For suspected acute typhoid, blood culture is the preferred diagnostic test, ideally collected before antibiotics. More than one blood culture may be needed; if culture is negative but suspicion remains high, the clinician may consider repeat cultures or other tests. Serology is less dependable because it cannot consistently distinguish current infection from past infection or vaccination and has false-positive results. The CDC clinical guidance states that blood culture is the diagnostic mainstay and that antibody-based serologic tests are not recommended because of false positives. This is also consistent with Park's Textbook of Preventive and Social Medicine, which describes isolation of S. Typhi from blood, bone marrow, or stool as the definitive diagnosis, with blood culture as the mainstay - Park's Textbook of Preventive and Social Medicine, Laboratory diagnosis of typhoid, p. text section.

So: do not start or continue typhoid treatment based only on S. typhi IgM/IgG results. A clinician should interpret them with fever duration, symptoms, travel/food exposure, complete blood count, malaria/dengue testing where relevant, and cultures.