Susceptibility of mice treated with cyclophosphamide to lethal infection with Leptospira interrogans Serovar pomona

Abstract

Mice not normally susceptible to infection with Leptospira interrogans serovar pomona were rendered susceptible to lethal infections by treatment with a single dose of 300 mg of cyclophosphamide (Cy) per kg administered optimally from 4 days before to 1 day after infection. Cy-treated mice with either passively or actively acquired antibody were protected from death. Blood levels of leptospires in infected untreated and in Cy-treated mice remained similar until 2 days after infection, when untreated mice cleared the leptospires. Soon afterwards, opsonizing and agglutinating antibody appeared. Cy-treated mice given spleen cells from other normal or specifically immune mice were protected from infection. An important factor in the natural resistance of mice to leptospiral infection appears to be their capacity to produce circulating antibody within 48 to 72 h. Applications are suggested for this animal model in vaccination and protection studies.

Following the course of human leptospirosis: evidence of a critical threshold for the vital prognosis using a quantitative PCR assay

“…Indeed, the three patients with estimated bacteremia to this level all died. Evidence for the concept of a critical threshold relating to lethality was previously obtained using a mouse model of leptospiral infection [10]. In one case (patient F), a decrease in the estimated number of circulating leptospires under the threshold of 10 4 leptospires ml −1 was observed, but this patient did not recover.…”

Following the course of human leptospirosis: evidence of a critical threshold for the vital prognosis using a quantitative PCR assay

“…Indeed, the three patients with estimated bacteremia to this level all died. Evidence for the concept of a critical threshold relating to lethality was previously obtained using a mouse model of leptospiral infection [10]. In one case (patient F), a decrease in the estimated number of circulating leptospires under the threshold of 10 4 leptospires ml 31 was observed, but this patient did not recover.…”

Antigens recognized by the human immune response to vaccination with a bivalent hardjo/pomona leptospiral vaccine

“…Immunoblotting sera from subjects 1-6 with har~o sonicate revealed that all produced 18M antibodies against the 15, 23 and 28 kDa components of hardjo LPS described previously [24]. Reaction with other hardjo antigens varied, although reactiun of IgM and/or IgG antibodies with the 34.5-35 kDa flagella doublet was observed with serum from most subjects.…”

“…It is also sisnificant that the vaocinees" sera protected hamsters from acute infection, similar to the protection reported for sera from naturally a~luired infections [20], in which anti-LPS ag-81urinating antibodies were involved. Although it was not possible to test anti-har~o antibodies for protective capacity it is reasonable to assume that they would also protect, in view of the correlation between agglutinatin& opsonizin8 and protective antibodies [13,24,25]. Our results thus confn-m that immunization of humans with protein-frec grown vaec~ne can induce the production of protective anti-LPS antibodies which appear to have a central role in immunity to infection, similar to the response following natural infection and to protection in animals [13,15,20].…”