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(1) Background: Scrub typhus (ST) is endemic to Nepal. It is often underdiagnosed and misdiagnosed due to non-specific clinical presentation coupled with limited microbiological facilities, leading to adverse clinical outcomes. This study aimed to assess the seroprevalence of scrub typhus in febrile patients attending Sukraraj Tropical and Infectious Disease Hospital (STIDH), Nepal, from August 2018 to April 2019. (2) Materials and Method: Blood/serum samples and clinical and demographic data of adult febrile patients (≥19 years) who attended or were referred to the hospital were collected after obtaining written informed consent from the participants excluding immunocompromised individuals. Collected blood/serum samples were subjected to hematological, biochemical, and serological tests. A serological test for scrub typhus was performed using the ImmuneMed scrub typhus rapid diagnostic test kit. Data generated were analyzed using SPSS software version 24.0. (3) Results: Amongst the 2070 febrile patients, 462 (22.3%) were seropositive to at least one etiological agent of febrile illnesses (scrub typhus: 253 cases, dengue: 101 cases, leptospirosis: 9, brucellosis: 52, malaria: 9 and kala-azar: 20 cases). Scrub typhus accounted for 12.2% (n = 253) of total febrile illnesses followed by dengue (4.9%, n = 101). Mixed seropositivity of scrub typhus with dengue, brucellosis, and typhoid was found in 12 (0.6%), 9 (0.4%), and 5 (0.2%) cases, respectively. Among 253 scrub typhus patients, 53.4% were female. Among the 154 patients, the most common symptoms were fever (100%), headache (79.2%), sweating (70.1%), breathing difficulty (51.3%), redness of the eye (43.5%), and pathognomonic eschar was observed in 9.1% patients. Fifty percent of scrub typhus patients had low platelet count and &gt;30% of patients had an elevated level of liver enzymes (such as serum glutamic oxaloacetic transaminase (SGPT) and serum glutamic pyruvic transaminase (SGOT). (4) Conclusion: Scrub typhus is a considerable cause of febrile illness in Nepal. Females apparently have a higher chance of acquiring scrub typhus. ST presents nonspecific clinical presentation. The diagnostic dilemma of typhus patients can be minimized by the early monitoring of ST-associated symptoms. The country's health system needs to be strengthened for early outbreak detection, and immediate response actions against scrub typhus to control the future outbreak of ST.

Seroprevalence and Clinical Features of Scrub Typhus among Febrile Patients Attending a Referral Hospital in Kathmandu, Nepal