Streptococcus equi genome changes during persistent infection
S. equi has been characterised as possessing a dynamic genome with the ability to diversify and decay; mutations relating to metabolic streamlining and the loss of virulence have been noted in chronically infective isolates (Harris et al., 2015). The endemicity of S. equi can, in part, be attributed to its ability to persist in the guttural pouch following an infection, surviving in a low-nutrient state yet intermittently shedding bacteria and thus exposing naïve animals.
Genomic decay during persistent infection may reduce transmissibility and result in a lessened ability to cause severe acute disease, such as with the deletion of the equibactin locus, which is linked to the development of lymph node abscesses; although, the organism undoubtedly remains infectious (Harris et al., 2015). Furthermore, individuals with residual immunity such as equids that are older or vaccinated, and foals with maternal antibodies can present with ‘atypical’ strangles where typical clinical signs are not presented (Prescott et al., 1982, Tscheschlok et al., 2018); this presentation may be caused by a reduction in virulence (Waller, 2016).
A complex interplay between the host and causative agent is suggested (Harris et al., 2015, Morris et al., 2021) in which genomic plasticity could play a central role; this is an opportunity for further research with an emphasis on understanding host, as well as pathogenic, factors such as immunity.
Global endemicity
Equids are widely used and transported between geographic regions and strangles continues to spread as rapidly as ever (Mitchell et al., 2021, Leadon et al., 2008). Strangles is endemic worldwide, with only Iceland remaining free from the disease, due to a self-imposed import ban of equids and geographical isolation (Björnsdóttir et al., 2017). Population analysis of 670 isolates from 19 countries (Mitchell et al., 2021) revealed the extent of the international transmission that results in the endemicity of strangles across the world. The international transmission of S. equi , as demonstrated by Mitchell et al. (2021), is in accordance with the first criterion of the World Organisation of Animal Health listing of terrestrial animal diseases. The other three criteria are demonstrated elsewhere (Björnsdóttir et al., 2017, Boyle et al., 2018); therefore, it was recommended strangles be added to this listing (Mitchell et al., 2021).
Clinical manifestation
Acute Streptococcus equi infection
Strangles is characterised by sudden pyrexia, mucopurulent intermittent nasal discharge and the abscessation of the submandibular and retropharyngeal lymph nodes (Timoney et al., 1998). Less common clinical signs include respiratory signs, pharyngeal swelling, lethargy, inappetence, dysphagia, depression, and the presence of chondroids (Rendle et al., 2021). Although strangles has a low mortality rate, severe swelling of abscesses in the lymph nodes can lead to significant inflammation, asphyxia and, ultimately, death (Gharieb et al., 2019).
Pyrexia can exceed 42°C (Boyle et al., 2018), and is typically accompanied by lethargy, occurring 3-14 days after initial exposure. Fever ordinarily precedes bacterial shedding by 1-2 days; thus, identification of its onset can be of paramount importance to isolate individuals and control outbreaks (Waller, 2014).
Pharyngitis can be significant, often with concurrent nasal discharge, inappetence, dysphagia, a mucoid cough, and laryngeal-associated pain (Boyle et al., 2018). Affected equids may stand with their heads in an abnormal, extended position (Waller, 2014).
As abscesses form and subsequently rupture, empyema of the guttural pouch or upper respiratory tract can occur. Intermittent expulsion of this thick highly infectious pus is important for the resolution of the infection and removal of bacteria (Boyle et al., 2018); it results in mucopurulent nasal discharge and a cough, present in around half of horses with guttural pouch empyema (Judy et al., 1999). Abscessation and pharyngitis can obstruct the upper respiratory tract, resulting in dyspnoea and dysphagia, alongside potential temporary laryngeal hemiplegia (Boyle et al., 2018).
Systemic and mucosal immune responses are evident 2-3 weeks post-infection, and this immunity wanes over time (Boyle et al., 2018). Hamlen et al. (1994) showed that 75% of foals exposed to S. equi6 months after recovering from strangles were protected from severe infection, corroborated by historical and contemporary literature (Todd, 1910, Boyle et al., 2018), although no animals were completely protected from mild clinical signs. The use of antimicrobial therapy has been demonstrated to interfere with the persistence of humoral immunity (Pringle et al., 2020a).
Neonates can derive protection from colostral antibodies from exposed dams, and subsequently, IgA and IgG in milk confer some protection by coating the upper respiratory and oral mucosa until the time of weaning (Galan et al., 1986). Individuals with residual immunity may develop a milder form of the disease with short-lived clinical signs, termed ‘atypical’ strangles, although these animals can still shed S. equi to susceptible animals (Sheoran et al., 1997, Prescott et al., 1982).
Complications ofStreptococcus equi infection
S. equi has the potential to spread haematogenously, via lymphatics, septic focus, or by direct aspiration of purulent material (Boyle, 2017). Common sites include the lung, mesentery, liver, spleen, kidney, and brain (Boyle et al., 2018, Sweeney et al., 1987); additional clinical signs are dependent on the location of abscesses. This presentation is known as metastatic or ‘bastard’ strangles and has been documented since the 17th century (Solleysel, 1664). Prevalence of these complications ranges from 2-28% across outbreaks (Spoormakers et al., 2003, Sweeney et al., 1987, Duffee et al., 2015); metastatic abscessation has consistently been shown to increase mortality (Ford and Lokai, 1980).
S. equi infection is the most common cause of purpura haemorrhagica, but vaccination with M-protein-containing vaccines, other bacteria, viruses, and neoplasia can similarly result in purpura complexes and vasculitis (Mallicote, 2015). Purpura haemorrhagica is caused by a type III hypersensitivity reaction, resulting in necrotising vasculitis secondary to immune-complex deposition (Whitlock et al., 2019). Its presentation can vary from innocuous to a potentially fatal complication (Boyle et al., 2018).
Myopathies can be seen with S. equi infection, with three predominant presentations (Boyle et al., 2018): muscle infarctions (Kaese et al., 2005) and rhabdomyolysis with either acute myonecrosis or progressive atrophy (Sponseller et al., 2005, Valberg et al., 1996).
Other complications associated with strangles include anaemia, agalactia, meningitis, septic arthritis, and endocarditis (Boyle et al., 2018).
PersistentStreptococcus equi infection
Once ruptured, abscesses of the retropharyngeal lymph nodes typically drain into the guttural pouches, resulting in guttural pouch empyema. If the purulent material is not cleared and loses fluid, this can form chondroids; both empyema and chondroids can act as chronic reservoirs ofS. equi (Newton et al., 1997a, Judy et al., 1999). This infectious material, inspissated or otherwise, has also been reported in the sinuses, albeit rarely (Newton et al., 1997b).
Carriage of S. equi occurs in equids that are chronically infected; most strangles cases are cleared within 6 weeks, but some animals can enter a carrier state (Newton et al., 1997a, Newton et al., 1997b). An average of 10% of infected individuals in an outbreak develop into carriers (Boyle et al., 2018, Sweeney et al., 2005); although, this figure may be an underestimate, with detection rates being limited by current diagnostic sensitivity (Pringle et al., 2019). Carriers intermittently shed bacteria into the environment, leading to recurrence and perpetuation of strangles within their herd as well as transmission to naïve individuals (Mallicote, 2015).