Nocardioform placentitis (NP)—now more descriptively referred to as focal mucoid placentitis (FMP)—is a unique form of equine placentitis that remains one of the most enigmatic challenges for breeders and veterinarians. First identified in 1985, FMP has since occurred episodically with outbreaks in 1998, 1999, 2011, 2017 and 2020. The most recent surge in 2020 was reported in Central Kentucky and in the Mid-Atlantic region. Sporadic cases of FMP have also been reported in South Africa, Italy, Australia, Brazil and New Zealand. Affected mares may suffer late-term abortions or give birth to small, weak, “stunted” foals due to placental insufficiency. These outcomes are not only devastating for breeders and owners but also impose a substantial economic burden on the equine industry. At the University of Kentucky’s Equine Reproduction Laboratory, our research focuses on improving our understanding of and management for this disease by developing innovative diagnostic and therapeutic strategies. 

The Enigmatic Disease  

The route of infection for FMP remains one of the most significant mysteries surrounding the disease. Unlike ascending placentitis, which originates from ascending bacterial infection through the cervix, FMP is characterized by unique mucoid lesions typically located at the base of the uterine horns. These lesions are often covered in a thick, tan, mucoid material and are sharply demarcated from healthy tissue. How bacteria reach this site remains unknown.  

The condition has been thought to be associated with soil-dwelling nocardioform bacteria such as Crossiella equi and Amycolatopsis species, though other non-nocardioform bacteria like Mycobacterium species and Pantoea species have also been isolated from clinical cases. Yet despite these associations, experimental attempts to induce the infection in mares by intrauterine inoculation of Crossiella equi at breeding and in pregnant mares via oral, intravenous and intranasal routes have been unsuccessful. Therefore, the pathogenesis of FMP remains obscure. What is clear, however, is that the environment plays a role. Outbreaks have repeatedly followed late summers characterized by unusually warm and dry conditions. 

Advancing Diagnostic Frontiers  

Detecting this condition at an early stage is crucial for effective treatment. While transabdominal ultrasound is a primary tool, it can miss early or small lesions because of the limited area that can be visualized in a large pregnant uterus. By the time overt clinical or imaging abnormalities are detected, the disease is already advanced, reducing treatment efficacy and increasing the risk of pregnancy loss.  

To address this limitation, our laboratory is pioneering the use of blood-based proteomics—an advanced approach that enables comprehensive analysis of the circulating protein profile. Preliminary studies have identified a panel of proteins that is significantly altered in mares with FMP compared to healthy controls. We are currently expanding this work to verify and validate the most informative biomarkers, focusing on those with the highest sensitivity, specificity and diagnostic accuracy. The development of a reliable blood-based screening test would represent a major advancement, allowing veterinarians to identify at-risk mares earlier and with greater confidence. Earlier detection would, in turn, facilitate timely therapeutic intervention before the disease progresses, ultimately improving pregnancy outcomes.  

Advancing Treatment Frontiers  

Current treatment protocols are largely empirical, as it is not yet fully understood which medications effectively penetrate the thick mucoid material to reach the bacteria. New research efforts led by Dr. Rebecca Ruby at the UK Veterinary Diagnostic Laboratory are focusing on measuring antibiotic penetration and identifying which drugs best reach the target site. Furthermore, by utilizing high-resolution RNA sequencing, we at the Equine Reproduction Laboratory are investigating the genes involved in placental inflammation. Identifying these “on/off” switches for inflammation—specifically Toll-like receptors (TLRs)—may allow for the development of targeted therapies that complement existing anti-inflammatory and antimicrobial treatments.  

How the Industry Can Help  

Solving the mystery of FMP requires a partnership between researchers and the horse industry. The industry can contribute by: 1.) Sharing samples: Providing blood samples and submitting placentas from suspected cases to diagnostic laboratories for research, 2.) Maintaining detailed records: Accurate mare histories help researchers correlate disease patterns with potential risk factors, and 3.) Participating in surveys: Answering surveys helps map the geographical spread and identify commonalities among impacted farms.  

Looking Ahead  

While FMP remains a complex puzzle, our efforts to develop reliable diagnostic biomarkers and targeted therapeutics aim to fill critical gaps in the management of equine FMP. Our goal in the Equine Reproduction Laboratory is clear: to improve live foal rates and pregnancy outcomes for mares and reduce the substantial economic loss associated with this disease. 

This is an excerpt from Equine Disease Quarterly, Vol. 35, Issue 2, funded by underwriters at Lloyd’s, London, brokers, and their Kentucky agents. It was written by Hossam El-Sheikh Ali, DVM, MVSC, PhD, Dipl. ACT, associate professor of equine reproduction, at the University of Kentucky’s Gluck Equine Research Center, in Lexington.