Efficacy Of Tilmovet® AC For PRRS Control By Water Medication In Weaned Pigs

Introduction

Porcine reproductive and respiratory syndrome (PRRS) is recognized as the most endemic and economically important disease of swine worldwide. PRRSV causing PRRS is responsible for respiratory disease in weaned and growing pigs, as well as productive failtures in sows.

It is well known that pulmonary alveolar macrophages (PAMs) are the primary target of PRRSV infection and location of virus replication. It has been demonstrated that tilmicosin exhibits PRRSV-antiviral effects when concentrated in the pulmonary alveolar macrophages (Du et al., 2011). Rapid uptake of tilmicosin throughout the respiratory tract and highest intracellular accumulation in comparison to other macrolide antibiotics in lung macrophages, is the basis for its blocking effect of PRRSV replication and the high antibacterial effect of Tilmovet (Blais and Chamberland, 1994; Hawser, 2022; Pridmore, 2018; Scorneaux and Shryock, 1998; Stoker et al., 1996; Stuart et al., 2008).

A reduction in clinical signs and performance improvements were shown in PRRS infected pigs when medicated with tilmicosin (Depondt et al., 2014). In most of these studies animals were experimentally infected with PRRSV and medicated with tilmicosin via feed (Benfield et al., 2002; Lehe et al., 2003; Molitor et al., 2001). Only a limited number of studies are published in which tilmicosin was administered via drinking water to control the PRRS infection after PRRSV inoculation (Batista et al., 2009) or PRRS naturally infected nursery pigs (Fraile et al., 2004).

The purpose of this paper is to describe two clinical cases of PRRSV-infected weaned pigs where Tilmovet AC (tilmicosin phosphate) was administered via water to control PRRSV infection and to present data on viremia, antibody titers, clinical and production parameters and severity of PRRS infection. 

Materials and methods

Study No 1

The study was conducted in Taiwan with animals from a farrow-to-finish herd infected with PRRSV. In total, 160 four-week-old weaned piglets from a PRRSV-infected herd were equally divided into four treatment groups (40 piglets/group; Table 1).

Table 1. Description of treatment groups in Taiwanese study

Parameters assessed: blood samples (20 pigs/group) for viremia assessment (qPCR) and PRRSV antibodies (ELISA Herd Check, IDEXX Laboratories) determination before/after Tilmovet water medication in different age groups (4, 6, 8, 10, 12 weeks of age). ELISA cut-off value: S/P ratio ≥ 0.4 = positive for antibody against PRRSV. Daily weight gain (DWG), survival rate (%), duration of PRRSV viremia, serum PRRSV load were determined. On the Taiwan farm, diverse bacterial pathogens (G parasuis, M hyopneumoniae, A pleuropneumoniae) were present during the experiment.

Study No 2

The study was conducted in a transition farm in Spain. The farm was selected based on PRRSV outbreaks two months before study onset and the presence of other respiratory pathogens (G parasuis, M hyopneumoniae). In total, 800 animals were divided into two groups at arrival. 

Group 1 - Tilmovet AC treatment at three time periods of five consecutive days (dose 15 mg/kg body weight). Between the three medication time periods, non-treatment periods of 14 days were established (Table 2). 

Table 2. Description of treatment groups in the Spanish study

Parameters assessed: blood samples for assessment of viremia (qPCR) and PRRSV antibodies (ELISA); PRRSV clinical signs (nasal discharge, cough, behavior, body condition), DWG, feed conversion rate, health status, mortality rate. ELISA cut-off value: S/P ratio ≥ 0.4 = positive for antibody against PRRSV. On the Spanish farm, diverse bacterial respiratory pathogens (G parasuis, M hyopneumoniae) were present during the study. 

Results and discussion

Study No 1

PCR results verify early PRRS infection in a low percentage of pigs. At the start of the study (4 weeks of age) and at 6 weeks of age, lower percentage of PRRSV-positive pigs were found in the Tilmovet-medicated group 1 (10% / 15%), group 2 (0% / 5%) and group 3 (0%, 25%) in comparison to the non-medicated control group (30% / 65%). A higher PRRS virus burden from trial onset until study end was determined in non-medicated pigs. This results in higher PRRSV antibody levels (S/P ratios) in the control group throughout the study (Figure 1). Tilmovet water medication led to depression of PRRS virus replication and to lower antibody titers in medicated pigs at 4, 6, 8, 10 and 12 weeks of age in comparison to the non-medicated pigs at these time periods.

Figure 1. PRRSV ELISA S/P ratio of the four treatment groups during the study

A retardation effect on PRRS infection in medicated pigs were determined based on Tilmovet water medication.

A higher survival rate from age week 4 to 12 was determined in the 2-time (95%) and 3-time (87.5%) Tilmovet medicated group in comparison to the control and the 1-time medicated group (82.5% each). Higher survival rate in tilmicosin medicated pigs is based on its PRRSV antiviral effect together with the very effective control of respiratory bacteria pathogens present on the farm.

A higher DWG was determined in the pigs with the 2-time and 3-time Tilmovet medication in comparison to the control and the 1-time medication group (Table 3)

Table 3. Body weight and average daily gain (ADG) of pigs in the four treatment groups

Study No 2

A higher level of PRRSV-positive pigs at the start of the study was identified in comparison to study 1. The percentage of pigs that were PCR-positive at the start of the study (3 weeks of age) was 51.25% in the control group and 45.57% in the Tilmovet treatment group. 

For the evaluation of the effect of Tilmovet water medication three subgroups were created according to the piglet's qPCR results (ct value) at the enrolment of the study. The three subgroups were composed of those pigs that were negative to qPCR (ct value > 40), those that had low viral load at the entrance (ct value between 30 - 40) and those animals with high viremia on the day of the enrolment (ct value < 30).

In PCR-negative pigs at the beginning of the study (3 weeks of age) a positive effect of Tilmovet water medication was determined. After the infection peak at 6 weeks of age the PRRS infection was reduced by 8% (week 8) and by 14% (week 10). In non-medicated pigs the percentage of positive pigs increased by 8% on week 8 and by 5% on week 10 (Figure 2). 

Figure 2. Evaluation viral load of negative piglets at study start, from the beginning to the end of the experimental trial

Low levels of PCR-positive pigs at the beginning of the study in Tilmovet medicated group showed a higher infection reduction by 25% (6 weeks of age) and by 47% at 8 weeks of age vs. the control group, in which the viremia decreased by 15% on age week 6 and 8% on age week 8 (Figure 3). 

Figure 3. Evaluation of viral load of low positive piglets at study start, from the beginning to the end of the experimental trial

In high level PCR-positive pigs at the beginning of the study, a similar infection reduction by 25% at 8 weeks of age and 40% at 10 weeks of age in the Tilmovet group vs. the control group with 29% (week 8) and 40% (week 10) was found (Figure 4). 

Figure 4. Evaluation of viral load of high positive piglets at study start, from the beginning to the end of the experimental trial

A higher survival rate at the study end was determined in the Tilmovet group (83%) in comparison to the control group (78%). Relative low survival rates in both groups were based on the highly pathogenic PRRSV strain and the first disease outbreak caused by this strain on the Spanish farm.

A higher DWG was determined in pigs with Tilmovet water medication in comparison to the control group (Table 4). 

Table 4. Body weight and average daily gain (ADG)* of pigs in the two treatment groups

A higher DWG was determined in pigs with water medication in comparison to the control group.

Conclusion

Study results were generated in farms being naturally affected by PRRSV infections. Different infection levels at study start were determined in farm 1 (low infection level) and farm 2 (high infection level). In both farms, secondary respiratory pathogens were present during the study.

3-time Tilmovet AC administration had the best effect on the clinical expression of PRRS infection as verified by differences in the S/P ratio obtained with the ELISA test, the daily weight gain and higher survival rate.

The positive effect of 3-time Tilmovet AC medication was shown after the viremia peak. In PCR negative pigs and low percentage of PCR-positives at the start of the study, a higher reduction of PRRSV infection was found in comparison to the control group after the viremia peak. This indicates a reduction of PRRSV replication and virus spreading in the pigs medicated post-weaning.

Tilmovet AC can help reduce PRRSV load in farms after the PRRSV viremia peak has been reached. The effect on reduction in groups with low percentage of PCR-positive and viremic pigs seems to be higher in comparison to groups with high percentage of positive and viremic animals.

Tilmovet AC medication programs in PRRS naturally infected herds with diverse viremia situations and the presence of respiratory bacteria pathogens (G. parasuis, M. hyopneumoniae, A. pleuropneumoniae) can effectively stabilise the PRRS infection situation and prevent severe PRDC infections in weaned pigs. A better effect is expected in viremic situations with a lower percentage of positive pigs.

Consequently, the implementation of Tilmovet AC 3-time water medication programs after farrowing can be considered as a highly effective tool to control PRRSV infections in PRRSV-viremic herds and with PRDC problems.

References are available on request