/jmm.0.000414","article-title":"Saccharomyces boulardii improves humoral immune response to DNA vaccines against leptospirosis","volume":"66","author":"Silveira","year":"2017","journal-title":"J Med Microbiol Sci"},{"key":"ref99","doi-asserted-by":"publisher","first-page":"995","DOI":"10.1007\/s10529-007-9346-1","article-title":"Biotechnological challenges of phage therapy","volume":"29","author":"Skurnik","year":"2007","journal-title":"Biotechnol. Lett."},{"key":"ref100","doi-asserted-by":"publisher","first-page":"915","DOI":"10.4269\/ajtmh.2008.79.915","article-title":"Case report: severe, symptomatic hypomagnesemia in acute leptospirosis","volume":"79","author":"Spichler","year":"2008","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref101","doi-asserted-by":"publisher","first-page":"620102","DOI":"10.3389\/fmed.2020.620102","article-title":"Focus on the gut\u2013kidney axis in health and disease","volume":"7","author":"Stavropoulou","year":"2021","journal-title":"J Front Med."},{"key":"ref102","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1186\/s40168-020-00991-x","article-title":"Antibiotic-associated dysbiosis affects the ability of the gut microbiota to control intestinal inflammation upon fecal microbiota transplantation in experimental colitis models","volume":"9","author":"Strati","year":"2021","journal-title":"Microbiome."},{"key":"ref103","doi-asserted-by":"publisher","first-page":"1417","DOI":"10.1086\/425001","article-title":"An open, randomized, controlled trial of penicillin, doxycycline, and cefotaxime for patients with severe leptospirosis","volume":"39","author":"Suputtamongkol","year":"2004","journal-title":"Clin. Infect. Dis."},{"key":"ref104","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1056\/NEJM198402233100805","article-title":"An efficacy trial of doxycycline chemoprophylaxis against leptospirosis","volume":"310","author":"Takafuji","year":"1984","journal-title":"N. Engl. J. Med."},{"key":"ref105","doi-asserted-by":"publisher","first-page":"95","DOI":"10.3390\/vaccines7030095","article-title":"Reduced renal colonization and enhanced protection by leptospiral factor H binding proteins as a multisubunit vaccine against leptospirosis in hamsters","volume":"7","author":"Techawiwattanaboon","year":"2019","journal-title":"Vaccine"},{"key":"ref106","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1038\/s41575-018-0011-z","article-title":"The gut\u2013liver axis and the intersection with the microbiome","volume":"15","author":"Tripathi","year":"2018","journal-title":"J Nat Rev Gastroenterol Hepatol."},{"key":"ref107","doi-asserted-by":"publisher","first-page":"2017","DOI":"10.1128\/microbiolspec.ARBA-0029-2017","article-title":"Antimicrobial resistance in Leptospira, Brucella, and other rarely investigated veterinary and zoonotic pathogens","volume":"6","author":"Trott","year":"2018","journal-title":"Microbiol Spectr"},{"key":"ref108","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1016\/S1672-0229(10)60026-5","article-title":"Identification of potential Leptospira phosphoheptose isomerase inhibitors through virtual high-throughput screening","volume":"8","author":"Umamaheswari","year":"2010","journal-title":"Genomics Proteomics Bioinformatics"},{"key":"ref109","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1590\/s1413-86702002000300006","article-title":"Leptospirosis as a cause of acute respiratory failure: clinical features and outcome in 35 critical care patients","volume":"6","author":"Vieira","year":"2002","journal-title":"Braz. J. Infect. Dis."},{"key":"ref110","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1089\/mdr.2015.0284","article-title":"In vitro antimicrobial susceptibility of pathogenic Leptospira biofilm","volume":"22","author":"Vinod Kumar","year":"2016","journal-title":"Microb. Drug Resist."},{"key":"ref111","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1186\/1475-2859-6-39","article-title":"Leptospirosis vaccines","volume":"6","author":"Wang","year":"2007","journal-title":"Microb. Cell Fact."},{"key":"ref112","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1016\/S0140-6736(88)91230-5","article-title":"Placebo-controlled trial of intravenous penicillin for severe and late leptospirosis","volume":"331","author":"Watt","year":"1988","journal-title":"Lancet"},{"key":"ref113","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1080\/03079450220136567a","article-title":"Comparison of an attenuated anticoccidial vaccine and an anticoccidial drug programme in commercial broiler chickens in Italy","volume":"31","author":"Williams","year":"2002","journal-title":"Avian Pathol."},{"key":"ref114","doi-asserted-by":"publisher","first-page":"294","DOI":"10.4103\/jfmpc.jfmpc_1414_21","article-title":"Covid-19 and leptospirosis, pulmonary involvement and response to steroids: A comparative observational study from a rural tertiary care center in Kerala","volume":"11","author":"Xavier","year":"2022","journal-title":"J. Family Med. Prim. Care"},{"key":"ref115","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1111\/apm.12935","article-title":"Characterization of CRISPR-Cas systems in Leptospira reveals potential application of CRISPR in genotyping of Leptospira interrogans","volume":"127","author":"Xiao","year":"2019","journal-title":"APMIS"},{"key":"ref116","doi-asserted-by":"publisher","first-page":"764","DOI":"10.1038\/s41396-021-01122-6","article-title":"Gut microbiota involved in leptospiral infections","volume":"16","author":"Xie","year":"2022","journal-title":"ISME J."},{"key":"ref117","first-page":"224","article-title":"An evaluation of the serological and epidemiological effects of the outer envelope vaccine to leptospira","volume":"66","author":"Yan","year":"2003","journal-title":"J. Chin. Med. Assoc."},{"key":"ref118","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1016\/j.cimid.2007.05.003","article-title":"Current status of leptospirosis in Japan and Philippines","volume":"30","author":"Yanagihara","year":"2007","journal-title":"Comp. Immunol. Microbiol. Infect. Dis."},{"key":"ref119","doi-asserted-by":"publisher","first-page":"108152","DOI":"10.1016\/j.biotechadv.2023.108152","article-title":"Recent advances in phage defense systems and potential overcoming strategies","volume":"65","author":"Yuan","year":"2023","journal-title":"Biotechnol. Adv."},{"key":"ref120","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1186\/s12864-015-1321-y","article-title":"Identification of three extra-chromosomal replicons in Leptospira pathogenic strain and development of new shuttle vectors","volume":"16","author":"Zhu","year":"2015","journal-title":"BMC Genomics"}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2024.1403765\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,25]],"date-time":"2024-04-25T10:59:28Z","timestamp":1714042768000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2024.1403765\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,25]]},"references-count":120,"alternative-id":["10.3389\/fmicb.2024.1403765"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2024.1403765","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,25]]},"article-number":"1403765"}}