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©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
Evaluating fever of unknown origin definitions in a tertiary care setting: Implications for diagnostic criteria revision
Pathik Dhangar, Prasan Kumar Panda, Ravi Kant, Rohit Gupta, Ruchi Dua, Ashutosh Tiwari, Sandeep Saini, Kavita Khoiwal, Yogesh Bahurupi
Pathik Dhangar, Prasan Kumar Panda, Ravi Kant, Department of Medicine, All India Institute of Medical Sciences, Rishikesh 249203, Uttarākhand, India
Rohit Gupta, Department of Gastroenterology, All India Institute of Medical Sciences, Rishikesh 249203, Uttarākhand, India
Ruchi Dua, Department of Pulmonology, All India Institute of Medical Sciences, Rishikesh 249203, Uttarākhand, India
Ashutosh Tiwari, Sandeep Saini, Department of Neurology, All India Institute of Medical Sciences, Rishikesh 249203, Uttarākhand, India
Kavita Khoiwal, Department of Obstetrics and Gynecology, All India Institute of Medical Sciences, Rishikesh 249203, Uttarākhand, India
Yogesh Bahurupi, Department of Community and Family Medicine, All India Institute of Medical Sciences, Rishikesh 249203, Uttarākhand, India
Author contributions: Dhangar P contributed to the data collection and data analysis and was involved in manuscript writing; Panda PK provided the concept, interpreted the analysis, critically reviewed the draft, and approved it for publication; Kant R, Gupta R, Dua R, Tiwari A, Saini S, and Khoiwal K reviewed the draft.
Institutional review board statement: The study was reviewed and approved by Institutional Ethics Committee, AIIMS Rishikesh (No. 43/IEC/PGM/2022), ensuring patient confidentiality, data protection, and adherence to ethical standards in research involving human participants.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: We declare that we have no conflicts of interest.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement- checklist of items.
Data sharing statement: It will be made available to others upon request to the corresponding author.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Prasan Kumar Panda, MBBS, MD, Professor, Department of Medicine, All India Institute of Medical Sciences, Room No. 409, Rishikesh 249203, Uttarākhand, India.
motherprasanna@rediffmail.com
Received: September 14, 2024
Revised: November 28, 2024
Accepted: December 23, 2024
Published online: June 20, 2025
Processing time: 214 Days and 22.9 Hours
BACKGROUND
Fever of unknown origin (FUO) remains a diagnostic challenge and was originally defined in 1961. Its classic criteria include fever ≥ 38.3 °C (≥ 101 °F) on multiple occasions, fever lasting three weeks or longer, and a diagnosis after one week of inpatient evaluation. However, these criteria may not fully encompass the varied clinical presentations seen in resource-limited settings such as India. The adaptation of FUO definitions to local healthcare contexts is crucial for enhancing diagnostic accuracy and optimizing patient outcomes.
AIM
To investigate the applicability of revised FUO criteria in a tertiary care setting in India.
METHODS
This longitudinal-exploratory study at All India Institute of Medical Sciences Rishikesh (January 2018–December 2022) analyzed 228 adult patients with fever ≥ 99.1 °F lasting over three days. Patients diagnosed within three days of admission were excluded. Data were collected retrospectively and prospectively using predefined FUO definitions based on durations of nondiagnosis (3-21 days, > 21 days), temperature ranges (99.1 °F-100.9 °F, ≥ 101 °F), and hospitalization durations (3-7 days, > 7 days). Descriptive statistics and comparative tests (Fisher's exact test, χ2 test) evaluated outcomes across definitions.
RESULTS
Among the proposed FUO definitions, Definition B (fever lasting 3-21 days, temperatures between 99.1 °F-100.9 °F, hospitalization > 7 days) predominated (40.8%), while only 2.2% met the classical criteria. Notably, 36.5% of Definition B patients remained undiagnosed after 7-10 days, despite 94% undergoing diagnostic workups within 21 days. Infection emerged as the leading etiology across definitions, without significant variation in outcomes or mortality during hospitalization (χ2 = 27.937, P = 0.142).
CONCLUSION
Adapting FUO criteria to local contexts improves diagnostic accuracy and treatment. Definition B (40.8% prevalence) showed practical utility, with higher mortality in patients discharged on empirical 'Anti-tuberculosis therapy'.
Core Tip: This study evaluates the feasibility of revising fever of unknown origin (FUO) diagnostic criteria in a tertiary care setting in North India. It proposes a new definition (Definition B), which includes fever lasting 3-21 days, temperatures between 99.1 °F-100.9 °F, and hospitalization for over 7 days. The findings highlight the predominance of infections as the leading etiology, the low applicability of classical FUO criteria, and the importance of adapting diagnostic frameworks to local epidemiology. This approach aims to enhance early diagnosis, optimize resource use, and improve patient outcomes in resource-limited settings.
