Porcine reproductive and respiratory syndrome (PRRS) is recognised as the most endemic and economically important disease of swine worldwide. Any effort directed towards the control of PRRS will have an important impact on the health status of pig herds and on the profitability of the swine industry.
It has been demonstrated that tilmicosin exhibits PRRSV-antiviral activities when concentrated in the pulmonary alveolar macrophages. The rapid uptake of tilmicosin throughout the respiratory tract of pigs and the highest intracellular accumulation in lung macrophages versus other macrolide antibiotics is the basis for Tilmovet®'s tilmicosin PRRSV replication blocking effect and its high antibacterial activity.
In several trials using PRRSV infected pigs, a reduction of PRRS clinical signs and performance improvements were shown in tilmicosin-medicated pigs. The majority of these studies are based on experimental PRRSV infections with animals medicated with tilmicosin via feed. Studies administered via medicated water to control PRRS infection after PRRSV inoculation or in naturally infected weaned pigs are limited. The objective of this article is to describe the results of two Tilmovet® water medication studies conducted post-weaning in PRRS infected herds with PRRSV viraemic pigs.
PRRSV pathogen and vaccination
Besides PRRSV-Type 1 (European subtype) and PRRSV-Type 2 (American subtype) various types and varieties of PRRSV can be found, which is due to ongoing mutation and recombination processes of PRRSV. As a consequence, highly pathogenic variants are created which, for example, can be found in Spain (Rosalia) or in China.
It is well known that Pulmonary Alveolar Macrophages (PAMs) are the primary target of PRRSV infection and the location of virus replication. PRRSV vaccines currently available have many limitations in terms of heterologous protection. Vaccines cannot eliminate the PRRS virus. In the case of highly aggressive virus types (Rosalia Type), insufficient immune response of vaccines leads to failure in PRRS protection, creating more complex infections often associated with PRDC.
Tilmovet® activities and antiviral effect
Tilmicosin is the active substance in Tilmovet® and is characterised by a broad range of activities:
- Intracellular accumulation (macrophages, neutrophils, epithelial cells, enterocytes, leucocytes) and activity.
- Antimicrobial activity (Actinobacillus pleuropneumoniae, Mycoplasma hyopneumoniae, Glaeserella parasuis, Pasteurella multocida, Bordetella bronchiseptica)
- Antiviral activity (PRRS)
- Anti-inflammatory effect
- Immunomodulatory properties
Tilmovet® provides unique pharmacokinetic activities when orally administered in pigs. Low serum concentrations, medium lung concentrations but very high alveolar macrophage concentrations lead to high presence at the respiratory infection sites. Tilmovet® (tilmicosin) accumulates rapidly in the lysosome of macrophages and neutrophils due to ion trapping.
The intracellular accumulation of tilmicosin (75:1) is much higher in comparison to other macrolide antibiotics like tylathromycin (28:1), tylosin (21:1), tylvalosin (12:1) or erythromycin (6:1). The two to six times higher intracellular accumulation of tilmicosin is the key factor for its high antimicrobial and antiviral effect.
Tilmicosin studies have shown that the PRRSV replication inhibition effect in alveolar macrophages is dose dependent and that the clinical and pathological effect of PRRSV infection is significantly reduced after both feed medication and water medication. In the majority of these studies, animals were experimentally infected with PRRSV and medicated with tilmicosin via feed. Only a limited number of studies are published in which tilmicosin was administered via water to control PRRS infection after PRRSV inoculation or in naturally infected pigs post-weaning. The use of Tilmovet® is an excellent strategy to stabilise PRRSV infection and to reduce the virus load during infection in PRRSV viraemia situations.
Tilmovet® administration feed vs water
Therapeutic Tilmovet® can be given in feed. However, because sick pigs have a reduced appetite and variable feed intake, and because medicated feed may also take time to prepare and deliver, Tilmovet® can be administered as a soluble formulation in drinking water.
Based on the restrictions on using medicated premixes, veterinarians and pig producers often use Tilmovet® water soluble as a highly effective alternative for disease management purposes.
PRRSV-positive herds post-weaning
The antiviral effect of Tilmovet® Oral Solution in PRRSV viraemic pigs was determined in two field studies; one conducted in Taiwan and one in Spain.
The Taiwan study was conducted in a PRRSV-positive herd (Type 1 PRRSV strain) post-weaning with pigs aged 4 - 12 weeks. In the herd, diverse pathogens (M. hyopneumoniae, A. pleuropneumoniae, G. parasuis, P. multocida) were present causing continuous respiratory problems post-weaning. 160 four-week old pigs were equally divided into four treatment groups (40 piglets / group).
Tilmovet® Oral Solution was used in three different treatment programmes:
- Group 1 - 5-day medication once (20 mg/kg body weight)
- Group 2 - 5-day medication twice (15 mg/kg body weight) with a 14 day medication stop in between
- Group 3 - 5-day medication three times (15 mg/kg body weight) with a 14 day medication stop in between treatments
- Group 4 - control, no treatment
Blood samples were randomly collected from 20 piglets in each treatment group at 4, 6, 8, 10 and 12 weeks of age for ELISA and qPCR testing.
PRRSV infection was found at 4 and 6 weeks of age at a low percentage of pigs in Group 1 (10 - 15%), Group 2 (0 - 5%) and Group 3 (0 - 25%) in comparison to the control pigs (30 - 65%).
The higher PRRSV burden in non-medicated control pigs resulted in higher PRRSV antibody levels (S/P ratios) ove the whole trial period (Figure 1). Tilmovet® water medication led to a depression of PRRSV replication and consequently to lower ELISA antibody titres in the three medicated groups over the whole trial period.
Tilmovet® treated pigs in Groups 2 and 3 exhibited a higher survival rate of 87.5% and 95% vs 82.5% in the control group (Figure 2), and a better weight gain of 0.380 kg and 0.360 kg, respectively, in comparison to the pigs in the control group (0.350 kg; Table 1).
The study in Spain was conducted in a transition farm which was affected by a PRRSV outbreak with the highly pathogenic Rosalia PRRSV strain. Animals on the farm were also affected by G. parasuis, M. hyopneumoniae post-weaning. 800 animals were divided into two treatment groups.
Tilmovet® Oral Solution was used in a 5-day medication programme three times (15 mg/kg body weight) with a 14 day medication stop in between and compared to a non-medicated control group. Blood samples for ELISA and qPCR determination and PRRSV clinical signs were determined at 3, 6, 8 and 10 weeks of age.
A higher level of PRRSV PCR-positive pigs at the start of the study (3 weeks of age) was determined in the control group (51.25%) and in the Tilmovet® group (45.57%) compared to the Taiwan study.
To evaluate the effect of Tilmovet® water medication in the Spain study, three subgroups were created according to the piglet's qPCR results (Ct value) at the enrollment of the study. The three subgroups composed of those pigs that were negative to qPCR (Ct value >40), those that had low viral load at study entrance (Ct value between 30-40) and those animals with high viraemia on the day of the enrolment (Ct value <30).
In pigs testing PCR-negative 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% in week 8 and by 14% in week 10. In non-medicated pigs the percentage of positive pigs increased by 8% in week eight and by 5% in week 10 (Figure 3).
Low level PCR-positive pigs at the beginning of the study in the Tilmovet® medicated group showed a higher infection reduction by 25% at 6 weeks of age, and by 47% at 8 weeks of age vs the control group, in which the viraemia decreased by 15% at 6 weeks of age and by 8% at 8 weeks of age (Figure 4).
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% at 8 weeks of age and 40% at 10 weeks of age was found (Figure 5).
A higher survival rate at the study end was determined in the Tilmovet® group (83%) in comparison to the control group (78%; Figure 6). Relatively 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 daily weight gain was determined in pigs with Tilmovet® water medication in comparison to the control group (Table 2).
Tilmovet® water medication in farms with low (Taiwan) and high (Spain) PRRSV infection levels shows a positive effect on PRRS clinical disease expression. The high PRRSV infection reduction in the case of Tilmovet® medication verify its stabilising effect of the PRRS infection situations in the presence of different respiratory bacteria pathogens. Implementation of Tilmovet® water medication programmes after farrowing is a highly effective tool to control PRRS n PRRSV-viraemic herds with PRDC problems.
References are available on request