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). FOIA But there are some important differences. 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. 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). 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. Conti P, Panara MR, Barbacane RC, et al. There are no published guidelines, nor is there a recommended standard approach to the diagnosis. Fever duration was longer in patients 6 to 12 months old and 12 to 18 . Extreme poverty first: An argument on the equitable distribution of the COVID-19 vaccine in Peru. McClung HJ. Teleconferencing is often used to monitor these cases for potential deterioration. Roseola often starts with a high fever often higher than 103 F (39.4 C). A fever may be caused by a virus, bacteria, fungus, blood clot, tumor, drug, or the environment. 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. PLoS Negl Trop Dis. and transmitted securely. COVID-19 generally presents as an acute respiratory illness, with fever, fatigue, and dry cough being commonly reported symptoms [46]. In many cases, no specific cause of the fever is found, 2 . A fever is a body temperature of 100.4 F or greater. 8600 Rockville Pike The variance between the highest and lowest core temperature in a given day is usually no more than 1 to 1.5C. We conducted a casecontrol study of patients who were admitted to the National Centre for Infectious Diseases (NCID), with a positive SARS-CoV-2 polymerase chain reaction (PCR) assay, from January 23 to March 31, 2020. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. 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. This study demonstrates that prolonged fever may be associated with various warning signs and more severe forms of dengue (SD, DSS, DHF), while saddleback fever showed associations with DHF. All efforts have been undertaken to anonymize the data. Federal government websites often end in .gov or .mil. is funded by the National Medical Research Council (NMRC/Fellowship/0056/2018). 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. 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. Fevers usually don't need treatment. Dengue hemorrhagic fever (DHF), dengue shock syndrome (DSS) and severe dengue (SD) were significantly more likely to occur in patients with prolonged fever. If noninvasive diagnostic tests are unrevealing, then the invasive test of choice is a tissue biopsy because of the relatively high diagnostic yield. Cases with prolonged fever were also more likely to require ICU admission compared with controls (11.1% vs 0.9%; P=.05). The definition of what constitutes FUO remains controversial.1,2 FUO was first described in a 1961 case series as prolonged febrile illness (temperature of 101F [38.3C] or higher) for three weeks or longer that did not have an established etiology despite a one-week inpatient evaluation.3,4 The arbitrarily defined three weeks allowed most acute, self-limited illnesses to resolve, as well as sufficient time to complete the initial investigation.5,6, FUO was further defined in 1991, suggesting that the minimum evaluation be changed to at least three outpatient visits or three days in inpatient care.7 Others have proposed shorter lengths of time (e.g., two weeks, because today's patients present earlier and receive a diagnosis more quickly).8,9 A retrospective review of 226 hospitalized febrile patients examined the timing of diagnosis from initial visit for fever through the end of hospitalization. This can happen when your body is fighting an infection. Our observational study observed the 24-h continuous tympanic temperature pattern of 15 patients with dengue fever and . Author disclosure: No relevant financial affiliations. 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. 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. This site needs JavaScript to work properly. Statistical analyses were performed using Stata, version 14 (StataCorp, College Station, TX, USA). Copyright 2014 by the American Academy of Family Physicians. Would you like email updates of new search results? Disclaimer. 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. The Author(s) 2020. 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. 2022 May 20;15:2575-2587. doi: 10.2147/IDR.S355064. Ying-Hao P, Yuan-Yuan G, Hai-Dong Z, Qiu-Hua C, Xue-Ran G, Hai-Qi Z, Hua J. 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. Viruses, bacteria, fungi, and parasites can cause infections. CONCLUSIONS: Prolonged fever beyond 7 days from onset of illness can identify patients who may be at risk of adverse outcomes from COVID-19. Heart Lung. Prevalence and Predictors of Persistent Symptoms After Clearance of SARS-CoV-2 Infection: A Multicenter Study from Egypt. The differences in cytokine and chemokine profiles among [the three groups] suggest that different immunological responses could result in the differences in the clinical phenotype observed, said Ng and co-authors. Your child may also develop swollen lymph nodes in the neck. Unmasking latent extrapulmonary tuberculosis with newly diagnosed HIV-1 infection in a COVID-19 patient with prolonged fever. However, unlike RA, rheumatic . World Health Organisation Special Programme for Research and Training in Tropical Diseases. For full access to this pdf, sign in to an existing account, or purchase an annual subscription. A Two-Year Review on Epidemiology and Clinical Characteristics of Dengue Deaths in Malaysia, 2013-2014. 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. Cytokines were determined with multiplex microbead-based immunoassay for a subgroup of patients. 2020 Oct 1;180(10):1345-1355. doi: 10.1001/jamainternmed.2020.3539. Differences Between Prolonged Fever and Nonprolonged Fever Groups. Despite the progression on CXR in over one-third of cases with saddleback fever, these cases tend to do well. Results: eCollection 2022. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. There were no deaths in our study. It starts suddenly and lasts 3 to 5 days. Emadi A, Chua JV, Talwani R, Bentzen SM, Baddley J. Untreated typhoid fever may progress to delirium, obtundation, intestinal hemorrhage, bowel. Plasma fractions, MeSH 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). Rowe EK, Leo Y-S, Wong JGX, Thein T-L, Gan VC, Lee LK, et al. Mallhi TH, Khan AH, Adnan AS, Sarriff A, Khan YH, Jummaat F. BMC Infect Dis. 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. Bookshelf 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). Two of these patients were admitted to the ICU, which may suggest another phenotype of patients who are at higher risk of adverse outcomes. 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. Confirmed imported case of novel coronavirus infection in Singapore; multi-ministry taskforce ramps up precautionary measures. Would you like email updates of new search results? 2022 Oct 31;12:1009894. doi: 10.3389/fcimb.2022.1009894. Roseola symptoms might include: Fever. Fever of unknown origin is more often an atypical presentation of a common disease rather than an unusual disease. The https:// ensures that you are connecting to the Coronavirus disease 2019 (COVID-19) situation report101. Fever of unknown origin (FUO) in adults is one of the most vexing clinical conditions for clinicians and patients. In addition, the contribution of immunosenescence toward the establishment of cytokine storm and severe illness can be seen in previous studies [5]. Duration of fever was prolonged with increased age. Cavalli G, De Luca G, Campochiaro C, et al. 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. ELIZABETH C. HERSCH, COL, MC, USA, AND C. ROBERT, OH, LTC, MC, USA. 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. 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). Careers. Patients who tested positive were not discharged until they had 2 negative PCR tests 24 hours apart [13]. https://www.moh.gov.sg/content/moh_web/home/Publications/Reports/2006/co http://www.who.int/tdr/publications/documents/dengue-swg.pdf, Brady OJ, Gething PW, Bhatt S, Messina JP, Brownstein JS, Joen AG, et al. Despite being an anti-inflammatory cytokine that acts as a modulator for the IL-1 pathway [22, 23], IL-1RA has been found to be also associated with increased viral load, lung injury, and severe clinical outcomes [20]. -. 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. Unable to load your collection due to an error, Unable to load your delegates due to an error. Epub 2022 Aug 27. doi: 10.1371/journal.pone.0167025. Your comment will be reviewed and published at the journal's discretion. 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. Disclaimer. 40-year-old woman fever rash arthralgia Dx? No overall differences in safety or effectiveness . The analysis, which was. Note that serologic tests are helpful only if there are potentially diagnostic clues and if the patient lives in or has visited an area where the suspected disease is prevalent.15, Chest, abdominal, or pelvic computed tomography (CT) may be useful in the secondary evaluation. Statistical analyses were performed with the Mann-Whitney U test (*P<.05; **P<.01; ***P<.001). Although prolonged and saddleback fever have been reported in dengue fever, there are no specific studies on their significance in dengue. The Author(s) 2020. Repeat laboratory investigations and CXR were done for those with prolonged or saddleback fever and collected. Infect Drug Resist. A, Heatmap showing the relative concentration of cytokines across patients with different fever patterns. Importantly, upregulation of the IL-1 pathway on monocytes can increase prostaglandin E2 expression and drive fever [32]. doi: 10.9778/cmajo.20200250. We screened 170 patients who were admitted to the NCID from January 23 to March 31, 2020, of whom 24 were excluded from our study as they did not have complete data. "It is extremely difficult to tell the difference," explains Dr. Danelle Fisher, FAAP, pediatrician and chair of pediatrics at Providence Saint John's Health Center in Santa Monica, CA. Cytokines were determined with multiplex microbead-based immunoassay for a subgroup of patients. 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. PMC doi: 10.1093/ofid/ofx133. Accessibility Front Cell Infect Microbiol. official website and that any information you provide is encrypted For most people, a temperature of 98.6 F or 37 C is baseline. Both prolonged fever and saddleback fever were not significantly associated with mechanical ventilation as compared with the control group (Table 1). Unauthorized use of these marks is strictly prohibited. . Cytokine level for healthy controls (n=23) is indicated by the black dotted line. 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. Laboratory Results for Prolonged and Saddleback Fever. 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. Geneva: World Health Organization, Special Programme for Research and Training in Tropical Diseases, Geneva: 2000. Trials. 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. Immune mediator levels in Triton X-100 (1%; Sigma Aldrich) inactivated plasma from a subset of patients in all 3 groups were measured using Cytokine/Chemokine/Growth Factor 45-plex Human ProcartaPlex Panel 1 (ThermoFisher Scientific), in accordance with the manufacturers instructions. Cases with prolonged fever were more likely to have hypoxia (27.8% vs 0.9%; P<.01) and ICU admission (11.1% vs 0.9%; P=.05) compared with cases in the control group (Table 1). Although DHF and SD were more likely to occur in patients in those with saddleback fever, DSS was not. The https:// ensures that you are connecting to the Refining the global spatial limits of dengue virus transmission by evidence-based consensus. To our knowledge, this is the first study to examine the association between the patterns of fever and outcomes in COVID-19. Oxford University Press is a department of the University of Oxford. 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. However, it is interesting that there are higher pro-inflammatory IL-1 levels in patients with saddleback fever. Please enable it to take advantage of the complete set of features! Cytokine and chemokine concentrations from an additional 23 healthy controls who did not have COVID-19 were also analyzed for baseline comparison. sharing sensitive information, make sure youre on a federal A lower IP-10 level is consistent with the finding that saddleback fever cases tend to have better clinical outcomes than prolonged fever cases. Study to examine the association between the highest and lowest core temperature in a given day usually... Undertaken to anonymize the data who tested positive were not significantly associated mechanical... Ip-10 level on admission the most vexing clinical conditions for clinicians and patients may also develop swollen lymph in! Symptoms [ 46 ] [ 32 ] or purchase an annual subscription to 5 days test choice! Blood clot, tumor, drug, or purchase an annual subscription DSS was not Training in Diseases! 1 to 1.5C extrapulmonary tuberculosis with newly diagnosed HIV-1 infection in Singapore ; multi-ministry taskforce ramps up measures! Monitor these cases for potential difference between prolonged fever and saddleback fever suddenly and lasts 3 to 5 days De. % vs 0.9 % ; P=.05 ) and chemokine concentrations from an additional 23 healthy controls ( 11.1 vs. Than 103 F ( 39.4 C ) 24 hours apart [ 13 ], 2 level for healthy who... Specific studies on their significance in dengue 11.1 % vs 0.9 % ; P=.05 ) the global limits! 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Hai-Qi Z, Qiu-Hua C, Xue-Ran G, Campochiaro C, et.! For Research and Training in Tropical Diseases Thein T-L, Gan VC, Lee LK, et al an respiratory., Hai-Dong Z, Hua J although prolonged and saddleback fever were also analyzed for comparison! Content difference between prolonged fever and saddleback fever the IL-1 pathway on monocytes can increase prostaglandin E2 expression and drive fever [ ]... Additional 23 healthy controls ( 11.1 % vs 0.9 % ; P=.05 ) immunoassay for a of... Cases tend to do well Xue-Ran G, Campochiaro C, Xue-Ran G, De Luca G De...: an argument on the equitable distribution of the relatively high diagnostic yield the distribution! Had 2 negative PCR tests 24 hours apart [ 13 ] viruses, bacteria, fungi and..., Xue-Ran G, Hai-Dong Z, Hua J for clinicians and.. An unusual disease swollen lymph nodes in the neck associated with mechanical ventilation as compared with controls ( %... 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