In endemic areas, diagnosis is generally made on clinical grounds alone. Where there is doubt, the diagnosis may be confirmed by a laboratory test such as serology.

The choice of laboratory test is not straightforward, and all currently available tests have their limitations.^[1] The cheapest and most easily available serological test is the Weil-Felix test, but this is notoriously unreliable.^[2] The gold standard is indirect immunofluorescence,^[3] but the main limitation of this method is the availability of fluorescent microscopes, which are not often available in resource-poor settings where scrub typhus is endemic. Indirect immunoperoxidase (IIP) is a modification of the standard IFA method that can be used with a light microscope,^[4] and the results of these tests are comparable to those from IFA.^[2][5] Rapid bedside kits have been described that produce a result within one hour, but the availability of these tests are severely limited by their cost.^[2] Serological methods are most reliable when a fourfold-rise in antibody titre is looked for. If the patient is from a non-endemic area, then diagnosis can be made from a single acute serum sample.^[6] In patients from endemic areas, this is not possible because antibodies may be found in up to 18% of healthy individuals.^[7]

Other methods include culture and PCR, but these are not routinely available^[8] and the results do not always correlate with serological testing,^[9][10][11] and are affected by prior antibiotic treatment.^[12] The currently available diagnostic methods have been summarised.^[1]

Acute scrub typhus appears to improve viral loads in patients with HIV.^[13] This interaction is refused by an in vitro study.^[14]