Effect of hatching system and prophylactic antibiotic use on serum levels of intestinal health biomarker diamine oxidase in broilers at an early age.

To overcome some of the disadvantages of conventional hatcheries, a new concept is being explored in the broiler industry: on-farm hatching. In on-farm hatching systems, broiler eggs are transported to the broiler house on day 18 of incubation. On-farm hatched chicks hatch in a low dust environment, are immediately exposed to light, and have instant access to nutrients and water. Previous studies reported that on-farm hatching systems provide birds with an improved intestinal health and a lower feed conversion rate; resulting in a reduced use of antibiotics. Although it is generally agreed that the intestinal health of on-farm hatched chicks is better, the causative factors remain largely unknown. To explore the effect of hatching system on intestinal development, a full factorial in vivo experiment was designed, taking into account commercial age (minus two days, D-1, D1 and D2) and hatching condition (hatchery-born, hatchery-born with Spectoliphen 100 (SL) treatment, and on-farm hatched using the NestBorn-system) as factors. To assess intestinal development, diamine oxidase (DAO) serum levels were measured. DAO, a highly active intracellular enzyme that is synthesised mainly by the intestinal mucosal cells, is generally used as an indicator for intestinal maturation and intestinal permeability (IP) in mammals and birds. Analysis of serum samples showed that serum DAO levels in hatchery-born chicks were significantly lower compared to their on-farm hatched counterparts on all four days, suggesting that the intestinal development in the latter took place earlier. However, the long-term effect was not explored in this study. An additional comparison between the hatching systems was made, not according to commercial age, but in reference to time of access to feed. In this comparison, no differences between the two groups were observed. Interestingly, in the hatchery-born chicks, no compensatory development of the intestines took place within the time span of this experiment. The effect of SL during the first days on intestinal development and IP of chicks remains poorly understood and requires further investigation.

The reduction of CSFV transmission to untreated pigs by the pestivirus inhibitor BPIP: a proof of concept.

5-[(4-Bromophenyl)methyl]-2-phenyl-5H-imidazo[4,5-c]pyridine (BPIP) is a representative molecule of a novel class of highly active in vitro inhibitors of the replication of Classical swine fever virus (CSFV). We recently demonstrated in a proof of concept study that the molecule has a marked effect on viral replication in CSFV-infected pigs. Here, the effect of antiviral treatment on virus transmission to untreated sentinel pigs was studied. Therefore, BPIP-treated pigs (n=4), intra-muscularly infected with CSFV, were placed into contact with untreated sentinel pigs (n=4). Efficient transmission of CSFV from four untreated seeder pigs to four untreated sentinels was observed. In contrast, only two out of four sentinel animals in contact with BPIP-treated seeder animals developed a short transient infection, of which one was likely the result of sentinel to sentinel transmission. A significant lower viral genome load was measured in tonsils of sentinels in contact with BPIP-treated seeder animals compared to the positive control group (p=0.015). Although no significant difference (p=0.126) in the time of onset of viraemia could be detected between the groups of contact animals, a tendency towards the reduction of virus transmission was observed. Since sentinel animals were left untreated in this exploratory trial, the study can be regarded as a worst case scenario and gives therefore an underestimation of the potential efficacy of the activity of BPIP on virus transmission.

Imidazo[4,5-c]pyridines inhibit the in vitro replication of the classical swine fever virus and target the viral polymerase.

Selective inhibitors of the replication of the classical swine fever virus (CSFV) may have the potential to control the spread of the infection in an epidemic situation. We here report that 5-[(4-bromophenyl)methyl]-2-phenyl-5H-imidazo[4,5-c]pyridine (BPIP) is a highly potent inhibitor of the in vitro replication of CSFV. The compound resulted in a dose-dependent antiviral effect in PK(15) cells with a 50% effective concentration (EC(50)) for the inhibition of CSFV Alfort(187) (subgroup 1.1) of 1.6+/-0.4 microM and for CSFV Wingene (subgroup 2.3) 0.8+/-0.2 microM. Drug-resistant virus was selected by serial passage of the virus in increasing drug-concentration. The BPIP-resistant virus (EC(50): 24+/-4.0 microM) proved cross-resistant with VP32947 [3-[((2-dipropylamino)ethyl)thio]-5H-1,2,4-triazino[5,6-b]indole], an unrelated earlier reported selective inhibitor of pestivirus replication. BPIP-resistant CSFV carried a T259S mutation in NS5B, encoding the RNA-dependent RNA-polymerase (RdRp). This mutation is located near F224, a residue known to play a crucial role in the antiviral activity of BPIP against bovine viral diarrhoea virus (BVDV). The T259S mutation was introduced in a computational model of the BVDV RdRp. Molecular docking of BPIP in the BVDV polymerase suggests that T259S may have a negative impact on the stacking interaction between the imidazo[4,5-c]pyridine ring system of BPIP and F224.