Adjuvant glycerol and/or dexamethasone to improve the outcomes of childhood bacterial meningitis: a prospective, randomized, double-blind, placebo-controlled trial.

BACKGROUND: Despite favorable meta-analyses, no study involving third-generation cephalosporins for the treatment of childhood bacterial meningitis has documented a benefit of adjuvant dexamethasone therapy if the outcomes are examined individually. METHODS: We conducted a prospective, randomized, double-blind trial comparing adjuvant dexamethasone or glycerol with placebo in children aged from 2 months through 16 years in Latin America. Ceftriaxone was administered to all children; children were randomized to also receive dexamethasone intravenously, glycerol orally, both agents, or neither agent. Primary end points were death, severe neurological sequelae, or deafness, with the first 2 end points forming a composite end point. A subgroup analysis for Haemophilus influenzae type b meningitis was undertaken. Intention-to-treat analysis was performed using binary logistic regression models. RESULTS: H. influenzae type b, pneumococci, and meningococci were the main agents found among 654 patients; dexamethasone was given to 166, dexamethasone and glycerol were given to 159, glycerol was given to 166, and placebo was given to 163. No adjuvant therapy significantly affected death or deafness. In contrast, glycerol and dexamethasone plus glycerol reduced severe neurological sequelae, compared with placebo; the odds ratios were 0.31 (95% confidence interval [95% CI], 0.13-0.76; P=.010) and 0.39 (95% CI, 0.17-0.93; P=.033), respectively. For neurological sequelae and death, the odds ratios were 0.44 (95% CI, 0.25-0.76; P=.003) and 0.55 (95% CI, 0.32-0.93; P=.027), respectively. Dexamethasone therapy prevented deafness in patients with H. influenzae type b meningitis only if patients were divided grossly into dexamethasone recipients and nonrecipients and if timing between dexamethasone and ceftriaxone administration was not taken into account (odds ratio, 0.27; 95% CI, 0.09-0.77; P=.014). CONCLUSION: Oral glycerol therapy prevents severe neurological sequelae in patients with childhood meningitis. Safety, availability, low cost, and oral administration also add to its usefulness, especially in resource-limited settings.

Mother-to-child Transmission of HIV From 1999 to 2011 in the Amazonas, Brazil: Risk Factors and Remaining Gaps in Prevention Strategies.

BACKGROUND: The purpose of the study was to estimate rates of mother-to-child transmission (MTCT) of HIV in the Amazonas, Brazil, and to identify the associated factors. METHODS: This was a retrospective cohort study of 1210 children born to HIV-infected women between 1999 and 2011 and enrolled before age of 18 months in a reference HIV/AIDS pediatrics service in Manaus. We used multivariable logistic regression to assess the effect of maternal, obstetric and prophylactic interventions on MTCT of HIV. RESULTS: Ten children were excluded because of undocumented maternal HIV status. Among 1200 children, 163 (13.6%) were lost to follow-up. We included in the analysis 1037 children with known HIV status. Of those, 68 children were HIV infected, resulting in a MTCT rate of 6.6% [95% confidence interval (CI): 5.3-8.3]. Among mothers, 76.1% had received antiretroviral therapy during pregnancy, 59.3% elective caesarean, and 9.7% were breastfed. Factors associated with lower odds of MTCT of HIV were antiretroviral therapy during pregnancy [odds ratio (OR): 0.26; 95% CI: 0.12-0.58], elective caesarean (OR: 0.48; 95% CI: 0.23-0.98) and with MTCT: being breastfed (OR: 4.56; 95% CI: 2.19-9.50). Transmission decreased from 7.5% in 2007-2008 to 3.2% in 2011, while breastfeeding decreased from 30.8% in 1999-2000 to 3.9% in 2011-2012. CONCLUSIONS: The HIV rate of MTCT is still high in the Amazonas and challenges for its prevention prevail including lost to follow-up and gaps in critical strategies such as antiretroviral use during pregnancy. More efforts are needed to increase the number of women and babies who successfully complete the prevention of MTCT cascade and work toward elimination of MTCT of HIV.

Neonatal infections: Case definition and guidelines for data collection, analysis, and presentation of immunisation safety data.

Maternal vaccination is an important area of research and requires appropriate and internationally comparable definitions and safety standards. The GAIA group, part of the Brighton Collaboration was created with the mandate of proposing standardised definitions applicable to maternal vaccine research. This study proposes international definitions for neonatal infections. The neonatal infections GAIA working group performed a literature review using Medline, EMBASE and the Cochrane collaboration and collected definitions in use in neonatal and public health networks. The common criteria derived from the extensive search formed the basis for a consensus process that resulted in three separate definitions for neonatal blood stream infections (BSI), meningitis and lower respiratory tract infections (LRTI). For each definition three levels of evidence are proposed to ensure the applicability of the definitions to different settings. Recommendations about data collection, analysis and presentation are presented and harmonized with the Brighton Collaboration and GAIA format and other existing international standards for study reporting.