Topic: The Equine Cyathostomin Problem- A Case of Anthelmintic Resistance or A Change in Diversity of Species?
Order Description
The introduction to give the background of the dissertation:
1. Introduction
Intestinal helminths are considered to be a major problem for the equine industry worldwide (Saeed et al., 2010) as clinically infected horses can suffer from loss of condition and performance due to reduced appetite, anaemia, diarrhoea, colic and ultimately death depending on the stage of infection (Urquhart et al., 1996). The most prevalent internal parasite group reported in today’s adult horse population are the strongyles which account for almost 50% of all helminth species found internally (Krecek et al., 1987). Previously, research focussed on large strongyles, Strongylus vulgaris, which were deemed to pose a considerable risk to domestic horses due to their high prevalence and pathogenic nature. However, research carried out since the introduction of ivermectin and moxidectin in the late 20th century has suggested that these macrocyclic lactones have significantly decreased the risk and severity of S. vulgaris infections (Love et al., 1999) and thus the shift in focus in parasitology research has changed to controlling the ever increasing threat from infection by small strongyles, Cyathostomins
1.1 Cyathostomin Research
Nowadays, Cyathostomin species are considered to be “the most important and life-threatening in horses today” (Lichtenfels et al. , 2002) partly due to the fact that almost 100% of horses are infected with at least one of the fifty two species of cyathostomins which have been reported (Reinemeyer et al., 1984) albeit in varying prevalence and intensities (Lichtenfels et al., 2002). Another reason for the heightened scientific emphasis on cyathostomins is the severe health problems that the nematode tribe can cause which are similar to those found in infections by large strongyles but appear to be more complex and have an associated higher fatality rate. Case studies have shown that large numbers of encysted larvae can cause fatal diarrhoea (Reilly et al., 1993) or result in cyathostominosis which is less common but nevertheless a deadly disease caused by the mass emergence of such larvae into the intestinal lumen (Figure 1) resulting in severe colitis (Lyons et al., 2000). Research has suggested that up to 50% of larval cyathostominoses result in death despite prescribed treatment with anti-inflammatories and anthelmintics (der Woude, 2014). However, anthelmintic resistance may have a role to play in the failure of such treatment for cyathostominosis and thus it is highly likely that such resistance is another reason why there has been a significant increase in research in this nematode in particular.
1.2 Anthelmintic Resistance
To date, the control and management of cyathostomins has relied heavily on the exclusive and regular use of anthelmintic drugs belonging to the three primary groups: benzimidazole derivatives (BZ), tetrahydropyrimidines (THP) and macrocyclic lactones (ML) and the drugs currently licensed for use against cyathostomin encysted larvae in the UK are Moxidectin (MOX) and 5-day fenbendazole (5d-FBZ) (Corning, 2009). Many veterinarians recommend using anthelmintics at regular intervals in classical parasite control which involves rotational treatment of the three different classes. The rationale dictating this type of treatment was simple: before the parasite is mature to lay eggs, the medicine should kill it to save the environment from contamination. The treatment would be repeated every six to eight weeks, as the parasite eggs would reappear after this time period. This type of treatment, also known as interval dosing, is still reported to be the favoured method of parasite control by the majority of horse owners, with a recent survey carried out in Scotland recording a figure of 80% of owners using regular anthelmintic treatments (Stratford et al., 2014). Interestingly, although 40% of owners believed they adopted a targeted dosing programme, the survey responses suggested that there was a general ignorance to what such regime involved.
Arguably the interval dosing approach to parasite control has been found to be advantageous in the control of some parasitic tribes such as Strongylus vulgaris, however the intensive, regular and continuous usage of the same groups of anthelmintic has contributed to the widespread development of resistance to the drugs commonly used (Shalaby, 2013) and it is becoming increasingly apparent that this can have an adverse impact on animal welfare and health (Keane et al., 2014). Resistance has been defined as being present when “there is a greater frequency of individuals within a population able to tolerate doses of compound than in a normal population of the same species and is heritable” (Prichard et al., 1980). Thus anthelmintic resistance occurs when a helminth population fails to display any decrease in response to anthelmintic treatment even when the tolerated maximum dose has been administered. Due to the increasing development of anthelmintic resistance in cyathostomin prevention and treatment, the interval dosing approach to control has been considered unsustainable.
Resistance to anthelmintics within the Cyathostominea tribe has been reported widely (Fisher et al., 1992), however it is not a new problem, as it was first reported in nematodes of sheep followed by cyathostomins of the horse for BZ category drugs only a few years after they were introduced in 1961 (Kaplan, 2004). Similar resistance has been found in THP type drugs (Kaplan et al., 2004; Traversa et al., 2007) with cases of reduced efficacy more recently reported for the macrocyclic lactones (MLs), particularly ivermectin (Traversa et al., 2009, Lyons et al., 2011, Molento et al., 2012 and Traversa et al., 2012). A number of factors have been considered to contribute to anthelmintic resistance such as high treatment frequencies, sub-optimal dosing rates, high stocking densities, the regular use of a single drug and off-label use of such drugs (Shalaby, 2013). Lack of veterinary consultation, size of refugia and climate conditions may also have variable effects on anthelmintic resistance development (Kaplan, 2004). Although there is continual debate on contributing factors, there is the general agreement that anthelmintic resistance can spread rapidly and the fact that there are currently no new anthelmintic drugs available to prevent against or treat cyathostomin encysted larvae is a reason for concern. In some countries, anthelmintic drugs are now only available by prescription in an attempt to make the use of such drugs more sustainable (Samson-Himmelstjerna et al., 2009).
1.3 An alternative theory – Cyathostomin Species Revolution?
The potential contributing factors of anthelmintic resistance have been well researched and documented and although it has been established that such resistance is a probable cause for the lack of reduction in Faecal Egg Counts (FEC) and decrease in Egg Reappearance Period (ERP) observed in cyathostomin studies, it must be considered that there may be other reasons for such a lack of response to treatment, especially at a time when there appears to be a scarcity of information on an alternative drug.
This study thus investigates the possibility that, instead, there has been a change in the prevalence and diversity of the various cyathostomin species which may subsequently affect the efficacy of the commonly used anthelmintics that were previously found to be effective for a different community structure. The proposed research will aim to investigate whether the statement “Empirical findings about (cyathostomin) ecology and community structures after horse necropsy tended to show that few species were consistently dominant across studies although no quantitative assessment is available” made by Salle and Cabaret (2015) at a recent World Association for the Advancement of Veterinary Parasitology (WAAVP) conference can be verified and substantiated utilising data from studies carried out since 1923.
The purported research will involve conducting a systematic review of papers which have recorded the prevalence, abundance and diversity of cyathostomin species for various reasons, depending on the objective of the study. Previous research which has involved quantifying cyathostomin species’ diversity and prevalence has categorically shown that the vast majority of cyathostomin burdens found in horses consist of less than ten species (Ogbourne, 1976; Reinemeyer et al., 1984; Torbert et al., 1986; Mfitilodze & Hutchinson, 1990; Gawor, 1995; Silva et al., 1999; Lichtenfels et al., 2001). Furthermore, it has been established that each horse is generally only infected with 5-10 of the more common species (Lichtenfels et al., 2001; Gibbons & Krecek, 2002).
In the early 20th Century it was agreed by a number of authors that Cylicostephanus longibursatus, Cylicocyclus nassatus and Cyathostomum catinatum were the three most common species found in horses worldwide (Anderson & Hasslinger, 1982; Reinemeyer., 1984; Mfitilodze & Hutchinson, 1990; Bucknell, Gasser & Beveridge, 1995; Silva et al., 1999). However these studies were carried out at a time when the only method of identifying cyathostomin species involved morphological examination of adult stages, carried out during a post-mortem examination of infected horses as species identification of eggs was not possible. Furthermore, the identification of the larvae was difficult and time-consuming using the keys of Lichtenfels (1975) and nomenclature recommended by Lichtenfels et al. (1998). Thus any data collected during this time would be subject to identification bias, particularly before 1997 when the morphologically similar Cylicocyclus nassatus and Cylicocyclus ashworthi were re-described by Lichtenfels et al. in an attempt to ensure that the Cylicocyclus ashworthi species was more accurately recorded. Consequently and interestingly, in a study performed four years later in Scotland, Cylicocyclus ashworthi was reported to be the most abundant species (Lichtenfels et al., 2001). More recent studies have attempted to eliminate any bias by utilising genetic markers for species identification, and in particular, the 26S-18S ribosomal DNA (rDNA) intergenic spacer (IGS) region was chosen as a molecular marker for a comparative sequence analysis of sixteen cyathostomin species (Kaye et al., 1998) which has produced more accurate identifications of species.
To the best of the author’s knowledge, the proposed research objective has not been carried out previously. A similar study carried out between 1989 and 2000 compared the prevalence of helminth species found during this period to those found in a comparable survey conducted in the same region twenty years previous (Chapman et al.,2002). However the objectives, time-scales and the fact that a specific type of helminth, cyathostomins, are being investigated in the present study distinguish it from any previous research in this field. The majority of research which has already been carried out has thus assisted the objective of the present study by summarising the most common species from the data collated, however there appears to be a lack of research relating to species diversity and prevalence changes during this time which ultimately may affect the efficacy of current anthelmintic treatments.
