A dose-response model using rhesus monkeys as a surrogate for pregnant women indicates that oral exposure to 10 7 CFU of Listeria monocytogenes results in about 50% stillbirths. Ten of 33 pregnant rhesus monkeys exposed orally to a single dose of 10 2 to 10 10 CFU of L. monocytogenes had stillbirths. A log-logistic model predicts a dose affecting 50% of animals at 10 7 CFU, comparable to an estimated 10 6 CFU based on an outbreak among pregnant women but much less than the extrapolated estimate (10 13 CFU) from the FDA-U.S. Department of Agriculture-CDC risk assessment using an exponential curve based on mouse data. Exposure and etiology of the disease are the same in humans and primates but not in mice. This information will aid in risk assessment, assist policy makers, and provide a model for mechanistic studies of L. monocytogenes-induced stillbirths.

Listeria monocytogenes, isolated from outbreaks in either human or nonhuman primate populations, was administered orally at doses ranging from 10 6 to 10 10 CFU. Four of 10 treated animals delivered stillborn infants. L. monocytogenes was isolated from fetal tissue, and the pathology was consistent with L. monocytogenes infection as the cause of pregnancy loss. For all pregnancies resulting in stillbirths, L. monocytogenes was isolated from maternal feces, indicating that L. monocytogenes had survived and had probably colonized the gastrointestinal tract. Antibodies and antigen-specific lymphocyte proliferation against Listeria increased in animals that had stillbirths.Listeriosis resulting from exposure to food containing the bacterium L. monocytogenes causes serious disease, with case fatality rates between 20 and 40% (33). Listeriosis is especially serious in susceptible populations such as immunocompromised persons and pregnant women (11,14,16,20,24,26,29,32,35). For healthy nonpregnant adults, listeriosis has a relatively low incidence, presumably due to its low infectivity in immunocompetent individuals.Pregnancy-related listeriosis primarily affects the fetus or neonate. The maternal reaction to the presence of Listeria infection is generally an influenza-like episode with fever, backache, and perhaps diarrhea (7,11,13,24,29). The effect of fetal Listeria infection is dependent on the point in gestation time when infection occurs. First-trimester infection leads to spontaneous abortion, whereas second-and third-trimester infections lead to preterm birth followed by neonatal illness or fetal death with preterm delivery of a stillborn (7,11,13).The rhesus monkey (Macaca mulatta), with a reproductive cycle and placenta comparable to those of humans (31), is widely used as an experimental model for human reproduction and development. As with humans, exposure to L. monocytogenes in pregnant nonhuman primates may result in abortions, stillbirths, or neonatal deaths (4, 27; J. Paul-Murphy, J. E. Markovits, I. Wesley, and J. A. Roberts, Lab. Anim. Sci. 40:547 [abstr.], 1990). For humans and nonhuman primates, the pathogenesis and morphological findings associated with stillbirths due to L. monocytogenes are essentially the same (1,4,28,37).Despite several epidemiological studies confirming the relationship between L. monocytogenes and specific foods (soft cheeses, undercooked chicken, paté, etc.) (2, 30), an infectious dose has not been established for healthy or susceptible human populations due to the delay between exposure and the onset of symptoms. The severe ramifications of the disease in highrisk human populations such as pregnant women precludes the use of humans in volunteer feeding studies. Recently, a draft risk assessment of L. monocytogenes in ready-to-eat foods (36) reviewed human epidemiological and animal study data. The risk assessment concluded that mouse studies provide the only acceptable data for developing dose-response information at this time and acknowledged the difficulty with the use of...

A large‐scale screening program was initiated to evaluate laboratory‐cultured blue‐green algae (cyanobacteria) as a source of novel antineoplastic agents. Approximately 1000 cyanophyte strains from diverse habitats were cultured to provide extracts for testing. The screening program identified the families Scytonemataceae and Stigonemataceae as prolific producers of novel cytotoxic compounds. Rates of rediscovery of known compounds were relatively low.

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