Background and Objectives: The epidemiology of scrub typhus caused by Orientia tsutsugamushi has been growing in Odisha, India. The most common symptoms include fever, cough, lymphadenopathy, eschar, and rash. In India, enzyme-linked immunosorbent assays (ELISA) and DNA real-time polymerase chain reaction (DNA RT-PCR) are the most commonly used methods to diagnose scrub typhus. We conducted this study to determine the pattern of symptoms and association between the findings of ELISA and DNA RT-PCR., Methods: This retrospective study was accomplished at the Kalinga Institute of Medical Sciences (KIMS), Bhubaneswar, OR, IND. We analyzed the data of adult patients admitted with scrub typhus between March 2022 and February 2024, and their blood samples were evaluated with both IgM ELISA and DNA RT-PCR. The IgM antibody levels against Orientia tsutsugamushi were detected by ELISA and expressed as optical density (OD) values. The bacterial load was assessed by RT-PCR and presented as cycle threshold (CT) values. The OD values > 0.5 and CT values < 40 were deemed positive diagnoses for scrub typhus. The symptoms were weighed for their incidence and co-occurrence. We correlated the OD and CT values of the study population. The R software version 4.4.1 (R Foundation for Statistical Computing, Vienna, AUT) was utilized for data analysis., Results: Of the 231 patients scrutinized, 170 were deemed eligible. Sixty-five (38.2%) participants were female. The median age of the study subjects was 44.5 (24.0-61.8) years. All of them had fever. Other symptoms (in decreasing order of incidence) were as follows: cough (139, 81.8%), lymphadenopathy (29, 17.1%), rash (26, 15.3%), abdomen pain (18, 10.6%), eschar (6, 3.5%), and seizure (2, 1.2%). Maximum co-occurrence was observed between cough, lymphadenopathy, rash, and pain in the abdomen with fever. It held good for both females and males. The study population's median OD and CT values were 2.8 (0.8-3.7) and 41.0 (36.0-42.0), respectively. The OD and CT values were positively correlated (r = 0.78, 95% CI = 0.71-0.83, p < 0.001)., Conclusion: The study participants had symptoms like fever, cough, lymphadenopathy, rash, pain in the abdomen, and eschar. Our findings suggest that ELISA and DNA RT-PCR could be used for scrub typhus diagnosis among patients with febrile illness for > 5 and ≤ 5 days, respectively. Both diagnostic methods were found to possess a positive correlation. The findings of ELISA and DNA RT-PCR must be probed further., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Institutional Ethics Committee, Kalinga Institute of Medical Sciences (KIMS) issued approval KIIT/KIMS/IEC/1755/2024. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Panigrahi et al.)