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Diagnosis of typhoid fever
Last reviewed: 06.07.2025
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Typhoid fever is diagnosed on the basis of prolonged fever, headache, increasing intoxication with the development of typhoid status, typical changes in the tongue, the appearance of flatulence, roseola rash, hepatosplenomegaly and changes in the peripheral blood.
Laboratory diagnostics of typhoid fever is based on the detection of the pathogen in the biomaterial and specific antibodies in the patient's blood. Of decisive importance is the detection of the pathogen in the blood (blood culture), urine (urine culture), feces (coproculture), bile (biliculture), as well as in the bone marrow, cerebrospinal fluid, roseola, pus or exudate.
In practical work, for the early diagnosis of typhoid fever, the most important is blood culture, which should be carried out throughout the febrile period. Blood from a vein in the amount of 5-10 ml is inoculated into a vial with 50-100 ml of 10-20% bile broth (the best results are obtained by inoculating in trypsin-soy broth). Positive results of blood culture are most often obtained with blood cultures in the first week of the disease, when bacteremia is most pronounced. From the second week of the disease, typhoid bacilli can be detected in feces, urine and duodenal contents. The highest percentage of typhoid bacilli is isolated from bone marrow cultures. In general, bacteriological confirmation of the diagnosis of typhoid fever can be obtained in 80-90% of patients.
Serological methods allow to detect specific antibodies in blood or antigens in biosubstrate. In practical work, the Widal reaction and RNGA (indirect hemagglutination reaction) using erythrocyte O-, H- and Vi-antigens are most often used. The Widal reaction is based on the detection of specific O- and H-antibodies-agglutinins in the patient's blood using the corresponding antigens. Positive results can be obtained from the 8-9th day of the disease. The Widal reaction can be positive in vaccinated and typhoid fever survivors, so the increase in antibody titer in the dynamics of the disease is of decisive importance. For more accurate detection of specific immune shifts in the patient's blood, the Widal reaction should be repeated with O- (IX and XII) and H-monodiagnosticums to exclude cross-reactions with salmonella of other groups.
More specific and sensitive are RNGA with erythrocyte O- and Vi-antigens and the Vi-hemagglutination reaction. These reactions are used for early diagnostics of typhoid fever. In RNGA, the concentration of O-antibodies increases in the dynamics of the disease, and the titers of Vi-antibodies do not change significantly. The Vi-hemagglutination reaction is of greatest importance when examining individuals suspected of being typhoid fever carriers.
Serological reactions for detection of specific antibodies in the patient's blood should be made from the 4th-5th day of illness, and then on the 2nd-3rd week and later. The diagnosis of typhoid fever is considered serologically confirmed with an antibody titer of 1:200 or higher or with an increase in the antibody titer by 2-3 times in the dynamics of the disease. When assessing serological reactions, it is important to take into account that an increase in the titers of specific O-antibodies indicates an acute infectious process, and the presence of only H- or Vi-antibodies indicates a previous typhoid fever or bacterial carriage.
For serological diagnostics of bacterial carriage and vaccine reactions, separate determination of specific antibodies related to IgM and IgG in ELISA is proposed. Detection of specific typhoid IgM indicates the current infectious process, and isolated detection of specific antibodies related to the IgG class indicates the vaccine nature of antibodies or previously suffered typhoid fever.
Differential diagnosis of typhoid fever
In practical work, typhoid fever in children often has to be differentiated from typhoid-like salmonellosis, paratyphoid fever, infectious mononucleosis, lymphogranulomatosis, yersiniosis, malaria, and in the initial period - from influenza, enterovirus infection and acute intestinal infection of other etiology.
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