BIOLOGICAL CONTROL OF DISEASE IN DOMESTIC ANIMALS SUMMARY Biological control describes situations in which a living antagonist

SUMMARY Biological control describes situations in which a living antagonist (a predator, parasite, or a pathogen) is distributed by man to lower pest (parasite) populations to acceptable sub-clinical densities or to keep the population at a non-harmful level. Ideally, biological control has no negative effects on the environment, whereas chemical control is not always so harmless. Laboratory and field observations have revealed many organis-ms, such as viruses, bacteria, Nematophagous fungi, and predators as antagonists to pathogenic bacteria, nematodes, tick of domesticated animals. However, only very few of these antagonists have shown promising qualities as biological control agents within veterinary science. Keywords: Bacteriophage therapy, Bio-Control, Nematophagous fungi, Predators, Probiotic 1. INTRODUCTION Biological control (bio-control for short) is the use of animals, fungi, or other microbes to feed upon, parasitize or otherwise interfere with a targeted pest species. Successful bio-control programs usually significantly reduce the abundance of the pest, but in some cases, they simply prevent the damage caused by the pest without reducing pest abundance (Lockwood, 2000). Biological control has been increasingly a focus for regulators over the last 20 years or so with many countries requiring risk assessments to be carried out to try to predict environmental risk. Some countries require analyses of risks and benefits, and decisions are made on the basis of this balance (Klein et al., 2011). The economic benefit from ecosystem services associated with biological control provided by naturally occurring predators and pathogens has been estimated to be vast (Power, 2010). Parasitic nematodes cause serious infections in small ruminants and, as one of the greatest causes for loss of productivity plus compromised welfare in grazing ruminants throughout the world, constitute a serious problem for small ruminant livestock producers (Perry and Randolph, 1999). The anthelmintic resistant gastro-intestinal (GI) nematode populations constitute a major problem especially in small ruminants in the subtropics and tropics, but are also a serious threat to livestock in the rest of the world (Conder and Campbell, 1995). Therefore, the objective of this paper is; ? To highlight biological control of disease in animals 2. PATHOGENS AND THEIR POTENTIAL IN BIOLOGICAL CONTROL 2.1. Bacteriophage Bio-Control in Animals and Meat Products Bacteriophages are viruses that attack bacteria and cause bacterial lysis. They are specific to the host that they infect and kill. Therefore, they do not have any effects on other living organisms besides bacteria. Thus, they are an attractive alternative to antibiotics and could be used to overcome bacterial infection and antibiotic resistance (Huff et al., 2013). However, one constraint that could limit the application of phage by the oral route is that the effectiveness of the administered phage is rapidly reduced by acid, enzymes, and bile (Joerger, 2003). Bacteriophages are ubiquitous in the environment from the oceans, soil, deep sea vents, hotsprings, the water we consume and the food we eat (Miedzybrodski, 2005). Bacteriop-hages are imbued with several traits which give them advantages over antibiotics (Sulakvelidze and Barrow, 2005). Phages are both self-replicating and self-limiting, they will only actively replicate as long as susceptible hosts are available. They can be targeted towards specific pathogens which prevents the disruption of commensal microf-lora (dysbiosis) often seen following treatment with broad spectrum antibiotics. Animal trials in the West have also shown that the administration of phages both orally and parenterally does not produce any abnormal histological changes, morbidity or mortality (Carlton et al., 2005). Phages may be used prophylactically, therapeutically and in the sanitizing of surfaces. Their use in the human food chain has been calculated to be more cost effective than other treatments such as irradiation, freezing or improving consumer hygiene in the kitchen (Mangen et al., 2007). Most PT trials in food producing animals have been directed against important zoonotic pathogens, principally E. coli, Salmonella spp., Campylobacter spp. and Listeria spp. Antibiotic resistance among some of these bacteria is a major and growing concern (Threlfall et al., 2000). Bacteriophage pose a constant threat to bacteria because of their overwhelming abundance and their ability to adapt to better infect their bacterial host (Seed, 2015). 2.1.1. Food producing large animals E. coli O157:H7 numbers in the rectum of Holstein steers were significantly reduced (by up to 1.5 log10 cfu compared with controls) by applying a high titre (1010 PFU) of phages at the recto-anal junction and a low titre (106?PFU) in the drinking water (Matthews et al., 2006). If the incidence of E. coli O157:H7 in live cattle can be reduced, human health and safety will be improved because there will be reduced transmission into the human food chain and therefore fewer human exposures (Hynes and Wachsmuth, 2000). 2.1.2. Poultry The high population density of chickens in conventional rearing systems, which can reach hundreds of thousands on a single farm, increases the risk of a rapid spread of disease and concomitant economic losses. However, the same high population density also favors the spread of phages through a flock, facilitating and reducing the cost of treating a large number of animals. One poultry disease which has been targeted by PT is colibacillosis, an E. coli infection which causes airsacculitis, pericarditis, perihepatitis in chickens and is a significant cause of morbidity and mortality in the industry (Huff et al., 2002). Colibacillosis: Escherichia coli are a commensal bacterium of the gastrointestinal tract of birds. Not all strains cause diseases; however, some strains cause disease following exposure to certain conditions, which may include abnormal prevalence over other commensals, a weakened host immune system, or adverse environmental conditions (Barnes et al., 2008). Avian Colibacillosis is a complicated disease characterized by different signs and symptoms, including numerous organ lesions, typically pericarditis, airsacculitis, perihepatitis, and peritonitis. In its acute form, it causes septicaemia. The disease leads to high economic losses worldwide following high mortality rates, carcass rejection, and condemnation at slaughter (Ewers et al., 2004). A study by Xie and colleagues (2005) investigated the effect of phages on neonatal diarrhea in chickens and Lau showed that bacteriophage therapy alleviates severe clinical Colibacillosis in chicks (Lau et al., 2010). Salmonellosis: Salmonella spp. has been targeted in several PT trials involving poultry. This pathogen is a major cause of acute bacterial enteritis in man, with over 180 000 cases of salmonellosis reported in the EU during 2004. Contaminated poultry and eggs are widely accepted as a major source of Salmonella spp. In addition, some serovars of Salmonella can cause morbidity and mortality in chickens and survive in the farm environment for prolonged periods of time (EFSA, 2006). Fiorentin and colleagues (2005) used bacteriophages isolated from free?range chickens to reduce Salmonella enteritidis PT4 colonization of broiler chicks. Atterbury and colleague (2007) demonstrated that the caecal colonization of both S. enteritidis and S. typhimurium in broiler chickens could be reduced by up to 4.2log10 cycles through the oral administration of high titre (1011 PFU) phage suspensions. The chickens treated with a probiotic and bacteriophages showed 10 times fewer bacteria in the ileum, caecum, liver and spleen than did untreated challenged chickens (Torro et al, 2005). Campylobacteriosis: another important zoonotic pathogen in poultry which has been targeted by PT is Campylobacter spp. Poultry are widely accepted as an important reservoir of Campylobacter spp. In the human food chain (Jacob, 2000). Campylobacters readily colonize the chicken gut and have been recovered from a large proportion of fresh poultry products (Kramer et al., 2000). Campylobacter numbers have been reduced in the caeca of broiler chickens by 1-2 log10 cfu following repeated doses of phages (Wagenaar et al., 2005). A study by Loc-Carrillo and colleagues (2005) also evaluated the ability of phages to reduce the intestinal colonization of campylobacters. Atterbury and colleagues (2005) found that the Campyl-obacter populations in the caeca of naturally colonized broiler chickens are generally lower when phages are also present. 2.1.3. Surface decontamination of meat Poultry products have been widely used to study the efficacy of phage treatments of meat surfaces. Unsurprisingly, Campylobacter and Salmonella have been the most frequently targeted zoonotic pathogens on chicken meat using such treatments. Experiments by Atterbury and colleagues (2003) and Goode and colleagues (2003) showed that the application of phages onto the surface of chicken skin artificially contaminated with Campylobacter jejuni led to a reduction of 1–1.3 log10 cfu within 24h. Combining phage treatment with freezing the skin sections at ?20°C was more effective than either treatment used independently (Atterbury et al., 2003). In a further trial, Goode and colleagues (2003) demonstrated that applying a high titre of phages could reduce S. enteritidis numbers on contaminated chicken skin to below detectable levels within 48h. A small number of studies have examined the efficacy of phages against Salmonella in chicken portions and processed products. For example, phages have been used to reduce numbers of S. typhimurium DT104 inoculated onto chicken sausages (Whichard et al., 2003). The control of Listeria monocytogenes in meats raises additional difficulties due to the ability of this pathogen to grow at low temperatures. In a study by Dykes and Moorhead (2002), bacteriophages alone had no effect on the growth of L. monocytogenes in beef broth. 2.2. Probiotics The word “probiotic” comes from the Greek words “pro” and “biotic,” meaning “for the life” (Gibson, 2000). It is thought to reduce potentially harmful bacteria from the intestine and to improve microbial balances in intestine and exert positive health effects on the host (Young, 2008). Today, the term “probiotic” refers to “live microorganisms which, administered in adequate amounts, confer a beneficial physiological effect on the host,” according to the Food and Agriculture Organization and World Health Organizati-on (FAO, 2002). The probiotic bacteria must fulfill the following functional aspects; it must be gram positive organism, survival after passage through acid and bile, adherence to the animal intestinal cells, able to grow in the gut, should have defined dosage regimes and durations of use, antagonism action against pathogenic and carcinogenic bacteria, it must show a specific health benefit measured by defined tests (in vitro and/or animal) (Vouloumanou, 2009). Four different mechanisms under research by which probiotics may defend against pathogens in the intestine: Probiotics may compete against pathogens for the same essential nutrients, leaving less available for the pathogen to utilize (A). They may bind to adhesion sites, preventing pathogen attachment by reducing the surface area available for pathogen colonization (B). Signaling of immune cells by probiotics may result in the secretion of cytokines, targeting the pathogen for destruction (C). Finally, probiotics may attack pathogenic organisms by releasing bacteriocins, killing them directly (D) (Bermudez, 2012). 2.2.1. Probiotics and animal health Salmonella spp. Campylobacter jejuni and Clostridium perfringens have been show to infect chickens and hens increasing the risk of contamination through the food chain resulting in a harmful condition both for poultry and human (Humphrey et al., 2007). So, probiotics act as a biological alternative in the preharvest control of Campylobacter, Salmonella, and Escherichia coli (Ricke et al., 2012). In horse, probiotic effects to the digestive compartment mainly caecum-colon. Fiber digestibility increased in the horse colon and modulated the balance of hindgut bacterial communities through supplementation with live yeast, consequently decreased risk of lactic acidosis (Jouany et al., 2008). Environmental stresses, mainly management methods, diet, etc. can affect swine production causing discrepancy in the intestinal diversity leading to a risk factor for pathogen infections (Gaggia et al., 2010). Weaning and post-weaning periods are the most stressful conditions in commercial porcine production resulting in transient drop in feed intake, inhibition of growth performance, negative influence on the immune function and the intestinal microbiota equilibrium finally leading to increased susceptibility to gut disorders, infections and diarrhea in the pigs (Modesto et al., 2009). The majority of the researches showed a health beneficial effect of probiotic applied in piglets; increasing the number of intestinal beneficial bacteria, reducing the load of pathogenic bacteria, enhanced defensive tools towards pathogenic invasion and increased villi morphology and function (Chaucheyras, 2010). 2.2.2. Probiotics and disease conditions Bacterial vaginosis: is considered as an overgrowth of anaerobic organisms combined with a loss of the protective lactobacilli normally found in the healthy vagina. Recently, daily oral intake of probiotic strains Lactobacillus rhamnosus GR-I and Lactobacillus fermentum RC-14, resulted in asymptomatic bacterial vaginosis patients reverting to normal lactobacilli dominated vaginal micro-flora (Reid et al., 2001). Inflammatory bowel disease: the luminal bacterial flora and immunological responses play a major role in initiation and perpetuation of chronic inflammatory bowel disease. Probiotics by their immunomodulatory and bowel flora manipulating properties show a promising effect in treatment of chronic inflammatory bowel disease (Schultz et al., 2000). Antibiotics associated diarrhea: is the most common complication of the most antibiotics therapy (Guarner, 2012). Antimicrobial treatment disturbs the ecological balance of the normal micro flora, which can result in diarrhea (Ciorba, 2012). Thirty nine percent (39%) of the hospitalized patients receiving antibiotics therapy which disrupt the flora which cause antibiotics associated diarrhea (Surawice, 2003).The normal gut flora possesses a quality called colonization resistance, which prevents the overgrowth of pathogens; some of these antibacterial effects may be caused by volatile fatty acids and a decrease in pH of the luminal contents (Bartlett, 2006). Administration of certain probiotics strains before and during antibiotic treatment reduce the frequency and/or duration of episodes of antibiotic-associated diarrhea and the severity of symptoms for the treatment of Lactobacillus GG, and Enterococcus, non-pathogenic yeast Saccharomyces boulardii are the most extensively studied strain of probiotics, has shown to be effective in both preventing and treating these forms of diarrhea (Mylonakis, 2001). A list of the probiotic species used in studies or in livestock feeding and health is shown in Table 1. Table 1: Some microbial species of potential use as livestock probiotics with their benefits. Microorganisms Animals Common Benefits Reference Pig Lactobacillus acidophilus Saccharomyces cerevisiae Limit constipation Decrease stress (Azevedo et al., 2012 and Price, 2010) Poultry L. animalis Reduce mortality Increase carcass quality and decreasing contamination (Reid, 2000) Cow L. animalis Increase feed efficiency, milk yield, quality Reduce risk of pathogen colonization (Agazzi et al., 2014) Horse Saccharomyces cerevisiae Limit diarrhea Avoid hindgut disorders (acidosis, colic) (Mackenthun et al., 2013) 2.3. Biological Control of Parasites The conventional system of control of gastrointestinal parasitic nematodes in cattle is based on the regular administration of anthelmintic chemical drugs in cattle herds; although farmers excessively use these drugs due to their growing inefficacy (Ramos et al., 2016). On the other hand, the use of anthelmintic drugs brings other problems i.e., the possible presence of drug residues in meat, milk or even in sub- products for human being consumption, which is considered as an important potential risk of public health (Beyene, 2016). Likewise, the anthelmintic compounds administered in the animals are eventually spelled together with the animal faeces to the soil contaminating the environ-ment and affecting beneficial microorganisms (Adler et al., 2016). 2.3.1. Nematophagous fungi as bio-control agent Many species of Arthrobotrys have been found to show the predatory activity against both plant and animal parasitic nematodes (Wang et al., 2013). Several researchers have studied different nematophagous fungi against root-knot nematodes (Singh et al., 2013). During the last decades the study of nematophagous fungi has gained great attention as a possible biotechnological and environmentally friendly way to reduce the gastrointestinal parasitic nematodiasis in ruminants (Ortiz et al., 2017). For animal parasitic nematodes, Duddingtonia flagrans has been extensively for is superior activity in reducing nematode larvae (Nagee and Mukhopadhyaya, 2001). The nematode trapping fungi Duddingtonia flagrans has gained a good reputation as an alternative of control, different to the chemical anthelmintic drugs; mainly because of the continuous and frequent use of such compounds have triggered an imminent presentation of anthelmintic resistance in parasites against most of commercially available anthelmint-ic drugs (Garcia et al., 2016). Nematophagous fungi possess the unique ability of trap nematodes and kill them. To capture nematodes they produce different types of trapping structure including adhesive networks, adhesive columnar, constricting and non-constricting rings or they use spore as infectious agents (Nordbring, 2000). Figure 1: Trapping weaponry of nematophagous fungi. Different types of trapping structure of nematophagous fungi. (a) Adhesive network, (b) attaching knob, (c) Non constricting, (d) Constructing ring, and (e) Adhesive- zoospores Source: (Giat, 2008). Figure 2: Trapped nematodes inside different trapping strictures. Mechanism of trapping nematodes: (a) nematode trapped inside constituting ring, (b) nematode trapped within adhesive network and (c) nematode trapped by adhesive hyphal knobs Source: (Jansson, 1997). 2.3.2. Bacteria Bacillus thuringiensis (Bt) is a gram-positive bacterium occurring naturally in the soil and on plants. Bt strains synthesize Crystal (Cry) and Cytolytic (Cyt) toxins, (also known as ?-endotoxins), at the onset of sporulation and during the stationary growth phase as parasporal crystalline inclusions. Once ingested by insects, these crystals are solubilized in the midgut, the toxins are then proteolytically activated by midgut proteases and bind to specific receptors located in the insect cell membrane, leading to cell disruption and insect death (Bravo, 2007). Bt Cry and Cyt toxins belong to a class of bacterial toxins known as pore-forming toxins (PFT) that are secreted as water-soluble proteins undergoing conformational changes in order to insert into, or to translocate across, cell membranes of their host. There are two main groups of PFT: (i) the ?-helical toxins, in which ?-helix regions form the trans-membrane pore, and (ii) the ?-barrel toxins, that insert into the membrane by forming a ?-barrel composed of ?sheet hairpins from each monomer (Parker and Feil, 2005). B. thuringiensis has the advantage of being harmless for humans, domestic animals and plants, and their proteins are highly biodegradable (Gomez, 2001), making it a suitable and viable option to perform biological control on the parasites that infect mammals (Siegel, 2001). Certain proteins have been used in goats and ewes infected with Haemonchus contortus, resulting in effective control against larval and adult stages of this parasite (Lopez, 2006). Furthermore, four strains of B. thuringiensis, exhibited to-xicity against Rhipicephalus (Boophilus) microplus, an ectopar-asite that affects cattle (Fernandez, 2010). 3. PREDATORS AND THEIR POTENTIAL IN BIOLOGICAL CONTROL Many tick bio-suppressors such as ants, beetles and many bird species are general predators that feed occasionally on ticks, therefore their populations do not depend on the sizes of the tick populations. General predators can sometimes affect the size of a tick population in nature, but manipulating their populations to reduce tick numbers would require large increases in the predator population, which could also cause large changes in populations of non-target species in natural areas (Symondson et al., 2002). 3.1. Mammals Some mammals are insectivorous. As an example, Sorex araneus prey on ticks and at times preferred them to alternative foods. Shrews seem to locate hidden ticks by their smell. Mice and rats are often cited as preying on ticks (Mwangi et al., 1991). Mammals are typically consuming ticks during self-grooming. For example, laboratory studies demonstrate that significant numbers of larval blacklegged ticks are consumed by white-footed mice during self-grooming (Shaw et al., 2003). Nevertheless, a high proportion of ticks encountering mice survive and feed to repletion, and abundance of blacklegged ticks are positively correlated with that of mice (Ostfeld et al., 2001). 3.2. Birds The most obvious vertebrate consumers of ticks are Buphagus spp., pan-African birds that specialize on ticks feeding on both wild and domestic large mammals. The daily intake of ticks by Buphagus spp. is reported to be in the hundreds (adult ticks) to thousands (nymphs) (Samish, 2000). Buphagus spp. populations have decreased along with reductions in the numbers of game animals, increased use of bird-poisoning acaricides and possibly also decreased tick populations (Robertson and Jarvis, 2000). Scrub jays were observed to spend 89% of their time searching deer for ectoparasites. In Africa, chickens are natural predators of ticks and actually pick ticks from the bodies of cattle as well as from the vegetation (Isenhart and DeSante, 1985). 3.3. Arthropods Occasionally, female arthropods are eaten by males. As an example, cannibalism of engorged females by males is reported mainly for argasid ticks. In ticks all unfed stages may parasitize engorged nymphs or females. Cannibalism is often found during overcrowding on a host, in laboratory colonies when there is a lack of host animals (Oliver et al., 1986). Nine genera of spiders from six families were reported to pray on five hard tick and two soft ticks’ genera (Carroll, 1995). Application of Solenopsis invicta (species of ants known to be tick predators) in the United States markedly reduced the number of anaplasmosis in seropositive cattle in Louisiana (Jemal and Hugh, 1993). 4. CONCLUSION AND RECOMMENDATIONS Probiotics can turn many health benefits to the human and animals. Probiotics industry also faces challenges when claiming the health benefits. Phage therapy has potential for control of both animal and zoonotic pathogens in cattle, pigs and poultry. The potential of combining antibiotic therapy and phage therapy, the use of phage cocktails, or the use of phage protein products may be the best areas for successful phage treatment of infections. Few promising examples of biological control of insects and parasitic nematodes are found in veterinary science. The lack of success may arise from lack of enough knowled-ge and industries about complex natural biological systems and the antagonists which may be found in nature. Based on the above conclusion the following recommendations are forwarded: ? They should be able to select one or more natural antagonists virulent to the different important pest organisms. ? To bring biological control from experimental to commercial success, scientists obviously need practical supports from food industry. ? Evaluation of the effectiveness of bio-control agents should involve consideration of long-term impacts rather than only short-term yield. ? The technician must carefully administered biological agents into animal tissues. ? The handling and application of biological control products should fit in with standard farm practice.