Frédéric Dallaire

Effect of prenatal exposure to polychlorinated biphenyls on incidence of acute respiratory infections in preschool Inuit children.

Objective We set out to assess whether environmental prenatal exposure to polychlorinated biphenyls (PCBs) is associated with incidence of acute respiratory infections in preschool Inuit children. Study design We reviewed the medical charts of 343 children from 0 to 5 years of age and evaluated the associations between PCB-153 concentration in umbilical cord plasma and the incidence rates of acute otitis media (AOM) and of upper and lower respiratory tract infections (URTIs and LRTIs, respectively). Results The incidence rates of AOM and LRTIs were positively associated with prenatal exposure to PCBs. Compared with children in the first quartile of exposure (least exposed), children in fourth quartile (most exposed) had rate ratios of 1.25 (p < 0.001) and 1.40 (p < 0.001) for AOM and LRTIs, respectively. There was no association between prenatal PCB exposure and incidence rate of URTIs or hospitalization. Conclusion Prenatal exposure to PCBs could be responsible for a significant portion of respiratory infections in children of this population.

Acute infections and environmental exposure to organochlorines in Inuit infants from Nunavik

The Inuit population of Nunavik (Canada) is exposed to immunotoxic organochlorines (OCs) mainly through the consumption of fish and marine mammal fat. We investigated the effect of perinatal exposure to polychlorinated biphenyls (PCBs) and dichlorodiphenyldichloroethylene (DDE) on the incidence of acute infections in Inuit infants. We reviewed the medical charts of a cohort of 199 Inuit infants during the first 12 months of life and evaluated the incidence rates of upper and lower respiratory tract infections (URTI and LRTIs, respectively), otitis media, and gastrointestinal (GI) infections. Maternal plasma during delivery and infant plasma at 7 months of age were sampled and assayed for PCBs and DDE. Compared to rates for infants in the first quartile of exposure to PCBs (least exposed), adjusted rate ratios for infants in higher quartiles ranged between 1.09 and 1.32 for URTIs, 0.99 and 1.39 for otitis, 1.52 and 1.89 for GI infections, and 1.16 and 1.68 for LRTIs during the first 6 months of follow-up. For all infections combined, the rate ratios ranged from 1.17 to 1.27. The effect size was similar for DDE exposure but was lower for the full 12-month follow-up. Globally, most rate ratios were > 1.0, but few were statistically significant (p < 0.05). No association was found when postnatal exposure was considered. These results show a possible association between prenatal exposure to OCs and acute infections early in life in this Inuit population.

Microbiological and Inflammatory Factors Associated with the Development of Pneumococcal Pneumonia

Pneumococcal pneumonia still is associated with a high mortality rate, despite appropriate antimicrobial therapy. Many gaps remain in the understanding of the pathogenesis of this deadly infection. The microbial and inflammatory events that characterize survival or death after intranasal inoculation of mice with an LD(50) inoculum of Streptococcus pneumoniae were investigated. Survival was associated with rapid bacterial clearance and low inflammation (surfactant and red blood cells in alveoli), but no neutrophil recruitment or lung tissue injury was noted. By contrast, death was preceded by strong bacterial growth that peaked 48 h after the infection and was associated with gradual increases in pulmonary levels of interleukin-6, macrophage inflammatory protein (MIP)-1alpha, MIP-2, monocyte chemoattractant protein-1, KC, and neutrophil recruitment. The injection of tumor necrosis factor-alpha or the addition of lipopolysaccharide or heat-killed S. pneumoniae to the inoculum enhanced early host response and survival. These observations may help develop appropriate markers of evolution of pneumonia, as well as new therapeutic strategies.

New Equations and a Critical Appraisal of Coronary Artery Z Scores in Healthy Children

BACKGROUND The aim of this study was to find the best model to obtain valid and normally distributed Z scores for coronary artery (CA) diameters in a large, heterogeneous population of healthy children. METHODS Echocardiography was performed on 1,033 healthy children. Several regression models were tested with height, weight, body surface area, and aortic valve diameter. The computed Z scores were tested for normal distribution and stability. RESULTS CA diameter was best predicted using regression with the square root of body surface area. The weighted least squares method yielded normally distributed and very stable Z-score estimates for all CA segments. In prepubertal children, aortic valve diameter was also a valid predictor of CA diameter. CONCLUSIONS This study shows two valid methods to estimate Z scores for CA size in children of all ages. Such Z scores are important for risk stratification in patients with Kawasaki disease.

Bat Rabies in the United States and Canada from 1950 through 2007: Human Cases With and Without Bat Contact

BACKGROUND Since the 1980s, rare cases of rabies in humans in Canada and the United States have been almost exclusively caused by the bat-variant virus. METHODS We reviewed indigenously acquired cases of bat-variant rabies in humans in Canada and the United States from 1950 through 2007. RESULTS Of 61 cases identified, 5 occurred after organ transplantation and were excluded from further analysis. A bite was reported by 22 (39%) of the case patients, 9 (16%) had a direct contact (i.e., were touched by a bat) but no history of a bite, 6 (11%) found bats in their home (2 [4%] in the room where they slept) but reported no direct contact, and 19 (34%) reported no history of bat exposure whatsoever. With the exception of California (8 cases) and Texas (7 cases), no state or province had >3 cases. Of the case patients, 76% were men, and 40% were 10-29 years of age. The median incubation period was 7 weeks (<10 weeks in 72% of cases). The incidence of bat-variant rabies cases increased from 2.2 per billion person-years in 1950-1989 to 6.7 per billion person-years in 1990-2007. Of 36 case patients with bat rabies described since 1990, 16 had no history of direct bat contact; 2 (13%) of the 16 would have qualified for rabies postexposure prophylaxis on the basis of exposure criteria expanded in 1995 to include bats that were in the same room as a sleeping person. The incidence of rabies for this type of exposure was 0.6 cases per billion person-years. CONCLUSION The true preventable proportion of cases and the number needed to treat with rabies postexposure prophylaxis to prevent 1 case would be useful information to inform the current guidelines.

A Review and Critique of the Statistical Methods Used to Generate Reference Values in Pediatric Echocardiography

Several articles have proposed echocardiographic reference values in normal pediatric subjects, but adequate validation is often lacking and has not been reviewed. The aim of this study was to review published reference values in pediatric two-dimensional and M-mode echocardiography with a specific focus on the adequacy of the statistical and mathematical methods used to normalize echocardiographic measurements. All articles proposing reference values for transthoracic pediatric echocardiography were reviewed. The types of measurements, the methods of normalization, the regression models used, and the methods used to detect potential bias in proposed reference values were abstracted. The detection of residual associations, residual heteroscedasticity, and departures from the normal distribution theory predictions were specifically analyzed. Fifty-two studies met the inclusion criteria. Most authors (87%) used parametric normalization to account for body size, but their approaches were very heterogeneous. Linear regression and indexing were the most common models. Heteroscedasticity was often present but was mentioned in only 27% of studies. The absence of residual heteroscedasticity and residual associations between the normalized measurements and the independent variables were mentioned in only 9% and 22% of the studies, respectively. Only 14% of studies documented that the distribution of the residual values was appropriate for Z score calculation or that the proportion of subjects falling outside the reference range was appropriate. Statistical suitability of the proposed reference ranges was often incompletely documented. This review underlines the great need for better standardization in echocardiographic measurement normalization.

Reference Values for Pulse Wave Doppler and Tissue Doppler Imaging in Pediatric Echocardiography

Background—In pediatric echocardiography, pulse wave Doppler, and tissue Doppler imaging velocities are widely used to assess cardiac function. Current reference values and Z scores, allowing adjustment for growth are limited by inconsistent methodologies and small sample size. Using a standardized approach for parametric modeling and Z score quality assessment, we propose new pediatric reference values and Z score equations for most left ventricular pulse wave Doppler and tissue Doppler imaging measurements. Methods and Results—Two hundred thirty-three healthy pediatric subjects 1 to 18 years of age were prospectively recruited. Thirteen pulse wave Doppler and 14 tissue Doppler imaging measurements were recorded. Normalization for growth was done via a complete and standardized approach for parametric nonlinear regression modeling. Several analyses were performed to ensure adequate Z score distribution and to detect potential residual associations with growth or residual heteroscedasticity. Most measurements adopted a nonlinear relationship with growth and displayed significant heteroscedasticity. Compared with age, height, and weight, normalization for body surface area was most efficient in removing the effect of growth. Generally, polynomial and allometric models yielded adequate goodness-of-fit. Residual values for several measurements had significant departure from the normal distribution, which could be corrected using logarithmic or reciprocal transformation. Overall, weighted parametric nonlinear models allowed us to compute Z score equations with adequate normal distribution and without residual association with growth. Conclusions—We present Z scores for normalized pulse wave Doppler and tissue Doppler imaging in pediatric echocardiography. Further studies are needed to define the threshold beyond which health becomes a disease by integrating other important factors such as ventricular morphology, loading conditions, and heart rate.

Efficacy of Recombinant Human Granulocyte Colony-Stimulating Factor in a Murine Model of Pneumococcal Pneumonia: Effects of Lung Inflammation and Timing of Treatment

The effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in a murine model of pneumococcal pneumonia was examined. Intranasal inoculations were 10(7) cfu/mouse (high inoculum) and 5 x 10(4) cfu/mouse (low inoculum) of Streptococcus pneumoniae, which induced severe or mild lung inflammation, respectively. With the low inoculum, rhG-CSF significantly improved survival when initiated 24 h or 10 min before, but not when initiated 24 h after, infection. Pretreatment with rhG-CSF significantly increased myeloperoxidase (MPO) activity in lungs 8 h after the infection and increased circulating neutrophil count 24, 48, and 72 h after infection. In contrast, rhG-CSF did not improve survival of animals infected with the high inoculum and did not increase MPO activity or neutrophil count in blood over those of sham-treated controls. These data strongly suggest that the severe inflammatory response typically observed in pneumococcal pneumonia recruits a maximum number of neutrophils in the lungs and thus masks the beneficial effect of rhG-CSF.

Value of amino-terminal pro B-natriuretic peptide in diagnosing Kawasaki disease

Background:  The aim of the present study was to investigate the diagnostic value of the N‐terminal B‐type natriuretic peptide (NT‐proBNP) in acute Kawasaki disease (KD) given that the clinical criteria and the current basic laboratory tests lack the necessary specificity for accurate diagnosis.

Long-Lasting Measles Outbreak Affecting Several Unrelated Networks of Unvaccinated Persons

Despite a population immunity level estimated at approximately 95%, an outbreak of measles responsible for 94 cases occurred in Quebec, Canada. Unlike previous outbreaks in which most unvaccinated children belonged to a single community, this outbreak had cases coming from several unrelated networks of unvaccinated persons dispersed in the population. No epidemiological link was found for about one-third of laboratory-confirmed cases. This outbreak demonstrated that minimal changes in the level of aggregation of unvaccinated individuals can lead to sustained transmission in highly vaccinated populations. Mathematical work is needed regarding the level of aggregation of unvaccinated individuals that would jeopardize elimination.