Inhibition of mycobacterial growth in vitro following primary but not secondary vaccination with Mycobacterium bovis BCG.

Despite the widespread use of the Mycobacterium bovis BCG vaccine, there are more than 9 million new cases of tuberculosis (TB) every year, and there is an urgent need for better TB vaccines. TB vaccine candidates are selected for evaluation based in part on the detection of an antigen-specific gamma interferon (IFN-γ) response. The measurement of mycobacterial growth in blood specimens obtained from subjects immunized with investigational TB vaccines may be a better in vitro correlate of in vivo vaccine efficacy. We performed a clinical study with 30 United Kingdom adults who were followed for 6 months to evaluate the abilities of both a whole-blood- and a novel peripheral blood mononuclear cell (PBMC)-based mycobacterial growth inhibition assay to measure a response to primary vaccination and revaccination with BCG. Using cryopreserved PBMCs, we observed a significant improvement in mycobacterial growth inhibition following primary vaccination but no improvement in growth inhibition following revaccination with BCG (P < 0.05). Mycobacterial growth inhibition following primary BCG vaccination was not correlated with purified protein derivative (PPD) antigen-specific IFN-γ enzyme-linked immunospot (ELISPOT) responses. We demonstrate that a mycobacterial growth inhibition assay can detect improved capacity to control growth following primary immunization, but not revaccination, with BCG. This is the first study to demonstrate that an in vitro growth inhibition assay can identify a difference in vaccine responses by comparing both primary and secondary BCG vaccinations, suggesting that in vitro growth inhibition assays may serve as better surrogates of clinical efficacy than the assays currently used for the assessment of candidate TB vaccines.

The impact of the National Patient Safety Agency intravenous fluid alert on iatrogenic hyponatraemia in children.

In March 2007, the National Patient Safety Agency (NPSA) issued an alert regarding intravenous fluid (IVF) prescription to hospitalised infants and children, to be implemented in UK hospitals by September 2007. Previously, the most commonly used IVF (0.18% saline/4% dextrose) has been associated with iatrogenic hyponatraemia, resulting in four deaths and one near miss since 2000. The alert recommended 0.45% (or 0.9%) saline/5% dextrose as maintenance IVF and banned 0.18% saline/4% dextrose. We audited practice and outcome in children receiving maintenance IVF in June 2007 (before guideline implementation) and June 2008 (after guideline implementation). In June 2007, 44 (30%) children were prescribed IVF, six received IVF not recommended by NPSA alert 22 and one became hyponatraemic. In June 2008, 56 (30%) children received IVF; one received IVF not recommended by NPSA alert 22 and became hyponatraemic. The median change in serum sodium levels for all children who received IVF not recommended by NPSA alert 22 [-5 (-15 to 0) mmol/l] was significantly greater than those who received IVF recommended by NPSA alert 22 [0 (-13 to +7) mmol/l, p = 0.002]. In addition, there was a significant (p = 0.04) reduction in the number of children who had electrolytes checked while on IVF after implementation of the guideline. Implementation of a new IVF guideline has been associated with less use of IVF not recommended by NPSA alert 22, resulting in less serum sodium level reduction. The only children who became hyponatraemic received IVF not recommended by NPSA alert 22. Despite the NPSA alert and guideline implementation, less children had electrolyte levels checked while receiving IVF.