Clinical management
Treatment of acute Streptococcus equi infection
Most equids with acute strangles exhibit non-specific signs of generalised respiratory infection with presentation depending on challenge dose and host immunity, often responding well with only supportive and nursing care (Rendle et al., 2021, Whitelegg and Saunders, 2021). Acute disease can quickly deteriorate into severe cases, emphasising the need for regular monitoring (Rendle et al., 2021).
Nursing for an animal with strangles is vital and wide-ranging: good nursing provision will include an environment that encourages rest, appropriate nutrition, regular monitoring (TPR), abscess management, and a quarantine protocol (Whitelegg and Saunders, 2021). A soft, calorific, and palatable diet alongside water, to facilitate deglutition, both provided from a height, can help equids with profound lymphadenopathy; assisted nutrition may be indicated (Rendle et al., 2021). The experience of individual equids must be considered during a strangles outbreak, as small changes in diet and environment can aid in assuaging the effects of infection with S. equi .
Individuals with visible lymphadenopathies require good supportive and nursing care, with a focus on facilitating the maturation and subsequent drainage of abscesses (Boyle et al., 2018); the use of a ‘hot pack’ can enhance this process. Surgical drainage may be required if the abscesses are not spontaneously rupturing, although care must be taken to ensure the abscess is mature to enable maximal drainage (Boyle et al., 2018). Once open, abscesses should be lavaged with saline or antiseptic solutions, followed by daily flushing so long as discharge persists (Rendle et al., 2021).
NSAIDs can be employed to provide analgesia and reduce pyrexia; it has been suggested that their use can slow the development of abscesses, but this claim lacks evidence (Rendle et al., 2021). Paracetamol has also been recommended since it does not inhibit inflammation but possesses anti-pyretic and analgesic actions, resulting in improved appetite and welfare (Rendle et al., 2021). Phenylbutazone or flunixin meglumine could also be considered (Boyle et al., 2018).
Antimicrobial therapy in strangles is controversial (Ramey, 2007): their use is encouraged between initial exposure and abscessation (Boyle et al., 2018). This window is not always adhered to since abscesses can develop within days (Timoney and Kumar, 2008). Although antimicrobial therapy can decrease the size of abscesses and should be considered in equids with stridor, dyspnoea or dysphagia on welfare grounds, their effects are limited following the detection of lymphadenopathy (Boyle et al., 2018).
Penicillin is the drug of choice for S. equi infection; however, population analysis (Morris et al., 2020) revealed that pbp2x mutations are emerging. This mutation is in the penicillin-binding site and is associated with penicillin resistance in Streptococcus pneumoniae(Maurer et al., 2012, Nichol et al., 2002). Penicillin resistance is variably seen in S. equi isolates (Fonseca et al., 2020, Clark et al., 2008, Johns and Adams, 2015) and constitutes a growing concern that clinicians will be less able to treat severely afflicted horses in the future. Antimicrobial therapy has a role in combatting S. equiinfections, but it must be employed judiciously on an individual tailored basis, with careful consideration to minimise the development of antimicrobial resistance (Jaramillo-Morales et al., 2022, Boyle et al., 2018).
Treatment of persistentStreptococcus equi infection
Persistent infections of the guttural pouch are typically treated with topical and prolonged systemic antimicrobial therapy (Boyle et al., 2018). Administration of penicillin systemically and an endoscopically-guided gelatin-penicillin mix topically, has been regarded as broadly successful (Verheyen et al., 2000).
The removal of purulent material and chondroids from the guttural pouches is required for the elimination of the carrier state (Boyle et al., 2018). Endoscopic intervention is preferable to surgical intervention due to inherent risks of general anaesthesia, surgical dissection around vital structures, and S. equi environmental contamination (Boyle et al., 2018). Topical application of 20% acetylcysteine (w/v) solution can facilitate drainage of non-inspissated mucopurulent material through the nasal passages by disrupting disulphide bonds, thereby reducing mucus viscosity (Boyle et al., 2018).
Specific treatment methods depend on the individual presentation and the type of material within the guttural pouches. Many carriers do not present with empyema or chondroids, and it has been reported that the carrier state can self-resolve without treatment (Pringle et al., 2019).
Outbreak prevention and management
Strangles was once considered an inevitability (Solleysel, 1664), but has since been demonstrated to be a very preventable infection (Rendle et al., 2021). Outbreaks can be prevented by limiting exposure to the infectious agent, through enacting rigorous biosecurity protocols, using appropriate quarantining and screening facilities, and understanding of the pathogenesis of S. equi (Boyle et al., 2018). Outbreaks of strangles are controlled through the cessation of movement to and from the farm, isolating animals that are infected and where infection is suspected. A tiered ‘traffic light’ system with segregation based on exposure and no mixing between groups should be adhered to (Boyle et al., 2018). Following the outbreak, all animals should be tested for exposure and persistent infection.
Long-term control strategies should consider the vaccination of unexposed animals, the identification and treatment of carrier animals, and caregiver education on clinical signs associated with acute disease (Duran and Goehring, 2021).
Vaccination
The ideal strangles vaccine should provide a high degree of protection against S. equi , a long duration of immunity, the ability to be administered intramuscularly safely, and permit the differentiation of infected from vaccinated animals (DIVA) (Waller and Jolley, 2007). DIVA capability is important since the current commercially available enzyme-linked immunosorbent assays (ELISAs) do not differentiate between recently exposed horses and those animals vaccinated with live-attenuated vaccines, with implications for screening animals, movement restrictions and disease control (Duran and Goehring, 2021).
The first strangles vaccines were developed in the 1940s, using heat-killed bacteria, conferring a limited degree of protection but often resulting in adverse effects, including injection site reactions and pyrexia (Bazeley, 1940a, Bazeley, 1940b, Bazeley, 1942a, Bazeley, 1942b, Bazeley, 1943). Cell-free variations of this vaccine still exist (Waller, 2014), although the incidence of adverse reactions and the lack of DIVA capability have limited their use. A recent attempt to combine the S. equi bacterin and recombinant SeM protein in a vaccine yielded promising results in mice, with all demonstrating a humoral response (Rosa et al., 2021); evaluation of its safety and efficacy in horses is ongoing.
M-protein-containing extract vaccines have demonstrated some efficacy in reducing the frequency and severity of disease; although adverse reactions are common and they possess no DIVA capability (Hoffman et al., 1991). In a double-blind randomised clinical trial in foals, 29% (17/59) of vaccinates developed cervical lymphadenopathy, compared to 71% (39/55) of sham-vaccinated controls (Hoffman et al., 1991). Commercially available options, although none are available in the UK, include Strepvax II (Boehringer Ingelheim), Equivac S (Zoetis New Zealand), and Strepguard (MSD Animal Health) (Duran and Goehring, 2021).
Live-attenuated vaccines have been at the forefront of strangles prevention since the early 21st century; a 10⁹ dose of an avirulent strain of S. equi , was shown to prevent lymphadenopathy in 100% (5/5) and 50% (2/4) of ponies, respectively, across two experiments conducted by Jacobs et al. (2000). The Equilis StrepE (MSD Animal Health) is administered submucosally, and the Pinnacle IN (Zoetis) is administered intranasally; they are commercially available in Europe and North America, respectively, as well as other countries intermittently (Duran and Goehring, 2021). Adverse reactions were reported upon intramuscular administration, and these live-attenuated vaccines possess no DIVA capability (Kemp-Symonds et al., 2007, Borst et al., 2011, Livengood et al., 2016, Lanka et al., 2010). Furthermore, the Equilis StrepE (MSD Animal Health) vaccine has been linked to S. equi replication, resulting in lymph node abscesses (Kemp-Symonds et al., 2007, Kelly et al., 2006, Mitchell et al., 2021, Harris et al., 2015).
Strangvac (Intervacc AB) is a recombinant fusion protein vaccine that is administered intramuscularly and has been shown to provide immunity in up to 94% (15/16) of ponies when challenged two weeks following third vaccination (Robinson et al., 2020). Strangvac has DIVA capability as the vaccine does not contain live S. equi , S. equi DNA nor the SeM and SEQ2190 antigens that are targeted by culture, PCR, or ELISA diagnostic tests (Robinson et al., 2018). Future studies will be needed to evaluate the utility of Strangvac (Intervacc AB) in clinical practice.
Vaccination as a tool for outbreak prevention has been limited by efficacy, safety, practicality, clashes with other vaccination schedules, DIVA capability, geographical restrictions, differences in circulating S. equi strains and owner compliance (Boyle et al., 2018, Mitchell et al., 2021). Advancements such as the Strangvac vaccine represent a promising development, potentially allowing vaccination to become a more efficacious control measure. However, continued work is required from veterinary professionals to build trust with owners and caregivers over the use of any strangles vaccines due to past difficulties (White et al., 2021).
Conclusion
Understanding S. equi is crucial to combatting strangles, and much work has been carried out to characterise its evolution (Holden et al., 2009), genome (Harris et al., 2015), epidemiology (Mitchell et al., 2021), survivability (Durham et al., 2018), resistance profile (Fonseca et al., 2020) and pathogenicity (Timoney and Kumar, 2008, Timoney, 2004). This increased understanding has enabled the development of more targeted diagnostic assays (Noll et al., 2020, Webb et al., 2013, Willis et al., 2021, Boyle et al., 2021), better outbreak prevention and management protocols (Rendle et al., 2021) and a safe and efficacious vaccine with DIVA capability (Robinson et al., 2020). These advances better equip clinicians and caregivers to treat and prevent strangles.
Further research is required to investigate the role of S. zooepidemicus as a primary respiratory pathogen in equids (Waller and Wilson, 2021, Waller, 2017), and to better understand the growing concern of antibiotic resistance in both S. equi and S. zooepidemicus (Fonseca et al., 2020, Johns and Adams, 2015). The success of S. equi as a pathogen can be attributed to the carrier state allowing infection to spread to naïve animals. Understanding the host and pathogenic factors that predispose equids to persistent infection and validating a gold-standard method of diagnosis will help prevent future outbreaks and safeguard animal welfare.
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