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).