{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T06:06:48Z","timestamp":1781762808243,"version":"3.54.5"},"reference-count":43,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,11,14]],"date-time":"2021-11-14T00:00:00Z","timestamp":1636848000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Bill &amp; Melinda Gates Foundation","award":["OPPGH5231"],"award-info":[{"award-number":["OPPGH5231"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Rickettsiae may cause febrile infections in humans in tropical and subtropical regions. From Madagascar, no molecular data on the role of rickettsioses in febrile patients are available. Blood samples from patients presenting with fever in the area of the capital Antananarivo were screened for the presence of rickettsial DNA. EDTA (ethylenediaminetetraacetic acid) blood from 1020 patients presenting with pyrexia &gt; 38.5 \u00b0C was analyzed by gltA-specific qPCR. Positive samples were confirmed by ompB-specific qPCR. From confirmed samples, the gltA amplicons were sequenced and subjected to phylogenetic analysis. From five gltA-reactive samples, two were confirmed by ompB-specific qPCR. The gltA sequence in the sample taken from a 38-year-old female showed 100% homology with R. typhi. The other sample taken from a 1.5-year-old infant was 100% homologous to R. felis. Tick-borne rickettsiae were not identified. The overall rate of febrile patients with molecular evidence for a rickettsial infection from the Madagascan study site was 0.2% (2\/1020 patients). Flea-borne rickettsiosis is a rare but neglected cause of infection in Madagascar. Accurate diagnosis may prompt adequate antimicrobial treatment.<\/jats:p>","DOI":"10.3390\/pathogens10111482","type":"journal-article","created":{"date-parts":[[2021,11,14]],"date-time":"2021-11-14T20:51:53Z","timestamp":1636923113000},"page":"1482","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Molecular Evidence for Flea-Borne Rickettsiosis in Febrile Patients from Madagascar"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0075-7199","authenticated-orcid":false,"given":"Christian","family":"Keller","sequence":"first","affiliation":[{"name":"Institute of Virology, Philipps University, 35043 Marburg, Germany"},{"name":"Infectious Disease Department and Diagnostic Department, Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rapha\u00ebl","family":"Rakotozandrindrainy","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Parasitology, University of Antananarivo, Antananarivo BP 566, Madagascar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vera","family":"von Kalckreuth","sequence":"additional","affiliation":[{"name":"International Vaccine Institute, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean No\u00ebl","family":"Heriniaina","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Parasitology, University of Antananarivo, Antananarivo BP 566, Madagascar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norbert Georg","family":"Schwarz","sequence":"additional","affiliation":[{"name":"Independent Researcher, 67227 Frankenthal, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gi Deok","family":"Pak","sequence":"additional","affiliation":[{"name":"International Vaccine Institute, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin","family":"Im","sequence":"additional","affiliation":[{"name":"International Vaccine Institute, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ligia Maria Cruz","family":"Espinoza","sequence":"additional","affiliation":[{"name":"International Vaccine Institute, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4875-1519","authenticated-orcid":false,"given":"Ralf Matthias","family":"Hagen","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Hospital Hygiene, Bundeswehr Central Hospital Koblenz, 56070 Koblenz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8967-9528","authenticated-orcid":false,"given":"Hagen","family":"Frickmann","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Hospital Hygiene, Bundeswehr Hospital Hamburg, 20359 Hamburg, Germany"},{"name":"Institute for Medical Microbiology, Virology and Hygiene, University Medicine Rostock, 18057 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean Philibert","family":"Rakotondrainiarivelo","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Parasitology, University of Antananarivo, Antananarivo BP 566, Madagascar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsiry","family":"Razafindrabe","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Parasitology, University of Antananarivo, Antananarivo BP 566, Madagascar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5432-3217","authenticated-orcid":false,"given":"Denise","family":"Dekker","sequence":"additional","affiliation":[{"name":"Infectious Disease Department and Diagnostic Department, Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrgen","family":"May","sequence":"additional","affiliation":[{"name":"Infectious Disease Department and Diagnostic Department, Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany"},{"name":"German Centre for Infection Research (DZIF), Hamburg-L\u00fcbeck-Borstel-Riems, 38124 Braunschweig, Germany"},{"name":"Department of Tropical Medicine II, University Medical Center Hamburg-Eppendorf (UKE), 20359 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4873-249X","authenticated-orcid":false,"given":"Sven","family":"Poppert","sequence":"additional","affiliation":[{"name":"Infectious Disease Department and Diagnostic Department, Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6043-7170","authenticated-orcid":false,"given":"Florian","family":"Marks","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Parasitology, University of Antananarivo, Antananarivo BP 566, Madagascar"},{"name":"International Vaccine Institute, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Korea"},{"name":"Cambridge Institute of Therapeutic Immunology and Infectious Disease, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Cambridge CB2 0SP, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1500","DOI":"10.1038\/s41598-018-37836-5","article-title":"Diversity of spotted fever group rickettsiae and their association with host ticks in Japan","volume":"9","author":"Thu","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Gillespie, J.J., Williams, K., Shukla, M., Snyder, E.E., Nordberg, E.K., Ceraul, S.M., Dharmanol\u00eda, C., Rainey, D., Soneja, J., and Shallom, J.M. (2008). Rickettsia phylogenomics: Unwinding the intricacies of obligate intracellular life. PLoS ONE, 3.","DOI":"10.1371\/journal.pone.0002018"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"114","DOI":"10.4103\/0972-9062.310863","article-title":"Clinical characteristics of Rocky Mountain spotted fever in the United States: A literature review","volume":"57","author":"Jay","year":"2020","journal-title":"J. Vector Borne Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1111\/j.1469-0691.2008.02637.x","article-title":"Clusters of Brazilian spotted fever in S\u00e3o Paulo State, southeastern Brazil. A review of official reports and the scientific literature","volume":"15","author":"Nunes","year":"2009","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1016\/j.ttbdis.2018.03.022","article-title":"Molecular detection of spotted fever group rickettsiae in ticks from Cameroon","volume":"9","author":"Vanegas","year":"2018","journal-title":"Ticks Tick. Borne. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1186\/s13071-017-2061-4","article-title":"Molecular and serological evidence of flea-associated typhus group and spotted fever group rickettsial infections in Madagascar","volume":"10","author":"Rakotonanahary","year":"2017","journal-title":"Parasit. Vectors"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1016\/j.ttbdis.2015.12.011","article-title":"Tick (Amblyomma chabaudi) infestation of endemic tortoises in southwest Madagascar and investigation of tick-borne pathogens","volume":"7","author":"Ehlers","year":"2016","journal-title":"Ticks Tick. Borne. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e28","DOI":"10.1086\/589868","article-title":"African tick bite fever in elderly patients: 8 cases in French tourists returning from South Africa","volume":"47","author":"Roch","year":"2008","journal-title":"Clin. Infect. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"138","DOI":"10.3201\/eid1201.050876","article-title":"Rickettsia felis infection, Tunisia","volume":"12","author":"Znazen","year":"2006","journal-title":"Emerg. Infect. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1016\/j.ttbdis.2016.02.010","article-title":"Molecular diagnosis of Rickettsia infection in patients from Tunisia","volume":"7","author":"Khrouf","year":"2016","journal-title":"Ticks Tick. Borne. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1093\/clinids\/21.5.1126","article-title":"Prevalence of antibodies to Coxiella burnetii, Rickettsia conorii, and Rickettsia typhi in seven African countries","volume":"21","author":"Dupont","year":"1995","journal-title":"Clin. Infect. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1023\/A:1007571412030","article-title":"Prevalence of antibodies to Rickettsia conorii, Rickettsia africae, Rickettsia typhi and Coxiella burnetii in Mauritania","volume":"14","author":"Niang","year":"1998","journal-title":"Eur. J. Epidemiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e0008641","DOI":"10.1371\/journal.pntd.0008641","article-title":"A systematic review of the untreated mortality of murine typhus","volume":"14","author":"Doppler","year":"2020","journal-title":"PLoS Negl. Trop. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"16","DOI":"10.4269\/ajtmh.16-0754","article-title":"Rickettsia felis Infection in Febrile Children, Ghana","volume":"96","author":"Sothmann","year":"2017","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1775","DOI":"10.3201\/eid1911.130361","article-title":"Common epidemiology of Rickettsia felis infection and malaria, Africa","volume":"19","author":"Mediannikov","year":"2013","journal-title":"Emerg. Infect. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1808","DOI":"10.3201\/eid2110.141825","article-title":"Possible role of Rickettsia felis in acute febrile illness among children in Gabon","volume":"21","author":"Mourembou","year":"2015","journal-title":"Emerg. Infect. Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"328","DOI":"10.3201\/eid1802.111372","article-title":"Rickettsia felis infection in febrile patients, western Kenya, 2007\u20132010","volume":"18","author":"Maina","year":"2012","journal-title":"Emerg. Infect. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"136","DOI":"10.4269\/ajtmh.17-0882","article-title":"Diagnosis of spotted fever group rickettsioses in U.S. travelers returning from Africa, 2007\u20132016","volume":"99","author":"Cherry","year":"2018","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_19","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":"Tsioutis","year":"2017","journal-title":"Acta Trop."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1111\/j.1469-0691.2011.03516.x","article-title":"Rickettsia felis: From a rare disease in the USA to a common cause of fever in sub-Saharan Africa","volume":"17","author":"Parola","year":"2011","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.ttbdis.2015.08.005","article-title":"High detection rate of Rickettsia africae in Amblyomma variegatum but low prevalence of anti-rickettsial antibodies in healthy pregnant women in Madagascar","volume":"7","author":"Keller","year":"2016","journal-title":"Ticks Tick. Borne. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e0006642","DOI":"10.1371\/journal.pntd.0006642","article-title":"Study on causes of fever in primary healthcare center uncovers pathogens of public health concern in Madagascar","volume":"12","author":"Guillebaud","year":"2018","journal-title":"PLoS Negl. Trop. Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.actatropica.2017.05.013","article-title":"Are brucellosis, Q fever and melioidosis potential causes of febrile illness in Madagascar?","volume":"172","author":"Boone","year":"2017","journal-title":"Acta Trop."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1099\/00207713-50-4-1449","article-title":"Phylogenetic analysis of members of the genus Rickettsia using the gene encoding the outer-membrane protein rOmp (ompB)","volume":"50","author":"Roux","year":"2000","journal-title":"Int. J. Syst. Evol. Microbiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"5757","DOI":"10.1128\/JCM.42.12.5757-5766.2004","article-title":"Use of highly variable intergenic spacer sequences for multispacer typing of Rickettsia conorii strains use of highly variable intergenic spacer sequences for multispacer typing of Rickettsia conorii Strains","volume":"42","author":"Fournier","year":"2004","journal-title":"J. Clin. Microbiol."},{"key":"ref_26","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":"Henry","year":"2007","journal-title":"Mol. Cell. Probes"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1853","DOI":"10.1371\/journal.pntd.0002382","article-title":"Understanding the persistence of Plague Foci in Madagascar","volume":"7","author":"Andrianaivoarimanana","year":"2013","journal-title":"PLoS Negl. Trop. Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1093\/jme\/tjv113","article-title":"The fleas of endemic and introduced small mammals in central highland forests of Madagascar: Faunistics, species diversity, and absence of host specificity","volume":"52","author":"Goodman","year":"2015","journal-title":"J. Med. Entomol."},{"key":"ref_29","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":"Walter","year":"2012","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Znazen, A., Sellami, H., Elleuch, E., Hattab, Z., Ben Sassi, L., Khrouf, F., Dammak, H., Letaief, A., Ben Jemaa, M., and Hammami, A. (2015). Comparison of two quantitative real time PCR assays for Rickettsia detection in patients from Tunisia. PLoS Negl. Trop. Dis., 9.","DOI":"10.1371\/journal.pntd.0003487"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.3201\/eid2407.180093","article-title":"Typhus group Rickettsiosis, Germany, 2010\u20132017\u2014Volume 24, Number 7\u2013July 2018\u2014Emerging Infectious Diseases journal\u2014CDC","volume":"24","author":"Rauch","year":"2018","journal-title":"Emerg. Infect. Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1097\/QCO.0000000000000298","article-title":"State of the art of diagnosis of rickettsial diseases: The use of blood specimens for diagnosis of scrub typhus, spotted fever group rickettsiosis, and murine typhus","volume":"29","author":"Paris","year":"2016","journal-title":"Curr. Opin. Infect. Dis."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e286","DOI":"10.1017\/S0950268819001390","article-title":"Diagnosis of spotted fever group Rickettsia infections: The Asian perspective","volume":"147","author":"Robinson","year":"2019","journal-title":"Epidemiol. Infect."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"926","DOI":"10.4269\/ajtmh.14-0699","article-title":"Molecular detection of fastidious and common Bacteria as well as plasmodium spp. in Febrile and Afebrile children in Franceville, Gabon","volume":"92","author":"Mourembou","year":"2015","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"s23","DOI":"10.1093\/cid\/civ893","article-title":"The relationship between invasive nontyphoidal salmonella disease, other bacterial bloodstream infections, and Malaria in sub-Saharan Africa","volume":"62","author":"Park","year":"2016","journal-title":"Clin. Infect. Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1086\/527443","article-title":"Murine Typhus: An unrecognized suburban Vectorborne disease","volume":"46","author":"Civen","year":"2008","journal-title":"Clin. Infect. Dis."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"70","DOI":"10.4269\/ajtmh.1999.61.70","article-title":"Short report: Prevalence of antibodies against spotted fever, murine typhus, and Q fever rickettsiae in humans living in Zambia","volume":"61","author":"Okabayashi","year":"1999","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1111\/j.1708-8305.2010.00435.x","article-title":"Murine typhus as a cause of fever in travelers from tunisia and Mediterranean areas","volume":"17","author":"Angelakis","year":"2010","journal-title":"J. Travel Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"319","DOI":"10.3201\/eid0303.970308","article-title":"Flea-borne Rickettsioses: Ecologic Considerations","volume":"3","author":"Azad","year":"1997","journal-title":"Emerg. Infect. Dis."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"s9","DOI":"10.1093\/cid\/civ693","article-title":"The typhoid fever surveillance in Africa program (TSAP): Clinical, diagnostic, and epidemiological methodologies","volume":"62","author":"Konings","year":"2016","journal-title":"Clin. Infect. Dis."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.actatropica.2017.10.002","article-title":"Presence of Borrelia spp. DNA in ticks, but absence of Borrelia spp. and of Leptospira spp. DNA in blood of fever patients in Madagascar","volume":"177","author":"Hagen","year":"2018","journal-title":"Acta Trop."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Mediannikov, O., Diatta, G., Fenollar, F., Sokhna, C., Trape, J.F., and Raoult, D. (2010). Tick-borne rickettsioses, neglected emerging diseases in rural Senegal. PLoS Negl. Trop. Dis., 4.","DOI":"10.1371\/journal.pntd.0000821"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.micpath.2014.09.008","article-title":"Looking in ticks for human bacterial pathogens","volume":"77","author":"Mediannikov","year":"2014","journal-title":"Microb. Pathog."}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/10\/11\/1482\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:30:02Z","timestamp":1760167802000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/10\/11\/1482"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,14]]},"references-count":43,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2021,11]]}},"alternative-id":["pathogens10111482"],"URL":"https:\/\/doi.org\/10.3390\/pathogens10111482","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,14]]}}}