Acute Undifferentiated Febrile Illness in Hospitalized Adults in Western and Central Provinces, Sri Lanka: High Levels of Coinfections and Clinical Misdiagnoses of Etiology

Acute undifferentiated febrile illness (AUFI) is an important cause of admission to hospitals in the tropics. We prospectively recruited inpatients with AUFI at three hospitals in Western (n = 540) and Central (n = 260) Provinces, Sri Lanka from January 2022 to May 2023. We obtained clinical and environmental exposure data, blood cultures, acute blood samples, and nasopharyngeal samples at enrollment and convalescent blood samples. Laboratory testing for dengue and influenza viruses, Leptospira, Rickettsia, and Orientia was conducted. Laboratory-confirmed etiology of AUFI was ascertained in 576 of 800 cases (72%). Dengue (n = 189/540), leptospirosis (n = 173/540), and scrub typhus/rickettsial infection (n = 57/540) were principal etiologies of AUFI in Western Province. Dengue (n = 69/260), leptospirosis (n = 61/260), and scrub typhus/rickettsial infection (n = 35/260) were causes of AUFI in Central Province. In both provinces, 82 of 800 cases of AUFI were because of influenza. There were no culture-confirmed cases of melioidosis or enteric fever. Of AUFI admissions, 96 of 800 were because of coinfections, with leptospirosis co-infection (n = 63/800) being most frequent. False-positive scrub typhus lateral flow immunoassays were seen in 22 of 234 patients with confirmed leptospirosis. 84 of 274 dengue cases and 118 of 289 leptospirosis cases diagnosed and managed clinically (before laboratory diagnosis) were incorrect diagnoses. Clinical diagnosis of AUFI is often suboptimal, and coinfections are common in our study areas. The need for widespread availability of comprehensive molecular and serological testing of AUFI patients is highlighted.