Listeria May Pose Serious Threat Early in Pregnancy

From their study of how Listeria affects the fetus, researchers suggest that infection with Listeria monocytogenes likely poses a greater risk of miscarriage in the early stages of pregnancy than has been appreciated.

"Listeria has been associated with adverse outcomes in pregnancy, but particularly at the end of pregnancy," said senior author Ted Golos, of University of Wisconsin-Madison, "What wasn't known with much clarity before this study is that it appears it's a severe risk factor in early pregnancy."

"The problem with this organism is not a huge number of cases. It's that when it is identified, it's associated with severe outcomes," said co-author Charles Czuprynski, professor at UW-Madison. Pregnant women are warned to avoid many of the foods that can harbor Listeria, and severe outcomes have resulted in a zero-tolerance regulatory policy for Listeria in ready-to-eat foods.

But Listeria infection in pregnancy may go unnoticed; the few recognizable symptoms are nearly indistinguishable from the discomfort most newly pregnant women feel. Yet "it has a profound impact on the fetus," said Prof. Golos, "That's familiar now because we've been talking about the same difference in Zika virus."

For the study, Sophia Kathariou, professor at North Carolina State University, provided a strain of Listeria that caused miscarriage, stillbirth, and premature delivery in at least 11 pregnant women in 2000. Four pregnant rhesus macaques at the Wisconsin National Primate Research Center were fed doses of the Listeria comparable to what one might encounter in contaminated food. Lead author Bryce Wolfe, a UW-Madison graduate student, monitored the speed and progression of Listeria's spread.

"What's particularly striking about the work Bryce did is the detailed information we now have about the organism," said Prof. Czuprynski, "she tracked it being shed in feces and showing up in the bloodstream. They did ultrasound analysis of the fetus, and could then show events in terms of where the organism was preceding fetal demise."

None of the monkeys showed obvious signs of infection before their pregnancies came to abrupt ends. But in tissue samples taken after each monkey experienced intrauterine fetal death, Wolfe found Listeria had invaded the placenta. "In that region there's a rich population of specialized immune cells, and it is exquisitely regulated," said Wolfe, "When you introduce a pathogen into the midst of this, it's not very surprising that it's going to cause some sort of adverse outcome disrupting this balance."

The researchers suggest the inflammation caused by the maternal immune response affects the placenta, preventing it from protecting the fetus. "It should be a barrier," said Prof. Golos, "But we're hypothesizing that the maternal immune system's attempt to clear the bacteria actually results in collateral damage to the placenta that then allows the bacteria to invade the fetus."

The results suggest Listeria (and perhaps other pathogens) may be the culprit in some miscarriages that usually go without diagnosed cause, but the bacteria's stealth and speed may still make it hard to control. "There are effective antibiotics available. It is treatable," said Wolfe, but "the fetus may be infected by the time anyone realizes the mother was infected."

The researchers plan to further investigate progression of infection and the maternal immune response to intracellular pathogens in pregnancy, in hope that such basic knowledge would help battle this and similar dangers, such as Zika virus.

The study, by Wolfe B et al, was published February 21, 2017, in the journal mBio.