Dose-Response of Listeria monocytogenes after Oral Exposure in Pregnant Guinea Pigs

Abstract

Listeriosis, a severe disease that results from exposure to the foodborne pathogen Listeria monocytogenes, is responsible for approximately 2500 illnesses and 500 deaths in the United States each year. Pregnant women are 20 times more likely to develop listeriosis than the general population, with adverse pregnancy outcomes that include spontaneous abortions, stillbirths, and neonatal meningitis. The objective of this study was to determine an infective dose that resulted in stillbirths and infectivity of selected tissues in pregnant guinea pigs. Pregnant guinea pigs were exposed orally on gestation day 35 to 10(4) to 10(8) L. monocytogenes CFU in sterile whipping cream. L. monocytogenes was recovered at 64, 73, 90, and 100% from the livers of animals infected with 10(5), 10(6), 10(7), and 10(8) CFU, respectively. In dams exposed to > or =10(6) CFU, L. monocytogenes was cultured from 50% of the spleen samples and 33% of the gallbladder samples. Eleven of 34 dams infected with > or =10(6) CFU delivered stillborn pups. L. monocytogenes was cultured from the placenta, liver, and brain tissue of all stillbirths. Dams that delivered nonviable fetuses after treatment with > or =10(7) L. monocytogenes CFU had fecal samples positive for L. monocytogenes at every collection posttreatment. On the basis of a log-logistic model, the dose that adversely affected 50% of the pregnancies was approximately 10(7) L. monocytogenes CFU compared with that estimated from a human outbreak of 106 CFU. Listeriosis in pregnant guinea pigs can result in stillbirths, and the overall disease is similar to that described in nonhuman primates and in humans.

Dose-Response Model for Listeria monocytogenes -Induced Stillbirths in Nonhuman Primates

“…Frequently, the available data are not sufficient to permit critical comparisons among closely related models. After examining several dose-response models (including exponential, logistic, Weibull gamma, and probit) and our previous experience with dose-response models for pathogens (11,21), we found them to predict similar effects near the LD 50 region for the doseresponse curve. At low doses, at which effects occur in Յ1% of FIG.…”

Dose Response of Listeria monocytogenes Invasion, Fetal Morbidity, and Fetal Mortality after Oral Challenge in Pregnant and Nonpregnant Mongolian Gerbils

“…However, only a single gerbil fetus in these groups was positive for L. monocytogenes out of over 100 samples of maternal organs, placentas, and fetuses analyzed. In contrast, L. monocytogenes was recovered from 25% and 64% of livers collected from guinea pig dams exposed to 10 4 CFU and 10 5 CFU, respectively (18). Additionally, only 50% of litters from 10 7 -CFU-treated gerbils were invaded, none of which showed L. monocytogenes-induced resorptions or stillbirths, whereas guinea pigs had fetal invasion in dams exposed to 10 5 CFU and stillbirths in all groups exposed to Ն10 6 CFU.…”

“…The FAO-WHO risk assessment for listeriosis during pregnancy estimates a 50% lethal dose (LD 50 ) of 1.9 ϫ 10 6 CFU for human fetuses (27). Previous studies using guinea pigs and nonhuman primates with fetal death as an endpoint have yielded LD 50 s of 2.00 ϫ 10 7 CFU and 8.45 ϫ 10 7 CFU, respectively (18,25). The 95% confidence intervals of these three dose-response curves overlap, but the inability of L. monocytogenes to interact with the guinea pig Met receptor during invasion has led some to believe that guinea pig susceptibility to the pathogen may not be equivalent mechanistically to that of humans (17).…”

“…Although guinea pigs and rabbits are susceptible to listeriosis when exposed orally, they posses a polymorphism in their Met receptors that affects invasion of cells such as hepatocytes, potentially making guinea pigs and rabbits less sensitive than humans to listeriosis (17). However, despite the difference in the Met receptor, studies in guinea pigs demonstrate that they are susceptible to listeriosis at about the same concentrations as nonhuman primates and humans (18), suggesting that other pathways play a role in fetoplacental invasion in these animals (19). Likewise, other invasion pathways independent of InlA and InlB have been suggested for mice (20).…”

Immune Status and the Development of Listeria monocytogenes Infection in Aged and Young Guinea Pigs

“…e 10 2 CFU dose used in this study was selected based on studies using guinea pigs demonstrating 100%, ca. 90%, 25% and 13 to 50% of animals becoming infected when challenged orally with 10 8 , 10 6 , 10 4 and 10 2 CFU L. monocytogenes, respectively [12,30]. Changes in T cell levels were used as a marker to gauge the immunomodulatory e ect of vitamin E supplementation and immune response to L. monocytogenes infection.…”