Infectious – bacterial and fungal
Placentitis: The incidence and aetiology of placentitis shows quite marked geographical variation, with higher incidence usually reported in the USA than Europe. From a diagnostic point of view, it is important to be aware that some cases of placentitis, particularly acute cases, are not evident macroscopically and require histologically confirmation (Whitwell 1988). Histology of normal and an obviously affected chorion are illustrated in Figures 4. In most countries, Streptococcus equi ssp. zooepidemicus and Escherichia coli infections are commonly encountered (Whitwell 1988; Hong et al. 1993a; Smith et al. 2003), but many other bacteria can be involved, including Pseudomonas aeruginosa, Klebsiella pneumonia, Actinobacillus spp., Staphylococcus spp. and Leptospira spp. Nocardiform actinomyctes have been a significant cause of focal placentitis in parts of the USA since the 1990s. Aspergillus and other mucor species are the most common cause of mycotic placentitis (Hong et al. 1993a).
Figure 4. a) Normal chorionic villi. b) Bacterial placentitis. The villi are expanded by dense infiltrates of neutrophils, sometimes surrounding colonies of bacteria (arrow, inset). c) Ischaemic necrosis of the cervical pole: full-thickness necrosis of the chorioallantois (N) with some mineralisation of the chorionic villi and neovascularisation at the junction between the viable and necrotic zones (arrow). d) Umbilical cord torsion: mineralisation of blood vessels and stroma (arrows) is often observed within the chorionic villi. H&E staining; a)-c) 20 × magnification; d) 200 × magnification.
Download figure to PowerPoint
Placental infection often results from ascending spread through the cervical canal (Platt 1975b) and is most common in later pregnancy. Focal placentitis is more likely to be related to haematogenous spread from the mare; it is less common in the UK, but the incidence of focal nocardioform placentitis has increased in the USA. This placentitis is usually associated with infection by the Gram-positive, filamentous, branching bacterium, Crossiella equi sp. nov. (Giles et al. 1993; Donahue et al. 2002; Cattoli et al. 2004), but other species of nocardioform bacteria can be involved (Bolin et al. 2004). The often focal distribution of the exudative mucopurulent and necrotising placentitis, most commonly centred on the ventral aspect of the junction of the placental horns and body, suggests a haematogenous route of infection rather than an ascending infection, but the route of entry and reason for the rise in incidence is currently uncertain.
Leptospirosis has been reported as a significant cause of fetal loss in horses in Kentucky and Northern Ireland, but is less commonly documented in other countries (Donahue et al. 1995; Donahue and Williams 2000; Whitwell et al. 2009). Most abortions result from infection by Leptospira interrogans serovars kennewicki or bratislava. When present, gross placental lesions include funisitis, nodular adenomatous hyperplasia of the allantois, oedema, areas of necrosis of the chorion, and necrotic mucoid exudate coating the chorion (Poonacha et al. 1993; Sebastian et al. 2005; Szeredi and Haake 2006). Histological lesions may include thrombosis, vasculitis, mixed inflammatory cell infiltration of the stroma and villi (Fig. 4b), cystic adenomatous hyperplasia of allantoic epithelium, and villous necrosis and calcification. Fetal lesions are variable, but may include hepatocellular dissociation, mixed leucocytic infiltration of the portal triads, giant cell hepatopathy, interstital nephritis, pulmonary haemorrhages, pneumonia, myocarditis and adrenocortical inflammatory infiltrates (Hodgin et al. 1989; Whitwell et al. 2009).
In general terms, the consequences of most types of chronic placentitis will be similar. The fetus/foal is usually growth retarded, probably as a combination of loss of functioning placental area, direct effects of inflammatory mediators on the developing fetus and prematurity. Not all foals born alive will be infected, but the risk of congenital sepsis may be increased. In 14 out of 17 cases of abortion with acute placentitis there was evidence of septicaemia in the foal (Whitwell 1988). It is important to remember that inflammation is not confined to the placenta, but also affects the uterus, stimulating production of prostaglandins (PGE2 and PFG2α) resulting in myometrial contraction and premature lactation (LeBlanc et al. 2002). In man, proinflammatory cytokines may have beneficial as well as negative effects, indirectly stimulating the fetal hypothalamic-pituitary-adrenal axis resulting in precocious maturation of the fetus and increasing the chance of survival if the fetus survives long enough to benefit from these influences (Gravett et al. 2000).
As well as the more common bacterial causes of placentitis, Leptospira spp. (Hodgin et al. 1989), Salmonella abortusequi (Madićet al. 1997), Campylobacter spp. (Hong and Donahue 1989) and Listeria monocytogenes (Welsh 1983) are examples of organisms that can cause systemic pathology in the fetus/foal as well as the placenta. Distinguishing infection acquired in utero from those acquired neonatally (usually associated with failure of passive transfer of immunity or other immunocompromise) may be difficult. The longer-term consequences for the foal will clearly depend on the extent of disease/pathology, but may include damage to respiratory function following pneumonia, neurological damage secondary to hypoxia, or septic arthritis. Interestingly, Whitwell noted an increased incidence of carpal flexion in cases of chronic placentitis (Whitwell 1988). In most cases, if a compromised foal is born alive in association with placentitis and survives neonatal critical care to thrive in an apparently satisfactory manner, lasting effects on its organ systems can only be speculated upon.
Mare reproductive loss syndrome/equine amnionitis and fetal loss: An unusual epidemic of early fetal loss (EFL), late fetal loss (LFL), fibrinous pericarditis, and unilateral uveitis occurred in the USA during the spring of 2001 – now referred to as mare reproductive loss syndrome (MRLS) (Cohen et al. 2003; Sebastian et al. 2008b). The same syndrome with lesser intensity recurred in 2002. The estimated economic loss from this syndrome in 2001 and 2002 together was estimated at approximately $500 million. Both EFL and LFL were characterised by the absence of specific clinical signs in aborting mares. Nonhaemolytic Streptococcus spp. and Actinobacillus spp. accounted for 65% of the organisms isolated from fetuses submitted for a post mortem examination during the MRLS outbreaks of 2001 and 2002. Reported gross lesions in LFL include pale brown, thick, oedematous placenta, a thick, oedematous, yellowish umbilical cord, and, in some fetuses, pulmonary oedema. Some foals born alive have hyphaema present at the time of delivery. Histopathological changes associated with LFL included funisitis, mostly affecting the amniotic portion, placentitis centred on the extra-embryonic coelom and pneumonia. In the early fetal loss cases, the fetus is often autolysed, but a degree of placentitis may be detected and turbid amniotic fluid was seen during transrectal ultrasound scan examinations of mares undergoing EFL (Sebastian et al. 2008a). Epidemiological studies suggest an association between the presence of eastern tent caterpillars (ETC) in pastures with MRLS. Experimental studies in pregnant mares by exposure to ETC, or their administration by stomach tube or with feed material, reproduced EFL and LFL. Currently, 2 hypotheses are proposed for MRLS. One proposes that an ETC-related toxin with secondary opportunistic bacterial invasion of the fetus leads to MRLS. The second hypothesis suggests that a breach of gastrointestinal mucosal integrity by barbed hairs (setae) of ETC leads to an opportunist bacteraemia and results in MRLS. It is interesting that the chorionic villi are not infiltrated by inflammatory cells as observed in classical ascending placentitis, and the route of infection from the mare to fetus and amnion requires further elucidation in the proposed hypotheses. In 2004, a similar equine abortion storm, named equine amnionitis and fetal loss, was reported from Australia and caterpillar exposure was again identified as a risk factor for the abortion (Cawdell-Smith et al. 2011; Todhunter et al. 2009)