Margaret L. Russell

Effect of Influenza Vaccination of Children on Infection Rates in Hutterite Communities: A Randomized Trial

CONTEXT Children and adolescents appear to play an important role in the transmission of influenza. Selectively vaccinating youngsters against influenza may interrupt virus transmission and protect those not immunized. OBJECTIVE To assess whether vaccinating children and adolescents with inactivated influenza vaccine could prevent influenza in other community members. DESIGN, SETTING, AND PARTICIPANTS A cluster randomized trial involving 947 Canadian children and adolescents aged 36 months to 15 years who received study vaccine and 2326 community members who did not receive the study vaccine in 49 Hutterite colonies in Alberta, Saskatchewan, and Manitoba. Follow-up began December 28, 2008, and ended June 23, 2009. INTERVENTION Children were randomly assigned according to community and in a blinded manner to receive standard dosing of either inactivated trivalent influenza vaccine or hepatitis A vaccine, which was used as a control. MAIN OUTCOME MEASURES Confirmed influenza A and B infection using a real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay and by measuring serum hemagglutination inhibition titers. RESULTS The mean rate of study vaccine coverage among eligible participants was 83% (range, 53%-100%) for the influenza vaccine colonies and 79% (range, 50%-100%) for the hepatitis A vaccine colonies. Among nonrecipients, 39 of 1271 (3.1%) in the influenza vaccine colonies and 80 of 1055 (7.6%) in the hepatitis A vaccine colonies had influenza illness confirmed by RT-PCR, for a protective effectiveness of 61% (95% confidence interval [CI], 8%-83%; P = .03). Among all study participants (those who were and those who were not vaccinated), 80 of 1773 (4.5%) in the influenza vaccine colonies and 159 of 1500 (10.6%) in the hepatitis A vaccine colonies had influenza illness confirmed by RT-PCR for an overall protective effectiveness of 59% (95% CI, 5%-82%; P = .04). No serious vaccine adverse events were observed. CONCLUSION Immunizing children and adolescents with inactivated influenza vaccine significantly protected unimmunized residents of rural communities against influenza. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00877396.

An adult formulation of a five-component acellular pertussis vaccine combined with diphtheria and tetanus toxoids is safe and immunogenic in adolescents and adults.

Pertussis is increasingly being recognized as an important cause of cough illness in adolescents and adults. To evaluate the safety and immunogenicity of an adult formulation of a five-component (pertussis toxoid, filamentous hemagglutinin, pertactin, fimbriae 2 and 3) acellular pertussis vaccine combined with diphtheria and tetanus toxoids, we randomly allocated 749 healthy adolescents and adults from 12-54 years of age recruited from five Canadian communities to receive either tetanus-diphtheria vaccine (Td), acellular pertussis vaccine (aP) or combined diphtheria-tetanus-acellular pertussis vaccine (TdaP). Subjects and personnel were unaware of the vaccine allocation. Antibody levels were measured before and one month postimmunization; adverse events were collected at 24 and 72 h and 8 to 10 days. Adverse events were reported in similar frequency amongst the three vaccine groups. Moderate pain at the injection site was reported less frequently in the aP group than the TdaP group (10.7% compared to 19.4%; relative risk 0.6, 95% confidence interval 0.3-0.9). Chills were reported less frequently after Td (5.3%) than after TdaP (12.5%; relative risk 0.4, 95% confidence interval 0.2-0.9). There were no statistically significant differences between recipients of Td and TdaP in tetanus and diphtheria antitoxin levels achieved. Antibody response against Bordetella pertussis antigens was vigorous in all groups although recipients of aP alone had higher levels of antibody levels against pertussis toxoid, fimbriae, and agglutinins and lower antibody levels against pertactin than did TdaP recipients. We conclude that this adult formulation 5-component acellular pertussis vaccine is safe and immunogenic in adolescents and adults and is a candidate vaccine for adolescent and adult immunization programs.

Adult formulation of a five component acellular pertussis vaccine combined with diphtheria and tetanus toxoids and inactivated poliovirus vaccine is safe and immunogenic in adolescents and adults.

Background. Pertussis is increasingly recognized as an important cause of cough illness in adolescents and adults. Purpose. To evaluate the safety and antibody response to a single dose of an adult formulation of a five component (pertussis toxoid, filamentous hemagglutinin, pertactin, fimbriae 2 and 3) acellular pertussis vaccine (aP) combined with diphtheria and tetanus toxoids (TdaP) and inactivated poliovirus vaccine (TdaP‐IPV) in adolescents and adults and to assess the response to a second dose of the acellular pertussis vaccine in a subset of the adults. Population and setting. The study addressed 1207 healthy participants (736 adults and 466 adolescents) recruited in five Canadian communities. Study design. In a randomized, observer‐blind, controlled clinical trial, adult participants received Td followed at a separate visit by aP, TdaP followed by IPV or TdaP‐IPV; adolescents received Td‐IPV followed at a separate visit by aP or TdaP‐IPV. A subgroup of adults was given a booster of aP 1 month after TdaP. Outcome measures. Antibody titers measured before and 1 month after each immunization; adverse events enumerated at 24 h, 72 h and 8 to 10 days. Results. The aP vaccine given by itself was associated with adverse events less frequently than were Td, Td‐IPV, TdaP or TdaP‐IPV vaccines, but reaction rates did not differ significantly among the latter products. The antibody response against Bordetella pertussis antigens was vigorous in all groups, although adults given the TdaP‐IPV vaccine had lower antibody titers against filamentous hemagglutinin, pertactin, diphtheria and tetanus antibodies than those given TdaP vaccine. Similarly adolescents given TdaP‐IPV had lower antibody titers against pertussis toxin, filamentous hemagglutinin, fimbriae and agglutinins than those given Td‐IPV and aP alone. A second dose of acellular pertussis vaccine was not associated with increased adverse events in adults but elicited increased antibody titers over that achieved by a single dose only against pertussis toxin. Conclusions. This adult formulation five component aP vaccine given as TdaP‐IPV is safe and immunogenic in adolescents and adults and is a candidate vaccine for adolescent and adult immunization programs.

Swine Outbreak of Pandemic Influenza A Virus on a Canadian Research Farm Supports Human-to-Swine Transmission

BACKGROUND Swine outbreaks of pandemic influenza A (pH1N1) suggest human introduction of the virus into herds. This study investigates a pH1N1 outbreak occurring on a swine research farm with 37 humans and 1300 swine in Alberta, Canada, from 12 June through 4 July 2009. METHODS The staff was surveyed about symptoms, vaccinations, and livestock exposures. Clinical findings were recorded, and viral testing and molecular characterization of isolates from humans and swine were performed. Human serological testing and performance of the human influenza-like illness (ILI) case definition were also studied. RESULTS Humans were infected before swine. Seven of 37 humans developed ILI, and 2 (including the index case) were positive for pH1N1 by reverse-transcriptase polymerase chain reaction (RT-PCR). Swine were positive for pH1N1 by RT-PCR 6 days after contact with the human index case and developed symptoms within 24 h of their positive viral test results. Molecular characterization of the entire viral genomes from both species showed minor nucleotide heterogeneity, with 1 amino acid change each in the hemagglutinin and nucleoprotein genes. Sixty-seven percent of humans with positive serological test results and 94% of swine with positive swab specimens had few or no symptoms. Compared with serological testing, the human ILI case definition had a specificity of 100% and sensitivity of 33.3%. The only factor associated with seropositivity was working in the swine nursery. CONCLUSIONS Epidemiologic data support human-to-swine transmission, and molecular characterization confirms that virtually identical viruses infected humans and swine in this outbreak. Both species had mild illness and recovered without sequelae.

Secular trends in the epidemiology of shingles in Alberta

Varicella vaccine was licensed in Canada in 1998, and a publicly funded vaccination programme introduced in the province of Alberta in 2001. In theory the vaccination programme might increase the burden of disease from shingles, making it important to develop baseline data against which future comparisons can be made. The studys aim was to describe the epidemiology of non-fatal cases of shingles for which publicly funded health services were utilized for the period 1986-2002. Shingles cases were identified from the records of Albertas universal, publicly funded health-care insurance system for 1986-2002. The earliest dated health service utilizations for ICD-9-CM codes of 053 or ICD-10-CA codes of B02 were classified as incident. Diagnostic codes at least 180 days after the first were classified as recurrent episodes. Denominators for rates were estimated using mid-year population estimates from the Alberta Health Care Insurance Plan Registry. Annual age- and sex-specific rates were estimated. We explored the pattern of rates for sex, age and year effects and their interactions. Shingles rates increased between 1986 and 2002. There was a sex effect and evidence of an age-sex interaction. Females had higher rates than males at every age; however, the difference between females and males was greatest for the 50-54 years age group and declined for older age groups. The increased rate of shingles in Alberta began before varicella vaccine was licensed or publicly funded in Alberta, and thus cannot be attributed to vaccination.

Safety and immunogenicity of a combined five-component pertussis-diphtheria-tetanus-inactivated poliomyelitis-Haemophilus b conjugate vaccine administered to infants at two, four and six months of age

Safety, immunogenicity and lot consistency of five-component pertussis combination vaccine (CPDT-IPV//PRP-T) in infants were compared to that of whole cell pertussis combination vaccine (DPT-IPV//PRP-T), as were separate and combined injections of CPDT-IPV and PRP-T. No significant differences in adverse event rates were observed between lots of CPDT-IPV//PRP-T or between separate or combined injections of CPDT-IPV and PRP-T. Minor differences in antibody responses were observed between lots of component pertussis vaccine. Higher concentrations of diphtheria and tetanus antitoxins were induced by separate than by combined injection of CPDT-IPV and PRP-T, but no other differences in immunogenicity were observed. Adverse reactions were more than twice as frequent after whole cell than after component pertussis vaccines. Antibody responses to pertussis toxoid, filamentous hemagglutin and pertactin were significantly greater after component vaccines, while the response to type 3 poliovirus was higher after whole cell vaccine. No significant differences were observed for other vaccine components. CPDT-IPV//PRP-T was safe and immunogenic in infants. Antibody results were similar to those observed in a Swedish field trial that demonstrated CPDT to be 85% effective in preventing clinical pertussis.

Conservation surgery for breast cancer as the preferred choice: a prospective analysis.

PURPOSE To describe the proportion of women who anticipate having breast-conserving surgery (BCS) versus modified radical mastectomy (MRM), the factors they considered when making treatment choices, the degree to which they perceived they had participated in and had control of the treatment decision, and to explore factors associated with type of planned surgery. PATIENTS AND METHODS Prospective cohort study conducted among patients attending a tertiary care hospital in Alberta, Canada from 1992 to 1995. Participants had a first diagnosis of localized unilateral breast cancer, and were, in the opinions of their surgeons, candidates for either BCS or MRM. RESULTS Of 157 participants, 71.3% anticipated having BCS and 28.7% anticipated MRM. Referents perceived to play an important role in decision making included self, doctor, and significant other. The two top-ranked items perceived to have influenced treatment choice were doctors advice and possibility of complete cure. Most women (60%) participated in treatment choice to the degree that they preferred, but only 13.6% received their preferred amount of information. The type of planned surgery was predicted by surgeon, contribution of doctor to choice of treatment, importance of breasts to sexuality, self-efficacy, and concerns about cancer recurrence from a multivariable logistic regression model. CONCLUSION Both patient and surgeon factors are important predictors of type of planned surgery. There is a gap between womens preferences and actual experiences with regard to information provided and patient participation in treatment choices, with womens desire for more information about their treatment being most prevalent.

Low Serum 25-Hydroxyvitamin D Level and Risk of Upper Respiratory Tract Infection in Children and Adolescents

Respiratory tract infections (RTIs) are very common worldwide. We prospectively demonstrate an association between low serum 25-hydroxyvitamin D level and increased risk of laboratory-confirmed viral upper RTI in children. Future studies should evaluate the role of supplementation to reduce RTIs.

Immunogenicity and safety of influenza vaccination in children with inflammatory bowel disease.

Background: Protection against vaccine‐preventable diseases is important in inflammatory bowel disease (IBD) because of increased susceptibility and severity of infection with immunosuppressive therapy. However, immunosuppressive therapy may affect vaccine response. This study aimed to evaluate immunogenicity and safety of influenza vaccination in children with IBD. Methods: In this prospective cohort study, 60 children with IBD and 53 healthy controls had serum collected for preimmunization hemagglutination‐inhibition antibody titers to the 2008 inactivated influenza vaccine components. Three to 5 weeks following vaccine [A/Brisbane/10/2007(H3N2), A/Brisbane/59/2007(H1N1), B/Florida/4/2006] administration, all participants had serum collected for postimmunization titers. A 4‐fold or greater increase between pre‐ and postimmunization titers indicated an immunogenic response; a postimmunization titer ≥1:40 indicated serologic protection. Children with IBD were classified into immunosuppression status by therapy. Results: Seventy percent, 72%, and 53% of children with IBD mounted an immunogenic response to H3N2, H1N1, and influenza B components, respectively. Among children with IBD, serologic protection was achieved in 95%, 98%, and 85% to H3N2, H1N1, and influenza B components, respectively. For influenza B, children with IBD were less likely to mount an immunogenic response compared to controls (53% versus 81%, P = 0.0009), and immunosuppressed children with IBD were less likely to achieve serologic protection compared to nonimmunosuppressed children with IBD (79% versus 100%, P = 0.02). The majority (98%) tolerated the vaccine. Conclusions: Although children with IBD achieve appropriate immunogenicity to influenza A, immunogenicity to influenza B appears to be diminished, especially with immunosuppressive therapy. (Inflamm Bowel Dis 2011;)

Longitudinal Study of Influenza Molecular Viral Shedding in Hutterite Communities

BACKGROUND The nature of influenza viral shedding during naturally acquired infection is not well understood. METHODS A cohort study was conducted in Hutterite colonies in Alberta, Canada. Flocked nasal swabs were collected during 3 influenza seasons (2007-2008 to 2009-2010) from both symptomatic and asymptomatic individuals infected with influenza. Samples were tested by real-time reverse-transcription polymerase chain reaction for influenza A and influenza B, and the viral load (VL) was determined for influenza A positive samples. RESULTS Eight hundred thirty-nine participants were included in the cohort; 25% (208) tested positive for influenza viruses. They experienced 238 episodes of viral shedding, of which 23 (10%) were not accompanied by symptoms. For seasonal and pandemic H1N1, VL peaked at or before onset of acute respiratory infection. For H3N2, VL peaked 2 days after the onset of acute respiratory infection, which corresponded to peaks in systemic and respiratory symptom scores. Although the duration of shedding was shorter for asymptomatic participants, the peak level of VL shedding was similar to that of symptomatic participants. Viral loads for children and adults revealed similar patterns. CONCLUSIONS Molecular viral shedding values follow symptom scores, but timing of peak VL varies by subtype. Asymptomatic infections are infrequent.