INFLAMMATION, INFECTION, OR BOTH? ROOT CAUSES OF ENDOMETRITIS


infection.1–4,7 Prolonged local antibiotic therapy has been proposed to disturb the vaginal or uterine micro- biome and disrupt the mechanisms that normally pre- vent molds or yeasts from becoming established.6,8 At present, although preliminary studies have been reported, the normal composition of a mare’suterine microbiome has yet to be established, and it is unclear to what degree it varies between physiological and pathological states.9 Indeed, it is more likely that the problem starts within the caudal reproductive tract, where antibiotics that “leak back” after intrauterine infusion disturb the “commensal” flora, resulting in an altered vaginal pHand, possibly, the elimination of bac- teria capable of secreting antifungal substances, all of which may reduce the barrier to fungal proliferation. Indeed, it has been proposed that the molds or yeasts that colonize the uterus are often harbored in a “reser- voir” in the vagina, vestibulum, and clitoral fossa1 and carried iatrogenically into the uterus during insemina- tion or other intrauterine treatments. Other factors thought to predispose to fungal endometritis include systemic immune deficiency or endocrine disorders1 and the presence of a necrotic focus in the uterus or va- gina, e.g., following dystocia or placental retention.10 While the response of fungal endometritis to treat-


ment is often described as poor, ease of resolution may in part depend on coinfection with other organ- isms, the duration of infection prior to diagnosis, and the identity of the causal organism. For example, Candida spp. have been reported to penetrate deeper into the endometrium and/or grow intracellularly, where they aremore resistant to clearance by antimi- crobials administered via the intrauterine route. Both intracellular colonization and an untreated reservoir of infection in the caudal reproductive tract are cited as explanations for the high rate of treatment failure and/or recrudescence.1,11


3. Clinical Signs and Diagnosis


Mares diagnosed with fungal endometritis are typi- cally oldermares with a prolonged history of difficulty in becoming pregnant, often associated with multiple attempts to treat other uterine infections or combat inflammatory reactions. In this respect, 95/128 (74%) mares diagnosed with fungal endometritis at Utrecht University during 1987 to 2001 were barren at the start of the breeding season.11 In common with other reports, most of the mares for which the information was recorded also had a recent history of intrauterine antibiotic therapy (52/60: 87%) and/or pneumovagina (58/152: 35%).Other factors commonly encountered in the history of mares with fungal endometritis include dystocia or retention of the fetal membranes (18%), early embryonic death (13%), and abortion (7%).11 Typically, mares suffering from fungal endometritis show obvious signs of uterine inflammation such as copious uterine fluid (33%)11 and vaginal discharge that can vary in color (white-grey-yellow) and consis- tency (thick mucoid to watery). Freeman et al.12


42 2022 / Vol. 68 / AAEP PROCEEDINGS


Fig. 1. The various morphological forms of fungi (white arrows) as detected cytologically. A, Elongated fungal hyphae; B, Yeast spores with characteristic capsule (engulfed by neutrophils); C, Pseudohyphae.


reported a greyish vulval discharge to be common among mares affected by fungal endometritis. Definitive diagnosis of fungal endometritis is usu-


namine silver stain)4 and extensive endometrial fibrosis, whether a predisposing cause or a result of the fungal infection, are associated with poor subse- quent fertility.10 Metabolic tests can help to better specify the iden- tity of fungal organisms, while DNA-based tests


ally based on a combination of cytological examination and aerobic culture of uterine material recovered using guarded swabs, cytology brushes, or low-volume lavage. If there is a suspicion of fungal endometritis, it is important to alert the laboratory since culture on low-pH, bacteria-inhibiting Sabouraud’sdextrose agar will reduce the likelihood of missing molds or yeasts due to bacterial overgrowth. In addition, a cul- ture should not be declared negative for fungi until 5days of incubation because fungal growth can be very slow.12 Cytological examination will often, but not always, reveal signs of an ongoing inflammation (e.g., frequent neutrophils) and may also reveal obvious yeast spores, pseudohyphae, or, less com- monly, elongated fungal hyphae (Fig. 1). Yeasts are oval to spherical in shape, are around 3 to 5mmin length, and typically have a surrounding capsule with alow affinity for dyes that, therefore, remains clear after staining.1,4 Candida albicans can easily be mis- diagnosed because cultured colonies resemble bacteria while, on superficial examination, a gram or Diff- Quick stained group of yeasts can be mistaken for staphylococci. Endometrial biopsies have also been advocated for the diagnosis of fungal endometritis, ei- ther as a more reliable source of material for seeding culture plates2 or for investigating the likely success of treatment; fungal elements deep in the endome- trium (more reliably identified using Gomori’smethe-


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