The Significance of Prolonged and Saddleback Fever in Hospitalised Adult Dengue. IL-1 is a pyrogenic cytokine that plays a central role in inflammatory diseases like arthralgia [23]. 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. Published by Oxford University Press on behalf of Infectious Diseases Society of America. 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]. Chi-square and Fisher exact tests were used to evaluate differences in proportions for categorical variables, while the Mann-Whitney U test was used to evaluate differences in medians for continuous variables. Available at: Wang D, Hu B, Hu C, et al. However, there was a proportion of patients from our hospital who displayed 2 patterns of fever: 1 group had fever persisting into the second week of illness, while the second group displayed a saddleback pattern of fever, similar to that previously observed in dengue [11]. Outcomes of COVID-19 Among High-Risk Individuals: A Study Comparing Febrile and Afebrile Presentation. bOnly 1 sample of paired values available. History and physical examination alone are often sufficient to diagnose uncomplicated infectious causes of fever . Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are nonspecific acute-phase reactants that are routinely part of the evaluation of febrile patients.5,28 An extremely elevated ESR (100 mm per hour or greater) suggests etiologies such as abdominal or pelvic abscess, osteomyelitis, and endocarditis. Further testing should include blood cultures, lactate dehydrogenase, creatine kinase, rheumatoid factor, and antinuclear antibodies. JAMA 2020; 323(11):10619. Self-recorded temperature monitoring for COVID-19 patients at home or community isolation facilities can be used to triage patients who need admission to the hospital. 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. doi: 10.1371/journal.pntd.0002412. Adverse outcomes were hypoxia, intensive care unit (ICU) admission, mechanical ventilation, and mortality. FOUR TYPES OF FEVERS - Read online for free. This content is owned by the AAFP. . 2014; 8: e2777 10.1371/journal.pntd.0002777 Although there are more than 200 diseases in the differential diagnosis, most cases in adults are limited to several dozen possible causes. eCollection 2022. It's usually a sign of infection. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. 7 days, a Singapore study reveals. Results: Antibiotics usually aren't prescribed just because a child has a fever that is lasting a long time. If the diagnosis remains elusive, 18F fluorodeoxyglucose positron emission tomography plus computed tomography may help guide the clinician toward tissue biopsy. 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. FOIA Another limitation of our study is that onset of fever was dependant on self-reporting by patients. Search dates: November 28, 2011; February 8, 2012; and April 18, 2014. Cases with prolonged fever were defined as patients with fever lasting >7 days. On repeat testing, prolonged fever was associated with a drop in hemoglobin and a rise in CRP and LDH (Table 2). 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. Cytokines were determined with multiplex microbead-based immunoassay for a subgroup of patients. In general, fever is defined as a temperature > 38C (100.4F). Dengue fever is an acute febrile illness with a duration of 2-12 days. The classic presentation is one of fever, malaise, diffuse abdominal pain, and constipation. Cases with saddleback fever were defined as patients with recurrence of fever lasting <24 hours, after defervescence, beyond day 7 of illness. 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. Prolonged fever (fever > 7 days duration) was present in 572 (20.1%) of patients. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. 2022 May 20;15:2575-2587. doi: 10.2147/IDR.S355064. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (. Adverse outcomes were hypoxia, intensive care unit (ICU) admission, mechanical ventilation, and mortality. Prolonged fever is associated with adverse outcomes in dengue viral infection. Notably, patients with prolonged fever had higher IP-10 and lower IL-1 levels as compared with patients with saddleback fever (Figure 1B). 2022 Dec;55(6 Pt 1):1044-1051. doi: 10.1016/j.jmii.2022.07.009. 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. Europe PMC is an archive of life sciences journal literature. Pediatrics 1975; 55:468. Cytokine and chemokine concentrations from an additional 23 healthy controls who did not have COVID-19 were also analyzed for baseline comparison. Safety and Efficacy of Imatinib for Hospitalized Adults with COVID-19: A structured summary of a study protocol for a randomised controlled trial. For cases with saddleback fever, fever recurred at a median (IQR) of 10 (812) days after symptom onset. Institutional research board ethics approval and written consent were obtained for the drawing of blood specimens from participants for cytokine analysis (ref: DRSB 2012/00917). Patients were categorized as having prolonged fever (lasting >7 days), saddleback fever (defined as recurrent fever which lasts for <24 hours, after defervescence beyond day 7 of illness), or controls if their fever was 7 days. Clipboard, Search History, and several other advanced features are temporarily unavailable. World Health Organisation Special Programme for Research and Training in Tropical Diseases. 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). Ahmed S, Mohammad WW, Hamid F, Akhter A, Afzal RK, Mahmood A. J Coll Physicians Surg Pak. Characteristics and outcomes of patients with COVID-19 admitted to hospital and intensive care in the first phase of the pandemic in Canada: a national cohort study. Accessibility Affiliations, Plasma immune mediator levels in COVID-19 patients experiencing different fever patterns. Hypoxia was defined as requirement for supplemental oxygen. Other illnesses and inflammation. Outcomes of interest were hypoxia, admission to the intensive care unit (ICU), need for mechanical ventilation, and mortality. CMAJ Open. This study was funded by the National Medical Research Council COVID-19 Research Fund (COVID19RF-001) and Agency for Science, Technology and Research (A*STAR) COVID-19 Research funding (H/20/04/g1/006) provided to the Singapore Immunology Network by the Biomedical Research Council (BMRC), A*STAR. Data Sources: A PubMed search was completed using the key terms fever of unknown origin, FUO, pyrexia of unknown origin, and inflammatory markers. doi: 10.1371/journal.pone.0167025. Comparisons between prolonged fever and nonprolonged fever group are summarized in Tables 1 and 2. 8600 Rockville Pike 2021 Nov 5;114(8):541-542. doi: 10.1093/qjmed/hcab138. 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. 2013 Sep 26;7(9):e2412. COVID-19; cytokines; fever; prolonged; saddleback. The average body temperature is 98.6 F (37 C). Angela Chow Li Ping, Brenda Sze Peng Ang, Chen Seong Wong, Cheng Chuan Lee, Ding Ying, Jun-Yang Tay, Kalisvar Marimuthu, Lawrence Soon U. Lee, Yee-Sin Leo, Li Min Ling, Li Wei Ang, Lin Cui, Mark I-Cheng Chen, Monica Chan, Mucheli Sharavan Sadasiv, Oon-Tek Ng, Pei Hua Lee, Poh Lian Lim, Sapna Pradip Sadarangani, Shawn Vasoo, Stephanie Sutjipto, Tsin Wen Yeo, Tze Minn Mak. Patients with saddleback fever appeared to have good outcomes regardless of the fever, they noted. Federal government websites often end in .gov or .mil. Moreover, cases with prolonged fever also showed significantly higher plasma levels of inflammatory biomarkers such as interleukin (IL)-6 (p<0.01), IL-1RA (p<0.05), and induced protein-10 (IP-10; p<0.001) compared with controls during the early acute disease phase. In one review, an ESR of 100 mm per hour or greater had a high specificity for malignancy (96%) and infection (97%), and its positive predictive value was 90%.29 A normal ESR has a high negative predictive value for temporal arteritis.28,30 An ESR that is not elevated has no diagnostic value and does not rule out neoplastic or other disorders.27 CRP level is a sensitive marker for infection and inflammation, but it is not sensitive enough to discriminate between disease processes.28 However, a more recent prospective study found that the chance of establishing a diagnosis was higher in patients who had an elevated CRP level and ESR.15, Procalcitonin is a newer marker specific for bacterial infection. Confirmed imported case of novel coronavirus infection in Singapore; multi-ministry taskforce ramps up precautionary measures. [The] lower IP-10 level [with saddleback fever] is consistent with the finding that saddleback fever cases tend to have better clinical outcomes than prolonged fever cases, they noted. Dengue hemorrhagic fever (DHF), dengue shock syndrome (DSS) and severe dengue (SD) were significantly more likely to occur in patients with prolonged fever. Depending on clinical clues, this may include liver, lymph node, temporal artery, or bone marrow biopsy. ; Singapore 2019 Novel Coronavirus Outbreak Research Team. 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. Communicable Diseases Surveillance in Singapore 2005. A larger sample size may help to identify if prolonged and saddleback fever could be used as predictors for adverse outcomes such as ICU admission, mechanical ventilation, or death. 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. 2013; 496: 504507. One review found that noninvasive procedures led to most of the diagnoses, whereas of the invasive procedures, biopsies had the highest diagnostic yield.4, Other recommended blood tests at this phase include cryoglobulins (elevated in endocarditis, systemic lupus erythematosus, leukemias, and lymphomas),15,35 complement studies, serologic tests, peripheral smear, serum protein electrophoresis, and thyroid function studies. Duration of fever was prolonged with increased age. Fever often occurs in response to infection, inflammation and trauma. QJM. Copyright 2023 American Academy of Family Physicians. Lohr JA, Hendley JO. 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. Search life-sciences literature (41,164,937 (41,164,937 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. None of the 3 patients who entered the ICU had culture-proven nosocomial infections, suggesting that the fevers observed in the ICU were likely related to COVID-19 infection. No overall differences in safety or effectiveness . Symptoms of RSV include runny nose, cough, fever, and . Bethesda, MD 20894, Web Policies Prolonged fever of unknown origin in children. The 4 cases who were excluded from the primary analysis demonstrated a saddleback pattern of fever that lasted >24 hours. Viruses, bacteria, fungi, and parasites can cause infections. Cases without prolonged or saddleback fever were included as controls. There are no published guidelines, nor is there a recommended standard approach to the diagnosis. A P value of<.05 indicated statistical significance. The .gov means its official. In conclusion, we reported on the prevalence, risk factors, cytokine profiles, and outcomes of patients with COVID-19 who had saddleback or prolonged fever. Emadi A, Chua JV, Talwani R, Bentzen SM, Baddley J. 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]. Would you like email updates of new search results? In many cases, no specific cause of the fever is found, 2 . Fevers usually don't need treatment. Demographic, Clinical, Laboratory, and Radiological Features of Prolonged and Saddleback Fever in COVID-19. It starts suddenly and lasts 3 to 5 days. Age-appropriate or potentially diagnostic clueguided cancer screening should be performed (e.g., colonoscopy in patients 50 years or older). For full access to this pdf, sign in to an existing account, or purchase an annual subscription. Biphasic Zika Illness With Rash and Joint Pain. CONCLUSIONS: Prolonged fever beyond 7 days from onset of illness can identify patients who may be at risk of adverse outcomes from COVID-19. The 2011 dengue haemorrhagic fever outbreak in Lahore - an account of clinical parameters and pattern of haemorrhagic complications. Coronavirus disease 2019 (COVID-19) situation report101. 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. Bookshelf 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). Outbreak Research Team members are listed in the Acknowledgments, Deborah H L Ng, Chiaw Yee Choy, Yi-Hao Chan, Barnaby E Young, Siew-Wai Fong, Lisa F P Ng, Laurent Renia, David C Lye, Po Ying Chia, National Centre for Infectious Diseases COVID-19 Outbreak Research Team, Fever Patterns, Cytokine Profiles, and Outcomes in COVID-19, Open Forum Infectious Diseases, Volume 7, Issue 9, September 2020, ofaa375, https://doi.org/10.1093/ofid/ofaa375. Were also analyzed for baseline comparison up precautionary measures, this may include liver, node., admission to the content of the fever is defined as patients with prolonged fever of unknown origin children. The diagnosis parasites can cause infections elusive, 18F fluorodeoxyglucose positron emission tomography plus computed tomography help... Outcomes regardless of the manuscript have been disclosed that the editors consider relevant to the intensive unit. 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