Department of Infectious Diseases, Tan Tock Seng Hospital, Correspondence: Deborah H. L. Ng, MBChB, MRCP(UK), MSc, MPH, Department of Infectious Diseases, Centre for Healthcare Innovation, 18 Jalan Tan Tock Seng, Singapore 308443 (. This content is owned by the AAFP. Chan SY, Tsai YF, Yen MY, Yu WR, Hung CC, Kuo TL, Chen CC, Yen YF, Huang SH, Huang TC, Huang SJ. Cytokines were determined with multiplex microbead-based immunoassay for a subgroup of patients. Federal government websites often end in .gov or .mil. 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. The levels of other immune mediators measured were not significantly different between groups. Epub 2022 Aug 11. 7 days, a Singapore study reveals. The global distribution and burden of dengue. Adverse outcomes were hypoxia, intensive care unit (ICU) admission, mechanical ventilation, and mortality. Over- or under-reporting of the onset of fever before admission could affect the number of patients found to have prolonged or saddleback fever. Unmasking latent extrapulmonary tuberculosis with newly diagnosed HIV-1 infection in a COVID-19 patient with prolonged fever. Effects of sericin and egg white on the inflammation of damaged skin in mice. eCollection 2016 May. 2021 Mar 8;9(1):E181-E188. In particular, fever was reported in about 72%98.6% of patients, usually lasting <7 days [4, 710]. There were no deaths in our study. Available at: Ministry of Health (MOH) Singapore. A lower IP-10 level is consistent with the finding that saddleback fever cases tend to have better clinical outcomes than prolonged fever cases. Although there were no significant differences in white blood cell counts or absolute values of lymphocytes and CRP, we found significant differences in plasma IL-6 and IP-10 levels between the prolonged fever and control patients. 2021 Jan-Feb;50(1):28-32. doi: 10.1016/j.hrtlng.2020.10.013. Prolonged fever of unknown origin in children. 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. All Rights Reserved. An official website of the United States government. Both COVID-19 and the common cold can include a runny nose, sore throat, and fever, says Dr. Fisher, and both can last between a few days or a week. Fever of unknown origin (FUO) in adults is one of the most vexing clinical conditions for clinicians and patients. Both prolonged fever and saddleback fever were not significantly associated with mechanical ventilation as compared with the control group (Table 1). McClung HJ. but the rest of the symptoms did not have a difference between the 2 serotypes. 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. The .gov means its official. Prolonged fever was defined as fever lasting more than 7 days. Roseola often starts with a high fever often higher than 103 F (39.4 C). Never give a child aspirin, as this increases the risk of . 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. 2022 Aug;14(8):321-326. doi: 10.14740/jocmr4791. A fever is a rise in body temperature. Normal body temperature can vary depending on the individual, the time of day, and even the weather. 2013 Oct 20;20(1):75. doi: 10.1186/1423-0127-20-75. The higher levels of IL-1 could initiate the first occurrence of fever, while the pro-inflammatory cytokines IL-21 and IL-22 mediate the activation of T cells and M1 macrophages [25, 26], which drive the recurrence of fever in saddleback fever cases. If there is no clear source of infection, then further testing should follow. Cases with prolonged fever were defined as patients with fever lasting >7 days. People who wish to treat a fever can try over-the-counter anti-fever medications, such as acetaminophen, aspirin, or ibuprofen. This site needs JavaScript to work properly. Statistical analyses were performed using GraphPad Prism, version 8. Dengue hemorrhagic fever (DHF), dengue shock syndrome (DSS) and severe dengue (SD) were significantly more likely to occur in patients with prolonged fever. The site is secure. Influenza (flu) and the common cold are both contagious respiratory illnesses, but they are caused by different viruses. Recommendations of the Scientific Working Group on Dengue. eCollection 2017 Summer. IL-1 is dual function cytokine that can act as both a transcription factor and a damage-associated molecular pattern (DAMP), which can be released by necrotic cells to promote and exacerbate inflammation via IL-1R1 [30]. Those with prolonged fever had a median duration of fever for 10 days (IQR 9-11 days) for prolonged fever cases, while fever recurred at a median of 10 days (IQR 8-12 days) for those with saddleback fever. A total of 2843 polymerase-chain reaction (PCR) confirmed dengue patients admitted to Tan Tock Seng Hospital from 2004 to 2008 were included in the study. 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. 2013 Jul;23(7):463-7. Unable to load your collection due to an error, Unable to load your delegates due to an error. However, there were no significant differences in the admission laboratory values between the control and saddleback fever groups. Duration of fever was prolonged with increased age. In addition, as these patients with saddleback fever tend to do well, there is also no need for repeat laboratory testing or CXR, as the results are unlikely to change management or clinical outcomes. Cases with prolonged fever were defined as patients with fever lasting >7 days. 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]. as they fulfilled overlapping criteria for prolonged and saddleback fever. 2022 Jul 26;2022(7):omac079. Coronavirus disease 2019 (COVID-19) situation report101. Prolonged fever (fever > 7 days duration) was present in 572 (20.1%) of patients. Out-of-hospital cardiac arrest and in-hospital mortality among COVID-19 patients: A population-based retrospective cohort study. A more recent qualitative definition requires only a reasonable diagnostic evaluation. 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. Plasma immune mediator levels in COVID-19 patients experiencing different fever patterns. 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]. Fever was defined as a temperature of 38.0C or higher. Additional searches included the Cochrane database, Essential Evidence Plus, the Agency for Healthcare Research and Quality evidence reports, and the National Guideline Clearinghouse. History and physical examination alone are often sufficient to diagnose uncomplicated infectious causes of fever . Front Cell Infect Microbiol. To investigate whether the fever patterns experienced by the patients are due to differences in immune responses, concentrations of 45 immune mediators were profiled. An official website of the United States government. JAMA Intern Med. There was no difference in types of diagnoses for those who met the strict 1991 definition compared with those who received a diagnosis in less than three weeks.10 Therefore, FUO may be assumed when no reasonable diagnosis is reached after an appropriate inpatient or outpatient investigation.2,6,1017 Table 1 compares the evolution of the definition of FUO.2,3,6,7,1017, Other subtypes of FUO are nosocomial, neutropenic, and human immunodeficiency virusassociated.7 These subtypes have different approaches to evaluation and are beyond the scope of this article.17, The etiologies of FUO have changed over time because of shifting disease patterns and new diagnostic techniques.14 There are more than 200 diseases in the differential diagnosis.4,15,17 In multiple case series, however, the etiology of FUO is limited to several dozen causes, and patients often have an atypical presentation of a common disease.2,6,18. Shivering, shaking, and chills Aching muscles and joints or other body aches Headache Intermittent sweats or excessive sweating Rapid heart rate and/or palpitations Skin flushing or hot skin Feeling faint, dizzy, or lightheaded Eye pain or sore eyes Weakness Loss of appetite Fussiness (in children and toddlers) Respiratory syncytial virus disease burden in community-dwelling and long-term care facility older adults in Europe and the United States: A prospective study, Viral aetiology and clinical characteristics of acute respiratory tract infections in hospitalized children in Southern Germany (2014-2018), Coronary Artery Plaque Composition and Severity Relate to the Inflammasome in People with Treated HIV, Sustained Virologic Suppression With Dolutegravir/Lamivudine in a Test-and-Treat Setting Through 48 Weeks, Impact of hypoalbuminemia on ceftriaxone treatment failure in patients with Enterobacterales bacteremia: a propensity matched, retrospective cohort study, About the Infectious Diseases Society of America, https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200430-sitrep-101-covid-19.pdf?sfvrsn=2ba4e093_2, https://www.moh.gov.sg/news-highlights/details/confirmed-imported-case-of-novel-coronavirus-infection-in-singapore-multi-ministry-taskforce-ramps-up-precautionary-measures, https://www.moh.gov.sg/news-highlights/details/seven-more-confirmed-cases-of-novel-coronavirus-infection-in-singapore, https://sso.agc.gov.sg/Act/IDA1976#pr25A-, https://doi.org/10.1101/2020.03.02.20029975, https://www.cdc.gov/coronavirus/2019-ncov/hcp/guidance-home-care.html, https://www.straitstimes.com/singapore/9-in-10-coronavirus-patients-housed-in-isolation-facilities, https://www.moh.gov.sg/news-highlights/details/56-more-cases-discharged-528-new-cases-of-covid-19-infection-confirmed, http://creativecommons.org/licenses/by-nc-nd/4.0/, Receive exclusive offers and updates from Oxford Academic. Federal government websites often end in .gov or .mil. Prolonged fever beyond 7 days from onset of illness can identify patients who may be at risk of adverse outcomes from COVID-19, said the researchers led by Dr Deborah Ng from National Centre for Infectious Diseases (NCID), Singapore, on behalf of the NCID COVID-19 Outbreak Research Team. The results of this study can be used to optimize placement of patients with COVID-19. Other illnesses and inflammation. doi: 10.1093/omcr/omac079. Please enable it to take advantage of the complete set of features! Please enable it to take advantage of the complete set of features! Conclusions: 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. Dengue fever is gaining importance in Singapore with an increase in the number of cases and mortality in recent years. Accessibility 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). Europe PMC is an archive of life sciences journal literature. Results: 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. Prolonged fever is associated with adverse outcomes in dengue viral infection. Outcomes of patients with COVID-19 in the intensive care unit in Mexico: A multicenter observational study. Antibiotics usually aren't prescribed just because a child has a fever that is lasting a long time. is funded by the National Medical Research Council (NMRC/Fellowship/0056/2018). Accessibility There was progression of infiltrates on the CXR for 72.2% (13/18) of cases with prolonged fever and 38.5% (5/13) in those with saddleback fever. Author disclosure: No relevant financial affiliations. Prolonged fever was also associated with lower platelet count and higher CRP compared with controls. Roseola symptoms might include: Fever. 2014; 8: e2777 10.1371/journal.pntd.0002777 Viruses, bacteria, fungi, and parasites can cause infections. Before 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. For cases with saddleback fever, fever recurred at a median (IQR) of 10 (812) days after symptom onset. The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). A Two-Year Review on Epidemiology and Clinical Characteristics of Dengue Deaths in Malaysia, 2013-2014. 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. The https:// ensures that you are connecting to the Patients with prolonged fever may have had higher levels of IL-1 earlier on before sample collection. A comprehensive history and physical examination should be performed if there are no localizing signs and symptoms in patients with prolonged febrile illness. Statistical analyses were performed with the Mann-Whitney U test (*P<.05; **P<.01; ***P<.001). Duration of rhinorrhea and cough was shorter in females than in males and in groups with birth weight 3 kg than in those with <2.5 kg. Demographics were similar across the 3 groups (Table 1); 7.0% (10/142) of patients had comorbidities, such as diabetes (n=4), ischemic heart disease (n=3), and asthma (n=3). Outcomes of interest were hypoxia, admission to the intensive care unit (ICU), need for mechanical ventilation, and mortality. The median age was 34 years of age (5 th - 95 th percentile: 17-59) and males comprised 1971 (69.3%) of study sub- Keywords: While prolonged fever was associated with a higher rate of ICU admission vs controls (11.1 percent vs 0.9 percent; p=0.05), saddleback fever was not, despite both being associated with hypoxia. 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). Cytokines were determined with multiplex View PDF Save to Library doi: 10.1093/ofid/ofx133. A fever is a rise in your body temperature. A. Ying-Hao P, Yuan-Yuan G, Hai-Dong Z, Qiu-Hua C, Xue-Ran G, Hai-Qi Z, Hua J. Your body temperature can vary depending . official website and that any information you provide is encrypted Prolonged fever lasting more than 7 days after illness onset can help physicians identify patients at high risk for adverse outcomes from COVID-19, according to a study. However, as the number of patients with prolonged fever requiring ICU admission is small in this cohort, further studies should be done to prove this correlation. Repeat CXR was not performed for cases in the control group and 1 case of saddleback fever. In one study of patients with FUO, chest and abdominal CT had high sensitivity (82% and 92%, respectively) and were recommended if the initial evaluation was unrevealing.15 CT specificity ranged from 60% to 70%, consistent with other case series.15,16 Echocardiography is recommended if there are clinical indications of endocarditis.5,20 Venous Doppler ultrasonography is indicated for suspected thromboembolism.20 Magnetic resonance imaging of the aortic arch and great vessels of the neck was shown to be helpful when vasculitis was suspected.36, Nuclear imaging studies are noninvasive, image the whole body, and can localize a potential infectious or inflammatory cause for FUO.5,14,19,3740 Recently, 18F fluorodeoxyglucose positron emission tomography technology has been evaluated for guiding further invasive testing, especially in patients who have an elevated ESR or CRP level.14,37 The 18F fluorodeoxyglucose is taken up by inflammatory and cancer cells because of their high rate of glucolysis.14,18,37 Several studies examining this method in patients with FUO found diagnostic yields ranging from 16% to 69%,15,37,38 with a high positive predictive value (93%) and negative predictive value (100%).39,40 A hybrid of CT and 18F fluorodeoxyglucose positron emission tomography has a higher diagnostic yield (sensitivity of 56% to 100%; specificity of 75% to 81%18). Cases without prolonged or saddleback fever were included as controls. 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.
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