Immunization Series Research Articles

Five year follow-up after primary vaccination against tick-borne encephalitis in children

BackgroundA first tick-borne encephalitis (TBE) vaccine booster in children is currently suggested 3 years after completing either a conventional (doses on Days 0, 28 and 300) or accelerated conventional (doses on Days 0, 14 and 300) TBE immunization schedule. This recommendation, however, may not be appropriate in cases where different TBE vaccines have been used interchangeably during the primary immunization series. MethodsTo provide robust data to better inform such recommendations, TBE antibody persistence was evaluated after 3–5 years in four groups of children (aged 5–15 years): two groups previously primed with three doses of Encepur® Children (conventional/accelerated conventional schedule); and two groups previously primed with two doses of FSME-IMMUN® followed by a third dose of Encepur® Children (conventional/accelerated conventional schedule). Immunogenicity was evaluated using neutralization (NT) assays based on both vaccine antigens as well as on the Enzyme Linked Immunosorbent Assay (ELISA). ResultsIn the two Encepur® Children groups (full series), protective NT titers of ≥10 were detected in 98–100% of children up to 5 years after their last primary vaccination, irrespective of schedule. In contrast, only 65–70% subjects in the FSME-IMMUN® Junior groups (mixed series) displayed NT titers ≥10 after 3 years. Thus, due to lower probability of achieving/maintaining long-term protective antibody levels (recently defined by the World Health Organization as an NT titer ≥10) after this time point, both FSME-IMMUN Junior groups were discontinued. ConclusionA strong antibody response persists for at least 5 years after full primary vaccination with Encepur® Children. The study thus provides support for extending the time interval for a first booster dose after primary vaccination (conventional/accelerated conventional schedule) with Encepur® Children from 3 to 5 years.

Duration of pertussis immunity after DTaP immunization: a meta-analysis.

Pertussis incidence is increasing, possibly due to the introduction of acellular vaccines, which may have decreased the durability of immune response. We sought to evaluate and compare the duration of protective immunity conferred by a childhood immunization series with 3 or 5 doses of diphtheria-tetanus-acellular pertussis (DTaP). We searched Medline and Embase for articles published before October 10, 2013. Included studies contained a measure of long-term immunity to pertussis after 3 or 5 doses of DTaP. Twelve articles were eligible for inclusion; 11 of these were included in the meta-analysis. We assessed study quality and used meta-regression models to evaluate the relationship between the odds of pertussis and time since last dose of DTaP and to estimate the probability of vaccine failure through time. We found no significant difference between the annual odds of pertussis for the 3- versus 5-dose DTaP regimens. For every additional year after the last dose of DTaP, the odds of pertussis increased by 1.33 times (95% confidence interval: 1.23-1.43). Assuming 85% vaccine efficacy, we estimated that 10% of children vaccinated with DTaP would be immune to pertussis 8.5 years after the last dose. Limitations included the statistical model extrapolated from data and the different study designs included, most of which were observational study designs. Although acellular pertussis vaccines are considered safer, the adoption of these vaccines may necessitate earlier booster vaccination and repeated boosting strategies to achieve necessary "herd effects" to control the spread of pertussis.

Multi-parameter exploration of HIV-1 virus-like particles as neutralizing antibody immunogens in guinea pigs, rabbits and macaques

Virus-like particles (VLPs) offer a platform to test the hypothesis that, since antibody binding to native envelope glycoprotein (Env) trimers results in HIV-1 neutralization, that native Env trimers presented in membranes may be useful for inducing neutralizing antibodies (nAbs) in a vaccine setting. So far, VLPs have not fulfilled this potential. Here, using a “shotgun” approach, we evaluated a wide cross-section of variables in a series of VLP immunizations. We identified 3 tentative leads. First, that VLP doses may not have been sufficient for optimal nAb induction. Second, that dampening the antigenicity of non-functional Env (for example uncleaved gp160) using either protease digests or IgG masking may be useful. Third, that guinea pig sera preferentially target non-conserved epitopes and exhibit relatively high background activity, suggesting that rabbits may be preferable as small animal vaccine models. Recent immunogenicity studies in rabbits appear to bear out all 3 of these leads.

Vaccination coverage and its determinants among migrant children in Guangdong, China

BackgroundGuangdong province attracted more than 31 million migrants in 2010. But few studies were performed to estimate the complete and age-appropriate immunization coverage and determine risk factors of migrant children.Methods1610 migrant children aged 12–59 months from 70 villages were interviewed in Guangdong. Demographic characteristics, primary caregiver’s knowledge and attitude toward immunization, and child’s immunization history were obtained. UTD and age-appropriate immunization rates for the following five vaccines and the overall series (1:3:3:3:1 immunization series) were assessed: one dose of BCG, three doses of DTP, OPV and HepB, one dose of MCV. Risk factors for not being UTD for the 1:3:3:3:1 immunization series were explored.ResultsFor each antigen, the UTD immunization rate was above 71%, but the age-appropriate immunization rates for BCG, HepB, OPV, DPT and MCV were only 47.8%, 45.1%, 47.1%, 46.8% and 37.2%, respectively. The 1st dose was most likely to be delayed within them. For the 1:3:3:3:1 immunization series, the UTD immunization rate and age-appropriate immunization rate were 64.9% and 12.4% respectively. Several factors as below were significantly associated with UTD immunization. The primary caregiver’s determinants were their occupation, knowledge and attitude toward immunization. The child’s determinants were sex, Hukou, birth place, residential buildings and family income.ConclusionsAlarmingly low immunization coverage of migrant children should be closely monitored by NIISS. Primary caregiver and child’s determinants should be considered when taking measures. Strategies to strengthen active out-reach activities and health education for primary caregivers needed to be developed to improve their immunization coverage.

The 7-valent pneumococcal conjugate vaccine elicits cross-functional opsonophagocytic killing responses to Streptococcus pneumoniae serotype 6D in children

BackgroundWe investigated the immune response to serogroup 6 with the opsonophagocytic killing assay (OPKA) in children aged 12–23 months of age after immunization with the 7-valent pneumococcal conjugate vaccine (PCV7) containing serotype 6B.MethodsBlood samples were obtained from 59 children who had blood sampling for medical examination. Immunization status against PCV7 was confirmed by immunization records and samples were categorized according to immunization status into a booster, primary, or control group. The OPKA was performed for serotypes 6A, 6B, 6C, and 6D.ResultsSubjects with no previous PCV7 immunization history showed opsonic activity for serogroup 6 in 5-30% (according to serotype). In subjects vaccinated with a 3-dose primary series, 81% showed opsonic activity for serotypes 6B and 6D, and 29% showed opsonic activity for serotypes 6A and 6C. Among subjects vaccinated with a booster dose, all subjects had opsonic activity against serotype 6B. Subjects in the booster group with opsonic activity against serotypes 6A, 6C, and 6D were 100%, 78%, and 89%, respectively.ConclusionsIn subjects aged 12–23 months, an immune response is elicited after a primary series of immunizations with PCV7 for serotypes 6B and 6D, and a booster dose enhances a cross reactive immune response against serotypes 6A, 6C and 6D.

Immunotherapy in Chronic Lymphocytic Leukemia: BCG Induced Long Term Remission

DOI: http://dx.doi.org/10.5915/15-1-12348 A case of chronic lymphocytic leukemia (C.L.L.) was treated with repeated administration of tumor dose Bacillus Calmette-Guerin (BCG). Following the first immunization series, the case has gone into complete remission and has remained so up to the time of this report, for about 9 years. The leukemic lymphocytes appeared to be null” cell type.

Seroprevalance of pertussis antibodies in maternal and cord blood of preterm and term infants

BackgroundThe resurgence of pertussis has resulted in an increased morbidity and mortality, especially among young infants. The aim of our study was to determine the antibody concentrations against pertussis antigens in cord and maternal blood in both preterm and term infant–mother pairs and to evaluate the efficacy of transplacental antibody transfer. MethodsAntibodies to pertussis toxin (PT) and filamentous hemagglutinin (FHA) in maternal and cord blood samples were measured by in-house enzyme linked immunosorbent assay (ELISA) in 100 preterm infant–mother and 100 term infant–mother pairs. Geometric mean concentrations (GMCs) of pertussis antibodies and cord:maternal GMC ratios were calculated. ResultsCord GMCs for anti-PT and anti-FHA in the preterm group were 13.15 and 14.55 ELISA U/ml (EU/ml), respectively. Cord GMCs for anti-PT and anti-FHA in the term group were 19.46 and 19.18EU/ml, respectively. Cord anti-PT GMC was significanlty lower in the preterm group (p=0.037). There were no differences between the groups with regard to maternal anti-PT and anti-FHA GMC. Placental transfer ratios for anti-PT and anti-FHA in preterms were 68% and 72%, respectively. The same ratios in terms were 107% and 120%, respectively and were significantly higher than those of preterms (p<0.001). Placental transfer ratios were even lower in preterms <32 weeks when compared to preterms ≥32 weeks and terms. There was a strong correlation between maternal and cord anti-pertussis antibody levels both in preterm and term infants. ConclusionsAnti-pertussis antibody levels were generally low in infant–mother pairs and would not be adequate to confer protection until the onset of primary immunization series. Transplacental anti-pertussis antibody transfers and antibody levels were lower in the cord blood of preterm infants, especially in those <32 weeks. These findings support the rationale for maternal immunization, which in combination with cocooning, could be a better option for preterm infants.

Prevalence of Pneumococcal Bacteremia in Children with Sickle Cell Disease Hospitalized for Management of a Febrile Illness

AbstractAbstract ▪3214▪This icon denotes a clinically relevant abstract Introduction:Children with sickle cell disease are at a high risk of death from pneumococcal bacteremia due to functional asplenia. The common practice for management of any fever in a child with sickle cell disease is in-patient antibiotic therapy for presumed bacteremia, until the blood cultures have remained negative for 48 hours. We hypothesize that interventions such as penicillin prophylaxis, use of polyvalent pneumococcal vaccine at 2 years of age in addition to the primary immunization series with pneumococcal conjugate vaccine 13 have decreased the prevalence of pneumococcal bacteremia in children with sickle cell disease. Outpatient management of an uncomplicated febrile illness may be a safe alternative. Methods:We conducted a retrospective chart review of children with sickle cell disease hospitalized with a fever at Children's and Women's Hospital between January 2006 and June 2012. We collected demographical parameters, temperature, white blood cell count and C-reactive protein level at the time of presentation as possible predictors of true bacteremia. The continuous variables were compared between the two groups (positive and negative blood cultures) using independent t-test. We also recorded the time to positivity of blood cultures, pathogens identified in positive blood cultures, serotypes and sensitivities of pneumococcal bacteria. Results:A total of 133 patients, aged 2 months to 18 years, met the inclusion criteria with 456 hospital admissions. The prevalence of culture proven bacteremia was 3.7% with only two (0.44%) cases of pneumococcal bacteremia. We have not had any patient with pneumococcal bacteremia reported since the start of pneumococcal conjugate vaccine 13, in May 2010. Both the patients with pneumococcal bacteremia were older than five years and had discontinued taking penicillin prophylaxis. The first patient was fully vaccinated with pneumococcal conjugate vaccine 7 but had not received polyvalent vaccine. She contracted a non-vaccine serotype (23B) that was susceptible to penicillin, ceftriaxone, and vancomycin. The second patient was partially vaccinated and acquired a serotype (23F) that is included in pneumococcal conjugate vaccine 7. The bacterium was resistant to penicillin but sensitive to ceftriaxone and vancomycin. In the analysis of predictors of bacteremia, the average C-reactive protein level was found to be 6.3mg/dL in patients with positive blood cultures and 4.5mg/dL in patients with negative blood cultures (p=0.02). The mean age of patients with positive blood cultures was 11 years compared to 7.4 years in patients with negative blood cultures (p=0.03). The differences in body temperature and white blood cell count between the two groups were not statistically significant. The average time to positivity measured from the time of collection was 25.4 hours. Discussion:Penicillin prophylaxis and complete immunization, in accordance with the centers for disease control and prevention guidelines are important for patients with sickle cell disease. Patients with an uncomplicated febrile illness may not necessarily need to be hospitalized to continue antibiotics. We support an outpatient care model proposed by Williams et al, comprising of a single 24-hour dose of ceftriaxone followed by oral cefixime for 5 days and follow-up telephone calls by a nurse. Good patient education may help ensure compliance with outpatient care. Outpatient management of an uncomplicated febrile illness will be more cost-effective and beneficial to the patients and families. With this approach, however, patients may not be fully protected against ceftriaxone resistant pneumococccal infections. Bacterial resistance patterns in the community should be brought under consideration when implementing such a model. Conclusion:The prevalence of pneumococcal bacteremia in children with sickle cell disease has decreased in the past few years. In our analyses, we found older age and an elevated C-reactive protein level to be statistically significant predictors of a positive blood culture. Disclosures:No relevant conflicts of interest to declare.

Survey of the Types of Cervical Lesions and HPV Genotypes Found in HPV-vaccinated Women

Introduction: The introduction of population-wide HPV (human papillomavirus) vaccination in young women has lead to a global re-evaluation of the overall need and frequency requirements for cytologic cervical screening. As a result, the gynecological algorithms for the detection of cervical lesions have been in flux in recent years in an attempt to optimize the various screening modalities while simultaneously balancing cost and effectiveness. In this study, we investigated the types of cervical lesions and HPV genotypes actually found in HPV-vaccinated women from a practical, real-world clinical perspective. Materials and Methods: Data was collected on a series of 297 consecutive women with HPV immunization. The following parameters were gathered: age, dates(s) of immunization(s), type(s) of vaccine, cytology results, and surgical biopsy results, if available. The presence of pre-vaccination HPV infection was also noted whenever possible. Specimens with abnormal cytologic results (as defined by an abnormal Pap smear result, including an ASCUS with a positive reflex high-risk HPV) subsequently underwent molecular screening for HR HPV using either the Hologic or the Roche method. All samples were then reflexed to the LiPA assay for specific genotyping. Results: Of the 297 women, 27 patients (9.1%) had an abnormal cytologic result. Two specimens had insufficient material remaining for molecular testing, and one specimen failed to run due to excessive clotting. Of the 24 remaining specimens, 21 (87.5 %) showed a positive HR HPV result on initial screening with the Hologic or Roche tests. Twenty-three samples were then successfully genotyped. Frequencies for the genotypes covered by HPV vaccination (HPV 16, 18, 6, and 11) were 17.4%, 4.3%, 4.3%, and 0%, respectively. Of note, the one patient with HPV 18 infection had received an incomplete immunization series, and one of the patients with HPV 16 had definite pre-existing cervical dysplasia before immunization. The most common HR HPV genotypes were HPV 39, 59, and 66 (17.4% each). The average number of HPV strains per patient was 2.6. Conclusions: Immunized women are not exempt from HR HPV infection. Although our data supports Gardasil ’s efficacy against HPV 16 and 18 infections, the current vaccination scheme offers only limited protection against cervical cancer. Our study clearly demonstrates that co-infection with multiple HPV strains, including combinations of both high-risk and low-risk types, is extremely common in immunized women; hence, continued careful screening by cervical cytology and/or HPV testing is critical in continuing to limit the morbidities of cervical cancer.

Importance of Timing of Maternal Combined Tetanus, Diphtheria, and Acellular Pertussis (Tdap) Immunization and Protection of Young Infants

Pertussis booster vaccine (Tdap) recommendations assume that pertussis-specific antibodies in women immunized preconception, during, or after previous pregnancies persist at sufficient levels to protect newborn infants. Pertussis-specific immunoglobulin G (IgG) was measured by IgG-specific enzyme-linked immunosorbent assay (ELISA) in maternal-umbilical cord serum pairs where mothers received Tdap during the prior 2 years. Geometric mean concentrations (GMCs) of pertussis antibodies and cord-maternal GMC ratios were calculated. One hundred five mothers (mean age, 25.3 years [range, 15.3-38.4 years]; mean gestation, 39 weeks [range, 37-43 weeks]) immunized with Tdap vaccine a mean of 13.7 months (range, 2.3-23.9 months) previously were included; 72 (69%) had received Tdap postpartum, 31 at a routine healthcare visit and 2 as contacts of another newborn. There was no difference in GMCs for pertussis-specific IgG in maternal delivery or infant cord sera for women immunized before (n = 86) or during (n = 19) early pregnancy. Placental transport of antibodies was 121%-186% from mothers immunized before and during pregnancy, respectively. Estimated GMC of IgG to pertussis toxin was <5 ELISA units (EU)/mL at infant age 2 months (start of infant immunization series). More infants of mothers immunized during pregnancy had pertussis toxin levels estimated to be higher than the lower limit of quantitation of the assay (4 EU/mL) through age 2 months (52% vs 38%; P = .34). Infants of mothers immunized preconception or in early pregnancy have insufficient pertussis-specific antibodies to protect against infection. Maternal immunization during the third trimester, immunization of other infant contacts, and reimmunization during subsequent pregnancies may be necessary.

Invasive pneumococcal diseases in birth cohorts vaccinated with PCV-7 and/or PHiD-CV in the province of Quebec, Canada

BackgroundThe 10-valent protein D pneumococcal conjugate vaccine (PHiD-CV) was licensed on the basis of immunogenicity studies and there are no published data on its effectiveness to prevent invasive pneumococcal disease (IPD). In the province of Quebec, Canada, PHiD-CV was introduced in the summer of 2009, replacing the 7-valent CRM197 vaccine (PCV-7). Transition to the new vaccine was recommended regardless of the number of PCV7 doses already administered. MethodsIPD rates in children born in 2007–2010 and observed up to the end of 2010 were computed from laboratory surveillance data. The main vaccine used for the infant primary immunization series (mainly 2 doses at 2–4 months) and the toddler (12 months) booster dose was inferred from the Quebec City Immunization Registry data. ResultsIPD rates were significantly lower in the cohorts exposed to PHiD-CV (35/100,000 person-years) as compared with those exposed to PCV-7 (64/100,000person-years; p=0.03). There was no breakthrough vaccine-type IPD case among children who had received ≥2 PHiD-CV doses for the primary series or a single PHiD-CV dose as a booster. There was also a statistically non-significant lower frequency of 19A and other non-vaccine types IPD cases in children exposed to 2+1 PHiD-CV doses as compared with those exposed to PCV-7. InterpretationResults are compatible with a high level of protection induced by PHiD-CV against IPD caused by homologous serotypes.

Incomplete Early Childhood Immunization Series and Missing Fourth DTaP Immunizations; Missed Opportunities or Missed Visits?

The successful completion of early childhood immunizations is a proxy for overall quality of early care. Immunization statuses are usually assessed by up-to-date (UTD) rates covering combined series of different immunizations. However, series UTD rates often only bear on which single immunization is missing, rather than the success of all immunizations. In the US, most series UTD rates are limited by missing fourth DTaP-containing immunizations (diphtheria/tetanus/pertussis) due at 15 to 18 months of age. Missing 4th DTaP immunizations are associated either with a lack of visits at 15 to 18 months of age, or to visits without immunizations. Typical immunization data however cannot distinguish between these two reasons. This study compared immunization records from the Oregon ALERT IIS with medical encounter records for two-year olds in the Oregon Health Plan. Among those with 3 valid DTaPs by 9 months of age, 31.6% failed to receive a timely 4th DTaP; of those without a 4th DTaP, 42.1% did not have any provider visits from 15 through 18 months of age, while 57.9% had at least one provider visit. Those with a 4th DTaP averaged 2.45 encounters, while those with encounters but without 4th DTaPs averaged 2.23 encounters.

Infant sleep after immunization: randomized controlled trial of prophylactic acetaminophen.

To determine the effects of acetaminophen and axillary temperature responses on infant sleep duration after immunization. We conducted a prospective, randomized controlled trial to compare the sleep of 70 infants monitored by using ankle actigraphy for 24 hours before and after their first immunization series at ∼2 months of age. Mothers of infants in the control group received standard care instructions from their infants' health care provider, and mothers of infants in the intervention group were provided with predosed acetaminophen and instructed to administer a dose 30 minutes before the scheduled immunization and every 4 hours thereafter, for a total of 5 doses. Infant age and birth weight and immunization factors, such as acetaminophen use and timing of administration, were evaluated for changes in infant sleep times after immunization. Sleep duration in the first 24 hours after immunization was increased, particularly for infants who received their immunizations after 1:30 pm and for those who experienced elevated temperatures in response to the vaccines. Infants who received acetaminophen at or after immunization had smaller increases in sleep duration than did infants who did not. However, acetaminophen use was not a significant predictor of sleep duration when other factors were controlled. If further research confirms the relationship between time of day of vaccine administration, increased sleep duration after immunization, and antibody responses, then our findings suggest that afternoon immunizations should be recommended to facilitate increased sleep in the 24 hours after immunization, regardless of acetaminophen administration.

A phase III randomized, controlled study to assess and compare the immunogenicity and tolerability of single and multi-dose vials of DTwP-Hib, a fully liquid quadravalent vaccine and their comparison with TETRAct-Hib vaccine in Indian infants aged 6–14 weeks

Both WHO and IAP encourage using combination vaccines, wherever feasible. The phase III trial reported here was conducted to assess and compare the immunogenicity, tolerability and safety of two quadravalent vaccines, Quadrovax(®) (new vaccine), and TETRAct-Hib(®) (available in the market) in a multicentre study, in India. In all, 361 infants aged 6-8 weeks were enrolled, out of which 339 completed the study. The vaccination was done at 6-10-14 weeks following EPI/WHO recommended immunization schedule. Blood samples were collected prior to the administration of first dose and one month after the third dose. Postvaccination, geometric mean titres for each component did not differ significantly between the single dose vial and multi dose vial subgroups and among the two study groups. Adverse events observed were within the range quoted in literature. Quadrovax(®) vaccine manufactured by SIIL was found to be safe, immunogenic and non-inferior to the comparator vaccine. The quadravalent vaccine is best recommended in the second year of life when children receive their booster dose at 15-18 months. It can be given to infants during primary immunization series at 6, 10 and 14 weeks of age when Hepatitis B vaccine is given in a separate arm or to infants at 10 weeks who receive the Hepatitis B vaccine separately following the 0, 6 and 14 weeks or 0, 1 and 6 months schedule.

Assessment Status of Immunization for Children Under 2 Years Old in Shahriar , Iran

Background: Immunization campaign is one of the most effective acts for improving community health, Yet under immunized groups, leave communities at risk for vaccine -preventable diseases. The objective of the present study is to assess status of immunization for children under 2 years old in Shahriar, Iran. Methods: This research is a cross- sectional study. Cluster sampling was used to select 210 children in the age group 18-24 month-old who were resident in Shahriar. Standard formats were used for collection of data. Descriptive and inferential statistics such as Chi-Squares, Fisher exact test, t-test, Anova, Bivariate and Logistic regression models were used to analyze the data. Results: The results show that vaccination coverage in children was higher than 90% and the highest percent of invalid vaccination (4.3%) was related to 4.5 months old children. 17.8 percent of the children partially vaccinated and 41.4 percent were vaccinated completely but with more than one month delay. The main reason for failure to immunize was mainly carelessness on health care providers and for delayed immunization was an inter-current illness. Characteristics that are strongly associated with the completion of the entire series of childhood immunization included the following: birth weight of child and number of growth monitoring visits in the second year of life. Characteristic, which is strongly associated with the delayed immunization more than one month, was center of childhood immunization. The most commonly barriers reported by the participants were waiting too long. Conclusion: There are barriers in vaccination delivery, each of barriers including the no efficient recall and reminder system, confusing vaccination orders, perceived contraindications, waiting too long, these factors was statistically associated with immunization status. It is now the time for a boost to be given to both quality and sustainability appropriate improvements and solutions should be introduced.

Inferior quantitative and qualitative immune responses to pneumococcal conjugate vaccine in infants with nasopharyngeal colonization by Streptococcus pneumoniae during the primary series of immunization

Background Heightened immunogenicity, measured one month after the primary series of pneumococcal conjugate vaccine (PCV), in African children was previously hypothesized to be due to increased rates of nasopharyngeal pneumococcal colonization during early infancy. Methods We analyzed the effect of selected vaccine-serotype (6B, 19F and 23F) nasopharyngeal colonization prior to the first PCV dose or when colonized for the first time prior to the second or third (2nd/3rd) PCV dose on serotype quantitative and qualitative antibody responses. Results Colonization prior to receiving the first PCV was associated with lower geometric mean antibody concentrations (GMCs) one month after the third dose of PCV and six months later to the colonizing-serotype. Colonized infants also had lower geometric mean titers (GMTs) on opsonophagocytosis activity assay (OPA) and a lower proportion had titers ≥8 against the colonizing serotypes (19F and 23F) post vaccination. Colonization occurring only prior to the 2nd/3rdPCV dose was also associated with lower GMCs and OPA GMTs to the colonizing-serotype. The effect of colonization with serotypes 19F and 23F prior to PCV vaccination had a greater effect on a lower proportion of colonized infants having OPA titers ≥8 than the effect of colonization on the lower proportion with antibody ≥0.35 μg/ml. Conclusion Infant nasopharyngeal colonization at any stage before completing the primary series of PCV vaccination was associated with inferior quantitative and qualitative antibody responses to the colonizing-serotype.

Implementation of Pertussis Vaccine for Postpartum Mothers

Issue: In Dec. 2006, due to concern over pertussis-related deaths of infants, the CDC recommended vaccinating women prior to pregnancy. Pertussis can cause serious illness in adults but symptomsmay be mild and resemble a common cold or bronchitis. The disease is potentially fatal for infants. The number of reported pertussis cases has been rising and the state of Pennsylvania has had 5 infant deaths since Dec., 2009. Most of the babies were under 6 months old and nearly 50% of the sources were parents. Even if vaccinated, immunity wanes andmay leave women of childbearing age vulnerable, possibly exposing a newborn to pertussis. Infants begin their pertussis immunization series at 2 months and aren’t fully protected until at least 3 doses. The only way to protect these babies is to vaccinate their caregivers.

Impaired hepatitis B vaccine responses during chronic hepatitis C infection: Involvement of the PD-1 pathway in regulating CD4+ T cell responses

Vaccination for hepatitis B virus (HBV) in the setting of hepatitis C virus (HCV) infection is recommended, but responses to vaccination are blunted when compared to uninfected populations. The mechanism for this failure of immune response in HCV-infected subjects remains unknown but is thought to be a result of lymphocyte dysfunction during chronic viral infection. We have recently demonstrated that PD-1, a novel negative immunomodulator for T cell receptor (TCR) signaling, is involved in T and B lymphocyte dysregulation during chronic HCV infection. In this report, we further investigated the role of the PD-1 pathway in regulation of CD4+ T cell responses to HBV vaccination in HCV-infected individuals. In a prospective HCV infected cohort, a poor response rate to HBV vaccination as assayed by seroconversion was observed in HCV-infected subjects (53%), while a high response rate was observed in healthy or spontaneously HCV-resolved individuals (94%). CD4+ T cell responses to ex vivo stimulations of anti-CD3/CD28 antibodies or hepatitis B surface antigen (HBsAg) were found to be lower in HBV vaccine non-responders compared to those responders in HCV-infected individuals who had received a series of HBV immunizations. PD-1 expression on CD4+ T cells was detected at relatively higher levels in these HBV vaccine non-responders than those who responded, and this was inversely associated with the cell activation status. Importantly, blocking the PD-1 pathway improved T cell activation and proliferation in response to ex vivo HBsAg or anti-CD3/CD28 stimulation in HBV vaccine non-responders. These results suggest that PD-1 signaling may be involved in impairing CD4+ T cell responses to HBV vaccination in subjects with HCV infection, and raise the possibility that blocking this negative signaling pathway might improve success rates of immunization in the setting of chronic viral infection.

Addressing Adolescent Immunization Disparities: A Retrospective Analysis of School-Based Health Center Immunization Delivery

We compared completion rates for adolescent immunization series administered at school-based health centers (SBHCs) to completion rates for series administered at community health centers (CHCs) within a single integrated delivery system. We performed a retrospective analysis of data from an immunization registry for patients aged 12-18 years. Patients were assigned to either an SBHC or a CHC during the study interval based on utilization. We used bivariate analysis to compare immunization series completion rates between the 2 groups and multivariate analysis to compare risk factors for underimmunization. We performed subanalyses by ages 12-15 years versus ages 16-18 years for human papillomavirus (HPV) and for the combination of HPV; tetanus, diptheria, and pertussis (Tdap); and tetravalent meningococcus virus. SBHC users had significantly higher completion rates (P<.001) for hepatitis B, Tdap, inactivated poliovirus, varicella, measles/mumps/rubella, and HPV for ages 16-18 years, and for the combination of HPV, Tdap, and MCV4 for ages 16-18 years. CHC users had higher completion rates for tetanus and diphtheria. SBHCs had higher completion rates than did CHCs for immunization series among those aged 12-18 years, despite serving a population with limited insurance coverage.

Evaluation of the Compliance With Recommended Procedures in Newborns Exposed to HBsAg-Positive Mothers

Maternal-infant transmission of hepatitis B virus (HBV) during birth carries a high risk for chronic HBV infection in infants with frequent subsequent development of chronic disease. This can be efficiently prevented by early immunization of exposed newborns. The purpose of this study was to determine the compliance with official recommendations for prevention of perinatal HBV transmission in hepatitis B surface antigen (HBsAg) exposed infants. Records of pregnant women at 4 sites in Switzerland, admitted for delivery in 2005 and 2006, were screened for maternal HBsAg testing. In HBsAg-exposed infants, recommended procedures (postnatal active and passive immunization, completion of immunization series, and serological success control) were checked. Of 27,131 women tested for HBsAg, 194 (0.73%) were positive with 196 exposed neonates. Of these neonates, 143 (73%) were enrolled and 141 (99%) received simultaneous active and passive HBV immunization within 24 hours of birth. After discharge, the HBV immunization series was completed in 83%. Only 38% of children were tested for anti-HBs afterwards and protective antibody values (>100 U/L) were documented in 27% of the study cohort. No chronically infected child was identified. Analysis of hospital discharge letters revealed significant quality problems. Intensified efforts are needed to improve the currently suboptimal medical care in HBsAg-exposed infants. We propose standardized discharge letters, as well as reminders to primary care physicians with precise instructions on the need to complete the immunization series in HBsAg-exposed infants and to evaluate success by determination of anti-HBs antibodies after the last dose.