Therapeutic DNA vaccination of vertically HIV-infected children: Report of the first pediatric randomised trial (PEDVAC)

Subjects: Twenty vertically HIV-infected children, 6–16 years of age, with stable viral load control and CD4+ values above 400 cells/mm³. Intervention: Ten subjects continued their ongoing antiretroviral treatment (ART, Group A) and 10 were immunized with a HIV-DNA vaccine in addition to their previous therapy (ART and vaccine, Group B). The genetic vaccine represented HIV-1 subtypes A, B and C, encoded Env, Rev, Gag and RT and had no additional adjuvant. Immunizations took place at weeks 0, 4 and 12, with a boosting dose at week 36. Monitoring was performed until week 60 and extended to week 96. Results: Safety data showed good tolerance of the vaccine. Adherence to ART remained high and persistent during the study and did not differ significantly between controls and vaccinees. Neither group experienced either virological failure or a decline of CD4+ counts from baseline. Higher HIV-specific cellular immune responses were noted transiently to Gag but not to other components of the vaccine. Lymphoproliferative responses to a virion antigen HIV-1 MN were higher in the vaccinees than in the controls (p = 0.047), whereas differences in reactivity to clade-specific Gag p24, RT or Env did not reach significance. Compared to baseline, the percentage of HIV-specific CD8+ lymphocytes releasing perforin in the Group B was higher after the vaccination schedule had been completed (p = 0.031). No increased CD8+ perforin levels were observed in control Group A. Conclusions: The present study demonstrates the feasibility, safety and moderate immunogenicity of genetic vaccination in vertically HIV-infected children, paving the way for amplified immunotherapeutic approaches in the pediatric population. Trial registration: clinicaltrialsregister.eu 2007-002359-18; 2007-002359-18/I

Evaluation of the central sleep apnea in asymptomatic children with Chiari 1 malformation: an open question

INTRODUCTION: Type I is the most common Chiari malformation in children. In this condition, the lower part of the cerebellum, but not the brain stem, extends into the foramen magnum at the base of the skull leading to intermittent brain hypertension. In symptomatic children, central sleep apneas are shown in polysomnography evaluation. A central apnea index of 1/h or more is considered abnormal, but >5/h is clearly considered pathological. Therefore, central sleep apnea evaluation in pediatric age may show great age-related variability. METHOD AND SUBJECTS: We present three patients who were assessed by polysomnography with two different scores for central sleep apneas published in the literature: the method by Scholle (2011) and the American Academy of Sleep Medicine scoring system (2012). CONCLUSIONS: We speculated that the Scholle scoring system can be more helpful in assessing children with asymptomatic Chiari 1 malformation for a closer follow-up. More studies are needed

Comparison of statistical models in a meta-analysis of fungicide treatments for the control of citrus black spot caused by Phyllosticta citricarpa

Meta-analysis has been recognised as a powerful method to synthetize existing published data from different studies through a formal statistical analysis. Several statistical models have been proposed to evaluate the effectiveness of treatments against plant diseases using meta-analysis, but the sensitivity of the estimated treatment effects to the model chosen has not been investigated in detail in the context of plant pathology. In this paper, four different statistical models were defined to analyse fungicide control trials with binary outcomes. These models were used to conduct a meta-analysis on the effectiveness of fungicide treatments against citrus black spot, a fungal disease caused by the quarantine pathogen Phyllosticta citricarpa. The models differed in the assumption made on the variability of the treatment effect (constant or variable between experimental plots) and in the method used for parameter estimation (classical or Bayesian). Odds ratios were estimated for two groups of fungicides, copper compounds and dithiocarbamates, widely applied for CBS control using each model in turn. Classical and Bayesian statistical models led to similar results, but the estimated treatment effectiveness and their associated levels of uncertainty were sensitive to the assumption made about the variability of the treatment effect. Estimated odds ratios were different depending on whether the treatment effect was assumed to be constant or variable between experimental plots. The size of the confidence intervals was underestimated when the treatment effect was assumed constant while it was variable in reality. Because of the strong between-plot variability, the 90 % percentiles of the odds ratios were much higher than the point estimates, and this result revealed that, in some plots, treatment effectiveness could be much lower than expected. Based on our results, we conclude that it is not sufficient to calculate point estimates of odds ratio when the between-plot variability of the treatment effect is strong and that, in such case, it is recommended to compute the predictive distributions of the odds ratio