Phase I trial of RV3-BB rotavirus vaccine: A human neonatal rotavirus vaccine

Introduction

RV3 is a human neonatal rotavirus strain (G3P[6]) that has been associated with asymptomatic neonatal infection and replicates well in the infant gut. RV3-BB rotavirus vaccine has been developed as a rotavirus vaccine candidate for administration at birth.

Methods

A single-centre, double-blind, randomised placebo-controlled Phase I study evaluated the safety and tolerability of a single oral dose of the second generation RV3-BB rotavirus vaccine (8.3 × 10⁶ FFU/mL) in 20 adults, 20 children and 20 infants (10 vaccine and 10 placebo per age cohort). Vaccine take was defined as seroconversion (a 3-fold increase in serum anti-rotavirus IgA or serum neutralising antibody (SNA) from baseline at day 28 post-dose) or evidence of RV3-BB viral replication in the faeces by RT-PCR analysis 3–6 days post-vaccination. RV3-BB presence was confirmed by sequence analysis.

Results

The RV3-BB vaccine was well tolerated in all participants, with no pattern of adverse events shown to be associated with the study vaccine. In the infant cohort, vaccine take was demonstrated in 8/9 infants following a single dose of vaccine compared with 2/7 placebo recipients. In the infant vaccine group, 5/9 infants exhibited either IgA or SNA seroconversion and 7/9 infants had evidence of RV3-BB replication on days 3–6, compared with 2/7 infants who seroconverted and 0/10 infants with evidence of replication in the placebo group. Two infants in the placebo group had serological evidence of a rotavirus infection within the 28-day study period: one demonstrated an IgA and the other an SNA response, with wild-type virus replication detected in another infant.

Conclusion

A single dose of RV3-BB rotavirus vaccine was well tolerated in adults, children and infants. Most infants (8/9) who received RV3-BB demonstrated vaccine take following a single dose. These data support progression of RV3-BB to Phase II immunogenicity and efficacy trials.     

Improvement in attitudes toward influenza vaccination in medical students following an integrated curricular intervention

Introduction

Vaccination of health care workers (HCW) reduces transmission of influenza among patients, yet uptake of vaccination remains low. If vaccination education is integrated into the early medical school curriculum, will student attitudes toward the vaccine change? The objectives of the study were to: (1) Determine influenza vaccination rates among entering medical students; (2) Assess the attitudes toward influenza vaccination; (3) Evaluate the effects of a multifaceted educational intervention on attitudes to vaccination.

Methods

Entering medical students were surveyed before and after an intervention at the beginning of the influenza season. This intervention provided by an inter-professional team, included education about influenza, importance of vaccination for HCWs, followed by vaccination administration practice, and ended with students vaccinating consenting classmates.

Results

The pre-intervention surveys and intervention were completed by 124 of 125 (99%) students. Pre-intervention survey revealed 60 (48%) of students had been previously vaccinated. Of the vaccinated students 91% had been recommended vaccination by their healthcare provider compared to 43% of non-vaccinated students. More positive attitudes were noted in the vaccinated students compared to non-vaccinated students: importance of vaccination (p < 0.01); HCWs should be vaccinated (p < 0.01); recommendation of vaccine to family and friends (p < 0.01). 97 (78%) students completed post-intervention surveys. Significant improvement in these attitudes was noted post-intervention compared to pre-intervention: importance of vaccination 93% versus 71% (p < 0.01); HCWs should be vaccinated 95% versus 83% (p < 0.01); recommendation to family and friends 93% versus 73% (p < 0.01); comfort with vaccine counseling 92% versus 41%; comfort with vaccine administration 84% versus 22% (p < 0.01).

Conclusion

Educating medical students and promoting the importance of vaccination early in a medical student's career using such an intervention is relatively simple and easily integrated into the curriculum. This intervention was successful in vaccinating all students, and demonstrated a marked positive shift in attitudes toward influenza vaccination.     

Broadening the age restriction for initiating rotavirus vaccination in regions with high rotavirus mortality: Benefits of mortality reduction versus risk of fatal intussusception

Introduction

Recently developed rotavirus vaccines have the potential to reduce diarrhea mortality in children in developing countries. Available data to date do not indicate risk of intussusception with these new vaccines. To avoid a potential unanticipated risk post-licensure, it is recommended that rotavirus immunization be initiated before 12 weeks of age when background intussusception rates are low. This policy could exclude a substantial number of children from vaccination, especially in developing countries where delays in vaccination are common.

Methods

We conducted a scenario analysis to assess the potential benefits of mortality reduction from rotavirus versus the risk of fatal intussusception when the first dose of the vaccine is strictly administered by 12 weeks of age compared with a free strategy with vaccine administered before 1 year of age using data on rotavirus disease, vaccine safety and efficacy, and current diphtheria–tetanus–pertussis vaccination rates, and by incorporating hypothetical risks of intussusception.

Results

In developing countries, assuming vaccine efficacy of 50% and 75% for doses 1 and 2, respectively, and a hypothetical sixfold and threefold increased relative risk of intussusception within 7 days of doses 1 and 2, respectively, initiating rotavirus immunization before 12 weeks of age would prevent 194,564 of the 517,959 annual rotavirus-associated deaths among children <5 years, while potentially resulting in 1106 fatal intussusception events. Administration of the first dose to infants up to 1 year of age would prevent an additional 54,087 rotavirus-associated deaths (total = 248,651) while potentially resulting in an additional 1226 intussusception deaths (total = 2332).

Conclusion

In developing countries, the additional lives saved by broadening the age restrictions for initiation of rotavirus vaccination would far outnumber the hypothetical excess intussusception deaths that would accompany such an approach.     

Barriers to influenza vaccination among pregnant women

Objective

Despite pregnant women's increased morbidity and mortality from influenza, vaccination rates remain low. This study intended to evaluate barriers to pregnant women's uptake of influenza vaccine.

Study design

A survey was designed that assessed participant demographics, knowledge, beliefs, attitudes, and general experiences with seasonal and 2009 novel H1N1 influenza. Associations between patient characteristics and vaccine uptake were then assessed.

Results

88 women completed the survey. Women who correctly answered >75% of knowledge questions regarding influenza were significantly more likely to accept the influenza vaccine (seasonal: p = 0.04, H1N1: p < 0.01). Conversely, patients who declined the vaccine were more likely to hold false beliefs, such as perceiving that the vaccine was not protective (seasonal: p < 0.01, H1N1: p < .01) and that they were not at risk for influenza (seasonal: p <  0.01).

Conclusion

The reasons for influenza vaccine declination in pregnant patients include lower levels of knowledge and unfavorable attitudes regarding the safety and efficacy of the vaccine, and suggest the importance of education as a tool to improve vaccination uptake     

Pandemic influenza A(H1N1)pdm09 improves vaccination routine in subsequent years: A cohort study from 2009 to 2011

Background

In 2009 the pandemic influenza virus A(H1N1)pdm09 emerged with guidance that people at risk should be vaccinated. It is unclear how this event affected the underlying seasonal vaccination rate in subsequent years.

Purpose

To investigate the association of pandemic influenza A(H1N1)pdm09 and seasonal flu vaccination status in 2009 with vaccination rates in 2010 and 2011.

Methods

Data were collected in 40 Dutch family practices on patients at risk for influenza during 2009–2011; data analysis was conducted in 2012.

Results

A multilevel logistic regression model (n = 41,843 patients) adjusted for practice and patient characteristics (age and gender, as well as those patient groups at risk), showed that people who were vaccinated against A(H1N1)pdm09 in 2009 were more likely to have been vaccinated in 2010 (OR 6.02; 95%CI 5.62–6.45, p < .0001). This likelihood was even more for people who were vaccinated against seasonal flu in 2009 (OR 13.83; 95%CI 12.93–14.78, p < .0001). A second analysis on the uptake rate in 2011 (n = 39,468 patients) showed that the influence of the vaccination state in 2009 declined after two years, but the diminishing effect was smaller for people vaccinated against A(H1N1)pdm09 than for seasonal flu (OR 5.50; 95%CI 5.13–5.90, p < .0001; OR 10.98; 95%CI 10.26–11.75, p < .0001, respectively).

Conclusion

Being vaccinated against A(H1N1)pdm09 and seasonal influenza in the pandemic year 2009 enhanced the probability of vaccination in the next year and this was still effective in 2011. This suggests that peoples’ vaccination routines were not changed by the rumor around the outbreak of A(H1N1)pdm09, but rather confirmed underlying behavior.     

Knowledge,attitudes and vaccination coverage of healthcare workers regarding occupational vaccinations

Objectives

Immunization of healthcare workers (HCWs) is a major issue for infection control in healthcare facilities. The aim of this study was to evaluate knowledge regarding occupational vaccinations, HBV, varicella and influenza vaccination rates and attitudes towards influenza vaccine among HCWs.

Design and setting

A cross-sectional survey was conducted in two wards (Medicine and Paediatrics) of a 1182-bed teaching hospital in Paris, France.

Methods

A standardized, anonymous, self-administered questionnaire was used.

Results

Of 580 HCWs, 395 (68%) completed the questionnaire. Knowledge about the occupational vaccinations of HCWs was low. HBV (69%), tuberculosis (54%) and influenza (52%) were the most cited vaccinations. Paediatric staff was more aware of influenza and pertussis immunizations (p < .05). HBV vaccination rate was 93%, among whom 65% were aware of their immune status. Influenza vaccination rate for 2006–2007 was 30% overall, ranging from 50% among physicians to 20% among paramedical staff (p < .05). Physicians based their refusal on doubts about vaccine efficacy, although paramedics feared side effects. Influenza vaccination was associated with knowledge of vaccine recommendations [OR = 1.75, 95% CI: 1.13–2.57] and contact with patients [OR = 3.05, 95% CI: 1.50–5.91].

Conclusions

Knowledge of recommended occupational vaccinations is insufficient in HCWs, except for HBV and influenza. Although the HBV vaccine coverage of HCWs is satisfactory, a large proportion of them is unaware of immune status. Influenza vaccine coverage remains low, especially among paramedical staff because of fear of side effects. As vaccine coverage is associated with knowledge, educational campaigns should be strengthened to increase the adhesion of HCWs to vaccinations.     

HPV vaccination among lesbian and bisexual women: Findings from a national survey of young adults

Background

Human papillomavirus (HPV) infection and associated cervical disease are common among all women, regardless of sexual identity, yet limited research has examined HPV vaccination among lesbian and bisexual women.

Methods

A national sample of lesbian and bisexual women ages 18–26 (n = 543) completed our online survey during Fall 2013. We used multivariable logistic regression to identify correlates of HPV vaccine initiation (receipt of at least 1 dose) and completion (receipt of all 3 recommended doses among initiators).

Results

Overall, 45% of respondents had initiated HPV vaccine and 70% of initiators reported completing the series. HPV vaccine initiation was higher among respondents who were students, had received a healthcare provider's recommendation, perceived greater positive social vaccination norms, or anticipated greater regret if they did not get vaccinated and later got HPV. Initiation was lower among those who perceived greater HPV vaccine harms or greater barriers to getting the vaccine (all p < .05). HPV vaccine completion was higher among initiators who had a college degree while it was lower among those who perceived a greater likelihood of acquiring HPV or who anticipated greater regret if they got the vaccine and fainted (all p < .05). Among HPV vaccine initiators who had not yet completed the series, about half (47%) intended to get the remaining doses.

Conclusions

Many lesbian and bisexual women are not getting vaccinated against HPV. Healthcare provider recommendations and women's health beliefs may be important leverage points for increasing vaccination among this population.     

The induction of breast milk pertussis specific antibodies following gestational tetanus–diphtheria–acellular pertussis vaccination

Background

Center for Disease Control and Prevention recommends vaccination of pregnant women with tetanus–diphtheria–acellular pertussis (Tdap).

Aim

To measure pertussis specific antibodies, total protein and their ratio in breast milk following gestational Tdap vaccination.

Methods

Women who received Tdap after the 20th week of pregnancy were recruited and unvaccinated women served as controls. Breast milk total protein, immunoglobulin A (IgA) to pertussis toxin (PT), filamentous hemagglutinin (FHA) and immunoglobulin G (IgG) to PT, FHA and pertactin (PRN) were measured. To overcome the dilution that occurs in the transition from colostrum to mature breast milk, we calculated pertussis specific antibody to total protein ratio.

Results

Pertussis specific IgA was the predominant pertussis immunoglobulin in the colostrum of Tdap vaccinated women with the geometric mean concentrations (GMCs) of IgA to FHA higher than for IgA to PT, 24.12 ELISA units/milliliter (EU/mL) vs. 8.18 EU/mL, respectively, p < 0.004. There were differences between the vaccinated women and controls in the GMCs of IgA to FHA and IgG to PRN in the colostrum, 24.12 EU/mL vs. 6.52 EU/mL, p = 0.01 and 2.46 EU/mL vs. <0.6 EU/mL, p = 0.03, respectively. The GMCs of total protein showed significant decline over 8 weeks in the vaccinated women and controls, p < 0.004. Among vaccinated women, there was significant decline in the GMCs of IgA to PT and FHA over 8 weeks, p < 0.001. The geometric mean ratio of IgA to FHA to total protein also declined significantly over 8 weeks in the vaccinated women, p < 0.01, demonstrating a true decrease, however, pertussis IgA was measurable at 8 weeks.

Conclusions

Select colostrum pertussis antibody levels were significantly higher among women vaccinated with Tdap during pregnancy compared with unvaccinated women. Among vaccinated women, maximal levels of pertussis specific IgA were in the colostrum but still detected at 8 weeks. Lactation may augment infant's protection against pertussis.     

Pharmacist-led Tdap vaccination of close contacts of neonates in a women's hospital

Background

Pertussis can cause severe illness and death in infants. Immunization of family members with the tetanus toxoid, reduced diphtheria toxoids, and acellular pertussis (Tdap) vaccine can decrease risk of pertussis infection among infants. A community pharmacy on a women's hospital campus implemented a Tdap vaccination pilot program.

Objective

To investigate the rate of Tdap vaccination among close contacts of neonates in a women's hospital pharmacy and to assess the impact of a coordinated pharmacy and hospital Tdap vaccination program.

Methods

The intervention entailed education from hospital staff who explained the risks of pertussis, advocated the benefits of vaccination, and encouraged family members to be vaccinated. In the on-site clinic or in the pharmacy, pharmacists administered vaccine to eligible patients. Rates of Tdap vaccinations in the intervention pharmacy with in-hospital vaccination were compared to comparison pharmacies without Tdap interventions.

Results

In the pre-study period (December 2008–November 2010), there were 31 Tdap vaccinations administered at the intervention pharmacy (mean = 1.3/month); during the study period (December 2010–November 2012), 2045 Tdap vaccinations were administered (mean = 85.2/month). In four comparison hospital-campus pharmacies, there were 77 vaccinations (mean = 0.8/month) during the pre-study period and 817 vaccinations (mean = 8.5/month) during the study period. There were 155 vaccinations administered in 44 area-community pharmacies (mean = 0.1/month) during the pre-study period and 2930 (mean = 2.8/month) during the study period. The intervention pharmacy had the highest average monthly rate of change in Tdap volume from pre-study to study period (83.9), compared to comparison hospital-campus pharmacies (7.7, p < .001) and area-community pharmacies (2.7, p < .001). During the study period, the estimated Tdap vaccination coverage per live births was 8.1% in the intervention pharmacy versus 5.5% in the comparison hospital-campus pharmacies (p < .001).

Conclusions

Tdap vaccination rates increased after implementation of the intervention program. This project illustrates how health systems and community pharmacists can collaborate to improve patient care.     

Hepatitis A vaccination coverage among adults 18–49 years traveling to a country of high or intermediate endemicity,United States

Background

Since 1996, hepatitis A vaccine (HepA) has been recommended for adults at increased risk for infection including travelers to high or intermediate hepatitis A endemic countries. In 2009, travel outside the United States and Canada was the most common exposure nationally reported for persons with hepatitis A virus (HAV) infection.

Objective

To assess HepA vaccination coverage among adults 18–49 years traveling to a country of high or intermediate endemicity in the United States.

Methods

We analyzed data from the 2010 National Health Interview Survey (NHIS), to determine self-reported HepA vaccination coverage (≥1 dose) and series completion (≥2 dose) among persons 18–49 years who traveled, since 1995, to a country of high or intermediate HAV endemicity. Multivariable logistic regression and predictive marginal analyses were conducted to identify factors independently associated with HepA vaccine receipt.

Results

In 2010, approximately 36.6% of adults 18–49 years reported traveling to high or intermediate hepatitis A endemic countries; among this group unadjusted HepA vaccination coverage was 26.6% compared to 12.7% among non-travelers (P-values < 0.001) and series completion were 16.9% and 7.6%, respectively (P-values < 0.001). On multivariable analysis among all respondents, travel status was an independent predictor of HepA coverage and series completion (both P-values < 0.001). Among travelers, HepA coverage and series completion (≥2 doses) were higher for travelers 18–25 years (prevalence ratios 2.3, 2.8, respectively, P-values < 0.001) and for travelers 26–39 years (prevalence ratios 1.5, 1.5, respectively, P-value < 0.001, P-value = 0.002, respectively) compared to travelers 40–49 years. Other characteristics independently associated with a higher likelihood of HepA receipt among travelers included Asian race/ethnicity, male sex, never having been married, having a high school or higher education, living in the western United States, having greater number of physician contacts or receipt of influenza vaccination in the previous year. HepB vaccination was excluded from the model because of the significant correlation between receipt of HepA vaccination and HepB vaccination could distort the model.

Conclusions

Although travel to a country of high or intermediate hepatitis A endemicity was associated with higher likelihood of HepA vaccination in 2010 among adults 18–49 years, self-reported HepA vaccination coverage was low among adult travelers to these areas. Healthcare providers should ask their patients’ upcoming travel plans and recommend and offer travel related vaccinations to their patients.     

Comparative varicella vaccine effectiveness during outbreaks in day-care centres

Background

Routine varicella vaccination for children >11 months was introduced in Germany in 2004 with three different vaccine brands available. In 2008 and 2009, we investigated seven varicella outbreaks in day-care centres (DCC).

Methods

Varicella disease and vaccination status of 1084 children was reviewed to evaluate vaccination coverage (VC), brand-specific varicella vaccine effectiveness (VE), and risk factors of breakthrough varicella (BV, >42 days after vaccination). A case was defined as a child with acute onset of varicella attending one of the respective DCC at the time of outbreak. Children with a previous history of varicella, age < 11 months, vaccinated at age < 11 months or <42 days before disease onset or during the outbreak were excluded from VE and BV risk factors analyses (adjusted for gender, age and DCC).

Findings

Of 631 children with available vaccination information, 392 (62%) were vaccinated at least once. Overall VE among 352 children eligible was 71% (95% confidence interval (CI) 57–81, p < 0.001) and differed significantly by disease severity and number of doses administered. Risk for BV was higher for 1 dose of Varilrix^® (RR = 2.8, 95%CI 1.0–7.8, p = 0.05) or Priorix-Tetra^® (RR = 2.4, 95%CI 0.7–8.3, p = 0.18) but lower for 2 doses of Priorix-Tetra^® (RR = 0.5, 95%CI 0.1–2.7, p = 0.41) than for 1 dose of Varivax^®.

Interpretation

Enhanced efforts to increase VC in Germany and 2 doses varicella vaccine might be successful to reduce the risk for BV. The evidence that VE and risk of BV are associated with vaccine brand needs further investigation.     

Vaccine specific immune response to an inactivated oral cholera vaccine and EPI vaccines in a high and low arsenic area in Bangladeshi children

Background

Immune responses to the inactivated oral whole cell cholera toxin B (CTB) subunit cholera vaccine, Dukoral^®, as well as three childhood vaccines in the national immunization system were compared in children living in high and low arsenic contaminated areas in Bangladesh. In addition, serum complement factors C3 and C4 levels were evaluated among children in the two areas.

Vaccinations

Toddlers (2–5 years) were orally immunized with two doses of Dukoral 14 days apart. Study participants had also received diphtheria, tetanus and measles vaccines according to the Expanded Program on Immunization (EPI) in Bangladesh.

Results

The mean level of arsenic in the urine specimens in the children of the high arsenic area (HAA, Shahrasti, Chandpur) was 291.8 μg/L while the level was 6.60 μg/L in the low arsenic area (LAA, Mirpur, Dhaka). Cholera specific vibriocidal antibody responses were significantly increased in the HAA (87%, P < 0.001) and the LAA (75%, P < 0.001) children after vaccination with Dukoral, but no differences were found between the two groups. Levels of CTB specific IgA and IgG antibodies were comparable between the two groups, whereas LPS specific IgA and IgG were higher in the LAA group, although response rates were comparable.Diphtheria and tetanus vaccine specific IgG responses were significantly higher in the HAA compared to the LAA group (P < 0.001, P = 0.048 respectively), whereas there were no differences in the measles specific IgG responses between the groups.Complement C3 and C4 levels in sera were higher in participants from the HAA than the LAA groups (P < 0.001, P = 0.049 respectively).

Conclusions

The study demonstrates that the oral cholera vaccine as well as the EPI vaccines studied are immunogenic in children in high and low arsenic areas in Bangladesh. The results are encouraging for the potential use of cholera vaccines as well as the EPI vaccines in arsenic endemic areas.     

Impact of human papillomavirus (HPV) vaccination on HPV 16/18-related prevalence in precancerous cervical lesions

Background

Vaccination against human papillomavirus (HPV) types 16 and 18 is recommended for girls aged 11 or 12 years with catch-up vaccination through age 26 in the U.S. Cervical intraepithelial neoplasia (CIN) grade 2 or 3 and adenocarcinoma in situ (CIN2+) are used to monitor HPV vaccine impact on cervical disease. This report describes vaccination status in women diagnosed with CIN2+ and examines HPV vaccine impact on HPV 16/18-related CIN2+.

Methods

As part of a vaccine impact monitoring project (HPV-IMPACT), females 18–31 years with CIN2+ were reported from pathology laboratories in CA, CT, NY, OR, TN from 2008 to 2011. One diagnostic block was selected for HPV DNA typing with Roche Linear Array. Demographic, abnormal Papanicolaou (Pap) test dates and vaccine status information were collected. The abnormal Pap test immediately preceding the CIN2+ diagnosis was defined as the ‘trigger Pap’.

Results

Among 5083 CIN2+ cases reported to date, 3855 had vaccination history investigated; 1900 had vaccine history documented (vaccinated, with trigger Pap dates, or unvaccinated). Among women who initiated vaccination >24 months before their trigger Pap, there was a significantly lower proportion of CIN2+ lesions due to 16/18 compared to women who were not vaccinated (aPR = .67, 95% CI: .48–.94). Among the 1900 with known vaccination status, 20% initiated vaccination on/after their trigger screening. Women aged 21–23 years were more likely to initiate vaccination on/after the trigger Pap compared to 24–26 year olds (29.0% vs. 19.6%, p = .001), as were non-Hispanic blacks compared to non-Hispanic whites (27.3% vs. 19.0%, p = .001) and publicly compared to privately insured women (38.1% vs. 17.4%, p < .0001).

Conclusion

We found a significant reduction in HPV 16/18-related lesions in women with CIN2+ who initiated vaccination at least 24 months prior to their trigger Pap. These preliminary results suggest early impact of the HPV vaccine on vaccine-type disease, but further evaluation is warranted.     

Single-dose varicella vaccine effectiveness in school settings in China

Background

Varicella vaccine has been available in the private sector in China for a decade as a single-dose regimen, but varicella vaccine effectiveness (VE) has not been fully examined in school settings yet.

Methods

A matched case–control study was carried out in elementary schools and daycares in Tai’an prefecture, Shandong province, China. Clinical diagnosis of varicella and breakthrough disease was used for this study. Four controls were randomly selected from classmates; two from classmates of the case and two from another class of the same grade without cases. Vaccination status, date of vaccination, and vaccine product received if vaccinated were collected from home and clinic immunization records. Vaccination status of all students in schools/daycares with varicella cases from home immunization records or parental recall was used to calculate vaccination coverage.

Results

The overall varicella VE was 83.4% (95% confidence interval 71.4–90.3%). Receipt of varicella vaccine five years or more years before the outbreak was significantly associated with breakthrough varicella (odds ratio = 4.7, P < 0.001), while age at vaccination (<15 vs. ≥15 months) was not (odds ratio = 1.5, P = 0.62). Varicella vaccination coverage was 41% with substantial variation across schools (range of 0–93.8%).

Conclusions

Single-dose varicella vaccine is highly effective in school settings. Maintaining limited vaccination coverage might shift varicella disease burden to older individuals, who are more prone to develop severe outcomes if varicella occurs.     

Antibody responses and protection stimulated by sequential oral-parenteral immunization of mice with rotavirus

Antibody responses and protection against shedding following oral challenge with murine rotavirus (EDIM) were determined in mice after sequential oral parenteral immunization. Oral immunization of 4-day-old BALB/c mice with live, heterologous rotavirus (RRV) stimulated serum rotavirus IgG but little serum or intestinal rotavirus IgA and small but significant (P < 0.001) reductions in EDIM shedding. Intraperitoneal immunization with inactivated EDIM at 29 days of age had similar effects. Sequential oral-parenteral immunization under these conditions stimulated small but significant (P < 0.001) increases in both rotavirus IgG and IgA titers and reduced shedding (P < 0.001) compared to individual immunizations. However, these responses were essentially additive, indicative of separate inductive/effector sites for mucosal and systemic immunity.     

What a pandemic teaches us about vaccination attitudes of parents of children with asthma

Background

During the recent pandemic, Influenza A/H1N1 vaccine uptake remained far below the targeted rates. Associated factors regarding vaccine refusal in the general population have been reported in many studies, however the reasons behind refusals for asthmatic children have not yet been identified. We aimed to investigate Influenza A/H1N1 virus vaccine acceptance for children with asthma, to determine the attitudes and beliefs of parents concerning Influenza A/H1N1 disease and vaccine and to identify the association of asthma control parameters with vaccination.

Methods

The parents of asthmatic children aged 6–18 years participated in a cross-sectional survey study in three pediatric allergy outpatient clinics. The survey measured demographic factors, asthma control parameters, vaccination rates, and beliefs and attitudes regarding Influenza A/H1N1 vaccine.

Results

Of the 625 asthmatic children, 16.8% (n = 105) were immunized with Influenza A/H1N1 and 45.7% (n = 286) with seasonal influenza vaccine. Educational background of parents (p < 0.001 and p = 0.002, for father's and mother's educational level, respectively), previous vaccination with seasonal influenza (p < 0.001), and having a family member vaccinated against Influenza A/H1N1 (p < 0.001) had a significant influence on vaccine acceptance, while fear of side effects (88.6%) was the major parental reason for refusing the vaccine. Asthma control parameters had no influence on uptake of the vaccine. Physician recommendation (84.8%) was important in the decision-making process for immunization. The statement “Children with asthma should receive swine flu vaccine” increased the likelihood of being vaccinated [OR: 2.160, (95%CI 1.135–4.111), p = 0.019].

Conclusion

Although asthmatic children are considered to be a high-priority group for Influenza A/H1N1 vaccination, we found low uptake of vaccine among our patients. Beliefs and attitudes rather than asthma control parameters influenced parental decisions for immunization. Understanding the underlying determinants for refusing the vaccine will help to improve vaccine campaigns in advance of a future outbreak.     

Estimating rotavirus gastroenteritis hospitalisations by using hospital episode statistics before and after the introduction of rotavirus vaccine in Australia

Introduction

Hospital discharge records and laboratory data have shown a substantial early impact from the rotavirus vaccination program that commenced in 2007 in Australia. However, these assessments are affected by the validity and reliability of hospital discharge coding and stool testing to measure the true incidence of hospitalised disease. The aim of this study was to assess the validity of these data sources for disease estimation, both before and after, vaccine introduction.

Methods

All hospitalisations at a major paediatric centre in children aged <5 years from 2000 to 2009 containing acute gastroenteritis (AGE) ICD 10 AM diagnosis codes were linked to hospital laboratory stool testing data. The validity of the rotavirus-specific diagnosis code (A08.0) and the incidence of hospitalisations attributable to rotavirus by both direct estimation and with adjustments for non-testing and miscoding were calculated for pre- and post-vaccination periods.

Results

A laboratory record of stool testing was available for 36% of all AGE hospitalisations (n = 4948) the rotavirus code had high specificity (98.4%; 95% CI, 97.5–99.1%) and positive predictive value (96.8%; 94.8–98.3%), and modest sensitivity (61.6%; 58–65.1%). Of all rotavirus test positive hospitalisations only a third had a rotavirus code. The estimated annual average number of rotavirus hospitalisations, following adjustment for non-testing and miscoding was 5- and 6-fold higher than identified, respectively, from testing and coding alone. Direct and adjusted estimates yielded similar percentage reductions in annual average rotavirus hospitalisations of over 65%.

Conclusion

Due to the limited use of stool testing and poor sensitivity of the rotavirus-specific diagnosis code routine hospital discharge and laboratory data substantially underestimate the true incidence of rotavirus hospitalisations and absolute vaccine impact. However, this data can still be used to monitor vaccine impact as the effects of miscoding and under-testing appear to be comparable between pre and post vaccination periods.     

Cluster randomized trial of a toolkit and early vaccine delivery to improve childhood influenza vaccination rates in primary care

Purpose

To increase childhood influenza vaccination rates using a toolkit and early vaccine delivery in a randomized cluster trial.

Methods

Twenty primary care practices treating children (range for n = 536–8183) were randomly assigned to Intervention and Control arms to test the effectiveness of an evidence-based practice improvement toolkit (4 Pillars Toolkit) and early vaccine supplies for use among disadvantaged children on influenza vaccination rates among children 6 months–18 years. Follow-up staff meetings and surveys were used to assess use and acceptability of the intervention strategies in the Intervention arm. Rates for the 2010–2011 and 2011–2012 influenza seasons were compared. Two-level generalized linear mixed modeling was used to evaluate outcomes.

Results

Overall increases in influenza vaccination rates were significantly greater in the Intervention arm (7.9 percentage points) compared with the Control arm (4.4 percentage points; P < 0.034). These rate changes represent 4522 additional doses in the Intervention arm vs. 1390 additional doses in the Control arm. This effect of the intervention was observed despite the fact that rates increased significantly in both arms – 8/10 Intervention (all P < 0.001) and 7/10 Control sites (P-values = 0.04 to <0.001). Rates in two Intervention sites with pre-intervention vaccination rates >58% did not significantly increase. In regression analyses, a child's likelihood of being vaccinated was significantly higher with: younger age, white race (Odds ratio [OR] = 1.29; 95% confidence interval [CI] = 1.23–1.34), having commercial insurance (OR = 1.30; 95%CI = 1.25–1.35), higher pre-intervention practice vaccination rate (OR = 1.25; 95%CI = 1.16–1.34), and being in the Intervention arm (OR = 1.23; 95%CI = 1.01–1.50). Early delivery of influenza vaccine was rated by Intervention practices as an effective strategy for raising rates.

Conclusions

Implementation of a multi-strategy toolkit and early vaccine supplies can significantly improve influenza vaccination rates among children in primary care practices but the effect may be less pronounced in practices with moderate to high existing vaccination rates.Clinical trial registry name/number: From Innovation to Solutions: Childhood Influenza/NCT01664793.     

Hepatitis A vaccine response in HIV-infected patients: Are TWINRIX and HAVRIX interchangeable?

Introduction

Hepatitis A virus (HAV) infection remains a health risk for human immunodeficiency virus (HIV)-infected persons. Seroconversion rates among HAV vaccinated HIV-infected patients have been shown to be reduced compared to the general population. Current guidelines regard HAV vaccines as interchangeable, however there no published data comparing their efficacy in HIV patients. Our study evaluated the impact of different factors, including type of vaccination, on the immunologic response to hepatitis A vaccination in HIV-infected patients in the HAART era.

Methods

This was a retrospective review of 226 HIV-infected patients at our clinic in Newark, NJ. Patients were eligible if at least one dose HAVRIX^® (1440 ELISA units) or TWINRIX^® (720 ELISA units) was administered and had anti-HAV antibody data pre- and post-vaccination. Numerous variables were evaluated for their effect on seroconversion.

Results

Seroconversion developed in 53.5% of the population. Responders had higher baseline median CD4 counts (446 versus 362 cells/mm³; P = 0.004) and lower median HIV RNA levels (475 copies/mL versus 5615 copies/mL; P = 0.018) than non-responders. Patients with CD4 counts > 350 cell/mm³ were more likely to respond than those with CD4 counts < 200 cell/mm³, 60% and 35%, respectively (P = 0.0498). Responders were also more likely to be virologically suppressed (48% versus 32%; P = 0.0024). TWINRIX^® recipients had a 7-fold increased probability of seroconversion when virologically suppressed and less likely to respond if the vaccination series was not completed (OR 0.42; 95% CI 0.18–0.96).

Discussion

Seroconversion rates to HAV vaccination are significantly impaired among HIV-infected patients. CD4 cell count and virologic suppression at vaccination impact response. Seroconversion among TWINRIX^® recipients appeared to be more sensitive to these factors and vaccine series completion in comparison to those administered HAVRIX^®. Among HIV-patients requiring hepatitis a and b vaccination, the advantage of TWINRIX^® over HAVRIX^® as a combination product should be reevaluated.     

Decline of varicella vaccination in German surveillance regions after recommendation of separate first-dose vaccination for varicella and measles–mumps–rubella

Background

Germany introduced routine varicella (V) vaccination in 2004. Due to a slightly increased risk of febrile convulsions after first-dose application of combined measles–mumps–rubella–varicella (MMRV) vaccine separate first-dose vaccinations with MMR and monovalent V vaccine were recommended in September 2011.

Methods

We compared V and MMR vaccinations in paediatric practices from two surveillance regions (Munich and Würzburg) one year before and after the change in the recommendation.

Results

A total of 1405/326 monthly reports were provided by a monthly average of 79/14 practices participating in Munich/Würzburg. V first-dose vaccinations (monovalent V or MMRV vaccine) declined by 12% in Munich (from 10.1 to 8.9 vaccinations per month and practice; p < 0.005) and by 4% in Würzburg (from 9.9 to 9.5; p = 0.620), respectively. First-dose vaccinations for MMR (MMR or MMRV vaccine) did not change significantly in both regions.

Conclusion

Acceptance of V vaccination depends in part on the use of combination vaccine.