Study showing doe-to-fawn CWD spread may have implications for deer herds

In the current study, the researchers evaluated maternal reproductive tissues and fluids, as well as fetal tissues from free-ranging white-tailed deer (WTD) naturally exposed to CWD for evidence of infectious prions through PMCA, the highly sensitive real-time quaking induced conversion (RT-QuIC) test, and bioassay with experimentally infected transgenic (genetically engineered) mice.

Bioassay is the only test that can determine the biological relevance of CWD deposition in these tissues. The scientists also retrospectively examined historical CWD surveillance data from three study sites in Arkansas, Tennessee, and West Virginia with a CWD prevalence higher than 20% for evidence of natural infection in WTD fawns 1 year or younger using Western blot and enzyme-linked immunosorbent assay (ELISA). 

In total, 5 of 16 free-ranging CWD-positive does (31.3%) were carrying at least one fetus with tissues with prion deposition. All 35 mice inoculated with CWD-positive reproductive tissue developed terminal clinical transmissible spongiform encephalopathy (TSE), characterized by signs such as unsteady gait, limb paralysis, and weight loss. 

RT-QuIC analysis of brain tissue from all bioassay mice inoculated with free-ranging WTD brain, uterus, or placentome also revealed the presence of amyloid protein seeding (ie, prions).

Early in utero CWD exposure

"Here we report the presence of the infectious CWD agent within fetal and reproductive tissues of free-ranging WTD, revealing that dams [does] can transmit the disease in utero to their offspring," the study authors wrote. 

Examination of historical surveillance data identified CWD-positive WTD fawns younger than 6 to 10 months old. "These findings suggest an earlier exposure to CWD than postpartum maternal saliva, blood, or environmental contact," the authors wrote, noting that fawns younger than 6 months aren't routinely incorporated into state CWD surveillance programs because traditional assays are not likely to detect infection.

Mathiason said mother-to-fetus CWD transmission likely occurs through blood. "We know that during gestation, lesions occur between the maternal and fetal interface, and that these lesions become blood filled," she said. "And so we also know that fetal-derived trophoblast cells are phagocytic [they can consume foreign particles, dead cells, or debris] and can transport themselves across the maternal-fetal interface."

"It is possible that these cells phagocytose CWD-infected white blood cells, as we know from previous studies, contain the infectious prion agent and carry them back to the fetal environment. This could be the initiation of in utero fetal CWD infections."

Role of highly sensitive tests

Mike Samuel, PhD, professor emeritus at the University of Wisconsin at Madison and a retired wildlife research biologist with the US Geological Survey, who wasn't involved in the study, said he was surprised by the high prevalence of CWD-positive fetuses in the study, when at least in the recent past, does in southern Wisconsin tested positive 10 times more often than fawns. 

"It's very interesting, and it's very puzzling," he said. and "It's hard to see what effect it [vertical transmission] has, because if it's killing fawns, I think we'd notice it" in faster deer population declines than expected by only adult CWD mortality. "One of the closest bonds we know about is between does and fawns, so it's been a mystery why there aren't more CWD-positive fawns. This study seems to confound that mystery."

A few factors could account for the difference between study and field data, he said, including the testing of different tissues in the study than are used for wild deer (ie, brain and retropharyngeal lymph nodes) or the use of more-sensitive testing methods that can detect CWD prions sooner (eg, RT-QuIC), which isn't approved for non-research applications.

Mathiason also attributed the higher-than-expected CWD-positive rate in fawns to highly sensitive amplification assays. "That's permitting us to be able to detect smaller and smaller quantities [of CWD prions] that may not have been noticed by conventional tests like IHC, ELISA, or Western blot," she said.

Samuel said that CWD-positive fawns may die of infection soon after they're born, although CWD clinical signs typically don't develop until 1.5 to 2 years after infection. 

"Maybe there's a tendency for CWD-positive mothers to not do as well at raising fawns, but that wouldn't be enough to explain it" Samuel said. "Another possibility is that these apparent infections are occurring in different tissues than we're used to sampling and through a very different route than the usual oral route, so maybe these don't turn into full-blown infections."

Sonja Christensen, PhD, an assistant professor in Michigan State University's Department of Fisheries and Wildlife, who likewise was not a study author, pointed out that results in the lab often look different from what is seen in free-ranging cervid populations. "There are a lot of uncertainties about what happened from when that fawn was born to when it showed up on a necropsy table or in the back of a hunter's truck," she said.

In addition, wildlife biologists are limited to hunter-harvested animals, and many hunters don't select fawns. "So certainly their data set probably reflected that," Christensen said. "And if anything, this provides some grounds for looking more at fawns in hunter harvests in the future for surveillance specifically for CWD."

'Something missing in the safety net'

Christensen said the study findings may have substantial implications for deer populations: "We now know that those fawns can be infected with CWD at birth and may be infectious to other animals much, much earlier—even if they look healthy. That has huge implications for wild-deer population trajectories, because now we have to be thinking of another risk factor on the landscape that's infecting animals within their own population."

She also noted that fawns often travel outside of their family unit when trying to establish their own home range. "With those excursions, if you have a positive fawn, more contacts might occur with other uninfected or susceptible deer outside of their regular family group," she said. "So that's another risk factor on the landscape."

The study, she added, shows that even a very young and seemingly very healthy fawn isn't necessarily CWD-free: "So really trying to be judicious with moving animals around and reducing the spread of potential contacts among deer that could be infectious when you don't really know their CWD status is really important."

Samuel said vertical transmission is unlikely to be significant and probably won't change management strategies, unless it can be shown that vertical CWD transmission is killing a large number of fawns. 

Female yearlings, which could have potentially been exposed to CWD for 1.5 years, have a 25% infection rate, compared with 35% for adult does. In contrast, CWD infections rise from 25% in yearling males to 50% over the following 1 to 2 years.

"There's obviously a lot more infection going on for males compared to females," he said. "While the paper is interesting and well done, I simply don't see how vertical transmission can be considered an important route of infection based on data from Wisconsin deer." 

Mathiason agreed that factors other than vertical transmission likely have more bearing on management strategies. "I just think as we see populations with increasing prevalence rates, it's a real issue," she said. "And if we think about placental materials being left in the environment, it's yet another contributor to infectivity within the environment as well."

Tom Hauge, MS, a wildlife biologist and retired director of wildlife management for the Wisconsin Department of Natural Resources, said the study results might encourage deer farmers to test fawns before moving them from one facility to the next.

"The industry, despite the USDA [US Department of Agriculture] having herd certification programs and things like that, has really struggled with it," said Hauge, who wasn't involved in the study. "An awful lot of herds that were certified CWD-free have somehow turned out to be positive. And so that points out that there's something missing in the safety net."