Canadian vaccine research networks: Vaccine safety resources for Canada.

The Public Health Agency of Canada / Canadian Institutes of Health Research Influenza Research Network (PCIRN), established in 2009 to undertake evaluative research to inform public health decision making in Canada, is now being replaced by the Canadian Immunization Research Network (CIRN), which will retain the mandate of PCIRN but expand it to all vaccines including influenza vaccine. CIRN is organized as a network of networks focusing on undertaking research in the areas of vaccine safety, adverse events following immunization (AEFIs), vaccine hesitancy, vaccine effectiveness, and vaccine coverage. CIRN's networks include: a clinical trial network; a laboratory network; a modelling and economics network; a network of social science and humanities researchers; a vaccine safety surveillance network; a hospital-based surveillance network; a clinic network to evaluate serious AEFIs; and a network that links vaccine research capacity in provincial health agencies and departments. PCIRN has contributed to Canada's vaccine safety surveillance system and has facilitated the translation of safety research into policy. Vaccine safety surveillance and research will remain a focus of the newly formed Canadian Immunization Research Network.

Evaluation of a rapid beta-lactamase test for detecting ampicillin-resistant strains of Hemophilus influenzae type b.

Chloramphenicol is presently the drug of choice in the initial treatment of serious infections due to Hemophilus influenzae type b. Rapid detection of ampicillin resistance in clinical isolates would facilitate early discontinuation of chloramphenicol therapy in patients infected with ampicillin-sensitive bacteria. A total of 160 strains of H. influenzae type b were tested with a one-hour acidimetric microassay for beta-lactamase activity. All ampicillin-resistant strains rapidly hydrolysed the beta-lactam ring of penicillin. When isolates were encoded and tested without knowledge of their MICs, the 40 ampicillin-resistant strains (MIC greater than or equal to 2 mug/ml) were readily distinguished from 120 sensitive strains. Rapid beta-lactamase assay is therefore a reliable detector of ampicillin resistance in H. influenzae type b.

Neonatal necrotizing enterocolitis associated with delta toxin-producing methicillin-resistant Staphylococcus aureus.

Delta toxin-producing coagulase-negative staphylococci previously have been associated with necrotizing enterocolitis in neonates. We identified three preterm infants (body weight, 845 +/- 59 g) infected with methicillin-resistant Staphylococcus aureus (MRSA) who had a similar clinical syndrome, characterized by pustular dermatitis, bacteremia and necrotizing enterocolitis accompanied by gastric residua, abdominal distention, hematochezia and pneumatosis intestinalis. MRSA was recovered from all three infants at infected skin sites, blood or venous catheters and from two of three infants in stool specimens. Two infants also had Staphylococcus epidermidis isolated from stool. All MRSA isolates had identical microbiologic profiles: four plasmids with identical molecular weights; coproduction of enterotoxins A and B; and the same antibiotic susceptibilities. Of one skin isolate, two blood isolates and two stool isolates of MRSA that were tested, all had characteristic delta toxin hemolytic activity. All culture supernatants of these isolates evaluated for delta toxin were positive by Western blot analysis. The two strains of S. epidermidis isolated from stool were negative for delta-like toxin by a standardized enzyme-linked immunoassay. The clustering of these cases, the similarity of the clinical syndrome, and the prior association of necrotizing enterocolitis with delta-like toxins produced by S. epidermidis, suggest that delta toxin-producing MRSA (or other S. aureus isolates) also may be etiologic agents in some cases of necrotizing enterocolitis in newborns.

Comparative safety of tetanus-diphtheria toxoids booster immunization in students in Grades 6 and 9.

BACKGROUND: Tetanus-diphtheria toxoids (Td) booster immunization is generally recommended for Grade 9 students (14- to 16-year-olds) but targeting younger students may enhance vaccine uptake or facilitate simultaneous vaccinations. However, earlier vaccination might cause greater side effects. This study was undertaken to compare the safety of Td vaccinations in students in Grade 6 (11 to 12 years old) and Grade 9. METHODS: A controlled, sequential assessment of Td vaccine, adsorbed, was conducted in one urban school district, starting with Grade 9 students. Grade 6 students were given Td concurrently with Dose 3 of hepatitis B vaccine. Adverse effects were assessed during visits 2 days after vaccination. Participation criteria, immunization technique and assessment procedures were standardized. RESULTS: Of 410 students vaccinated, 204 in Grade 9 and 206 in Grade 6, 391 (95.4%) were assessed in person. Nineteen missed follow-up visits but telephone interviewers established that none missed school because of vaccine side effects. At follow-up Grade 6 students more often reported deltoid pain with arm movement (35.2% vs. 10.8%, P < 0.001). Injection site redness > or = 50 mm in diameter was present in 12.2% of Grade 6 and 3.6% of Grade 9 students (P < 0.001) whereas swelling > or = 50 mm diameter was present in 22.4 and 10.8%, respectively (P < 0.01). Fewer than 10% of subjects took analgesics for injection site pain. Only 5 students (1.3%) rated Td site morbidity as severe/unacceptable. Hepatitis B site morbidity was minimal in comparison. CONCLUSION: Td boosters were moderately reactogenic in adolescents. Younger students more often experienced injection site morbidity but considered it bearable. Booster immunizations can reasonably be offered within the age range of 11 to 16 years.

Endotoxinemia and thrombocytopenia during neonatal necrotizing enterocolitis.

Thrombocytopenia frequently complicates neonatal necrotizing enterocolitis (NEC) and has been postulated to result from absorption of bacterial endotoxins from the injured gut. The authors tested blood obtained during 47 episodes of NEC for endotoxin-like activity (ELA), using a Limulus amoebocyte lysate assay and found 23 patients (49%) had positive results. Concentrations of ELA in plasma ranged from 0.26 to 300 ng/mL of Escherichia coli equivalent activity, with a geometric mean of 1.1 ng/mL. Serial platelet measurements were available from 40 infants, 11 (28%) of whom had nadir counts below 100,000/mm3 following NEC onset. Nine of 19 infants (47%) with ELA in plasma and only 2 of 21 without (9.5%, P less than 0.05) developed thrombocytopenia, suggesting that endotoxinemia may indeed contribute to platelet depletion during NEC.

Vaccines for prevention of head and neck infections.

Many current vaccines are directed against pathogens that infect the upper airway on their way to causing greater damage elsewhere in the body. This article focuses on vaccines against pathogens that contribute importantly to infections of the head and neck per se. The discussion includes vaccines for diphteria, mumps, measles, HIB infections, and infections caused by Streptococcus pneumoniae.

Assessment of parent education methods for infant immunization.

OBJECTIVE: To assess whether a video about infant immunization could inform parents as well as human counselling (oral presentation). METHODS: Core information for parents about infant immunization was identified and packaged in an instructional video and a scripted oral presentation. Volunteer prenatal classes were randomly assigned a video or oral presentation. Participants completed pre- and post-test questionnaires covering the same 16 items. Scores were compared for each question and as a group means, using Fisher's exact test, 2-sided. RESULTS: 227 subjects participated, including 102 men and 124 women. Groups were similar in terms of gender mix, parenting experience and recent reading about immunization. Pre-test knowledge scores were similarly low between groups. Post-test scores were much higher but did not differ significantly between groups. CONCLUSIONS: In a prenatal classroom setting, video and oral presentations were equally effective in conveying key information about infant immunization.

Evaluation of ready-to-use and multi-dose influenza vaccine formats in large clinic settings.

Large immunization clinics are commonly held to deliver influenza vaccine to seniors and others. Vaccine is typically dispensed from multi-dose vials but pre-filled syringes are now available, offering time savings for vaccinators. To determine if the higher purchase price of such syringes is offset by savings in time and injection supplies, we did a controlled comparison of syringe and vial formats in two large, concurrent, community-based influenza vaccination clinics. Vaccine preparation and immunization times were carefully documented along with costs for vaccine purchase, storage and injection supplies. Servicing 1,000 clients required 27 nurse hours using syringes and 36 hours using vials but the savings for personnel ($234) and supplies ($1,190) using syringes were exceeded by higher vaccine cost ($2,090 premium) and extra storage costs ($260) for bulkier packaging. Depending upon product and packaging style, programs using vials are cheaper by $709-$926 per 100 doses delivered compared to using pre-filled syringes.

Population-based surveillance of invasive group A streptococcal disease in British Columbia: 1996 to 1998.

OBJECTIVE: To identify and describe all cases of invasive group A streptococcal (GAS) infection occurring in British Columbia during a two-year period. DESIGN: Active, laboratory-based surveillance with supplemental case description. SETTING: Forty community and regional hospitals and the provincial laboratory participated, encompassing all health regions. POPULATION STUDIED: Entire provincial population from April 1, 1996 to March 31, 1998. MAIN RESULTS: Over the 24-month surveillance period, 182 eligible cases were identified, yielding a mean annual incidence rate of 2.3/100,000. Patients ranged in age from two to 91 years, with a mean of 39.1 years. Soft tissue infections accounted for 89 of 130 cases (68.5%) with a defined clinical syndrome, 20 of which were necrotizing fasciitis. Injection drug use was described in 55 patients, who, as a group, were younger, more likely to have soft tissue infections and less likely to die of infection than nondrug users. Other risk factors for infection included HIV infection (19 patients); skin damage (26 patients, damage independent of injection drug use); chronic illness (27 patients); and immunosuppresion (three patients). Death from GAS infection occurred in 15 of 131 (11.5%) cases with known outcome, yielding an annual case fatality rate of 1.9/million population. Among necrotizing faciitis cases, the mortality rate was 30%. CONCLUSIONS: Invasive GAS infections are rare in British Columbia and tend to involve persons with chronic illness or prior skin trauma, especially injection drug abuse, which accounted for nearly half of the cases.

Evaluation of Haemophilus influenzae type b conjugate vaccine (meningococcal protein conjugate) in Canadian infants.

OBJECTIVE: To assess adverse effects and immune responses with a three-dose series of Haemophilus influenzae type b meningococcal protein conjugate (PedvaxHIB or Hib.OMP) vaccine, including any immunological response alterations from concurrent administration with routine vaccines for infants. DESIGN: Randomized, controlled trial with treatment group crossover for dose 3. SETTING: Two public health units near Vancouver. PARTICIPANTS: One hundred and ten healthy infants eight to 14 weeks old were enrolled; 105 completed the study (95%). INTERVENTIONS: All participants received two doses of diphtheria-pertussis-tetanus (dpt) vaccine (at two and four months of age) and one dose of measles-mumps-rubella (mmr) vaccine at 12 months. In each instance, Hib.OMP was given either concurrently in another limb or after a delay of two weeks (after dpt) or four weeks (after mmr). MAIN OUTCOME MEASURES: Adverse effects, particularly fever and local erythema, were monitored by parents for 72 h after each dose of Hib.OMP vaccine. Five blood samples were taken at prescribed intervals to assess responses to each dose of Hib.OMP and to selected other vaccine antigens. MAIN RESULTS: Follow-up was obtained after all 322 doses of Hib.OMP. Local adverse effects were infrequent and mild: 13% had redness, 17% tenderness. Systemic effects in those given Hib.OMP alone included fever in 8%, irritability in 29%. Anti-polyribose-ribitol phosphate (prp) responses to Hib.OMP were not impaired by coadministration with dpt or mmr vaccines, nor were tetanus or diphtheria antitoxin levels or rubella or measles response rates affected. After two doses of Hib.OMP, 92% were seropositive and 64% had greater than 1.0 µg/mL of anti-prp. After three doses, 100% were seropositive and 82% exceeded 1.0 µg/mL. CONCLUSION: Hib.OMP vaccine was well tolerated, immunogenic and compatible with vaccines routinely given to infants in Canada.

Effect of reminder notices on the timeliness of early childhood immunizations.

OBJECTIVE: To determine whether reminder notices would improve the timeliness of toddler-age vaccinations. DESIGN: Prospective, randomized, controlled trial. POPULATION STUDIED: Two convenience cohorts of 320 children due to receive either measles-mumps-rubella (MMR) vaccine (at 12 months of age) or diphtheria-pertussis-tetanus (DPT)-inactivated polio (IPV)- Haemophilus influenzae type b (Hib) booster vaccine (at 18 months of age). SETTING: Suburban community. INTERVENTIONS: Parents of the identified children were randomly assigned either to a group to receive a reminder notice of pending vaccinations or a control group that did not receive a notice at a ratio of 1:1. Immunization uptake was assessed eights weeks after the initial due date for vaccination. RESULTS: Information was obtained for 224 children in the MMR group and 227 children in the DPT-IPV-Hib booster group. MMR uptake within eight weeks of the due date was about 90% in both the test and control groups, probably because of publicity surrounding a local college-based measles outbreak. In the DPT-IPV-Hib group, reminder notices had no effect; the uptake rates within eight weeks of the due date were 73.7% to 75.2%. Delays in immunization resulted mostly from parents' scheduling problems and provider-recommended delays. More than half of the parents whose child had delayed immunization did not recall receiving the reminder notice. CONCLUSIONS: Mailed reminders did not increase on-time immunization rates in the second year of a child's life. A telephone call or a more memorable reminder notice may be better suited to catch the attention of parents.

The Canadian Immunization Monitoring Program, ACTive (IMPACT): Active surveillance for vaccine adverse events and vaccine-preventable diseases.

For almost 25 years the Canadian Immunization Monitoring Program, ACTive (IMPACT) has been conducting active surveillance for severe adverse events following immunization (AEFIs) and vaccine-preventable diseases in children. The network, which consists of volunteer paediatric infectious diseases investigators at 12 tertiary care paediatric hospitals, is an important component of Canada's AEFI monitoring. The network employs nurses at each of the sites to search for and report possible AEFIs to local, provincial and national public health authorities. The active nature of the surveillance ensures a high level of vigilance for severe AEFIs in children.