Efficacy of different ionophore-nicarbazin combination products in coccidiosis challenge model

I. INTRODUCTION

Coccidiosis caused by unicellular protozoa from the genus Eimeria is one of the major veterinary challenges in the poultry industry, causing annual losses of more than $14 billion worldwide (Blake et al., 2020). Eimeria spp. need to invade intestinal epithelial cells to replicate. This leads to destruction of the intestinal epithelia, inflammation, reduced nutrient absorption and secondary infections such as nonspecific enteritis (also referred to as dysbacteriosis), and necrotic enteritis. In some cases, coccidiosis leads to intestinal hemorrhages and increased mortality. Although coccidiosis major detrimental effect remains impaired performance – increased feed conversion ratio (FCR) and reduced body weight gain (BWG). Eimeria parasites are well adapted to the host and the industrial production settings and quite robust in the environment. Thus, eradication strategies are not feasible, and coccidiosis requires continuous management programs based on in-feed anticoccidial use or vaccination. The latter can provide good coccidiosis control when properly applied, but also might increase the risk of intestinal inflammation and respective drop in performance (Stanev et al., 2021). Therefore, the majority of poultry producers nowadays can only rely on in-feed anticoccidials to prevent the negative effect that Eimeria spp. exert on broilers health, welfare, and performance (Noack et al., 2019). However, the capability of Eimeria to develop resistance towards different anticoccidial drugs might compromise their effect on the field. Due to the synergistic and complementary effect of ionophores and nicarbazin, combination products are the backbone of the in-feed anticoccidial programs worldwide, providing enhanced efficacy, at reduced dose of the individual components, thus increased safety margins and reduced risk of resistance development (Chapman and Rathinam, 2022). This study aims to investigate the efficacy of different ionophore-nicarbazin combination products to a contemporary Eimeria spp. isolate, containing E. acervulina, E. maxima and E. tenella, all of them originating from the Netherlands and respectively the extend of resistance development.

II. METHOD

Conway and McKensey (2007) have described a methodology for estimation of the efficacy of different anticoccidial drugs in poultry. Based on that methodology, the current study aimed to assess the efficacy of different ionophore-nicarbazin combination products using 400 male, day old, Ross 308 birds in wired floor battery cages (5 birds each) distributed in 8 treatment groups: 1) Uninfected Untreated Control (UUC); 2) Infected Untreated Control (IUC); 3) Monensin 50 ppm + nicarbazin 50 ppm (MON+NIC); 4) Salinomycin 50 ppm + nicarbazin 50 ppm (SAL+NIC); 5) Narasin 50 ppm + nicarbazin 50 ppm (NAR+NIC); 6) Maduramicin 3.75 ppm + nicarbazin 40 ppm (MAD+NIC); 7) Semduramicin 15 ppm + nicarbazin 40 ppm (SEM+NIC L) and 8) Semduramicin 18 ppm + nicarbazin 48 ppm (SEM+NIC H), with 10 replicates per treatment. Birds were reared in coccidia free environment during the first two weeks of life to avoid immunity development against coccidiosis. No anticoccidial drug was provided during this period. At day 14 all birds were individually weighed and provided with feed supplemented according to the allocation listed above. At day 16 all birds, except for the UUC group, were individually gavaged with 1 ml of a mixed coccidia inoculum containing 130 000 E. acervulina, 22 000 E. maxima and 8 000 E. tenella sporulated oocysts, all from a recent field isolate originating from the Netherlands. Half of the birds from each group were individually weighed, sacrificed and lesion scored at day 22. The remaining birds followed the same protocol at day 23 and all remaining feed was weighed. Efficacy of the treatments was assessed based on oocyst shedding (oocyst per gram of feces or OPG), species specific mean coccidiosis intestinal lesion scores (MLSs) for the three Eimeria spp. used for the inoculation according to Johnson and Reid (1970) and total mean lesion score (TMLS) being the sum of the three individual species specific MLSs, body weight (BW) at day 14 and day 23, daily weight gain (DWG) day 14-23, daily feed intake (DFI) day 14-23 and feed conversion ratio (FCR) day 14- 23. Data were analyzed using ANOVA and Fisher’s LSD test was used for mean comparison (P < 0.05). Test animals were humanely handled. The study was conducted according to Good Clinical Practice and approved by the Poulpharm Ethical Committee.

III. RESULTS

There were no significant differences in mortality between the treatments (2 birds in UUC and one bird in MON+NIC and NAR+NIC each) and was not related to the challenge. Overview of the parasitological results is provided in Table 1. Mean lesion scores for the three major Eimeria species in broilers, TMLS and OPG were significantly higher in the IUC compared to UUC, demonstrating effective infection model.

TMLS on day 22-23 in all treatments, except NAR+NIC, were significantly reduced compared to IUC. Highest reduction was recorded in SEM+NIC H which was significantly lower compared to all other treatments, except SAL+NIC. None of the products significantly reduced E. acervulina lesions at day 22-23 compared to IUC. E. maxima lesions at day 22-23 were significantly reduced in SEM+NIC H, SAL+NIC and MON+NIC compared to IUC. Only NAR+NIC did not significantly reduce the lesions of E. tenella compared to IUC.

None of the combination products reduced oocyst shedding (total OPG) at day 23 in comparison to IUC.

Table 1 - Overview of parasitological. parameters per treatment group.

An overview of the performance results is provided in Table 2. BW at day 23, DWG and DFI were significantly lower and FCR significantly higher in IUC compared to UUC demonstrating effective infection model.

All products provided DWG improvement compared to IUC. Highest improvement was recorded in the SEM+NIC H group, which was the only group not differing from UUC, completely alleviating the effect of the challenge. Thus, according to Chapman (1980) the isolate can be considered sensitive to SEM+NIC H only. All other treatments were significantly different to both UUC and IUC indicating partial resistance. The least effect was recorded in the NAR+NIC treatment, with DWG significantly lower than all other combination treatments. FI was impaired in all treatments, except SEM+NIC L and H groups, which were not different from the UUC. All treatments improved FCR compared to IUC and were not significantly different from UUC except for NAR+NIC group which was significantly higher than UUC.

Table 2 - Overview of zootechnical performance per treatment group.

IV. DISCUSSION

When assessing overall efficacy of anticoccidials to different strains, it is important to consider both parasitological and zootechnical parameters. The results of the study indicate that all ionophore-nicarbazin combinations are still effective in controlling coccidiosis, as none of the treatments demonstrated complete resistance. The above is evidenced by their wide use in commercial poultry production.

Resistance development is inevitable and well correlated with previous exposure of the field strains to specific anticoccidial products (Stanev et al., 2021). In line with this, the recent Dutch field isolate showed certain reduced sensitivity especially for products widely used for long time such as NAR+NIC. On the other hand, products that the isolate was naive to like SEM+NIC provided highest improvement compared to IUC and was not different from UUC indicating complete sensitivity.

Presented at the 35th Annual Australian Poultry Science Symposium 2024. For information on the latest and future editions, click here.