Elizabeth Holt

Randomized, placebo-controlled, double blinded trial of dexamethasone in African children with sepsis

OBJECTIVE To determine the effect of moderate dose dexamethasone administered before antibiotics on the outcome of African children with sepsis. METHODS The design was a randomized, double blinded, placebo-controlled trial of dexamethasone (0.2 mg/kg) vs. placebo given intravenously before antibiotic therapy. Patients were recruited from the patient populations at two missionary hospitals. Primary outcome variables were determined before analysis of data. RESULTS Seventy-two children with sepsis were enrolled in the study. Treatment with dexamethasone was not associated with improved outcome for any of six outcome variables: survival to discharge (83%, dexamethasone group; 89%, placebo group); hemodynamic stability at 48 h (33%, dexamethasone group; 49%, placebo group); median length of hospital stay (11 days, dexamethasone group; 11 days, placebo group); normal at discharge (90%, dexamethasone group; 75%, placebo group); normal at follow-up (90%, dexamethasone group; 72%, placebo group); and afebrile at 48 to 72 h (61%, dexamethasone group; 44%, placebo group). CONCLUSIONS These data indicate that a moderate dose of dexamethasone given before antibiotic therapy did not improve outcome in the pediatric patients with sepsis whom we studied.

Successful immunization of infants at 6 months of age with high dose edmonston-zagreb measles vaccine

A group of 2097 Haitian infants 6 to 11 months of age were randomized to receive Schwarz or Edmonston-Zagreb strain measles vaccines containing 10− to 500-fold more vaccine viral particles than standard potency vaccines. No unusual adverse reactions were noted. Edmonston-Zagreb vaccines were more effective than equivalent doses of Schwarz vaccines as measured by the proportion of vaccinated children with measles antibody concentrations ≥200 mIU/ml 2 months after vaccination and the persistence of antibody at 18 to 24 months of age. High titer Edmonston-Zagreb vaccine administered at 6 months of age induced antibody concentrations ≥200 mIU/ml in 83% of infants by plaque reduction neutralization and 93% of infants by enzyme-linked immunosor-bent assay with high rates of antibody persistence at 12 to 24 months of age. The World Health Organization recommends high titer Edmonston-Zagreb measles vaccines for routine use at 6 months of age in areas where measles is an important cause of mortality in young infants.

The utility of verbal autopsies for identifying HIV-1-related deaths in Haitian children

Objective:To determine whether deaths among Haitian infants born to HIV-1-sero-negative women could be distinguished from deaths among children born to HIV-1-seropositive women using the verbal autopsy technique. Methods:Mothers of 315 Haitian children who died were interviewed about events leading to the childs death. Three physicians independently reviewed interview data and determined the probable cause of death without knowledge of maternal HIV-1 status or hospital records. The underlying causes of death assigned to the infants were analyzed to determine whether maternal HIV status could be predicted. Results:There was good agreement among the physicians (χ = 0.62) and 90% agreement between hospital records and the verbal autopsy diagnosis. Compared with children born to HIV-1-seronegative women, deaths in children born to HIV-1-seropositive mothers were more likely to be ascribed to a presumptive diagnosis of AIDS (37 versus 21%; P = 0.01). The sensitivity and specificity of verbal autopsies for identifying deaths associated with maternal HIV-1 infection ranged from 37 to 59% and from 69 to 79%, respectively, depending on the classification system used. The predictive positive value of a death believed to be consistent with pediatric HIV-1 infection was 26–30% and the predictive negative value was 85–90%. Conclusion:Verbal autopsies may be useful for distinguishing certain causes of death, but have limited utility for distinguishing deaths associated with maternal HIV-1 infection from deaths among children born to HIV-1-seronegative women.

Meningitis and pneumonia in Guatemalan children: the importance of Haemophilus influenzae type b and Streptococcus pneumoniae

OBJECTIVE To determine the epidemiology of Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae invasive infections in hospitalized Guatemalan children. This is an important issue since Hib vaccine has not been incorporated into the routine immunization program in Guatemala and information from hospital records in 1995 indicated a low incidence of Hib and S. pneumoniae as causes of meningitis and invasive infections. METHODS Children who were hospitalized in Guatemala City with clinical signs compatible with bacterial infections were evaluated for evidence of Hib or S. pneumoniae infection. Normally sterile body fluids were cultured, and antigen detection was performed on cerebrospinal fluid (CSF) and pleural fluid. RESULTS Of 1 203 children 1-59 months of age hospitalized over a 28-month period, 725 of them (60.3%) had a primary diagnosis of pneumonia, 357 (29.7%) of meningitis, 60 (5.0%) of cellulitis, and 61 (5.1%) of sepsis and other conditions. Hib was identified in 20.0% of children with meningitis and S. pneumoniae in 12.9%. The average annual incidence of Hib meningitis was 13.8 cases per 100 000 children under 5 years of age, and 32.4% of meningitides caused by Hib and 58.7% of S. pneumoniae meningitides occurred prior to 6 months of age. Case fatality rates were 14.1%, 37.0%, and 18.0%, respectively, for children with Hib, S. pneumoniae, and culture-negative and antigen-negative meningitis. Prior antibiotic therapy was common and was associated with significant reductions in CSF-culture-positive results for children with other evidence of Hib or S. pneumoniae meningitis. CONCLUSIONS Improvements in case detection, culture methods, and latex agglutination for antigen detection in CSF resulted in identification of Hib and S. pneumoniae as important causes of severe disease in Guatemalan children. Using a cutoff of > 10 white blood cells per cubic millimeter in CSF would improve the sensitivity for detection of bacterial meningitis and help estimate the burden of bacterial meningitis in Guatemala and other developing countries.

Pediatric Invasive Pneumococcal Disease in Guatemala City: Importance of Serotype 2.

Introduction: To inform estimations of the potential impact of recently introduced pneumococcal conjugate vaccine (PCV), we report results of 11 years of pre-PCV surveillance for invasive pneumococcal disease (IPD) among children in Guatemala City. Methods: Cases of IPD in children younger than 5 years were identified by active surveillance at 3 referral hospitals in Guatemala City from October 1996 through 2007. Clinical and demographic data were obtained, and isolates of Streptococcus pneumoniae from normally sterile sites were serotyped using latex agglutination and confirmed by Quellung reaction. Results: Four hundred fifty-two cases of IPD were identified with a case fatality rate of 21%. Meningitis was the most common cause of death (77% of all deaths) and occurred more often in infancy (median age 5 months) than other clinical syndromes. Of the 137 isolates serotyped, type 1 (26 cases, 17%), type 2 (25 cases, 16%) and type 5 (18 cases, 12%) were the most common. Serotype 2 was associated with a higher case fatality rate (28%), higher rate of meningitis (68%) and occurred in younger infants (median age, 3.5 months) than other common serotypes. Recently introduced PCV13 includes 73% of observed serotypes in the study. Conclusion: Infants with IPD presented at a young age. Serotype 2, rarely reported as a significant cause of IPD and not included in available PCVs, was a common cause of disease in this population. PCV13 introduction in Guatemala, begun in 2013, may not have as great an impact in disease reduction as has been observed in other countries.

Effectiveness of pediatric practice consultation on missed opportunities for immunization.

ObjectiveTo evaluate the effectiveness of pediatric practice consultation in reducing missed-opportunity rates at eight pediatric sites in Baltimore, Maryland. The overarching goal was to decrease the occurrence of missed opportunities from 33% to 15% for the first, second, and third diphtheria and tetanus toxoids and pertussis vaccines during visits at which children were eligible for the vaccines.DesignThe effect of an in-office educational program alone at four sites is compared with the educational program and a consultation on office vaccination practices at four matched sites. All eight sites received a small grant (

Maternal IgG1 and IgA antibody to V3 loop consensus sequence and maternal-infant HIV-1 transmission

2,000) to fund practice changes. The medical records of children making visits before and after the interventions were audited to determine missed-opportunity rates. The policies and operations and the knowledge, attitudes, and practices of physicians and nurse practitioners at each site were also assessed.ResultsThe four education-consultation sites experienced a statistically significant 14% net reduction in the missed-opportunity rate relative to the education-only sites. This positive effect, however, was largely due to an increase in missed opportunities at one education-only site. There was a 10% increase in the missed-opportunity rate among the education-only sites and a 4% decrease among the education-consultation sites; neither change was statistically significant. Two of the three sites that reduced missed opportunities were matched health maintenance organizations (HMOs). Shortly after the interventions, both HMOs implemented tracking and follow-up information systems, which were planned before the interventions.ConclusionsThere is no evidence that either the educational program alone or the educational program and consultation combination reduced missed opportunities. The findings suggest that improved tracking and follow-up data systems and vaccination of children at sick visits may reduce missed opportunities.

Estimating vaccination coverage using parental recall, vaccination cards, and medical records

MatemaI lgG1 aod IgA antibody to V3 loop coosensus seqwnce and matemaI-infant HIV-1 trtmsmissioa Markham R.B.; Coberly J.; Ruff A.J.; Hoover D.; Gomez J.; Holt E.; Desormeaux J.; Boulos R.; Quinn T.C.; Halsey N.A. USA LANCET 1994 343/8894 (390-391) Maternal-infant transmission of HIV-I occurs in l3-40% of pregnancies. Studies of transmission of maternal immunity to HIV antigens have used antigens from viruses not represented of clinical isolates and have been conflicting. Using a consensus peptide sequence based on HIV isolates found in Haiti, we found that Haitian mothers who transmitted infection to their offspring had significantly higher mean concentrations of IgGl antibodies to the V3 loop of the primary neutralising domain of the viral envelope (gp 160) than non-transmitters (P = 0.02). Concentrations of IgA antibody to this domain were similar in transmitters and non-transmitters.