Hemolytic uremic syndrome (HUS) is typically a complication of enterocolitis from Shiga toxin-producing Escherichia coli. Streptococcus pneumoniae-associated HUS (SP-HUS) is less frequent, accounting for ~5% of HUS cases in children. It is most associated with invasive pneumococcal disease (IPD) that presents with pneumonia. Pediatric SP-HUS mortality has been reported as 3-12%. This study aimed to describe the epidemiology of pediatric SP-HUS in Canada by conducting a secondary analysis of the national pediatric IPD surveillance data from 1991-2019.

BACKGROUND: Before implementation of the first conjugate IPD vaccine program in 2002, invasive pneumococcal disease (IPD) accounted for most severe, invasive bacterial infections in Canadian children. Conjugate vaccine programs in children were implemented with the expectation that the burden of disease from IPD would improve. OBJECTIVES: To describe the changes in Canadian epidemiology of pediatric IPD before and after the implementation of conjugate pneumo-coccal vaccine programs. DESIGN/METHODS: The Canadian Immunization Monitoring Program, Active (IMPACT) captures all in- and out-patient lab-confirmed IPD cases presenting at its 12 tertiary care pediatric hospitals across Canada. Nurses abstract case details from the hospital chart onto a standardized report form. Case isolates are serotyped at a central reference laboratory. All participating centers have local ethics and/or administrative approvals. RESULTS: From 2000-2014 IMPACT centers identified 3,328 IPD cases. Annual case numbers decreased by 48% (323 to 168) over this time period. Annually, vaccine preventable serotypes accounted for on average 89% (n=288) of cases in the pre-conjugate vaccine era (2000-2003) and 34% (n=56) in the post-13-valent conjugate vaccine era (2011-2014), with 73% (n=41/56) due to serotypes 19A, 3 and 6a. The age distribution of cases shifted upward over the time period with 16% (n=204) of cases occurring in children 5 years of age and older in the pre-vaccine era compared to 32% (n=217) in the post 13-valent vaccine era. This shift was due to decreases in cases occurring in children 0-4 years of age, rather than a significant increase in the number of cases occurring in older children. The most frequent presentation of IPD was radiologic-confirmed pneumonia (n=1119), with complicated pneumonia (pneumonia with empyema or pleural effusion) accounting for 36% (405/1119) of cases, followed by bacteremia only (n=919) and meningitis (n=532). The proportion of cases presenting with complicated pneumonia increased significantly (from 6% -24%; p<0.0001) between the pre-conjugate and post 13-valent conjugate eras. The proportion of cases presenting with meningitis did not change over the time periods (15% pre-conjugate era vs. 16% post-13-valent conjugate era; p=0.46). However, the proportion of meningitis caused by vaccine preventable serotypes decreased significantly (from 85%-26%; p<0.0001). CONCLUSION: The epidemiology of pediatric IPD has changed with the introduction of conjugate vaccine programs. IPD has been reduced by almost 50% in the post-13-valent conjugate vaccine era and vaccine sero-types account for just one-third of cases. However, complicated pneumonia is seen more frequently in the post-13-valent conjugate vaccine era.

In 2011 and 2012, a nationwide Canadian vaccine safety surveillance network rapidly collected safety data from healthcare workers (HCW) during the first weeks of the annual influenza vaccination campaign. This network provided the first available post-marketing safety data on seasonal influenza vaccines with information on background rates as a comparator. In 2012, these data were used to investigate a possible safety concern regarding a particular vaccine. An online questionnaire was provided to participating HCW two weeks before the annual influenza vaccination campaign for controls, and eight days after influenza vaccination for vaccinees. Control and vaccinees were requested to report health events occurring in the seven days prior to receiving the questionnaire. Control data were used to calculate background rates. HCW reporting a severe event were followed-up by telephone within 48 hours of the online report to validate the report and check on their health status. More than 22,000 vaccinated HCW were enrolled and surveyed over two seasons and > 90% reported no severe event following vaccination. Validated severe event rates were similar in vaccinated HCW and unvaccinated HCW (2.2% vs 2.3%; p < 0.70). The questionnaire was accurately completed for most reported symptoms, matched the validated report and was able to detect events of interest. Prior to the safety concern, the implicated vaccine was in use at one centre. Reassuring safety data were provided to public health authorities 48 hours after the vaccine was temporarily suspended. Data from this and similar networks can be used for rapid evaluation of vaccine safety and for safety assessment as required by the European Medicines Agency in 2015.

Acute respiratory tract infections caused by Streptococcus pneumoniae(SP) are a leading cause of morbidity and mortality in young children and the elderly. In 2002, Alberta introduced a pneumococcal universal immunization program for children, using Prevnar 7 (PCV7). In this study, we assess the economic impact of PCV7 on the Alberta health care system. Using active surveillance data from Alberta, we examine the net costs averted as a result of a decline in PCV7 serotypes, accounting for the increase in costs due to serotype replacement. We also calculate the magnitude of herd immunity in terms of costs averted. We find that following the introduction of PCV7 (2003-2008), the number of cases of invasive disease caused by vaccine serotypes declined significantly across all ages. Specifically, by 2008, there was considerable evidence of herd immunity as the incidence rates had declined nearly 100% across all ages. However, non-PCV7 cases, on the other hand, increased. Assuming serotype replacement is a result of the introduction of PCV7, net costs averted are in the range of $5 million as a result of the implementation of PCV7 universal vaccination in Alberta. Over the time period, direct protection resulted in net cost savings of $2.6 million, and indirect benefits $2.4 million; the indirect benefits derived by elderly populations were more than one third of the total benefits derived across the population. This study is unique in that it uses validated surveillance data from Alberta to retrospectively assess the economic benefit of a public health policy, and describes the distribution of benefits across different segments of the population. From 2003 to 2008, the cumulative cost impact of introducing PCV7 in the childhood immunization program to the Alberta health system is approximately $5 million, half of which were a result of herd immunity.

To estimate the economic burden of lost productivity and health care resource use associated to tobacco in the Brazilian population among smoking and non-smoking/ex-smoking employees. A structured search was performed on MEDLINE database (via PubMed) using the MesH Database terms in accordance with the following terms ((“Costs and Cost Analysis” [Mesh]) AND (“Smoking” [Mesh]) AND (“ absenteeism” [Mesh]) AND (“presenteeism” [Mesh])), as well as the cost of absence days due to health events retrieved from national labor legislations; and average wage was retrieved from the Brazilian Institute for Geography and Statistics (IBGE) 2.013. The disease costs related to tobacco are Cardiovascular disease (CVD) BRL 27,845.32; stroke BRL 20,591.24; Chronic obstructive pulmonary disease (COPD) BRL 21,328.59; pneumonia BRL 1,111.82; lung cancer BRL 67,225.83; other cancers BRL 85,524.46. When comparing the productivity and absence days, the smokers lose 62.1% more days than nonsmokers and 41.34% than ex-smokers, which corresponds to BRL 1,326.62 in terms of annual monetary average cost. Additionally, it was found that the life expectancy of male smokers corresponds to 75.30 years; for females, it already was 79.77 years. That means a loss of 5.03 and 4.5 years, respectively, when compared to the expected useful lives of the the nonsmoking population. Therefore, smoking employees can cost, on unproductive days, almost 3 times more than non-smokers and 2 times more than ex-smokers, besides the cost related to the treatment of stroke, COPD and CVD, and others.

In Canada, a 13-valent conjugate polysaccharide pneumococcal vaccine (PCV13) has recently been licensed for immunocompetent adults aged 50 years or older, as well as children over the age of 5. Currently, a 23-valent pneumococcal polysaccharide vaccine (PPV23) is recommended for high risk adults and all seniors. The health benefits and economic value of vaccinating Canadian adults with PCV 13 instead of PPV 23 is unknown. Compared to PCV13, PPV 23 covers 11 additional serotypes but may not be as effective for the 12 shared serotypes due to PCV13 being a conjugate vaccine as opposed to a polysaccharide. The objective is to develop a model that compares the health and economic consequences of PCV13 as compared to PPV23 in Canadian adults aged 50+. We developed a base simulation model for an entire population of providing PCV13 to children less than 2 years of age and simulating the herd effects to the greater population. Vaccinating adults older than 50 years of age with either PCV13 or PPV23 was then compared to the base model, and the health and economic consequences examined across each scenario. Health impacts included invasive pneumococcal disease and pneumococcal related disease. Invasive disease is caused by Streptococcus Pneumococcal and is clinically presented as: meningitis, bacteremia and invasive pneumonia. Pneumococcal related disease is non invasive and has many different etiologies, the main clinical presentations include: otitis media (in base model for children only), and non-invasive pneumonia. Costs and QALYs were contrasted between the two adult vaccination strategies. Compared to PPV23, PCV13 was associated with 0.278more cases of invasive pneumonia, 0.061more cases of bacteremia, 0.002more cases of meningitis, and 27.997less cases of pneumococcal related disease per 100,000. Compared to PPV23, the incremental cost effectiveness ratio associated with PCV13 was $10,028 per additional QALY gained. Compared to PPV23, vaccinating adults with PCV13 is cost effective.

Several years after the seven-valent pneumococcal conjugate vaccine (PCV7) was introduced in Canada and elsewhere, routine infant vaccination has led to near eradication of invasive pneumococcal disease caused by vaccine serotype strains in both children and adults. There have also been significant declines in pneumococcal-related disease including lobar pneumonia and otitis media. These declines have been offset, to some extent, by increases in nonvaccine serotype disease. Serotype 19A, which is often highly resistant to antibiotics, has become predominant. In most populations, however, the magnitude of replacement disease is much lower than the magnitude of decline in invasive pneumococcal disease with the use of PCV7. There is increasing evidence that three PCV7 doses provide protection that is nearly identical to that of four doses. New 10-valent and 13-valent pneumococcal conjugate vaccines were recently approved in Canada. These vaccines increase pneumococcal serotype coverage including serotype 19A (present in the 13-valent vaccine). Many provinces and territories have incorporated the 13-valent vaccine in their vaccination programs.

Quelques années après l’adoption du vaccin conjugué heptavalent contre le pneumocoque (PCV7) au Canada et ailleurs, la vaccination systématique des nourrissons a suscité la quasi-éradication des pneumococcies invasives causées par les souches des sérotypes vaccinaux, tant chez les enfants que chez les adultes. On a également observé une diminution importante des maladies liées au pneumocoque, y compris la pneumonie lobaire et l’otite moyenne. Ces diminutions ont été contrebalancées, dans une certaine mesure, par l’augmentation des maladies à sérotypes non vaccinaux. Le sérotype 19A, qui est souvent hautement résistant aux antibiotiques, prédomine désormais. Dans la plupart des populations, cependant, la magnitude d’une maladie de remplacement est beaucoup plus faible que celle de la diminution des pneumococcies invasives attribuables au vaccin PCV7. De plus en plus de données probantes indiquent que trois doses du vaccin PCV7 assurent une protection presque identique à celle conférée par quatre doses. Les nouveaux vaccins conjugués 10-valent et 13-valent contre le pneumocoque ont récemment été approuvés au Canada. Ces vaccins accroissent la couverture des sérotypes pneumococciques, y compris le sérotype 19A (présent dans le vaccin 13-valent). De nombreuses provinces et de nombreux territoires ont intégré le vaccin 13-valent à leur programme de vaccination.

SUMMARYLarge-scale population-based studies have reported a significant increase in invasive pneumococcal disease (IPD) in those with underlying haematological or solid-organ malignancy, but limited condition-specific data are available on rates of IPD in the adult population. A retrospective chart review of all patients with IPD (identified prospectively) in the province of Alberta, Canada (population ~3·3 million) was conducted from 2000 to 2004 to study the epidemiology of IPD. Rates of IPD in patients with various haematological and solid-organ malignancies were determined by obtaining the number of these patients at risk from the provincial cancer registry. Compared to the attack rate of IPD in the adult population aged ⩾18 years (11·0 cases/100 000 per year, 95% CI 10·44–11·65), there were significantly increased rates of IPD in those with lung cancer (143·6 cases/100 000 per year, OR 13·4, 95% CI 9·3–19·4, P<0·001) and multiple myeloma (673·9 cases/100 000 per year, OR 62·8, 95% CI 39·6–99·8, P<0·001). More modestly increased rates of IPD were found in those with chronic lymphocytic leukaemia, acute myeloid leukaemia, acute lymphoblastic leukaemia, and Hodgkin's and non-Hodgkin's lymphoma. There was an increased prevalence of serotype 6A in those with these underlying malignancies, but no other serotypes predominated. Fifty-three percent (48/83) of cases were caused by serotypes in the investigational 13-valent pneumococcal conjugate vaccine (PCV13), and 57/83 (69%) of the cases were caused by serotypes in the 23-valent pneumococcal polysaccharide vaccine (PPV23). The incidence of IPD in adults with certain haematological and solid-organ malignancies is significantly greater than the overall adult population. Such patients should be routinely given pneumococcal polysaccharide vaccine; this population could also be targeted for an expanded valency conjugate vaccine.

independent of an ASD diagnosis. with ASD and ADHD repre-sent a specific subtype of ASD, with identifiable characteristics. METHODS/ ANALySIS: A retrospective chart review was conducted. Information gathered included sex, age, IQ, communication profile, Autism Diagnostic Observation Schedule, Autism Diagnostic Interview, adaptive skills and Conners Parent Rating Scale subscale scores. Hierarchical linear models were used to estimate the effect of sex and diagnosis on raw Conners index scores, after controlling for age and adjusting for the correlation among individuals of the same family. An interaction between group and sex was introduced into the model in order to estimate within group gender effect and the effect of diagnosis within each gender. RESULTS: Data from 72 children diagnosed with autism were analyzed. Of these, 15 (20.8%) met the DSM- IV criteria for ADHD, with 2 (13.3%) meeting criteria for the hyperactive impulsive profile, 7 (46.7%) the inattentive profile and 6 (40%) meeting the criteria for the combined profile. When using a less conservative cutoff, an additional 39 (54%) children diagnosed with ASD demonstrated at least six symptoms of hyperactivity, impulsivity and or inattention. Only 18 (25%) children diagnosed with ASD displayed no symptoms of ADHD. Girls with ASD were more likely to be hyperactive and impulsive whilst unaffected sibling males were inattentive. SIGNIFICANCE: These data suggest that there are at least three differ-ent subtypes to describe the presentation of ADHD symptoms in children diagnosed with ASD. The three subtypes are the asymptomatic, sub clinical and a clinical group. This adds strength to the dimensional approach to classifying and interpreting symptoms in children diagnosed with autism. This challenges the present DSM-IV criteria which fail to recog-nize the coexistence of ADHD in ASD. columbia BACKGROUND: A 7-valent pneumococcal conjugate vaccine (PCV7; 4, 6B, 9V, 14, 18C, 19F, and 23F) has reduced morbidity and mortality associated with invasive pneumococcal disease in infants and children. We report safety and immunogenicity results for a 13-valent conjugate vaccine (PCV13; additional serotypes 1, 3, 5, 6A, 7F, 19A) when given with routine vaccines in Canada. METHODS: Healthy infants were randomized (1:1) to receive PCV7 or PCV13 at age 2, 4, and 6 months with DTaP-IPV-Hib at age 2, 4, and 6 months and tetanus-conjugated meningococcal C vaccine at 2 and 6 months. Antibody responses against meningococcal C, Haemophilus influenzae type b, and pertussis antigens in all subjects, and against pneumococcal serotypes in PCV13 subjects, were measured 1 month after the 6-month dose. Local and systemic reactions and adverse events were evaluated. Non inferiority of response to concomitant vaccines for PCV13 compared with PCV7 was declared if the lower limit of the 95% CI for the difference in proportions of subjects achieving pre-specified antibody levels was >−0.10. RESULTS: Target antibody responses to

Objective: Rabies virus has the highest case to fatality ratio of any infectious disease; however, vaccines and immunoglobulins are available for pre-and post-exposure prophylaxis.Due to the risk of possible hypersensitivity reactions, repeated booster doses of rabies vaccine should be administered only when necessary to people at risk of exposure.It is recommend that antibody testing be performed 2 years following primary immunization, followed by the administration of a booster dose if the neutralizing antibody titre falls below 0.5 International Units per ml (IU/ml).The objective of this work was to determine if the recommended testing interval following primary immunization is sufficient to maintain adequate antibody titres in healthy adults.Methods: During the establishment of the rabies laboratory at the NML in 2007, all employees determined to be at risk of exposure were vaccinated against rabies virus.Rabies vaccine was administered in 3 doses on days 0, 7, and 21.Antibody levels were monitored one month post-vaccination and subsequently every 6 months.Data from this testing were analyzed to determine if the vaccinated employees maintained adequate antibody titres for a minimum of 2 years following primary immunization.Results: The antibody titres of 12 employees were assessed 1 month after vaccination and subsequently every 6 months.All 12 employees demonstrated an acceptable antibody titre 1 month after vaccination, although the titres of 2 of the 12 employees were very low (0.5 IU/ml and 0.65 IU/ml).These 2 employees received a booster dose of vaccine immediately.Two other employees demonstrated a substantial drop in titre when subsequently tested 6 months later, resulting in a decision to administer a booster dose of vaccine to these employees who work directly with rabies virus.The antibody titre of these 4 employees has remained high throughout the follow-up testing intervals.Conclusions: Had the recommended testing interval of 2 years been followed, the antibody levels of 4 of the 12 employees may have potentially fallen below the acceptable level of 0.5 IU/ml.This indicates that some healthy individuals may not maintain an antibody titre of 0.5 IU/ml for at least 2 years following primary immunization.All persons at risk of exposure, especially those persons working directly with the live virus, should be monitored carefully.It may be advisable to administer a booster dose of vaccine 1 year following the primary vaccine series to reinforce antibody levels in individuals receiving pre-exposure vaccination for rabies virus.

independent of an ASD diagnosis.Children with ASD and ADHD represent a specific subtype of ASD, with identifiable characteristics.METHODS/ ANALySIS: A retrospective chart review was conducted.Information gathered included sex, age, IQ, communication profile, Autism Diagnostic Observation Schedule, Autism Diagnostic Interview, adaptive skills and Conners Parent Rating Scale subscale scores.Hierarchical linear models were used to estimate the effect of sex and diagnosis on raw Conners index scores, after controlling for age and adjusting for the correlation among individuals of the same family.An interaction between group and sex was introduced into the model in order to estimate within group gender effect and the effect of diagnosis within each gender.RESULTS: Data from 72 children diagnosed with autism were analyzed.Of these, 15 (20.8%) met the DSM-IV criteria for ADHD, with 2 (13.3%) meeting criteria for the hyperactive impulsive profile, 7 (46.7%) the inattentive profile and 6 (40%) meeting the criteria for the combined profile.When using a less conservative cutoff, an additional 39 (54%) children diagnosed with ASD demonstrated at least six symptoms of hyperactivity, impulsivity and or inattention.Only 18 (25%) children diagnosed with ASD displayed no symptoms of ADHD.Girls with ASD were more likely to be hyperactive and impulsive whilst unaffected sibling males were inattentive.SIGNIFICANCE: These data suggest that there are at least three different subtypes to describe the presentation of ADHD symptoms in children diagnosed with ASD.The three subtypes are the asymptomatic, sub clinical and a clinical group.This adds strength to the dimensional approach to classifying and interpreting symptoms in children diagnosed with autism.This challenges the present DSM-IV criteria which fail to recognize the coexistence of ADHD in ASD.

Methods 10 patients (5 M, 5 F) were enrolled, with mean (range) age 11.4 (4.5–16.3) years at IVP treatment. All patients received a 3-day infusion of IVP (0.5 mg/kg/day for the first dose; 1 mg/kg/day subsequently), followed by 1-day infusion monthly or 3-day infusion every 3 months until resolution of MRI documented bone inflammation. Weight and height were measured prior to first IVP, at 1year, and at final follow-up, and results were transformed into ageand gender-matched z-scores. Hotelling's test on the bivariate height and weight differences between 2 time points was performed.

A previously well, nine-month-old, Canadian-born, Caucasian infant presented with one month history of cough, irritability, and poor weight gain. Her past medical history was significant for open-heart surgery at age four months, with repair of a ventricular septal defect, closure of an atrial septal defect, and ligation of patent ductus arteriosus. There were no operative complications. Her development was normal for age. She had received her routine immunizations.There was no known infectious diseases contact or exposure to farm animals.