Are We Willing to Accept a Degree of Loose Stools in Piglets During the Post-Weaning Period in the Era of ZnO Ban and Reduction of Antimicrobial Use?

Post-Weaning Diarrhea (PWD) due to Enterotoxigenic E. coli (ETEC) in pigs is a worldwide economically important disease associated with abnormal fecal consistency and higher use of antimicrobials. Currently, strategies for prevention and control of PWD due to ETEC are the in-feed use of ZnO and antimicrobials, e.g. colistin. However, new European regulations have been established resulting in the ban of ZnO by 2022, combined with more stringent advice on prudent use of antimicrobials and general reduction in the antimicrobial use. In the field, clinical fecal consistency is one of the most important evaluation criteria for efficacy of the currently used and novel alternative strategies to prevent and control PWD due to ETEC. Many of these alternative strategies reduce the number of pathogenic bacteria in the gut, resulting in a decreased clinical severity of PWD. This leads to an improved fecal clinical score, although a temporary deterioration in fecal consistency might still occur within the most critical period of PWD. In order to assure a long-lasting and sustainable reduction in antimicrobial use, a change in attitude towards evaluation of clinical efficacy of alternative strategies be should taken by both swine farmers and their field veterinarians. Abbreviations: CVMP: Committee for Veterinary Medicinal Products; ETEC: Enterotoxigenic Escherichia coli; FCS: Fecal Clinical Score; IAV-S: Influenza A Virus – Swine; LT: Thermo-labile Toxin; Medium Chain Fatty Acids (MCFAs); PCV-2: Porcine Circo Virustype 2; ppm: Parts Per Million; PRRSV: Porcine Reproductive and Respiratory Syndrome Virus; PWD: Post-Weaning Diarrhea; STa: Thermo-Stabile Toxin a; STb: Thermo-Stabile Toxin b; Stx2e: Shiga-Toxin 2e; ZnO: Zinc Oxide Received: September 23, 2020

isolated from cases of PWD urges the need for alternative control measures [14][15][16][17][18]. From the late 1980's onwards, several studies on zinc supply to post-weaned piglets have been performed. Several nutritional studies demonstrated the effects of dietary zinc oxide (ZnO) in the prevention and healing of PWD [19]. Therefore, ZnO has been admitted in the prevention and control of PWD at levels up to 3,000 parts per million (ppm) through the feed for a maximum of 14 days post-weaning. However, the Committee for Veterinary Medicinal Products (CVMP) has recently decided that the use of ZnO in post-weaning diets should be phased out the latest by 2022 throughout the EU [20]. Several alternative strategies have been explored to increase intestinal health and decrease incidence of PWD due to E. coli in post-weaned piglets [21][22][23]. Overall, inclusion of additional dietary fiber and reduction of crude protein levels in post-weaning diets seemed to be an effective nutritional strategy that may counteract the negative effects of protein fermentation in the pig gut [22,[24][25][26]. Although specific fermentable carbohydrates combined with reduced crude protein content altered the microflora and fermentation patterns in the gastrointestinal tract of post-weaned piglets, these favorable effects did not necessarily result in increased growth performance [27]. Other feeding strategies were more focused on feed consistency, thereby feeding more coarsely ground meal to the post-weaned piglets [28].
Coarsely ground feed meals change the physico-chemical conditions in the stomach, thereby increasing concentrations of organic acids which lower the pH. This promotes growth of anaerobic lactic acid bacteria and reduces survival of E. coli during passage through the stomach [28]. Fermentation of undigested dietary protein and endogenous proteins in the large intestines yield putative toxic metabolites that can impair epithelial integrity and promote enteric disorders such as PWD [29]. Incidence and severity of PWD may also be influenced by addition of probiotics to the diet, which may change the fermentation profile and thus promote gut health [30]. Furthermore, Medium Chain Fatty Acids (MCFAs) can neutralize bacterial metabolites in the small intestine [31]. However, efficacy of these alternative strategies is variable among different farms and over time, depending on multiple inferring factors such as specific feeding strategies and equipment, type of housing and climate control, number of piglets per pen or presence of other concurrent pathogens (e.g. PRRSV, PCV-2, IAV-S, …)

Fecal Clinical Score: an Objective Look at PWD
In order to score fecal consistency during PWD, a Fecal Clinical Score (FCS) was developed with a fecal consistency score from 0 to 4 with and appropriate description [32,33] and applied under field conditions to objectively assess the fecal consistency during the post-weaning period (Table 1) throughout time and in the presence of multiple persons assessing the clinical fecal consistency [34][35][36]. The fecal clinical score is extensively described and illustrated in Table 1. Under field conditions, clear advantages have been observed in using the FCS to evaluate the effect of specific preventive or prophylactic interventions during the post-weaning period [34][35][36]. Table 1: Fecal clinical score from 0 to 4 with a realistic picture and a generic description of the consistency and the ratio between the liquid and solid fraction within the fecal material. coli F4 or E. coli F4 and F18 vaccine has demonstrated efficacy against PWD due to F4-ETEC or F4-ETEC and F18-ETEC [32,33].
Immunization against the F4-ETEC and F18-ETEC pathogens resulted in decreased severity and duration of PWD clinical signs, as determined by FCS, and reduced fecal shedding of F4-ETEC and F18-ETEC [32,33]. The reduced clinical signs were based on the absence of fecal droppings with an FCS above 2, according to the previously described FCS (Table 1). This means that a temporary deviation of FCS from normal fecal consistency (FCS = 0) should be acceptable as long as the FCS does not increase to FCS levels of 3 or 4. These scores are characterized by a higher volume of liquid as compared to solid material in the fecal droppings. Moreover, these registration studies [32,33] have also shown that when FCS temporarily increasing up to 1 or 2, no negative effects on piglets' performances were present since an increased weight gain was demonstrated following vaccination with the E. coli F4 vaccine [32].

Conclusion
In conclusion, several novel strategies towards PWD due to ETEC have been applied or will be introduced in the field in the near future. Many of these strategies impact the reduction in the number of pathogenic bacteria that may induce or impact PWD due to ETEC. This reduction of pathogenic bacteria clearly impacts the clinical signs of PWD, however, in many cases a temporary deterioration in fecal consistency may occur, although the impact on piglets' performance remains minimal. Therefore, a new attitude towards evaluation of the clinical efficacy of alternative strategies to prevent or control PWD due to ETEC should be taken by both swine farmers and their field veterinarians in the near future. Only through a drastic change in attitude, we will collectively be able to prevent or control PWD due to ETEC without a risk to increase the use of antimicrobials and thus compromise the current process towards prudent use of antimicrobials resulting in a long-lasting and sustainable reduction in antimicrobial use during this critical phase in swine production worldwide.