This study aims to evaluate the performance of a novel in-house scrub typhus group (STG) ELISA developed in the Mahidol Oxford Tropical Medicine Research Unit (MORU, Bangkok, Thailand) for scrub typhus IgM and IgG using the United States Naval Medical Research Center (NMRC) produced antigens compared to the “gold standard” reference IFA, and PCR, to detect IgM and IgG antibodies, and to determine whether the in-house STG ELISA can be used as a sero-epidemiological screening tool and/or stand-alone test for the diagnosis of scrub typhus without having to follow up with an IFA test. The gene discussed is CD40LG; the disease is scrub typhus.