Relevance of lipopolysaccharide levels in HIV-associated neurocognitive impairment: the Neuradapt study.

Contributory factors to HIV-associated neurocognitive disorders (HAND) have been shown to include age, co-morbid infections, medication toxicity, virological, genetic and vascular mechanisms, as well as microbial translocation of lipopolysaccharide (LPS), which is suspected to trigger monocyte activation and increase trafficking of infected cells into the brain. In this study, our aim was to assess the degree of neurocognitive impairment in a group of randomly selected HIV-infected patients and investigate potential risk factors, including LPS plasma levels. Furthermore, we evaluated the relevance of LPS as a potential marker for screening patients with mild neurocognitive impairment. LPS plasma levels were compared among patients with HAND and those with no HAND. As LPS has also been shown to be elevated in hepatitis C co-infection, the analysis was stratified according to the presence or not of hepatitis C virus (HCV) co-infection. Differences between groups were evaluated using chi-square tests and Kruskal-Wallis non-parametric tests. Stepwise logistic regression was performed to identify independent risk factors for HAND in the subgroups of HCV-positive and negative patients. A p value <0.05 was considered significant. Analyses were conducted using SPSS® software. From December 2007 to July 2009, 179 patients were tested (mean age 44, 73 % male, 87 % on treatment, 30 % HCV co-infected, median CD4 504/ml and 67 % with viral load below 40 copies/ml). HAND was identified in 40/179 patients (22 %), the majority displaying asymptomatic neurocognitive impairment or mild neurocognitive disorder. Univariate analysis showed that age, illicit drug use, hepatitis C co-infection, prior AIDS-defining events, CD4/CD8 ratio and LPS plasma levels were significantly associated with HAND. The median LPS level was 98.2 pg/ml in the non-HAND group versus 116.1 pg/ml in the HAND group (p < 0.014). No differences were found in LPS values between subgroups of impairment. There was a clear association between LPS levels and HAND in the HCV-positive group (p = 0.036), while there was none in the HCV-negative group (p = 0.502). No difference in degree of hepatic fibrosis was found between the HAND and non-HAND groups. In conclusion, LPS levels were associated with HAND in the HCV-positive group, while, in the HCV-negative group, age and pro-viral DNA were the only variables independently associated with HAND. There was no difference in degree of liver disease as predicted by score of fibrosis between HAND and non-HAND groups. The role of HCV co-infection and higher LPS levels in the pathogenesis of HAND in patients with viral suppression on treatment requires further investigation.

Antibiotic prescriptions in French day-care centres: 1999-2008.

OBJECTIVE: Trends in antibiotic prescriptions among children attending day-care centres (DCCs) were studied before and after campaigns promoting prudent antibiotic use and the introduction of pneumococcal conjugate vaccine. DESIGN AND SETTING: Cross-sectional studies were conducted on a two-stage cluster sample of children aged 3 months to 4 years attending DCCs the Alpes Maritimes in France between January and March in 1999, 2004 and 2008. Antibiotic treatments given in the previous 3 months and their indications were studied. INTERVENTIONS: A local public health intervention promoting prudent paediatric antibiotic prescriptions was implemented in 2000 and followed by a nationwide campaign in 2002. MAIN OUTCOME MEASURES: Trends in the number and type of antibiotic prescriptions, and indications for antibiotic use, over the study period. RESULTS: 217, 254 and 279 children provided information in 1999, 2004 and 2008, respectively. The proportion of children who had received antibiotics within the previous 3 months fell from 58.5% (95% CI 51.7% to 65.2%) in 1999 to 29.7% (95% CI 24.4 to 35.5) in 2008. The number of treated episodes/child dropped from 0.99±1.14 to 0.35±1.16 (p<0.00001). Otitis media accounted for an increasing percentage of antibiotic use, rising from 35.3% (95% CI 29.0% to 42.2%) to 56.0% (95% CI 46.3% to 66.6%). Prescriptions for third-generation cephalosporins increased from 26.0% (95% CI 20.4% to 32.5%) to 49.5% (95% CI 39.2% to 59.7%). CONCLUSIONS: Paediatric antibiotic prescriptions dropped significantly following campaigns and the introduction of pneumococcal immunisation in France. Improvements are still needed regarding indications and choice of compounds.

Trends in nasopharyngeal carriage of Streptococcus pneumoniae among children attending daycare centers in southeastern France from 1999 to 2006.

Pneumococcal nasopharyngeal carriage, serotype distribution, and penicillin-susceptibility were monitored among children attending daycare centers in France from 1999 to 2006 to assess the impact of pneumococcal conjugate vaccine and antibiotic-reducing policies. Pneumococcal carriage remained stable. Immunization rates reached 68% in 2006. Serotype distribution shifted significantly from vaccine serotypes to vaccine-related and nonvaccine serotypes. Antibiotic treatments fell by 50%.