Protection against vaccine preventable diseases in children treated for acute lymphoblastic leukemia.

BACKGROUND: The objective of this retrospective study was to assess protection against vaccine preventable diseases (VPDs) in children treated for acute lymphoblastic leukemia (ALL). PROCEDURE: Clinical characteristics and vaccination records were collected. Antibodies against VPDs were measured after completion of chemotherapy and after a booster dose of vaccine. Immunization status of household members was evaluated. RESULTS: Sixty children were included. Median interval between the end of chemotherapy and enrolment in the study was 13 months (range 1-145). At ALL diagnosis, 81.3% of the children were up to date with their vaccination schedule. This proportion decreased to 52.9% at enrolment. Among the parents, 21% were up to date with their immunization schedule and 42% had received seasonal influenza vaccination. After chemotherapy, less than 50% of the patients were seroprotected against tetanus, diphtheria, polio 3, Haemophilus influenzae type b (Hib), and mumps and no more than 80% were seroprotected against polio 1 and 2, measles, rubella, and varicella. After a booster dose of vaccine, the rate of protection increased to over 90% for each of the following antigens: TT, DT, polio 1, Hib, measles, and rubella. Nevertheless, polio 3, mumps, and varicella-zoster virus antibodies titers/concentrations remained below seroprotective thresholds in over 20% of the patients. CONCLUSIONS: After chemotherapy for ALL, most of the children were not protected against VPDs. As the majority mounted a robust response to booster vaccines, efforts need to be done to improve protection against VPDs by implementing a systematic vaccine booster schedule. This could also be helped by reinforcing household members' immunization.

Awareness of cytomegalovirus and risk factors for susceptibility among pregnant women, in Montreal, Canada.

BACKGROUND: Advances in diagnostic and therapeutic modalities for congenital cytomegalovirus (CMV) infection have generated a mounting interest in identifying mothers susceptible to CMV. The objectives of this study were to evaluate the prevalence and socio-demographic determinants of CMV susceptibility and CMV awareness, among pregnant women, in Montreal, Quebec. METHODS: Between April and December 2012, women delivering at Centre Hospitalier Universitaire Sainte Justine were recruited for the study. Stored serum from the first trimester of pregnancy was tested for CMV IgG. Knowledge about CMV and socio-demographic characteristics were collected via standardized questionnaire. RESULTS: Four hundred and ninety one women were enrolled in the study. Overall, 225 mothers (46%) were seronegative for CMV, and 85% (n = 415) were unaware of CMV or the associated risks in pregnancy. Significant risk factors for CMV seronegative status included Canadian vs. foreign born (aOR 6.88, 95% CI 4.33-10.94), and high vs. low family income (aOR 4.68, 95% CI 2.09-10.48). Maternal employment status was the only significant predictor of CMV unawareness, with unemployed mothers at the highest risk (aOR 85.6, 95% CI 17.3-421.3). CONCLUSIONS: Nearly half of pregnant women studied were at risk of primary infection, and yet, the majority was unaware of potential risks associated with CMV. Canadian born mothers and those with a high socioeconomic status were more likely to be CMV seronegative. Increased education about CMV infection, through public health interventions and obstetrician/pediatric counseling, is needed for all pregnant women.

Pediatric Pleural Empyema in the Province of Quebec: Analysis of a 10-Fold Increase Between 1990 and 2007.

BACKGROUND: Although the frequency of pneumonia has decreased over time, an increase in pleural empyema has been observed in different settings worldwide. This study assessed the epidemiology of community-acquired pediatric pleural empyema in the province of Quebec through validation of cases found in a hospitalization discharge database. METHODS: We used the national administrative database of hospitalization to identify children (6 months-14 years) hospitalized for pleural empyema or pleural effusion with drainage from January 1990 until December 2007 and reviewed their medical charts. Patients with pleural effusion secondary to chest trauma, thoracic surgery, malignancies, cardiac failure, or metabolic disorders were excluded. RESULTS: Predictive positive value (PPV) of empyema code in any position among discharge diagnostics in the administrative database was 86.5% (95% confidence interval: 81.9%-90.3%). After chart revision, 292 met the inclusion criteria. Age-adjusted incidence of pleural empyema in the pediatric population increased from 0.23 in 1990 to 4.01/100,000 person-years in 2007. A bacterial pathogen was identified in 46.5%; Streptococcus pneumoniae (Sp) (42%) and S pyogenes (30%) were most frequent. There was no obvious change in the PPV and proportions of children with chronic disease or asthma and in identified pathogens over time, but an increase in pre-admission respiratory symptoms duration (from 3.8 days to 5.7) and nonsteroidal anti-inflammatory drug use (from 0% to 19%) was observed. CONCLUSIONS: From 1990 to 2007, we observed a 10-fold increase in the incidence of pediatric hospitalizations associated with pleural empyema. This increase preceded the introduction of a pneumococcal conjugated vaccine program in Quebec. Sp remained the major pathogen identified.

Evaluation of several approaches to immunize parents of neonates against B. pertussis.

BACKGROUND: Parental immunization ("cocooning") is a potentially effective strategy to protect neonates against Bordetella pertussis. The objective of this study was to evaluate three approaches to parental immunization: (1) current practice (single dTap dose to adolescents, one additional dose recommended in adults); (2) promotion of vaccination in the maternity ward, with vaccine offered in the community; and (3) promotion and administration of vaccine in the maternity ward. METHODS: We conducted a two-phase study of postpartum women in a tertiary care obstetric-pediatric hospital in Montreal, Canada. In Phase I, mothers completed a standardized questionnaire regarding pertussis knowledge, attitudes and immunization status. Interviews provided information on cocooning and pertussis vaccination, and invited parents to receive the vaccine in the community. In phase II, information was provided (no questionnaire) with vaccination offered in the maternity ward before discharge. RESULTS: Phase I included 101 participants; Phase II, 244. Baseline knowledge on infant disease severity and adult vaccine recommendations was poor. Only 6% of women were considered protected. In Phase I, 56.3% and 62.5% of eligible mothers and fathers, respectively, were willing to receive the vaccine; only 5.4% and 8.7% were immunized in the community. In Phase II, 53.1% and 62.6% of mothers and fathers, respectively, would accept vaccination; 46.9% of mothers and 60.5% of fathers were immunized onsite (p<0.01). CONCLUSION: Offering dTap vaccine in the maternity ward is an effective approach to promote cocooning and increase vaccine uptake. The generalizability and cost effectiveness of this strategy should be investigated further.

Novel influenza A (H1N1): clinical features of pediatric hospitalizations in two successive waves.

OBJECTIVE: To describe and compare the characteristics of children hospitalized with novel influenza A (H1N1) during two successive waves. METHODS: This was a medical chart review of all children hospitalized in a French Canadian pediatric hospital in Montreal in the spring and fall of 2009 with a positive real-time polymerase chain reaction for novel influenza A (H1N1) and flu-like symptoms. RESULTS: We included 202 children with a median age of 4.9 (range 0.1-18) years. Demographic and clinical features of the children in the two waves were similar. One or more underlying medical conditions were found in 59% of the children. Clinical findings at admission were: fever (98%), cough (88%), congestion/rhinorrhea (58%), gastrointestinal symptoms (47%), oxygen saturation below 95% (33%), sore throat (20%), and neurological symptoms (9%). Admission to the intensive care unit was required for 22 (11%) children, and 14 patients needed respiratory support. During the second wave, the median duration of stay was shorter (3 vs. 4 days, p=0.003) and oseltamivir was used more often (84% vs. 40%, p<0.001). CONCLUSIONS: Children hospitalized during the two successive waves of H1N1 were mainly school-aged and suffered from moderate disease. Although clinical features and severity of disease were similar, oseltamivir was prescribed more frequently and the length of hospital stay was shorter in the second wave.

Impact of early transcranial Doppler screening and intensive therapy on cerebral vasculopathy outcome in a newborn sickle cell anemia cohort.

Transcranial Doppler (TCD) is used to detect children with sickle cell anemia (SCA) who are at risk for stroke, and transfusion programs significantly reduce stroke risk in patients with abnormal TCD. We describe the predictive factors and outcomes of cerebral vasculopathy in the Créteil newborn SCA cohort (n = 217 SS/Sß(0)), who were early and yearly screened with TCD since 1992. Magnetic resonance imaging/magnetic resonance angiography was performed every 2 years after age 5 (or earlier in case of abnormal TCD). A transfusion program was recommended to patients with abnormal TCD and/or stenoses, hydroxyurea to symptomatic patients in absence of macrovasculopathy, and stem cell transplantation to those with human leukocyte antigen-genoidentical donor. Mean follow-up was 7.7 years (1609 patient-years). The cumulative risks by age 18 years were 1.9% (95% confidence interval [95% CI] 0.6%-5.9%) for overt stroke, 29.6% (95% CI 22.8%-38%) for abnormal TCD, which reached a plateau at age 9, whereas they were 22.6% (95% CI 15.0%-33.2%) for stenosis and 37.1% (95% CI 26.3%-50.7%) for silent stroke by age 14. Cumulating all events (stroke, abnormal TCD, stenoses, silent strokes), the cerebral risk by age 14 was 49.9% (95% CI 40.5%-59.3%); the independent predictive factors for cerebral risk were baseline reticulocytes count (hazard ratio 1.003/L × 10(9)/L increase, 95% CI 1.000-1.006; P = .04) and lactate dehydrogenase level (hazard ratio 2.78/1 IU/mL increase, 95% CI1.33-5.81; P = .007). Thus, early TCD screening and intensification therapy allowed the reduction of stroke-risk by age 18 from the previously reported 11% to 1.9%. In contrast, the 50% cumulative cerebral risk suggests the need for more preventive intervention.

G6PD deficiency, absence of alpha-thalassemia, and hemolytic rate at baseline are significant independent risk factors for abnormally high cerebral velocities in patients with sickle cell anemia.

Stroke is predicted by abnormally high cerebral velocities by transcranial doppler (TCD). This study aimed at defining predictive factors for abnormally high velocities (>/= 2 m/sec) based on the Créteil pediatric sickle cell anemia (SCA) cohort composed of 373 stroke-free SCA children. alpha genes and beta-globin haplotypes were determined. Biologic parameters were obtained at baseline. alpha-thalassemia was present in 155 of 325 and G6PD deficiency in 36 of 325 evaluated patients. TCD was abnormal in 62 of 373 patients. Multivariate logistic regression analysis showed that G6PD deficiency (odds ratio [OR] = 3.36, 95% confidence interval [CI] 1.10-10.33; P = .034), absence of alpha-thalassemia (OR = 6.45, 95% CI 2.21-18.87; P = .001), hemoglobin (OR per g/dL = 0.63, 95% CI 0.41-0.97; P = .038), and lactate dehydrogenase (LDH) levels (OR per IU/L = 1.001, 95% CI 1.000-1.002; P = .047) were independent risk factors for abnormally high velocities. This study confirms the protective effect of alpha-thalassemia and shows for the first time that G6PD deficiency and hemolysis independently increase the risk of cerebral vasculopathy.

Patient-reported outcomes of deferasirox (Exjade, ICL670) versus deferoxamine in sickle cell disease patients with transfusional hemosiderosis. Substudy of a randomized open-label phase II trial.

BACKGROUND/AIMS: There is increasing evidence demonstrating the value of transfusions in sickle cell disease (SCD). However, resultant iron overload can be life threatening if untreated. Chelation therapy with deferoxamine requires parenteral infusions that can negatively impact quality of life and adherence to treatment. METHODS: As part of a phase II trial, SCD patient-reported outcomes were evaluated. One hundred and ninety-five patients were randomized (2:1) to receive oral deferasirox (5-30 mg/kg/day) or deferoxamine (20-50 mg/kg, 5 days per week); 121 had previously received deferoxamine. RESULTS: At each time point, significantly more patients who had previously received deferoxamine were 'satisfied/very satisfied' with deferasirox, or found treatment to be 'convenient/very convenient' compared with deferoxamine (p < 0.001). In these patients, fewer hours were lost from daily activities with deferasirox than deferoxamine treatment. Most patients (77%) preferred deferasirox, and more were willing to continue taking deferasirox than deferoxamine at end-of-study (84 vs. 11%, respectively). CONCLUSIONS: Patients with SCD are therefore more satisfied with deferasirox, which has a lower impact on daily activities than deferoxamine. Given the high levels of satisfaction, it is likely that quality of life will be improved. These results also suggest that treatment adherence with deferasirox may be better than with deferoxamine, which should lead to improved long-term outcomes.

Long-term results of related myeloablative stem-cell transplantation to cure sickle cell disease.

Allogeneic hematopoietic stem-cell transplantation (HSCT) is the only curative treatment for sickle cell disease (SCD); nevertheless, its use has been limited by the risk of transplantation-related mortality (TRM). Between November 1988 and December 2004, 87 consecutive patients with severe SCD ranging from 2 to 22 years of age received transplants in France. Cerebral vasculopathy was the principal indication for transplantation (55 patients). All the patients received grafts from a sibling donor after a myeloablative conditioning regimen (CR). The only change in the CR during the study period was the introduction of antithymocyte globulin (ATG) in March 1992. The rejection rate was 22.6% before the use of ATG but 3% thereafter. With a median follow-up of 6 years (range, 2.0 to 17.9 years), the overall and event-free survival (EFS) rates were 93.1% and 86.1%, respectively. Graft versus host disease (GVHD) was the main cause of TRM. Importantly, cord blood transplant recipients did not develop GVHD. No new ischemic lesions were detected after engraftment, and cerebral velocities were significantly reduced. The outcome improved significantly with time: the EFS rate among the 44 patients receiving transplants after January 2000 was 95.3%. These results indicate that HLA-identical sibling HSCT after myeloablative conditioning with ATG should be considered as a standard of care for SCD children who are at high risk for stroke.

Long-term follow-up of pediatric sickle cell disease patients with abnormal high velocities on transcranial Doppler.

Cerebral arteriopathy can be detected in children with sickle cell disease (SCD) by transcranial Doppler (TCD). Abnormally high velocities are predictive of high stroke risk, which can be reduced by transfusion therapy. We report the results of the screening of 291 SCD children followed in our center, including the clinical and imaging follow-up of 35 children with abnormal TCDs who were placed on transfusion therapy. We postulated that patients with normal MRA findings and abnormal TCD velocities that normalized on a transfusion program could be safely treated with hydroxyurea (HU). We report their outcome (median follow-up of 4.4 years). Of 13 patients with normalized velocities on transfusion, 10 had normal MRAs, and transfusion therapy was stopped and HU begun. Four of these ten patients redeveloped high velocities off transfusion, so currently only six remain transfusion-free. Six other transplanted patients remain transfusion-free. Abnormal TCD velocities detect a high-risk group, justifying the research for suitable transplant donors. Multicenter studies comparing HU therapy to long-term transfusion might help identify which patients can avoid transfusion and its complications while avoiding vasculopathy.