The clinical features of typhoid fever are nonspecific. So diagnosis of typhoid fever should be considered if a traveler returning from developing country with fever, especially from Indian subcontinent, and Latin America or in developing countries any patient with fever. Other diagnosis to be considered in case of fever and international travel are malaria, hepatitis, bacterial enteritis, dengue fever, rickettsial infections, leptospirosis, amebic liver abscesses, and acute HIV infection etc.
A positive blood culture is the only confirmatory test for diagnosis of typhoid fever and other laboratory tests are not diagnostic. There may be non specific laboratory changes like leukopenia and neutropenia in 15% to 25% of the cases of typhoid fever and also moderately elevated liver function tests and muscle enzyme levels.
The definitive diagnosis of enteric fever is done by isolation of Salmonella Typhi or Salmonella Paratyphi from blood, bone marrow, other sterile sites, rose spots, stool, or intestinal secretions. The positive blood culture is 90% during the first week of infection and decreases to 50% by the third week. A low yield of positive result in infected patients is related to low numbers of salmonellae (less than 15 organisms/ml) and/or to recent antibiotic treatment. Bone marrow culture yield is 90% despite approximately 5 days of antibiotic therapy. Even if bone marrow culture is negative, culture of intestinal secretions (best obtained by a noninvasive duodenal string test) can give a positive result for typhoid fever. If bone marrow and intestinal secretions are cultured together, it can give more than 90% positive result anytime during Salmonella infection.
There are other serologic tests also like classic Widal test which is for “febrile agglutinins”, but none of these tests are sufficiently sensitive or specific to replace culture methods especially in developed countries. Some new tests are being developed like PCR (Polymerase chain reaction) and DNA probe assays to detect S. Typhi in blood.