The effect of BCG and C. parvum on the mortality from S. aureus septicemia in mice

An immunosuppressed mouse model was devised to test the effects of various immunostimulators in the prevention of mortality from S. aureus septicemia. CDF₁ male mice were given i.p. either BCG, in doses of 10⁶, 10⁴ or 10² CFU, or 0.5 mg C. parvum at varying intervals before bacterial challenge. Four days before injection of S. aureus, 300 mg/kg Cytoxan was given i.p. In four days, the time at which the WBC count was less than 100/mm³, a lethal dose of S. aureus (1.68 ± 0.20 x 10⁵) was given i.v. For S. aureus infection without pretreatment, the D50 was day 6. BCG (10⁶) CFU prevented significant death (D50 > 50 days) at pretreatment intervals of 3, 7, 14, 28 and 42 days. A dose response was seen for smaller BCG doses. C. parvum was as effective as BCG when given 3 days before infection, but lost some of its protective effect by day 42. Isoniazid treatment eliminated the protective effect of the BCG. Several different strains and preparations of BCG were equally effective. The data suggest that the non specific stimulation of the RES that accompanies immunotherapy may be reducing bacterial infections in the immunosuppressed host. The prolonged survival of certain patients on immunotherapy regimens may be in part due to an increased ability to cope with bacterial infections.