The aetiology and prevention of larval cyathostominosis (LC) is a hazy area to say the least. The use of larvicidal anthelmintics such as fenbendazole and moxidectin has been the mainstay of the prevention of this disease for decades, but reliance on this method alone is not sustainable. Benzimidazole resistance is now widespread across the UK, rendering it useless in many instances (Lester et al., 2013; Stratford et al., 2014). Reduced length of action for the macrocyclic lactone (ML) drugs has been widely reported in the UK over the last 10 years (Tzelos et al., 2017; Molena et al., 2018). This has been regarded by many as a precursor to the development of anthelmintic resistance (AHR). Indeed, alarmingly, the first concrete report of ivermectin and moxidectin resistant cyathostomins has just been published in the US (Nielsen et al., 2020). The horses harbouring these parasites were imported from Ireland and, given the high levels of equine movement globally, we should assume that ML resistant cyathostomins are likely to become widespread. The take home message is that in the long run we can expect more frequent outbreaks of LC in vulnerable populations, with inadequate tools to treat it.
In light of the above, clinicians (especially those working with youngstock) may be increasingly unsure as to the best way to manage the risk and treatment of LC. The aim of this article is to clarify what is known and provide updates on advances in this area.
Risk factors for larval cyathostominosis
LC occurs when large numbers of encysted larvae simultaneously develop and exit the large intestinal mucosa. This “mass emergence” is more likely in horses with heavy mucosal burdens in the late winter/early spring; it is more common in young horses but can occur at any age (Giles et al., 1985; Mair, 1993; Reid et al., 1995; Walshe et al., 2020). Contributing factors are poor pasture management combined with lack of effective anthelmintic treatment to eliminate, or prevent build-up of, infection. Treatment with ivermectin in horses with heavy mucosal burdens is also linked to the onset of LC (Walshe et al., 2020); hence, this drug should be used with caution in animals with suspected high mucosal burdens. Outbreaks are often seen in neglect cases or poorly managed yards but, importantly, may increasingly occur due to AHR.
Clinical signs of LC vary in severity and include rapid weight loss, diarrhoea, ventral oedema, abdominal pain and signs of endotoxaemia (Mair, 1993, 1994; Murphy et al., 1997; Love et al., 1999; Bodek et al., 2010; Walshe et al., 2020). LC has also been reported to cause caecal compromise, and so should also be a differential diagnosis in colic cases (Mair et al., 2010). There should be a high index of suspicion for LC in young horses presenting with the above signs, especially when combined with a history of poor worm management and when more than one animal is affected. A positive faecal egg count (FEC) is often absent, as disease occurs before the larvae have developed to adults and the females have started producing eggs (Giles et al., 1985; Murphy et al., 1997; Walshe et al., 2020). Red larvae in faeces are the textbook image for diagnosis of LC, but again, these are not always seen. The incorporation of the novel redworm ELISA (Tzelos et al., 2020) into the diagnostic toolkit may help to improve confidence of diagnosis where there is doubt; for example, high levels of antibody would support a positive diagnosis (Walshe et al., 2020).
Once a diagnosis of LC is suspected, supportive treatment to address any fluid and protein loss, coupled with anti-inflammatory and anthelmintic treatment, should be commenced. Immunosuppressive doses of prednisolone (1mg/kg) are advised 24 to 48 hours before anthelmintic treatment, to be tapered down gradually according to clinical response (Nielsen and Reinemeyer, 2018; Walshe et al., 2020). Moxidectin (0.4mg/kg) or five-day fenbendazole (10mg/kg) are both recommended to treat LC as they have larvicidal activity. However, resistance to fenbendazole is now widespread (Lester et al., 2013; Stratford et al., 2014), so, unless you have recent faecal egg count reduction test (FECRT) data from the same yard proving efficacy, then its use is not advisable. There are also data showing that fenbendazole may induce a greater inflammatory response than moxidectin (Steinbach et al., 2006); therefore, it may also be clinically preferable to use moxidectin. In cases with persistent pyrexia, non-steroidal anti-inflammatories (NSAIDs) can also be administered (Walshe et al., 2020). Furthermore, systemic antibiotic use may be indicated in moderate to severely affected cases, due to bacterial translocation across severely damaged mucosa (Kelly and Fogarty, 1993; Bodecek et al., 2010; Walshe et al., 2020). A recent case series reported that severely affected animals had persistent pyrexia and signs of endotoxaemia despite anthelmintic, steroid and NSAID administration (Walshe et al., 2020). Broad spectrum antibiotics (enrofloxacin 7.5mg/ kg PO and metronidazole 25mg/kg PO) were used in these cases, and resulted in recovery.
Co-grazing animals which have the same risk factors, but are clinically well, should also be assessed for risk of disease, and treated with prednisolone and moxidectin accordingly. Unfortunately, FEC are not useful to identify at-risk horses, as they have frequently been reported as low/absent in LC cases (see above). Thus, the redworm ELISA may also be useful in this instance to further evaluate risk. If in doubt, however, it is better to treat.
Dealing with the underlying lack of control
Once cases have been treated, it is important to find out what has led to the outbreak and implement measures to prevent future outbreaks. Much of this process will be based on clinical history (eg was monitoring and treatment in place? Which drugs were used, and when? Were they given at adequate dosage? Are they effective against mucosal stages? Are pastures routinely poo-picked and rotated?). However, there may be increasing numbers of examples where apparently adequate control was in place – yet clinical cases have still occurred. In these instances, AHR should be strongly suspected and FECRTs are recommended on any remaining untreated animals on the yard (American Association of Equine Practitioners, 2019). On larger establishments, FECRT (including monitoring for early egg reappearance for MLs) should be used routinely to monitor drug efficacy. Further routine advice for future worm control will be covered below.
Advice for routine prevention
With regards to routine prevention of LC, much advice is unchanged over recent years (Figure 1). The aim is to break the cycle of transmission over spring, summer and autumn to prevent build-up of infective larvae on pasture and reduce infection intensity. This is followed by larvicidal treatment in early winter. Superimposed on this is an increasing emphasis on the use of FEC to inform targeted treatment of high-shedding individuals, and thus reduce selection for AHR. As anthelmintics can be bought without a prescription, uptake for targeted strategies using FECs is not as high as it could or should be. FECs and the ELISA are often of equal or greater cost than a wormer, so there is certainly no financial incentive to use them. Furthermore, a recent behavioural survey revealed that the threat of AHR was not enough to encourage FEC use in owners; however, increased “self-perceived” knowledge regarding anthelmintics and FECs led to higher intended uptake (Rose Vineer et al., 2017). Therefore, knowledge transfer events to engage owners in the science may be the best way forward to increase uptake for practice-led worm control programmes.
As egg reappearance rates shorten, and cases of AHR increase, clinicians may find themselves in a catch-22 situation – anthelmintic will need to be given more frequently to prevent disease yet, in turn, this selects more strongly for AHR. The solution isn’t rocket science; simply the best way to reduce transmission under these circumstances is good old regular poo picking and effective pasture management. On many larger establishments, poo-picking is often deemed to be too time consuming and the existential threat of AHR is not enough incentive to employ additional staff to do this. Sadly, in time, their hand may be forced by outbreaks of LC which will be far more costly.