Comprehensive Review on Equine Placentitis

Placentitis is estimated to affect 3 to 5% of pregnancies. In recent years substantial developments have been made on equine placentitis and a comprehensive review is timely. Etiopathogenesis, epidemiology, diagnosis and treatment, and research models for the four morphologic types of placentitis (i.e., ascending, nocardioform, diffuse, and multifocal) are discussed. 

1. Introduction

Placentitis, an important cause of late-term pregnancy wastage, is estimated to affect 3 to 5% of pregnancies in Thoroughbred mares.^1,2  Late-term pregnancy wastage generates several million dollars of losses to the equine industry each year due to the lost expense of producing a pregnancy (e.g., stud fees, semen transport, feed, vaccinations, veterinary services, etc.). In addition, late-term pregnancy loss may cause emotional stress to the owner with high expectations for the foal from a particular mating. Therefore, means to manage and to prevent pregnancy loss are warranted.

Placental pathology/insufficiency was identified in a large retrospective study as being responsible for greater than 60% of pregnancy losses due to abortion, stillbirth, and neonatal death (up to 24 h postdelivery) in central Kentucky.³  Two additional retrospective studies conducted several years apart by the same referral diagnostic laboratory supported the finding that placentitis is the most common cause of late pregnancy loss in mares.^4,5  Outside North America, placentitis has been identified as an important cause of pregnancy loss in mares in Brazil,^6,7  France,⁸  and Australia.⁹  However, in the United Kingdom umbilical cord pathology (e.g., torsion and entrapments) was the leading cause of pregnancy loss in submissions received by one diagnostic laboratory.¹⁰ Differences between the United Kingdom and other parts of the world may be accounted for by the methodology applied to diagnose placentitis, type of placentas presenting lesions submitted for pathologic examination, and the presence of certain microorganisms (e.g., nocardioform organisms), as well as potential differences in true incidence. 

In recent years, substantial advancements have been made regarding our understanding of equine placentitis through controlled and field studies carried out in different parts of the world. Reviews covering equine placentitis have been published,^11,12 with one recent review emphasizing the immunologic aspects of the preterm delivery in mares.¹³ The following review aims to present a comprehensive review of classical and recent findings regarding equine placentitis.

2. Etiopathogenesis and Epidemiology

Several infectious agents have been recovered from placentitis cases; bacteria are responsible for the large majority of cases and fungi for the minority (Table 1). Bacterial agents commonly associated with placentitis include Streptococcus equi subspecies zooepidemicus, Escherichia coli, Streptococcus equisimilis, Klebsiella pneumoniae, Pseudomonas aeruginosa, Leptospira sp., Crossiella equi, and Amycolatopsis species (Amycolatopsis kentuckyensis, Amycolatopsis lexingtonensis, and Amycolatopsis pretoriensis)^2,4,8,14 (Table 1). Fungi associated with equine placentitis primarily include Aspergillus ssp. and Candida albicans.⁴ Mixed bacterial and fungal infections have been reported in ascending, however, less commonly. Anecdotally, it seems that some cases start with bacterial placentitis and then fungal secondary infections follow the primary bacterial infection.

The incidence of leptospiral infections causing abortions is highly variable across the years in central Kentucky.^4,5,15 In North America, the serovar Pomona type Kennewicki is the most important type associated with Leptospiral abortions in mares¹⁶; however, in other parts of the world, the serovars Bratislava, Grippotyphosa, Copenhageni, Autumnalis, Hebdomadis, Arborea, and Icterohaemorrhagiae are more commonly associated with abortion in mares.¹⁷ Environmental conditions such as precipitation and flooding are alleged to be important in the dissemination of the bacteria from wildlife to horses, which are considered incidental hosts. Wild animals including raccoons, white-tailed deer, striped skunks, opossums, and foxes are known to harbor the serovar Pomona and are thought to serve as a source of infection for pregnant mares.^5,18

Based upon morphologic lesions and suggested pathogenesis, there are four types of equine placentitis: ascending, focal mucoid (nocardioform), diffuse (hematogenous), and multifocal⁵ (Fig. 1). Ascending placentitis, the most frequent type of placentitis, is commonly associated with beta hemolytic streptococci and coliforms⁵ (Table 1). Nocardioform placentitis is commonly associated with Gram-positive branching bacilli, Crossiella equi and Amycolatopsis species (Fig. 2).^14,19 Recently, two new species of Streptomyces (Streptomyces atriruber and Streptomyces silaceus) have been isolated in nocardioform placentitis cases.²⁰ A multifocal distribution pattern is rare but is sporadically seen in isolated cases in association with fungi or bacteria.^4,5 Diffuse placentitis is diagnosed in isolated cases in association with bacteria or fungi, or during outbreaks in association with Leptospirosis (Fig. 1D).
 

Nocardioform placentitis has periodically been the predominant type of equine placentitis in central Kentucky^4,21 with the 2010–2011 foal crop season in central Kentucky experiencing an exceptionally high number of nocardioform cases (Fig. 3). Conjunctly, Crossiella equi and Amycolatopsis ssp. were responsible for 85% of the cases submitted during that period,¹⁴ with lesions compatible with nocardioform placentitis present without an identified isolate in the remainder of cases. Based on these cases it seems that Crossiella equi infections may be more likely to result in abortion, whereas infections with other type actinomycetes tend to result in live but premature foals.¹⁹ It is worth noting that, to date, nocardioform organisms have only been isolated from clinical placentitis cases and not from the environment.¹⁹

Bacteria causing nocardioform placentitis and other actinomycetes that affect horses differ in their propensity to infect not only the fetal membranes but also the offspring in utero. For instance, mares affected by Cellulosimicrobium cellulans in Kentucky present mucoid placentitis associated with severe fetal lesions.²² Similarly, the actinomycetes Cellulosimicrobium sp and Cellulomonas sp, along with other nonspecific bacterial species, have been associated with mucoid placentitis and fetal lesions in equine amnionitis and fetal loss, reported to occur with ingestion of processionary caterpillars in Australia.²³ Conversely, actinomycetes causing nocardioform placentitis do not infect the fetus in utero as reported in other types of mucoid placentitis; the bacterial infection in nocardioform placentitis is restricted to the chorioallantois.¹⁹

Infectious agents associated with ascending placentitis seems to enter the uterus via the vagina/ cervix and then colonize the caudal pole of the chorioallantois (Fig. 4).¹¹ [...]