Due to the enigmatic presentation of rash, fever, headache, etc. that was similar to a number of viral and other bacterial diseases, diagnosis of scrub typhus presented a serious, often difficult to diagnose problem. It was first generally recognized and reported locally within the “Tsutsugamushi Triangle” of the Asia-Pacific rim, based on symptoms, from the early 20th century by British scientists in India, Burma, Malaya, and throughout Japan by Japanese scientists. It was not until the 1930’s that the disease was successfully separated from other typhus-like fevers, particularly endemic or murine typhus.
PHYSICAL MANIFESTATIONS OF SCRUB TYPHUS
Scrub typhus spreads to individuals through the bite of infected larval mites (chiggers). The chigger bite is often painless and may not be noticed. Early diagnosis of scrub typhus can be difficult because many symptoms can present with a high fever. The history of exposure to endemic areas and presence of a rash, together with the occurrence of an eschar caused by the bite can be diagnostic. Symptoms can be variable from patient to patient, but the most common symptoms are fever, headache, body aches, and sometimes rash. Lymphadenopathy chills (even including shaking), conjunctival infection, anorexia, and general apathy may also occur. The fever may reach 104-105°F (40-40.5°C ). Approximately 50% of patients with primary infection develop an eschar at the inoculation site (see figures below).
Symptoms usually occur about ten days following exposure (mite bite). Onset is often abrupt, with high fever, headache, malaise, and myalgia. Rash on the trunk of the body usually follows a few days later. Additional manifestations of scrub typhus can also include enlargement of the spleen, cough, pneumonitis, and delirium or encephalitis. Severe CNS involvement (seizure or coma) is rare. 
A minority of patients (but up to a third or more) may experience acute hearing loss. Pulmonary involvement, with cough, tachypnea, or pulmonary infiltrates can also be present. Respiratory compromise may progress, especially in the elderly. If the patient does not receive antibiotic treatment, symptoms may last for more than 2 weeks. Antibiotic treatment usually results in patient recovery within 36 hours.
DIAGNOSTIC PROCEDURES
We review here a number of diagnostic tools that can be easily used in research facilities. However, a practical method for agent detection that can be deployed in the field or in rural settings where the patient is first seen is the ultimate target for diagnostic methods. In some cases, final confirmation of scrub typhus in a patient examined under less than ideal conditions may eventually make use of the research facility, but treatment of a sick patient depends on rapid, easy diagnosis.
There remains a critical need for a cheap, accurate, rapid diagnostic tool for scrub typhus. Commercial interest in producing products to assist with diagnosis of this disease is weak. Scrub typhus, despite it wide geographic range and an increasing number of cases, remains an orphan disease, with respect to interest from commercial interests. This is due to the small commercial market involved, often in underdeveloped countries unable to pay for the tests. Thus the primary interest in developing diagnostic procedures has been through the US DoD (Kelly et al, 2002).
Diagnostic methods can be divided into two groups: serological and molecular-based. Details of these are given on two accompanying pages. Reviews of the range of diagnostic materials can be found in recent papers by Koh et al., 2010 and Luce-Fedrow, et al., 2015.
Sub-pages on diagnostic procedures:
On this site, the sub-page on Serological Diagnostic Techniques includes information on the Weil-Felix test, immunofluorescence assay (IFA), enzyme-linked immunosorbent assay (ELISA), indirect immunoperoxidase test (IP), Immunochromatographic Dipstick Tests.
The sub-page on Molecular Diagnostic Techniques includes information on PCR, qPCR and DNA sequencing.