{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T08:02:33Z","timestamp":1778227353135,"version":"3.51.4"},"reference-count":51,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T00:00:00Z","timestamp":1740096000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Fever of Unknown Origin (FUO) is a diagnostic challenge in pediatrics, often stemming from zoonotic infections. In southern Israel, brucellosis and rickettsiosis are endemic and share overlapping clinical features, making diagnosis difficult. We compared the demographic, clinical, and laboratory characteristics of pediatric brucellosis and rickettsiosis to aid in distinguishing between these diseases and guide early empirical treatment. Methods: We performed a retrospective cohort study, conducted between 2005 and 2020, on children who tested positive for either rickettsia or brucella. Data on demographic, clinical, laboratory, treatment, and outcome parameters were analyzed using descriptive, univariate, and multivariate statistical methods. Results: Overall, 775 patients were included, 440 with brucellosis and 335 with rickettsiosis. The majority of patients were of Bedouin ethnicity (99.5% and 90.7%, respectively). In univariate analysis, brucellosis was associated with male gender, young age, limping, anemia, and prolonged hospitalization duration. Rickettsiosis was characterized by high-grade fever, rash, headache, thrombocytopenia, elevated C-reactive protein (CRP), and gastrointestinal, respiratory, and neurological symptoms. Mortality rates were low in both groups (\u22640.5%). In multivariate analysis, brucellosis was associated with limping (odds ratio = 7.27; with 95% confidence interval of 5.15\u201310.38), hemoglobin &lt;10 mg\/dL (2.01; 1.14\u20133.64), age &lt;5 years (1.95; 1.25\u20133.07), warm season (1.84; 1.31\u20132.59), and male gender (1.57; 1.10\u20132.25). Rickettsiosis was associated with a rash (9.06; 3.91\u201324.9), CRP \u22655 mg\/dL (4.03; 1.86\u20139.81), headache (3.01; 1.75\u20135.30), thrombocytopenia (2.61; 1.23\u20136.06), leukopenia (1.88; 1.19\u20132.98), and temperature \u226539.0 \u00b0C (1.66; 1.03\u20132.68). Conclusions: Brucellosis and rickettsiosis differ demographically and clinically in FUO cases. These findings highlight the importance of distinguishing between the two diseases for early diagnosis and targeted management, ultimately improving patient outcomes.<\/jats:p>","DOI":"10.3390\/jcm14051465","type":"journal-article","created":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T11:08:50Z","timestamp":1740136130000},"page":"1465","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Comparison of Brucellosis and Rickettsiosis in Children: A Retrospective Cohort Study"],"prefix":"10.3390","volume":"14","author":[{"given":"Idan","family":"Lendner","sequence":"first","affiliation":[{"name":"Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva 84101, Israel"},{"name":"Pediatric Infectious Disease Unit, Soroka University Medical Center, Beer Sheva 84101, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2307-1370","authenticated-orcid":false,"given":"Moshe","family":"Shmueli","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva 84101, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siham","family":"Elamour","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva 84101, Israel"},{"name":"The Pediatric Day-Care Unit, Soroka University Medical Center, Beer-Sheva 84101, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Galina","family":"Ling","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva 84101, Israel"},{"name":"The Pediatric Day-Care Unit, Soroka University Medical Center, Beer-Sheva 84101, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shalom","family":"Ben-Shimol","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva 84101, Israel"},{"name":"Pediatric Infectious Disease Unit, Soroka University Medical Center, Beer Sheva 84101, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1007\/s12519-011-0240-5","article-title":"Fever of unknown origin in children: A systematic review","volume":"7","author":"Chow","year":"2011","journal-title":"World J. Pediatr."},{"key":"ref_2","unstructured":"(2024, December 04). Epidemiological Situation of Rickettsioses in EU\/EFTA Countries. Available online: https:\/\/www.ecdc.europa.eu\/en\/publications-data\/epidemiological-situation-rickettsioses-euefta-countries."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Dean, A.S., Crump, L., Greter, H., Schelling, E., and Zinsstag, J. (2012). Global burden of human brucellosis: A systematic review of disease frequency. PLoS Negl. Trop. Dis., 6.","DOI":"10.1371\/journal.pntd.0001865"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"102174","DOI":"10.1016\/j.tmaid.2021.102174","article-title":"Vector-borne and zoonotic infections and their relationships with regional and socioeconomic statuses: An ID-IRI survey in 24 countries of Europe, Africa and Asia","volume":"44","author":"Saydam","year":"2021","journal-title":"Travel Med. Infect. Dis."},{"key":"ref_5","unstructured":"(2025, January 26). Rickettsial Diseases | CDC Yellow Book 2024, Available online: https:\/\/wwwnc.cdc.gov\/travel\/yellowbook\/2024\/infections-diseases\/rickettsial-diseases?utm_source=chatgpt.com."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1089\/vbz.2014.1726","article-title":"Epidemiological, diagnostic, clinical, and therapeutic aspects of Brucella bacteremia in children in southern Israel: A 7-year retrospective study (2005\u20132011)","volume":"15","author":"Fruchtman","year":"2015","journal-title":"Vector Borne Zoonotic Dis."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Yagupsky, P., Morat, P., and Colmenero, J.D. (2019). Laboratory Diagnosis of Human Brucellosis. Clin. Microbiol. Rev., 33.","DOI":"10.1128\/CMR.00073-19"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"117280","DOI":"10.1016\/j.jns.2020.117280","article-title":"Brucellosis","volume":"420","author":"Shakir","year":"2021","journal-title":"J. Neurol. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1093\/jpids\/piz092","article-title":"Factors Associated with Single and Recurrent Bacteremia in Childhood Brucellosis","volume":"9","author":"Farahvar","year":"2020","journal-title":"J. Pediatr. Infect. Dis. Soc."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.meegid.2014.03.014","article-title":"Genotyping, evolution and epidemiological findings of Rickettsia species","volume":"25","author":"Merhej","year":"2014","journal-title":"Infect. Genet. Evol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Klein, D., Beth-Din, A., Cohen, R., Lazar, S., Glinert, I., Zayyad, H., and Atiya-Nasagi, Y. (2020). New Spotted Fever Group Rickettsia Isolate, Identified by Sequence Analysis of Conserved Genomic Regions. Pathogens, 9.","DOI":"10.3390\/pathogens9010011"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2117","DOI":"10.3201\/eid2708.203661","article-title":"Spotted Fever Group Rickettsioses in Israel, 2010\u20132019","volume":"27","author":"Cohen","year":"2021","journal-title":"Emerg. Infect. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1080\/00365540500540459","article-title":"Murine typhus is a common cause of febrile illness in Bedouin children in Israel","volume":"38","author":"Shalev","year":"2006","journal-title":"Scand. J. Infect. Dis."},{"key":"ref_14","first-page":"175","article-title":"Murine Typhus: Clinical and epidemiological aspects","volume":"43","year":"2012","journal-title":"Colomb. M\u00e9d. CM"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Spernovasilis, N., Markaki, I., Papadakis, M., Mazonakis, N., and Ierodiakonou, D. (2021). Mediterranean Spotted Fever: Current Knowledge and Recent Advances. Trop. Med. Infect. Dis., 6.","DOI":"10.3390\/tropicalmed6040172"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Guirao-Arrabal, E., Mu\u00f1oz-Medina, L., Anguita-Santos, F., Vinuesa-Garc\u00eda, D., and Hern\u00e1ndez-Quero, J. (2021). Empirical treatment with doxycycline of fever of intermediate duration. Eur. J. Clin. Microbiol. Infect. Dis., 40.","DOI":"10.1007\/s10096-021-04322-2"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"25","DOI":"10.7326\/0003-4819-117-1-25","article-title":"Treatment of human brucellosis with doxycycline plus rifampin or doxycycline plus streptomycin. A randomized, double-blind study","volume":"117","author":"Ariza","year":"1992","journal-title":"Ann. Intern. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1128\/AAC.41.1.80","article-title":"Treatment of human brucellosis with doxycycline and gentamicin","volume":"41","author":"Solera","year":"1997","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_19","first-page":"155","article-title":"A Prospective Study of Brucellosis in Children: Relative Frequency of Pancytopenia","volume":"24","author":"Afify","year":"2014","journal-title":"Iran. J. Pediatr."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Jin, M., Fan, Z., Gao, R., Li, X., Gao, Z., and Wang, Z. (2023). Research progress on complications of Brucellosis. Front. Cell. Infect. Microbiol., 13.","DOI":"10.3389\/fcimb.2023.1136674"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1016\/S1473-3099(07)70286-4","article-title":"Human brucellosis","volume":"7","author":"Franco","year":"2007","journal-title":"Lancet Infect. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1093\/brain\/110.1.213","article-title":"Clinical categories of neurobrucellosis. A report on 19 cases","volume":"110","author":"Shakir","year":"1987","journal-title":"Brain"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e397","DOI":"10.1016\/j.amjmed.2022.04.018","article-title":"Murine Typhus-Induced Myocarditis","volume":"135","author":"Madan","year":"2022","journal-title":"Am. J. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1093\/clinids\/21.2.283","article-title":"An overview of human brucellosis","volume":"21","author":"Young","year":"1995","journal-title":"Clin. Infect. Dis."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"D\u00edaz, R., Casanova, A., Ariza, J., and Moriy\u00f3n, I. (2011). The Rose Bengal Test in human brucellosis: A neglected test for the diagnosis of a neglected disease. PLoS Negl. Trop. Dis., 5.","DOI":"10.1371\/journal.pntd.0000950"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Kato, C.Y., Chung, I.H., Robinson, L.K., Austin, A.L., Dasch, G.A., and Massunga, R.F. (2013). Assessment of Real-Time PCR Assay for Detection of Rickettsia spp. and Rickettsia rickettsii in Banked Clinical Samples. J. Clin. Microbiol., 51.","DOI":"10.1128\/JCM.01723-12"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.eimc.2012.08.001","article-title":"Usefulness of rickettsial PCR assays for the molecular diagnosis of human rickettsioses","volume":"31","author":"Portillo","year":"2013","journal-title":"Enferm. Infecc. Microbiol. Clin."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.ijid.2023.03.012","article-title":"Serological cross-reactivity between spotted fever and typhus groups of rickettsia infection in Japan","volume":"130","author":"Aita","year":"2023","journal-title":"Int. J. Infect. Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e481","DOI":"10.1016\/j.ijid.2011.03.019","article-title":"Seroprevalence of Rickettsia typhi and Rickettsia conorii infections in the Canary Islands (Spain)","volume":"15","year":"2011","journal-title":"Int. J. Infect. Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.mimet.2008.12.012","article-title":"Evaluation of serological tests for the diagnosis of rickettsiosis in Denmark","volume":"76","author":"Svendsen","year":"2009","journal-title":"J. Microbiol. Methods"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Cohen, J., Cohen, P., West, S.G., and Aiken, L.S. (2013). Applied Multiple Regression\/Correlation Analysis for the Behavioral Sciences, Routledge. [3rd ed.]. Available online: https:\/\/www.taylorfrancis.com\/books\/mono\/10.4324\/9780203774441\/applied-multiple-regression-correlation-analysis-behavioral-sciences-jacob-cohen-patricia-cohen-stephen-west-leona-aiken.","DOI":"10.4324\/9780203774441"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1214\/aoms\/1177730491","article-title":"On a Test of Whether one of Two Random Variables is Stochastically Larger than the Other","volume":"18","author":"Mann","year":"1947","journal-title":"Ann. Math. Statist."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1728","DOI":"10.3201\/eid2706.204902","article-title":"Brucellosis Outbreak Traced to Commercially Sold Camel Milk through Whole-Genome Sequencing, Israel","volume":"27","author":"Bardenstein","year":"2021","journal-title":"Emerg. Infect. Dis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1016\/j.jiph.2015.12.006","article-title":"Outbreaks of brucellosis related to the consumption of unpasteurized camel milk","volume":"9","author":"Garcell","year":"2016","journal-title":"J. Infect. Public Health"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/S1473-3099(06)70382-6","article-title":"The new global map of human brucellosis","volume":"6","author":"Pappas","year":"2006","journal-title":"Lancet Infect. Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2295398","DOI":"10.1080\/07853890.2023.2295398","article-title":"Brucellosis: Epidemiology, pathogenesis, diagnosis and treatment\u2014A comprehensive review","volume":"55","author":"Qureshi","year":"2023","journal-title":"Ann. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"E521","DOI":"10.1097\/INF.0000000000003303","article-title":"Serologic Diagnosis of Acute Rickettsiosis in Children in Southern Israel","volume":"40","author":"Sharabi","year":"2021","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"54","DOI":"10.5312\/wjo.v10.i2.54","article-title":"Osteoarticular manifestations of human brucellosis: A review","volume":"10","year":"2019","journal-title":"World J. Orthop."},{"key":"ref_39","first-page":"4687840","article-title":"Brucella Septic Arthritis: Case Reports and Review of the Literature","volume":"2016","author":"Elzein","year":"2016","journal-title":"Case Rep. Infect. Dis."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2","DOI":"10.7861\/clinmed.2021-0790","article-title":"Rickettsial illnesses, a leading cause of acute febrile illness","volume":"22","author":"Premaratna","year":"2022","journal-title":"Clin. Med."},{"key":"ref_41","unstructured":"Yu, X., Ismail, N., and Walker, D.H. (2024, September 21). Rickettsiae, Medical Microbiology, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK7624\/."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1093\/infdis\/150.3.419","article-title":"Hematologic Changes in Brucellosis","volume":"150","author":"Crosby","year":"1984","journal-title":"J. Infect. Dis."},{"key":"ref_43","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":"Zhang","year":"2019","journal-title":"Emerg. Microbes Infect."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1007\/BF01647728","article-title":"Rickettsiosis-associated hyponatremia","volume":"15","author":"Mouallem","year":"1987","journal-title":"Infection"},{"key":"ref_45","unstructured":"Paddock, C.D., Guerra, M.A., Childs, J.E., and Swerdlow, D.L. (2024, September 21). Rocky Mountain Spotted Fever (Rickettsia rickettsii), Principles and Practice of Pediatric Infectious Disease: 3rd ed., Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK430881\/."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Herberg, J., Pahari, A., Walters, S., and Levin, M. (2009). Infectious Diseases and the Kidney. Pediatr. Nephrol., 1235\u20131273.","DOI":"10.1007\/978-3-540-76341-3_52"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"103340","DOI":"10.1016\/j.amsu.2022.103340","article-title":"The prevalence of the syndrome of inappropriate antidiuretic hormone secretion (SIADH) in brucellosis patients: Systematic review and meta-analysis","volume":"74","author":"Mohamed","year":"2022","journal-title":"Ann. Med. Surg."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1186\/s12879-023-08138-7","article-title":"Presentation of severe brucellosis in 5-year-old boy\u2014Challenges and results","volume":"23","author":"Dinikina","year":"2023","journal-title":"BMC Infect. Dis."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Lin, I.F., Lin, J.N., Tsai, C.T., Wu, Y.Y., Chen, Y.H., and Lai, C.H. (2020). Serum C-reactive protein and procalcitonin values in acute Q fever, scrub typhus, and murine typhus. BMC Infect. Dis., 20.","DOI":"10.1186\/s12879-020-05058-8"},{"key":"ref_50","unstructured":"Olsen, S.C., and Bricker, B. (2024, November 10). Brucella, Medical Microbiology, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK8572\/."},{"key":"ref_51","first-page":"636","article-title":"Treatment of brucellosis: A systematic review of studies in recent twenty years","volume":"4","author":"Alavi","year":"2013","journal-title":"Casp. J. Intern. Med."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/5\/1465\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:40:08Z","timestamp":1760028008000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/5\/1465"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,21]]},"references-count":51,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2025,3]]}},"alternative-id":["jcm14051465"],"URL":"https:\/\/doi.org\/10.3390\/jcm14051465","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,21]]}}}