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.

High frequency of primary mutations associated with antiretroviral drug resistance in recently diagnosed HIV-infected children.

INTRODUCTION: The aim of our study was to analyse the frequency of primary mutations associated with HIV drug resistance in a population of children born to HIV-infected mothers. DESIGN: A prospective study included newly HIV-diagnosed children treated at two public paediatric hospitals. PATIENTS AND METHODS: Clinical and antiretroviral therapy (ART) data were collected in mother-child pairs. HIV-1 subtyping and ART resistance mutations were assayed in children by sequencing a region of HIV pol gene. RESULTS: A total of 67 children were enrolled: 22 less than 12 months of age, 20 between 1 and 5 years and 25 between 6 and 14 years. Six (9.0%) children had viral strains with at least one primary mutation associated with resistance to reverse transcriptase and protease inhibitors. A significantly (P = 0.019) higher frequency of resistance (22.7%, n = 5/22) was found among children aged < 12 months. Fourteen children (20.9%) had a subtype B HIV-1 strain and 53 (79.1%) had an inter-subtype B/F recombinant variant. DISCUSSION: A high percentage of recently diagnosed infants were found to carry primary ART resistance mutations. Limited options for ART of HIV-infected children might lead to increased HIV-associated morbidity and mortality. Thus, consideration should be given to mandatory screening for primary ART resistance before initiating therapy for infants aged < 12 months in countries where HIV mother-to-child transmission is still present, such as in Argentina. This will allow for the rationalized and individualized use of drugs and will contribute to the increased cost-effectiveness of local health systems.

National Immunization Commission: strengthening evidence-based decision making in Argentina.

In Argentina, the National Technical Advisory Group on Immunizations is represented by the National Immunization Commission (CoNaIn), an organization created by the Ministry of Health in 2000. Recently, the Argentine government has decided to prioritize vaccination as a state policy, emphasizing this strategy as a sign of social equity so CoNaIn was restructured to increase its capacity to formulate sound and evidence-based recommendations. The commission shall consist of a group of immunization experts, representatives of scientific societies, the immunization program and the Ministry of Health. Its functions include the formulation of recommendations on the introduction of vaccines into the immunization program. The recommendations are based on technical, programmatic and social criteria. This decision-making process transparent with the support and advice of experts and scientific societies and guided by available evidence decisions help strengthen the Ministry of Health immunization policy generating greater confidence and support from the population and health professionals.

The current situation of meningococcal disease in Latin America and recommendations for a new case definition from the Global Meningococcal Initiative.

The Global Meningococcal Initiative (GMI) is an international group of scientists and clinicians with expertise in meningococcal disease (MD). It promotes MD prevention through education and research. Given geographic differences in disease epidemiology, prevention strategies (e.g., vaccination) should be country-specific to ensure local needs are met. However, regional policies/recommendations and standardized disease diagnostic criteria should be implemented to improve surveillance and control strategies, and allow for more robust data comparisons. Consequently, the GMI convened a meeting with Latin American representatives to discuss the burden of MD and vaccination practices/policies, and consider if the global GMI recommendations could be tailored. The group determined that as robust, uniform epidemiologic data are required to make informed health-policy decisions, it would be useful to first summarize the regional situation herein (including disease surveillance, case definitions, epidemiology, vaccination and outbreak control strategies) and then determine a consensus-based meningococcal case definition for use throughout the region.

An epidemiologic surveillance of Shiga-like toxin-producing Escherichia coli infection in Argentinean children: risk factors and serum Shiga-like toxin 2 values.

BACKGROUND AND AIMS: Shiga-like toxin (Stx)-producing Escherichia coli (STEC) infection is an ongoing health issue that can lead to serious complications, including hemolytic uremic syndrome (HUS) and death. This study assessed demographic and epidemiologic information of STEC infection among Argentinean children. METHODS: A prospective surveillance of 2435 screened children (age, 0.5-15 years) presenting with watery diarrhea and/or bloody diarrhea was undertaken to evaluate the clinical course of STEC infection. RESULTS: Prevalence of STEC infection was 4.1% among subjects presenting with watery diarrhea for ≤ 5 days' duration, bloody diarrhea for ≤ 36 hours' duration, or both. Incidence of STEC infection was significantly higher in the subjects with bloody diarrhea. Ninety-three STEC+ children underwent further evaluation, of whom 8 (8.6%) developed HUS. White blood cells, particularly neutrophils, were abnormally elevated at screening in 5 of 8 HUS subjects. Quantifiable serum Stx-2 values were noted within 24 to 48 hours after the onset of bloody diarrhea in 3 HUS subjects using a validated chemiluminescence assay, with levels quickly dissipating by HUS onset. CONCLUSIONS: Results suggest that young STEC-positive children with bloody diarrhea and exhibiting neutrophilic leukocytosis in the early course of their diarrhea are at risk for HUS progression. The observation of measurable concentrations of Stx-2 levels in the early post-bloody-diarrhea period and rapid dissipation at the time of HUS onset requires further evaluation.

Evaluation of minority populations of HIV type-1 with K103N and M184V drug resistance mutations among children in Argentina.

BACKGROUND: The aim of this study was to describe the frequency of minority populations of viruses carrying mutations K103N and M184V in drug-naive HIV type-1 (HIV-1)-infected children, and to further evaluate their effect on the selection of drug-resistant viruses within highly active antiretroviral therapy (HAART). METHODS: Newly diagnosed vertically HIV-1-infected children were evaluated. The HIV-1 pol gene was sequenced for subtyping and antiretroviral drug resistance analysis. Standard genotypic sequencing and sequence-selective real-time PCR (SPCR) to quantify minority viral populations were used. RESULTS: From December 2004 to July 2006, we included 35 children who were studied at baseline and during their first HAART regimen (follow-up median time 29.4 months). Of them, 82.9% were infected with intersubtype B/F recombinant variants. At baseline, all children had a drug-susceptible viral population that was studied by bulk sequencing. SPCR showed that 4 children had between 2-10% of M184V, 11 had <0.7%, 18 had no detectable mutation and 2 could not be amplified. No K103N minority populations were found. Once under HAART, children who had 2-10% of M184V at baseline further selected it in percentages >20% in less time than those with -0.1-0.6% or without minority populations (P=0.01). CONCLUSIONS: It was shown that having 2-10% of M184V at baseline enhanced its selection in high percentages in a short time after HAART initiation. Further research regarding the presence of minority quasispecies before initiation of HAART in large paediatric populations should be undertaken to evaluate their clinical effect during HAART.

Guiaveta: guía para el establecimiento de sistemas de vigilancia epidemiológica de enfermedades transmitidas por alimentos (VETA) y la investigación de brotes de toxi-infecciones alimentarias

[Prólogo] Los sistemas nacionales de información en salud han mejorado substancialmente, sin embargo aún no pueden precisar cuantas personas contraen enfermedades transmitidas por alimentos (ETA) contaminados en la Región, para alcanzar mejor eficacia en los programas de prevención y control de estas enfermedades. Las enfermedades diarreicas, incluida el cólera, están señaladas entre los principals problemas de salud pública y donde los alimentos y el agua contaminados son fuentes importantes de contagio. La información disponible en la Región, indica que las ETA están entre las primeras cinco causas de muerte en niños menores de cinco años, tienen una incidencia promedio de cuatro episodios diarreicos anuales por niño y muestran anualmente un franco aumento en la morbimortalidad. Ante tal problemática, el Consejo Directivo de la Organización Panamericana de la Salud, en su XXXV Reunión realizada en Septiembre de 1991, ratificó la aprobación del Plan de Acción 1991-1995 del Programa Regional de Cooperación Técnica en Protección de Alimentos de la OPS, recomendado por la VII Reunión Interamericana sobre Salud Animal a Nivel Ministerial, en su Resolución III, de abril de ese mismo año. Uno de los propósitos del Plan de Acción aprobado dice: "establecer una comunicación permanente de información de alerta epidemiológica para la selección y aplicación de medidas sanitarias de prevención y control de las ETA". Para alcanzar tal propósito y para promover el desarrollo y perfeccionamiento de los sistemas nacionales de vigilancia epidemiológica de las ETA, se elaboró la guía que se presenta en este documento, en consulta con expertos nacionales e internacionales. La guía incluye además, los procedimientos básicos para la investigación epidemiológica de los brotes de las ETA. La información derivada de las investigaciones que se realicen mediante esta, enriquecerá el conocimiento científico sobre el comportamiento de los agentes etiológicos, sobre las fuentes de infección que provocan sufrimiento humano, así como la vulnerabilidad de los agentes ante las medidas sanitarias aplicadas.