Placentitis is a common cause of late-pregnancy abortion in mares and poses a significant threat to fetal and neonatal viability. Diagnosis has been challenging making it increasingly common to treat all pregnant mares with antibiotics for five to seven days each month during late gestation. However, this poses long-term risks of widespread bacterial resistance against antibiotics.
Drs. Barry Ball, Igor Canisso and Mats Troedsson explain a test that has shown progress in identifying new biomarkers that can assist in the diagnosis of bacterial placentitis. Their work was first published in the University of Kentucky College of Agriculture’s Equine Disease Quarterly.
Bacterial agents commonly associated with the occurrence of placentitis include Streptococcus equi subspecies zooepidemicus, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Leptospira spp, nocardioform bacteria (Crossiella equi, Amycolatopsis spp) and others. Except for leptospiral and nocardioform placentitis, most cases of bacterial placentitis are thought to originate due to bacterial invasion via the cervix. Therefore, these cases of ascending placentitis usually start at the cervical star and spread from there. Infection of the placenta results in subsequent infection of the fetus and in the release of prostaglandins from the inflamed placenta, which ultimately leads to abortion or delivery of a premature foal with bacterial sepsis.
Effective treatment of placentitis requires early diagnosis prior to the appearance of clinical signs, such as premature udder development with or without the streaming of milk and/or vulvar discharge. Currently, ultrasonographic evaluation of the placenta is used to detect early cases of placentitis and to implement treatment to prevent abortion and delay premature labor. While this practice has allowed more effective treatment and has improved the outcome in many cases, it is often not practical to ultrasound every mare repeatedly during late gestation. In addition, early stages of placentitis can be missed during ultrasonographic examination, and the technique is also prone to false positive diagnoses, resulting in unnecessary treatment.
In the absence of an accurate and practical method to detect early, subclinical cases of placentitis, it has become increasingly common to treat all pregnant mares with antibiotics for five to seven days each month during late gestation. The long-term risk of developing widespread bacterial resistance against antibiotics and the development of “superbugs” should be of great concern, not only to the breeding industry, but to veterinary medicine as well as human health. Additional diagnostic tools are therefore needed to accurately identify pregnant mares with early stages of placentitis and to specifically target these mares for treatment.
The equine placenta synthesizes and metabolizes progestagens, which are critical for pregnancy maintenance. Experimentally, mares that develop chronic placentitis often have increased plasma progestin concentrations, whereas mares with acute placentitis often demonstrate a rapid drop in plasma progestin concentrations. Repeated measurement of plasma progestin concentrations in mares with placentitis can be a useful method to identify mares at risk for abortion or premature delivery.
Serum estrogen concentrations are elevated in pregnant mares between 150-310 days of gestation. The predominant estrogens in pregnant mares include estrone, equilin, equilenin, estradiol- 17ß, and estradiol-17α. Determinations of serum concentrations of estrone sulfate are useful in pregnancy diagnosis and to monitor fetal viability. Researchers have observed that mares aborting from placentitis had serum estrogen concentrations below those normally detected in pregnant mares. Preliminary studies in our laboratory indicate that in mares with experimentally induced bacterial placentitis, concentrations of estradiol-17ß sulfate may decline precipitously after infection, also suggesting that maternal estrogen concentrations may be useful as an early marker of placental insult.
In addition to endocrine monitoring, measurement of acute phase proteins in blood may also be a useful biomarker for placentitis in mares. Serum concentrations of acute phase proteins are elevated when inflammation is present. This group of proteins is mainly produced by the liver in response to an inflammatory stimulus. The major acute phase protein in the horse is serum amyloid A (SAA), whereas the minor acute phase proteins include haptoglobin and fibrinogen.
In ongoing research at the Maxwell H. Gluck Equine Research Center, mares with experimentally induced placentitis have a rapid and dramatic elevation in SAA within two days after intracervical inoculation with Streptococcus equi subspecies zooepidemicus. Although SAA appears to be a very sensitive indicator for acute bacterial placentitis, it is also a very nonspecific indicator, as many other acute inflammatory conditions may result in an elevation of SAA.
Ultimately, it appears likely that more than one biomarker may be required for accurate and early detection of placentitis in the mare. Ongoing research will address these needs and evaluate the utility of these markers in mares under field conditions.