Serologic Studies of Primary Epidemic Typhus and Recrudescent Typhus (Brill-Zinsser Disease)

Abstract

Summary Two distinct serologic patterns were observed in complement fixation (CF) tests on 172 sera from 70 patients suffering from infections caused by Rickettsia prowazeki. The acute phase sera from 30 of the patients required 4 to 8 units of antigen in order to demonstrate maximum antibody titers; moreover, serum inactivation at 60°C for 30 min markedly lowered antibody titers. This group of patients also developed Weil Felix titers of 1:160 or greater between the 10th and 20th days of illness and showed no significant evidence of cross-reacting murine typhus CF antibodies. These 30 patients illustrate the clinical, epidemiologic and serologic characteristics of primary epidemic typhus. In contrast, acute phase sera from the remaining 40 patients gave almost identical antibody titers with both 1 and 8 units of antigen and these titers were not altered by serum inactivation at 60°C instead of 56°C for 30 min. This group of patients did not develop Weil Felix titers greater than 1:80 but did develop rising cross-reacting murine typhus CF antibodies. As a group these patients also demonstrated a dramatic rise in epidemic typhus CF antibody titers between the 7th and 10th days of illness. These 40 patients illustrate the clinical, epidemiologic and serologic characteristics of classic Brill-Zinsser disease. The sharply contrasting serologic patterns demonstrated in the immune responses of primary epidemic typhus and Brill-Zinsser disease add confirmation to Zinsser's hypothesis, which states that typhus occurs in a secondary (recrudescent) as well as a primary form. These findings also add to the accumulating data which point toward there being substantial physicochemical differences in the properties of primary and secondary immune response antibodies. The presence of the high antigen requirement (HAR) and heat labile (HL) phenomena can be demonstrated regularly in acute phase primary epidemic typhus sera; this observation implies that when diagnostic laboratories are testing for CF antibodies in such sera, 4 to 8 units of antigen and less than 58°C serum inactivation should be employed. The probable presence and significance of the HAR and HL phenomena in other infectious diseases is discussed.