There were no significant changes in laboratory findings when repeated at the point of fever, except for a rise in platelet and lymphocyte counts (Table 2). Fever, face edema, fatigue, fungal infection, malaise, . However, there were no significant differences in the admission laboratory values between the control and saddleback fever groups. FOUR TYPES OF FEVERS - Read online for free. Prolonged fever of unknown origin: a record of experiences with 54 childhood patients. A Two-Year Review on Epidemiology and Clinical Characteristics of Dengue Deaths in Malaysia, 2013-2014. Your comment will be reviewed and published at the journal's discretion. Prolonged fever was also associated with lower platelet count and higher CRP compared with controls. Comparing the difference between prolonged fever cases and saddleback fever cases, we found an increased IL-1 level and lower IP-10 level on admission. Bethesda, MD 20894, Web Policies Figure 1 outlines a diagnostic approach to patients with prolonged febrile illness and FUO.1,2,47,1520,23,27, Hospitalization may be considered at any time during the evaluation, especially if the patient exhibits signs of a critical illness. The authors have declared that no competing interests exist. Repeat CXR was not performed for cases in the control group and 1 case of saddleback fever. Unauthorized use of these marks is strictly prohibited. Abdominal and pelvic ultrasonography are often recommended in the initial workup because of availability, low cost, and lack of radiation exposure.15 After the initial evaluation is complete and if there is no diagnosis, the patient is considered to have FUO, and a secondary evaluation should be considered. The classic presentation is one of fever, malaise, diffuse abdominal pain, and constipation. . Lohr JA, Hendley JO. If noninvasive diagnostic tests are unrevealing, then the invasive test of choice is a tissue biopsy because of the relatively high diagnostic yield. Patients with saddleback fever appeared to have good outcomes regardless of the fever. Meanwhile, the levels of IP-10 in patients with saddleback fever was lower than those with prolonged fever (p<0.001) at a level almost matching that in controls. Patients with prolonged fever are more likely to develop hypoxia and have a more pronounced inflammatory response in comparison with those in the saddleback fever group, which is also reflected in the different cytokine profiles between the 2 groups. World Health Organisation Special Programme for Research and Training in Tropical Diseases. 2022 Oct 31;12:1009894. doi: 10.3389/fcimb.2022.1009894. Careers. But normal body temperature can range between 97 F (36.1 C) and 99 F (37.2 C) or more. Infections predominate early in FUO diagnoses, and the longer FUO remains undiagnosed, the less likely it is caused by an infection.27 After infections, the etiology of FUO transitions to noninfectious inflammatory diseases and malignancies, which can guide subsequent testing. eCollection 2017 Summer. It's usually a sign of infection. Patients with prolonged fever may have had higher levels of IL-1 earlier on before sample collection. Refining the global spatial limits of dengue virus transmission by evidence-based consensus. Sixty-nine percent of them were male with a median age of 34 years. Extreme poverty first: An argument on the equitable distribution of the COVID-19 vaccine in Peru. Fever of unknown origin is more often an atypical presentation of a common disease rather than an unusual disease. Potential conflicts of interest. 2015 Sep 30;15:399. doi: 10.1186/s12879-015-1141-3. An official website of the United States government. 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Fever of unknown origin has been described as a febrile illness (temperature of 101F [38.3C] or higher) for three weeks or longer without an etiology despite a one-week inpatient evaluation. We conducted a hospital-based casecontrol study of patients admitted for COVID-19 with prolonged fever (fever>7 days) and saddleback fever (recurrence of fever, lasting <24 hours, after defervescence beyond day 7 of illness). In patients with saddleback fever, higher levels of IL-1, IL-21, IL-22, and SDF-1 were observed compared with control patients. In addition, IP-10 has also been reported to be associated with increased viral load, lung injury, ICU admission, and mortality [21]. Interestingly, there are also higher plasma levels of IL-1RA in patients with prolonged fever compared with control patients. Oxford University Press is a department of the University of Oxford. Murthy S, Archambault PM, Atique A, Carrier FM, Cheng MP, Codan C, Daneman N, Dechert W, Douglas S, Fiest KM, Fowler R, Goco G, Gu Y, Guerguerian AM, Hall R, Hsu JM, Joffe A, Jouvet P, Kelly L, Kho ME, Kruisselbrink RJ, Kumar D, Kutsogiannis DJ, Lamontagne F, Lee TC, Menon K, O'Grady H, O'Hearn K, Ovakim DH, Pharand SG, Pitre T, Reel R, Reeve B, Rewa O, Richardson D, Rishu A, Sandhu G, Sarfo-Mensah S, Shadowitz E, Sligl W, Solomon J, Stelfox HT, Swanson A, Tessier-Grenier H, Tsang JLY, Wood G; SPRINT-SARI Canada Investigators and the Canadian Critical Care Trials Group. Background: If there is no clear source of infection, then further testing should follow. Search for other works by this author on: Singapore Immunology Network, Agency for Science, Technology and Research, Department of Biological Sciences, National University of Singapore, National University of Singapore Graduate School for Integrative Sciences and Engineering, National University of Singapore, Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, National Centre for Infectious Diseases COVID-19 Outbreak Research Team. HHS Vulnerability Disclosure, Help MeSH Plasma fractions were isolated from blood samples of COVID-19 patients collected during the acute phase (median post-illness onset, 6 days). Clipboard, Search History, and several other advanced features are temporarily unavailable. Cases without prolonged or saddleback fever were included as controls. Adverse outcomes were hypoxia, intensive care unit (ICU) admission, mechanical ventilation, and mortality. B, Comparison of immune mediator levels in patients with prolonged fever (n=11), patients with saddleback fever (n=8), and patients with fever that lasted 7 days (control; n=56). 2017 Jun 22;4(3):ofx133. Statistical analyses were performed with the Mann-Whitney U test (*P<.05; **P<.01; ***P<.001). 8600 Rockville Pike ELIZABETH C. HERSCH, COL, MC, USA, AND C. ROBERT, OH, LTC, MC, USA. Higher heart rate and respiratory rate and lower oxygen saturation (spO2), systolic and diastolic blood pressure (BP) were associated with prolonged fever compared with controls (Table 1). In addition, as these patients with saddleback fever tend to do well, there is also no need for repeat laboratory testing or chest X-ray, as the results are unlikely to change management or clinical outcomes, they said. Cases with prolonged fever were defined as patients with fever lasting >7 days. Front Cell Infect Microbiol. -, Huang C, Wang Y, Li X, et al. Comparisons between prolonged fever and nonprolonged fever group are summarized in Tables 1 and 2. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. Repeat laboratory investigations and CXR were done for those with prolonged or saddleback fever and collected. In hypoxic conditions, it can trigger the expression of chemokines that attract neutrophils and monocytes to the ischemic tissue [31]. Previous testing (ESR, complete blood count, electrolyte panel, chest radiography, urinalysis, blood culture) may be repeated periodically to evaluate for trends as the illness evolves. Statistical analyses were performed using Stata, version 14 (StataCorp, College Station, TX, USA). Khalaf M, Alboraie M, Abdel-Gawad M, Abdelmalek M, Abu-Elfatth A, Abdelhamed W, Zaghloul M, ElDeeb R, Abdeltwab D, Abdelghani M, El-Raey F, Aboalam H, Badry A, Tharwat M, Afify S, Elwazzan D, Abdelmohsen AS, Fathy H, Wagih Shaltout S, Hetta HF, Bazeed SE. If there are no potentially diagnostic clues, the patient should undergo a minimum diagnostic workup, including a complete blood count, chest radiography, urinalysis and culture, electrolyte panel, liver enzymes, erythrocyte sedimentation rate, and C-reactive protein level testing. Copyright 2023 American Academy of Family Physicians. Erythrocyte sedimentation rate and C-reactive protein levels should be measured in the initial workup of a patient who has prolonged febrile illness without a clear source. Confirmed imported case of novel coronavirus infection in Singapore; multi-ministry taskforce ramps up precautionary measures.2020. These patients required prolonged periods of observation and symptomatic treatment. Patients with prolonged fever had higher induced protein -10 and lower interleukin-1 levels compared with those with saddleback fever at the early acute phase of disease. A more recent qualitative definition requires only a reasonable diagnostic evaluation. Clinical and laboratory predictive markers for acute dengue infection. Saddleback fever was present in 165 (5.8%). Several diagnostic algorithms have been suggested for FUO, but few are supported by evidence from prospective studies.17 Region-specific serologic tests, more advanced radiologic studies, and more invasive diagnostic procedures can be guided by potentially diagnostic clues. Mucosal bleeding, anorexia, diarrhea, abdominal pain, nausea or vomiting, lethargy, rash, clinical fluid accumulation, hepatomegaly, nosocomial infection, leukopenia, higher neutrophil count, higher hematocrit, higher alanine transaminase (ALT) and aspartate transaminase (AST), higher creatinine, lower protein and prolonged activated partial thromboplastin time (APTT) were significantly associated with prolonged fever but not platelet count or prothrombin time (PT). Ng DH, Wong JG, Thein TL, Leo YS, Lye DC. Before In contrast, cases with saddleback fever showed no significant change upon repeating their laboratory tests. Those with prolonged fever had a median duration of fever (interquartile range [IQR]) of 10 (9-11) days for prolonged fever cases, while fever recurred at a median (IQR) of 10 (8-12) days for those with saddleback fever. The elevation of circulating IL-1RA may reflect overactive IL-1 activation, which has been reported to associated with severe outcomes in COVID-19 [24]. Biphasic Zika Illness With Rash and Joint Pain. A fever may be caused by a virus, bacteria, fungus, blood clot, tumor, drug, or the environment. eCollection 2016. Keywords: Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; BP, blood pressure; CRP, C-reactive protein; CXR, chest x-ray; ICU, intensive care unit; LDH, lactate dehydrogenase. Empiric trials of antibiotics or steroids rarely establish a diagnosis and are discouraged in the management of patients with FUO, unless there are clinical indications.5,17,19,21,22 Consultation with a subspecialist (e.g., infectious disease specialist, rheumatologist, hematologist/oncologist) is appropriate at any point in the evaluation. Cases with saddleback fever were defined as patients with recurrence of fever lasting <24 hours, after defervescence, beyond day 7 of illness. Disclaimer. Available at: Ministry of Health (MOH) Singapore. When compared with controls, both prolonged and saddleback fever were associated with hypoxia, with the highest rate seen in cases with prolonged fever (27.8 percent and 14.3 percent vs 0.9 percent for prolonged and saddleback fever vs control, respectively; p<0.01 and p=0.03 for each respective comparison). The search included reviews, case series, meta-analyses, and randomized controlled trials. Flu is caused by influenza viruses only, whereas the common cold can be caused by a number of different viruses, including rhinoviruses, parainfluenza, and seasonal coronaviruses. Chan SY, Tsai YF, Yen MY, Yu WR, Hung CC, Kuo TL, Chen CC, Yen YF, Huang SH, Huang TC, Huang SJ. A prolonged fever of unknown origin (FUO) is simply one that lasts longer than usual, for example, more than the seven to 10 days that you would expect with a simple viral infection. Grasselli G, Greco M, Zanella A, Albano G, Antonelli M, Bellani G, Bonanomi E, Cabrini L, Carlesso E, Castelli G, Cattaneo S, Cereda D, Colombo S, Coluccello A, Crescini G, Forastieri Molinari A, Foti G, Fumagalli R, Iotti GA, Langer T, Latronico N, Lorini FL, Mojoli F, Natalini G, Pessina CM, Ranieri VM, Rech R, Scudeller L, Rosano A, Storti E, Thompson BT, Tirani M, Villani PG, Pesenti A, Cecconi M; COVID-19 Lombardy ICU Network. This study aims to examine the prevalence of prolonged and saddleback fever in dengue as well as their associations with dengue severity. Saddleback fever was significantly associated with hypoxia (14.3% vs 0.9%; P=.03) but not ICU admission (0.9% vs 0.0 %; P=1.00) compared with those in the control group. Fevers usually don't need treatment. A more recent article on fever of unknown origin in adults is available. Additional microbiological investigations, such as blood and urine cultures, influenza and respiratory viral multiplex PCR, dengue NS1 and serology, were ordered at the discretion of the primary treating clinician. 2020 Oct 1;180(10):1345-1355. doi: 10.1001/jamainternmed.2020.3539. Concentrations of 45 immune mediators in plasma were quantified using a 45-plex microbead-based immunoassay. Such facilities free up hospital beds to enable sicker patients to be optimally managed. At the initial encounter, testing for common infections should include a complete blood count with differential, electrolyte panel, liver enzymes, urinalysis with culture, blood culture, and chest radiography. The mean duration of symptoms and signs before diagnosis (28.4 13.2 versus 45.0 30.8 days; P < 0.05), . Additional references were identified from the articles reviewed. The analysis, which was. Never give a child aspirin, as this increases the risk of . Since its first report in Wuhan, China, in December 2019, COVID-19 has rapidly spread, becoming a pandemic with more than 3 million confirmed cases [1]. Both prolonged fever and saddleback fever were not significantly associated with mechanical ventilation as compared with the control group (Table 1). Pediatrics 1975; 55:468. Seven more confirmed cases of novel coronavirus infection in Singapore. COVID-19 generally presents as an acute respiratory illness, with fever, fatigue, and dry cough being commonly reported symptoms [46]. Bookshelf The presence of prolonged or saddleback fever in dengue patients should therefore prompt detailed evaluation for complications of dengue, as well as early investigation to evaluate for development of nosocomial infection. In conclusion, we reported on the prevalence, risk factors, cytokine profiles, and outcomes of patients with COVID-19 who had saddleback or prolonged fever. Open Forum Infect Dis. One limitation of the study is the small sample size of our cohort. But there are some important differences. QJM. In this study, saddleback fever was defined as temperature >37.5C with defervescence of at least one day, followed by a second peak lasting at least one day. Disclaimer. Methods We conducted a hospital-based case-control study of patients admitted for COVID-19 with prolonged fever (fever >7 days) and saddleback fever (recurrence of fever, lasting <24 hours, after defervescence beyond day 7 of illness). 2016 Dec 9;11(12):e0167025. eCollection 2022. However, it is interesting that there are higher pro-inflammatory IL-1 levels in patients with saddleback fever. We conducted a hospital-based case-control study of patients admitted for COVID-19 with prolonged fever (fever >7 days) and saddleback fever (recurrence of fever, lasting <24 hours, after defervescence beyond day 7 of illness). People who wish to treat a fever can try over-the-counter anti-fever medications, such as acetaminophen, aspirin, or ibuprofen. On repeat testing, prolonged fever was associated with a drop in hemoglobin and a rise in CRP and LDH (Table 2). https://www.who.int/docs/default-source/coronaviruse/situation-reports/2 https://www.moh.gov.sg/news-highlights/details/confirmed-imported-case-o https://www.moh.gov.sg/news-highlights/details/seven-more-confirmed-case World Health Organization. Prolonged fever beyond 7 days from onset of illness can identify patients who may be at risk of adverse outcomes from COVID-19. There were no deaths in our study. A total of 142 patients were included in the study; 12.7% (18/142) of cases had prolonged fever, and 9.9% (14/142) had saddleback fever. Some children also may have a sore throat, runny nose or cough along with or before the fever. J Microbiol Immunol Infect. Human immunodeficiency virus and appropriate region-specific serologic testing (e.g., cytomegalovirus, Epstein-Barr virus, tuberculosis) and abdominal and pelvic ultrasonography or computed tomography are commonly performed. Data were collected for the remaining 110 patients from this cohort as controls; 57.0% (81/142) of all study subjects were male, and the median age (interquartile range [IQR]) was 42 (3154) years. A larger cohort might help to improve our understanding of these patients. All efforts have been undertaken to anonymize the data. Roseola symptoms might include: Fever. For full access to this pdf, sign in to an existing account, or purchase an annual subscription. doi: 10.1371/journal.pntd.0004575. as they fulfilled overlapping criteria for prolonged and saddleback fever. Woon YL, Hor CP, Hussin N, Zakaria A, Goh PP, Cheah WK. McClung HJ. Europe PMC is an archive of life sciences journal literature. Patient information: See related handout on fever of unknown origin in adults, written by the authors of this article. Ying-Hao P, Yuan-Yuan G, Hai-Dong Z, Qiu-Hua C, Xue-Ran G, Hai-Qi Z, Hua J. Upon admission, all patients underwent a chest x-ray (CXR), admission full blood count (FBC), renal and liver panel, C-reactive protein (CRP), lactate dehydrogenase (LDH), and nasopharyngeal swab for SARS-CoV-2 PCR. [Open Forum Infect Dis 2020;7:ofaa375]. 2021 Nov 5;114(8):541-542. doi: 10.1093/qjmed/hcab138. JAMA Intern Med. Rowe EK, Leo Y-S, Wong JGX, Thein T-L, Gan VC, Lee LK, et al. Physicians may consider stopping antimicrobials if all investigations are unyielding and patients remain hemodynamically stable. Eleven patients with prolonged fever, 8 patients with saddleback fever and 56 patients with fever lasting 7 days (controls) were evaluated at the first time point of blood sample collection upon hospitalization (median of 6 days postillness onset) (Figure 1A). 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