A study of vaccine-induced immune pressure on breakthrough infections in the Phambili phase 2b HIV-1 vaccine efficacy trial.

INTRODUCTION: The Merck Adenovirus-5 Gag/Pol/Nef HIV-1 subtype-B vaccine evaluated in predominately subtype B epidemic regions (Step Study), while not preventing infection, exerted vaccine-induced immune pressure on HIV-1 breakthrough infections. Here we investigated if the same vaccine exerted immune pressure when tested in the Phambili Phase 2b study in a subtype C epidemic. MATERIALS AND METHODS: A sieve analysis, which compares breakthrough viruses from placebo and vaccine arms, was performed on 277 near full-length genomes generated from 23 vaccine and 20 placebo recipients. Vaccine coverage was estimated by computing the percentage of 9-mers that were exact matches to the vaccine insert. RESULTS: There was significantly greater protein distances from the vaccine immunogen sequence in Gag (p=0.045) and Nef (p=0.021) in viruses infecting vaccine recipients compared to placebo recipients. Twenty-seven putative sites of vaccine-induced pressure were identified (p<0.05) in Gag (n=10), Pol (n=7) and Nef (n=10), although they did not remain significant after adjustment for multiple comparisons. We found the epitope sieve effect in Step was driven by HLA A∗02:01; an allele which was found in low frequency in Phambili participants compared to Step participants. Furthermore, the coverage of the vaccine against subtype C Phambili viruses was 31%, 46% and 14% for Gag, Pol and Nef, respectively, compared to subtype B Step virus coverage of 56%, 61% and 26%, respectively. DISCUSSION: This study presents evidence of sieve effects in Gag and Nef; however could not confirm effects on specific amino acid sites. We propose that this weaker signal of vaccine immune pressure detected in the Phambili study compared to the Step study may have been influenced by differences in host genetics (HLA allele frequency) and reduced impact of vaccine-induced immune responses due to mismatch between the viral subtype in the vaccine and infecting subtypes.

The use of liposomal amphotericin B in the management of Xylohypha bantiana mycosis in a dog.

Xylohypha bantiana is a rare neurotropic fungal infection reported in humans, dogs and cats. In dogs it has only been identified on post mortem examination and thus no successful treatments have previously been reported. Amphotericin B is a potent antifungal drug with a low therapeutic index because of its nephrotoxicity. Liposomal encapsulation of the drug has resulted in much safer use in humans. This article reports a case of Xylohypha bantiana infection in a dog that was diagnosed antemortally and managed with liposomal amphotericin B, which resulted in the prolongation of quality of life for an infection that invariably results in rapid death.

Dental disease indices and caries-related microflora in children with glycogen storage disease.

OBJECTIVE: To establish the levels of dental caries, bacterial dental plaque, gingivitis and caries-related microflora in children with glycogen storage disease (GSD). Patients with GSD are treated with regular intakes of glucose polymer and uncooked cornstarch to prevent hypoglycaemia. Dental health data are scarce. STUDY GROUP: The study group comprised 21 children with GSD attending the Great Ormond Street Hospital for Children. OUTCOME MEASURES: These included the number of decayed, missing and filled teeth, and surfaces in both the primary and permanent dentitions, plaque and gingivitis scores. Both plaque and saliva were collected from each child and cultured for Mutans streptococci, Lactobacilli and Candida. RESULTS: The study group included 13 boys and eight girls, aged from 2.7 to 15.5 years. Four of the 21 children had some caries experience. The mean dmft was 0.5 and the mean DMFT, 0.06. Mean plaque and gingivitis scores were 4.8 and 5.9, respectively, for plaque and gingivitis adjacent to the primary teeth, and 11.6 and 12 for those related to permanent teeth. CONCLUSIONS: Only a small proportion of the children had caries experience but most were found to have plaque associated with both primary and permanent teeth. Preventive care should be targeted to improve plaque control thus minimizing the risk of developing periodontal disease as adults.

Ectopic calcification of rat aortas and kidneys is reduced with n-3 fatty acid supplementation.

Supplementation with essential fatty acids has been shown to prevent the experimentally induced ectopic calcification of the kidneys known as nephrocalcinosis. Male Sprague-Dawley rats were fed a semi-synthetic diet supplemented with different essential fatty acids while being injected for a period of 10 days with calcium glubionate. After 3 weeks their kidneys and aorta were removed and the respective calcium content measured compared to the control, saline injected animals. Lipoic acid-EPA, fish oil (EPA rich) as well as the EPA monoester reduced the calcium concentration of both the kidneys and the aorta towards control values. Lipoic-EPA was the best absorbed of the three compounds and its combination of anti-oxidant together with EPA lowered the calcium content of both the aortas and the kidneys.

A new nebulizer for atomic spectrometry.

The rotating disc nebulizer has been redesigned with respect to the principle parameters that determines its analytical performance. The flow pattern of the aerosol attained has been optimized by altering the shape of the inner chamber of the nebulizer to obtain optimum aerodynamic characteristics. The optimum angle of impact and "free flight" distance has been established using particle size distribution and mass transport efficiency as criteria. Analytical characteristics have been determined by monitoring the emission signal from aqueous standards. The accuracy has been assessed by using reference steel samples. Using standard solutions of different viscosity the performance of the nebulizer with respect to viscosity changes of the sample has been compared with that of a commercial Meinhardt nebulizer. The rotating disc nebulizer has been less affected by changes in viscosity making it possible to use this nebulizer with slurry and oil samples.

Ethanol loading in an inductively coupled plasma.

Changes to the fundamental and analytical parameters of a plasma have been investigated when ethanol has been added to aqueous or organic solutions. Excitation temperature, electron number density, and intensity of the H(alpha) line increased when ethanol has been added to aqueous solutions, while an electron density decrease and signal reduction have been found when ethanol has been added to xylene. The sensitivity has been improved for all ethanol concentrations when water has been the solvent, but the reverse has been found for xylene solutions.