RecurrentBurkholderiaInfection in Patients with Chronic Granulomatous Disease: 11‐Year Experience at a Large Referral Center

The epidemiology of Burkholderia infection in persons with chronic granulomatous disease is poorly understood. We used species-specific polymerase chain reaction-based assays and genotyping analyses to identify 32 strains representing 9 Burkholderia species among 50 isolates recovered from 18 patients with chronic granulomatous disease. We found that recurrent pulmonary infection with distinct Burkholderia strains is common in chronic granulomatous disease.

Monocyte‐Derived Dendritic Cells from HIV Type 1–Infected Individuals Show Reduced Ability to Stimulate T Cells and Have Altered Production of Interleukin (IL)–12 and IL‐10

Monocyte-derived dendritic cells (MDDCs) have been used in therapeutic vaccination for cancer. A small number of studies have employed a similar approach to vaccinate human immunodeficiency virus (HIV)-infected individuals. We have thus analyzed the functional properties of MDDCs generated from HIV-infected individuals who either are receiving highly active antiretroviral therapy or are therapy naive. There was no difference in the MDDC phenotype or efficiency of MDDC generation between HIV-infected individuals and healthy control subjects. Despite this, the MDDCs derived from both groups of infected individuals were severely impaired in their ability to stimulate the proliferation of allogeneic T cells. Furthermore, production of interferon-gamma was reduced in T cells stimulated by MDDCs. These functional changes may be at least partly explained by reduced interleukin-12 and increased interleukin-10 secretion on stimulation with lipopolysaccharide and CD40 ligand. Our findings suggest that MDDCs used in therapeutic vaccination of HIV-infected individuals may show reduced potency.

Invasive Aspergillosis Due toNeosartorya udagawae

Invasive aspergillosis (IA) is most commonly caused by the morphospecies Aspergillus fumigatus. However, genetic-based methods indicate that organisms phenotypically identified as A. fumigatus actually constitute a mold complex, designated Aspergillus section fumigati subgenus fumigati.

Polymerase Chain Reaction Adjustment in Antimalarial Trials: Molecular Malarkey?

Antibodies to Variant Surface Antigens ofPlasmodium falciparum–Infected Erythrocytes Are Associated with Protection from Treatment Failure and the Development of Anemia in Pregnancy

In pregnancy-associated malaria (PAM), Plasmodium falciparum-infected erythrocytes (IEs) express variant surface antigens (VSA-PAM) that evade existing immunity and mediate placental sequestration. Antibodies to VSA-PAM develop with gravidity and block placental adhesion or opsonize IEs for phagocytic clearance, helping to prevent maternal anemia and low birth weight in infants.

New Evidence about Brown v. Board of Education: The Complex Effects of School Racial Composition on Achievement

Uncovering the effect of school racial composition is difficult because racial mixing is not accidental but instead an outcome of government and family choices. Using rich panel data on the achievement of Texas students, we disentangle racial composition effects from other aspects of school quality and from differences in abilities and family background. The estimates strongly indicate that a higher percentage of black schoolmates reduces achievement for blacks, while it implies a much smaller and generally insignificant effect on whites. These results suggest that existing levels of segregation in Texas explain a small but meaningful portion of the racial achievement gap. (c) 2009 by The University of Chicago. All rights reserved..

Power to Detect the Effects of HIV Vaccination in Repeated Low‐Dose Challenge Experiments

Simulation studies were conducted to estimate the statistical power of repeated low-dose challenge experiments performed in nonhuman primates to detect the effect of a candidate human immunodeficiency virus vaccine. The effect of various design parameters on power was explored. Results of simulation studies indicate that repeated low-dose challenge studies with a total sample of size 50 (25 animals/arm) typically provide adequate power to detect a 50% reduction in the per-exposure probability of infection resulting from vaccination. Power generally increases with the maximum number of allowable challenges per animal, the per-exposure risk of infection in control animals, and the proportion of animals susceptible to infection.

Misclassification of Drug Failure inPlasmodium falciparumClinical Trials in Southeast Asia

Most trials of antimalarials occur in areas in which reinfections are possible. For Plasmodium falciparum, reinfections are distinguished from recrudescences by polymerase chain reaction analysis of 3 polymorphic genes. However, the validity of this approach has never been rigorously tested. We tested for misclassification in 6 patients from clinical trials in Thailand and Cambodia who were classified as being reinfected by the standard polymerase chain reaction protocol. Using heteroduplex tracking assays and direct DNA sequencing, we found that 5 (83%) of 6 patients were misclassified. Misclassification in this manner overestimates the efficacy of antimalarials and delays the recognition of decreasing therapeutic efficacy, thus delaying potential changes in policy.

Outbreak of Life‐Threatening Coxsackievirus B1 Myocarditis in Neonates

In the summer and fall of 2007, we observed a unique cluster of cases of severe coxsackievirus B1 (CVB1) infection among Chicago area neonates. Eight neonates had closely related strains of CVB1 that were typed at the Centers of Disease Control and Prevention; 2 other neonates had CVB infections, 1 of which was further identified as serotype CVB1. All had severe myocarditis; 1 neonate underwent heart transplantation, and 1 died of severe left ventricular dysfunction.

Toxicodynamics of Itraconazole: Implications for Therapeutic Drug Monitoring

We explored concentration-toxicity relationships for itraconazole among 216 patients. Logistic regression revealed a progressive increase in the probability of toxicity with increasing concentrations of itraconazole. Classification and regression tree analysis suggested that 17.1 mg/L of itraconazole (measured using a bioassay) was the concentration level at which the population of patients was separated into 2 groups, each with a high and a low probability of toxicity.