Pathophysiology of Gastro-intestinal Nematode Infections in Ruminants
I.Maqbool 1, Z.A. Wani2, K.H. Bulbul3, I.M. Allaie,2 R.A. Shahardar4, Aiman Ashraf5 and S.R.Tramboo5
1Veterinary Assistant surgeon, Department of Sheep Husbandry, Kashmir
2Assistant Professor, Division of Veterinary Parasitology, F.V.Sc. & A.H, SKUAST-K, Shuhama, Srinagar, J&K, 190006.
3Associate Professor, Division of Veterinary Parasitology, F.V.Sc. & A.H, SKUAST-K, Shuhama, Srinagar, J&K, 190006.
4Professor & Head, Division of Veterinary Parasitology, F.V.Sc. & A.H, SKUAST-K, Shuhama, Srinagar, J&K, 190006.
5Contractual lecturer, Division of Veterinary Parasitology, F.V.Sc. & A.H, SKUAST-K, Shuhama, Srinagar, J&K, 190006.
Abstract
Parasitic infections of the gastrointestinal tract are one of the major causes of diseases in man and animals. In case of animals, the major pathogenic parasites of the gastrointestinal tract are nematodes, particularly of the family Trichostrongylidae, trematodes such as Fasciola hepatica and Schistosoma bovis, and protozoan parasites, belonging to the genus Eimeria, while in humans, the principal pathogenic gastrointestinal nematodes are hookworms and Ascaris. These parasites result in changes in body composition, blood, enzymes as well as hormones. Many of the pathological findings reflect the clinical signs, for example, poor body condition and weight loss, while others relate to specific changes within the gastrointestinal tract. There are a number of characteristic changes in blood constituents, the most notable being hypoalbuminaemia and commonly, a depression in the serum total protein concentration. Abomasal parasitism is associated with characteristic increases in the concentration of pepsinogen in the blood and this finding has become the basis of a useful diagnostic test for abomasal trichostrongylosis. Therefore, this review focusses on pathophysiological effects of gastrointestinal nematode parasites particularly in ruminants.
Key words: Gastrointestinal, nematodes, parasites, pathophysiology.
Introduction
Gastro-intestinal nematodosis infection continues to be a major constraint on animal productivity throughout the world (Mac Rae, 1993). Disease caused by nematodes both in clinical and subclinical presentations result in major losses to animal health and production (Charlier et al., 2009). Blood feeding species are particularly pathogenic, but lumen developing nematodes also impair metabolism and cause negative nitrogen balance (Parkins et al., 1973). Major GI nematodes of ruminants include Haemonchus spp., Ostertagia spp., Cooperia spp., Nematodirus spp., Bunostomum spp., Strongyloides spp., Trichostrongylus spp., Oesophagostomum spp., Chabertia spp., Trichuris spp. and Cappillaria spp.
Generalized life cycle of GI nematodes
Major species of GI nematodes affecting ruminants belong to family Trichostrongylidae (Haemonchus, Telodorsagia, Cooperia, Trichostrongylus and Nematodirus) (Soulsby, 1982). In general life cycle of nematodes can be divided into two phases a) Free living phase in the environment and b) Parasitic phase in the host. The eggs are passed in the faeces of the host and under suitable conditions, infective third stage is produced within four to six days. Following ingestion of infective larvae, exsheathment of the retained sheath occurs before the parasitic life cycle begins.
Generalized effects of GI nematodes include:
- Utilisation of host’s nutrients g. Ascarid worms
- Utilisation of host’s non nutrient substances like:
Blood: Haemonchus, Hookworms; Tissues: Chabertia, Trichostrongylus; Intestinal obstruction: Ascaris; Changes/reduction in the absorptive surface of intestine (intestinal nodular worms of ruminants e.g. Oesophagostomum.
- Damage to host tissues
At the time of entry: Hookworms, Strongyloides; During migration: Ascarids, Hook worms, Lungworm; After reaching prediliction site: Ostertagia, Oesophagostomum.
- Tissue changes like
Hypertrophy: Spirocerca, Gongylonema; Hyperplasia: Ostertagia; Neoplasia: Gongylonema, Spirocerca; Metaplasia: Lungworms.
Besides these various secretory & excretory products of parasites are toxic which are absorbed by host leading to various disease conditions.
Pathophysiology:
Pathophysiology deals with study of convergence of pathology with physiology. Pathology describes conditions typically observed during a disease state, while as physiology is the biological discipline that describes normal processes or mechanism operating within an organism.
Pathophysiology of nematode infection has been focused on three main areas:
- Mechanisms of appetite depression
- Changes in gastrointestinal function
- Alterations in protein metabolism
Mechanism of appetite depression:
Reduced appetite is considered as the major factor contributing to impaired nutrition in parasitized animals (Skyes and Coop, 1977). Abomasal parasites alter gut motility and reduce the rate and flow of digesta and abomasal volume (Dynes et al., 1998). Two hypothalamic neuropeptides, neuropeptide Y (NPY), and corticotropin-releasing factor (CRF) appear to play key physiological roles in the regulation of energy homeostasis by modulating feed intake (Horbury et al., 1995). Others factors include distension of the reticulo-rumen, abomasum or intestine, raised circulating secretin, gastrin and cholecystokinin (CCK) levels that affect the appetite of the animals infected with GI nematodes.
Changes in gastrointestinal function
Pathogenesis due to diarrhoea:
Diarrhoea is one of the most severe health concerns faced by grazing sheep worldwide., it leads to loss of bodyweight and condition, causes soiling of the wool around breech of the animal and contaminated meat carcasses in the abattoir (Broughan and Wall, 2007; Jacobson et al., 2009). GI nematode parasites (mainly T. circumcinta and Trichostrongylus spp.) are major cause of diarrhoea in grazing sheep, particularly in animal of post weaning age (Sargison, 2004). Heavy infection with intestinal parasites such as Trichostrongylus spp. leads to severe atrophy, decreased villous, cryptic ratios and goblet cell hyperplasia as well as sloughing of enterocytes into the intestinal lumen due to increased turnover of GI mucosa (Holmes, 1985). Basic mechanism of diarrhea reveals that secretion in the GI tract exceeds absorption (Ratnaike, 2000). Causes of malabsorption can be broadly grouped into three categories a) Mucosal damage b) Secretagogues c) Osmotic pressure. Direct mucosal damage is caused by the presence of helminth parasites resulting in decreased villous, cryptic ratios and other damage to mucosal architecture (Farthing, 2003). Secretory diarrhoea is caused by the actions of various physiological mediators, such as prostaglandins (PG) E2. These markedly increase intracellular messengers such as cAMP and calcium resulting in disruption of tight junction proteins in the intestinal epithelium and change in net flux of ions across the intestinal epithelium. Osmotic pressure is caused by the presence of osmotic reagents such as undigested food in the intestinal lumen. This reduces the capacity of intestinal tissue to carry out its normal function i.e., establish an osmotic gradient to absorb water from the lumen leading to fluid retention and watery diarrhoea.
Acid inhibition and parietal cell loss:
Acid is generated in the parietal cells in the fundic region by an H+, K+-ATPase (proton pump) which has a high oxygen requirement. Excretory-secretory (ES) products/chemicals are responsible for blocking of the proton pump. ES products interfere acid production with the complex physiological regulation of the parietal cell loss (Schubert, 1994). Worm excretory/ secretory products may not be direct parietal cell inhibitors, but could inhibit histamine secretion by enterochromaffin like cells. Worm chemicals could act by stimulating inflammation and release of cytokines such as IL-1 and TNF-ᾳ (Potent inhibitors of Parietal cells) (Robert et al., 1991; Beales & Calam, 1998). Large numbers of eosinophils and neutrophils accumulate in parasitized tissues and both cell types are capable of extensive tissue damage through their oxidative bursts (Crabtree, 1991). Eosinophilic chemotactic factors have been found wide range of parasites including O. ostertagi (Klesius et al., 1986). Parietal cells with diluted canaliculi and degenerative changes typical of necrosis (Karam.1993) have been reported in calves infected with O. ostertagi (Murray et al. 1970), or T. axei (Ross et al., 1971) and in sheep infected with O. circumcinta (Scott et al., 2000).The rapidity of acid inhibition after adult worm transfer and the equally rapid recovery when parasites are removed by anthelmintic treatment suggest parasitic chemicals may be responsible (Dakkak and Daoudi A, 1985; Scott et al., 2000). Neither adult nor L4 Ostertagia or Haemonchus survived for long in solutions the same pH as normal abomasal contents. Raising the pH may increase egg laying capacity of certain worms e.g., for haemonchosis, it was maximum between 4 & 4.5.
- Hyperpepsinogenaemia:
Hyperpepsinogenaemia usually occurs before abomasal pH and serum gastrin increase (Jennings et al., 1966). It has been attributed to increased leakage back into blood through junctions of immature cells in the gland and failure of pepsinogen conversion to pepsin when abomasal pH rise (Jennings et al., 1966).
Hypergastrinaemia:
Increased circulating gastrin levels in abomasal parasitism (Lawton et al., 1996) may have multiple effects as gastrin plays a central role in gastric physiology. Gastrin is the principal acid secretogogue during a meal (Blair et al., 1987). It acts as a key growth factor in maintaining the architecture of the fundic mucosa and is essential in maintaining the proton pump in the parietal cells. Gastrin does stimulate Parietal cells directly but principally act by increasing histamine secretion from ECL cells. Low luminal pH acts as a brake on gastrin secretion and influences G-cell and D cell numbers as well as gastrin and somatostatin mRNA levels. Removal of acid feedback has been accepted as a major cause of hypergastrinemia in parasitized animal. Parasite ES products may stimulate the G cell or cause the release of inflammatory mediators known to stimulate gastrin secretion such as Histamine TNF-ᾳ and IL-1β (Lehman et al., 1996). Inflammation is an attractive explanation for serum gastrin remaining high when abomasal pH returns to near normal levels around patency (Lawton et al., 1996). Despite increased gastrin synthesis, antral tissue gastrin becomes depleted in parasitized animals either because of hypersecretion or physical damage to the G- cells. Cell demage is a likely explanation for the absence of hypergastrinemia when abomasal pH increased in sheep infected with a strain of O. circumcincta which forms nodules mainly in the pylorus and causes massive antral thickening and inflammation (Simcock et al., 1999).
Abomasal microbes:
Rumen microbes are largely inactivated in the unparasitized abomasum (Simcock et al., 1999). Bacteria survive in greater numbers as the pH rises in the parasitized sheep. Aerotolerant bacteria were increased in abomasal contents of O. ostertagi infected calves (Jennings et al., 1966). Soluble microbes from abomasal microbes and abomasal contents with a raised pH from parasitized sheep both inhibit gastrin release from ovine abomasal tissue in vitro. Abomasal parasitism is associated with increase in depth and weight of fundic mucosa and altered cellular composition of glands. Local lesions are centered on parasitized glands which are dilated and lined by flat epithelium devoid of secretory cells and surrounding gland show mucous cell hyperplasia with fewer parietal and chief cells. A similar generalized histopathology is seen after adult O. circumcincta transfer (Scott et al., 2000) and in haemonchosis, in the non-nodular areas in Ostertagia infection (Scott et al., 1988). Stretching of the glands by the larvae is generally assumed to be a key factor, probably causing cell loss by disrupting the interaction of epithelial cells with the basement membrane. Inhibition and loss of parietal cells occurs rapidly (1-2days after adult O. circumcincta transplant) (Scott et al., 2000). Mucous cell hyperplasia and inhibition of the differentiation of the parietal and mature chief cells is promoted by the EPG family of peptides that includes: EGF, TGF-ᾳ, Amphiregulin Heparin –binding EGF.
Alterations in protein metabolism
Alterations in protein metabolism have been well documented in ruminants harbouring monospecific infections with either abomasal or intestinal nematodes (Fox, 1997). Intense changes in protein metabolism may be consistently found to involve decreased muscle synthesis and increased urinary nitrogen excretion (Hammerberg, 1986). Because of the well-recognized loss of plasma proteins into the gut lumen and cellular damage at the mucosa occurring during nematode infections of the abomasum and duodenum, it has been assumed that protein is being lost in faeces or not absorbed; however, this loss has proved not to be as significant as postabsorptive protein catabolism in these infections(Hammerberg, 1986). Only when the colon and cecum are involved in protein-losing infections is the loss of protein into the faeces significant. The mechanisms by which gastrointestinal nematode infections result in such altered host metabolic states are not known, but suggestions have been made that parasites directly or indirectly alter gut hormone levels.
Conclusion
Helminth parasites can have a wide range of pathophysiological effects on the host as they reside in intestinal wall gastrointestinal tract and cause a variety of disorders like diarrhea, dysentery, vomiting, lack of appetite, hematuria, abdominal distension, loss of weight, abdominal pain, nausea, and iron deficiency anemia. In addition to these effects these parasites are associated with marked disturbances in heart function and the nervous, immune and urinary systems. Improvement of personal and environmental hygiene is very important to prevent from infecting by those intestinal parasites followed by strategic deworming of livestock against pathogenic gastrointestinal nematode parasites. There is also a need to examine in greater detail the factors which can modulate pathophysiological responses by the host to parasitic infections.
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