The value of the enzyme-linked immunosorbent assay (ELISA) for the serological diagnosis of typhoid or paratyphoid fevers was tested with a collection of five sets of sera from 23 individuals who had no history of
Salmonella
infection from a nonendemic area (set 1) and from 143 patients from a highly endemic area (sets 2 to 5). The test was performed with a crude cell envelope fraction derived from
Salmonella typhi.
On the basis of results with sera in set 1, titers >160 (inverse of serum dilution) for immunoglobulin M (IgM) or >500 for IgG were regarded as signifying a specific antibody response. These titers were occasionally exceeded in sera in set 2, derived from patients with no clinical or laboratory evidence of
Salmonella
infection. In presumptive cases of typhoid or paratyphoid fevers (culture positive and agglutination negative or vice versa; 13 patients, set 3, and 26 patients, set 4, respectively), IgG antibodies were encountered more frequently than IgM, but some sera were negative in each group. In 81 confirmed cases (culture and agglutination positive, set 5) IgG antibodies were detected in at least one of the paired sera from all patients, and the IgG titers were higher (median 3,500) than those of the IgM antibodies (median 600). There was no evidence of a significant difference in IgM or IgG titers between acute- and convalescent-phase sera. The titers of 10 paired sera from patients from whom
S. enteritidis
, bioserotype paratyphi A, was isolated were somewhat lower than those of 84 patients with
S. typhi
isolation (serogroup D). There was some correlation between O antigen agglutination and IgM enzyme-linked immunosorbent assay, but otherwise the titers in the two serological tests varied independently. Of 11 patients in set 3 (2 patients with serogroup B agglutinins omitted), 1 belonged to blood group O, in contrast to 54 group O among 107 agglutination-positive patients, a distribution not necessarily reflected by the enzyme-linked immuno-sorbent assay. This study has provided good evidence that the enzyme-linked immunosorbent assay can serve as a valuable aid to the diagnosis of
Salmonella
infection in an endemic area, as a substitute for the agglutination test.