Humoral immunity against Francisella tularensis after natural infection

Forty-two subjects with acute tularemia were studied for the occurrence of C-reactive protein (CRP), and 73 subjects with acute tularemia or experience of the disease within the last 11 years were studied for immunoglobulin M (IgM), IgA, and IgG class-specific antibodies, agglutinating antibodies, and complement-fixing antibodies to Francisella tularensis by using an enzyme-linked immunosorbent assay (ELISA), the tube agglutination test, and a complement-fixing ELISA. The incubation time between infection and the outbreak of symptoms varied from 1 to 10 days, averaging 6.5 days. Elevated CRP concentrations were found in all samples taken in the first 6 days of illness, when the antibodies generally were absent. The highest CRP values, up to 165 mg/liter, occurred in the earliest samples and then decreased rapidly, being undetectable (less than 1 mg/liter) from 1 month after the onset of symptoms. Simultaneous though individually varying formation of IgM, IgA, and IgG class-specific antibodies to F. tularensis was demonstrable by ELISA in all the tularemia patients during the acute stage. In most cases, these antibodies appeared 6 to 10 days after the onset of symptoms, i.e., about 2 weeks after infection, reached their highest values at 4 to 7 weeks, and, despite a decreasing trend in their level, were still present 0.5 to 11 years after onset of tularemia, as demonstrable by the agglutination test and by the complement-fixing ELISA. Of the three methods used, ELISA for IgM, IgA, and IgG proved to be the most efficient for the early serodiagnosis of tularemia.