Frequency of PCV-2 viremia in nursery piglets from a Spanish swine integration system in 2020 and 2022 considering PRRSV infection status.

BACKGROUND: Porcine circovirus 2 (PCV-2) poses a significant economic threat for the swine industry, causing a range of diseases collectively referred to as porcine circovirus diseases (PCVDs). Despite PCV-2 vaccine effectiveness, the need for monitoring infectious pressure remains. PCV-2 coinfection with other pathogens like porcine reproductive and respiratory syndrome virus (PRRSV) can exacerbate disease severity and lead to PCV-2-systemic disease cases. Monitoring both PRRSV and PCV-2 in co-infected farms is crucial for an effective management and vaccination programs. The present cross-sectional study aimed to determine PCV-2 antibody levels in piglets at weaning and PCV-2 and PRRSV viremia in pooled serum samples at weaning (vaccination age) and at 6 and 9 weeks of age from a Spanish swine integration system in 2020 (48 farms) and in 2022 (28 out of the 48 analysed previously). RESULTS: The frequency of PCV-2 detection in pools of piglet sera was 2.1% (2020) and 7.1% (2022) at vaccination age but increased at the end of the nursery period (10.4% in 2020 and 39.3% in 2022) in both years. Co-infections between PCV-2 and PRRSV were detected in a significant proportion of PRRSV positive farms (15% in 2020, and 60% in 2022). PCV-2 antibody levels (ELISA S/P ratios) at weaning were lower in PCV-2 qPCR positive farms at different sampling time-points (0.361 in 2020 and 0.378 in 2022) compared to PCV-2 qPCR negative ones (0.587 in 2020 and 0.541 in 2022). The 28 farms tested both years were classified in four different epidemiological scenarios depending on their PCV-2 virological status. Those PCV-2 qPCR negative farms in 2020 that turned to be positive in 2022 had a statistically significant increase of PRRSV RT-qPCR detection and a PCV-2 antibody levels reduction, facts that were not observed in the rest of the scenarios. CONCLUSION: This epidemiological study in farms from the same integration system determined the occurrence, in 2020 and in 2022, of PCV-2 and PRRSV infections in piglets during the nursery period by using pooled serum samples.

A New Sampling Approach for the Detection of Swine Influenza a Virus on European Sow Farms.

Swine influenza A virus (swIAV), which plays a major role in the porcine respiratory disease complex (PRDC), is eliminated from the respiratory tract within 7-9 days after infection. Therefore, diagnosis is complicated in endemically infected swine herds presenting no obvious clinical signs. This study aimed to investigate the right time point for sampling to detect swIAV. A cross-sectional study was performed in 131 farms from 12 European countries. The sampling protocol included suckling piglets, weaners, and nursery pigs. In each age group, 10 nasal swabs were collected and further examined in pools of 5 for swIAV by Matrix rRT-PCR, followed by a multiplex RT-PCR to determine the influenza subtype. SwIAV was detected in 284 (37.9%) of the samples and on 103 (78.6%) farms. Despite the highest number of animals with clinical signs being found in the nursery, the weaners were significantly more often virus-positive compared to nursery pigs (p = 0.048). Overall, the swIAV detection rate did not significantly differ between diseased or non-diseased suckling and nursery piglets, respectively; however, diseased weaners had significantly more positive pools than the non-diseased animals. Interestingly, in 9 farms, different subtypes were detected in different age groups. Our findings indicate that to detect all circulating swIAV subtypes on a farm, different age groups should be sampled. Additionally, the sampling strategy should also aim to include non-diseased animals, especially in the suckling period.

A double-blind, placebo-controlled, randomized trial of PXT3003 for the treatment of Charcot-Marie-Tooth type 1A.

BACKGROUND: Charcot-Marie-Tooth disease type 1A (CMT1A) is a rare, orphan, hereditary neuromuscular disorder with no cure and for which only symptomatic treatment is currently available. A previous phase 2 trial has shown preliminary evidence of efficacy for PXT3003 in treating CMT1A. This phase 3, international, randomized, double-blind, placebo-controlled study further investigated the efficacy and safety of high- or low-dose PXT3003 (baclofen/naltrexone/D-sorbitol [mg]: 6/0.70/210 or 3/0.35/105) in treating subjects with mild to moderate CMT1A. METHODS: In this study, 323 subjects with mild-to-moderate CMT1A were randomly assigned in a 1:1:1 ratio to receive 5 mL of high- or low-dose PXT3003, or placebo, orally twice daily for up to 15 months. Efficacy was assessed using the change in Overall Neuropathy Limitations Scale total score from baseline to months 12 and 15 (primary endpoint). Secondary endpoints included the 10-m walk test and other assessments. The high-dose group was discontinued early due to unexpected crystal formation in the high-dose formulation, which resulted in an unanticipated high discontinuation rate, overall and especially in the high-dose group. The statistical analysis plan was adapted to account for the large amount of missing data before database lock, and a modified full analysis set was used in the main analyses. Two sensitivity analyses were performed to check the interpretation based on the use of the modified full analysis set. RESULTS: High-dose PXT3003 demonstrated significant improvement in the Overall Neuropathy Limitations Scale total score vs placebo (mean difference: - 0.37 points; 97.5% CI [- 0.68 to - 0.06]; p = 0.008), and consistent treatment effects were shown in the sensitivity analyses. Both PXT3003 doses were safe and well-tolerated. CONCLUSION: The high-dose group demonstrated a statistically significant improvement in the primary endpoint and a good safety profile. Overall, high-dose PXT3003 is a promising treatment option for patients with Charcot-Marie-Tooth disease type 1A.

Effect of Edema Disease Vaccination on Mortality and Growth Parameters in Nursery Pigs in a Shiga Toxin 2e Positive Commercial Farm.

Diseases caused by Escherichia coli are recognized as major problems in the swine industry, one of them being edema disease (ED). Importantly, the current decrease in antibiotic use may cause difficulties in controlling the disorders caused by E. coli. Therefore, this study assessed the efficacy of a commercial vaccine against ED in nursery pigs from a farm with previous history of ED. A total of 1344 pigs were monitored; half of them were randomly assigned to a vaccinated group (VG) and the other half to a non-vaccinated group (NVG). The vaccine was administered at 7 days of age. Animals received a pre-starter feed with 2500 ppm of zinc oxide (ZnO) for 2 weeks and a starter feed without ZnO for another 3 weeks. Pen-group weights were recorded at 28 (weaning), 42 (end of pre-starter phase), and 63 days of life (end of nursery phase). Death/culling rates, average daily gain (ADG), and average daily feed intake (ADFI) were calculated for each group at each phase. The overall relative risk of dying/being culled for a pig in the NVG was 5 times higher than that of the VG group but increased to 12 times higher during the starter period. ADG and ADFI were also significantly higher in the VG group for that period. Vaccination against ED significantly reduced pig losses and improved ADG and ADFI, particularly when ZnO was not used.

Symptomatic Val122del mutated hereditary transthyretin amyloidosis: Need for early diagnosis and prioritization for heart and liver transplantation.

BACKGROUND: Hereditary transthyretin (ATTRv) amyloidosis is an autosomal dominant disease linked to transthyretin gene mutations which cause instability of the transthyretin tetramer. After dissociation and misfolding they reassemble as insoluble fibrils (i.e. amyloid). Apart from the common Val30Met mutation there is a very heterogeneous group of non-Val30Met mutations. In some cases, the clinical picture is dominated by a rapidly evolving restrictive and hypertrophic cardiomyopathy. METHODS: A case series of four liver recipients with the highly clinically relevant, rare and particularly aggressive Val122del mutation is presented. Medical and surgical therapeutic options, waiting list policy for ATTRv-amyloidosis, including the need for heart transplantation, and status of heart-liver transplantation are discussed. RESULTS: Three patients needed a staged (1 patient) or simultaneous (2 patients) heart-liver transplant due to rapidly progressing cardiac failure and/or neurologic disability. Domino liver transplantation was impossible in two due to fibrotic hepatic transformation caused by cardiomyopathy. After a follow-up ranging from 3.5 to 9.5 years, cardiac (allograft) function was maintained in all patients, but neuropathy progressed in three patients, one of whom died after 80 months. CONCLUSIONS: This is the first report in (liver) transplant literature about the rare Val122del ATTRv mutation. Due to its aggressiveness, symptomatic patients should be prioritized on the liver and, in cases with cardiomyopathy, heart waiting lists in order to avoid the irreversible neurological and cardiac damage that leads to a rapid lethal outcome.

Diversity of influenza A viruses retrieved from respiratory disease outbreaks and subclinically infected herds in Spain (2017-2019).

The present study was aimed to assess the diversity of influenza A viruses (IAV) circulating in pig farms in the Iberian Peninsula. The study included two different situations: farms suffering respiratory disease outbreaks compatible with IAV (n = 211) and randomly selected farms without overt respiratory disease (n = 19). Initially, the presence of IAV and lineage determination was assessed by qRT-PCR using nasal swabs. IAV was confirmed in 145 outbreaks (68.7%), mostly in nurseries (53/145; 36.5%). Subtyping by RT-qPCR was possible in 94 of those cases being H1avN2hu (33.6%), H1avN1av (24.3%) and H1huN2hu (18.7%), the most common lineages. H3huN2hu and H1pdmN1pdm represented 7.5% and 6.5% of the cases, respectively. As for the randomly selected farms, 15/19 (78.9%) were positive for IAV. Again, the virus was mostly found in nurseries and H1avN2hu was the predominant lineage. Virus isolation in MDCK cells was attempted from positive cases. Sixty of the isolates were fully sequenced with Illumina MiSeq®. Within those 60 isolates, the most frequent genotypes had internal genes of avian origin, and these were D (19/60; 31.7%) and A (11/60; 18.3%), H1avN2hu and H1avN1av, respectively. In addition, seven previously unreported genotypes were identified. In two samples, more than one H or N were found and it was not possible to precisely establish their genotypes. A great diversity was observed in the phylogenetic analysis. Notably, four H3 sequences clustered with human isolates from 2004-05 (Malaysia and Denmark) that were considered uncommon in pigs. Overall, this study indicates that IAV is a very common agent in respiratory disease outbreaks in Spanish pig farms. The genetic diversity of this virus is continuously expanding with clear changes in the predominant subtypes and lineages in relatively short periods of time. The current genotyping scheme has to be enlarged to include the new genotypes that could be found in the future.

Viral and bacterial investigations on the aetiology of recurrent pig neonatal diarrhoea cases in Spain.

BACKGROUND: Neonatal diarrhoea represents a major disease problem in the early stages of animal production, increasing significantly pre-weaning mortality and piglets weaned below the target weight. Enteric diseases in newborn piglets are often of endemic presentation, but may also occur as outbreaks with high morbidity and mortality. The objective of this study was to assess the frequency of different pathogens involved in cases of recurrent neonatal diarrhoea in Spain. RESULTS: A total of 327 litters from 109 sow farms located in Spain with neonatal recurrent diarrhoea were sampled to establish a differential diagnosis against the main enteric pathogens in piglets. In total, 105 out of 109 (96.3%) case submissions were positive to one of the examined enteric organisms considered potentially pathogenic (Escherichia coli, Clostridium perfringens types A and C, Transmissible gastroenteritis virus [TGEV], Porcine epidemic diarrhoea virus [PEDV] or Rotavirus A [RVA]). Fifty-eight out of 109 (53.2%) submissions were positive for only one of these pathogens, 47 out of 109 (43.1%) were positive for more than one pathogen and, finally, 4 out of 109 (3.7%) were negative for all these agents. Escherichia coli strains were isolated from all submissions tested, but only 11 of them were classified into defined pathotypes. Clostridium perfringens type A was detected in 98 submissions (89.9%) and no C. perfringens type C was found. Regarding viruses, 47 (43.1%) submissions were positive for RVA, 4 (3.7%) for PEDV and none of them for TGEV. CONCLUSION: In conclusion, C. perfringens type A, E. coli and RVA were the main pathogens found in faeces of neonatal diarrheic piglets in Spain.