{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T13:19:38Z","timestamp":1784899178148,"version":"3.55.0"},"update-to":[{"DOI":"10.1371\/journal.pntd.0010354","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,6,16]],"date-time":"2022-06-16T00:00:00Z","timestamp":1655337600000}}],"reference-count":55,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2022,5,31]],"date-time":"2022-05-31T00:00:00Z","timestamp":1653955200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:p>Murine typhus, which is caused by<jats:italic>Rickettsia typhi<\/jats:italic>, has a wide range of clinical manifestations. It has a low mortality rate but may result in meningoencephalitis and interstitial pneumonia in severe cases. Comparisons of complete genome sequences of<jats:italic>R<\/jats:italic>.<jats:italic>typhi<\/jats:italic>isolates from North Carolina, USA (Wilmington), Myanmar (B9991PP), and Thailand (TH1527) identified only 26 single nucleotide polymorphism (SNP) and 7 insertion-deletion (INDEL) sites in these highly syntenic genomes. Assays were developed to further define the distribution of these variant sites among 15 additional isolates of<jats:italic>R<\/jats:italic>.<jats:italic>typhi<\/jats:italic>with different histories from Asia, the USA, and Africa. Mismatch amplification mutation assays (MAMA) were validated for 22 SNP sites, while the 7 INDEL sites were analyzed directly on agarose gels. Six SNP types, 9 INDEL types, 11 total types were identified among these 18 isolates. Replicate DNA samples as well as comparisons of isolates with different passage and source histories gave consistent genetic typing profiles. Comparison of the SNP and INDEL markers to<jats:italic>R<\/jats:italic>.<jats:italic>typhi\u2019s<\/jats:italic>nearest neighbor<jats:italic>Rickettsia prowazekii<\/jats:italic>demonstrated that the majority of the SNPs represent intra-species variation that arose post divergence of these two species while several INDEL sites also exhibited intraspecies variability among the<jats:italic>R<\/jats:italic>.<jats:italic>prowazekii<\/jats:italic>genomes that have been completely sequenced. The assays for the presence of these SNP and INDEL sites, particularly the latter, comprise a low technology gel method for consistently distinguishing<jats:italic>R<\/jats:italic>.<jats:italic>typhi and R<\/jats:italic>.<jats:italic>prowazekii<\/jats:italic>as well as for differentiating genetic types of<jats:italic>R<\/jats:italic>.<jats:italic>typhi<\/jats:italic>.<\/jats:p>","DOI":"10.1371\/journal.pntd.0010354","type":"journal-article","created":{"date-parts":[[2022,5,31]],"date-time":"2022-05-31T17:38:00Z","timestamp":1654018680000},"page":"e0010354","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":12,"title":["Genetic typing of isolates of Rickettsia typhi"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6963-6849","authenticated-orcid":true,"given":"Cecilia Y.","family":"Kato","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0048-7843","authenticated-orcid":true,"given":"Ida H.","family":"Chung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0869-0264","authenticated-orcid":true,"given":"Lauren K.","family":"Robinson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina E.","family":"Eremeeva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6090-1810","authenticated-orcid":true,"given":"Gregory A.","family":"Dasch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,5,31]]},"reference":[{"key":"pntd.0010354.ref001","first-page":"37","volume-title":"Murine typhus.","author":"B Tselentis","year":"2010"},{"issue":"4","key":"pntd.0010354.ref002","first-page":"237","article-title":"The ecology of murine typhus-a critical review","volume":"75","author":"R Traub","year":"1978","journal-title":"Trop Dis Bull"},{"key":"pntd.0010354.ref003","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1086\/527443","article-title":"Murine typhus: an unrecognized suburban vector-borne disease","volume":"46","author":"R Civen","year":"2008","journal-title":"Clin Infect Dis"},{"key":"pntd.0010354.ref004","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.actatropica.2016.10.018","article-title":"Clinical and laboratory characteristics, epidemiology, and outcomes of murine typhus: A systematic review","volume":"166","author":"C Tsioutis","year":"2017","journal-title":"Acta Trop"},{"issue":"2","key":"pntd.0010354.ref005","doi-asserted-by":"crossref","first-page":"457","DOI":"10.4269\/ajtmh.16-0197","article-title":"Opossums and cat fleas: New insights in the ecology of murine typhus in Galveston, Texas","volume":"95","author":"LS Blanton","year":"2016","journal-title":"Am J Trop Med Hyg"},{"issue":"11","key":"pntd.0010354.ref006","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1097\/INF.0000000000001954","article-title":"Murine typhus in south Texas children: An 18-year review.","volume":"37","author":"A Howard","year":"2018","journal-title":"Pediatr Infect Dis J"},{"issue":"3","key":"pntd.0010354.ref007","doi-asserted-by":"crossref","first-page":"412","DOI":"10.3201\/eid1603.091028","article-title":"Murine typhus in Austin, Texas, USA, 2008.","volume":"16","author":"J Adjemian","year":"2010","journal-title":"Emerg Infect Dis"},{"key":"pntd.0010354.ref008","first-page":"1267","article-title":"Outbreak of Rickettsia typhi infection\u2014Austin, Texas, 2008.","volume":"58","author":"Centers for Disease Control and Prevention","year":"2009","journal-title":"MMWR Morb Mortal Wkly Rep"},{"issue":"10","key":"pntd.0010354.ref009","doi-asserted-by":"crossref","first-page":"1613","DOI":"10.3201\/eid1410.080571","article-title":"Rickettsia typhi and R. felis in rat fleas (Xenopsylla cheopis), Oahu, Hawaii.","volume":"14","author":"ME Eremeeva","year":"2008","journal-title":"Emerg Infect Dis"},{"issue":"7","key":"pntd.0010354.ref010","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1089\/vbz.2010.0117","article-title":"Urban focus of Rickettsia typhi and Rickettsia felis in Los Angeles, California.","volume":"11","author":"KF Abramowicz","year":"2011","journal-title":"Vector Borne Zoonotic Dis"},{"key":"pntd.0010354.ref011","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1603\/ME11291","article-title":"Two pathogens and one disease: detection and identification of flea-borne rickettsiae in areas endemic for murine typhus in California","volume":"49","author":"ME Eremeeva","year":"2012","journal-title":"J Med Entomol"},{"key":"pntd.0010354.ref012","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1089\/vbz.2012.1173","article-title":"Flea-borne rickettsioses in the north of Caldas province, Colombia.","volume":"13","author":"M Hidalgo","year":"2013","journal-title":"Vector Borne Zoonotic Dis"},{"key":"pntd.0010354.ref013","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.3201\/eid1906.121400","article-title":"Murine typhus in humans, Yucatan, Mexico","volume":"19","author":"K Dzul-Rosado","year":"2013","journal-title":"Emerg Infect Dis"},{"issue":"6","key":"pntd.0010354.ref014","doi-asserted-by":"crossref","first-page":"e20190009","DOI":"10.1590\/0037-8682-0009-2019","article-title":"First description of a clinical case of murine typhus in Campeche, Mexico.","volume":"52","author":"S Blum-Dom\u00ednguez","year":"2019","journal-title":"Rev Soc Bras Med Trop"},{"key":"pntd.0010354.ref015","doi-asserted-by":"crossref","first-page":"779","DOI":"10.3109\/00365548.2014.943283","article-title":"Murine typhus in elderly patients: a prospective study of 49 patients","volume":"46","author":"C Tsioutis","year":"2014","journal-title":"Scand J Infect Dis"},{"key":"pntd.0010354.ref016","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1001\/archinte.159.8.872","article-title":"Murine typhus as a common cause of fever of intermediate duration: a 17-year study in the south of Spain","volume":"159","author":"M Bernabeu-Wittel","year":"1999","journal-title":"Arch Intern Med"},{"key":"pntd.0010354.ref017","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.medmal.2015.01.009","article-title":"Epidemiological, clinical and laboratory features of murine typhus in central Tunisia.","volume":"45","author":"A Aouam","year":"2015","journal-title":"Med Mal Infect"},{"issue":"1","key":"pntd.0010354.ref018","doi-asserted-by":"crossref","first-page":"pii:E3","DOI":"10.3390\/tropicalmed3010003","article-title":"Tick-, flea-, and louse-borne diseases of public health and veterinary significance in Nigeria.","volume":"3","author":"O Oguntomole","year":"2018","journal-title":"Trop Med Infect Dis"},{"issue":"1","key":"pntd.0010354.ref019","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.medmal.2019.06.003","article-title":"Emergence of murine typhus in La R\u00e9union, France, 2012\u20132017.","volume":"50","author":"G Grouteau","year":"2020","journal-title":"Med Mal Infect."},{"issue":"4","key":"pntd.0010354.ref020","doi-asserted-by":"crossref","first-page":"952","DOI":"10.4269\/ajtmh.18-0076","article-title":"High morbidity due to murine typhus upsurge in urban neighborhoods in Central Israel","volume":"100","author":"E Rogozin","year":"2019","journal-title":"Am J Trop Med Hyg"},{"issue":"5","key":"pntd.0010354.ref021","doi-asserted-by":"crossref","first-page":"972","DOI":"10.4269\/ajtmh.14-0806","article-title":"Clinical and Epidemiological characteristics of scrub typhus and murine typhus among hospitalized patients with acute undifferentiated fever in Northern Vietnam","volume":"92","author":"S Hamaguchi","year":"2015","journal-title":"Am J Trop Med Hyg"},{"issue":"1","key":"pntd.0010354.ref022","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1080\/22221751.2019.1599696","article-title":"Rickettsia typhi infection in severe fever with thrombocytopenia patients, China.","volume":"8","author":"SF Zhang","year":"2019","journal-title":"Emerg Microbes Infect"},{"key":"pntd.0010354.ref023","doi-asserted-by":"crossref","first-page":"e3327","DOI":"10.1371\/journal.pntd.0003327","article-title":"Pregnancy outcome in relation to treatment of murine typhus and scrub typhus infection: a fever cohort and a case series analysis.","volume":"8","author":"R McGready","year":"2014","journal-title":"PLoS Negl Trop Dis"},{"issue":"12","key":"pntd.0010354.ref024","doi-asserted-by":"crossref","first-page":"652","DOI":"10.5694\/j.1326-5377.2011.tb03152.x","article-title":"Murine typhus returns to New South Wales: a case of isolated meningoencephalitis with raised intracranial pressure.","volume":"194","author":"NG Simon","year":"2011","journal-title":"Med J Aust"},{"issue":"1","key":"pntd.0010354.ref025","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1111\/j.1708-8305.2012.00678.x","article-title":"Severe murine typhus with shock and acute respiratory failure in a Japanese traveler after returning from Thailand","volume":"20","author":"N Sakamoto","year":"2013","journal-title":"J Travel Med"},{"issue":"1","key":"pntd.0010354.ref026","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1186\/s12879-017-2385-x","article-title":"Acute-phase diagnosis of murine and scrub typhus in Belgian travelers by polymerase chain reaction: a case report.","volume":"17","author":"C Theunissen","year":"2017","journal-title":"BMC Infect Dis"},{"issue":"6","key":"pntd.0010354.ref027","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.4269\/ajtmh.2012.11-0794","article-title":"Murine typhus in returned travelers: a report of thirty-two cases","volume":"86","author":"G Walter","year":"2012","journal-title":"Am J Trop Med Hyg"},{"issue":"2","key":"pntd.0010354.ref028","doi-asserted-by":"crossref","first-page":"317","DOI":"10.3201\/eid1902.120601","article-title":"High seroprevalence for typhus group rickettsiae, southwestern Tanzania","volume":"19","author":"T Dill","year":"2013","journal-title":"Emerg Infect Dis"},{"issue":"5","key":"pntd.0010354.ref029","doi-asserted-by":"crossref","first-page":"932","DOI":"10.4269\/ajtmh.12-0325","article-title":"Inter- and intra-operator variability in the reading of indirect immunofluorescence assays for the serological diagnosis of scrub typhus and murine typhus","volume":"88","author":"R Phetsouvanh","year":"2013","journal-title":"Am J Trop Med Hyg"},{"issue":"4","key":"pntd.0010354.ref030","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1093\/infdis\/161.4.791","article-title":"Diagnosis of acute typhus infection using the polymerase chain reaction","volume":"161","author":"M Carl","year":"1990","journal-title":"J Infect Dis"},{"issue":"1","key":"pntd.0010354.ref031","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1111\/j.1574-695X.2011.00910.x","article-title":"Development of a duplex real-time PCR for the detection of Rickettsia spp. and typhus group rickettsia in clinical samples","volume":"64","author":"S Giulieri","year":"2012","journal-title":"FEMS Immunol Med Microbiol"},{"issue":"1","key":"pntd.0010354.ref032","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.mcp.2006.06.002","article-title":"Development of quantitative real-time PCR assays to detect Rickettsia typhi and Rickettsia felis, the causative agents of murine typhus and flea-borne spotted fever","volume":"21","author":"KM Henry","year":"2007","journal-title":"Mol Cell Probes"},{"key":"pntd.0010354.ref033","doi-asserted-by":"crossref","first-page":"e0003487","DOI":"10.1371\/journal.pntd.0003487","article-title":"Comparison of two quantitative real time PCR assays for Rickettsia detection in patients from Tunisia.","volume":"9","author":"A Znazen","year":"2015","journal-title":"PLoS Negl Trop Dis"},{"issue":"3","key":"pntd.0010354.ref034","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1128\/JCM.02786-13","article-title":"Loop-mediated isothermal amplification for Rickettsia typhi (the causal agent of murine typhus): problems with diagnosis at the limit of detection.","volume":"52","author":"S Dittrich","year":"2014","journal-title":"J Clin Microbiol"},{"issue":"7","key":"pntd.0010354.ref035","doi-asserted-by":"crossref","first-page":"e0003884","DOI":"10.1371\/journal.pntd.0003884","article-title":"Development of recombinase polymerase amplification assays for detection of Orientia tsutsugamushi or Rickettsia typhi","volume":"9","author":"CC Chao","year":"2015","journal-title":"PLoS Negl Trop Dis"},{"issue":"3","key":"pntd.0010354.ref036","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1128\/jcm.28.3.530-534.1990","article-title":"Detection of murine typhus infection in fleas by using the polymerase chain reaction","volume":"28","author":"L Webb","year":"1990","journal-title":"J Clin Microbiol"},{"key":"pntd.0010354.ref037","first-page":"43","volume-title":"Genetic, biological and serological differentiation of Rickettsia prowazekii and Rickettsia typhi. In J. Kazar, editor. Rickettsiae and Rickettsial Diseases. Vth International Symposium.","author":"ME Eremeeva","year":"1996"},{"issue":"4","key":"pntd.0010354.ref038","doi-asserted-by":"crossref","first-page":"413","DOI":"10.4269\/ajtmh.1996.54.413","article-title":"Genotypic identification of murine typhus rickettsia in rats and their fleas in an endemic area of Greece by the polymerase chain reaction and restriction fragment length polymorphism","volume":"54","author":"Y Tselentis","year":"1996","journal-title":"Am J Trop Med Hyg"},{"key":"pntd.0010354.ref039","first-page":"275","volume-title":"Rickettsia and Coxiella","author":"RF Massung","year":"2011","edition":"2"},{"issue":"1","key":"pntd.0010354.ref040","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1101\/gr.2.1.14","article-title":"Mismatch amplification mutation assay (MAMA): application to the c-H-ras gene.","volume":"2","author":"RS Cha","year":"1992","journal-title":"PCR Methods Appl"},{"issue":"2","key":"pntd.0010354.ref041","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.ygeno.2003.08.005","article-title":"Genotyping with TaqMAMA.","volume":"83","author":"B Li","year":"2004","journal-title":"Genomics"},{"key":"pntd.0010354.ref042","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1111\/j.1749-6632.2009.04526.x","article-title":"Closing the gaps between genotype and phenotype in Rickettsia rickettsii","volume":"1166","author":"ME Eremeeva","year":"2009","journal-title":"Ann N Y Acad Sci"},{"issue":"3","key":"pntd.0010354.ref043","first-page":"158","article-title":"The rickettsial diseases of Southern Africa: a review of recent studies","volume":"5","author":"J. Gear","year":"1954","journal-title":"S Afr J Clin Sci"},{"issue":"3","key":"pntd.0010354.ref044","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1128\/iai.16.3.853-860.1977","article-title":"Biological properties of Rickettsia prowazekii strains isolated from flying squirrels","volume":"16","author":"DR Woodman","year":"1977","journal-title":"Infect Immun"},{"issue":"4","key":"pntd.0010354.ref045","doi-asserted-by":"crossref","first-page":"455","DOI":"10.4049\/jimmunol.60.4.455","article-title":"Infection of guinea pigs with massive doses of rickettsiae of epidemic and murine typhus","volume":"60","author":"F Perez Gallardo","year":"1948","journal-title":"J Immunol"},{"key":"pntd.0010354.ref046","doi-asserted-by":"crossref","first-page":"1935","DOI":"10.2307\/4579347","article-title":"Endemic typhus of the southeastern United States: the reaction of the white rat.","volume":"44","author":"KF Maxcy","year":"1929","journal-title":"Pub Health Rep"},{"issue":"2","key":"pntd.0010354.ref047","doi-asserted-by":"crossref","first-page":"408","DOI":"10.4269\/ajtmh.19-0383","article-title":"Oxford Nanopore MinION sequencing enables rapid whole genome assembly of Rickettsia typhi in a resource-limited setting","volume":"102","author":"I Elliott","year":"2020","journal-title":"Am J Trop Med Hyg"},{"issue":"13","key":"pntd.0010354.ref048","doi-asserted-by":"crossref","first-page":"3525","DOI":"10.1093\/nar\/gkg623","article-title":"MAVID multiple alignment server","volume":"31","author":"N Bray","year":"2003","journal-title":"Nucleic Acids Res"},{"issue":"2","key":"pntd.0010354.ref049","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1128\/IAI.00952-07","article-title":"Genomic comparison of virulent Rickettsia rickettsii Sheila Smith and avirulent Rickettsia rickettsii Iowa","volume":"76","author":"DW Ellison","year":"2008","journal-title":"Infect Immun"},{"issue":"5","key":"pntd.0010354.ref050","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1101\/gr.103564.109","article-title":"Genomic, proteomic, and transcriptomic analysis of virulent and avirulent Rickettsia prowazekii reveals its adaptive mutation capabilities","volume":"20","author":"Y Bechah","year":"2010","journal-title":"Genome Res"},{"issue":"1","key":"pntd.0010354.ref051","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1006\/mpat.1996.0005","article-title":"Deletion in the 190 kDa antigen gene repeat region of Rickettsia rickettsii","volume":"20","author":"M Matsumoto","year":"1996","journal-title":"Microb Pathog"},{"issue":"2","key":"pntd.0010354.ref052","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1093\/nar\/27.2.573","article-title":"Tandem repeats finder: a program to analyze DNA sequences","volume":"27","author":"G. Benson","year":"1999","journal-title":"Nucleic Acids Res"},{"issue":"17","key":"pntd.0010354.ref053","doi-asserted-by":"crossref","first-page":"5842","DOI":"10.1128\/JB.186.17.5842-5855.2004","article-title":"Complete genome sequence of Rickettsia typhi and comparison with sequences of other rickettsiae","volume":"186","author":"MP McLeod","year":"2004","journal-title":"J Bacteriol"},{"key":"pntd.0010354.ref054","first-page":"365","article-title":"Primer3 on the WWW for general users and for biologist programmers","volume":"132","author":"S Rozen","year":"2000","journal-title":"Methods Mol Biol"},{"issue":"8","key":"pntd.0010354.ref055","doi-asserted-by":"crossref","first-page":"1596","DOI":"10.1093\/molbev\/msm092","article-title":"MEGA4: Molecular Evolutionary Genetics Analysis (MEGA) software version 4.0.","volume":"24","author":"K Tamura","year":"2007","journal-title":"Mol Biol Evol"}],"updated-by":[{"DOI":"10.1371\/journal.pntd.0010354","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,6,16]],"date-time":"2022-06-16T00:00:00Z","timestamp":1655337600000}}],"container-title":["PLOS Neglected Tropical Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0010354","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,6]],"date-time":"2023-02-06T21:18:47Z","timestamp":1675718327000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0010354"}},"subtitle":[],"editor":[{"given":"Allen L.","family":"Richards","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2022,5,31]]},"references-count":55,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2022,5,31]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pntd.0010354","relation":{"new_version":[{"id-type":"doi","id":"10.1371\/journal.pntd.0010354","asserted-by":"object"}]},"ISSN":["1935-2735"],"issn-type":[{"value":"1935-2735","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,31]]}}}