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. Communicable Diseases Surveillance in Singapore 2005. If there is no clear source of infection, then further testing should follow. 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. Woon YL, Hor CP, Hussin N, Zakaria A, Goh PP, Cheah WK. Published by Oxford University Press on behalf of Infectious Diseases Society of America. Some children also may have a sore throat, runny nose or cough along with or before the fever. When there are no clear localizing signs or symptoms, clinicians should expand on the patient's symptoms and historical information, looking for potentially diagnostic clues to guide the evaluation (Table 4).1720,25,27 This is a continuous, iterative process.1921 Potentially diagnostic clues lead to a diagnosis in 62% of patients, although clues can be misleading because they are found in 97% of patients.1517, If no potentially diagnostic clues are found, a minimum diagnostic workup should be performed. Nature. doi: 10.1371/journal.pntd.0004575. This suggests that in patients with prolonged fever, close monitoring for deterioration should be instituted, while patients with saddleback fever who remain well and do not require supplemental oxygenation are unlikely to require close monitoring in the hospital, explained Ng and co-authors. doi: 10.1093/ofid/ofx133. Cytokines were determined with multiplex microbead-based immunoassay for a subgroup of patients. Untreated typhoid fever may progress to delirium, obtundation, intestinal hemorrhage, bowel. Cytokines included granulocyte-macrophage colony-stimulating factor (GM-CSF), epidermal growth factor (EGF), brain-derived neurotrophic factor, beta-nerve growth factor (bNGF), basic fibroblast growth factor (FGF-2), hepatocyte growth factor (HGF), monocyte chemoattractant protein (MCP) 1, macrophage inflammatory protein (MIP) 1, MIP-1, RANTES (regulated on activation, normal T cell expressed and secreted), chemokine (C-X-C motif) ligand (CXCL) 1 (GRO-), stromal cellderived factor 1 (SDF-1), interferon (IFN) gamma-induced protein 10 (IP-10), eotaxin, IFN-, IFN-, interleukin (IL) IL-1, IL-1, IL-1 receptor agonist (IL-1RA), IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12p70, IL-13, IL-15, IL-17A, IL-18, IL-21, IL-22, IL-23, IL-27, IL-31, leukemia inhibitory factor (LIF), stem cell factor (SCF), tumor necrosis factor (TNF-), TNF-, vascular endothelial growth factors A and D (VEGF-A, VEGF-D), platelet-derived growth factor (PDGF-BB), and placental growth factor (PLGF-1). Both prolonged (27.8% vs 0.9%; P < .01) and saddleback fever (14.3% vs 0.9%; P = .03) were associated with hypoxia compared with controls. The site is secure. 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). Notably, in a study of 3 COVID-19 patients, peak IL-1 appeared to precede the nadir of lung function [33], which may herald worsening inflammation. Patients with saddleback fever appeared to have good outcomes regardless of the fever. We wish to thank members of the Singapore Immunology Network Wilson How, Norman Leo Fernandez, Olaf Rtzschke, and Bernett Lee for their assistance with the multiplex microbead-based immunoassays and data analyses. Conclusions: In health, body temperature is regulated around a set point of 37 1C, and a circadian temperature rhythm exists in which the highest temperature of each day occurs around 6 p.m. eCollection 2022. Disclaimer. Fever was defined as a temperature of 38.0C or higher. This apparent difference in IL-1 between prolonged fever cases and saddleback fever cases may have occurred due to dynamic immune response and the time point of sample collection. 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. Saddleback fever was present in 165 (5.8%). The 4 cases who were excluded from the primary analysis demonstrated a saddleback pattern of fever that lasted >24 hours. 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. Outcomes of interest were hypoxia, admission to the intensive care unit (ICU), need for mechanical ventilation, and mortality. Compared with prolonged fever, saddleback fever did not show many significant associations except for diarrhea, abdominal pain, clinical fluid accumulation, hematocrit and platelet change, and lower systolic blood pressure. Extreme poverty first: An argument on the equitable distribution of the COVID-19 vaccine in Peru. The .gov means its official. JAMA Intern Med. Because there are no guidelines to the approach of the febrile patient, most evaluation recommendations are based on expert opinion.17 On initial presentation, most clinicians perform a history and physical examination in pursuit of an infection. Copyright 2023 American Academy of Family Physicians. Although prolonged and saddleback fever have been reported in dengue fever, there are no specific studies on their significance in dengue. Such facilities free up hospital beds to enable sicker patients to be optimally managed. The median age was 34 years of age (5 th - 95 th percentile: 17-59) and males comprised 1971 (69.3%) of study sub- A fever may be caused by a virus, bacteria, fungus, blood clot, tumor, drug, or the environment. PMC This suggests that in patients with prolonged fever, close monitoring for deterioration should be instituted, while patients with saddleback fever who remain well and do not require supplemental oxygenation are unlikely to require close monitoring in the hospital. 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. eCollection 2016. 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. The results of this study can be used to optimize placement of patients with COVID-19. Lancet 2020; 395:497506. Rash. 2022 Dec;55(6 Pt 1):1044-1051. doi: 10.1016/j.jmii.2022.07.009. Two of these patients were admitted to the ICU, which may suggest another phenotype of patients who are at higher risk of adverse outcomes. CMAJ Open. Bethesda, MD 20894, Web Policies doi: 10.1371/journal.pone.0167025. Cytokines were determined with multiplex View PDF Save to Library Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. 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. Federal government websites often end in .gov or .mil. Home or community isolation facilities and the other iterations for positive cases are commonly used globally to isolate positive patients [34, 35]. Clinicians should perform a comprehensive history and examination to look for potentially diagnostic clues to guide the initial evaluation. 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). The author(s) received no specific funding for this work. HHS Vulnerability Disclosure, Help National Library of Medicine Cases without prolonged or saddleback fever were included as controls. Hypoxia was defined as requirement for supplemental oxygen. Cases with prolonged fever had a median duration of fever (IQR) lasting 10 (912) days. Singapore reported its first imported case of COVID-19 in a traveler from Wuhan on January 23, 2020, followed by its first locally transmitted case on February 7, 2020 [2, 3]. However, unlike RA, rheumatic . The findings of the study are useful for informing the optimal placement of patients with COVID-19, the researchers pointed out. Comparisons between prolonged fever and nonprolonged fever group are summarized in Tables 1 and 2. See permissionsforcopyrightquestions and/or permission requests. Oxford University Press is a department of the University of Oxford. In hypoxic conditions, it can trigger the expression of chemokines that attract neutrophils and monocytes to the ischemic tissue [31]. There were no deaths in our study. Keywords: Roseola often starts with a high fever often higher than 103 F (39.4 C). Plasma immune mediator levels in COVID-19 patients experiencing different fever patterns. The https:// ensures that you are connecting to the PLoS Negl Trop Dis. Prolonged fever beyond 7 days from onset of illness can identify patients who may be at risk of adverse outcomes from COVID-19. as they fulfilled overlapping criteria for prolonged and saddleback fever. If noninvasive diagnostic tests are unrevealing, then the invasive test of choice is a tissue biopsy because of the relatively high diagnostic yield. 2015 Sep 30;15:399. doi: 10.1186/s12879-015-1141-3. Based on this study, patients with saddleback fever who remain well can be monitored in the community, while patients who have fever for >7 days should be admitted for closer monitoring. Fever of unknown origin (FUO) in adults is one of the most vexing clinical conditions for clinicians and patients. 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). Europe PMC is an archive of life sciences journal literature. Epub 2022 Aug 11. Coronavirus disease 2019 (COVID-19) situation report101.2020. The different prognoses for these 2 groups of patients have implications for the distribution of increasingly burdened hospital resources given the exponential rise in cases worldwide. Antibiotics usually aren't prescribed just because a child has a fever that is lasting a long time. Available at: Ministry of Health (MOH) Singapore. Roseola symptoms might include: Fever. Approval for data collection by retrospective chart review with a waiver of written informed consent from study participants was granted by the Singapore Ministry of Health under the Infectious Diseases Act as part of the outbreak investigation [14]. All Rights Reserved. 2022 Oct 31;12:1009894. doi: 10.3389/fcimb.2022.1009894. Blue and red represent low and high concentrations, respectively. PLoS One. This corresponded with a rise in CRP and LDH seen in cases with prolonged fever, which are known to be associated with adverse prognostic factors in COVID-19 [15, 16]. Federal government websites often end in .gov or .mil. 2013 Oct 20;20(1):75. doi: 10.1186/1423-0127-20-75. 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