Emergence of Fatal PRRSV Variants: Unparalleled Outbreaks of Atypical PRRS in China and Molecular Dissection of the Unique Hallmark

Porcine reproductive and respiratory syndrome (PRRS) is a severe viral disease in pigs, causing great economic losses worldwide each year. The causative agent of the disease, PRRS virus (PRRSV), is a member of the family Arteriviridae. Here we report our investigation of the unparalleled large-scale outbreaks of an originally unknown, but so-called “high fever” disease in China in 2006 with the essence of PRRS, which spread to more than 10 provinces (autonomous cities or regions) and affected over 2,000,000 pigs with about 400,000 fatal cases. Different from the typical PRRS, numerous adult sows were also infected by the “high fever” disease. This atypical PRRS pandemic was initially identified as a hog cholera-like disease manifesting neurological symptoms (e.g., shivering), high fever (40–42°C), erythematous blanching rash, etc. Autopsies combined with immunological analyses clearly showed that multiple organs were infected by highly pathogenic PRRSVs with severe pathological changes observed. Whole-genome analysis of the isolated viruses revealed that these PRRSV isolates are grouped into Type II and are highly homologous to HB-1, a Chinese strain of PRRSV (96.5% nucleotide identity). More importantly, we observed a unique molecular hallmark in these viral isolates, namely a discontinuous deletion of 30 amino acids in nonstructural protein 2 (NSP2). Taken together, this is the first comprehensive report documenting the 2006 epidemic of atypical PRRS outbreak in China and identifying the 30 amino-acid deletion in NSP2, a novel determining factor for virulence which may be implicated in the high pathogenicity of PRRSV, and will stimulate further study by using the infectious cDNA clone technique

Optimization of heart rate lowering therapy in hospitalized patients with heart failure: Insights from the Optimize Heart Failure Care Program

Background Hospitalization is an opportunity to optimize heart failure (HF) therapy. As optimal treatment for hospitalized HF patients in sinus rhythm with heart rate ≥ 70 bpm is unclear, we investigated the impact of combined beta-blocker (BB) and ivabradine versus BBs alone on short and longer term mortality and rehospitalization. Methods and results A retrospective analysis was performed on 370 hospitalized HF patients with heart rate ≥ 70 bpm (150 BB + ivabradine, 220 BB alone) in the Optimize Heart Failure Care Program in Armenia, Azerbaijan, Belarus, Georgia, Kazakhstan, Russia, Ukraine, and Uzbekistan, from October 2015 to April 2016. Results At 1 month, 3 months, 6 months and 12 months, there were fewer deaths, HF hospitalizations and overall hospitalizations in patients on BB + ivabradine vs BBs alone. At 12 months, all-cause mortality or HF hospitalization was significantly lower with BB + ivabradine than BBs (adjusted hazard ratio [HR] 0.45 (95% confidence interval [CI] 0.32–0.64, P < 0.0001). Significantly greater improvement was seen in quality of life (QOL) from admission to 12 months with BB + ivabradine vs BBs alone (P = 0.0001). With BB + ivabradine, significantly more patients achieved ≥ 50% target doses of BBs at 12 months than on admission (82.0% vs 66.6%, P = 0.0001), but the effect was non-significant with BBs alone. Conclusions Heart rate lowering therapy with BB + ivabradine started in hospitalized HF patients (heart rate ≥ 70 bpm) is associated with reduced overall mortality and re-hospitalization over the subsequent 12 months. A prospective randomized trial is needed to confirm the advantages of this strategy