Randomized, controlled trial comparing Rhodococcus equi and poly-N-acetyl glucosamine hyperimmune plasma to prevent R equi pneumonia in foals.

BACKGROUND: Hyperimmune plasma raised against ß-1→6-poly-N-acetyl glucosamine (PNAG HIP) mediates more opsonophagocytic killing of Rhodococcus equi (R equi) than does R equi hyperimmune plasma (RE HIP) in vitro. The relative efficacy of PNAG HIP and RE HIP to protect foals against R equi pneumonia, however, has not been evaluated. HYPOTHESIS: Transfusion with PNAG HIP will be superior to RE HIP in foals for protection against R equi pneumonia in a randomized, controlled, blinded clinical trial. ANIMALS: Four hundred sixty Quarter Horse and Thoroughbred foals at 5 large breeding farms in the United States. METHODS: A randomized, controlled, blinded clinical trial was conducted in which foals were transfused within 24 hours after birth with 2 L of either RE HIP or PNAG HIP. Study foals were monitored through weaning for clinical signs of pneumonia by farm veterinarians. The primary outcome was the proportion of foals that developed pneumonia after receiving each type of plasma. RESULTS: The proportion of foals that developed pneumonia was the same between foals transfused with RE HIP (14%; 32/228) and PNAG HIP (14%; 30/215). CONCLUSIONS AND CLINICAL IMPORTANCE: Results indicate that PNAG HIP was not superior to a commercially available, United States Department of Agriculture-licensed RE HIP product for protecting foals against R equi pneumonia under field conditions.

Antibody activities in hyperimmune plasma against the Rhodococcus equi virulence -associated protein A or poly-N-acetyl glucosamine are associated with protection of foals against rhodococcal pneumonia.

The efficacy of transfusion with hyperimmune plasma (HIP) for preventing pneumonia caused by Rhodococcus equi remains ill-defined. Quarter Horse foals at 2 large breeding farms were randomly assigned to be transfused with 2 L of HIP from adult donors hyperimmunized either with R. equi (RE HIP) or a conjugate vaccine eliciting antibody to the surface polysaccharide ß-1→6-poly-N-acetyl glucosamine (PNAG HIP) within 24 hours of birth. Antibody activities against PNAG and the rhodococcal virulence-associated protein A (VapA), and to deposition of complement component 1q (C՛1q) onto PNAG were determined by ELISA, and then associated with either clinical pneumonia at Farm A (n = 119) or subclinical pneumonia at Farm B (n = 114). Data were analyzed using multivariable logistic regression. Among RE HIP-transfused foals, the odds of pneumonia were approximately 6-fold higher (P = 0.0005) among foals with VapA antibody activity ≤ the population median. Among PNAG HIP-transfused foals, the odds of pneumonia were approximately 3-fold (P = 0.0347) and 11-fold (P = 0.0034) higher for foals with antibody activities ≤ the population median for PNAG or C՛1q deposition, respectively. Results indicated that levels of activity of antibodies against R. equi antigens are correlates of protection against both subclinical and clinical R. equi pneumonia in field settings. Among PNAG HIP-transfused foals, activity of antibodies with C՛1q deposition (an indicator of functional antibodies) were a stronger predictor of protection than was PNAG antibody activity alone. Collectively, these findings suggest that the amount and activity of antibodies in HIP (i.e., plasma volume and/or antibody activity) is positively associated with protection against R. equi pneumonia in foals.

Gastrointestinal sequelae after surgery for necrotising enterocolitis: a systematic review and meta-analysis.

OBJECTIVES: To document what types of gastrointestinal sequelae were described after surgery for necrotising enterocolitis (NEC) and to analyse their frequency. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Medline, EMBASE and the Cochrane library (CENTRAL) from 1990 to October 2016. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: We included studies, which provided original data on the occurrence of gastrointestinal sequelae in patients surviving surgery for NEC. Meta-analysis and metaregression to assess heterogeneity were performed for studies including 10 or more patients with gastrointestinal strictures, recurrence of NEC, intestinal failure (IF) and adhesion ileus. RESULTS: Altogether 58 studies, including 4260 patients, met the inclusion criteria. Strictures were reported to occur in 24% (95% CI 17% to 31%) of surviving patients, recurrence of NEC in 8% (95% CI 3% to 15%), IF in 13% (95% CI 7% to 19%) and adhesion ileus in 6% (95% CI 4% to 9%). Strictures were more common following enterostomy (30%; 95% CI 23% to 37%) than after primary anastomosis (8%; 95% CI 0% to 23%) and occurred more often after enterostomy without bowel resection than with bowel resection. We found considerable heterogeneity in the weighted average frequency of all sequelae (I2 range: 38%-90%). Intestinal outcomes were poorly defined, there were important differences in study populations and designs, and the reported findings bear a substantial risk of bias. CONCLUSIONS: Gastrointestinal sequelae in neonates surviving surgery for NEC are frequent. Long-term follow-up assessing defined gastrointestinal outcomes is warranted.