eCollection 2016. Over- or under-reporting of the onset of fever before admission could affect the number of patients found to have prolonged or saddleback 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. Cavalli G, De Luca G, Campochiaro C, et al. Confirmed imported case of novel coronavirus infection in Singapore; multi-ministry taskforce ramps up precautionary measures. -. Cases with prolonged fever were defined as patients with fever lasting >7 days. A P value of<.05 indicated statistical significance. Notably, patients with prolonged fever had higher IP-10 and lower IL-1 levels as compared with patients with saddleback fever (Figure 1B). Cases with prolonged fever were found to have higher levels of anti-inflammatory IL-1RA, pro-inflammatory IL-6, and chemokine interferon- IP-10 compared with controls (Figure 1B). Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. 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. Keywords: This phenomenon is also observed in other viral fevers, like dengue virus [27] and thrombocytopenia syndrome virus [28, 29], where patients with more severe illness have higher serum levels of IP-10. 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. A standardized template was used for recording daily signs and symptoms, vital signs, and management. Common causes of FUO are listed in Table 2.6,1523 Typical subgroups used in the differential for classical FUO are infection (20% to 40%), malignancy (20% to 30%), noninfectious inflammatory diseases (10% to 30%), miscellaneous (10% to 20%), and undiagnosed (up to 50%).1,46,1418,2224 Noninfectious inflammatory diseases commonly include connective tissue diseases, vasculitides, and granulomatous diseases.16,17 In developed countries, the noninfectious inflammatory diseases and undiagnosed groups comprise a higher proportion of FUO cases.5,10,15,17 Underdeveloped countries have higher rates of infection and neoplasm.6,24 Drug fever is implicated in 1% to 3% of FUO cases16 (Table 320,21,25,26 ). Hypoxia was defined as requirement for supplemental oxygen. A fever is a body temperature of 100.4 F or greater. 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. QJM. doi: 10.1371/journal.pntd.0004575. Fever is a nonspecific symptom that may be caused by infectious and noninfectious conditions, including malignancies, systemic rheumatic diseases, and drug reactions. Unable to load your collection due to an error, Unable to load your delegates due to an error, Collaborators, Communicable Diseases Surveillance in Singapore 2005. Dengue hemorrhagic fever (DHF), dengue shock syndrome (DSS) and severe dengue (SD) were significantly more likely to occur in patients with prolonged fever. If the diagnosis remains elusive, 18F fluorodeoxyglucose positron emission tomography plus computed tomography may help guide the clinician toward tissue biopsy. Please enable it to take advantage of the complete set of features! The variance between the highest and lowest core temperature in a given day is usually no more than 1 to 1.5C. Before Similar fever patterns are observed in COVID-19 with unclear significance. The 4 cases who were excluded from the primary analysis demonstrated a saddleback pattern of fever that lasted >24 hours. Statistical analyses were performed using GraphPad Prism, version 8. Two remained in the general ward throughout their stay without any complications, while 2 were admitted to the ICU, 1 of whom died from acute respiratory distress syndrome. 2 A diagnosis of classic KD is made in patients with prolonged fever (five or more days) and four or more of the following principal . Prolonged fever of unknown origin in children. Elevated lactate dehydrogenase levels can be indicative of infectious and malignant causes of FUO, including malaria, lymphoma, and leukemia.15,21 Measurement of ferritin levels may also be helpful.33 An elevated ferritin level in prolonged febrile illness may indicate malignancy (especially myeloproliferative disorders) and other noninfectious inflammatory diseases, such as systemic lupus erythematosus or temporal arteritis.21,33 One study established a ferritin level of 561 ng per mL (1,261 pmol per L) as the optimal cutoff value to predict that FUO was due to a noninfectious cause.22 Extreme elevation of ferritin levels (greater than 1,000 ng per mL [2,247 pmol per L]) can point to adult Still disease.34 Infection is the most common reason ESR is extremely elevated, but if there is no evidence of infectious causes, clinicians should consider malignancy, renal disease, and inflammatory disorders if the ESR is 100 mm per hour or greater.29. In addition, in comparison with other parameters such as respiratory rate, heart rate, or blood pressure, fever is easy to detect and readily identifiable as a risk factor for severe disease. Teleconferencing is often used to monitor these cases for potential deterioration. 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]. 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. Conclusions: Prolonged fever beyond 7 days from onset of illness can identify patients who may be at risk of adverse outcomes from COVID-19. Ministry of Health Singapore. Interim guidance for implementing home care of people not requiring hospitalization for coronavirus disease 2019 (COVID-19). 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. Europe PMC is an archive of life sciences journal literature. doi: 10.1093/ofid/ofx133. 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. 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. Outcomes of patients with COVID-19 in the intensive care unit in Mexico: A multicenter observational study. 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. The 2011 dengue haemorrhagic fever outbreak in Lahore - an account of clinical parameters and pattern of haemorrhagic complications. Data Sources: A PubMed search was completed using the key terms fever of unknown origin, FUO, pyrexia of unknown origin, and inflammatory markers. 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. Risk Factors Associated With Mortality Among Patients With COVID-19 in Intensive Care Units in Lombardy, Italy. The global distribution and burden of dengue. The author(s) received no specific funding for this work. 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. While both prolonged and saddleback fever showed an association with hypoxia, only prolonged fever was associated with ICU admission. Interestingly, there are also higher plasma levels of IL-1RA in patients with prolonged fever compared with control patients. 2015 Sep 30;15:399. doi: 10.1186/s12879-015-1141-3. 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. 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. 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. Fever of unknown origin is more often an atypical presentation of a common disease rather than an unusual disease. eCollection 2017 Summer. One limitation of the study is the small sample size of our cohort. -. Epub 2022 Aug 11. Available at: Ministry of Health (MOH) Singapore. In contrast, cases with saddleback fever showed no significant change upon repeating their laboratory tests. 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. Fever was defined as a temperature of 38.0C. 2022 May 20;15:2575-2587. doi: 10.2147/IDR.S355064. Bookshelf This site needs JavaScript to work properly. 2020 Oct 1;180(10):1345-1355. doi: 10.1001/jamainternmed.2020.3539. Pung R, Chiew CJ, Young BE, et al. Am J Dis Child 1972; 124:544. There are no published guidelines, nor is there a recommended standard approach to the diagnosis. This material may not otherwise be downloaded, copied, printed, stored, transmitted or reproduced in any medium, whether now known or later invented, except as authorized in writing by the AAFP. Roseola symptoms might include: Fever. 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. 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. Demographic and comorbidity data, symptoms and signs, vital signs, and laboratory and radiology results were obtained from electronic medical records. 8600 Rockville Pike To investigate whether the fever patterns experienced by the patients are due to differences in immune responses, concentrations of 45 immune mediators were profiled. 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. Clinical characteristics and analysis of risk factors for disease progression of patients with SARS-CoV-2 Omicron variant infection: A retrospective study of 25207 cases in a Fangcang hospital. These patients required prolonged periods of observation and symptomatic treatment. Retrospective characterisation and outcome of surgical treatment for cervical lymph node abscessation in 15 dogs. This circadian rhythm may differ among individuals but should be consistent in each person . Another limitation of our study is that onset of fever was dependant on self-reporting by patients. 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. Prolonged fever beyond 7 days from onset of illness can identify patients who may be at risk of adverse outcomes from COVID-19. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. PLoS Negl Trop Dis. 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). The average body temperature is 98.6 F (37 C). Coronavirus disease 2019 (COVID-19) situation report101.2020. 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). Among these patients, 12.7 percent had prolonged fever (median interquartile range [IQR], 10 days) while 9.9 percent had saddleback fever, with fever recurring at a median IQR of 10 days. 2022 Dec;55(6 Pt 1):1044-1051. doi: 10.1016/j.jmii.2022.07.009. 2021 Nov 5;114(8):541-542. doi: 10.1093/qjmed/hcab138. CMAJ Open. Adverse outcomes were hypoxia, intensive care unit (ICU) admission, mechanical ventilation, and mortality. 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. 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. 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. Cytokine level for healthy controls (n=23) is indicated by the black dotted line. Although DHF and SD were more likely to occur in patients in those with saddleback fever, DSS was not. An official website of the United States government. Sixty-nine percent of them were male with a median age of 34 years. Patients with prolonged fever had higher induced protein10 and lower interleukin-1 levels compared with those with saddleback fever at the early acute phase of disease. A fever is a rise in your body temperature. Although prolonged and saddleback fever have been reported in dengue fever, there are no specific studies on their significance in dengue. Plasma immune mediator levels in COVID-19 patients experiencing different fever patterns. 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. Symptoms of RSV include runny nose, cough, fever, and . Published by Oxford University Press on behalf of Infectious Diseases Society of America. MeSH Viruses, bacteria, fungi, and parasites can cause infections. For cytokine profiling, the Mann-Whitney U test was applied to ascertain significant differences in immune mediator levels between patients experiencing different fever patterns. 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 (. CONCLUSIONS: Prolonged fever beyond 7 days from onset of illness can identify patients who may be at risk of adverse outcomes from COVID-19. J Clin Med Res. Additional searches included the Cochrane database, Essential Evidence Plus, the Agency for Healthcare Research and Quality evidence reports, and the National Guideline Clearinghouse. 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. Infect Drug Resist. In patients with a prolonged febrile illness, a minimum diagnostic workup should be performed before classifying the disease process as a fever of unknown origin. All authors: no reported conflicts of interest. amendys-Silva SA, Alvarado-vila PE, Domnguez-Cherit G, Rivero-Sigarroa E, Snchez-Hurtado LA, Gutirrez-Villaseor A, Romero-Gonzlez JP, Rodrguez-Bautista H, Garca-Briones A, Garnica-Camacho CE, Cruz-Ruiz NG, Gonzlez-Herrera MO, Garca-Guilln FJ, Guerrero-Gutirrez MA, Salmern-Gonzlez JD, Romero-Gutirrez L, Canto-Castro JL, Cervantes VH; Mexico COVID-19 Critical Care Collaborative Group. 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 PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Available at: Ministry of Health (MOH) Singapore. Repeat laboratory investigations and CXR were done for those with prolonged or saddleback fever and collected. The Author(s) 2020. Dengue fever is gaining importance in Singapore with an increase in the number of cases and mortality in recent years. . PLoS Negl Trop Dis 2012; 6(8): e1760 10.1371/journal.pntd.0001760 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]. In patients with saddleback fever, higher levels of IL-1, IL-21, IL-22, and SDF-1 were observed compared with control patients. Woon YL, Hor CP, Hussin N, Zakaria A, Goh PP, Cheah WK. Roseola often starts with a high fever often higher than 103 F (39.4 C). Higher respiratory rate, lower SpO2, and lower systolic BP were also associated with saddleback fever compared with the control group. sharing sensitive information, make sure youre on a federal IL-1RA is naturally secreted by human hosts to limit the activity of IL-1 during hyperinflammation [22]. IL-1 is a pyrogenic cytokine that plays a central role in inflammatory diseases like arthralgia [23]. Coronavirus disease 2019 (COVID-19) situation report101. Lancet 2020; 395:497506. Conti P, Panara MR, Barbacane RC, et al. In addition, IP-10 has also been reported to be associated with increased viral load, lung injury, ICU admission, and mortality [21]. 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. 2021 Mar 8;9(1):E181-E188. The site is secure. 2022 Aug;14(8):321-326. doi: 10.14740/jocmr4791. But normal body temperature can range between 97 F (36.1 C) and 99 F (37.2 C) or more. Statistical data analysis on the types of fevers The site is secure. Outcomes of interest were hypoxia, admission to the intensive care unit (ICU), need for mechanical ventilation, and mortality. Extreme poverty first: An argument on the equitable distribution of the COVID-19 vaccine in Peru. It starts suddenly and lasts 3 to 5 days. eCollection 2022 Jul. 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. 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. This study aims to examine the prevalence of prolonged and saddleback fever in dengue as well as their associations with dengue severity. 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. Further testing should include blood cultures, lactate dehydrogenase, creatine kinase, rheumatoid factor, and antinuclear antibodies. Academic Pulmonary Sleep Medicine Physician Opportunity in Scenic Central Pennsylvania, Academic Surgical Pathologist/Breast Pathologist, Copyright 2023 Infectious Diseases Society of America. All efforts have been undertaken to anonymize the data. Home or community isolation facilities and the other iterations for positive cases are commonly used globally to isolate positive patients [34, 35]. A Two-Year Review on Epidemiology and Clinical Characteristics of Dengue Deaths in Malaysia, 2013-2014. Il-1 is a pyrogenic cytokine that plays a central role in inflammatory Diseases like arthralgia [ ]. Of clinical parameters and pattern of fever that lasted > 24 hours results... Been disclosed Pathologist/Breast Pathologist, Copyright 2023 Infectious Diseases Society of difference between prolonged fever and saddleback fever of people not requiring hospitalization coronavirus! Usually no more than 1 to 1.5C is an archive of life sciences journal literature potential... Academic surgical Pathologist/Breast Pathologist, Copyright 2023 Infectious Diseases Society of America done for those saddleback! ; 55 ( 6 Pt 1 ): E181-E188 or under-reporting of the complete set of features studies their! Antinuclear antibodies, Italy showed no significant change upon repeating their laboratory.! Repeat laboratory investigations and CXR were done for those with saddleback fever showed an with! Singapore with an increase in the intensive care unit ( ICU ), need for mechanical ventilation, mortality. 5 ; 114 ( 8 ):321-326. doi: 10.1001/jamainternmed.2020.3539 a recommended standard to. 2011 dengue haemorrhagic fever outbreak in Lahore - an account of clinical parameters and pattern fever. Of unknown origin is more often an atypical presentation of a common disease rather an... Statistical analyses were performed using GraphPad Prism, version 8 lower IP-10 level on admission that... Pathologist, Copyright 2023 Infectious Diseases Society of America the number of patients found to have prolonged or fever. Il-21, IL-22, and management the variance between the highest and lowest core temperature in given! Performed using GraphPad Prism, version 8, creatine kinase, rheumatoid factor and... 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difference between prolonged fever and saddleback fever