Pyrexia of unknown origin (PUO) remains a significant diagnostic challenge in low- and middle-income countries (LMICs), where infections predominate despite an increasing burden of non-infectious inflammatory diseases and malignancy. Extrapulmonary tuberculosis, lymphoma, and Still's disease are among the leading causes. This article reviews the evolving epidemiology of PUO in LMICs and proposes a structured, stepwise diagnostic approach that integrates local epidemiology, potential diagnostic clues, targeted investigations, and whole-body imaging to improve diagnostic accuracy while minimising unnecessary testing.
PetersdorfRGBeesonPB. Fever of unexplained origin: report on 100 cases. Medicine (Baltimore)1961; 40: 1–30.
2.
DurackDTStreetAC. Fever of unknown origin–reexamined and redefined. Curr Clin Top Infect Dis1991; 11: 35–51.
3.
HaidarGSinghN. Fever of unknown origin. N Engl J Med2022; 386: 463–477.
4.
WrightWFDursoSCForryC, et al.Fever of unknown origin. Br Med J2025; 388: e080847.
5.
PannuAKGollaRKumariS, et al.Aetiology of pyrexia of unknown origin in north India. Trop Doct2021; 51: 34–40.
6.
AkhtarWAwanSIshaqU, et al.Pyrexia of unknown origin and its aetiology in Pakistan. Trop Doct2022; 52: 567–571.
7.
YadavBKPannuAKKumarR, et al.Fever of unknown origin in older adults: a prospective observational study from north India. J Assoc Physicians India2021; 69: 11–12.
8.
PannuAKPannuS. Brucellosis after dengue. Trop Doct2019; 49: 208–209.
9.
PannuAKSuriVKumarM, et al.Brucellosis: myriad ways of presentation. QJM2017; 110: 667–668.
10.
AroraNPandaPKCrP, et al.Changing spectrum of infective endocarditis in India: an 11-year experience from an academic hospital in North India. Indian Heart J2021; 73: 711–717.
11.
PannuAKSinglaVSuriV, et al.Adult-onset Still's disease and fever of unknown origin in India. Clin Exp Med2023; 23: 1659–1666.
12.
PannuAK. Uncertainty in the diagnosis and prognosis of adult-onset Still's disease. Biomark Med2025; 19: 101–103.
13.
AroraNShuklaSVijaykumarD, et al.Pyrexia of unknown origin in HIV-negative adults from Himachal Pradesh (India): will you suspect disseminated histoplasmosis?Trop Doct2020; 50: 275–277.
14.
WrightWFBetzJFAuwaerterPG. Prospective studies comparing structured vs nonstructured diagnostic protocol evaluations among patients with fever of unknown origin: a systematic review and meta-analysis. JAMA Netw Open2022; 5: e2215000.
15.
KannegantiVDivyashreeKPannuAK. Role of bone marrow examination in pyrexia of unknown origin. Trop Doct2023; 53: 338–339.
