Helminthology

Author: J BOOMKER
Diagram credit: J BOOMKER

Classification and life cycles

Helminthologists use the Linnaean binomial or trinomial system, which is periodically updated to include new species or revisions of existing ones. The classification presented below is by no means complete, but should be sufficient for the purposes of the veterinarian. The 3 main phyla of worms dealt with in this textbook are the nemathelminthes (nematodes), cestodes and trematodes.

Nematodes (roundworms)

Classification

Life cycles of the Nematodes

Nematodes have 2 basic types of life cycles: the direct (monoxenous) and indirect (heteroxenous) types. The direct life cycle is, as the name implies, direct and is simple and uncomplicated; an intermediate host is not present (Figure 1). The indirect life cycle, however, is more complicated and there may be one or more intermediate hosts (Figure 2). These may be molluscs, arthropods, mammals and even humans. The general life cycles are discussed here, while specific life cycles are discussed in more detail when dealing with the worms themselves.

General principles

Life cycles show some variation within the different groups, but there are distinct similarities, i.e. four larval and one adult stage (Figure 3). Each stage is separated from the next by a moult, during which time the cuticle is shed. When laid, the eggs of both these groups of nematodes contain 4 to 8 blastomeres and are said to be segmented. Further development takes place and eventually the larva is fully formed and ready to hatch. The conditions necessary for survival and hatching of the eggs include sufficient moisture, the presence of oxygen, and a temperature of about 26°C. Under these conditions, the eggs will hatch in about 24 hours. Development is slowed down at temperatures below 10°C and is accelerated as the temperature rises. Above 40‒45°C the eggs will die. The eggs, L1, L2 and L3, are collectively referred to as the free-living stages, since they occur outside the host.

Figure 1 Schematic representation of a direct life cycle.

Figure 2 Schematic representation of an indirect life cycle.

Once the larva is fully developed, the eggs hatch. Moisture is essential for the survival of the 1st stage larva and temperature requirements are the same as for the eggs. The larva feeds on bacteria in the substrate and grows, and then enters the first moult (M1) to form the second larval instar or stage. Like the L1, the L2 will also feed on bacteria in the substrate, it grows and eventually undergoes the second moult (M2) to form the third larval stage, also known as the infective stage. The L3 usually retains the skin or cuticle of the M2 and is called a sheathed larva. The L3 cannot feed because of this sheath, and is therefore dependent on food accumulated during the first 2 stages. The sheath protects the larvae against desiccation. Under cool, moist conditions the larvae remain active for long periods – some surviving for months before they die. A rise in the temperature activates the larvae, with resultant depletion of their food reserves. They migrate from the faeces when a thin film of moisture is present and move horizontally to the nearest herbage – and then migrate vertically. Migratory patterns are random and influenced by moisture and temperature. The larvae are attracted to diffuse light and become more active as temperatures rise. They retreat into their sheaths to conserve moisture and cease moving under dry, sunny conditions. The L3 must now enter the definitive host to develop further – failing which they will die.

After having entered the final or definitive host, the larvae (L3) will cast off the sheath of the second moult, start feeding, and after a variable period they will moult (M3) to the fourth stage (L4). The fourth larval stage grows rapidly and during the later stages, the first indications of sexual differentiation become apparent. After a period of inactivity, the fourth stage larvae will moult (M4) to the fifth stage. The fifth stage worms are young adults. They grow, and will develop to be the mature, reproductively active adult worms (Figure 3).

The larvae of the Nematodirus spp. – the long-necked bankrupt worms of sheep and goats – develop inside the egg and only when they have reached the infective stage (L3), will the eggs hatch, should the environmental conditions be favourable. The infective larvae may enter their respective hosts: (1) per os (that is, they are eaten with the food when the animal feeds, as happens in the majority of the trichostrongylid and strongylid nematodes); (2) percutaneously (by entering through the skin by means of enzymes and physical action, as is seen with the hookworms or Ancylostomatidae); or (3) by both methods (Bunostomum spp.). Details are provided when the worms are discussed individually (below).

Figure 3 Representation of a nematode life cycle.

Subclass Adenophorea

Life cycle of the Trichinelloidea

This superfamily contains two families: the Trichinellidae and the Trichuridae. The Trichinellidae have an intricate life cycle that starts with the ingestion of meat containing L1 infective larvae, which develop into adults within 2 to 3 days. The females are viviparous, producing larvae as soon as 6 days after infection. The larvae penetrate the intestinal wall and are distributed throughout the body via the thoracic duct, the right heart, the lungs and the left heart. Larvae penetrate the sarcolemma of the striated muscles – especially the more active ones like the tongue, intercostal muscles and diaphragm. Here they encyst and coil in a characteristic spiral or pretzel-like fashion.

The Trichuridae have a direct life cycle. The egg contains the L1, which is also the infective stage, and the final host must eat it before further development occurs. The prepatent period is around 2.5 to 3 months.

Subclass Secernentea

Life cycle of the Rhabditoidea

These nematodes have an interesting life cycle in that they can be either parasitic (homogonic) or free living (heterogonic). Female worms in the small intestine of a host produce eggs by parthenogenesis, each containing a fully developed, sheathed first stage larva – either male or female. The male larvae moult four times to develop into freeliving males (heterogonic pathway). The female larvae develop into free-living females after four moults (heterogonic), but some female larvae moult only twice into an infective third larval stage (homogonic). Free-living Strongyloides produce eggs that can also follow the homogonic pathway. Infection takes place percutaneously and the larvae moult in the lungs (M3). L4 migrate up the trachea and are swallowed to reach the intestines – where they develop into adult females only. The developmental period is 7 to 9 days. Transmammary migration occurs and infective larvae are present in the milk of sheep and cattle from the 8th to the 19th day after parturition.

Life cycle of the Ancylostomatoidea

Three types of life cycle are seen with the Ancylostomatinae (genus Ancylostoma). These are per os infections, where the L3 are eaten either with contaminated food in grown dogs or through the milk in puppies, or infection may take place percutaneously. In case of oral infection, the L3 penetrate the gastric glands in the stomach or the glands of Lieberkühn in the small intestine, where they stay for a few days. They then emerge and moult to the fourth and subsequent stages. With percutaneous infection the larvae (L3) end up in the capillaries or lymphatics and are passively transported to the lungs, where they moult to L4. These are coughed up, swallowed and end up in the intestine where they mature into adults. This type of life cycle is similar to tracheal migration, as is seen in ascarids.

The Bunostomatinae infect their host either only percutaneously (Gaigeria) or both percutaneously and orally (Bunostomum). With percutaneous infection the life cycle is similar to that of Ancylostoma, which in turn is similar to tracheal migration of the ascarids.

Life cycle of the Strongyloidea

The life cycles of the Strongylidae and Chabertiidae are direct, as is discussed under “General Principles” (Figure 3).

In the Syngamidae (Syngamus), the L3 develops in the egg. The infective larvae may remain in the egg and infection occurs when the egg is eaten, or the larva may hatch from the egg and be eaten, or the egg or larvae may be ingested by a paratenic mollusc, which is then eaten by the final host.

Life cycle of the Trichostrongyloidea

The life cycles of this superfamily are direct – but some adaptations are noteworthy. In the Dictyocaulidae the eggs may hatch in the respiratory tract or the intestines before being voided with the faeces. The resulting L1 rapidly moults to L2 and L3, and the latter must be ingested for the life cycle to continue. Once ingested, L3 lose their sheath, penetrate the intestine, remain a while in the mesenteric lymph nodes, and are passively carried to the lungs. Here they penetrate into the alveoli, moult to the fourth stage, and move to the bifurcation of the trachea where they mature into adult worms.

In the Molineidae (Nematodirus), the larvae also develop to the third (infective) stage inside the egg. When good rains fall the larvae hatch simultaneously and are eaten by the final host.

Life cycle of the Metastrongyloidea

These nematodes live in the respiratory tract of their respective hosts and have indirect life cycles. Metastrongylus makes use of earthworms as intermediate hosts. Thus, eggs are eaten by the earthworm – in which they hatch – and the resulting larva moults twice to reach the L3 (infective) stage. Once the earthworm is eaten by the final host, the L3 are liberated, which penetrate the small intestine of the final host, and remain in the mesenteric lymph nodes for a short while. The larvae reach the lungs by way of the right heart and moult twice again (M3 and M4) before reaching adulthood.

Muellerius has the same life cycle as Metastrongylus and uses gastropods as intermediate hosts. Oslerus has a direct life cycle. The worms occur in nodules in the trachea and bronchi of dogs and shed many larvated eggs that end up in the lungs. The dam transfers infective L1 to the puppies by licking and cleaning them. These larvae are subsequently ingested, pass through the wall of the small intestine and eventually end up in the lungs via the right heart. They pass through the alveoli and form nodules in the bronchi and trachea, where they mature into the adults. Depending on the species, Filaroides has either a direct or an indirect life cycle.

Life cycle of the Oxyuroidea

The oxyurid life cycle is monoxenous – the infective L2 developing inside the egg. Eggs containing the infective stage are ingested by a final host, the eggs hatch in the intestine, and the larvae moult twice to the adult stages.

Life cycle of the Ascaridoidea

Ascarids are parasites of the gastrointestinal tract and the females produce as many as 2 million eggs per day. The eggs have a thick shell, are highly resistant to adverse climatic conditions, and may survive up to 5 years. The L1 develops and moults inside the egg and the L2 in the egg is the infective stage, which hatches when the intermediate or final host ingests the egg. The parasitic development is complex.

There are several types of life cycles involving three, two or one host. Three-host life cycles involve a primary intermediate host, a second intermediate host, and then the final host. This is seen in those ascarids that parasitise fishes and reptiles. Two-host life cycles involve only one intermediate host and the final host, and occur in the ascarids that parasitise mink and other fur animals in Europe and America. In our domestic mammals only one host, the final host, is involved, and a number of special adaptations of the life cycle have become necessary for the ascarids that parasitise these animals.

  1. Tracheal migration (Figure 4): L2 hatch in the host, and migrate to the liver, where they develop to L3. From the liver the L3 move to the lungs and then to the alveoli, the bronchi and trachea. They are coughed up and swallowed, and end up in the intestine, where they develop into adults. The entire life cycle takes place within the same host. This type of life cycle is seen in Ascaris suum, Toxocara (seldom) and Parascaris equorum.
  2. Intestinal migration (Figure 5): L2 and L3 develop in the wall of the intestine and the adults develop in the lumen – again in the same host (Toxascaris leonina).
  3. Transmammary migration (Figure 6): the mother is infected and L2 larvae remain dormant in her tissues until the end of pregnancy. Under the influence of the hormones terminating pregnancy, the larvae are released, to appear in the milk. When the young suckle, they acquire the infection. This type of life cycle is seen in Toxocara vitulorum.
  4. Somatic/transplacental migration (Figure 7): the L2 migrate from the tissues of the mother across the placenta to the liver of the foetus and then to the lungs, where L3 develops, and then via the trachea and oesophagus to the intestines where the adults develop (Toxocara canis). This type of infection is also known as prenatal infection.

Life cycle of the Heterakoidea

Eggs are unsegmented when laid and develop outside the host to the third larval stage, which is also the infective stage. Once ingested, the eggs hatch and the larva follows the intestinal migration route to eventually reach adulthood. The prepatent period is 24 to 36 days. The eggs of both Heterakis and Ascaridia can survive in earthworms (paratenic hosts), and it appears that earthworms are an important source of infection for free-roaming chickens and pigeons.

Figure 4 Ascarid life cycle – tracheal migration.

Figure 5 Ascarid life cycle – intestinal migration.

Life cycle of the Habronematoidea

Eggs or larvae of Habronema and Draschia are excreted with the faeces. The eggs hatch and the worm larvae (L1) are eaten by the larvae of certain flies, in which they develop. Development is synchronous, in that by the time the fly larva pupates, the worm larva has reached the infective stage. The fly that emerges carries the infective larvae and must be eaten by the final host for further development to occur. Nematode larva may also leave the fly through the proboscis, and when the fly feeds around the lips or on sores the larvae enter the host.

Life cycle of the Thelazioidea

These worms, which occur in the conjunctival sac of cattle, have an indirect life cycle. The female worm produces large numbers of larvated eggs, which are present in the secretions of the eyes. Flies of the genus Musca act as intermediate host, and ingest these eggs. In the fly, the larvae hatch and moult to the infective L3 stage. Once the larvae have reached the infective stage they migrate to the mouthparts of the fly, and when the fly feeds on another animal, the larvae are transferred. The adult stage is reached after about 1 month. The life cycle is similar to that of the ovoviviparous filarid nematodes (Figure 8).

Life cycle of the Spiruroidea

The families Gongylonematidae and the Spirocecidae belong to this superfamily. The Gongylonematidae are parasites of a wide range of vertebrates and use insects as intermediate hosts. The species occurring in ruminants use dung beetles or cockroaches, whereas those in ducks and hedgehogs use grasshoppers. Eggs of the worms are eaten by insects, and the larvae hatch and develop to the infective stage in the haemocoel of the insects. The insects need to be consumed before the life cycle will commence.

The Spirocercidae include the helminth genera Spirocerca of carnivores, and Ascarops and Physocephalus of suids.

Figure 6 Ascarid life cycle – transmammary (lactogenic) migration.

Figure 7 Ascarid life cycle – somatic/ transplacental (prenatal) transmission.

Spirocerca uses a dung beetle as intermediate host and a variety of animals as paratenic hosts. Eggs produced by the female worm are voided in the faeces and are ingested by a dung beetle. The infective stage develops in a delicate capsule in the haemocoel of the insect. The various paratenic hosts acquire the infective larvae by eating dung beetles. In these hosts, the larvae are encapsulated on the stomach, mesentery, or liver of mammals, and on the crop of poultry. Dogs are infected when they eat infected dung beetles or paratenic hosts. The larvae are released from the tissues and migrate in the wall of the stomach to reach the small arteries, and enter the walls of these arteries. From here they migrate (still in the walls of the arteries) to the thoracic aorta and eventually reach the oesophagus, where they produce large nodules which may become neoplastic.

Ascarops and Physocephalus also utilise beetles, including dung beetles, as intermediate hosts. Once eaten, the larvae are released and resume their development in the stomach mucosa.

Life cycle of the Filarioidea

The filarids are nematodes that generally occur within tissues such as the heart muscle, blood vessels, skin and adnexa – or free in the abdominal cavity. These nematodes – with the exception of Parafilaria – cannot pass their eggs or larvae to the outside, which implies that they need sucking insects as their intermediate hosts, and they thus have indirect life cycles.

  1. Some filarid females (e.g. Parafilaria) bore a small hole through the skin and lay their eggs through the hole on the surface of the skin (Figure 8). The walls of the eggs are very thin and rupture easily, liberating the larvae. Face flies ingest the eggs and larvae, and in the flies the larvae develop to the infective L3. The L3 migrate to the proboscis of the flies and are released when the flies feed again.
  2. Other filarids produce live larvae that are released in the blood or other body fluids (Figure 9). The larvae are known as microfilariae (L1) – which are ingested by the intermediate hosts (the bloodsucking flies), such as Stomoxys, mosquitoes, Simulium and the tabanids. The microfilariae develop into the infective L3, which migrate to the mouthparts of the flies and are transmitted when the flies feed again. Setaria, Dirofilaria, Dipetalonema, Onchocerca and Elaeophora have this type of life cycle.

Figure 8 Filarid life cycle in which eggs are laid on the host.

Figure 9 Filarid life cycle in which microfilariae are produced in the host.

Cestodes (tapeworms)

As with the nematodes, there are also several orders of tapeworms. However, only the order Cyclophyllidea occurs in domesticated animals, and it is thus the only one for which the classification is presented.

Life cycles of the cestodes

The cestodes or tapeworms of veterinary importance have an indirect life cycle with one intermediate host – which may be either a vertebrate or an arthropod. Tapeworms do not lay eggs in the traditional sense, but periodically shed the last few proglottids, in which eggs are contained. The proglottids rupture releasing the eggs, which in turn have to be ingested by the correct intermediate host. Several types of larvae are encountered in the intermediate hosts:

  1. Cysticercus (Figure 10): This is a fluidfilled cyst with a single scolex, also known as a protoscolex. It occurs in muscular or nervous tissue of vertebrates and is the larva of Taenia saginata, Taenia solium, Taenia ovis or Taenia hydatigena.
  2. Coenurus (Figure 11): Similar to a cysticercus, but with numerous scoleces. It occurs only in nervous or connective tissue of vertebrates, and is the larva of Taenia multiceps and Taenia serialis.

Figure 10 Schematic representation of a cysticercus with invaginated scolex.

Figure 11 Schematic representation of part of a coenurus with multiple invaginated scoleces.

Figure 12 Schematic representation of a strobilocercus.

Figure 13 Schematic representation of part of a hydatid cyst.

Figure 14 Schematic representation of a cysticercoid.

  1. Strobilocercus (Figure 12): The scolex is connected to the cyst by a chain of asexual proglottides. Once ingested by the final host, these are digested so that only the scolex remains. It occurs in vertebrates and is the larva of Taenia taeniaeformis.
  2. Hydatid (Figure 13): This is a large, fluidfilled cyst, lined with germinal epithelium from which numerous scoleces ('hydatid sand') are produced – that either lie free or occur in bunches surrounded by germinal epithelium (brood capsules). Sometimes daughter cysts, complete with germinal epithelium, occur within or on the outside of the cyst. This larva is found in the liver and lungs (and sometimes the nervous tissue) of vertebrates, and is the larval stage of Echinococcus.
  3. Cysticercoid (Figure 14): This is a single scolex embedded in a small solid cyst. It is usually found in arthropods and is the larva of the anoplocephalid tapeworms such as Moniezia, Thysaniezia, Avitellina, and probably Stilesia.

The developing cestode larvae are also referred to as metacestodes and need to be eaten by the final hosts for the life cycle to continue. A herbivore (ruminants) or omnivore (pigs or primates) is the intermediate host of the taeniid tapeworms, while arthropods are the intermediate hosts of the anoplocephalids, the dilepidids, the davaineids and the hymenolepids. The Mesocestoididae have two intermediate hosts: the first an arthropod in which a cysticercoid occurs, and the second a reptile, bird or small mammal, in which a tetrahyridium occurs.

Table 1 Veterinarians’ guide to most common species of tapeworms in South Africa

The tables below attempt to summarise and simplify veterinary tapeworms for the practitioner and the student. In this scheme, the tapeworms are subdivided into 3 main groups (ruminant, human and carnivore) according to the main host of the strobilar stage (adult tapeworm). Zoonoses are indicated with an asterisk.

Herbivore tapeworms

Tapeworm Intermediate host (larval cyst/metacestode) Final host (adult worm/strobilar stage)
Moniezia spp. Oribatid mite Cattle, sheep, goats
Avitellina Oribatid mite Cattle, sheep, goats
Anaplocephala Oribatid mite Horses

Human tapeworms

Tapeworm Intermediate host Final host
Taenia solium Pigs (Cysticercus cellulosae) Humans
Taenia saginata Cattle/antelope (Cysticercus bovis) Humans

Carnivore tapeworms

Tapeworm Intermediate host Final host
*Taenia multiceps Sheep and goats (Coenurus cerebralis) Domestic and wild carnivores
Taenia ovis Sheep and goats (Cysticercus ovis) Domestic and wild carnivores
Taenia hydatigena Sheep (Cysticercus tenuicollis) Domestic and wild carnivores
Taenia serialis serialis Rabbits/rodents (chinchilla) Domestic and wild carnivores
Taenia taeniaeformis Rodents Domestic and wild carnivores
*Echinococcus granulosus Cattle and sheep (hydatid cyst) Domestic and wild carnivores
Dipylidium caninum Fleas and lice Domestic dogs and cats

*Zoonoses

Trematodes (flukes)

Classification

Life cycles of the Trematodes

The trematode life cycle is always indirect and the three flukes that are of importance in domestic animals all use freshwater snails as an intermediate host. The life cycles of the two most important flukes, Fasciola and Calicophoron, are illustrated in Figure 15. Although Fasciola occurs in the bile ducts of the liver, and Calicophoron in the rumen, their life cycle is identical. Eggs are released with the faeces and must be freed from the faeces, i.e. when they fall into water, before they hatch – allowing the miracidia to escape.

The miracidia must enter the intermediate host within 3 hours of hatching or they will die. In the snails, the miracidia form sporocysts and rediae – daughter and granddaughter rediae. The granddaughter rediae give rise to the cercariae which leave the snail. The cercariae form metacercariae on the surface of the water or on vegetation. When ingested by the host, they excyst, migrate to their predilection sites, and develop into the adults.

The life cycle of the Schistosoma mattheei – which infects ruminants – is slightly different from that of other trematodes, in that the eggs are laid within the venules and capillaries of the mesenterium, or the bladder. The eggs penetrate the tissues with the aid of their spines and proteolytic enzymes secreted by the miracidium – to reach the lumen of the intestine or the bladder. The eggs are passed out in the faeces, and when deposited in water they hatch within minutes. The miracidia enter the appropriate snails where they form primary sporocysts and each sporocyst will in turn produce secondary and metasporocysts, the cercariae developing from the latter. The cercariae leave the snail and enter the final host percutaneously or per os. Once in the final host, the cercariae lose their forked tails and are now known as schistosomulae. The latter migrate to the lungs and then against the blood flow to the portal veins of the liver – where they attain sexual maturity. They then migrate to the capillaries of the mesentery or the bladder, and start laying eggs. Note that there are no rediae or metacercariae in the schistosome life cycle.

Figure 15 Life cycles of some trematodes of domesticated animals.

Epidemiology

Introduction

Epidemiology, as per definition, is the study of the interrelationships of the factors that determine the occurrence, frequency and distribution of a parasitic condition or a disease – in a given animal population. As with infectious diseases, the occurrence of helminth parasites is also influenced by the epidemiological triad – namely, the availability of a susceptible host (Host) and a viable parasite (Agent), and the dissemination/transmission of the parasite to the host (Disseminator). Any change in the interaction between the host, the agent or the disseminator, may influence the occurrence of a parasitic condition. For example, South Africa is divided into climatic zones or rainfall areas, as indicated in Figure 16. Because climate appears to be the single most important factor that can cause a disturbance in the equilibrium of the triad, one would thus expect helminths to be less numerous in the semi-arid areas. In addition, the carrying capacity in these dry areas is usually low, as is the host density per unit area. The summer rainfall area generally has a higher rainfall, a greater carrying capacity, and the helminth burden is higher in animals living here. However, one should also take the climatic preferences of the helminths themselves into account; some only occur in the winter rainfall area, while others occur in one or more climatic zones.

Figure 16 The climatic zones of South Africa (after Reinecke, 1983).

Epidemiological factors that influence the occurrence of Helminthoses

Although the reasons for the occurrence of helminth infections are complex, the 4 basic factors involved are summarised in Table 2, and discussed below using the framework derived from the excellent work of Urquhart et al. (1992). These factors should be borne in mind when investigating an outbreak of helminthosis on any farm. It is therefore imperative to obtain as complete a history pertaining to the outbreak as possible, before deciding on the control programme and investing in expensive control measures.

An increase in the numbers of infective stages

Contamination of the environment

Biotic potential: This may be defined as the capacity of an organism to be a biological success, as measured by its fecundity. Thus, Haemonchus and Ascaris produce many thousands of eggs each day, while Trichostrongylus and Nematodirus produce very few. In the case of the trematodes, the division of each redia gives rise to several hundred cercariae. The biotic potential of cestodes varies considerably: some Taenia species produce only one larval stage per egg, while Echinococcus produces several thousand protoscoleces per hydatid cyst – which was derived from a single egg.

Stock management: The stocking density can influence the level of contamination of a pasture, and is especially important in nematode and cestode infections where multiplication does not take place outside the final host. It has the greatest influence where climatic conditions are optimal in the summer rainfall areas for certain nematodes, and the winter rainfall areas for others – thus determining their occurrence.

Table 2 Factors affecting the epidemiology of parasitic diseases.

An increase in the number of infective stages Contamination of the environment Biotic potential
Stock management
Immune status
Hypobiosis
Development/survival of infective stages Microhabitat
Seasonal development
Stock management
An alteration in host susceptibility Existing infections Diet
Pregnancy and lactation
Steroid therapy
New infections Intercurrent infections
Anthelmintic treatment
Hypersensitivity
The introduction of susceptible stock Absence of acquired immunity
Absence of age immunity
Longevity of infective stages
Genetic factors Between breeds
Between species
Sex
Strain of parasite
The introduction of infection Introduction of new stock
Effluent
Intermediate hosts

 

Host immune status: The role of the host’s immune status is an important consideration in the epidemiology of nematode infections, in particular. Young animals are generally less resistant than adults and a predominance of young animals on a particular farm could easily lead to an outbreak of one or other helminthosis. Ewes, nannies, sows – and to a lesser extent, cows – become more susceptible to helminth infections towards the end of pregnancy and early lactation (peri-parturient relaxation of immunity (resistance) or PPRI/R). In most parts of the world, parturition in grazing animals is synchronised to occur when the climatic conditions are most favourable for pasture growth, but they are then also most suitable for the development of the free-living stages of helminths. The implication is that PPRR results in increasing contamination of pastures – as the number of susceptible animals increase.

Hypobiosis: The epidemiological importance of this period of dormancy is that the resumption of larval development usually occurs when conditions are optimal for the free-living stages to survive, and this leads to increasing contamination of pastures. It often coincides with parturition, when the females’ immunity and resistance to infection is also low.

Development and survival of the infective stages

The microhabitat: The climatic requirements of the free-living stages of nematodes have already been discussed. In addition to optimal climatic factors – soil structure and drainage, vegetation type and the formation of a layer (mat) of vegetation on the soil (humus, compost) influence the suitability of the microhabitat as far as the survival of the infective stages is concerned. The mat is well-developed in older pastures and retains sufficient moisture and air bubbles to ensure even temperatures and high humidity. The use of rotational grazing with different species of animals and alternating grazing with cultivation reduce the extent of the mat and thus also parasite survival. In arid areas, pasture growth is negligible and a mat seldom develops. The latter also occurs with overgrazing. Similarly, a high ground-water table is important for the development and survival of the intermediate hosts of liver and conical flukes. The development and survival of helminth eggs or larvae within faeces also depend on temperature and moisture. Cattle dung remains in its original form for much longer than sheep pellets; the moisture trapped inside a dung pat therefore remains for much longer than in sheep pellets and provides an ideal microhabitat for nematode larvae to survive for weeks or even for months.

Seasonal development: In South Africa – which is essentially a subtropical country – there may be several successive generations of helminths during the course of the year, while in the northern hemisphere, or in countries with distinct wet and dry seasons, the number of helminth generations may be limited. Multiple generations are encountered in particular with helminths that have a short developmental period, such as the trichostrongyles of ruminants. However, seasonal development depends – to a very large extent – on optimal climatic factors being present, and these will obviously influence the time of appearance of the larvae on the pastures, the survival rate of especially the infective stages, and, eventually, their numbers.

Stock management: The availability of infective helminth stages is affected by certain management practices. A high stocking density increases the level of contamination. Mowing pastures, i.e. reducing the height of the plants, also enhances the availability of the infective larvae. Scarcity of grass may cause animals to feed closer to faeces than they would normally do. Shorter pastures may be beneficial in reducing the parasite load as the larvae are more susceptible to changes in climate and humidity, and the free-living stages are thus more vulnerable. Similarly, the season during which time parturition occurs may influence the intake of helminths significantly. Where lambs or calves are born out of season, the numbers of infective helminth stages are usually low and the likelihood is that infection will occur only once the animals are older and stronger – and are more capable of coping with the helminth concerned.

Factors affecting susceptibility to infection

Effects on an existing infection

Existing infections can be altered in adolescent or adult stock that harbour non-clinical helminth infections.

  • Diet: Adequately fed animals can withstand the effects of helminth infections better than those in poor condition. Animals infected with H. contortus which have an adequate dietary iron intake may be able to maintain their haemoglobin levels. However, during winter, when food is scarce and of poor quality, iron intake becomes insufficient to maintain haemoglobin levels, with the result that the animals become anaemic and may die. This is especially important in small stock.
  • Pregnancy and lactation: When animals are born during spring, the greater part of pregnancy is during winter. Nutrition is inadequate and this influences foetal growth rate and birth mass of the new-born. Under these circumstances, even low worm burdens can have a detrimental effect on food conversion of the mother – causing poor milk production and stunting of the new-born animal.
  • Steroid therapy: Steroids are widely used in therapy, and it is known that they suppress the immune system – thus increasing the host's susceptibility to helminths and their effects. Egg production by nematodes is increased after steroid therapy and greater pasture contamination occurs.

Altered susceptibility to the acquisition of new infections

  • The role of concurrent infections: The interaction of various helminths, or helminths with other pathogens, results in an increasing severity of the consequences of the helminth infection. This is the case with H. contortus and the Eimeria spp. of the coccidia. It may also occur when animals are simultaneously infected with abomasal and intestinal nematodes.
  • The effect of anthelmintic use: Infections with some worm species result in premunity of the host – in other words the continued presence of small numbers of the parasite stimulates host immunity. If this balance is disturbed by the administration of anthelmintics, re-infection may occur. Teladorsagia circumcincta is a case in point where removal of the adult worms by the administration of anthelmintics results in hypobiotic or arrested larvae being mobilised to continue their development to adults – resulting in a higher adult burden than existed previously.
  • Hypersensitivity: in many cases the immune response to parasites is associated with IgE and a hypersensitivity reaction. When this occurs in the intestine, there is increased permeability of the intestinal wall to macromolecules such as protein and the loss of these molecules into the lumen of the intestine. The loss of excessive amounts of protein results in poor growth and wool production in immune sheep that are subjected to a heavy larval challenge.

Parasitism resulting from the movement of susceptible stock to an infected environment

Absence of acquired immunity: Dictyocaulus viviparus in sheep and the cysticerci of Taenia saginata in cattle elicit a good immune response in young animals. However, when adult animals not previously exposed to these worms are infected – this results in severe disease and stock losses.

Absence of age-associated immunity: Immunity to helminths develops with age following exposure to relatively small parasite burdens. Adult animals not previously exposed to helminth infections are at risk when introduced into an endemic area.

Longevity of infective stages: When ecological conditions – e.g. climate, temperature and particularly humidity – are optimal, the infective stages of many worms can survive for extended periods, including those nematodes that develop inside the egg (Nematodirus and the various ascarids), and those that utilise intermediate hosts. These infective stages are then able to infect successive groups of young animals and may cause disease within a few weeks after infection. Where the climate is less favourable, their longevity is reduced, and only one or fewer groups of animals will be infected.

The influence of genetic factors

  • Between host species: Many of the economically important parasites are capable of infecting a wide range of hosts – which vary in their susceptibility. Most parasites, however, show some degree of host specificity. For example, cattle are more resistant to the effects of Fasciola hepatica, which usually kills sheep, while goats seem to be more susceptible to the pathogenic effects of the common intestinal trichostrongyles than cattle or sheep. This is probably because of the length of time that the host and parasite have been associated. This factor has been exploited for integrated helminth control programmes. For instance, rotational grazing with sheep and cattle or sheep and horses, respectively, leads to lower helminth burdens in both species.
  • Between breeds: It has been shown that certain breeds of sheep are more resistant to H. contortus infections than others, while the same breed may be more susceptible to another nematode. However, there are responders and non-responders in every flock or herd in terms of their ability to develop resistance to internal parasites – and it is recommended by some experts that animals within the population – with poor resistance – should be culled.
  • Gender: There is some evidence that entire male animals are more susceptible to the effects of internal parasites, and this could be important in areas where males are not routinely castrated, or where androgens are used to fatten animals.
  • Strain of helminth: It is recognised that some species of helminth have strains or variants that vary in their infectivity and pathogenicity. In addition, anthelminthic resistant strains may be introduced or arise – which can cause control measures to be ineffective.

Introduction of infection into a clean environment

Introduction of infected stock: This is one of the most important methods of acquiring unwanted helminth species, and it occurs especially when moving breeding stock from one country to another. Quarantine restrictions are generally poor or non-existent as far as helminths are concerned. Examples of such events are the introduction of Parafilaria bovicola into Sweden – either by infected cattle or via infected flies. Similarly, the incidence of heartworm, Dirofilaria immitis, has increased dramatically in the USA and Australia with the increasing movement of humans and their pets. This is because the mosquito vector was already present in these countries.

The role of effluent: The transfer of helminth infections by manure has been reported. In Europe and the USA, the prevalence of cysticercosis in pigs has increased dramatically on farms where human sewage was applied to the pastures. The application of pig slurry to pastures grazed by sheep has also led to pneumonia caused by the migration of ascarid larvae.

The role of infected intermediate hosts: Several helminth infections are transmitted by vectors, notably flies, and these may introduce an infection into areas previously free of that infection. Birds may also play a role in disseminating intermediate hosts – e.g. waterfowl can carry snail eggs suitable to host Fasciola spp. on their feet.

Immunity to helminths

Types of immunity

Innate immunity (also referred to as natural, non-specific or constitutional immunity). This type of immunity is characterised by the parasite failing to establish infection in a host which is physiologically unsuitable No immune process is involved. For a review of non-specific immunity, see Rumyantsev (1998).

Acquired immunity: This is an adaptive immune response on exposure to a parasite and is antigen specific. The efficacy of the immune response is genetically determined. There is extensive genetic variability of resistance within populations and natural or artificial selection processes can result in resistant breeds. Vaccination can induce acquired immunity. Acquired immunity to parasites is reviewed in detail by Stear and Wakelin (1998).

Premunity: In this state the host is protected from further infection with a specific parasitic species following ongoing, low-grade infection with that parasite. Premunity prevents the consequences of infection with newly ingested larvae. This phenomenon has been observed in infections with gastrointestinal parasites, such as the strongyles. With premunity the adults in the host are usually smaller and the females have reduced fertility. Premunity must not be confused with the process of ‘self-cure’ that results in expulsion of adults following the ingestion of massive numbers of larvae.

Introduction to helminth immunity

The immune response to helminth parasites is classified by immunologists as a Th2 skewed response – which involves T-helper cells (CD4) and elicits an antibody response. The Th2 response to helminth infections is normally characterised by an increase in white blood cells, antibodies, mast cells, and by goblet cell hyperplasia. The effector mechanisms may vary depending on the tissue or organs in which the parasites are localised (see later).

In addition to the Th2 response, helminths also stimulate a Treg or immune-modulatory response. Treg cells are specialised CD4+ T regulatory (Treg) cells that maintain self-tolerance and immune homeostasis by suppressing the activation, proliferation and effector functions of various immune cells that limit or suppress immune processes. The Treg response plays a role in down-regulating the immune response and in reducing the inflammatory response which allows helminths to persist in the host tissues. It may also be the mechanism regulating host-parasite tolerance seen in some helminth infections. The immunemodulating effect of helminths may have an effect on co-infection with other microorganisms such as bacteria and viruses – either exacerbating or suppressing the effects of the disease caused. This down-regulation of the immune response may also have a suppressive effect on vaccination against various diseases, so leading to ineffective immunisation.

The complexity of the immune response to helminths is further complicated by the ability of the developmental stages of some parasites to escape the effects of the immune response or to survive the effects of mediators released by effector cells during the immune response. The immune response against helminths may result in some pathology in the host. The development of granulomas in response to migration of helminths through the tissues – for example in the lungs, liver or blood vessels – may have serious consequences for the host. The immune response in the intestinal tract causing expulsion of worms may also cause severe enteritis – resulting in dehydration, malabsorption and weight loss, which are all detrimental to the host and may even cause the death of severely affected animals.

The immune response against helminths in tissues

Helminths in host tissues generally induce an antibody-dependent cell-mediated cytotoxic (ADCC) response. This includes the production of IgE, IgG and IgA antibodies. Eosinophils, neutrophils and macrophages are the main effector cells of this response, and produce the characteristic tissue changes associated with nematode parasitism. As part of this response, antibodies coat and attach to specific antigens on the parasites – so allowing effector cells to attach to the Fc regions of the bound immunoglobulins. This antigen fixation triggers the release of toxic substances from the effector cells. For example, nitric acid released by macrophages may kill worms or inactivate their eggs. Parasites in tissues often also cause a granulomatous inflammatory reaction that isolates the worms in the tissues – thus preventing them from further migration and development. The granulomas that develop as a consequence of this inflammatory reaction may have markedly deleterious effects on the host, depending on which tissues or organs are affected.

Tissue-dwelling parasites, however, have defensive mechanisms protecting them from the effects of the host’s immune response. Some can evade inactivation by producing enzymes that neutralise the toxic substances secreted by the effector cells, or they may stimulate the production of immunoglobulins such as Ig M that block the ADCC response. Some parasites like F. hepatica secrete immune-modulatory substances that supress lymphocyte production and kill eosinophils.

The immune response to helminths in the gastrointestinal tract (GIT)

Gastrointestinal helminths trigger degranulation of mast cells, resulting in the release of Ig E – which causes fluid and electrolyte loss into the intestinal tract. This gives rise to increased intestinal motility and permeability – which causes the elimination of larvae and expulsion of adults from the tract. Ig A on the surface of the intestinal mucosa will help to neutralise enzymes secreted by the worms and will prevent them from feeding from the intestinal mucosa. Gastrointestinal parasites may, however, evade the immune mechanisms by secreting immunomodulatory substances which neutralise the toxic substances secreted by effector cells of the host’s immune response.

Host factors that may affect immunity to helminths

It is generally accepted that animals suffering from malnutrition are more likely to develop clinical signs as a result of helminth infection. Research trials indicate that protein supplementation in poorly-nourished animals increases their resilience to parasitic infections. Whether this is due to a direct effect on the immune response or whether it merely mitigates the effect of GIT nematodes on the host – namely reduction of feed intake and loss of protein from the GIT – remains unknown.

A phenomenon known as peri-parturient relaxation of immunity or resistance (PPRI or PPRR) is observed in pregnant and lactating ewes. It is characterised by an increase in the number of eggs shed in the faeces, and it is currently thought not to be the consequence of immunosuppression, but to have a nutritional cause. The effects of PPRI are mitigated by feeding supplementary protein or by the early weaning of lambs.

Vaccination against Helminths

Because of the complexities of the immune response to helminths and the current poor understanding of the immune mechanisms involved, vaccine development against economically important worms has been slow.

Early research into the development of anti-parasitic vaccines employed irradiated larvae of various helminths and was successful in developing a vaccine against certain cestodes (Taenia and Echinococcus spp.), and also the nematodes Ancylostoma sp. and Dictyocaulus viviparus. Developing vaccines against the gastrointestinal helminths of ruminants proved to be a more difficult problem: the use of irradiated larvae produced good results in mature sheep, but it was ineffective in lambs – the class of animal most in need of protection against parasitic infections. Subsequently various protein antigens obtained from the parasites, either worm extracts or recombinant antigens, were assessed for their immunising and protective abilities.

Another approach was to use proteases obtained from bloodsucking parasites as antigens to disrupt the absorption of nutrients by the parasites, as this approach had been used with some success in the development of a vaccine to control the tick Boophilus microplus. Various proteases obtained from Haemonchus contortus were selected for testing: two gut-derived antigens, H 11 and H-gal-GP, which are ‘hidden antigens’ not normally exposed to the host-induced high levels of antibodies that attached to the brush border of the intestinal mucosa – resulting in interference with the digestive enzymes needed by the parasites to digest their blood meal. A vaccine containing these protease antigens induced malnutrition, reduced fecundity and weakness of the worms, and also expulsion of H. contortus in infected animals. In addition, the vaccine was effective in young lambs and ewes around the time of lambing, at which time natural immunity usually is weak or non existent.

One disadvantage of the use of ‘hidden antigens’ in a vaccine is that the immunity is not boosted by natural infection, and so vaccination must be repeated at intervals. Trials conducted in various countries, including South Africa, have shown that the vaccine which is known as Wirevax, gives significant protection against infection with H. contortus in young sheep and pregnant ewes. Technical data on efficacy and safety are currently being reviewed by the registration authorities, and it is expected that this vaccine will be ready for marketing as a commercial product in South Africa within the next few years (now registered and commercially available).

Serodiagnosis of helminth infections

Immunological tests are not routinely used for the diagnosis of helminth infections, partly because the reaction against the intestinal helminths is not specific, and partly because it is easier, faster and cheaper to examine faeces for the presence of eggs. However, it is necessary to use serodiagnosis for a number of important infections where ova are not produced and/or present in the faeces of the infected animals. Some of the conditions in which the use of serodiagnosis is required, include infections with heartworm (Dirofilaria immitis) in dogs, visceral larval migrans (Toxocara canis), trichinosis (Trichinella spiralis), fasciolosis, and Ancylostoma caninum infections in humans. In all these infections the ELISA is the most useful serological test.

Control of helminths of veterinary importance

Introduction

There are various good reasons why veterinarians and animal owners should control helminth infections in animals. Either the parasitic stage of the helminth (in the host) or the free-living stages in their habitat may be targeted by appropriate control measures. Both can be targeted. If both methods are used simultaneously it is referred to as an integrated approach.

Chemical treatment using anthelmintics has been the method of choice for decades because of its efficacy, relative ease of use, and affordability. Although many new anthelmintics have been developed in the last two decades, the increasing development of resistance to anthelmintics has been problematic in the small-stock farming sector in particular. A number of strategies have been developed to reduce the use of anthelmintics, in order to prevent or retard the development of resistance.

Rationale for the control of helminth infections

Economic losses: Helminth infections of livestock can cause economic losses as a result of production loss and/or by causing mortalities. In the livestock industries, control of the infections by anthelmintic treatment is used to reduce production erosion caused by effects such as weight loss.

Clinical disease: In both farming and in companion animal medicine, helminth control is done to treat and/or to prevent the development of clinical disease.

Zoonoses: Veterinarians are responsible for the prevention of infection and the treatment of animals with helminths – which may infect humans.

Ethical considerations: It is unethical not to treat animals suffering from helminthosis.

Controlling helminths in the host

Anthelmintics: The anthelmintics are chemicals used for the prevention and treatment of helminthosis in animals. While the currently available anthelmintics are relatively safe and highly effective, the emergence of anthelmintic resistance has prompted helminthologists to advocate a different and sustainable approach – particularly in small stock – to deal with helminth infections that require regular treatment (see below).

Worm-resistant animals: The ability of individual animals within a population to mount a protective immune response to resist worm infections has been recognised and the possibility of breeding worm-resistant animals was suggested. This approach became particularly important when Haemonchus contortus in sheep flocks  developed a high rate of anthelmintic resistance. The most intensive research on this aspect has been done at the CSIRO, in Australia. Their Nemesis Project demonstrated that although the heritability of worm resistance was low compared to that of most production traits, it was feasible to select resistant Merino rams that could be used to increase a flock’s resistance to H. contortus – which in turn would allow less frequent use of anthelmintics to adequately control the infection. Similar breeding initiatives have also recently been initiated in South Africa to increase the resistance of sheep to H. contortus infections. Immunological studies have recently shown that sheep that are more resistant to H. contortus had a more effective immune response characterised by a higher production of the Th2 effectors including eosinophils, IgE, mast cells, IL-5, IL-13, and TNF required to protect the animals from the effects of the infection (see under immunity) .

FAMACHA system: This system – developed by Francois Malan, a South African veterinarian – measures the degree of anaemia in individual animals caused by infection with blood-sucking worms such as H. contortus. The colour of a sheep’s conjunctival mucosa is compared with the various grades of anaemia on a colour chart (Figure 17). This allows identification of individual animals in a flock that should be treated. The use of the FAMACHA system reduces the number of treatments per flock, since some animals are more resistant than others and do not require frequent treatment. This system can also be used to select more resistant animals for the purpose of breeding resistant sheep.

Vaccination: A vaccine against  H. contortus for use in small stock has recently been registered in South Africa. This vaccine invokes immunity in young and pregnant animals (the most vulnerable groups) to the helminthoses. In field trials the vaccine has been shown to kill more than 90% of the worms present in the intestine and also reduces the number of eggs produced – resulting in less contamination of pastures (see further discussion under immunity).

Nutrition: It is well known that animals on higher planes of nutrition are more resistant to helminth infections. Protein supplementation of the diet of worm-infested animals has been shown to increase their resilience to the clinical effects of worm infestations.

Figure 17 The FAMACHA chart.

Controlling helminths in the environment

Various strategies have been developed to reduce the numbers of the non-parasitic stages of parasites on pastures.

Removal of faeces: Regular removal of faeces reduces the burden of nematode eggs and non-infective stages on the pasture. In the case of cysticercosis caused by Taenia species where humans are the intermediate host, the deposition of human faeces on pastures must be prevented by making toilets readily available.

Alternate grazing: Since most helminths are species-specific, it is generally accepted that grazing different host species on a rotational basis in camps will reduce the build-up of helminth numbers.

Rotational grazing: Rotating grazing over a number of camps reduces worm numbers. This is particularly important on irrigated pastures where there can be a massive build-up of infective stages.

Stocking density: High stocking densities will cause a build-up of worm eggs and larval stages on pastures.

Avoiding infected areas: Wet, marshy (vlei) areas where the intermediate hosts of trematodes occur, should be avoided during danger periods.

Biological control: A nematophagous fungus, Duddingtonia flagrans, has been investigated for its ability to control infective larvae on pastures. Livestock are fed spores of the fungus which then pass out unharmed in the faeces, to germinate on the pastures. The fungus then infects and kills nematode larvae.

Good results have been reported in the literature – but safety testing is still in progress.

Integrated control: Integrated control is the implementation of a combination of chemical, biological and environmental procedures used jointly or sequentially against the background of an understanding of the ecology of selected target parasites (see SIPM below).

Anthelmintic remedies

The usual control of veterinary parasitic helminths relies heavily on the use of anthelmintic drugs (anthelmintics). Anthelmintics are used either as prophylaxis (preventative), to treat infected animals (metaphylactic), or as a curative measure in clinically infected animals. There is a wide range of chemical compounds that are active against helminths, but only a small proportion of these are registered for commercial use.

The discussion in this section focuses on those anthelmintic groups currently registered for use in South Africa, and some of the relevant issues around them. For specific control measures for a particular helminth, see the accounts under the relevant worm.

The history of veterinary anthelmintics in South Africa

Before the advent of modern anthelmintic compounds, herbal preparations were used for endoparasitic control. They were generally highly ineffective and such huge losses were caused by H. contortus and Oesophagostomum infections in sheep and goats that an avid search was launched at the turn of the 19th century for specific, effective anthelmintic compounds. A wide variety of substances ranging from household cleaners, fuels, and tobacco extracts were tested.

At the beginning of the 20th century it was discovered that various arsenicals, especially in combination with copper sulphate and nicotine, had a highly specific activity against H. contortus – although these compounds had a narrow safety margin.

This led to the development in South Africa of one of the first non-herbal anthelmintic remedies in the world known as “Government Wireworm Remedy”. At that time, this remedy appeared to be so effective that Sir Arnold Theiler suggested that H. contortus could be eradicated by treating all sheep before moving them onto a pasture that had not been grazed by susceptible animals for a year.

Despite their serious limitations, the arsenical mixtures and phenothiazine made it possible – at relatively low cost – to stabilise small ruminant production to some extent.

However, as a result of an intensive international search for more suitable compounds, in the late 1950s the organophosphate compounds were discovered and heralded a spate of new, safer, and effective anthelmintics over a period of three decades. Phenothiazine and the arsenicals have since disappeared from the market, having been replaced by the chemicals that are in general use today

Although the mode of action of some of the current anthelmintics is still not clearly understood, the effect of most groups can be classified as being one of two actions: cellular disruption or neuromuscular paralysis.

Currently-registered anthelmintics

Organophosphates (OPs) (e.g. dichlorvos, trichlorfon)

The organophosphates have largely been replaced as veterinary anthelmintics by more modern remedies because of their relative toxicity in the host, poor effect against immature stages, narrow safety margins, and toxicity for the environment. Dichlorvos incorporated in a plasticiser was useful as a slow-release anthelmintic which maintained a therapeutic concentration – thus increasing its safety margin. Dichlorphen is still used as a cestodicide in small animals. Trichlorfon is used in ruminants in South Africa, to treat anthelmintic-resistant H. contortus strains in sheep. In some countries it is still used in horses because of its high activity against Gasterophilus larvae (bots), ascarids and oxyurids. OPs inhibit acetyl cholinesterase, with the result that excessive acetylcholine accumulates in the worm, causing continual stimulation of nerve endings and resultant lethal spastic paralysis.

Benzimidazoles (e.g. fenbendazole, mebendazole, albendazole, febantel, triclabendazole)

This group was introduced in the 1960s with the launch of the first generation thiabendazole. Numerous other related compounds were discovered subsequently. It is a large family of chemicals that has a wide spectrum of activity against roundworms; they all have an ovicidal effect and a wide safety margin. Some of these compounds (also referred to as benzos) are active against cestodes and trematodes. Triclabendazole is useful as a fasciolicide, because it is highly effective against immature flukes. They are most effective in ruminants and horses in which the passage though the GIT is slowed – respectively by the rumen and the caecum – thus prolonging contact time with the parasites.

Slow-release or sustained-release boluses have been used in small ruminants in various countries. In horses, the benzos are useful for mature strongyle removal but are less effective against migrating larval stages. Some resistance to these compounds has been seen in the cyathostomes or small strongyles. The benzimidazoles are also still widely used in pigs, small animals, and birds. The benzimidazoles bind with tubulin in the mitochondria of cells, preventing microtubule formation by interfering with its polymerisation – and thus have a wide range of effects on roundworms and sometimes against cestodes and trematodes.

Imidazothiazoles (levamisole)

Levamisole is the sole member of this group. In contrast to the benzimidazoles, levamisole is rapidly excreted and exerts its effect during a relatively short period of high concentration in the vicinity of the parasites. It is effective against most nematodes, but has no activity against cestodes and flukes, and it is not ovicidal. Although it has an acceptable safety margin, its use in animals in poor condition is contraindicated. It should also be used with caution in horses. Levamisole causes paralysis by acting as an agonist of the nicotinic acetylcholine receptors in the nerve ganglions of parasitic nematodes.

Halogenated salicylanilides (e.g. resorantel, niclosamide, rafoxanide, closantel) and the substituted phenols (e.g. disophenol, nitroxynil)

The members of these groups are mainly bound to the plasma proteins in the bloodstream. They are therefore mainly effective against parasites such as adult flukes and blood-sucking intestinal worms, such as H. contortus. Some salicylanilides have an effect on the immature stages of flukes – probably due to slow excretion and persistence in the blood over a period of weeks. Niclosamide and resorantel are used in ruminants and small animals for their activity against cestodes. The two chemical groups act by causing energy depletion resulting from the uncoupling of oxidative phosphorylation.

Macrocyclic lactones (avermectins and milbemycins)

The macrocyclic lactones (MLs) are derived from soil bacteria of the genus Streptomyces. They are classified into two main groups – the avermectins and the milbemycins. Avermectins include ivermectin, abamectin, doramectin, eprinomectin, and selamectin. The milbemycins include milbemycin and moxidectin. The MLs have a broad and potent effect against a wide range of parasites at low dosage rates, and their persistence in the body makes them highly effective as anthelmintics. The efficacy will vary with the specific ML and different parasites. The MLs are active against immature nematodes including hypobiotic larvae, and also some arthropods including some of the ectoparasites. The MLs can be given orally, as pour-ons, as injectables, or can be applied locally for the treatment of external parasites. They can be used in a wide range of domestic and other species.

Because they are excreted in the faeces, the toxicity of these drugs for dung-processing insects is, however, of concern. Under conditions of high ambient temperatures, ML degradation is rapid (7-14 days) – but lowering of the temperature increases its half life considerably and its degradation is thus much slower during the winter months in cold climates. The MLs are highly effective in cattle, sheep and pigs against most of the common nematodes; in horses they are used to control stomach worms, bots, strongyles and cyathostomes.

In dogs the MLs have been used to prevent heartworm infection and for the treatment of roundworms in the GIT. Selamectin is used for the control of intestinal parasites and for the control of fleas in dogs. MLs have been used off label in rabbits, rodents, birds, reptiles, and exotic and wild animal species.

Anthelmintic resistance against MLs is evident and it should be noted that there is cross resistance between the avermectins and the milbemycins. The mode of action of this group is on the glutamate-gated chloride channel receptor in nematodes – which results in paralysis of the parasite. It therefore does not affect cestodes and trematodes.

Isoquinalines (e.g. praziquantel, epsiquantel)

The isoquinalines have high activity against cestodes in ruminants, dogs, horses and poultry. They are useful for the treatment of the hydatid tapeworms such as Echinococcus granulosus in dogs. They have no activity against nematodes. The isoquinalines interfere with the regulation of intracellular Ca2+ concentrations which impairs the parasite’s motility and function.

Tetrahydropyrimidines (e.g. pyrantel, morantel, oxantel)

This group is still widely used because it is an affordable broad-spectrum anthelmintic against gastrointestinal nematodes. They are effective against adults and larvae in the intestinal lumen, but do not affect the migratory larval stages. These chemicals are used in most domestic animals, as a suspension, a drench, or in tablet form. They have a similar action to levamisole and their use is therefore contraindicated in debilitated animals.

Piperazine

This is a cheap active ingredient, effective against ascarids in all animal species and has a wide safety margin. Its main use in South Africa is in dogs, cats, birds, and pigs.

Nitroscanate

This is used in dogs as a broad-spectrum dewormer against nematodes and a wide range of tapeworms. The active ingredient has a similar effect to that of the substituted phenols – namely uncoupling oxidation.

New anthelmintic groups

Aminoacetonitrile derivatives (monepantel)

This compound has a novel activity since it interferes with nematode specific nicotinic acetylcholine receptors, and is highly effective for the treatment of gastro-intestinal nematodes. It is therefore indicated for the treatment of anthelmintic resistant strains of intestinal nematodes.

Spiroindoles (derquantel)

Derquantel is registered only in combination with abamectin to treat and control the adult and L4 intestinal roundworms of sheep. It is particularly useful for the control of resistant strains of H. contortus.

Cyclic octadepsipeptides

These are currently used in combination with praziquantel (for cestodes) as a treatment for ascarids and hookworms in cats.

Testing and regulation of anthelmintics in South Africa

The regulation and registration of anthelmintics in South Africa is controlled by the Department of Agriculture, Forestry and Fisheries (DAFF), in accordance with the Stock Remedies Act, Act 36 of 1947. The registration of anthelmintics is based on submission of data on efficacy, host safety, safety to the consumer of the products (meat, milk and fibre) obtained from treated animals, and also environmental impact.

The requirements for registration have been laid down by various technical experts over the years, and are in line with international guidelines. The Class system of classifying the efficacy of nematocides (class A, B, C and X) (Reinecke, 1983) has been replaced with the following definitions:

“Control”: a minimum efficacy of 90% against a parasite is required before it may be listed on the label of an anthelmintic product. A table of the parasites and stages that qualify, must appear on the label.

Aids in the control”: this is applicable if the efficacy of an anthelmintic product is less than 90%, but still above 60%. The list of parasites for which the product aids control must be stated on the label.

The remedies used for the cestodes of ruminants are graded by using a different system, as is shown in Table 3.

Some current shortcomings of the registration of remedies in South Africa are:

  • The cost and time delays of repeating in South Africa, sometimes unnecessarily, trials already performed overseas.
  • Incomplete guidelines for the required tests leading to varying requirements.
  • The slow process of evaluation.
  • Lack of expertise of the evaluators.
  • Lack of proper law enforcement by DAFF at sales outlets to ensure that only registered products are sold.

The registration of generic products

Generics are chemicals for which the original patent has expired. This allows companies other than the one which did the original research and development to manufacture the active ingredients. Generics are subject to the same registration requirements as the original patented active, because other factors such as the specific formulation can affect activity and efficacy. Although the quality of raw materials of generics may vary considerably depending on their origin, generic remedies are not necessarily inferior, but they may in fact have improved activity due to technological advances and formulation improvements. They are usually more affordable than the original product.

Table 3 Grading of cestodicides claiming efficacy against cestodes for ruminants in South Africa.

Class Definition
1 100% effective in >80% of flock
2 100% effective in >60% of flock
3 100% effective in 50% of flock
X Ineffective

Label coding for anthelmintic products

Anthelmintic products registered for ruminants in South Africa must carry coded labels that reflect the anthelmintic group. See Table 4 and Figure 18.

Methods of application of anthelmintics

Anthelmintics are available in various physical forms for administration, depending on the nature of the chemical, the method of administration, and the species involved. Some of the formulations used are discussed below:

Parenteral: some anthelmintics can be administered as injectables – e.g. levamisole and the macrocyclic lactones. They are sometimes combined with vaccine antigens.

Transdermal: formulation of some products with a carrier that allows absorption through the skin (e.g. ivermectin, abamectin, benzimidazoles) – either as a pour-on or a spot-on.

Oral: probably the most widely used method of administering anthelmintics; the form varies according to species, either as liquid drenches delivered by syringes, medication of feed or water, or by administering orally as tablets or pastes.

Table 4 Current coding of anthelmintics registered for ruminants in South Africa.

Group code Class Examples
1 Macrocyclic lactones Ivermectin
2 Benzimidazoles & Probenzimidazoles Fenbendazole Febantel
3 Imidazoles Levamisole
4 Halogenated salicylanilides Rafoxanide
5 Nitrophenols Nitroxynil
6 Sulphonamides Clorsulon
7 Organophosphates Haloxon
8 Isoquinoline Praziquantel
9 Miscellaneous

 

Figure 18 An example of a product label.

Definition of dose rates and indices used for anthelmintics

Therapeutic dosage (TD): the dose chosen as a balance between efficacy and safety. In practice this can vary between region, worm, and animal species. For example, in the past the TDs for sheep were assumed to be suitable for goats, but it has since been shown that goats have a higher metabolic rate and therefore may require a higher TD.

Minimal effective dose (MED): the minimal effective dose differs for different endoparasitic species, and therefore the dose recommended for a specific product is set high enough to be effective against the most tolerant, and economically important worm species.

Safety index (SI):a ratio between the LD50 and the TD – i.e. SI = LD50/TD. For some compounds the SI differs between species and even between breeds. For example, collies are so sensitive to ivermectin at the TD indicated for the treatment of gastrointestinal nematodes in dogs, that the use of the drug is contraindicated in this breed. The SI may also vary for the same compound – depending on the route of application.

Efficacy spectrum: an inexact term that refers to the range of endoparasites for which an anthelmintic is effective.

Treatment regimens

The appropriate treatment regimen will be determined by the type of animal/farming system and the most economically important helminth parasite to be controlled. The methods have different risks and benefits.

Interval dosing: synchronised treatment of the entire group of animals (or single animal) at intervals, based on the egg reappearance periods after treatment. This method applies strong selective pressure on the helminth populations.

Strategic dosing: dosing at set times based on epizootiological information which involves the treatment of entire groups of animals (or a single animal). This can be seasonal – for example strategic dosing before winter (May) and after winter (October).

Tactical dosing: this regimen is adapted to a changing situation, i.e. dosing in response to challenges and clinical signs when they occur.

Selective dosing: this method applies treatment only of those animals with significant faecal egg counts or other signs of infestation – e.g. anaemia as detected with the FAMACHA chart. This allows the establishment of naturallyacquired protective immunity while minimising anthelmintic use, but it is less useful in yearlings because of inadequate acquired immunity.

In-feed dosing: anthelmintics can be added to the feed using various strategies:

Continuous dosing: this is year-round, daily treatment. This treatment regime places very high selective pressure on helminth populations – which can contribute to the emergence of anthelmintic resis tanc e.

Single treatment dosing: certain anthelmintics are registered to be added to the feed. These are single-dose anthelmintics which need to be added to the feed at the dose appropriate for the animal to be treated, and in an amount of feed that will be taken at one feeding.

Judicious use of anthelmintics

It is essential to use anthelmintics judiciously to ensure optimal efficacy and to prevent the development of resistance.

  • Correct identification of the helminth involved: this should be done based on one or more diagnostic methods and confirmed at an expert laboratory whenever possible
  • Correct chemical for the control of the helminth must be selected.

Dosing technique must be correct.

  • Correct dose must be delivered. Dosing equipment must be carefully calibrated to ensure this.
  • Proper regimen for farming system: for example, an intensive farming system under irrigation will require more frequent dosing than an extensive system.
  • Monitoring the efficacy of dosing using the faecal egg count reduction tests.

Adverse reactions or side effects to anthelmintics

Toxicity: toxicity caused by anthelmintics is usually as a result of overdosing. The anthelmintic most commonly involved is levamisole, because it has a narrow safety margin. Levamisole overdosing is usually caused by a failure to dilute concentrates correctly, the incorrect estimation of the weight of animals, or faulty calibration of syringes.

Moxidectin is an ML which is deposited in the fat in normal animals – from where it is slowly released. Toxicity may therefore occur in thin animals because they are unable to store moxidectin, so resulting in animals being exposed to blood levels above the safety index.

Side effects: some anthelmintics cause unwanted effects in the target animal, for example oxyclozanide used in lactating cattle may lead to a drop in milk production. Some ivermectin formulations cause swellings of the skin in goats which may lead to suffocation if injected into the neck area.

Injuries: pharyngeal injuries can be caused by damaged or sub-standard dosing equipment.

Residues: there may be residual levels of anthelmintics in the milk or meat of treated animals. Manufacturers are required to determine a withdrawal period after treatment, after which the internationally designated maximum permissible levels are not exceeded.

Anthelmintic resistance

Anthelmintic resistance is defined as a heritable reduction in the sensitivity of a helminth population to the action of a drug. There are two theories about how this arises:

  • Inherent existence of drug-tolerant helminths
  • Genetic mutations induced by selective pressure applied using anthelmintics.

Some of the factors that contribute to the development of resistance are:

  • High treatment frequency.
  • Continuous use of a single active over a long period.
  • Targeting and timing of mass treatment.
  • Placing treated animals into a ‘worm-free’ camp after treatment (no opportunity to dilute the resistant gene).
  • Incorrect dosage.

The worm resistance situation in South Africa

Since small stock tend to require more frequent anthelmintic treatment than cattle, most cases of worm resistance occur in sheep and goat parasites such as Haemonchus contortus, Teladorsagia and Trichostrongylus spp. In the case of H. contortus some strains have been identified that are resistant to up to 5 different chemical groups. There is anecdotal evidence of resistance of the milk tapeworm, Moniezia, to niclosamide. Horse cyathostomes (small strongyles) have been shown to be resistant to the benzimidazoles and pyrantel (see helminths of horses).

Detection of anthelmintic resistance

It is essential to distinguish anthelmintic resistance from anthelmintic inefficacy. The latter can be caused by using the incorrect dose (under-dosing), faulty dosing equipment, using the wrong product, or an expired batch. Helminth resistance can occur on farms following the introduction of resistant strains – most often via infected stud animals – or frequent and long-term use of a specific active. If resistance is suspected, there are various tests that can be done to confirm this:

Faecal egg count reduction test (FECRT)

This method can be used for all gastrointestinal worm genera and is the main screening test used because of its ease of performance. The principle used is to compare the faecal egg counts of animals before and after treatments with various anthelmintic groups. The ideal is to use previously untreated young animals randomly allocated to a group of 15 animals – for each of the groups of anthelmintics to be tested. An untreated control group must be sampled as well for comparison.

Faecal egg counts performed on samples taken on the day of treatment are compared with those of a second set taken 10-14 days after treatment. The results are evaluated as follows:

FECR % = [1-(T2/T1 x C1/C2) x100]

where T and C represent the means of the treated and controls and the subscripts 1 and 2 the counts before and after treatment, respectively. The results of this will give an indication of the presence of resistance. The RESO method can also be used to evaluate the results.

More advanced tests

The FECRT is a relatively insensitive test and should only be used for screening purposes. It should be followed up by other additional laboratory tests such as the Egg Hatch Test, Larval Development Assay, Larval Motility/Paralysis Test, and PCR (H. contortus only). These are done at specialist laboratories.

The importance of refugia

Refugia is the term applied to the various stages of parasitic worms on the pasture that are not exposed to anthelmintics. It has been estimated that as much as 97% of the worm population occurs on the pasture in the form of ova and hatched larvae – and that only 3% are found in the host. Thus, if all sheep in a flock are dosed, 3% of the total worm population is exposed to chemical treatment. If the sheep are left on the same (infected) pasture, the surviving helminth progeny will be swamped by the overwhelming numbers of susceptible worms in refugia – thus diluting the genes in the worm population. The rate of selection for resistance is therefore negligible. However, if the entire flock is dosed and then moved to worm-free pastures, the entire cohort of parasites that develops on the new pasture is the progeny of resistant worms, and selection for resistance is accelerated.

It has been known for almost 20 years that it is essential for the untreated stages to survive on pastures so that they have a diluting effect on anthelmintic resistance genes. In practical terms this means that the “drench-all-and-move” system of treating and then moving animals to clean pastures must be avoided, because there will be no susceptible worms in refugia and only the progeny of resistant worms will survive and be present on the pasture. Farmers, and even veterinarians, resist this approach of maintaining refugia, probably because it seems counterintuitive and the farmer may even suspect that this is a marketing ploy to promote anthelmintic sales. However, research has shown that maintaining worms in refugia is vital to preventing or slowing the development of worm resistance to anthelmintics.

Preventing the development of anthelmintic resistance in worm populations

The main strategies for reducing the likelihood of worm resistance developing, or for slowing its development are:

Quarantine treatment of animals: all new animals should be kept in quarantine and dosed sequentially with two different active groups, before they are introduced into the rest of the herd/flock. Not adhering to this practice is the most common reason for the spread of resistance from stud farms where the animals are subjected to an intensive treatment regimen.

Reducing the frequency of anthelmintic usage: this can be done by using Targeted Selective Treatment (TST) strategies. The various methods for choosing animals for selective treatment are discussed below.

Vaccination against H. contortus will help reduce the number of treatments for this worm in stock and will boost immunity in young and pregnant animals.

Maintaining refugia: this concept is pivotal to understanding and preventing anthelmintic resistance in livestock. It must be applied as part of sustainable Integrated Parasite Management (SIPM), which is discussed below.

Targeted selective treatment (TST) of animals

It is a fact that within a flock or herd the vast majority of worms occur in a small number of hosts. This occurs because of the variability of the host’s ability to resist infection or to develop resistance with age. There is also a third category of animals, namely those that are resilient or able to resist even large worm burdens. In practice this differentia susceptibility of animals in a flock or herd results in some being apparently unaffected by verminosis, while others may die. The treatment of entire flocks causes a high selective pressure on the worms to develop resistance. If, however, susceptible animals can be identified, a smaller percentage of worms are selected for resistance, while a higher percentage of untreated worms are voiding eggs that will hatch into susceptible progeny – thus ensuring susceptible worms in refugia. This system of identifying animals that require treatment should then also be used as part of the selection process to identify animals for culling. This will ensure that the resistance of the flock as a whole to helminths will improve. Methods of identifying and targeting individual animals to be treated have been developed and tested.

FAMACHA system for categorising anaemia: the FAMACHA chart helps identify animals suffering from clinical anaemia, and can only be used for identifying small stock infected with blood-sucking worms. The FAMACHA chart, which was developed in South Africa, has been tested in various countries, and with favourable results. In addition, using the Best Linear Unbiased Prediction analysis – the heritability of the clinical results detected by FAMACHA compared favourably with haematocrit determination of anaemia. In summary, the FAMACHA method was found to be practical for on-farm application, although its effect on production still needs to be evaluated.

Targeted Selective Treatment (TST) based on production parameters: this method can be applied to non-blood-sucking worms such as Teladorsagia and Trichostrongylus – in which anthelmintic resistance has been detected. Various parameters such as Body Condition Scoring (BCS) and milk production are used to evaluate the performance of the host animal, as a measure of their immunity or resilience to worm infection. These approaches have been applied successfully, for example, in mutton sheep and dairy goats.

Sustainable integrated parasite management (SIPM)

No single worm-control method is sufficient for managing worms. For example, reducing drenching frequency alone is not necessarily sustainable if the correct ecological controls are not applied. The onus is on veterinarians and veterinary companies to encourage a responsible, multi-pronged approach to worm control, in order to ensure sustainability. There is advice available from most of the reliable and reputable companies marketing anthelmintics, and there are also systems available on the web such as the information provided at: www.afrivetplana.co.za, as shown below.