
Development of new diagnostic tools for scrub typhus infections
Principal Investigator : Jeanne Salje, University of Oxford/ Department of Microbiology
Project Status : On-going
Project Summary
The goal of the project is to isolate human derived antibodies to be used in to developing new technologies for diagnosing scrub typhus. These antibodies will form the basis of a large future funding application on the development and commercialization of new diagnostic tools for scrub typhus in collaboration with FIND, the leading not-for-profit organisation dedicated to accelerated diagnostic development for febrile illnesses.
Scrub typhus is one of the most severe rickettsial infections and a leading cause of acute undifferentiated fever in many parts of Asia. Caused by infection with the mite-borne bacterium Orientia tsutsugamushi (Ot), it is endemic across the Asia-Pacific, a region that includes two thirds of the world’s population. Locally acquired cases have recently been described in the Middle East and Latin America, and there is evidence for the presence of a related bacterium in Africa. This suggests that the disease may be more widespread than previously appreciated. Infections present with generic symptoms (headache, fever, rash) and given the low awareness amongst physicians scrub typhus is often not suspected. If not treated promptly with the appropriate antibiotic, infections can rapidly lead to multiple organ failure and death. Ot is intrinsically resistant to many front-line antibiotics including fluoroquinolones, ß-lactams and aminoglycosides. However, scrub typhus infections are highly responsive to treatment with an alternative antibiotic, doxycycline. Therefore, rapid and accurate diagnosis is essential for securing good outcomes amongst patients.
There is currently no commercially available diagnostic test that has a high sensitivity and specificity at the time of presentation and that can be considered a gold standard for diagnosing scrub typhus infections early. New diagnostic approaches to detect scrub typhus infections are urgently required. If correctly identified, scrub typhus can easily be treated with cheap and available antibiotics (doxycycline), however it does not respond to commonly used broad-spectrum antibiotics and the consequence is preventable patient mortality. Additionally, inappropriate antibiotic overuse is associated with the development of antimicrobial resistance (AMR). This is a growing problem across the globe, with particularly rapid spread in many parts of Asia where the use of broad-spectrum antibiotics is often not regulated, and an early diagnosis could enable targeted use of drugs. Rapid and affordable diagnostic tests for scrub typhus and other doxycycline-responsive pathogens, which are a leading cause of bacterial infections in many parts of Asia, would have a substantial impact on inappropriate antibiotic use globally.